Document rp269p8Ej6BkJ4MqNEME5ELKa

Vulcan Materials Company CHEMICALS DIVISION / P. 0. SOX 112*3 . WICHITA. KANSAS 57277 TELEPHONE 315 524-4211 THOMAS A. ROBINSON, Ph. 0 DIRECTOR ENVIRONMENTAL AFFAIRS January 22, 1979 / Docket Officer Docket No. H-079, Room S-6212 U.S. Department of Labor, OSHA Third Street and Constitution Avenue, N.W, Washington, D. C. 10210 Dear Sir: Vulcan Materials Company, Chemicals Division, is a producer of 1,2-diehloro- ethane (ethylene dichloride) and as such wishes to submit comment on the OSHA request for information on 1,2-dichloroethane as published in 43 FR 56910, December 5, 1978. , Under the auspices of the Manufacturing Chemists Association, Vulcan is parti cipating in an in-depth, inhalation toxicology study of the effects of ethylene dichloride (EDC)on rats and mice. Inhalation was chosen as the route of expo sure since it represents the route of exposure most likely to be encountered in the workplace. The total toxicological study consists of five segments. An 18month exposure bioassay study was conducted to evaluate effects of the chronic exposure to EDC and was supported by a concurrent clinical chemistry study of the long-term effects of EDC on various biological parameters. These studies were conducted by Dr. Cesare Maltoni, Bologna Tumour Institute and by Dr. F. Spreafico, Mario Negri Institute, respectively, and the final reports of these studies are expected to be ready shortly. In addition, studies are in progress on the effects of EDC on metabolism, teratogenicity and reproduction. The tera togenicity study is basically complete and the final report will be forthcoming in the near future. The reproduction study will be completed later this year. In an interim final report on the 18-month bioassay study, Maltoni stated that "no 'specific' type of tumour has been found in treated animals (rats and mice)." Maltoni further stated, "No relevant changes in the incidence of tumours, normally occurring in the bred (sic) of mice used, has been observed." With respect to the rat study, he stated, "No relevant changes in the incidence of tumours normally occurring in this bred (sic) of rats used has been observed, following the treatment, apart from a moderate overall increase of benign mammary tumours (fibromas and fibroadenomas) in treated rats when compared to SL 080810 Docket Officer, Docket No. H-079 January 22, 1979, Page 2 controls, however, without a dose-response relationship, within the exposed groups. This phenomenum has been observed in correlated long-term bioassays of other compounds in the same animals, suggesting a possible roie of stress." Maltoni concluded with the statement, "On the basis of present data, it may be stated that in our experimental conditions DCE has failed to show specific carci nogenic potentialities," and "The presented data may be considered almost conclusive." NIOSH Revised Criteria Document In our review of the NIOSH Revised Criteria Document on EDO, * we noted that the document does cite the long-term bioassay study of Maltoni, but we believ that in essence NIOSH inappropriately disregards the study and did not give it the consideration which it merits. For example, the document focuses on the marginal increase of benign mammary tumors in the Sprague-Dawley rat, (a strain with a known propensity , for the spontaneous development of mammary tumors) and appears to place more emphasis on this occurrence than it does on the general findings of the study. It should be noted that the incidence o_mammary tumors in separate controls of 39/90 is not of significant difference from the 46/90, 41/90, 29/90, and 40/90 observed in animals exposed to 150, 50, 10, and 5 parts per million EDC, respectively. The document continues in stating that "(v^hile increases in tumor incidences were not significantly different from controls at this level, increased incidences did occur, and higher levels of exposure may result in still greater incidences of tumors." The document fails to mention that initially.the highest exposure level was greater than 150 ppm but was reduced, due to signs of severe acute toxicity. A higher exposure level than 150 ppm might have yielded no meaningful study at all, due to this observed effect. The NIOSH document indicates that there is no epidemiological evidence to associate EDC with human cancers and writes off the existing seven epidemio-' logical studies relative to the human exposure to EDC as referring only to physiological alterations and morbidity. We submit that if EDC is a potential human carcinogen of any significance, the incidence of such cancers would most likely have shown up in at least one of these studies. Occupational Exposure to Ethylene Dichloride - Revised Recommended Standard, NIOSH, September, 1978. ' SL 080811 Docket Officer, Docket No, H-079 January 22, 1979, Page 3 In addition, the document refers to the skin painting study by Dr. B. M. Goldschmitt of the Institute of Environmental Medicine, New York University. This study showed no increased incidence of tumors following application of EDO to the skin of mice. Further testing of EDO as an initiating agent for the tumor-promoter phorbol myristate acetate "for more than one year, (the com bined treatment) yielded one animal (in 30) with one papilloma." A papilloma is a benign tumor of the epithelium, similar to a wart, and may have a virus as a causitive agent. Again, the NIOSH document discounts this negative finding in stating, "This study was not originally intended to test the carcinogenicity of ethylene dichloride per se when applied to skin. Greater numbers of experi mental animals and greater quantities of ethylene dichloride applied to the skin would be necessary before any definitive conclusion could be made. NIOSH therefore considers the carcinogenic potential of ethylene dichloride via the dermal route to be undetermined at this time." NIOSH, -in the revised criteria document, than places great emphasis on th findings of positive mutagenicity in Salmonella typhinurium bacteria with the inconsistent statement that "(w[hile the relation of mutagenisis to carcinogeni city is not firmly established, the consistent, positive mutagenicity findings support a conclusion that ethylene dichloride be considered a carcinogen. " (Emphasis added). Please note that they do not say a "potential carcinogen" but a "carcinogen." From the general tenor of the criteria document* we get the distinct impres sion that selective interpretation of the studies cited above was used to yield only that information which would support the document's recommended exposure limitations and workplace standards. Although we do not challenge the findings of the NCI, where the route of exposure to EDC was via gastric intubation, we submit that this route of exposure is not typical of that encountered in the workplace and the high dose of EDC used in this study would correspond to a daily dose of about 7 grams for an individual weighing 150 pounds. NIOSH Recommended Exposure Limitations and Work Practices Having reviewed the NIOSH revised criteria document, we believe that the recommended permissible exposure limits of 1 ppm time-weighted average, for a 10-hour workday, 40-hour workweek, and the recommended ceiling concentration of 2 ppm, as determined over a 15-minute sampling period, are presently unjustified and not substantiated by any existing evidence that EDC is a significant potential-human carcinogen. Our belief is supported by the fact that these PEL, limitations are more restrictive than those currently SL 080812 Docket Officer, Docket No. H-079 January 22, 1^79, Page 4 in effect for vinyl chloride and acrylonitrile, chemicals which have been associated with human cancers. In addition, we find that the workplace standards, regarding personal protective equipment and clothing, regu lated areas, decontamination of equipment, mandatory showers, and the provision of clean work clothing on a daily basis, are more restrictive than the current standards for vinyl chloride and acrylonitrile. Therefore, based on the negative findings in the epidemiological studies and the nega tive results of the two separate animal studies (Maltoni and Goldschmitt), we believe that the recommendations contained in the criteria document are not warranted and have not been justified. Emergency Temporary Standard We believe that the preponderance of evidence presently available, relative to the routes of exposure most likely to be encountered in the workplace, indicates that an ETS is not necessary. Recommendation We recommend that the results of the toxicological studies currently-in pro gress be considered in the evaluation of the necessity of imposing a more stringent standard for the occupational exposure to EDC. Since these studies will be completed in the near future, we believe that a delay by OSHA, on further action to modify or issue an occupational standard specific to EDC, is justifiable and warranted. Sincerely yours TAR:bl Thomas A. Robinson SL 080813 IN REPLY REFER TO: D-203 106. United States Department of the Interior BUREAU OF RECLAMATION ENGINEERING AND RESEARCH CENTER P.0. BOX 25007 BUILDING 67, DENVER FEDERAL CENTER DENVER, COLORADO 80225 JAN 18 1979 Docket Officer Docket No. H-079, Room S6212 U.S. Department of Labor, OSHA Third Street and Constitution Avenue, NW Washington DC 20210 1 Subject: Review of Request for Comments and Information on Occupational Exposure to 1, 2-Dichloroethane (ER 78/1189) Sir: We have no special expertise concerning toxicological, metabolic, hereditary, carcinogenic, and other epidemiological studies related to occupational exposure to 1, 2-Dichloroethane. The current threshold limit value (XLV) for this material is not proposed to be changed, and Reclamation has adopted the limits as established by the American Conference of Governmental Industrial Hygienists. Other than the utilization of this material in limited laboratory quantities for the analysis of paints and polymer concrete, this request and proposed standard would have no effect on the operations or mission of the Bureau of Reclamation. Very truly yours John C. Peters Environmental Specialist SL 080814 ETHYL CORPORATION TOXICOl-OGY AND INDUSTRIAL HYGIENE DEPARTMENT J&riiYL Tower* 451 Florida Baton Rouge. Louisiana 70801 January 30, 1979 3 Docket Officer, Docket H-079 Room S6212, U.S. Department of Labor_ Occupational Safety and Health Administration Third Street and Constitution Avenue, N.W. Washington, D.C. 20210 Gentlemen: The attached document is submitted in response to the request for information on: Occupational Exposure to 1,2-Dichloroethane {Ethylene Dichloride-EDC) published in 4^ Fed.Reg. 56910 (December 5, 1978) . I appreciate the opportunity to submit this material. Sincerely, GTH:ws Attachment - 4 copies Director SL 080815 A SUBMISSION by Ethyl Corporation in response to the request December 5, 1978 of Eula Bingham, Assistant Secretary of Labor, for information to be used in developing a Standard for: 1,2-DICHL0R0ETHANE Note: The information given in the following pages addresses in turn each of the eleven categories of information requested in the Notice published in the Federal Register on December 5, 1978, p. 56910. Ethyl Corporation Baton Rouge, Louisiana January 25, 1979 SL 080816 1 Background and Comments 1,2-Dichloroethane (Ethylene dichloride-EDC) is usually manufactured by the liquid-phase reaction of chlorine with ethylene in the presence of a metal halide catalyst. No by products are formed. The crude EDC is passed over to a fractio nating tower where the refined product is recovered in a yield of 96-98%. An alternative manufacturing process involves the reaction of ethylene, hydrogen chloride and air in a catalystbed made up of copper chloride with other metal chlorides. This "oxychlorination" process is preferred when an excess of hydrogen chloride is available. EDC has been an important commercial chemical since the early part of this century. Since 1948, growth in commercial use has greatly expanded as this material came to be commonly used as a starting material for vinyl chloride. In 1972, 93% of the vinyl chloride produced in this country was based on EDC. Future usage of EDC will be greatly influenced by any OSHA and EPA regulations which are promulgated for EDC. The chemical industry, of course, is very interested that its workers are not over-exposed to noxious chemicals. At the same time, overly restrictive regulations increase production costs and can there by jeopardize the workmen's jobs if particular chemical prodducts become too high priced for the intended use. Besides the use of EDC for the manufacture of vinyl chloride, in another major application Ethyl utilizes EDC as a component of the lead scavenger system in leaded gasoline. This application goes back to the 1920's when it was discovered that EDC and EDB (ethylene dibromide) can be blended in gascJine to produce a synergistic scavenger mix. The halide atoms react with the lead atoms during gasoline engine combustion to produce lead salts which temporarily vaporize and clear from the engine before sol) ^tying. The introduction of any alternative formulation of anti knock additive would require additional time-consuming testing SL 080817 2 and research in the current model lead-tolerant emission control systems. EPA would require a complete evaluation before accep tance of any new scavenger components under the terms of the recent amendments to the Clean Air Act. Thus, regulating EDC out of gasoline might result in eliminating the use of lead antiknock additives. Though the amount of leaded gasoline used in the U.S. is declining because of conversion to unleaded gaso line, the use of leaded gasoline is expected to continue to be of major importance because its markets are worldwide. It is widely recognized that lead antiknocks are "energy savers". The elimination of EDC as a "scavenger" in leaded fuels would severely reduce the utility of this energy saving additive. The result would be a significant increase in the nation's crude oil usage. The production and utilization of unleaded gasoline results in 5 to 6% more crude oil usage as compared to leaded gasolines. Furthermore, the oil industry would be unable to produce the required volumes of gasoline during the next three or four years without lead antiknocks being available. This is because additional, very expensive, refinery process equipment would have to be installed to produce the necessary volume of high-octane blending stocks. EDC has other important commercial uses. It is employed as a basic raw material for the manufacture of trichloroethylene, perchloroethylene, 1,1,1-trichloroethane (methyl chloroform), ethylene amines, vinylidene chloride and a variety of smaller scale uses. The NIOSH Criteria Document Revision (DHEW-NIOSH Publication No. 78-211, September 1978) does not recognize that EDC may be a minor component of a solution in some of its uses. According to the definition used by NIOSH, "The term ethylene dichloride refers to all physical forms of the compound and its solutions". The document further defines "occupational exposure to ethylene dichloride" as work in any area in which ethylene dichloride is produced, stored, used, packaged or distributed. The combination of these two definitions would make the Standard all inclusive SL 080818 3 for any material containing traces of EDC. This would work an unnecessary and unreasonable hardship on many businesses and industries. For example, every service station in the country would be required to monitor employees for personal exposures and to have preplacement physical examinations for all workers, annual physical exams, maintain records for 30 years, etc. There is no potential benefit from all this expense with regard to service station employee exposures to EDC. The concentration of EDC in gasoline is so low that there is no likelihood of anyone being exposed over the recommended 1 ppm TWA or 2 ppm ceiling. While all attempts to measure EDC near gas stations or busy roads have shown levels to be below the limits of detection, extrapolation from EDB measurements lead to an estimation of well under 1 ppb. Therefore, it is unreasonable to require every service station in the country to incur the expense of monitoring, medical exams, and record keeping. There are likely to be other situations where EDC is a minor impurity in a product where similar unreasonable expenses will be required. We doubt that the intention of the proposal for a regu lation was to cover situations where exposures can be deduced to be insignificant. The regulations covering other known car cinogens specify a concentration in solution below which the regulation does not apply. It is only logical to use the same reasoning in developing an EDC regulation. In the original benzene standard proposed by OSHA, there was no exemption of dilute solutions. This fact caused an un reasonable burden on many industries. OSHA recognized this and modified its proposal to exclude solutions containing less than 0.5% benzene. OSHA did exempt gasoline stations from the original standard. By the same logic, gasoline stations should be exempted from an EDC standard. However, to be consistent and reasonable, and to prevent unwarranted cost burdens on other industi.ies, an exemption for low concentrations of EDC in solution should Le specified. SL 080819 4 1. Metabolism It is essential that further metabolism research be conducted before promulgation of a revised TWA workplace standard for exposure to EDO. EDC has been shown by NCI to be biotransformed in laboratory animals to a variety of metabolites, including monochloroacetic acid, which depresses enzymes including glutathione. However, no attempt was made to correlate dose dependent biological effects with degrees of enzyme saturation. Recent Dow studies have shown that a "no effect" level may indeed, be achieved in rats exposed to vinyl chloride, depending upon the degree of glutathione saturation. Such studies on EDC should demonstrate a safe level of exposure. NCI made no attempt to demonstrate that the species or strains selected for their bioassay were appropriate. They should conduct sufficient metabolism studies to elucidate the exact in vivo biotransformation steps, pharmacokinetics, active forms, and in vitro correlation data. A sound scientific study could be designed using the following steps: A. In vivo rat metabolite profile characterized, and pharmacokinetic parameters identified, following administration by inhalation exposure. (Oral administration may lead to a different metabolite profile due to differences in membrane barrier metabolism of the stomach versus the lung.) B. Tn vitro rat metabolites identified and correlated with in vivo metabolites. (In vitro systems could include rat lung, liver and kidney tissues). C. In vitro human metabolites identified as in Step 2. Positive correlation would confirm that the rat was the most appropriate species. Negative cor relation would indicate that other rat strains or animal species should be evaluated. D. Conflicting results between Professor Maltoni and NCI could then be resolved by repeating the above steps by the oral route. Difference in metabolic SL 080820 5 profiles and pharmacokinetic parameters could account for tumor formation in the NCI study and lead to identi fication of the active metabolite(s) involved. 2. Toxicity and Related - Carcinogenicity Studies The conclusion drawn by NCI that EDC is carcinogenic in rats and mice is of questionable scientific validity for the following reasons: A. Intubation of EDC over a long period of time is an unacceptable method of exposure to EDC. EDC is an acute and chronic irritant. F. Weiss has re ported that EDC erodes the membranes of the gastrointestional tract. It is not surprizing that con tinued irritation of the stomach with EDC produces an adverse response. 2 Robbins and Angell in "Basic Pathology" state that "protracted chronic inflammation predisposes to squamous cell carcinomas; furthermore, neglected cases may become deeply invasive and metastasize to surrounding tissues". This type of inflammation was very probably elicited in the EDC animal feeding. NCI made no attempt to determine the acute or chronic irritating e'ffect of EDC. Clearly this was a major deficiency of the study. B. In addition to the squamous cell conclusions as discussed above, the NCI study does not show a dose response relationship among other neoplastic lesions, based on an analysis of the "target organs". The NIOSH criteria document indicates there s a d se response but this is incorrect. As shown in tie table below, based on data from Table Al, A2, B1 and B2 of the NCI 1,2,Dichloroethane Assay Report (No. 107-06-2), a dose response is clearly absent. SL 080821 HEMANGIOSARCOMAS 6 Rat Target Tissue Spleen Liver Pancreas Stomach Subcutaneous Large Intestine Low Dose Males Females 6/50 1/50 1/50 2/50 2/50 2/50 High Dose Males Females 2/50 1/50 1/50 1/50 1/50 1/50 1/50 In regard to NIOSH's statement that there was a statistically significant increased incidence of adenocarcinomas of the rat mammary gland, it should be recognized that the incidence of spontaneous mammary gland tumors in the Osborne-Mendel rat has been re ported by N.P. Page and others to be as high as 32%. NCI reported 10% in Controls, 2% at Low Dose and 36% at High dose, all within the distribution range of spontaneous tumors. A dose/response relationship was also not demon strated in the female B6C3F1 mice in regard to the mammary adenocarcinomas, (low-18%; High-15%) and endo metrial tumors as indicated in the NCI report. Evalua tion of the apparent dose/response in both sexes in regard to lung adenomas, as well as endometrial tumors, cannot be made without historical background data on spontaneous incidences. C. Inhalation is the method of choice for the study of the potential carcinogenicity of EDC. Dr. Cesare Maltoni of the Cancer Center, Bologna, Italy, has, of course, carried out such a study. His rats and mice showed in creases only in mammary tumors due to EDC exposure. These increases, he says, are not dose related and very characteristically run at about the 50% incidence level for each dose (150, 50, 10 and 5 ppm) as compared to about a 38% incidence level in untreated controls. SL 080822 7 Dr. Maltoni explains that this increase in tumorformation is, in his opinion, related to a chemical irritancy effect and to an upset in body chemistry and not to any inherent carcinogenicity of EDC. Dr. Maltoni reports that the mammary tumor increase is characteristic, and of the same order of increase, for a variety of other chemicals not considered to be car cinogens. Included in this group are such relatively innocuous chemicals as Fluorocarbons 11, 12 and 22. Inherent in the NCI gavage approach is that no conside ration is given to the fact that the bioavailability and pharmacokinetics of EDC are affected by the route of 3 administration. As J.G. Wagner states: "The metabolites formed after one route of admini stration may be different than those formed after another route of administration." 4 Wagner says further: "Drug metabolism may take place in the gastro intestinal wall during the absorption process, in the liver, and in various tissues of the body, particularly in the lung and kidney." 5 These thoughts are further developed by H.M. Bolt : "However, it has to be considered that biological action of a xenobiotic does not only depend Oi. the biochemical target mechanisms of the latter, but is also largely influenced by pharmacokinetic factors -" The foregoing aspects may explain why the gavage study appears to show a carcinogenic effect while the in halation data are negative. Of considerable importance is the fact that workers ;.ro exposed to EDC by inhalation, not ingestion. Clearly the Maltoni study is more meaningful to worker health than the NCI study. SL 080823 8 The NCI study also failed to consider possible indirect mutagenic effects upon intestinal bacteria. These effects may very well be the basis for the con flicting results obtained by Professor Maltoni. The EPA, moreover, recognized the need for further investi gations before final conclusions are drawn. Food Chemical News announced in 1978 that the EPA felt that additional work was required on EDC. However, to date, NCI has not approved additional research. SL 080824 9 References 1. Weiss, F., Arch, f. Gewerbepath. u Gewerbehyg., 15, 253 (1957) . 2. Robbins, S.L. and Angell, M. , "Basic Pathology", 2nd Ed., 1976, W.B. Saunders Co., p. 117. 3. Wagner, J.G., "Fundamentals of Clinical Pharmacokinetics", First Edition, 1975, Drug Intelligence Publications, Inc. p. 356. 4. Ibid, p. 34. 5. Bolt, H.M., "Pharmacokinetics of Vinyl Chloride", Gen. Pharmac. Vol. 9, 1978, pp 91-95. SL 080825 10 3. Human Epidemiology No human epidemiological study has been made. However, records of Ethyl Corporation contain the health histories of employees potentially exposed to EDC during the company's entire developmental and manufacturing experience with it. Our Medical Department has observed no unusual adverse health effects on workers exposed to EDC. 4 - Medical Surveillance Each employer should conduct a medical surveillance program for all employees who are or will be exposed to EDC and following emergency situations resulting in potentially hazardous exposure. The employer should provide each employee exposed to EDC in excess of the action level with the opportunity for medical examinations performed under the supervision of a licensed physician who has been apprised of reason for the examination and of the nature of the employee's work exposure. Workers who are or may be exposed to EDC in excess of the action level should have pre-placement medical examina tions and annual medical examinations with emphasis on the liver, kidneys, lungs, cardiovascular system, nervous system, gonads, and skin. Laboratory tests should include tests of liver function, a complete blood count, urinalysis, spirometry and any other tests the physician deems appropri ate . When the tests performed show abnormalities, the tests should be repeated as soon as is practical, preferably within one month. If, at the time the employee is examined, uhe physician advises withdrawal of the employee from poten tial exposure to EDC, the employee and employer shall be so advised by the examining physician. Emergency Exposure - Each employee exposed to EDC during an emergency shall be afforded medical surveillance as determined by the examining physician to be appropriate. SL 080826 11 5. Respiratory Protection Full face piece, positive pressure air supplied respi rators are normally used for EDC in the manufacturing areas where vapor concentrations are expected to be high. A full face-piece, organic vapor canister mask is allowed for emergency escape purposes. Half face-piece organic vapor cartridge masks are permitted in some operations where concentrations are not expected to exceed 500 ppm. Personal and ambient air monitoring results at Ethyl facilities show EDC concentrations well below permissible limits (see Section 7). Therefore, respiratory protection is not required for routine job functions, i.e. collecting quality control samples and making unit rounds. Full face canister masks are located in the operating areas for emergency use only. Supplied air respirators are utilized for vessel entry or maintenance jobs where exposures to EDC are antici pated. Half face-piece organic vapor cartridge respirators are used in barge loading operations. 6. Use and Production Technologies Engineering Controls, including... Engineering controls are used to minimize workers' exposure to airborne - levels of EDC. When new equipment is installed, the design provides for such controls. A rou tine maintenance program ensures that all engineering controls, ventilation and physical control systems are maintained in efficient working order at all times. Special Process Equipment A. All pumps in the processing area have mechanical seals. B. Quality control sampling of process streams is conducted via a continuous circulating loop, using a three-way valve. This avoids the need to flush lengths of pipe to get a representative process sample, thereby eliminating large spills and splashes. SL 080827 12 C. The field sample booth is equipped with a stan dard laboratory hood to control vapors during routine analysis. D. The process areas are constructed as open struc tures to eliminate confined spaces where EDC concentrations would tend to accumulate. E. The unit control room is situated remotely from the process area. Clean make-up air and airconditioning is provided. Ventilation -- The production area is located outside, and natural ventilation is obtained. All quality control samples are analyzed under standard laboratory fume hoods to reduce potential exposures. Housekeeping -- Emphasis is placed on cleanup of spills, periodic inspection, repair of equipment and leaks, and proper storage of materials. Emergency escape routes are kept clear at all times. EDC process drains are diverted to a special collection pit for EDC reclaimation. Sanitation Practices -- Emergency showers, eye-wash stations and hand-washing facilities are well marked and readily available in the work area. Any clothing accidentally wetted by EDC is removed immediately and the skin washed thoroughly with soap and water. Protective Clothing -- Because EDC is a liquid under ambient conditions, impervious protective clothing is required for various jobs. During operations or maintenance procedures where splashing, spilling, spray ing, etc., or skin contact could occur special clothing is required, i.e. when collecting quality control samples impervious gloves and goggles are mandatory. Eye Protection -- Goggles are required during all tasks where eye contact with EDC is possible. Good hygiene practices are enforced at all times. SL 080828__ 13 Warning Devices and Labels... The following cautions and first aid advice is con sidered appropriate, and should be posted and disseminated in all appropriate places. WARNING HARMFUL IF INHALED, SWALLOWED OR ABSORBED THROUGH SKIN. CAUSES EYE IRRITATION Avoid breathing vapor. Keep container closed. Use with adequate ventilation Avoid contact with eyes, skin and clothing. Wash thoroughly after handling. FIRST AID: If inhaled, remove to fresh air. If not breathing, give artificial respiration, preferably mouth-to-mouth. If breathing is difficult, give oxygen. Call a physician. In case of contact, immediately flush eyes or skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Call a physician. Wash clothing before reuse. 7. Employee Exposures Number of employees exposed full time, BR - 36; Hen - 12 Number of employees exposed part time, BR - 114; Hou - 38 With few exceptions, exposures have generally been low e.g. <5 ppm. Area monitors indicated <3 ppm. Area and personnel monitoring of Ethyl's Baton Rouge plant has produced the following specific data: SL 080829 TABLE I Workplace and Ambient Levels of EDC 14 Area Concentration (ppm) Range Mean Ethyl - Baton Rouge (Hydrocarbon Manuf.) Ethyl - Baton Rouge (Hydrocarbon Maintenance) 0.1-5.6 1.6-13.5 1.6 5.7 Ethyl - Baton Rouge (TEL Manufacturing) Ethyl - Houston (CHA Section) Ethyl - Houston (Laboratory) Ethyl - Houston (TEL Manufacturing) Ethyl - Houston (EDC Barge Loading) <0.02 0.02-2.6 0.02-1.24 0.02 -0.24 0.3-3.4 1.0 0.5 0.06 1.4 Comments 33 Samples 23 Below 1 ppm 3 Samples 2 Below 5 ppm Reboiler change c 2 Samples None Detected 14 Samples 7 Below 1 ppm 3 Samples 2 Below 1 ppm 9 Samples 8 Below 0.2 ppm 6 Samples 3 Below 1 ppm SL 080830" 15 8,9. Technological and Economic Feasibility of Reducing Employee Exposure Exposures of workers to EDO vapor can be minimized if certain standard procedures are followed at all stages of production. The following basic provisions can be incor porated into such operating procedures. As additional methods of control are devised, they can be implemented wherever appropriate. Routine operation -- Where a local exhaust ventilation or collection system is used, it can be so designed and maintained as to minimize EDC concentrations in air. Air from the exhaust system must not be recirculated into the workroom. Good housekeeping practices should be exercised at all times. Smoking is prohibited in process areas, except in designated areas. Abnormal/emergency operation -- When vessel-opening, or entry of equipment which may contain EDC, is required, appropriate special procedures should be employed. Any worker involved in these tasks should be required to use adequate personal protective equipment, including a respirator and protective clothing. A formalized written vessel entry procedure is established and follow'ed. The appropriate respiratory protective equipment should always be available for use during emergencies. Fire fighting procedures have been established and appropriate equip ment provided. Cost of compliance Capital, BR Houston Annual, BR Houston Differential First Year Operating Cost r BR Houston 10 ppm $460,000 153,000 248,000 83,000 141,000 47,000 1 ppm $655,000 220,000 322.000 108.000 181,000 60,000 Cost for operating at levels below 1 ppm become very high and lower levels are, we believe, unnecessary. SL 080831 16 10. Analytical and Sampling Methods Sampling Method Collection Medium: SKC 600 mg charcoal tubes Flow Rate: 100 cc/min. Pump: DuPont constant low flow pump Model 125 Method: Collect in worker's breathing zone for minimum of 7 hours during working shift for personal samples. Stationary samples collected in same manner. Calculation: tota! ug found x 24.45 = Vol. in 1 x MW exposure ppm r Analytical Method Collection Medium: SKC 600 mg charcoal tubes Eluant: Reagent grade carbon disulfide with pentane as internal standard. Desorption Conditions: Cool eluant in dry ice, add charcoal from sample tube and place in wet ice bath for thirty minutes with occasional agitation. Gas Chromatographic Conditions: Chromatograph: Hewlett-Packard 5710 with flame ionization detector Column: 1/8" x 25' 30% Se-52 on Gas Chrom Q, 80/100 Mesh Injector Temperature: 150C Oven Temperature: 100C Isothermal Detector Temperature: 300C Carrier Gas: Helium Flow Pate: 30 ml/min. Analytical Precision: Unknown Analytical Accuracy: + 10% Low Detectable Limit: 5 ug SL 080832-- 17 11. Whether an ETS Issuance is Appropriate The issuance of an Emergency Temporary Standard is not appropriate. There is no indication of any manufac turing or user emergency. SL 08083? BF ' Chemical Division February 1, 1979 The BFGoodrich Company Chemical Division 6100 Oak Tree Boulevard Cleveland, Ohio 44131 216-524-0200 William C. Becker Division Vice President Employee Relations and Public Affairs Docket Officer Docket No. H-079 Room S6212 U. S. Department of Labor 0SHA Third Street & Constitution Washington, D. C. 20210 Ave., Subject; 0SHA request for information on 1,2-dichloroethane Dear Sir: BFGoodrich Chemical Division appreciates this opportunity to respond to OSHA's request for information regarding 1,2-dichloroethane (ethylene dichloride). We have many years' experience in the manufacture of EDC and do not know of any evidence of a grave danger to the health of our employees, calling for immediate action. Therefore, it is our belief that there is no need for an emergency temporary standard for ethylene dichloride (EDC). We base this position on two facts. There is no scientific data, to our knowledge, to support imposing an emergency temporary standard. Our personnel monitoring has shown that we have already attained low levels of EDC exposure. Following are answers to the questions you have posed. Human epidemiology. BFGoodrich Chemical Division has manufac tured and processed EDC at its Calvert City, Kentucky, plant for 15 years, converting it to vinyl chloride. We also make chlorine and ethylene at this site. Therefore, our employee exposures at this plant tend to be mixed and few employees can be identified whose principal exposure would have been to EDC. Meaningful epidemiology study, at this point, is not possible. Medical surveillance procedures. BFGoodrich Chemical Division believes that appropriate medical surveillance should be directed at identifying the effects of chronic exposures to EDC. Acute effects will be self-evident and readily identified with the exposure situation. SL 080834 2- - Th BFGoodrtch Company Chemical Division In looking for evidence of chronic toxicity, we feel medical surveillance efforts should be directed at examination of the liver and kidney, which are the organs principally affected. We believe the best means for identifying liver and kidney damage is by chemical examination of the blood and urine for evidence of organ damage. We also believe that the employee's health will be best protected by allowing the examining physician a wide latitude in the choice of tests to be used. We feel that requiring specific bio-chemical tests will tend to freeze the examination into a fixed format and will discourage physicians from regularly changing their examination procedures as new and better tests are identified in the course of medical progress. An annual, interval history and appropriate bio-chemical tests for liver and kidney damage, would constitute an appropriate medical surveillance procedure. Specifically, we see no need or value in a "hands-on" examination by a physician except when the bio-chemical studies indicate some problem and the examination becomes a natural part of the follow-up examination. Appropriate respiratory protection. At our Calvert City facility, EDC is manufactured and processed in a liquid state in open air operations. Almost all vinyl chloride manufacturing operations at Calvert City involve EDC. Physically, EDC is much less volatile than VCM. Therefore, the respirators already assigned to employees for vinyl chloride provide adequate protection against EDC exposure The respiratory protection requirements for EDC should be selected in conjunction with present respiratory equipment required for vinyl chloride. Our present vinyl chloride respiratory program consists of: Not over 1000 ppm - Type C, supplied air respirator continuous flow type, with half facepiece. Unknown, or above 1000 ppm - Open circuit, self-contained breathing apparatus, pressure demand type, with full facepiece. While there might be some concern for eye protection using half mask respirators, they can be, and frequently are, supplemented with monogoggles or a faceshield to provide suitable eye protection Production technology. Please refer to EPA-450/3-73-0Q5-b entitled "Survey Reports on Atmospheric Emissions from the Petrochemical Industry, Volume II" and EPA-450/3-73-006-C entitled "Engineering and Cost Study of Air Pollution Control for the Petrochemical Industry, Volume 3: Ethylene Dichloride Manufacture by Oxychlorination." SL 080835 -3- Tbe BFGoodrich Company Chemical Division i Employee exposures. The Calvert City plant has five gas chromatographs for ambient area monitoring of EDC and VCM. Each GC has 10 sample collection points and each point is sampled and analyzed twice per hour, or a three minute cycle per point. Several points have multi-probes. In the EDC manufacturing area where there is the highest potential exposure, about 25 percent of the readings are greater than 5 ppm EDC, and 20 percent are greater than 10 ppm EDC. The EDC manufacturing area employs about 50 people. A limited number of six-hour personnel samples there averaged 2.75 ppm, with a median sample of 2.27 ppm and a maximum of 8.96 ppm. The highest exposure job was the roving operator who averaged 3.33 ppm for 10 samples. Reducing employee exposure and complying with complete 1,2dichloroethane standard at the lowest level of exposure feasible. BFGoodrich believes that any exposure levels to be considered for comment must be specified before we can make intelligent comments on the amount of money to be invested in achieving those levels. Costs, as demonstrated by other standards, increase by orders of magnitude as lower levels of exposure are considered. We chose, in conjunction with the VCM control program, to estab lish an internal target of five ppm EDC on a time weighted average. On the average, we met that goal. Since we do not see any need for changing the present- OSHA standard, we have not estimated the cost of compliance with a new standard. Analytical and sampling methods. We use the Bendix Flasher Method for personnel monitoring at our Calvert City plant. The combined sampling and testing error associated with per sonnel monitoring for EDC has been determined to be i 17 percent. Whether issuance of an emergency temporary standard is appropriate. An emergency temporary standard is authorized by law only when employees are exposed to grave danger to health, and the ETS is immediately necessary to protect employees from such danger. The Goodrich experience in manufacturing and processing EDC has not shown such a grave danger to our employees. Indeed, industry-wide, we know of no evidence of such danger. Results of the animal studies are conflicting. Although the National Cancer Institute gavage studies are positive, preliminary results on the Manufacturing Chemists Association (MCA) in halation study conducted by Dr. Maltoni are negative. Pre liminary MCA teratology study results do not support evidence of a grave danger. In summary, our experience in manufacturing EDC and our knowledge of the relevant facts are not consistent with the existence of any danger, let alone one which can be reasonably characterized as "grave." SL 080836 -4- The BFGoodnch Company Chemical Division As we said, it is the position of the BFGoodrich Chemical Division that no emergency temporary standard be issued at this time. We realize that there are other specific proposals now being considered by OSHA. However, the framework of the questions in this request for information makes it inappro priate to address other proposals and we assume the oppor tunity to comment on these will be afforded to us should OSHA choose to act in reliance on them. Sincerely , WCB:mm SL 080837 \ Diamond Shamrock Law Department - Chemicals February 2, 1979 Docket Officer Docket No. H-079 Room S-6212 U. S. Department of Labor, OSHA Third Street and Constitution Avenue, N.W. Washington, DC 20210 Re: 1,2-Dichloroethane (ethylene dichloride) Gentlemen: In response to your request for information dated December 5, 1978 (43 Federal Register 56910), we will submit to you as promptly as possible data and comments on the above matter. Our submission will include exposure and toxicological data and economic and technological feasibility analyses, as well as comment on the appropriateness of issuing an Emergency Temporary Standard. Additional time is required to organize our data and put it in context, so that our submission will be more fully responsive to your request, as well as to the recently published revised recom mendations of the National Institute for Occupational Safety and Health. At this time, we can say that we are unaware of any data, including the NCI data referred to in your request, which demonstrates the need for an Emergency Temporary Standard. We estimate that our response will be completed within the next two weeks. In the meantime, should you wish to discuss this matter, please call me at (216)694-5268. Very truly yours, R. W. Hill Senior Counsel /njw SL 080838 Diamond Shamrock Corporation 1100 S'jpcr or Avenue Cleveland, Ohio 44114 Phone 216634-5000 Paul F. Deisler, Jr. Vice President Health. Safety & Environment Shell Oil Company One Shell Plaza P.O.Box 2463 Houston.Texas 77001 February 2, 1979 TOE Docket Officer, Docket No. H-079 Room S6212, U.S. Department of Labor, OSHA Third Street and Constitution Avenue, N.W. Washington, DC 20210 Dear Sir: This letter and its attachments are submitted in . vO the request for information on 1,2-dichloroethane (EDC) published December 5, 1978, at page 56910 of Volume 43 of the Federal Register. We have had insufficient time to address fully all the complex issues raised in the EDC query and in companion requests for information also published on December 5, 1978. We anticipated this situation and asked for additional time to address ' issues; a copy of our December 18 request is attached. Because we have r ived no reply, we are supplying the best answers possible in relatit to EDC within the short response time available. The attachments address the eleven questions presented at 43 F.R. 56910 and support the following positions: 1. The relevant EDC literature is inadequate to support the NIOSH-proposed limits for occupational exposures. Toxicology studies appearing in the literature are limited primarily to acute exposures; epidemiological studies usually are anecdotal. 2. No data exist to show that unreasonable risks to human health accompany exposures which comply with current standards. 3. Long-term EDC toxicology studies nearing completion are designed to help supply knowledge where deficiencies exist now. 4. NIOSH recommendations for EDC exposure standards cannot be supported because they place unjustified emphasis on exposure by gavage whereas the principal industrial exposure is by inhalation of low concentrations of vapor. SL 080839 Docket Officer, Docket No. H-079 Page 2 5. Available information does not support an emergency temporary standard for EDO exposures. We urge that OSHA re-examine available literature and evaluate the relevance of the various elements found there. We believe that such a re-examination will lead OSHA to agree with our conclusion that compliance with current occupational exposure standards for EDC is free of unreasonable risk to human health. We urge OSHA to await public scientific review of EDC toxicology studies now nearing completion and that OSHA conduct a "Regulatory Analysis" as described in Executive Order 12044. Very truly yours, P. F. Deisler, Jr. Vice President Health, Safety and Environment SL 080840 December 18, 1978 Shell Oil Company ATTACHMENT 1 Oi'h' Sr ell Plaza P C 24G3 Tutor> 77GC1 Honorable Eula Bingham Assistant Secretary Occupational Safety 6 Health Administration U. S. Department of Labor Third Street and Constitution Avenue, N.W. Washington, DC 20210 Dear Dr. Bingham: The Shell Oil Company and its subsidiary, Shell Chemical Company, wish, to comment on your questions concerning epichlorohydrin and 1,2-dichlrreethane (43FR56907 e_t seq) The details requested in the announcement arc complex and varied. We feel that the time deadlines of January 19, 1979, and February 5, 1979, respectively, for Lho two chemicals will not permit an appropriately detailed reply. 'Jhe t ime frame is further exacerbated by the effect of the Christmas holiday season in which many of those who will be involved in developing the replies arc not now available, nor will they be until after the first of the y.a.. Accord: !y, wc request the granting of a -hO-day extension beyond the stated re:.; o:: i ve deadlines for comments. Safety f. Industrial Hygiene SL 080841 (1) Metabolism, including intermediate as well as final metabolites The National Institute for Occupational Safety and Health (NIOSH), in its March 1976 Criteria Document, states that "No information on meta bolism of ethylene dichloride by humans was found in the literature" (1). Like NIOSH, we are unaware of information concerning human metabolism of EDC. Studies involving metabolism of EDC in animals are few in number and we are unable to augment the list of literature references contained in the NIOSH Criteria Document (2). OSHA is aware of ongoing animal metabolism studies supported by the Manufacturing Chemists Association (MCA) and being conducted at the Mario Negri Institute in Milan. These particular studies began about a year ago and represent one segment of a comprehensive series of studies of various aspects of EDC toxicology being sponsored by the MCA, It is MCA's policy to provide final reports promptly to interested agencies. Shell is an active participant in these MCA activities. rn'-C--r-i-t-e--r-i:a----f-o--r---a---r-e-c-o-m-mended standard ___ Occupational Exposure to EDC, NIOSH, March, 1976, p. 72. (2)Ibid, pp 68-72. SL 080842 (2) Toxicity, tumorigenicity, carcinogenicity, teratogenicity and/or mutagenicity, including- the effects ofpotential co-factors as related to each of these The Manufacturing Chemists Association (MCA) is sponsoring long term animal tests involving inhalation of EDC. This work, being conducted by Dr. Maltoni, is nearing completion: 12-month exposures at several concentration levels are complete and associated pathology studies are progressing. It is Shell's expectation that results will be reported by the second quarter of 1979. A second MCA-sponsored study focuses on teratology: this study is being performed by Dow Chemical Company and we expect a final report by the second quarter of 1979. A third MCA-sponsored study involves reproductive effects. Exposures for the reproductive studies have been completed and skeletal evaluations are in progress. We expect that this study will be completed by the third quarter of 1979. Final reports will be provided promptly to interested agencies. Shell has participated in each of these MCA activities by contributing both financial and scientific support. We have no information to offer on the effects of co-factors and have been unable to find any suggestions of EDC-related co-factors in the literature. SL 080843` (3) Human epidemiology (employee populations and those otherwise exposed) Shell has no epidemiological data relating only to EDC exposures. Those epidemiological data which Shell has reviewed are confounded by simul taneous exposures to other agents. Those studies labeled as "epidemiologic" in the NIOSH Criteria Document (3) are largely anecdotal in character and often involve simultaneous exposure to other chemical agents considered to be toxic (e.g., carbon tetrachloride, benzene). Another confounding factor is the lack of data concerning individual smoking histories; this factor can have an impact on results. Unfortunately, some of the clinical data noted in the NIOSH Criteria Document under the epidemiology section are incomplete and it may not be possible to correct these deficiencies because the data were collected a long time ago. T37Criteria for a recommended standard ___ Occupational Exposure to EDC, NIOSH, March, 1976, pp, 46-57. SL 080844- (4) Appropriate medical surveillance procedures Medical surveillance procedures for EDC are difficult to define in the absence of an evaluation of the final results from Dr. Maltoni's inha lation study. Pending the outcome of that work. Shell is unable to define appropriate medical surveillance procedures if, indeed, any appear to be scientifically indicated. Shell's medical surveillance objectives include the application of appropriate medical techniques and procedures of modern preventive medicine. Our philosophy in medical surveillance is that "single purpose" tests do not substitute for more complete medical profiles once scientific justification for surveillance is established. Shell's medical surveillance programs currently include virtually all our employees routinely exposed to EDC despite the fact that we have no specific EDC medical surveillance program. People exposed to vinyl chloride and epichlorohydrin are included in special annual medical surveillance programs; it is these populations which are likely to experience EDC exposures also. It is possible that personnel having occasional potential exposures to EDC might not be included in one of our annual special-surveillance programs. These individuals are encouraged to participate in our voluntary periodic examination program. SL 080845 (5) Appropriate respiratory protection A standard for regulation of EDC exposure should provide for employee protection through use of appropriate respiratory protection. The NIOSH EDC Criteria Document recommends only air-supplied equipment. If the NIOSH recommendations are adopted, air purifying respi rators would not be permitted, except for evacuation or escape, because of the "poor warning properties" of EDC at the recommended environmental limit of 5 ppm TWA and 15 ppm over 15 minutes (peak). The Document reports that the odor threshold of EDC is 3 to 100 ppm based on three literature ref erences. Our experience indicates that the odor threshold is much closer to 3 ppm than 100 ppm. It appears therefore that more definitive information is required to substantiate the claim of poor warning properties. However, regardless of the odor threshold, we believe that the decision on whether to permit air purifying respirators should be based on the efficiency of these devices in removing EDC from ambient air, and their service life. If removal efficiency and service life are adequate to protect employees, they should be permitted. Research on service life of chemical cartridge respirators for organic vapors in general (Nelson, et al, Am. Ind- Hygiene Assoc. J. 37:514) and EDC in particular (Nelson, et al, Am. Trid."Hygiene Assoc. J. 3^":391) indicates that breakthrough of EDC will not occur over a TO-hour shift with an ambient lev.el of 100 ppm, assuming moderately heavy exertion (37 L/min breathing rate) for the entire shift with respirator cartridges containing 80 grams of carbon per pair of cartridges. SL 080846 (6) Uses and production technology Shell's primary use of EDC is as a chemical intermediate which is subsequently converted to vinyl chloride. More than 95 percent of our needs for EDC are supplied by our own manufacture. Sales of EDC by Shell to others have been on an occasional basis only (mostly for export) and have amounted to less than one percent of our production. Shell's second use of EDC is as a gasoline additive. None of our EDC production is used directly in motor gasoline. Rather, we purchase an additive "cocktail" containing pre-mixed EDC, alkyl lead, and ethylene dibromide from one or more of several suppliers. Production technology involves the direct chlorination of ethylene and the oxychlorination of ethylene with hydrogen chloride. This technology is licensed from another party and we are not at liberty to disclose the relevant details. (7) Employee exposures (actual or potential) in each use and production facility,. including: (a) the levels and specific conditions of such exposures, (b) the number of employees involved in each exposure situation At about ten Shell blending locations, a gasoline additive "cocktail is blended with appropriate hydrocarbon streams to prepare motor gasoline (4), The premixed additive "cocktail" contains alkyl lead, a class of compounds long regarded as toxic. As a result of concerns over potential exposures to alkyl lead, work practices in gasoline blending facilities have, for many years, been characterized by extraordinary caution. Gasoline blending is highly automated and the premixed additive is metered and blended into the gasoline via in-line blending. It is not surprising, therefore, that our attempts to obtain reliable and quantitative measure ments of employee exposure to EDO at gasoline blending facilities have not been successful because ambient EDO levels are below our limits of detection. At Shell's two EDC production facilities, we have compiled personal monitoring data involving 2199 samples over the three-year interval 1976-7778. These samples cover all aspects of our EDC production activities, both normal operations and shutdowns, and all job categories, including operator, shipper and various crafts. Analytical procedures and sampling techniques are recognized standard methods. The results in the following table are from "lapel-type" samples of ambient air and many samples were collected while the person was wearing an approved respirator. The actual employee exposures were lower than the levels reported below for the ambient air. Hence the levels recorded serve only to indicate the potential exposure which would have occurred in the absence of a respirator. Personal Monitor, 8-hour TWA Number of Samples Percent of Samples Cummulative Percent of Samples < 1 ppm 1-5 ppm 5-10 ppm 10-50 ppm > 50 ppm 1459 571 95 66 8 66.3 26.0 4.3 3.0 0.4 66.3 92.3 96.6 99.6 100 Exposure situations fall into two main categories which will be labeled "normal" and "occasional" for the purposes of this answer. In the "normal" category are those exposures of operators and maintenance personnel "normally" assigned to EDC production facilities. A total of approximately T*7See attachment A(6), supra. SL 080847 70 operators is "normally" involved at the two Shell sites and work activities involve potential EDC exposures during the entirety of the work week. In addition, approximately 70 maintenance personnel are assigned to EDC production units: of this total, about one-half finds week-long duties at the EDC unit and the other half rotates to other areas outside the EDC facilities where their skills are required. "Occasional" exposures to EDC occur during shutdowns of production units (approximately 25 days per unit per year) when additional maintenance personnel refurbish operating units. "Occasional" exposures also will be experienced by non-EDC personnel who enter EDC production facilities sporadically and by labaratory personnel who use or test EDC. SL 080848 (8) Technological and economic feasibility of reducing employee exposure (9) Economic and technological feasibility of complying with a complete 1,2-dichloroethane standard at the lowest level of exposure feasible It is not possible to answer these questions satisfactorily at this time because meaningful estimates of the costs of complying with possible OSHA actions regarding EDC require: 1. Definition of the target level(s) of interest; 2. Detailed target-oriented engineering designs with subsequent cost estimating. We do not believe that such studies should be undertaken until there is some reasonable showing of need. However, we do have some general comments to offer. Our deligent efforts to reduce employee exposures to vinyl chloride and other chemicals have controlled potential EDC exposures to very low levels. Virtually all personal monitoring data (5) show that employees encounter work-place environments having ambient air levels of EDC well below existing standards. Furthermore, actual exposures are even lower because respirators are worn frequently in those work areas where significant inhalation exposures of EDC are possible. In theory, it is possible to place employees in continuously-worn life support systems akin to space suits but practical experience indicates this is totally impractical in an EDC manufacturing environment. Such "space suits" are awkward and pose new perils to those encumbered with them. In theory, it is possible to encase a petrochemical unit in an enclosure, but this too is totally impractical from the standpoint of operating the facility. In addition, such enclosures can create additional dangers to employees. We believe this action would be an unwarranted waste of resources. Looking to the specifics of our EDC production facilities, moni toring experience has shown that the potential for high exposures is greatest at two locations near the end of the processing scheme. One is the EDC recovery facility and the second is at the furnaces and reboilers. These locations have a common feature - both contain coke deposits which are exposed during shutdowns and other de-coking procedures. Coke has a rela tively high capacity for adsorbing EDC, and when vessels and/or lines are opened, the exposed coke desorbs EDC. We know of no way to eliminate this phenomenon. Therefore we use respirators in these operations since this is the only practical way to avoid EDC exposures which would otherwise be objectionably high. T5TSee attachment A(7), supra. SL O8O849 (10) Analytical and sampling methods used and evidence of~~their preci sion and accuracy EDC analysis in our Industrial Hygiene Laboratory is according to NIOSH Method SI22. This involves a charcoal sampling tube, desorption with carbon disulfide and analysis in a gas chromatograph equipped with flame ionization detection. With this method we have obtained satisfactory calibration at the 0.5 ppm level based on a 10 liter air sample. The desorption efficiency at the 1 ppm level is satisfactory U 88%); however we do not know if desorption efficiency will be a limiting factor at lower EDC levels. Any EDC standard should allow flexibility in analytical and sampling method as long as acceptable precision and accuracy can be achieved. For example, our manufacturing locations presently use a plastic bag/GC technique as part of their exposure monitoring for a variety of airborne substances. This flexibility should be encouraged as long as acceptable results are obtained. SL 080850 (H) Whether issuance of an Emergency Temporary Standard ~is appropriate Section 6(c) of the OSH Act is specific in regard to when an Emergency Temporary Standard (ETS) is appropriate. The Secretary must find that a substance poses a "grave danger" to,workers and that the ETS is "necessary to protect employees". NIOSH's Revised Recommended Standard ... Occupational Exposure to Ethylene Dichloride (6) is based primarily on animal tests which have, at best, a tenuous relationship to occupational exposures to EDC. The animal tests using rats and mice involved intragastric intubation of EDC in amounts equivalent to 5 and 10 percent of body weight. Occupational exposures to EDC involve drastically different quantities of material relative to body weight and a completely different route of exposure. Occupational exposures to EDC are low and involve inhalation. NIOSH itself considers "... the evidence for a carcinogenic potential of ethylene dichloride via inhalation to be inconclusive" (7). Despite intense scrutiny, there is no evidence that occupational exposures which comply with existing OSHA regulations pose an unreasonable risk to human health. Hence exposure to EDC at levels which meet current regulations do not pose a "grave danger". Under these circumstances, an ETS is inappropriate and can not be supported. It is especially inappropriate to undertake such precipitous action in view of comprehensive and multifaceted EDC studies underway and nearing completion under the auspices of MCA. T5T--'------------------- f ' ^Revised Recommended Standard ... Occupational Exposure to Ethylene Dichloride (1,2-Dichloroethane), NIOSH, September, 1978. ^^Ibid at p. 5. SL 080851 %.fr; Stauffer Chemical Company WWeessttpnonrrtt, rCnonnnnoeic-ttii/c-uiitt f0lc6n8n8n0 // TTeqlI. I(D2r0i'3W) 222-3n0n00/ /("aCKaiable"C"tS^,taufchem 7 CERTIFIED MAIL RETURN RECEIPT REQUESTED February 5, 1979 Docket Officer Docket H-079 U.S. Department of Labor Third Street & Constitution Ave., Washington, D.C. 20210 N.W im Dear Sirs: This letter is to confirm a telephone conversation on January 24, 1979 between Mr. Robert Cluck on behalf of OSHA and the undersigned. Mr. Cluck assured me that the February 5, 1979 deadline for information on ethylene dichloride (see Fed. Reg. December 18, 1978) could be informally extended to March 5, 1979. Additional time will also be necessary to respond to a new NIOSH revised recommendation for EDC, published on January 4, 1979. ' Based on the foregoing, Stauffer Chemical- Company intends to respond to the December 5, information request and the revised NIOSH recommendations by March 5, 1979. GLF:mep Very truly yours STAUFFER CHEMICAL COMPANY Law Department -.5 (52 American Petroleum Institute 2101 L Street, Northwest Washington, D.C. 20037 202-457-7228 Daniel B. Rathbun Vic* President February 5, 1979 Docket Officer Docket No. H-079 Room S6212 U.S. Department of Labor Occupational Safety and Health Administration Third Street and Constitution Ave. Washington, D.C. 20210 Dear Sir: API is pleased to respond to OSHA' s request for information on ethylene dichloride (EDC) (43, Federal Register, 56910, December 5, 1978). The petroleum industry's interest in EDC stems from its use in catalytic reforming operations as well as its use as a lead scavenger in leaded gasoline. In catalytic reforming, EDC is injected in small measured amounts into the feed stock to prevent contaminants from poisoning the catalyst. The EDC once injected, is decomposed in the reforming operation. The only potential exposure to EDC occurs when it is transferred to storage tanks prior to injection. A recent trend in the petroleum industry is to substitute other chemicals for EDC in reforming operations, which, like EDC, provide a source of chlorine which is the necessary agent to reduce the likelihood of poisoning the catalyst. The second and more important use of EDC in the petroleum indus try is as a lead scavenger in motor gasoline. EDC exposure within refineries associated with lead-blending operations and subsequent exposures to EDC in motor gasoline handling operations are extremely low. EDC, along with ethylene dibromide (EDB), is part of an antiknock package which also contains organic lead. This package is normally provided in premixed form to refiners by antiknock suppliers. The precautions which are taken to prevent exposure to the lead also control exposure to the EDC. This package is handled under tightly controlled conditions, and when blended directly into motor gasoline, the EDC and lead are diluted to a level which does not pose a hazard. This dilution and the precautionary measures taken distinguishes EDC exposures in the petroleum industry from exposures in other industries. An equal opportunity employer SL 080853 Page Two February 5, 1979 In response to OSHA's March 17, 1978,, Federal Register notice, API conducted a short-term program to monitor EDB. As part of the same study, we attempted to monitor EDO; however, the limits of the analytic technique used made it impossible to detect EDC at the extremely low concentrations present around service stations and bulk terminals. A rough estimate of EDC exposures can be made using the data gathered in API's EDB monitoring program. The "lead package" contains equal weights of EDB and EDC; the vapor pressure of EDC is 5.75 times that of EDB. Given this information, EDC exposures under "ideal" conditions is 5.75 times the EDB exposure. The following test results on ED3 were reported to OSHA on May 16, 1978: Exposures in service stations (based upon approximately 30, full shift samples) ranged from 0.24 ug/m3 to 0.90 ug/m3 under normal operating conditions. One sample was 2.90 ug/m3 when a customer drove off with the hose still in the tank causing a large spill. In addition, sampling data was obtained from refineries and marketing terminals. Exposures in refinery blending operations were 0.2 ug/m3 and in unloading the TEL [tetraethyl lead] package were 3.2 ug/m3. Exposures in marketing (tank truck bottom loading) were 0.2 to 0.8 ug/m3. Extrapolating from the EDB test data, it is estimated that EDC exposures are: Service Stations Refinery Blending TEL Package Unloading Marketing 1.38 ug/m3 to 5.18 ug/m3 1.15 ug/m3 18.4 ug/m3 1.15 ug/m3 to 4.6 ug/m3 After reviewing the National Cancer Institute study and the NIOSH Criteria Document on EDC, we have concluded that the scientific evidence which has formed the basis of the Federal Register notice on EDC is extremely weak. I have attached a review of these two documents which API has prepared. The major conclusion of this review is that, based upon the data presently available, a valid determination of the carcinogenic potential of EDC can not be made. SL 080854 Page Three February 5, 1979 A standard for EDCf when developed, must consider the unique characteristics present in industries' various applications of EDC. Requirements must be tailored to suit particular situations for manufacture or use. A standard which treats all situations as if they were identical results in unnecessary breadth of regulation and is wasteful of society's limited resources. The exposure limit when set should be based on sound scientific criteria. Ancillary requirements involving medical surveillance and monitoring should be structured to support implementation and maintenance of the appropriate exposure limit. Finally, the standard, as a whole, should ensure that the placement of regulatory burdens is necessary to maintain worker health, appropriate in the work setting affected, and consistent with the best use of society's limited health resources. Sincerely Daniel B. Rathbun SL 080855 COMMENTS OF AMERICAN PETROLEUM INSTITUTE (API) TO OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION (OSHA) REQUEST FOR INFORMATION ON ETHYLENE DICHLORIDE API believes that any alteration of the current standard on ethylene dichloride (EDC) would be premature due to the inadequacies in the National Cancer Institute study upon which the OSHA request for information document is based. API believes that before the question of EDC's carcinogenicity can be satis factorily answered, the deficiencies in the NCI study outlined below must be corrected, and an adequately controlled scientific study must be conducted. A. Chemicals - Analysis of the EDC utilized in the study "suggested a purity greater than 90 percent and showed the presence of 11 minor contaminants." (Page 5) This indicates that up to 10 percent of the chemical fed to the animals were other contaminants which could be carcinogenic. The dosages given animals utilized in the study ranged from 47 mg/kg/day to 299 mg/kg/day. (Page vii) Thus, the animals could conceivably be receiving between 4.7 mg/kg/day to 29.9 mg/kg/day of contami nants. With no analysis given of the 10 percent contaminants, it is impossible to attribute to EDC any effects observed. B. Dosage Preparation - The report states that "the solu tions given the animals were considered generally stable for ten days under the indicated storage conditions." (Page 5) Although stability studies were performed on the pure chemical, no such studies were performed on the chemical with the vehicle. As such, it is impossible to assess whether there was significant chemical breakdown and in fact the percentage of contaminants was even higher than 10 percent. C. Statistical Analysis - API would initially point out that the "Cochran-Armitage Test" referred to (page 17), is, in reality, a chi-square test developed by Cochran with a variation suggested by Armitage. This procedure as utilized in this report apparently attempts to analyze whether there is a linear trend of greater numbers of tumors with increasing dosage. The procedure could be used to demonstrate a dose-response relationship. The data presented in the report is not sufficient for independent calculations of the figures presented. We are unable to deter mine the calculations utilized to obtain the P value for pooled vehicle controls as the P must be obtained by some comparison to historical controls utilized in the Hazleton Laboratories. No data is presented on these historical controls, if, in fact, this V Bioassay of 1,2 dichloroethane for possible carcinogenicity; USDHEW, PHS, NIH, NGI; Tech. Report #86; 1978 2/ International Agency for Research in Cancer; monograph, 139, Cl 977 SL 0808S6 2- - is the manner in which the P was determined. Furthermore, in examining Tables 3-6, in many instances the P of the pooled control value is a highly significant difference in tumor incidence as compared to the historical controls. NCI has the burden of explaining these mystifying results. If there is no rational explanation for the pooled control group developing a significant tumor incidence as contrasted to the historical control, it cannot be unequivocally stated that tumors developed by animals in a group given EDC were due to administration of the chemical. We would further point out that the tumor incidence found in the untreated animals was completely dismissed in the analysis presented. In some instances, there appears to be significant tumor incidence in the untreated controls as contrasted to the vehicle treated controls. These results should have been explained. The report states "two types of control groups were used . . . and a pooled vehicle control group which combined the vehicle controls from the studies of 1,2-dichloroethane, 1,1,2-trichloroethane, and trichloroethylene. The pooled control rats were of the same strain, were housed in the same room, were tested concurrently for at least one year, and were diagnosed by the same pathologist." (Page 17) The report does not state whether the pooled control rats were from the same batch and whether they were all of the same age. We would further point out that it is strange that the mice were tested with significantly higher dosages than the rats. It should also be noted that .the mice that developed tumors had primarily been treated with such dosages. It is also noted that rather than treating with a specific dose through the duration of the experiment, the dosages given were "time weighted". That is, an initial dosage was given, the dosage was lowered for a period of time, and then the dosage was increased above the initial dosage. We suspect, in the absence of further elucidation, that the reason for application of this unorthodox procedure was that it was necessary to give the animals a lower dose in the second stage of the experiment because they were experiencing highly toxic reactions. When the animals had sufficiently recovered, apparently the dosages were once more significantly increased. This would suggest that the initial dosages given overwhelmed the metabolic systems of the animals, thereby producing results which are highly suspect. We will now concentrate on discrepancies noted in the raw data and the test results reported in the tables. In Table A-1, dealing with the male rat, no hemangiosarcomas in the circulatory system .are noted. Yet Table 3 lists seven hemangiosarcomas of the circulatory system. The total of all hemangiosarcomas listed in Table A-1 is nine. SL 080857 3 In a discussion of the circulatory system of the female rat, no hemangiosarcomas are reported in the appendix while four are reported in the table. We also question whether it is justifiable to add the cumulative numbers of tumors of adenocarcinoma and fibroma. Neither of these tumors alone show a linear dose response. The response of the high dose and lack of response in the low dose in the adenocarcinoma suggest a threshold effect. The data on the fibroma suggests mitigating effects and does not yield a true dose response. We would further point out that the onus is on NCI to show evidence that fibroma and adenocarcinoma results should be combined. If one considers combining all tumors, one can easily determine by performing statistical analysis that in experiments involving male and female rats, the total tumor incidence is not significant. Such statistical analysis would compare untreated with low and high dose animals. While no tumors in male mice are highly significant, no dose response is apparent. Such high dosage effects argue mild carcinogenicity at best. It should also be noted that the first tumors were observed at 81 weeks when the animals were receiving 1.5 times the time weighted dosage. The low dosages are non-significant. We would also question the validity of combining data from lymphomas and polyps. D. Conclusion - We conclude that because of the deficien cies in the NCI study, the data cannot be used to determine whether or not EDC is carcinogenic. The impurity of the chemi cal, discrepancies between the raw data and data reported in the tables, lack of explanation of statistical analysis utilized, lack of explanation of the differences in incidence of tumors in untreated controls and vehicle treated controls and highly irregular data shown in the tables often showing no linear dose response effect would tend to invalidate any results that might otherwise be called conclusive. Because of the irregularities in this study, it is clear that no determination or extrapolation of possible carcinogenicity of EDC to humans can be made. Comparison with Properties of Ethylene Dibromide While ethylene dichloride and ethylene dibromide are structurally similar and thus in some respects have comparable physical properties, the toxicological properties vary consider ably as the following discussion shows. Because of this, no attempt should be made to apply an ethylene dibromide standard to ethylene dichloride. SL 080858 4 Carcinogenesis While we question the validity of the NCI report on ethylene dichloride, it should be noted that the number of tumors produced in both rats and mice by ethylene dichloride was significantly lower than those produced by ethylene dibromide. Thus, while studies indicate that ethylene dibromide may be carcinogenic, there is no basis for deciding that ethylene dichloride is either non-carcinogenic or is a very mild carcinogen. This statement was echoed in a report from the National Cancer Institute (1) " 1 ,2-dichloroethane was much weaker (emphasis added) than the analogue (1,2-dibromoethane) and induced only a few stomach tumors in rats." Mutagenicity Ethylene dichloride also appears to be much less mutagenic than ethylene dibromide. In a recent study by Rannug (2) involv ing revertant mutation of E.Coli and Salmonella Typhimurium, ethylene dibromide was found to be second highest in mutagenic activity of a group of halocarbons tested in E.Coli. In Sal monella, ethylene dibromide was shown to be extremely mutagenic. In both of these studies, ethylene dichloride induced the least number of mutations of all components tested. In Salmonella, TA1535, ethylene dibromide (10 micromoles) induced 1438 revertants. Ethylene dichloride at this concentration induced 54 revertants. In the revised Criteria Document (3), the work of Rannug (4) is cited as listing ethylene dichloride as a "moderate mutagen along with a potent mutagen when applied together with liver enzymes." However, this work was published in 1977, a year earlier than Rannug's more recent work on ethylene dichloride (referred to above) where it was suggested that ethylene dichlor ide might be mildly mutagenic. Teratogenicity The studies performed to date on ethylene dichloride have not shown any teratogenic effect although they have shown some effects on reproduction and fertility. In a study (5) where chickens were given 250 and 500 ppm EDO in mash for a period of two years, no effect was seen on growth, semen characteristics or fertility in chickens. A tolerance of 100 ppm in the diet was recommended. The authors found similar results with no teratogen icity in studies on the rat (6). Vozovaya (7-9) has found var ious effects of EDC alone and with gasoline inhalation exposure in rodents. The author found decreased fertility, increased number of still births, and decreased viability of the progeny. It is stressed, however, that the concentrations of EDC used were exceedingly high (e.g. 400 ppm). In addition, the author observed no teratogenic effects. On the basis of the work to date, it is SL 080859 5 suggested that EDC is not teratogenic an : may have only .. mild effect on reproduction and fertility at . igh concentrations. Further work is indicated. It should be stressed that the majority of pathological effects discussed in the initial NIOSH Criteria Document (10) were based on tests involving high concentrations of EDC. It should be further noted that the data taken from the NCI report and used in the revised criteria standard (3) has been incor rectly reported. The dosage given in mice (page 7) was approx imately 100 and 200 mg/kg; not 50 and 100 mg/kg as reported. Si 08860 REFERENCES 1. Weisburger, E. K.; Env. Health Perspect, 2_1_, 7, ( 1977) 2. Rannug, U. et al; Chem-Biol. Interact, 20(1), 1, (1978) 3. NIOSH; Revised Recommended Standard ... Occupational Expo sure to Ethylene Dichloride (1,2-dichloroethane) September, 1978 4. Rannug, U. et al; Toxicol. Environ Health, 2, 1019, (1977 5. Alumot, E. et al; Food Cosmet. Toxicol. 11' 1 1 1 , (1976) 6. Alumot, E. et al; Food Cosmet. Toxicol. 14, 105 , (1976) 7. Vosovaya, M A.; Gig. Sawit, 1_, 25 ( 1974) 8. Vosovaya, M. A.; Gig. Tr. Prof. Zabol. , 1_, 20, (1975) 9. Vosovaya, M. A.; Akush. Ginekol, J?, 66, ( 1 973) 10. NIOSH; Occupational Exposure to Ethylene Dichloride (1,2dichloroethane) March, 1976 SL 080861 DOW CHEMICAL U.S.A. f February 5, 1979 BARSTOW BUILDING 2020 DOW CENTER MIDLAND. MICHIGAN 48640 Docket Officer Docket No. H-079 Room S 6212 U. S. Department of Labor OSHA Third Street and Constitution Avenue, N.W. Washington, D.C. 20210 SUBJECT: Request for Information on 1,2-Dichloroethane, Federal Register, Vol. 43, No. 234, December 5, 1978, page 56910 Docket No. H-079 Dear Sir: This correspondence is in response to the above referenced request for information on 1,2-dichloroethane (EDC). The Dow Chemical Company believes that the available data does not warrant the issuance of an Emergency Temporary Standard for EDC. In reviewing the animal carcinogenicity data base on EDC, we are faced with the widely divergent results of the National Cancer Institute gavage study, which showed positive results in rats and mice, and those of Professor Maltoni's inhalation study, co-sponsored by a group of U.S. producers (under the auspices of the Manufacturing Chemists Association (MCA)) and European EDC producers, which produced no carcinogenic re sponse in rats and mice at exposure levels up to 150 ppm. While the results of both studies must be considered for possible regulation of EDC, it is well-documented that in the typical occupational setting, inhalation is by far the predominant route of exposure to EDC. There fore, the Maltoni study is more applicable to judging possible human cancer risk due to EDC. We believe the only conclusion that could be drawn from the inconsistent results of the Maltoni and NCI studies is that, at most, EDC might be a relatively moderate to low potency car cinogen. Until the reasons for the anomaly of these two study results can be determined, perhaps due to the differing routes of administration, peak versus continuous dose, or other differences, we believe that any action by the agency to regulate EDC would be precipitous and unnecessary to protect the worker. AN OPERATING UNIT OH THE DOW CHEMICAL COMPANY SL 080862 cfRAO// m-Vdle WL'1 Docket Officer February 5, 1979 page Two In regard to human experience, we know of no reports of human cancer associated with EDO exposure, even though this material has been manu factured and used in large volumes for over 35 years, with thousands of workers exposed for long periods of time. Industry has long been aware of both the acute and chronic toxicity of EDC, and has taken appropriate precautions to protect employees from what have been recognized as the symptoms and effects of overexposure to this material. (See Attachment A, for example). If there indeed was a causal relationship between EDC exposure and cancer, it would have been recognized by now. Furthermore, since the largest percentage (approx. 80%) of EDC is used for vinyl chloride (VCM) manufacture, the occupational exposure controls instituted for VCM 5 years ago have resulted in a parallel reduction of EDC exposures. Therefore, any possible risk of EDC exposure has already been reduced in a significant portion of the workplace where EDC is present. Because of the major ongoing toxicity research on EDC which will be com pleted within the year, we believe that any regulatory action should be deferred until the results of this research are available, so that a better-informed decision can be made. We would like to bring to your attention the studies being conducted under the auspices of the MCA as part of the current research program on EDC. These include: 1. The previously mentioned Maltoni inhalation study on Sprague-Dawley rats and Swiss mice, exposing the animals to 0, 5, 10, 50, and 150 ppm EDC, 7 hrs./day, 5 day/week, for 18 months. This study is completed and a final report is expected from Dr. Maltoni shortly. 2. Clinical Chemistry determinations on animals exposed by Professor Maltoni, conducted by Dr. Federico Spreafico of the Mario Negri Institute in Milan, Italy, which is also completed and a report expected soon. 3. Metabolism work by Dr. Spreafico at Mario Negri, to be completed in 1979. 4. A teratology study conducted at Dow, on rats and rabbits exposed to 100 and 300 ppm EDC, has been completed and a final report will be issued shortly. 5. A one generation reproduction study in rats, also being conducted at Dow, is in progress, and will be completed in 1979. SL 080863 Docket Officer February 5, 1979 Page Three The MCA will provide final reports on all the above studies to OSHA as soon as they are available. It is obvious that the results of these studies will significantly add to the data'base on EDC and should be appropriately considered in arriving at a regulatory position on EDC. To place the results of the Maltoni and NCI studies in perspective, additional toxicity studies are being undertaken to elucidate the effects of differing routes of administration of EDC on its metabolism and mechanisms of potential toxicity. We plan to have the results of this research available within the year, and believe that OSHA should await its outcome before proposing further restrictive regulation of EDC. We are concerned about the feasibility of meeting an unreasonably low ceiling level for EDC, such as the 2 ppm 15-minute ceiling recently recom mended by NIOSH. Our experience for semi-volatile organic materials such as EDC indicates that 15-minute ceiling concentrations will generally ex ceed the 10-hour TWA level by a factor of 10 to 20. We urge that any consideration of a ceiling value in addition to a TWA permissible exposure level involve careful cost/effectiveness analysis. The remainder of our response is devoted toward the specific information requested in the Federal Register notice. Because of the intervening holidays during the comment period when many key resource personnel were unavailable, we have been unable to complete our data for submission at this time. However, our conversations with personnel in the Health Standards Office of OSHA have assured us that pertinent information will be accepted for a reasonable time beyond February 5, and we plan to have the remainder of our data submitted within the next 4 to 6 weeks. Enclosed are the following: Attachment A Spencer, H. C., et. al, Vapor Toxicity of Ethylene Dichloride Determined by Experiments on Laboratory Animals, A.M.A. Archives of Industrial Hygiene and Occupational Medicine, November 1951, Volume 4, pp. 482-493. Attachment B Our material safety data sheet for EDC, which lists the properties, hazards, and reactivity of the material, appropriate handling pre cautions, first aid measures, and spill, leak, and disposal procedures. Attachment C An outline of the sampling and analytical procedures used by Dow to measure concentrations of EDC in the workplace. The method used is essentially that recommended by NIOSH, with some minor modifications. Attachment D Our medical surveillance program for workers with potential exposure to EDC. SL 080864 Docket Officer February 5, 1979 page Four Attachment E - t A table of end uses for EDO, along with estimates of the relative volumes of EDC consumed in each. We expect that our data and comments will be given due consideration and will aid in arriving at a reasonable and appropriate regulatory decision by the agency. Very truly yours, ^.y i" s- C. C. Kazmierski Inorganic Chemicals Department 2020 Dow Center (517) 636-0184 cah SL 080865 ATTACHMENT A Vapor Toxicity of Ethlyene Dichloride Determined by Experiments on Laboratory Animals H. C. SPENCER, Ph.D. V. K. ROWE, M.S. E. M. ADAMS, PH.D. D. D. MeCOLLISTER, BS. AND D. D. IRISH, Ph.D. MIDLAND, MICH. Reprinted, with additions, from the A. M. A. Archives of Industrial Hygiene and Occupational Medicine, November 1951, Vol, 4, pp, 432-493 Copyright, 1951, BY Auebican Medical Association 555 North Doar&orn Street Chicago 10, let. ^fluff'd and PttbHshtd in tht United States of Amerieo SL 080866 Reprinted, with additions, from the A. it/. A. Archives of Industrial Hygiene and Occupational Medicine, November 1951, Vol. 4, pp. 482-493 Copyright, 1951, by American Medical Association VAPOR TOXICITY OF ETHYLENE DICHLORIDE DETERMINED BY EXPERIMENTS ON LABORATORY ANIMALS H. C. SPENCER, Ph.D. V. K. ROWE, M.S. E. M. ADAMS, Ph.D. D. D. McCOLLISTER, B.S. AND D. D. IRISH, Ph.D. MIDLAND, MICH. ETHYLENE dichloride (1,2-dichloroethane) is widely used as a constituent of fumigants, as a commercial solvent, and as a chemical intermediate. The early pharmacological and toxicological literature has been reviewed by von Oettingen1 and by Heppel and associates -; both acute5 and chronictoxicity studies have been reported. The present experimental work was carried out as a part of a comparative study of the toxicity of vapors of the four chlorinated hydrocarbons: ethylene dichloride, trichloroethylene, tetrachloroethylene, and carbon tetrachloride. These studies were undertaken so that the health problems associated with the use of these materials could be more fully evaluated. In this comparative study considerable emphasis was placed on quantitative measures of acute toxicity (for the rat) in terms of both capacity to kill and capacity to cause injury (nonfatal). It has been felt that acute toxicity is as important for From the Biochemical Research Department, The Dow Chemical Company. A summary of this work was presented at the Eleventh Annual Meeting of the American Industrial Hygiene Association, in Chicago, April 27, 1950. 1. von Oettingen, W, F.: The Halogenated Hydrocarbons: Their Toxicity and Potential Dangers, J. Indust. Hyg. & Toxicol. 19:349-4*18, 1937. 2. (a) Heppel, L. A.; Neal, P. A.; Endicott, K. M,, and Porterfield, V. T.: Toxicology of Dichloroethane: I. Effect on the Cornea. Arch. Ophtli. 32:391-394 (Nov.) 1944. (6) Heppel, L. A.; Neal, P. A.; Daft, F. S.; Endicott, K. M.; Orr, M. L., and Porterfield, V, T.: Toxicology of 1,2-Dichloroethane: If. Influence of Dietary Factors on the Toxicity of Dichloroethane, J. Indust. Hyg. & Toxicol. 27:13-21, 1945. (c) Heppel, L. A.; Neal, P. A.; Perrin, T. L.; Endicott, K. M-, and Porterfield, V. T.: The Toxicology of 1,2-Dichloroethane: III. Its Acute Toxicity and the Effect of Protective Agents, J. Pharmacol. & Exper. Therap. 84:53-63, 1945. (d) Heppel, L. A.; Porterfield, V. T., and Sharptess, X. E.: Toxicology of 1,2-Dichloro ethane: IV. Its Detoxication by I.-Cystinc, DL-Mcthionine and Certain Other Sulfur Contain ing Compounds, ibid. 91:3S5-394, 1947. (e) Heppel, L. A.; Neal, P. A.; Perrin, T. L.; Endicott, K. M., and Porterfield, V. T,: The Toxicology of 1,2-Dichloroethane: V. The Effects -of Daily Inhalations, J. Indust, Hyg. &: Toxicol. 28:113-120, 1946. 3. (a) Sayers, R. R.; Yant, W. P.; Waite, C. P., and Patty, F. A.: Acute Response of Guinea Pigs to Vapors of Some New Commercial Organic Compounds: I. Ethylene Dichloride, Pub. Health Rep, 45:225-239, 1930. (6) Heppel and others.-^ SL 080867 2 industrial hygiene as is chronic toxicity. Accordingly, more satisfactory means of measuring acute toxicity and of obtaining useful information by comparing the results with measures of chronic toxicity have been explored. EXPERIMENTAL PROCEDURES Material Tested.--Ethylene dichloride, CH;C1-CH-C1, 5s a colorless liquid of a specific gravity of 1.256 at 20 C. (water 1), with a melting point of --35.5 C. and a boiling point of 83.5 C. It is soluble in water to the extent of 0.S1 gm. per 100 gm. at 20 C. and is freely miscible with alcohol and with ether. Ethylene dichloride is stable at moderate temperatures and burns with difficulty. The material used in this experimental work consisted of four individual samples of a commercial product, all purified by redistillation. The infrared-absorption spectra of these samples indicated purities of at least 99.7%. The only impurity identified was trichloroethylene. Source and Feeding of Animals.--The albino rats were raised in this laboratory of stock originally obtained from the Wistar Institute of Anatomy and Biology in 1938. They were maintained on a modified Sherman diet consisting of freshly ground whole wheat (55%), dried whole milk (25%), dried extracted liver (12%), dried brewer's yeast (5%), iodized table salt (2%), and calcium carbonate (1%). The guinea pigs were of a heterogeneous stock purchased from a commercial breeder. They were fed a commercial rabbit chow 41 (complete ration), alfalfa hay, and cabbage. The albino rabbits were a heterogeneous stock raised in this laboratory on the same chow ** (complete ration) and alfalfa hay. The rhesus monkeys were imported animals, kept in the laboratory for several months before use. They were fed a variable diet of a commercial laboratory chovv,st> peanuts, fruits, and vegetables. Single Exposures.--A glass-walled chamber of about 160-Iitcr capacity, similar to that previously described,4 5was used. Two large copper tubes (closed with rubber stoppers) were soldered into the monel top of the chamber so that rats could be introduced conveniently after a vapor concentration had been established. A constant air flow was maintained through the chamber, the lowest rate for any experiment being about 15 liters per minute and the highest about 30 liters per minute. The desired vapor concentration was obtained by metering liquid ethylene dichloride at a constant rate into the tube through which air entered the chamber, heat being applied at the point of vaporization as needed to effect complete volatilization. All vapor concentrations with animals in the chamber were checked repeatedly from time to time by combustion analyses; the results averaged better than 90% of the calculated theoretical con centrations of ethylene dichloride. The rats were introduced in groups of 3 to 12 within a period of 15 seconds and were removed through the chamber door within a similar interval of time at the end of the exposure. It was shown by a continuously recording analyzer that the animals were introduced without appreciable alteration of the vapor concentration. All the rats were selected on the basis of general appearance and apparent good health, males and females being used in approximately equal numbers. Animals that received single exposures were observed as to their behavior, body weight changes, and time of death. Survivors were observed for two to three weeks, or until it was certain that they had fully recovered from the effects of the exposure as judged by appearance, behavior, and recovery of weight. Special groups of rats, separate from those used to determine the relationships between intensity of exposure and survival, were examined for evidence of organic injury at varying times following the single exposures. Repeated Steen-Hour Exposures.--A metal chamber of about 450-liter capacity was used for exposures at 200 ppm; and a rectangular galvanized shect-uictal box of about 1,700-liter capacity was used for exposures at 400 and 100 ppm. The concentration of 200 ppm was attained by 4. (a) The rabbit chow used was that made by the Ralston Purina Company, St. Louis. (6) The laboratory chow used was that made by the same company, 5, Irish, D. D., and Adams, E. M.: Apparatus ami Methods for Testing the Toxicity of Vapors, ludust. Med- 9:1-4, 19-10. SL 080868 ns of r the 'scific .p.t of freely utures of a these vleue. stock were dried e salt They how 41 before =, and i that were after ;h the dghest liquid r, heat pot by were iQsure. ithout males osures j were ,m the -special -ity of lowing .d for pacity icd by Louis city of 3SJ 33 . j \ l I 3 passing a metered amount of air through a vaporizer containing liquid ethylene dichloride and into the constant air flow entering the chamber. The other concentrations were obtained by metering liquid ethylene dichloride and vaporizing this into the air flow entering the chamber.By means of a continuously recording analyzer, it was shown that in every case the vapor was uniformly held within 10% of the desired concentration of ethylene dichloride. In the repeated exposure experiments the vapor concentration was established after the animals had been placed in the chamber. This was done by atomizing the required amount of ethylene dichloride into the chamber with thorough mixing of the chamber air by means of fans, and then starting the air flow and the ethylene dichloride feed so as to maintain the concentration. All of the animals used in these experiments were carefully selected on the basis of general appearance, body weight, and growth during a preliminary period of observation. In each experiment two groups of controls were used, well-matched with the experimental animals in respect to number, age, sex, and body weight. The "unexposed controls" were simply main tained in the animal quarters, while the "air-exposed controls" were exposed repeatedly to room air in a chamber similar to that used for the ethylene dichloride-exposed animals. Routinely, the animals were exposed seven hours daily, five days a week. Throughout the experimental period each animal was weighed twice a week and observed frequently for general appearance and behavior. Growth curves were drawn for each group, and records were kept of food consumption and mortality. During the course of the experiments, periodic hematological examinations were made on several groups of animals. Failing aiuimals were killed for examination when moribund or nearly so. All survivors were killed and examined for evidence of organic injury on the day following the last exposure. Examination for Organic Injury.--All of the animals examined for organic injury were fasted overnight, weighed, and then killed by decapitation. The gross appearance of each animal was observed, and the lungs, heart, liver, kidneys, spleen, and testes were weighed. Tissues from these organs were saved for the preparation of hematoxylin-and-eosin-stained sections, and in many instances sections of the following were prepared also: adrenal gland, pancreas, stomach, intestine, bone marrow, urinary bladder, ureter, lymph nodes, muscle, brain, and optic nerve. Frozen sections of the liver and a kidney were stained with Sudan IV and Oil Red O. In many cases blood was obtained at the time of autopsy for the determination of the following: urea nitrogen0 and/or total nonprotcin nitrogen; serum phosphatase7; plasma prothrombin clotting time by a modification of the method of Quick.0 Likewise, in many cases a portion of the liver was frozen with solid carbon dioxide (dry ice) for subsequent lipid analyses. Total lipid was determined gravimetrically on an .alcohol-ether extract; phospholipid was calculated from the total phosphorus content; free and esterified cholesterol were deter mined by separation as the digitonide and use of the Liebermann-Burchard reaction, and neutral fat was calculated by difference. Wherever possible, the t-test3 was used in comparing the mean values obtained on the ethylene dichloride-exposed groups with those of the air-exposed controls or unexposed controls as designated; probability values (P) of less than 0.05 indicated a significant difference. RESULTS OF SINGLE EXPOSURES OF RATS Mortality from Single Exposures.--The total number of rats used and the num ber that died from each exposure are listed in Table 1. From the data at 1,000, 1,500, ,3,000 and 12,000 ppm, the exposures producing' deatli in 0.01, 50, and 6. Barker, S. B.r The Direct Determination of Urea in Blood and Urine, J. Biol. Chem. 152:453-463, 1944. 7. Hoffman, W. S.: Photelometric Clinical Chemistry, New York, William Morrow & Co., 1941, p. 13S-149. 8. Quick, A. J.; Stanley-Crou n, M,p and Bancroft, F. W.: Study of the'Coagulation Defect in Hemophilia and in Jaundice, Am. J. M. Sc. 190:501-51 1. 1935. 9. Fisher, R. A.: Statistical Methods for Research Workers, cd. 7, Loudon, Oliver & Bojd, Ltd., 1933. SL 080869 4 99,99% of the rats were determined statistically according to the method described by Litchfield and Wilcoxon.10 These points were plotted on log-log ordinates and the lines AB, AT, and CD (Chart 1) drawn to represent the exposures producing death in essentially all of the rats (L. D.w.n!>), 50(L. D,30), and essentially none of the rats (L. D.o.oi), respectively. The average factors for determining 19/20 confidence limits were 1.09 for the L. D.^ points and 1.45 for tlw ooints represent ing the two extremities. Table 1. --Mortality of Rats Exposed to Various Concentrations of Ethylene Dichloride for Single Periods CHsCl-CHs-Cl ConeeaAtr--u--t-l-o--n--.- - PPM Me./L. 20.00) 81.0 12.000 4S.fi S.0QG 12.1 1,000 1,000 800 600 300 e.i 4.0 3.2 2.4 1-2 Period of Exposure, Hr. 0.1 0,2 0.3 0.4 0.6 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 1.0 o.s 0.7 1.0 1.6 2.0 s.o 4.0 5.0 6.0 2.0 3.0 4.0 C.O 7.0 6.0 6.0 7.0 8.0 7.0 6.0 7-0 8.0 7.0 To tul Number of Hats 10 20 20 20 10 10 41 52 41 W 42 * 43 3) 22 22 44 32 41 51 40 40 23 20 10 24 41 10 30 10 32 31 32 30 20 33 20 20 Number That Died 0 0 16 20 10 0 0 0 4 22 30 38 30 22 0 1 1 1 6 24 35 22 20 0 1 2 7 24 7 6 17 20 10 0 3 4 0 Cross Response.--Ethylene dichloride produced a considerable depression of the central nervous system, sufficient at 22,000 ppm to cause deaths within 0.4 hour. At 12,000 ppm and at lower concentrations this depressant action resulted in varying degrees of "drunkenness" but not unconsciousness or death within the duration of the exposures employed. The inactivity or stupor and the slowness of response to handling observed at vapor concentrations of 3,000 ppm and lower may have been due, in part at least, to toxic injury other than the depression of the central nervous system; the prolonged exposures at these lower concentrations produced appreciable organic injury. 10. Litchfield, J. T., Jr., and Wilcoxon, F.: A Simplified Method of Evaluating Dosc-EfFect Experiments, J. Pharmacol, & Exper. Tlierap, PC :99-l 13, 1949, SL 080870 5 Deaths of rats tended to occur at three different time intervals and in such a manner as to suggest three separate toxic actions of fatal degree. At 20,000 ppm deaths occurred in deep anesthesia during the period of exposure, undoubtedly due to depression and paralysis of function of the central nervous system. At all vapor concentrations a large proportion of the rats died rather suddenly and quietly a few hours after being removed from the chamber, showing marked cyanosis, reduced body' temperature, stupor or coma, and failing respiration. The character of this response and its sudden development often after apparent full recovery suggest "shock" or cardiovascular collapse. All other deaths occurred over a period of two to seven days with progressive loss of weight and other evidence of toxic effects. These deaths appeared to be the result of injury to the kidney. Organic Injury,--Special groups of animals were killed and examined for evi dence of organic injury at various intervals of time after receiving exposures within Chart 1--Vapor toxicity of ethylene clichloride. Line AB represents single exposures pro ducing death in 99.99% of the rats; Line XY, single exposures producing death in 50/i', and Line CD, those producing death in 0,01 Vo- Line EF represents the most severe single exposures without detectable adverse effect in rats. Point G represents the most severe repeated exposures of rats without detectable adverse effect; Point II, of rabbits; Point I, of monkeys and guinea P>gs- the range bounded by ABCD (Chart 1). The evidence of organic injury consisted of the following: decrease in body weight; increase in weights of liver and kidneys; increase in blood urea nitrogen; increase in plasma prothrombin dotting time; decrease in serum phosphatase; increase in liver lipids; histopathological changes in kidney, liver, and adrenal. The histopathological changes were most pronounced in the kidney' and consisted of varying degrees of tubular damage, ranging from slight parenchymatous degen eration of the epithelium to complete necrosis and accompanied by interstitial edema, congestion, and hemorrhage. Animals showing severe renal damage had extremely high concentrations of urea nitrogen in the blood. SL 080871 6 In the liver the histopathological changes ranged from slight congestion and slight parenchymatous degeneration to marked hemorrhagic necrosis. Although a few diffusely distributed fat globules were found in some of the severely affected livers, typical "fatty degeneration" was not observed. The adrenal changes were limited chiefly to congestion and hemorrhage, although in the most severely affected animals there was some parenchymatous degeneration of the adrenal cortex. Only at vapor concentrations above 3,000 ppm was there evidence of pulmonary congestion and edema. Single Exposures Having Ho Adverse Effect.--The studies made to determine the nature of the toxic effects caused by the inhalation of ethylene dichloride vapor were extended to permit an estimation of the single exposures of maximum intensity without any evidence of toxic injury. The resutts of these experiments using groups of four to six female rats are summarized in Table 2. From these data the line EF (Chart 1) was located by inspection to represent the most severe single exposures which were without detectable adverse effect on rats. Table 2.--Single Ethylene Dichloride Exposures Having No Adverse Effect on Female Rais CHjCI-CH-CI Co&centratioa 12,000 3.000 1.000 300 200 49.6 HU 4.0 1.2 0.3 Without Adverse ErTeet oj 0.3 1-5 3.0 r,o WithEfAfedcvterse 0:2 0J> 3,0 5^ RESULTS OF REPEATED SEVEN-HOUR EXPOSURES Concentration: 400 PPM (1.62 Mg. per Liter).--(a) Rats: Groups of 15 male arid 15 female rats, subjected to repeated seven-hour exposures, experienced severe intoxication. No female rat survived more than 10 exposures in 14 days, and no male rat survived more than 40 exposures in 56 days. In additional groups of 20 male and 20 female rats each, given two and three exposures, mortality was high (60^>), Surviving animals were killed and exam ined for significant changes as compared with groups of unexposed controls. The experimental animals showed a rapid loss in body weight and a slight increase in the weights of the liver and the kidneys. Histopathological examination of the tissues revealed slight cloudy swelling of the liver with a few large fat vacuoles, principally centrolobular in distribution; no significant changes were observed in the kidneys or other organs examined. Analyses of the livers from the female rats indicated a slight increase in the total lipid content, due chiefly to an increase in neutral fat. There was no significant difference between the values obtained on the experimental and control groups so far as the following determinations on the blood were concerned: urea nitrogen, nonprotein nitrogen, serum phosphatase, and plasma prothrombin dotting time. (b) Guinea Pigs: Groups of eight male and eight female guinea pigs were sub jected to repeated seven-hour exposures. These animals experienced such severe intoxication that no male guinea pig survived more than 10 exposures in 14 days and no female survived more than 24 exposures in 32 clays. SL 080872 i and ough aticm there mine ,-apor nsity 'oups s EF sures Rats 11 7 Additional groups oE two male guinea pigs each were killed after 1, 3, 4, and 10 exposures and examined for significant changes as compared with a group of unexposed controls. The experimental animals showed a rapid loss in body weight and an increase in the weights of the liver and the kidneys. Histopatholcgical examination of the tissues revealed slight-to-moderate central fatty degeneration of the liver and slight-to-moderate cloudy swelling of the tubular epithelium of the kidneys; no alterations were observed in the other tissues examined. An average blood nonprotein nitrogen concentration of 91.6 mg. per 100 cc. was obtained on the ethylene dichloride-exposed animals, compared with an average of 61.6 for the controls; the average blood urea nitrogen values were 42.S and 20.2 mg. per 100 male hree >amThe -c in the .oles. 1.1 in rats '.e in i the ,lucid and Still* ere day* i l_ i i i i.i I i i i i i i i i i i i i i i i i i O l4 *8 *2 AS T9 84 $8 ti2 140 154 TIME-DAYS ON EXPERIMENT tiii (63 182 II 196 Chari 2.--Growth curves of male and female rats that were repeatedly exposed for seven hours to a 200-ppm ethylene dichloride vapor. Table: 3.--Final Average Body Weights and Organ Weights from Male and Female Rats That Wer: Exposed to 200 PPM Ethylene Dichloride for 151 Seven-Hour Periods in 212 Days Croup Sex L'ocxpostftl (controls) Air-exposed (controls). T y Exposed to 200 ppm cth> lea* dichloride .................... Unexpoaed (controls)... Air-expoiied (control*). Exposed to 200 ppm ethylene dichloride ................... T M M M Eats 11 1?. 11 11 0 0 Av. Body Wc.. Gni! 226 220 223 m 338 251 Organ Weights. Cm./loo Cm. Body Wt. - ----------------------------------------- Lung Heart Liver KIdueys Spleen ...0-73 0.40 2.76 0.76 0 21 ....0.71 o.ss 2,43 0,G3 0.13 0.71 0.3d 2.S7 o.so 0.13 0.70 0 35 2,.*W o.co 0.1C 0.7S 0.01 0.31 2.23 0.02 0.18 o.ro 0 AS 0.33 2.43 0,03 0.1G 0.70 ST 080873 8 cc., respectively. No appreciable deviation from the contra. s was evident in the ' e of serum phosphatase or plasma prothrombin clottir:: :e. Rabbits: Two male rabbits and one female rabbit t. rated 165 exposures in . , days with no evidence of intoxication as judged by g-. d appearance and behavior, mortality, and body weight during the course of t' periment. At the termination of the experiment no adverse effects were note gross and micro scopic examination of the tissues, nor from the folk- -g determinations: organ weights, blood nonprotein nitrogen, urea nitrogen, sen. . phosphatase, and plasma prothrombin clotting time. (<f) Monkeys: Two male animals that were subjected to repeated seven-hour exposures experienced rapid and severe intoxication. One monkey, killed in a moribund state after eight exposures, showed the following changes as compared with control monkeys: enlargement of the liver with increases of neutral fat and esterified cholesterol content; marked degeneration and vacuolation of liver cells; moderate degeneration of the epithelium of the renal tubules with cast formation and distention of the lumens; and increased plasma prothrombin clotting time. The second monkey, killed after 12 exposures, showed similar changes but of consider ably milder degree. Hematological values obtained on these monkeys, either mid way in the experiment or terminally, showed no significant changes as compared with values obtained in one to three preexposure examinations. Concentration: 200 PPM (0.81 Mg. per Liter).--(a) Rats: Groups of 15 male and 15 female rats tolerated 151 exppsures in 212 days and showed no evidence of adverse effects as judged by general appearance and behavior, growth (Chart 2), mortality, final body and organ weights (Table 3), periodic hematological exam ination, and gross and microscopic examination of the tissues. Determinations of blood nonprotein nitrogen, urea nitrogen, serum phosphatase and plasma prothrom bin clotting time yielded no abnormal results as compared with control values. Analyses of the livers for total lipid content, phospholipid, neutral fat, and free and esterified cholesterol likewise presented no evidence of adverse effect. (b) Guinea Pigs: Groups of eight male and eight female guinea pigs tolerated ISO exposures in 246 days. The experimental groups did not appear to grow as well as the control groups (Chart 3). However, the final body weights (Table 4) were significantly different from the control weights only in the case of the male guinea pigs. Organ weight studies (Table 4) revealed no significant deviations from the control values. The blood urea nitrogen, nonprotein nitrogen, serum phosphatase, and plasma prothrombin clotting time values were normal. Micro scopic examination of the tissues revealed no evidence of organic injury except that about half of the guinea pigs examined (both sexes) exhibited slight paren chymatous degeneration of the liver, with a few fat vacuoles diffusely distributed. Liver-lipid analyses indicated on the average a slight increase over the controls in total lipid, phospholipid, neutral fat, and free and esterified cholesterol. Concentration: 100 PPM (0.105 Mg. per Liter).--(a) Rats: Groups of 15 male and 15 female rats were subjected to repeated seven-hour exposures. The male rats tolerated as many as 151 exposures in 211 days and the female rats as many as 142 exposures in 19S days without evidence of adverse effects as judged by general appearance and behavior, mortality, growth, final body and organ weights, periodic hematological examination, and gross and microscopic examination of the tissues. SL 080874 mt in e and U the nicronrgan lasma ,-hour in a '.pared -t and cells; nation . The :sider mldipared male nee of rt 2), examans of hromalutrs. and crated ow as ale 4) : male ations sertuii -Iicrocxcept paren! mted. rols in r> male le rats as 142 eneral riodic issues. 9 The values for blood nonprotein nitrogen, urea nitrogen, serum phosphatase, and plasma prothrombin dotting time and the results of studies of the total lipid phos pholipid, neutral fat, and free and esterified cholesterol of the liver were all normal. (b)^ Guinea Pigs: Groups of eight male and eight female guinea pigs were sub jected to repeated seven-hour exposures. The males tolerated 121 exposures in 170 days and the females 162 exposures in 226 days and showed no evidence of adverse effects as judged by mortality, growth (Chart 4), final body and organ weights (Table 5), blood nonprotein nitrogen, urea nitrogen, serum phosphatase, plasma, prothrombin clotting time, and gross and microscopic examination of the tissues. Analyses for the total lipid, phospholipid, neutral fat, and free and esterified cholesterol of the liver produced only normal results. o zo 30 *0 $0 co ro o too no 120 130 143 ao so *70 NUMBER OF SEVEN-HOUR EXPOSURES L.i I -Li 1 1 I 1 f 1 i t L_t. f I f 1 \ t t f ? f ( * t t ! t. Lj 0 14 25 42 51 TO 04 53 n2 125 140 154 165 152 135 Zio 224 230 TIME-DAYS ON EXPERIMENT Chart 3.--Growth curves of male and female guinea pigs that were repeatedly exposed for seven hours to a 200-ppm ethylene dichloride vapor. Table 4.--Final Average Body Weights and Organ Weights from Male and Female Guinea Pigs That Were Exposed to 200 PPM Ethylene Dichlerride jar 1 SO Seven-Hour Periods in 24S Days Croup Sex l>Dex posed (coatfoU).. Air-eipotwd (controls).. F I' Exposed to 200 ppm ctbyloae dkh\oride ................. UneXp03ed (controls).* F M Air-exposed (controls). J^po^d to 200 ppm ethylene dicblorifitf ............... M M Bees' 7 8 Av. Body Cm! 857 16 7 750* 8 627 8 $29 S 700f Organ Weights, Om./lCO Gin. Body Wt. Luus 0-77 0.70 Heart 0 2G 0,27 Liver 3.16 2.90 Kidueya 0.52 0.59 Spleen 0 10 0.13 ... 0S7 0.27 3.01 0,50 0.12 0.72 0,29 2.70 0 63 0.13 0.29 0,75 0.SS 2.S3 0 67 0.13 0,37 0 91 0,32 3.131 0.71 0.12 0 40 Compared * F= >vlf0h.03o. lr-exposed control-,: < p =0011. SL 080875 10 An additional grot:;- of 20 female guinea pigs that received 14 exposures in IS days likewise failed to show any evidence of adverse effects when judged by the same criteria. (c) Rabbits: Two male rabbits and one female rabbit tolerated 17S exposures in 248 days without evidence of adverse effects as judged by general appearance and behavior, growth, final body and organ weights, and gross and microscopic- examination of the tissues. Studies of the blood nonprotein nitrogen, urea nitrogen, serum phosph '.tase and plasma prothrombin clotting time also failed to reveal any evidence of a -se effects. (d) Mor : Two male monkeys were subjected to 148 seven-hour exposures in 212 da} J exhibited no evidence of adverse effects as judged by general appearance ar.a behavior, periodic hematological examination, growth, final body and organ weights, and gross and m roscopic examination of the tissues. O 10 20 30 40 30 CO TO CO 00 100 |!0 120 NUMBER OF SEVEN-HOUR EXPOSURES l I l I I I I I i I I I i I I I 1 1 I I II t 1 1 I 0 14 29 42 56 To 64 39 112 126 140 164 168 TIME-DAYS ON EXPERIMENT Chart 4.--Growth curves of male and female guinea pigs that were repeatedly exposed for seven hours to a 10O-ppn> ethylene dichloride vapor. Table S.--Average Final Body Weights and Organ Weights from Male and Female Guinea Pigs That Were Exposed to 100 PPM Ethylene Dicklorhle for as Many as 162 Seven-Hour Periods in 226 Days Group Sex Caexposed (coatrote)...................... F Alrexposed (controls) --....... T xpo?d to 100 ppm ethyleoe diihlorifJe ....................................... F Unerased (coGtroU)............. . Expo.p.l to 100 ppm ethylene dkhlorltln ....................... ...-- M M Pigd 7 8 5 S 7 Ay, 1' V,q Gn* . 553 f ii Lun Heart 0-53 0.23 0.7$ 0.2*5 . n. ----- Liver Kldoey* 2.70 Q.W 2.0t O-'.O ------ Spleen o.Itf 0.13 -------^ T3te3 712* SSI 0.73 0.7U 0.23 0.23 3.27* 2.07 0.37 0.C0 0-12 u.U 0.13 833* 0.73 0.20 2,91* 0.C0 O.ll 0,13 Compared \vlth unexposed controls: * F = > 0 03. SL 080876 arcs ance Opic jgen, an)' tures aeral body J for -\sU-3 0H 0.15 n SIGNIFICANCE OF RESULTS Toxicological studies for the purpose of industrial hygiene are intended to yield, first, information on the nature of the toxic effects that may be anticipated in human subjects and, second, quantitative measures of toxicity that may be utilized for the evaluation of intensities of exposure in industry. The observations reported here as well as those published previously 11 1r2eveal a variety of toxic effects, depending primarily on vapor concentration and duration of exposure but also on species and individual susceptibility. A quite meager experience with toxic effects in human subjects I: has been reported by means of which the results obtained with animals may be checked or verified. Ethylene dichloride has an unquestioned depressant action on the central nerv ous system and may be expected to cause in human subjects varying degrees of "drunkenness" and unconsciousness by this action, which may terminate in death. Human experience has verified this depressant action. Vapor concentrations high enough to cause marked central depression also produce irritation within the respiratory system. The organic injury produced in the Uver and the kidneys of various species of animals would certainly be expected in human subjects, and such organic injury has been found in a few cases in which human subjects had ingested liquid ethylene dichloride. The deaths of rats a few hours after a single exposure, and possibly some of those deaths observed by Heppel and associates/11 suggest a rapidly developing func tional impairment, such as collapse of the cardiovascular system. Hueper and Smith lsb reported a human death apparently due to circulatory failure. Actual hemorrhage may be partly responsible for these sudden deaths; certainly, they are not due to the injury of liver and kidney, which may be responsible for delayed deaths. The outstanding acute toxic effects produced by ethylene dichloride are degen eration, necrosis, and hemorrhage of the liver, the kidneys, and the adrenals. Such effects have occurred in human subjects following ingestion and are always to be anticipated in greater or less degree. The toxic effects to be expected in human subjects after excessive repeated exposures without obvious acute effects will probably be organic injury of the liver, the kidneys, and the adrenals. The corneal opacity observed by Heppel and associates 3:1 in the dog and the fox were not observed in any of the species employed in this study, nor has it been observed in human subjects. The quantitative data on acute toxicity represented by the lines AD, XY, CD, and EF (Chart 1) appear to be useful measures of the capacity of ethylene dichlo- 11. Lehmann, K. B., and Flury, F.: Toxicology and Hygiene oE Technical Solvents, Berlin, Julius Springer, 193S. Heppel and others.- Sayers and others.31 12. (o) Hamilton, A., and Hardy, H. I,.: Industrial Toxicology, New York, Paul B. Hoeber, Inc., 1949. (b) Hueper, \V. C., and Smith, C.: Fatal Ethylene Dichloride Poisoning, Am. J. M. Sc. 189:77S-7S4, 1935. (c) Hulst, J. P, L,; Stecnhauer, A. J., and Kcddc, D. L.: Fatal Ethylene Dichloride Poisoning, Nederl- tkljschr. geneesk. 30:406-407, 1946. (d) McNally, \V. D., and Fostvcdt, G.: Ethylene Dichloride Poisoning, Indust. Med, 10:373-374, 1941, (c) PoLibal, J,: Cnsop. lek. ecsk. 86:1-S, 1917 (Czechoslovakian), abstracted, Chetn. Ahst. 42:9S7c, 194S; Two Cases of Fatal Poisoning with Symmetrical Dichlorocthanc (ClLCl-CILCl) After Oral Intake, Czech. M. J.. no. 7, pp. 203-206 (Feb. 21, 1947); abstracted, J. Indust. llyg. & Toxicol. 30:60, 194S, (/) Wirtschaftcr, Z. T., and Schwartz, E. D.: Acute Ethylene Dicldoride Poisoning, ibid. 21-.126-131, 1939. SL 080877 12 ride to cause injury and to kill in single exposures. The significance of these data for human subjects could be determined with greater certainty if similar data on other species were available. Other published data on acute ethylene dichloride vapor toxicity 5 show that no other species of laboratory animals is appreciably more susceptible than the rat and that most species are not remarkably more resistant. Almost all species suffered serious or fatal injury from one or but a few seven-hour exposures at less than 1,000 ppm. Accordingly, it would appear reasonable to use the data represented by CD and EF (Chart 1) for evaluating the toxicological significance of the single exposures for human subjects. These data may not be applicable, however, at high concentrations, greater than about 1,000 ppm, since minimal anesthetic effects may occur in shorter intervals of time than are indicated by EF. The quantitative data on chronic toxicity, represented by points G, H, and 1 (Chart 1), agree on the whole quite well with data published previously.5* It inay be concluded with considerable assurance that human subjects will tolerate regularly daily seven-hour exposures to vapor concentrations as high as 100 ppm without injury. This figure has been generally accepted for many years as the threshold limit for industrial exposure. The outstanding characteristic of these quantitative data is the proximity of G, H, I, EF, and CD (Chart 1), This suggests that an exposure of excessive degree is very likely to be one that produces acute effects and that chronic intoxication without such acute effects is improbable. SUMMARY Rats were exposed to ethylene dichloride vapor for single periods on a varying concentration-time basis. The results were treated statistically and permitted the graphing of lines representing the single exposures causing death in 0.01, 50, and 99.99fo of the animals. Additional exposures were made in order to determine the most severe single exposures which were without detectable adverse effects in rats. Typical results were ns follows: LDw--0.S3 hour at 12,000 ppm, 2.75 hours at 3,000 ppm, 7.20 hours at 1,000 ppm. LDo.oi--0.23 hour at 12,000 ppm. 1.02 hour at 3,000 ppm, 3.70 hours at 1,000 ppm. No adverse effect--0.1 hour at 12,000 ppm, 0.3 hour at 3,000 ppm, 1.5 hour at 1,000 ppm. Four animal species were exposed for seven hours daily, five days a week, to ethylene dichloride vapor for six months. Maximum vapor concentrations without adverse effect were as follows: rabbit, 400 ppm; rat, 200 ppm; monkey and guinea pig, 100 ppm. The toxic effect from single exposures, as observed on experimental animals, consisted of depression of tire central nervous system, lung irritation, and organic injury of the liver, the kidneys and the adrenal glands. The significant chronic effect appears to be hepatic and/or renal damage. It is concluded that for uniform daily exposures of about seven hours' duration there is little probability of any adverse effect on human subjects if the ethylene dichloride concentrations arc kept below 100 ppm. ACKNOWLEDGMENT The authors arc indebted to Mrs. Nora'oclte T. Williams for the analytical work ou lipid constituents of the liver. Printed ond Published in the United States of America SL S0878 f ATTACHMENT B MATERIAL SAFETY DATA SHEET PAGE: i DOW CHEMICAL U.S.A. MIDLAND MICHIGAN 48640 EMERGENCY PHONE: 517-636-4400 EFFECTIVE DATE: 22 DEC 78 PRODUCT CODE: 30457 PRODUCT NAME: ETHYLENE DICHLORIDE MSD: 0166 INGREDIENTS (TYPICAL VALUES-NOT SPECIFICATIONS I ETHYLENE DICHLORIDE SECTION 1 PHYSICAL DATA : 99.5 : BOILING POINT: 83.7C (182.7F) VAP PRESS: 67.0 MMHG 8 20C VAP DENSITY (AIP=1): 3.42 APPEARANCE AND ODOR: COLORLESS, : SOL. IN WATER: 0.8 G/100G 0 : SP. GRAVITY: 1.250 8 25/25C : % VOLATILE BY V.OL: 100 CHLOROFORM-LIKE LIQUID. 20C SECTION 2 FIRE AND EXPLOSION HAZARD DATA FLASH POINT: 13C (56F) : FLAMMABLE LIMITS (STP IN AIR) METHOD USED: TAG CLOSED CUP. : LFL: 6.24 VOL. UFL: 16% VOL. EXTINGUISHING MEDIA: FOAM, C02, DRY CHEMICAL. WATER FOG FOR LARGE FIRES. SPECIAL FIRE FIGHTING EQUIPMENT AND HAZARDS: VAPOR IS HEAVIER THAN AIR AND MAY TRAVEL CONSIDERABLE DISTANCE TO A SOURCE OF IGNITION AND FLASH BACK. WEAR SELF-CONTAINED BREATHING APPARATUS. IGNITION TEMPERATURE 413C (775F). WATER IS LIGHTER THAN EDC AMD CAN BE USED AS A BLANKET TO EXTINGUISH FIRE. KEEP VAPORS AWAY FROM POSSIBLE IGNITION SOURCFS. SECTION 3 REACTIVITY DATA STABILITY: AVOID OPEN FLAMES, WELDING ARCS OR OTHER HIGH TEMPERATURE SOURCES WHICH INDUCE THERMAL DECOMPOSITION. AIR AT 413C (775F). INCOMPATIBILITY: AVOID ALKALI, OXIDIZING MATERIAL, AMINES. HAZARDOUS DECOMPOSITION PRODUCTS: HYDROGEN CHLORIDE. HAZARDOUS POLYMERIZATION: WILL NOT OCCUR. IGNITES IN SECTION 4 SPILL, LEAK, AND DISPOSAL PROCEDURES ACTION TO TAKE FOR SPILLS (USE APPROPRIATE SAFETY EQUIPMENT): EXTINGUISH SOURCES OF IGNITION. SMALL SPILLS: MOP UP, WIPE UP OR SOAK UP IMMEDIATELY. REMOVE TO OUT OF DOORS. LARGE SPILLS: CONTAIN LIQUID? (CONTINUED ON PAGE 2 ) (R) INDICATES A REGISTERED OR TRADEMARK NAME 0" THE DOW CHEMICAL COMPANY SL 080879 1 MATERIAL SAFETY DATA SHEET PAGE: 2 'DOW CHEMICAL U.S.A. MIDLAND MICHIGAN 48640 EMFRGENCY PHONE: 517-636-4400 EFFECTIVE DATE: 22 DEC 78 PRODUCT (CONT'D): ETHYLENE DICHLORIDE PRODUCT CODE: 30457 MSDI 0166 SECTION 4 SPILL, LEAK, AND DISPOSAL PROCEDURES 'CONTINUED) ACTION TO TAKE FOR SPILLS (USE APPROPRIATE SAFETY EQUIPJ .T): (CONTINUED) TRANSFER TO CLOSED METAL CONTAINERS. DISPOSAL METHOD: SEND SOLVENT TO A RECLAIMER OR INCINERATE IN EQUIPMENT EQUIPPED WITH AN HCL SCRUBBER ACCORDING TO LOCAL, STATE, AND FEDERAL REGULATIONS. CONTACT THE DOW CHEMICAL COMPANY FOR ADDITIONAL HELP. REFER TO CHEMICAL SAFETY DATA SHEET 5D-18, MANU FACTURING CHEMISTS ASSOCIATION, 1825 CONNECTICUT AVENUE, N.W., WASHINGTON, D.C. 20009. SECTION 5 HEALTH HAZARD DATA INGESTION: MODERATE SINGLE DOSE ORAL TOXICITY: LD50 RATS 680 MG/KG. MAY BE HARMFUL AND IRRITATING IF INGESTED. EYE CONTACT! PAIN, MODERATE IRRITATION, AND POSSIBLY TRANSIENT CORNEAL INJURY. SKIN CONTACT: PROLONGED CONTACT - SOME IRRITATION. IF CONFINED TO THE SKIN, MAY CAUSE A BURN. SKIN ABSORPTION: LD50 2800 MG/KG RABBIT. TCXICITY IS LOW , BUT MAY BE ABSORBED IN TOXIC AMOUNTS IF CONTACT IS PROLONGED OR EXCESSIVE. INHALATION: MAY BE IRRITATING AND MAY CAUSE CENTRAL NERVOUS SYSTEM DEPRESSION. OSHA GUIDE AND ACGIH TLV 50 PPM. EFFECTS OF OVEREXPOSURE: REPEATED PROLONGED EXPOSURE MAY CAUSE LIVER INJURY, CENTRAL NERVOUS SYSTEM DEPRESSION, NAUSEA, DIZZINESS, DRUNKENNESS. NCI STUDY INDICATES THIS MATERIAL IS AN ANIMAL CARCINOGEN VIA GAVAGE STUDIES AT THE MAX. TOLERATED DOSE (MTD) AND 1/2 MTD IN RATS AND MICE; MALTONI INHALATION STUDY UP TO 150 PPM IN RATS AND MICE SHOWS NO CARCINOGENICITY. SECTION 6 FIRST AID PROCEDURES: FIRST AID--NOTE TO PHYSICIAN EYES: IRRIGATE WITH FLOWING WATER IMMEDIATELY AND CONTINUOUSLY FOR FIFTEEN MINUTES. REFER TO MEDICAL PERSONNEL. SKIM: IN CASE OF CONTACT, IMMEDIATELY FLUSH SKIN WITH PLENTY OF WATER FOR AT LEAST 15 MINUTES WHILE REMOVING CONTAMINATED CLOTHING. CALL A PHYSICIAN. WASH CLOTHING BEFORE REUSE. INHALATION: REMOVE TO FRESH AIR IF EFFECTS OCCUR. CALL PHYSICIAN AND/OR TRANSPORT TO MEDICAL FACILITY. IF RESPIRATION STOPS, GIVE MOUTH-TO-MOUTH RESUSCITATION. INGESTION: IF SWALLOWED, INDUCE VOMITING IMMEDIATELY BY GIVING TWO GLASSES OF WATER AND STICKING FINGER DOWN THROAT. CALL A PHYSICIAN. (NEVER GIVE ANYTHING BY MOUTH TO AN UNCONSCIOUS PERSON). NOTE TO PHYSICIAN: (CONTINUED ON PAGE 3 ) (R) INDICATES A REGISTERED OR TRADEMARK NAME OF THE DOW CHEMICAL COMPANY SL 080880 MATERIAL SAFETY DATA SHEET PAGE: 3 DOW CHEMICAL U.S.A. MIDLAND MICHIGAN 48640 EMERGENCY PHONE: 517-63b'4400 EFFECTIVE DATE: 22 DEC 78 PRODUCT CCONT'D): ETHYLENE DICHLORIDE PRODUCT CODE: 30457 HSD: 0166 SECTION 6 NOTE TO PHYSICIAN: FIRST AID--NOTE TO PHYSICIAN (CONTINUED) (CONTINUED) EYES: may CAUSE CORNEAL INJURY OP BURN. STAIN FOR EVIDENCE OF CORNEAL INJURY. IF CORNEA IS BURNED, INSTILL ANTIBIOTIC STEROID PREPARATION FREQUENTLY, CONSULT OPHTHALMOLOGIST. SKIN: MAY CAUSE MODERATE IRRITATION. CHRONIC EXPOSURE MAY CAUSE DEFATTING TYPE OF DERMATITIS. TREAT AS ANY CONTACT DERMATITIS. RESPIRATORY: ANESTHETIC OR NARCOTIC EFFECT MAY OCCUR. GOOD WARNING PROPERTIES. ADMINISTER OXYGEN IF AVAILABLE. BRONCHODILATORS, EXPECTORANTS, AND ANTITUSSIVEs MAY BE OF HELP. ORAL: HIGHLY TOXIC. MAY CAUSE CHEMICAL PNEUMONIA IF ASPIRATED INTO LUNGS. DANGER OF CHEMICAL PNEUMONIA MUST BE WEIGHED AGAINST TOXICITY WHEN CONSIDERING EMPTYING THE STOMACH. IF LAVAGE IS PERFORMED SUGGEST ENDOTRACHEAL AND/OR ESOPHAGOSCOPIC CONTROL. SYSTEMIC: MAY CAUSE KIDNEY DAMAGE. MAY CAUSE LIVER DAMAGE. MAY CAUSE ADRENAL DAMAGE. MAY CAUSE DPUNKENESS. MAY CAUSE NAUSEA OR VOMITING. MAY INCREASE MYOCARDIAL IRRITABILITY. AVOID EPINEPHRINE OR SIMILAR ACTING DRUGS IF AT ALL POSSIBLE. ALCOHOL CONSUMED BEFORE AND AFTER EXPOSURE MAY INCREASE INJURY. CONSULT STANDARD LITERATURE. NCI STUDY INDICATES IT IS AN ANIMAL CARCINOGEN. SECTION 7 SPECIAL HANDLING INFORMATION VENTILATION: RECOMMEND CONTROL OF VAPORS TO SUGGESTED GUIDE. RESPIRATORY PROTECTION: NIOSH APPROVED RESPIRATORY PROTECTION REQUIRED IN ABSENCE OF PROPER ENVIRONMENTAL CONTROL. FOR EMERGENCIES, A SELF-CONTAINED BREATHING APPARATUS OR A FULL-FACE RESPIRATOR AS APPROVED BY NIOSH IS RECOMMENDED. PROTECTIVE CLOTHING: CLEAN BODY COVERING CLOTHING. IN ADDITION, RUBBER GLOVES, BOOTS, APRON DEPENDING'UPON THE EXTENT AND SEVERITY OF EXPOSURE LIKELY. ' EYE PROTECTION: SAFETY GLASSES WITHOUT SIDE SHIELDS. WASHING FACILITIES NEAR WORK AREA. SECTION 8 SPECIAL PRECAUTIONS AND ADDITIONAL INFORMATION PRECAUTIONS TO BE TAKEN IN HANDLING AND STORAGE: KEEP DRY TO MAINTAIN QUALITY AND REDUCE CORROSION. BULK QUANTITIES SHOULD BE PADDED WITH NITROGEN. AVOID EYE AND SKIN CONTACT AND THE BREATHING OF VAPORS, ADDITIONAL INFORMATION: -------- LAST PAGE (R) INDICATES A REGISTERED OR TRADEMARK NAME OF THE DOW CHEMICAL COMPANY THE INFORMATION HEREIN IS GIVEN IN GOOD FAITH, PUT NO WARRANTY, EXPRESSFD OR IMPLIED, IS MADE. Slj 080881 > ATTACHMENT C DOW CHEMICAL U.S.A. January 8, 1979 MIDLAND, MICHIGAN 43640 AIR SAMPLING AND ANALYSIS OF 1,2-DICHL0R0ETHANE (EDC) USING ACTIVATED CARBON ADSORPTION, CARBON DISULFIDE DESORPTION AND GAS CHROMATOGRAPHY WITH FLAME IONIZATION DETECTION The following air sampling and analytical parameters are being followed to minimize the migration and displacement of EDC from the activated carbon collection media and to maximize the collection and analytical efficiency. Sample Collection (Activated Carbon Adsorption) For collecting personal air samples, small battery operated pumps are used with air drawn through a commercially available 1 gram PCB (Pittsburgh Coconut Base) 12X30 mesh activated carbon tube at a flow rate of 150 mL/min. The total air volume in a 4 hour work day is 36 Liters. Short term area or excursion air samples are obtained using a 1 gram tube and an air flow rate of 500 mL/min. Total air volumes do not exceed 5 Liters. Sample Preparation (Carbon Disulfide Desorption) The following procedure has proved satisfactory in the desorption of EDC from activated carbon. [1] Carbon disulfide (10 mL) is cooled to dry ice temperature. [2] The carbon granules are slowly added to the cold CS^. [3] The sample is agitated for at least 30 min on a mechanical shaker. Standard Preparation Standards of EDC are routinely prepared by injecting a measured volume of EDC into a known volume of CS^ with a 10 pL syringe. AIM OPERATING UNIT OF THE DOW CHEMICAL COMPANY SL 080882 0 ( 1,2-Dichloroethane (EDC) Page 2 Sample Analysis Analysis is performed by gas chromatography/flame ionization detection. The following gas chromatographic conditions are employed. Column: 10'xl/8" 20% Carbowax 20M + 2% KOH on 80/100 Supelcoport Temperatures: Column: lOO^C (isothermal) Detector: 300C Detection: FID @ 1024 to 2 Injection: 2 pL on column Gas Flows: Nitrogen: 30 mL/min Hydrogen: 30 mL/min Air: 240 mL/min Recovery Efficiency Known concentrations, or "spikes", of EDC are prepared and submitted with each set of field samples. Recoveries average 90+5%. Several techniques have been used. [1] Use a microLiter syringe to inject a known amount of EDC directly into a 100 Liter Saran bag and then aerate the known mixture from the bag onto the 1 gram activated carbon tube at the same air flow rate and total air sample volume as field samples. [2] A known amount of EDC has been injected into a U-tube through which air is swept. An activated carbon tube is attached to the downstream side of the U-tube to adsorb the chemical as it evapo rates. [3] A known amount of EDC has been injected directly on the charcoal bed. [4] Phase equilibrium recoveries have been determined. [5] A known concentration of EDC in nitrogen in a cylinder has been flow controlled through 1 gram commercial charcoal tubes. Again, the carbon tube and air flows used were the same as those used in obtaining field samples. In addition to EDC, other contaminants known to be present in the v/ork environment were added to the cylinder for determining recovery efficiencies. No humidity work has been done. SL 080883 ATTACHMENT D The following tests are done on workers with potential exposure to EDC: A) Preemployment and B) Periodically Every two years on those over age 40 and every four years on those under age 40: History and Physical Exam Pulmonary Function (FVC+FEVj_) ECG Chest X~Ray Tonometry (over age 40) Audiogram Laboratory Work: CBC Urinalysis Stools for Occult Blood (over age 40) GGTP SGOT SGPT Alkaline Phosphatase Blood Sugar BUN Cholesterol Total Protein A/G Ratio Uric Acid Bilirubin Serum Protein Electrophoresis (one time only) Alpha 1 Antitrypsin (if alpha 1 globulin is low) C) Annually - Laboratory work as listed above on everyone. REF/ns 1/16/79 SL 080884 ATTACHMENT E U.S. ETHYLENE DICHLORIDE END USES USE Intermediate for: VOLUME, AS % OF TOTAL Vinyl Chloride 80+ Trichloroethylene 2 1,1,1-Trichloroethane 4 Vinylidene Chloride 2 Perchloroethylene 3 Ethylene Diamines 2 Lead Scavenger 2 Export 4 Miscellaneous 1 (includes other chemical intermediates, extraction solvent, reaction/carrier solvent, polysulfide rubber production, cleaning solvent, grain fumigant, adhesives, paint and coating diluent, manufacture of polycarbonate resins) SL 080885 n c) E. I- du Pont de Nemours Company Wilmington, Delaware i989a LEGAL DEPARTMENT February 5, 1979 Docket Officer Docket No. H-079 Room S6212 U.S. Department of Labor Occupational Safety & Health Administration Third Street and Constitution Avenue, N.W. Washington, D.C. 20210 Sir: Occupational Exposure to 1,2-Dichloroethane The attached statement is submitted on behalf of E. I. du Pont de Nemours and Company (Du Pont) in response to OSHA's request for information on the above subject pub lished at 43 Fed. Reg. 56910. We request that our state ment be made part of the record on occupational exposure to 1,2-dichloroethane. For reasons more fully stated in our attached com ments, it is our position that: No need for an emergency temporary stan dard has been shown. NIOSH's 1978 recom mendation is based solely on a study in which animals were force fed, a route of exposure not found in workplaces. Other current experiments based on dermal and inhalation exposure routes have shown no unusual tumorogenic effects. A standard on occupational exposure to 1,2-dichloroethane should contain an ex emption for antiknock compounds and fuels which contain these compounds. Due to the presence of lead in the antiknock compounds, employee exposure is closely limited. The use of air purifying respirators may be appropriate at workplace exposures of less than 50 ppm. Initial studies have shown these less cumbersome respirators may be an effective means of protecting employees. SL 080886 Docket Officer 2 February 5, 1979 We appreciate this opportunity to participate in the hearing record. If you have any questions, please feel free to contact me at (302) 774-9036. Very truly yours, '0 (L^-* B. Anne Gwynn Attorney Environment Division AG:kes Attachments SL 080887 f) DU PONT'S RESPONSE TO OSHA'S REQUEST FOR INFORMATION ON OCCUPATIONAL EXPOSURE TO 1,2-DICHLOROETHANE (EDC) In 43 Fed. Reg. 56910, OSHA requested information on the following items: (1) Metabolism, including intermediate as well as final metabolites. (2) Toxicity, tumorigenicity, carcinogenicity, teratogenicity and/or mutagenicity, including the effects of potential co-factors as related to each of these. (3) Human epidemiology (employee populations and those otherwise exposed). (4) Appropriate medical surveillance pro cedures. (5) Appropriate respiratory protection. (6) Uses and production technologies. (7) Employee exposures (actual or potential) in each use and production facility, including: (a), the levels and specific conditions of such exposures, (b) the numbers of employees in volved in each exposure situation. (8) Technological and economic feasibility of reducing employee exposure. (9) Economic and technological feasibility of complying with a complete 1,2-dichloroethane standard at the lowest level of exposure feasible. (10) Analytical and sampling methods used and evidence of their precision and accuracy. (11) Whether issuance of an Emergency Temporary Standard is appropriate. Items 1-3 Du Pont's Haskell Laboratory has not performed any toxi cological or epidemiological studies on 1,2-dichloroethane (EDC). However, an initial literature search on the chemical was made in 1975 and updated in recent months. Summaries of the data are attached as Exhibits A and B. SL 080888 2 No adverse health effects known to be attributable to exposure to EDC have been observed in Du Pont employees. Item 4 Extensive medical surveillance should only be required at exposure levels for which there is a reasonable possibility of harmful health effects. Such surveillance should include an annual physical consisting of completion of a health history questionnaire, an examination by or under the supervision of a physician, a posterior-anterior chest x-ray, a urine evaluation for albumin and sugar and blood, hematology to include hemoglobin, hema tocrit and white blood count, blood chemistry to include glucose, BUN, SGOT, alkaline phosphatase, creatinine, LDH and bilirubin. Item 5 NIOSH stated in its Revised Recommended Standard, DHEW (NIOSH) Publication No. 73-211, that only supplied-air or selfcontained respirators should be used. While we aaree that these respirators should be required for employee exposures above 50 ppm, we believe that the use of air purifying respirators may be appro priate at lower concentrations. Studies performed by G. 0. Nelson and C. A. Harder1 and subsequent studies performed by Nelson and A. Nicholas Correia^ show that organic vapor cartridges with charcoal sorbent can absorb EDC at airborne concentrations of 50 ppm for greater than eight hours. If further experimentation verifies appropriate cartridge service life under workplace conditions, use of air purifying respirators, which are less expensive and less burdensome to wear, should be permitted. Item 6 Du Pont does not manufacture EDC but purchases it for use as a component of Motor Fuel Antiknock Compound (MFAC). MFAC is prepared by blending EDC with tetraethyl lead and/or tetramethyl lead and other components. The compound is sold to oil refiners who blend it with motor fuels. Item 7 MFAC is produced at Du Pont's Chambers Works at Deepwater, New Jersey, Antioch Works at Antioch, California, and Beaumont Works at Beaumont, Texas. IAm. Ind. Hyq. Assoc. J., July, 1974, p, 391, Attached as Exhibit C. 2 Am. Ind. Hyg. Assoc. J., September, 1976, p. 514, Attached as Exhibit D. SL 080889 At Chambers Works, EDC is received by ship, tank truck and tank car; the other two locations receive it in .tank cars. EDC is pumped into storage tanks from which it is transferred to blending tanks and the blended product pumped to storage tanks. The entire system is closed. Potential workplace exposure exists when connecting and disconnecting unloading lines from the carrier, during tank gaging and during sampling at various points in the operation. The numbers of employees potentially exposed to EDC at each location including operators, laboratorians, mechanics and supervisors, are: Chambers Works Beaumont Works Antioch Works 104 23 69 Data from personnel monitoring performed from 1975 to the present show the following workplace concentrations: Chambers Works Average 8-hr. TWA Maximum 8-hr. TWA EDC Handling Finished Product Handling Beaumont 0.5ppm 0.02ppm 2.2ppm 0.18ppm EDC Handling Finished Product Handling Antioch Finished Product Handling - 0.lppm 0.OSppm 0.5ppm 0.14ppm 0.Olppm During carrier connect-disconnect operations, sampling and tank gaging, short-term exposures reach a maximum of 25 ppm. Employees performing these functions wear respirators and impervious gloves. Item 8 As shown from the monitoring data noted in our response to Item 7, a closed system protects employees during the blending and storage of antiknock compounds. Further reduction of employee exposures is unnecessary. The unloading, sampling and gaging operations involve only infrequent, intermittent exposures. Exposures of this type should be lowered through the use of personal protective equipment, not through the installation of expensive engineering controls. Item 9 Du Pont can presently comply with the current OSHA per missible exposure limit of 50 ppm', the ACGIH intended change of 10 ppm, and the 1976 NIOSH proposal of 5 ppm (lOhr work day). SL 080890 We cannot comment on the economic and technological feasibility of complianc with a standard at the lowest level of exposure feasible as we do not know what OSHA considers this level to be. We feel that the permissible exposure chosen should be that level which protects employees against adverse health effects of the chemical. We do not feel that employers should be forced to needlessly exoend resources to lower exposure beyond a safe level. Item 10 We have successfully used the NIOSH Method P&CAM 127 (Organic Solvents in Air) to monitor airborne EDC atthe con centrations encountered in our operations. Further study is necessary to determine the precision and accuracy over a range of EDC con centrations . Item 11 As there is already an OSHA permissible exposure limit in effect for 1,2-dichloroethane and no adverse health effects have been observed at that level, we perceive no "grave danger" to employees and believe that the promulgation of an emergency temporary standard is unwarranted. Any standard proposal should follow the prescribed Section 6(b) standard development process. If a new permanent standard is promulgated, we recommended that OSHA adopt a permissible exposure level of 10 ppm, the level re commended by the American Conference of Governmental Industrial Hygienists in its Notice of Intended Changes for 1978 TLV's. The ACGIH level is based on recent European occupational experience showing chronic effects resulting in neurologic changes, gastroin testinal problems, and liver and kidney impairment at levels greater than 75 ppm and absent at concentrations lower than 25 ppm.- The 1978 NIOSH recommended level of 1 ppm is based solely on a National Cancer Institute carcinogenic study in which rats and mice were fed EDC in corn oil by gastric intubarion, an atypical route for industrial exposure. Recent studies which assess the carcinogenic potential of EDC by the most probably routes of industrial exposure - inhalation and dermal do not show any unusual .tumorogenic effects. "In an ethylene dichloride inhalation study being conducted in Italy by Dr. C. Maltoni, animals were exposed to ethylene dichloride for 2 years and observed until the end of their natural lives. (Exposure levels in this study are 0, 5, 10, 50, and 150 ppm). No evidence of any exceptional tumors in rats or mice have been found following 100 weeks of exposure (6). Also, Dr. B. M. Goldschmidt has informed NIOSH of bioassays of 1,2dichloroethane being conducted at the New York University Institute of Environmental Medicine. Groups of 30 female mice received skin applications of 1,2-dichloroethane for more than one year. None of the animals developed skin tumors, and autopsies did nor reveal any unexpected internal lesions or tumors (7). "4 ^Criteria for Recommended Standard . . . Occupational Exposure to Ethylene Dichloride HEW Pub. No. (NIOSH) 76-139 (1976). ^NIOSH Current Intelligence Bulletin 25. No. 78-149. DHEW (NIOSH) Pub. SL 080891 5 Additional Comments An EDC standard should contain exemptions for products such as antiknock compounds, which contain mixtures of EDC and tetramethyl and/or tetraethyl lead, and for fuels which contain these antiknock compounds. The manufacture and handling of antiknock compounds is very closely controlled because of the toxicity of the lead compound components. Limiting work place exposure to these lead compounds automatically controls the release of EDC to a safe level. If the airborne lead concentration in the workplace ^is maintained at the current OSHA permissible level of 0.075 mg/m", the maximum concentrations of EDC which can be present at various temperatures are: Temperature (C) 10 20 25 30 Calculated EDC Concentration (ppm) 3.0 2.0 2.0 1.0 As all of the EDC concentrations.are well below the 1978 ACGIH recommended level of 10 ppm as well as NIOSH's 1976 recommendation of 5 ppm, these antiknock compounds should be exempted from an EDC standard. We also request that OSHA exempt mixtures of motor fuels containing EDC from all aspects of any potential EDC regulation. While we do not have direct measurements of workplace concentrations of EDC in the handling of gasoline containing EDC at a gasoline service station, we have measured the concentration of ethylene dibromide (EDB), another component of leaded gasoline, to which a person would be exposed in a service station environment. The con centration of ethylene dibromide (EDB) as detected by a personal air sampler, averaged over 2 hours, was less than 0.1 ppb- A grab sample taken at the vehicle filler pipe showed a maximum concentration of 1-2 ppb. Details of these measurements are given in Exhibit E. Current leaded gasolines contain 2.0g of lead/gal., l.Og of EDC/gal, (0.0 37. by weight) and approximately l.Og of EDB/gal Based on the measured values of 0.1 ppb of EDB, the workplace con centration of EDC under these same conditions would be 0.5 ppb as measured by the personal monitors with a maximum of 4-8 ppb as measured by the 5-minute grab sample at the vehicle filler pipe. SL 080892 EXHIBIT A LITERATURE SEARCH* 1,2-DICULOROETHANE (ETHYLENE DICHLORIDE, EDC} I. ACUTE TOXICITY A. Oral a) Values human rats LDLO** LD100 ld50 ld50 ld50 mice ldlo ld50 dogs j^LO LD100 rabbits LD50 lar unsoecified: dog LD50 LD100 guinea pig ld50 LD100 rabbits LDS 0 LD100 rats young LD50 LD100 adult tLD50 Ld10G senile LD50 LD100 845 mg/kg 5 6 ml 6SO mg/kg 680-770 mg/kg 770 mg/kg (670-890) 600 mg/kg 910 mg/kg 2,000 mg/kg 2,500 mg/kg 910 mg/kg 1.3 ml/kg 1.9 ml/kg 0.6 ml/kg 1.2 ml'/kg 0.S ml/kg 1.6 ml/kg 1,135 + 78 mg/kg 2,000 mg/kg 625 + 50 mg/kg 1,500 mg/kg 560 + 38 mg/kg 1000 mg/kg - * Literature Search done 11/25/74. ** Specific gravity 1,1-Dichloroethane = 1.776 1,2-Dichloroethane = 1.256 LDlq = lowest lethal dose LD100 " lethal dose to 100" of test animals LD50 = lethal dose to 505 of test animals (1) (3) (1) (3) (4) (1) (3) (1) (3) (3) (2) (2) (2) * (2) (2) (2) (12) (12) (12) (12) (12) (12) SL 080893 2 A- Oral (Continued) mice young adult senile b)* Effects ld50 LD100 LD50 LD100 LD50 LD100 1,308 + 79 mg/kg 3,000 mg/kg 1,120 + 192 mg/kg 2,500 mg/kg 725 + 33 mg/kg 1,500 mg/kg (12) (12) (12) (12) (12) (12) Isomer unspecified: rats 1-2 ml/kg death at 10-16 hours Results: bradycardia, bradypnea, total atrio ventricular block, cessation of respiration, due to "action on the central nervous system and in particular the respiratory centers." (28) rats 1.0 ml/kg rabbits 0.5 ml/kg Results: 24-72 hours: "reversible dystrophic changes in the liver" 4-5 days: decrease in fat content of hepat'ocytes, appearance of cells with 2-3 nuclei 6-8 days: necrotic foci disappeared (31) rats 0.7 ml/kg Results: decreased rate of oxidative phosphoryla tion in liver mitochondra (32) rabbits 1.2 ml/kg Results: marked increase in fibrinogen content of the blood, acceleration of clotting reaction (41) rabbits 0.9 - 1.7 ml/kg Results: toxic pulmonary edema, "accompanied by a series of changes in the blood." (42) B. Skin a) Absorption rabbit LD50 LD50 o to Q 3890 mg/kg 3.89 ml/kg (3.40-4.46) 2,800 mg/kg (1) (4) (3) SL 080894 3 Skin (Continued) Isomer unspecified: rabbits 10 mg/1 in air Results: decreases respiration and glycolysis, and cytochromic oxrtase in red blood cells, caused a dec " in activity of serum enzymes, i c.g cholines terase, affects membrane cermeability of renal cells. (29) b) Irritation rabbits Score 2* - "trace of capillary injection" Eye rabbit Score 3* (4) dog corneal opacity (16) D. Injection a) Subcutaneous rats LD50 LD5Q 500 mg/kg 1,000 mg/kg (1) (3) mice ldL0 rabbits LD100 b) Intraperitoneal 380 mg/kg 1,200 mg/kg 1,600 mg/kg - (3) (1) (3) rats mice LDso ldlo LD50 600 mg/kg 250 mg/kg 470 mg/kg (1) (1) (6) c) Intravenc . -b dog mice ^LO LD100 LD100 LD0 1 175 mg/kg 175 mg/kg 0.25 ml/kg 0.125 ml/kg (1) (3) (5) (5) 0.075 ml/kg 0.2 ml/kg 0.4 ml/kg 10% increase in urine protein(34 30% incr<sase in urine protein(34 56% increase in urine protein(34 Skin irritation scores run from 0 (no effect ) to 10 (necrosis) Eye irritation see as run from 0 { no effect) to 20 SL 080895 E. Inhalation 1 mg/1 = 247 ppm and 1 ppm = 4.05 mg/m^ at 25 C, 760 mm Hg a) Values humans rats tclo lclo LC5? maximum t ime 4 hours survived 12 min. 1 hour 7 hours 4,000 ppm (1) 1,000 1,000 20,000 3,000 300 ppm ppm ppm ppm ppm (1) (3) (3,10) (3,10) (3,10) mice rabbits guinea pigs pigs rats * no effect times 6 min. 1.5 hours 7 hours 12,000 ppm (8,10) 1,000 ppm (3,10) 200 ppm (8,10) LC100 9,000 ppm (3) lcL0 lclo 7 hours unspecified 3,000 ppm (1) 1,000 ppm (7) ^LO LCioo LC 2 hours 7 hours 9,000 mg/m 3 (1) 3,000 ppm (3) 3,000 ppm (1) LC50 lC50 LC50 0,53 hours 2.75 hours 7.20 hours 12,000 ppm (8) 3,000 ppm (3) 1,000 ppm (8) LC 0.01* LC 0.01 LC 0.01 0.23 hours 1.02 hours 3.70 hours 12,000 ppm (8) 3,000 ppm (8) 1,000 ppm (8) no effect level 0.1 hours 0.3 hours 1.5 hours 12,000 ppm (8) 3,000 ppm (8) 1,000 ppm (8) lethal dose deep narcosis "few minutes" 30 minutes 150,000 PPm (9) 12,000 ppm (9) slight symptoms 8 hours 1,000 ppm (9) TC LC^q = lowest toxic concentration = lowest lethal concentration = concentration lethal to 5m of test animals LC100 = concentration lethal to 1005 of test animals Lc0.01 = concentration lethal to 0.015 of test animals SL 080896 5 b) Effects rats, guinea pigs, rabbits, monkeys 100-400 ppm 7 hours Results: "depression of the central nervous system, lung irritation, and organic injury of the liver, the kidneys, and the adrenal glands." (8) rabbits Results: 300 ppm time unspecified no significant changes in the blood and spinal marrow, with the exception of "toxic granulation in granulocytes of about 20%." (24) rabbits Results: levels and time unspecified liver damage, kidney lesions, and "less marked degenerative signs in other organs." (25) Isomer unspecified: rats Results: 10 mg/1 4 hours decrease in cholinesterase activity serum: 37-431 decrease plasma: 23% decrease brain: 16.4% decrease spinal cord tissues: 16.7% decrease liver: 27.8% decrease pancreas: 20.3% decrease heart: 29% decrease pylorus: 31.2% decrease (33) CHRONIC TOXICITY A. Oral cows 100 ppm 22 days 500ppm, 10 days then 1000 ppm, 12 days Results: no loss of appetite, no decrease in milk production (13). Levels of 1000 ppm produced concentrations of less than 0.25 ppm in the cow's milk (14).' Isomer unspecified: rats fed maize, sugar beets Results: no change function treated with 0.1-0.5% EDC time unspecified in blood composition or liver (30) SL 080897 6 B. Inhalation a) Spencer, et. al. (8,15) 400 ppm rats up to guinea pigs up to Results: 40 7 hour exposures 24 7 hour exposures no survivors, no tumors, increased liver and kidney weights, histological changes in liver and kidney rabbits 165 7 hour exposures Results': maximum for no effect 200 ppm rats 157 7 hour exposures Results: maximum for no effect guinea pigs 180 7 hour exposures Results: histological changes, no tumors 100 ppm rats, male 115 7 hour , female 142 7 hour guinea pigs. male f female 121 162 7 hour 7 hour res rabbits monkeys 178 148 7 hour 7 hour exposures Results: no adverse effect "The significant chronic effect appears to be hepatic and/or renal damage." * (8) b) Heppel, L. A. et. al. (17) 1000 ppm 7 hours/day 5 days/week guinea pigs survived 2 exposures tats survived 3-14 exposures rabbits survived 2-64 exposures dogs, cats, monkeys 23-55 days low mortality Results: fatty changes in liver 400 ppm 7 hours/day 5 days/week rats, rabbits, guinea pigs Results: liver damage high mortality survived 177 exposures SL 080898 7 b) Heppel, L. A. et. al. (Continued) 200 ppm rats Results guinea pigs Results rabbits monkeys 125 exposures greater than normal mortality, mild pulmonary congestion 125 exposures greater than normal mortality, histological changes 125 exposures ' no effect 125 exposures no effect 100 ppm rats survived "many" experiments; no lesions guinea pigs monkeys c) rats, guinea pigs, rabbits, cats 6 hour/dav 5 days/week 500 ppm uoxic to all in 13 weeks 100 ppm tolerated for 17 weeks (19) d) rabbits levels unspecified "chronic poisoning" Results: most severe damage in liver, decrease in lipids of leukocytes, kidney degeration and necrosis, deterioration of kidney function. (25) e) ' rabbits 0.6 - 0.15 ml/kg/hour Results: "bradycardia,...cardiac excitability, and a progressive decrease in the blood pressure to death." (23) f) rabbits 3000 ppm "chronic exposure" Results: "A direct poisoning effect on the bone marrow is concluded." (24) Isomer unspecified: g) rats 5 mg/1 Results: 3.5 months changes which "reflect pathological excitation followed by decreased functional activity of the entire central nervous system." h) rats .05 -:.01 mg/1 3-5 hours/day Results: changes in conditioned reflexes histological changes in the brain. Both disappeared when removed from exposure. i) rabbits 2 mg/m^ 3 hours/day 8-10 months Results: did not affect antibody formation (18) (22) (20) SL 080899- 8 j) rabbits 100 mg/rn 3-4 hours/day 7-11 months Results: depressed antibody formation, changes in liver and kidneys (21) rabbits 10 mg/m3 3-4 hours/day Results: "not toxic" 7-11 months (21) k) rats 5 mg/m3 4 hours/day 1-9 months rats 1) rats 3 mg/m^ and 120 mg/m^ gasoline 4 hours/day 1-9 months Results: "considerable changes of the estrus cycle and its periodicity," a decrease in total number of cycles, number of leukocytes and phagocytic activity not affected (27) 30 mg/m3 plus 1210 mg/m3 gasoline vapors Results: 4 hours/day 6 mos. prior to and during pregnancy "changes in duration of estrus cycle," decrease in fertility, weight, and muscle efficiency of neonates, increased lethality in progeny, no abnormalities in following gerneration (26) -II. ADDITIONAL EFFECTS* * A. Mutagenicity a) wheat seeds 1 ml for 1 day Results: 0.3% dominant mutations 1.8% recessive mutations (35) b) Drosophila melanogaster 0.07% 4-8 hours Results: increased number of recessive mutations and occurrence of non-divergence of X-chromosome. (36) c) Drosophila melanogaster levels and time unspecified Results: increased frequency of recessive lethal mutations, no influence on non-divergcnce of chromosomes in radioresistant organisms (37) d) Drosophila melanogaster levels unspecified Results: 1 day treatment: 25-30% mutations, more pronounced in males il hour treatment: 2.6% mutations (38) SL 080900 9 B. Other organisms a) Invertebrates in water 0.1 mg/1 maximum concentration for "normal biological activity" (39) b) maize prolonged storage with EDC in tropics may affect seedling growth (40) c) 0.455M kills Vibrio (bacteria) 0.065M prevents fermentation of sugar by yeast (5) Isomer unspecified: d) marine pinperch TLra* 150-175 mg/1 (59) e) mole crickets 150 ml/m 2 Results: effective in controlling these insects (43,44) f) spore-forming bacteria, molds 300 g/m^ Results: no molds developed, spore-forming bacteria developed normally (48) IV. METABOLISM a) readily absorbed from the gastro-intestinal tract or the lungs, absorbed to a lesser extent from the skin (10) b) mice 0.05 - 0.17 g/kg injected 10-45% expired unchanged 12-15% expired as C02 51-73% urine 0-0.6% feces 0.6-1.3% remaining intraperitoneally ' Major metabolites: S-carboxymethylcysteine thiodiacetic acid , chloracetic acid Minor metabolites: 2-chloroethanol S,S1-ethylene bis cystein (45) c) rats route and dose unspecified Major metabolite in urine: N-acetyl-S- ( -hydroxyethyl) cysteine Secondary metabolite: S- (3-SS-hydroxyethyl) cysteine (46)* *TLm = median threshold limit SL 080901 10 V. HUMAN TOXICITY "Ethylene dichloride is toxic by inhalation, by contact with skin or mucous membranes, or by oral intake. Prolonged excessive, or repeated exposures to the product in any form are hazardous. The signs and symptoms of excessive absorption to be watched are: headache, mental confusion, depression, fatigue, loss of appetitie, nausea, vomiting cough, loss of sense of balance, and visual disturbances. There may also be diarrhea with bloody stools, suppression of urine, swelling of face, jaundice, and blood in the urine." The signs and symptoms of EDC poisoning 'bre the result of injury to the kidneys, adrenal glands, skin, lungs, and to the digestive and nervous system. The clinical picture varies with the type of exposure and the amount of the chemical product which is absorbed,, either at one or at repeated times." (54) A. Oral Patty (10) states that EDC "does present a problem from oral ingestion," as evidenced by the number of poisoning fatalities (see below). Effects include CNS depression, gastrointestinal irritation, increase in clotting time, and injury to liver, kidneys adrenals, and lungs. Should an ingestion occur, vomiting should be induced and epsom sales administered. (5.4) B. Skin a) Irritation and sensitization -- If held close to the skin EDC can cause severe irritation with moderate edema and necrosis (10). Repeated or prolonged contact "may cause a rough, red, dry skin due to extraction of fatty materials" (10). "In certain rare cases, the dermatitis may be caused by hypersensitivity to ethylene dichloride" (54,55). Should skin contact occur, remove all contaminated cloth ing, wash the area well and apply an ointment containing lanolin. (54) b) Absorption EDC can be absorbed through the skin, although "it takes quite large doses to cause serious systemic poisoning." (10) i C. Eye This chemical and its vapors can cause irritation, burning, and lachyrimation. Serious damage can occur if the substance is not removed promptly. Exposed eyes should be washed with water for 15 minutes. (10,54) SL 080902 11 D. Inhalation Symptoms of both actue and chronic vapor poisoning are irritation of the eyes, nose, and throat, headache, mental confusion, dizziness, and vomiting. EDC "has the ability to cause injury to the liver and kidney from eith excessive single or repeated exposures" (56). Borisova reports that concentrations greater than 6 mg/m3 "causa vasoconstriction, decreasing light-sensation of the eyes, and reflex changes in rate, depth, and rhythm of respir ation ii (11) In the event of overexposure to EDC, remove the subje ct immediately and do not administer adrenal in. (54) Threshold a) Single Exposures - not more than once a wee:k 7 hours 1 hour 0.1 hour 200 1 ,000 2 ,000 (56) (56) (56) b) Repeated Exposures Threshold Limit Value (ACGIH ) 50 ppm (200 mg/m3) CeiJ ir.g Value 50 ppm 100 ppm Peak Value (not more than 5 min. not more than one in 3 hours for an 8 hour day) 200 Recommended Russian Threshold `1 pp, (1) (56) (1) ppm(l) (11) c) Odor Levels 50 ppm 100 ppm 200 ppm 17.5 mg/m^ 23.2 mg/m3 barely detectable not unpleasant' pronounced, not unpleasant detected only by those with acute sense of smell average level of detection (10) (10) (10) (11) (11) The odor of EDC is sweetish and can be adaoted to at lower levels; therefore, it is "probably not sufficiently striking to be considered a significant warning of hazardous chronic exposure." (10) F. Poisoning ; Several cases of EDC poisoning have been reported in the literature. "The late appearance and non-specificity of the clinical symptoms and signs" ischaracteristic of such cases, causing one author to warn that "lack of symptoms even several hours after ingestion or inhalation should not be taken as a reassuring sign." (51) SL 080903 a) 1-1/2 year male ingestion amount unspecified Symptoms: 9 hours: no change in EEG 19 hours: pathological changes in nervous system observed 24 hours after infusion-diuresis treatment: ______ ______ normalization of EEG _________ b) 14 year male ingested 15 ml (for intoxication) Symptoms: 2 hours: headache, staggering, vomiting 6 days: died Autopsy: liver necrosis and resultant hypoglycemia, increase in clotting time, renal failure, and hypercalcemia. (51) ingestion 2 oz. Symptoms: 2 hours, 5 hours: 22 hours: nausea, faint dazed cyanosis, death (5) d) 18 year male ingested 50 g (suicide) Effects: death at 18 hours, "basically caused by generalized intravascular clotting accompanied by irreversible shock." Autopsy: "intense necrotic and hemorrhagic enteritis, widespread erosion of the intestinal mucosa and petechial bleeding subendocardially and supercardially in the kidneys and in the bladder epithelium." (52) e) Poisoning victims isomer, amount, route unspecified Autopsy: renal failure, swelling and protein dystrophy in tubular epithelium, decrease in glomerular DNA and RNA. (47) f) Worker treating grains with Granosan (70% EDC, 30% carbon tetra chloride) Effects: died with "severe lesions in liver and kidneys" (53) g) Worker Effects: inhalation levels unspecified fatal, hyperemia and edema of lungs, degenerative changes of kidney, damage to liver and adrenals. (14) h) 27 workers inhalation Effects: non-fatal, CNS depression, semiconsciousness, and hepatorenal syndrome. (57) i) Russian plane factory using EDC Effects: number of cases of illness, mostly intestinal and nervous disorders, and number of days lost due to illness were 100% greater in departments using EDC than in rest of the plant. (5r j) Russian factory inhalation (isomer unspecified) Effects: "chronic hepatitis, chronic gastritis, dystrophy of the myocardium, astenovegetative syndrome, vegetative polyneuritis, and allergy." Polyethylene polyamine had synergistic effects with EDC. (55) SL 080904 REFERENCES - 1,2-DICIILOROETHANE (ETHYLENE DICIILORIDE, EDC) / 1. The Toxic Substances List (1974). 2. Kagramanov, B. G. Azerb. Med. Zh. 49(7):65-8 (1972). In Azerbaijan ian, English Sun-nary from Chemical Abstracts (CA78 :53573m) . 3. World Health Organization Summary (1970):C--0951. 4. Smyth, H. F. et. al. Am. Ind, Hyg. Assn. J. 30(5):470-6 (1969). 5. Von Oettingen , W. F. J. Ind. Hyp , To:-:. 19 ( 3) : 3 4 9-4 3 6 ( 19 37). 6. Baganz, H. et. al. Arznaimmitta1-Forsch. 11:902-5 (1961). Summary from Chemical Abstracts (CA56:6309c). 7. The Toxic Substances List (1973). 8. SDencer, H. C. et. al. (1951). 9. MR 13-121. A.M.A. Arch. Ind. Hva. Occun. Med. 4:432-93 -- '' 10. Patty, F. A. p. 1230-4., Industrial Hygiene and Toxicoloav, Vol. II (1963), ~^ 11. Borisova, M. K. Gig. Sanit. 22 (3) : 13-19 (1957). Summary from Chemical Abstracts (CA51:12384f). 12. Savchenko, M. F. Gig. Sanit. 32 (3) : 31-5 (1967). English translation p. 349-54. 13. Sykes, J. F. andA. K. Klein J. Assoc. Offic. Agr. Chemists 40:203-6 (1957). Summaryfrom Chemical Abstracts (CA51:5320dj . 14. ''Evaluation of the Hazards to Consumers Resulting from the Use of Fumigants in the Protection of Food." FAO (1965). 15. Shubik, P. and J. L. Hartwell Survey of Compounds Which Have Been Tested for Carcinogenic Activity PHS 149 Supplement I (195 7p". 4 8. 16. Heppel, L. A. et. al. A.M.A. Arch. Opthamol. 32:391 (1944). 37. Heppel, L. A. et. al. jT~Ind. "Hyg. Tox. 28 : 113 (1946). 18. Dmietrieva, N. V. et. al. Gig. Sanit. 36 (4) :20-5 (1971). Summary from Chemical Abstracts (CA75:18022s). 19. Hofmann, H. Th'. et. al. Arch. Toxikol. 27 (3): 248-65 (1971). In German, English summary from Chemical Abstracts (CA75:61562e). 20. Shmuter, L. M. Gig. Sanit. 37(2) :36 -- 40 (1972). In Russian, English summary from Chemical Abstracts (CA76:149673y). 21. Navrotskii, V. K. et al. Tr. S'ezda Gig. Ukr. SST, 8th 1970 (Pub. 1971) 224-6. In Russian, English summary from Chemical Abstracts (CA77:71060v) 22. Tolgskaya, M. S. Gig. Sanit. 27(2):S509 (1962). In Russian, English summary from Chemical Abstracts (CA57:1223f). 23. Loscalzo, B. et. al. Lavoro umano 11:554-66 (1959). Summary from Chemical Abstracts (CA55:26234b). 24. Lioia, N. et. al. Folia. Med. 42:1238-54 (1959). Summary from Chemical Abstracts (CA54:4908f). 25. Lioia, N. et. al. Folia. Med. 42:1400-8, 1524-57 (1959). Summary from Chemical Abstracts (CA54:13433 e,f,g.h). 26. Vozovaya, M. A. Akush. Ginekol. 1973 (9) : 66-8. In Russian, English summary from Chemical Abstracts (CAS0 :34236y) . 27. Vozovaya, M. A. Akush. Ginekol 4 7(12) ;65-- 6 (1971). In Russian, English summary from Chemical Abstracts (CA77:29874p). 28. Saitanov, A. 0. et. al.- Gig. Tr. Prof. Zabol. 13(7):49-50 (1969). In Russian, English summary from Chemical Abstracts (CA71:121894u and (CA73:107695q). 29. Petrun, N. M. et. al. Farmakol. Toksikol.30(3):356-8 (1967). In Russian English summary from Chemical Abstracts (CA57 : 52291y). 30. Vcrob'eva, N. M. Vo?. Ratsion. Pitan. 1969(5):123-6. In Russian, English summary from Chemical Abstracts (CA73:65416s). SL 080905 REFERENCES - 1,2-DICHLOROETHANE (ETHYLENE DICHLORIDE, EDC) - 2 - 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. Chernukha, F. S. Farmakol. Toksikol. 1973 (8); 143-50 . In Russian, English summary from Chemical Abstracts (CA80:128950d). Natysuk, M. V. et. al. Farmakol. Toksikol. 37 (1) : 92-3 (1974). In Russinan English summary from Chemical Abstracts (CA30:128965n). Slyusar, M. P. Vonr. Gig. Tr. Prof. Zabol. Gornorudn., Khim. i Mashinostroitel. Prom. Sbornik p. 92-100 (1953). In Russian, English summary from Chemical Abstracts (CA53:5506c). Ploa, G. L. and R. E. Larson Tax. Apnl. Pharm. 7:37-44 (1965). Kozhanova, N. N. and H. N. Zoz Agrokhimiya 1966 (11) :123-4 . In Russian, English summary from Chemical Abstracts (C.--.66 : 8372x) . Sakarnis, V. Genetika 5(12) :39 -- 95 (1969). In Russian, English summary from Chemical Abstracts ' (CA72 :129677s). Sakarnis, V. Vestn, Leningrad. Univ. Biol. 1970 (1):153-6. In Russian, English summary from Chemical Abstracts (CA73:32801k). Rapoport, I. A. Doklad/. Akad. Nauk. S.S.S.R. 134:1214-17 (1960). In Russian, English summary from Chemical Abstracts (CA55:8675h). Lobacheva, L. L. Rybnoe. Khoz. 33 (7) :71-4 (1957). English summary from Chemical Abstracts (CA51:18355e), Caswell, G. H. et. al. Empire J. Exptl. Agr- 26:365-72 (1958). Summary from Chemical Abstracts (CA53 : 9 5 5 4 i) . Kagramanov, B. G. et. al. Uch. Zap. Azerb. Med. Inst. 36:30-31 (1971). English summary from Toxline" Kagramanov. B. G- Azerb. Med. Zh. 47(3):79-31 (1970). In Russian, English summary from Toxline. Vinnichenko, I. F. Tr. Kishinev. Sel'zkokhoz. Inst. 88:90-2 (1972). In Russina, English summary from Chemical Abstracts (CA79:1328). Vinnichenko, I. F. Tr. Kishinev. Sel'skokhoz. Inst. 66:182-91 (1971). In Russian, English summary from Chemical Abstracts (CA79:1304). Yllner, Sven. Acta. Pharmacol. Toxicol. 30(3-4):257-65 (1971). Summary from Chemical Abstracts (CA76:68S67n)., Alumot et. al.* Fate of Pesticides in Env., Gor. (1972), p.495-501. Kamenko, V. M. Vrach. Delo. 1973(11):72-7. In Russian, English summary from Chemical Abstracts (CA80:104584m). Pod 1 yapol' skaya, 0. P. Tr. Vses. Nauchn.-Issled. Inst. Zerna i Produktc ego Pererabotki No. 43:69-93 (1963). English summary from Chemical Abstracts (CA61:7633f). Secchi, G. C. and L. Alessio Epatologia 17 (3) :279 -- 39 (1971). In Italian, English summary from Chemical Abstracts (CA77:135890a). Hinkel, G. K. et. al. Kinderaerztl. Prax. 37(5):209-16 (1969). In German, English summary from Toxline. Yodaiken, Ralph E. et. al. Arch. Env. Health 26(5):281-4 (1973). Schoenborn, H. et. al. Klin. Wochshr. 48 (13) -.322-4 (1970). Guarino, A. and N. Lioia Folia. Med. 41:676-90 (1958). Engish summary from Chemical Abstracts (CA53:576g). Chemical Safety Data Sheet SD-18 (1947) (C-951). Voshchinina, G. I. et. al. Mater. Konf. Molodykh. Nauch. Rab. Nizhnego Taqila, Med. Sekts., 2nd, p. 18-20 (1969). In Russian, English summary from Chemical Abstracts (CA78:7459a). Torkelson, T. R. et. al. Pest Control 34(7):13-18, 42-50 (1966). Chenoweth, M. B. et. al. Ann. Rev. Pharm. 2:363-93 (1962). Kozik, I. V. Gig. Tr. Prof. Zabol. 1(1) :31 --8 (1957). In Russian, English summary from Chemical Abstracts (CA51:9974d). McKee, J. E. et. al. Water Quality Criteria 2nd ed. (1963), p.178. SL 08090S EXHIBIT 3 UPDATE OM U-X.ERATU R E _S 5 A RC H ETIIYLEME DICHLOHIDE A. Carcinogenic Potential 9 1,2-Dichloroethane was administered by gavage* 5 days a week for 73 weeks to groups of 50 male and 50 female rats and mice. Initial dosage levels for the chronic bioassay were selected on the basis of a preliminary' subchronic toxicity test. Subsequent dosage adjustments were made during the course of the chronic bioassay. The timeweighted average high and low doses were 95 and 47 mg/kg/ day, respectively for rats of both sexes. The high and low time-weighted average doses for the male mice were 195 and 97 mg/kg/day, respectively, and 299 and 149 mg/kg/day, respectively, for the female mice. .. For each species, 20 animals of each sex were placed on test as vehicle controls. These animals were gavaged with corn oil at the same times that dosed animals were gavaged with the 1,2-dichloroethane mixtures. Twenty animals of each sex were placed on test as untreated con trols for each species. These animals were not intubated. A statistically significant positive association between dosage and the incidence of squamous-cell carcinomas of the forestomach and hemangiosarcomas of the circulatory system occurred in the male rats, but not in the females. There was also a significantly increased incidence of adenocarcinomas of the mammary gland in female rats. The incidence of mammary adenocarcinomas in female mice were statistically significant. There was a statistically significant positive association between chemical administration and the combined incidences of endometrial stromal polyps and endometrail stromal sarcomas in female mice. The incidence of alveolar/bronchiolar adenomas in both male and female mice was also statistically significant. SL 080907 Under the conditions of this study, 1,2-dichlorcethane was carcinogenic to rats, causing scuamous-cell carcinomas of the forestomach, hemangiosarconas, and subcutaneous fibromas in'male rats and causing mammary adenocarcinomas in female rats. This compound was also to be carcinogenic to mice, causing mammary adenocarcinomas and endometrial tumors in female mice, and causing alveolar/bronchiolar adenomas in mice of both sexes (1). C. Maltoni in Italy is conducting an inhalation study in rats and mice under the sponsorship of MCA and seme European companies. After 100 weeks of exposure at 0, 5, 10, 50 and 150 ppm (90 animals/sex level), Maltoni has found no evidence of any exceotional tumor in rats and mice. Pathological examination and a final report are not expected for a year or more (19). Ethylene dichloride was administered intraperitoneally, 3 times a week for 8 weeks to groups of 20 mice. Three dose levels were used 20, 40 and 100 mg/kg. Twenty-four weeks after the first injection, the nice were sacrificed and their lungs examined. The pulmonary adenoma response was not significantly greater than the response of vehicle-treated control mice (20). - B. L. Van Duuren is conducting a study of the chemical structure, reactivity and carcinogenicity of nine halocarbons, one of which is ethylene dichloride. This study is sponsored by the U.S. National Science Foundation, Division of Advanced Environmental Research and Technology. The work is being done at New York University. B. Mutagenic Potential 1. Ethylene Dichloride Ethylene dichloride was a weak mutagen in the Ames test (2,3,10,13). Activation with a rat liver micro somal system did not increase its mutagenicity. It did not preferentially inhibit the growth of DNA polymerase-deficient (pol A^-) E. coli (10). f 1,2-Dichloroethane had no effect on the chromosome breaking effect and the influence on satellite association in human lymphocytes though a strong toxic effect was induced (17). -2 - SL 080908  1,2-Dichloroethane had no effect on the induction of lysis on 2. coli K39(X) (17). 2. Metabolites of Ethylene Dichloride It is metabolised in mammals to chloroacetic acid, probably though chloroethanol and chloroacetaldehvde (3,4,5). ' Chloroacetaldehyde was mutagenic in tests with Salmonella typhimurium strain TA 100 but it had only weak activity in strains TA 1535, TA 98 and TA 1538. Chloroethanol was mutagenic in strain TA 100 in the presence of rat liver microsomes but only weakly active without microsomes. There was a weak reversion of TA 1535 but not of th,_ other strains. Chloroacetic acid was not mutu.-enic in any of the strains tested (3,9). Chloroacetaldehyde showed only feeble genetic activity and chloroethanol was completely inactive in inducing forward mutations in two strains of yeast-Schizosaccharomvces pornbe and Saccharomyces cerevisiae (6). Chloroacetaldehyde was mutagenic in S. coli (7). Chloroacetaldehyde, but not chloroacetic acid, was mutagenic in Salmonealla typhimurium TA 1535, Chloro ethanol gave a weak mutagenic response only at high concentrations ($). C. Teratogenic Potential and Effects on Reproduction The reproductive activity of male and female rats was not affected when the rats were fed fumigated mash containing ethylene dichloride residue levels of 250 and 500 ppm for two years (11). This paper does not mention the presence of any tumors but it does report on the effect on growth and various biochemical parameters. Reproductive studies were carried out with leghorn chickens during the course of a two-year feeding study. They were fed fumigated mash containing ethylene chloride residue levels of 250 and 500 Dpm. The- fertility of the hens and cocks and the hatchability of the eggs were not affected (12) . 3 SL 080909 e Exposure of female rats to dichloroethane at 57 mg/m^ daily for four hours during six months and then during the whole gestation period, produced no general toxic symptoms in the females. It did produce reduced fertility, reduced pup weight at birth and increased stillbirth race. Also observed were reduced viability of the first generation offspring, and retarded gain in weight, prolonged astrous period and high perinatal mortality among the first generation females. No deviations were noted in the second generation offspring (13,14 When inhaled at 500-1000 rag/m^ four hours daily for one to ten days, it penetrated into the uteri and ovaries of non pregnant rats.- It was detected in the fetuses when inhaled at 1000 mg/m3 on days 10 through 13 or 10 through 17 of gestation. It was also found in the milk of lactating rats following one four-hour exposure (15). o Exposure to small concentrations of vapors of dichloroethane (concentration and level not specified in the abstract) had only a temporary effect on the estrous cycle of female rats. When rats were exposed to it until days 17 to 19 of gestation, there was an increase in the death rate of the embryos and a loss of embryos at preimplantation (16). REFERENCES 1". Unpublished Data, National Cancer Institute (1977). 2. Fishbein, L.; Mutat. Res. 32, 267-308 (1976). 3. McCann, J. et al; Proc-. Nat. Acad. Sci. USA 72_(8) , 319 0-93 (1975) 4. Yllner, S.; Acta Pharmacol. Toxicol. 30, 257-65 (1971). 5. Heppel, L. A. and V. T. Porterfield; J. Biol. Chem. 176, 763-69 (1948). 6. Loprieno, N. et al; Cancer Res. 36 , 253-57 (1977) . 7. Hussain, S. and S. Osterman-Golkar; Chem.-Biol. Interact. 12(3-4) 265-7 (1976).8 9 10 11 8. Rannug, V. et al; Chem.-Biol. Interact.; l_2 (3-4), 251-63 (1976). t 9. Ames, B. N. and J. McCann; IN: Screening Tests in Chemical Carcinogenesis; edited by H. Bartsch et al; IARC, No. 12, 493-504 (1976) . 10. Brem, H. et al; Cancer Res. 34_( 10) , 2576-9 (1974). 11. Alumot, E., et al; Food Cosnet. Toxicol. 14 (2), 105-10 (1976). -4 - SL 080910 REFERENCES (CONTD) 12. Alumot, E. et al; Food Cosmet. Toxicol. 14_(2), 105-10 (1975). 13. Vozovaya, M. A.; Gig. Sar.it. -(7), 25-3 (1974). (CA 82:1190 1?). 14. Vozovava, M. A.; Gia. Tr. Prof. Zabol. -(7), 20-3 (1975). (CA 83*:202446z) . " ' 15. Vozovaya, M. A. and L. K. Malyarova; Gia. Sanit. -(6), 94-6 (1975). (CA 83:109403y). 16. Vozovaya, M. A.; Gig. Sanit. -(6); 100-2 (1976>. (CA 85:73056n). 17. Kristoffersson, U.; Hereditas 78, 319 (1974). 18. Rannug, U. and C. Ramel; J. Tox. Environ. Health 2_, 1019-29 (1977). 19. Unpublished Information, C. Maltoni. 20. Theiss, J. C. et al; Cancer Res. -37, 2717-20 (1977). SL 080911 SL 080912 Respirator Cartridge Efficiency Studies: V. Effect of Solvent Vapor o. o. c.nci.son jnj a. HAiinrit f,i)n rrort tAirr**\*nr Lu1wut**rft IJirtmtitf, Cahfo/ttim W.E'ff Wr kj* i/rttritili'fA d>< lltti of arcinir vap-vv titplnlur u^ri-irH fw III *pl*rnt vapofl *i*.t (jui ltuKi<lui; jriintJlu't. tul Im, flli.ttv I'to -rt, imliMi, V. r pimfd iT<^ tap*1' ir mliturn I'-j 't'l thf r and (St di>nilrrj*rt iu iirrlr jilott ih i ICrrt dHrttur |l ll>). MonilorinK cmlnur* onul Ihr rsrtrij;r It (bntplcltlr titwfjfrJ. 'W (mii| jnj bit-lillKvMitfi (iturt U from flu a>l*:>r; 1ii`i t.-.llcrm -.ral (i;U4i>iin nl tiMinj natuii.iMr |,-i irnvr/l. lift t*Ti**lJ| (jil un ti wt crej'<r j -ily lof (lit ft> |iMr<ri,!V Alia, (lx tljS^r (It lf fiSn" point of il* t >!'uil, ('re PTe.iirr * lit* *t ! of j'letUJ. \Cnr ' *7111, ! trmriif. ddtrjtic* Iht sr.ibv if of Uiitnl ns.fH.Ilf of It* tavif *ljiil Kilitnti and thoit toluol* in vntr. Tf. tflrrl of (t:Kt*urif6i s Iko)' iWiicIi dm* wjj trrlf(l|r In*>(!' ilrd and fcutd fa roofarca l lb* luff fm Killfrb t^wjiloii. o H Inlrnducfjoil MmH rnHI<i ISTrn ni:TH in a verity nf papers verssly pinportlonjl to the flow fate. That Js, doubting the flow through the cjrirdgT* will halve the effective service life if V.1 de * concerning respirator cartridge efficiency. s The previous reports have described nur pro M gram goals,* (be luting apparatus,* develop* other teAt parameter* remain the same. The pr:tcnt mvesrigaiiun sought to dftsr- mine how the cartridge service lie varies mcrtl of a mctlmmc.il btcailiing simulator,1 with the type nf tuKent vapor a Jin: bed. V.'e o:uJ a comparison of lle cl feels of slcady- inve;:igj:ed 1*1 sofv;nt vapors and gaie* stjle amt puts a ling How.' ar.d compared observed brc.dethiough times We observed no significant difference in u.i!i the n.a;i calc-J.ilcd Iron the adiorp- cartridge s^niee life between steady-Male lion isotherm ar.d the M:clenbu?g equation. ami |>ti!raiing flow. Hoc coni mi ns to basic This report, in some respects, respresents an adrofption theory; equilibrium K'tvxrn ibe vapor ami ;n.\'KKnt shmiM be praclical'y Instantaneous.' We discarded she breathing jimulhiof, therefore, and in alt subvquonl Jesting emp1 *ycd steady-stare flow. We also observed that the amount of solvent adsorbed at a given Icmpcr-sure. humidity, and concentration is essentially constant {see Figure 1) and is independent of ilic flow rale in the range normally avo dated with human breathing. Since the equilibrium rates arc so rapid. the time to reach t predetermined brcilihrough it in* That wk N'fv<*>t4 rdr ni h.Hii W U* Ui**m twit* Ai*J( Ktrir CMMwlaA m Figure I. ComwiuMiu a^udeJ u a function of How rst*. * SL 08091 H! fstemuifl of the investigation by Freedman fl at* Our standard rest comMinrn included a lohtn* cvn.'cnlrtlum of IfhV ppm, 5C^n rc1s*i% humidity. amt 513-hitr min flow, ri|tm alenl to a nuKl-ri-iif) hr.%* ute af tV) If m/min Mir volants tcsl'd in cluded airmail, alcohol', .iclctatcs, cl ones, lelinrt. amines, anti chlorinated iri> dials Some preliminary inv r^if.itions n Jie effect of concentration (125 to 20 .M >p) were also initialed. Experimental Procedure The Jf pnratus tried to generate ard nionior the tes! concentrations is hjocaffy the .jot; as that described in refs. 2 and 4. Several minor changes appear in Pi cure 2 The humidifier now consists of a Lucife eserso.r with a If'el swirch and sotemud olve assembly lo n-iriiiam a cciisUttl water 'olurr.e A I26w;itt vpot he re- on the eservoir I'-oirum controlled by a humidity Ttonilor holds rhr humidity conttjut. A 2-inth plug of gh>M wool ,,rlJtd in Mil* oKenl sapor injcctii'ii port aids in oapor.itnj lhe solvents, especially those with hiehcr oiling points Mam'ninin" Hie block temscidtufr as dote lo the boding point 2S lossiblc esnids decomposing rbc solvent .ir.d dogging the nccjfe. The ael-otcJ cars :an dug down;:'earn further smooths vd-.-.nt vaporation irregularities. Jlity, 1974 r*t-nr* I. S*.hfmai,< diagram f dual cM/i<Fge tuildrr t iC''re t Hre.iLrhruu^S <ur'<> fuc trufiiilirt buhn% in She tvagt SO" in fJT*C. Atftffkaa fn.firiuW If *fic*i* Aiuh iaiirw ivumat The cartridges were vacuum-dried and stored in a cabinet for at least 2 day* at 50e* relative humidity nd 22'C* Two cartridges were tested .mllanetjusly in the parallel configuration ih-v.rr in Figure ! The test jus enf-ud ihroigh a 35/25 ground brass socket iom. and pissed Ihrough ihc cartridges hek! in i .'idual polyethylene adapters. A noJi red .ilun in urn luu* sings, se cured with wing nuts, collected the down* m stream gases and conduced them to the common sample outlet. Type I cartridges (sec ref. 4 for cartridge Hfuie I Urejllhrugfi cvnn for fa) Un.Mo' ujs r.rJ tJuisira* and Kwlmg in ihe nnftt 61* in IS6*C inJ T1* H I6I*C* rtifec- llvtly. Ti*e - ( figure S. Rrotltmn flu: vu fur moriKhW^n Sutifle ifl ihf ranpei t*)| -24' u* 16 *C red f&J tor ! lire I ifu/e t. in ihe 14 rc. rr tat |V (.Dryti for iKvholl bcil* to 100*C .xJ r#*| IJIL* Killing in the ran;ar 40* in IS0*C tlM - l-i(iir* f. Rtt^Libniu|li fw uiim t.'it. irg in (hr nnen (a| J1* to 104* *nd (b) M2* So ti^C. Ar**t itt* 1 r ft*i n r Tft l M4n* t 1 b en : *f,r - 11ttn C w*11j}*nr ?#!.* IA ot. 11 C MrtKiflol Alft *|fft|*| fryiRi| #e*ivtiii #1 1 A y t 1 >lvl n J I h >b2 41 j> 1 1 n 1 IP () v pre.^f* ti JO'C TrrJ lift........... <rn. ifac ** , c (/) TABLE 1 Voiuao Aa;o1 (il* ** t(4 c chorcool UJS E*prirM4t 'r**ttevth r't*t *U (*1'1 ` 169 (in) Si (tin) V 1 |M ft\* T 4atbft0 M . ial*M tdiorftW 9r wf, o* rvrboK 'loi" * * M903 'loal ,, tp* r *t M/l) (i/il M/l) M/4) - 10.1 72, < 2 10 4 71. 1 1 J4.3 7.0* 111.4 4,14 M2.* 3.3 4 144. 7 1.73 1 ?*. 7 i.: 0.0*12 <7.0*44 0.0 753 9.0470 0.0477 0.6443 0.0430 144 144 141 141 144 U7 141 59.1 37. S S3 .9 39.7 40 .0 S!4.J 34.9 73.3 14.4 1 `0 *4 .3 11 14 13.7 *4 , 7 11.2 4<,J 73.4 M3 lift 103 MS J,* 27 \ 193 133 MM 733 0.214 0.334 0.332 0.311 0.359 0.347 0. 1*4 9.244 9.377 0.3*7 0.4 7} 0 .4 J2 0.373 0.430 0.334 0.4 ft 7 0.311 9.440 0.33 0 474 0.3*4 0 033 0 071 0.072 - 44.7 *71. 12, s `14.1 43.4 37 .4 47.9 71.4 9*. 1 14.4 49, S 12. 14 7,7 S.C3 11*.* 4.24 111.7 7. 134.1 3, 117.9 |14*. 1.17 1 . SC 0.1370 0.1114 9.10(1 9.U21 9,09*1 O.CMl 0.0141 0.0771 O.C70*S l.It!1* 0.07U 0. e* jh (44 144 143 14f 144 144 143 14 7 147 111 Ml 139 S3 .4 33.3 33.7 33.4 13.7 S3.* S3.3 34,7 13.0 33.7 33.0 33.7 0.2 4.2 47,0 74.0 3.3 43.3 43.3 41.4 101 :o7 74 :<o 70.4 * .0 11 I l2 230 1*4 1 IS Ml <4.4 )1 1 233 J77 97.0 73,4 107 121 VI.1 n- M3 743 701 74.3 101 23 7 0.0093 0 . J 0 4 9.011 0.03I 0.07* 0.141 9.12* 0.132 0,14* 0.J14 0.23* o.:&: 9.14* 9.233 9.344 0.241 0.34? 0.431 9.340 9.291 0.499 0.312 0.373 o-itr 0,344 9.304 0.471 6.10 9.323 0.343 0.342 0.110 0.4ft `9.499 0.132 9.312 0.091 9.133 4.133 0.11? 4.043 0.030 O.Ol* 9.079 0.047 0.941 9.011 0.030 SL 080914 >* TALn t .Ci n.f uej) t (C'J Yper I4ri taiou*er* (Terr) 011 tu* Im e e* ( fte1*c i| JS'C Vo Il( th * rtn ( MM* fftcKt th*ree*l f ip#riif*t11 LL!i^l_LLLZ^> \\ lio\ ':! Ml I Ml fn | ft . 1*1 **"l ( t/i) 1 |5\ (I/I) 4*1 4 #4*(!( * rt I U 04 ` t'ii U(kyl Ylnrt tAlerlt* ClNr l eh teriJo 7 Ch [Arlpfap in* * Altfl cMertt* [ *CK 1 o rifnimt ;. C>* 1 * f **;. ethp lfiro)<n 1 * C* In rebut fr.* 2 Ch1e re-J eihflbulae# 1 * Ck!ereptntip t CNlef9cr<!ap*e(me CM#r*teet*ft t -Cfc ( t eh*Hof 4<Chlerotei*<i* 1 CNlefehtfisne ) 1 C N1 *f*ei h j|) N*pt tut *m i . i j. j 12 i ;s,: ** J 40 J i'>,l 77.3 SS.7 iCl l 11I i j: til ; ts; : 152.: in. i*/i j ;mo mo 153 too 2 7? 9,M0n <3 J'JIO1* J u I J1* 0,0'-S 0 03 2 9* 2*9 0.0 O.QT)7k J.OMI* 40.3 :j,t 0.0*71* 3 00 I^ o.omi ?.ti MIS 0 074 7 J .OIji" :.4 2.2 * 0 0411 0 0511* J ,9'i.^ ;i? ui Ml Ml Us 147 1*3 Ml 14Me Me t', ' Me ] S3 I1I iS .7 SS.7 54.1 Se.l it 5 33 1 0.33 3. 5.4 u.i 10 5 :i s 0.7 44 10 . 7 5) i 44,4 M. 11 4 44 . J it. 7 too ;01 ; -> i o orci s.cei o ac 0 31* 0,0)( },:n 2 , J4 0 04( o.Lia J.1S7 0.14.' 0 .an J o m: 0,194 0.- a C-.-5 J . 1 1 3 7-0 ill 57.4 ) 3:. j 31. 1 INI MS 0.1)1 o.:ti 0 Ml o.:: i CM* 7. Mi 3 7,0 St.I ,1 i)t U7 77. i 54 .1 35.1 107 V, J 55.5 i; 34 3 35.7 St .5 >1.4 :o.s 9. ,r, I or, 131 AS, 1 122 I'M !< 5 1-7 4 177 'll JOS III to: Ml 11J 0.741 0 . J to o u; 0 4 71 o.j-u 0.5 14 0.437 0 17 3.3:0 9.439 0.109 0 4 77 9.547 8.574 0 .Ml 0 M J- 0.3*1 8.Mi 0.741 0.5 J t 0.473 0.4*3 0.4 W j.C'i j. o To 0 Ml 7,C14 0 040 ; .oio 0 iIo 0 001 . O 050 . 0.0 l J 0.303 0.313 J, J12 H iit f* tnt tojutnyuf u o jtiiu ty iv u tn o f 8TA LC i (Continued) 0*1(Ht fc # t r tojwT DVrfuelen tlrflirllll .01UI4 itl'M Eipir:*inrit v* 101 t 7 1r ;rt*< ri'*?SA 11 U3\ ?*f -t. ''1Se If *t :j*c (C*) ii Jrr) t :s*c (('/'"!) Mf foil Ml] 4 c, 1 reel 1 h Mi `W (Mi <> .1 ' J1\ (A. A) `"153 1100 (c/M <1r..i ( 11 O Pi eh Jo ri M >. 6 reh * nut e *n* to.: ir>M' 1.2 0i <i< to nin l*he 1 .l-Olchlerertixn- n 36.5 ill. 1,J01<h1$ re inMtir 33. 1 1 t.M?MMervetlt?nr 1, M 01 c* leruf re|* in* 41.5 44.4 <1* .1 !***- 1 , 3.131 . 104 t,4 PI(M4rtiiy| m* <i 011 h |*rN*n it * * 142 t y.; it 4 0.10)7 24 1 0.0: s'* 111 ) ,?y to 142 17,5 0.JJO7 J 0: *4 * j.ia >.16 it. 0 To l( 0.Jiu* J . 0 6 -4 (** 147 145 M3 1M M; 145 J47 146 Ml ii. 4 10,1 is.: 3. 7 SJ.2 3 3,5 J3.a 25.5 58.3 40.1 124 225 si .3 33.5 3S.I :7,t 34 , r " 47 6 MS : J I'. Al \ 7 70 <4,7 ss.t ;?.) 13.3 11 J lftl 129 in? 132 20* 219 : 37 0.914 3,:s: 0.101 5,111 0 t: 7 J 0*2 ) it? o 1 *: 0 7M 0 )i ' 0 tli o.ou 0 116 0,714 0 ,2'M 0. it3 ft Ml j 00 0.JC' } 45! 0.0 M ft.JM u 5 3 4 3.334 ft 313 0 ft| 0 ,M 1 5,402 0 o* 3 816 0,* J7 3 *5 5 0 M 5,311 - 1r1(b|eriJr9 :M4t1ef 1 Mrihri (iiKfreta T r.eAter**r hr 1r* 1,1.7-Tr1chleie then* ),2.1 T r)<hjereprop*** A1 .2 ?4 16 5 JJ1.4 1)6 lit1. 3 1*5 31 4 17.9 :1 i.nttt e .u" U J 04"'- n , * 7 a 2 j 144 35 . '3. 2 32 4 1 71 0 |SS > 74e 3.413 0 050 HI 54.2 4(4.4 \* t til (*.;i2 0.510 0.316 1 <4.| M .3 1 >1 f'5 0.:\ ft. 4:1 0.623 8.0 11 143 SO .1 71.1 M2 :04 0.5T7 3.5*1 3.77) 8 Ml 1 1* l* 2 tl 1 l 32 221 0.441 8 * J 4 3 *13 , SL 080915 Tff fIf* tOf I < * * f f c* 1 r*tt ft f \ << J.l.l.J-Ntri. th | r Ft in TAbLC I (cufliwiyfd) VP*r 4 f .''C btffutlca It :i'c (6*/*e) V|tu*4 <**ret t t.D* k 1 |*c in'1 tip r t1mtAt 4 I b f t * ' " *'_* i l in 'IV fM*| T (6\ %4X i*I > ft. m\ i u/u V* i (hr 1 4>*l*ttb#4 4ltba4 *l ' 'ii| lict 4 (t/t) f*t\ * \i/a 7*' *t. 4 I f,tl4/H(i' m.2 9! 1 14.3 : <1 *. :i 9.01:6 0 , j 7 ? 7 j.ii':: 144 55 4 7* 1 40 0 147 0 4 7 1 0 54* 0.477 143 11.7 137 11* Jo* 3,734 3.435 5 91 u*. 55.1 10 4 lit 2 14 0 109 9 . IF 1 1.37 ffFUcf J r 1 6c * * tintjctl r**t hi,t :si 0.CL 71 Hi 54.1 > I 3 >17 1*7 0 .7 < 2 0 if l 4 1.13 * AtrtiUt^ Uithji telc i:i s?. t 173 2" H*t| 1'M.it* :i. i 3* l 11 h f l Kltitt r:. 2 a. 1 47. s *7. 3 11S(l ro? **7 ( uttiu H9ff \ 1(1 tin r,h lOt 5 J: 1 : <. j *1171 <*<* t< tlu l > 1 tV(f1 <(l(| H'J.i 111.5 122.I 4,.; 1 A4fif * iy 1 ; * t. i j. * 0.3*71 0,3".' 1 Zli 1 0,07*0 0,0 :: i ^ 0. a 1 0. n1* .1. `4*6 0 , Ju J J 144 11! ' l4S 14* \ I". 14$ Ml 145 [4* 144 IS 4 4 5 ,A 40 A 54. 57.1 *5. J it. 1 55. >5.0 54.1 12. 1 <6.5 5? 3 U 1 44.1 (4. 7 44 5 45 .0 10 4 ;;5 71, | >*. 0 75.1 ii, i II. C 101 77 4 34. ^ 7C 1 >4.5 14J. A : 55 17: |66 115 144 1 4* 164 2.1 3.3*7 0 . J4l 0 :\i 0.242 9.525 0.JI* 9.;t* 3.115 0,151 0 . 34 4 0. 151 3.214 C It) 7 5 k 0 .267 9. 3S0 0 511 0.4*5 0 4tM 9 107 a. 5*1 9.507 3.5*9 9.117 0.45* 9.537 C. 44 ] 0.5*5 0,447 9. 514 9.973 0 0C C . 09 j.ai* 9-023 9.04] 9.3:i 0.529 S/1 v a n t YipiT b* (<*.' Olffi/litn t 2 C f:-V*4d Itfliln* C*"t. ] , 5.0 1 **' h .`llttityl jt<: < `fit ( / l iitnrt IF*jy l 4<ftatt M'..: 14 5.1 ir.9 ! .'t; <*.; 10 1^ ' if- 7h ................1 7twl irfif 2 -1>ut jnmtf 3- i rnl i*r, 4.M#<y|7- ftll 6iTt* V4*<t|Tl ,`ltjf f < lv|>i`ltt 7,4* !v t .*i4 it>n* ;tf . `in,* 2 * H* 1*< #*.`f * fi, l **.' i r>>.t . J. *f. .2 :*.f jo:.5 j *:, 7 n; ?<* 4 in.*: :7,j 11". 5 1*" * l.ti'.r j irt. j Ji*. 5 7 i.; J" 6 it 7.* a,5 :. \.4 U-,;. It ('119 rt.O-CJ .> , ,t"2ll^ o.r('77h 0 .t' roo O.l'T'-O 1 0 . p 7: I'.tt;.1' r I.f.it1' TA0L ( (CuAllAlicd) v t r -1 (`it ' el'if t m l (:ih 1. *f er 1 *r r 111 4., hit* : = . ) b't, iIvm( i4ttrbf4 rf* t af c 1 rt`vn 'r. Mox- 1 1 tovi * (A/7) (f/l) m x ioa\ e ? rk < 4 ^ <2.1 40 Ml lu 164 5 A<> I<* to 2 ir.fj lf.*l 1A 7 J74 1A0 117 H K'S 51 .1 35 . 7 55.5 A0,6 j: a 67. A 7f 0 57. J H1 1** : js J02 60,* AA 9 5* .1/ 5b. 4 w. 1 it. A A t 3 "4.4 Kit Ml OS 5 1 M l J '* 211 1 75 It. I .: r.j. j 7U ,C '1.1 ( 1,0 C4.T VA . t 1 1 1 1 7 J l '* 14 1 If 1 Mil l H t t e !'. :m Ill i:a ) >4 :n 4<i* 214 5 Ml M7 : ci.j k.< V9.J 14* A , ji* P.."i 9. MS 0 4J6 0 its 0.444 1*1, 1) 4 M> 0.451 9.02$ 4.914 * i 0 .i< ;* k* t " 9. Ml 3.50S 0 3 1 3.15$ 0.221 9 m 0,33: 0.465 9. US 0 14* 0. >33 9m 9.016 0.915 t* , .*< 7 a 4-lit 0 4i'f .1 . 4t`4 (1 . \ `A * 41; 9.4 2 3 9.41* 0,11! 0.4*.'J 9.&2I (1.4(1* 9.MS 9 417 c,5.*r 0.4M 9.541 i It C 9 5*9 9,47? 0.4*5 9.4*2 0.359 9,93? 4.0C* S* ,9l 0 90S Q.OUi 9 074 * SL 080916 40Q Kifftt TABLE 1 (.Cmwmiu^) 1tKt vtitr Vl|7 blf7ulion *(fit lent Ye 1u*e k'*l(ht 7 n>e11*At 1 It. i*lt ftftkr**6 " r *1 if ' r5 0" Vc;' IP t : o c tC J1*C (T*er) (mr(4il (.!) ekifceal ()* V. (th) * :n\ (p| n| *104 (!) '.,k ( / I ) Vo/ r7ooV* fl/t) (I/I) t (l/l) C*t. OtlMkutyt 1<yc1k - It! 149,4 in. i - 0 .04491' 0.9454** 0.00,9* 162 43.S 101 123 :u 0 )'$ 0.472 0.195 147 a.4 70.4 It ,1 171 0 . S6S 0 4 7 7 0.3ti 0 305 1-3 67.9 111 126 :$ 0 til 0.120 0.510 C.JQJ 3,3-Ola#vh7' hit*** Methyl tyeitiyehtiha Cye)*kan( CytJ*iIN* 2.2,4-Ty|* thy 1 - p*tan* *ta 'tvtky 1 eye l*fv vim* 2k. 1 34.g *i.; 71 , t id. 7 IJ.3 414 0 ,9 I* l 19 1 0 0f9S 121 o.ajfi'' its f O.C'24k 77 1 o.ort ik 70.4 o a 7csh 96. 5 91.S 100.9 :< 6 IS .4 16 ,t a .osn* 0 . fl 4 16*1 a.asrt1' i6A *2.4 < 0.7 71,1 M ? o.iii 0.1 u 0.221 9.020 H'7 43.5 t: .o 41 I 1 "7 o.; i * 0 2tl 9.333 0.921 IM ii.o 52.1 hi 6 171 o.m o,:: o 9 3 3 4 9 0) H'4 64.7 f;. 2 V- , 1* 1 74 0.1*4 3 2 03 o 271 0 C 36 iM tJ , \ 61,7 :.) 179 0.216 o :it 9 3)7 0 9 24 15 ' 17.1 IS.4 (00 in g.:?: o.m 9.401 * 47. i 41 1 (to . 4 1* 6 0.360 0 .141 0.4i0 9 bit 16 0 17. 74.2 o.l III 0.209 0.319 0.412 o.o ik ICO 57.5 61.5 m .5 191 0.259 0. Jyo 0 440 0.04$ J ttlf I9?4 A tn rfk o n In d u s tria l t t y f l * 1** - f lic * la tu tn J o u rn o ! Sklvtat IHnn1 Cj*T. 1,3.5-Cytlo* homrUM 2,2,5*Tft ip;hy 1 - 5*Ifhy l |4*"* 2- Cyc leeci mi TABLE 1 {Continued) Vi{kt IP ic*> Ytyo 1 pr*i\ur4 ft 29'C crfr) SIffwJo ((l11At X 2i*C Yeh4Iurc*#*l tti (til cheti*l L i p* r i fiit i \ brut e *> r F* ll> V5 *99*. (ii" (*i"l () ni<ui*rrk*4 We, ItlMtt i<lierki4 t l *i*. e 110\ 4V^'is tcrkon* t fl'l) (i.c* (*/sl (|/t) US.5 -- - 124. 5 12.3 147. t ISO 150 174 4.2 * 1.13 P. ?i * -- -- - -- -* o.a7.''1 161 o.ossH 1C.'. 0.0444* 0 ,0k 2** a tjs"11 v.osso* 162 l ?: ift 164 63 4 44.2 47.4 70,3 43.3 57.7 137 246 47.6 to 0 K.fl 16.5 94.5 76.2 70.1 J01 113 19 .3 e l .1 221 170 i vs 15" 0.34* 0.435 0.S34 a.246 a. :is 0,4 4 4 0.341 3 >45 3,140 0.116 0.393 0.624 o :>7 0.497 0.393 0.490 0.439 o.stx 0*00* o.cci 0.007 0.027 0.017 Aaiitct ^ ltl) | ikUt It ky1aala* llfprayylaata* Pyafyliala* 0Utkyl4in# wtyl*at>* T t ( f t h y 1 *!* Olyrapy SI l tayrayjl*at n# *4.7 :i*o 4.7 1714 14.4 7? SI. S 47| 47, | 24 7 55.5 77. s II* 7$ 4,t 4k 2 110 11.2 1 10.3 0.1300* e.ia:ih a.mu11 0.0179* C.4I7** ,0A91 0.0177 0.0?$4 0 .0 44 7H 0,064 7h IM II.) 12.4 17.4 91.3 o.ms 0 020 0.041 0. ISO 1C1 70.0 17.1 71 .7 "4 e 0.03? o.oto 0.291 16| 19,1 40.5 49,7 270 0 .361 0.C41 0.179 0.241 160 40, 63,6 75.1 194 9 14? 0.162 0.27| 0.134 ): 41.S "0.9 1 H >30 o,; io 0.217 0. J >5 0.732 If 0 42.1 16. ft 105 211 0 2! 0.249 0.351 0. ICO >k2 4 S. 9 116 125 271 o.m o.m 0.429 4.011 1(11 5k. \ II . 1 1?4 0 107 0,141 0.424 0.032 176 41.2 91.0 (PS 726 0.3?t 0 . 340 0.4 It 0 P 40 171 47.0 77.0 67.1 lit 0.257 0.211 0.370 0.469 SL 080917 ' * * Aa * ft# t k Coftt. Cy e) **'# iy l *# t *t Eifcjty l iift* It CC#) Vapar it :vc 1 AH(.K UoAimucJl Mlfw lan c a# f f i e k (t c c :-*K (t*:/ic) rhirrt) i>i tea 11 7ipcf>*'' * - ! lr. 'it-. ' ( fcl 1 ( t 1 ' ! ( * 1 If. iitltenr 4 ftf r . | . t . < ft r J V.v ff/ll liy\J * lUU', (t/ll U/*) *ri |li| tier 4< 1 ; vu. . t fl*a*1 (fc/11 3 .. ) . :j4 IS* 1 .V 1 O.Ot^ u? 44 1 112 W* t"'t </. ' i: u.4 n 7.1*4 0 . I4 ( |M 4 " 14, i ; *c o 5-4S o >*: " j sg J , 9U7 ij{r l 1 i-iu U#th j l ; *4t tr Aery1*11rila 1 Py/U'in# 1 rpi <ft If ra-1 J e f in* J.Jf <*ICy 1 thlftO 1 * 1 -Siirap rapirt* ^ J -1 j h j n # 11l1 A cat i c Aft)'J r i At *2 .4 j>4 77.1 (>7t 1 91.1 U u*,: IS.4 1 i* V \: 9 IN, * * 3 Ul .s 1.4 I l l .4 Mj.S T 3 * , f. T 0 CWJ ' 5 .I9VJ p .ps:<` o p*:i,k fl t'A*t >' .1*11> ' 0,9`5 1 .1 i` " '< n ,n r*. i*1 It 0 : j : it./'. : 7.7 * r g "( 1 y , .* 3.11 r a,.:; 140 SI ,c 4 4.5 41 .1 1 *> A t.4 *s o , i; i 4 . t 'i O.QU ICO i.'.H : i:t " o . *. ti; u , r i T 1 C * 9.90* tr: t4 1 U- lit ;2 i*,'.;t g w-k 3.4*9 v.0`fc ; \f *<, <4 4 ' M ' . `* v ''* 0 , iS ' o i*f> u. o 14 Uf :s lit. M' . f' i *; 9 , t i; 4 3 49 o.g JRI 4 1 ,V 14 1 V ," 'f 1 .k"` 1,3 `>o - ltd *J,2 14'. j f 4 t:. 4> . 4 4u *. J K fci* 14A ss 7 7.1* t:; :-i g.i.'a 9 . ? 7 i y.iM 1 \t * M ,n l? n* : p. i * g p o.$*: ti.fl'i" S; o * 1 SglWM Vlfdf 1/ i :s*e C<-* A (Teri } TABLE 1 (CeeiMBed) 01 t u * l a >i ecaffli.fftt t ?<"* l tolgot fti i real l lot)* Ci<tt r > ttM 11 1S (4*) T; r'*\ *.M (4 0 Vf. ititiftt tdi* 'S*4 f ft r wf, *f (it .. ft t\\ 't/M ll3\ (i/%> 1 iua\ vc/i) o|ht wittr i4i*tltd " 'n prf t. eiftan^ (f/l) ultral1C"ft* . ;.W al Kf 1 Ktiitr1 I MMkfirnt1 144, $ 14* J.riltoD'lNyl J fe J<9 2.3 o*Jec. ` *'944l'` g atiy* liO uo ut Si.7 U.J SS .1 9 i. l i i it; j:3 ly S ; i} ?M.S u.; NS o , < i o. s -1 g :or 9 . * 3 g. ) q 1.17* }.li; 0.4SI7 * .479 fl.OlO X 3 K 3 5* 3 3 r A fat* X | a 5* 5 ac 'AUTat. nli> I4f 1 *i lap lt- Ts ;-e 1 j.-J ; j, 1 4,3 it far tt\ T)pa 2, kAvrnit MttNu fr ttrtrUct pai r ire S'. t ` 3 t i-r th* rpft 1 imJ fftlu)*<aW tfi* j. * Mt <Nl724.t l* *e. - <V 9.A (t 1 sw]/N .1 V i 3,0 i fnr tlia Typo 2, l#f, |# "Pal* rr*ctlli," eilcuiatka* < *f 'c(eultt4 ft** a * '...ii - V *Ut*4 Typa 1 ciftrU ;ti. kCl(uliU4 noa Ctllklui i ri^uit it 9,^ [0,49 r1 '111 / 11 f "''hi Aar* tt It 79,# a)/**l iitJ r * JP 11 ClUlilAtaJ t r j a ^ *i e L114* ij'prji i it . ftiV (# Art. 7], * u<* J fjp* ? eartriJ(ti. I h O ' SL 080918 tut?, 1974 to live upsliejrti ci'iiccnliJlu'ii} (or t?nh sol vent ri '.liow-n ns a (urn Inm of l"ne 11>< figures ) u tJ ihe tumpfcle ndvoiplion br.Tuiy (tom 1'iiit.tl hrcalilimi(:li in tidal t,ntinfj-c 'jhjfativn fot each nf the sohcnij and g.i.es lesled. "Fable I helpt ivmnurire ihe dal* shown hi Figv 4 through 13. Hire solvcnls me anangej by classes, and widun claves by ('oiling punt. will* the movi volatile tortipound shown fust. "flic limn to ri .u.h 1%, 10*1'^ and 9'7 "f. hrcakllmnrgh and ihe re spective weights adsorbed are shown for each solvent. This tilde shows that, within rach ilass of solvent, ihe moil vol ititc solvent bn.tls through tint. As the boiling piiuls of ihe mtvenn wilbin a class increase, however, the trend eventually reverses At ioptic poini ihe breakthrough time acitrally dftn,jtfs with riving solvent boiling j oints Thu occurt for each elm of suhritl. Table I aKo iftusUatcs bow the weight of sofvenl adsnibed varies with the sapor pres sure at well as ihe bulling point. Within each sotvcnI class Ihe weiehi adsorb'd is both an hicreaitng function id the boiling point ami a decreasing funclitm of the vipor pressutc-- the two being interrclaied Thu It show a to be the case for 1%, KKe, and 100% break ihrougli. There dala can he used, ihetcfine. to approximate ihe wlight adsorbed of an untested solvent oner its claw and boiling point or vapor prrssure are known. Table f alio gives the diffusion coefficients and the activjted carbon weights and votumes nceJrd in the theoretical calculation of Ihe breakthrough limes. Il also shows the weights of wafer adsorbed Note ihe rela tively large amount of wjler adsorbed in connection wi.h more Vola*ile solvents, espe cially (hose that are miscible with waier. Cate ufouon of A real through Times The ability to predict the cartridge break through mathematically for any volvcnt that may be encountered would be useful. Initial CJrtridje brr.it Ihrmigh cin be calculated from |ff-r..H-irr * r, " AttlC " U) svherc ft = inmml cnstr idge breakthrough time tmin). y y- * molar volume at the sysicin icmpcnlure rnd pressure <24 t (ilcis/mulc at JtJ'C, 7611 loir). ur *= weight nf snburi adsorb*. J per gram or aclivinied carbon (gin/pm). Wt ** weight of activated carbon (Em). / Af * molecular weight oT the con- timinant (grn/mole). ^ Q B oh Tow rate (liters/min) / C * t pvt ream gas concentration f ppm). All the terms can be measured or calcuhiled escept w. The weight of solvent ad sorbed is extremely ihtficull to predict, since it is a complex furiclion of ihe nature of Ihe .vfnrbenl and solvent v.-por. Therofote, equation I is useful imlv if the weight is determined expennienudiy. Ldimniio is of the hrcaVthroirvh lirnc t m be cafcuUlcd, however, from llic adsorption isolherm and the McrUenbu'g equation Tlu- adsorption iudficrm for miiroporou* achorbents yields the maximum weiglu of scdvcfii eJ.orlx^d at lotnl iiibon saturation and can be calcuUird by w, - plY.txp j (I) where M-, * equilibrium static adsorptive c*pjiiiy per unit weight carbon (gru/gm). p n density of solvent (gm/cm1). IFi ** tot-|| volume of adsorption space (cmVgni), 8 ** micropoiosily constant for the carbon. T = temperature <"K). * aUiriity coefficient or solvent va,por fur the activated carbon. MtHeikttn tt'ifffff dtu*citHHin JnUfttnl (t, -- salttraled VBpor picwure (tore) fsn Ilk vot'cul .il k lojx r.iturc p = sa(|udibiinm pulnl pressure of tbc Solveni vapm (toirt, This jdsoTption isolherm holds for any micTopomiit adsorb m ami is valid only it temperatures bvloj. liic crilual lempciature of the vapor. I he H and II terms arc Interrclacd ond dspend - il, >r ltie riiuic of the udvoilknt lire uflniily im Ifiocnt fl chirauen.es ihe adsoipuon of a given vapor wilh rcjpcut to nmiil.tr vapor sikucd .is a 4111 slimfnrd Gem-rally hcnrcnc is chtisen, its ft becomes 1 tX) liy difimtion Ilk* affmiiy coefhcicfil is independent of Ihe tirnperatjre and practically mdepindcnt id the porosity. Ihe fl term can lx delcrniined expertmenially or approximated by p P V e* P*Af V* "" v. M,/i O) where r, v, molar volume for Ihe un known nod standard solvent (cm/molc). r, r. " pimlion for the unknown TAtn r. it C ir M i Iff fhirsurciiiit iihI T(il Cwdil'O'n UvJ fi ir Ciliuljiini VVi ij lit Sol vent & ifv* r heJ. from At]-orpiion luuherm Cjrrntlff type Pjf . n, e, 12 Uins .1 tti sm/i.i.'l tin mi .i u .it]-, i r 111' n ip itf, 1^. (tm'/jml fV| rtt <*f puroul), fl ltoifttMint. I (lKl Attirtii|r cvf ftHurni S-Oii* JlrU vspiir |<irtvurr, p, Itorr) St'liml vjfwif p-TissTf 0 '(r.ri rpm.f llitrrj OtS OH 1 0 x to* 051 x I0` 795 391 SteTsHerlVand V See Table I o :* o rt q ii>l.uneJ 11|h i inkni.all) fo.p.i ciphi iiiiJ votunif mr iMimiKKU- 7 MUX Ml ' C~Bvrs11il] < C^r;lrfnlici *nd T(l CiHiJilvMl UW fur l*icihfitnu||h lime Of:u1irnnv' fri>m Mrcllinhurf EqiP aiiun CrrirhJse type f.piaWrr 12 WetfM .-.f mtvri't j'hmivJ |*, per wrifltl of kr|io!t<1 urM (;ni/rrn f C Jilmn tnooy. pr k in/rmSj Cr. o ^eilmnjl ^rr j >>f cjibtm. A (rn-'l hjnil o tif Virtriilfrt Iflfll. fl 1 Imw i n. Q r lii<fi/rmn \ 1. ilt rn.it '.tiftiiLt. km`/(ml Dr m.t'tr id f< mi 'c. J Itm) Viv.- ttly if sir *q.>r itft.m, tfr?i/cm-t> Den illy i >| ,i*r - * i|h >r si k ji rn. fttt Cf me im 1] llrejtlhrtiiirh ctmcr nk.iUim. t\ Ippml Intel n>nstnn.iium. Ct Ippml Miilt^1-if '*tq-hl. At (fiH( mold VuiJ v* lunie. t', tern'/rn'l Carouse '`Itfo-r. 1* t<m*) DdfuiH>r| focifmcal il 25PC. O Itm-'/itc) See Table 1 o.m yj i i ij.3 *5 0 IM 1 HWJCM u x ia to tOtiO % 0.43 TO St* Table f 0 1|9 }9t 1 J1 3 77 OUT 1 lix to-* IJ x lO TO toco a 0 II w *A1 ij*t mil ''j0 IJO. HH'l.itntJ ffion ihe vj Cfirmittrv iii.J ^Ariiri. SL 080919 0?60 4CJ July, 1974 anti s'.aulwd solvent {c.d-n(at* f from Sudden's linn). P, P, ** iy'vrnt density for ihe uuIno-kn a.itj stand ird solvent (ji'u/cmM Kt, Kt, ** m< .cctd.u wcirhlv for ihe un known j<nl vt.mdmd f gu/mole). VI the pararrelen needed to solve ihe adsorption isotherm are given in fables I through V. Comparison of the tetujl ei- peim entjl v.ifucs of iv, are also shown In T iil'fes IV nun V Nok ihnl tjtc more volahl1.' iujiciuIv vku1 the yivaic'it deviation /tom ihc caJeul.ileii sjftirs This is Out* pri marily to ifie preferential stFscupiiiMi 0/ ilie v.alir vj|>of present. In theory, ihc .iJsorption iso: bet m described by equation 2 is viili.1 oolj lor a single sapor in air; tl ik1 ("let Is coinpMing ads^rrdon by water or any other \a;sjrs Cven by expanding the ad'orpton isolhcrtn to include muhiplc va por sjileus, it is stdl ditficult to prettier to i*hal Client highly polar materials such as TAIIf r. IV C<)ni(>tiiii<n flf Cjlculiff il .mil f :rvtd AJtmpison Copacily rf I y(x ) l jitridcct l^r `,o:nl ^rhtnix1 A.Nuipt(*( CjJtitlj i.- S.'litnl A ff<riy O^ttKicrl, h< Tnlurn( | lent fteth mjT F ilmol Pfi'(>j-inl n OitJ^ul m Tt `jmliI AS <- r h V1 <KtoftJt t Lhpt clitattdi 1 Chi turmrji't 1 Ctd(>rkfl'ul*ji< CSVn Its.'fiir ISn hloi < r rlijn< . f.? tJi III- liwtfijnf 1 4 DkM'HnhuUnf ir-Du liliXuknitnr p 1 Uj* 1 )* r H' 0 41J1* 0l> 6lb t*4 1 OJ* 1 U0w 0 H1* 10*1' u> 1 11* 0 f r," 0 VU' 1 21' 1 JM ONriw i ti, * 'trt 1 0 04JJ 0 M6 0011 tll^l 00 1X4 sir 0 M2 OOOS 0< II n rv6 0 191 0 M.J 0 101 0 4S6 0 MS 0 *M C jh ul jlrd pi limn ] fci`/r-nl US 0 JUJ 0 140 0 04* 0731 04)9 0 49] OUl 0016 0 119 0 J53 0 476 0'69 0 M4 0 ! 55 o?;o 0151 EX'viution from Ol tfnrd f'M + IS * ?2 4- 0.7 4167 4 49 4 12 - 35 - 49 4 100 4 149 4 49 4 90 4 19 4 114 4 2> - 46 - 66 Oitofobircn 0 16' 1,1 1-rr>hl>>njcftianc r.0' 1 1C Kw l< r 1. Ii inJ r PW briMoilh|t(at 1 JI' A1rih)1 jctljif l rht- t jkft tt U 1 10' mrijir r in'1 0 41 J 0 7JJ 0 677 r 0! 0 :u U Mo u 't'7 051* 0172 0 690 0 965 0 in 0442 0 515 4 JJ 4 6.5 4 19 - as 4 5* 4 26 4 1: It >l htl Sc 1`tnlj i r(alt 1141S.1-1' U SP4 0616 h Mfl 0M7 - 19 - 6i Ijif c^'jitit'i mm |i jtlljl prftMllf. p, tl IOOO ppm it 0 76 Unr. 1h< oin* nifd vi/xif f rrtturr. f>4 ii laltn Ffitm t jfe'e I *E iprrtmriHj| tjlixi nl) Imm itt 4 from pjnclion u*in( J<b`* *qualinn. ^Ctk ulntd from nguilnkii J utinj iriulir vnlunui. Co < o co Antrtkttn /fiJntniii/ A\U'CUuU'*t ftttttttftl walcr will interfere with ifie normal nJsorplion provewes cf nr|Mui<; vapors Cur* renify there is cm vali .butory method of correction Jo: this inlcrfercnce.* * As was ptvnoTv niemiumd. n-, iv ihe weight adsoiKif ii 1, ot s.iluraliou--lfi.tr is, at |fH)i/i brc.iklhrot: h Imir.d brrj'klhr'nqdt, however, occurs long bcfo.e t lie equilibrium adeurptive capacity k established NrvcrtJic* fess. such breakthrough times c-.n be esti mated from the Mecklenburg ct,unlron once H'( has been deteinvncd The Mecklenburg equal ion slates that 401 and pt * carbon density fgm/cm1). A * crovs-sec:innai area of ihc adsor bent bed (cm7). V " carbon volume (cm'), n > number sif eaitrnl c\ Is'slsiil. C# u assault cuiptemrsimn (ym/lilcr). i * lcd depth (cm). a< sjvcibe surface area ftm'/Cfn)A * Jijmelcr of gunule fern). O " mass sclucuy ihrjugh cartridge (gm/cm-sctl. n vbcosity of the air-fas lirrarn (gm/cm-sccj. 1> where C _ MCt "24 1 r , KKK^.t yv>p, u 60.4m t - ViA V,n * 0.967 D*, p. = denviiy of j*r vapcTf tire.im fgm/tm4J f) *- diffmitm CfHrffrcrcnt fcni'/vjc). Cv = brciLihrough concentration (ppm J. Ct assault concent ration (ppmf. V, *= void volume (emVfrn). Hquauon f is gertcrafly useful only for Ct/Ci < 0 2--that is, for breakthroughs TAIItF V Cvnipjflwi^ i C*feutjttd 4-ut OlierveJ Sdopp'ion C'^p .tnv t,f Tfrc 2 CaiM(ln* for Sr<rjl Adiif|)iivt or-ii,,r- C*K-l.i fed f)<vui[nn Solvent Autt r 2 flu* i> i>nc 2-1 V'li 2 Ilf i i*m nc Alfinf'jr Cor trivicnl. p 0 t.w1.19* 1 47* Ohvfivtd lrih/|;mi| 0 1 15 0 ;/* <1 Jit 0 S-4J Irorit Equ >iHin 2 fjrM/priip V 2)6 9 160 04)7 049) fforu Otnfrvfd (M 7> 4 22 -11 >12 fv-iime lit one Ifff I.T*f Nr (tlMf Dei. jut 1 0" 1 1 46h 1 *5' )05J 0 2 7* 0 vu 0411 n-ro 0 55) V 22J 0.519 0 5TJ UM4 0441 - 41 )} >1) >11 >20 Mclhj 1 J*niof tlOpkn-ice III 1)1 HI- If Uihuivl 'nine ot;*1 IJ 9|*l t n*1 i 25 1 0041 0 179 0429 0 JH0 0*.l 0 166 0 171 . 0 166 4 49 > 7) --14 - 2.9 *\li. tiiiti'itl'-ktim pjitijt fimurt. j tUUO ppm > t)?b luff, Ihc **>- fiml k.'jvf fnvwiir, f', *vl.L(n litwn fuhlr I. ''I t*ccinur*!-> Vdli*c (jttn fttKit tel 4 *(' 1I0-: lit ii livni J iiu'n i.uilar olum(t 'H-^KvUlcJ Iron) pataehtMt usihe Sujjdtni cqualitin. [ JUN ihjn 2Hrr 11k* pUi'k-U'd and -x.tu.il bml.lhrruirh Imio a t* mum pare. I in Tahir VI .met V M. In grntfjl, IN' predated tunes .nr siimeSj| nti*f t'f'l'Mmiif ilijn i!h< _ d. terminal expx:iinimf-il'j ll>>j jg.iin inn hr op'ained by staler > tcnik'iuy lo iv. cuosr llic aviilylOiajunp:^ "i i*Tri Tables VI and VII show conclusively that appr^T,ir;a> lucikrhrrugh Umrs can imled be i jiry'jtcd. hut only if the 3c1e vi.i-lccl ur ban is v.f!l tbaiat i cured Appftutm.i:t )y Iwmiy-fivr variable^ unm be kno*n, how ever, before luch calculations can be inui- htU. tvr4 HlrJ. (here have been .Etlrrnpix **. Amplify Ik'se calrul.iiuirs by relating she lic.ikrln ouj^h lime or wc.ght adsorbed ibrcrlly to a Mnrlc properly of llic snlvcm such -is lioit* ng molecular weight, vapor presrare. or diffusion oh Hu inn. IficsC inerstTuplific.ilionv gcnrrafly fail. houoei, since so many interrelated sari.,He* play a role ui ad? or pi ton. t.ffrct of Cvncentft:iutn , In a prduturury inveslig.ilion we varied liit concentration, from 125 lo 1000 ppm for T*f1U VI ConipJMOMi vf Ti rj* red and .* .iimI 1'J- !Ue.tMhrooh _____ Titiri. 1 yr< f f.,rl.i C a' .li'fij If'i'i Meet It r bur $ I q-ij'i t M >Tfri-|1 T mf MtlWKll (mm) Uv,,( I'vcMmmlal Ads.-i I'fJ (mtn> U>mf { ilciiljiril Wrifhl Ad^oil'nl from 6Ji(>ipiiun liuilirrm fmiqf Orn/rrte T ulvruf "Vjlfnf Mrih jncf I'lhannl h-I'i jnnl n Jl i.l mol i I'rnijriol 7J 1 94 J 9J 7 0J 2# P 7|> 4 11 J to: 74 | 19 i H0 10.1 67 6 IIS i:n J0J W6 95 S $> 6 79 t tor 129 fl6 94 I Mrtliil i,l>!o'ii!r 1 rr>>1 (lilonJ 1 t Wo rffopinc 1 CMofohnrf nt Dt; lih wMin hmr 1.2 Oichftifo^iKtnt 1.4 DkMaioNunt i-IK'hlnuihrntcnt CMorufortn 1.1.2 TrHMoofikne o nj ss 74 J n} lor 106 U0 101 rov n? 7i a 10 III 41 0 70 4 n Jl 6 ar i 96 4 99 6 61 0 91 7 39 .11 6 64 | 27 1 99 7 *(- J 99 a 91 9 91 0 76 1 to* C*bon IcIvacMiMide bit Wor rvili) Fuk 77 n IflJ 7! a fP4 77 ) 99 J Mlh>i KtliU j: s JIT 90 J Fihtl ivtiiit (vb J 69 1 If 3 -f Propjl aemte 7 % 119 14 9 iV-Uulyt acrlic 77 1 III 77 (J rr Ptnijl crlair 72 ft 74 J 69 1 leu ccHidiiiom: J) 1 til tn: mm. SJ1 * rblive humiJjiv, and lO'C CaftfVjt eharvcifii'iici .*rt tu.umtrited In TaMci 11 arnt rrc America* ftnlitHr>ui ftytirnf dtjorbi/Mir Journal TAtll K vn Con i' rdon of 1`rcJivied anj Aim it 1*!- lire jIthrow;h Tmir'., Type 3 C.srirMJ,ri C jlcuf ttrtl front t- l(.lltr.rur| 1 qouio* M-*trr jl 7 M> t * V tmffd tn-r.-) Um t.liin| L^'i Mai* J Eipuini(niil WeieM Wei, hi Ailiorlul frurn Ail'in lird AdiuijMicn hoiliffm fimnl fmin) 2 hill .n*r* 2 IVn1 .ri-nf J-Hr fijronr J" t PI 9 to-* in i 5 J fN t U7 116 103 12) 1JI 102 n I'cnf me fi 1 It ij'if r rir^llf A ! .oil me n 1 )i. me r.O 7 52 J 79 1 76 3 'll 77 6 91 7 J01 19 4 90 \ 76 6 89 3 17 1 79 2 7? 7 Mt'b^l in'ine flht lir< r N llii'jt. '""if IS > ImiiIi jmm- 13 4 40 3 lb) 75 s 3) 6 99 3 143 96 9 300 92.1 123 84 4 t r'.l iufli!iiifirn 5 1 % Me rif mill. JO'-- feljiive l'>hmiJir|r, and 20*C. Catirulrr ch,rji.itn'.'>ci ft tummjrirrd in TiMu II and lit. 407 benzene and from 50 lo IfHMJ ppm for ace tone, and mensural the effect on *crvi;e life. The characteristic $ *!'j" J hr ik- through times for these solvenis appear in figures M and 15 AIsIiote-Ji ihc time lo rc^eh a given brent lb rough inert isrx ns the coiKcntr;t:ion dicmrislicv, ihi bi e a Vl Enough limc -ccncenlraiion relationship is ,,ot in verse')' proprriioml ;r. one might imuitivcly suspict. Mowcwr, a lep.iriilmnc plot of the break ifuough lime (*or example, tl KKJ- ) as a function of if j < uicenlj.il ion yields the Imrar Tc1ahor*bip shown in figure 16 The resultant enipiiual conations lor the straight lines are: 1 fia i-'miH * M x in* x c,- for benrenc l.i x in1 v Cp_r>4C lor acetone where fitr-t-i Is the hm* in mmuies to achieve a IOTj breakthrough, and O is the upstream assault eon cniralion in parls per million. These resubs conform to i'u basic Freundlich equation sad have been demon strated previously by Traust nnd Hermann * figure |l. llrfali.XiU(H cur-n for I,r* I ear* rriilgrs. tl fii<nn iinxr rtjlirn* of Nnnt T h carlfi<l|t p*ir containcJ i I) (m of actittrtd (jrton and wti Ic'lrd l a How ralt of j? .1 liint/mtn and JOT rr1liv humidiiy rurunrpre tte have vaammed the service lives of organic vapor respirator caririJfcs exposed to arornaiict, alcohols, act tales, alkanes, ke tones, amines, and chlorinated mate rats. We assaulted the cartridges under standard ized cond'lions and monitored ihc dounsircum concent rut ion to cartridge tatursifm. The standard lest conditions included a sol- SL 080921 'I <'0 Fifvr* tj Ilifilltifm^h for t>(y 3 cur- a* ivtmui wnmlnioni *u. inf. E ai h Larmrffe |>>ir ci'oijinr.t 3.? i m of i-n- tj fJ fnhn J ai IfttfJ )| * IIixjv rat? .( 5).l I.ier/m!n anil 50' rclame KunmUy. I'lfure U. 'The I0~ brf jlllomiyh Pmc M (uiKliui ul clK(!uiiim tor IfiUfAt jhJ MtMnr venl concentration of 1000 ppm, .M)1?*- rclalive huniidiiy. and 3 tk'w of 53 3 litcrs/min. Measured breakihrough timet Agreed reasonably with calculated values obi lined front the ad tor prion isotherm ami Mt-eU coburg equation, In gcnrijd. ihc sKDvjied car tuh. IW bon luis a greater affinity lor the Its* volatile msilniuls The rel.iiivr humidity grcally influence* (lie amount of solvent vapor adsorbed, sig nificantly decreasing the activated c nbon't afHnily lor solnhlc rr wjKr-solubtc solvent*. A brief investigation droned that rbc ef fect or toi.icntrjiimi break (brcu^ti time conforms lo the basic I'reundlich equation flffrrcnro J. Ruck r.. Q Q Kthoft, f. 1.. Imtlrlrn, R F l''lirifn. *nJ tJ I. Hcsf|;k*ii. Rfipiu- tor C-**tr>.t|- VITicirncy StuWv 3, tlAprik farniJ IX'.S", irttr /,,J tfyf All J. iS: Il>s IHJJI. 1. Ncl.un.tr II, spj l) M Rf\pif,iti,r C-iMiiiift rff.cir.ic> Smdio H lr<rjf uf le<t AM.cipVfM Amtr t*iJ. ft if Ast. t. J* MO llJ3' 3. Nfl'nn G O. R E lolinien, C". I- .tnd R. T) 'Tjjl.iif: Rr furiilor Cp1mJ;c Effi ciency Tau.Kei Iff \ *1r;Ill'll<1 llrtalhinr Mictiirr tf ^imirlile Human Rri pi ration. A'rr. tut tilt Ait t. /J 7*5 f|0|J> 4. NcU,*n. f? (1, and r, A FtjrJcr Kt.piraior Cariridj-f Mtuicncy ViiJi't' JV. KHnli td Stcrpjv Sl.Ue ipj Pli'oiirf ] |w At'ter, f</ ur .< / II m II J 3 Smivl. M . ipit S ,(Vin>' At fti-r C IIJ ID 1 Kc**t, New Voit (10701 6. firciImpT R W, U I. EtfScr, imj A j p. M. llapMr'ri Secskf livti r>f Hrifimlur t jr- In.'iri t'ce^m Several Ctauci of Oipiik Va pors A*xr* .W ft> t An. / I* 5HI'7.> 1. Ferry. 3 ft trdp t Urmtcet I r*?< erit' Hunt- b> pp*. trd ed pp. <)t JJ9. McGiau IWI, New Fork 11 '>?(. 1. Waller, I*. I, fed.); Chrmitlry amt fftytirt of Cart*, pp, 115-116. Dcliler. New York ttutj. t. Traml. C. L, and fl Jt. Hermann: The Ad* ioip:ion of AliphtliC Acelale Vapijra onlo Ac(pv.plr<1 Cail'on, Aftrr. tnj. II*f, Att. J, JO.' d'jr llcr J Short Course The annual J7/r>rf Cvurxr in / itmiontrnlals of ftuimtriaf ffygienr will be presentetl at the Kciiering LaNitatofy, Univrr^ily of Cincinnati, from October 14-27, T97J. The ccu^e, half lecture-half bborainry, v.ill be conducted by the gradmie bcufty of the Dcpiiiment of rnvironmentil 1le,i>lh The ila** svill be limited to 20 partiopmts, on^l the course fee i* kuOO. Tor infotmaii-Mi ccntz^l Ho^iriJ Ayer, Kettering Laboratory, 3273 Kdcn Avenue, Cim.innait. Ohio 45219. (513) H72-5708. OnT'illor Analysis of Quarlz in Rcs[>iral>lc Co;il Dust by Infrared Absorption and X-ltuy Diffraction UOIHJU W. nu TOMAN. SAM Z. TOMA. anJ HTI.TN W. LANG Ali/nirf tttul Xnfrty ftrtfottk Onirr. Rutratt t>( ^finrt. 1/ brfo'f'ppf'if tif h'tfr iat, /*prirhrpfi, /Viirri i tiatm An IcJrrrrrt tprefrenncftle and an Indi pcudml X-ety ififfrtrllcrn mdW nr dr>f(- cpfd tor Mir in*t)tK nf --*fi i.i* Up airborne Tt'ptrjl-'r coat rlitt. S(n0`l*l') If imb tlms tW I'rorolum tan he iim I Cor tnilplt of Ihr from t fi>'ch nrmhruoc fitter -mi-* 'i ai K milt lor pif^>n .1 fjPN|lm by ()r* stfiiTn^ I `tfinrtintTif and Sjt.fj Achnlrii.iralion (lit "i l) In il* r .l'iroiiinit pfiijniri. Scui:bili fnva r Km fhjii 10 h otil.io. iTd*. Iftr nutbi'J, are r<r.i<u>jMy pneisc -Hti [iiuil ? mrrkt lul'nrn rtem. Hair mritr tk) K loitirtil b) I lie laiut iilibil.ry of Irae p.tnrfi \iKad ui( tn hul't vr<r,<' 1 4 vl t triudttitf ulf visont. jt'y (mu ih* inllt.liun Fillrr <9 a (Pi-jit area cf j n ni.f Itlkr wlibh Is HUlUdy tr.lr rrrd-lf an-parr nf nhl Hi * *ti^k X-nf .................... I, lilts i pibuJil * luhlaiillil litonu In m cn urnrrjli an<l allcmJjNl i nutHffy. Itolh Mii-ihod*. In prlndptt, arc capable of uc< "lib wide tar trip1 of tol*d nulrrlalf- Infroilueliori rpHL ANALYSTS OH RTSHRADLE DUS t'i fv of im|Hwt.ii:cc to jndtittinl lijgieiihls bccju.e or ihc tcndciuy of this foim of dust 1q produce vjruuii types of puhm* nicy diicsM'1 mi< h iu siluk'ds or coal work er** pneomovcmr-si* (ctimnirpr'ly known as blJcV lung disc. >c). On^1*? ai'd other r:-:c sihea pufymorjT'i ire of pari:;ul.ir iulcrcil because of their tnsicilyd At MSA, coaf mi.ie tlutt sjrr.rV? arc *pot-cHccVcd for quarti. t nccnlfai',. :i us'mg a Durenu-developed infrared HaficJ-r pc Mel procedure v\lmh rerjtnns the cnnilnning of several sstmpfes to prt>v*de id'ipr.iic sensi tivity. Thiv method is dmc-consnmirvg and high indmdual cspr'^urcs to qu, rli tan be overlooked due tn composite sampling A procedure with sufficient semilivfty to pro vide for the analysis of 100 fig or test of quart* collected on a single membrane filter was south). A rapid procedure is required, since it is .anticipated rhat over 100 sample* per day wall lie j.ufj/ed. MdiilH ( (aflwnrroal pivdiMi Juti M aw1! miM bp llrf Hi,rri* *r M'"i Other mcthcxls available did nol appear adeqtf.ile. Wet chon lent prm edu re* such u ihc weft-known l^lvilic Me.bod employing phosplioiic acid, diffrrenli.il tficrmal matysit, optical rniermtopy, and p.-imp a pine anily- % are iraccurate, irtsenviln. and lime coiivuinirig.1 * As K common with many solids, it i* diflicull M diirrmirc quartr acuirabfy by mofccuTar spcclroscnpy for physical rjihif than chemical reason* This and the diffi culty of obtaining reproducible sianilards will be explained subsequently. Infrared and X-r.iy diffiaction appear in be the best tech niques available.'* Ihc samples are pel letItetl m ft rclaliveSy inert matrix malcri.tl such as pol.isiium hrrmirlc for infrared or starch for X-r>y diffraction. The concept of using the collection filler Itself * t matrix is not new. The use of silver membrane fillers was investigated by Leroux and Powers.' Samples col lee led on silver membrane fiber', were analysed for quarti u>ing X-ray diffracliun. This tech nique was subsequently tried by Ouimtcd* and by Knight er of.* Knight noted that Ihc 411 SL 080922 * , .** ^ if "jj** \ , ` * ^ ***,* ** . ';, ' ^ ?, /7, * * -1 / //'**.; v. ^^' `'v 41/ w^-t -c^- .< : v:1- ^ f+r^' : - ', * - --f.,- "*-1--^* T'i;^ -','v--[ f--,.--i, r ~-; --r/i -n--:',r.i.B-p:i,^-ifiitfa` iia?n;''''*';.!'-''s' -'j *>.>j-*-fc"'-frcir;trjvfn^%^<^ntivrfc --Vijjin; Pv - r- *'.j# * * i,, ' v%^ _ * ;' , ; { <5-. --i" * -,w*' m , *. `11 ,:-4 ,rr * ., >kiri<,u jj" , , _* ':t" '**.*:T_*iY/-v,,* ''* EXHIBIT D Tht thevry of solvent vapor adsorption on activated carbon is reviewed. Calculated and experimental cartridge service hie values are compared usin^ various breathing rates, relative humidities, concentrations and solvent vapors. Cartridge service life (the 10% breakthrough time) can be estimated from the empencal expression: t irl = 2.4 X 10S wc (a + b!)/C MQ Carbon weight (w.), relative solvent volatility (a, b and !) conce::tration (C), molecular weight ('A) and breathing rate (Q) all play a vital role in cartridge performance predictions. Respirator cartridge efficiency studies: - ViJ3. summary and conclusions* i GARY 0. NELSON nnd A. NICHOLAS CORREIA livvri'nsc Livermore Laboratory, University of California, Livermore, Cali/orma S4SS0 i -t' * ' t *v.*.'. .;r -.t vn I>V^k>'wjT 'r,^'Wi"-!vS4r/*r *'?* 4- * w- \'/*`"*1 .***' *4 f ,,^ *v* r-rvs. *yAt r4>? C*-:"*rK*'**r1f- * --'**'*>''*-"Jy.* * * .' 5 ' *"- * '* ^ ; ; * `#m * ?V~~<V"-V.v.\; ' ^Xwf* C.`.` ,, * ' ' T"t"_' T " ' - : *- ;*-? - s i'*'-'" - #* -' * k '- .' - "-- t'~V""vf 't>1 '">f*.y ; i ',\zt-:*'.,<**, '_ V- ` w /.< 4 < - i ['rf.'ffc 1, .* ** ' *-'** *" * ^ -i ^ ^-*-v ,l',7 '- ' >' A'} ,'V^s . ,, : . * ^r* ,/*( ,!.. `y.-* *4V- - ^ V^k'f * - * . . ^ p k I1 * ." 1 Introduction Many user; feel that if cartridges arc stai.ijnd The amount of experimental cartria "PERMISSIBLE CARTRIDGE FOR. OR service life data is sparse. There have bes GANIC VAPORS," their effectiveness is guar hov.-cvcr, a great number of reports generated in anteed against all organic vapors. The prevail the literature concerning activated ca'b' :i which ing rule of thumb indicates that a cartridge can is die prime adsorbing ingredient in organic be used until the contaminant vapor is de vapor respirator cartridges. However, the prob tected inside the mask. However, this may lem exists in selectively extracting die relevant prove a burden for those persons with a mod data and applying it in a simplHied SariiFiu to erately developed sense of smell or for those the field industrial hygiene problems related to contaminants which have a high odor tlnesh- r.sniratory protection. old, but a relatively low threshold limit value. Even individuals with the most acutely developed olfactory senses would experience great difficulty detecting 10 ppm carbon tetracliU)ridc, I ppm vinyl chloride or 0.1 ppm acrolein. Clearly, there is a eompelhug need to know the limitations and duration of cartridge effective ness if maximum icspiratory protection is to lie achieved. The purpose of this report is to summarize our 5-year respirator cartridge study.1,7 V.'a v,:!' (1) describe activated carbon, the primary car tridge ingredient, and the vapor cnirapmcnt process; (2) show how fundanvant.il ntRoipiiou theory is used to predict service life and e.na; role each variable plays; (.'>) test the them die d models with experimental data and show where discrepancies exist; and (4) icducc die theo retical complexities end propose a relatively Tin*i wik win perfi"nctl untlcr (tic .Vrnii't f U S- Ktfl*3fvS iX, \inJvf et'n- t4k't N. \V-74m5 -*4. simplified empirical expression which will pu>vidc valid estimations of respirator cartridge Nf>nCn--(hi< cpo(( Mat prHf.irtd as au acdi>n< ot \rmV- peiformance. >(kn^*Wfd hy (h* l**'UCl SMIM Co** frtnienf Nrtlhff ilt nor (h Cmtvtf t`iu*fp)` Itc .-,iuh /. t'ltscl- These icsults and ctpintions can not only fMH'At of {Nrlr tottfr t any warMrtty, Sth<f 3n)f t>( jlinr fftif*' >cC, nor -tty r? ilu'w' rnt|*l.`>4`i s, nt tkc*, "f itjv!ivJ. ot itiy lie used to evaluate cartridge service liro chart aetcristics, but can also be applied to any proc Ky f`'r thf acitiMi,/, comp'-tf nf't pr um o( .viy tt- KirntjtJAn, .tpptr.utu puttiu-t tf prtn.r^t *1. J, ffptvH'Mfi ttu( ll\ u* wJuU Ri't infntipt piltAftfjy jsvuvkl n'v'I'U. ess using higlj-gr.isle activated carbon as the ndsoiliitig. media. This includes charcoal sain- 'T* flml *! ivtfc<V, *** pjy* *^0 , , 514 S> SL 080923 nndgs been, tied in which rgame yroblevant ion to ;ted to ! pnrize v.` will ry ccrpm-nt irption 1 '.'.hz; retinal wure thso- ioVtfly ?! Pr' pridge >t only ; mar- ' ?,`OC- a> the -.im- on TABLE 1 Manufacturing Specifications of Organic Vapor Half-Mask Respirator Cartridges.* MANUFACTUaSH ATtfFfCJrt GAltC,1l C<3, MCGSL NO. ft 51 TOTAL CAfttlO`1 WEIGHT, r wf fb 74 3o`:ch and Uomo Ci?r.tjj{* Cjn-gjl Co, Qr^J^'C '/.ioor cn A02I, Cfl 2021 50 30 Mi.^c S*fty Applinc* Co, 44135 459315 76363** 52 63 St 5961 74 Scott Avfaiion eooov 502 OV,# 30 as SV-l-h MjrtufjchJi'tng Co. 7500 1 69 V/d.'sart R 21 37 42-. :r. :A usi :>n f'.Vg'L'.t tf b L*i cirtfuJj;*. *-5<.i;lr-c;:-.r'e;; resp-.f-vor CTCcpt wnere- oNu* *11* indicated, CAftnON DENSITY, 0.43 0 43 <j 43 0.33 0 <0 0,43 0.43 0 40 0 46 0.14 o.'..; CAPB3N (IASS P?t.*a;um PtroUum P*ti'Ol*rum Coconut_ Coconut Various Pvtrol^viri Pf'troN-jm f'ntroltum potroi^um P?frcl*nm pling tubes, iuli face mask canisters, as well a> large bed industrial processes. Experimental Respirator cartridges The typical organic vapor half-mask respirator cartridge is a plastic or metal case which con tains from 25-40 g of adsorbing media. Cur rently the only material used is activated car bon. Sometimes the carbon is impregnated with metallic salts to enhance its acid gas adsorption characteristics. However, the only material that takes an active pan in the sorption process is the highly porous carbon. Activated carbon can be manufactured from literal!) any material which contains car bon in its elemental or chemically bound form. Seaweed, coffee grounds, coal, and peach pits have been used, but currently all of the carbon tts-J in the rv-pi'atory protective field origi nates from a coconut shell or petroleum base. Tiic coconut variety is the more traditional material, but die petroleum base material is enjoying an upswing in popularity and is cur rently used largely for economic reasons. Tlieve two types are shown in the electron micro graphs in Figure l. The size generally varies from S to 20 mesh with an average parriclc diameter of appro vimately 0.5 to 1 mm. 'I he coconut base is more angular while the petro leum base is mo, e nearly spherical. Both types exhibit the highly developed microporous sur face required for maximum adsorption. The MSA (Model 44135--coconut base)* and the AO (Model R-5I--petroleum base) P.cfwtfn^e A cor-pAny or product parr* djei not imp'v auprov.il or r*jo^n.\idALon of cite product by th* Ufliventf* of Cilif/rniA cr : '* U.5. Eftsrvy Heiorch A l*vdopm?ftt Admov .m'/.c-i tn us <cluMon of other* that may be suitable Figure l - Electron micrographs ot coconut and pe troleum bass activated carbon granules. iff.-. ,* I--, *'!. H/'J'*"* 4i ,;r. if'"" 515 i i ifcv. " ' V, ;. -afySi ! L ;**-* .- 7 ?>**** 4 i -v'ftSSi -. . t * "Wv,. I - ,17V'V 1 .-WA*; ! W& i "-L'-au"- SL 080924 Flj.-s isniritisn I i i i FX`Jr'-` Schematic at the appvipjs used to pro duce t.nn-rm corirsn'/otions ol so.mn; vapor in hu midified r. 2'iS 3'A ;oo ')?'! ;t;-<? -ajn Ffflyr-.' ^-Czrr.pzri'cri nt U'ir.tiy st,rd? ai.tf pu/sa!ing do// verst!/ rft.v? i Th$ sl-p/jc*? [if* /s ;n* do.v jnd trtd*p*n'jqr,? of llo.v L/nt;zrrmty. wort: c!i m fur testing because they were rep resentative < f the commsrei dly ;u.ulablc car tridge types !see Table I). Their complete speci fications are outlined in Table I of Reference 6 Breathing simulator It was originally thought that pulsating rather than a steady-state flow would yield a more accurate estimate of cartridge performance. Thus we constructed the mechanical breathing simnlat. shown in Reference I. Such a device produces work rates of 0, 2Ui, 4p5t 622, 830, and 1107 kg-m/min with a corresponding min ute volume (average flow) of U.0, 20.6, 29.S, 36.7, 53.3, and 71.4 liters/min respectively. The breathing simulator proved useful during the early stages of our testing program, but it later was discontinued and only steady flow techniques were utilized. Preparation of test atmospheres Figure 2 shows the apparatus for producing test concentrations. Laboratory compressed air passes over a water reservoir. A heater in the reservoir, activated by a humidity controller, automatically maintains any preset relative hu midity. The humidified airflow is set and meas ured with a mass flowmeter. The solvent is in jected with a pulseless microflow pump through a heated needle where it is vaporized. The gas mixture then passes through the cartridges to be tested. Two flame ionization detectors con tinuously monitor both the upstream and down stream concentrations. This system is described m great detad it: Keference 2, and modificatains ..re e'vcn in .".eterences 4-6. Cartridge preconditioning and testing Cartridges were firs; vacuum dried at for at least 24 horns at I ICTC to determine the dry weight of the activated carbon. They were then preconditioned in a humidity cabinet for pe riods up to one week to a constant weight and the amount of water uptake was noted. Early in the testing program, cartridges were tested individually to determine if there were any laree differences in performance at a given set of conditions. However, little differ ence wjs noted, and wc began testing car tridge pairs. Ail the data shown in this report are based on results using a two-cartridge sys tem. Base testing conditions were 1000 ppm solvent vapor, 53.3 liters/min, 22C and a 50C3 precorulitroning anti test relative humidi ty, However, we departed from these values, depending on the specific variable of interest, Thu time to reach lOTr breakthrough sigp ded the end of effective cartridge service life. Testing, however, was continued until they were completely spent and total saturation was achieved. The weight of ad-orbed solvent va por and m.iistcre was determined by the tech nique outlined in Reference 4. Results Effect of flowrate Cartridge were tested from 14 to 71.4 liters/ 516 Sotfr'S* vj;$ i > ii i i SL 080925 tSmm IZ- !S i ; = iZ~ ii-y^ !3J - 12: ,, C4r:sn tP.ncM: _1 Z 100- 20 - - SO ,-- 20 _ 40 20 ao Test fnl I re 2. 1iJ i >_/ -- ". ICO Figure 6 -The service I Is as ? function of noth stores end use humic1 :y /. \'jA cartridge; at 10Cu ;i3m 1-chuf.% humidity, ftie service lift e/p-'n-roes a s gr 'icj.it rlduat.an. 30 10 20 Te'ot rit'jn- - *C 40 Figure 7Calculated cartridge rn-'o-irianco as 0 function of temperature. Bmif t eron m t.^es a;" dimmis ad between 1-10/, wth a ir' iC'C r.je in temperature. Chloroform *#th> chloroform Trtchloroethylene- Z 40 - 1.1,2-Trtchtoroettun* fr>'.::cF^V: .**.* *'* .* m 1 ,2.3-Trtchloro* pro;.f 40 30 120 150 Tic? -- -.in 220 Figure 3-Service life Curves for the trichlarmatad hydrocarbon family showing the breakthrough per centage as a function at fme. The service time cannot be directly related to a single solvent prop erty but is a complex /unction of the vapor, carbon type and ambient conditions. r.W,, V/////y/'a /jr f '/////// / / ' / Gr-iinule / Figure 9-The adsorption pmoess f/tnlaculss diffuse into the carbon granule, aro attracted by vender V/aals forces, and then are condensed in the micropores. Pi 518 % TA3LE III u,,c rewtive HUMIDITY 1000dhsakthrough time mul riPtiSR ar rT,l sro'u".* i ilAHVE HUMIOI fv . :*. r/.'i 0 70 50 65 80 200 50 65 w 90 0 94 \.02 o0.o0a7 0 37 0 *U 0 *5 1.02 0 94 003 0.91 0 35 0 00 11..0050 0 94 0.59 0.83 0 07 001,00044* 0 63 0 73 01.0o1s 0 *5 0.H4 00 672/ Hie djia ha -* btffa normalized fo 30*75, t;s and slur.*.;* 50 0 05 i CO 0 77 0.56 00.5406 Ss;:*ntw, n't Effect of reia The wa:;.a prufound Figure 5, to ative humic {?.) the eiiac vapor cor.cj urn or stop humidity ai Figure 6 sht bined infiue humidity do above 65/o Union is mi ty correction These data ermceniratio and use hur reference co: Effect of term The only tor between 20been done, i ing undiituc. and calculati 7 shows the several solve Such calculat times are dim 10C rise in Effect of sotvWe have me vent vapors cohols, alka nated mater through cup trichlorinntC'. In gengreater afr'in I Iowaver, cu the cartridge por property plex funcrlo: carbon, and tions. This i< lion on calcand tlteorctlc Effect of cartr Cartridge so amount of c: Afn*ftCJrt kw*u4i>'i4J f SL 080926 It "4 t if f it Jry ' hen pc- and v-s-here it a (fir- vtlf:50ft sVs- ppIT, id i r.idi- lues, rrest. '- ?=' : life. they l MS t vateeh- lirs/ s` i 'r ii. V V- th?Tt J , v- Fi^ura 4-The ears i* hie as a function of con.sn- tru'.nn. Test enn--; : am include 2 of 53,3 l.tcrc/mm at iQJ/j rulutive hurrmhiy. Decreasing the concentration ty a factor o` 10 genera.',`y m- fh* service .'..`a four to five times min with both a 'steady-stats and polluting flow the biv'if' ; M'-'i.'.lator. Tvokal r!t-> j!. sing the iCi:: bictd.thrv. jk tune fur soi.enta i Ian.`ion .v: tlowrats are shown in Figuii 3. No sigmfiec;.'. service lire difference was observed between the two flow types at 1000 ppm. Tilts conforms to adsorption theory which. pred.ts tlut the amount of solvent ad sorbed on a given ictivated carbon is independ ent, of flowrate and depends only on concentra tion, temperature, humidity and solvent type. The breakthrough time, therefore, is governed only by the aw-'ge flow rather than the uni formity of flow, IJ.ised on these results, testing with the breathing simulator was discontinued, and all subsequent testing was done with the steady-state mode. Figure 3 al-o shows that the breakthrough time is inversely proportional to flowrate. Thus, halving the finwtnw will essentially double the service life if the other conditions remain the same. We have observed no violations of this law during normal breathing conditions (see Table II). However, for extremely thin cm bon beds or for flows greater than 200 litcrs/min (far outside the realm of human respiration) some deviation may occur. Effect of concentration F.xarnples of the effects of concentration Oil cattridge performance arr shown in Figure 4 The time to any given breakthrough percent ([..) conformed to the expression ti, = a.C 1 (1) fui'ur* 5 -Th? vf.-.'.ce Me as a fy-.lan of use hu midity Vitimr vo.-.ur content cinrtc not aopreciobly .if, : corf-'j-; p'-'s.v ro.at.vr n-i ' sty, 0- -- ''.* *'- on-fj at ,;ft% .v v.h' re C is die challenge concentration and a. ;u:d h, arc constants for a riven set of experi mental conditions. In other words, the service life is inver.cly proportional Ui the log of the concentrate a. The average value for b at 10% breakthrough was --0.07 for a concentration range of i(j-`'0D() ppm. Thus if the service time is known at one vapor concentration, the serv ice life at other cuneentrations can be appro.cirntittd by t, = t,,' (O'. C)-'3 (2) where t./ is the known time at a concentration C' and C is new concentration at which the time t,, is d - . d In generJ if the concentration is dimin ished by a factor of 10, the service time will m. reuse by a .'actor of 4 or !). "I Ins is consistent with adsorp on theory which predicts that less solvent is adsorbed at lower concentrations. TA31E II Br*-utNna Rjta as a Function of Work Rats AVERAGE DREATrliNG won* fJ.srL tirn .'nir-ri WORK PAT" 01SATHINC RATC :kg m/mimi <uters/.ui> Li.`Nt Moil SiMf*.`*y H.v,.yy hiv/ 0 203 415 62^ 820 110/ U 21 30 37 55 75 I :tfy'!*i,|l ,'Cl SL 080927 517 7TT ' " 'V?*,'* : :4i'- ``Si;** *? *,r^ _-- -r'm "y'W .1->pvv+ '* -r )j3E I1 -_ . ' 4S-- siVRO i 1, ef-zm 1 '-b OS 3 r.rras ora 10*C r`Sti in lodes diffuse d by V3ndar in tbs micro- im Effect of relsti/e humidity The water vapor content of the ambient air has a profound effect on cartridge performance. Figure 5, for example, shows: (I) that high rel ative humidities do pres., the sets ice life, and (2) the effect is more pronounced as the solven' vapor concentration aim,inches. The equilibri um or storage conditions as well as the use humidity also govern cartridge ettectivensss. Figure 6 shows a typical example of the com bined influence of both effects. Increasing the humidity depresses the service life, especially above 65% humidity. Below 50% the contri bution is minimal. Breakthrough time humidi ty- correction factors are given in Table Ilf. These data were obtained from solvent vapor concentrations of IOQij ppm. The 50To storage and use humidity is arbitrarily defined as the reference condition. Effect of temperature The only temperature used for our testing was between 20-25'C. Much previous work has been done, however, at other temperatures us ing undiluted solvent vapors, and the results and calculations are well documented.3 Figuie 7 shows tile calculated 10% breakthrough for several solvents as a function of temperature. Such calculations indicate that the breakthrough times arc diminished between f-10% with cadi 10C rise in temperature. Effect of solvent-vapor We have measured the service life for 131 sol vent vapors and gases including aromatics, al cohols. alkanes, ketones, amines and chlori nated materials. An example of the break through curves is shown in Figure S for the trichlorinated hydrocarbons. In general, the activated carbon has a greater affinity for the less volatile materials. However, currently no method exists to relate the cartridge service life to a single solvent sa por property. The breakthrough time is a com plex function of the solvent vapor, activated carbon, and the prevailing experimental condi tions. This is explained more fully in the sec tion on calculations where both experimental and theoretical va!";s are given. Effect of cartridge size and configuration Cartridge service life depends directly on the amount of carbon available. Tf one doubles the size of the adsorption bed, the service time will also be doubled. Cartridge configuration or shape plays no role in performance exceed in exceptionally thin beds. One ; loblem which may inhibit perform ance is eh" 'tiding caused by an incompletely filled cartel ge. This would be rer-e, however, for we have never observed a single example of channeling in the 2COO cartridges we hate tested. Commercial filling mri cartridge case scaling techniques minimize loose carbon pack ing by allowing the case cover to exert a slight spring tension on the carbon fill. Calculation-, Introductory theory A Isorptiou theory has ch./tced significantly over the pan 50 ycais, `I h : I n'gr.ar and Bc.T ccpj.itions have yielded to the Dubinin and Pi 1 iayi / I.orption i'`a'"m- crgi-'t-q'-s has-'d on potent!::! theory* *, is ; ill net suffi ciently developed to cope with complex mix tures of solvent vi-pors, or to correct for the presence of water vapor. The following discus sion will, however, help clarify fundamental theory and give the reader a better understand ing of the wav organic vap. ir respirator car tridges function. The adsorption process for a single car bon granule is shown in a cross section in Figure 9. Here the tiir-vapoi mixture is shown (lowing aeioss the granule. As the vapor dif fuses into the pores, it migrates to the carbon surface and condenses in the pores. The pores continue tn fill until some maximum value is achieved, depending on prevailing conditions. A high degree of pore filling is noted at high couccntr.'.!, r.s of relatively nonvolatile solvent vapors. An .i, cmhlage of adsorbing carbon gran ules produces the situation shown in Figure 10. Here the concentration at any point in the bed is shown as a function of bad depth, and Lhe shading on the cartridge offers a visual indica tion of the relative amount of solvent adsorbed. The assault or challenge concentration is indi cated as C(, and the curve generated is gen erally termed the adsorption wave. Figure 10(a) shows the cartridge adsorbing el! the vapor in the firsc layers of the cartridge. Figure 10(b) shows the first layers com pletely saturated, and the intermediate layers partially saturated. Initial breakthrough is just Arn-ncort i.Hytrr.ji i-.ncut'Qn JOU-VM. 519 SL 080928 * !i4 At I .4 & m .-gs ".38 ;,sr it 43 -rJsorpcfcn niV-i Li'lC,r -- The terms W, and B are interrelated, and can be determined experimentally for each car bon type by the technique outlined in Refer ence 6. Typical value; are 0.6 and i.2 x I0_s respectively. The affinity coefficient fi charac terizes the absorption of a given vapor with respect to benzene (tor which p ~ l by defini tion). The /3 term can cither be determined by experiment or approximated by ,,_ where M . 0.0113M M oil p /> , end Jspth -- 'j) <bi (O Figure 20-C.vtr!'!,;** loading patterns and migration o/ tbe adsorption v/ovs through tne Carbon as o lunetio" ol tim? beginning on the downstream carcriilds surface. Figure 10(d) shows tin: cartridge almost com pletely saturated at 50-i breakthrough. The breakthrough curve, which shows' tlie effluent cartridge concentration as a function of time, is actually a mirror image of the shape of the adsorption wave. p, ii-iu = solvent densiiy for the unknown and standard solvent (p/cm3), M, M tfii -- molecular weights for the un known and standard solvent) %! mole) The term w, is the weight atLurbed at total saturation--that is, at lOOfo breakthrough, ftiitcil breakthrough, however, occurs long be fore the equilibrium adsorptive capacity is established. Nevertheless, such breakthrough times can be estimated from the Mecklenburg or the modified Wheeler equation. The Mecklenburg equation The Mecklenburg equation states that r '*]tb w,n,Ail l. ( <1G \ 0H! V \ ST QC j.Z awP,- \ 7 ] \ /'sD j n (Cb/C, <*> The adsorption isotherm To ascertain the service life, one must first calculate the amount of solvent vapor present at cartridge saturation. This can be done using the adsorption isotherm which states that maxi mum weight of solvent adsorbed can be caktlated from jw, = P\V, exp j --Jjp-llog (p,/p)l- (J) where w, equilibrium static adsorptive capacity per unit weight carbon fy/g). P -- density of solvent (g-'env). \V,, * total volume of adsorption space (vmVg). B = tnicruporusity constant for the car bon, T -- temperature (fO, /J = affinity coefticivnt of sulvcnt v.ipor for the activated carbon p, = saturated vapor pressure (kl'a) for th: solvent at temperature T. and p = equilibrium partial pressure of the solvent vapor (klki). where and C MC, " 2-1,2 :< 10* ' O = l0(jn as QV,f>. bOAn z = V/A. th = breakthrough time (min) Pe = carbon density (g/cm3). A = cross-sectional area of the adsorb ent bed (cmJ). V = carbon volume (cm*), n = number of cartridges tested, C,, = assault eoncentraricm (g/liter), 7. = bed depth (cm), a,. = specific surface area (enr/g), d - diameter ot granule (cm), G = mass velocity through cartridge (g/em-'Scc). y = viscosity of the air-gas stream (g/ cm-sec). u, - density of air-vapor stream fg/cm3), D = diffusion cnet ficicnt (cm:'see), C,, 11 breakthrough concentration (ppm), C( = assault concentration (ppm), V, = void volume (cmVg), Q = flowrate (liters/min). 520 SL 080929 SOLVENT B*nx*n* Strtiinef Toiun* IlODTOpi^Ci* Butanol* Pjrtanc-l* Vift*l c.h!;nh'sf Ethyl ehlanda* 1-Chl0ro&ut.im Chlorobtnzeo* Oichloromtthai ^Oichli CMorofi W*trty( Tfichlorojthyl* CfOort utrpcK aciut. Einyl ittiatet Propyl acutv.v Butyl ct35* Actt'J**' Actoof 2-0uUnon** * OiUObgfy) K*tr C/elaht* * Haptan#** * Ethyl* OiethyUmino* Oip^OPyl min^ MBA c-mrid tAO **AO eirtn.l tfUso humic; or .uu.'i carii i i Ra'erj.: x L<J t,1 charac- v;pjr !th V. llilllli- :r "i i U> 1. unkr.o'.vn 3 -'t**.1). Ilur the un- olvint) 3/ Jed at total 5.1k through. )r:> lung be- icity is w.ikth rough Je'd.L-nburg l 3 L (5) n) thts adsorb- iv'.'d, itv-r). Lra* g). !f1 jfc e.irtrij"'.* 1 stream (3/ Jani (g'urrr), r.-. sou), v.ion (ppm), span. `-""Irf 1V3 TAOLEIV C?.--p-,r',oi> cf fjp^nmsntat and Calculated 10*^ Oreakthrpuah at P?-C IP", 8f'iAKTH9UuCH Tl'.1 rciwV;?*r 3n;r* V*tHarsl* lioprnpa.iol* PB sjrnj'i3'-o..'i** Virtyi C* Ofti*' E!*'fl .-i' ' '* I CMjr=b.:-oe' Cntorabtnt^n j* OicHlorp^;fiar** oOif ''croi******' ChfafO^rm" Mathvt ehlu/ofvm* TrlCh^P^Ol?1^yl*n*, Carbon Porehfor'otwy 1* Mrihyl ,ici[3ti* Ethyl a?n,C*r Propyl Butyt ac-tat** ACoton^r Aeton*' 2-9utanon*#* Oiljobutyl K.fa-,.** Pntan*44 Cy;lwfc**ir*44 Mythylam*i*44 Ethylaminn* * Diothyljrmn** DtproD/lamtn#** CONCEN. tratio.n FRLAC7 .V C (?PVI m Mi:*) US soo 2000 1930 ice: 1CC0 1COO 1000 1000 12C05CCCOO0 11C07000 2s5o0 iroo 1 -. ' ::.o l1oCcCo0 ic:o =00 0000 IM0 1000 2SQ 2000 1000 . 1000 1000 1000 1000 ICO 1000 jcao 11C0OCOO 1000 1000 510C00 1COO 11C0C000 1000 1ioCo-7o0 1000 150000 2000 1000 toco 1000 toco ion 11C20O50O00 1000 2000 icoo 5 3.3 5523..30 53,3 2355536033..33573 52,3 f5.33..33 455033,33 4430 S555233i.-..3333 5533.-33 5533.33 s5a3..3a 53.3 S55333...333 53.3 5533.,33 - 555333*..333 53.3 5533..33 5533..33 555333.333 1 555333...333 55553333...3333 S55233.333 555333...333 5555J313.,3333 52.3 CA LCULA.TE3 rtsr RELATIVE ;MECKLE.'iauas WHEELER HUMIDITY (;m tQ. (.IVQI1.4) 555000 2500 5a0o 4111456909V 3 m114 32 n 55550000 :.-> 121 173B r 5s0o. 17550 l 5500 19373 2 S5O0 332..5; SO 2300 9500 50 555000 21.5 S3 68*91 93 D 132 30.3 1236129,.19 S5O0 50 251 15016.3 2500 55*J00Q H822 44 31782362.4 50 73 0 926500 50 5500 115 115 US 511001405 5500 19601.4 2900 90 5500 60 S5Q0 50 605 955000 5f 0Q 5500 50 19993146*,.444 97,4 64866 2 14577745777.,.1666 12*. IU4S9.1 11979 9 1521.77 41165136 4 no 110 31n27o24 111166142316047 9 3 9566 23 31 4 681 773.226 1286/2 2a.c 13109.7 246496256 107773999,.11l 123 35831.8 111 ;u 411m18C504464 9900 83 9900.88 132 6398173.,2n 14577723555...4404 110242 9466.,1/ no 49 a 31.9 SO 141 i ;o EQUUA6T1ION (Mt.N) 3/7 is5o9.4 112276/r 21lj4l325 rr 98 7 -O.S J7 5 11309 / --i2S:*2J3363.5641 7733,.35ft 04/i.9orr 4147..57 124 15419.9 736279...624 f f ns.a 71e3ff 71.-1128 718933.,.91' rf r r 7627..42rr 41198709707.1 n98o49..n03 trtr 101 m6i/5 41245047 0 666d..77tf tf 495406..946ft 1751973..41 71 0 44.7 no t AO t.wn(j:t. reusis'Jsi b-.,e. ta s f/pur. AO c lnnC,:., cscsauc bin, 01 Z t/pur. f tU'ie h'trniCJJr fbtrsitiOri from Table (It cxp*.at- ME.-n (M!M 315354 4L 9 101 2111610381147^.1 1263.2 1451-1.7 17270.0 5222.75 8luY3/ 8679,03 131 30.0 13127.3 25027.4 56 1 88C34S.,099 11462366.0 45.9 88.4 9608..44 53 0 2A*i 96.7 66.3 6541..5i 5934..14 83 3 71.3 565 143 7367..79 c86a24..03i 17.9 33 6 ro.s 105 Aie*nc2o i`7jAfrni Myt r * Ayiojij'.oe jOtiatuf. 521 ??>*''If **>in;;; I-*ab-a";7f ,-a., 1 ,w Ii^rrr'f . --rr> . . , ft,..1, .vSfjjJ SL 080930 *r i |<;2* ! i' ^ .i /< ,r'T L >- . 4. f: r%. .% r .--eazg| , J ,5Sg }; *r<: ? '4fS ;a uac : 'S3 * a -v*S 11 (/ -'afjjL r - * 53 -jt j'- -.$^S3 =* *.7oft.*. ** > .1 1 Wit t- >^4 :m across the particle (cm/min), nod we is the ''eight of the carbon (gj. "gore II shous a cumpar'son of curves ca'cul.v.u fr*1 r:t the Wheeler ur.n Mc^o'enburg equations with actual data tor toluene. Both calculated curves haxe approximate!; t.t_- tame shape as the experimental curve between 0 and 40(7- breakthrough, but are disple. .! by vary ing degrees from the actual data. C.nmparison of actual and theoretical service lif t values for 109I- breakthrough at 22C are sh- xn ia Table IV, Fivura 11 -Comparison of calcuftied and experi mental Prewm'-purje carves for tp'we. Tests .`/am martial I "Z ; p,uc, Z,'/, le'stivo h , c . -- ty sc i j,..: litem/mm. i.ii i0 ;'..e.itttnreugtt pcc-r from Eq. (In) is alto stinwn. T/ie saloirlated curves closely ape; nmata the shape and mosmtudj of the expiring,csl data from 0-40% fire-ifuftrough. The terms- A, V. n, z, a,, d and V, are all constants for a given cartridge type, M, D, y and pt arc constants pertaining to tiic solvent vapor and air mixtures, and Q, CB, C,, Ci arid G are variables, depending on the prevailing ambient conditions. Further explanation and exantp'ex of the constants and v.ui.ibles 'arc worked out in detail in References 5 and 6. Use of the Mecklenburg equation, although surprisingly accurate (see Table IV for com parisons with experimental values), is hindered because of its complexity and the general un availability of many of the experimental con stants. Development of a simple empirical estimate cariiulge service life hon to The equations shown in the prcc:...ug section arc ba-cd on tiic best available adsorption th.'nry, and ..re indeed great aid la predict ing cartridge Serv.es drawbars: th !'. differ ence hef cut the actual .md the;r -tiiu! i;r-.'ice Itie ts ''g.uiieant, evp.toni'iy v.hen using r-elatt.ety volatile materials; and (2) such expres sions are complicated and require knowledge of the ambient conditions as well a* the physi cal properties of the solvent vapor and acti vated .Mrbon. It would be of <onxidernble benefit, therefore, if e -elativdy simple expres sion could be develop. , .h;ch would be of use to the field industrial hygienist uv wall as other safety personnel in the industrial community. W I a throuer.,.,: (ire) atration (p: C Vfiix^r^ Wv enclosure lar weight through a breathing amount of m a time t w wucrc w :s sorbent - as where wll( adsorbed a through th solvent co is represer Figure 12.is shown at c The Wheeler equation The modified Wheeler equation represents a major simplification in the breakthrough time calculation.1,M') It can be expressed as t CoQ [ Wa moo-xQ On C,/C,,) where and C,, " M Ci/24.2 X to" K. -- I h i V,v- J V- - U4(l0t'0Q/n.\)l/t d-VJ. Here fc. is the ad-orption rate cunxtant (min-1), v, represents the superficial velocity Figure 12 - Percent bre.ikthroupa (rote of solvent vapor adsorbed) as a function of ume. Typically only 2V. of the solvent vapor oenntratad the cartridge a{ 10 breakthrough. 522 1075 I Figure 10-v ppm as a fu/ Chlorinated . ,"**1c ffx SL 080931 irp-~--.--,i.i-m u., l- [IIS k cur'-Ci V.-.'ibure L- n^tii Lhc same 0 .md ;b*. -ary- hr.'.Hbon jinisi for pn Tabic I i j section IS: ditfer3 -.ernes Jv; rvla- t vxprcsJowr;dge Je phvsi- 5! ^i- ;r;~,i~--ui, j e\rresJe uf use as other huuitv. ` ja/venr y/zicaUy tt'"d hi Consider a closed environment containing a vapor which is distributed homogeneously throughout its volume. At room temperature (22,C) and pressure (100 kPa). the concen tration ( ppm) can be represented by r _ 2-;: x icd w, "" MV (7) where w\ is tile weight of vapor (g), V is the enclosure volume (liteis) ar.d Nt is the molecu lar weight. If this concentration is drawn through a cartridge of weight w,; (g) 'at a breathing rate of Q (liters min), the resultant amount of vapor which contacts the adsorbent in a time t (min) is w CMQ; 24.2 X t0H we (8) where w is the weight of vapor per weight ad sorbent g/g). The term w can also be expressed as W - \V,j +- v.g O') where w.n is the amount of vapor actually adsorbed and w;. is the amoum which passes through the cart.idge wiadjorbed. Let us arbitrarily define the practical serv ice life of the cartridge aj t,,,4, the time reepuir^d to achieve lCKi breakthrough. The amount of solvent coming in contact with adsorbent w is represented by the cross-hatched area in Figure 12. The amount actually adsorbed, w,,,i, is.shown as the white cross-hatch-.d area while the vapor which penetrates the cartridge, w,,, is the grey cross-hatched area. Assuming w,, is small enough to neglect, Eqs. (S) and (P) can be comhined and rearranged to. Figure IJ-V/eighf solvent vapor adzorbad at 1CQO ppm PI a function of norma/ boiling point for monochlaematad hydrocarbons. TA3LS V Solvent Class CoeHieienta SOILING ?0!N 7 soever ty?e wancvscci COC-eelC; 6?its A3 AceMtu* AJVan Arrin4* ^onachland*** DthioF>uf TftcnlaFHjii Ti`--ici-4-- S*t :o to too feO 'O ibsj so u :oo 80 toil) -is to ::3 to t3 23J -33 tT ZiJ 40 :3 ::j Cj ta . zo 73 ZVJ -0.C30 -0 \t> 0 035 0 It 0 037 0 031 0 032 -o c:: *o o;o c \0 o.cooa 0.0071 0.C322 0.0024 O.C033 0.0*023 o o::3 0,034 3 0.C055 0.C5 n .dd rlure 11rr, -- 24.2 X IQ1-1 w, w,d CMQ (10) All the parameters of Ecj. (10) are known evt- cept w.,a which is a com'; :x function of the solvent physical properties as well as the con centration. Wj.i can be calculated for 1000 ppm (termed w"*! or the we-ght adsorbed at the reference concentration) fr >m tits data in Reference 5 rkng experimental breakthrough lim.es delermnei! bs, Pie 1!) .'lasses of solvent vapors. wai, must in ime manner be re lated to some cndly determined property so that w5aJ for ui'testcu vapors can be estimated knowing only a single physical property. Several propeities were considered. Among them were molecular volume, density, vapor pressure, boiling point, critical tempera ture, magnetic susceptibility, "and molecular weight, Tlie normal boiling point was chosen because of its general availability and good correlation ns an increasing function of the solvent weight adsorbed. An example of w'\,,i as a function of normal boiling point is shown in Figure 13 for munochlorides. The best straight line has been determined using a first-degree fit. This was done for each of the ten classes of compounds, and the coefficients are shown in Table V. Therefore, knowing the solvent vapor class and the boiling point, the weight adsorbed at 10% breakthrough at lCbO ppm can be calcu lated from waj = a + ht (U) where a (intercept) and b (slope) are the co efficients from Table V and : is the boiling point in degrees Celsius. As previously mentioned, w0*^ is depend ent on concentration but not affected by flow rate of minor temperature fluctuations. As the concentration decreases, the relative amount A:na,icJl Ir.leUtiil Hl; jOIIS'IAL 523 1 -2?--4V/ 3p! 70W; `I .-..irb.wj-.cdisr-* i ! 'ZJ& i jagssS *W iS&ij * -a; SL 080932 . .-.ya'CVr^S; 'wa- .Viifciiarm*; 6*1l--i a Aft 3 * of vapor adsorbed a.Uo decreases. If the w3,,t is plotted as a function of concentration on lo garithmic <...'Ordinates, a linear relat'onsliip is observed as shown by the examples in Figure 3 1-1. Puis line takes the form = fcC" (12) where is the weight adsorbed, m is the slope the line, and k *s a constant. -\t the reference concentration, 1000 ppm, ww be comes aJS w%,i = k (tCOO)1" (13) * Dividing Ei[. (12) by Eq. (13). aa $ We htive determined in experimentally for the ten materials shown in Tabic VI. The average value was found, to be 0.36 or approximately the cube root of iho concentration ratio. ix ! i Combining Eq.v. (!0; and (14) and letting m equal 1/3 yields t u>% LT 24 2 X 10** W,. 1 / C\ CMQ J'^'llOUitj (15) Combining Eqs. (.1 1) and (15) and simplifying terms yields 0.31 L ICO J_ J_1_I L t 1. 1 *300 Cci't-fttrat.ien - ppm FF/'ur* te-V/eijOt of solvent vapor ,Tlsorb*d as a function of concentrations. t l%.2.4 X 1 (d wr Ca -b bt) C-'-1 MQ (15) od of service life estimation over a broad - This expression can be use ! to calculate the range oh flows, concentrations, humidities, and 10% breakthrough time by obtaining M and solvent vapois. t from handbook values, C by estimation or measurement, wc by weighing or from Table Summary I, Q from Table ll, and a and b from Table J VI. This equation is a good approximation in We hate determined the service life for organic the 0-40C temperature range, but a humidity vapor earl;idv.es cutler a wide variety of tlow, factor must be added for unusually humid con concentration, humidity and sotvent vapor ditions (see preceding section on relative hu conditions. Cartridges were challenged with midity) or if the carbon has been stored in a vapor and air mixtures anti the downstream damp environment. concern rations vvere measured with a flame Comparison of Eq. (16) with the Meck ionmat. in detector. a lenburg and Wheeler equations for 10% break Service life was found to be inversely through is shown in Table IV and Figure 11, proportional to the flowrate, and no differ In general, F.q. (16) shows the best agreement ences were observed between steady itate and with experimental values, especially at the pulsating flow. The log of the scivtce time at higher concentration using relatively vola any breakthrough percent was inversely pro- tile materials. This expression does have sev portion.-.l to the log of the concentration over eral disadvantages: (1) Only the 10% break- a concentration range of 50 to 3000 ppm, through time can be calculated, (2) It cannot C.-t ridge effectiveness was decreased at adequately deal with star cut mixtures anti storage or use humidities above 05% with use (3) no provisions arc made for materials with humidi'v exhibiting the dominating effect. The more than one function.il group In spite of service time was found to bp directly propor these deficiencies, I'q. (16) offers a i.ipitl meth- tional to the amount of carbon available, but C, V s,. '.ice ttm. favorably w calculated tV equations. Ackno: S''WFl number of i cantly to th fully acknov for their ass gram. We a Thomas Ta. F. Barry fc data red:.: and F neer our efforts m a. References 1. Rccir, V. R. E. In Cartridge sign. ,!**' 524 S,0!?<ri^r. *97S mmp SL 080933 j1 i i i 1 j ii ried js 3 [a broad [ties, and I organic j of flow, at vapor gcd with xnsrresm a flans inversely o dn'ier- and ; ;:m= at ic y prolot over lmom jsn>d.l ,ic |'W!h use Uci. The } prnporabia. be; *--7,, :5,`o TABLE VI Experimental Values for the Slope (m) of the Line Obtained When the Weight Adsorbed at 1G% Breakthrough is Plotted as a Function of Concentration on Logarithmic Coordinates 0 :*v/(.unin* Acston* Q*nzn* W** in* Mef-iyl iMoPc'ai'.'Ti M-'tV/l 3**t,i(* (''V-Vanot Cvsan t*trachland* Vinyl ehlQnd* cast-noce MSA AO MSA MSA AO MSA MSA M SA MSA AO CONCENTRATION RANC tsom) 25O-Z0ZO ico-:aco 125-IOCQ ico ;cco 25o-s:co ICC-2CC0 503-2000 750-2000 50-iCCO Av^rag# = SLCPi 0,22 0 23 0.22 0.50 0,10 0.2S 0.46 0.30 0 34. 0.56 0 3'> 0 IS did not depend appreciably on temperature. Volatile materials, especially the first members of each homologous group (i.e., methanol, methyl amine, methyl chloride, etc.) exhibited relatively short breakthrough times. An empirical expression to estimate the service time v/a> derived which compares f.v.^t.iidy with experimental v-u,;us and those calculated from five Mecklenburg and Wheeler equations. Acknowledgments Since this program began 5 years ago, a number of individuals have contributed signifi cantly to the success of the project. We grate fully acknowledge Joe Lipera and '.Valter Ruch for their assistance in initiating our testing pro gram. We also wish to thank Robert S. Flint, Thomas Tnssin, Joe R. Parlagreco.-and Patrick F. Barry for their help in programming and data reduction, and to thank Robert D, Taylor and Bemell J. Dequeue for their skillful engi neering support. We would also like to express our appreciation to Charles T. Prevo for his efforts in developing our empirical expressions. References I, Root, W. E., 0. 0. Nflson, C. L. Lindeken, R. E. Johnson and D. J. HoookinS: Respirator Cartridge Efficiency Studies: T, Experimental De. sign, Am. /.-/, Hyj. Asu'C. /. .f h 105 f 1972). NErsoN, C. 0. and O. J, HodC/ONS; Respirator Cartridge Efficiency Similes: ft. Preparation of Test Atmospheres. Am. hid. H\p. Assoc. 1. JJ.l 10 (1972). 3. Nelson, G. 0.. R. E. Johnson. C. L- Linds;an and R. D. Tayior: Respirator Cartridge Effi ciency Studies: [II. A Mechanical Breathitt; Ma chine lo Simulate Human Respiration, Am. hid. Hjg. Assoc. J. jJ 715 (10?:) 4 Nfeson, G. 0. and C. A. Ms.-idfr: Respirator Cartridge Efficiency Studies; IV. Effects of Steady Stale and Pulsating Ffosv. Am. Ind. Hyg. Assoc. J. JJ.797 (1972). 5. Nelson, G. O. and C. A. Houser: Respirator Cartridge Efficiency Studies: V. Effects of Sol vent Vapor. Am. Ir.d. IIyC- Assoc. /. JJ.391 (197-1). 6. Ne.lson, G. Q., C. A. I [arisek and B. E. Bicler: Respirator Cartridge Elficiettcy Studies: VI. ef fect of Concentration, Lawrence J evermore Lab oratory, Rcpt. UCRL-76134 (Nov. 1974), 7. Nelson, C. 0., A, M. Correu and G. A. Harder: Respirator Cartridge Efficiency Studies: VII. Effect of Relative Humidity and Tempera ture, Lawrence Livermore Laboratory, Rept, UCRL-7739n (Aug- 1575.) S. SviiSF.K, M. and S- Cffnv: Active Carbon, pp. 103-135, Elsevier Publishing Co.. New York (1970). 9. Jonas, L. A, and J. A. Reiirman: Predictive Equations in Gas Adsorption Kinetics, Carbon 11:59 (1973). 10. Jonas, L. A. and J. A. Remrman: The Rate of (las Adsorption by Activated Carbon, Carbon 12.05 (1974). Secetitad Ms I 13, 107s it# : :* -t-fc i.'* i EXHIBIT E AIRBORNE CONCENTRATIONS OF ETHYLENE DIBROMIOE (ED3) IN A GASOLINE SERVICE STATION ENVIRONMENT Exposure to EDB in air from gasoline was tested in a ser vice station environment at Du Font's Petroleum Laboratory on July 17, 1975 by fueling 83 automobiles with 1577 gallons of gasoline contain ing 1.61g lead/gal. The fueling was performed by two operators who wore personal air monitors during the 1 hour and 50 minute operation. These monitors sampled the air at the breathing level of the operator by drawing a known volume of air through charcoal absorption tubes. Upon completion of the test, the charcoal was treated with carbon disulfide (CS2) and the CS2 extracts were analyzed by gas chromatography. In addition, a continuous air sample, using charcoal absorbers, was taken at a point 55 ft. up wind and at a point 35 ft. down wind of the pump island during the fueling operation. The charcoal from these air samplers was also extracted with CS2 which was then analyzed by ias chromato graphy. In addition to the charcoal air samplers, samples of ambient air were collected in previously evacuated containers and later analyzed by electron capture gas chromatography. One sample of air was taken near vehicle filler pipe during fueling, and one air sample was taken on the pump island. The CS2 extract of the charcoal was analyzed by gas chromatography using the same procedure recommended by NIOSH. SL 080935 Results are given below: Atmospheric EDB Concentration In Service Station Environment 89F., 4 mph Wind from SW Sample Site Up Wind Down Wind Pump Island Personal Air Monitor (Averaged Over 2 hours) Vehicle Filler Pipe (5 minute grab sample) Concentration of EDB Measured* Less than O.lppb Less than O.lppb Less than O.lppb Less than O.lppb l-2ppb Electron Capture Gas Chromatography. SL 080936 UNION CARBIDE CORPORATION CHEMICALS AND PLASTICS P.O.BOX 8361, SOUTH CHARLESTON. W. VA. 25303 February 22, 1979 // Docket Officer, Docket H-079, Room S6212 United States Department of Labor Third Street and Constitution Avenue, N.W. Washington, D.C. 20210 1Effi 5/2/7 HUE Subject: Request for Information Occupational Exposure to 1,2-Dichloroethane Occupational Safety and Health Administration (43 FR 46910) Union Carbide Corporation, a producer and user of 1,2-dichloroethane since be fore 1330, desires to submit Information to the Occupational Health and Safety Administration on the subject of occupational exposure to 1,2-dichloroethane as requested (43 FR 56910). Union Carbide Corporation appreciates the granting of additional time by OSHA to permit it to more fully evaluate its data and to reply more fully to the request for Information. We have reacted positively to the National Institute of Occupational Safety and Health's recommendation that worker exposures to 1,2-dichloroethane be reduced to 5 ppm TWA 8 by setting an internal standard at this level; however, we do not endorse the further reduction of worker exposure now recommended by NIOSH nor do we believe that NIOSH has fully provided information in its Criteria for a Recommended Standard . . . . Occupational Exposure to Ethylene Dichloride (1,2-Pichloroethane) dated March 197g~to support its previous reconmendation. The United States Department of Health, Education and Welfare, National Cancer Institute has conducted a Carcinogensis Bioassay of 1,2-Dlchloroethane by dosing rats with 95 mg/kg/day and 47~ mg/kg/day and mice with 97 mg/kg/day to 299 mg/kg/ day by gavage. The oral administration of ethylene dichloride caused fore stomach cancers, hemanglosarcomas of multiple organs, subcutaneous fibromas and mammary cancers in rats and breast, uterine and respiratory cancers in mice. Assuming that a 70 kilogram worker is exposed to a workplace concentration of 50 ppm for an eight hour time weighted average and that bioassay studies by ingestion can be extrapolated to inhalation exposure, then the worker's dosage would be 16 mg/kg/ day or 34% of the lowest animal dosage in the study. If worker exposure is limited to 5 ppm for an eight hour time weighted average, then the dosage would be only 3.4% of the lowest rat dosage in the study, again assuming that ingestion bioassay data is directly related to inhalation and/or absorption of the material. SL 080937 - 2- Union Carbide Corporation believes that there is an acute toxicity hazard from the high exposure of workers to ethylene dichloride via ingestion, inhalation and skin'absorption and that current regulations`and work practices are adequate protection from these hazards. It also does not believe that the NCI study provides any basis for NIOSH's new recomnendation that worker exposures by inhalation be reduced to 1 ppm TWA 10 with a ceiling value of 2 ppm for a 15 minute sample, along with its recommendations regarding personal protective equipment and clothing. Regarding the data on ethylene dichloride requested in the Federal Register, Volume 43, Page 56910, we have the following: "(1) Metabolism including intermediates as well as final metabolites." Under the management of the Manufacturing Chemists Association, Union Carbide is a cosponsor of a study of ethylene dichloride metabolism. Results of this study when completed will be made available to OSHA by MCA. "(2) Toxicity, tumorigenicity, carcinogenicity, teratogenicity and/ or mutagenicity including the effects if potential cofactors as related to each of these." Exhibit A of this letter contains a summary of acute toxicity studies done by the Union Carbide Corporation Chemical Hygiene Fellowship at Mellon Institute of Research. Exhibit B contains an annotated bibliography on ethylene dichloride compiled by -- E. I. duPont de Nemours and Company, made available through the Manufacturing Chemists Association. A chronic inhalation toxicity study with teratology and reproduction studies managed by Manufacturing Chemists Association (Union Carbide Corporation is a co sponsor) is underway in Dr. Cesare Maltoni's laboratory in Italy. This study Involving exposure of rats to 150, 50, 10 and 5 ppm ethylene dichloride has shown ho indication of carcinogenicity in preliminary results at 104 weeks. The final report is now being prepared and will be made available to OSHA by MCA when issued. "(3) Human epidemiology (employee populations and those otherwise exposed)." Union Carbide Corporation has made no formal epidemiological studies of exposed employee populations; there have been no indications of chronic toxicity observed in our exposed employees over the period of our manufacture and use of ethylene dichloride from the 1930's to the present day. If the National Institute of Occupational Safety and Health chooses to make such a study, our record will be made available. "(4) Appropriate medical surveillance procedures." . Union Carbide Corporation makes medical surveillance available to its employees on a regular basis. This medical surveillance includes: SL 080938 -3- (1) A medical history (2) A general physical examination (3) Blood studies including a complete blood count and blood enzyme analysis (4) Routine urinalysis (5) Chest X-ray (6) Pulmonary function test (7) Vision and glaucoma tests (8) Electrocardiograms for older employees (9) Audiograms Results of this medical surveillance are made available to the employee and to his personal physician if he so directs. Union Carbide Corporation believes that.its regular medical surveillance program is adequate for employee protection. Medical records are kept indefinitely. A program is under way to store and process employee medical data by computer. "(5) Appropriate respiratory protection." Union Carbide Corporation supplies the following respiratory equipment for employee protection: (1) Respirator with full face piece and self-contained air supply with optional pressure demand or continuous flow modes. These are used for emergency situations including, if necessary, entry into confined spaces. (2) Respirator Type C with full face piece and continuous air supply from certified breathing air cylinders via hose. These respirators are used for maintenance operations in cluding entry into confined spaces. (3) Respirator with full face piece and organic vapor cannister. These cannister gas masks are used for escape purposes and for emergency situations in the open where exposure con centrations are low. The respirator program meets the requirements of 29 CFR 1910 134. Employees are trained in their use. The respirators are regularly inspected and maintained. Respirators are cleaned and serviced after each use. "(6) Uses and production technologies." Union Carbide' Corporation originally produced ethylene dichloride as a byproduct of ethylene glycol manufacture via the chlorohydrin process. With the development SL 080939 -4of ethylene glycol by direct ethylene oxidation, ethylene dichloride was manu factured by'the catalytic liquid phase chlorination of ethylene. This process is currently in use at UCC's Taft, Louisiana and Texas City, Texas plants. Manufacture of ethylene dichloride at UCC's South Charleston, West Virginia plant was discontinued in 1969. Essentially all the ethylene dichloride produced at Texas City, Texas and Taft, Louisiana Is converted to ethylene amines at Taft, Louisiana. Catalytic amounts of ethylene dichloride are used in organic chemical production at UCC's Port Lavaca, Texas, Ponce, Puerto Rico, Texas City, Texas and Taft, Louisiana. Ethylene dichloride was used for vinyl chloride manufacture at UCC's South Charleston, West Virginia and Texas City, Texas plants prior to 1969 when vinyl chloride production was discontinued. "(7) Employee exposures (actual or potential) in each use and pro duction facility including: (a) the levels and specific conditions of such exposures, (b) the numbers of employees involved in each exposure situation." The following tabulation shows actual UCC employee exposures as well as the numbers of employees involved. The number of employees exposed at UCC's Port Lavaca, Texas and Ponce, Puerto Rico plants where ethylene dichloride is used in catalytic quantities was not determined but it is quite small. SL 080940 1.2 OICHLOROETHANE UCC OCCUPATIONAL EXPOSURE MONITORING LOCATIONS AND sue , ATMOSPHERIC M E ASUREMENTS . ESTIMATED NUMBER * WORK AREA SAMPLES PERSONNEL EXPOSEO PER NUMBER CONCENTRATION IN PPM MONTH COLLECTED GEO ARITH MEAN MEAN RANGE PERSONNEL SAMPLES tt ALL SAMPLES NUMBER CONCENTRATION IN PPM COLLECTED GEO ARITH MEAN MEAN RANGE 8 HOUR TWA SAMPLES NUMBER CONCENTRATION IN PPM COLLECTED GEO ARITH MEAN MEAN RANGE Ponce, Puerto Rico Plant Port Lavaca, Texas Plant Texas City, Texas Plant Taft, La. Plant Not Determined . Not Determl ned 40 ' 30 22 0.35 0.35 0.35-0.35 107 0.35 0.35 0.35-0.35 45 46 0.71 2.32 0.1-18.2 45 124 0.1.4 14.10 0-400.00 117 2.26 6.52 0.10-46.8 0.16 1.66 0-28.26 10 79 156 0.62 9.18 0.04-375.70 ' 72 0.27 2.59 0.01-83.61 47 0.23 0.29 0-0.35 0.82 1.25 0.1-4.40 0.08 1.02 <0.01-14.10 0.19 0.20 0.05-1.20 TOTAL DIVISION 348 0.36 9.38 0-400.00 341 0.33 2.11 0-83.61 181 0.16 0.66 0-28.26 SL 080941 R.E.Peele/slh 2-13-79 h ] 'r 6- - - '.'(8) Technological and economic feasibility of reducing employee exposure." Union Carbide Corporation, in response to NIOSH's initial recommendation has set an internal standard of 5 ppm TWA 8 for exposure via inhalation. For its pro cesses. and plants `this limit appears to be feasible as shown in the preceding tabulation of employee exposure and work space monitoring. The feasibility of further reduction in employee inhalation exposure would require more time for study. Based on our studies, ceiling exposure limits would pose a more serious problem than achieving low average exposures. In our closed processes, leakage, spills and equipment malfunctions more often cause employee exposure via inhalation than do normal operations. Union Carbide Corporation, while agreeing that the NIOSH recommendations regarding protective clothing and equipment are possible, does not believe that such stringent requirements are necessary or reasonable. UCC provides impervious clothing where there is a high likelihood of skin contact with ethylene dichloride. Employees whose clothing is wetted by ethylene dichloride are discarded and replaced at no cost to the employee. The NIOSH recommendation that employees be provided with clean work clothes daily appears to be based on the unproven assumption that cloth ing will adsorb ethylene dichloride from the work space air. The NIOSH recommendation that the regulated area be washed thoroughly at the end of each shift along with the absence of an action level recommendation is not feasible in UCC's plants nor do we believe it to be necessary. Such washing at frequent intervals is more likely to cause employee exposure to water bearing ethylene dichloride and is certain to make the workplace very uncomfortable and unpleasant. Where there Is no mention of the subject, the term wash thoroughly implies that wipe tests will be used for monitoring. The impracticality of this ' test was pointed out in the testimony on the acrylonitrile standard. In regards to employee exposure via Ingestion, UCC provides clean ventilated spaces for employees to eat and the necessary facilities for washup prior to eating. There appears to be little likelihood of employee exposure via this route. In general. Union Carbide Corporation regrets tha't it cannot comment more fully on this area due to the lack of definition as to what the rules governing reduction of employee exposure may be whether there will be an action level and whether there will be exemption of products containing small amounts of residual ethylene dichloride. In testimony on previous OSHA standards, we have been strong advocates of performance criteria and limits on the area where the standard is applicable. We do not believe that the specification standards recommended by NIOSH are necessary or reasonable, and they diffuse effort and increase the cost of employee protection. "(9) Economic and technological feasibility of complying with a complete 1,2-dichloroethane standard at the lowest level of exposure feasible." The request for information is confusing and not answerable within the time con straints imposed by the request. A complete 1,2-dichloroethane standard at the lowest level of exposure feasible must obviously be technologically feasible. Dispite the fact that OSHA states that economic feasibility cannot be used in evaluating standards, obviously if a standard is not economically feasible, then manufacture of the product being regulated will be suspended. Thus the request for information becomes a request to comment on the feasibility of a feasible standard. SL 080942 - 7- After.reviewing the information received as a result of this whole request, OSHA should request comments on standards involving various exposure levels. The standards for comment should clearly show the nature of the whole standard under consideration, i'.e., performance versus specification, action level versus no action level, product exemption versus no product exemption. "(10) Analytical and sampling methods used and evidence of their pre cision and accuracy." The method of employee inhalation exposure monitoring used by UCC is essentially that recommended by NIOSH in its 1976 Criteria Document. Air samples are collected with activated charcoal and calibrated sample pumps, desorbed with carbon di sulfide, and analyzed by gas chromatography. Analytical methods for wipe testing are those recommended by NIOSH. "(11) Whether issuance of an Emergency Temporary Standard is appropriate." Union Carbide Corporation believes that issuance of an Emergency Temporary Standard is inappropriate at the present time for the following reasons: (1) Toxicity studies in animals and humans to date show no indication that the present occupational exposure limits imposed by OSHA in 29 CFR 1910.1000 do not provide an adequate margin of safety for workers exposed to inhalation _ of ethylene dichloride. (2) The National Cancer Institute study of ethylene dichloride via ingestion by gavage which indicates that it may be carcinogenic is not directly relatable to inhalation exposure and involved variable exposure, the average of which was approximately three times the dosage at the present limit set by OSHA. In any event, the NCI study involving variable dosage by gavage showed many of t'he cancers at the point of injection, i.e., the rats fore stomach and the respiratory tract. By any reasonable evaluation the NCI study indicates the need for further study under constant conditions instead of the obvious conclusion that ethylene dichloride is car cinogenic and should be rigidly controlled. (3) The ethylene dichloride toxicity study sponsored by the EDC producers and managed by the Manufacturing Chemists Association is in its final report phase. This study covers metabolism, teratogenicity, reproduction study, and chronic inhalation at 150, 50, 10, and 5 ppm. The study will obviously provide data in areas where OSHA lacks knowledge, thus it would appear to be essential to the decision as to whether an ETS is appropriate. This study in a preliminary review has not shown that ethylene dichloride is carcinogenic. (4) The NIOSH Criteria Document issued in March 1976 indicated that the primary occupational health problems resulted when employees failed to observe the OSHA limit of 50 ppm TWA 8 and when good manufacturing and work practices procedures SL 080943 8- were not observed, i.e., handling ethylene dichloride in open buckets, using EDC as a solvent in poorly ventilated spaces and failing to remove clothing which became saturated with liquid ethylene dichloride. If OSHA chose to enforce the current regulation vigorously, the need for a new regulation would be moot. Union Carbide Corporation appreciates the opportunity to provide information as requested by OSHA in 43 FR 56910. We are very concerned regarding the safety and health of our employees and those of our customers. We will continue to cooperate with OSHA and NIOSH in improving employee safety, however, we are concerned that new regulations may be promulgated without proper studies and careful evaluation of current regulations. LAC/db Attachments L. A. 'Crisorio SL 080944 EXHIBITS SL 080945 2c\ai>ci Exhibit' A ncl* Oral Dosa, LD<o an 101 in Corn Oil if-at 0.7/ (0.67 to 0.8Q) Ycrjn 0.91 (0.87 to 0.95) E./h. rabbit 0.91 (0.86 to 0.97) pa*As* -nlo Skin Xboorptlon, 1 8*7 Pjibblt Dob --------- <---------- 3.C? (3.10 to 4.46) nl./kfj. 2qX* Inhalation. Savor* kidn7 injury (Spac. Rpt. 10-46;- 1947) 200 ppa. 1 far. killed 1/10 rate, 0/10 rabbit*, 4/10 nieo 20C0 ppa. nic#. 1 br. 0/10, 2 hr. 6/10, 4 hr. 9/10 2000 ppa. rats. 1 hr. 0/6, 2 hr. 2/6, 4 hr. 12/12 COCO ppa, rabbito. 30 ala. 1/4, 1 hr. 1/4, 2 hr. 4/4 ~53 . 32&4 (Baplac** B-1309) hyl< Eidilorlde zjlzza Dichlorldo. alto "Oayfixao* 60) 1--A a Jt - 1 _ A. M____t Card 1 Card 2 (Sp*c. Rpt. 10-13; 1947 uiloss notad , 3265 (Raplacoe B-1310 and B-1313) J leno Dlchlorlda t l 4i .P Card 2. Vi'ii W,' N| SL 080946 t .. MANUFACTURING CHEMISTS ASSOCIATION 1825 CONNECTICUT AVENUE. N.W. WASHINGTON, D. C. 20009 (202)483-6126 December 26, 1974 TO: SUBJECT: Ad Hoc Planning Group on Ethylene Dich-loride (EDC) Literature Survey on EDC' Gentlemen: Dr. R. S, Waritz has kindly made available an annotated bibliography on EDC, compiled by E. I. du Pont de Nemours & Company. A copy is attached for your information'and files. Sincerely, 4*. M. Ad Hoc Planning Group on EDC MF:meh enclosure RECEIVED JAN S 1975 H, R. GUEST SL 080947 fETHYLENE DIc7iLORID~EDO ' ii ACUTE TOXICITY A. Oral i) Values human LDI,o` LD100 rats LD50 ld50 LD50 mice ldlo W>50 dogs ldlo "l00 rabbits . LD50- somer unspecified: dog 11 LD50 LD100 guinea pig LDS0 LD100 rabbits LD50 LD100 rats young LD50 LD100 adult LDS0 LD100 senile LD50 LD100 845 mg/kg 56 ml 6so mg/kg 6 80-7 70 Ttvj/kg 770 mg/kg (670-890) 600 mg/kg 910 mg/kg 2,000 mg/kg 2,500 mg/kg 910 mg /kg 1.3 ml/kg 1.9 ml/kg 0.6 ml/kg 1.2 ml/kg 0.8 ml/kg 1.6 ml/kg ' 1,135 + 7C mg/kg 2,000 mg/kg 625 + 50 mg/kg 1,500 mg/kg 560 + 38. mg/kg 1000 mg/kg * Specific gravity 1,1-Dichloroet.hane = 1.776 1,2-Dichlorocthane = 1.256 LDj0 = lowest lethal dose LdVqo = lethal- do.se to 1001 of test animals = lethal dose to 501 of test animals it/ it 'jf re/^ Ul /r/fj (1) (3) U) (3) (4) . (1) (3) (1) (3) (3) (2) (2) (2) (2) (2) (2) (12) (12) (12) (12) (12) (12) SL 080948 OrnJ (Continued) mice young adult senile b) Effects ld50 LD100 LD50 LD100 LD50 LD100 1,308 + 79 ing/kg 3,000 mg/kg 1,120 + 192 mg/kg 2,500 mg/kg 725 + 38 mg/kg 1,500 mg/kg (12) U2) (12) (12) (12) (12) Isomer unspecified: rats 1-2 ml/kg death at 10-16 hours Results: bradycardia, bradypnea, total- atrio ventricular b]ock,.cessation of respiration, due to "action on the central nervous system and in particular the respiratory centers." (28) rats.. 1.0 ml/kg ..... rabbits 0.5 ml/kg Results: 24-72 hours: "reversible dystrophic changes in the liver'.' 4-5 days: decrease in fat content of hepatocytes, ~ appearance of cells with 2-3 nuclei 6-8 days: necrotic foci disappeared (31) rats 0.7 ml/kg Results: decreased rate of oxidative phosphoryla tion in liver mitochonura (32) rabbits 1.2 ml/kg Results: 'marked increase in fibrinogen content of the blood, acceleration of clotting reaction (41) rabbits 0.9 - 1.7 ml/kg Results: toxic pulmonary edema, "accompanied by a series of changes in the blood." (42) Skin Absorption rabbit ld50 IjD50 LD50 3890 mg/kg 3.89 ml/kg (3.40-4.46) 2,800 mg/kg (1) (4) (3) 'fr*-*('-t*'fpi-T.*: SL 080949 D. Skin (Continued) Isomer unspecified: rabbits 10 mg/1 in air Results: decreases respiration and glycolysis, and cytochromic oxidase in red blood cells, caused a decrease in activity of serum enzymes, including cholines terase, affects membrane permeability of renal cells. (29) b) Irritation rabbits Score 2* - "trace of capillary injection" (4) Eye rabbit dog Score 3* corneal opacity * (4) (16) Injection a) Subcutaneous rats LD50 LD50 mice ldL0 rabbits ldl.o LD100 b) Intraperitoneal rats LD5, 0. mice ldLO LDS0 c) Intravenous 500 mg/kg 1,000 mg/kg 380 mg/kg 1,200 mg/kg 1,600 mg/kg 600 mg/kg 250 mg/kg 470 mg/kg (1) (3) (1) (3) (1) ' (1) (6) dog ldlo * LD100 LD100 LD0 175 mg/kg 175 mg/kg 0.25> ml/kg 0.125 ml/kg (1) (3) (S) (5) mice 0.075 ml/kg 0.2 ml/kg 0.4 ml/kg 10% increase in urine protein(34) 30% increase in urine protein(34) 56% increase in urine protein(34) Skin irritation scores run from 0 (no effect) to 10 (necrosis) Eye irritation scores run from 0 (no effect) to 20 SL 080950 y L\ Inhalation * 1 mg/1 = 247 ppm and 1 ppm = 4.05 mg/m3 at 25*0, 760 nun Hg a) Values humans rats ^LO t?lo 1,0 5 Q maximum * time 4 hours survived 12! min. 1 hour 7 hours 4,000 ppm {1) 1,000 1,000 20,000 3,000 300 ppm ppm ppm ppm ppm (1) (3) (8,10) (8,10) (8,10) no effect times 6 min. 1. 5 hours 7 hours 12,000 ppm (8,10) 1,000 ppm (8,10) 200 ppm (8,10) mice LC100 - 9,000 ppm (3) rabbits lcL0 lclo 7 hours unspecified 3,000 ppm (1) 1,000 ppm (7) guinea pigs LC100 2 hours 9,000 mg/m3 {1) 3,000 ppm (3) pigs LC 7 hours 3,000 F?m (1) rats ^5 LCS0 LCS0 0.53 hours 2.75 hours 7.20 hours LC 0.01* 0.23 hours LC 0.01 1.02 houi.-sj LC 0.01 3,70 hours 12,000 ppm (8) 3,000 ppm (8)1,000 ppm (B->. < 12,000 ppm (3) 3,000 ppm (8) 1,000 ppm (8) no effect level . lethal dose 0.1 hours 0.3 hours 1.5 hours "few minutes" deep narcosis 30 minutes 12,000 ppm (8) 3,000 ppm (8) 1,000 ppm (8) 150,000 ppm (9) 12,000 ppm (9) slight symptoms , 8 hours 1,000 ppm (9) = lowest toxic concentration = lowest lethal concentration I,C50 = concentration lethal to 50% of test animals LC100 = concentration lethal to 100% of test animals LC0.01 = concentration lethal to 0.0.U of test animals SL 080951 -5- b) Effects rats, guinea pigs, rabbits, monkeys 100-400 ppm 7 hours Results:, "depression of the central nervous system, lung irritation, and organic injury of the liver, the kidneys, and the adrenal glands." (8) rabbits Results: 300 ppm time unspecified no.significant changes in the blood and spinal marrow, with the exception of "toxic granulation in granulocytes of about 20%.M (24) rabbits Results: levels and time unspecified liver damage, kidney lesions, and "less marked degenerative signs in other organs." (25) Isomer unspecified: rats Results: 10 mg/1 4 hours decrease in cholinesterase activity serum: 37-43% decrease plasma: 23% decrease brain: 16.4% decrease spinal cord tissues: 16.7% decrease liver: 27.8% decrease pancreas: 20.3% decrease heart:. 29% decrease . pylorus: 31.2% decrease- (33) CHRONIC TOXICITY A. Oral cows 100 ppm 22 days SOOppm, 10 days then 1000 ppm, 12 days Results: no loss of appetite, no decrease in milk production (13). Levels of 1000 ppm produced concentrations of less than 0.25 ppm in the cow's milk (14). Isomer unspecified: rats fed maize, sugar beets Results: no change function treated with 0.1-0.5% EDO time unspecified in blood composition or liver (30) SL 080952 li. Inhalation a) Spencer, et. al. (8,15) 400 ppm rats ' up to guinea pigs up to Results: 40 -7 hour exposures 24 7 hour exposures no survivors, no tumors) increased liver and kidney weights, histological changes in liver and kidney rabbits 165 7 hour exposures Results: maximum for no effect 200 ppm rats Results; guinea pigs Results 100 ppm 157 7 hour exposures maximum for no effect ISO 7 hour exposures histological changes, no tumors rats, male 115 hour exposures , female guinea pigs. male 142 121 hour exposures hour exposures rabbits monkeys female Results 162 17 8 148 no adverse hour hour hour effect exposures exposures exposures "The significant chronic effect appears o be- hepatic .... and/or renal damage." (8) b) Heppel, L. A. et. ,al. (17) 1000 ppm 7 hours/day 5 davs/week ., guinea pigs survived 2 exposures rats( survived 3-14 exposures rabbits survived 2-64 exposures dogs, cats, monkeys 23-55 days low mortality Results: fatty changes in liver 400 ppm 7 hours/day rats, rabbits, guinea pigs Results: liver damage days/week high mortality survived 177 exposures SL 080953 b) Hcpptel, L. A. et. al. (Continued) `.200 ppm rats Results: gu-inea pigs Results: rabbits * monkeys 125 exposures greater than normal mortality, mild pulmonary congestion 125 exposures greater than normal mortality, histological changes 125 exposures no effect 125 exposures no .effect 100 ppm rats survived "many" experiments; no lesions guinea pigs monkeys c) rats, guinea pigs, rabbits, cats 6 hour/day 5 days/week 500 ppm toxic to all in 13 weeks 100 ppm tolerated for 17 weeks (19) d) rabbits levels unspecified "chronic poisoning" Results: most severe damage-in liver, decrease in lipids of leukocytes, kidney degeration and necrosis, deterioration of kidney function. . (25) e) rabbits 0.6 - 0.15 ml/kg/hour Results: "bradycardia,...cardiac excitability, and a progressive decrease in the blood pressure to death." (23) f) rabbits 3000 ppm "chronic exposure" Results: "A direct poisoning effect on the bone marrow is concluded." (24) Isomer unspecified: g) rats 5 mg/1 Results: 3.5 months changes which "reflect pathological excitation followed by decreased functional activity of the entire central nervous system." (16 h) rats i) rabbits * .05 - .01 mg/1 3-5 hours/day Results: changes in conditioned reflexes histological changes in the brain. Both disappeared when removed from exposure. - 2 mg/m3 3 hours/day 8-10 months Results: did not affect antibody formation (22) (20) SL 080954 changes m liver and kidney: rabbits 10 mg/m^ 3-4 hours/day Results: "not toxic" 7-11 months (21) >:) rats rats 5 mg/m" 4 hours/day 1-9 months Results mg/m^ and 120 mg/m^ gasoline 4 hours/day -1-9 months "considerable changes of the estrus cycle and its periodicity," a decrease in total number of cycles, number of leukocytes and phagocytic activity riot affected (27) 1) rats 30 mg/m plus 1210 mg/nr3 gasoline vapors hours/day 6 mos. prior to and during pregnancy Result: "changes in duration of estrus cycle," decrease in fertility, weight, and muscle efficiency of neonates, increased lethality in progeny, no abnormalities in following.gerncration * (26) I. ADDITIONAL EFFECTS A. Mutagenicity a) wheat seeds 1 ml for 1 day Results: 0.3% dominant mutations 1.8% recessive mutations (35) b) Drosophila melanogaster 0.07% 4-8 hours Results: increased number of recessive mutations and occurrence of non-divergence of X-chromosome. (36) c) Drosophila melanogaster levels and time unspecified Results: increased frequency of recessive lethal mutations, no influence on non-divergence of chromosomes in radioresistant organisms (37) d) Drosophila melanogaster levels unspecified Results: 1 day treatment: 25-30% mutations, more pronounced in males 1 hour treatment: 2.6% mutations (38) SL 080955 ii. Other, organisms .a) Invertebrates in water 0.1 mg/1 maximum concentration.for "normal biological activity" b) mai2e prolonged storage with EDC in tropics may affect seedling growth c) 0.455M 0.065M kills Vibrio (bacteria) prevents fermentation of sugar by yeast Isomer unspecified: (40) (5) d) marine pinperch TLm* 150-175 mg/1 e) mole crickets 150 ml/m2 Results: effective in controlling these insects (43,- f) spore-forming bacteria, molds 300 g/m^ Results: no molds developed, spore-forming bacteria developed normally METABOLISM (48) a) readily absorbed from the gastro-intestinal tract or the lungs, absorbed to a lesser extent from the skin (10) > t>L mice 0.05 - 0.17 g/kg injected 10-45% expired unchanged 12-15% expired as CO2 51-73% urine 0-0,6% feces 0.6-1.3% remaining intraperitoneally Major metabolites: S-carboxymethylcysteine thiodiacetic acid chloracctic acid Minor metabolites: 2-chloroethanol S,S'-ethylene bis cystein c) ' rats * route and dose unspecified Major metabolite in urine: N-accty1-5-( -hydroxyethy 1) cysteine Secondary metabolite: S- (f7> -SS-hydroxyethy 1) cysteine (45) (46) n - median threshold limit SL 080956 M TOXICITY "Ethylene-dichloride is toxic by i nha 1 at ion, by contact skin or mucous membranes, or by oral intake. Prolonged sive, or repeated exposures to the product in any form are ardous. The signs and symptoms of excessive absorption to be zhed are: headache, mental confusion, depression, fatigue, s of appetitie, nausea, vomiting cough, loss of sense of balance, visual disturbances. There may also be diarrhea with bloody ols, suppression of urine, swelling of face, jaundice, and od- in the urine." The signs and symptoms of EDO poisoning ; the result of injury to the kidneys, adrenal glands, skin, igs, and to the digestive and nervous system. The clinical picture ries with the type of exposure and the amount of the chemical aduct which is absorbed, either at one or at repeated times." (54) Oral Patty (10) states that EDC "docs present a problem from ral ingestion," as evidenced by the number of poisoning fatalities me below). Effects include CKS depression, gastrointestinal ritation, increase in clotting time, and injury to liver, kidneys irenals, and lungs. Should an ingestion occur, vomiting should be induced and psom sales administered. (54) Skin """ * a) Irritation and sensitization * If held close to the skin EDC can cause severe irritation with moderate edema and necrosis (10). Repeated or prolonged contact "may cause a rough, red, dry sk-in due to extraction of fatty materials" (10). "In certain rare cases, the dermatitis may be caused by hypersensitivity to ethylene dichloride" (54,55). Slvouid skin contact occur, remove all contaminated cloth ing, wash the area well and apply an ointment containing lanolin. (54) b) Absorption EDC can`be absorbed through the skin, although "it takes quite large doses to cause serious systemic poisoning." (10) C. Eye This chemical and its vapors can cause irritation, burning, and luchyrimation. Serious damage can occur if the substance is not removed promptly. Exposed eyes should be washed with water for 15 minutes. (10,54) SL 080957 D. Inhalation Symptoms of both actue and chronic vapor poisoning arc.* irritation of the eyes, nose, and. throat, headache, mental confusion, dizziness, and vomiting. EDC "has the ability to cause injury to the liver and kidney from eith excessive single or repeated exposures" (56) . ' Borisova reports that concentrations greater than 6 mg/m^ "cause vasoconstriction, decreasing light-sensation of the eyes, and reflex changes in rate, depth, and rhythm of respiration." (11) In- the event of overexposure to EDC, remove the subject immediately and do not administer adrenalin. (54) E. Threshold a) Single Exposures - not more than once a week 7 hours 1 hour 0.1 hour 200 1,000 2,000 (56) (56) (56) Repeated Exposures Threshold Limit Value (ACGIH) 50 ppm (200 mg/m^) Ceiling Value 50 ppm 100 ppm Peak Value (not more than 5 min. -.not more than one in 3 hours for an 8 hour day) 200 ssian Threshold 1 PP, (1) (56) (1) pp:n(l) (11) c) Odor Levels 'C / = 50 ppm 100 ppm _200 ppm 17.5 mg/m^ (- 23.2 mg/m^) barely detectable not unpleasant pronounced, not unpleasant detected only by these with acute sense of smell average level of detection ?3 r*, t7 The odor of EDC is sweetish and can be adaoted to at lower levels; therefore, it is "probably not sufficiently striking to be considered a significant warning of hazardous chronic exposure." (10) (10) (10) (ID (11) (10) Poisoning .? Several cases of EDC poisoning have been reported in the literature. "The late appearance and non-spdeificity of the < 0 clinical symptoms and signs" is characteristic of such cases, causing one author to warn that "lack of symptoms even several hours after ingestion or inhalation should not be taken as a rref,al5sts.nurrii`nngn estignnn. " .. / (51) SL 080958 ----- -- I'umuu/ijiuu in nervous system observed 24 hours after infusion-diuresis treatment: normalization of EEG -b) 14 year male ingested.15 ml (for intoxication) Symptoms: 2 hours: headache, staggering, vomiting 6 days: died . Autopsy: liver necrosis and resultant hypoglycemia, increase in clotting time, renal failure, and hypercalcemia. (51) c) ' ingestion 2 oz. Symptoms: 2 hours: 5 hours: 22 hours: nausea, faint dazed cyanosis, death (5) d) 18 year male ingested 50 g (suicide) Effects: death at 18 hours, "basically caused by generalized intravascular clotting accompanied by irreversible shock." Autopsy: "intense necrotic and hemorrhagic enteritis, widespread erosion of the intestinal mucosa and petechial bleeding subendocardially and supercardially in the kidneys and in the bladder epithelium." (52) e) Poisoning victims isomer, amount, route unspecified Autopsy: renal failure, swelling and protein dystrophy in tubular epithelium,', decrease in glomerular DNA and RKA. (47) f) Worker treating grains with Granosan (70% EEC, 30% carbon teti chloride) * Effects: died with "severe lesions in liver and kidneys" g) Worker Effects: inhalation levels unspecified fatal, hyperemia and edema of lungs, degenerative chances of kidney, damage to liver and adrenals... (14) n) 27 workers inhalation Effects: non-fatal, CNS depression, uemiconsciousncss, and hepatorenal syndrome. (57) i) Russian plane factory using EDC Effects: number of cases of illness, mostly intestinal and nervous disorders, and number of days lost due to illness were 100% greater in departments using EDC than in rest of the plant. j) Russian factory inhalation (isomer unspecified) Effects: "chronic hepatitis, chronic gastritic, dystrophy of the myocardium, assttecrn, ovo.jot.it: vo syndrome, vegetative polyneuritis, and allergy." Polyethylene polyamine had : synergistic effects with EDC. (55) 'J o nyder/smw 4 --7 "* '-i*- " i SL 080959 1. Tilc Toxic Subsi-anccs__ i i y / *i j . .2 Kacjr amanov',, B. G. Azcrb. __M__e_d__. __Z__h__49(7) : 65-8 (1972). I r. ArcrUi: inn, English Summary from Chemical Abstracts (CA78 : 5 3 5 7 3:n) . 3. World.Health Organization Summary (1970):C--0951- 4. Smy th, H. F. et. al. Am. ind. Hyg. Assn. J. 30 {S) : 470-6 (1909) 5. Von Octtingen, W. F. J. Ind. Hyg. Tox. 19(8):349--430 (1537). 6. Baganz, H. et.\al. A__rzneiirunittcl-Forsch. 11:902-5 (1961). Summary from Chemical Abstracts (ca'5~6 foToTdT .7. The Toxic Substances List (1973). 8 Spencer, H. C. ct. al. A.M.A. Arch. Ind. Hyg. Occup. .Med. 4:482-93 1951). . 9. MR 13-121. 0.- Patty, F. A. p. 1280-4. Industrial Hygiene and Toxicology, Vol. II (19.63), 1. Borisova, M. K. Gig. Sanit. 22(3):13-19 (1957).. Summary from . Chemical Abstracts (CA51:12~3 84 f) . 2 Savchenko, M. F. Gig. Sanit. 32(3): 31-5 (1967) . English translation p. 349-54. 3. Sykes, J. F. and A. K. Klein J. Assoc. Offic. _A__gr. Chemists 40:203-6 (1957). Summary from Chemical Abstracts [CA51:5320d). .4. "Evaluation of the Hazards to Consumers Resulting from the Use of Fumigants in the Protection of Food." FAO (1965). 5. Shubik, P. and J. L. Hartwell Survey of Compounds Which Have Been Tested for Carcinogenic Activity PHS 149 Supplement I (1957), p. 4K 6. Heppel, L. A. et. al A_ .M.A. Arch. Oothamol. 32:351 (1944) .7. Heppel, L. A. et. al. J Ind. Hyg. Tox. 28:113 (1946). 8 Dmietricva, N. V. et. al. Gig. Sanit. 36(4):20-5 (1971). Summary from Chemical Abstracts (CA75:18022s) 9. Hofmann, H. Th. et. al. Arch. Toxikol. 27(3):248-65 (1971). In German,^English summary from Chemical Abstracts (CA75:61562e) 0. Shrnuter, L. M. Gig. Sanit. 37 (2):36-40 (1972). In Russian., English summary fi'*n Chemical /abstracts (CA76:149673y) . Navrotskii, V. K. et al. Tr. S'ezda Gig. Ukr. SSR, 8th 1970 (Pub. 1 224-6. In r'ussian, English summary from Chemical Abstracts (CA77:7!0G0 Tolgskaya, M. S. Gig.__Sanit. 27(2); 8509 (1962). In Russian, English summary c~r~. Chemical Abstracts (CA57 :1223f) . Loscalzo, n_ et. al. Lavoro umano 11:554-66 (1959). Summary from Chcmicai Abstracts (CA55:26234b). -- Lioia, N. et. al. Folia. Med. 42:1233-54 (1959). Summary from Chemical Abstracts (CA54:4 908f) Lioia, Ii. oc. al. Folia. Med. 42 : 1400-8, 1524-57 (1959). Summary from Chi--"-al Abstracts {CAli4 :13433 e,f,g.h). Vozovaya, ,M. A. Akush. Ginekol. 1973 (9) :66-8. In Russian, English summary from Chemical Abstracts (CA80:34236y). Vozovaya, M. A. Akush. Ginekol 47(12):65-6 (1971).. In Russian, F.nglish 'summary*.from Cliemic.il Abstracts (CA77 : 29S74p) . Saitanov, A. 0. et. al. Gig. Tr. Prof. Zabol. 13(7):49-50 (1969) In Russian, English summary from Chemical Abstracts (CA71:121894u anc (CA73:107695q). Petrun, N. M. et. al. Farmakol. Toksikol. 30(3) : 356-8 (1967). In Russi English summary from Chemical aBseracts (CA67 : 5229ly). Vorob'eva, N. M. Vop.__Ka_tsion:__Pi tan. 1969 (5) : 123-6 . In Russian, English summary fro;:i Chemica i Abstracts (CA73 : 6 54 16s) . SL 080960 i. Chernukha,- F. S. F.i rmnko) . Toksikol. 1973 ( 3) : 148-50. In Rui-siun, * 2. English summary from* ChomicVa T "Abstracts {CAHO : ] 2 8 9 5 Od) . Natysuk, M. V. et. al. Farmnkol. Toksikol. 37(1) r92-3 (1574). In Russ in,ap English sunm.ary from Chc-mTcal Abstracts (CA30: 1239C5n) . 3. Slyur.ar, H. P. Vonr. Gig. Tr. Prof. Zabol. Gorr.orudn., Khim. _i .nhnTnTk p. 9~2-100 (1953). In Russian, English summary"Iron Clu-mi'cal' Abstracts (CA53:5506c). Ploa, G. L. and R. E. Larson Tox. Aupl. Phnrn. 7:37-44 (1965). 5. Kozhanova, N. N. and M. H. Zoz Aqrokhimiya 1966 (11) : 12 3-4 . In Russian, English summary from Chemical /abstracts (CA66:3672x) . <f. Sakarnis, V. Genotika 5 (12): 89-95 (1969). In Russian, English summary from Chemical Abstracts (CA72:129677s) . 7. Sakarnis, V. Vostn. Leningrad. Univ. Biol. 1970 (1): 153-6. In Russia; English summary from Chc-micnl Abstracts (CA73:32BOlk). 3. Rapoport, I. A. Doklndy. Akad. Hank. S.S.R.R. 134:1214-17 (I960). In Russian, English summary from Chemical Abstracts (CA55:8675h) . 9. Lobachcva, L. L. Rvbnoe. Khoz. 33 (7) :71 -- 4 (1957). English summary from Chemical Abstracts (CA51:18355c). 0. Caswell, G. H. et. al. K.m p ire J . Ex p 11. An r. 26 : 365-72 (1950). Summary from Chemical Abstracts (CA.53 : 95 54 i ) . 1. Kagramanov, B. G. et. al. Uch. Zap. Azerb. ted. Inst. 36 : 30-31 (1971) English summary from Toxline. --? * Kagramanov. B. G. Azerb. Med. Zh. 47(3):79-81 (1970). In Russian, English summary from Toxline. Vinnichenko, I. F. Tr. Kishinev. Sel'zkokhoz, Inst. 88:90-2 (1972). In Ruscina, English summary from Chemical Abstracts (CA79:132B). i , Vinnichenko, I. F. Tr. Kishinev. Sel1skokhoz, Inst. 66:182-91 (1971); In Russian, English summary fiom Chemical Abstracts (CA79:13C4). ) . Yllncr, Sven. Acta. Pharmacol. Toxicol. 30 (3-4):257-65 (1971). Summary-from Chemical Abstracts (CA76:68867n). Alumot et. al. Fate of Pesticides in Env.~, Gor. (19 72), p. 495-501. Kamenko, V. M. Vrcch. Polo. 1973 (11) : 72-7 . In Russian, English summary from Chemical Abstracts (CABO : 104 534m) . Pod 'ynpol'skaya, 0. P. Tr. Vsos. Nauchn.-Isslod. Inst. Serna 1 Frouuk ego__Perorabot:kji Ko. 4 3:69-93 (1963), English summary from Chemical Abstracts (CA61 : 7633f ). Sccclii, G. C. and I,. Alessio Epatclonia -17(3) : 279-39 (1971). I n Italian, -Engl .i r.h summary' from C'hcmica i*~Abstrncts (CA77 :135390a) IJinkel, G. j:. et. al. F.inderacrztl. Prax: 37(5) i209-16 (1969) German, English summary from Toxline. in Yodaiken, Ralph E. et. al. Arch. Env, Health 26(5}:2B1-4 (1973) Schocnborn, H. et. nl. Klin. Mochshr. 4S(13):C22-4 (1970) Guarino, A. and N. Lioia _F__o__lia. Med. 41:676-90 (1958). Engish summary from Chemical Abstracts (CA53:576g). Chemical . Safety Data Sheet ED-10 (1947) (C-951). Voshchinina, G. I. et. al. Mater. Konf. Molodvkh. Nauch. Rab. Nizhnego Taqila, Med. Sekts., 2nd, p, 18-20 (1969). In Russian, Englis summary from Chemical Abstracts (CA78:7459a). Torkelson, T. R. et. al. Pest Control 34(7) -.13-18, 42-50 (156C). Chenoweth , M. B. et , al ann Rev. Pharm. 2:363-98 (1962) . Kozik, I. V. Gig. Tr. Prof . Zabol. 1(1) 31-3 (1957) In Russian, English summary from Chemical Abstracts (CA51 5 9 7 4 d) . E. et. al. Watei Quality Criteria 2nd cd. (1963) 17! SL 080961 Diamond Shamrock Law Department - Chemicals March 2, 1979 Docket Officer Docket No. H-079 Rm. S-6212 U. S. Department of Labor, OSHA Third St. and Constitution Ave., Washington, D.C. 20210 -----------------------------------------N.W. Re: 1,1-Dichloroethane (ethylene dichloride) Gentlemen: Supplementing our letter of February 2, 1979, we herewith submit data and comments in response to your request of December 5, 1978 (43 Federal Register 56910) regarding the desirability of reducing the present exposure limit on ethylene dichloride. Diamond Shamrock's Electro Chemicals Division produces ethylene dichloride (EDC) as a precursor for other solvents and markets it primarily for use as a metal cleaning solvent. Our Plastics Division produces EDC as an intermediate in the production of vinyl chloride monomer (VCM), and our Process Chemicals Division uses ethylene dichloride in the manufacture of various specialty chemicals. 1. Exposure Data Diamond Shamrock produces EDC at two plants, both located in the Houston, Texas area. In our Independence VCM Plant, EDC produced from the reaction of chlorine and ethylene is cracked to form VCM and hydrogen chloride. The VCM is stored for shipment to customers or to our own PVC produc tion facilities nearby. The by-product hydrogen chloride is combined with ethylene in an oxyhydrochlorination process to form more EDC, which is then used to produce more VCM. At our Deer Park Solvents Plant, EDC is produced by direct chlorination of ethylene and by the oxyhydrochlorination process. SL 080962 Diamond Shamrock Corporation 1100 Superior Avenue, Cleveland, Ohio 44114 Phone: 216 694-5000 Docket Officer, Docket No* U. S- Department of Labor, March 2, 1979 Page Two H-079 OSHA Exhibit 1 describes EDO exposures at our VCM plant during the period June 1 through December 31, 1978. It shows exposures of administrative, laboratory, production and maintenance workers in terms of eight-hour time-weighted averages, the individual employee's job classification, and the number of samples taken. Exhibit 2 describes exposures at our Deer Park Solvents Plant during the period February 1, 1976 thr ugh September 30, 1978. These eight-hour time-weighted average were developed by our statistical environmental monitoring j.ogram, first imple mented in February of 1976. Under our program, we cannot break down the daily time-weighted averages to determine the minimum and maximum exposure levels or the duration of such levels. It should be noted, however, that the highs reported in Exhibit 2 are attributable to leaks which were promptlydetected and repaired. We presently have only preliminary exposure data from our two plants which use EDC in the manufacture of specialty chemicals, but we are continuing to monitor at both. Thus far, exposures at both plants have been found to be within the limits speci fied in 29 CFR 1910.1000. Comparison of Exhibits 1 and 2 shows that VCM Plant exposures are much lower than those at the Solvents Plant. In the former, the eight-hour time-weighted averages are seldom over 1 ppm. In the latter, monthly averages are generally below 5 ppm, but they are seldom below 1 ppm, and there are occasional excursions. These differences are explained by the fact that the Independence VCM Plant, completed in early 1978, incorporates the latest technology and was designed to meet or exceed current governmental emission control and exposure requirements. The exposures are the result of "fugitive" emissions (i.e., those emissions remaining after the imposition of controls). In effect, the VCM plant is a closed system. In contrast, the direct chlorination and oxyhydrochlorination facilities of the Solvents Plant were built in 1957 and 1967 respectively, before current exposure and emission controls were conceived or employed in the industry. They are not closed systems, and it would require a very substantial and uneconomical investment to enclose them. SL 080963 Docket Officer, Docket No. U. S. Department of Labor, March 2, 1979 Page Three H-079 OSHA 2. Toxicology Diamond Shamrock had three short-term toxicological tests performed on EDC by Bio-Tox Laboratories, Spencerville, Ohio. The three tests were an Ames test, a host-medicated assay and a dominant lethal test. These screening tests are qualita tive indicators of possible mutagenicity. Copies of the test data are enclosed as Exhibit 3. The Ames test and hostmediated assay indicated no mutagenic activity for EDC. The Ames test result is of questionable value, since there is no way to verify whether the EDC evaporated during the 48-hour incubation period the test requires. The dominant lethal test indicated that, for a single dose exposure, there were no observable effects. In the subacute administration (5 days), however, there were fewer embryos. We believe you are familiar with the various toxicological studies being conducted under the auspices of the Manufacturing Chemists Association. We are a participant in those studies and expect that they will determine the significance of effects observed in the above-mentioned dominant lethal test. MCA chose inhalation studies to provide a more reliable indica tion of teratological and reproductive effects than a repeti tion of the dominant lethal tests would have provided, since inhalation represents the most common means of human exposure. The inhalation tests are of longer duration and greater sophis tication and so provide a much better indication of biochemical behavior. We believe it would be only prudent for the agency to postpone any action on EDC until completion of the very substantial program of studies undertaken by MCA. Certainly, to initiate a rulemaking with only the somewhat dated NCI data would appear wholly unwarranted in the absence of any other evidence that EDC presents a hazard. 3. Reduction of Exposure Levels Roughly 80 percent of U. S. production of EDC goes to make VCM. To the extent that our VCM plant exposures are typical, SL 080964 Docket Officer, Docket No. U. S. Department of Labor, March 2, 1979 Page Four H-079 OSHA it would appear that very low levels have already been achieved by that segment of the industry. This is probably due to the fact that VCM is produced in a closed system either in new plants, or in plants substantially modified to comply with OSHA and EPA regulation of VCM exposures, as well as FDA requirements. On the other hand, our Solvents Plant is somewhat typical of plants producing EDC for non-VCM end uses. It is much older and is not enclosed. Because of its age, some major items of equipment would probably have to be replaced because the would not be adaptable to modern control techniques. We wish to note that we have under way a number of project the effect of which will be to reduce levels of exposure t^ EDC at our Solvents Plant. These include the conversion fi. open-top dryers to closed vessels and the use of a new type of product filter which would eliminate personnel exposure while changing cartridges. We also have under way a new waste water treatment facility which will enable us to eliminate our sump, a substantial source of EDC emissions for us. In addition, we are installing an enclosed process sewer in our perchloroethylene process area. As we see it, the question is not whether the exposure level can be reduced, but whether it ought to be reduced by regula tion at this time. Nevertheless, we have made an analysis to determine the feasibility and cost of additional steps to further reduce Solvents Plant EDC exposures. We see no pur pose in submitting that information at this time given the lack of evidence warranting a reduction. Our analysis makes clear, however, that, while such reduction may be feasible, its cost (we estimate it at $5 million to $10 million) would raise serious questions about the profitability of continuing the operation. 4. Epidemiology We are not able to include epidemiological data with this submission. However, we have undertaken a project of correlating medical data of our Solvents Plant employees with EDC exposure data for the years 1975 through 1978. SL 080965 Docket Officer, Docket No. U. S. Department of Labor, March 2, 1979 Page Five H-079 OSHA In over 20 years of operation, during which over a million tons of EDC were produced, we have observed no detrimental effect upon employee health as the result of EDC exposure. This has continued to be the case, since the inception of our medical surveillance program several years ago. Accord ingly, we would expect that this project will demonstrate that there is no correlation between EDC exposure and adverse health effects. 5. Appropriateness of Emergency Temporary Standard Clearly, there is no reason to issue an Emergency Temporary Standard under Section 6(c). To do so, the Secretary must first determine that employees are exposed to "grave danger" from exposure to substances determined to be toxic and that an emergency temporary standard is necessary to protect employees from such danger. In our view, neither element of that test is met by data currently available. The National Cancer Institute studies referred to in the Agency's December 5, 1978 request do not establish the exis tence of a human hazard. The MCA-administered studies mentioned above, while not complete, appear to suggest that EDC is not an animal carcinogen, mutagen or teratogen. The Bio-Tox studies conducted at our request also did not demon strate these effects. , Accordingly, if animal data can be said to indicate human risk, we believe these tests do not indicate it. In fact, they fail to demonstrate that EDC is even an animal carcinogen. We are aware of the dangers in relying on negative epidemio logical data. However, it is not a question here of whether such data should be allowed to offset positive animal data. In the absence of replicated animal studies, considerable weight must be given to the substantial data suggesting that chlorinated solvents have not been shown to cause disease in man. Chlorinated solvents exhibit a relatively consistent toxi cological response (e.g., potency, dose and type of effect) within a strain of bacteria or animals, but these results cannot be extrapolated to predict the response of another strain of bacteria or animal, much less the response of human beings. SL 080966 Docket Officer, Docket No. U. S. Department of Labor, March 2, 1979 Page Six H-079 OSHA Some of the chlorinated solvents have been shown to be weak bacterial mutagens and weak animal carcinogens. If one excludes the B6C3F1 mouse, however, these chemicals do not generally elicit a carcinogenic response in the wide variety of animals which have been employed in the toxicology bio assays funded either by the chemical industry or the National Cancer Institute. The available human epidemiological data, including those reviews contained in the NIOSH Criteria Documents, show no case of human cancer caused by exposure to any one of these chlorinated solvents. The lack of cancer induction by these common solvents becomes critically significant when it is understood (a) that they have been in production for nearly half a century, far beyo* the required latency period for cancer induction, (b) that the production volume has long been over a million tons annually, (c) that distribution of these materials is world wide, and (d) that exposure controls have only recently been established. This means that, with millions of man-years of exposure to the chlorinated solvents, there is no evidence that they have caused cancer. In addition, recent govern mental studies designed to establish whether the presence of chlorinated solvents in public drinking water presented significant health hazards found no evidence of cancer or other human diseases. Surely this lack of evidence cannot be disregarded. From the foregoing, one must conclude that lowering the present exposure limit for EDC will neither alter nor improve the health of exposed employees. To the contrary, a reduction in the present limit would require the expenditure of a great deal of money from which there will be little benefit. We believe that we must use our limited resources on controls which provide maximum benefit for each dollar expended. 6. Possible Alternative Actions Under the circumstances, it is our recommendation that, rather than require a reduction of the exposure limit based upon the National Cancer Institute data, OSHA should at most consider promulgating a regulation which would require moni toring EDC exposures and medical surveillance and encourage training and good housekeeping programs. SL 080967 * Docket Officer, Docket No. U. S. Department of Labor, March 2, 1979 Page Seven H-079 OSHA Secondly, OSHA should undertake a critical evaluation of the National Cancer Institute study, as well as the various MCA studies when they become available. Certainly these data, together with data submitted in response to this inquiry, should put the Agency in a far better position to determine what reduction, if any, might be appropriate. We appreciate the opportunity to make this submission. Should you have any questions or if we can help in any way, please contact the writer at 216/694-5268. oars, R. W. Hill Senior Counsel /njw Enclosures SL 080968 r * PERSONNEL SAL iUNG LOG SHEET MPLE 0. DATE JOB CLASSIFICATION EMPLOYEES NAME / 2 J> y p7 /<2 y 7 2. ? y sr* 7 'r $L ^1 --sy ST /_ ZjT./r-^, f/y /yfr t/y/yp C/v/-7<? tZZ- yp^-y / >V?^or / c/t</7? c/*/-7s- //*-//~?9 c/z^f/zr r / X1 ......... f/zz/yp- E~Z7<Zf/z^/yy ZZ>/j Cs^r* y e/z'z/y? C/yt/y? c/w/yz JZ)ZZ- 2/7 s 7t,y~ f/zt/yp AVVc. pA-~ ?/3-Z/-?<Z C- &f?o p-A-- c/zt/yp ^y-sy c/y//-? 9 /7"^y cP/ j9c+*~*!^0^i^o-o, c/yt/yfr A^7" f^yjOa^-n /A-'" SL 080969 S.S. NUMBER TIME f REMARKS VCM PPM i r EDC PPM MASK NORN 9.s~ S^y3? \8>Ay. ipy-. !----------;P/7 py. p yy. /5"^,J,. *szj- /<?. ,93- /9.tT(r p. sZ><y> </ -c/ /^3 p yy. Z Sr/^. /S~~~PvA. pyL-. ^-- -- --. ,?y . .. s*yy Lpy>. *M * -< / J V- p .--/2> p/ y'/'cr 7 py -^y-c7 3Z.JTCT ! <c. <y 2. ~? 5! 7./ _i .s~~ i / 5- y*^i> I PERSONNEL SAILING LOG SHEET *1 PERSONNEL SA: ING LOG SHEET `iPLE DATE JOB CLASSIFICATION EMPLOYEES NAME S.S. NUMBER TIME JK2 mtA /SL-2- ./2<?/2-?/# REMARKS VCM PPM EDO PPM MASK WORN / .7/a/7? y '7 7-if <7 7^--->- 2 7/3/ 78 --<7 s y 7/3/77 2^7,0^^ /y>s--y 2 1 7/3/7.I. 7 CT /)r> ^T) 7^,-- V' 2 > Zl//2/7% /-/&->,/. C2z>a--v,'/n`-~ / 7 C/ //(// (77f) 2 7//2/~7? 7/3<2- (2p>tS-S'a 7e> *s'/ "t/z/n? 7 //^2 C7/} / 7hs-- ? -?//2-/73 S/f '/`/ T^Lsr^/,/' 2 7//Z/79 127223 ?or^ / 7//2 /7P >/iyky7~ 2?r*?s-r; 7/,-- / 7/7/27. 22/3cZ- . 27/y y 2z>^~ < 7/2/27. 2227 <2,-7^^ 2s- 7 ///IT.. 4/so/ CO f 7//9/75/" g ?//*1/7? , jrmm / vo 'J H* 7/3/79 C7jr7(^2~w ^ MV- 7 7y~ 7 2^ i i 2S~2',, s* ML5* >6-. S'4ss 9/-. 9 4sf & A*>. 7 6~. 77,-. / 77S/s-. r~y? ^ * </c?2J --------------t-j-- 9-2,-. .2-*? /2a . /3~* /V/5 -5 /t/=7 -/ A/o ./ /t2s> . /-3 s'iy? 3.32/ s7y 4 39 s/'o . - fC? s2o /^7 . /7- 2^b . ^7 A/e> 7.72 //'ey ./? A/a .20 /7a - M>? /To ; ->j //> A/ys 1--------------- SAMPLENO. DATE 1 JOB CLASSIFICATION n 2 C> 2l 7,1 7J 2.5^ ?*: ? -? 2? ?/ 72 TT Z.C'&fe//^y<H (ZjyO^-,1 "' '?//*> /"TP (2 /-/C. ^ n if ^v* *?// 9/? S* -h--s--t-iS--~-P------y--^------?4>-- --7r/--^`--9L,f /7" ?* -----Z-~->--/,-->--V---- /ZoM-X.,* '-' 7Z/e>/yp ryv - V/*~*-^* t4- y/z^/yp- cZe~-- -?//*> /? ? r 7*. tX<7 r -- >~r/----2-wC--/-t7-"P~ y/y a /yp --/-<-->--^----- /-yO--7 ------- i/jf/y? 7^ */J X* y / - y/2.c/-}<? r/z *1 O 7/2C/y^ ----*-f---------- y/zZ/y?- m, r ' f ' Cc>7mA^- y/y/T/yp <--7--/-V--^-----O7"n-c' ^s,, _ y/y. c/y 9 cn ty o CD UoJ __ - . . .' PERSONNEL S. iFLING LOG 'SHEET f ') EMPLOYEES NAME S.S. NUMBER' TIME P/y PXP/^-. REMARKS VCM PPM EDC PPM MAI wo: 1 . A^t> /. ^T . 3*7 Jts'ezj 7. J-7 /^c> . -57T 2l^r> . -// .0? Mo t - /Ap P'XL. PJ^. t <P/-. . /7 M-o - 3'^' S-0> . >5-- /12> /22. <7 Ma PS^. ............ .02 M> - ---------------------------------1 I "I PERSONNEL SAILING LOG SHEET * M?LE 1 0. DATE JOB CLASSIFICATION EMPLOYEES NAME S.S. NUMBER TIME i*.CYfL+t 7 . f / y ^ -- - REMARKS VCM PPM EDC PPM MAS I VORi / ? ; ~ - > 7 y . 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F*xL. 1 ' f* | T 1 rrj` lr ' I ' REMARKS VCM PPM EDC PPM MAS! wor: .2. /V ' 1------- 2r x/x . 5"'X /A. /-5V /ze? Xfy , X-z - -35" SZ& i . pxr XP-^ - xv //r> .XX /iyc> . /-? Si'* . // 'Z'tr . xy . r-/ St> 1 . XX" j 1 r. ----^--^----5---"----> } r. 'AMPLE NO. DATE I JOB CLASSIFICATION 2C? 7/1-7/-7? $c7/*7 / ZJL_____ 7c>s~ PERSONNEL SAMPLING LOG SHEET EMPLOYEES NAME S.S. NUMBER TIME t ` 2*/^. j--------------------i REMARKS VCM PPM EDC PPM mas; WORi . Jr Sb. . V? . 5V S' CtO1 o00 V-0O CTl V ..* t1 j i * J . FERSONMEl X (U'u'ii J. of. 2. I aKVLXKC! LOO SHEET <b' ( \ S' "* PERSONNEL bAMBLING LOG SHEET AMPLE MO. DATE JDS CLASSIFICATION J7 So I'r/ir/yf l/SU^r'... A-<~, BMP LOOTS NAME S.S. NUMBER. TIME ,*r.-- REMARKS VCM PM EDC PPM <0.0? .*2r K vr J --*%V KM-!VWW . t&r* o co o lo sr co 1 (, h..... 'H it l -------- --- fa I PERSONNEL .'FLING LOG SHEET r\ /'G <0 ^ / 9 / P" - f% > r^ PERSONNEL SAMPLING LOG SHEET MPLE 0. DATE JOB CLASSIFICATION ts/z-'t/-?? O /(/zerZ-rP- EMPLOYEES NAME . . S.S. NUMBER TIME REMARKS VCM PPM EDC PPM rz^. (i * s . <r/ -- /, 9^ MASK WORM . .i i (n tr1 o 00 . o 'JO oCo ri 1......................................................... .... 1 .. *11 i 1 * il \MPLE '10 . DATE JOB CLASSIFICATION / //-// ^//yyr _ /A-7->g 3 /2-7 ? 7-^A'^ '/- 4^-7- 7>? /-? /-7f? r*l <r>^-y? it /*) HY /2-?c-7^ fiyy li2c#- Fm/isitJ - 9 ^?>:> //^ ^ 4/7 /X 4 . "I '7-5^ >?A ^^/fet OpcXjT**. fl '> ; / <r/-z x>.-w . U2 /J .v>-7f? 1t.>nLY.':z rec.^ tf . // > <r!?u /!/ rr /A - Ip-y '-1 <T? 4 4, V 7?tW. ^7 A 4. -jVzVcf. ? tX-'Xo-ytf itr,'/ ,-rv i'<ho rPJi? 4 tfrittrY ''/'" ("7'/4.. tcrn ^07->^ ' Pi? '{>rr-? /X-Xl-tG t>2J farl'KiT fc-ZftAAj.- M0O<030> >2 7 1 }t?rriiOf>r.?.-rr<r>F /<? -27-7S VOf fi?i:ZAT*Z_____ f k PERSONNEL SAVING LOG SHEET * p rCf+srtS'/Z - f y 7 't\ / x ? EMPLOYEES NAME S.S. NUM3ER TIME 1 REMARKS VCM PPM EDC PPM x.Lp mas: wop.: /Jr ^ .. /f'.- j? 7' <* //I A.=* <r A F> f-lt? ^ 7'/, X . -*' /i' . bV /Jr ,\fr X'- /J c ? AJn . c'?ct Pj-) 0 Ap f-liz S It? r F>,21 (O 0 A 1 k) CS APx s x'o /. 4- > X><^i f- /c . .H'l , /S' r> /U<r> r^r Ply? &1/Z . r,.l\/~/*. bLk `Jvt-v'-tiA '* /-- '7^5 1 ./T 7 JLJ F> - H r> i ! , 'A i1 i /. i' ;<n ,\j<r> X.V'5 po. -, PERSONNEL SAVING LOG SHEET Interoffice Correspondence ' 1 -- __ To: From: Date: K. W. Sanders J. R. Whitflll January 10, 1979 Subject: PERSONNEL EXPOSURE TO EDO IN THE SOLVENTS PLANT O 118-C Listed below is a tabulation from February 1976 to October 1978 of personnel exposure to EDO in the Solvents Plant. These results are for an eight hour TWA in ppm by volume. Vie started using the statistical environmental monitoring program in February 1976, how ever, data is available back to 1973. DATE Feb., March , & April 1976 May, June, i July 1976 Aug., Sept. & Oct. 1976 Nov., Dec. & Jan, 1977 February 1977 March 1977 Apri 1 1977 May 1977 June 1977 July 1977 August 1977 September 1977 October 1977 November 1977 December 1977 January 1978 February 1978 March 1978 Apri 1 1978 May 1978 June 1978 July 1978 August 1978 September 1978 NO. OF SAMPLES 135 63 363 43 44 61 47 48 46 57 41 . ' 48 54 46 40 46 51 50 48 48 54 54 65 59 AVG. LOW 2.25 0.01 0.99 0.01 2.77 0.01 2.05 0.01 4.31 0.4C 3.18 0.05 4.37 0.09 2.83 0.01 2.98 0.01 1.62 0.01 1.89 0.01 1.80 0.01 5.28 0.01 3.48 0.01 3.72 0.01 1.82 0.01 1.67 0.01 1.77 0.01 2.01 0.01 2.20 ' 0.01 3.79 0.05 6.09 0.11 3.74 0.10 4.26 0.01 HIGH 26.3 6.8 31.9 17.8 27.1 35.2 61.0 24.4 22.0 18.0 13.3 15.9 85.6 39.3 23.3 8.2 5.5 9.6 16.8 22.3 36.8 34.0 40.7 74.1 Diamond Shamrock SL 080983 B* /. -- ^ I I io/iox Kesearcn Laboratories, !nc. 553 NORTH BROADWAY SPENCERVILLc, OHIO 45S87 PHONE (419) 547-4196 MUTAGENIC STUDIES July to December 1975 PREPARED BY: . C CONDUCTED FOR: , Bio/Tox Research Laboratories, Inc 553 North Broadway Spencerville, Ohio 45887 :: Electro Chemicals Division .Diamond Shamrock Chemical Company v *. P. 0. Box 191 Palnesville, Ohio 44077 Mr. Jack Borror SUPERVISED BY; C Mamdouh H. Abou-Youssef, Ph.D., . Project Manager Tana L. Joy, M. T. (ASCP) Lab Supervisor SL 080984 Introduction There is considerable evidence chat, with few exceptions, 12 3 4 carcinogens are mutagens. ' * ' This supports the desir ability of using this type of rpid and economical test system as a pre-screening technique to pinpoint potentially dangerous chemicals among the thousands of chemicals to which humans are exposed. A great deal of evidence that carcino gens are mutagens has been obtained using very sensitive and simple bacterial systems for detecting chemical mutagens. Such systems are generally inexpensive, allow the screening of large number os chemicals in a relatively short period of * time, and most proximal carcinogens exhibit genetic activity when tested. 1'2 ' 5 ' 6 Since many of the chemical carcinogens require metabolic activation in vivo, it becomes necessary to employ either a mammalian host or an appropriate in vitro enzyme system to carry out the essential activation of these compounds. The Host-Mediated Assay technique was developed by Gabridge 7 and Legator to bridge the gap between in vitro microbial studies and definitive tests in mammals. In this assay, the mammal, during treatment with a potential chemical mutagen, is injected with an indcator microorganism in which mutation fre quencies can be measured. After a sufficient time period, the microorganisms are withdrawn from the animal and the induction g of mutants is delcrmined. The host-mediated assay is partic ularly suited to identify those agents requiring activation by more than a single tissue or organ. SL 080985 References Cited 1. Ames, B. N., The Detection of Chemical Mutagens with Enteric Bacteria. Tn Chemical Mutagens: Principles and Methods For Their Detection. A. Hollaender (Ed.), Plenum Press, New York and London (1971). - * . J 2. Ames, B. N., A Bacterial System For Detecting Mutagens and Carcinogens. In Mutagenic Effects of Environmental Contami nants. M. E. Sutton & M. 1. Harris (Ed.) Academic Press, New York (1972). 3. Ames, B. N., Lee, P. D. & Durston, W. E. An Improved Bacterial Test System for the Detection and Classification of Mutagens and Carcinogens. Proc. Nat. Acad. Sci., U.S.A. 70:782-786 (1973). 4. McCann, J. and Ames, B. N. A Simple Method for Detecting Environmental Carcinogens as Mutagens. Annals of New York Acad, Sci. in press (1975). 5. McCann, J., Spingarn, N. E., Kobari, J., and Ames, B. N. Detection of Carcinogens as Mutagens; Bacterial Tester Strains with R Factor Plasmids, Proc, Natl. Acad. Sci., U.S.A. 72 (1975) 979-983. 6. Zimmerman, F. K. Induction of Mutatic Gene Conversion by Mutagens, Mutation Res. 11:327 (1971). 080986 7. Gabridge, M. G. and Legator, M.S. A Host-Medicated Microbial 'Assay for the Detection of Mutagenic Compounds, Proc . Soc. Exp11. Biol. Med. 130:831 (1969). 4 8. Legator, M. S. and Mailing, H. V. The Host-Mediated Assay, % A Practical Procedure for Evaluating/Potential Mutagenic Agents in Mammals. In Chemical Mutagens, A. Hollaender (Ed.) Plenum Press, New York and London (1971). SL 080987 I. In Vitro Mutagenicity Test Methodology 1. Test Organisms: Four (4) histidine-dependent strains of S. typhimuriun (TA-1530, TA-1535, TA-9S and TA-10Q) and two (2) tryptophan-dependent strains of E. Co 1i (B/rWP^ and B/r-WP^-hcr) were used, 2. Mutation Test Media for S. typhimurium: Minimal agar media was prepared by dissolving in distilled water (800 ml), successively, MgSO^.lt^O (0.2 gm), citric acid H20 (5.0 gm), K^HPO^ (10.0 gm), NaNH^PO^ (3.5 gm), and agar (15.0 gm). The media was sterilized by autoclaving. Before pouring plates, 200 ml of sterile 20% glucose was added to the media. 3 Mutation Test Media for E. Coli: Minimal agar media was prepared by dissolving in distilled water (800 ml), succes sively, (NH4)2 S04 (1.0 gm), KH2P04 (20.0 gm), MgS04 (0,1 gm), trisodium citrate (0.05 gm), and agar (15.0 gm). The pH was adjusted to 7 with KOH and the media was sterilized by autoclaving. Before pouring plates, 200 ml of sterile 2% glucose was added to the media. 4. Top Agar: Top agar was prepared by dissolving 0.6 gm agar and 0.6 gm NaCl In 100 ml distilled water. Top agar was sterilized by autoclaving. The top agar was used for both E. Coli and S. typhimuriun mutation test; 5 ug/ml trypto phan and 50 uM histidine-HCl/50 uM biotin were added to top agar, respectively. The trace of tryptophan and histidine SL 080988 i in' the top agar allows the bacteria on the plates to under go several divisions; this gro is necessary in many'cases for mutagenesis to occur. * Procedure 4 % 1. To tubes containing 2-5 ml of top agar, kept at 45C in a water bath, 0.1 ml of tester strain culture was added. The tubes were then mixed and poured onto the center of petri plates of minimal agar media. 2. After the top agar had hardened, compounds we;a added to the plates. One (1) to five (5) ug of the compound was added near the edge of the plate with a spatula. 3. Controls of spontaneous mutation and positive controls using nitrofuran for E. Coli and B-propiolactone for S. typhimuriun were included for each tester strain on separate plates. 4. Plates were incubated at 37C for 48 hours. Results are reported as (+) for positive, (-) for negative or (-) for questionable. Explanation of Table Table I summarizes in vitro results of the compounds tested for mutagenic activity. Salmonella typhimurium TA-1530, TA-1535 TA-98 and TA-100, and E. Coli ATCC 023231 and ATCC (723233 were used as indicators. Results are reported as (-) , ( + ) or (*) . SL 080989 r r\ u TABLE I In Vitro Results of 1,2 Dichloroethane Tested for Mutagenic Activity. Compound E. Coll ATCC-23231 ATCC-2 32 33 1,2 - Dichloroethane (-) (-) In Vitro TA-1530 (-) Positive Control B-propiola c tone C = 63 (NItrofuran) (-) <-) <-> (+) (-) (NT) (-) sign Indicates that no mutagenic activity was detected (NT) Not tested S. Typhtmurium TA-1535 TA-98 (-) (-) % ` TA-100 (-) (+) (NT) (+) (NT) . (+) (NT) SL 080990 r XI. Sub-Acute Host-Mediated Assay Materials 1. Animals; Swiss male albino mice, weighing 18-23 grams were used A * fc 2. Test Organism: Histidine-dependent S. typhimuriurn TA-100 was used. The tester strain was inoculated into tryptone broth and incubated for two hours at 37C before used. 3. Media: a. Minimal agar media was prepared as mentioned earlier (in vitro mutagenicity test). b. Tryptone agar media was prepared by dissolving 10 gms of tryptone and 15 gms agar in 1000 ml distilled water. The media was sterilized by autoclaving. ' A. Compounds: Three (3) levels of test chemical compounds were dissolved or suspended in 10% ethanol saline. ( Proced ure* * 1. Mice were divided into four (A) groups of ten (10) mice each. 2. Groups of mice were treated as follows: Treatment Number of Animals * High level 10 Intermediate Level 10 Low Level 10 Negative Control 10 All animals were dosed orally by intubation for five days. SL 080991 3. The. tester strain of S. typhimurlum (TA-100) was diluted 1:10 with tryptone broth and incubated for 2 hours at 37C. before use. Two milliliter of the resulting suspension was injected intraperitoneally into each mouse. 4. All mice were killed four (4) hours later and 2 ml of sterile saline was injected intraperitoneally. As much fluid as possible was removed aseptically from the peritoneal cavity and put in sterile tube. 5. Ten-fold serial dilutions of each peritoneal exudate yielding a concentration series from 10 -0 through 10 - 7 were made in sterile saline. 6. For enumeration of total bacterial counts, 10 -`7 and 10 dilutions were plated on tryptone agar; three (3) plates per sample, 0.1 ml per plate. 7. For total mutant counts, 10 ^ and 10 ^ dilutions were plated on minimal agar; three (3) plates per sample, 0.2 ml per plate. 8. Plates were incubated at 37C.; tryptone agar plates for .I 18 hours; minimal agar plates for 40 hours. 9. Bacterial scoring was calculated as follows: CFU/ml of sample/plate =^ ' ---y1 on-i es ^ 1 a L e x 5 (mutant) No. plates 10 (total count) CFU/ml x dilution factor - CFU/ml in undiluted sample Mutation frequency (MF) Total mutants Total bacterial count SL 080992 Explanation of Tables Table II summarizes the host-mediated assay results for mutagenic activity. The compound was administered orally to mice for five (5) days. . Conclusion* Test was considered negative since the mutation frequency of test compound was not significantly greater than that of negative control *The EDC study, and the conclusions drawn therefrom, was part of a study conducted by Diamond Shamrock encompassing numerous other compounds. i SL 080993 4r TABLE II Host-mediated Assay Results following Sub-acute Administration (Intubation) of 1,2 Dichloroetbane*in Mice. Comp ound Concentration mg/kg/day x 5 Mean MF* MFt/MFc** 1,2-Dichloroethane 450 45 4.5 5 X 10-7 3 X 102 X 10 1.2 0.8 0.5 * Mean MF = Mean Mutation Frequency Mean total mutant cells3 ^ Mean total bacterial cells Mean total mutant cells = total mutant cells per 10 mice 10 ^Mean total bacterial count total bacterial count per 10 mice 10 ** MFt/MFc = Ratio between mean mutation frequency of test chemical (MFt) and mean mutation frequency of negative control (MFc).c (MFt/MFc)C = Mutation Frequency of experimental sample Mutation Frequency of control sample MFt/MFc = 1.00 for control sample SL 080994 . III. Dominan c Lethal A s s a v Objective The objective of the dominant lethal study was to evaluate the mutagenic potential of 1,2 dichloroethane when given orally to sexually mature male rats, A 4 Haterials 1. Test Chemicals The test chemical was received from Electro Chemicals Division, Diamond Shamrock Chemical Company on July 8, 1975. 2. Positive Control* 3 Cytoxan R , brand of cyclophosphamide, was obtained from Mead Johnson Company, Evansville, Indiana. 3. AnimaIs Sexually mature'male and female rats (11-14 weeks old), Sprague-Dawley derived rats were obtained from Spartan Research Animals, Haslett, Michigan and from Flow Labs, Dublin, Virginia. Methods 1. Housing All rats were housed in wire bottom cages suspended over litter. Males were housed individually or with one (1) female during breeding. Females were individually housed during quarantine and after breeding. Commercial rat feed in pellet form (Purina Rat Chow - Ralston Purina Company, SL 080995 St. Louis, Missouri) and water were available ad libitum at alltimes. C 2. Dosing Dosing solutions or suspensions*were prepared in peanut oil. The positive control solution was prepared by dissolving cyclophosphamide in sterile distilled water to make 20 mg/ml. Peanut oil was used as negative control solution. 3. Dosage Groups a. Acute Treatment The male rats were divided into selected dosage groups for an acute (single oral dose) study. Positive control rats were dosed intraperitoneally. Rats assigned to test compounds were dosed orally The experimental design was as foilows : Compound 'Group No. of Males Treatment 1,2-Dichloroethane . 1 2 3 4 10 17.5 mg/rat 10 35.0 mg/rat 10 70.0 mg/rat 10 140.0 mg/rat Positive Control 1 10 40.0 mg/rat \ Negative Control 1 40 2.0 ml/rat * Doses were administered at a constant volume of 2 ml/rat. b. Subacute Treatment The male rats were divided into selected dosage groups for the subacute study. Animals were dosed orally by C SL 080996 intubation for five (5) consecutive days at a total dose equal to the dose employed on the previously cited acute study. The experimental design was as follows: Compound Group No. of Ma les Treatment/Day For 5 Days* 1,2-Dichloroethane 1 2 3 4 10 3.5 mg/rat 10 7.0 mg/rat 10 14.0 mg/rat 10 28.0 mg/rat Positive Control Negative Control 1 10 40.0 mg/rat 1 40 2.0 ml/rat * Doses were administered at a constand volume of 2.0 ml/rat 4. Mating Males in the acute studies were placed in breeding cages immediately after dosing, while males in the subacute studies were placed in breeding cages after the fifth dose. Each male was paired with one, 11-14 week old, virgin female rat for seven (7) days. On the seventh day each male was removed and placed with a new female. This procedure was repeated weekly for eight (8) weeks. t 5. Maintenance and Observations Females were received five (5) days prior to mating, checked for illness, and isolated individually until they were placed with males. SL 080997 w^ After seven (7) days vith males, the females were again housed individually for 12 days. They were then sacrificed on day 19 and necropsie'd. Uteri were removed, implantation sites examined, resorptions and formed fetuses were counted, 4 and fetal deaths were noted. Percent fertility, number of implantations, and number of resorptions were recorded by week. Males were observed daily for compound effects. Food and water intake of both sexes were monitored daily for changes. 6. Statistical Methods l '! Fertility, implantation sites per female, and number of deaths per gravid female were compared by use of the Student's-t test. All groups were compared to the positive control and to their respective negative control groups (PC. 01). Results 1. Mortality - f. Table III summarizes the results of the acute and subacute percent survival of male rats treated with 1,2-dichloroethane, Deaths were recorded according to dose of compound per rat. The only death during the studies occurred in week three in a high dose subacute male. SL 080998 Table hi Male Treatment And Percent Survival 1,2-D1CHL0R0ETHANS Acute tudy Single Dosage (mg/rat) Yteeks 12 35 6 7 8 17.5 35 70 xko 100 100 100 100 1C^ 100 100 100 100 100 100 100 10 w 100 100 ' 100 ; 100 100 100 100 1 100 * 100 100 100 100 100 100 100 100 100 100 1C Negative Control Positive Control 100 100 100 100 100 100 100 100 100 100 100. 100 100 100 100 100 * Subacute Study * " - + * * 5 Daily Dosages (mg/rat) .3-5 7 Hi 28 V/eeks 12 3 6_ 1 I / 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 10 c .100 100 100 100 .100 100 . 100 100 100 100 90 90 90 90 90 90 Sl> o809" 4 2. Fertility C Results of percent fertility for test chemicals are shown in Tables IV and V. These tables show no differences in A the percent fertility in the acute or .subacute- studies when compared with the saline negative control group results. 3. Implant Sites Results of average implants per gravid female are shown In Tables VI through VII. The acute study (Table VI) shows that the test chemical has no effect on the implant sites. However, the subacute study (Table VII) indicates that there were instances of weekly implantation sites c per female being lower than the negative control. A. Resorption and Fetal Death ( Tables VIII and IX show results of average resorptions per gravid female for acute and subacute studies on 1,2- i dichloroethane. There were no significant differences between test and negative control groups in the acute study (Table VIII). There was one Instance of weekly resorptions being higher than negative control at 28 mg/rat in the subacute study (Table IX). However, there was no dose relationship in number of resorptions across groups on a total basis. C SL 081000 Single Dosage (mg/rat) t 1 2 - -rs Table iv Percent Fertility 1,2-DICHLOROETHANE Acute Study V* Weeks 3 h16 7 ' Cumulative 8 Mean 17.5 35 70 140 90.0 100.0 90.0 100.0 100.0 100.0 100.0 100.0 90.0 100.0 100.0 90.0 90.0 100.0 100.0 100.0. 80.0 70.0 100.0. . 100.0 90.0 100.0 90.0 100.0 80.Q ; 100.0 100.0 100.0 100.0 100.0 ' 80.0-" -*< 80.0 Negative3 Control . Positiveb Control 85.0- 97.5 95.0. 97.5- 97.5 90.0 97.5 80.0 90.0 100 ;0 100.0- 90.0 _ 90.0 . J40.0 a . Peanut Oil Cyclophosphamide * 97.5. 20.0 97.50 96.30 91.30 92.50 , 94.69 76.25 1 .un (4.63) (5.18) (11.26) (10.35) . (4.71) (29-73). T SL 081001 ri f Table y Percent Fertility 1,2-DICHLOROETHAME Subacute Study 5 Daily Weeks Dosages Cumulative Standard (mg/rat) 1 2 3 4 1 6 1 8 Mean Deviation 3.5 7 14 2*8 90.0 90.0 100.0 100.0 90.0 90.0 70.0 80.0 100.0 100.0 100.0 90.0 ( 90.0 1 100.0 .100.0 '100.0 100.0 . 100.0 100.0 90.0a` 100.0' 100.0 100.0 100.0 100.0 . 70.0 \ 90.0 60.0. 80.0 'V 6o.o 88.9 ,);77.8 91-25 . 86.25 91.25 94.58 * Negative** Control (* Positive Control 85-0 80.0 97*5 95.0 97.5 97-5 90.0 100.0 100.0 .. 90.0 90.0 90.0 97.5 40.0 97.5 20.0 ; 94.69 76.25 (9.9D (15.06) (14.58) * (4.71) (29.73) b" Male died on last day of breeding period: c" Peanut Oil " Cyclophosphamide non pregnant female may not have been bred. V / /'N O cry CO S L 081002 ^ n 4 C Table vi Average Implants Per Gravid Female 1, 2-DICHL0F.0STHAi;S Acute Study 1/eek Dosage (mg/rat) 17.5 . 35 11 140 Negative a Control Positive Control 1. 14.1 2 14.1 3 14.3 1-3 Ave. 14.2 -- 4 5 6 13-5 1^1.3 14.1 7 14.7 8 12.6 4-8 Ave. Mean 13.8 i 14.0 (S.D.) c (0.65) 14.4 14.6 14.6 14.5 14.0 14.3 14.7 12. 8 13-7 13-9 . 14.1 (0.64) 13-3 13.0 14.2 15.0 13.6 13.1 12.0 11.7 14.5 13.8 , 14.4 13.5 13.8 .. ; ' 13.3 12.1 12.9 13-1 * 14.8 14.6" 14.0 14.0 13.7 . 14.6 13.9 13.8 12.5 .14.0 13.2 14.3 14.1 14.0 12.5 12.9 13.6 13-7 . (0.58) 14.0 i.f ; t ` 14.0 -* , 13.8 ; 14.2 ` * t ** > v .1. ;i9' .#5* 12.6 13.7 -,13.9. v . i; *12.7 (o'. 78) (0.83) ' ` J (i.yi) a Peanut Oil b Cyclophosphamide S. D. = Standard Deviation SL 081003 X % Week Table vn Average Implants Per Gravid Female 1,2-DlCHLOHOETKAMS Subacute Study 5 Daily Dosages (mg/rat) 1 14 28 Negative Control - Positive Control 1 14.1 14.2 `2 12.1 11.0 `'3 13.8 13-6 1-3 Ave. 4 13.3 12.9 ll.2-NC 12.`6~N 5 / 13.0"$' 14.1 6 13.3 12.3 7 13.6 12.3-N .8 12.9" .. 11.8 U-8 * Ave. ; I2.8rw .12.6*$ 16.0 13.8 14.0 13.3 13.7 13.4 14.6 . 13.5 12.9"n 11.8"$ 13.8 13.4 . 12.9 13-2 11.8"N 14.9 13.312.9~n ll. ? A 13.0 14.2 12-0 13-8 13.3 14.6 14.6 14.0 14.0 14.0 14.2 ' Mean 13.0 (S.D.)A (0.96) 12.7 (1.15) 13.6 (1.22) 13.2 (1.03) . 13-9 (0.83) 15.0 11.7 12.1 ' 12.9 14.0 13.9 13.2 12.5 9.5 .. . 12.6 .12.7 (1.71) a= Peanut Oil * ` , -' Cyclophosphamide . Significantly decreased (P<0.01) = Standard Deviation SL 081004 Table vm C 'Average Resorptions Per Gravid Female ' 1,2-DICHL0R0STHANE Acute Study YJeek 17-5 Dosage (n ~/rat) 35 70 140 Negative Control Positivi Control .1 2 3 1-3 Ave. ^ .* 4 y. / 5 6 : 7 8 y. .. . 4-8 Ave. 1.10 . 0.80 0.67 0. 86 0.80 0.70 0.60 . ' 0..80 1.10 i. 0.80 O.56 1.^10 0.50 0.82 0.67 0.67 0.40. 0.80 0.60 0.63 1.25 0.^3 1.20 0.96 0.50 1.33 0.70 ' 0.78 1.20 0.90 0.38 1.20 0.50 0.94 .0.69 0.71 0.69 0.90 1.30 0.80 0.38 0.63 O.78 0.^9 0.72 1.64 0.77 0.97 0.8 0.92 i 4.75 2.67 3.10 .3.51 2.50 1.00 0.67 0.50 `V* l'.oo * ... 1.13 Mean 0.82 (s.d.;)C (0.189) 0.70 (0.308) 0.92 (0.363) 0.76 * 0.87 (0.356) (0.347;. -2.02 (1.488) Peanut Oil * ***= Cyclophosphamide c*= Significantly decreased (P<_0.01) * t * . * " '' ' 4 . V SL 081005  V7eek Table IX Average Resorptions Per Gravid Female A 1,2-DICHL0RQ5THAN5 Subacute Study 5 Daily Dosa hSs (ng/rat) 3-5 1 14 28 Negative a Control Positive Control 1 1.11 1.14 1.11 0.70 0.94 2 1.56 1.50 1.60 1.33 0.69 3 1.00 1.20 0.70 i.67+N 0.71 ' 1-3 Ave. 1.22 1.28 1.14 1.23 0.78 *4 0.90 1.20 1.20 1.44 0.49 `5 1.56 0.50 0.60 1.11 0.72 6 0.78 1.56 1.20 1.33 7 0.80 0.89 ' O'. 50 0.75 e - 0.l4 1.0CT .0. 88 0.51 .4-8 . Ave. ' 0.84 1.03 " ,-v' /. . 0.88 Mean 0.98 1.12 0.97 (S.D.)d (0.457) (0.338) (0.370) 1.03 * 1,11 (0.398) 1.64 0.77 '0.97 * 0.92 0.87 (0.347) 4.75 2.67 3.10 \ 3.51 '2.50 1.00 0.67 0.50 1.00 1.13 2.02 (1.488) (P =<.01) . _ , / ./ ^ Peanut Oil = Cyclophosphamide ^*= Significantly elevated *= Standard Deviation :' ; (P =<[.01) SL 081006 f Conclusions* Statistical analysis of the data comparing numbers of implants and dead per litter in control versus test groups indicate' that 1,2-dichloroethane may be suspect. We suggest that 1,2-dichloro ethane be tested again. *The EDC study, and the conclusions drawn therefrom, was part of a study conducted by Diamond Shamrock encompassing numerous other compounds. \ SL 08l7 ALBERT C. CLARK VICE PRESIDENT TECHNICAL DIRECTOR \3 MANUFACTURING CHEMISTS ASSOCIATION 1825 CONNECTICUT AVENUE, N.W., WASHINGTON. D.C. 20009 TELEPHONE; (202) 328-4240 TELEX 89617 (MCA WSH) December 18, 1978 Docket Officer U. S. Department of Labor Occupational Safety and Health Administration Third Street and Constitution Ave., N. W. Washington, D. C. 20210 Subject: Dear Sir: Request for Information--Occupational Exposure to 1,2-Dichloroethane, Do, cket No. 11-079 t / ' Please be advised that the following studies on 1,2Dichloroethane (EDC) are being administered by the Manufacturing Chemists Association (MCA). Inhalation--being conducted by Professor Maltoni of Mont edison and Dr. Spreafico of "Mario Negri". Exposures have been completed and the pathology is in progress. (See my letters dated December 22, 1978 and June 6, 1978, sent to the Honorable Eula Bingham, Assistant Secretary of Labor.) Metabolism--being conducted by Dr. Spreafico of "Mario Negri". Teratology-being conducted at The Toxicology Research Laboratory, The Dow Chemical Company. Reproduction-being conducted at The Toxicology Research Laboratory, The. Dow Chemical Company. i As is MCA's policy, all final reports will be sent to the appropriate government* agencies as they become available. Sincerely, SL 081008