Document L3nqRmpwywOBq6qxqjOE6KYw

/ /, Opinion toatoW JANUARY 1981 Where science is uncertain, cooperation is needed The Supreme Court struggled with the so-called benzene case for a long tune, almost its entire 1979-1960 term, before deciding finally to avoid the real issue Actually, there are several issues involved in this case at that vague front where legal consider ations confront scientific evidence or lack of scien tific evidence. But the prune issue that was to have been resolved in the case of the Industrial Union Department (AFL-CIO) versus American Pet roleum Institute was how much regulatory agen cies must consider cost-benefit factors in making rules. The court chose to ignore that issue. It must now wait, apparently, until the coke ovens emis sions case later this term to deal with cost-benefits and regulatory rules. Implicit in that question is the relative impor tance of benzene. It is a basic chemical. Should that be a consideration in a regulatory agency's attitude toward it? It is clear, for example, that vinyl chloride would never have reached the mar ket place had the Toxic Substances Control Act (TSCA) been in place those many years ago. In stead, Industry and the regulators reached a work ing understanding that allows the huge industry to continue, while workers appear to be adequately protected. That is not to say that the same questions arise over benzene that were confronted in the vinyl chloride regulation. For one thing there is the evi dence of the effects of the chemical. For another, there are the apparent inconsistencies in the Occupauonal Safety and Health Administration (08HA) benzene exposure rules. For example, why are service station attendants excluded? A benzene exposure limit of 10 ppm had been long accepted despite evidence that benzene at higher exposures was linked to leukemia. But when a study at an Ohio Pliofilm plant indicated an excessive number of leukemia cases at what were reported to be lower exposures. OSHA issued an emergency standard. That emergency standard, challenged in court, never saw the light of day. And the data from the Pliofilm plant subsequently revealed much higher exposures to benzene. Nevertheless, the agency went ahead with a permanent standard of i ppm maximum exposure. That standard was overturned by a Federal court in New Orleans, which held that the agency must weigh the costs of meeting its proposed rules against the benefits derived. OSHA argues that its Congressional mandate is solely to protect the worker, not to be involved in economic balancing acts. They have a point. The problem is that there is no check and bal ance against that position. That is, who looks out for the other side. Our form of government has prospered on a system of checks and balances. But the only immediate check on regulators is the Administration itself. This is a dilemma for the regulated as well as the regulators. The result has been confrontation m courts. And the courts have been ill-equipped or reluctant to de%l with the real issues. In the benzene case, the Supreme Court did not really confront the scientific issues. Four Justices held that OSHA was perfectly within its rights to enforce a lowered exposure standard. Four others argued that the agency didn't have enough evi dence to lower the standard. And Justice Ftehnquist held the judiciously unique position that the Occupational Safety and Health Act was uncon stitutional. That still leaves open the question of how much evidence is enough to mark an agent carcinogenic. No one wants to have to count dead bodies, which, in essence, is what happened in the vinyl chloride case. The truth is that many questions remain about carcinogenicity and testing for carcinogens. Short-term tests, such as the Ames Salmonella tests, remain limited, despite the fact that a bat tery of such tests is now available. Moreover, bio assays on animals are dependent on the protocols and the care with which such tests are performed Some tests are proven more valid than others. In addition, some basic questions about carcinogenic ity remain unanswered. For example, why, and how. and Is there a threshold, and what about cumulative factors? The truth is that science has a lot more to do before it can let the courts make these kinds of decisions. Meanwhile we must have effective con trols against exposure to carcinogenic agents. Such controls can only come about through cooperative efforts of industry, unions, scientists and the regulators.--Irvin Schwartz 6 Readers Respond URL 03608 Salary compression Editor: An associate of mine gave me a ropy of your first issue of Industrial Chemical Sens. 1 read it with inter est and filed for a subscription. Now then, being a subscriber may 1 be allowed to be critical? Your first article. Salary Survey, was both informative and interest ing. One big question did arise. A graph plotting plant workers against chemists twith B.S.l is shown. I find no explanation of this graph within the article, however. I believe the graph depicts salary increases or track record of these two groups rel ative to the consumer price index. If in fact this is the case I think you may have missed an excellent op portunity to publicize a matter of great concern to many engineers and other scientific workers. This concern is commonly called salary compression or salary erosion. It is evident in the loss of real salary gains (and subsequent buying poweri by these professionals when compared to employees primarilycovered by ihe cost-of-living-allow ance (COLA) provisions of bargained-for contracts. Salary com Over 70 gases are available in Matheson Lecture Bottles. pression is a major, real concern oi your specified readership, the in dustrial chemist. At the end of the article is a block item giving some of the details of how your survey was conducted and what you hope to do with it in the future. 1 am impressed and eager to see more. 1 do. however, feel that in addition to this type of information, similar data gathered from indus trial chemists is pertinent and valu able. If in fact vou do "want the companies to give more thought to issues that concern (your) readers' employment conditions it seems imperative that you survey your readers. I am looking forward to more of your publication. Please continue to perform this service for us. r John R. Katzfey Western Electric. Chicago Air/Allene/Ammonla/Argon Boron Trichloride/Boron Trifluorlde 1, 3 Butadlene/n-Butane/l-Butene Cls-2-Butene/Trans-2-Butene Cis & Trans-2*Butene/Carbon Dioxide Carbon Monoxide /Carbonyl Sulfide Chlorlne/Chlorotrlfluoroethylene Cyclopropane / Deuterium 1-1 Dlfluoroethylene Dlmethylamlne inetroift 15 ietroffi52*A Dimethyl Ether 2-2 Dimethylpropane ^ Ethane/Ethyl Chloride Ethylene Ethylene Oxide Freon 12 Freorfl3 B1 Freorfl4 Freoif21 uoropropylene :n/Hydrogen Bromide len Chloride Fluoride ien Iodide/Hydrogen Sulfide ie/ Isobutylene/Methane Bromide/3*MethyIbutenel Chloride/Methyl Fluoride Mercaptan/Monoethylamlne lethylamlne/Neon/Mltrlc Oxide/Nitrogen Oxide / Perfluoropropane/Oxygen rout Pentafluorlde/Propane ne/SlIlcon Tetrafluorlde/Sulfur Dioxide Hexafluoride / Sulfur Tetrafluoride lylamine/Vinyl Bromide/Vinyl Methyl Ether Of course Matheson has more gases than other suppliers but you should know that over 70 of them are available in Lecture Bottles, designated in our catalog. Lecture Bottles are convenient small f2* x 15"). high pressure steel cylinders. Perfect for experiments requiring small quantities of gas. They allow you to buy only the amount you need and eliminate the storage of large unwanted materials. Don't forget that Matheson buys back its Lecture Bottles so that you never have to get stuck with a disposal problem. There is also a full line of equipment to handle gases in L.B. quantities including pressure reducing regulators. Gases in any quantity, think Matheson. Gases in small quantities, think Lecture Bottles. All of these gases are available from any Matheson facility. pyfatheson r ^ ) lyndhurst, N] 07071 tQU MORE INFORMATION CIRCLE 203 BCAOfBS SERVICE CARD 6 nhomi nala on computer Editor: I have just reviewed \ ol. 1. No. 1 of Industrial Chemical Sews and find it to be an outstanding publication. Its mix of articles and advertise ments makes it worth my while to examine each and everv page. I would like to congratulate you on your efforts. With regard to the article "How to plug into a computer listing of chemical information," I would like more information on this system. Would you give me the name and address of the person whom I should contact to get hooked up and where to get a copv of the 307-page book about the data base.' James R. Gram Sorthuest Indiana Criminal and Toxicology Laboratory, Gary, Ind. tEditor's Sole: For further informa tion on the Chemical Information System, contact Stephen R. Heller. CIS Coordinator, MIDSD. PM-218. Environmental Protection Agency. 401 M Street SW. Bashingron, DC 20460.) Correction Editor: A correction on the Wu-lungtnn Wire page of the October issue-- less than 10 part? per billion (ppb) of nitrosamines is. the USDA tolerance for meats--not 10 parts, per million (ppml. This new publication will be well received and read by numerous in dustrial chemist? throughout the L',S. I'm glad to have received your first issue. Marvin E Winston Winston Laboratories. Ridgefield Park, SJ. INDUSTRIAL CHEMICAL NEWS News of the Week URL 03609 for the fourth quarter of 83% to $80.9 machine can add a nucleotide to a idizing agent converts the resulting million over the fourth quarter of growing DNA chain on a solid sup phosphite to a phosphate. 1979. Sales for the company rose port every 30 minutes. Their scien Bio Logicals1 chemistry was de 28.8% to $284 million from the same tists have constructed chains greater veloped by organic chemistry pro period in 1979. than 20 nucleotides long and are ex fessor Kelvin K. Ogilvie, McGill For the full year, sales at Texasgulf ploring die upper limit. When ready University, Montreal, and the ma increased 38.1% and earnings shot up for delivery at the end of April 1981, chine was designed with assistance 137.8%. The company nad 1980 the machine will cost $19,500. from Waters Associates, Milford, earnings of $326 million on sales of The Vega Biochemicals machine, Mass. Genetic Instruments1 chemis $1.1 billion compared with 1979 which is already available at $49,500, try was developed by organic chem earnings of $137 million on sales of is currently wedded to chemistry that istry professor Marvin Caruthers, $789 million. still takes three hours to add a nu University of Colorado, Boulder, and Ethyl Corp. had a good fourth cleotide. Vega spokesmen say, how the machine was designed by molec quarter, but aid not do so well for the ever, that their machine has flexibil ular biologist Leroy Hood, California full year. Fourth-quarter earnings ity in programing, and design that can Institute of Technology, Pasadena. totaled $24.7 million, an increase of be adapted to any chemistry devel Vega Biochemicals uses a 10-ml 12.3% over fourth-quarter 1979. Sales oped in the future. glass reaction flask, formed by joining were essentially flat--$432 million The Bio Logicals and the forth top and bottom by a standard taper last quarter against $431 million the coming Genetic Instruments ma joint. Reagents and solvents enter in year Defore. chines carry out reactions by passing sequence through the fritted glass top But full-year earnings at Ethyl fell reagents and solvents in sequence and are removed through a fritted 8% to $89,7 million from the year be over a solid support in a column. Solid glass bottom. Chemistry is based on fore, whereas sales were increasing 5% supports may be functionalized silica the phosphotriester method, in which to $1.74 billion from 1979. gel or controlled-pore glass. Chemis a deprotected 5'-hydroxy] of a nu try for both is based on the phosphite cleotide already on the chain couples method. In this method, a protecting with a nucleotide whose phosphate is Automated DNA/RNA synthesizers debut group such as di-p-anisylphenyl- esterified with one protecting and one methyl is removed from the 5'-hy- reactive leaving group. Vega's chem droxy group of a nucleotide already istry was developed by biochemist on the solid support and the hydroxyl Keiichi Itakura, City of Hope Re A new competitor has appeared in the group couples with a 3'-phosphinyl- search Institute, Duarte, Calif., and race to develop automated machines nucleoside bearing a very reactive Vega's engineers designed the ma to synthesize deoxyribonucleic acid leaving group on phosphorus. An ox chine. (DNA) sequences for genetic engi> neering. The introduction of such a machine by Bio Logicals, Toronto, Report probes chemical reproductive hazards Ont., last week has come hot on the heels of the commercial appearance j Some chemicals pose a real hazard to duction for both men and women. of another such machine by Vega/ human reproduction, both for men And evidence derived from geo Biachemicals, Tucson, Ariz., in thel and women, and the^task of identi graphical patterns, time trends, and last week of 1980. A third entrant, fying which chemicals these are and specific environmental factors suggest Genetic Instruments Co., may bring how best to protect people from them that chemicals may be involved in a machine to market at the end of is going to be incredibly difficult. other cases where the specific cause of 1981. That, in essence, is the conclusion of difficulty has not been pinpointed. Bio Logicals spokesmen say their thejust-released report ofthe Council Animal studies are promising and on Environmental Quality, "Chemi probably essential for pinpointing the cal Hazards to Human Reproduc specific agents responsible for adverse tion." effects. In an analysis of 21 chemicals The report, which was prepared that affect both animals and humans, under contract by Clement Asso there is "a reasonably close concor ciates, is a comprehensive literature dance between effects reported in review of the subject, and its conclu humans and in one or more experi sions are not likely to provoke any mental animal." With one exception, surprise among workers in the fielcl. humans were affected at doses similar But they are not intended to. It was to or smaller than those that affected prepared, according to CEQ staffers, the most sensitive test animal. How to pull together what is known about ever, there is no consistent pattern as the reproductive hazards of chemical to which animal will be the most substances so that the council can sensitive. Thus, useful animal testing assess whether there is something it must involve studying many species should do about the problem. to find the most sensitive--a lengthy The present state of scientific and expensive process, and one likely knowledge about reproductive haz to give many "false positives" since ards is roughly comparable to what there seem to be many agents that was known about carcinogens in the affect animals but not humans. A early 1960's, the report says. Here are really useful in-vitro prescreening some of its findings. test--analogous to the Ames test for Ogllvio; dovolopod ehomMry for Bb There are clear examples of chem carcinogenicity--has not been found LogfcoN' DNA oynth--ixor icals interfering with normal repro yet for reproductive hazards. 12 C&ENJan. 26. 1981 Casarett and DouWs The Basic Science of Poisons SECOND EDITION Macmillan Publishing Co., Inc. Sew York Collier Macmillan Canada. Ltd. Torom>' Bnilltere Tindall Lontiiir. URL 03610 Contents V 9 t0 ^ UNIT I General Principles of Toxicolog\ rHrTD 1 Origin and Scope of ToxicolorLons J Casarett and Margaret C. Bruci "l Evaluation of Safety Toxicologic Evaluation Curtis D. Klaassen and John Docll 3 Absornnon. Distnoution. and Excretion of Toxicants Curtis D. Klaassen 4 Metabolism ofToxic Substances Robert A. Neal < Factors Influencing Toxicolor John Doul: 6 Chemical Carcinogens John H. Weisburgek and Gary M. Williams 7 Genetic Toxicology WlLLIAM G. THILLY AND HOWARD L. LlBEF. 5 Teratogens Raymond D. Harbisos UNIT II Systemic Toxicology 9 Toxic Responses of the Central Nervous System Stata Norton 10 Toxic Responses of the Liver Gabriel L. Plaa , ]] Toxic Responses of the Kidney Jerry B. Hook 12 Toxic Responses of the Respiratory S'stem Daniel B. Mlnzll and Roger O. McClellan 13 Toxic Responses of the Eye Albert M. Potts and Leonard M. Gonasun Xili .3 1) 56 7C 139 15^ 17 206 232 24E 275 Xi' CONTENTS 14 Toxic Responses of the Blonc Roger P. Smitp 15 Toxic Responses of the Reproductive System Robert L. L>j\o- UNIT III Toxic Agents 16 PesticideSheldon D Mcrth' 1" Metal-Pai l B Hasp-jond and Robert P. Beetles IS Solvents and Vapors Herbert H Cornisi' 19 Raci.v.ion and Radioactoc Materials Charles H Hobbs and Roger O McClellan 20 PlasticJohn altian 21 Toxins of Animal Oricir Frederick W. Oehsu. John F. Brown. ast> Murray E Fowler 22 Phvtoioxicolog\ John M. Kjngsblr\ UNIT IV Environmental Toxicology 23 Food Additives and Contaminants Wendell W. Kilgore and Ming-Yu Li 24 Air Pollutants Mary O. Amdur 25 Water and Soil Pollutant* Robert E. MF.szrR and Judd O. Nelson UNIT V Applications or Toxicology 2t- Forensic Toxicolo?' Randall C. Basil? and Robert H. Cravey 311 332 357 40Q 46$ 4*57 53: 55" 57E 593 60S 632 661 URL 03612 I (IN I t M > Ciir,i:^l To\icolo.n' Barrv H. Ri'mack oriJ kovrr.7 G Phtrco . Orcunatioral Toxicoio?' Robcrt R. Lm'WERY? Repjlatory Toxicolor* Morton Corn Toxicolocv and the Law Rob S. McCutchtov IVDEO, x, 677 69^ 7j c 7^7 7-.; URL U3b13 \ Chemical & Engineering News 1 1 55-- 16th Sc, N.W., Washington, D.C. 20036 Editor: Michael Heylin Managing Editor: William F. Fallwell Assistant Managing Editors: David M. Kiefer, James H. Kriwer, Donald J- Soisson Staff Editor: Ernest L. Carpenter Senior Editors: Earl V. Anderson (New York), Wilbert C. Lepkowski, Howard J. Sanders Associate Editors: Jeffrey L. Fox, Rebecca L. Rawls, Richard J. Seltxer Assistant Editors: Doron Dagani. Pamela S. 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(For list of offices see page 67) 2 CAENMay 4,1961 Letters A* (f /- / / , - / Industrial chemistry course SIR: Yotr recent discussion (CAEN, Feb. 9, page 43) regarding academic vs. industrial or chem ical engineering thinking and preparation of students was read with much Interest. I have been concerned with the matter for some time, and have spent many an hour with my industrial friends in discussion regarding graduates and how much training was necessary to "fit" them for their new job. Our department has begun to attack the problem by implementing a new "industrial chemistry" major. This program has been met with much enthusiasm and cooperation from our local industry, and Is apparently being met with equal enthusiasm by our students and adminis tration. We expect to share some of our costs, ideas, and personnel--through seminars, lab oratory interaction, guest (industry) lectures, and internships. I know that others have had successful ex periences along similar lines, and would not be a bit surprised to see that the traditional "standoffishness" (on both sides) will soon give way to a spirit of cooperation. After all, when ever I have discussed the matter one-on-one l have found that we are not so far from our brothers after all; it Is the larger group meeting which leads to arguments--perhaps that is the nature of the human being Thomas Neil Associate Professor of Chemistry, Keene State College, N.H. On studying cancer causes SIR; I read with interest the report called Science Update--Biochemistry in the March 2 issue. On page 29 the subject of research into causes for cancer is discussed. I wonder H the reason our nation has failed to find the means by which cancer is started is because most of the effort, such as that of the National Cancer institute, has been directed towards finding a "chemicals" cause instead of a natiral biological causa, as discussed in the article? As a result of Congress and Ihe Delaney clause of the Food & Drug Act, we have been in a position of their having predetermined that there are indeed sinister causes for cancer. Too bad research cannot be conducted in the proper atmosphere instead of being directed by people with no knowledge of science. Consultant, Grinds, Calif, R. W. Lillie More on nuclear arms race SIR: You will no doubt receive several letters whieh state that the article on die nuclear arms race does not belong in CAEN. As a reason the writers will state that H is not chemical or sci entific in native, and thus has no connection with the American Chemical Society. Let me suggest to these people, and others, another point of view, another way of thinking. A$ a chemist (or other scientist) you are prac ticing a science which is of great Interest to you. of great value to you, other than as a mere means of livelihood. Most of you think that it is important that chemistry (and all science) con tinue to exist and continue to progress. The ex istence of science and the progress of science are something to which you attach a high valu ation. Those who have studied the nuclear war sit uation agree that the degree of probability of a nuclear war is pretty much a random phenom enon: The chance of nuclear catastrophe in creases.as the number of weapons increases, as the proliferation-increases. and as time goes on. The chance of nuclear catastrophe is now high and constantly increasing: it is now "four minutes to midnight." A major nuclear war will not destroy mankind, but will demolish the technologically advanced nations. Chaos will reign. Transportation will come virtually to a standstill. Energy supplies, including electricity, will almost vanish When you flip the switch the NMR instrument will not come on, the centrifuge will not spin, the ac celerator will not bombard nuclei. Most science libraries will disappear in smoke, because most are located in or near cities. Chemical Abstracts will not get the information to abstract, end its computers will not alphabetize A large per centage of chemists will be dead, because they too are located in or near cities. The science of chemistry will come virtually to a standstill. Please, if you have any love of chemistry (and science in general), and a desire for its continued development, then join in the efforts to reduce the possibility of nuclear catastrophe. Kent State University R. Thomas Myers TCDD In hexaehlorophene SIR: i have previously called attention to the 2,3,7,6-tetrachlorodibenzodioxin (TCDD. dioxin) contamination of 2,4,5-T and Its "effects" on Vietnam veterans exposed to agent orange as being insignificant owing to the low and brief exposures involved (CAEN, Nov. 12, 1979, page 50). In particular I pointed out that the Seveso. Italy, accident with TCDD involved a factory making hexaehlorophene. which was and still is used by many doctors and nurses and which was removed from general use in antiseptic soaps in the early seventies after being implicated In the deaths of newborns (C&EN, July 7. 1990, page 50). However, I could not find any literature references to show hexaehlorophene being analyzed for TCDD, although Whiteside, in his New Yorker article "The Pendulum and the Toxic Cloud," July 25,1977, page 30, mentions the association of contaminated 2,4,5-trichlorophenol being common to both 2.4,5-T and hexaehlorophene, and the detection of very low levels of TCDD in hexaehlorophene in 1976. i now have found mention in an analytical procedure for hexaehlorophene residues (Van Auken, 0. W., Hulse, M,, "Hexaehlorophene." Continued on page 58 URL 03b14 URL 03615 International Regulatory Aspects For Pesticide Chemicals VOLUME I TOXICITY PROFILES Amber Gaston Vettorazzi, M.D., M.S., Ph.D. Food Safetv'Prograrr Division of Environmental Health Vv orld Health Organization Geneva, Switzerland CRC PRESS, INC. Bki Raton. Florida 334?) T Alii.I ()l CONTLNTk Jntrojuenoi.............................. Profiles.................................... Acephatc.............................. Acrylonitrile........................ Aldnn.................................. Alleinnr................................. Amitroii.............................. Aramitel.............................. Arsenates (calcium and lead i Azmphos-eihv 1.................... Azinphos-methyi.................. Benorm i................................ BHC (technical cr30Cs,........ Bmapacni............................. Bioresmethrir......................... faromomethanc..................... Bromopho:.......................... bromophos-ethvl................ Bromopropylau.................. Af\-bjt\,am:n..................... Camphechlo:........................ Carrafc!................................ Cantar................................... Ca:ra:\.................................. Carbenriazirr......................... Carooj'urar............................. Carbon disulfide.................. Carbon tetrachloriae.......... Carbophenothion........ Cartap.................................... Chinomethiona;.................... Chlorbenside.......................... Chlordane.............................. Chloraimeform....................... Chlorfenson .......................... Chlorfenvinpnos.................... Chlormequat.......................... ChloTobenziiate? ................ C'nioropicrin........................... ChloropropylateCi................ Chic:; :haIo:;;i ...................... Chlorpropham...................... Chlorpyrifo'.......................... Chlorpynfos-methyl.............. Chlorthion1?........................... Coumaphos............................. Crufomaie............................... Cyanofenphos........................ Cvhexaiin............................... 2.4-D...................................... 1 3 4 5 6 ( .f .8 .9 1C 10 11 i: 1? I? 115 lr lr 10 ,2u 21 ,21 22 25 .26 .26 .27 .28 *>c .29 .30 .30 .31 .31 ,31 32 35 URL 03616 3 )amino7uJ-....................................................................................................................... .. ................................................................................................. .................................... ?' Dcmcion and related compound....................................................................................... ?" Pialito-................................................................................................................................3 Diallau ...............................................................................................................................38 Diazmon'v.' .........................................................................................................................38 Dichlofluanid.....................................................................................................................39 Dichlorvos...........................................................................................................................40 2.6-Dichloro-4-nitrohenzenamine (Diehloran)............................................................. 4J Dteofo.................................................................................................................................. 42 Dieldrir............................................................................................................................... 4* Dimcihnait........................................................................................................................ 44 Dimethnn...........................................................................................................................44 Dtnoear.............................................................................................................................. 44 Dioxaihior............................................................................................................ '........... 45 D:nhn\ 1 .........................................................................................................................4* Dirhenwamin-. ................................................................................................................ 45 Diaua................................................................................................................................... 4" DisuMoio;............................................................................................................................ 4F DNOC................................................................................................................................ 44. Doom................................................................................................................................... 49 EdifenpnOi ........................................................................................................................ 49 Endosultar.................................................................................................... 50 Endnr................................................................................................................................... 5! Ethctor................................................................................................................................52 Eihmicnearr .....................................................................................................................52 Etmoi....................................................................................................................................5 - Einowaujr........................................................................................................................... 55 URL 03617 Eih\ iencdihromio-............................................................................................................. 54 fcihylenrdichioric; ............................................................... 5- hthyicnr oxtd-......................................................................................................................55 Eenanupno:.........................................................................................................................56 Eenbutatm oxidt................................................................................................................ 56 Fenchlorphos .....................................................................................................................5" Fenitrothior........................................................................................................................5" fensulfoihion.....................................................................................................................5? Fenlhion .............................................................................................................................59 Fenun compounds (triphenyliin acetate, chloride, and hydroxide)........................... 59 Ferbam.................................................................................................................................60 Foipet...................................................................................................................................61 Formothion.........................................................................................................................62 Hcptaehlor .........................................................................................................................62 Hexachloroben2ene (HCB).............................................................................................. 6? Hvdrocen cyanide............................................................. 64 Hydrogen phosphide.........................................................................................................65 Imazalt!.............................................................................................................. I.............. 65 Iprodion:..................... 65 Lcptophp;................................................................................... 66 Lindane (pamma-BHC).................................................................................................... 67 MalaihionT .......................................................................................................................68 Maleic hidrazide.................................................................................................................69 Mjncpreh........................................................................................................................... 70 Munch................................................................................................................................. 70 Mor.'^mtiJopnc ................................................................................................................. "! Mcth]d;unu.*j........................................................................................................................ ?T Mcihomyi........................................................................................................................... 7} Mctho.wehlo:........................................................................................................ MevinphOi........................................................................................................ 74 MGK 264 i....................................................................................................................... 74 Mircx.................................................................................................................... 75 Monocrotophos.................................................................................................................. 75 Monuror...............................................................................................................................76 Nabarr........................................................................................................... -...................76 OmetnoatL.................................................................................................................... .. ."6 GrganomercuriaL............................................................................................................... 77 Paraoua;.............................................................................................................................."" Pararhior.............................................................................................................................. 7F Parathion-methyl............................................................................................................... 79 2'Phrnylpheno!................................................................................................................... 7^ Pnoraic............................................................................................................................... SO Phosalone........................................................................................................................... SO Piiosme:............................................................................................................................... SI Pnosphamiaor............................................................................................. PI Piperonvi buioviat............................................................................................................. ST Pirimicarr............................................................................................................................S' Pinmiphos-meth\i..............................................................................................................S5 Prepare::-...................................................................... St' Propnan................................................................................................................................ S" Propiner..............................................................................................................................S7 Propovu:............................................................................................................................. PyTethnns............................................................................................................................SQ Quimozrne..........................................................................................................................9;' Strobane l ..........................................................................................................................91 2.4.5-Trichlorophenox> Acetic Acid............................................................................... 91 Tecnazenc............................................................................................................................91 Thiabendazole..................................................................................................................... 97 Thiomeior.. . . 9? Thiophanaie-meihy)........................................................................................................... 9.'5 Thiram..................................................................................................................................94 Trichlorfon..........................................................................................................................95 Trichloronai........................................................................................................................6 Triforine..............................................................................................................................96 Vamidoihion........................................................................................................................96 Zectran?.............................................................................................................................. 97 Zineb.................................................................................................................................... 97 Ziram.................................................................................................................................... 9S References........................................................... -..................................................................99 URL 03618 TABLE 3 Listing of Pesticides With Acceptable Daily Intakes (ADls)......................................... IJ1 References............................................................................................................................... Uc table: Summarv of 'IomcoIolmc.iI D.u.i on Winch Acceptable Daily Intake Fjgure> Are Bascc................................................................................................................................ 151 Rrference>..................................................................................................................................... table? Guide to Monographs........................................................................................................ 191 References............................................................................................................................199 TABLE 4 Listing of Common and Chemical Names foT Pesticides Mentioned in the Manual.................................................................................................................. 201 Glossars ....................................................................................................................................... 206 References............................................................................................................................ 2J0 Index............................................................................................................................................. 21 ? URL 03619 URL 03620 Pesticide Manufacturing and Toxic Materials Control Encyclopedia Edited by Marshall Sittig P K'^uA_ . Loo- NOYES DATA CORPORATION Park Ridge, Nsia Jersey. USA. 19BD URL 03621 Technically fpeaking Legislation imposing strictures on substances that might harm the environment often limit discharges to a few parts per million. For a fresh look at what a small figure this is, consider that one part per million is equal to: --One inch in 16 miles; --One minute in two years; --A one-gram needle in a ton of hay; --One penny in $10,000; --One ounce of salt in 62.500 pounds (of food); --One drop of Vermouth in 80 "fifths1^--a very dry martini! Ref: Chemecoiogy, May 1971 URL 03622 Technically fpeaking Legislation imposing strictures on substances that might harm the environment often limit discharges to a lew parts per million. For a fresh look at what a small figure this is, consider that one part per million is equal to: --One inch in 16 miles; --One minute in two years; --A one-gram needle in a ton of hay; --One penny in $10,000; --One ounce of sail in 62,500 pounds (of food); --One drop of Vermouth in 80 `'fifths'--a very dry martini! Ref. Chemecology, May 1971 URL 03623 fJUSpauJ Ajp fjBA --1>si4441, oe ut uinouueA jo 00jp uo-- :(pooj io) spunod 009'Z9 ui wes jo eogno euo-- 000 0 it Uj Auusd eutf- :Aeq |o uot ui etpeeu unjO-euo y-- SjmX oam ui ainunu euo-- *.siuj 91 ut you* euq-- :oi tenbe %t uoirnu; jed pad atto jeqj iepfsuoo `e ctqt jn&t tieurs iruM it tfooi qsait joj 'uoidiuj jed sued oj se&jegasip muiii ueyo luauiuoJiAue egi uuey wfl*u l*yj seouetsqns uo tunpuis Buisoduji uoaeisiOen 6u;>fOddf fi||D>juq50X Technically Jpeaking Legislation imposing strictures on substances that might harm the environment often limit discharges to a few parts per million. For a fresh look at what a small figure this is, consider that one part per million is equal to. -One inch in 16 mites: -One minute in two years; --A one-gram needle in a ton of hay: --One penny in $10,000: --One ounce of salt in 62,500 pounds (ol food); --One drop of Vermouth in 80 "fifths"--a very dry martinil Ref. Chemecofogy. May 1971 I TOXICOLOGY OF PESTICIDES Wayland J. Hayes, Jr., M.D., Ph.D. Professor of Biochemistry Center in Environmental Toxicology. Department of Biochemistry Vanderbilt University School of Medicine Nashville. Tenn. t i. Formerly Chief Toxicologist. Pesticides Program. National Communicable Disease Center U.S. Public Health Service t s t. The Williams & Wilkins Company/Baltimore URL 03624 % t fi 2.2.7.4 TOXICOLOGY OF PESTICIDES 56 vatioD--not the casual result of a test with some other purpose. Any study designed to reveal a dosage producing no effect should contain, in addition to a control group receiv> ing no toxicant, one or more groups of subjects given larger dosages fully expected to produce measurable effects of the compound. Since such tests are almost always prolonged, partic ular attention must be given to the number of subjects assigned to each group so that the number available at the end of the study will be adequate to reach a statistically significant result (see Section 2.2.7.11. There are several reasons for placing the expression, "no effect" in quotation marks. First, many studies reveal effects that are obvious, reproducible, and highly significant from a statistical standpoint but of questiona ble biological significance. Depending on cir cumstances, an example might be partial inhi bition of an easily regenerated enzyme. There is no substitute for judgment in toxicology Second, as discussed in one of the following sections, the effects of small dosages of toxic compounds may be beneficial and thus qualita tively different from the effects of larger dos ages. Third, failure to detect any effect by an elaborate scheme of testing does not exclude the possibility that an effect would have been detected if some other scheme had been used. Rapid progress has been made recently in chemical detection of toxicants or their metab olites. Analytical chemists have already achieved such skill that they easily measure biologically unimportant traces of several pes ticides. Biochemists and physiologists are not far behind. For these reasons, it is generally recognized that what is needed is a "no significant effect1' or "no adverse effect" level, that is, a level that causes no detectable injurious effect. There is no complete substitute for long-term tests, but increasing attention must be given to evaluat- ing the biological significance of observed ef fects that involve no demonstrable injury to health. A toxicologist may do as much harm by unnecessarily condemning a compound as by failing to detect and to prevent a real toxic hazard. The Lowest Effect Level as a Practical Toxi cological Measurement. As already men tioned, it usually is impractical to use such a large number of subjects per group that the possibility of a rare (<1%) but highly undesir able effect, such as neurotoxicity or carcino genesis, can be excluded in the lower dosage range. This problem is not of such importance as may appear at first because the frequency of an effect can be increased by increasing the dosage--just one reason for using injurious dosages in long-term studies. Thus, the exist ence of a highly undesirable effect of a particu lar compound can be taken into account in the selection of a safety factor A more serious objection from a purely scientific standpoint is the imprecision of finding the highest "do significant effect" level. From a statistical point of view, it would be preferable to employ for safety evaluation the lowest effect level, that is the smallest one at which a meaning ful, injurious effect or even a relevant, harm less effect is detected This implies: ( i that the "no significant effect" is determined in order to put a limit on what is meant by the smallest effect level; but (iKthe more objective, positive finding is used for safety evaluation: and (c> the nature of any injurious effect observed will be taken into acoount in choosing a safety factor. The matter of safety factors based either on the "no significant effect" dosage level or oo effective dosage levels is discussed in Section 9.1.4.1 Threshold Levels as Biological Facts. The practical difficulty in establishing a "no effect" level for a particular compound using a manageable number of experimental animals and the more complex problem of extrapolating a safe level for man must not be permitted to obscure the fact that thresholds do exist The toxicologist faced with a single limited experi ment would be wise to recall the impossibility of proving a negative. The logician faced with a complete lack of supporting evidence would be wise not to press pure logic too far and conclude that no threshold exists so that even a single molecule may represent a hazard. At pointed out by Friedman (1973), the question of the existence of a threshold is a problem of biology, not of mathematics or of probability. In not a single instance has the absence of ft threshold been demonstrated. On the contrary, concentrations are known at which compounds with the highest biological activity are inac tive. For example, as described by Friedman (1973), limitation of vitamin A intake to 104 of the minimal required dosage leads to severe deficiency disease and yet it constitutes a dos age of 3.6 x 1015 molecules per kilogram of body weight or a concentration of 6 x 10'* M in the body. In a similar way, ineffective levels of vitamin D and vitamin B,, (where the daily requirements are only 10 pg/day and 1 Mg' day, respectively) are 4 x 10-11 M and 1 > 10~i: M. By conservative estimates, postmeno pausal women and adult men have 1.5 x 10' molecules of estradiol per kilogram of body weight or the equivalent of 2.6 x 10-l- M. For tetrachlorodibenzdioxin, reported to 56 *m studies. Thus, the existdesirable effect of a particuoe taken into account in the ity factor. A more serious irely scientific standpoint is f finding the highest "no level. From a statistical mid be preferable to employ ion the lowest effect levei. >t one at which a meanmgt or even a relevant, harm ed This implies: fa > that the ct" is determined in order to it is meant by the smallest the more objective, positive safety evaluation; and t njurious effect observed will ount in choosing a safety ifety factors based either on t effect'' dosage level or or vels is discussed in Section s as Biological Facts. The in establishing a "no effect" lar compound using a manf experimental animals and problem of extrapolating a i must not be permitted to lat thresholds do exist The vith a single limited expen se to recall the impossibility ive The logician faced with " supporting evidence would ess pure logic ioo far and hreshold exists-so that ever may represent a hazard. As ledman 11973. the question ` a threshold is a problem of tthematics or of probability stance has the absence of a nonstrated. On the contrary, known at which compounds biological activity are inac- as described by Friedman of vitamin A intake to 10r) 4mred dosage leads to severe and yet it constitutes a dos` molecules per kilogram of concentration of 6 x 10" M imilar way. ineffective levels vitamin B,. i where the daily only 10 day and 1 Mg are 4 x 10-'1 M and 1 * rvative estimates, postmenoi adult men have 1.5 x 1CF adiol per kilogram of body valent of 2 6 x 10-M. odibenzdioxin. reported to 57 FACTORS INFLUENCING TOXICITY * 2.2.7.4 have an LD 50 value of 0.0006 mg/kg in guinea pigs, a harmless dose would still produce a concentration of 1.9 x 10~' M in guinea pigs. For botulinum toxin, where talk of activity in terms of molecules has long been common, an amount of toxin that would produce absolutely no effect in mice would repre- $eni a dosage of 4.2 x 107 molecules per kilogram or a concentration in the mouse of 7 10"17 M, assuming a molecular weight of 900.000. Values of the same orders of magnitude apply to some carcinogens An ineffective amount of affatoxin in the rat determines a dosage of 9.6 x 10`* molecules per kilogram and a concentration of 1.6 x 10-" M. However, many strong cardnogens are less potent. For 1.2,5,6-dibenzanthracene, methylcholan- threne. and 3,4-benzpyrene administered by different routes, the ineffective concentration m the body ranges from 1 x 10" ' to 1 x 10~1 M Of course, the limiting level is even higher for compounds that are not inherently very active. For example, an ineffective amount of Aramite* as a carcinogen involves a concentration of 3 x 10-1 M. Hutchinson (1964) and later Dinman (1972) suggested that 10* molecules per cell is the limiting concentration for biological activity, whether pharmacological or injurious. As pointed out by Friedman (1973), there are about 6 x 2013 cells in a 70-kg human body, from which it follows that the suggested limiting level for activity is 8.6 x 10J5 molecules per kilogram or about 1 x 10" M. The demonstrated no effect levels for vitamin D, vitamin B ., and estradiol (10~n to lCF^Mj are so low that the corresponding thresholds may be somewhat lower than the limiting level of 1 x Id' just discussed. The same reasoning applies to the thresholds of toxic action of tetrachlorodibenzdioxin and botulinum toxin and the threshold of carcinogenic action of allatoxin. Further evidence that the limiting concentration for the activity of a few highly active compounds is less than 10~* M is the report that certain pheromones have thresholds of the order of 1 x 10-17 M. Of course, these values do not prove that the limiting concentration is ever less than lO-* M in susoeptible cells, sinoe some compounds, such as botulinum toxin, have an extremely high affinity for the cells on which they act, and their distribution in the body at critical dosage nay be very uneven. However, exactly what concentration is limiting is far less important than the fact that thresholds do exist even for the most active compounds. No one doubts that the existence of deficiency conditions proves that minimal or threshold concentrations of vitamins, horraones, and other beneficial compounds are required for proper action. There is no chemical or other scientific reason to suppose that there is an inherent difference in the dosageresponse relation of injurious compounds. Beneficial Effects of Small Dosages. Schulz (1886) may have been the first to observe stimulation from very lw concentrations of poisons. He investigated the effect of mercuric chloride, iodine, bromine, arsenous acid, chromic add, formic add, and salicylic add on yeast and concluded that, when sufficiently diluted, all of them can increase the vitality of yea6t over a longer or shorter period of time, Only e few years later the bacteriologist, Hueppe (1896), stated the rule that has come to bear his name; "Every substance that kills and destroys protoplasm in certain concentrations, inhibits development in lower concentra- tions, but acts as a stimulus and increases the potential of life at even lower concentrations beyond a point of neutrality." In stating this prindple, Hueppe mentioned certain apparent exceptions. He also acknowledged the inde* pendent discovery of the rule by Arndt and Schulz, A spedal, universally accepted instance of the benefidal effects of small dosages involves the reactions of plants to what are now called essential trace elements. A plant cannot live if even a single one of these metals or metaloids is completely absent from the medium in which the plant is grown, but an excess of any one or them is injurious. This is the law of optimal nutritive concentration. Recognition of it must be credited to Gabriel Bertrand even though he may never have stated it concisely in publication. The relationship of beneficial and harmful effects of trace elements was implied in the discussion that followed his presentation on "complementary nutrients" at the Fifth International Congress of Applied Chemistry held in 1903 in Berlin (Bertrand, 1903). Personal communications from his son, Dr. Didier Bertrand, and one of his students, Dr. Rene Truhaut, establish that Gabriel Bertrend presented the law of optimal nutritive concentration in his courses at the Sorbonne from 1906 through 1930, Later, Didier Bertrend (1962a, 1962b, 1969) generalized the law and expressed it in mathematical form, As reviewed by Townsend and Luckey (1960) and in a very different way by Smyth (1967), evidence has continued to accumulate that small dosages of many compounds are beneficial even though larger dosages of the same compounds are injurious. Townsend and Luckey tabulated many examples from the URL 03626 - ,, < !>. .' ': ' -. - . uL. "f`r" -'. ' 'f- - ' '- T .! ''*-' .ihsji URL 03627 Ola URL 03628 David, you've knocked atriek P. McCurdy off Goliath. Now what? ... ................. Richard A. Coccola ........................... Donald P. Burke Senior Editor....................................... Meyer Lurie Associate Managing Editor ... Robert T. Martinott When Ralph Nader first took to the field in the mid-60s with publication of his "Unsafe At Any Speed," he saw Aieietewl Managing Editor..... John W. Price. Jr. Assistant Managing Editor....... Herbert C. Short himself as jousting with corporate giants. Even a firm the size of General Senior Editor................................ Kenneth Brooks Motors was not so big that it did not feel Senior Editor..................................................... IrvinSchwartthze steel of his lance, take pause, even CSSeeonnpiiyoorrCEEhddieiittoof.rr.......................................................................................................J...o....h..Hn..o.M.m.....e.WrMSlniitttaoornnrWernerssotummebwlea.yIst. was an appealing As Irving Kristol picture in noted at a DEPARTMENTS meeting of the Chemical Manufacturers Environment..................................................... IrvinSchwarAtzssociation several years ago, Ameri International................................... Albert H. Kislln cans have never been really anti-busi Management................................ W David Gibson ness. But they certainly have had a large MPraordkaeottsio..n............................................................................K...e..n..n..e..t.h....BrJooohknsRivoirestreak of anti-big-business in them--in neasarch.......................................Gordon M. Grafl fact, anti-bigness, period. Dragon-slay Spaeialtiee ............................... PatriciaL. Layman ing was part of this nation's mystique Top of tha Nows............. Joseph F. Dunphy, editor Richard B. Roberts. Steven Leveen, William D. Kosman Art ............Robert P. McAuiey. associate director long before Teddy Roosevelt made a sport of busting trusts. And the country has benefited, for the most part. Sybil Collins But as we enter the 1980s, perhaps we Copy ................. Kathryn MuNer, Patricia Knowles Reprints..........................................Frances Regan CW NEW8WIRE ...................... Richard B. Roberts should ask ourselves some questions. Have those Goliaths we used to fear become an endangered species that we MoGRAW-HILL SERVICES Eeenemies ..........................................Eric B. Herr News Bureaus............... Ralph R. Schulz, director Michael Johnson, editor may one day miss? Have those Davids we used to cheer bred too fast and gone too far? Have they assumed some of the Atlanta, Stan Fisher; Chicago, Dennis Chase: Cleveland, Arthur Zimmerman; Detroit, Oavtd Whiteside; Houston, Robin Neesham; Loe An trappings of Goliaths? Has the slaying of Goliaths upset the political "ecology" of this country to such an extent that the geles, Marvin Petal; Sen Francisco, Margaret field is being left to the biggest predator Ralston Drossei; Washington, Robert E. Farrell. of them all--Big Government? Perhaps Bonn, Robert Ingersotl; Brussels, James Smith; London, James Trotter; Madrid, Jules Stewart; those Goliaths had been playing a criti cal role in decentralizing and defusing Milan, Lois Bohon, Jeff Ryser; Moscow, Peter J. Harm; Paris, John Tempiaman; Sao Paulo, Ernest McCrary; Singapore, Colin Gibson; Stock holm, Robert Skole; Tokyo, Robert E. Lee; Zurich, Laura Pliarski. governmental powers, in helping main tain a certain balance of power between government and the individual. The questions are not as far-fetched CIRCULATION Director................................................ Lynn Elliott Assistant Director........................ Donna ErDeWItt as they seem. The track record of Gol iaths these past few years has not been impressive. Nader, with one slim vol BUYERS' GUDE Manager ................................ Joseph A. Callahan Assistant......................................Mildred Rlmondl ume, humbled one of the country's larg est corporations and helped set in mo tion legislation that has hobbled a major SERVICES Director of Servieos............. Raymond F. Fremed tervicos Associate..................... Sylvia M. Larkin industry. The tiny snail darter, whose existence wasn't even known a short time ago, with the help of environmental friends, held up construction of a major BUSINESS DEPARTMENT Director of Business................James G. Methven Advertising Service Mgr........ Astrid Chahmirian Director of Production............. Verna M. Retziaff Assistant Production Manager..... Ronald Tuosto MARKETING COMMUNICATIONS Mktg. Research Mgr........................ Bertha Chase Marketing Services .................... Suzanne Murphy dam. Two obscure city reporters played a key role in ousting a President. And one of those same reporters, with the help of a fifth column of court clerks, has taken on.the U.S. Supreme Court in a book called The Brethren. On TV, Mike Wal lace, master of his medium, has little trouble cowing normally powerful adver Advertising Seles Manager......Howard M. Mager saries. And now we have the spectacle of Publisher .............H. John Swogsr, Jr. the once-mighty Chrysler going hat in hand to Washington, victim not only of its own frailties but of an increasingly costly and complex matrix of rules and regulations. Ford could be next. And if multi-billion dollar Chrysler and Ford are having problems, what hope is there for little XYZ Chemical Co.? In little more than a decade, the U.S. chemical industry has been smothered with upwards of 30 health and environ mental enactments. At least eight, including the Toxic Substances Control Act, are major acts passed by Congress only since 1969. Indeed, one expert observer of the chemical industry, whose views we respect, sees an industry virtually run--not just regulated, but run-- from Washington and state agen cies before the end of the decade. Those who fear the alleged bigness of business and concentration of corporate power like to hold Big Oil up as their prime example. But it's a poor choice, at least nowadays, as even a casual look at our third-quarter CW 300 review shows (Nov. 21, 1979, page 88). The table lists the 34 largest U.S. oil and gas compa nies. The largest--Exxon--posted sales of $77 billion for the latest 12 months. That's a lot of money, to be sure. But it represents only 21% of the total 12month figure for the entire group. Other such "large" firms as Mobil and Texaco accounted for about 10-11% of the total. And such "large" companies as Shell, Conoco, Sun and ARCO are in the 2-4% range. Concentration? Nonsense. And bigness in this context has little mean ing. The table listing chemical compa nies on page 34 of the Nov. 21 issue presents a similar picture. These figures tend to pale beside those contained in the government's budget. Moreover, it took chemical "giant" Du Pont some 200 years to top $10 billion in sales. The Department of Energy cleared that mark at birth without production. The power in this country has moved from the board rooms to a cancerous complex of regulatory agencies and organizations in the Federal City and state capitals--to the alphabet soup of EPA, OSHA, DOT, EEOC, FTC, SEC, IRS. .. .(Note that none of the first five existed when Nader first published his book.) When all the Goliaths are slain, who will protect the little Davids--and the rest of us--from the biggest Goliath of them all? Patrick P. McCurdy January 2. 1980/Chemical Week S In terms of regulation, URL 03629 you ain't seen nuttin yetEditor-m-Chief___Patrick P. McCurdy Managing Editor--................Richard A. Coccola Eaocutivo Editor..........-..............Donald P. Burk* "Well, how do you think the '80s will Sonlor Editor....................................... Moyer Lurie Aoooeioto Managing Editor . ..Robert T. Martinott look?" 1 asked, passing the butter. "Look," he said, munching on a Asoiatent Managing Editor..... John W. Price, Jr. luncheon roll. "We cannot paint a Aeaiatant Managing Editor....... Herbert C. Short picture of what the chemical industry Senior Editor................................ Kenneth Brooks will look like in 1990. But we can try to Senior Editor................................. Irvin Schwartz Senior Editor...................................... Homer Starr Senior Editor................................ John M. Wlnton Copy ChiOl ....................................... Milton Werner DEPARTMENTS Environment........................... -.......Irvin Schwartz Mtemational.................................. Albert H. Kislln identify the half dozen most important factors that will gradually change it." "Sounds reasonable," said 1, sagely. "Just using the cancer issue as an example, in the next few years the government is going to be identifying a Management.-.............................. W. David Gibson whole list of things that are suspected of PRMreaosrdekuaecrttcsioh..n................................................................................................................GK...eo..nr..dn..oe..nt.h..M..B...r..oGJorokahsftnRivolreccaieunstilnyg cancer. Some will be found suffi hazardous that efforts will be Speclattias .............................. Patricia L. Layman made to take them off the market. But Top of the Nows..............Joseph F. Dunphy, editor; just the fact that they're on a list . . . Richard B. Roberts, Steven Leveen, William D. Kosman Art Director................................Robert P. McAuley For example, the OSHA regulations will provide for 20 of them on a priority list Photo Editor................................................... SybilCollinswith another 300 right behind those 20 Copy ..................Kathryn Muller, Patricia Knowles as suspected human carcinogens for Reprints.......................................... Frances Regan CW NEWSWIRE....................... Richard B. Roberts regulatory purposes ... As soon as those lists come out, people will design McQRAW-HILL SERVICES Economics ........................................... Eric B. Herr Mews Dhtmus................ Ralph R. Schulz. director Michael Johnson, editor Atlanta, Stan Fisher; Chicago, Dennis Chase; Cleveland, Arthur Zimmerman; Detroit, David Whiteside; Houston, Robert E. Lee; Los Angoioa, Marvin Petal; San Francisco, Margaret Ralston away from those materials, whatever they happen to be." Recalling the speed with which "con tains no chlorofluorocarbons" embla zoned aerosol cans at the first hint of a problem, I had to agree. The man across the table continued. Droaeel; Washington, Robert E. Ferrell. "As a consequence, the actions of OSHA Bonn, Robert Ingersoll; Sruessh, James Smith; London, James Trotter; Madrid, Jules Stewart; and a couple of other agencies in devel oping a list of carcinogens is going to Milan, Lois Bolton, Jeff Ryser; Moscow, Peter J. Hann; Paris, John Tempieman; Sao Paulo, .Ernest McCrary; Singapore, Colin Gibson; Stock holm, Robert Skole; Tokyo, Robert Neff; Zurich, Laura Pllarskl, directly impact on materials that are going to be available. So purchasing is going to be a different game in the future... as to what to buy, how to buy CIRCULATION Director.......................... ...................... Lynn Elliott Assistant Director ....... ....... Donna E. DeWitt-KIng it and how much it's going to cost.. . . "Or take production. The government is moving very heavily into the process BUYERS' GUIDE ..... ............................ Joseph A. Callahan area. Under TSCA, they are going to be deciding some things as to how you AwifttM ........................... Miidred Rtmondi make products. So even in the produc SERVICES Director of Services..............Raymond F. Framed Sendees Aaecclata----- ------------ Sytvia M. Larkin tion process, government regulations that are being developed under TSCA and a couple of other laws will to some degree determine how you produce BUSINESS DEPARTMENT things" Director of Business............... James G. Methven Advertising Service Mgr.........Astrid Chahmirlan Director cl Production.............Verna M. Retziafl Aaaistenl Production Manager......Ronald Tuosto "But............" I found myself mum bling. "And not only that, but you've got the life-cycle concept, which they're pushing MARKETING COMMUNICATIONS Mktg. Research Mgr................ -.... Bertha Chase Marketing Services ................... Suzanne Murphy now with asbestos. They are proposing now that they will decide what uses are reasonable for asbestos, or where there Advertising Seles Manager.....Howard M. Mager are substitutes. And they'll allow the substitutes on the market, but you phase Publisher ______.H. John Sweger, Jr. out of asbestos. And they will now begin to set a total poundage of asbestos for all uses. And they will gradually reduce that every year." "Maybe that's not such a bad idea for a product like asbestos." "Maybe. But how do you administer it? How do they decide who gets it in terms of use, who makes it. . . etc.? Do you allow 12% in hair dryers, or 2%, as against, say, 35% in brake lining? Once you get into the question of the govern ment saying you can have a million pounds a year, you're faced with who's allowed to make and Bell that million pounds and who is allowed to use it." "I see what you mean. The govern ment would become the allocator." "Right. You're also faced with their ultimate objective, which, in effect, is to phase it down to an irreducible mini mum. Work it down, and say there are only 12,000 pounds that can be used, and at the end of the life-cycle process, that will be all that is permitted. And it gets into very, very complicated decisions by management as to their share of this and how it's going to be worked out to customers . . . It's a quota system. The question will be whether or not there will be a quota for your product and whether you'll have access to it." "Sounds like George Orwell's 1984," I muttered over coffee. "So what are you going to do?" he continued. "You'll phase away from it now. That's the whole objective--to phase you out of it So you'll be faced with an allocation system ... a quota system. The thinking--even with big quotas--is that in 10 years, you literally won't know how you're going to get it "Maybe it's not such a good idea after aU." "I'm not saying it's good or bad. But it will be a whole different set of rules, a new game, sort of like war. Further more, there's the compliance problem. Everyone's complaining about govern ment regulation. But the burden of regu lation isn't even here yet. Take the whole mass of regulation that the chemical industry will live under in the '80s-- none of it, effectively, has been put into place yet." "You mean, this is just the begin ning?" "You ain't seen nuttin yet." "I think I'll have another drink." Patrick P. McCurdy January 23. 1980/Chamicol Week 5 A Unique Industrial Development In A Major Growth Area On The Carolina Coast. Cooper Landing Industrial Center is 1,913 acres of prime industrial property. It's located just north of the growing port of Charleston, S. C., an area with one of the best labor and economic climates in the country. A deep water tanker dock, a barge dock, on-site rail facilities and easy access to the interstate highway system meet all of your transportation needs. And Char'eston is served by four major airlines. Energy sources have been planned into Cooper Landing, with an abundant supply of electrical energy, natural gas and large-quantities of fresh water available. Charleston, just 30 minutes from the site, is one of America's most historic cities. It is a medical and academic center, and nearby are 65 miles of ocean beaches and year round golf, tennis, fishing and boatina. Chemical Week/January 23, i960 Cooper Landing is the perfect location for a variety of industrial uses. It is particularly suited to the needs of chemical process industries, and Amoco's complete environmental studies will facilitate obtaining building permits. Cooper Landing Industrial Center is one of the few remaining deep water industrial sites on the east coast. Improved building sites from 25*750 acres are immediately available. Before you make a plant site decision, call Mr. J. O. Hemphill, Project Manager, 803/884-6151, or write for our brochure. m Amoco Realty Company Developer P.O.Box 987 Clements Ferry Road Mt. Pleasant, S. C. 29464 Area Code: 803/884-6151 URL 03630 Science URL 03b31 Brain lumor risk in petrochemical workers Epidemiologists struggle to sort out tenuous evidence that points to elevated Incidence of brain tumors among petrochemical workers Jeffrey L. Fox C&EN, Washington The current effort to show a link be tween exposures to petrochemicals and the incidence of brain tumors among workers in the petrochemical industry is stretching epidemiology' to its limits. Some critics even argue that epi demiologists risk a tumble by leaning somewhat beyond the reasonable limits of their science. This possibility was apparent at the recent workshop sponsored by the New York Academy of Sciences at which was assembled a blue-ribbon group of epidemiologists and other authorities familiar with brain tumor incidence in humans and in experimental animals (C&EN, Nov. 3, page 6). Some observers at the workshop could not help concluding that establishing a firm link between brain tumor incidence and employ ment in the petrochemical industry may prove very difficult. Moreover, even if established, that link may Bobbins: bring the best minds together represent the result of practices long since outmoded. Many naive ana dangerously sloppy procedures of several decades ago have been elimi nated. But sloppy procedures still exist, and other procedures that are gen uinely thought to be safe well might be otherwise. Thus, the petrochemi cal industry--and any other industry, for that matter--must rely on im perfect early warning systems, such as those mustered by epidemiologists, to ferret out potential health hazards in the workplace. Epidemiologists often refer to their preliminary surveys as "hypothesis generating" devices. The current hypothesis, being voiced by epide miologists working for the Occupa tional Safety & Health Administra tion, for the National Institute for Occupational Safety & Health, and for the National Cancer Institute, is that the incidence of brain tumors among petrochemical employees is anywhere from 1.5 to 2.5 times higher than the incidence in the general population. Several other epidemi ologists, some of them employed by the petrochemical industry but others without such ties, do not find evi dence for elevated incidence. These disagreements were by no means reconciled during the New York Academy of Sciences workshop. "Polarizations came to mind dur ing preparation of this meeting," says workshop organizer and epidemiolo gist Irving P. Selikoff. "We're con scious of this. But we were taught it was good to find causes of disease. Now, when causes in industry are found, there's no automatic pat on the back." There are also no auto matic pats on the back when someone finds the obverse, no evidence for causes, he could have added. Epidemiologic evidence regarding brain tumors is anything but straightforward. Many factors could serve to show the intense analytic ef forts under way at the Texas*petro chemical plants, including facilities run by Union Carbide in Texas City and Dow Chemical in Freeport but also at other installations owned byTexaco, Mobil, and Gulf Oil. For instance, the incidence of brain tumors in the general population in the U.S. is on the rise, according to Maitonl: dosage and route ere important Lawrence Garfinkel of the American Cancer Society. The rise is not a sharp one; it applies more to men than women; and it follows no immediately obvious pattern. Also, the apparent rise in incidence might be due, in part, to improved diagnostic procedures and to better reporting of cancers. Quibbling about statistics and how to analyze them is just the sort of ac tivity that preoccupies many of the epidemiologists now scrutinizing the petrochemical industry. There are plenty of good reasons for the quibbling--scarce data, reliance on old records of questionable validity, and sharp differences on how to ap proach an issue are all factors. "It is clear there is a rise in the risk of brain cancer," asserted NIOSH's Anthony Robbins at the beginning of the workshop. "From the point of view of the workers, we've been too slow in recognizing that risk. We are attracting attention to this issue |by having a public workshop]--not to blame anyone. But until you bring the best minds together, you don't solve the problem." What Robbins said was echoed often during the three-day meeting, particularly by his colleagues from NIOSH and OSHA. Their concerns, quite properly, revolve around the principle of ensuring the health of workers. But those concerns can act like a centripetal force, continually drawing one's attentions back to Nov 10 1&80 C&EN S3 Animal studies provide troublesome hints Ideally, the results of carefully controlled animal studies of carcinogens will complement epidemiology, confirming suspicions about humans by referring to systematic data about mice and rats. Bui a good case may be made that animal studies are sometimes mis leading and can be prejudicial to the epidemiologist, for example, humans might be more, less, or altogether in sensitive to a particular chemical that induces cancer in rats and mice. How often such discrepancies crop up is not so important here. The point is that the existence of bad or even good animal studies can send epidemiologists off on an oriented search, but a wild goose chase nevertheless. To anyone who is strict about the conduct of scientific Investigations, the question of Initial biases--of whatever nature--is bound to be troublesome. Thus, conscientious epidemiologists are likely to find themselves trapped in a paradox: wanting and needing helpful clues about enigmatic human health problems, but also wishing to avoid one of the worst pitfalls in science--namely, relying on false premises. There is plentiful animal data tor the epidemiologists searching for causes of human brain tumors to review. Scien tists have Identified several dozen chemical compounds that can cause brain tumors In various animals, in cluding mice, rats, hamsters, rabbits, and nonhuman primates. When tested, however, many of these chemicals do ngt cause cancer consistently from one type of animal to another. Moreover, the adatomic site of tumors caused by a particular agent can vary from one species of animal to another. This lack of consistency is fairly commonplace in animal lasting programs. It's a compli cating factor that helps to muddy oth erwise limpid clues now available. Not all brain tumors are alike. The major kind of tumor being followed in the epidemiologic studies is called a glioma. The spontaneous incidence of gliomas in mice is "exceedingly low," according to Italian toxicologist, Cesare Maltoni of the University of Bologna. Thus, the in cidence of gliomas arising after expo sure to various chemicals is a relatively reliable test system, he says. Nonethe less, that incidence also varies ac cording to how the chemicals are ad ministered to the animals--by feeding, injection, implantation, or inhalation, "it is important to know the dosage and route by which a carcinogen gains en trance," Maltoni emphasizes. Other observations of animals un doubtedly will complicate the assess ment of the human health question. For example, there is the matter of varying susceptibility to particular cancercausing agents during an animal's life span. "Embryos and newborn animals are far more sensitive to many agents than are adult animals," Maltoni notes, referring to the incidence of central nervous system tumors. This age-dependent variation in sus ceptibility is pronounced in Erythrocabus patas, a species of reddish, African monkey being studied by Jerry M. Rice and colleagues at the National Cancer Institute in Bethesda, Md. "We cannot get central nervous system tumors by injection of carcinogens into adults," he says about such animals. "They need to have very early exposure during gesta tion to develop tumors later, two to three years after birth." To Rice, these results suggest that there may be periods in life when hu mans are particularly or peculiarly sus ceptible to developing certain kinds of tumors. Thus, induction of brain tumors in adults "might have occurred very much longer in the past," he notes. What alt this means regarding work place exposures to putative carcinogens and the incidence of brain tumors is difficult to say. And when these obser vations are tied into a widely held view of how cancer develops, the story looks even more complex. Many scientists believe that cancer develops in two phases, called initiation and promotion. An early event, initiation, caused by one type of chemical, may not cause a tumor unless followed by exposure to (usually) other types of chemicals, called promoters. Thus, the search for a single type of workplace exposure to explain brain cancer inci dence might be misguided. Imagine the following situation. One group of adults, when children, either had a particular disease, took a certain medicine, or was exposed to some other "initiating agent," whereas another group of adults avoided that agent. Then during adulthood, members from both groups were met with an onslaught of many "promoting agents." Some such promoting agents might be found in the workplace, particularly when that workplace is a petrochemical facility. But other kinds of workplaces and alto gether different kinds Of environments also might provide some of the adults with deleterious promoting agents. Sorting through all these possibilities to identify the culprit agents could prove a formidable challenge. Studies of animals are introducing further complications. For example, some scientists contend that virus par ticles are associated with chemically induced brain tumors in mice. Other scientists dispute the importance and even the existence of such particles. Their importance to human brain tumors is unknown. Other observations eve puzzling. Why, for instance, does a particular chemical produce primarily brain tumors without affecting other organs'? Access of the chemical to such organs partly accounts for their differing sensitivity. But other metabolic Influences, including either different activation or detoxification in various organs, also could be important, according to Paul Kleihus of the Uni versity of Frieburg In West Germany. Thus, for instance, enzymes in the brain cells of rats are slow to rid DNA there of certain kinds of damage. Long-lived damage might lead to brain tumors dur ing the later life of such animals. By tar, the most puzzling phenome non is one noted by Maltoni and his colleagues. Varying the dose and the means by which it's administered for some carcinogens can cause system atic fluctuations in brain tumor incidence In animals. Thus, an elevated dose of vinyl chloride, for example, induces few (or no) brain tumors, whereas a lower dose may induce many such tumors. This "masking" phenomenon departs significantly from the typical observation that tumor incidence rises directly in proportion to the dose of carcinogen an animal receives. If such a phenomenon pertains to human brain cancer, the search for pertinent workplace hazards may be tortuous indeed. UHL 03632 workers and their environment. Thus, well-intentioned beliefs can predis pose one to look for clues more zeal ously in one place than in another. This is not meant to say that OSHA or KIOSH officials are tailoring their investigations to distort the truth. But these epidemiologists clearly are instilled with the belief that the workplace, particularly a modern etrochemical facility, can and must e safeguarded. That committment, which was on clear display among many of the federal officials at the workshop, is naturally even stronger among offi cials of unions representing the pet rochemical workforce. ``We must identify the job pieces where cases of brain cancer have appeared to see if there's a common denominator," says Raphael Moure of the Oil, Chemical & Atomic Workers International Union. ``What are the locations in the plant?" Once that's known, he says, ``conditions can be improved and ex posures minimized." Like Moure, Sheldon Samuels of AFL-CIO now assumes that the risk for brain tu mors is elevated for workers in pet- 34 CSEN Nov 10 1&BC URL 03633 Thomas: analysts tugfftsf tfavalad risk rochemical plants. "The failure to identify specific agents is a disap pointment, but not an insurmount able difficulty," he says. Although a fear about elevated brain cancer incidence certainly is justifiable, the statements of the two union officials indicate they have al ready gone from fear, to belief, to plan of action. Here again, their profes sional commitments more or less make that course inevitable. But it Many chemicals induce brain tumors in animals fc-Aeatylamlnofluorene Acrylonitrile 1-Aryl-3,3-dlalkyttrlazen$ Azoethane* Azoxyethane* Azoxymethane Butylnitrosourea Cycaaln 1,2-Oiethylhydrazlne Dlethylnltrosamlne* Diethyl sulfate* Dlmethylbenzanthracene Dimethyl sulfate* Elaiomycin Ethyl methaneaulphonale Ethylnttroeobiuret* Ethylnllrosourea* 1 'Methyl- 2-benzyl-hydrazine* Methyl methaneaulphonate Methylnitrosouraa* Methylnitrosourethane (intraplacenta!) Procarbazine* Propana aultono Propylene Imine Pyrrolizidine alkaloids Vinyl chloride v / \) a at*Ti>cal: ca- cross tnr placenta to nOwca 6r,- ttmcirs a o*ispnn botaoa. Vicin' A***KJ*' at a WOS- comes when many of the epidemiol ogists are arguing over whether there is any elevated risk. If the risk is the same as that faced by the general population, it &eems a rather striking challenge to the petrochemical in dustry to improve the workplace. `Tm puzzled by the widespread nature of the problem (of brain tumor incidence]," says H. Michael Utidjian of Union Carbide. "It seems wide spread over many populations and work classes, sometimes extending to white collar workers. 1 don't know of any other case of occupationally re lated cancer where it's appeared over such a wide range of workplaces." It is "oversimplistic," he adds, to say conclusively that brain tumors are due to exposures in the chemical in dustry. Several epidemiologists have con cluded that brain tumor incidence, at least among some petrochemical workers, is not elevated. For example, one such study was conducted by Chi-Pang Wen of Gulf Oil's medical and health resources division of the company'6 oil refinery in Texas--the same installation included in an NCI survey. Wen says his study "repre sents the largest retrospective cohort study of refinery workers to date in North America in terms of length of observation (44 years of employment experience) and person-years of ob servation." And he concludes that "the results indicate no increased risk of brain tumors among workers at this Texas refinery." He and NCI's Terry L. Thomas (and her collaborators) differ sharply in their conclusions. "Our analyses suggest that refinery workers have an elevated risk of brain cancer," Thomas says. And it's possible that current studies "underestimate" that risk, she adds. Eventually, their differing conclu sions have to be reconciled: They are, after all, looking at overlapping (al beit not identical) populations. Hence, it seems that discrepancies in analytic methods and in deciding what information to include stand in the way of reconciliation. Yet other epidemiologists, looking at different workplaces, come up with all kinds of puzzling clues. Michael R. Alderson of the Institute of Cancer Research in the U.K. has surveyed eight refineries there and concludes there is no increased risk for brain cancer, although preliminary evi dence for increases in malignant melanoma (skin cancer) is being fol lowed up, he says. "But even if you accept some of the U.S. data, the firoblem of brain cancer is in no way ike other hazards." Hints from other surveys provide a kaleidoscope of incongruent obser Wtn: rstutts Indicate no Incraastd risk vations. Women more than men em ployed in the Swedish chemical in dustry might be at greater than nor mal risk for brain cancer. Workers in the rubber tire building industry in the U.S. are also at greater than nor mal risk, says Thomas Mancuso of the University of Pittsburgh School of Public Health. But so are workers in the electrical machinery and also paper (and allied products) indus tries. And so also are workers in cer tain segments of the transportation industry, according to epidemiolo gists at the University of Southern California in Los Angeles. Epidemiology is very much an outgrowth of clinical medicine. Ac cording to one wag, epidemiologic surveys are often really "hunches, shored up with statistics." However, the fact is that many clinicians have hit upon important medical treatments by following up their hunches. The same phenome non may be at work among the epi demiologists scrutinizing brain cancer incidence. Hence, the possibility that they are onto something means that their surveys, no matter how prelim inary, cannot be disregarded. All of this close scrutiny also may serve a broader purpose. For example, Selikoff and his colleague William J. Nicholson at Mount Sinai School of Medicine in New York City find evi dence of higher incidence for other kinds of cancer besides brain tumors among several groups of industrial workers. "Brain tumors may be `the canary' for locating other cancer risks," Nicholson says. Thus elevated risks of diseases, such as lung cancer and malignant melanoma, cited by several of the epidemiologists at the New York Academy of Sciences workshop well could prove to be a more significam public health prob lem than brain cancer. D n?. ?=: Security is: having Air Products as your alkyl amines supplier. URL 03634 Consider our investment in programmed expansion. ? It took a big commitment to get where to Gt alkyl amines plant, at St. Gabriel, times. But your first move should be a ' we are: the world's No. 1 producer of Louisiana. review of our alkyl amines brochure. j C1-C4 alkyl amines. All told, our annual alky) amines Well be glad to send you a copy. Just That commitment is on-going. production capacity is 235 million write or call. Air Products and We are currently expanding our pounds and growing. An impressive Chemicals, Inc., Industrial Chemicals methylamines plant at Pensacola, figure. But what really matters for Division, Box 538, Allentown, PA Florida. In 1976, we went on-stream you, the amines user, is this: over 95% 18105. Phone: (215) 398-8973. | with the world's largest-capacity C2 of what we produce, we produce for I sale. A long-term supply contract with Air Products could be a very wise move. Particularly, in these uncertain We wont run out on you. Januvy 23, IMO/Chamlcal WMfc 37 CPI weighs in with costly toxicology labs URL 03635 Mobay's new toxicological testing lab oratory in Stilwell, Kan., was dubbed a "palace of science" by company board member Karl Buechel at the plant dedi cation last November. The $6-million, 60,000-sq.ft. facility at Mobay's test farm is only one of a series of "palaces" that chemical companies have been building lately to meet the expanding needs for toxicological testing under developing government regulations. New labs built by Stauffer, Allied, Monsanto and Shell during the past year have been even more costly. Only very expensive, highly automated precision equipment can turn out reliable, repro ducible data from a variety of toxicologi cal tests. But that hasn't stopped companies like Dow and Du Pont, pioneers in toxic testing, from expanding their facilities. Du Pont is enlarging its Haskell Labs by 30%, at a cost of some $8 million. And Dow is adding 28,000 sq./t. to the labora tory at its Midland, Mich., plant. Under Strain: "The rapid escalation of requirements for toxicology data has placed a strain on private and public facilities that conduct toxicology re search," explains Konrad Weiss, presi dent of Mobay. "This made it obvious that, from a practical and scientific standpoint, the corporation's require ment in this area could be met only with a new facility." Why did Shell build a 60,000-sq.ft. toxicological testing lab at its suburban Houston research complex? The compa ny, first among petroleum companies to build such a unit, rattles off a series of reasons: The need for space for long term animal studies, the improved quali ty and better scheduling it would provide, the possible opportunity to improve procedures and follow up on testing experiences, and Shell's signifi cant increase in spending for toxic test ing made a new lab necessary. Donald Stevenson, director of the Shell lab, says, "Building our own lab was a good busi ness derision." Stauffer, with its emphasis on agricul tural chemicals, had some experience with toxic testing before it built its new 60,000-sq.ft. lab at Farmington, Conn. The company has two labs in California (at Mountain View and Richmond) to do as Chemlcti Week/Jsnuuy 23. 1980 Animal mating al new labs include equipment like this computerized scale at Monsanto. metabolism and acute toxicity testing. "The quality issue was the main reason we built our own lab," says Wayne C. Jaeschke, vice-president for environmen tal services. Going Outside: Having its own toxi cological-testing facilities doesn't mean a company does all of its own testing. The range of work done by outside labs runs from 70% by Allied to an "overflow of about 10% " for Dow. In April 1979 Allied completed a $1.4 million, 17,000-sq.ft animal laboratory. The more in-house work done the more expertise developed at a company' Another 25,000-sq.ft. lab has been requested from the board. "With the addition, we could take on much of the longer-term studies," says Harry J. Robinson, Allied's vice-president for medical affairs. Both Monsanto and Shell hope to keep 70% of the testing work in-house. In fact, Monsanto already is studying an addition to its new 47,000-sqit. lab in order to stay with that percentage. The $12-million lab, dedicated in the fall of 1978, is expected to reach the 70-30 ratio in the third quarter of this year. Shell will reach it by 1983. Its lab has just started to receive test animals. `The more in-house work done, the more expertise is developed within the organization and the better understand ing a company has of its products," says Roger Folk, director of Monsanto's Envi ronmental Health lab. Growth PsHstw. Charles Reinhardt, director of Du Pont's 113,000-sq.ft. Haskell labs, says that only 20% of the company's toxic work goes to outside labs. Ground has been broken for the expansion that will increase lab space to 150,000 sq.ft. and staff to 265. The expansion will be completed by the summer of 1981. Dow, with its $12.4-million/year envi ronmental science and health-data-gath- ering budget, has decided that its 138,000-sq.ft toxicology-testing lab at Midland has gotten big enough. The company will be expanding new toxicolo gy-test labs at its Freeport, Tex. plant. Looking Book: Several of the labs, notably those of Monsanto and Stauffer, were located near universities so that they could overcome expected staffing problems by attracting people to a "learning environment." Stauffer's Jaeschke says the company has had "good success" attracting scien tists. But Monsanto's Folk says staffing has been a major problem. "It's hard to build up the expertise within a group and the communications that make a lab work." Monsanto also had some major air handling and temperature-control prob lems during startup of the laboratory. `The state-of-the-art of humidity con trol is not there yet," Folk says. Stauffer'B Jaeschke Bays its lab also had some initial operating problems, but "nothing major." Looking back, Jaeschke would like to have built in more storage and staff space. But he asserts that he is pleased with the deri sion not to go with a "clean-dirty spaces," as many labs did. He says such a layout is not cost-efficient. Dow's ' Perry Gehring agrees, saying that a clean-dirty area is a "waste of money." , - Stauffer uses limited access as a control. Monsanto's lab is also limited- access, but Folk says any expansion would include a clean-dirty area for long-term testing. There will probably be more differing views as more chemical companies devel op their own toxicological testing labs. It seems to be the wave of the future for the chemical industry. D