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DU 039654 DUP 0949300 Haskell's Mission: Identifying the Risks Society today is acutely aware that many natural and man-made substances within the environment carry'some risk to health and safety The Haskell Laboratory for Toxicology and Industrial Medicine--one of industry s first major test centers for toxicology--was established m 1935 as part of the Du Pont Company's program to protect its employees, its customers and the public from such hazards. The Du Pont Company is committed to selling only products that can be manu factured. transported, consumed and disposed of without harm to workers, consumers or the environment. The company is managed with the conviction that ail injuries are preventable and tharili identified nsks to health can be contained. This does not mean that all risk can be eliminated--most endeavors contain a degree of risk. It does mean that risk can be controlled. The chemical industry has made possible many products widely used m contemporary society. Man-made fibers. finishes, plastics, agricultural chemicals and pharmaceuticals are all created by this industry Basic chemicals also are essential ingredients m the productive processes of other major industries. However, many of these chemicals are flammable, corrosive or toxic, and Du Pont recognizes its responsibility to insure that risks associated with its products are controlled. Haskell Laboratory is an essential element in imple menting this philosophy Its primary job is to determine the toxic properties of chemical compounds and the precautions Ans.vsis of P.ocd urine and tissuexeezs r^sxe~ $ patnz.ccy sectionzusv ~ere Dr A....am .</3_ss patr.z.ocvmanage: studies tissues :z -ee vr.ezte: res: zempeunds^ve caused abncma.ities rtasxe.. employees sncv/r. on tror.t save: starting at top and moving ciockwise are Wa*ter Kon.ecxr -left. 3nc Scccv Moore ;..n.-ra. rdemists A.ice Erwin c-oiog:st Lames Pussei, mc.ogist Terrv Greer . r.n.c.an and '<\'aace Sess.cks technician nasKeJ Labe:atorrzcerates m 105 00C square fee: or soace and w:zn a staffer about 225 An addition preser.t.y under gSEsiruCbon add another 45 00Q square leer __- Centra. ReseaiciL&IDeveiccmen: DepartmentE I du Fen; 2e Nemc-is and Cc me AcuCrruonpgytrcrgr.dTDteylEawCarre '.5856 DU 039655 DUP 0949301 fel!5liS5tggJL'.:..:il!JMi wrtmi r= 'rip T.~r,o v*es : irr.~r.rrcr:- that are required to use them safely What effects might the compound have if it is inhaled, swallowed, absorbed through the skin or splashed into the eye? Are there dangers if it combines with other sub stances? Could its disposal be harmful to the environment? Could an unintended use have dangerous side effects? These are the kinds of questions posed to Haskell's staff every day. Answers are sought through batteries of laboratory tests. Haskell determmes the degree of toxicity and the acceptable exposure levels at which the compound can be manufactured and used, utilizing laboratory animals m studies that can consume a few days or several years Many of its long-term tests are tor carcinogenicity : whether the substance causes cancer i. and considerable I attention is being devoted to I development of short-term i tests or assays that might help | identify carcinogenic compounds. The findings of Haskell's I studies, whether on new I compounds or existing I compounds used m Du Pont I products or processes, have a [number of uses They are.an .research .eading tc .mgrcvemer.is :r. :.he. resting process is an ongoing actsv.tv a: Haskeu Tr.;s c:sn ,s used :n 2 sncrt-cenr, assay :c identify Ccss;3e zarcmogens "~ important and sometimes decisive factor in whether to produce the compound at all. They are useful in the design or modification of industrial processes to achieve an acceptable level of safety. Many of the studies are required to comply with government laws or regulations. Haskell does not.work m a vacuum. Its scientists and managers are urconstant contact with Du Pont's manufacturing groups and top management. It is part of a companywide safety and health program that mcludes the monitoring of employee health Ar.irr.a, testing :or.s:::jtes a ma'crgcrtior. riaske:. s woik -Vf-.ite .ancra:c:^.:sts s:e most ttmrr.oTLV usee and :he nest pcssic.e ar.mr.a. rare ;s creviced on both an individual and group basis and the review of plant procedures by trained safety and health auditors. Laboratory personnel work with company engineers on plant design and with lawyers on product labeling. Organizationally, Haskell is part of the Central Research and Development Department, which reports directly to Du Pont's Executive Committee. An increasing emphasis on long-term studies and govern mental requirements has necessi tated larger staff and facilities. To keep up with such needs, the laboratory was enlarged by 40 percent m 1967 and by 70 percent in 1976. An addition which will increase the laboratory by another 40 percent is presently under construction, and is due to be completed by mid-1981. Whereas nme employees worked at Haskell m 1935. the lab has 226 employees today. 2 DUP 0949302 DU 039656 A New Idea in American Industry " 'We will run up against__ difficulties For instance:'the operating department will want to know 'why the laboratory doesn t produce something.' The saies department will want to know why the laboratory works up data that might make our customers believe our products are 'unsafe.'But we are embarked on our campaign with determin ation and it is only a question of time before the world recognizes that a very constructive thing has been done " Lammot duPont at the dedication of Haskeil Laboratory. 1935.L_. formalized program of medical surveillance for employees. TheJiazards became both more numerous and more complex1 when Du Pont was transformed from a maker of explosives to a diversified chemical manufacturing^ company in the years following World War I. Workers exposed to carbon disulfide when manufacturing cellophane and rayon were showing toxic effects. Those making tetraethyl lead, the-gasoline antiknock Tbs .s a scer.e mnr: ir.e :r:g:na. -iasked 24bcraiorv beSToated .n 1535 Ka:rerne Pa.dra The decision to build a laboratory for toxicology and industrial medicine was in its time, as a newspaper account then described it, a new idea in American industry,'' It was not. however, the first Du Pont Company action to make the workplace as safe as possible. Du Pont was founded in 1802 to manufacture explosives. The hazard in producing black powder was self-evident, and the company invoked stringent safety procedures. Employee safety became a keystone of company policy Health problems also were an early concern, and Du Pont was among the first American companies to provide a additive, faced the danger of lead porsomng It was discovered m the early 1930 s that beta-naphthylamme. an intermediate used :n the making of coal tar dy~s..-as related to an unusually high incidence of employee bladder tumors In response to these problems. DuPont initiated extensive'engineering and process improvements, it examined and treated affected employees, and it developed closed production systems that reduced exposure below the level that could be measured by the instruments of the time Equally important, the company launched a program to prevent such incidents from happening in the future and. at the recommendation of Medical Director George Gehrmann, constructed a laboratory of industrial toxicology to research such questions The facility was opened m 1935 on the site of Du Font s Experimental Station near Wiimingtom Delaware. It was named for Harry G. Haskell. Sr.. who as Director of the High Explosives Department has been credited with creating the company's Medical Division. Eighteen years later the laboratory moved to the present 386-acre site on the Maryland-Delaware border near Newark, Delaware 3 DUP 0949303 DU 039657 Seeking the Acceptable Exposure Level i Toxicology is the study of adverse effects of chemicals on various types of biological systems, including man. "All things are poisons . said the 16th century' scientist Paracelsus Only the dose decides that a thing is not poisonous, . . The point is still valid and is essential to an understanding of industrial medicine. Everything is potentially toxic it is the dcse wmch determines effect. 3y limiting the amount and frequency of exposure, it is possible to identify a level of dosage at which a hazardous substance has no significant adverse effects. Haskell's task is to find that acceptable exposure level. The classic procedure is to expose laboratory animals to test compounds: identify clinical signs that may be produced, find the dose-effect relationship, and project the findings to human situations. As awareness about human biochemistry increases, and as the tools of measurement become more sophisticated-- measurement m parts per billion is now common--the demand grows for a greater number and diversity of tests. There is also a corresponding increase m the time, complexity and cost involved m toxicological studies. Acute tests, in which the exposure to a chemical is of short duration, are distinguish able from chrome tests, where exposure to generally lower concentrations of a chemical occurs over a long period of time. Tests are divided not only between acute and chronic but also by the manner m which a compound is administered: by inhalation, Tbp The :eqv>ai examination and weighing c: ammais is an jnpcr.ar.: z s HaA wn.cr.s `makes n uitSiibei 4 A I DUP 0949304 DU 039658 MW ingestion, skin absorption or eye contact. Test animals are selected according to their similarity to man. For example, a rat s digestive process and respiratory system are generally similar to that of a human. Obviously, there are differences between animals and humans: nonetheless, the results of animal testing have proved to be highly useful in the study of health hazards in man. Attention to detail is vital x this kind of operation. The environment must be rigidly controlled to rule out extraneous factors, thus, laboratory air is filtered to prevent microorgan isms from conveying diseases which would bias test results. Because animals must be known to be free of disease, they are quarantined upon arnval. Thereafter, they are cared for by an expert staff headed by a veterinarian, fed a balanced diet and housed in environmentally controlled living quarters. The First Step "Thehrst step m testing is not m the laboratory but :n the library Haskell's information specialists compile all available information about a compound. A variety of data bases linked to the laboratory via computer terminal provides abstracts and bibliographic references- to published papers, many of which exist m Haskell's library. The library offers some 5,000 titles, as weil as subscriptions to approximately 300 foreign and domestic journals The result of this research is a report describing the sub stance--its physical properties and whatever is known of its acute and chronic toxicity including carcinogenicity, and its effects on wildlife and humans. The report will also incorporate information on the compound's teratogenicity > its ability to cause malformation in fetuses! and mutagenicity uts ability to induce basic alterations m genetic material! In some cases the report provides enough information to make the required decision. When it does not. it is heipfui m deciding which tests need to be conducted. Because they often work with hazardous chemicals, all laboratory employees strictly observe safe handling pre cautions. A Quality Assurance Committee monitors laboratory procedures to guarantee the accuracy of test results and interpretations. 5 DUP 0949305 DU 039659 Establishing a Baseline Short-term cr acute studies, me ::rs: step :r. the testing process are usedhe obtain .r.:c:mat:en cn inherent toxicity ar.d to establish a baseiine for' further vverk Cr.e initial study estabhsr.es the LD50 cr LC50. the dose cr concentration level ca.cu.atec to be fatal to one-half tr.e ar.imai population tested. While the nature of the cr.emical and its application determine the exact procedure, a basic test protocol exists. Oral, .nnalation. and dermal ocular studies may be conducted, with observation both during and after the exposure period. An oral study" is undertaken by exposing groups of white laboratory rats to multiple dcse levels. After the Jethai dose level, is established, the surviving rats are observed fohtwo weeks for clinical signs. JT7 If the substance tested is a -gas. dust, vaporhfume or mist, an inhalation study is under taken. In this instance .groups of rats are exposed "to the substance for a single four-hour period at different exposure levels. Since a substantial per centage of adverse effects from chemicals m piant situa tions involve the skin, acute dermal studies may also be "'ssr.r.p u-.i rtfs 5 r: .'S :a:s a rssr -.?* i-.trf.s:~ir. i I DUP 0949306 6 DU 039660 conducted. Skin irritation tests are of relatively bnef duration, lasting from 24 hours to three days, and generally coincide with acute oral and inhalation studies. Hair is clipped off the backs of rabbits or guinea pigs and a test compound is applied directly to the skin to gauge the resultmg irritation. Haskell also tests for allergic sensitization, and when animal tests allow the setting of safe levels, volunteers are used to test compounds where substantial skm contact is likely--as in hosiery or fibers used for carpet. These volunteers wear patches on the arm or leg, and regular checks are made to determine whether skm irritation results. A compound which can be spilled onto the skin can also come into contact with the eye. Thus, eye tests generally are conducted on rabbits while skm tests are under way. Such tests include a measure of the difference an eye wash can make if applied soon after exposure, simulating the time a worker needs to reach an eye wash station in a plant. The next step in the testing process is subacute studies to determine whether the material produces cumulative effects and what organ or organs are primarily involved. Typically, rats are exposed to one-fifth the LD50 or LC50 for 10 exposures over a two-week period. Some animals are sacrificed and the tissues examined by patholo gists at that point while others undergo a 14-day recovery period to see if effects of the exposure are reversible. Based on the acute and subacute studies, the matenal may be classified on a scale ranging from extremely toxic to relatively harmless. cO TJ tOu OtoJ o t t * 4 K DU 039661 Short-Tferm Assays Long-term aruma; tests, Haskell wasone of the rraditionaiy employed tc first industrial toxicological determine whether a chemical laboratories to use a salmonella/ ' can cause cnronic toxicity and liver microsome test developed cancer, cost substantial sums of., by Dr. Bruce.N. Ames, professor money--sometimes m excess of. of biochemistry at the University' tr.ree-cuarterso: a million dollars of California. The Ames test per compound--and take measures a chemical's ability several years to complete. Test to induce mutations in specific facilities and the supply of suit strains of bactena. Because a high able test animals are limited, and proportion of known carcinogens toxicologists and pathologists are m short supply As large numbers of compounds have been cause mutations in the Ames test, a compound that is mutagenic m this test is a candidate for more specific tests for carcinogenicity. Other assays that measure mutagenesis, transformation or DNA damage in cultured mammalian ceils are bemg evaluated for possible routine use at Haskeil. In this fast-changing field, no test has been sufficiently validated to constitute a reliable determinant of carcinogenesis. However, short-term assays have shown their value m helping set pnonnes for long-term animal tests. DUP 0949308 Above, .'r. a modification otitre standard Ames assay gases suer, as narcaikanes are tested tor mutageruc activity 5aczena are exposed to a zest gas .ncubated let 48 hours and then examined :or mutations Here oioiogist ,,ames Pussell is piacmg petri s.snes containing oaczer.a site seared cr.ambers 'Top .e.n. Haskett is investigating a two-stage rest :cr rumor .rutiaticn and promotion Two weexs alter a compound is appued tc me mouse s oacx 'arpromoter cr.emca. .s applied to accelerate a react.or. mat m,got omerwise occur airy alter a much .onger certod oi time Lent- Btoiogtst Macyiar.e Grant is weignng a ohermca: prat wl. be used :n roe Chinese hamster ovary CHO: test The CMC rest is one ot severarmutagerucity screens used cvHaskeu 8 DU 039662 -fin Adequate Margin of Safety Acute toxicity is relatively easy to recognize. Much more difficult to identify are effects from relatively low concentrations--parts per million or even parts per billion--accumulated over a prolonged period of time. To simulate these conditions. Haskell conducts studies using white rats or otnfer laboratory animals and lasting either 90 days or a lifetime, usually about two years. As m short-term studies, compounds may be admin istered to the animals orally, dermally or by inhalation, and the effect upon a control group is compared with the effect upon several groups repre senting different dose levels. The test may involve as many as 120 rats per sex per level for a two-year study. Blood and urine samples are analyzed at intervals during the study, and m a two-year test some animals will be sacrificed and examined at one year to determine the onset of tumors or other effects and to provide a reference point on tumor development. The objective in these long-term tests is to find an exposure level which when extrapolated to humans will produce no ill effects. Haskell can then advise the concerned industrial department and I 1 others that exposures limited to that level--aiong with engi neering controls and medical surveillance--should provide an adequate margin oT safety for workers or customers. ^ Sometimes Haskell recommends that a material not be used at all. as when it tested a Brommated biphenyl the company had found effective m protecting synthetic fibers against fire. As a result of toxicological data developed m a chronic oral study at Haskell. Du Pont decided to drop the compound. Teratology and Reproduction A chemical or drug with no known adverse effect upon thosecommg into direct contact with it at a particular concen tration may still adversely affect developing fetuses or future generations. Thus, Haskell conducts teratogenic (and sometimes reproduction) studies if women of childbearing potential are likely to be exposed to alchemical In teratoge.l.c studies, pregnant rats are exposed to test compounds for a period during gestation, and fetuses are examined for skeletal and other abnormalities. In reproduction studies, rats are exposed to the test substance and then mated m an effort to determine whether any effects are transmitted from one generation to another Six-htter. threegeneration reproduction studies may be conducted alone cr as par. Of a two-year testing program. Carcinogenicity Until fairly recently, it was thought that only a few substances caused cancer m :w-c raa.-r ,V :r.$ -es: .5 ?*:.-e."e.v: :x.::; r..'decree cacnr-cyed :echr..?:a~s s-:~. is rer-v j.ree: wsa; prccecr.ve r.cmnr w;:.- i se.:-7zr::a.r.c :rd ur.-nd. rc'cArr area cO -o ,,9 oco oCOo o CO DU 039663 ! humans--a textbook published in the early 1950's mentioned only three unadulterated agents We now know the list is much longer, although chemicals that are carcinogenic may have other serious toxic effects as well and may have already been tightly controfled as toxic substances. One reason for the diffi culty m recognizing human carcinogens is that 20 years or more may pass between exposure to a carcinogen and the appearance of cancer. Further complicating the problem is the lack of an exact correlation between animal and human carcinogens. ; If there is reason to control a chemical which poses a carcinogenic risk, actions are taken ranging from increased safety measures to abandoning production altogether. A large proportion of Haskell's twoyear tests are undertaken to determine whether a substance is carcinogenic and to establish a no-detectable effect exposure level. This permits the estab lishment of an acceptable level of exposure m the workplace or assures safe use of the product. For like other toxic effects, carcinogenesis is related to dose, and exposure can be limited to acceptable levels. 10 ii < DU 039664 DUP 0949310 Seeking iUmormalities i Instruments today are capable of measuring very small amounts cf a material. For example, a chemical particle on the head of a pm which is invisible even when magnified one thousand times can be detected by a high-pressure liquid chromatograph This instrument can measure concentrations as low as one-half part per billion. One result of this ever-increasing ability to identify materials at very low levels and of scientists' growing knowledge has been the discovery of contaminants of which man was previously unaware. Using these and other instruments Haskell scientists conduct analyses at regular intervals during the testmg process to establish baselines and seek abnormalities that may result from compounds administered m the studies. As m all areas, everything hinges on the accuracy of the data, and extra care is taken in laboratory procedures to assure that the results are accurate and complete Biochemistry Blood and urine analyses and metabolic studies are among the services performed by Haskell's biochemists to determine what happens when a chemical gets into the body They want to know such things as how much This ar.a.vucarmaruioic aJows Hasxe.. scientists :c gsnetate ftncwn 3tmcs?ne::c ccncen::a::cn5J5: ::~zruc vapors nv contfttr.g air Sew temperature and pressure Sztmar. Henry :s me chemist of the chemical is absorbed, how it is eliminated and whether it is chemically altered. In addition to its toxicological work, the biochemistry group also offers an analytical service for the laboratory and particularly for its industrial hygienists. For example, a plant physician may want help m establishing biological monitoring programs for workers exposed to a solvent: or a manufacturing department may want to establish the efficiency of absorbent materials used m worker respiratory masks. Pathology The last step in the testing process is taken by pathologists who perform autopsies on sacrificed animals, then examine the tissues microscopically Approximately 20.000 tissues can be generated m the course of a long-term study--more than 30 tissue samples from each of 640 animals--and the experienced eye of highly trained pathologists is needed to detect abnormalities. If tumors appear with a greater than normal frequency or within a shorter than usual time span, the determination of whether this is the result of the test material or of some unrelated factor is often difficult. Statistics Assistmg throughout the testmg and evaluation process are Haskell biostatisticians. They provide advice on such questions as the number of animals required for a statistically valid study, the dose level that will achieve a sufficient level of safety or the significance of abnormal findings by the pathologist. In short, whenever numbers are involved, the statistician is also involved. 11 DUP 0949311 DU 039665 IfcriMgaaaMAi Top; In order to determine possible detrunenutieffects of'Jie rest rompounas. the tissues from expenmentai anima.s exposed to a themicas are subiected to microscopic examination Dr Ki P lee staff pathologist examines a kidney tissue com exposed rats Top right. Computer systems are used :c collect and analyze test daoa Pesearcr, toxicoiogtst Dr Craig Wood examines'.the results of a recent tcxicoiogica. study 'left; 3iood counts ofammais are conducted on an automatic biood red counting apparatus to cnecktcr toxic effects of test cnemicais Here curucai cnemist Walter Kcmecki places a samp*e ofdiluted blood into the.counter 12 DU 039666 DUP 0949312 New Rentiers of Knowledge or Concern Increasingly, Haskell Laboratory ;s called upon to perform tests that extend beyond traditional acute and chronic toxicological studies. Some of these tests have been undertaken for years: others represent new frontiers of knowledge. For example Combustion/pyrolysis studies may be conducted to determine the harmful effects of gases generated when a substance bums. Chickens may be used to eval uate delayed neurotoxicity. Potentiation studies may be undertaken to gauge the effect of combining one compound with another. II Pharmacokinetic studies may belemployed to learn even more about the effects of .chemicals present in the body over,a period of tune. Genetic Toxicology Genetic toxicology studies are also expanding. In addition to the Ames assay and Chinese hamster ovary test, described previously, Haskell is estabkshlngHhcTevaluating new tests to measure the mutagenic and carcinogenic potential of com pounds. One such test is the sisterchromatid exchange assay. In this assay toxicologists observe the exchange of genetic material m dividing chromosomes. The test provides another indication of genetic damage and it can be performed with mammalian cells in culture (m vitroi or m live animals (m vivo). In another genetic toxicology test, rat liver cells are used to determine whether a chemical interacts with DNA by mea- sunng DNA repair. This test is very important because freshly isolated liver cells metabolize chemicals m a way very similar to m vivo metabolism. Here oiaogisi Paui Orjbe :s conducting a modified range finding Study on hJuegill sunhst which will give an indication as :o the toxicity ofthe test chemical This will be roilowed by a more dehmtive study to determine the LC50--the concentration which is ;echai to 50% o/a test population during a specified time period The results of these kinds of tests supply the toxicologists with valuable information to set priorities for higher level testing. There is a need, however, to develop additional assays designed to identify potential mutagens and carcinogens. Since different chemicals have different properties and are metabolized differently, no single assay will provide all the necessary information. Haskell's goal is to set up a senes of assays that will allow scientists to evaluate the genetic hazards of chemicals on a case-by-case basis i i f 13 DUP 0949313 DU 039667 Haskell's aquatic section also tests the ability of fish to absorb and store a compound dissolved m water--agnchemicais or heavy metals for instance The purpose is to determine whether eating such fish couid prove dangerous to humans or animals. In addition, spill situations can be simulated by using a cyclically flowing system which generates pulses of a chemical m water Aquatic Toxicology A chemical is to be barged up a river What are the potential hazards of a spill? A plant environmental coordinator needs help m preparing a demonstration project for the Environmental Protection Agency Haskell supplies the answers and the help. Any company impact on the aquatic environment is likely to appear on the agenda of Haskell's aquatic toxicologists, who offer consulting services and conduct and oversee tests on everything from complex plant effluent to compounds that are candidates for marketing Again, a general pattern is followed. The most basic study mvolves acute static toxicity, in which fish are exposed to test compounds in standing water to determine a lethal concentration. Dynamic acute studies utilize constantly renewed exposure solutions in flowing water, which is more relevant to the real environment and assures more meaningful results. The use of invertebrates such as daphnia (water Teas) m chronic studies provides subtle information on reproduction and growth as well as lethality m relatively short periods of time. Microbiology One of the major new areas of emphasis for Haskell microbiology is the microbial biodegradation of non-pesticide organic chemicals Tests will provide estimates of the rates at which natural mixtures of soil and water can break down a compound into simpler mole cules. Microbial degradation studies will also be used to determine if harmful chemicals are produced as a result of the decomposition process. If this occurs, waste treatment methods may have to be altered. Occasionally, it will be necessary to examine specific environmental effects of test compounds, such as how the carbon, nitrogen or suifur cycles m the soil and water would be affected by contact with a compound. These studies will allow Du Pont to plan more efficiently and economically for the transport and storage of chemicals and the disposal of wastes generated m their synthesis. DUP 0949315 DU 039669 Rart of a Companywide Effort Almost everything Haskell does is for use outside its walls The laboratory is part o; companywide effort to provide safe products and an acceptable working environment, and it interacts frequently with individuals and institutions outside Du Pont. Within Du Pont An important part of the Haskell team is the corps of industrial hygienists who visit plant sites to advise on equipment and procedures which will assure worker safety. Whiie such contact most often is initiated by Du Pont's plants and industrial depart ments, the process also works the other way around, as when laboratory personnel have a finding they want to share with the company's manufacturing units. This is m keeping with Du Pont's policy of releasinggny information/ others--either inside or outside the company--to act with greater safety A basic goal when working with highly toxic materials is to isolate the. worker from the chemical. Haskell's industrial hygienists may recommend that a new plant be designed to contain the material within pipes, tanks or other vessels., or even within a sealed-off and automated /'building within a building'' where access is allowed only for maintenance and then through air locks. Haskell's industrial hygien ists measure and monitor exposure levels at plant locations. Some times changes are needed in existing facilities, such as an improved ventilation system. Dikes may be needed around Di Char.es Bernhardt :eft. director o! HasxeL Laboratory spends a substantia. proportion or his _ time meeting with. representatives olDp Pont s manufacturing departments Hessnown here w,:;-. Dr JohnDaiv Jr oi tne Petrochemicals Department DUP 0949316 A portable duan:nat..e lace-nt test svstem .s usee dv ztar.ts :: .make sue"respirators r.t crccer.v ,s also usee :r. respiratiznTeseartr. creeds Here .naustr.a, r.ygien.sts'JosephLcstma/c ::gr.t anc Dr Orr:n Skretved: demonstrate hew me system wents DU 039670 asiiHas Zsr.zaz: a":" s::ePi:sls zr. s&mpus :S it Jnpcrzar.: par: sf Hastens wzflTrze:? ass.star.: n::ec:s: D:'3.a:ne .VcKs.zx zzpr.z .-;s.u D: Cr.ai.es nir.e c.j'tsa. piczessor stpsx.zsucgy-srlcpcczzpatcr.a. rzed:c:r.e ifr-'ze l'n;- ersizv:: Ca..ppr^^Sc5od. sfMeQ:c:r^e:.r: Sar.F:anc:scc ' --- - =-' To further ensure that levels of chemicals found in the work place are safe for employees. Du Pont's Acceptable Exposure Limits Committee develops guidelines for permissible ex posures based on human expenence and/or animal tenacity studies. The AEL Committee consists of toxicologists, industrial hygien ists. occupational physicians and information specialists. This group establishes AEL's (acceptable exposure limits) for materials produced or used within Du Pont and involving sufficient volume and/or potential worker exposure. Responsibility for medical surveillance of employees rests with Du Ponts Medical Division. It examines employee histories for adverse impacts on health and analyzes blood and urine at frequent intervals. If anything unusual is found, more testing is done and the employees' work practices are carefully reviewed. Instances of employee cancer are recorded m a cancer registry established m 1956 to provide the data for epidemiological studies. Depending upon the circumstances, notice of Du Pont's experience will go to affected employees, customers, government agencies, other produceis~and the media. Du Pont s top management is intimately involved m safety and health matters. The Environ mental Quality Committee reports directly to the Executive Committee and coordinates activity m this area. Day-to-day contact is maintained through a liaison committee composed of departmental management representatives and Haskell coordinators. Outside Du Pont Haskell scientists and managersare m frequent contact with commercial toxicology laboratories, with which Haskell sometimes contracts to supplement its own work. Likewise, they are m close touch with government agencies like the Environmental Protection Agency, the Occupa tional Safety and Health Adminis tration and the National Institute for Occupational Safety and Health, which recommend and administer the myriad laws and regulations on public and worker safety and health. There are also regular contacts with the aca demic and scientific communi ties, m a two-way sharing of information. Another important association is with CUT. the Chemical Industry Institute of Toxicology, which Du Pont and other companies created and support to undertake toxicity studies and non- propnetary research on widely used chemicals. Among the chemicals CUT selected for early testing were chlorine. ethylene and toluene, the latter frequently used m solvents and paints and as an intermediate m many chemical processes. Finally. Haskell provides emergency information on product formulation and/or toxicity, as well as recommendations on safe handling and antidotes, to physicians, poison control centers, hospitals and other chemical companies. 17 DUP 0949317 DU 039671 The Haskell staff numbers around 225, more than 20 per cent of whom have doctorate degrees. Almost half the staff have a bachelor's degree or hrgher, and there are four medical doctors and seven veterinarians, several of whom also have Ph.D. degrees. Molecular biology and microbiology, acquatic toxicology, chemistry and biochemistry, biostatistics and pathology are among the disciplines represented. Since 1935, over 200 articles written by Haskell scientists have been published m the scientific literature and over 10,000 reports have been issued. Each year the laboratory tests approximately 700 chemical substances for potential hazards. In 1979, approximately 1200 tests were conducted. Haskell's animal population numbers about 10,000, 9 percent of them rodents. Haskell is located on Elkton Road (Delaware Route 2: Maryland Route 279) just off Interstate 95 between Elkton, Maryland, and Newark. Delaware, just a few minutes from the University of Delaware campus. Above Tv."- :ew wines present.v ur.ae: ozns^uc:.or. are scnec. *c be cornp.ei.ee cv '.951 DUP 0949318 Credits Bootee: design is by Lyons Studies' W.Mur.gtcn Detaware Fboiogiapr.v .sbv Ke.::. Meyers w.tr v.e loticwmg exceptions :r.e Sar. Francisco p.cf-re :r. :r.epage '.7 .s by Cr.ristcpne: Spr.r.grr.ar. z: BAcxStar: pictures oiDr Reinnara: on page 16 ana p: azoc analysis on c.e iron: ccventop .er. are cv Denn.s 3racx 3.acx Starr ana pictures on exueme i.gr.t s,ae or :z . er ana on page 3 are Jem Du Fen: proto hies DU 039672