Document ymQoJ4YzBRvNqYY4dkg228VNV

R&S 136584 ESTABLISHING EXPOSURE TO VINYL CHLORIDE VAPOR 3Y BREATH ANALYSIS AND CONTINUOUS ENVIRONMENTAL SURVEILLANCE by Edward D. Baretta*, Richard. D. Stewart, M.D.*, and John E. Kutchler** * -Department of Environmental Medicine, Marquette University School of Medicine, Milwaukee, Wisconsin Environmental Health Section, Biochemical Research Laboratory, The Dow Chemical Company, Midland, Michigan For Presentation at the American Industrial Hygiene Conference St. Louis, Missouri May 13-17, 1968 R&S 136585 ABSTRACT An environmental survey was conducted to determine the tiraeweighted average exposure (TWA) of a group of chemical plant workers to vinyl chloride (VCl) vapor. This survey featured continuous multipoint air sampling and an alysis^ using an infrared spectrophotometer. The inhalation exposure data were digitized and recorded on paper tape for subsequent computer analysis and derivation of daily TWA values for each worker. A breath sampling program was conducted concurrently with the environmental survey, and a series of breath decay curves relating post-exposure breath concentration to vapor exposure were derived from the data. To validate the breath curves derived from on-the-job data, post-exposure breath curves were also constructed from breath data obtained following human exposures to controlled concentra tions of VCl vapor. The close agreement between post-exposure breath concentrations at the corresponding TWA's obtained by each of the methods suggests that either method is valid for estimating the worker's individual daily exposure to VCl, and provides further evidence that breath analysis is a useful in dustrial hygiene technique for evaluating exposure to vinyl. chloride vapor. R&S 136586 INTRODUCTION The question that may arise following an environmental survey is whether the chemical vapor concentrations measured are truly representative of the exposure being experienced by the workmen* Evaluation of the ranges of atmospheric concen trations and estimates of time-weighted average concentration (TWA) are all too often based on a few spot samples obtained under conditions which are not representative of all phases of a given operation. Necessarily, a true picture of vapor exposure would have to be based upon continuous monitoring of air in the workman's breathing zone during his entire workshift. Obviously, even when possible, this task is made difficult and often im possible by the large number and variety of tasks performed by today's modern chemical plant worker. Fortunately, improvements in automatic monitoring and data processing equipment have provided the means to a more satisfactory solution. Sequential samplers and automatic analyzers and re corders can now be used to monitor several locations or operations' simultaneously, thus providing much more valid data on which to base estimates of chemical exposure. The application of computer technology to industrial hygiene provides a means of managing the large volume of data generated by continuous monitors.'1' 2- - Meanwhile, a supplementary technique of measuring in halation exposure has been developed. The realization that the toterl body burden of a volatile chemical is diiectiy re lated to its concentration in expired air led to the develop ment of techniques for collecting and analyzing breath samples to better personalize the exposure experience of individual workman. Studies by Stewart, et al_. showed that exposures could be characterized by measuring the concentration of vapor in the breath at various time intervals following exposureand comparing these against breath decay curves already established. Thus, breath decay curves have been constructed for several common solvents for use in judging the severity of chronic or acute exposure to volatile organic chemicals.^^^ These breath decay curves were; for the most part, con structed from data obtained from controlled human exposures to relatively constant vapor concentrations. More recently, however, breath sampling programs have been used in the chemical plant and breath data collected from workers following their workshifts were combined with environmental survey data to construct additional 7 sets of breath decay curves. In this study of human exposure to vinyl chloride (VCl) vapor, breath decay curves obtained by each of the above methods, R&S 136587 R&S 136588 3- - controllea human exposures and on-the-job breath sampling were for the first time compared in an attempt to judge their equivalence and to demonstrate that: (1) Either method can be used to establish useful breath decay curves; (2) These curves provide a reliable index for evaluating the time-weighted average exposure of workers exposed to VC1 vapors; (3) Breath analysis^ because of its usefulness in establishing TWA, might be useful as a'rapid diagnostic tool, as a screening aid when used in conjunction with regular health inventory programs, or as a technique complementing the industrial hygiene survey in assessing exposure to VCl vapors. ENVIRONMENTAL SURVEY MID BREATH SAMPLING FOLLOWING ON-THE-JOB EXPOSURE Monitoring the Plant Atmosphere The chemical installation surveyed was a closed structure housing several separate chemical processing operations. A job survey was first conducted for each of four job classifications to determine the work areas frequented by men ip) R&S 136589 4- - them and the time spent in each area. For each classification, five sampling probes were then strategically placed in those areas which best represented the workman1s exposure day. A sixth probe was placed outside and charcoal and silica gel fil ters were placed in the sampling line to assure a clean air reference. The sample probes consisted of 3/8 inch O.D. Saran tubing through which air samples were drawn by means of a vacuum pump to a centrally located infrared spectrophotometer. The sampling rate was adjusted to an air flow of 17.5 liters/min The spectrophotometer was equipped with a 10-meter'path-length gas cell and was capable of detecting 5 ppm VCl. By previous calibration, the VCl concentration was directly proportional to absorbance up to about 1,000 ppm at the measured wave length, 10.63H . A schematic diagram of the sampling system is shown in Figure 1. Sampling was executed sequentially with a set of 6 two-way solenoid valves controlled by a timer which advanced the sampling location every 5 minutes. A visual account of transmittance was recorded on a strip chart recorder. Meanwhile the data were recorded in digital form on paper tape by a tape punch and digitizer programmed to record 3 equally spaced transmittances during the last half of each 5-minute sampling period. 6- - Figure 2 describes the exposure profiles (frequency distributions) for the four job classifications studied during this survey. These profiles show the percentage of time that concentrations exceeded the levels shown. They summarize several tens of thousands of individually measured concentrations and reduce them to single curves. Figure 3 shows the corrective trend brought about by actions undertaken to re duce the atmospheric concentration of VCl over the 7-month period during which the study was conducted. Only two job classifications warranted extensive study, but men in all four classifications were asked to participate in the breath sampling program. Breath Sampling Programs Three separate breath sampling programs were conducted concurrently with the environmental plant survey, as shown by the boxed portions in Figure 3. Each worker was asked to collect three breath samples daily, the first on his arrival home from work, the second 5-10 hours later and a final sample before re turning to work the following day. The samples were collected by providing each man (on a daily basis) with three breath 4 pipettes. The pipetpes were constructed from short lengths of 20 mm. soft glass tubing to which had been welded at each end, R&S 136590 5- - The transmittance data furnished by the spectrophoto meter was converted to absorbance and reduced to concentration according to Beers law: Abs = Log., n (X., - X ) Where: X^ = base line response X = response at total absorption X^ = response at location i i = 2,3,4,5,6 Finally, Concentration = K (Absorbance) Where K = a proportionality constant R&S 136591 The taped data were processed by a Burroughs 5500 Computer at The Dow Chemical Company Computation Research Laboratory. The computer was used to calculate the mean and standard deviation of concentrations at each location for each 8-hour workshift. Finally, time-weighted average concentrations were calculated for each job classification using the timelocation data obtained from the job surveys. As described elsewhere'1', the weighted percent of time during which concen trations exceeded several pre-chosen levels was also computed for use in establishing exposure profiles. R&S 136592 8- - DATA ANALYSIS The decay curves for the breath vinyl chloride con centrations were constructed by step-wise multipleregression using a digital computer. An empirical relationship of the form Cone = f (TWA, TIME) was selected from a choice of several terms, each based on TWA and/or TIME. The resulting regression equation best represents the ordered relationship between breath vinyl chloride concentration, time-weighted average exposures and post exposure time. The breath decay curves each have an associated standard error of regression which can be used to compute the confidence band for any chosen level of significance. The 95% confidence band for the mean of a group of observations was chosen in this case to describe the statistical error associated with the breath data and the regression technique. CONTROLLED HUMAN EXPOSURES Exposure Chamber Operation Three experimental human exposures to VC1 were conducted at nominal concentrations of 50, 250, and 500 ppm. The exposure chamber was a room measuring 41 ft. by 6 ft. by 7^ft. The room had a continuous positive air supply and exhaust system capable 7- - R&S 136593 the threaded portion of a 2-dram (8 ml.) screw-cap glass vial. (Figure 4). The overall length of the pipette was about 9 inches so it could be conveniently and inconspicuously transported to and from work in a lunch bucket. The plastic caps were lined with 6 layers of Saran film identical to that used for the construction of Saran air sampling bags. A 3/32 inch hole, pre-drillea through one of the caps provided a means of withdrawing samples. The Saran liners pro vided an effective gas barrier so that vapor losses were held to less than 10% for a holding period of about 3 days. Samples were drawn from the pipettes with a 1 ml. Hamilton gas-tight syringe and analyzed in an Aerograph A-6003 gas chromatograph using N2 carrier gas and a hydrogen flame detector. Separations were made with a 6 foot, 1/8 inch I.D. stainless steel column packed with Carbowax 2QM alkaline on Chromosorb W 60/80 mesh acid washed. When collecting a sample, the subject was asked to remove the caps, place the pipette to the lips, and breath normally in through the nose and out through the pipette three times, then to expel the fourth breath completely through the tube, quickly capping the tube, thus trapping alveolar air of the lungs. The importance of writing the name, date, exact time of sampling, and the workshift most recently completed, on the label attached to each pipette, was stressed. -10- gas chromqtograph were calibrated before each experiment and at intervals throughout the exposure day. Each 73$ hour exposure day included a one-half hour lunch period in an uncontaminated area outside the exposure chamber midway between two 3h hour exposure periods. The TWA concentration was calculated on the basis of a hour workshift to more closely agree with the plant work schedule. Clinical and Laboratory Procedures Each subject had been under careful medical surveillance by the medical department for a number of years and each was given a complete medical examination a few days prior to the VC1 exposures. Included were complete urinalysis, CBC with sed. rate and retie, count, SGOT, SGPT, 24-hour urine for hippuric and mendalic acids, and urobilinogen. Each subject received a repeat physical exam one hour before entering the exposure chamber. This examination included temperature, blood pressure, TR, neurological examination, breath and blood samples, and a questioning concerning any personal com plaints (headache, nausea, sore throat, etc.). After entering the chamber, total expired breath samples were collected every hour by having the subject breath out through a Saran tube leading to a Saran plastic collection bag located R&S 136594 R&S 136595 9- - of maintaining a slight negative pressure. Continuous distri bution of the chamber air was achieved by recirculating the air with a squirrel cage fan through a series of inlet and outlet ducts spanning the length of the chamber. The VCl was metered into the duct leading from the squirrel cage fan so that it entered the room atmosphere via the recirculation system at a rate sufficient to maintain the desired atmospheric concentration. VCl was introduced into the system from a pressurized cylinder through a coil made from 6 feet of 1/8 inch I.D. stainless steel tubing leading through a rotometer and finally through a short piece of rigid Saran tubing into the circulating air duct. A heating tape wrapped around the stainless steel tubing helped to volatilize and thus stabilize the flow of the vapor. The concentration of VCl in- the chamber was constantly monitored with a Perkin-Elmer Infrared Spectrophotometer equipped with a 10-meter path-length gas cell. A sampling probe, consist ing of h inch O.D. Saran tubing was centrally located during the exposure to represent the breathing zone of all subjects within the chamber. This probe was portable, however, and was used periodically to check and to balance out concentration gradients within the chamber. Breathing zone air samples were collected in breath pipettes and analyzed periodically as a check against the infrared monitor. Both the infrared, spectrophotometer and R&S 136596 -12- even those five were unable to detect it even with forced inspiration 5 minutes after the onset of exposure. Three of four subjects reentering the chamber after lunch were able to detect a faint odor of VC1. One subject could detect a faint odor upon deep inspiration up to about 15 minutes after entering the exposure chamber. The exposure had no noticeable effect on neurological responses or in the results of mental coordination or manual dexterity tests conducted during the exposure period. All clinical laboratory studies performed in the post-exposure period were normal and unchanged from pre-exposure values. The concentration of VC1 in the exhaled breath of subjects within the chamber was not significantly different from that con centration present in the exposure chamber at the time the mea surements were made. From past experience it has been noted that exhaled breath concentrations are significantly lower than ambient concentrations when the subject vapor is either easily and rapidly metabolized by the body, e.g., benzene, styrene,5 alcohols, etc., or when it has a low vapor pressure and is extremely soluble in the blood fat and body tissue, e.g., carbon tetrachloride, chloro form, tetrachloroethylene, etc. We assume from this observation that vinyl chloride rapidly comes to equilibrium with the blood and body tissues and probably is neither rapidly metabolized nor readily retained by the body tissues. 6S9i -11- outside the chamber. Tidal volume and total expiratory capacity were measured in the morning and again late in the afternoon exposure periods. 37 Subjective and neurological responses were measured upon entering the chamber at 15 minutes and at hour intervals there after. Flannagan Coordination and Crawford Manual Dexterity Tests were conducted in the mid-morning and afternoon hours. Breath sampling commenced immediately upon leaving the exposure chamber. A cumulative 24-hour urine sample was collected and a bloodsample was drawn the following morning for SGPT, LDA, alkaline phosphatase, BUN, creatinine and Bilirubin. Results From a subjective standpoint no serious untoward affects were noted at any of the exposure concentrations. The only com plaints were those of two subjects who reported headache and some dryness of the eyes and nose during the 500 ppm. exposure experi ments . No odor was detected by anyone entering the exposure chamber at 50 ppm. At 250 ppm all four subjects entering the chamber initially reported that they could detect a very slight odor of 4 the chemical. Five of the seven subjects entering the exposure chamber at 500 ppm were able to detect the odor of VCl, however, R&S 136598 -14- Plant Survey Ten workmen participated in the plant breath sampling program, producing a total of 91 usable sets of data. Ten percent of the breath samples collected were discarded because of pipette leakage, faulty seals, and poor sampling techniques. Absolute breath levels range from about 20 ppm in one sample taken in early postexposure period after an 8 hour TWA of 250 ppm to barely detectable levels (0.03 ppm) in samples taken after exposures at TWA's below 50 ppm. The extremely broad day-to-day variation in-the TWA's experienced by workmen during the period in which the breath sampling program was being conducted is demonstrated for three shifts of men bearing job classification "Coagulator Operator" in Figure 6. This illustration is presented to point out the fallacy of judging TWA's on the basis of spot sampling techniques. Even with continuous sampling, astute judgment and some educated guesswork may be required in estimating the degree of hazard encountered by a workman in the area. The remarkable correlation between breath concentration and TWA made it possible to construct the series of breath decay curves shown in Figure 7, with confidence bands only slightly wider than those from controlled human experiments. The close similarity between these curves and those constructed from controlled exposure data are further illustrated in Figure 8. R&S 136599 -13- TWA BREATH DECAY CURVES Controlled Exposures A total of 13 men participated in the three controlled chamber exposures at nominal concentrations of 50, 250, and 500 ppm producing a total of 160 valid breath data points. Five of the 6 subjects exposed to 50 ppm were reexposed at 500 ppm two days later. There was no measurable residual vinyl chloride de tected on the breaths of the subjects prior to the second ex posure. Serial breath sampling was initiated immediately upon leaving the exposure chamber and continued up to 20 hours follow ing the exposures. Table I shows the analyzed concentration to which the subjects were exposed. Calculations of the mean and standard deviation of exposure concentration are based on chart readings from the Infrared Spectrophotometer taken at 5-minute intervals over the two-3^ hour exposure periods. The TWA is for the total 7^5 hours which includes the \ hour lunch period in an uncontaminated atmosphere. The final breath decay curves intended for use as an index to VCl exposures were adjusted to TWA concentrations of 50, 250, and 500 ppm. (Figure 5). A 100 ppm decay curve was interpolated from the available data using regression analysis. These curves are presented with the calculated 95% confidence bands for the mean of a group of observations. R&S 136600 -16- This information can be used to provide the same health and economic advantages already cited. The decay curves presented by the authors are intended as an index of exposure for vinyl chloride and are based on a daily exposure duration of 7.5 hours for the controlled ex posures and 8 hours for the on-the-job study. Similar indices in use, or in various stages of development, reflect the need for similar studies with others of the more widely used organic chemicals. Certain vapors having extremely high solubility in the blood, fat and body tissue, and especially those which are not easily metabolized have a slight cumulative effect so that the increase in body burden may be detectable by a gradual upward shift in the breath decay curves following repeated daily ex posures until a steady state is reached. In the case of vinyl chloride, the body burden is extremely low by the end of a normal 16-hour decay period so that breath decay curves are not notice ably affected. There were no significant changes in either clinical or laboratory findings resulting from the controlled human exposures to 50, 250, and 500 ppm VCl. Neither were there complaints nor changes in neurological responses which could be attributed to exposures at these concentrations. Odor was not detectable upon -15- CONCLUSIONS The object of the environmental health survey is to identify .the atmospheric contaminants, determine their con centration and to relate this to the health hazard, if any, which they present. If one is to judge hazard by concentration measurements then those measurements must accurately describe the exposure on a continuing personal basis. A carefully con ducted survey combining continuous analysis of work room atmos phere with a comprehensive job study has certain benefits. For example, data useful in describing the exposure hazard, both acute and TWA, being experienced by workmen is obtained, and concurrently, information useful in establishing cycles or ex posure trends may help to reveal operational inefficiences and equipment malfunctions. Correcting these problems not only re stores a healthful work environment, but often results in bonus savings by reducing raw material and product losses. As a complementary technique, breath analysis has the advantage of personalizing each worker's integrated daily exposure^ however, some basis of comparison is needed in order to establish an exposure level from breath decay data. A reliable index of ex posure in the form of pre-established breath decay curves makes it possible to estimate the average daily exposure on the basis of a few serial breath samples taken in the postexposure period. R&S 136601 R&S 136602 CONTROLLED HUMAN EXPOSURE TO VINYL CHLORIDE No. Subjects TWA 7.5 hrs. _ (pwn) 6 43 4 248 4 459 7 (3.5 hrs) 491 Actual Chamber Cone. (ppm) 7 hrs. STD Me an + Dev 59 2 _j_ 261 8 493 + 7 491 + 5 Range Hi Lo 65 289 518 525 53 243 471 475 -17- entering the exposure chamber at 50 ppm. Although a slight odor was detected by most subjects at 250 and 500 ppm, olfactory fati gue was quite rapid and the odor could no longer be preceived within five minutes following the onset of exposure. R&S 136603 R&S 136604 Figure 1. Schematic diagram of infrared sampling system. Figure 2. Exposure profiles expressed as concentration vs. exposure frequency distribution for four job classifications. Figure 3. Weekly mean TWA exposure levels measured during the survey. Figure 4. Breath sampling pipette used to collect samples for G. C. analysis. Figure'^,' Breath decay curves. Constructed from breath data collected from workers during environmental survey. (8 hours) Figure 6. Daily and shift variations in exposure concentrations. "Coagulator Operator" Figure 'S. Breath decay curves based on controlled human exposure to 50, 250, and 500 ppm VCl (7.5 hours). Figure 8. Comparison of breath decay curves derived from plant survey data with those from controlled human exposures ' ' S 'T. A, -'C-t' Table I. Chamber concentrations and TWA calculated on the basis of 7.5 hr. work day including an 0.5 hr lunch period in an uncontaminated atmosphere. REFERENCES 1. Peterson, J. E., Hoyle, H. R. , Schneider, E. J. : Am. Ind. Hvcr. J- 27:180 (Mar 1966) . 2. Stewart, R. D., Gay, H. H., Erley, D. S-, Hake, C. L., Schaffer, A. W.: "Human Exposure to Tetrachloroethylene Vapor: Relationship of Expired Air and Blood Concentra tions to Exposure and Toxicity," Arch. Environmenta1 Health, 2:516-522, (May) 1961. 3. Stewart, R. D., Gay, H. H., Erley, D. S., Hake, C. L., Peterson, J. E.: "Observations on the Concentration of Trichloroethylene in Blood and Expired Air Following Exposure of Humans," Amer. Ind. Hyg. Assoc. J., 23:167-170, (April) 1962. 4. Stewart, R. D., and Rowe, V. K.: "Quinze Ans D'Etudes Sur Le 1,1,1-Trichloroethane," Archives Des Maladies Professicnnelles. 28:194-201, 1967. 5. Stewart, R. D., Dodd, H. C., Baretta, E. D., Schaffer, A. W. "Human Exposure to Styrene Vapor," Arch. Envir. Health, (In Press). 6. Stewart, R. D., Dodd, H. C., Baretta, E. D., Gay, H. H.: "Experimental Human Exposure to Tetrachloroethylene," Presented at the National AIHA Conference, May 1-5, 1967, Chicago, Illinois. (Manuscript in preparation) 7. Stewart, R. D., Dodd, H. C., Baretta, E. D., Schaffer, A. W. Mutchler, J. E.: "Chronic Overexposure to Benzene Vapor," Presented at the Sixth Annual Meeting of the Society of Toxicology, March 23-25, 1967, Atlanta, Georgia. (Manuscript in preparation.) 8. Saran bags. Supplied by Allen, R. E., Inc., 233 West Ohio Street, Kenton, Ohio. co O) O) o R&S EXPOSURE PROFILES -l#UR JOB CLASSIFICATIONS TIME-WEIGHTED % OF TIME THE CONCENTRATION EXCEEDED THAT SHAWM 909961. S9d SCHEMATIC DIAGRAM OF THE INFRARED MONITORING SYSTEM OUTSIDE AIR STATION I 9 X WORK AREA STATION 3 STATION 5 ________ iI STATION 2 I STATION 4 ! STATION S Q I9 9 I r-~l, ! j r r-_ "o i o 6 6 6" J R&S 136607 SUMMARY time-weighted mean EXPOSURE = O.OI o lI ) CjPj L____i i=2 Where C\ - mean concentration at Station i Pj = per cent of time spent at location i during normal work activity R&S 136608 609901. SSb 240 WEEKLY MEAN EXPOSURE LEVELS MEASURED DURING SURVEY 220 200 180 160 O COAGULATOR OPERATOR o DRYER OPERATOR BLENDER"PACKAGER POLYMER OPERATOR 140 TIME-WEIGHTED MEAN CONCENTRATION , PPM 100 80 60 40 20 0 till) .iitii__ 1 1 ! 1 1 DECEMBER JANUARY FEBRUARY cw- Xv--i T | U>i 11____1__L_1_J__1 J J__I 1 1 _J__Li__ fill! MARCH APRIL MAY JUNE R&S 136610 R&S 136611 R&$> 136612