Document O1GvKvwpY17EYLJNQvnV0oM6j

Jinn-, tnr,i >th the vertical ail(l can be expressed a,, ibutions. Therefore, nitions of concentral ipling must be sUffi.' rage concentrations :ted at Hanford dur. ditions indicate that . least one hour are atisfy the normality :ases a few hours of saury. However, the iso re<|uire that the il parameters exhibit ampling period. But nal variations of the era, this no-trend rere difficult to satisfy is lengthened. Therend the no-trend re s conflict it becomes ,o evaluate diffusion f a field testing prot superadiabutic conin the field tests conittempt is being made u which 1) will pro 's for engineers con cern of air pollution nose evaluating diffu se experimental data (*. A.; Mteurrjlair<?( Works. RlchUnd. \* Amrien MetroruJo*lcl H. <.: A Ktuorometrte cmliotu lUtllutuKlml Science* .* C\mt(tNny( Jtfchlartil. W*sb from Spirit re number 3 umn of page he article: Duplicating fetter. Sep- vX.yYi.u_xd-- Ou4,c(jz ]lf^ $cife Handling Procedures for Compounds ^-/w) Developed by the Petro-Chemical Industry CHARLES HENRI HINE, M.D.. Ph.D.. Consulting Toxiculogiit N. W. JACOBSEN, Supervisor, Safety end Industrial Hygiene Shell Development Company, Emeryville. California rfHls paper describes the methods used in J. establishing safe handling procedures fQ1- petro-chemical compounds originating j,, the Shell Development laboratories. Prob lems concerned with safe handling of chemjcsls in u research and development Inborntory difTer from those in a manufacturing company. These differences occur because the number of persons exposed is fewer, the quantity of compounds is smuiler, the time ,,f contact is shorter, the number of com pounds is greater, procedures are more (tried, and information about the toxicity it less complete and frequently lucking. In the Shell Development Compnny, it is management's responsibility to see that con ditions are as safe as it is practicable to mtke them, and to insure that persons work ing with new compounds, processes and ap plications, know the hazards involved and the precautions to be taken. To meet this responsibility effectively, management de pends upon information and recommenda tions prepared by the following stnfT groups: 1) the Safety Board, composed of mem bers of management whose decisions de lineate policy relating to industrial hygiene aid safety matters; t2) the Snfety Comnittee, a group of technical and non-techaical personnel appointed by the manager tl the laboratories, to study specific safety problems and review recommendations thich are made by its subcommittees; (3) Departmental Safety Committees, which *** appointed by, and are responsible to, the Department Heads. , e*wnted lit the Sixth Annual IniUl.lrlsl HntUi Con- T***' Houxton, Texas. October I, 1053. Jh- Hiwt Is also Associate Clinical Professor of Phann- *nd Toxieolocr. University of California. Sehool Medicine. San Francisco, and Associate Clinical Pro- f Industrial Toxicology. School ot PubUe Health, vbtrtlty of California. Ocrkelry. In addition, professional personnel, en gineers trained in industrial hygiene and siifety, and the toxicologist, serve in an ad visory capacity. Upon these persons falls the immediate responsibility of evaluating hazards and making recommendations for safe handling procedures. The extent to which each of these groups und persons may participate depends on the magnitude of the problem. The problem is defined in terms of (1) toxicity of the compound, (2) the number and training of exposed persons, and (3) in dustrial hygiene aspects of preparation anil development. Requests for investigation into the haz ard of a process or the toxicity of a new compound may originate from several sources. The most usual source is by per sonal request from a chemist or engineer in charge of a project. This exchange of information is usually carried but on an informal basis unless the number of per sons involved is' sufficiently large, or the toxicity of the compound is sufficiently great, to warrant its investigation by a sub committee of the Snfety Committee. In the hitter case, formal recommendations are made by the subcommittee following its in terviews with the toxicologist, the industrial hygiene and safety engineers, and following their inspection of the process. Requests for information may also originate from the Market Development Department. This de partment coordinates and disseminates tox icological information to the other Shell Companies mid potential customers. The majority of experimental work in toxieology is coordinated through this department. Re ports made to this group'are usually more formal and represent a more studied opin ion. Occasionally, investigations are origi- EM002987 Jtwr. tar,i natod by the toxicologist as a result of his findings of intoxication in exposed person nel. More extensive animal testing may be subsequently undertaken and industrial hy giene practices are reviewed together with existing engineering design and safe hand ling precautions. As has been outlined, the first step in es tablishing safe handling procedures is to define the toxicity of the compound. In the case of older compounds, this may already be established and reference can be made to published duta of experimental and clin ical nature. However, with new compounds, there are but two approaches: (1) to ex plore the compound in terms of theoretical, biochemorphology (relation of chemicnl structure to biological activity) and (2) to apply experimentation. Biochemorphological studies require an intimate knowledge of pharmacology, biochemistry. and path ology. This is the method of preference when there is a limited quantity of com pound, when it is closely related structural ly to well known compounds, or when it is in a stage of embryonic development. Tox icity data of an experimental nature are de veloped by studying the effects of the com pound, usually on laboratory animals and occasionally on man. Since 193C, Shell De velopment has maintained a research pro gram with a nearby medical school through which toxicological evaluations can be made. The extent of the toxicological investiga tion depends upon the stage of development of the compound in the research laboratory and the need for additional toxicological information. In the early stages, informa- tion of u simple nature as to acute toxicity classes and skin- and eye-irritating pro. perties is generally all that is required. |n other words, an attempt is made to integral* the development of toxicological duta with the orderly market development of th* agent. In preliminary toxicological test,, information is obtained on the approximate quantity of the chemicul which will kill a laboratory animal. These tests are made by exposing an animal to the vapors, placing the compound on the skin or in the stomach. Having obtained this information, tiie datt are then translated by one of two methods; either by reference to procedures similar to those described by Hodge und Sterner* (Table I), or by reference to compounds familiar to the chemist through previous experience. In the'first method, one defines the toxicity of the compound, using com mon terms, with reference to the quantity necessary to produce deuth in a rat or rab bit by a specified route of administration (Table I). As the development of the com pound passes to the pilot plant stage, addi tional information is obtained. Experiments are then designed to determine the effects of repented exposures to varied concentra tions of <1lists and vapors, repeated contact with the skin and repealed daily ingestion ot small quantities in the diet. By these tests an attempt is made to define the following levels of exposure: (1) those which produce no significant change in behavior, activity and growth of an animat, (2) those which Hnwix, K. C., und STKnnkh, J. II.: Tatmtathm ( Toxicity Hhium*. Atnrr. Itvu. /tiooi. (Juurfrrlf. 10:4, 03 (December). 1040. Toxicity Rating I 2 3 4 6 0 Commonly Used Term F.xtremely Toxic Highly Toxic Moderately Toxic Slightly Toxic Practically nun*toxlc Relatively harmtet* TABLE I. . Combined Tabulation of Toxicity Classes Vsrioua Route* of Administration LD50 Single Oral Doe*. Rate Inhalation 4 Hr. Vapor Expoa. Mortality of 2/6*4/6 Rata LUGO Skin Rabbits 1 mgm. or lett/kg <10 ppm 6 mgm. or teea/kg 1*60 mgm. 10*100 6*43 mgm. 60*600 mgm. 100*1000 44*340 mgm. 0,6*6 Cm. 1000-10,000 .36-2.81 (im./k( 6*16 Cm. 10,000*100,000 2.82-22.68 Gm./kr 16 Cm. and more > 100.000 22.0 or morn Cm./kg Pmhabie lethal lino for Man A taate. I grain 1 tcanp<Mm 4 ce. 1 ox. 30 Cm. 1 pint 260 Cm. 1 quart l quart luil" will chan clu>n that II CO Thet Com einl icul ilill'e mis ' live also tion. age turn ruth date Corr aid ph.v men the tim< witl mei1 ntiv quit elm mul tier irri infi suit for ten '1 pro lien tali Ida Cllll fes tor thi exj hn: me sol llo Ue far of tin mi h ir W - n ; r `: : r : : 3 . J . - j i EM002988 -- ; rr- UJ| pr> V I June, lost nature as to acute toxicity n- and eye-irritating pro- ally all that is required. In attempt is made to integrate of toxicological data with irket development of the minary toxicological tests, btained on the approximate chemical which will kill a al. These tests are made by mu! to the vupors, placing the skin or in the stomach. 1 this information, the data ted by one of two methods; nee to procedures similar to by Hodge and Sterner* y reference to compounds chemist through previous he first method, one defines the compound, using corn 's reference to the quantity <duce death in a rat or rab- ed route of administration he development of the comthe pilot plant stage, addi- on is obtained. Experiments ed to determine the effects osures to varied concentreud vapors, repeated contact d repented daily ingestion of in the diet. By these tests uide to define the following e: (1) those which produce hange in behavior, activity in animal, (2) those which *4 STTOtNOt J, H.: Tabulation of trr, tlf/O. Amh. Quarterly, . IS49. -ASSES LD8Q Skin lUbblU aum. or haa/ke 13 mn. 'MO nura. 2.B1 -2Z5* Cm./kx t or more Gm./kjf Probable Lethal Dm* for Han A tut*. 1 train 1 l*Apoon 4 ee. 1 ox. 30 Cm* 1 pint 250 Cm. 1 quart >1 quart Industrial Hygiene Quarterly -US will just produce abnormal organ weight changes, minimal tissue damage or minimal change in the function of an organ, and (3) that which is incompatible with survival of ,i considerable portion of the test species. These tests may run from 30 to 90 days. Compounds which are assured of commer cial production will be given even more crit ical evaluation in terms of levels producing different types of injury over extended peri ls of time. In uddition to defining the rela tive toxicity of a compound, nn attempt 1h also made to ascertain its mechanism of ac tion, probable detoxication and rate of stor age and elimination from the body. This in formation serves as a basis for developing rational antidoting procedures. At an early date, information is made available to the Company's nursing staff as to suitable first aid measures and to the attending panel of physicians as to desirable methods of treat ment of exposed personnel. In addition to the methods of animnl experimentation, at times controlled experiments are carried out with human volunteers. By such direct measures, information may be obtained rel ative to the minimal quantity of vapors re quired to produce threshold sensory changes, such as, olfactory stimulation, eye and mucous membrane irritation, central nervous system effects (or possible skinirritating and sensitizing properties). Such information is useful in helping establish suitable maximum allowable concentrations for the compound (and in defining the po tential dermatological problem). The second approach is to analyze the problem in terms of the number and quali fications of personnel; for example, is it a laboratory, an intermediate scale or a semi plant problem? Initial studies are usually conducted or directed by a few skilled pro fessionals working under excellent labora tory conditions. Consequently, exposures at this level are minimal. These persons are expected to familiarize themselves with the hazard of their operation and to take com mensurate precautions. If they desire conaultation on safe handling, the services of the health conservation group are available. Regulatory measures for this group are largely unnecessary. When a larger number of persons becomes involved in a problem, the degree of supervision from the health *nd safety standpoint must be increased. For example, if requests are made of other departments for investigation of the physi cal and chemical properties of the com pound, some Information must lie transmit ted with the sample as to its toxicity, skinirritating properties and expiosibiiity. When the compound progresses to the pilot plant stage, a study is made by both the depart mental Safety Committee and, if requested, by subgroups of the Safety Committee as well. The final step in definition is to survey the industrial hygiene aspects of prepara tion and development. This is the responsi bility of the supervisor of safety and indus trial hygiene. His responsibilities in the ini tial phase of an investigation are usually to suggest what protective clothing is suitable and whether the process demands u barri cade or special ventilation. In intermediate and pilot stage operations, additional meth ods for control are investigated and recom mendations made. These may include tech niques for waste disposal, procedures for decontamination, and selection of additional protective equipment. At present, air an-. alyses for special contaminants are not car ried out on a routine basis; however, deter minations of this type can be performed in instances where there have been specific complaints or when physical examination through the Company's health conservation program has uncovered evidence of intoxica tion. General compulsory health appraisals are not conducted on a Company-wide basis; however, all personnel in the semi-plant areas and those exposed to unusually hazard ous substances are covered in our health conservation program. As a part of this pro gram, u preliminary assessment of the in dividual's status is made prior to his period of exposure, and re-examinations are con ducted at intervals commensurate with xthe degree of hazard. When possible, data ob tained from these examinations are coordi nated with environmental findings. The clinical laboratory examinations which are a part of this health evaluation program usually include routine blood and urine analysis, bleeding and' clotting time and icterus indices determinations. Liver and kidney function tests are done when ever indicated. Biochemical tests which indi-. cate the quantity of toxin in a body fluid or EM002989 i i i i tu June. I !tr,; excreta, or alterations in normal biochem istry, are utilized more rarely. These ex aminations also provide a check on the en gineering design and prescribed protective measures. Another method which has been found useful in early assessment of possible intoxication is to require all personnel with complaints associated with chemical expo sure to report immediately to the toxicolo gist for interview and examination. A record of these complaints and findings is crossfiled under the suspected ascent. This facilitates determination of the number and kind of complaints associated with any particular chemical or process. VVe usually describe the number of complnints and the cases of alterations in physical and laboratory find ings in terms of man hours of exposure, in computing rates, we find the potential hours of exposure can easily be ascertained by re ference to payroll cards, since cost account ing is kept in terms of man hours expended on a particular project. So far, methods of determining the de cree of hazard encountered in particular processes or from handling specific chemical substances and the methods used in recogni tion of resulting altered physiology have been presented. To establish safe handling procedures, it is necessary to establish en gineering control and adequate medical supervision and care; however, this is not enough. The individuals concerned must be cognizant of specific precautionary methods and impressed with the necessity for apply ing these at all times. This is accomplished by formal and informal discussions. The most common method of disseminating in formation is by interview with the Depart ment Ucud and those persons who will be directly concerned in the project. Close liai son is maintained with the head of Experi mental Plants so that as new compounds are scheduled for manufacture the Safety En gineer and the First Aid group may be alerted to the necessity for carrying out their functions. Occasionally, discussions may take a more formal turn and a group. meeting will be held on a conference basis,. with discussion augmented by demons! r.v tion of toxic elfccls in animals. At I lie r(,. . quest of certuin department heads. th>jr Safety Committees have received lecture on the general aims of the health conserva. tion program and the methods for establish ing safe handling of compounds, to hett(.r acquaint their stair with this activity. 1 A safety manual has been prepared f,,r general use and it is the responsibility ,,f every employee who is in laboratory nr vclopment work to become familial- with the procedures outlined in this manual. Thpr is a general section on chemical hazards ami background information on toxicity; this includes a list of the maximum allowable concentrations for a number of compound* found in the laboratory. Certain compounds are designated as being so hazardous that they require a Hazardous Work Hermit prior to their use. In this way, it is possible for the Safety Engineer to inspect an ex tremely hazardous process, or one invulv. ing very toxic chemicals, before any ex posure has occurred. The final method for dissemination of information is by circula tion of current abstracts pertaining to safe ty, industrial hygiene and toxicological mat ters among nil professional personnel. These abstracts are prepared from current litera ture by a rotating committee, reviewed by the toxicologist, and disseminated as an ad dendum to the lists of new material avail able in the library. The results of this program have been most satisfactory. No fatalities have c- curred from chemical exposure in the en tire history of the Shell Development Com pany. Intoxications from exposure to'com pounds have been kept to a minimum, ns hu lost time due to injury. Finally, a back ground of know-how in handling compounds safely has been developed, which can be transmitted to the tnauufacturiag com panies and to potential users of the com pounds. iie new Yong university. Post-Graduate Medical School, Department of In Tdustrial Medicine together with the College of Engineering presented a course in Air Pollution, May 10 to 21. This comprehensive two-week training period in cluded lectures on all phases of Air Pollution, presented by recognized authorities in the field. ' EF002990