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washington^rf^tr URL 05005 House backs payments for Agent Orange exposure light of the studies of health effects on animals. More Last week the House of Representatives passed a bill than 613 million Ib/year of aniline itself are used in (H. R. 1961) that would pay some benefits to Vietnam the U. S. for producing isocyanates, rubber chemi veterans for exposure to Agent Orange, even though cals, dyes, pigments, hydroquinone, and drugs and all of the scientific evidence is not yet in. It would pesticides. More action is expected from the agency provide for temporary disability or survivors' bene in March. fits for diseases that may be linked to herbicide expo sure during the conflict Specifically, it would autho ASABCO reaches a I--d expoure accord rize payments if the veterans showed signs of a ASARCO, the United Steelworkers of America and certain liver disorder--porphyria cutanea tarda-- the Occupational Safety and Health Administration within one year of leaving the region, or if they last week signed an agreement outlining how the showed signs of soft tissue sarcoma within 20 years company will reduce worker exposure to lead in four of leaving. The program is expected to cost $4.7 mil primary lead smelters. The agreement, which is lion the first year and no more than $6 million annual based on joint studies conducted by the parties, sets ly during the five years it is in effect. By that time, up specific schedules for implementing controls. Com the $100 million epidemiology study of the veterans-- pany officials estimate that the plans will be costly-- the largest ever conducted--is expected to be com possibly reaching $7-8 million in ASARCO's Omaha, pleted by the Centers for Disease Control. Then, Neb., refinery operation alone over a period of years. sponsors say, the compensation issue will be reevalu But they also say that innovative new approaches ated. The bill now moves to the Senate, which has like the negotiated lead package make a significant been less active than the House on the issue. improvement over the traditional adversary tone that has characterized safety and health discussions about" EPA Ms industry do tssts on a nylon precursor OSHA standards in general for the last few years. The Environmental Protection Agency seems inclined The four plants covered by the agreement include to accept industry's plan to run health-effects tests Omaha; the smelters in El Paso, Tex.; East Helena, on cyclohexanone, a key intermediate for producing Mont.; and Glover, Mo. The worker-exposure control nylon. EPA gave a preliminary okay to the plan last plans call for improving ventilation, enclosing some month, and a final decision is expected after mid- processes or workspaces, and cleaning up more fre February. Cyclohexanone is commercially important; quently. Other improvements include providing clean more than 766 million Ib/year are produced. The in rooms, filled with filtered air, and mobile equipment dustry is coordinating work on the tests through the similarly equipped, as well as periodically inspecting Industrial Health Foundation's Cyclohexanone Study the worksites. Moreover, research will be conducted Group, of Williamsburg, Va. Final reports on two key to develop more controls to further reduce exposures. tests are due on Apr. 30. RuduMiaua ordare a halt on ttie um of EDB Looking ter the right test for nBnss Environmental Protection Agency head William D. / A question the Environmental Protection Agency is Ruckelshaus on Feb. 3 ordered an immediate halt to / wrestling with concerns the right way to set up the use of ethylene dibromide (EDB) as a fumigant on / health and environmental testing for aniline and its stored grain and as a spot fumigant on grain milling derivatives. While the agency has a wealth of infor machinery. The emergency suspension is the stron mation on exposure and release of these substances, gest action EPA can take under law. EPA plans to it has been more difficult to set up the health and recommend maximum permissible residues on grain environmental testing. EPA thinks that one way to and grain products and to set federal tolerance levels, avoid unnecessary tests is to examine "structure-ac Ruckelshaus said, "to eliminate EDB from the diet." tivity relationships"--in this case, testing a set of Ruckelshaus emphasized that the public should not representative chemicals in several proposed subcate- be alarmed. "What we're talking about here is long gories: aniline, monochloroanilines and polychloroanj- term health effects," he said, citing EPA analyses lines, mononitroanilines and polynitroanilines, and ha- that eating products containing EDB could increase lonitroanilines. EPA is working with the Aniline Assn, cancer risk over a lifetime. No action was taken on as well as with the Synthetic Organic Chemical Man the case of possible EDB residues in citrus, Ruckel ufacturer's Assn, on the issue. Tests already done shaus noted, because the agency needs more time to have persuaded EPA that an epidemiological study of study the data and to work out the international workers exposed to the anilines may be needed in trade problems. 40 ChantcaJ WMk/Fttruary S, 1064 L J*-/, **!>' URL 05006 In order to estimate the maximum potential risk of developing a tumor from exposure to 2,4,5-T contain ing 0.1 ppm TCDD, Dow used the very conservative "one-hit" model and upper 99% confidence limits for extrapolation from the data on rate. Since the incidence of tumors was greater in female rats in the Dow study, that frequency was used to calculate the potential for tumor formation In a female backpack sprayer. Even with this very conservative approach, the extrapolated annual risk was only 0.4 per million women who had applied 2,4,5-T each day, 5 days par week, 4 months per yr for 30 yr. In other words, there miQht be one tumor per 2,500,000 such female back pack sprayers per year, notwithstanding that there are probably none who fall in this category. - In contrast, what is the potential for developing cancer from exposure to known carcinogens? Based on data presented by Dr. Richard Wilson of Harvard during the 1978 OSHA carcinogen havings (8), the relative risk for a backpack sprayer Is very small compared to exposure to cigarette smoke, alcohol, saccharin, aflatoxin, chlorinated chemicals In water, and various forms of radiation. RELATIVE RISK OF CANCER PER MILLION PEOPLE EXPOSED PER YEAR Female backpack sprayer applying 2,4,5-T containing 0.1 ppm TCDD, 5 days per week, 4 months per yr, for 30 yr. 0.4 Smoking cigarettes 1200 Being in a room with a smoker 10 Eating and drinking Charcoal broiled steak, 0.25 lb per week . 0.4 Water in Miami or New Orleans 1.2 Diet soda (saccharin), 1 per day 10 Milk (aflatoxin), 1 pint per day or cheese equivalent 10 Peanut butter (aflatoxin), 4 tbsp per day 40 Beer (alcohol), lean per day 20 Exposure to radiation One transcontinental flight per year 0.5 Frequent airline passenger 15 Living in Denver vs. New York 10 Average U.S. diagnostic medical X-rays 10 Living in brick vs. wood building 5 Natural background at sea level 15 Sunbathing or mountain climbing (skin cancer, curable) 5000 According to these figures, being in a room with a smoker or drinking one diet soda per day ie 25 times more hazardous than 30 yr of spraying 2,4,5-T contain ing the maximum permissible level of 0.1 ppm TCDD; so is drinking milk, eating cheese or peanut butter, all of which may contain aflatoxins permitted by the Food end Drug Administration at levels up to 20 parte per billion. Exposure to various forms of radiation such as from traveling by air, living at high elevations, or even sunbathing is also more hazardous than being a back pack sprayer applying only 2,4,5-T for 30 yr. RESPONSES TO THE RPAR All responses to the RPAR are available for Inspec tion In EPA's Federal Register office, room 401 in the east tower of Waterside Mall et 401 M Street SW in Washington, O.C. Also available are most of the 179 references cited by EPA in their risk document (PD 1) which was published In the Federal Register on April 21,1978. . By the end of November about 2800 Individual responses had been logged In and assigned by EPA to more than 2500 persons or organizations. According to Dr William A. Wells, Acting Director of EPA's Special Pesticide Review Division, only aoout 20 to 40 responses are substantive and backed by data from scientific studies. The rest are only "testimonials," either from users who cite the need for continued registration and report no harm from exposure to 2.4.5- T for up to30yr, or from Individuals who claim to have suffered harmful effects or are afraid they might if they were exposed even to spray drift. Review by Dow of ail the responses on file in EPA Indicates they are better than 86% in favor of continued registration of this useful herbicide. Major respondents include Dow with 13 volumes of risk rebuttal information Including copies of 158 documents or reports not cited by EPA in PD .1. Dow also submitted 8 volumes of benefits data for uses in flee, grazing lands, forests, and rights-of-way, again completely documented with copies of ail cited refer ences. Other respondents are the National Forest Products Association (NFPA) who have recently con ducted an exposure study under actual field conditions to obtain more representative data than the additive "worst case" estimates used by EPA in its PD 1 for 2.4.5- T. Various user groups also responded collective ly and individually, such as the National Cattlemen's Association, the National Rica Growers Association, and various Farm Bureaus. Major responses by activists were submitted by Friends of the Earth (FOE), the Environmental Defense Fund (EDF), Citizens Against Toxic Sprays (CATS), and several other coali tion groups. According to EPA'S log of responses to the RPAR, only one number Is assigned to letters which appear to originate from one source. For example, individual submissions from 32 foresters with firsthand expe rience using 2,4,5-T for up to 30 yr were all given one accession number because they all worked for Inter national Paper Company, albeit in various locations around the country. Each of Dow's submissions during the past 7 months was listed separately under one accession number. Similarly, only one number was given to numerous submissions by Friends of the Earth under different cover letters. On the other hand, EPA curiously assigned individual numbers to each post card or note received from various members of several families from email villages in Oregon end Arkansas. To avoid the potential for bias either way, the distribu tion of "for" and "against" responses repotted herein is based on Individual entries In EPA's log rather than according to the EPA accession numbers assigned to them. ji'v- SCIENCE/TECHNOLOGY CONCENTRATES this Hi _j0_ sfroca Jmcka radioactive' xaotppes in gndns showed agestn the rangit on yitertLlThe dftiestpreviojisly dawCWcks west* Western Greenland and wet* inflljr'of pf two i.-phenpl- mCaeties'fitiiea Tqtfifflif r'lry otigoethydene ii -* *-*?&> *t. - ^ billionyearn. bridges of -~a --i-^'- 'uqfcctre<ting urahyJ ionsfrem >Tfe^^^W'Wddi:Awani i ->- K^u|S.o^t^M^-imd'.n;o^u%ic phase,' according rpthe 1983 Welch; Award inCheoristry win be given ^ 4 '".tLaipd cowprkers from the insii- "^To Henry Taube,.a chemistiy professor at Stanford OrganidCheanstry and- General Chemistry Y University, ''for his decades of leadership and tfetJ3ivei*i!y of Pamu, Italy [Atfjac. Chen, rbif. >3 p dedication" in fhe held of inorganic chemistry. The feJfggU 2, 563 (1983)J. vThe researchers find that tfWith a 70-fold excess ofligand, 98% of the uxany^ion snt in aqueous strixrtion is extracted as either a -2:1 complex with the ligand. 'Jhe .presence tif onetaf cations in the solution, even in large j^s^.-iauscsB, doernbt change the total uranyl ions extracted, "S'~hnd die other cations are themselves not removed ward, one of the more prestigious m tfhemistry, of a gold medaUion, and J>l5p,jQ00. Taube ive it.'it the^iSfekji Faurtibrtaon'b*j*quet in in November. "Taube is considered to be a scientist'' in the w*a of inorganic reaction field.for decades," S. Jaeey,piuaidmt of the foundation. so^wtion. Thetmuvjft ions can be recovered * Y.^' mahout 90% yield from die organic phase, suggesting -Ji diat theligands ought have apph- ' ^icatemvin fiw deccrntanaiftatien and tecovefy of uranir. ifrpm liquid wastes, bean crop yields 15% or pathologist Howard . ifultural jtesearch. 4i yfela redudtensdaitaed and USDA scientists found in............. as a. jpa^.CfUae `braky : theSBQodnr behavior of certain 'of qza^;teafe^^ ................. ^ fell about f'ltffillW&ad air.^Sulfur dioxide at low Hun, a-ffjtiysic&lh arii yields, Tmt wqx> ^>hrtter*l of nutrition aftd focMi Kieaoe^ reduced fidds \usetts Institute of Technology.Vew stl `f.\- gven^e ozone maoyf>CTn-g?t)wing in fesA/$gr? H % witfe+<he mine & ~ average for AaaveriigeofB.G5 ppm^ ; ^^eans^rown-in 'dry aofi. ' . ,_j as "teM^pBOM' -i,rvw V i*f\o - * s'y. ri&.K 1 p*e l2 November 30, 1983 PESTICIDE & TOXIC CHEMICAL NEWS ...For 3-(3,5-dichlorophenyI)-N-(l-methylethyI)-2,4-dioxo-l-imidazoHdmecarboximide and its I metabolite 3-(3,5-dichlorophenyl)-2,4-dioxo-l-irmdazolidinecarboximide, 60 p.p.m. in or on grapes. ... For iprodione and its non-hydroxylated metabolites, 0.8 p.p.m. in eggs; 0.4 p.p.m. in fat, meat and meat byproducts (except kidney and liver) of cattle, goats, hogs, horses, and sheep; and 3.0 p.p.m. in kidney and liver of cattle, goats, hogs, horses, and sheep. -- For iprodione and its non-hydroxylated and hydroxylated metabolites, 0.3 p.p.m. in milk. The companion petition would set a food additive tolerance of 300 p.p.m. in raisins, and feed additive tolerances .of 1,000 p.p.m. in Taisin waste and 225 p.p.m. in dried grape pomace for residues of iprodione, its isomer 3-(l-methylethyl-N-3,5-dichlorophenyl-2,4dioxo-imidazolidinecarboximide and its metabolite 3-(3,5-dichlorophenyl)-2,4-dioxo-li midazolidinecarboxi mide. Amended was a Rhone-Poulenc petition which would have set a tolerance for residues of iprodione, its isomer, and its metabolite of 7.0 p.p.m. in or on lettuce (See April 13, 1983, Page 4). The crop was re-designated as "lettuce (head)" and the tolerance level was changed to 15.0 p.p.m. Merck filed a petition to set a tolerance for thiabendazole of 0.1 p.p.m. in or on dry beans. The fungicide is 2-(4-thiazolyl)benzimidazole. Amended was a Merck petition to set tolerances for residues of thiabendazole of 12.0 p.p.m. in or on cantaloupes; 5.0 p.p.m. in or on strawberries; and 0.5 p.p.m. in or on tomatoes (See Oct. 6, 1982, Page 12). The petition was amended to delete the proposal for tomatoes, and to increase the requested tolerance in or on cantaloupes to 15.0 p.p.m. An EM Industries petition to set tolerances for residues of triforine of 0.01 p.p.m. in or on almonds; and 0.1 p.p.m. in or on almond hulls (See Dec. 26, 1981, Page 4) was amended to increase the requested tolerance for almond hulls to 0.2 p.p.m. The fungicide is N,N'-f 1,4-pipe razinediy!-bis(2,2,2-trichloroethy!idene)]-bis( formamide). Also amended was a Pennwait petition to set tolerances for residues of thiophanatemethyl of 1.0 p.p.m. in or on cucumbers, melons, pumpkins, and squash; 5.0 p.p.m. in or on rice; 10.0 p.p.m. in or on grapes (fresh); and 15.0 p.p.m. in or on rice straw (See Sept. 1, 1982, Page 5). Deleted were the proposed tolerances for fresh grapes, rice, and rice straw. The fungicide is dimethyl-[(l,2-phenylene)bis(iminocarbonothioy!)]bis(carbamate), its oxygen analog dimethyl-4,4*-0-phenylenebis(allaphanate), and its benzimidazole-containing metabolites. Withdrawn was a Pennwalt petition which would have established food additive tolerances for residues of thiophan&te-methy! of 50.0 p.p.m. in raisins and 35.0 p.p.m. in pineapples, and feed additive tolerances of 125.0 p.p.m. in dried grape pomace and 20.0 p.p.m. in rice hulls (See Sept. 1, 1982, Page 5). URL 05008 fsHOI SHORT-TERM TESTS FOR CANCER NOT READY YET, CABINET GROUP TOLD A background paper prepared for the Cabinet level group which is looking at toxic torts and victim compensation legislation (See June 1, Page 3) told the Cabinet Council on Legal Policy that the relevance of short-term testing for human carcinogenicity is at present "a matter of presumption." November 30, 1983 Page 13 PESTICIDE & TOXIC CHEMICAL NEWS In a lengthy discussion of the difficulties of extrapolation of bioassays in general and short-term tests specifically, the draft paper said an international collaborative program had found the short-term tests to have "variable success, much interlaboratory variation and different ability to detect different classes of carcinogens." Paraphrasing the authors of the study, F. J. De Serres and J. Ashby, the background paper said: . . At present, the best test predicts with an accuracy of approximately 80%, with most tests having an accuracy of 60-70%. To place this in perspective, the accuracy of a prediction by flipping a coin will be 50%. Therefore, much more has to be done to make the short-term tests an adequate replacement for the chronic bioassay. The relevance to human carcinogenesis is still a matter of presumption since there has been no extensive tet against human carcinogens and non-carcinogens. However, evaluating one test, the Ames assay, it was found to predict 75% of the carcinogens (28), but the test has not been evaluated against human non carcinogens." The document leaned heavily in a listing of carcinogens on the reports of the International Agency for Research on Cancer (See July 13, Page 2), but published also a tabulation from Lancet by W. T. Blot and J. F. Fraumeni in 1975 setting forth estimates of the "proportions of cancer deaths attributed to causes" in the U.S. The tabulation: Proportion of Cancer Deaths in the United States Attributed to Causes* Factor Percent Cancer Deaths _ fe Tobacco Alcohol Diet Food Additives Sexual Behavior Occupation Pollution Other Best estimate 30 3 35 1 7 4 2 18 Range 25-40 2-4 10-70 -5b-2 1-13 2-8 < 15 120,000 12,000 140,000 4,000 32,000 16,000 8,000 72,000 afrom Ref. 7 ^Allowing for a possible protective effect of antioxidants. The paper added a series of caveats, including that the approach doesn't compensate for multiple exposures, but said the estimates "remain the best ones presently possible." OMB KILLS PMN SITE-LIMITED EXEMPTION "EXPERT REVIEW" REQUIREMENT The Office of Management and Budget sent OTS back to the drawing boards on its longpending proposal for exempting site-limited intermediates and some low-volume chemicals from Premanufacture Notification. The OMB disapproval of the proposal arrived at OTS Nov. 29, although it was dated Nov. 15 -- before the PMN Significant New Use Rule comments of OMB's Qiristopher DeMuth drew widespread Congressional charges of "interference" (See Nov. 23, Page 20). OMB told OTS: 28 ter 5, 1983 PESTICIDE & TOXIC CHEMICAL NEWS Auchter said he had not seen the memo listing the 116 "until the recent publicity brought it to my attention." He pointed out that each page of the memo said the draft bears no official endorsement and, "It should not be reproduced nor reported upon as official OSHA policy." Charges that OSHA is planning to "eliminate the files" on the 116 are "absolutely untrue," Auchter said, adding: the 13 years of its history, OSHA has accumulated literally hundreds of cubic feet of paper :rds which have exceeded the storage capacity of the file cabinets in the agency's xtorate of Health Standards Programs. There was almost no control over this pile of paper lie past years. OSHA had never cleaned or updated any of its health standards files, sed or inactive files were placed in boxes and containers of all types and simply pushed corners. As a result, many cubic feet of valuable agency records were misplaced, arded or otherwise improperly disposed of over the years. iin proud that in recent months, in conjunction with the National Archives and Records #ice (an agency of the General Services Administration), OSHA has conducted a major 4 clean-up and archiving operation in the Directorate of Health Standards Programs. This ^resulted in the preparation of over 125 cubic feet of records for permanent, retrievable itge. These documents are awaiting transfer to the appropriate Federal Records Center. H' , I believe, is the first time in the agency's history that the records of valuable agency Wth standards development have been properly achieved." During questioning, Auchter dramatized the point, stating his Administration had opened up the closet, let some light in and stirred some dust. The few partisan sparks of the hearing occurred as Gaydos questioned the OSHA inspection and enforcement record, asking if it wasn't fair to assume that some companies were being let off the hook by settlements. Rep. Erlenborn (R--111.) countered that as a former prosecuting attorney, he knew that 90% of criminal cases are handled by plea bargaining and Rep. Gaydos rejoined, "If I'm a worker, I don't want anyone plea bargaining with my life." Gaydos asked specifically about standards for benzene, formaldehyde, toluene and 1,1,1 -- trichloroethane. Auchter replied that the problem has been one of documenting exposure. The standard on the last of these has been slowed, he said, because it was indicated that industry would switch to one of three more dangerous substances. On formaldehyde, he said, OSHA could not document that it was a carcinogen at or below the levels of the OSHA standard of 3 p.p.m. Asked why he would not err on the side of protection by issuing emergency temporary standards on substances, Auchter responded, "It would be irresponsible for me to take an action I knew in my heart was illegal," an argument he used earlier in hearings on ethylene dibromide (See Sept. 14, Page 22, and separate story). ESTYLE, NON-CHEMICAL CAUSES OF CANCER POINTED OUT A seminar held by the American Council on Science and .Health in New York Oct. 4 brought from various speakers the statements, according to ACSH press releases, that: --"Not only do our environmental health problems go far beyond those attributable to industry, but many of today's problems are trivial compared to some that have existed in the past" -- Dr. Merril Eisenbud, Director of the Laboratory for Environmental Studies, New York University Medical Center. October 5, 1983 Page 29 PESTICIDE & TOXIC CHEMICAL NEWS -- "Cancer is certainly much more talked about than it was in previous decades, but this is not in itself evidence that cancer rates among non-smokers of a given age are rising. In fact, examination of mortality data indicates that there has been no generalized increase in non-respiratory tract cancer over the past three decades. This does not, of course, guarantee that all recently introduced chemicals, pesticides, pollutants and habits are harmless. Yet, it does guarantee that to concentrate only on new environmental agents as possible causes of cancer, while discounting the role of long-established aspects of our way of life, is to ignore the possibility of preventing many common cancers" -- Dr. Richard Peto, Reader in Cancer Studies, University of Oxford. URL 05011 HEARING LIKELY TO BE REQUESTED ON SUSPENSION OF EDB FOR SOIL FUMIGATION A hearing is expected to be requested by Great Lakes and Ethyl Corp. on the emergency suspension of the soil fumigation use of ethylene dibromide (EDB). At press time, no suspension or cancellation hearing requests bad been filed with EPA (See Sept. 28, Pages 2, 15, and 25). The agency initiated emergency suspension and cancellation actions Sept. 30. In summary, the agency: suspended the soil fumigation use which amounts to 90% of the pesticide use of EDB; cancelled, effective Sept. 1, 1984, the use as a quarantine fumigant on citrus fruits, tropical fruit and certain other fruits and vegetables; and cancelled all other uses, except some minor uses, effective in 30 days unless a hearing is requested. It is probable that the cancelled uses will not be contested. Suspension hearing requests, if any, have to be filed this week. Depending on results of continuing monitoring of flour, baked goods, milk, meat, poultry, and grain, the agency might ultimately take emergency suspension action against the uses of the pesticide as a spot fumigant and as a fumigant on stored grain and grain and flour milling machinery. Minor uses retained with restricted use classification and label changes include: Fumiga tion of stored beehives and hive platforms to control wax moths, use on vault-stored clothing and furniture, usein USDA's Japanese Beetle control program, and termite control. For continuing fumigation uses, protective clothing, respirators and other exposure reduc tion techniques are being required under interim regulations. EPA will set tolerances for EDB per se, probably 100 p.p.b. The agency said the EDB tolerances will be set to "regulate residues of EDB which may continue in the human diet as a result of delays in these cancellation actions pending hearings, in stored commodities previously fumigated, imported foods, or from other causes." Currently, tolerances for EDB are included as tolerances for residues of inorganic bromides, with a 125 p.p.m. total tolerance for residues of inorganic bromides in grain, resulting from use, generally, of a mixture of methyl bromide and EDB. In about two months, Richard Johnson, Registration Division, OPP, EPA, noted last week, the agency should have enough monitoring data to decide whether to issue an emergency suspension order for the grain and milling machinery uses. At a Sept. 30 briefing for interested parties, Johnson said the decision on the phase-out for citrus was the "toughest" aspect of the decision and that one more season of citrus use "is all we can live with" because the use presents "very serious health hazards." September 19, 1983 Page 51 FOOD CHEMICAL NEWS Shore also criticized the Administration's support of legislation to permit the interstate shipment of State-inspected me*r (See FOOD CHEMICAL NEWS, July 25, Page 40). She also faulted the federal program, citing changes in inspection procedures, increased linespeeds, and lack of supervision which have resulted in an "impending public health crisis." A recent survey by the union representing meat inspectors of its members, Shore said, showed that 80% believe that the regulated industries control the federal meat and poultry inspection program. URL 05012 NATURAL DIETARY ANTIOXIDANTS MAY HAVE IMPORTANT ROLE IN CANCER PREVENTION Dietary intake of natural antioxidants, such as vitamin E, 0-carotene, selenium, glutathione, and ascorbic acid, could be an important aspect of the body's defense mechanism against the great variety of natural mutagens and carcinogens contained in the human diet, Dr. Bruce N. Ames proposed in the Sept. 23 issue of Science. Ames, Chairman of the Department of Biochemistry, University of California (Berkeley), suggested that the geographic differences in cancer rates, thought to be due mainly to life-style factors such as smoking and dietary carcinogens and promoters "also may be due m good part to less than optimum amounts of anticarcinogens and protective factors in the diet." "Diet, which provides both carcinogens and anticarcinogens, is extremely likely to be (a). . . major risk factor" in cancer, second only to tobacco smoking," Ames said. Listing 16 examples of naturally-occurring mutagens and carcinogens in foods, the scientist "emphasized that no human diet can be entirely free of mutagens and carcinogens and that the foods mentioned are only representative examples." 'The human dietary intake of 'nature's pesticides' is likely to be several grams per day -- probably at least 10,000 times higher than the dietary intake of man-made pesticides," Ames pointed out, commenting: 'There are health costs for the use of these natural pesticides, just as there are for man-made pesticides, and these must be balanced against the costs of producing food." ". . . Little information is available about the toxicology of most of the natural plant toxins in our diet, despite the large doses we are exposed to," he noted suggesting, "Many, if not most, of these plant toxins may be 'new' to humans in the sense that the human diet has changed drastically with historic times." "By comparison," he said, "our knowledge of the toxicological effects of new man-made pesticides is extensive, and general exposure is exceedingly low." "Laboratory studies of natural foodstuffs and cooked foods are beginning to uncover an extraordinary variety of mutagens and possible carcinogens and anticarcinogens," Ames noted, commenting on the following 16 examples of natural mutagens, teratogens and carcinogens in the human diet: (1) Safrole, estragole, methyleugenol and related compounds, present in many edible plants, such as "natural" sarsaparilla rootbeer, and black pepper, are carcinogens in rodents and several of their metabolites are mutagens. (2) Hydrazines, found in edible mushrooms, are carcinogens and mutagens. September 19, 1983 1 1 W>OD CHEMICAL NEWS (3) Linear furocoumarins, such as psoralen derivatives, widespread in plants of the Umbelliferae family, such as celery, parsnips, figs and parsley, are potent light-activated carcinogens and mutagens. (4) The potato glycoalkaloids solanine and chaconine are strong cholinesterase inhibitors and possible teratogens. (5) Quercetin and several similar flavonoids are mutagens in a number of short-term test systems. Flavonoids are extremely widespread (daily levels close to 1 g) in the human diet. (6) Quinones and their phenol precursors, which can react to generate mutagens and carcinogens, are widespread in the human diet. Mutagenic anthraquinone derivatives are found in plants such as rhubarb and in mold toxins. (7) Theobromine, a relative of caffeine, has been shown to be genotoxic in a variety of tests, to potentiate (as does caffeine) DNA damage by various carcinogens in human cells, and to cause testicular atrophy and spermatogenic cell abnormalities in rats. Cocoa powder is about 2? 'obromine and therefore humans may consume hundreds of milligrams of theobromine a day from chocolate. Theobromine is also present in tea. (8) Pyrrolizidine alkaloids, which are carcinogenic, mutagenic and teratogenic, are present in thousands of plant species, some of which are ingested by humans, particularly in herbs and herbal teas and occasionally in honey. (9) The broad (fava) bean, a common food of the Mediterranean region, contains the toxins vicine and convicine at a level of about 2 percent of the dry weight. (10) Allyiisothiocyanate, a major flavor ingredient in oil of mustard and horseradish, is one of the main toxins of the mustard seed and has been shown to cause chromosome aberrations in hamster cells at low concentrations and to be a carcinogen in rats. (11) Gossypol, a major toxin in cottonseed that accounts for about IX of its dry weight, causes pathological changes in rat and human testes, abnormal sperm, and male sterility, and appears to be a carcinogen as well. (12) Sterculic acid and malvalic acid are toxic cyclopropenoid fatty acids present in cottonseed oil and other oils from seeds of plants in the family Malvacel, such as cotton, kapok, okra, and durian. Another possible source of human exposure is consumption of fish, poultry, eggs and milk from animals fed cottonseed. The toxicity of these fatty acids could be due to their ease of oxidation to form peroxides and radicals. (13) Leguminous plants such as lupine contain potent teratogens. (14) Sesquiterpene lactones are widespread in many plants and some have been shown to be mutagens. (15) The phorbol esters present in the Euphorbiacea, some of which are used as folk remedies or herb teas, are potent promoters of carcinogenesis. (16) Alfalfa sprouts contain canavanine, a highly toxic arginine analog that is incorporated into protein in place of arginine. In addition to these 16 examples, Ames listed coffee, alcohol, mold carcinogens, nitrite, nitrate and nitrosamines, rancid fat, and the burnt and browned material from heating protein during cooking as mutagens or carcinogens present in the human diet.