Document omQzYGYVO5nQrvVNMwxQqXvgr

/*t4c-4t>Tt*j Fese/vtctf tflo*rs /C.-J>J- 7 7 s/'f/r? RSV 0010789 Monsanto MFC - Dayton (CO,'OlVJDtrr./LOCATION! SPECIAL ITVPE OF R6POT REPORT C a rl R. M c M illin A REVIEW OF T ill: CAHC 1NOCF.N LITERATURE OF 125 CHEMICALS REPT NO: m r c - D A - 771 AUTHORS: * 10S8 iMcMISt COPY NO.: / TITLE: REPORT NO. JOB/PROJECT NO. OATE PERIOD COVERED TITLE MRC-DA-771 103.1020 18 April 1978 1 March 1978 - 31 March 1978 P?CE APt ift7i IV 1 A REVIEW OF THE CARCINOGEN LITERATURE OF 125 CHEMICALS AUTHORS: Carl R. McMiTlfrr ?^i * fj ? \ l^"J i ** i Liuu i< lu \ l }' Uvi . ABSTRACT: The first task of EPA Contract 68-02-2773 is to identify 20 significant atmospheric carcino gens. Sampling and analytical methodology based on porous polymer sorbants and gas chroma tography/mass spectrometry will then be devel oped for 15 of these chemicals. In order to identify significant carcinogens* the literature has been reviewed for about 125 chemicals to determine whether they should be considered carcinogens for this project. Different criteria must be used to define what tests results indicate carcinogenicity depending on the use to which the resulting list is intended. For this program* some chemicals have been included on **he possible carcinogen list based on a limited amount of short-term mutagenicity data. If these lists should be used for other purposes* it would be expedient to review the literature cited and draw the appropriate conclusions based on other guidelines. COMPANY CONFIDENTIAL This document is the property of Monsanto Company and t(i ivCfpf<*i responsible for its safekeeping and disposition, tt contains CONFIDENTIAL INFORMATION which must not be reproduced, revealed to unauthorized persona or sent outside the Company without proper authorization. RSV 0010790 DISTRIBUTION COPY NUMBER ~1 2-4 5 6 5 9 10 11 12 13 ;4 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 37 33 34 Technical Reports Library, R2C St. Louis Central Files Dayton R. C. Binning Dayton D. J. Dahm J. S. Harris, G5ED Dayton St. Louis L. . Klein, G5EA St. Louis G. D. Rawlings Dayton G. A. Richardson Dayton B. G. Ward St. Louis D. L. Zanders Dayton J. M. Sutler Dayton T. H'j.ynes R. F. Ivory Dayton Dayton R. C. Peck Dayton R, B. Reznik Dayton R. J. Schatz, E3SA St. Louis J. J. Brooks Dayotn E. C. Eirr.utis Dayton D. J. David Dayton w. M. Haynes Dayton C. R. McKillin Dayton T. A. Orofino Dayton J. V. Pustinger Dayton A. 0. Snyder Dayton L. 3. Stevens Dayton D. S. West Dayton H. L. Williams Dayton T. G. Linxveiler Dayton F- J. Winslow/D. B. Nelson Dayton C. J. Eby Washington F. C. Meyer St. Louis B. C. Caste BioLabs, I ABSTRACT ONLY *R. K. Flitcraft - Dayton *May request a copy from the Dayton Library M 10MIC) COMPANY CONFIDENTIAL When no longer needed, or upon request, return this report to Central Filet. Dayton. RSV 0010791 Introduction The first task of EPA Contract 68-02-2773 is to identify 20 sig nificant atmospheric carcinogens. Sampling and analytical meth odology based on porous polymer sorbants and gas chromatography/ mass spectrometry will then be developed for 15 of these chemi cals. In order to identify significant carcinogens, the literature has been reviewed for about 125 chemicals to determine whether they should be considered carcinogens for this project. Different criteria must be used to define what test results in dicate carcinogenicity depending on the use to which the result ing list is intended. For this program, some chemicals have been included on the possible carcinogen list based on a limited amount of short-term mutagenicity data. If these lists should be used for other purposes, it would be expedient to review the literature cited and draw the appropriate conclusions based on other guidelines. For this project, a probable carcinogen generally has at least some positive animal data coupled with positive mutagenicity data from at least one well established mutagenicity test or several muta genicity tests which have not been as extensively validated. The mutagenicity tests which were considered fairly well established include the Ames Salmonella typhimurium test and the enhancement of viral transformation tests (e.g. B. C. Casto), with the E. coli (pol A) differential toxicity and the Drosophila tests also con sidered important. Animal carcinogenicity tests were considered less significant if they were conducted more than 5-10 years ago, tested by the subcutaneous route of administration demonstrating only local tumors, utilized only a few animals, or reported no concurrent control animals. Dr. B. C. Casto, BioLabs, Inc. - Northbrook, Illinois, has been a consultant for Monsanto Research Corporation on this EPA contract. MONSANTO RESEARCH CORPORATION RSV 0010792 Cheraical Acetaldehyde Acetone Acetonitrile Acrolein Acrylonitrile Aldrin Allyl Chloride Aniline Anthracene Benz(a)Anthracene Benzene Benzidine Benzo(a)Pyrene Benzoquinone (Quinone) Benzoyl Percxide Benzyl Chloride Biphenyl Bis(Chloromethyl)Ether Butadiene Captan Carbon Disulfide Carbon Tetrachloride Chloracetic Acid Chlordane Cresol Chlorobenzilate Chloroform Chloroprene Chloropropane Chrysene Cumene Hydroperoxide DDT INDEX i MONSANTO RESEARCH CORPORATION FJ3S 1 2 3 4 6 7 8 9 10 11 12 14 15 16 17 18 19 20 21 22 23 24 26 28 29 30 31 33 35 35 37 38 RSV 0010793 Index - Continued Chemical Di-tert-Butyl Peroxide De (2-Ethylhexyl)Phthalate 2 t 3-Diaminoanisole Diazinon o-Dichlorobenzene p-Dichlorobenzene Dichlorobenzidene Dichlorobutene Dichlorodifluoreme thane 1,1-Dichloroethane Dichloronapthoquinone Dichlorophenol Dichloropropene Dichloropropionic Acid Dichlorovinyl Dimethyl Phosphate (Dichlorovos) Dime thy1acetamide Dimethylamine Dime thylhydrazine Dinitrotoluene Dioxane Diphenyl Oxide Disodium Methanearsonate Durst an Endosulfan Endrin Epichlorohydrin Eptam Ethanol Ethyl Benzene Ethylene Ethylene Dibromide Ethylene Dichloride Page 39 40 42 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 73 MONSANTO RCSSAMCM CORPORATION RSV 0010794 Index - Continued Chemical Ethylene Glycol Ethylene Oxide Ethylenimine Fluoranthene Formaldehyde Guthion Heptachlor Hexachlorobenzene Hexachlorobutadiene Hexamethylenetetramine Hydrazine Hydroquinone Kelthane Malathion Maleic Anhydride Mercaptobenzothiazole Methyl Bromide Methyl Chloride Methyl Ethyl Ketone Methyl Methacrylate 4,4'-Methylene Bis (2-Chloroaniline) Methylene Chloride Methylenedianiline Methylstyrene Morpholine Naptha 1-Naphthlamine Napthalene Napthoquinone 1-Napthyl Methylcarbamate Nitrobenzene Nitrophenol iii MONSANTO RESEARCH CORPORATION Page 74 75 77 78 79 81 82 83 85 86 87 88 85 90 91 92 94 95 96 97 98 99 100 101 102 103 104 106 107 108 109 110 RSV 0010795 Index - Continued Chemical Nitrosodiroethylamine Nitrochlorobenzene Parathion Pentane Pentachlorophenol Phenol Polychlorinated Biphenyls Propanol Propylene Oxide Pyrene Sorbic Acid Styrene Sulfolane Tetrabrorooethane Tetrachlorcethane Tetrachloroethylene Tetraethyl Lead Toluene Toluene Diisocyanate Toluenediamine Toxaphene Trichlorfon Trichloroethane Trichloroethylene Trichlorofluoromethane Trichlorophenol Urethane Vinyl Acetate Vinyl Bromide Vinyl Chloride Vinylidene Chloride Xylene iv MONSANTO NCSCANCN CONPOftATfON Paqe 111 112 113 114 115 117 118 120 121 123 124 125 127 128 129 130 132 134 135 136 137 13S 139 140 142 143 144 145 147 148 149 151 RSV 0010796 Acetaldehyde Acetaldehyde Is possibly a carcinogen promoter*1, but no refer ences to it as a carcinogen or mutagen were found in Toxline or Cancerline. Two references by Nakahara and Mori in 1939 and 19402 demonstrated no tumors in rats fed acetaldehyde in their food for more than 300 days. It is probably not a carcinogen. ]Davies, J. C., "Co-Carcinogenesis with Respect to the Contents of Cigarette Tobacco", R. Soc. Health J. 3(6), 296-301, 1973. 2Hartwell, J* L., "Survey of Compounds Which Have Been Tested for Carcinogenic Activity, Second Edition", National Technical Information Service Number PB 216 478, 1951. 1 MONSANTO ACSCAACH.COftPONATtON RSV 0010797 Acetone Acetone (2-propanone, dimethyl ketone, CAS No. 67-64-1) has been extensively tested for carcinogenic activity both by ^ itself and as a negative solvent control for other chemicals1. No significant positive results could be found on Cancerline or Toxline for acetone. It is also negative on most in vitro tests and is used as a negative solvent control for many chemicals in these tests. 1Survey of Compounds Which Have Been Tested for Carcinogenic Activity, National Cancer Institute* PHS-149, Volumes 1, T7 3# 5, 6 and 7. 2 MONSANTO RCSCAftCM CORPORATION RSV 0010796 Acetonitrile The only data suggesting that acetonitrile is a carcinogen is a reference citing equivocal results from a 2-year rat study1. it is considered a non-carcinogen for this project* JFuller, B., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. Acrolein Acrolein appears to be toxic and reduces ciliary action of the bronchial epithelium1*2 but is not mutagenic in S. cerevisiae3 or dominant lethal mice tests'*. Acrolein has been found to be a mutagen to the TA1538 and TA98 strains of S. typhiaurium5. It will be considered to be a possible carcinogen for this project. Production and Persistence It is estimated that 6.5 x 106 Kg is emitted per year, primarily associated with acrylic acid manufacture6. Other estimates are 4.2 x 10s Kg/yr released from 2.8 x 107 produced7 and a produc tion of 2.8 x 107 produced in 1974 with a 6.7% growth forecasted through 1979. It has an atmospheric half life estimated at 2.6 hours9. Its boiling point is -88"C and it has a vapor pressure of 220 ram at 20"C10. iShabad, L. M. et al., "The Feasibility of Preventing the Effects of Carcinogens on Man", Kazan Med. 2h (5), 92-93, 1973. ^Terrell, J. H. and Schmaltz, I., "Cigarettes: Chemical Effect of Sodium Nitrate Content", Science 160, 1456, 1968. Izard, C., "Mutagenic Effects of Acrolein and its Two Epoxides, Glycidol and Glycidal, in Saccharomyces Cerevisiae", C. R. Acad. Sci., Ser. D., 276 (23), 3037-3040, 1973. "Epstein, S. S., et al., "Detection of Chemical Mutagens by the Dominant Lethal AsBay in the Mouse", Toxicol, Appl. Pharmacal. 23, 288-325, 1972. `Bignarai, M. et al., "Relationship Between Chemical Structure and Mutagenic Activity in Some Pesticides: The Use of Salmonella Typhimuriun and Aspergillus Nidulans", Mutat. Res. 6 (3), 243-244, 1977. &MRC Source Assessment Data Base, July 1977. TFuller, B., et-al., "Preliminary Scoring of Organic Air Pollu tants", National Technical Information Service Number PB 264 442, 1976. SAllport, J. # et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 4 MONSANTO MCSCANCH COAPOffATION RSV 0010800 Acrolein References - Continued 9Padding, S. R., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co., N.Y., 1977. 5 MONSANTO*jmcAneit^eoAPoRATION RSV 0010801 Acrylonitrile Positive Antes tests1 E. coll mutation testsl2 and viral transfor mation enhancement tests3 have been reported along with negative recessive lethal Drosophila melanogaster and negative Vicia faoa chromosome aberration tests4. Human epidemelogical evidence points toward acrylonitrile being a carcinogen5. Additionally, one-year interim report from the Manufacturing Chemists' Association of on-going ingestion and inhalation studies of acrylonitrile in laboratory rats report the rats developing a variety of tumors including carcinomas6. Based on these findings, acrylonitrile is being placed on the probable carcinogen list for this project. Production and Persistence It is estimated that 3.7 x 105 Kg is emitted per year7.* (Another estimate is 9.6 x 106 Kg per year6). Acrylonitrile has a boiling point of 77C and a vapor pressure of 100 mm at 23*C9. lMilvey, P. and Wolff, M., "Mutagenic Studies with Acrylonitrile", Mut. Res. 48 (3-4), 271-278, 1977. 2Venitt, S. et al.f "Mutagenicity of Acrylonitrile (Cyanoethylene) in Escherichia Coli", Mut. Res. 4_5, 283-288, 1977. 3Personal communication with 3. C. Casto on 9 February 1978. uAllport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 5"Acrylonitrile Linked to Cancer on Workers", Chem. Eng. News, 55, 6, 1977. 6Finklea, J. F., "Acrylonitrile" Am. Ind. Hyg. Assoc. J. 38, 417-422, 1977. 7MRC Source Assessment Data Base, July 1977. 9Fuller, B., et al., "Preliminary Scoring of Organic Air Pollutants" National Technical Information Service Number PB 264 442, 1976. ?Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co., New York, 1977, 6 MONSANTO IteseAACMiCOftmORATtON RSV 0010802 Aldrin Aldrin has been found to cause neoplasia in two strains of mice1 and tumors in weanling rats12. Aldrin is converted into dieldrin in the environment3 and dieldrin is a carcinogen at 0.1 ppm in dietary exposure to mice4. Thus the sale and production of aldrin was suspended5. Kany other animal studies have been con ducted with questionable results6, and some in vitro tests have been negative7. Since there is enough data to suspend production of aldrin, it will be considered a probable carcinogen for this project. Production and Persistance It is estimated that 4.5 x 106 Kg aldrin were produced in 19716. Another production estimate is 1.1 x 107 Kg/year (1976)8. 1Song, J. and Harville, W. E., "Carcinogenecity of Aldrin and Dieldrin on Mouse and Rat Liver", Fed. Proc. 2_3, 336, 1964. -Deichmann, W. B., et al., "Tumorigenicity of Aldrin, Dieldrin, and Endrin in the Albino Rat", Ind. Med. Surg. (10), 426- 434, 1950. burster, C. F., "Aldrin and Dieldrin", Environment 12. (8), 33-45, 1971. "Epstein, S. S., "Prevention - Environmental Exposure: An Over view, Including the Role of Pesticides", Third International Symposium on Detection and Prevention of Cancer, 5, 1976. 5Epstein, S. S. "Case Study 5: Aldrin and Dieldrin Suspension Based on Experimental Evidence and Evaluation and Societal Needs", Ann. N.Y. Acad. Sci. 271, 187-195, 1976. 6"Aldrin", in IARC Monographs on the Evaluation of_Carcinoqenic Risk of Chemicals to Man, Volume 5, 25-38, 1974. 7Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogeneaia Essays, IAAC Sci. Pub. No. 10, 161-181, 1974. sFuller, B. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 7 MONSANTO RESEARCH CORPORATION RSV 0010803 Allyl Chloride Allyl chloride {3-chloropropene, CAS No. 107-05-1) is on the NIOSH Safety Alert List. No references have been found on the Toxline, Cancerline or the Stanford Research Institute study on hazard priority ranking1, to indicate that allyl chloride is a carcinogen or mutagen. A recent reference, however, reports chat allyl chloride is a mutagen in S. typhimurium, S. cerevisiae, and E. coli test systems2. It is therefore classified as a poss ible carcinogen for this project. Production and Persistence It is estimated that 4.2 x 105 Kg is emitted per year from stationary sources3. Another estimate is 2 x 10s Kg released from a production of 1.3 x 10 Kg per year**, and a production estimate of 1.3 x 10 Kg in 1972s. it is reported to take 27 minutes for 501 of the allyl chloride in a 1 ppm solution to evaporate at 25C. It has a half-life with HO radical of 21 hours, with 03 radicals of 9 hours, and hydrolyzes with a halflife of 7 days4. It has a boiling point of 45"C, a vapor pres sure of 340 mm at Z0"C, and a solubility of 3.3 gm/16. !Brovn, S. L. et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Infor mation Service Number PB 263 161, 1975. `McCoy, E. C., et al., "Genetic Activity of Allyl Chloride", Mutat. Res., 57;, 11-15, 1978. MRC Source Assessment Data Base, July 1977. Brown, S. L. et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 164, 1975. Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 443, 1976. Verschueren, K., Handbook of Environmental Data on Organic Chem icals, Van Nostrand Reinhold Co., New York, 1977. 8 MONSANTO KCSCAACH CORPORATION * RSV 0Q108G*t The IARC nonograph on aniline1 reports that aniline is probably not a carcinogen and that what early researches believed was cancer frost aniline was most likely due to impurities such as benzidene. It has tested negative on a. differential growth E. coli test (pol A)12 and on S. typhimurium strains TA1535, 1537, 100 and 98 with and without microsame*3. It has also been reported negative in reversion to prototrophy in Aspergillus nidulans (meth3 ) and several other tests3. It was classified negative/inadequate in one of the latest reviews3 and will be considered a probable non carcinogen for this project. 4 1IARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man, Volume 4, 27-36, 1974* 2Fluck, E. R., et al., "Evaluation of a DNA Polymerase-Defecient Mutant of E. Coli for the Rapid Detection of Carcinogens", Chem. Biol. Interact. 15, 219-231, 1976. 3Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 9 "**mTM *"*V** 9JR?|AT,OM RSV 0010805 Anthracene Anthracene is on the NIOSH Suspected Carcinogen List because of two 1955 references. In the first reference cited (1), anthra cene was found to be non-carcinogenic orally and interperitoneally. But when injected in 550 doses over a two-three year period (6 times/ week - total dose 4,5 g/rat) S out of 9 rats developed local fibrosarcomas. It is now known that multiple injections can sometimes cause fibrosarcomas. Recent studies (2) have shown anthracene to be a non-carcinogen and it i'3 presently being used as a non-carcinogenic standard on studies to develop short-term assays for carcinogens (3-6)1 1 Schaall, D., "Prufung von Naphthalin und Anthracen auf Carcerogene Wirking an Ratten", Zeitschrift fur Krebsforschung 60, 697-710, 1955. 2 Stanton, M. F., Hiller, E., Wrench, C., and Blackwell, R., J, Natl. Cancer Institute 9 (3) , 867-877, 1972. 3 Pienta, R. J. et al., "Morphological Transformation of Early Passage Golden Syrian Hamster Embryo Cells Derived from Cryopreserved Primary Cultures as a Reliable in vitro Bioassay for Identifying Diverse Carcinogens", Int. J. Cancer 19, 642-655, 1977. h DiPaolo, J. A. et al., "Quantitation of Chemically Induced Neoplastic Transformation of BALB/3T3 Cloned Cell Lines", Cancer Research 32,, 2686-2695, 1972. 5 Purchase, I. F. H., et al., "Evaluation of Six Short Term Tests for Detecting Organic Chemical Carcinogens and Recommendations for Their Use", Nature 264, 624-627, 1976. 6 McCann, J. et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test" Assay of 300 Chemicals", Proc. Natl. Acad. Sci. (USA) 72, 5135-5139. 1975. 10 MONSANTO RESCAftCH COjjt^OfftAtfbN RSV 0010806 Benz(a)Anthracene Benz (a)anthracene (1,2-benzanthracene, CAS No, 56-55-3) is well known as a carcinogen. It is carcinogenic orally, subcutaneous ly and topically for mice1. It is one of the standard carcino gens used to evaluate the validity of short-term tests and will be considered a probable carcinogen for this project. Production and Persistence It is estimated that less than 100 kg/year is emitted from carbon black furnaces, the only stationary source cited for this chemi cal12. It is emitted in the exhaust from gasoline engines (61.7 mg/kg exhaust tar) and diesel engines (2.3-15 yg/ra3 exhaust)1. It has been detected in the air, soil, food, and cigarette smoke condensate1. It has a boiling point of 400"C.1 1"Benz(a)Anthracene" in IARC Monographs on the Evaluation of Carcinogenic Risk of the Chemical to Man, Volume 3, 45-68, 1973. 2MRC Source Assessment Data Base, July 1977. 11 MONSANTO IteSCANCM CORPORATION RSV 0010807 :>&>, ` ' .0; '. ':.v ' ";::v--^gs^ng- Benzene (CAS Ho. 71-43-2) is one<Of the industrial substances sus pected of carcinogenic potential''to aan afl liatsd by the American Conference of Governmental Industrial Hygienists1 and will soon be controlled as a carcinogen*' -Ttie International Agency for Re search on Cancer2 reports animal: data which "do not permit the conclusion that carcinogenic activity has been demonstrated" In human data they support a relationship-betweem-erposure to benzene or benzene mixtures and the development of leukemia. Along with some positive studies*, mahyi^ftfreAcerf occur in the literature where bensene "is a negativetsolVeivt'Contxal/in animal studies4. In spite of these references,' it-ie'betiWved''that benzene induces chrofnosomal7damage in aniB%alS;and Uns and is a known carcinogen. An assessment of theair polititibn^aspeots of bensene has been conducted*. Since benxene-is^beirtg'coritrolled as a carcinogen, it will be considered a probable^ carcinogen for. this project*. . Production and Persistence It is estimated that 1 x 10 kg benzene, ii emitted per year wi*h solvent evaporation from degreasing' operations 'contributing over 70% of the total7. Another estimate'is: 4. xr10*r. kg per year re leased from commercial uses of benzene** It reacts rapidly with HO (tj- " 3 days) but slowly with ROa^andOj and has a 2.IS log partition coefficient3. Its boiling-point is 80.1*C and it has . vapor pressure of 76 sn at 20"C-- V vf.-? ''4V`: '"Threshold Limit Values for Chemical Substances in Workroom Air Adopted by ACGIH for 1977", American'Conference of Governmental Industrial Hygienists, 1977` - :/r\ ' ,' 2"Benzene", in XARC Monographe-theiEvaluation of. Carcinogenic Risk of Chemical:: to*;jten?#^Vbi'uM^?r^20^iU2/ 1974. 3Brown, S. L. etal.,;?Rea^earcl^?rogram:xon Barard Priority Ranking of IfewufaetUred>.C)Miid'car4%^to^ Informa tion Service Hus8ervPB^2rt#i02^W75. ., 4Survey of Coapounds^Kh^Ay^ve^Been -Teatetfvfor.-Carcinogenic ys-'i -^Irr". . Candidate itlon^ Service Walker;t;r-^ ' Techitlca^ RSV 0010808 Eenzidine is reported to be carcinogenic in the rtu .se, rat, hamster, and possibly in the dog1. Given orally, it has produced bladder carcinoma in the dog after a long latent period and liver tumors in the rat and hamster. Benzidine was a carcinogen to nice when given p.o. either by stomach intubation or in food'. These references, along with many others in Toxline and Cancer line show that benzidine should be considered a probable carcinogen. Production and Persistence It is estimated that 4.7 x 10* Kg is produced per year'. A release factor of G.015 is assumed which would give 7 x 10* Kg released per year. This is probably too high since benzidine is well known as a carcinogen. Perhaps 7 x 10' Kg would be closer to reality. it reacts with OH and with a t 1/2 of one dayu. It has a boiling point of 402*C5 and can be sublimed1. '`"Benzidine" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 1, 80-86, 1972. -Vesselinovitch, S. D., et al., "Factors Modulating Benzidine Carcinogenicity Bioassay", Cancer Res. 3_5 (10) 2314-2819 , 1975. 'Fuller, B., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 'Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 163, 1975. Verschueren, K., Handbook of Environmental Data on Organic chemicals. Van Sostrand Reinhold Co., N. Y., 1977. 14 MONSANTO eeSEANCM CONDONATION RSV 0010810 Benzo(a)Pyrene Benzo(ajpyrene (3,4-benzpyrene, CAS No. 50-32-8) is a well es tablished carcinogen following many different administrations including oral, skin, subcutaneous and intratracheal routes1. Positive results have been reported with mice, rats, guinea pigs, monkeys, newts, hamsters, and ducks1. It will be considered a probable carcinogen for this project. Production and Persistence Although not manufactured in quantity, it is a by-product of com bustion. It is estimated that 8.3 x 105 kg per year is released from stationary sources with 96% of this coming from: 1) coal refuse piles, outcrops and abandoned mines, 2) residential ex ternal combustion of bituminous coal, 3) coke manufacture, and 4) residential external combustion of anthracite coal2. It has a boiling point of 311C at 10 mm and 475C at 760 mm1. 1"Benzo (a) Pyrene" in IARC Monographs on the Evaluation of Car cinogenic Risk of the Chemicals to Man, Volume 3, 91-136; 1973. 2MRC Source Assessment Data Base, July 1977. 15 MONSANTO ACSSA^CH COfWfO^ATlON , RSV 0010811 Benzoquinone (Quinone) 1940 and 1941 Japanese references1 state that 3/87 mice painted with benzoquinone (in benzene) developed skin cancer with 9/87 papillomas after 200 days compared to 0/46 skin cancers and 1/46 papillomas for the benzene control. Skin painting with a benzene solution in 1953 was said to cause 16/80 ear duct carcinomas?. In 1954 and 1956, inhalation experiments with a total of 50 treated mice were conducted with negative results*3.2 By subcutaneous injection, 24 rats were tested with negative results in 19573. More recent references show that benzoquinone does not decrease hatchability of the Drosophila melanogaster4, is not mutagenic toward Drosophila or cultured human leukocytes4, produces no increase in recessive sex-linked lethal mutations in Droso phila and did not significantly alter the rate of chromated translocations or breaks in leukocytes5. No other significant data were found in Toxline, Cancerline, or the "Survey of Compounds which Have Been Tested for Carcinogenic Activity". Benzoquinone is therefore, to be considered a probable non carcinogen for this project. iTakizawa, N., "On the Carcinogenic Action of Certain Quinones", Proc. Imperial Acad. (Tokyo) 1, 309-312, 1940. 2Tiedemann, H. Ztschr. Naturforsch. 8b, 49-50, 1953. 3"para-Quinone" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 15, 255-264, 1977. "Vogel, E., "Differential Sensitivity of Immature and Mature Oocytes of Drosophila Melanogaster to the Induction of Dominant Lethals Following Treatment of Mono- and Polyfunc tional A2lridine Analogues", Mutat. Res. 1, 250-253, 1972. 5Lueers, H. and Obe, G., "Possible Mutagenic Activity of P-Benzoquinone", Mutat. Res. 15, 77-80, 1972. 16 MONSANTO NtSBANCH CONDONATION RSV 0010812 T. Benzoyl Peroxide Benzoyl peroxide (CAS No. 94-36-0) was extensively tested in mice and rats between 1962 and 1967 by six authors on more than eleven hundred animals1. Benzoyl peroxide is on the NIOSa Suspected Carcinogen list because in one of these studies, 1/30 mice devel oped a squameous papiloma after application of benzoyl peroxide in benzene to the skin. No recent mutagen or carcinogen references could be found on Toxline or Cancerline. It has been found nega tive in a dominant lethal mouse test, on an E. Coli(pol A) mutagen test, and a Micrococcus pyogenes test2. There is very little doubt that benzoyl peroxide should be considered a non-carcinogen. Purvey of Compounds Ifhich^ Bave; Been Tested for Ctrcinooen Act ivity, n<n, FHg-149, Voium i&6i-"iyrr--------------------------------------------------------- zAllport, J.et al., "A; Stt|9y^.of ,Industrial Chemicals for Testing*>vNational Technical Number PB 274 264, 1977. 17 Data on Candidate Information service V.4 . _____ eoMbaraTiow RSV 0010813 & Benzyl Chloride Benzyl Chloride (a-chlorotoluene, CAS No. 100-44-7) has been found positive on a differential growth E. coli (pol A) mutagen test1. It is also positive on a subcutaneous rat test at 2.1 g/kg (51 weeks) in 3/14 rats and at 3.9 g/kg in 6/S rats2. It is weakly mutagenic in S. typhimurium tests at 2 mg/plate3, and is considered carcinogenic in rats by the IARC4. It is considered a probable carcinogen for this project. Production and Persistence In 1972 it was estimated that 3.6 x 107 kg was produced with 6570% of this going towards the manufacture of butyl phthalate and 30-35% towards other organic products2. Production has been esti mated at 4.5, 3.2 and 4.1 x 107 kg in 1974, 1975 and 1976 and is predicted to grow at 5-7% per year through 19804. It has a boil ing point of 179*C and vapor pressure of 1 ram at 22*C5. iFluck, E. R., et al., "Evaluation of a DNA Polymerase - Deficient Mutant of E. coli for the Rapid Detection of Carcinogens", Chem. Biol. Interact., 15. 219-231, 1976. 2"Benzyl Chloride" in I&RC Monographs on the Evaluation of Car cinogenic Risk of Chemicals to Man, Vol. 11, 1976. *McCann, J. et al., "Detection of Carcinogens as Mutagens: Bacterial Tester Strains with R Factor;Plasmids", Proc. Nat. Acad. Sci., 72; 979-983, 1975. 4Allport, J. at al.,' "AvStudy of Industrial Data on Candidate Chemicals for-^Testing.^-WafclonalfTechnical Information Service Number PB. 27<r"264; : *~:r 5Verachueren, K., Handbook. <of . Environmental Data on Organic Chemicals, Van NostrendyRs^niioi<L co> >?W*V., 1977, ir RSV 0010814 ' Biphenyl There is one reference which shows subcutaneous biphenyl (diphenyl, CAS No. 92-52-4) to induce an excess of tumors in mice1. No other references could be found in Canceriine or Toxline which would support that data. Biphenyl is therefore placed on the possible carcinogen list for this project. Production and Persistence It is estimated that 9.2 x 104 Kg biphenyl is emitted per year from the manufacture of.polychlorinated biphenyls2. Since the production of polychlorinated biphenyls has been stopped, this source of biphenyl emissions has probably ceased tc exist. It has a boiling point of'254*C9. ' 1 "Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities, of Selected Pesticides and Industrial Chemicals", National' Technical Information Service Number PB 223 159, 1966. 2MRC Source Assessment Oats Base, July 1977. 3Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Beinhold Co., N.Y. , 1977. RSV 0010815 Bis(chloromethyl) ether (BCME, dlchloromethylether, CAS No. 542-88-1) is carcinogenic to mice following inhalation, skin application and subcutaneous administration1. It is also carcinogenic to rats by inhalation and subcutaneous administration1. Epidemilogical data suggestsMt is also a human carcinogen1. It is being regulated as a carcinogen and will be considered a probable carcinogen for this project. Production and Persistence It is estimated that less than 100 Kg BCME is emitted per year12. A primary source of emissions is in the production of polymethy lene pol>phenyl isocyanate2. Its production in 1974 was estimated to be less than 450 Kg3. In water the half life of BCME is 38 sc.onds and in the air (50% relative humidity) its half life is 25_minutes3, has a boiling point of 104*C3. 25 minutes3. it ha* a boiling point oc . \t 1"Bis (Chloromethyl)- Ether" in 1MC Monographs on the Evaluation of Carcinogenic RlskofCh--licals tior Man, volume 4, 231*238, 1974. 2MRC Sourae Assessment Datm: BaserJuly 1977. 3Radding# S'. B., et al., ^"B#y^iew of ^he Environmental Fate of Selected Chemicals", national" `technical information Service Number PB 267 121, 1977. 20 Butadiene 1,3-Butadiene (CAS Ho. 106-99-0) haa not been estensively tested for mutagenicity or carcinogenicity* No references could be found on Toxline, Cancerline, or in the seven collected volumes of Survey of Compounds which Have Boen Tested for Carcinogenic<Activity on tests conducted although there is interest in a possible relationship between styrene-butadiene rubber plants and neoplasms of the lymphatic and hematopietic tissue1. Butadiene will be considered a probable non-carcinogen for this project. *Smith, A* H. and Ellis,,L*r ."Styrene Butadiene Rubber Synthetic Plants and Leukemia" (Letter to Editor) , J. Occup. Med. 19 (7) , 441, 1977. 21 MONtA*crO ftCSCAftCR COftPOAATION RSV 0010817 Captan Captan has been found to be a potent mutagen, in both prokaryote and enkaryote test systems too numerous to list. It has also been found to produce heptomas in mice* . Because of the many positive mutagenicity tests along with a marginally positive mouse carcin ogenicity test, Captan has been placed on the probable carcinogen list. Production and Persistance It is estimated that less than 100 Kg per year of captan is emitted:. (Another estimate is production of 8.1 x 10* Kg per year with 0.01 released or 8 x 104 Kg per year emitted3.) 1"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemials", National Technical Information Service Number PB 223 159, 1966. 2MRC Source Assessment Data Base, July 1977. 3Puller, B., et al., "Preliminary Scoring of Organic Air Pollu tants", National Technical Information Service Number PB 264 442, 1976. 22 * MONaaimr'iitscAncH coftPOftarioM RSV 0010818 Carbon Disulfide There is nothing in Toxline or Cancerline to indicate that carbon disulfide is a carcinogen or a mutagen. One industrial epiaemilogical study showed carbon disulfide to have no correlation with incidence of cancer1.* *DiVito, G. and Soni, G. L. r "The Incidence of Infectious Diseases, Hemopathies, and Neoplasms in Workers Exposed to Carbon Disulfide", Folia Mad. (Hapoli), 46 (11), 972-979, 1963. 23 RSV 0010819 Carbon Tetrachloride Carbon tetrachloride (tetrachlorome thane, CAS No. 56-23-5) has been reported to produce liver tumors in the mouse, hamster, and rat following administration by inhalation and oral ingestion1. It was not a mutagen as tested by several microbial systems . Carbon tetrachloride is considered a probable carcinogen for this project. Production and Persistence It is estimated that 1.2 x 107 * Kg of carbon tetrachloride is emitted per year3. Another estimate is a production of 4.5 x 10 kg with 2.7 x 107 Kg released4. A document is available on the air pollution assessment of carbon tetrachloride*. Estimates of carbon tetrachloride production include 4.5 x 10* Kg (1970) 4.8 x 10 Kg, 7.3 x 10 Kg (1974)7 and 5.3, 4.1, and 3.8 x 10 Kg for 1974, 1975, and 197612. It is forecasted that the 1975-1976 decline will continue. The half life of carbon tetrachloride in the water is about 70,000 years4, and in the troposphere it is about 10 years7. It is estimated to have a half life of 10-33 weeks toward atmospheric photodegradation5.* The boiling point of carbon tetrachloride is 76.7"C and it has a vapor pressure of 90 mm at 20"C. For a review of its production, uses and biolog ical activity, see the Fishbein article9. 1"Carbon Tetrachloride* in XARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 1, 53-60, 1972. 2Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 3HRC Source Assessment Data Base, July 1977. 4Brown, S. L., et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. -Johns, R., "Air Pollution Assessment of Carbon Tetrachloride", National Technical Information Service Number PB 256 732, 1976. *Fuller, B. , et al., "Preliminary Scoring of Organic Air Pol lutants", National Technical Information Service Number PB 264 442, 1976. 24 RSV 0010820 Chloracetic Acid Chloracetic Acid (monochloroacetic acid, CAS No. 79-11-8) has been reported as being carcinogenic in mice when injected subcutaneously at 100 mg/kg1. The primary reference, however, does not report a statistical difference in tumors and reports data with the test chemical not much different than the control mice2. In other tests, chloracetic acid was negative when given to 6 rats as 0.005-0.1% of their diet for 208 days3 and negative when given at 46.4 mg/kg in the water of 72 mice for days 7-28 followed by 149 ppm in their diet for another 17 months''. It has also been found non-mutagenic by B. subtilis5 and S. typhimurium5-0 tests in vitro. All of these demon strate that chloracetic acid is not a mutagen and is not a carcinogen. 'X20SH Suspected Carcinogens list, 1976. ;"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals. Volume 1.", National Technical Information Service Number PB 223 159, 1968. 'Fuhrman, F. A., et al.. Arch. Inst. Pharmacodym., 102, 113125, 1955. "Innes, J. R. M., et al., J. Nat. Cancer Inst. 4_2, 1101-1114, 1969. -Elmore, J. D., et al., "Vinyl Chloride Mutagenicity via the Metabolites Chlorooxirane and Chloroacetaldehyde Monomer Hydrate," Biochem. Biophys. Acta 442, 409-419, 1976. *Rannug, U., et al., "The Mutagenicity of Chloroethylene Oxide, Chloroacetaldehyde, 2-Chloroethanol and Chloroacetic Acid, Conceivable Metabolities of Vinyl Chloride," Chem. Biol. Interact. 12 (3-4), 251-263, 1976. 26 MONSANTO RKSCAJtCM CQMOWATtOH, Chloracetic Acid References - Continued7 7Bartsch# H., et al.# "Human# Rat and Mouse-Liver Mediated Mutagenicity of Vinyl Chloride in S. Typhimurium Strains," Int. J. Cancer, 15 (3)# 429-437# 1975. BMalaveille, C., et al.# "Mutagenicity of Vinyl Chloride, Chloroethyleneoxide# Chloroacetaldehyde and Chloroethanol," Biochem. Biophys, Res. Cobid. 3 (2) # 363-370# 1975. 27 MONSANTO aCSCANCH CONDONATION RSV 0010823 Chlordane Chlordane has been found to be a carcinogen to mice in a study conducted by the National Cancer Institute1. It is also a mutagen in tests like the enhancement of viral transformation12. It is considered a probable carcinogen for this project* Production and Persistence It is estimated that 1.1 x 107 Kg per year of chlordane is produced3.* * * 1"Bioassay of Cb'ordane for Poesible Carcinogenicity. (CAS No. 57-74-9)"/ National Technical Information Service Number PB 271 977/ISL. 2Personal communication with B. C. Casto on 9 February 1978. 3Fuller, B., et al., "Preliminary Scoring of Organic Air Pollu tants", National Technical Information Service Number PB 264 442, 1976. 28 RSV 0010824 Creeola Cresols (primarily o-cresol) have been shown to be promoters of carcinogenicity when given with initiators such as 3,4-benzpyiene (Kaiser), dimethylbenzanthracene1 or in complex mixturesOn the other hand, normal adults excrete about 30 mq of volatile phenols per day of which 90% is p-cresol**. Thus, cresols are probably not carcinogens but could be promoters.l 2 3 4 lBakke, 0. M. and Midtvedt, T., "Influence of Germ-Free Status on the Excretion of Simple Phenols of Possible Significance in Tumor Promotion", Experimentia, 26 <5), 519, 1970. 2Bock, F. G., et al., "Composition studies on Tobacco. XLIV. Tumor-Promoting Activity of Subfractions of the Weak Acid Practical of Cigarette Smoke Condensate", J. Nat. Cancer Inst., 47 (2), 429-436, 1971. 3shustova, M. N. and Samiolovich, L. N., "Blastoraogenicity of Neutralized Soots from the Sulfate Shop of a Coke Plant", Gig. Sanit., 36 (7), 103-104, 1971. l4Bone, E. S. , et al., "The Production of Urinary Phenol by Human Gut Bacteria", (Meeting Abstract), J. Med. Microbiol. 9 (2), vi 1976. 29 4 MONIANTO. ROIAMH .CONfMATtON a Chlorobenrilate Qilorobenzilate {CAS No. 510-15-6) has been fouvJ to produce heptcmas in mice when aAninistered orally1 **3,* and is listed by the U. S. Commission on Pesticides and Their Relationship to Environmental Health as a group B chemical (positive results in one or more animal species at 0.01 significance level)4. Several short term tests have been negative for Chlorobenzilate5. For this project, it is considered a probable carcinogen. Production and Persistance A 1976 reference6 cites a production of 9 x 105 Kg per year and it is said3 that the 1971 production was 1 x 106 Kg. linnes, J. R. M., et al., "Bioassay of Pesticides and Industrial Chemicals for Tumorigencity in Mice. A Preliminary Note", J. Nat. Cancer Inst., 4j2, 1101, 1969. 2"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Technical Information Service Number PB 223 159, 1966. -"Chlorobenzilate" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 5, 75-81, 1974. 4Jurek, A., "Carcinogenicity of Pesticides", Roczn. Panstw. Zakl. Hig. 25 (5), 563-576, 1974. ^Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogenesis Essays, IARC Sci. Pub. No. 10, 161181, 1974. ^Fuller, B. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 30 MONSANTO NCSKANCM CONDONATION RSV 0010826 Chloroform Some of the current literature*"** indicates that chloroform is a carcinogen. Even though more date is required before a final determination is made, the positive data on mice and rats suggest that chloroform be placed on the probable carcinogen list for this project. Production and Persistence It is estimated that 1 x 10* Kg chloroform is emitted per years. Another estimate is 1.7 x 107 Kg per year6 emitted. Production estimates are 1.3 x 10 Ko per year7, 1.1 x 10 Kg per year, and 1.1 x 10 Kg per year'. About 96% of production is con verted to chlorodifluoromethane. Zn the troposphere chloroform degrades slowly with a 10 year half life7. It reacts with HO radical with a t 1/2 of 13 hours7 and hydrolyses with a t 1/2 of 3000 years6*7. The log partition coeficient is 1.97 for chloroform6. It has a vapor pressure of 160 nsn at 20*C and a boiling point of 62*C9. It takes only 16-25 minutes to evaporate 50% of the chloroform from a 1 ppm solution at 25*C.* 2 3 4 S 6 7 *IARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man, "Chloroform", Volume 1, 61-65, 1972. 2Powers, M. B. and Yoelker,'R. W., "Evaluation of the Oncogeric Potential of Chloroform by Long-Term Oral Administration in Rodents" (Meeting Abstract), Toxicol. Appl. Pharmacol. 37, 179, 1976. 3Renne, R. A. et al., "Pathology of Long-Term Oral Administra tion of Chloroform in Rodents" (Meeting Abstract), Toxicol. Appl. Pharmacol. 37, 179-180, 1976. 4"Chloroform Tagged as Carcinogen in Mice", Chem. Eng. News 54, 6, 1976. SMRC Source Assessment Data Base, July 1977. 6Brown, S. L., "ResearchProgramonHaxard Priority Ranking of Manufactured Chemi rm1i"yrMatita|l^techBlctl Information Service Number PB 263 -'V' - 7Radding, S. R., et al. ,/"Reviev of the Environmental Pate of Selected Chemloals.% atiooalTiKdihioal-'-Information Service Number PB 267 i2l>~197775 Chloroform References - Continued u'. --vv -i < . rSf- v. : - ' . . ; -p't ; ' r-: .- /.{ -i.:.;.' 8Fuller-? EreliminaryScoringof. Organic Mr Pollutants?, national Technical Information:Service Humber PB 264:442/ 1976#; 'C Vt -y.'x ^ 9Veractmaran, K.i^HandboolCrof BnvirOnmantal Data on Organic Chemicals* Van Hostrand Reinhold Co# H.T* * 1977. Chloroprene Chloroprene (2-chloro-l,3-butadine, CAS No. 126-99-8) although known to be toxic was not considered to be a suspected carcino gen until three Russian papers linked occupational exposure of chloroprene to skin and lung cancers1"'13.2 Since that time, a short-term viral enhancement4 test at 125 ug/ml5 and S. typhimurium (Ames) tests6 have been positive, while long-term rat and mouse studies have been negative7'0. A review of health records and death certificates for DuPont Corporation employees exposed to chloroprene convinced investigators that no excess of any disease similar to that seen for vinyl chloride had been observed3. However, some increase in lung cancer has been seen in this population3. It has also been found to accelerate the growth of transplanted Crocker murine sarcoma in the rat10. Thus, chloroprene lies on the border between a possible and a probable carcinogen. It will be classifed as a possible carcinogen for this project. Production and Persistance It is estimated that 7.5 x 10* Kg chloroprene is emitted per year 11 Another estimate is 2.7 x 10* Kg/year released10. Some estimates of production are about 1.8 x 10 Kg/year1012, 1.6 x 10 Kg/year13, and 1.8 x 10 Xg and 1.6 x 10 Xa in 1974 and 1975 with 4% annual growth predicted through 1981*4. Because of its low soluability and high volatility, it will soon migrate to the atmosphere*3.. * m the atmosphere it is said to have an atmospheric half life of less than 10 hours because of OH radical reaction13. Its boiling point is 59.4*C and it has a vapor pressure of 200 am at 20"C*3. 1 Khachatryan, B. A., "The' Bole of Chloroprene in the Process of Skin Neoplasm Formation", Gig, Tr. Prof. Zabol. 1, 54-55, 1972 2Khachatryan, B; A., *The Occurrence of Lung Cancer Among People Working with Chloroprene", Problems, in Oncology 18, 85, 1972. 3Khachatryan/ E. A., *Lung Cancer Incidence Among Chloroprene Handling Workers", Yopr. Onkol. 18; 85-86, 1972. 4Casto, B.C. et al. r "A*say of Industrial Chemicals in Syrian Hamster Cells for Enhancement of Viral Transformation", Proc. Am. Assoc. Cancer Res. 1, 155, 1977. j- 5Personal Communication withr B. C. Casto on 9 February 1978. 1' " - .. -. 33 flON RSV 0010829 Chloroprene References * Continued sBartsch, H., et al., "The Predictive Value of Tissue-Mediated Mutagenicity Assays to Assess the Carcinogenic Risk of Chemicals", IARC Sci. Pub. No. 12, 467-491, 1976.- ~ 7Zilfyan, Y. N. et al., "Experimental Study of Chloroprene for Carcinogenicity", Yopr. Onkol. Z3, 61-65, 1977. 6Zilfyan, V. N. et al., "Results of a Study of Chloroprene for Carcinogenicity", Zh. Eksp. Xlin. Med.; 15, 54-57, 1975. .mmj . , . {z - . * 9Lloyd, J. if., "Cancer Sisks Among Workers Exposed to Chloro prene", Ann. N. Y. Acad..-Sciv? 271, 91-93,; 1976. 10Brown, S. L., et al, "Research Program on Hazard Priority Ranking of Manufactured Chemicals*, National Technical Information Service Number PB 263 164, 1975. 11MRC Source Assessment Data Base, July 1977. l2Puller, B., et al.*, "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 19Redding, S. B., et al., "Review of. the Environmental Pate of Selected Chemicals", NTIS No. PB 267 121, 1977. l**Allport, J., et al., ".A Study.of Industrial Data on Candidate Chemicals for Testing",'1 National. Technical,;information Service Number PB 274 264, 1977. r*: :-:i 15Verschueren, K., Handbook of.EnvixOiimanta1 Data on Organic Chemicals, Van Nostrand Reinhold Co.,N. Y.r 1977. 34 ............. .. RSV 0010830 Chloropropane No reference to carcinogenic or mutagenic action of chloropropane could be found in Toxline, Cancerline, or any of the other references consulted* Itis probably a non-carcinogen and will be considered as such for this project. i35 Chrysene Chrysene (benz (a) phenanthrens, CAS No. 218-01-9) is fairly well established as a weak carcinogen. It has produced skin tumors in mice following repeated painting and 2-20 mg injected subcutaneously in mice produced tumors after a long induction period1. It is also a mutagen causing 16? revertants per microgram12. It is considered a probable carcinogen for this project. Production and Persistence Although chrysene is not a manufactured chemical* it is a product of combustion and found widely dispersed in the environ ment. Xn one test of automobile exhaust, 12 micrograms were found after one minute of operation1. In the atmosphere, 150490 pg chrysene has been found per gram organic particulate matter1. It has a boiling point of 488*C3. 1 "Chrysene" in IARC Monographs on the Evaluation of Carcino genic Risk of the Chemical to Man, Volume 3, 159-177, 1973. 2McCann, J., et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsome. Tests Assay of 300 Chemicals", Proc. Nat. Acad. Sci., USA, ,7^ (12) , 5135-5139, 1975. 3Verschueren, L., Handbook of Environmental Data on Organic Chemicals, Van Nostrand jteinnoid co., N. Y#f 1977. 36 V?T-:^rV Cumene Hydroperoxide Cumene hydroperoxide (dinethylbenzyl hydroperoxide) is cited as being a carcinogen but at 34 and 90 mg/kg did not induce statis tically significant dominant lethal effects in mice1 #*2.3 * Cumene hydroperoxide is said to cause neoplasias in mice both by inhala tion at 304 mg/kg* and subcutaneously at 10 g/kg** On the basis of the two animal studies, it is considered a possible carcinogen for this project. Production and Persistence it is estimated5 that the 1974 production was 1.4 x 10* Kg. Another estimate of production6 is 9.1 x 10 Kg per year with a production loss factor of 0.015 or 1*3 x 107 Kg/year. It has a vapor pressure of 1 non at 70"C6. Because of its low volatility and Moderate solubility in water, it is not likely to remain in the atmosphere5. Photochemical and HO radical reactions are likely pathways for transformation of peroxides in the atmosphere with a half-life of less than a few hours5. ? Epstein, S. S. and Shafner, H., "Chemical Mutagens in the Human Environment", Nature 219, 385-387, 1968. 2Epstein, S. S., et al.f "Detection of Chemical Mutagens by the Dominant Lethal Assay in Mouse", Toxicol. Appl. Pharmacol. 23, 288-325, 1972. 3From NIOSH Suspected Carcinogens - Radiation Research Supple ment 3, 193, 1963. `'From NIOSH Suspected Carcinogens - J. Nat. Cancer Inst. 32# 825, 1966. 5Radding, S. B. at al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977*. *Fuller, B. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical "Information Service-Number PB 264 442, 1976. 37 DDT DDT {l,l,l-trichloro-2,2-di-(4-chlorophenyl) ethane, CAS No. 50-29-3) has both positive and negative in vivo and in vitro data. It was negative in feeding studies oY dogs and monkeys1 and in a differential growth E. coli (pol A) mutagen test12. Given orally, it produced liver cell tumors in several strains of mice and some of its metabolites produced lung tumors in mice2. It is positive in a recessive lethal Drosophila test3. All things considered, it is probably a carcinogen and will be classified as one for this project. Production and Persistence In 1971, 2 x IQ7 Kg was the estimated production1. In 1971 it was found in the air in concentrations of 0.1 ng/m3 to 1.56 ug/a3.* * The soil half life is estimated to be 15 years1. It has a vapor pressure1 ofl.9 x 10"7m at 20"C and a melting point of 74*C. 1 "DDT and Associated Substances" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man", Volume 5, 83-124, 1974. 2Fluck, E. R., et al.V "Evaluation of a DNA PolymeraseDeficient Mutant of'S. Coli'-for the Rapid Detection of Carcinogens", Cham* Biol* Interact., 15, 219-231, 1976. 3Vogel, E., "The Relation-Between^Mutational Pattern and Concentration by Chemical^ Mutagensin. Drosophila", 1ARC Sci. Pub. No. 12, 117-137^ 1976. 38 "AM- OMSAWSTT-'Oc.aCSC-iA*'mC-<H;! -C5O_. SMljO-SA. T ION RSV 0010834 Di-tert-Butyl Peroxide Di-tart-butyl peroxide (bis(l,l-dimethylethyl) peroxide, CAS No. 110-05*4) ha* been found to induce malignant lymphomas in 7/35 mice which inhaled 100 mcM of this chemical1. Skin applications on mice did not prove to be carcinogenic*2.* {Tertbutyl hydroperoxide has also been found negative by skin application tests on mice9'4.) Di-tert-butyl peroxide is on a list of "suspected carcinogens" studied for environmental fate9. Since the positive mice test results were by the inhalation route which has fewer false positives than injection, di-tert-butyl peroxide will be considered a possible carcinogen for this project. Considering the type and date (1963) of the positive tests, however, negative short term in vitro mutageni city data would probably change its classification to a probable non-carcinogen by the criteria used for this project. Production and PerilsLance Production is estimated to be 3 million pounds per year5.* * * It is only slightly volatile but moderatly soluable in water. Thus most of the di-tert-butyl peroxide will remain in the water system. In the water the presence of >1 ppm Fe2+ and leads to decomposition to acids and alcohols with ti/2 <10 hourss. In the atmosphere photochemical and HO radical decomposition lead to a ti/2 of 79 hours5. iKotin, P. and Falk, H. L., Radist. Res. (Supp. 3), 193-211, 1963. (From PHS-149; Survey of Compounds Which Have Been Tested for Carcinogenic Activity.) 2Saffioti, 0. and Shubik, P., Nat. Cancer Inst. Monog., 10, 489-507, 1963. (From PHS-149.) Sfioshing, H., et al., Gann 61 (2), 121-124, 1970. (From PHS-149.) 4Van Duaren, B. L., ei al., J. Nat. Cancer Inst., 39, 12171228, 1967. (Proa PHS-149.) ;^iW't sRadding, S. B., et al., "Review of the Environmental Fate of Selected Chemicals"* National Technical Information Service Number PB 267 121, 1977. ,i`r Pi(2-Ethylhcxyl)Phthalate Di(2-ethylhexyl)phthalate (DEHP, dioctyl phthalate, dop, CAS No. 117-81-7 is a high volute plasticizer which had *n the past been considered virtually nou-toxxc as judged by various acute and chronic tests1. Although early animal tests (dog, guinea pig, rat) were negative12,3 at least one source* now cites neoplastic effects in rats orally given 43.2 g/kg (96 weeks) di(2-ethylhexyl)phthalate. Although this dose is rather high, there are also several ref erences which show this chemical to be both mutagenic and tera togenic4"* *1*2*.* * *It is therefore classed as a possible carcinogen for this project at least until the present carcinogen bioassay being conducted is concluded13. Production and Persistence It is estimated that 2.6 x 10s Kg DEHP is emitted per year from stationary sources14. Other estimates are 2.0 x 10* Kg produced and released15 and 1.8 x 10 Kg produced in 1974 l6. It is said to biodegrade rapidly in water and sludge17. In the air it reacts with-the HO:radical with a half-life of one day1 s. It has a boiling-point of 305"C and a vapor pressure of 1.2 mm at 200"C18. 1 Documentation of the Threshold Limit Values for Substances in Workroom Air, American Conference of Governmental Industrial Hygienists, P. 96-97, 1976. : .Vi* . r,,. TV ' 2Shubik, P. et al., "Survey ,o-Compounds Which Have Been Tested for Carcinogenic Activity, Supplement I", National Technical Information Service Number PB:216 248, 1957. 3Fuller, B., et al., "Preliminary Scoring of Organic Air Pollu tants" ,-National Technical Information Service Number PB 264 443, 1976. 4Singh, A.R., et al. "Mutagenic and Antifertility Sensitivies of Mice to Oi-2-Ethylhexyl Phthalate (DEEP) and Dimethoxyethyl Phthalate (CMEP)," Toxicol. Appl. Pharmacol. 29 (1), 35-46, 1974. .^vVV.v " sMathur,S*P.,"RespirometriC'Evidence of the Utilization of DiOctyl and Di-2 EthylhexylPhalate Plasticisers", J. Environ. Oual. 3(3), 207-209, 1974. 40 CORPORATION RSV 0010836 Di(2-Ethylhexy1)Phthalate References - Continued 6Peakall, D. B., "Phthalate Esters: Occurrence and Biological Effects", Residue Reviews !54, 1-41, 1975. {177 references). 7"Recent Progress in Safety Evaluation Studies on Plasticizers and Plastics and Their Controlled Use in Japan", Environ. Health Perspec. 17, 203-209, 1976. 8Singh, A. R., et al., "Mutagenic and Anti Fertility Sensitivities of Mice to Phtholic-Acid Esters", J. Anim. Sci., ^8(1), 216, 1974. 9Taylor, F. and Corcoran, E. F., "Biodegradation of Phthalic Acids and Esters", Contract No. ES-00994-02 from National Inst, of Env. Health Sci., 19 75. 10Autain, J., "Toxicity and Health Threats of Phthalate Esters" Review of the Literature", Environ. Health Perspec. 3-26, 1973. llYagi, Y., et al., "Teratogenicity and Mutagenicity of a Phthalate Ester", Teratology 1, 259-260, 1976. 12Dillingham, E. 0. and Autian, J., "Teratogenicity, Mutagenicity and Cellular Toxicity of Phthalate Esters", Environ. Health Perspec. 2 81-89, 1973. 13Landon, J. C., "Carcinogenesis Bioassay of Di(2-Ethylhexyl) Phthalate", Contract from National Cancer Institute to Tracor Jitco, Inc., 10/76-9/77, 1977. 1 **MRC Source Assessment Data Base, July 1977. 15Brown, S. L. et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals",' National Technical Information Ser vice Number PB 263 163, 1975. 16Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Nuntoer PB 264 *44, 1976. 17Saeger, V. W. and Tucker, E. S., "Biodegradation of Phthalic Acid Esters in River Water*and Activated Sludges", Appl. Environ. Microbiol. 31. (1), 29-34, 1976. 18Verschueren, K., Handbook of Environmental Data on Organic Chem icals, Van Nostrand Reinhold Co., New Vork, 1977. 41 RSV 0010837 2,3-Diamlnoaniole 2,4-Diaminoanisole (4-methoxy-ra-phenylenediajnine) was non* mutagenic in the L51170Y mouse lymphoma cell test1 and negative on rat skin*2 (in combination with other chemicals) and mouse skin3 * (the sulfate form) carcinogen tests* It did not produce dominant lethal mutations in rats1*. It has been shown to be mutagenic in S* typhimurium5"67,* usually with S-9 activation. It also induced sex-linked recessive lethal mutations in Drosophila malanogaster* (sulfate form) with peak activity in the active germ cells (spermatids and spermato cytes) . Preliminary results from an NCI study indicates that rats and mice fed this chemical (0.12 - 0.24%) had an excess of site specific (thyroid and skin) malignant tumors9> 10. Also two epidemiologic studies suggest excess cancer among cosmeto logists9. Diaminoanisole is on the NIOSH Safety Alert list for its carcinogenic potential10 and will be considered a probable carcinogen for this project. Production and Persistence NIOSH is unaware of any current domestic production but cites that it is imported on the, order of 25f000 pounds per year10. Calmer, K. A.,et al., "The Mutagenic Assay of Some Hair Dye Components Using the Thymidine! Klnane Locus of L51178Y Mouse Lymphoma Cells", (Meeting Abstract), Toxicol, Appl. Pharmacol 37 (1), 108, 1976. 2Kinkel, H. J. and Holzmaxm, S., "Study of Long-term Percuta neous Toxicity and Carcinogenicity, of Hair Dyes (Oxidizing Dyes) in Bats", Food Coernet-Toxicol. 11 (4), 641-648, 1973. 3Burnett, C. et al., "Long-Term Toxicity Studies on Oxidation Hair Dyes", Food Cosmet. Toxicol, 31 (3), 353-357, 1975. '`Burnett, C., et al., "Dominant Lethal Mutagenicity Study on Hair Dyes", J. Toxicol. Environ. Health (3), 657-662, 1977. sDybing, E. and Thorgeirssoa, 6:-S., ^Metabolic Activation of 2.3-Diaminoanisole, a Hair-Dye. Component", Biochem Pharmacol. 26 (8) 729-734,. 1977, ; i . .;*** -. vW r 6Dybing, E. and Auna', T:Y "aexachrorobensene Induction of 2.4-Diaminoanisole Mutagenicity: In Vitro", Acta Pharmacol. Toxical. 40(5), 575-583, 1977. (24. references) 2,3-Diaminoanisole References - Continued 7Ames, B. N., et al., "Hair Dyes are Mutagenic. Identification of a Variety of Mutagenic Ingredients*, Proc. Natl. Acad. Sci. (U.S.A.) 72^(6) / 2423*2427, 1975. aBlijleven, M. G., "Mutagenicity of Four Hair Dyes in Droso phila Helanogaster", Mutat. Res- 4 (2), 181-185, 1977. 9"Health Hazards* 2,4-Dianinoanisole", Occupational Safety and Health Reporter, 7 135), .1331,.1978. 10"2,3-Diaminoanisole (4-etboxy-m-phenylenediamine) in Hair and Fur Dyes", Current.Intelligence. Bulletin 19, January 13, 1978. : v.~f Diazinon Diazinon has been reported to be slightly teratogenic in rats when given on the eleventh day of gestation . An increase in chromatid breaks has been noted in the lymphocytes of humans after ingestion of phosphate insecticides including Diazinon and in cultivated human lymphocytes3* On the otherhand, Diazinon has been found to be non-mutagenic in Salmonella typhenurium mutation tests1*. Diazinon also does not cause mutations in the 5-MT E.coli test5, the WP2 TRY - to prototrophy E. ooli test6, two other E.coli tests7 or a S. cerevisiae mitotic gene conversion test . Tne majority of the information indicates that Diazinon is prob ably not a carcinogen. \ Kimbrough, R. D. and Gaines, T. B., "Effect of Organic Phosphor ous Compounds and Alkylating Agents on the Rat Fetus", Arch. Environ. Health, 1, 805-808, 1968. 2Trinh-van-Bao, et al., "Chromosome Aberrations in Patients Suffering Acute Organic Phosphate Insecticide Intoxication", Humangenetik 2, 33-57, 1974. 3Tzoneva-Maneva, M. T. et al., "Influence of Diazinon and Lindane on the Mitotic Activity and the Caryotype of Human Lymphocytes, Cultivated in vitro", Bibl. Haematol. Basel, 3_8 (1) 344-347, 1971 . **Marshall, T. C. et al., "Screening of Pesticides for Mutagenic Potential Using Salmonella Typhimurium Mutants", J. Agric. Food Chem. 24, 560-563, 1976. 5Mohn, G., "5-Methyltryptophan Resistance Mutations in Escherichia Coli K-12", Mutat. Research 20 (1), 7-15, 1973. 1 Ashwood-Smith, M. J., et al. , "Mutagenicity of Dichlorvous", Nature 240, 418-419, 1972. 7Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogenesis Essays, IARC Sci. Pub. No. 10, 1974. 44 o-Dichlorobenzene A negative animal study of o-dichlorobenzene (CAS No. 95-50-1) has been conducted1, but it was a short term (<6 months) study which would not be expected to show carcinogenicity. A few positive case studies have been reported, but with insufficient supporting evidence to show cause and effect*2. A few in vitro tests have been conducted3'* 5. In Aspergillus nidulans, 200 mg/ ml for 60 minutes causes an increase in reversion to methionine prototropy from 3x10s to 5xl06 reversions6. It was negative in a S. typhimurium spot test at 1-5 ul in eight strains6. Be cause of the limited positive test data on systems which have not been extensively evaluated, o-dichlorobenzene will be considered a probable non-carcinogen (with some significant positive data) for this project. `Survey of Compounds Which Have Been Tested for Carcinogenic Activity, NCI, PHS-149, Volume 1. -"Ortho- and para-Dichlorobenzenes", in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 7, 231-244, 1974. 3Guerin, M., et al., "Inhibitory Action of Chemical Carcinogens on Mitoris of Rat Lung Cell Cultures. 2. Comparative Study of Carcinogenic and NOncarcinogenic Substances," C. R. Soc. Biol. 165, 2255-2258, 1971. `Prasad, I., "Mutagenic Effects of the Herbicide 3*, 4*Oichloro-propionanilide and its Degradation Products," Can. J. Microbiol. 16, 369-372, 1970. 5Prasad I., and Pramer, D., "Mutagenic Activity of Some Chloroanilines and Chlorobenzenes," Genetics, 60, 212-213, 1968. i Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing," National Technical Information Service Number PB 274 264, 1977. 45 MONSANTO ftCMAACH COftPOi|ATIO* * RSV 0010841 P-Dichlorobenzene Many negative animal studies of p-dichlorobenzene (CAS No. 10646-7) have been conducted1, but all of them have been short term (<9 months) studies which would no- be expected to show carcinogenicity. A few positive case studies have been reported but with insufficient supporting evidence to show cause and effect2. A few in vitro tests have been conducted3*5. It is reported that p-dichlorobenzene is a mutagen to higher plants and causes chromosonial breaks6. In Aspergillus nidulans, 200 mg/ml for 60 minutes causes an increase in reversion to methi onine prototropy from 3xl06 to llxlO6 reversions7. Because of the limited positive test data on systems which have not been extensively evaluated, p-dichlorobenzene will be considered a probable non-carcinogen (with some significant positive data) for this project. 1 Survey of Compounds which Have Been Tested for Carcinogenic Activity, NCI, PHS-149, Volumes 1, 2, and 3. : "ortho- and para-Dichlorobenzenes," in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 7, 231-244, 1974. 3 Guerin, M.f ot al., "Inhibitory Action of Chemical Carcinogens on Mitosis of Rat Lung Cell Cultures. 2. Comparative Study of Carcinogenic and Noncarcinogenic Substances," C. R. Soc. Biol. 165, 2255-2258, 1971. 4 Prasad, I., "Mutagenic Effects of the Herbicide 3\ 4'Dichloro-propionanilide and its Degradation Products," Can. J. Microbiol. 16, 369-372, 1970. 5Prasad, I., and Pramer, D., "Mutagenic Activity of Some Chloroanilines and Chlorobenzenes," Genetics, 6, 212-213, 1968 6 Brown, S L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Infor mation Service Number PB 263 162, 1975. 7Allport, J., et al., NA Study of Industrial Data on Candidate Chemicals for Testing," National Technical Information Service Number PB 274-264, 1977. 46 ^HOMSAMTO AUVAVtOK CORPORATION Dichlorobenzidene 3,3'-Dichlorobenzidine (CAS No. 91-94-1) has been found to be carcinogenic in the rat following oral and subcutaneous admin istration and in the hamster after wral administration1'2. Many other positive responses are noted in Toxline and Cancer line and it is considered a probable carcinogen for this project. Production and Persistance It is estimated that 2.1 x 106 Kg is produced per year with 4.5 x 103 Kg per year released3.* Other estimates of production are 1.6 x 106 Kg in 19711 and 2.1 x 10* Kg per year4. Dichloro benzene is somewhat reactive towards R02 (t 1/2 * 40 days) and very reactive towards BO and O* (t 1/5 1 day)3. Its melting point is 133"C*. 1 "3,3'-Oichlorobenzidine* in IAKC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 4, 49-55. 1974. 2Stula, E. P t et al., "Experimental Neoplasia in Rats from Oral Administration of 3,3-Dlchlorobensidine. . . Toxicol. Appl. Pharmacol. 31 (1) 159^175, 1975. 3Brown, s. L.et al*;^"Research Program.`on Hasard Priority Ranking of Manufactured Chemicals* J.: National Technical Informa tion Service Number P8 263163,1975.: . -V ' "f.l.si . y * . ** * . i> 4Fuller, B., et al.,v"Prelimii*ery_Scoring of Organic Air Pollu tants", National Technical^Infoimation^Service Number PB 264 442, 1976. " -- Dichlorobutene 1,4-Dichlorobutene-2 is a mutagen of salmonella typhimurium with microtomes enhancing the effect1. 3,4-Dichlorobutene-l is also a mutagen in that system with or w.thout NADP, giving 490 reverts/ umol with NADP and 345 reverts/ymol without NADP . Trans-1,4dichlorobutene-2 has been found to be a weak ^ carcinogen to ICR/HA Swiss mice when given by subcutaneous injection or by interparenr.al injection but not by skin application2. It was found not to be a tumor initiator in a two-stage test2. Because of the carcino genic and mutagenic data, it has been placed on the probable car cinogen list for this project. Production and Persistence It is estimated that 8.7 x 10s Kg is emitted per year in the manu facture of polychi oroprene3, and has a boiling point of 158 aC<*. lBartsch, B. et al., "Alkylating and Mutagenic Metabolites of Halogenatad Olefins Produced by Human and Animal Tissues", Proc. Am. Assoc. Cancer Res. 17, 17, 1976. 2Van Duuren, B. L. et al., "Carcinogenic Activity of Di and Tri functional *-Chloro Ethers and of l,4-Dichlorobutene-2 in 1 CR/ HA Swiss Micg", Cancer Research 35, 2553*2557, 1975. *MRC Source Assessment Data Base, July 1977. uVerschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold to., N. V., 197?. 48 RSV 0010844 Pi chlorodifluoromethane Dichlorodifluoromethane (Freon-12) has been shown to be non-muta- genic in s. typhinuriixn teats* but nay cause some (mutagenic?) changes in conidia formation in Neurospora crasaa*2. More infor mation is needed on the mutagenic and carcinogenic potential of Freons. No other information could be found on Cancerline or Toxline. At the present time, it appears as if Freons are non- carcinogens. iAndrevs, A. W., et *1., Identification of Endogenous and Exogenous Mutagenic Compounds"* '4th Carcinogenesis Bioassay Program, Orlando, Florida*. February 1976. 2Stevens, S,, et al., "Phenotypic and Genetic Effects in Neuro- spora Crassa Produced by Selected Gases sad Gases Mixed with Oxygen", Develop, Ind, Microbiol. 13,^346-353, 1971, in-; Ta r 49 1,1-Dlchloroethane The primary reference cited for l,1-dichloroethane (CAS No. 7534-3) in the NIOSH Suspected Carcinogen list1 shows very minor teratogenic effects even at the highest concentration used (6000 ppm)* Although there are many references to 1,2-dichloroethane, Toxline and Cancerline provided no significant references on the mutagenicity or carcinogenicity of 1,1-dichloroethane. A recent report from the National Cancer Institute2 disclosed findings indicative of a possible carcinogenic potential for this compound but could supply no conclusive evidence. They found dose related marginal increases in mammary adenocarcinomas and in hemangiosarcomas among female rats and a statistically significant increase in the incidence of endometrial stromal polyps among dosed female mice. For this project it will be classified as a possible carcinogen. Production and Persistence It is estimated that 2.6 x 10 Kg of dichloroethane is emitted per year from stationary sources3. 50% of the 1,1-dichloroethane will evaporate from a 1 ppm water solution at 25*C in 22 minutes4. It has a boiling point of 57.3*C and a vapor pressure of 180 on at 20*C4. 1Schwetzr B. A., et al., "Embro- and Fetotoxicity of Inhaled Carbon Tetrachloride, 1,1-Dichloroethane and Methyl Ethyl Ketone in Rats", Toxicol. Appl. Pharmol.,28, 452-464, 1974. 2National Cancer Institute Draft Summaries of Bioassay Reports, 1,1-Dichloroethane", Chemical Reg. Rep. 1 (45), 1597-1598, 1973. ~ 3KRC Source Assessment Data Base, July 1977. 4Verschueren, K., Handbook of Environmental Data on Qraaaie Chemicals, Van Nostrand Reinhold Co.f N. Y., 1977. 50 RSV 0010846 Dichloronapthoquinone Dichloronapthoquinone (Dichlone) did not cause point mutation in a microbial test system1* It has, however, been found to cause reticulum cell sarcomas (Type A) in 9/64 mice when injected sub cutaneously in B6C3F1 or B6AKF1 strains of mice compared to 14/613 reticulum cell sarcomas for the subcutaneous controls2 This was significant at a .01 confidence level. Because of the limited number of mice involved, and the lack of'other references on Cancerline and Toxline, dichloronapthoquinone will be considered a possible carcinogen for this project.' Production and Persistance It is estimated that 900 Kg/year are esdtted from stationary sources3. Dichloronapthoquinone has a melting point of 193C and a 7.84 vapor density4. j. ' d"' ** - r' v-v. r `Anderson, K. J. et al., "Evaluation of Herbicides for Possible Mutagenic Properties", J. Aor.. Food Chcm. 20V649-656, 1972. Evaluation of Carcinogenicr>TterafMtb9enlc^uid Mutagenic Activities of Selected Pesticides and^InduatrikliCMs^cals*, National Technical Information Servic, Nber^PBi-:52J>159, 1968. 3MRC Source Assessment Data Verschueren, K. , H^feookr^q,f, ft^roSsirom Daftbon Organic Chemicals. Van No TTTT7 cr Dlchloropropene 1,3-Dichloropropene at 1 ppm for six months has shown to have no adverse effects*. Both the cis and trans isomers are mutagenic to TAX535 and TA100 S. typhimurium strains without activa tion12'34. It will be considered a possible carcinogen for this project. Production and Persistence It is estimated that 6 x 107 pounds of a dichloropropane/ dichloropropene mixture is manufactured a year5. Assuming 50% dichlorcpropene, 3 x 107 pounds is released a year. It is said to react with OH and Oj with a t^/2 " 3 days* and in water tl/2 7 days5. It has a boiling point of *04#C and 50% of a 1 ppm water solution will evaporate in 31 minutes6. 1Torkelson, T. R. and Oyen, T,, "The Toxicity of 1,3-Dichloropropene as Determined by Repeated.Exposure of Laboratory Animals*, Am. Indust. Hyg. Assoc. J., 30 (S), 217, 1977. 2DeLorenzo, P., et al, "Mutagenicity of Pesticides Containing 1,3-Dichloropropene* Cancer Res., 37. (6),- 1915-1917, 1977. 3Bignami, M., et al., "Relationship Between Chemical structure and Mutagenic Activity in Some Pesticides 1 The Dse of Salmo nella Typhimurium and Aspergillus Nidulans", Mutat. Res. (3), 243-244, 1977. 4 Neudecher, T., et al., "In Vitro Mutagenicity of the Soil Nematiclde 1,3-Dlchloropropene", Experientia, 33^ (8), 10841085, 1977. sBrown. S.L.,*t al., "Research Program; onBatard Priority Ranking of - Manufactured Chsml cals" national Technical Information Service Rumber:Pfe263 162^I975*-^-- - tri; * . 6Verschue*> Hawfhnrrir of tEnvironmant,^V.<Pata on organic Chemicals, Van Nostrand Reinhold Co. r H/vY. # 1977. 53r RSV 0010649 Dichloroproplonlc Acid Dichloropropionic acid (Dalapon) ia a herbicide which has been found non-mutagenic in a S. typhiauriun test1* No other signif icant data have been found, so it has been placed on the probable non-carcinogen list* t* * V\ Jr!'` . * . r . -' ' .Cf-'-X- -V *"i- '* -**-. .. y" fi' * \ - : -- . C ` * ''Sm - vio' 1 Anderson, K* J., et al*> "Evaluation of.Herbicidesfor Possible Mutagenic Properties* r JV i Pood 60*656 ,vl?72. -S DlchlorovinyX Dimethyl Phosphate (Dichlorvoa) Dichlorovinyl dimethyl phosphate (OOP) haa been shown to be muta genic in many different short-term tests1, including S.typhimurium tests2, but has been shown to be non-carcinogenic by oral and in halation studies in rats and mice3 Because of the mutagen studies, ODP is to be listed on the possible carcinogen list for this project Production and Persistence . It is estimated that 200 Kg/ycar is emitted from stationary sources4.' It has a boiling point of 120#C at 14 mm5. lFahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogenesis Essays,IARC Scientific Publication No. 10, p. 161-181, 1974. v. *'/** zShiraser, Y., et al., "Mutagenicity Screening of Pesticides in the Microbial System", Mutat. Res. 40, 19-30, 1976. 'Bioassay of Dichlorvos for FossiMe'-Carcinogenicity, CAS No. 6273-7", National Cancer Institute NCI-CCr-TR-10, National Technical Information Service Number PR-270 833/656*.. 1977. 4mrc Source Assessment Data Base, July 1977* . 5verschueren, K., Handbook of Envii riiiiimntal Data on Organic Chem icals, Van Nostrand Reinhold co. ,N^j,Y> ,19^7. '<. :c\` -C' - :r - '^ v-.v ` \.W* 5."5* X3^-,`:v jye-.'rf*. '-&W; RSV 0010851 Dimethyl amine Dimethylamine (methanamine, N-methyl) has been reported to com bine with nitrates or nitrates both in vitro and in vivo (by saliva or intestine flora) to form the carcinogen called dimethylnitrosamine or nitrosodimethylamine (more than 20 references in Toxline). Dimethylamine may also combine with ozone and nitrogen tetroxide in the atmosphere*. In Toxline and Cancerline there are 74 and 16 references respectively which deal with mutagenic or carcinogenic aspects of dimethylamine. These references, along with those in chemical Abstracts appear to indicate that although dimethylamine is a potent co-carcinogen, it is not by itself carcinogenic. For th*s project# it will be considered a non-carcinogen but will be considered when cofactors are evaluated. *Dushutin, K. K. and Sopach, E. D., "The Role of the Reaction of Dimethylamine with Nitrogen Tetroxide and Ozone in Atmospheric Pollution", Gig. Sanit. 7, 14-18, 1876. 57 :H>COf9909y^JlON RSV 0010853 Dimethylhydrazine 1,1-Dimethylhydrazine (CAS No. 57-14-7) has been found to be carcinogenic in mice after oral administration1. It also causes tumors of the colon in rats {but not swine, dogs, or guinea pigs perhaps because of toxicity) fed 30 mg/kg dimethylhydrazine*2. Many other positive references are found in Toxline and Cancerline and it is considered a probable carcinogen for this project. Production and Persistance Production is estimated at <5 x 10s Kg in 19731/3'4, with 3.01 fraction of dispersion4. Since it is polar, non-volatile, and soluble in water, there would not be a significant transfer to the atmosphere3. It reacts with oxidizing materials in the at mosphere4 and has an expected half life of 2.1 hours by reaction with the HO radical3. Dimethylhydrazine has a boiling point of 63.3"C and a vapor pressure of 157 mm at 25"C4. *"1,1-Dimethylhydrazine" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 4, 137-143, 1974. 2wilson, R. B., "Species Variation in Response to Dimethylhydrazine", Toxicol. Appl. Pharmacol. 38<3) ' 647-650, 1976. 3Radding, S. B., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. Dorigan, J., et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 444, 1976. 58 ' MONSANTO KCIKMCH CONVOCATION RSV 0010854 Dinltrotoluene 2,4-Dinitrotoluene has been found by the National Cancer Insti tute to be non-carcinogenic to mice but carcinogenic to r ts . rt has been placed on the probable carcinogen list for this project* Production and Persistence It is estimated that 400 Kg dinitrotoluene is emitted per year from stationary sources2. K has a boiling point of 300 C . ^National Cancer Institute Draft Summaries of Bioassay Reports 2,4-Dinitrotol uene", Chem. Reg* Rep. 1, (45), 1596* 1978. 2mrc Source JUsessment^Daia'Base/'July 1977. 3Verschueren, K., Handbook of Environmental Data on Organic Chemicals* Vwi NostrandReinholdCo., N. i., 1977. 59 RSV 0010655 Dioxane/. 1,4-Dioxane (CAS No. 12>-91-1) has been shewn to be carcinogenic to rats1'*2 and guinea-pigs3 *by oral administration. It produced malignant tumors of the nasal cavity and liver in rats and tumors of the liver and gall bladder in guinea-pigs . It was also active as a promoter in a two-stage skin carcinogenesis study in mice but produced no carcinogenic effect in one inhalation study in rats*. For this project, it is considered a probable carcinogen. ProAjcticn and Persistence The 1972 production has been estimated to be 6.3 x 106 Kg3'5'6 and the 1973 production of 7.4 x 106 Kg3#, with most of this being released to the environment6. In the atmosphere it reacts with the HO radical with a half-life of 9.6 hours*'6. It has a boiling point of 101*C and a vapor pressure of 30 mm at 20C and 37-39 mm at 25C3'5'7. . f 'Kociha, ft. J. et al., " 1,4-Dioxane: Correlation of the Results of Chronic Ingestion and Inhalation Studies with its DoseDependant Fate in Rats", Aerosp. Med. Res. Lab; (Tech.Rep.) AMRLTR-125, 345-354, 1975. 2Argus, M.F., et al.# "Dose-Response and Ultrastructural Alter natives in Dioxane Carcinogenesis"# Eur. J. Cancer 9 (4), 237243, 1973. 3*1,4-Dioxane*# in IARC Monographs on the Evaluation of Carcino genic Risk of Chemicals to Man# Vol. 11# 247-256# 1976. l4Torkelson, T. R. Study in Rats", 1974. et al.# "1,4-Dioxane. II. Toxicol. Appl. Pharmacol. 2-Year Inhalation 30 (2), 287-298# sDorigan# J. et al. # "Preliminary Scoring^ of bw.acted Organic Air Pollutants"# National Technical information Service Number PB 264 444#. 1976. i - 6Brown, S. L. et al., "Research Program^on-fjarard Priority Ranking of Manufactured*Chemicals", Nitldftai^trichnical* Infor mation Service Nunber PB 263 164* 1975.^,3;' 7t - -r err- 'Ver^chueren, K.# Handbook of"Environmental*Data* on Organic- Chemical s. Van Nostrand Relnhold Co.# New York# 1977. Diphenyl Oxide No positive or negative data could be found for diphenyl oxide (phenyl ether, CAS No. 101-84-8) on Toxline, Cancerline, or in the Survey of Compounds Which Have Been Tested for Carcinogenic Activity (Volumes It is, therefore, listed as a probable non-carcinogen for this project. 61 * a 'MWdU^tq-WKsgaecH' fcbeeoMnpbyt RSV 0010857 Disodium Methanearsonate Disodium methanearsonate has been cited as being carcinogenic, but no further data is given in this reference . Zt has been found to be non-rautagenic when tested with 5 strains of S. typhinurium, mitotic recombination of S. cerevisiae nd relative toxicity assays in E. coli and B. subtilis12. In all tests except the B. subtilis, the chemical was tested using the S-9 aicrosome activation. Methanearsonates have also been tested for mutagenesis by other authors3'4. The lack of confirming data from Toxline or Cancerline and all other indications other than the first reference demonstrate that this chemical is probably a non-carcinogen. 1Pullerr B., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 2Simmon, V. F., et al., "In Vitro Mutagenic Studies of Twenty Pesticides", Toxicol, Appl. Pharracol., CD 109, 1976. 3Shirasu, Y., et al., "Mutagenicity Screening of Pesticides in the Microbial System", Mutat* Rea., 4, 19-30, 1976. ^Anderson, K. J., et al., "Evaluation of Herbicides for Possible Mutagenic Properties", J. Agr. Food Chem., 20, 649-656, 1972. 62 , MOMSAWTO ACSCAJtgH, COMOftAJJ0N RSV 0010658 w Dursban Dursban has been shown to be more toxic to the repair deficient strains of B. subtilis and E* coli than in repair proficient strains of these organisms* It was not, however, found to be a mutagen on S* typhimurium assays or on the mitotic recombination of S. cerevisiae\ It is considered a non-carcinogen for this project* Simmon, V* P*, et al., *ln Vitro Mutagenic Studies of Twenty Pesticides", Toxicol. Appl. Pharmacol* 21 (U* 109, 1976. 63 RSV 0010859 Endosulfan Endosulfan has been found to marginally increase (P * 0*05) the total number of tumors and the pulmonary adenomas in mice given the compound orally1. Endosulfan has been found to be non-rautagenic in three different E. Coli mutagen tests2. In a National Cancer Institute study3, endosulfan was found to be non-carcinogenic to mice and non-carcinogenic to rats. Because of the limited amount of positive carcinogenic data and the many nega tive studies, endosulfan has been placed on the probable non carcinogen list. 1 "Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activ ities of Selected Pesticides and Industrial Chemicals", National Technical Information Service Number PB 223159, 1968. 2Fahrig, R, "Comparative Mutagenic Studies with Pesticides" in Chemical Carcinogen Essays, IARC Sci. Pub. No. 10, 1974. National Cancer Institute Draft Summaries of Bioassay Reports", Chem. Reg. Rep. 1 (45), 1608-1609, 1978. 64 RSV 0010860 ' `J4V Endrin Endrin (CAS Ho. 72-20-9) ha* been reported to cause chromosome breakage in cells2. Endrin was non-mutagenic by a S.typhimurium test using mouse liver micronones and has tested negative on several E. coli tests*. Bat feeding studies (up to 100 ppm) shoved no increase in tumor incidence*. Endrin will be considered a probable non-carcinogen for this project. 1 Grant# W. F., "Cytological Effects of Environmental MutagensPesticides#" Mutat, Res. 21 (4)# 221,222, 1973. 2Van DVbk# P- and Van de-Yoorde# H>, "Mutagenicity Versus Carcinogenicity of Orgaaoehlorlde Znpectacides"# Meded. Fac. Landbouwvet., Rijksunlv# Gent.# 41(2), part 2# 1491-1498# 1976 3Fahfig R. #--"Cospara&vR? Mutagenicity? Studies with Pesticides", in IARC Sci. Pub. Ho^lOy-161rl81^ 1974. ; :V - ^ : - - 4"Endrin" in XARC Monographs 6n the Evaluation of Carcinogenic Risk of Chassis to Kan^Voluaie S, 157-171, 1974. ,SPTi 5 -O' ITION RSV 0010861 wV' TSr. Epichlorohydrin Epichlorohydrin (chloromathyl oxirane, l-chloro-2,3-epoxy propane, CAS No. 106-89-8) has bean reported to be carcino genic in mice by subcutaneous injection and active as an initi ator in a two-stage skin carcinogenesis study in mice1* Epichloro hydrin is also a typhimurium causing chromosome aberrations, mutating S. typhimurium in a host mediated assay and E. coli, and Neurospera crassa*2. It will be considered a probable car cinogen for this project. Production and Persistence It is estimated that 2.2 x 10s Kg is emitted per year3. Pro duction in 1973 was estimated324 to be 1.6 x 10 Kg, 1.5 x 10 Kg and 8.2 x 7 Kg on another recent estimate5 * of 2,2 x 10 Kg. The production is expected to grow 4-5% a year2. In the atmosphere epoxides have a half life of 3 to 11 hours4. Epichlorohydrin has a boiling point of 117*C and a vapcr pressure of 12 am at 20"C*. 3"Epichlorohydrin* in XARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 11, 131-139, 1976. 2Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 3MRC Source Assessment. Data Base, July 1977. ^Redding, S. B.,~et al.', "Review ofthe environmental Fate of Selected Chemicals",'National Technical Information Service Number PB 267 121, 197T. <. ; sFuller, -B, et- al."Preliminary Scoring' of Organic Air Pollutants", National7Technical Information Service Number PB 264 442, 1976. ' 6Verschueren, K., HarwdbcxSXof Environmental Data on Organic Chemicals, Van Nostraid Relnhold co., N. Y., 19^7. 66 - iM*-..-> RSV 0010862 Eptam (ethyl di-n-propylthiocarbamate, CAS No* 759*94-4) wee negative in a bone marrow chromosomal aberration test when fed to rata at 1/S LD50 (LD50 - 1630 mg/Kg)1.: Eptam may have had an effect on Vida faba2. Xt. Is cited as . belonging to the C4 classification of pesticides3 (negative; but in only one species of animal) but also:referenced as being a neoplastic agent1*. Neither of these primary'references could be found on Cancerline/ Toxline, Medline* or the entire collection of the "Survey of Compounds Which Have Been Tested for Carcinogenic Activity". For this project it will be classified as a non carcinogen. *Kurinnyif A. I., "Mutagenic Activity of Some Pesticides, Derivatives of Urea, Carbamic and Thiocarbaaic Acids", Tsitol. Genet. 11 (4), 357-359, 1977. 2Hakeek, H. and Shehab, A., "Cytological effects of Eptam and Cotoran on Vicia Faba", Egypt. J. Bot.f16(l-3), 303-311, 1974. ' V;: .: 3Jurek, A., "Carcinogenicity- of Pesticides", Roczn. Panstv. takl. Hig., 2S-(5), 561-576/51974; ^ ' v - : . \ . ,,xr:.? ' v.-- 4Dorigan, J., et al., "Preliminary Scoring of Selected'Air Pollutants, Appendix. XX"i National Technical Information Service Number PB-264 444,l'l?76~` 67 Ethanol Much has been written about the mutagenicity or carcinogenicity of ethanol1,. (87 reference! in Toxline) with both positive and negative results, it has been tested extensively In animal systems4. In general it is considered a non-carcinogen and non-imitrgen and has been removed from the latest NIOSH Suspected Carcinogens list. It will be considered a probable non-carcinogen for this project. ^Rydberg# ;U. and-Skerfuing#-S# "The Toxicity of Ethanol. A Tentative .Risk Evaluation** Adv.~Sxp. Ned. Biol.* 85B# 403-419# 1977. (57 references) ZBraun#:iR.f and Schoeneick, J. "Influences of Ethanol and Carbon Tetrachloride on the Mutagenic Effectivity of Cyclophosphamide in the BoSt-Mediated Assay with Salmonella Typhimurium," Mutat# Res. 31 (3), 191-194# 1975. 3Charbey, R.C.# et al.^^XraluationNof^the Effect of Ethanol on the Frequency of Micronuclei'in'the Bone Marrow of Swiss Mice." Mutat, Res,; 43,(3),. WhichSurvey of Compounds Have-Been Tested for Carcinogenic Activity# KIH, PAS-149, Volumes 1# 2# 3# 4# 5* 6# and 7. Ethyl Benzene No data have been ound to indicate that ethyl benzene is a muta gen or a carcinogen. A review of its use as a fragrance is noted*. Ethyl benzene has been found non-carcinogenic to rats, guinea pig, rabbit and monkey by inhalation and to rats orally2. It is negative on the viral enhancement of hamster cell transformation3. It is therefore classified as a non-carcinogen for this project. lOpdyke, D. L. , "Monographs on Fragrance Raw Materials Ethyl benzene", Food Cosset. Toxicol. 13, Suppl., 803-804, 1975. 2Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Infor mation Service Number PB 263 161, 1973. Personal communication from B. C. Caston on 9 February 1978. 69 MONSANTO- ft**CARC>f pOftPOftATlQN Ethylene No data was fourti to indicate that ethylene is a mutagen or a carcinogen. It is also a normal metabolite of the human body. It is therefore classified as a probable non-carcinogen for this project. 70 MONftAfcTO' *CSCA*eif COftPOHATfON :k. ; RSV 001086b Ethylene Di.brotti.de Ethylene dibromide {1,2-dibromoethane, ethylene bromide, CAS No* 106-91-4) has been found to produce squamous-cell carcino mas of the forestomach in mice and rats after its oral adrainstration1. It has also been reported to be mutagenic in Salmonella typhimuriua, Escherichia coli, Neurospora crassa, Saccharomyces cerevisiae, Tradescantia. Serratia marcescens, and Drosophila melanogaster test systems12 3 ** 4 Ethylene dibromide will be considered a probable carcinogen for this project. Production and Persistence It is estimated that 8.9 x 10s Kg of ethylene dibromide is emitted per year from stationary sources. Another reference cites a production of 1.43 x 10 Kg with 1.3B x 100 Kg released*. Other references cite production of 1.5 x 10'3 * Kg (1974) 7, 1.4 x 10 Kg , and 1.5 x 10 Kg, 1.2 x 108 Kg for 1974 and 19752. The use of ethylene dibromide in gasolina is predicted to drop by 10% a year through 1980 while its use as a fumigant may be terminated by EPA action in light of the above animal studies2. Its air pollution potential has been assessed4. Atmosphere oxidation of alkyl halides is reported to have a half life of less than 20 hours while the half life of HO radical attack is 234 days7. It boiling point is 131.6"C and it has a vapor pressure of 11 bbb at 25*Cl. 1"Ethylene Dibromide", in IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, Volume 15, 195-209, 1977. 2Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 3Fishbein, L., "Industrial Mutagens and Potential Mutagens I. Halogenated Aliphatic Derivatives", Mutat. Res. 32, 267-308, 1976. 4Johns, R., "Air Pollution Assessment of Ethylene Dibiomide", National Technical Information Service Number FB 256 736, 1976. 5MRC Source Assessment Data Base, July 1977. Brown, L. L., et al., "Research Program on Hazard Priority Ranking of ManufacturedChemicals", National Technical Infor mation Service Number PB 263 161,* 1975. 7Radding, S. B., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. 71 iCOMPQMATION RSV 0010867 Ethylene Oibromide References - Continued 9Fuller, B., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 72 MONSANTO' NCSCAftC* COWEQUATION . . RSV 0010668 Ethylene Dichlorlde Ethylene dichloride (1,2-dichloroethane, ethylene chloride, CAS NO. 107-06-2) has been found in preliminary results to be carcinogenic when fed to male and female rats by the National Cancer Institute1. Ethylene dichloride fed rats had a signi ficant excess of site-specific malignant and non-malignant tumors. In other studies its has been negative by inhalation in rats, guinea pigs and monkeys but mutagenic to fruit flies*2. Because of the positive animal studies, it is included on the probable carcinogen list for this project. Production and Persistance It is estimated that 6.7 x 107 Kg ethylene dichloride is emitted per year from stationary sources3. Other references cite a production of 3.9 x 109 Kg produced with 2.1 x 108 Kg released4, 4.2 x 109 Kg (1973) 5 produced, and production of 4.2 x 109 Kg, 3.6 x 10* Kg, and 3.6 x 109 Kg in 1974, 1975, and 19766. An air pollution assessment of ethylene dichloride has been made2. Ethylene dichloride reacts slowly with provides with a half life of 1000 days and is resistant to photochemical degradation2. The HO reaction half life has been estimated to be 234 hours7. It has a boiling point of 83.5C and a vapor pressure of 61 mm at 20C. *"New Findings on Two Carcinogens Reported to Subcommittee by NIOSH", Occupational Safety & Health Reporter 7 (35) 1331, 1978. 2Johns, R., "Air Pollution Assessment of Ethylene Dichloride", National Technical Information Service Number PB 256 733, }976. 3MRC Source Assessment Data Base, July 1977. 4Brown, S. L., et al., "Research Program on Ha; ard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. sDorigen, J., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Service Number PB 274 264, 1977. Selected Information 6Radding, S. B., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. 7Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co., N. Y., 1977. 73 ct AOCAJtCW:CO*0*ATlO V RSV 0010869 Ethylene Glycol Although ethylene glycol (1,2-ethanediol) ha* been reported to give neoplastic effects at 4 gm/kg on mouse skin1, no other con firming reports of carcinogenicity or mutagenicity have been found. Many reports indicate that ethylene glycol is non-carcinogenic in different species by various routes of administration. These in clude 18 tests reported in 8 articles before 1950 on rats, mice, and rabbits in food, drinking water, interveneously, subcutaneous ly, intermuscularly, and via inhalation - all with negative re sults12. More recently, tests have been negative for ethylene glycol3 in cluding subcutaneous rat tests4, subcutaneous newborn mice tests5,6 and inhalation tests using rat, guinea pig, rabbit, dog, and monkey5. It is also negative in the Salmonella test for mutagens7'8 All in all, ethylene glycol will be considered a non-carcinogen for this project. 1 Fuller, B. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 444, 1976. 2Hartwell, J. L., "Survey of Compounds Which Have Been Tested for Carcinogenic Activity", National Technical Informational Service Number PB 216 478, Page 36, 1951. 3Homburger, F., "Carcinogenicity of Several Compounds", National Technical Information Service Number PB 183 027, 26 pp., 1968. uMason, M. M., "Toxicology and Carcinogenesis of Various Chemicals Used in the Preparation of Vaccines", National Technical Infor mation Service Number PB 195185, 55 pp., 1969. 5Derse, P. H., "Injection of Newborn Mice with Seven Chemical Ad juvants to Help Determine Their Safety", National Technical In formation Service Number PB 195 153, 135 pp., 1969. 6Coon, R., et al., "Animal Inhalation Studies on Ammonia, Ethylene Glycol, Formaldehyde, Dimethylamina, and Ethanol", Toxicol. Appl Pharmacol. 16(3), 646-645, 1970. 7McCann, J., et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300 Chemicals", Proc. Nat. Acad. Sci. (USA) 72 (12), 5115-5139, 1975. 8Allport, J. et al., icals for Testing", PB 274 264, 1977. "A Study oc Industrial Data on National Technical Information Candidate Chem Service Number 74 MONSANTO AOSAACH CONDONATION Ethvlene Oxide Ethylene oxide (oxirane, 1,2-epoxyethane, CAS No. 75-21-8) has been found negative on skin painted mice and subcutaneously injected rats^. Short term inhalation tests (6 months) on dogs, mice, rats, rabbits, guinea pigs, and monkeys were negative1. An excess of tumors were found in mice exposed to ethylene oxide treated ground-corncob bedding as an experiment not designed to test for carcinogenicity of ethylene oxide1. Ethylene oxide is a mutagA in Salmonella tYphimurium, Neurospora crassa and Orosphila melanogaster tests**'12. It will be considered a possible carcinogen for this project based on the in vitro mutagenicity data. Production and Persistence It is estimated that 4.5xl0*kg ethylene oxide is emitted per year from stationary sources3. Other estimates of production includes 1,8x10* kg produced with 4,5x107 * kg released1*, 1.8xl09kg produced5, 1,8x10* kg produced in 19746, 1.9x10* kg produced in 19751, and 1,6x10* and 2.0x10* produced in 1974 and 19752. Its primary use as an intermediate is expected to grow at 4.7-5.2% per year until 19802. . Dispersed in the atmosphere, epoxides would be oxidized by HO radicals with a 3-11 hour half life Its reaction with HO radicals has also been estimated to give half lifes of 1.6 days4 and 23 hours*. It has a boiling point of 11C and a vapor pressure of 1095 rod at 20C7. 1 "Ethylene Oxide" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 11, 157-L67, 1976. 2 Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing," National Technical Information Service Number PB 274 264, 1977. 3 MRC Source Assessment Data Base, July 1977. Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Service Number PB 263 164, 1975. Dorigan, J., et al., "Preliminary Scoring of Selected Organic Air Pollutants, National Technical Information Service Number PB 264 444, 1976 75 MONSANTO* iACM COftPOffATfON Ethylene Oxide References - Continued i 8 8 8 8 "Redding, S. L. et al., *Reviev of the Environmental Fate of selected Chemicals,* National Technical Information Service Number PB 267 121, 1977. 7Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co, 197/. 76 > MONSANTO AUCAACH. COftPORATION RSV 0010872 f --- Ethyleniwine Ethylenimine (Aziridine, CAS No. 151-56-4} is well documented as being a potent mutagen, and is used as a mutagen in many plant studies (S33 references on Toxline to its use as a mutagen or carcinogen) It has also oeen found to be carcinogenic in at least two strains of mice following oral administration and pro ducing liver-cell and pulmonary tumors1. Subcutaneous injection of single doses in suckling mice produced increased incidence of lung tumors in males. Subcutaneous injection in oil produced local tumors in rats1* It is considered a probable carcinogen for this project. Production and Persistance It is estimated that 2.7 x 10** Kg is released to the environment cer year*2.3 Estimates of production are 2.3 x 10s Kg, 1.4 x 106 Kc, 2.2 x 10s Kg (1974), and 2.3 x 106 Kg per year2*5. EthylenimMiinue1; infinitelvyj oswoxluuab/alec xinu wwaautcexr5f, wbaassxvic. f, aatniwd polar,t and*- could t^he^ _r_ _e_ rfore^ bVe^ ae.mx.paected ^tao Wb^e - v.aery ^s1loa.w^ ^to^ ^e^sac^ape from wmataer ^tAo the atmosphere1*. Its reaction with HO in the atmosphere has ueen found to have a half-life of 1.5 days2, 47 hours4 and 56 hours1*. It has a boiling point of 56*C and a vapor pressure of 160 mm at 20*C1. ^Aziridine" in IARC Monographs on the Evaluation of Carcino genic Risk of Chemistry to Man, Volume 9, 37-46. 1976. -Brown, s. L. et al., "Research Program on Haaerd Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 164, 1975. 3Allport, J. et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. "Redding, S. B., et al., "Review off the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. 5Fuller, B. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 77 'MONSANTO- RSV 0010873 Fluoranthene Fluoranthene (CAS No. 206-44-0) was tested for carcinogencity in 1935 and 1936 on mice by shin (0.31 in benzene for 501 days) and oral (10 ng for 18 months) routes of administration with negative results K Arcos and Argus reported in 1974 that in 1963 or 1964 others had found fluoranthene negative by sub cutaneous tests in XVII nc/Z strain of mice2, and is generally considered non-carcinogenic2. Recent tests of mouse skin application, alone or followed by croton oil, were negative after 15 months and 20 weeks respectively3. It has been tested on TA96, 100 and 1537 strains of S. typhimurium for mutagencity **. It is considered a probable non-carcinogen for this project. lSurvey of Compounds Which Have Been Tested for Carcinogenic activity, IBJIr~VHS-149, VP1UBH 1.--------------------------------------------------- 2Arcos, J. C. and Argus, M. F., Chemical Induction of Cancer, Volume IIA, Academic Press, Hew York, 1974, pp. 26, 237. 3Hoffman,D., et al., J. Hatl. Cancer Inst. 49, 1165-1175, 1972. hRao, T. K., et al., "Environmental Mutagenesis of EnergyRelated'Effluents", Genetics, 83,S60, 1976. 78 M4AMXO. ReSEAmCKjCOMFOSATlON .Vv *rf yl " RSV 0010874 I I( I I I I I I I I I I J JW MB*1' >* . .' *i>.' *"1-'.^*,V ?*. - ;. `_ - l i\! <;' i,'v v -i. * U" FYgrnaldafcyde (natKnalf n#r methyl aldehyde, CAS No. 50-00-0) hu been fimhnd far carcinogenicity with negative results on many animal epeclee in short tern(usually lessthan a year) tests1. However# 1300 mg/kg <65 seeks) caused neoplastic effects in rats2 end 1 ml of 0.4% formaldehyde >** spindle cell saroonss and fibrosarcoma at the injection site of-4/10 rats evaluated at least 649 days3. Formal- dehyde has been shown ,to be a mtagen in Dmen|h1 la nalanogastar# E. ooli, barley, Vida faha, ysast, and vixalLranaCffl'setion enhancsnent tests4'6# but negative cn the moi dominant lethal test'. Pdc this project formaldehyde will be corsidaradciC pTa^hle grxaipgaP ST V-. * >?v- - Production and _V*> It is estimated that 4.1x107. kgfbnmlrWiyde is emitted per year from stationary sources with 82% of this*being ftea charcoal manufacture and catalytic cracking in petro&einlfefiiiihg*. Other estimates of production include 2.6x10* kg prcduaed and;2.4x107 kg; released2/ 2.6xl09 kg prodixaed and .4x107 kg releaeed4, 2.63d0^)dg%^roducrf (1974).*, and 2.9x10* kg and 2.6x10- kg produoed in.1973 and 19754; -Bib production of formaldehyde is projected to grow iy 4-5% par yearin the next' fiva years10. In solution it is essentially ncrij-volatiie^ buttin' the air itwill met with HO radical with a half lifa;af#;6 Jfconi* ar(1.2 hours4; As a gas it has a boiling point of -21.C and? a v^br^proesur* of 1946-ian at 25C? Its envizoEUBital^ fate# biological#.ai&lindronamntal effects have been studied1K -v:'"-- .... ~y; -j - ;-.vf : >}*-' . - 5V-. Purvey of Qmicals. Itiich BavBeen,Tested for Carcinogenic Activity, National Caho^lrista^7vilBiL4$^ StolaB*~l',''2f:'3, 4; and 5. ^Dorigan, J., et alV,rPryliadnatY?gooring of Selected Qrgaziic Air Pollutant;," National Tacimical lnfcrnntion ServicNt*tmi^l2^ 445, 1976. Survey of XJrolcnls ... Formaldehyde References - Continued u r. .L -Tt-fX-l*.- ..-i. 7Ei3tein, S. S., etal., "Drttficfriori^of Cltelrul Aitagene fey the Dominant Xnthal Aasay in the Mciisa,*;~itadcial. Applr WwuiaeboT. 23. 299-325, 1972. two souco* ... frit, *tadding, 5. X*., etal., OnicalB," National 1977. vt. imf yriii^irt ! of Selected kticn* Hater FB 267 121, 1 ^11 port, J., et el., ,"A Stufo~a^3duitel&^ for Testing, " TWhnfrMt Qwoirwl* iuter FB 274 264, m?*1 Atlantic TVenwrrh 0bcp,, "-X\hs^W&?g^i^\of fle1^hi^ Potmfr1nl Environ mental Ocntandnentas fnrael<4irfyda? (ftrepefed flafroU, ffcticrial Technical Infdxneticn Servio^-SMc |B. 254^639, .1976, . . _ vv.r-_-V', -wy^'v ' -V: * * *.- - *.-. . - ' y '} -.'i'1 80 RSV 0010676 Heptachlor The IARC monograph on heptaehlor (heptachloro-tetrahydro " nethanoindene, CAS No. 76-44-8) shows this compound to have both positive and negative data, with more negative than positive1. It is a mutagen as tested by the enhancement of viral transformation12. Recent NCI tests3 with rats and mice demonstrated that heptachlor is a carcinogen for the liver in mice under the conditions of their bioassay. It is considered a probable carcinogen for this project. Production and Persistence It is estimated that 1.1 x 104 Kg heptachlor is emitted per year from stationary sources4. Estimates of production include 2.7 x 106 Kg (1971) 1 and 2.7 x 10* Kg produced5. It has a melting point of 954C and a vapor pressure of 3 x 10~4 mm at 25C1 1"Heptachlor in IARC Monograph on the Evaluation of Carcino genic Risk of Chemicals to Man", Volume 5/ 173-191, 1974. 2Personal communications with'B. C. Casto on 9 February 1978. 3"Bioassay of Heptachlor for Possible*Carcinogenicity, CAS No. 76-55-8", National Technical Information Service Number PB 271 967. < 4MRC Source Assessment Data Base, July 1977. sDorigan, J.,et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 445, 1976. 82 Hexachlorobansane Hexachlorobenzene (benzene bexachloride, CAS No. 118-74-1) induces microsomal enzymes1. Is only slightly teratogenic 2 and tests positive/negative3 and negative2 on the dominant lethal test in rats. When fed to rats it was non-carcinogenic1*, ard by S. typhimuriun tests (using mouse liver microsomes) it was negative 5 Hexachlorobenzene was, however, mutagenic when tested with Saccharomyces cerevisiae at 100 ppm* and when fed to 6 week old Syrian golden hamsters at concentrations up to 200 ppm it induced heptomas, hemangiomas and thyroid adenomas in a dose response manner7, it la tlarefore considered a possible carcinogen for this project* Production and Persistence It has a ti/2 % 2 days in the air-reacting with OH to fora pentachlorophenal. Its production .is estimated to be 1.3 x 106 pounds per year and 0*3 x: 10* pounds is used in a dispersive manner as a fungicide for a total'of 0*5 x 10s pounds released6. It has a boiling point of 322^326"C*. *Dybing, E. and Aune, T*, "Hexachlorobenzene induction of 2,4Diaminoamide Mutagenicity in Vitro", ' Acta Pharmacol Toxicol. 40 (5), 575-583, 1977. 2Khera, K. S., "Hexachlorobenzene: Teratogenicity and Dominant Lethal Studies in Rats", Toxical. Appl* Pharmacol. 29, (1), 109, 1974. rf ' V. Epstein, S. S., et al* / "Detection; of . Chemical Mutagenes by the Dominant Lethal Assay^iik'the Mouse", Toxical. Appl. Pharmacol. 23, 288-325, 19$2. ^, . Boyland, E., et al. v V\ > "Kidney*.Toeors in Sate Following Treatment with 2-Acrtylaminofluorene/ Tryptophan, and 14-Saccharolactone and the Failure of Substance# Ifhlch- Cause Porphyrinuria to Induce Tumors", pp. 58-S9:in,British Empire-Cancer Campaign 1963 - Part 2i Scientific-Reports7j pp* 19&3* _ ____,,_______,_____________. .v _ac. Landbouwwet., Rljksunly. 'Cent,' 41" (2) part 2, 1491-1498 , 1976. 6Guerzoni, M. E*, et al., "Mutagenic Activity of Pesticides", Hexachlorobenzene References - Continued :Cabral, J. R. p., et al., "Carcinogenic Activity of Hexachloro benzene in Hamsters", Nature 269 (5628), 510-511, 1977. '5rown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals*, National Technical Information Service Number PB 263 161, 1975. nerschueren, R., Handbook of Environmental Data on Organic Chemical, Van Nostrand Reinhold Co., New York, 1977. 84 Hexachlorobutadiene Hexachlorobutadiene injected I.p. in mice apparently caused no lung adenomas 1 . A two year study with rats on diets contain* ing hexachlorobutadiene showed no effects at 0.2 mg/kg/day or less, but renal tubular adenomas and adenocarcinomas at 2 and 20 mg/kg/day2,3. A reproduction study also showed no effects at 0.2 but effects at 20 mg/kg/day. At the high doses some toxicity was also evident. A 90 day feeding study (0.3-30 ppm) on Japanese quail showed little effect of this chemical . NIOSH has a safety alert out on the basis of the above tests and it is considered a possible carcinogen for this study. Production and Persistance It is estimated that 8 x 106 pounds is produced in the USA with 7. 3 x 106 poinds being released per year*. It reacts with OH and Oa with a tl/2 of less than one day and has a low water* soluabilitys. The boiling point of hexachlorobutadiene is 210C with a vapor pressure of 22 ran at 100C6. *Test for Carcinogenicity of Organic Contaminants of United States Drinking Waters by Pulmonary Tumor Response in a Strain of Mice," Cancer Res. 21 <B), 2737,2720, 1977 2Results of a Two-year Chronic Toxicity Study with Hexa chlorobutadiene in Rats (Meeting Abstract) Toxical. Appl. Pharmacol. 41 (1), 204,1977. 3Kociba, R. J., at al., "Results of a Two-year Chromic Toxicity Study with Hexachlorobutadiene in Rats," Am. Ind. Hyd. Assoc. J., 38 (11), 589-602, 1977. > "Reproduction Study in Japanese Quail Fed Hexachlorobutadiene for 90 days," Toxical. Appl. Pharmacol. 22 (2), 255-265, 1974. sBrown, S. L., et al." Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Infor mation Service Number PB 263 161, 1975. 6Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand R$inhoid Co., N.Y., lW. ------------ 85 WOWSAMTO j * RSV 0010881 Hexamethylenetetramine Hexamethylenetetramine (CAS No. 100-97-0) has been extensively tested in both rats and mice*. Almost all of these tests show that this chemical is non-carcinogenic when given either orally (up to 5% of drinking water) or subcutaneously (25 gm/Kg)z. It has been tested on z. coli differential growth (pol A) test with positive results which was considered a false positive3. It has also been reported to be non-mutagenic to Drosophila, positive in oral mouse dominant lethal test, negative in an interperitoneal mouse dominant lethal test, and positive on a chromosomal aberraation test in cultured lyphocytes1*. Hexamethylenetetramine will be considered a non-carcinogen (with some positive data) for this project because of the extensive negative animal data. 1"Survey of Compounds Which Have Been Tested for Carcinogenic Activity", PHS-149, Volume 1 - Number 1230, Volume 3 - Number 847, Volume 4-Number 1234,. Volume 5 - Number 704, Volume 6 Number 534, 2Della Porta, G., etal., "Non-Carcinogenicity of Hexamethylenete tramine in Mice andrRats", Food. Cosine t. Toxicol., 6 (6), 707- 715, 1968. - 3Fluck, B. R. et al. / "Evaluation, of a DMA. Polymerase - Deficient Mutant, of Z. COli forthe^Rapid Detection of Carcinogens", Chem. Biol. Interact. 15, 219-231, 1976. 4Allport, J. et al.,r"A- Study of Industrial Chemicals for Testing"; National Technical Number PB 274 264, 1977. Data on Candidate Information Service 86 ________WMBsmeii <fem*o*kTioN RSV 0010882 IM3razlna Hydrazine (diamine, CAS ht>. 302-01-2) tee been shown to be carcinogenic in mice after oral and 4n^iT7rr1lrrsiti1 adninistraticn aid in rats following oral ackronistratian1. it was negative in hawters after oral adbninistra- tion1. Hydrazine is considered a carcinogen for this project. Production and Persistence Zt is estimated that 3.5x1013k* g hydrazine is emitted per year2. In 1966, production of hydrazine was 7x10* kg per year with more than 70% of this going toward rocket fuels1. In 1971 it was estimated that production was 1.4xl06 kg and 1.7x107 kg in 1974 3`*t*. Hie demand for hydrazine is ejected to increase 15-17% a vear txitil 1985H. Hydrazine is polar, non- walatile and water mlmhla mijjntlnqi mat it will not transfer to the atmosphere at significant rates3* Cbddaticn by HO radicals in the gas phase is reported to be rapid with a half life of less than ana hour3. It has a boiling point of 113C and a. vapor piLuasurr of 16 an at 20C5. 1 "Hydrazine" in IAHC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Ualune 5, 127-136, 1974. ZMC Source .Wsaes--pnt- Ham .Base, JUly 1977. 3Radding, S. B., etal., "Review of the Ehvixcraental Fate of Selected Oswricals," Matinnal TUdmical Information Service Water 6 267 121, 1977. **AIIpnrt, J., etal., "A Study of Industrial Data on Candidate Chemicals for lusting," National Technical Information Service timber PB 274 264, 1977. Syerschueren, X., Handbook of Environmental Data on Organic Chemicals, van Nsti'sd Iteinhold Co., N* Y., 197t, Hydroquinone Hydroquinone is listed on the NIOSH Suspected Carcinogen list, but it is apparently there by. mistake. The 1955 reference cited1 shows 20 mg of hydroquinone applied to the skin of nice (in benzene) developed only one tumor out of 22 surviving mice as conpared with one tumor out of 22 surviving mice for the croton oil con trol. A more recent reference cites hydroquinone as a bladder carcinogen when implanted in cholesterol pellets producing 32% tumors vs. 12% for the cholesterol control2 Hydroquinone is said to be an inhibitor of 3,4-benzpyrene carcinogenesis3, in active as a promoter4, and slightly active as a promoter5 of carcinogenesis.. Hydroquinone has been reported:as more toxic to repair deficient E. coli (pol a") indicating that xt may induce DMA damage6, but negative in inducing itiblotic resistance- in Micrococcus pyrogens6. Chromosome aberrations have been.noted, in several plant systems after treatment with hydroquinone6. These mutagenic references almost place hydroquinone on the possible carcinogen list, but they involve test systems which have not been extensively eval uated. Hydroquinone will be considered a probable non-carcinogen (with some significant positive data) for this project. 1Roe, P. J. C. and Salaman, M. H., "Further Studies on Incomplete Carcinogenesis", British J. of Cancer, 9, 177-203, 1955. 2Boyland, E. et al., "Further Experiments on Implantation of Materials into the Urinary Bladder of Mice", Cancer, 18, 575-561, 1964. ,(y British J. of 3Van Duuren, B. L. and Goldschmidt, B. M., "Cocarcinogenic and Tumor-Promoting Agents in Tobacco". J. Nat'l. Cancer Inst., 56, 1237-1242, 1976. -- u"Study of Tobacco.Carcinogenesis. XIII. Tumor-Promoting Sub fractions of the ffeakly Acidic Fraction", Toxline. >_. ~ ' ... . . Vi: ''-il'<-' ^Interaction between* Hydroquinone < and Cigarette Smoke Condensate in Short-Tera.Skin Teats for Carcinogenicity", Toxline. 6Allport, J.^ dtt.aio^"A, StU(Jy^of .Industrial. Data on Candidate Chemicals fb^:testlhg"-,^ Mationa^fTe^mical 'Information Service Number PB 274i24V1977. ., Kelthane Kelthane has been found non-mutagenie to E. coli bacteria in the WP2 TYR to prototrophy test1. It is considered a probable non-carcinogen for this project. < xAshwood-Smith, M. J., "Mutagenicity of Dichlorvos", Nature 240, 416-419, 1972. 89 Malathion Malathion has been demonstrated not to be a teratogen1 and Ames et.al consider it not to be a mutagen*2. It has been ound to be a non-mutagenic in four test systems3, and a study by the National Cancer Institute found it to be non-carcinogenic to rats and noncarcinogenic to mice4. Malathion was found non-mutagenic by a dominant lethal test in mice5 but was a slight promoter in rats when given with dimethylbenz (a) anthracine". For this project Malathion is classed as a probable non-carcinogen. ^Kimbrough, R. D. and Gaines, T. B., "Effect of Organic Phos phorous Compounds and Alkylating Agents on the Rat Fetus", Arch. Environ. Health, 1^6, 805-808, 1968. :McCann, J., et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300 Chemicals", Proc. Nat. Acad. Sci. (USA), 72, 5135-5139, 1975. -Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in.Chemical Carcinogenesis Essays, International Agency for Research on Cancer-Scientific Publication No. 10, p. 161-181, 1974 . uNational Cancer Institute Draft Summaries of Bioassay Reports", Chem. Reg. Rep. 1^ (45), 1597-1618, 1978. 5Jorgensen, T. A., of Ten Commercial (1) , 109, 1976. et al., "In Vivo Mutagenesis Investigations Pesticides", Toxicol. Appl. Pharmacol. 31. Silinskas, K. C., and Okey, A. B., "Protection by DDT Against Mammary Tumors and Leukemia During Prolonged Feeding of 7,12-Dimethylbenz (a) anthracene to Female Rats", J. Nat'l. Cancer Inst., 55 (3), 653-653, 1975. 90 Maleic Anhydride Only one 1963 reference cites maleic anhydride as a carcinogen1. In this paper three rats of an unspecified species were injected 550 times with maleic anhydride. Two of the three rats developed fibrosarcomas at the injection site* No other indications could be found in the literature which suggests that maleic anhydride may be a mutagen or a carcinogen in any test systems. In the atmosphere maleic anhydride could be expected to be converted rather rapidly to maleic acid for which no evidence has been found to suggest it has any carcinogenic or mutagenic potential. Since maleic anhydride has some degree of toxicity and is a lacramator, animal studies will probably show it to be a non carcinogen. 1Dickens, F. and Jones, H. E. H., "Further Studies on the Carcinogenic and Growth*Inhibitory Activity of Lactones and Related Substances", British Journal of Cancer, 17, 100*108, 1963. Mercaptobenzofchla role Mercaptofasnzothiazole (2-fcenzothiazolethiol, Captax, CAS No. 149-30--4) was one of the 80 chemicals evaluated as having the greatest potential for environmental effects*2. The study they cite is a negative mice feeding study2 in which two groups of 36 mice of slightly different strains were given 464 mg/kg mercaptobenzothiazole in gelatin orally on days 7-28 and then 1492 ppm in their diet for 17 months with no increase in tumors found. Seventeen mouths is a little on the short side for carcinogen evaluation by present standards. In another study3 it was given orally and subcutaneously at 100 and 215 mg/kg respectively to two mouse strains (36 mice per strain). It was found to cause a statistically significant (0.01 level) increase in type A reticulum cell sarcomas when given subcutaneously. It may have been tested for mutagenicity*4 and teratogenic activity but the results are unclear5. Because of the limited tests thus far conducted, more in vivo or in vitro data might change its classification, but it will be considered a possible carcinogen for this project. Production and Persistence The production of mercaptobenzothiazole is estimated at 6x10 pounds per year with the release of 6xl04 pnmds per year1. It is reactive towards RO (tS"8 days), BO vc4*l day) and O3 (tS*9.6 hrs.)1 'Brown, S. L. et al, "Research Program on Hazard Priority Rank ing of Manufactured Chemicals," National Technical Information Service Number PB 263 161, 1975. 2Innes, J. R. M., et al*,. J. Nat. Cancer Inst. 42, 1101-1114, 1969. (From PHS-149; Survey o Compounds Which Have Been evaluated for Carcinogenic Activity.) 3"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals, Volume 1." National Technical Information Service Number PB 223 159, 1968. '`Evaluation of Carcinogenic, Teratogenic and Mutagenic Acti vities of Selected Pesticides and Industrial Chemicals. Volume III." National Technical Information Service Number PB 223 161, 1968. ^ * - r- . r j v- f. 'rtfch V Mercaptobenzothiazole References - Continued 5 "Evaluation of Carcinogenic/- Teratogenic and Mutagenic Act! vitlea of StUcUd FnUcldM and induatrial Chemical*, volume U." National Technical Information Service Number PB 223 160, 1968. . ' I' > i. .. * r"?- j. Methyl Bromide Methyl bromide has been tested on barley and is said to be a methylating compound1. No other references were found on the mutagenic or carcinogenic potential of methyl bromide so it has been placed on the probable non-carcinogen list. i B I 8 * !Ehrenberg, L., et al., "On the Reaction Kinetics and Mutagenic Activity of Methylating and Beta-Halogenoethylating Gasoline Additives", Radiat. Hot. 14 (3), 185-194, 1974. 94 f No data have been found indicating that methyl chloride (chloromethane, CAS No. 74-87-3) ia a carcinogen (e.g. Toxline, Cancer line Survey of Compounds) . However# it doea appear to be a muta gen to salmonella typhimurium* Because of the close correlation between mutagens and carcinogens# methyl chloride has been placed on the possible carcinogen list. Production and Persistence It is estimated that 2.3 x 107 Kg methyl chloride is emitted per year from stationary sources*. Another estimate3 is 7.6 x 10 Kg/ year released from a production of 2.1'x 10* Kg. Other pro duction estimates are 2.1 x 10* Kg# and 2.2 x 10* Kg# 1.6 x 10 and 1.7 x 10* Kg produced in 1974# 1975, and 1976# with a pro jected growth of 6% per year11'5. Reaction in the atmosphere with the HO radical is slow with a half-life of about one year3. It taxes 27 minutes for 50% of a 1 ppm water solution to evapor ate at 25*C* Methyl chloride has a boiling point of -24"C and a vapor pressure of 3800 ns (5 atm), at 20"C and 2150 mm (2.83 atm) at 25C4'61 * 3 4 5 1 Andrews# A. W. et al.# "A Comparison of the Mutagenic Properties of vinyl Chloride and Methyl Chloride", Mutat. Res. 40 (3) , 273-275# 1976. "MRC Source Assessment Data Base, July-1977;- 3Brown, S. L. et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals*, National Technical Information Service Duster PB263 164/ 1975;: - 40origan# J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 445, 1976. 3 ' i;' : 5Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National-Technical Information Service Number PB 274 264, 1977* >.f i*; --V ` *Verschueren, K., Handbook' of: Environmental Data on Organic Chemicals, Van Nostvand Reinhold ecu,: New York, 1977* . 95 RSV 0010891  - - _3y,- .if' - -Mr. 5r.#.K , :,5f:.*; Methyl Ethyl Katont .'W Methyl ethyl ketone (HEX, 2-butanone) is included on the NIOSH Suspected Carcinogen list because of a teratogenic reference and as a priority pollutant. MEK does appear to be embryotoxic, feto* toxic, and perhaps teratogenic when tested at high concentrations (1000*3000 ppm)1*2. Rat feeding studies conducted in 1939 and 1940 were negative3*4. Mouse skin application tests in 1965 of mixtures containing MEK were generally negative In the absence of ben2o(a)pyrene5. MEK has also been tested on TA 1535, 1536, 1537, and 1538 strains of S. typhinuriuro bacteria (Ames Test) and on E. coli WP2 - try mutagen tests with both being negative5. No other references could be found on Toxline.or Cancerline which indicate that MEK is a mutagen or a carcinogen. It Is considered a probable non-carcinogen for this project** 2 3 * * 6 Schvetz, B. A., et al., "Embryo-and Fetotoxicity of Inhaled Carbon Tetrachloride, 1,1-Dichloroethane and-Methyl Ethyl Ketone in Rats", Toxicol. Appl. Pharmacol..28 (3), 452-464, 1974. -;"'v 2Embryo Toxicity and Feto Toxicity of Inhaled Carbon Tetrachlor* ide, 1,1-Dichloroethane, and Methyl Ethyl Ketone in Rets", Toxicol. Appl. Pharmacol. 2J> (1), 123, 1974i 3Nakahara, W. and Mori, K., Proc. Imp. Acad., Japan, 15^, 278281, 1939. (From Survey of Chemical Which-Baa Been Evaluated for Carcinogenic Activity). wNakahara, W. and Mori, K., Proc. Imp. Acad., Japan, Cann 34, 143-145, 1940. (From Survey of Chemicals Which Rave Been Evaluated for Carcinogen Activity). -Horton, A. W., et al.. Cancer Research 25,i!7S>-1763, 1965. (From Survey of Chemicals Which Have BeenEvalttated for Car cinogenic Activity). -- - r 6Shirasu, Y., et al., "Mutagenicity^WxMf&li^ * Pesticides in the Microbial System", Mutat. Res., 40,-19-30, 1976. 96 WOMSAMTO WaA*C*f < . ' V\\ ' RSV 0010892 Methyl M>thaerylt Methyl methacrylate is on the NXOSH Suspected Carcinogen list because of a paper which shows that 0.25 mg/kg of the compound (1/5 1*0$ o) caused 8% of the rat fetuses to have gross abnormal ities (hemangiomas) but no skeletal malformations, A search of the literature could find no other references indicating methyl methacrylate to be a mutagen or a carcinogen# It is therefore listed as a probable non-carcinogen for this project. 1 Singh, A# R. et al, "Embryonic-Fetal Toxicity and Teratogenic Effects of a Group of Methacrylate Esters in Rats*, J. Dental Research, 51, 1632-1638, 1972. 97 MONSAMmitaSAJICHiCPMQftATlOM <** 4,49 -Methylene Big (2->Chlogoanlll_ne)_ 4,41-Methylene bis(2-chloroaniline) or MOCA (CAS No. 101-14-4) has been found to be a carcinogen in mica and rata after oral administration and produces distant tumors in the rat after sub cutaneous administration1, it is an OSHA regulated carcinogen2. Many other positive references are found in Toxline and Cancer line and it la considered a probable carcinogen for this project Production and Persistence It is estimated that 4.5 x 104 Kg is emitted per year from a 3 x 106 Kg production^. Other estimates of production are 1.52.5 x 10* Kg in 19701 and 3.5 x 106 Kg in 19721*4*5. The re action with the HO radical in the atmosphere is estimated to yield a half-life of 12 hours4 or one day^ while the O3 haif- life is one day and the ROo half-life is 39 days-5, It is said to have a melting point off 110`C1 and a negligible vapor pressure ,*4,4'-Methylene Bis(2-Chloroaniline)" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 4 6B-7irT37T:--------------------------- ----------------------------------------------------------------- *OSHA Compliance Guide, 29 CFR Part 1910# 1978. 3Brown, S. L. , et al., "Research ing of Manufactured Chemicals", Number PB 263 162, 1975. Program on Hazard Priority National Technical Service Rank ^Radding, S. B., et al., "Review of the Environmental Pate of Selected Chemicals", National Technical information Service Number PB 267 127, 1977. sDorigan,-J., et al., "Preliminary Scoring of Selected Organic Air Pollutants", National.Technical Information Service Number PB 264 445, 1976. 98 RSV 0010894 MothylT* rHiorlde There ere no positive date on methylene chloride (dichloromethane) in Toxline*or Cancerline. Interim results of carcinogenic tests in a two-year inhalation study involving nearly 2#000 animals ex posed to concentrations of methylene chloride as hi^t as 3500 ppm were negative1. One recant report cites methylene chloride as being a positive in the Ames test2. Methylene chloride is still considered a non-carcinogen.for this project until further testing is completed because of the negative NCI animal data. Methylenedianiline The IAftC monograph1 on methylenedianiline (4,4-diaminodiphenyl methane# bis(p-aminophenyl) methane, CAS No. 301-77-9) indicates both positive and negative data have been obtained from animal testing of the compound. Given orally to rats, it was found to be non-carcinogenic. Apparently methylenedianiline is on the NIOSH safety alert list (this list has been requested from NIOSH) and because of significant positive results12'3 it can at least be considered a possible carcinogen. Production and Persistance It is estimated that 2.6 x 104 Kg is emitted per year from sta tionary sources4. The production has been estimated to be 5 x 10* Kg# 7 x 10s Kg# and 1 x 106 Kg in 1965, 1966, and 19721. It has a melting point of 93C and a boiling point of 231C at 11 mm5. 11ARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man - Volume 4# 79--85# 1974. 2Schoental# R.# "Carcinogenic and Chronic Effects of 4,4'Diaminodiphenylmethane# an Rpoxyresin Hardner", Nature 219 # 1162-1163# 1968. 3Steinhoff# D. and Grundmann# E., "Zur Cancerogenen Wirkung von 4#4,-Diaminodiph3nylmethan und 2#4,-Dia^iinodiphenylmethan,, Naturioissenschaften 7# 247-248# 1970. 4MRC Source Assessment Data Base# July 1977. 5Verschueren, K. # Handbook of Environmental Data on Organic Chemicals# Van Nostrand Reinhold Co.# New York,-15*77 100 ft*OM*ANtQ,fpn4*CH. COaPOftATlON ; -At. i - >** , RSV 0010896 Methylstyrene One reference cited in the NXOSB Suspected Carcinogen list shows methylstyrene to be a teratogen1. Permissible exposure limits have been determined for methylstyrene2. Application of methyl styrene to rabbit3 inhalation or rat skin3** demonstrated only a reversible4 irritating response to the chemical. Other toxic responses have been noted in rats, rabbits5, and housefly larvae6, but no indication of carcinogenic or mutagenic responses were found on Toxline or Cancerline. `Gigiena i Santariya, 34, 40, 1969. volume of Hygiene and Sanitation) (Translated in a different :"Toxic substances. Proposed Occupational Safety and Health Standards for Alkyl Benzenes, Cyclohexane, Ketones, and Ozone", Fed. Regist. 40 (196), 47262-47313, 1975. ?"Effect of Alpha-Methylstyrene and Tert-Dodecyl Mercaptan on the Skin of Animals", Vop. Gig. Tr. Profzabol., Mater. Nauch. Konf.? p. 247-249, 1972. Reversible Damage to the Skin of Experimental Animals Subjected to the Inhalation of Butadiene and Alpha-Methylstyrene", Mater. Nauch. Sees., Posoyashck. 50-Letiyu Obrazov. SSSR, Omsk. Gas. Med. Inst.i p. 871-873, 1972. sEffeet of Isopropylbenzene and Alpha-Methylstyrene on Leucopoiesis", Farmakol Tokaikol, 3B (4), 491-492, 1972. 6"Effect of the Hastes from Phenol Production on Housefly Larvas", Hater. Konf. Molodykh. Uch. Stud., Posvyashch. 50-Letiyu SSSR; p. 375-377, 1973. 101 RSV 0010897 Morpholine Morpholine {diethyleneimide oxider tetrahydro-1, 4-isooazine, CAS No. HO- 91-6) is cited in one reference as aausing neoplastic effects in the mouse after oral administration of 6.33 w'kg over 28 weeks1. This refers to a study (with no control animals) in which 40 swiss mice (2GM.20F) were given neutralized morpholine in their food2. After 40 weeks, S malignant lynphcnas and 5 lung were found in the surviving 38 animals. (When given in oratoinaticn with nitrite, many more timers were found.) In another study, 100 g/kg morpholine as 0.5% of the diet for rats produced no tuners, but 0.5% sodium nitrite aided gave 7 timers3. Many other studies have been conducted with sodiun nitrite add to produce nitroscrorpholine in vivo and in vitro. In Russian studies, morpholine in the air in 0.003- 0.07 mg/I concentrations for four months caused nutagenic chrcnoscmal aberrations in bone marrow in ratsu and guinea pigs. The future classify cation of morpholine requires more data, but for this project it will be considered a possible carcinogen. Production and Persistence It is estimated that I x 107 emitted per year1 Kg is produced and 5.5 x 106 Kg is 1Dorigan, J., et al., "Preliminary Scoring of Selected Organic Air Pollu tants. Apperriix III.," National Technical Information Service Nuntoer PB 264 445, 1976. 2GreerdLatt, M-, et al., J. National Cancer Inst. 4 (5), 1029-1034, 1971. (Fra FHS-I49; Survey of Cfcspcisids Which Have Been Tested for Carcinogenic Activity) 3Sarder, J. and Binkle, G., Z. Kreheforsch 73 (1), 54-66, 1969 (Fran PHS149) ^Fcmenko, V. N- and Strekalovs, K. B., "Mutagenic Action of Sene Industrial Poisons as a Fmctlcn of Concentraticn and Q^oeure Time," Tbksikol. Nov. Prcm-Khitt. ^tesfaehestv. 13. 51*57, 1973. (CA 79, 14322B) f ^ v * * t* \ SMigukina, N. V., "Evaluation of ths Danger of Mxpholine airing Chronic Action," TOksiXol. Nov. PrcnuKhim. Veshehestv. 13, 92-100, 1973. (O* 79, 143345) 102 a* M&l4fe MCSCAflCM^taitSOfUTION n jp,; us*?. RSV 0010898 1 Slaptha Naptha (coal tar naptha) was found in the report "Preliminary Scoring of Organic Air Pollutants* (PB 264 446) cited as a recognised carcinogen* Actually napthas vary in composition de pending on their source with coal tar naptha being mainly benzene and its homologs1* Prom other sources nantha could be principally paraffins# methanol and acetone# or gasoline Even as a mixture# naptha is not found in the Survey of Compounds Which Have Been Tested for Carcinogenic Activity. Of the primary ingredients of naptha# only benzene is a recognized carcinogen and since it is covered separately# naptha will be dropped from consideration. 1-Haphthlaminw 1-Naphthyl amine (alpha-^irthylandne, CAS No. 134-32-7) had no carcino^nic effect when given orally to hamsters and both oral and subcu taneous tests with mice give inconclusive results1, in dogs, it was demonstrated that 1-naphthylamine, if carcinogenic at all, was less so than the 2-isomer1. Other tests on dogsl2, hamsters, mice rats, and rabbits3 4 show that 1-naphthylamine may be carcin ogenic and also it is generally contaminated with the 2-isomer which is a potent carcinogen1'*. It is an OSHA regulatec car cinogen (Code of Federal Regulations 29 CFR 1910.1004) whether or not it is truly a carcinogen**. It is also a positive on the S. typhimurium test5, and an enhancement of viral transformation test6. For these reasons, it is considered a possible carcinogen for this project. Production and Persistence Production has been estimated to be- 5 x 10s Kg in 19637 and 3.2 x 106 Kg in 1974*. It reacts with oxidizing materials in the atmosphere7 and reacts with the HO radical in air with a 12 hour half-life*. It has a boiling, point of 300.8"C and a vapor pressure of 1 nun at 104.3"C7. ' * l"l-Naphthylamine" in IARC Monographs on the Evaluation of Car cinogenic Risk of Cheaacals to*Hair, Volume 4, 8f-96, 19 74. 2Hartwell, J. L., "Survey of Compounds Which Have Been Tested for Carcinogenic Activity, Secbnd Edition", National Technical Information Service Number PB/216 478, 1951. 3Shubik, P., et al., "Survey:of Compounds Which Have Been Tested for Carcinogenic Activity* Supplement I", National Technical Information Service Number:,PB>216 248, 1957. 4OSHA Compliance Guide, 29CrRPartl910, P. 298-300, 1978. 5McCann, J., ei al., "Detection.of..Carcinogens as the Salmonella/Micro8ome:.Test">'`Proc;r Nat. Acad. (12), 5135-5139, 1975. 7 s iT :v Mutagens in Sci. (USA) 72 I RSV 0010900 1-Napthlasine References - Continued .'7? ; ' V > x' **v^riiip'i'w--. Ac ` - Ir *''' :: ^'1 -'. - '" 6Personal communication -wfltK'TfJ- C. Casto on 9 February 1978 7Dorigan, Ji. et- a # "Pr*Ufldaacy. Scoring of Selected Organic Air Pollutants"V^atic^l^^B^E^!^^Z|ic^Batioa Service Number PB 264 445/ 1975.' '/'* * ?*' Raddig, S. B#/et>;ij^Fate of Selected Chwtfcal**/ ^atnuFjdcImlcal Infornation Service Number Pf> 267 121 Napthalene Napthalene (CAS No. 91-20-3) has generally been negative when given to rats and mice by various routes of aministration (includ ing 10 g total oral dose over 33 months) with only a few tumors reported by other authors in experiments without control animals1 It is generally considered to be a non-carcinogen by various au thors2. It has been tested in G46 S. typhimurium and K-12 E. coli strains-. Another reference reports negative results for S. typhimurium strains TA 98, 100, 1535 and 15374. Napthalene considered a probable non-carcinogen for this project. is Survey of Compounds Which Have Been Tested for Carcinogenic Activity, NCI , PHS-i49 , Volumes 1, i, ancl 4. 2Arcos, J. C. and Argus, M. F. , Chemical Induction of Cancer, volume IIA, Academic Press, New York, ry7T7--^ugeT"T5T7~'7T77 and TTT. !Kraemer, M. et al., "S. Typhimurium and_ E* Coli to Detect Chemical Mutagens*, Naunyn Schraiedeberg* Arch Pharmakol, 284, 46R, 1974. 'McCann, j. et al., "Detection ofCarc^inogens as Mutagens in the Salmonella/Microsozns Test: Assay of *300 Chemicals", Proc. Nat. Acad. Sci. (USA), 72 (12) 5135-5139, 1975. 106 MONSANTO eastANC*- COAPQNATtOM < Napthoquinone Napthoquinone is on the NXOSH Suspected Carcinogen list because of a 1940 Japanese reference1. In this paper a-napthoquinone (in benzene) painted on daily on the back of mice caused 3/77 skin cancers and 11/77 papillomas compared to 0/46 akin cancers and 1/46 papillomas tor benzer.s alone on nice surviving 200 days. S-Napthoquinone produced no cancers or papillomas out of 25 mice surviving 200 days. A survey of recent literature from Toxline, Cancerline, and the Volumes 1-7 of the "Survey of Compounds which Have Been Tested for Carcinogenic Activity" found no pertinent references. Since the only positive reference is outdated and used benzene as the solvent, napthoquinone is being placed on the probable non-car cinogen list for this project. ^akizawa, N., "On the Carcinogenic Action of Certain Quinones", Proc. Imperial Acad. (Tokyo) 16, 309-312, 1940. . . -H .... . 1-NapthyI Methylcarbamate The primary reference to this compound carcinogenic potential from a Russian journal has not been obtained. Another Russian reference from the same year1 declares that 2-napthyl methylcarbamate is carcinogenic while 1-napthyl methylcarbamate is non-carcinogenic. 1-Napthyl methylcarbamate tested on male and female mice of two strains was ound to'be non-carcinogenic*2. No other references were found in Cancerline to indicate that this chemical is a carcinogen. There are negative mice feeding studies (18 months) and rat intergastic studies reported3, it is probably a non-carcinogen based an: thev available literature. ( * !Zabezhinskiy, M. A., Investigations on Possible Carcinogenic Effects of Beta-Sevin", Vopr.Onkol. 16(11), 106-107, 1970. 2"Evaluatiori of Carolnogroi'C^Teirjrtogeiiic, and Mutagenic Act ivities of Selected Ferticd*aajidlridt2*trial Chemicals, National Technicla Information Service Number; PB-223. 159, 1968. 3Survey of Compounds Which Have Been Tested for Carcinogenic Activity, NCI, PHS-149, Voluess 5 and 6. 103 NitrabtnstM Although on structural basis nitrobenzene (CAS Mo. 98*95*3) has been predicted to be a carcinogen, there was ng positive indi cation from actual tests of the chemical, cited in "Air Pollution Assessment of Nitrobenzene?.1, or on Caheerline or Toxline. It has been reported to induce sex-linked recessive lethal mutations in Drosophila melanogaster when administered as a vapor for 8-10 days2. With only one in vitro positive test reported, nitro benzene will be considered a non-carcinogen (with some positive data) for this project. a'-- ^rigan/J. shd^Hdbhao^J^'Air^Pbrirtitltott AsBesaeent of Nitro benzene1*, Nation^ 7%chiHballStfSriB^ 776, Hay 1976*. Number PB-257 r.-. rtf' 2Allport, J.r/et al^, aJ^;Stu4^/bfvIndustrialData on Candidate Chemicals: for:TsstingT^WatlonaliTecknical1 information service Number PB 274 264^1977r Mitrophenol No data on the carcinogenicity of nitrophenols could be found on Cancerline or Toxline but p-nitrophenol has been found to be mutagenic by one teat system and non-mutagenie by five other test systems1. When comparing S. typhimuriua test results with other systems, Ames classified nitrophenol as a non-mutagen2. For this project, nitrophenols will be classed as probable non carcinogens. ^ahrig, R., "Comparative-Mutagenicity Studies with Pesticides" in Chemical Carcinogenesis Essays, International Agency for Research on Cancer-Scientific Pub lication No. 10, P. 161-181, 1974. 2McCann, J. efc al.j "Detection of Carcinogens as Mutagens in the Salmonella/Microsoime Tests Assay of^ 300 Chemicals", Proc. Nat. Acad. Sci* (USA) 72, 5135-5139, 1975. UP WT'OfliA RSV 0010906 v>* ;. .- ?.' At' There are such data shoving nitrosodimethylamine (dimethylnitrosaraine) to be a potent carcinogen* It has, therefore, been placed on the probable carcinogen list 'for this* project, in the final selection of carcinogens, however, it nay not be advantageous to select this oonpoxmd. This is because 'nitrosodimethylamine rapid ly decomposes in sunlight12, under normal conditions is of no sig nificance as an air pollutant2,* and is generally only found in the air near certain manufacturing plants which had (now repaired) leaks in their system2. Production and Persistence1 Nitrosodimethylamine is emitted irf less than 100 Kg/year quan tities from the dimethylhydrazlne1 stationary sources* One esti mate of production is lesa-than 450 Kg/year*. Photolysis of nitrosodimethylamine is reported to be rapid with a half life of leas than one hour5.6 It has a boiling point of 152 C*. 11ARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man - Volume 1, 95-106, 1972. 2 Bretschneider, X. and Mats, J- , "Occurrenceand Analysis of Nitrosamines in Air" . in Environmental N-Nitxoso Compoundj , Analysis and Formation, iAftc.Sci. PuD.-NO. 14,.395-3^9, 1976 3Fine, D, H, at al. ,.."H^W^roao Compounds ia^Alr and,Mater", in Environmantal^ S-SltrosorCompounds . Inilviii and Formatlon. IAS6 Sci, Fab. Ho.-------- **MRC Source Assessment Dat^ Baea^'JuIy'1977.^ . * 5Raddlng, S.~ B, et ai.y "ReyiavjOfthaBnvironaental Pate of Selected Chemicals*/ national Technical^Information Service Munber, PB'267121, 1577i^^^' 6Verschueren; x.y Handbobtt'ofrBnviTdnsmnt^VData on Organic Chemicals, -;Van NoscraadfAeinnoid-co.^Mev York, 1977. Ill mULTi - RSV 0010907 Nifcrochlorobenzen* Nitrochlorobenzene (chloronitrobenzene) has been found to mutate Salmonella typhimurium1 and is indicated as a carcinogen causing neoplasms in another reference summary sheets while listed as not tested in the same appendix*2. For this project it will be con sidered a possible carcinogen. Production and Persistence It is estimated that 3 x 102 Xg nitrochlorobenzene is emitted per year from stationary sources3.4 * An estimate of production is 6.4 x 107 Kg, produced of each of the isomers in 19672. Nitro chlorobenzene reacts with oxidizing materials in the atmosphere2. In the soil, microflora decomposes this chemical in 64 days'. The m,p, and 0-isomers have boiling points of 236, 242, and 245c with a vapor pressure of 10 ma.at 25"C2. 'LOi. _r: i. Cardiff, R. G., et al., "Halogenated Organics m Tap Water: A Toxicological Bvaluatloo-^i`n'cThe Environmental Impact of Water Chlorination, NaticaalAtechaL&cal' information. service Number CONf 751095," p. 213-228; 197^17 ^ 2Fuller, B., et al., "Preliminary Scoring.of Organic Air Pollutants", National Technical Information Service Number PB 264 441, 1976. r .V rrlyyV i.fcr:.:-' 3MFC Source Assessment Data Base, July 1977 i . 4Verschuren, X. , Handbook of^BnvlronmentalData on Organic Chemicals,' Van Nostraodvlkeiniiold-oo.,iiMrYork, 197 7. Parathion Nothing was found in Cancerline to indicate that parathion is a mutagen or carcinogen. The NIOSH Suspected Carcinogen list ref erence cites parathion as being a slight teratogen only when given in sufficient quantity as to cause toxic poisioning to be appar ent in the dams1. It has been found to be non-mutagenic by several different in vitro tests2, but does cause an antimitotic action in cells.3 It is therefore classified as a probable non carcinogen for this project. Kimbrough, R. D. and Gaines, T. B., "Effect of Organic Phosphorus Compounds and Alkylating Agents on the Rat Fetus", Arch. Environ. Health, 16, 805 - 808, 1968. r.C . .. > NT 2Fahrig, JU, "ComparativeMotagenlc*Studieswith Pesticides", in Chemical Carcinogen Essays, XARC^Scientific Publication No* 10, 1974. ` r . . *... :.*i . -*o ref --" 3Grant, W. fjj "CytologicalEffifot*vo^Ehviron*ental Mutagens - Pesticides", Mutat. Res*. 21 (4), '221*222, 1973* 3*;# RSV 0010909 Pentane Although n-pentane is cited as a carcinogen in one reference1, no primary references could be found to substantiate this alle gation from Toxline, Cancerline, or the Survey of Compounds Which have been Tested for Carcinogenic Activity* It is said that aliphatic hydrocarbons may be co-carcinogens2. For this project pentane will be considered a non-carcinogen. . <' 3 ` 'Fuller,. B. et al. ^Preliminary Scoring, of Organic Air Polluta^Ptsy<a>atiocaIVymchnicalj-InfogTsetiop Service. Humber . ' .'j ; . rit' ' / - ' : ' 2SawicJciB ,""ChemcalvCopbaiticm and,; Potential Genotoxic 127-157,* HOm 16# Pentachlorophenol i Pentachlorophenol (CAS No. 87-86-5) ham found negative in acme rel atively short studies on rabbit akin and orally in rats# and cats1. More recently it has been found negative in two strains of mice both orally and subcutaneously2. Pentachlorophenol is also negative in Drosophila tests3# in a host-mediated assay in mice4# and other microbial systemss. Some authors consider pentachlorophenol a known mutagen6, and there are other positive as well as negative short term tests reported7. It is also positive at the 100 yg level in the hamster embryo adenovirus enhancement assay8. For these reasons, pentachlorophenol will be considered a possible carcinogen for this project for the first round of evaluations. Prodcction and Persistence One estimate of production is 2.1 x 107 Kg (1969 capacity) and a aonsixtpticxi of 2.3 x 107 Kg in 19759. Zn the soil it dwjrmton ocrpletely in >72 days?0. It has a boiling point of 310"C and a vapor pressure of 1.1 x 10"* mn at 20"C*. 1Deichaan# et al.# (1944) in Survey of Compounds Which Rave Been Tested for Carcinogenic Activity# J. L. Hartwell# editor# Nat ional Technical Information Service Number PB 216 478# 1951. 2"Evaluation of Carcinogenic# Teratogenic# and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Technical Information Service Number Ffi 223 159# 1968. 3Vogel, E. and Chandler# J. L. R., "Mutagenicity Testing of Cyclamate and Some Pesticides in Drosophila Melanogaster", Experientia 30 (6), 621-623# 1974. ^Buselmaier# W., et al.# "Comparative Investigations on the Mutagenicity of Pesticides in,Masnaliap Test Systems"# Mutat. Res. 21 (1)# 25-26, 1973. 5Anderson* K. J.# et al.# "Evaluation of Herbicides for Possible Mutagenic Properties", J. Agr. Focal Chem. 20 (3)# 649-656, 1972. sDaugherty, R. C. and Piotrowska# K. # "Screening by Negative Chemical Ionization Mass Spectrometry for Environmental Con tamination with Toxic;Residuest Application- to Human urines", Proc. Natl. Acad. Sci 73 (6), 1777-1781# 1976. 7Fahrig# R.# "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogenesis Essays* XARC Sci. Pub. No. 10, 161- 181# 1974. -- 115 Pentachlorophenol References - Continued 'Personal communications with Dr. Bruce Casto, 2/17/78. *Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 446, 1976. 3Verschueren, Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co., New York, T57TT^ 116 *0SAMTO RtSCARCH C0*P0*AT0* Phenol Phenol (hydroxybenzene, CAS No. 108-95-2) has been reported to give rise to papillomas after administration on mouse skin1'l2. Phenol haa also been reported negative by injection and negative on the skin of mice3. It haa recently been given in combination with other chemicals3.5 In mutagenicity tests, phenol has been found to be mutagenic to Drosophila, revert E. coli to streptomycin independence, and induce chromosome breakage in the root tip of Allium cepa while being inactive in reverting Neurospora crassa to adenine prototrophy . Phenol is also said to cause second chromosome breaks in Drosophila, cause chromosome breaks in Vicia and Allium sativum and it is teratogenic in chickens5. One must also remember, however, that normal adults excrete approxi mately 30 mg of volatile phenols per day in their urine (mainly p- cresol and phenol) produced by gut bacterial metabolism of tyro sine6. Phenol has tested negative in a micronucleus test7. The only positive animal tests were conducted in the 50's with later negative results. The positive in vitro tests are with systems which have not been extensively evaluated. Although it is a borderline chemical, phenol will be considered a probable non carcinogen (with some positive data) for this project. lSalaman, M. H. and Glendenning, O. M., Brit. J. Cancer, 11 , 434444, 1957. -Boutwell, R. K. and Bosch, D. K., Cancer Research 1, 413-424, 1959. 3Survey of Confounds Which Have Been Tested for Carcinogenic Activity, NIH, PHS-149, Volumes 3,4,5,6, and 7. 4Allport, J., et al., "A Study, of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 5Brown, S. L. et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 164,. 1975. 6Bone, E. S., et al., "The Production of Urinary Phenols by Human Gut Bacteria" (Meeting Abstract). J. Med. Microbiol. 9^ (2), p. vi, 1976- . .. / 7Hossak, D. J. and RichardsonV J. C.. "Examination of the Potential Mutagenicity of Hair Dye Constituents Using the Micronucleus Test", Experientia, 33 (3), 377-378* 1977. 117 >RATION RSV 0010913 Polychlorinated Biphenyls Polychlorinated biphenyls (PCB, chlorinated diphenyls, Aroclors, Kanechlors) have been cited extensively in the literature as carcinogen*l'12.3 * On close inspection, nany of the carcinogenicity studies on PCB's have bean questionable9'1* or negative5 and the increase in cancer among PCB workers has been ques tioned* The latest NCI study of PCB's was negative but they concluded that from the open literature PCB's are probably promoters of carcinogenesis. The PCB's fall.on the border between possible and probable carcinogens using the criteria for this project. Because of the positive animal studies1'7, it will be classed as a probable carcinogen for this project. .... - ":t; ; Production and Persistence y It is estimated that l.SxlOVkg is esUtted per year6. Other estimates of production arel.4xl07 kg, 2.5x10* kg, and 1.8x107 kg (1974)*"*) - Production of FCE'# has been phased out within the last year so,emissions should have dropped to zero. PCB's are essentially non-volatile, but evaporation to the atmosphere is thought-to > bei important1-* Reaction with HO radical predicts a half life of 26 days*. They have a boiling point of 365-390*C and a vapor pressure less than 1 am at 25C10 . 1 "Polychlorinated Biphenyls" in IARC Monographs on the Evalua tion of Carcinogenic Risk' of Chemicals to Man, Volume 7, 261- 289, 1974. : V' ' * - 2lloyd, J. tf., et al, "PolychlorinatedBiphenyls", J. occup. Med. 18 (2), 109-113, 197*.1*1 > : ;: 3Andrews, . J., etal., "PCB Diet" Science 180 (4083), 255- 257, 1973.: .. I polychlorinated Biphenyls Reference* - Continued i t i 7NI0SH Suspected Carcinogens 1976 edition. aMRC Source Assessment Data Base# July *77, *Brown# S. L.f et al., "Research Program on Ranking of Manufactured Che^cala," Motional Technical Information Service Number PB 263 162# 1975. 1Eborigan, J., et al.# "Preliminary Scoring of Organic Air Pollutant*#" National Technical information service Number PB 264 446* 1976. > tedding, S. B., et al., -Rovi.* of Selected Chemical*/" National Technical Information service Number PB 267 121# 1977. * '* Propanol In 1939 and 1940, propanol (propyl alcohol, CAS No, 71-23-8) was found non-carcinogenic in rat feeding studies1'2. The only cur rent references which could be found were by Gibel et al. who re fer to tumor formation after oral (50g/Xg) and subcutaneous (6gm/ Kg) administration of propanol to rats3 and an E. coli test1*. The studies which have been conducted on isooropancl have been neg ative5. Propanol will be considered a probable non-carcinogen (with some significant positive data) for this project. ^akahara, W. and Mori,. K., Proc- Imp. Acad., Japan 15, 278-281, 1939. 2Nakahara, W. and Mori, K., Gann 33, 143-145, 1940. ' ; ' vr3Gibel, w., et al., "Smperiaaxrtal Study on Cancerogenic Activity of Propanol-1, 2-Methylpropanolrl and 3-Methylbutanol", Arch. Geachwulstforsch 4 (1), 19-24, 1975* ^ . ; i-yis**; .. . 'Gibel, W., et%al.Studie*m:tfh#Toxicityand Mutagenicity of Single Fusel Oil Coappnsents on E. ColiVActa Biol. Med. Ger. 22, 843-852, 1969. 'T . * > "iTfSZ:. .iv-' vlC' 5A Isopropyl Alcohol and lsopxopy^.OilsJ in-1ARC 'Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, Volume 15, 223-243, 19,77. . 120* i S: i.V' RSV 0010916 < \. Propylene Oxidw Propylene oxide (methyloxirane, 1,2-epoxypropane* CAS No. 75-569) has been reported to cause local sarcomas in a limited num ber of rats after subcutaneous injection1. It was negative in relatively short-term (*200 days) studies in rats* guinea pigs, rabbits and monkeys given propylene oxide by inhallation1' . By in vitro tests* transformation of hamster aells3 occurred at 250 mg/ ml". It is also reported to cause reversion to adenine* pro totrophy in Neurospora erases and cause recessive lethal mutation in Drosophila melanogasters "F--or this project it will be considered a possible carcinogen. Production and Persistence It is estimated that 4.4x10* kg propylene oxide is emitted per year6. Other production estimates include 7.5x10s kg per year7, 8.0x10* kg (1974)** 8.0x10 kg (X975)1* and 7.0x10 kg (1975)5 with U. S. consumption predicted to grow by 9-10.5% a year from 1975 to 1980s. If dispersed iu the atmosphere* epoxides would be oxidized by BO radicals with a half life of 3-11 hours* The rate constant and half life for HO radical reaction predict a 23 hour calf life for aliphatic epoxides5. Propylene oxide has a boiling point of 33.9C and a vapor pressure of 596 me at 25*C7. 1 "Propylene Oxide" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 11, 191-199* 1976 2Rowe * L. K.* et al., "Toxicity of Propylene Oxide Determined on Experimental Animals** Arch. Industr. Hlth.* 3^3, 226-236* 1956. . 3Casto* B. C* et al. "Aasay of Industrial Chemicals in Syrian Hamster Cells for Enhancement of Viral Transformation" (Meeting Abstract), Proc. Am. Assoc. Cancer Res., 18* 155, 1977. `personal communication with B. C. Casto on 9 February* 1978. ^Allport, J.* et al, "A Study of Industrial Data on Candidate Chemicals for Testing*" Rational Technical Information Service Humber PB 274 264, 1977. ' . *MRC source Assessment Data*Base, July 1977. . .1. .. .. _ , 7Dorigan;-Jiw Selected Air Pollutants/* lWtional Techiii^al^lnfbrmation Service Humber PB 264 446, 1976V *#"*&'*:? - Vr` H f's. * . --..... tf?.;,.:;; m --.j: JRS V 0010917 Propylene Oxide References - Continued ii&l :'` 8Redding, S. B., et al., "Beyle* of the Environmental Fate of Selected Cftemical^rV Netifeqdl Technical Information Service Number PB 267 121, 1577.........` - 122 pyrtaa Pyrene (CAS No. 129-00-0) has generally beentested on mouse skin with negative results1. It has also been reported negative on mouse skin followed by croton oil or.preceded by benzo(a)pyrene . It is usually considered to be non--carcinogenic * and has been reported as non-mutagenic to S* Typhimuriua strains TA 98, 100, 1535 and 1537*3. It is considered a non-carcinogen for this pro ject. :s*c. .\i* \ V. V- *- t#r 1 S^ ^urvf ejyy of Compounds Mhic_h_Havefc_e__e__n_ _T__e__sted for Carcinogenic A--ctivi-t--y----,---T---W- X" -H----B-------T----4---9---V----V--eolusme:s--1>--*3^ ** and T. 2Arcos, J* Q*. and Argus, rlii; Chemical-Induction of Cancer, Volume IIA, Acadeaic PreS*r^:'WSf TorXr l7iiv pages 210 and 237. 11 :a^-f UfAV'J *i.LzsZ**,x. 3McCann, J. et al., CMsinoSmriis as Mutagens in the salmonella/Kicrosorae ^emieals*, Proc. Hat. Acad. Sci. (CSA) /'72'; Jv*- . , ^123 r-a* BorbicAcld Sorbic Acid (2#4*hexadienolc raeid#\CAS'lfo. 110-44-1) is a widely used food perservative* In 1966 and'1968# Dickens et al. re ported several rat studies with sorbicracid. In these tests (using 6-12 rats) -sorbic add injected subcutaneously at 2 mg/ injection in oil or water sometimes caused local fibrosarcomas at the injection site1"* * Given in the - drinking water at 0.1 gm/1# no effects were seen9* It is now known that the pH of the injected solution may cause local fibrosarcomus in some strains of rats, in more recent dose response studies# rats4 and mice5 (groups of ''IOC animals) were given 0# 1.5, or 10% of their diet as sorbic acid with no carcinogenic response. Also sorbic acid with 1000; ppm parasorbic acid gave no carcino genic response6. Several in vitro tests (eg B* subtil*s) have been negative for sorbic acid but positive for reaction products of sorbic acid and sodium nitrite7* Better subcutaneous tests should be conducted on sorbic acid# but the negative results on the recent large scale feeding, tests and negative in vitro results suggest that sorbic acid should beconsidered a noncarginogen at the present time*" 'Dickens, F., et al.# Brit. J. Cancer 20# 134-144, 1966. 2Dickens# F. and Wayforth# H. B., Brit. Emp. Cane. Camp. 46, 108, 1968. 3Dickens# F., et al.# Brit. J. Cancer# 22# 762-768, 1968. 4Grant, I. F., et al., "Long-Term Toxicity of Sorbic Acid in the Rat," Food Cosmet. Toxicol. 13 (1)# 31-45, 1975. *Hendy, R. J., et al. # "Long-Term .Toad.city Studies of Sorbic Acid in Mice," Food Cosmet. Toxicol. 14 (5), 381-386# 1976. 6Kason# F. L. # et-al., "Long-Term Toxicity;bg Parasorbic Acid in Rats#" Food Cosmet. Toxicol/. 14 (5)'#v'387-394, 1976. _ 7Kada# T*# Additives Sci. Pub. ;'?X( "''r.'l " .-X;-"' "Mutagenicity andXarcjn^gehiclty Screening by the Rec-Assay/and ^eVessidn'Procedures#" No. 12# 105-11S#'1976* of Food IARC 124 \ . "`V ass RSV 0010920 . Styrtnt Styrene (vinyl benzene, CAS No. 100-42-5) ha* been found to be both positive1*2 and negative9 on the Salmonella typhimurium mutagen teat after activation with S-9 microaomes. Without S-9 activation it has been found negative by this teat1'9. In other systems, styrene was found positive on a host-mediated fon#ard mutation, gene-conversion yeast system but negative in this system with microsomes only (not host-mediated) . It was negative on a Chinese hamster cell test1*, in Drosophila melanogaster and S.pombe mutation test5, and in enhancement of viral transforma tion tests6. It would thus appear that a metabolic product of styrene is a weak mutagen and styrene should probably be con sidered a possible carcinogen. Production and Persistence It is estimated that 5.6 x 106 Kg styrene is emitted per year from stationary sources7. Another source estimate 2.0 x 109 Kg (1975) produced8. It has a 1.28 relative chemical reactivity in the atmosphere (where methane is sero,rbutane is 1.27, 2-pentane is 1.58 and 2-butene is 15.S)9'10. Styrene has a 145.2*C boil ing point and a vapor pressure of 5 m at 20*C9. ,i >-ri v . si'. 1DeMeester, C. et al., "Mutagenic Activity of Styrene and Styrene Oxide", Arch. Xnt.\Physiol. Biochim., 65 (2), 398-399, 1977. -- 2Vainio, B., et ml., "A Study.on the Mutagenic Activity of Styrene and Styrene Oxide", Scand. J". Work Environ. Health, 2(3), 147-151, 1976. 3Stolz^D.7B*,;v?Mutag^ieityr:eeting of^Styrene and Styrene Epoxide in SalmbneHa'T^phimuriufi*/>BUll. Envirbn. Contam. Toxicol., 17, (6), 739-742r; Xt?.7;.Vd* -- l*Lopri*no, , - et^U^^4ilSegenleityv6f^Industrial Compounds: Styrene and? its Possible-Metabolite Styrene Oxide", Mutat. Res., 40(4), 317-324, I97di;V*': V- 125 Styrene References - Continued sAllport, J. et al., "A Study of Industrial Chemicals for Testing*, National Technical Number PB 274 264, 1977. Data on Candidate Information Service ^Personal communication with B. C* Casto on S February 1978. 7MRC Source Assessment Data Base;.Juiy 1977. ^Fuller# B. et al.# "Preliminary Scoring of Organic Air Pollu tants" , National Technical Information Service Number PB 264 442 # 1976. -Verschueren# K. , Handbook of Environmental Data on Organic Chemicals# Van Noatrand.-Reinhold^co. # N. Y. # 19?7. 1 Yeung# C. K. K. and Phillips# Cw R. #.."Estimated of Physiological Smog Sympton Potential from Chemical Reactivity of Hydrocarbons" Atm. Environ. 7[, 1973. 126 m MONSANTO' CORSORATION v j&rZlpfc'- -- RSV 0010922 Sulfolane Sulfolane (tetnhydrothiophene,-l-diuxide, CAS No. 12633-0) was one of the eighty chemicals selected as having the greatest potential environmental effects l. Carcinogenicity and mutagenicity were not cited as reasons for its selection. No data could be found in any of the references searched pertaining to mutagenicity or carcinogenicity of this chemical. It is considered a probable non-carcinogen for this project. ^rovn, S. L. et al. "Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Information Service Number PB 263 161, 1975. 127 MONSANTO RCSCANCM .CORPORATION RSV 0010923 Tetrabromoethane Tetrabromoethane (CAS No. 79-27-6) was one of eighty chemicals having potential for environmental effect*1. Zt has tested negative in some short term (92 day), limited exposure (15 min./ day) tests on rats, mice, rabbits and guinea pigs12. It has tested positive in a E. coli (pol A+, pol A -) differential s.growth mutagen test but negative in typhimurium strains TA1530 and TA 15353'1*. With only one in vitro positive test (which has not been extensively validated) tetrabromoethane will be considered a probable non-carcinogen for this project. 1Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Infor mation Service Numbers PB 263 162, 1975. 2Gray, A. W. A., Arch. Ind. Hyg., 2. 407-419, 1950. (From PHS149: Survey of Compounds Which Have Been Tested for Carcino genic Activity) 3Brem, H., et al., "The Mutagenicity and DNA-Modifying Effect of Haloalkanes," Cancer Res. 34, 2576-2579, 1974. "Rosenkranz, H. S., "Mutagenicity and DNA-Modifying Activity: A Comparison of Two Microbial Assays," Mu tat. Res. 41 (1), 61-70, 1976. 128 MONSANTO ~RESEARCH CORPORATION <4:.- r *. RSV 0010924 '!* 1 !. HI f Tetrachlozoethane 1,1,2,2-Tetrachloroethane (CAS No. 79-34*5) has been found to be mutagenic in the Salmonella typhimurium system for TA 1530 and TA 153S strains1. It has been cited as a carcinogen based on a Na tional Cancer Institute bioassay2 where it was found to be a car cinogen for mice but not for rats3. It is therefore considered a probable carcinogen for this project. Production and Persistance It is estimated that 0.4 x 103 Kg is emitted per year from sta tionary sources (in making trichloroethylene from ethylene)1*. Evaporation of 50% from a 1 ppm solution of water at 25*C will occur in 56 minutes5. It has a boiling point of 146.4C and a vapor pressure of 5 mm at 20C5. 20*C5 Water solubility is 2.9 gnv/1 at ' ''-.a? 1 Brem, H., Stein, A. B., and Rosenkranz, H. S*, "The Mutagenicity and DNA-Modifying Effect of Haloalkanes", Cancer Res. 34, 2576-2579, 1974. ' 2Kraybill, H. P., "Origin, Classification and Distribution of Chemicals in Drinking Water with an Assessment of their Carcin- I ogenic Potential", in The Environmental Impact of Water I Chlorination, Oak Ridge National Laboratory, National Technical Information 'Service Number CONF 751096, p. 229, 1976. 1 3 Che mi cal Regulation Reporter 1^ (51), 1861, 1978. | 4MRC Source Assessment Data Base, July 1977. * sVerschueren, K. , Handbook of Environmental Data on Organic Chemicals, Van NostrAidRelnhold Co., New York, 1978. " 129 Tetrachloroethylene The NTIS document "Air Pollution Assessment of Tetrachloroethylene" cites extensive toxicological data but reports no evidence of car cinogenicity, mutaaenicitv or teratoaenicitv for tetrachloroethylen (perchloroethylene, CAS No. 127-18-4) in humans. Also no difference in the incidence of tumors were observed between con trol and experimental rats exposed to 300 or 600 ppm of tetra chloroethylene. A recent report by NCI however, has shown tetrachloroethylene to be a liver carcinogen in S6C3F1 of both sexes. Tetrachloroethylene has, therefore, been assigned to the PROJABLE carcinogen list. Production and Persistance It is estimated that 7.8 x 107 Kg tetrachloroethylene is emitted per year from stationary sources with solvent evaporation from degreasing operations accounting for better than 99% of that quantity3. Other estimates of production are 3.0 x 10B Kg (1975)u, 3.3 x 108 Kg produced and 2.6 x 108 Kg releaseds, and production of 3.3 x 10 Kg, 3.1 x 10s Kg, and 3.0 x 108 Kg in 1974, 1975, and 1976. A 1976 forecast projected a yearly growth of 3-4% but in light of the NCI carcinogen study, lower standards for occu pational exposure from NIOSH, and a decrease in fluorocarbon use, the production of tetrachloroethylene is expected to decree**.5. It is not photoactive and has an expected HO radical reaction half-life of 8 days5. Another reference cites photodegradation with a half-life of 2 days2. Evaporation of 50% from a 1 ppm water solution at 27*C will take only 24-28 minutes7. It has a boiling point of 121.2*C and a vapor pressure of 14 mm at 20SC7. `Fuller, B. B., "Air Pollution Assessment of Tetrachloroethylene", National Technical Information Service, Number PB-256 731, 99 pages, 1976* 2 "Bioassay oT Tetrachloroethylene for Possible Carcinogenicity CAS No. 127-18-4", National Technical Information Service Number PB 272 940/ SL. 130 Tetrachloroethylene References - Continued 3MRC Source Assessment Data Base, July 1977. ``Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National-Technical Information Service Number PB 264 446, 1976. sBrown, S. L. et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. *Allport, J. et al., "A Study of Industrial Chemicals for Testing", National Technical Number PB 274 364, 1977. Data on Candidate Information Service 7Verschuereiv K., Handbook of Environmental Data on Organic Chemicals, van Nostrand Reinnoid CO., N. Y., 1977. 131 RSV 0010927 'g"ip pg.1 '------------------------------ Tetraethyl Load Tetraethyl lead <tetraethyl plumbane, CAS No. 78-00-2) found to induce lymphomas when injected subcutaneously natal mice1 although the significance of this test has tioned2. Oral doses were not found to be teratogenic3 has been into neo been ques and an epidemiological study found no health hazard from occupational exposure4. Tetraethyl lead has been found to cause ONA fragmentation and to enhance viral transformation in hamster embryo at the 12.5 ug level5. Tetraethyl lead is considered a possible carcinogen for this project. Production and Persistence One estimate of release to the environment is 1.3 x 10 Kg per year6 from a production of 1.4 x 108 Kg. The release figure notes that most of this is through use in gasoline where it is converted to lead halides and some lead phosphates6. Another set of figures cites a release of 6.6 x 106 Kg from a production of 1.6 x 108 Kg in 19737. The 1971 production has been estimated to be 2.4 x 108 Kg2. The production of tetraethyl lead is ex pected to decrease rapidly from these figures because of regu lations requiring less lead in gasoline2. In the air it has half-life of 2-3 days from reactions with BO and 03 radicals6*'. It has a boiling point of 200*0 (decomposes) and a vapor pressure of 0.15 rasa at 20*CS. g Epstein* S. S. and Hantel, N.-, "Carcinogenicity of Tetraethyl Lead:, Experientia, _24 (6), 580-581, 1968. 2"Tatraathyl and Tetramethyllaad", in IABC Monographs Evaluation of carcinogenic Risk of Chemicals to Man, 150-160, 1973. on the Volume 2, Kennedy,-G* L., etal., "Teratogenic Evaluation of Lead Compounds in Nice and Rata", PoodCgsmat. Toxical. 3 (6), 629-632, 1975. 4Robinson, T. Jt., "Baalth, How Can It Be Measured", HEW Publ. (NIOSH), 76 134, 114, 30,1976. -Personal communication with" Z>r. Bruce C. Casto 2/17/78. 132 m S SRMP Tetraethyl Lead References - Continued .'V m 6Brown, S. L., et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals*, National Technical Information Service Number PB 263 164, 1975. 7Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 446, 1976.8 8Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold co., new Yorx, l^YV. 1 J 133 RSV 0010929 Toluene An extensive search of Cancerline and Toxline along with the NTIS document "Air Pollution Assessment of Toluene"1 and the Stanford Research Institute ha2ard priority ranking*2 failed to find data which would indicate that toluene is a carcinogen. It tested negative3 in a differential growth mutagen test using E. coli (pol. A) and will be considered a non-carcinogen for this project. talker, P., "Air Pollution Assessment of Toluene", National Technical Information Service.Number .PB 2S6 735, 1976. zBrovn, S. L. et al., 'Kesearcti Program `on Hazard Priority Rank ing of Manufactured Chemicals*, National Technical Information Service Number P*.23 v_,f ,. 3Fluck, E. r; et al. # *^vfuat^MTof^?niX Polymerane-Oeficient Mutant of E. Coli for the-Rapid Detection of Carcinogens", Chem. Biol. Interact. 15, 219-231,:1976. , 134 Toluene Diieocyanate There ie no data on Toxline or Cancerline to indicate that toluene diisocyanate is a mutagen or a carcinogen* 135 MOMJkAM^Q, ACSCA/tC-H confpffaj.iftN vs Toluenediamine Toluenediamine (toluene-2,4-diamine, CAS No* 95-80--7), generally used as a hair dye, has been fbwd by several studies to be non-carcinogenic when applied to the skin of mice1*l2 and rats3 * although the same data can be interpreted to show increased lung tumors and total tumors in the test groups1*. Toluenediamine has been reported to produce hepatomas in rats when fed at 9.1 percent of diet for 35 weeks5 or 11 gta/kg for 36 weeks6. In rats, 280 mg/Kg (35 weeks) subcutaneously is reported to cause neoplasms7. It has also been found to casue morpohological transformation in primary Syrian hamster embryo cells. It also mutates Salmonella typhinimtirium strains TA 1538 and TA 98 at 0.5 ug/ml when acti vated with the S9 microsomes6*8. With positive in vivo and in in vitro tests, toluene-diamine will be considered a probable carcinogen for this project. Production anJ Persistence One estimate of production is 2.9 x 107 Kg per year with 0.015 as a fraction of production loss7. It has a boiling point of 292*c and a vapor pressure of 1 m at 106.5C7. lGiles, A. L., et al., 'Dermal Carcinogenicity study by NouseSkin Painting with 2 ,4-Toluenediamine Alone or in Represenative Hair Dye Formulations", J. Toxical. Environ. Health _1 ( 3), 4 33440, 197b. ^Burnett, C., et al, "Long-Term Toxicity Studies on Oxidation Hair Dyes", Food Cosset. Toxicol. 13 (3), 3S3-357, 1975. 3Kinkel, H. J. and Holxaenn, S., "Study of Long-Tera Percutaneous Toxicity and Carcinogenicity of Heir Dyes (Oxidising Dyes) in Rats'# Food Cosset. Toxicol. 11. (4), 641-648, 1973. `'Bridges, B. A. end Green, M. H. , "Carcinogenicity of Hair Dyes by Skin Painting in Mice* (letter to Editor), J. Toxicol. Environ. Health 2 (1), 251-252, 1976. 5Shah, M. J. et el., "Comparative Studies of Bacterial Mutation andHeaster Cell Transformation Induced by 2r4-Toluenediaaine" (Meeting Abstract), Proc. Am. Assoc. Cancer Res. 1, 22, 1977. 6Caneer Research 29, 1137, 1969. 7Dorigan, J. et el., "Preliminary Scoring of Organic Air Pollutants National Technical Information service Number PB 264 445, 1976. 5Pienta, R. J et el., "Correlation of Bacterial Mutagenicity and Hamster Cell Transformations with Tumorigenicity induced by 2, 4-Toluenediamina", Cancer Lett. (Amsterdam) 2 d/2) , 45-52, 1977. 136 > . * ; *.v.: ^. :. - ktiOM'b RSV 0010932 Toxaphene No significant data were found to indicate that toxaphene is a mutagen or a carcinogen. It tests negative on the dominant lethal test for mice^, It has been placed on the probable non carcinogen list for this project.1 1 Epsteinf S. S. et al.^s/Detection of Chemical Mutagens by the Dominant Lethal Aasay ih* tKe Mouser Toxicol, Appl. Pharmacol, 23, 288-325, 1972. - 137 f. .' ty.&..IJTl ,IyON RSV 0010933 / . .. /f,* Trichlorfon Trichlorfon has been found to be carcinogenic to mice, rata, and cats given orally, subcutaneously, cutaneouely, or intermuscularly. It has also been found to be mutagenic by at least five different test systems. It is, therefore, to be considered a probable car cinogen. Production and Persistance It is estimated that 100 Xg/year of trichlorfon is emitted from stationary sources1.1 1MRC Source Assessment Data Base, July 1977.' - -ji- 138 Trichloroethane A National Cancer Institute bioassay of 1,1,1-trichloroethane found no correlation between this chemical and any cancers which developed in the control versus the test rats and mice1. It was negative on an enhancement of viral transformation test2, it has been placed on the non-carcinogen list for this project. -- . .'vi1-:' r, 1 "Bioassay of 1,1,1-Trichloroathanefor Possible Carcinogenicity , Carcinog. Tech. Rep. Ser. - Nat'l. Cancer Inst. (U.S.); ISS NCI-CG-TR-3, 70 pp., 1975. Personal communication with B. C. Casto on 9 February 19796. TrlcbJ oroethvlenc Trichloroethylene (trichloroethene, TCE, CAS No. 79-01-6) has been found to induce a high incidence of hepatocellular carcino ma in B6C3F1 mice of both sexes by NCI l. It has also been found to be weekly mutagenic in E. coli and to TA100 strain of S. typhimurium (0.8-2.0% vapor dose response when exposed one hour) in the presence of activated microsomes 2. A review of the production, uses and environmental effects has been compiled by Fishbein 3. TCE is considered a probable carcinogen for this project. Production and Persistence It is estimated that 1.6xlCs kg of TCE is emitted per year with 95% of that coming from solvent evaporation in degreasing operations1*. Another estimate is a production of 1.93x108 kg with 1.95vl0 kg released5. Other production estimates6"7 include 1.8xl08 kg (1974) and 1.3x10* kg/year, with about 60% of the production released to the environment*. Production has also been reported to be 1.8x10* kg (1974)/ 1.3x10* (1975) and 1.4x10* kg (1976) with a 1% decling predicted for future years2. Since that prediction# OSHA has lowered the standard for occupational exposure and NCI found that TCE causes tumors in mice which will mean a much greater decline in the expected production2. TCE has a high ataospheric ohotodegredation rate with a half life of 0.3 days at sear level*. Other sources predict atmospheric reaction with the HO radical with a half life of 36 hours6 or less than 50 hours5* With its high volatility and low water soluability. it is expected to fairly rapidly migrate into the atmosphere. ' Xn^fact 50% of a 1 ppm solution will evaporate from water at 25 C in 19-24 minutes9. Its boiling Doint is 86.7C and it has a vapor pressure of 60 mm at 20 u9. "Carcinogenesis Bioassay of Trichloroethylene, CAS No. 79-016" National Cancer Institute Carcinogenesis Technical Report Services, Number 2, February 1976(NCI-CG-TR-2). Allport, J, et al., "A Study of Industrial Data on Candidate Chemicals for Testing,* National Technical Information Service Number PB 274 264, 1977. Fishbein, L., "Industrial Mutagens and Potential Mutagens I. Halogenated Aliphatic DerirVatlxatt^VMUtat, Res. 32, 267-308, 1976. Trichloroethylene References - Continued 4KRC Source Assessment Data Base, July 1977. * * * %.. sBrovn, S. L., et al.V "Research Program on Hazard Priority Ranking of Manufactured Chemicals*" National Technical infor mation Service Number-PH; 263 161, 1975. eRadding, S. L., et al., "Review of the Environmental Fate of Selected Chemicals,"'National Technical Information Service Number 267 121, 1977, , ... 7Fuller, B., et al.^"Preliminary Scoring of Pollutants," National'Technical Information PB 264 442, 1976, 7\ * Organic Service Air Number 0Fuller, B. B., "Air Pollution Assessment of Trichloroethylene," National Technical Information Service Number PB 256 730, 1976. 9Verscheoren, K., Handbook of Environmental Data on Organic chemicals. Van Nostrand AeinhoIdCo.V'N. k* * 1?Tf.--------------------------------------------------------------------------------------- 141 "LV V -r >**$3 ;7%'.k?'.:. .' Trichlorofluoronethane In mice, tri ch loro fluoromethane (Freon* 11, F-ll) in combination with the insecticidal synergist piperonyl butoxide increased the incidence of malignant heptomas while Freon-11 by itself was found to be non-carcinogenicA* No other carcinogenic data was on Freon* 11 and it has been found to be non-mutagenic in Salmon ella typhimurium tests with and without microsonal activation-2*. Preliminary results from an NCI bioassay shows no difference between control and treated male or female rats3. It is probably not a carcinogen. ! ::t .. it.'- . :i 'Epstein, S. S., etal., "Synergistic;Toxicity: and Carcinogenicity of *Freonsf. and Piperonyl Butoxide?Nafcure. 214, 526-528, 1967. * .- *** 2Uehleke, H.f et al., "Metabolic Activation of Haloalkanes and Tests in vitro:-fox Mutagenicity",; Xennbiot1ce 7 (7), 393--400, 1977. -'.a 3NCI preliminary .data on tric&lorofluoroaethane, 7 ' -VC- . - . ' ,0 i'O /. - ; :t Nov. 27, '*'* ' 1976. . ' - *- r :,;r t< ..............* V *V.' V."l4 ' t ol?;. . .-r. * 'vKr: xr.. -;* !^ --x RSV 0010938 Trichlorophenol Trichlorophenol (2,4,6-trichlorophenol, Dowicide 2S, CAS No. 8806-2) has been found to be a carcinogen in mice when given orally but not subcutaneously1#z. 7/72 heptomas, 6/72 pulmonary adenomas, and 7/72 reticulium cell sarcomas were found. (2,4,5-trichlorophenol was only evaluated by subcutaneous route1 and was found negative by this route of administration, as was 2,4,6-trichlorophenol). Trichlorophenol may cause abnormal pollen in broad bean plants3. No other pertinent literature reference were found on Toxline or Cancerline to substantiate or refute the carcinogenic potential of trichlorophenol. It has been placed on the possible carcinogen list for this project. Production and Persistence It is estimated that 5 x 10*2 Kg trichlorophenol is emitted from stationary sources per year4. Since this is used as a pesticide, non-staticnary sources (or total production) should be considered. It completely disappears in soil suspensions in S days5. Tri chlorophenol <2,4,6) has a boiling point of 244.5C and a solubil ity of 800 mg/1 at 2S*C5. ^Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Tech nical Information Service Number PB.223 159, 1968. 2Innes, J. R. M., et al., "J. Nat. Cancer Inst., 42, 1101-1114, 1969. 3"Cytological Effects of Pesticides. V. Effects of Some Herbicides on Vicia Faba", Cytologia 39 (4), 663r643, 1974. 4MRC Source Assessment Data Base, July 1977. 5Verschueren, K., Handbook of Environmental Data on Organic Chemicals. Van Nostrand Meinhold Co., New York, 19VT. 143 RSV 0010939 Urethane* Urethane (ethyl carbamate, CAS No. 51-79-6) has been shown to be carcinogenic in mice, rats and hamsters following administration by the oral, inhalation, subcutaneous or intraperitoneal routes1. It generally causes lung tumors, lymphomas, hepatomas, melanomas, and vascular tumors. With all of this positive data, urethane is considered a probable carcinogen for this project. Production and Persistence The only production data which could be found cited production from one US coupany with data not given and production below 454 Kg from a second company1. It has a boiling point of 183*C and sublimes at 102*C at 54 nsn Hg, and is volatile at room temperature1. "The name urethane is sometimes applied to high molecular weight polyurethanes used as forms, elastomers and coatings. . Such products are not made from the chemical urethane and do not generate it on decomposition. 1 "Urethane" in IABC Monographs'on the Evaluation of Carcinogenic Risk of Chemicals to Man, volume 7, 111-140, 1974. RSV 0010940 Vinyl Acetate Vinyl acetate (CAS No. 108-05-4) has been found to be non-carcinogenic in rats at 2,500 ppm for 4 hrs./day for 12 months by C. Maltoni*. It has also been found negative on mouse skin12, mouse sebaceous glands3,* 5 a6 nd S. typhimurium tests1*"''. Both commercial vinyl acetate7 * and repeated tests of purified vinyl acetate9 have been found to be mutagenic at a level of 150 ug/ml in viral transformation, vinyl acetate will be considered a possible carcinogen for this project for the first round of evaluations. Production and Persistance It is estimated that 6.8 x 10s Kg is emitted per year from stationary sources9. Another estimate is a release of 7.8 x 10* from a production of 5.5 x 10 Kg10. It reacts with oxidizing materials in the atmosphere10, and has a boiling point of 73C and a vapor pressure of 83 on at 20*C11. 1"Survey of Compounds Which Have Been Tested for Carcinogenic Activity, 1972 - 1973 Volume*, 0* S. Department of Health, Education and Welfare, DHEW Publication No. (NIB) 75, Public Health Service Publication No. 149. 2Garibyan, D. K. and Papoy&n, S. A., "Study of the Blastomogenic Activity of Certain Chemical Substances Using a High-Speed Test Method", Gig. Sanit. , 74-76, 1977. 3Garibyan, D. K. and Papoyan, S. A., "Ose,of .Sebaceous Gland Reactions as a Test for Rapid 'Detenninatfin of .Carcinogenic Activity of Chemicals*^. Nekot. Itogi Izuch. Zagryazneniya Vnesh Sredy Kanstserogen, Veschestoamij 112-115,'1972. uMcCann, J. et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test", Proc. Nat. Acad. Sci. (USA) 72(12), 5135-5139, 1975. . .-`.X . . K: 5Bartach, H.,. et al.,. "AlkylatingandrMutagenic.Mat&bolites of Halogenated Olefins Produced by, Bvkan end Animal Tissues", Proc VAm. Assoc. Cancer Res. 1J, 17, 1976; ~ 6Bartsch, H. et al., "The Predictivd' Val^of^TXssue - Mediated Mutagenicity Assays to Assess1 the Carcinogenic Risk of Chemical IARC Sci. Pub. No. 12, 467-491,1976. v' l -^.. 7Casto, B. C. et al, % "Assa^.,of:tIndustrialjChemicals in Syrian Hamster Cells for%Bnh^c^^^v}?iral2%%foriaationr#(Meeting Abstract) , Proc. Am,]; ^T# -155, 1977. ^Personal Communicationwith^e. C.Casto on"9 ' _ .s * .. *.-i ;> ~T *' - r-* v. f- : V' r ' 9mrc Source Assessment'Data.:.Baser- July-1977^. February 1978. '- ^- - 10Dorigan, J. et al., Preliminiy;:SCOring' of Selected Organic Air Pollutants"-, Nat^onal^TedhnicalE'llifprMtion Service Number PB 364 446, 1976^^.- " i. 11 11 Verschueren, K. , Handbook og gnvironieihtar Data on Organic Chemicals, Van Nostrand JtaiJihold/CO,Ae*'XorJt, 1977. . r ~. *Vtfasf Z. v." - > ' -- v , : RSV 0010942 Vinyl Broai.de Vinyl bromide (bromoethylene# CAS No. 593-60-2) has not been tested very much. It was not found on the Survey of Compounds Which Have Been Tested for Carcinogenic Activity and from Can cerline and Toxline only one author has conducted in vitro tests on it. In this test# Salmonella typhinurium strain TA100 was found to give a dose-response mutation frequency of 26 and 9 revertants per micromole per hour with and without the S9 liver microsome fraction1. It was also found that liver frac tions from human biopsies converted vinyl bromide to more mutagenic compounds. Another study by the same authors demonstrated that vinyl bromide is activated by the liver homogenates in the same manner as vinyl chloride. Although there is not much data with which to base any decision# vinyl bromide will be considered a possible carcinogen for the firwt phase of this project. Production and Persistence It is estimated that 4x1013 2* kg/year of vinyl bromide is emitted from stationary sources.3 '' 1 Bartsch* H. et al.f "Alkylating and Mutagenic Metabolites of Halogensted Olefins Produced by. Human.and Animal Tissues#" Proc. Am. Asaoc. Cancer Bias. 17;.-17 *"1976: 2Barbin# A.# et al.# *X#iver-Mcroscme-liediated Formation of Alkylating Agents fron Vinyl.Bromide and*Vinyl Chloride#" Biochem. Biophy*. Re#;, Coifaa?67^ $96-403, 5 3 MRC Source Assessment Data Base# July"1977. 147 RSV 00109*3 Vinyl Chloride vinyl chloride (CAS No. 75-01-4) has been found to cause lung tumors, mammary carcinomas and angiosarcomas in mice following exposure by inhalation1. Similiar exposure for rats produces angiosarcomas of the liver and other organs, qrmbal gland carcinomas and nephroblastomas1. In view of the extreme rarity of angiosarcoma of the liver in the general population, 16 cases in vinyl chloride workers is evidence of a causal relationship. It has also been found to be a mutagen.of' S. typhlmurium (Ames test) 12 3and in enhancement of viral'.transformation Production and Persistance It is estimated that 1.4x10s kg is emitted per year4. The 1973 production of vinyl chloride was 2.4x10s kg in the United States of which 97% was used for production of polyvinyl chloride1. 1974 EPA estimate was 9x10s kg released to .the atmosphere1 A Other estimates of production are 2*5x10* >)cg-r(i9>74),s and 2.5x109 kg, 1.9x10s kg and 2.6x10s kg in 1974, 1975, and 19766. The demand for PVC is expected to increase at an annual rate of 8-10% through 19816. In the atmosphere it reacts with the HO radical with a 12 hour half life*. It has a boiling point of -14 C and a vapor pressure of 2660 on at 25 C7. 1 "Vinyl Chloride" in IARC Monographs-bn'the Evaluation of Carcinogenic Risk of Chemicals to Nan,. Volume 7, 291-305, 1974. 2 Bartsch, H., et ai., "The Predictive Value of Tissue - Mediated Mutagenicity Assays to Assess the Carcinogenic Risk of Chem icals,: IARC Sci. Publ NO. 12, 467-491, 1976. 3 Verschueren, K.,Handbook of Environmental Data on Organic If*Chemicals, Van Nostrand Reinbold^ Co;, -Y. 1977. 4 Personal comaunication with B. C. Casto on 9 February 1978. 5 MRC Source Assessment Data Base,.July. 1977. Raddiing, S. B., et al., "Review,;of tlM| knVironmental Fate of Selected Chemicals," National Technical"Xdormation service Number PB 267 .121, 1977. 7 Allport, J., et al., ,."jl&Studf9|r?3> Chemicals for Testing,.* Nati vice Number PB 274 "" Candidate iilvlnf&fmatlon Ser Vinylidene Chloride Vinylidene chloride (1,1-dichloroethylene, CAS No. 75-35-4) has been found to be mutagenic in the Salmonella typhiraurium testl~3 and in a metabolizing in vitro system with E. coli K124. It has also been reported to be carcinogenic in rats and rabbits5 and in preliminary studies 200 ppm were carcino genic to rats and mice by inhalation6. One reference concludes that airborne*emissions of vinylidene chloride are not likely to pose a significant risk to the general population7, vinylidene chloride has been placed on the probable carcinogen list for this project. Production and Persistence It is estimated that 2.1 x 105 Kg are emitted a year from stationary services, with 70% of this coming from the oxychlorinatlon of ethylene dichloride6. Other estimates of production.and release,^reproduction.of.2.7x 107 Kg with 4. 1x10 5 Kg released9, production^of ',Kg with 1.4 - 1.8 x 106 emitted and af'5*''10%`growth'rate predicted7, 1.2 x 108 Kg produced with l^lnX 10* Kg released10, 7.7 x 107 Kg produced from 1$73.^ growth predicted11 and 2.7 x 10?:Kg produced'in^liwlf^'^Thig.Pj^and HO reactions are estirmted to give Ieas*than*i ^ww-da*' *yjtlr life10 while another reference citee^HO helf^lijfe ^f*i^6'hoursi?. Evapora tion of 50% from a 1 ppaMsoluion*atl25#C will occur in 22 minutes13. It has :a~vepor.!p&s*ure'`of J517 mm'.at 25"C and a boiling point of 37*C.l. '' iBartsch, H. et al.,, ''Alkylating .and Mutagenic Metabolites of Halogehated Olefihs ^oduged^fay`Bpman and Animal Tissue", Proc. Am. Aasoc. CancerRis*'i7',V 177.1976.'................... 21ARC, "Information. Bulletin^m^^|isuryeyi6f Chemicals being Tested for Carcinogenicity*7> International'Agency for Research on Cancer, Lyon, Bulfetia Mo.'5, July 1975. 3Bartsch, H./et al. ,;?&Rr^iSw-Vi Value of Tissue - Mediated Mutgenlcity*Jttsats*lttv'Assess the'Carcinogenic Risk of Chemicals*, IARC Sci. Pub.,,Wo..12;.467-491, 1976. ``Greim, H. CV^et and. Potential Carcinogenicity ^bFx cChhiolorinaSds HtHyienes^aa-a Punction of Metabolic Oxdrane Formation",Biochem. Pharmacol., 24, 2013- 2017, 1975v .-