mfety in the chemical laboratory
edited by MALCOLM M . RENFREW University 01 idaha MOSCOW, Idaho 83843
Toxic Chemicals: Understanding TLV's Rudolph Gerlach Muskingum College. New Concord, OH 43762 Contrary to popular belief, man's exposure to, and concern for, toxic substances is not a recent phenomenon. A reasonably strong case can he made to support the theory that the fall of the Roman Empire was a t least partially due to lead poisoning of the leaders and other elite resulting from food and water consumption from lead utensils. Later, in the 16th century, Paraeelsus and Agricola were prominent in making popular the practice of using alchemy for the preparation of medicines (I). In particular, Paraeelsus stressed the importance of minerals as well as plants as sources of medicine. This led him to the use of mercury compounds, even though practice had shown them to be toxie. The intentional ingestion of potentially toxic substances continued throuah the 19th century when it was common pr& tice to test new compounds by tasting (2). Recognition that certain materials were hazardous also occurred relatively early. As early as 1775, Percival Pott was reporting the high incidence of scrotum cancer among London chimney sweeps (3). Events of more recent times have increased awareness of toxic substances in the air. A killer smog over the Meuse Valley of Belgium in December, 1930, resulted in 60 deaths in excess of the normal for that period. Farm animals were also stricken with SOz poisoning (4). A similar smog over Donora, Pennsylvania, lasted for 4 days in October, 1948. At least 20 deaths were directly attributed to toxic fumes (4). Legal efforts to protect the general population of the United States from undue exposure to toxie substances began in 1903 when a federal law was passed prohibiting the over-the-counter sale of a poisonous substance as a medicine. This law was the consequence of a death resulting from the use of an uncontrolled quantity of arsenic compound as a beauty aid. In 1939 the Federal Drug.Act was ~ a s s e d I. t reauired the
I
Rudy Geriach received his BS in Chem istry from MuskingumCaiiegs, his MSfrom Ohio State University, and his PhD from Waiden University. He is currently on the teaching stall of MuskingumCollege. Also. lor the last five years he has served as a Consultant to the J.T. Baker Chemical Company, primarily serving as an instru* tor in their Hazardous Chemical Safety School. At Muskingum College his teaching responsibilities inqlude analytical chemistry and chemical safety. His reSearch interests lie in lhe area of environmental chemistry.
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Journal of Chemical Education
testing of compounds administered to humans. Legislation has proceeded to the point that now the burden of protecting the employee is placed on the employer. This has been accomplished through the passage of several laws hy the federal government. Some of the more important ones are: 1) Occupational Safety and Health Act (OSHA) of 1970 2) Clean Air Act (CAA) of 1970 3) Federal Water Pollution Control Act (FWPCA) of 1972 4) Federal Food, Drug, and Cametie A d of 1938 5) Federal Hazardous Substances Act of 1970 6) Poison Prevention Packaging Control A d of 1970 7) Toxic Suhstances Control Act (TSCA) nf 1Mr. " . A " . "
8) Resource Recovery and Conservation Act (RCRA) of 1976 9) Hazardous Communication (OSHA)
Scientific Background In order to establish regulations controlling the exposure of employees to toxie substances certain parameters must he Legally established. Among these are certain definitions of terms. These definitions are published in the Federal Hazardous Suhstances Act of 1964 (FHSA). An appropriate definition of what constitutes a toxic chemical appears in Dorland's Medical Dictionary. I t is given as, "Any or chemical which when ingested. inhaled. ~~, absorbed. or when aonlied to. inierted into ,, ~~, or drr.rlo& within the body. in relstiwly smnll amuunts, by itn rhemiral artion may cause damage to structure or disturbance of function." Although this is essentially the operational definition upon which our laws are based it is not a quantitative statement. I t does not state what "relatively small quantities" are or what constitutes "damage to structure or disturbance of function". There are other defined terms that are useful hut certainly not the required statements for quantizing efforts to protect employees from overexposure to toxic suhstances. Among these are (5): ~~~
1) Acute toxicity-"effect manifested on short exposure on single contact, ingestion, or inhalation" 2) Chronic toaicity-"is that effect ohserved when a toxicant acts on body
tissue over a long period of time, days or years" In other words, the evaluation of the toxicity of chemicals must be performed in the lahoratory. From a purely scientific viewpoint the evaluations would be performed on humans since it is they who are to he protected. However, moral, legal, and ethical considerations have always somewhat limited such studies. We have come a long way since Harvey Wiley, the first Chief of the Bureau of Chemistry of the US. Department of Agriculture and the person responsible for the enforcement of the Food and Drug Act of 1906, used human volunteers in "poison squad experiments". According to a 1968 study, the presently accepted toxie levels for toxic chemicals were estahlished in the following ways (6): 1) Human experience in
industry 2) Human volunteer experiments 3) Chronic animal inhalation studies 4) Animal injection studies 5) Analogy
38% 11% 20% 5% 24%
The use of humans to ohtain toxicity data is becoming more difficult to do, and therefore more animal studies are being used. The transfer of results obtained withexperimental animals to humans is difficult because there are differences in ahsorption, distribution, excretion, and metabolism in addition to anatomical differences. On the other hand, human data lack experimental control, and interpretation may be eomplicated by other factors. These include the subject, dose duration of exposure, sex, race, temperature, altitude, humidity, sensitivity, and the many stresses under which humans operate. Therefore, animal studies are used even though the extrapolation of toxicological data from animals to humans is often difficult and sometimes inadvisable. Current acute toxicity studies on animals are hased upon what is known as LDm (lethal dose 50) which was developed in 1937 by Trevan as a graphic index of toxicity (7). The LDm of a substance is that quantity required to kill 50%of an animal population in 14 days. The route of entry is specified, and the dose is usually reported as milligrams per kilogram body weight. Living animals are usually sacrificed for tissue studies. (Continued on page A102)
The animal species used in such studies is often the rat, but others such as mice, dogs, ducks, birds, and monkeys also are used. Note that the LDw makes no indication of the physical well-being of the 50% of the population which survived. When the toxicant is airborne the term LCWis used. Other terms are LDlo and LCm. These are the same as those above except that they measure the dose far a 10%kill. NIOSH also uses L D b (Lethal Dose Low): the lowest dose, other than LDw, of a substance intraduced by any route, other than inhalation, over any given period of time in one or more divided portions and reported to have caused death in humans or animals. Obviously, the exposures to humans which will produce LDso or LDlo are too severe for acceptance by any society. An attempt to determine tolerable limits has been undertaken for many years by the American Conference of Governmental Industrial Hygienists (ACGM). The organization yearly publishes a booklet listing the toxicity levels mouo for a new " , of chemicals (81. ,~. The ACGlH has the rrgisterrd trademark "TLV" (Threshuld Limit Value) as the term used to express tolerable concentrations. The TLV of a compound is an estimate extrapolated from some defined damage to humans or animals at higher concentrations or by drawing analogies between similar com~ounds.Quite often the" are determin& hy takiig a c o n r c n t r a r i & ~ . ~of ) l the LDw. It rs hased upon the assumptiun that rume concentration docs exist where nu in~
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~
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Journal of Chemical Education
jurious effect will occur no matter how often the exposure is repeated Although most threshold limits have this huilt in safety factor it is im~ortantto realize that this safety factor & not of Large enough magnitude to assure safety in cases of grass deviations from the normal work environment. As an example, the ACGIH booklet states that continuous work a t 90 OF, or extended overtime which extends the work week from 40 hours to 50 hourslweek, might be considered as gross deviations (9). TLV values are based upon an average population and so do not apply to individuals who are hvoersensitive to a varietv of industrial cheGicals. Methods have been published for detecting hypersensitive people (10,Il). The ACGIH reports these concentrations in three ways: 1) TLV-TWA-The Time-Weighted Average exposure usually over an eighthour work day. 2) TLV-STEL-The maxim* Short Term Exposure Limit to which the average worker can be exposed without experiencing either irritation, irreversible tissue damage, or narcosis. 3) TLV-C-The Ceiling value is the value not to be exceeded even for an instant. The logic behind the TLV-TWA value is that a worker's exposure is not uniform but rather varies thrauehout the workshift. I t is " expressed mathematically as:
("""""") (""7) time A +
TLV-TWA =
I t is important to note that most reported TWA values are based upon a40-hour work week. Therefore, work facilities adapting unique work schedules, such as the 10-hour day, may be flirting with the gross deviation mentioned earlier. TLV-STEL involves the fact there may be short term exposure to concentrations which exceed TLV-TWA. I t places time and concentration limits on such excursions beyond TLV-TWA. The concentration will vary from compound to compound but the time limit is the same for all, four 15-minute excursions beyond TLV-TWA per day, but 60 minutes must o m between each one. STEL's are based on at Least one of the following criteria (12): 1) Adopted TLV's including those with a "C"or "ceiling" Limit 2) Pennsylvania Short Term Limits for Exposure to Airborne Contaminants (PA Dept. of Health, chap. 4, Act 432, Rev. Jan 25,1968). 3) OSHA Occupational Safety and Health Stds., 40 FR 23073, May 28, 1975 4) NIOSH criteria for recommended standards for occupational exposure to specific substances The ACGIH cautions that STEL values are not to be used as engineering design c r teria. (Continued on page A1051
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total time worked per shift
+
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TLV-C regulates those substances that are predominantly fast-acting in their effects. The Occupational Safety and Health Act, passed in 1970, incorporated the 1968 ACGIH list and in effect made it mandatory. However, the ACGIH trademark registration has Led NIOSHIOSHA to designate another set of terms. PEL, Permissable Exposure Limit, replaces TLV. Most PEL'S are time-weighted average levels for an eight-hour exposure. Many are the same value as TLV-TWA. NIOSHIOSHA also defines an IDLH, Immediately Dangerous to Life and Health. It is an estimate of the "maximum level from which one could eseane within 30 minutes without any esrape-impairing symptoms or any irrewraible health effrrtr" (13). One must exercire considerable caution when using these values because an exposure to toxies quite often involved more than one substance. All of the ahove methods involve single chemical exposure. In many cases of multiple exposure the toxic effects are additive. An example would be acetone and formaldehyde. In some cases the exposure may result in synergistic effects. Ethanol and chlorinated hydrocarhons give such an effect. Some chemicals give an antagonistic effect. Welders often experience a combination of nitrogen oxides and iron oxides. These two toxies act antagonistically. The -~~~ACGIH recommends that in the ahsenceof information to thecontrary the toxic efleuu of a multiple exposure he considered additive (1.1). Mathematically this means ~~~~~
~
~
~~~
~
~
~
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where C represents the measured atmospheric concentrations and T is the corresponding threshold limit. If the sum exceeds 1, then it is to he assumed that TLV has been exceeded. The TLV, PEL, and IDLH values also fail to account for the accumulation of certain chemicals such as heavy metals in the body. It is difficult to assess this danger because the accumulation may he arising from very small exposure concentrations. In addition these permissible exposure levels as published by ACGIH and NIOSHIOSHA are designed to protect only the worker. They fail to address the more difficult problem of protecting the unborn child who is carried into the workplace by pregnant workers. Chronic toxicity is much more time consuming and expensive to determine than acute. Such tests typically involve 400 carefully cared for animals over a period of 2 years.. They are divided into a control group and three others that each receive a different constant dose. Equal numbers of males and females are used throughout. They are fed and given medical examinations during the test period. A total of 20 are sacrificed a t 3 months, 6 months, 1 year, and 1.5 years. The remainder are sacrificed a t the end of the test period. Autopsies of the sacrificed animals involve over 1800 tissue examinations and the medical evaluations involve over 40,WO physicals. The total cost for such an investieation can he over $300.000 (15). " The magnitude of our current prohlems in collecting toxicological data become appar-
ent when it is realized that the ahove studies have been conducted on only a fraction of the seven million plus chemical compounds that are currently known to man.
Reliable toxicological data are both difficult and expensive to obtain. The extrapolation of animal test datais somewhat dubious many times and thus casts doubt on the validity of the stated permissible level of exposure for humans. However, such data are often the best information we have for the protection of workera and students. It behooves all of u s to make use of the available information in our quest to protect ourselves and others. Knowledge is power only when it is applied.
(1) Asimov, I. "&no& Biographical E n c y e l d i a of Scienn and Technolow"; Doubleday: Gwded City. NY, 1961: P 58. (2) Car% D. E.; Fernando. Q. J. Ckm. Edve 1979.56, 284. (3) Ottoboni,M."TbeDmeMakea thePaiaoo":Vineo"ta Books: Berkeley, 19% P 140. (4) Llppert.F. W. "The Associationof HumanMortality wfh Air Pollution: Sfstiatieal Analysis": University ~ i - f i l m s International: Ann Arbar, MI, 1981: p 7. (5) "Hazardam Chemical Safety"; J. T. Baker Chemical Co.:PhiUi~sbum,NJ, 198": chap 3, p 2. (6) Ref.5, p 8: ser.tsn.483. W. ROC.R. (7) nevsn, (8) "TLVaforChemiurlSub8tantantantantanndPhysical Asen* in the Workroom Envimnment with Intended Changd': ACGIH: Cincinnati,1980. (9) "TLVs for Chwieal Substancesand Phylieal Agents in the Workroom Environment with Intended C h a n g ~far 1981.85": ACGIH: Cincinnati. 19W. p 8. (10) Stoker, H. E.; Scheel, L.D. J. Occup. Med. 1913,15, 564. (11) Stoker, H. E.; Mountain, J. T.; Scheel, L. D. Ann. N Y Acod. Sei. 1968.151,388.
(141 Ref. 9, p 47. (15) Ref. 5, chap 3. p 15.
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Volume 63 Number 4
April 1986
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