Document 7Me3p8movwgao21NJY7RQ7yxa

Monsanto MKC - Dayton ICO ZO>V 101 ftVIOCA TlOwi SPECIAL rrvRt o# RfFORti . REFOR1 1 2S C IIFM 1C A LS AUTHORS` I REFT NO M < C - D A - 7 l t iT IE AI I , '.V II'<.W Me M l 1 1 i n Ol HIT C A R tlN n r.l ? I.iriU A T U R J k* 'U>jo**.*' O? MRC-DA-77I 10). 1_Q20_ 18 April 1878 1 March 1878 - J1 March 1978 RECE!' OPR c`< A REVIEW OF THE CARCI'.OGf. LITERATURE OF 125 CHEMICAL*! authors ca n r McMitnklTTr- * :1 J | irj i-r . . `I 1 i i L.I *J f jj iHLi} I Uvi . asstract The first task of EPA Contract 68-02-277) is to identify 20 significant atmospher.c carcino gens. Sampling and analytical methodology based on porous polymer sorbants and gas chroma tography/mass spectrometry will then oe devel oped for IS of these chemicals. In order to identify significant caicinogcir, tha literature has been reviewed for about 125 chemicals to determine whether they should be considered carcinogens for this project Different criteria must he used to define what tests results indicate carcinogenicity depending on the use to which the resulting list is intended, for this program, tone chemicals have been .included on the possible carcinogen *liatjbased on a limited1 amount of short-term mutagenicity data, if these lists should be used for other purposes, it would be expedient to? revivy^ths literature citea and draw th atiproporiatg concisions based or other guidelines 1 C 0 1*1 P 'A >f V M FI a E N ri A I TThhiu* fflloooimeennii }}* ti haproi o| MAnjofio uompar/and in* iU'M'I t rSSP9lllt}e|<OI,lll 4 |idpnilon|iSc4nja,n$ CONFIDENTIAL INFORMATION VK.injmull'niljbe APrddicea (' aeitd ,io y'>'vtne''ib psrtonf g itntloulid* Ihf Corein Uloet pitnJiifalihociiatiliT HONS 021907 COPY NUMBER * Technical Report* Library, R2C......... St. Louis 2-4 central File* Dayton S R, c. Sinning c D. J. Dahn Dayton Dayton 7 J. S. Karri*, G5ED St. Louis L. E. Klein, C5E A St. Louis 9 C. D. Rawlings Dayton 10 C. A. Richardson Dayton 11 B. G. Ward St. Louis 12 0. L. Zanders Dayton 13 J. m. Butler 14 T. Hughe* 15 R. F. Ivory 16 R. c. Peck Dayton Dayton Dayton Dayton 17 R. B. Reznik Dayton IS R. J. schatz, E3SA St. Louis 19 J. J. Brooks 20 E. C. Etmutis Dayotn Dayton 21 D. J. David Dayton 22 w. M. Hayne* Dayton 23 C. R. HcMillm Dayton 24 T. A. Orofino Dayton 25 J. V. ?ustinger Dayton 26 A. D. Snyder Dayton 27 L. B. Stevens Dayton 2 D. S. west Dayton 29 H. L. Williams Dayton 30 T. G. Linxweiler Dayton 31 F. J. Winslow/D. B, Nelson Dayton 32 C. J. Eby Washington 33 F. C. Meyer St. Louis 34 B. C. Casto BioLabs, X) ABSTRACT ONLY . K. Flltcratt Dayton Hay request a copy from the Dayton Library COMPANY CONFIDENTIAL. Whan no longer needed. or upon i*qt)*|t?teti<rq this . rapttrt to CantrallFil** Daytori Introduction The :irst task of EPA Contract 68-02-2773 i* 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 IS of these chemi cals. In order to identify significant carcinogens, the literature has been reviewed for about 12S 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. Tor this program, some chemicals have been included on tha 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 pos.tivc animal data coupled with positive mutagenicity data from .it 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 typhimunum test and the enhancement of viral transformation tests (e.g. B. C. Casto), with the E. coli (pol A) differential toxicity and the Drotophila tests also con sidered important. Annal carcinogenicity tests were considered less significant if they were conducted mere 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. ? C. Casto, Biobabs, Inc. - Northbrook. Illinois, has been a consultant for Monaanto Research Corporation or. this *:pa contract. lhfo6$XrfTb>)<sB'ta814oltPoMT{oA ' HONS 021909 Chemical Acetaldehyde Acetone Acetonitrile Acrolein Acrylonitrile Aldnn Allyl Chloride Aniline Anthracene Benz(a)Anthracene Benzene Benzidine Benzol a)Pyrene Benzoquinone (Ouinone) Benzoyl Peroxide Benzyl Chloride Biphenyl Bis(Chloromethy1)Ether Butadiene Ceptan Carbon Disulfide Carbon Tetrachloride Chloracetie Acid Chlordane uresol Chlorobenzilare Chloroform Chfloroprene CBlofopJopa ne crjrysene Cumene HyjJtopero'acle 0fr INDEX i MONSA{IT0t*EK*ftCt C0^0K4T)O|( 1 2 3 ...............4"" 0 7 a 9 10 11 12 11 15 16 17 ie 19 20 21 22 21 24 26 26 29 :o 31 33 35 36 37 38 HONS 021910 index - Continued Chemical Di-tert-Butyl Peroxide De (2-Ethylhexyl)Phthalate 2,3-Diaminoamaole Diaimon o-Dichlorobenzene p-Dichlorobenzene Dichlorobenzidene Dichlorobutene Oichlorodifluoremethane 1,1-Dichloroethane DichloronapthoquinOne Dichlorophenol Dichloropropene Diehloropropionic Acid Dichiorovinyl Dimethyl PhOSDhate (DichlorovosI Dimethyl acetamide Dimethylamine Dimethyl hydrazine Dmitrotoluene Dioxane Diphenyl Oxide Disodium Methanearsonate Durst an Endoaulfan Endrin Cp-xhiorohydrin Eptam Ethanol Ethyl Benzene Ethylene Ethylene bibronude thyI4ni Didhlcjride : *2* 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 7i1 73 *0N*ANTaae*<*ftdMfc:bftFoitATiaNa*i MONS 021911 Index'* continued Chemicai Ethylene Clycoi Ethylene Oxide Ethylenimme Fluoranthene Formaldehyde Cuthion Heptachlor Hexaehlorobenzene Hexachlorobutadicne Hexamethylenetetramine Hydrazine Hydroqumone Ke1 thane Malathion Maleic Anhydride Mercaptobenzothiazole Methyl Bromide Methyl Chloride Methyl Ethyl Ketone Methyl Methacrylate 44`"Methylene Bis(2*Chloroani 1 me) Methylene Chloride Methylenedianilme M""'h\1 styreno Morpholine Naptha 1-Naphthlaoune Napthaiene. Napthoquinone 1-Mapthyl Methylcarbamate Nitrobenzene Nlffrophefloi ili fxHS4Nf0* e3aA*cnTcD*eORAfiem*BJ Pge 74 75 77 78 79 81 82 82 85 86 97 38 99 90 91 92 94 95 96 97 99 99 100 101 102 103 104 7 06 107 108 109 Ul MOMS 0219U Index - Continued Chemical Nitroaodimethylamine Nitrochlorobenaene Parathion Pentane Pentachlorophenol Phenol Polychlorinated Biphenyl# Propanol Propylene Oxide Pyrene Sorbic Acid Styrene Sulfolane Tetrabromoethane Tetrachloroethane Tettachloroethylene Tetraethyl Lead Toluene Toluene Diisocyanate Toluenediamine Toxaphene Trichlorfon Tnchloroethane Trichloroethylene Trichlorofluoromethane Triehlorophenol urethane Vinyl Acetate Vinyl ftronide Vinyl Chloride vinylidene. Chloctde ........... ............ .................. Page 111 111 111 114 ns n? 118 120 121 121 124 125 127 128 128 130 132 114 135 13C 137 138 138 140 142 143 144 145 14? 148 US I 0 .nOMSArtfO #Bta*ltul4C0l|l,fiAA|rif)rf HONS 021913 Acetaldehyde Acetaldehyde is possibly a carcinogen promoter1, but no referencee to it as a carcinogen or mutagen were found in Toxline or Cancerline. Two references by Nakahara and Mori in 1919 and y40J demonstrated no tumors in rats fed acetaldehyde in their food for more thin 300 days. It is probably not a carcinogen. 'Davies, iT. C., *Co-Carcmogcnosi5 w;th fiespect to the Content"! .dfiOibavvtte .Tobacco,". Jl. .Soc. Health.J. .93() , |296-^01, 1973 ||:sarix3S[inteidcal 0 Ionsant4 wsoftftcn coercidrsiONf*' HONS 021914 Acetone Acetone 12-propanone, dimethyl ketone, CAS No, 67-S4-1) he* 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 .* vitro tests and is used as a negative solvent control for many chemicals in these tests. ^Survey of Compounds Which Have Been Tested for Carclnoeenid 'Activityi National-Cancer Institute, PHs-149, volumes ^,7. ............................. t.................... t pqHS*Nto!Aiss*nc*l 4oe|oMTlP" HONS 021915 Acetonitrile The only data euqqestmg that acetonitrile is a catcino9n u a reference citing equivocal reiulte from a 2-year rat study. It is considered a non-carcinogen for this project. 'Fuller, B., et el., "Preliminary Scoring of Organic Mr Pollutants", National Technical Jr formation Service Number ttfi W, 442. 1971. i A dobsANTo mese*c>ucoaei>a*rigN 4 HONS 021916 Acrolein Acrolein appears to be toxic and reduce* ciliary action of the bronchial epithelium11 * but is not mutagenic in S. cerevieiae} or dominant lethal mice tests'*. Acrolein has b*"cn found to be a mutagen to the TA153B and TA98 strains of S. typhimuriun4. It will be considered to be a possible carcinogen for this project. Production and Persistence It is estimated that 6.5 x 10* Kg is emitted per year, primarily associated with acrylic acid manufacture*. Other estimates are 4.2 x 10s Kg/yr released from 2.8 x 107 produced7 and a produc tion of 2.8 x 10' produced in 1874 with a 6.7% growth forecasted throuch 1979*. It has an atmospheric half life estimated at 2.6 hours'* Its boiling point is -88*C and it has a vapor pressure of 220 mm at 20C,,. 'Shabad. L. M, et ai., "The Feasibility of Preventing the Effects of Carcinogens on Man", Kazan Med. Ih (5), 92-93, 1973. Terrell, J. H. and Schmeltz, I., "Cigarettes. Chemical Effect of Sodium Nitrate Content". Science 160, 1456. 1968. -Izard. C., "Mutagenic Effects of Acrolein and its Two Fpoxides. Glycidol and Glycidal, in Saccharomyce* Cerevisiae*. C. ft. Acad. Sci . Ser. D., 276 (23). 3037-3040, 1973. "Epstein, S. S.. et al., "Detection of Chemical Mutagens by the Dominant Lethal Assay m the Mouse*, Toxicol, Appl. Pharmacal. 23, 288-325, 1972, -Bianami, M. et al.. 'Relationship Between Chemical structure and Mutagenic Activity in Some Pesticides: The Use of Salmonella Typhimunum and Aspergillus Hidulans", Mutat. Res. 6 (3). 243-244, 1977. *MRC Source Assessment Data Base, July 1977, Tuilet. 6., et al . "Preliminary Scoring of Organic Air Pollu tants'. National Technical Information Service Number PB 264 442, 1976. Allport, J., et al,, "A Study of Industrial Data on Candidate Chemicals for Testing*National Technical Information Service Mumbai PB 274 264 . 197* ? IMPNSaMTf *MB-MNKOmPOMA 110* tf HONS 021917 Acrolein References * Continued 'Padding, S. R.. at al., "Review of the Environmental Fate of Selected Chemicals", National Technical information Service Number PB 267 121. 1977. BVt" en , K. > iHandbookof Environmental Data on Organic dhlrflfcaiii v*rt MttRanj Heuihold Co,-.it#.y|.i lSI7. 4 viMPS**ro *est*CHtc0*peAciereat HONS 021918 Acrylonitrile Positive Ames tests' E. coli mutation tests*2 i and viral transfor mation enhancement tests3 4 have been reported along with negative recessive lethal Drosophila melanogaater and negative Vicia* faba chromosome aberration tests1*. Human epidemelogica 1 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 carcinomas5. Based on these findings, acrylonitrile is being placed on the probable carcinogen list for this project. Production and Persistancc It is estimated that 3.7 x 10s Kg is emitted per year7.* (Another estimate is 9.6 x 10f- Kg per year9). Acrylonitrile has a boiling point of 77C and a vapor pressure of 100 mm at 230C9. Milvoy, p. and Wolff, M., "Mutagenic Studies with Acrylonitrile", V.ut. Res. 48 ( 3-4), 271-278 , 1977 . Vemtt, S. et al., "Mutagenicity of Acrylonitrile (Cyanoethylane) in Escherichia Coli", Mut. Res. 4Jj, 283-288, 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", National Technical Information Service Number PB 274 264, 1977. i "Aerylonitrile Linked to Cancer on Workers", Chem. Eng. News, 3_5, 6, 197 7 . Finklea, J. F., "Acrylonitrile" Am. Ind. Hyg. Assoc. J. 38, 4 17 - J. 7 2 , 1977. 'MRC Source Assessment Data Base, July 1977. "Fuller. B*., ei al., "Preliminary Scoring of Organic Air 'PDllJitancs* National Technical Information Service Number PB 264 442, 1976. Verschueren, K. , Handbook of Environmental Data on Organic . Chemicals', ;Va& Npstrard Reinhold no'. . New. York. 19.77.i 6 ' ImOnsAnTP ^EsiAnqH.'coaPo^ATioNt MQNS 021919 Aldrln Aldrin has been found to cause neoplasia in two strains of mice1 and tumors in weanling rata*2. Aldrin is converted into dieldrin in the environment3 * and dieldrin is a carcinogen at 0.1 ppm in dietary exposure to mice1*. Thus the sale and production of aldrin was suspended5. Many other animal studies have been con ducted with questionable results6, and some in vitro tests have been negative . ^ Since there is enough data to suspend production of aldrin, it will be considered a probable carcinogen for this project. Production and Persistence 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. *Song, J. and Harville, W. E., "Carcinogenecity of Aldrin and Dieldrin on Mouse and Rat Liver", Fed. Proc. 2_3, 336, 1964 . 2Deichmann, W. B., et al., "Tumorigenicity of Aldrin, Dieldrin, and Endrin in the Albino Rat", Ind. Med. Surg. 3j) (10), 426 434, 1950. JWurster, C. F., "Aldrin and Dieldrin", Environment 13 (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 Laved on SKpcrimental Evidence and Evaluation and Societal Needs", Ann. N.Y. Acad. Sci. 271, 187-195, 1976. 6"Aldrin-', in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 5, 25-38, 1974. 7Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogenesis Essays, IARC Sci. Pub. N<J. 10, 161-181, 1974. ^Fullsur, IB. et al., .Preliminary Scoring of OrgapJlc AirIPpllutants" f National! Technical! tnformatiion Service Kumber JPR J 2$4i 442. 119261 ' j 71 ' lM&NSi(N>d RESEARCH IcORPOAATIOrd ; | MONS 021920 Allyl Chloride Allyl chloride (3-chloropropene, CAS No. 107-05-1) i on the NIOSH Safety Alert List. No references have been found on thu.- Toxline, Cancerline or the Stanford Research Institute study on hazard priority ranking1, to indicate that allyl chloride is a carcinogen or mutagen. A recent reference, however, reports that allyl chloride is a mutagen in S. typhimurium, S. cerevisiae and E. coli test systems*2. It is therefore classified as a poss ible carcinogen for this project. Production and Persistance It is estimated that 4.2 x 10s Kg is emitted per year from stationary sources3. Another estimate is 2 x 106 Kg released from a production of 1.3 x 10 Kg per year4,* and a production estimate of 1.3 x 10 Kg in 1972*. It is reported to take 27 minutes for 50% of the allyl chloride in a 1 ppm solution to evaporate at 25C6. It has a half-life with HO radical of 21 hours, with 03 radicals of 9 hours, and hydrolyzes with a half life of 7 days4. It has a boiling point of 45C, a vapor pres sure of 340 mm at 20C, and a solubility of 3.3 gm/1. 'Brown, S. L. et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Infor mation Service Humber PB 263 161, 1975. 2McCoy, E. C., et al., "Genetic Activity of Allyl Chloride", Mutat. Res., 57, 11-15, 1978. 3MRC Source Assessment Data Base, July 1977. 4Qrown, 9. L. et al., "Research Program o.' Hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number JPB 26 3 164 , 1975. 5 Dori$anf jf Preliminary scoring tof `Selected Organic Air Pollutants?,; National Technical Information Sarvica Number PB 264 44 3. 1926.- Veqstouf reJf Kl,l Handbook, ot Environmental Data bn pnagiefChen^ 5iSISJ*i3dlft*intoid co.RiHe5-imK.U9VT 8 4 4oNSANtolReseAMC cdRPdniTidNf. HONS 021921 Aniline -""i s The IARC monograph on aniline* reports that aniline is probably not* a carcinogen and;that what early researches believed was cancer from 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 microsomes3. It has also been reported negative in reversion to prototrophy in Aspergillus nidulans (methj ) 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. 11ARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Mani Volume 4. 27-36, 1974. 2Fl'uck, E.r R.., et ,alj, fEvaiuation of a'DNA Polymer a se^-Defecient Mutant of E.'Coli for the Rapid Detection.of Carcinogens", Cheat* Biol. OLntisEaci.-. 15. 219-231. 197$. ndldata Service 9 k*e:e4KTCt RESEARCH c6rRORA'SICB< ( MONS 021922 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 nan-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) 5 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 bo a non-carcinogen and it is presently being used as a non-carcinogenic standard on studies to develop short-term assays tor carcinogens (3-6). l Schmall, D., "Prufung von Naphthalin und Anthracen auf Carcerogene Wirking an Ratten", Zeitschrift fur Krebsforschung 60, 697-710, 1955. ' - Stanton, M. F., Miller, E., Wrench, C., and Blackwell, R., J. Natl. Cancer Institute 49 (3), 867-877, 1972. ' 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 Bioassav for Identifying Diverse Carcinogens", Int. J. Cancer 19, 642-655, 1977. ' DiPaolo, J. A. et al., "Ouantitation of Chemically Induced Neoplastic Transformation of 3ALB/3T3 Cloned Cell Lines". Cancer Research 32, 2686-2695, 1972. 5 Purchase, I. F. H., at al., "Evaluation ot Six Short Term Tests for Detecting Organic Chemical Carcinogens and ' .Recowaendatinps tfAc fheit Use"; ^U1;ur4 64^ :624-647, |ljp7. * iMtAntT.f J.I at? fif r "petfedtiirv 6C Carcfnpgens fcf MjtaleKs Eo the sJlmdnilli/rEf rofomfe lTe*t,"l 'Assay Jot 3|0Q p!emical, Ptac. fcJattU Afcadi.lSci; .C4SA1 .72* 5135-55139L fL925.. MONS 021923 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 kq/year is emitted from carbon black furnaces, the only stationary source cited for this chemi cal2. It is emitted in the exhaust from gasoline engines (61.7 mg/kg exhaust tar) and diesel engines (2.3-15 .g/m' exhaust!-. It has been detected in the air, soil, food, and cigarette smoke condensate1. It has a boilinc point of J00c.1 `"Benz(a)Anthracene" in IARC Monographs on the Evaluation of Carcinourmto Risk of the Chemical to Man, Volume 3, 45-68, 19.73. 2MrfCl Sojbjcie Assessment pata (Basel JUlvll977. *1 MONSANTO neseAhCt4CCPOBATIOH tf HONS 021924 Benzene Benzene (CAS No. 71-43-2) is one of the industrial substances sus pected of carcinogenic potential to man as listed by the American Conference of Governmental Industrial Hygienists' and will soon be controlled as a carcinogen. The 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 between exposure to benzene or benzene mixtures and the development of leukemia. Along with some positive studies3, many references occur in the literature where benzene is a negative solvent control in animal studies". In spite of these references, it is believed that benzene induces chromosomal damage in animals and man5 and is a known carcinogen. An assessment of the air pollution aspects of benzene has been conducted5. Since benzene is being controlled 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 is emitted per year wi * h solvent evaporation from degreasing operations contributing over 70% of the total7. Another estimate is 4 x 107 kg per year re leased from commercial uses of benzene'. It reacts rapidly with HO (t,% - 3 days) but slowly with RO- and Oi and has 3 2.15 log partition coefficient-. Its boili.no point is 80.1C and it has a vapor pressure of 76 mm at 20C. '"Threshold Limit Values for Chemical Substances in Workroom Air Adopted by ACGIH for 1977", American Conference of Governmental IndustrialHygienists,1977. "Benzene", in "IARC Monographs on the Evaluation of Carcinogenic Risk of Chemical to Man", Volume 7, 203-222, 1974. 'Brown, S. L., et al., "Research I'rogram on Hazard Priority Ranking of Manufactured Chemicals", National Technical Informa tion Service Number PB 263 162, 1975. `Survey of Compounds Which Have Been Te-ted for Carcinogenic Acti v~ity~j PHS-149, National Cancer Institute. ' ' 5Allport, J., t|alft, f4 Study of Industrial Data onCandidate Chemicals for Tasting , National Technical Information Service Number PB 274 264,.- 1977. c Walker, ,P. ,} rflaf iFJ>ll|iipfi .Assessment! of benzenfe1; ,| Nations 1 TecBmiail InforlatiOrl fexrict tlumbci TB ;25i f34tllfeT6. 12 . as*A/frf qce*oii^Tp* y MONS 021925 Benzene References'- Continued V?.C Source Assessnent Data Base,* July 1977. '.crschueien, K., Handbook of Environmental Data on Organic Chem icals, Van Nortrand Peinhold Co.fc N. 1977. 1 n8 HONS 021926 Benzidine Benzidine is reported to be carcinogenic in the mouse, 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 mice when given p.o. either by stomach intubation or in food2. These references, along with many others in Toxline and Cancer line show that benzidine should be considered a probable carcinogen Production and Persistance It is estimated that 4.7 x 106 Kg is produced per year!. A release factor of 0.015 is assumed which would give 7 x 101* Kg released per year. This is probably too high since benzidine is well known as a carcinogen. Perhaps 7 x 103 Kg would be closer to reality. It reacts with OH and with a t 1/2 of one day1-. It has a boiling point of 402'CS and can be sublimedi . :"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. _35 (10), 2814-2619, 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 Manufacture^ Chemicals", National Technical Information Service Number PB 263 163, 1975. * Verschuaran, K., Handbook of Environmental Data on Organic Chaa>ioHaxAva rttoatranS RfcintodldiCo. * N. Y; .a 19J7 .' 14' <0NS*4T<a*efEitar< fcORPonp-riciNW-. HONS 021927 Benzo(a)Pyrene Benzo(a)pyrene (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 ducks'. 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 10s 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 bo i 1 i ng pc ,,nt of 311C at 10 mm and 4 7 5 "0 at 760 mm ' . VBerifco(a)Pyrene" in IARC Monographs on the Evaluation' of car cinogenic Risk of the Chemicals to Man, Volume 3, 91-136, 1973. 2J4RC Source Assessment Data Base, July 1977. L5 **on$auto* fqpaORvrjOii > HONS 021928 Bcnzoqulnon< (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 carcinomas2. In 1954 and 1956, inhalation experiments with a total of 50 treated mice were conducted with negative results3. 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 meianogasteru, is not mutagenic toward Drosophila or cultured human leukocytes1* , 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 leukocytes'5. no other significant data were found in Toxiine, 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. 'Takizawa, N., "On the Carcinogenic Action of Certain Quinones", Proc. Imperial Acad. (Tokyo) ^6, 309-312, 1940. :Tiedemann, H. Ztschr. Naturforsch. 8b, 49-50, 1953. ' "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 Lathals Following Treatment of Mono- and Polyfunc tional 'Aziridine Analogues", Mutat. Res. 14^, 250-253, 1972. hueers, H. ^nd Obe, G., "Possible Mutagenic Activity of P-nenzoquinpne", Mutat. Res. 15, 77-80, 1972. 16 MONS 021929 Benzoyl Peroxide Benzoyl peroxide {CAS^No. 94-36-0) was extensively tested in mice and rats between 1962'jand 1967 by six authors on more than eleven hundred animal9l. JBenaoyl peroxide i3 on the NIOSH Suspected Carcinogen list because in one of these studied 1/50 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 Cancer line. 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 `Survey of Compound*-Wljicl gave Been Tested for Carcinogen Act ivity, NCI, FHS-14?, folume 1961-1967. -Aliport, .1. ct al. *A Study of Industrial Data on Candidate iChemicals for Tcstisig j,fjaiiohalt Xechnicai Information! S.eryice INumber >B 274 ^641 |l917E 17 MONS 021930 Benzyl Chloride Benzyl Chloride (a-chlorotoluene, CAS No. 100-44-7) ha3 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 (SI weeks) in 3/14 rats and at 3.9 g/kg in 6/8 rats*2. It is weakly mutagenic in S. typhimurium tests at 2 mg/plate3, and is considered carcinogenic in rats by the IARC2. 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 63 70* of this going towards the manufacture of butyl phthaLate and 30-J5* towards other organic products'. Production has been esti mated at 4.5, 3.2 and 4.1 v 10' kg in 1974, 1975 and 1976 and is predicted to grow at 5-7t per year through 1980". It has a boil ing point of1 179C and vapor pressure of 1 mm at 22C5. * 'Fluck, E. R., et al., "Evaluation of a DNA Polymerase - Deficient Mutant of E. coli for the Rapid Detection of Carcinogens", Chen. Biol. Interact., IJj, 219-231 , 1976. '"Benzyl Chloride" in IARC Monographs on the Evaluation of Car cinogenic Risk of Chemicals to Man, Voi. 11, 1976. 3McCann, .7., et al., "Detection of Carcinocens as "utacens: Bacterial Tester Strains with R Factor Plasmids", Proc. Nat. Acad. Sci., 72, 979-983, 1975. '`Allport', J. , et al., "A Study of Industrial Data on Candidate .Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. ' 5Verschueren, K., Handbook of Environmental Data ci. Organic ChemicalsYantNostrand Rernhold o., N.Y-. lS}^ 18 AJONSAnTCL RESEAfJCH CORPORATION HONS 021931 Biphenyl There ie one reference which shows subcutaneous biphenyl (diphenyl, CAS No. 92-52-4) to induce an excess of tumors in mice*. No other references could be found in Cancerline 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 lO1* 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 to exist. It has a boiling point of 254C3. '"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Technical Information Service Number PB 223 159, 1968. ZMRC Source Assessment Data Base, July ,1977. 'ueren, K., Handbook of Environmental Data on Orqanic al{, Van Nostrand, ReinhcId Co., N.Y. 1*77. 19k 1 MotsaHrO B8sEA*CK|ciDRPSDS*rie^# MONS 021932 Bis (Chloromethyl) Ether Bis(chloromethyl) ethar'(BCME, dlchlororaeth'ylether, CAS No. 542-88-1) is carcinogenic to mice following inhalation, skin application and subcutaneous administration1. It is also carcin ogenic to rats by inhalation and subcutaneous administration1 . Epidemilogicai data suggests it is also a human carcinogen1. It is being regulated as a carcinogen and will be considered a probable carcinogen for this project. Production and Persistance It is estimated that less than 100 Kg BCME is emitted per year2. A primary source of emissions is in the production of polymethy lene polyphenyl isocyanate2. Its production in 1974 was estimated to be less than 450 Kg3. In water the half life of BCME is 38 Su_-onds and in the air (50% relative humidity) its half life is 25 minutes3. It has a boiling point of 104C3. 1"Bis'Chloromethyl) Ether" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 4, 231-238, 1974. 'mrc Sourse Assessment Data B*e. July 1377. 'Radding, S. B., tt al., "Review of the Environmental Fate of Selected Chemicals.". National .Technical (Information Eervice Number io AH ICS SUE* SCSI kInIb MONS 021933 Butadiene I,3-Butadiene (CAS No. 106-99-0) has 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 Been Tested for Carcinogenic Activity on tests conducted although there is interest in a possible relation ship 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. Hi and Ellis, L., 'Styrene .Butadiene Rubber Synthetic Plants and LeuJcemia* (Letter to Editor"), TJ. Occup. Med. 19 (7), 441, 1977 **on;a|<tc|NeJeArcB fcdnCona MONS 021934 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 mice1 . 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 emitted0. (Another estimate is production of 8.1 x 10s Kg per year with 0.01 released or 8 x 101* Kg per year emitted3.) '"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemials", National Technical Information Service Number PB 223 159, 1968. ZMRC SduTrctf AtfsAsstoent Data Base, July 1970. Jpy ^ ^ taqta 264 4 B ml , *Deal i m i Cnnei nn a t n i & i r POllU~ MONSAN-fOlRtsfeArttri CORPOSMTlOfJ > HONS 021935 Carbon Dlaulfide There is nothing in Toxline or Canceriine to indicate that carbon disulfide is a carcinogen or a mutagen. One industrial epidemilogical study showed carbon disulfide to have no correlation with incidence of cancer1. `DiVitO, and Sommi, G. L., "The Incidence of Infectious Diseases,, Haraopathies, and.Neoplasms min Wnuorrnk.eeris Exposed to Carbon' Difcu|fldte*> iFsliti Hid. i CNanoli.) i Cl), ; 912^91%, 19.6 3, 23 tuossfKpo nsssAscHicoftPonArio^ * MQNS 021936 Carbon Tetrachloride Carbon tetrachloride (tetrachloromethane, CAS No. 56-23-5) his 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*2. 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 108 kg with 2.7 x 107 kg released". A document is available on the air pollution assessment of carbon tetrachloride5.6 Estimates of carbon tetrachloride production include 4.5 x 1O0 ka (1970)', 4.8 x 1O0 kqS 7.3 x 1O0 kg ( 19 74) 7 and 5.3, 4.1, and 3.8 x 10s kg for 1974, 1975, and 19762. It is forecasted that the 1975-1976 decline will continue. The half life of carbon tetrachloride in the water is about 70,000 years'", and in the troposphere it is about 10 years'. It is estimated to have a half life of 10-33 weeks toward atmospheric photodegradation5. The boiling point of carbon tetrachloride is 75.70C and it has a vapor pressure of 90 mm at 20C. For a review of its production, uses and biolog ical activity, see the Fishbein article9. `"Carbon Tetrachloride" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 1, 53-60, 1972. Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PK 274 264, 1977. 5MRC Source Assessment Data Base, July 1977. "Brown, S. L., et al., "Research Program on Hazard Priority Rankinc of Manufactured Chemicals", National Technical Information Service Number P3 263 161, 1975. Johns, R., "Air Pollution Assessment of Carbon Tetrachloride", National Technical Information Service Number PB 256 732, 1976. 6Fuller, B. , et al. "Prel imtnary (Scqriqgiof| Organic Air Pol lutants", NationalfTechnical Information:Service Number PB 264 442, 1976. 24 .-MOiSAmo Bs*Ajt(}HkqpB`V>C4r'l MONS 021937 Carbon'. Tetrachloride References - Continued Radrting, S. B. , et 1. , "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. sVersctuie^en, K.Handbook o Environmental,Data og Organic Chemicals, Van Nostrand Reinhold Co., N. Y., 197?/ 5Fishbein, L., "Industrial Mutagens and Potential; Mutagens, I. H*l4fcatied Alirhatiji D*ri>4ti4esl,lMjfcat4tR.; 1976. '' ' }264 4 4oNSA(ii1o^B5E4RC)f SontoBfT|p(Hk HONS 021938 ChSor Jceflib iAtid) Chloracetic. Acid ;\n\onOchldr6cfcel|ifc tafcidl N<J.l 79-H'-8)j fas betrj reported on being carcinogenic? in {nice when! injected | subcutaneous 1/ at 1 90 mgj'lCg 1 .} *^ht primary reference, Jh&w'ever* does not report J statistical di f fere nee " i n tumors and reports data with the test chemical not much different than the control mice'. In other tests, chloracetic acid was negative when given to 6 rats as 0.005-0^lt of tjieir ,diet for 208 days,3 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 months1*. It has also been found non-mutagenic by B. subtilis5 and S. typhimurium9"9 tests in vizrs. All of these demon strate that chloracetic acid is not a mutagen and is not a carcinogen. ' 'nioSH 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. 3Fuhrman, F. A., et al., Arch. Inst. Pharmacodym., 102, 113 125, 1955. ``Innes, J. R. M., et al., J. Nat. Cancer Inst. 42, 1101-1114, 1969/ 5Elmore, J. D., et al., "Vinyl Chloride Mutagenicity via the Metabolites Chlorooxirane and Chloroacetalachyde Monomer Hydrate," Biochem. Biophys. Acta 442, 409-419, 1976. 6Rannug, u., et al., "The Mutagenicity of Chloroethylene Oxide, Chloroacetaldehyde, 2-Chloroethar.ol and Chloroacetic Acid, Conceivable Metabolities of Vinyl chloride," Chera. Biol. Interact. 12 (3-4), 251-263, 1976. 26 MONSANTO RESEARCH CORPORATION,* HONS 021939 Chi'oraet{ic A9i.fl Re fc ronces | Continued 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. BKalave:lle, C.. et al., "Mutagenicity of Vinyl Chloride, Chloroethyler.-oxide, Chloroacetaldehyde and Chloroethanol," Biochem. Biophys. Res. Comm. 6_3 (2), 3t>3-370, 1975. 27 MONSANTO RESEARCH CORPORATION HONS 021940 Chlordano Chlordane has boon found to be a carcinogen to mice in a study conducted by the National Cancer Institute'. It is also a mutaqcn in tests like the enhancement of viral transformation'. It is cons: ere1, a probable carcmoucn for this project. Production and iersistance it is estimated thatl.i x 10" produced ?. Kc tor year of chlordane is '"Bioassay of Ch'ordane for Possible Carcinogenicity. (CAS No. 57-74-9)", National Technical Information Service Number PB 271 977/1SL. '2Personal communication with B. C. Casto on 9 February 1978. ^Fuller, B., et al., "Preliminary Scoring of Organic Air Pollu tants"^ National Technical Information Service Number PB 26 442{ 1976. MONSANTO RESEARCH CORPORATION M HONS 021941 ere soL.'. Cri.'Eals |{pritnaiii.lyj o-cresol) have been shewn'to bo promoters of! cnrcJnogenfcaty! whefi given`with initiators such as 3,4-binzpyifcriej khfsfcOIfaitiethyibdnzdntaiJscerie1} or m complexi mi xtlurds4 On tire <$ihfr4 hand " rtormal adul'ts 'excrete about 30 mq of volatile phenols per day of which 901 is p-cresol1'. Thus, c re so Is are probably not care iropens but could be promoters. Rakke, 0. M. and Midtvocit, T., "Influence or Gere-Free Status on the Excretion of Simple Phenols of Poss-.ole Significance : r. Tumor Promotion", Experimentu, 26 (5), 519, 1970. 'sock, t. a, , ct ul., "CompoF i t ion studies on Tobacco. XLIV. Tumoi--Promoting Activity of Subfractions of the Weak Acid Fraction of Ciqarctte Smoke Condensate", 7. Nat. Cancer Inst., 47 (2), 429-436, 1971. 'Shustcva, M. N. and Samiolovich, L. N., "Blastomocemcity of Neutralized Soots from the Sulfate Shop of a Coke Plant", Gig. Sanit., 36 (7), 103-104, 1971. ``Bone, E. S., al., "The Production of Urinary Phenol by Human Gut Bacteria", (Meetinq Abstract), J. M?d. Microbiol. 9 (2), vi, 1976. " 29 MONSANTO RESEARCH CORPORATION 021^2 HONS Chlorobenzilato Ci.Ionxc.nziiato (CAS No. 510-15-6) h. i.-; bvon found to pntrhice hcj-'tomas in mice .gic:i administered orally *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) . Several short term tests have been negative for Chi orobor. z i 1 a to -. Cor this project, it is considered a probable carcmooen. Production and i'e rsi stance A 1 9 76 reference' cites a nrodu.-t ion of 9 x 10 Kg nor year and it is said? that the 1971 product ion was 1 >: !0` Kg. Innes, J. R. M., et al., "Eioassay of Pesticides and Industrial Chemicals for Tumorigencitv in Mice. A Preliminary Note", J. Nat. Cancer Inst. - 4_2, 1101 , 1969. .'"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Tecnnical Information Service Number PB 223 159, 1968. "Chlorobenzilate" in 1ARC Monographs on the Evaluation of Carcinogenic his* of Chemicals to Man, Volume 5, 75-81, 1974. "Jurek, A., "Carcinogenicity of Pesticides". Roczn. Panstw. Zakl. Hig. 25 (5), 563-576, 1974. ^Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinogenesis Essays,. 1ARC Sci. Tub. No. Id, .161 181, lW. -----------*------------------------ 'Fuller, B. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442. 1976. 30 MONSAMXO eeSBARCHlCORPaRABaN.a MQNS 021943 Chloroform Some of the current 1iterature1~4 indicates that chloroform is a carcinogen. Flvcn though more data is required before a final determination is made, the positive data on mice and rats suggest that chloroform be placed on the probable carcinogen iist for this project. Product ion and Pcrsistanca It is estimated that 1 x 10' Kg chloroform is emitted per year'. Another estimate is 1.7 x 107 Kg per year' emitted. Production estimates are 1.1 x 10e Kg per year7, 1.1 x 10" Kg per year9, and 1.1 x 106 Kg per year'. About 96% of production is con verted to chlorodifluoromethane. In 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 mm at 20C and a boiling point of 62C?. It takes only 18-25 minutes to evaporate 50% of the chloroform from a 1 ppm solution at 25"C9. . !IARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man, "Chloroform", Volume 1, 61-65, 1972. 'Powers, M. B. and Yoelker, R. W. , "Evaluation of the Oncoceric Potential of Chloroform by Long-Term Oral Administration in Rodents" (Meeting Abstract), Toxicol. Appl. Pharmacol. 37, 179, 1976. 'Renne, 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 5, '6, 13 1. 6MRC Source A&sessment Data Base. July 1977. 6Brown, S. L., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 163, 1975. 7Radding, S. R., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information*Service Number PB 26/ 121, 1977. 31 MONSAtfro aese/CfcCWJWapfcNAYidN' MQNS 021944 Chloroform References - Continued Fuller, 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 Chemical!. Van Noatrand Reinhold Co., N.Y., 1J77. 32 MONSANTO RESEARCH CORPORATION HONS 021945 ChloirOprsne. Chloroprene (2-chiuio- ; , i-butadino, CAS l.'(-69-8) although known to be toxic w.is not considered to be a suspected carcino gen until three Rutsian papers linked occupational exposure of chloroprene to skin un.i lung cancers'-'. Since that time, a short-term viral on!: m -cr.onf test at 125 .. t *1 ' and S. typhi- murium (Ames) test cc been positive, while lore-term rat and mouse studies h.iv-. t-on negative review- of healtn records and death i i cates for DuPont Per pc: ation employe, r; ox|.>osed to chloropr. convinced invest: -.a-ors that no excess of any disease similar to that seen for vi.-yi chloride had been observed1. However, s .me Increase in 1cancer has been seen in this population . It h-.s also been found tc accelerate the growth of transplanted Crocker murine sarerm.a tr. the Thus, chloroprene lies or the border between a possible and a probable carcinogen. it will be classifed as a -..cssiijIi- carcinogen for this project. Production and Persistence It is estimated that ~.5 x 10' Kg chloroprene is emitted per vearl:. Another ost-mate is 2.7 x 10' S': year released*-. Some estimates of prciucti v are aoout l.S x 11' year' - ; , 1.6 x 108 Kg/year- , and 1.3 :< 10' Kg and 1.6 x 10 Kg m 1974 and 1975 with 4 annual growth predicted throuuh 1991-'. Because of its low sciuabiiity and high vo.a t i 11 ty, it will socr. migrate to the atmosphere-'. In the atmosphere it is said to have an atmospheric half life of less thar. 10 hours because of OH radical reaction''. its boilmc point ic i-?.4rC anc it has a vapor pressure of '00 mm at 20*C''. 1Khachatryan, E. A., "The Sole of Chloroprene m the Process of Skin Neoplasm Formation", C-ig, Tr. Prof. Zabol. 1_6, 54-55, 1972. Khachatryan. E. A., 'Tne Occurrence of Lung Cancer Among People Working with Chloroprene", Problems in Oncology 1_9, 85, 1972. 3Khachatryan, E. A., "Lung Cancer Incidence Among Chloroprene Handling Workers", Ycpr. Onkol. 1_8. 35-96, 197.:. 4Casto, B. C. et al., "Assay of Industrial Chemicals in Syrian Hamster Cells for Enhancement of Viral Transformation", Proc. Am. Assoc Cancer Res. lj|, 155, 1977. 'Personal Communication with B. C. Casto a:. 9 February 1978. 33 MONSANTO RESEARCH CORPORATION HONS 021946 Ch LcropniV-? Re {< ronca:;, - Continued r Bartsch, H., et al., "The Predictive Value of Tissue-Mediated Mutagenicity Assays to P6scss the Carcinogenic Risk of Chemicals', I ARC Sci. Pub. NO. 12, 467-491, 1976. Zilfyan, V. N. et al., "Experimental Study of Chloroprene for Carelrncenicity", Vopr. Onkol. 23, 61-65, 1977. '2ilfya:i, V. et al., "Results of a Study of Chloroprene for Carcinogenicity", Zh. Eksp. Klin. Med. 1_5, 54-57, 1975. Lloyd, J. W., "Cancer Risks Among Workers Exposed to Chioroprsne", Ann. N. Y. Acad. Sci . 27_1 , 91-93, 1976. Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 164, 1975. ::MRC Source Assessment Data Base, July 1977. Fuller, B., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 442, 1976. 1`Radding, S. d., t al., "Review of the Environmental Fate of Selected Chemicals", NTIS No. PB 267 121, 1977. 1 * Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 1sVerschueren, X., Handbook of Environmental Data on Organic Chemicals, Van Noetxand Reinhold ,1977. 34 fMONSANTO RESEARCH CORPORATISM ' MONS 021947 frlilo Hop ifopine No reference to cjrcinoijenic or inutaqeme jaion of chloropropane could be found in Toxline, Cancer 1ino, or any of the other references consulted. It is probably a non-carcinoqen and will be considered as such for this project. 35 MONSANTO RESEARCH CORPORATION HONS 021946 Chrysene Chrysene (benz (a) phcnanthrene, CAS No. 218-01-9) is fairly well established as a weak carcinogen. It has produced skin tumors in mice following repeated painting ar.d 2-20 mg injected subcutaneously m :r.:ce produced tumors after a long inducticn period1. It is also a mutagen causing If,7 rovertants per microgram- . It is considered a probaole carcinogen for this project. Production and Perslstance Although chrysene is not a manufactured chemical, it is a product of combustion and found widely dispersed in the environ ment. In one test of automobile exhaust, 12 micrograms were found after one minute of operation'. In the atmosphere, 150190 ..g chrysene has been found per gram organic particulate matter1. It has a boiling point of 498C'. 1 "Chrysene" in iAPC Monographs or. the Evaluation of Carcino genic Risk of the Chemical to Man, Volume 3, 159-177, 1973. 'McCann, J., et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300 Chemicals", Proc. Nat. Acad. Sci., USA, 7_2 (12), 5135-5139, 1975. 3Verschuren, L., Handbook of Environmental Data on Organic Chariifcals, Van Nostrand Rsinnoid te., N. t., 1377. 36 MONSANTO RESEARCH CORPORATION MONS 021949 Cfcmehe pt^drbpajroxide Cu-v'uv hv.lrope roxide Mimorhy Hw-nzyl !..: rox 1 de t is cited as >' 1 ri' i notion but at 4 .mrt 90 m< did not mtiur.' statis tically yiunificant dominant lethal offe.Ls in mice1-'. Cumene hy.tvoj'oroxi do is said to cause neoplasms in nice both :>v mhnla- t: m at 104 mnkij1 and subcutaneously at 10 'ku ' , On file basis c: bo -two num.il studios, it is considered a possible :n rc ; notjon for 'his proieot.. ` P rod action and Pe rs i stance It :s estimated *hnt the i 9 74 prcduc t lor. was i.4 x 10-' K-;. Another estimate o: production' is 9,1 x i (T kv- per year with a production less factor of 0.013 or 1.3 x 10' Ky/year'. It has a taper iresauro of 1 mm at '0*C'. Because cf its low volatility and moderate solubility in water, it is not likely to remain in the atmosphere'. Photochemical and iiO radical reactions are likely pathways for transformation of peroxides in the atmosphere with a half-life of less than a few hours: . My stem, 3. 5. ar.d Shafr.er, . , "Chemical .Yutaeer.f in the H cr.ar. Mn.vi ronr.er. t " , Nature 2\ : , i?:--387, 1 363 . -Epstein, 5. A., et al . , "detect ion of Trentra. Mutagen? : . :r.o Dominant Lethal Assav in. V.ouse", Toxic:.. A col. Pharmacol. 3 3, 25c-:.:5, 19 "2. ' '?rc~ SZOSH Suspected Carcmctens - Radiation Research Su-cnie- nver.t ?, ** 5 V- i. `` 'FromNIOSM Suspected Carci.nocons - T. Nat. Cancer Inst, 37, 829, 1966. -- sRadding, S. B. et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. :Fuller, 8. et at., "Preliminary Scorina of Organic Air Pollutants", National Technical Information Service Nuiflber P3 264 442, 1976. 37 MONSANTO RESEARCH CORPORATION MONS 021950 DDT DDT {1,1,1-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 of dogs and monkeys 1 and in a differential growth E. coli (pol A) mutaaen test'. Given orally, it produced liver cell tumors in several strains o: mice and some of its metabolites produced lung tumors in mice-'. It is positive ir. a recessive lethal Drosophila test:. All things considered, it is probably a carcinogen and will be classified as one for this project. Production and Persistance In 1971, 2 x 107 Kg was the estimated production'. In 1971 it was found in the air in concentrations of 0.1 ng/m- to 1.56 .g/m3. The soil half life is estimated to be 15 years1. it has a vapor pressure1 of 1.9 x 10"7mm at 20"C and a melting point of 74C. "DDT and Associated Substances" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man" Volume- 5, 3 3-124, 1974. :Fluck, E. R., et al., "Evaluation of a DNA PolymeraseDeficient Mutant of E. Coli for the Rapid Detection of Carcinogens", Chem. Biol. Interact., 1, 219-231, 1976. -Vogel, E., "The Relation Between Mutational Pattern and Conceivtration by Chemical Mutagens in Drosophila", IARC Sci. Pub. No. 12, 117-137, 1976. 38 MONSANTO RESEARCH CORPORATION " HONS 021951 Cil-fcert-lftity II Pelrdxide Di-tert-buty1 peroxide (bis(1,1-dimethylethy1) peroxide, CAS No. 110-05-4) has been found to induce malignant lymphomas in 7/J5 mice which inhaled 100 mcM of this chemical1. Skin applications on mice did not prove to be carcinogenic'. (Tertbutyl hydroperoxide has also been found negative by skin application tests on mice-'*.) Di-tert-butyl peroxide is on a list of "suspected carcinogens" studied for enviror-ner. t a 1 fate'. Since the positive mice test results were by the inhalation route which has fewer false positives than injection, di-tort-butyl peroxide will be considered a possible caiemogen for this project. Considering the type and date (1961) of the positive tests, however, negative short term in vitro mutageni city data would probably chance its classification to a probablo non-carcinogen by the criteria used for this project. Production and Persis-ance Production is estimated to be 3 million pounds per year1. It is only slightly volatile but noderatly soluable in water. Thus most of the di-tert-buty1 peroxide will remain in the water system. In the water the presence of >1 ppm Fe * and Mr.'1 leads to dccompcs i 11 cr. tc acids and alcohols with ty -10 hours'. In the atmosphere photocher:eai and HO radical decomposition lead to a ti/y cf 79 hours-. :Kotin, P. and Falk, H. L., Sadist. Res. (Supp. 3), 193-211, 1963. (From PHS-149; Survey of Compounds Which Have Beer. Tested for Carcinogenic Activity.) -'Saffioti, IJ. and Shubik, P.. Nat. Cancer Inst. Monoo. , 10, 4u9-af/, l>dJ. (Fv'.t niC-149.) ?Hoshinc, H , et si., Gann 61 (2', 121-124, 1970. (From PHS-14S.) '`Van Duaren, B. L. , et al., J. Nat. Cancer Inst., 39.' 1217 1228, 1967. (From PHS-149.) sRadding, S. B., et al., "Review of the Environmental Fate of Selected Chwnr.uals", National Technical Information Service Number PB 267 121, 1977. 39 MONSANTO -RESEARCH ^CORPOHABlONftf- MONS 021952 Pi (2-EthylhcfcyljPhthalate Di (2 -cthylhexyl)phthalate { n :' 1 f', dioctyl phthalate, TOP, CAS Mo. 117-81-7 is a high -.'Dlurr plasticizer which had <n the uast been considered VI It sally non-toxic as j uriced by various acute aod chronic test s'. Alt ou-jh cirly an.'.r'.il tests (doq, uet.nea pio, rat) were i e : it i ve , at least one source ' now cites neoplastic effects m : a t . ora'ly h 'on 4 1.2 g.'kq t>.*6 weeks ) d j f 2-<" hylhc-xv 1) pht ha 1 ate . a l t : .ouch this dose is rather high, there are also several ref- or*1:* cos which show this chertical to be both mutsconic and t,:ra- to.:, It is therefore classed as a possible carcinogen for this project a least until the present rarcir.ocen bioassay be i r. g conducted is one 1 uded 1 '. , Production and Persista.nce It is estimated that 2.6 x 105 Kg DEHP is emitted per year from stationary sources1*. Other estimates are 2.C x 17* Kg produced and released 1: and 1.3 x 10* Kc produced m 19*4 :f. It is said to biodegrade rapidly m water and sludge- . In the air it reacts with the HO radical w\t.o a half-life of one day- . it has a bci'-i'.c ocint of 385C ar.d a vacor oressure of -- at 2oo"c''. ` '` Dec .i.-.ontat ion of the Threshold hint Values for fttstances i n Workroom Airi American Conference of Governmental industrial Hygienists, P. 96-97, 1976. S.hubik, P. et al., "Survey of Compounds Which have Been Tested for Carcinogenic Activity, Supplement I", National Technical "nfornation Service Number PB 216 248, 1967. Puller, B., et al., "Preliminary Scoring of Cruanic Air Pollu tants", National Technical Information Service Number pb 264 4 4 3, 19 /b . ``Singh, A. R., et al., "Mutagenic and Anti fertility Sensitivies of Mice to Di-2-Ethylhexyl Phthalate (DEHP) and Dimethoxyethyl Phthalate (DMEP1," Toxicol. Appl. Pharmacol. 29 (1), 35-46, 1974. `Mathur, S. P., "Respirometric Evidence of the Utilization of DiOctyl and Di-2 Ethyl hexyl r-halate Plasticizers", J. Environ. Qiial. 3(3) 207-^09, 1974. 40 MONSANTO RESEARCH CORPORA TiON HONS 021953 DI (2f Efchylhexyl) Phthalate Reference's - Continc J 6Peakall, 0. n., "Phthalate Esters: Oci-viilvicu and Bioloctical Effects", Rosni'je ev/:; 1-41, I 7 ~ 3. (1 ~ reference!'1 . "Recent Proves; u " ''il v !t : . :; e v:i P 1 a s t: c and Plastics n:u: r lie: t ? ':: i: .in" , Knvt ren . i o i 1 h. Pe r spec . 1_7 , 21 3 - 2'9 , 1 ' 7 C . 'Singh, A. R. , f. a!., of Mice to pht hoi 19.74. i Esters" , ' . Fertility Sons. 11 v. t r-s . An. i~. Sci . , 3R ( 1 ) , ? 16 , "Taylor, n . F. ir. : Ccvcran, F. F., " P : ndrmil 11 on of Phthalic Acids and Kster.n" , C - -. *. r-ac t No. from National Inst, of Env. Health Sci., 1975. ``Autain, .J. , "Toxicity and Hoalt.n Threits of Phthalate Esters" Review o: the i t r a: .re", i.-.vi rrr.. He ll .!: Perspec. 4, 3-26, 1973. ' : Vaoi, V., et : i . , " : r n c c ten . c 11 y "urauenicity c: a Phthalate Ester", To : jtolo.:. i 4 , C : > - J , 1 3 ' . : -Dill lnqhair., d Aetian, .:. , "7- r at-teen: ei tv, Met a .:-?n i city and Cell :1a: 7- ty Pn.thaljto Fste.-s", Environ, seal'.:: Pe r s pe c. 2 * ' - ' ^ ` ^ . ; 'Landon, J. 7., "Carc;:tcsor.es;s Sioass st 3: :2-EthyIhvxy11 Phthalate", Jor,: r.ict from Nat tom1. 7an.eer Institute to Tracer Jitco, Inc.,10'76-9'7'', 1977. ,UMRC Source Assessment Data Rase, July i?77. sBrown, S. L. et al., "Research Program on Hazard Priority P.ankinc of Manufactured Chemicals", National Technical Information Ser vice Number np Jr 3 ! ?, !?7S. Doiigan, J. et al., "Preliminary Scoring of Selected Oraanic Air Pollutants", N a * ion 11 Technical I r. f. mot ion Service Number pb 264 444, 1976. 17Saeger, V. W. and Tucker, E. S., "Biodegradation of Phthal ic Acid Esters in River Water and Activated Sludges", Appl. Environ. Microbiol. 31_ (1), 29-34, 1976. `8Verchucrcn, K., Handbook of Environmental Hata on Organic Chem icals , Van Nostirid keinhold to.. New York, 1977. 41 MONSANTO RESEARCH CORPORATION MONS 021954 2,1' -Di'amiriOaniao 1 e 2 , 4-Diaminoar.isolc (4-methoxy-m-pheny lened iarni ne! was nonmu tnuoni c in the 1.51173V mouse lymphoma cell test- and negative or. rat skin" ( ir. combination with other chemicals) and mouse sun 1 (the sulfate !or:n; carcinogen tests. It d:d no*, produce dominant letliai mutations in rats1*. It lias been shown to be nutaaenic in S. tyghimur i urv ** , usually with S-9 activatrcn. I: also induced sex-1 inked recessive lethal mutations m Drosophila malanocaster' (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 - 0.245) had an excess of site specific (thyroid and skin) malignant rumors'- ". Also two epidemiologic studies suggest excess cancer among cosmeto logists'. Di ami.noan l sole is on the NIOSH Safety Alert list for its carcinogenic potential and will be considered a probable carcinogen for this protect. Production and Persisiiar.ci N! 2SH .s unaware if any current domestic product tor. but cites that it is imported or. the ^rder of 25,000 pounds per year' . Palmer, K. A., : <j 1 . , "The Mutagenic Assay r>: Sene Hair Dye Components Cs-.-.u the Thyr.idtr.e Kinane Locus mi LSI 178V Mouse Lvmphoma Cells", (Meeting Abstract), Toxicol, Aopl. Pharmacol ij; (1) , 108 , 1976 . Xinkel, H. J. anc Holzmar.n, F.. , "Study of Lone-term Percuta neous Toxicity and Careincoor.iciiy of Hair Dyes (Oxidizing Dyes) in Rats", Food Cosir.et. Toxicol. 1_1 (4), 641-648, 1973. Burnett, C. ot al., "Long-Term Toxicity Studies on Oxidation Hair Dyes", Food Cosmet. Toxicol. 31^ (3), 353-357. 1975. 'Burnett, C. , -at al . , "Dominant Lethal Kutacenicity otedy on Hair Dyes", J. Toxicol. Environ. Health 2 (3), 657-662, 1977. ;Dybing, E. and Thorgeirsson, S. S., "Metabolic Activation of 2,3-Diaminoanisole, a Hair-Dye Component", Biochem Pharmacol. 26 (8) 729-734, 1977. "^byblng, E. and Aune, T., "Hexachlorobenzcne Induction of 2,4-Diaminoanisole Mutagenic *'* In Vitro", Acta Pharmacol. Toxical. 40(5), 575-583, 19'.. (24 references) 42 Monsanto research corporator MGNS 021955 2', 3-Diaminoanisole References - Continued 7Ames, B. N., et al., "Hair Dyes are Mutagenic. Identification of V.u or' Mutagenic Ingredients", Proc. Natl. Acad. Sci . ft'.S.A.) 72 (6) , 2423-2427, 1973. 8Blijleven, W. G., "Mutagenicity of Four Hair Dyes in Droso phila Melanogaster", Mutat. Res. 8 (2), 181-185, 1977. '"Health Hazards; 2,4-Diarainoanisole", Occupational Safety and Health Reporter, 7 (35), 1331, 1978. *0 "2,3-Diaaii.aanifole (4-raethoxy-m- phenyleneuiamine) in Hair and fur Dyes". Current Intelligence Bulletin 19, January 13, 197* 43 MONSANTO RESEARCH CJDRPOrtAYBSrt HONS 021956 tsss Uiazinon has boon i-:'o:io.l to bo slightly toratouenic in rats when given on the o!o ontli Jay or' gestation'. An increase in chromatid breaks has been noted i :i the lymphocytes of humans after inqesun of : r.c sprate insecticides including Diazinon' arid in cultivate: hunt lymphocytes . On the ot her ha no , ;. at::. o;; has been round . v me non-mutageni c in dal monel la typ.ho.~-.: ; u:~. mutation tests'. biacinon also uevs cause rut a t ions -ho 3-VT K'.coli test , the WP2 TRY - t. ; ' t col: test , other t.coli tests or a 5. cerevis;a- r: .-tic dene crn-.-c ; s : st . Tr.e majority cf the ::.:'crr.ation indicates that Oiazinon is prob ably not a carcmv Kimbrough, R. ". m. : ' a ir.es, T. 3., "effect of Orcanic Phosphor ous Compounds and. A1 vl atinu Acents on the ?.a: fetus", Arch, lav: rot'. Health, >, 335-80S, 1968. T r i n ft-Van-3ac , o t .1., "Chroroscr.e Abe rr it: eras in Patients Suffering Acute ; r ran i.c Phosphate insecticide Intoxication", Humanger.et i V. 2, 19 '4 . Tzoneva-Maneva, V. 7. et al., "Influence of Diazinon and Lir.dane on the Mitotic Activity and the Caryotype of Human Lymphocytes, Cultivated - ", Dibl. iiaenatoi. Basel, 3J3 (1) 344- 34 7, 1971 . 'Marshall, T. u. et "Screening of Pesticides tor Mutagenic Potential Us ins Salmonella Tvohimuriurn Mutants", J. Agric. Food Chen. 2_1_, 560-56 3, 19 "6. 'Mohn, G. , "5-Methvltrvstophan Resistance Mutations in Escherichia Coli K-12", Mutat. Research 20 (1), 7-15, 1973. ` Ashwood-Smith, M. J., et al,, "Mutaaenicity of Dichlorvous", Mature 240, 418-419, 1972. ?Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chwdc*lCarcinogenesis Essays, 1ARC Sci. Pub. J4o* 10, 1974. . 44 MONSANTO RESEARCH CORPORATION MONS 021957 O-Dichloroben zone A negative animal study of o-dichlorobcnzene (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 repotted, but with insufficient supporting evidence to chow cause and effect . A few f .. tests have been conducted . in. Aspergillus nidulans, 200 mg/ ml for 60 minutes causes an increase in reversion to methionine prototropy from 2.\10'- to 5x10' reversions' . It was r.eoative in a S. typhimurium spot test at 1 --r ul in eight strains' . Be cause of the limited positive test data on systems which have not been extensively evaluated, o-diehiorobenzene will be considered a probable non-caicinccer. (with some significant positive data) for this project. 'Survey of Compounds Which Have Peer. Tested :-r Carcinogen;.; Activity, NCI, P)S-li9, Volume :"0rtho- and para-Dichlorobenzem s ', :r. iA AC Monographs or the Evaluation of Carcinogenic Risk cf Chemicals to Man, Vc 1 7, 2 31 -- 24*1, 1974 . 3Guerin, M., et ai., "Inhibitory Action of Chemical Carcinogens on Mi toris of Rat Lung Cell Cultures. 2. Comparative Study of Carcinogenic and Noncarcinogenic Substances," C. R. Soc. Biol. 165, 2255-2258, 1971. huosad, I., "Mutagenic Effects of the Herbicide 3`, Dichloro-prcpiononiiide and its Degradation Products," Can. J. Microbiol. 1JS, 369-372, 1970. -Prasad I., ?nd Pramer, D., "Mutagenic Activity of Some Chloroanilines and Chlorobenzenes," Genetics, 60, 212-213, 1968. fcAllport, J., et el., "A Study of Industrial Da^a on Candidate Chemicals for Testing," National Technical Information Service dumber PB 274 264, 197J. . 45 MONSANTO RESEARCH CORPORATION HONS 021958 g-f afbnitorc>nztnc Many negative animal studies of p-dichlorobenzene (CAS No. 106- 10-7) have been conducted1, but all of them have been short term (<9 months) studies which would not be expected to show carcinogenici *:y. A few positive case studies have been reported but with insufficient supporting evidence to show cause and effect' . A few J : tests have been conducted . It is reported that p-dichlorobenzene is mutagen to higher plants and causes chromoscr.ial breaks'". In Aspcruillus nidulans, 200 mg/ml for 60 minutes causes an increase ir. reversion to methi onine prototrdpy from 3x10' to llxl0` reversions'. Because of the limited positive test data on systems winch have not been extensively evaluated, p-dichlorobenzene will be considered a probable non-carcir.cgen (with some significant positive data) for this project. '* Survey of Cc.~.;zounds which Have seer. Tested for Carcinogenic Activity, NCI, rhS-:-:9, Volumes 1. 1, mi 3. "ortho- and ^ ara-T ichlcrcbenzer.es, " m IAHC Monographs on the Evaluation cf Carcinogenic Risk or Chemicals to Man, Volume 7, 231-244, 1974. " ' Guerin, >t., ot a 1., "Inhibitory Action of Chemical Carcinogens on Mitosis of ?.at Lung Cell Cultures. 2. Comparative Study of Carcinoaenic and Ncr.carcir.ogenic Substances," C. R. Soc. Biol. 165, 2255-2258, 1971. "Prasad, I., "Mutagenic Effects of the Herbicide 3', 4*Dichloro-propionanilide and its Degradation Products," Can. J. Microbiol. 1_6, 369-372, 1970. ''Prasad, I., and Pramer, D., ".Mutacemc Activity of Some^ Chloroonilines anc Chlorobenzenes," Genetics, 6_0, 212-213, .'368 Brown, S. L.. et al., "Research Program on Hazard priority Ranking of Manufactured Chemicals," National Technical infor mation Service Number PB 263 162, 1975. 7Aliport# J., et al., "A Study of Industrial Data on Candidate Chemical* for Testing," National Technical Information Service Numbexk PB. 74r264 . 1977. 46 KTMMMMrgllESEAmeM 'CORPORATION > MONS 021959 jP10*dit>b*nfc l dfena 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 oral administration . Many other positive responses are noted in Toxline and Cancer line and it is considered a probable carcinogen for this project. Production and Persistence It is estimated that 2.1 x 1011 Kg is produced per year with 4.5 x 10 ' Kg per year released2. Other estimates of production are 1.6 x 10 c' Kc in 1971 ! and 2.1 x 10' Kg per year-. Di chloro benzene is somewhat reactive towards RO- (t 1/2 - -JC davs) arid very reactive towards HO and 03 (t = 1 day)-. its mating point is 133C1. ' l"3,3'-Dichlorobenzidine" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 4, 49-55 , r9"74. "otul'u, E. F., et a).., "Experimental Neoplasia in Rats from Oral Administration cf 3,3-Dichlorobonzidinr. . .", Toxicol. Appl. Pharmacol. 31 (1) 159-176, 1975. 'Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Informa tion service Number PB 263 163, 1975. `Fuller, B., et ai , 'Preliminary Scoring of Organic Air Pollu tants", National Technical Information Service Number PB 264 442C 497C. ' 47 fuoiNSANTO RESEARCH CORPORATION ' HONS 021960 1,4-Dichlorobut''ne-2 is a mutagen of Salmonella typhimurium with microtomes enhancing the effect1. 3,4-Dichlorobutene-1 is also , a mutagen in that system with or without NADP, giving 490 reverts/ .mol with NADP and 345 rcverts/'.mol without NADP1 . Trans-1,4- dichlorobutem.'-/ has been found to be a weak carcinogen to ICR/HA Swiss mice when given by subcutaneous in;oc:ion or bv interparenta 1 injection but not by skin application- . It was found not to be . a tumor initial r n a two-stage test . Hecause of the carcino genic and xti.ri' data, it has bee- : 1 a -ori or. the probable car cinogen list for this project. Production and Persistance It is estimated that 8.7 x 10- Kg is emitted per year in the manu facture cf polychloroprene `, and has a coiling point of 158C*. Sartsch, It. et al., "Alkylating and Mutagenic Metabolites of Halogegatad Olefins Produced by Human and Animal Tissues", Pros. Am. Assoc. Cancer Res. 1_7, 17, 19 76. :Van Duuren, B. L. et al., "Carcinogenic Activity oi Di and Tri functional a Chloro Ethers and of l,4-Dichlotobutene-2 in 1 CR/ HA Swiss Mice", Cancer Research 3j>, 2553-2557, 1975. 3MRC Source Assessment Data Base, July 1977. ``Verschueren, K., Handbook of Environmental Data on Organic Chemicals,. Van Nostrand Reinhold Co., N. 48 MONSANTO RESEARCH CORPORASBJN1* 0Zl9bl MONS M ch 1 ort>dl I yuoy<<ne Qiaije Dichlorodifluoromethanc (Freon-12) has been shown to be non-muta- genic in s. typhimuriun tests1 but may cause some (mutagenic?) changes in conidia formation in Neuro3pora crassa7. More infor- -n =3 aticn is needed on the mutagenic and carcinogenic potential of icons. No other information could be found on Cancerline or Tox line. At the pres-nt time, it appears as if Freons are non- carcinoqens.* 49 ;Andrews, ^ V. , et al., "The Identification of Endogenous and Exogenous Mutagenic Compounds", 4th Carcinogenesis 3ioassay Program, Orlando, Florida, February 1976. `Stevens, S., et al.r "Phenotypic and Genetic Effects in Neurospora Crassa Produced by Selected Gases and Gases Mixed with Oxygen", Develop. Ind. Microbiol., 12, 346-353, 1971. 49 ^MONSANTO eESeAOOl'tOnPORATlON'* HONS 021962 ifl-Olch U rotfnane The primary reference cited for I,1-dichloroethane (CAS No. 75*4 -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 or. 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 henangiosarcomas among female rats and a statistically significant increase in the incidence of endometrial stromal polyps among dosed femaie mice. For this project it will bo classified as a possible carcinogen. Production and Persistance It is estimated that 2.6 x 10' Kg of dichloroethane is emitted per year from stationary sources'. 50*. of the 1,1-dichloroethane will evaporate from a 1 ppm water solution at 25C in 22 minutes'". It has a boilmc point of 57.3C and a vapor pressure of 180 mm at 20*C". 'Schwetz, B. A., et al., "Embro- and Fetotoxicity of Inhaled Carbon Tetrachloride, 1,1-Dichloroethane and Methyl Ethyl Ketone in Pats", Toxicol. Appl. Pharmol., 29_, 452-464 , 1974. 'National Cancer Institute Draft Summaries of Bioassay Reports, 1,1-bichloroethanfe", Chemical Rec. Rep. (45), 1597-1598, 1973. ' 3MRC Source Assessment Data Base, July 1977. kvrschueren, K., Handbook of Environmental Pete on Organic Chemicals, Van Nostrand Rainhold Co., N. Y., 1977. 50 MONSANTO1 RESEARCH EORpCRATlOlfli MQNS 021963 Dichloronapthoquinone Dichloronapthoquinone (Dichlone) did not cause point mutation in a microbial test system'. 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 controls-. 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 emitted from stationary sources3. Dichloronapthoquinone has a melting point of 193C and a 7.84 vapor density1".I * 3 I An*ieijo;i, K. .1. (*i al., "Fvaluation of Herbicides for Possible Mutagenic Properties", J. Aar. Food Chem. 20, 649-656, 1972. 'Evaluation oi Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Technical Information Service Number PB-223 159, 1968. 3mrc Source Assessment Data Base, July 1977. II varschueren, A., Handbook of Environmental Data on Organic Chemicals. Vn Noacrand Re inHoi3 Co., tf. ,Y., 1977. ' 51 ' MONSANTO RESEARCH CORPORATION m HONS 021964 Da.ctfl.6ropheftdl Nothing was found in Cancerline to indicate that dichlorophenol is a carcinogen or a mutagen. A 1959 reference' (1*) cit'ed'in the N1 OSH Suspected Carcinogens list shows 2,4-dichlorophenol may be a promoter or co-carcinogen when applied to the skin of mice in combination with benzene and dimethylbenzanthracine. Other than .he above reference, dichlcrophencl is not listed in the "Survey of Compounds which have been Tested for Carcinogenic Activity", because of the lack of data, dichlorophenol has been placed on the probable no.n-carcinoge.n list as a possible promoter. Boutwell, R. K. and Borch, 0. K., "The Tumor-Promoting Action of Phenol end Related Compounds for Mouse Skin", Cancer Research IS, 413-42?, 1959. 52 bllfe>AslUQWBSkeARC>CDRPpRA<DW MQNS 021965 Dlchloropropene : , J-Dichloroproc>ene at 1 ppm for six months has shown to have no adverse effects'. Both the cis .and trans isomers are'mutagenic to TA1535 and TA100 S. typhimurium strains without activationJ"l`. It will be considered a possible carcinogen for this project. Production and Persistance It is estimated that 6 x 107 pounds of a dich1oropropane/ dichlotopropene mixture is manufactured a year'1. Assuming 50% dichlorcpropene, 1 x 107 pounds is released a year. It is said to react with OH and 03 with a tj/2 = 3 days, and in water ti/2 = 7 days5. It has a boiling point of 104C and 50% of a 1 ppm water solution will evaporate in 31 minutes^. 'Torkelson, T. R. and Oyen, F., "The Toxicity of 1,3-Dichloropropene as Determined by Repeated Exposure of Laboratory Animals", Am. Indust. Hyg. Assoc. J., 3j[ (5), 217, 1977. :DeLorenzo, F., et al., "Mutagenicity of Pesticides Containing l,3-0ichloropropene" Cancer Res., 3j_ (6), 1915-1917 , 1977. 3Bignami, M., et al., "Relationship Between Chemical Structure and Mutagenic Activity in Some Pesticides: The Use of Salmo nella Typhimurium and Aspergillus Nidulans", Mutat. Res. 46 (3), 2a3-.-,44, 1977. vH'udecher. T. , et al., "In Vitro Mutagenicity of the Soil Nematicide 1,3-Dichloroprooene", Experiei.tia, 33 (8), 1084 1085, 1977. ~ 5Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 162, 1975. H'erschueren, *., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co,. K. Y.. .19177. 53 MONSANTO *EKA*CH*Cl>P6RATlbtf * HONS 021966 Dichloropropionlc Acid Dichloropropionic acid (Dalapon) is a herbicide which has been found non-mutagenic In a S. typhimurium test1. No other signif icant data have been found, so it has been placed on the probable non-carcinogen list. 1 Anderson, K. J., at al., "Evaluation of Herbicides for Possible Mutagenic Properties", J. Agr. Food Chem., 20, 649-65*, 1972., 54 |*fertsrfr# pESfAnCHfcoilPO^AfrlO* HONS 021967 Dlchlorovtnyl Dimethyl Phoaphato (Dlchlorvoa) Dichloroviny1 dimethyl phosphate (DDP) hae boon shown to bo muta genic in many different short-term teste1, including S.typhimurium tests'', but haa been shown to be non-cercinogenic by oral and in halation studies in rata and mice1. Because of the mutagen studies, DDP is to be listed i,n the possible carcinogen list, for this project Production and Persvstance It is estimated that 200 Kg/year is emitted from stationary sources1'. It has a boiling point of 120"C at 14 mm' . Fahrig, R., "Comparative Mutagenicity Studies with Pesticides", in Chemical Carcinocenesis Fssays, IARC Scientific Publication No. 10, p. 161-181, 19'4. Shiraser, Y., et al., "Mutagenicity Screening of Pesticides in the Microbial System", Mutat. Res. 0, 19-30, 1976. -Dioassay of Dichlorvos for Possible Carcinoyenicity, CAS No. 62 73-7", National Cancer Institute NCI-CG-TR-10, National Technical Information Service Number PB-270 937/656, 1977. * . t t |* fcMRC Svurce Assessment Data Base, July 1977. Werscbuaran, K., Handbook of Environmental Data on Organic ChemLcals* Van Nostrand Relnhoid co... N.~ l.. 19/17.' 55 >dNlAiiTaimscHCI C<**OR|Tjof< b MONS 021968 Dimethylacetamide Dimethylacetamide was negative in an mitotic index test for epidermal hyperplasia*. It is cited in the NIOSH Registry of Toxic Effects of Chemical Substances as being teratogenic to rats after I.P. injection. One reference was found in the Survey of Chemical Substances Which Have Been Tested for Carcinogenic Activity (19CS-1969) in which rats were given the chemical ;ntergastrically at 0.1 - 30 mg/d. for 260 doses2. The tumors found do not appear to be related to dose. No other references could be found in Cancerline or Toxline which would suggest that dimethylasetamide is a mutagen or a carcinogen, so it will be classified as a probable non-carcinogen for this project. Rieger, M. M., 'Cosmetic Science: 1975 Literature Survey", Cosmet. Perfum. , 9_1 (4), 25-36, 1976. -Hadidian*, 1968. , et al., " J. Nat. Cancer Inst., 41 (4), 985-1036, S6 RtSEAPCH C0P*t08vrg>v | MONS 021969 Dimethylamlne Dimei-hy lamine (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 dimethylnit rosamine or r.itrosodimethylomine (more than 20 references in Toxline). Dimethy lamme may a 1 :so combine with ozone and nitrogen tetroxide in the atr.osphe rc '. In Toxline and Cancerline there are and 16 re fe ren.ee s respectively which deal with mutagenic or carcinoaenic aspects of dine thylamine. These references, along with those in chemical Abstracts apooar to indicate that althouqh dimethy lair.me is a potent co-carc mogon, it is not by itself carcinogenic. For this project, it will be considered a non-carcinogen but will be considered when cofactors are evaluated. 'Dusnutm, F.. K. an.: iv-ach, :. J., " : he Rale of the Reaction of Dime thylamhe-with Nitrogen .Tetroxide and Ozone in Atmospheric Pollution" , fGig.t Sahit. | 7, J 1-5-13,; 19 76. o. pqNS*f<TOf^ES3ARCh corporation* T | HONS 021970 Dl%thylhydrazine 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 me'kg dimethylhydrazine2. Many other positive references are found in Toxline and Cance-line and it is considered a probable carcinocer. for this project. Production and Persistance Production is estimated at <5 x 105 Ku m 1973- with j 1.7'. fraction of d i spers ion1*. Since it is polar, non-volati le , and soluble in water, there would not be a significant transfer to the atmosphere'. It reacts with oxidizing materials in the at mosphere1' and has an expected half life of 2.1 hours by' reaction with the HO radical'. Dimethylhydrazine has a boiling point ci 6 3.3*C and a vapor pressure e* 157 m- at 25"C1'. : " 1,1-Dinethy lhydraz ine' in 1APC Xcn.'.-rjt.-.s rn the Eva luat; nr. r : Carcinogenic Els'* of ChemicaTTTo yr,,' Volume 4. 137-14?, : 'a-g. "Wilson, R. B., "Species Variaticr pcr.se to Dimethvihvdrazine", Toxicol. Appl. Pharmacol. 38(3), b-J'-hSi, 1976. ' *tedding, S. B., et al., "Review of the (environmental Fate of Selected Chemicala", National Technical Information Service Nunber PB 267 121, 1977. I. J,, et al. ,;"Preliminary Sc cring of Selected Organic ^Nation ill T^chqical Information Service Number 58 g M(9<SA|rqDinKSE4ftCH corporation > HONS 02X971 Dinitrotoluene 2,4-Dinitrotoluene has been found by the National Cancer Insti tute to be non-carcinoqenic to mice but carcinogenic to rats*. It has been placed on the probable carcinogen list for this oroject. Production and Persistance It is estimated that 100 Kg dinitrotoluene is emitted per year frm stationary sources-. It has a boiling point of 300*c*. "National Cancer Institute Craft Sururanes of lUoassay Reports 2,4-Dinitrotolueno", chen. <>eg. Rep> (45)^ 1598( 1978_ MRC SofliMb Aaaaafeaent Data Base, July 19 77'. Verschucren ( K., .!!.ir.J:.co< a:' ~r.v. rsr. mental Chemical^, i^aR Npstrand ReinhcTiTCo., ,fl. ,'i., on Organic " 55 aowsA-noiRE5Eanca corporation!*! MONS 021972 Dioxanc and guinea-piqs3 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'1. For this project, it is considered a probable carcinoqen. Production and Persistence The 1 972 production has been estimated to be 6.3 x 10'-' Ka'-r >' and the 1973 production of 7.4 x 13' Ku', with most of this being released to the environment". In the atmosphere it reacts with the HO radical with a half-life of 9.6 hours*'-. It has a boilino point of 101'C and a vapor pressure of 30 mm at 20C and 3 7- 39 mm at 25"C!*S'". Kociha, R. J. et al., " 1,4--icxar.e : Correlation of the Results of Chronic Ingestion and Ir.r.a I at : ~r. Studies with its Oose- Dependa.it Fate n Rats', Aercsc. >Vd. Res. Eab- -Tech. Rer. > A.VRl. TR-125, 346-354, 1975. * ' Argus, X. F. , et al., "Dose-?< sper .-o ani Cl trastructural Alter natives m Dioxane Carcinecer.es : s " , Eur. J. Cancer 9 ,4), 2 37 24 J, 1973. ' " 1,4-Dioxa:ie', m 1 ARC Mor.ocrat'hs on the Evaluation of Carcino genic Risk of Chemicals to .Van, Ycl. 11, 247-256, 1976. 'Torkeison. T. R. et al., * 1, 4 - Cicxar.e. 11. 2-Year inhalation .*tudy in Rats', Toxicol. Atrl. Pharmacol. 30 (23, 287-298. 1974. '-- 'Doriga.n, J. et al., 'Preliminary Scoring of su.ected Organic Air Pollutants", National Technical Information Service Number PB 264 444, 1976. *Prown, S. 1.. e| *4viorch Pr9raro on Hazard Priority # Ranking of Manufactured Chemicals", National Technical* Infor mation Service Nuaber PB 263 164, 1975. nvirrr.mental .Data on Organic riheidi CCut 4 New Tctki 1$7&. of**!* nsAR>6 c*>*otA(ribif < MONS 021973 Diphenyl Oxide Mo 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 Beer. Tested for Carcinogenic Activity (Volumes it is, therefore, listed as a probable non-cnrc:nogon for this project. 61 P|Mo|<SA4Tfc RlSC^RCH COpiJORATlOt* MONS 021974 Disodium Methanearsonate Disodium methanearsonate has been cited as being carcinogenic, but no further data is given m this reference'. It has been found to be non-mutagemc when tested with 5 Strains of S. typhimur ium, mitotic recombination of S. cerevis: j<_> und relative toxicity assays in E. coli and 3. subtilis". Ir. all tests except the B. subtilis, the Chemical was tested using the S-9 microtome activation. Methanearsonates have also been tested for mutagenesis by other authors'1'. The lack of confirming data from Toxline or Caneerlir.v ir..: a;l other mcicat '.ms other than the first reference demonstrate that this chemical is probably a non-carcinogen. Fuller. 9., et al., V: el ir.;.-.irv Srcrir.a o: .''rcar.ic Air Pollutants", National Technic:: : rfcrr.it: or. Service i~.be r PB 264 442, 1976. Sin-son, V. F., et al., "in Vitro Mutagenic Studies r: Twenty Pesticides", Toxicol. Appl. r.-.arr arc:., 3^ U', 'Shirauu, Y., et al., "Mutagen:c:ty Screening of Pesticides in the Microbial System", Mutat. Res., 40, 19-30, 13Tb. V. Jerson, K. J., et al., "Evaluation of Herbicides for Possible Mutagenic Properties", J. Agr. Food Che.-.., 20, 649-6S6, 1972. 2 a,<ONSA>iTotRE%E4ftci) cc^gcR^Ticti MONS 021975 Pursban 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. tyohimurium assays or on the mitotic recombination of S. cerevisiae*. It is considered a non-carcinogen for this project. 1 Simoon, vf P., et/ al., mSn Yitrc Mutagenic Studies of Twenty Pesticide**, ;TpxiiCOL.iAPDl. Pharmacol. 37 (1), 109, 1976. 3 MGNS 021976 Endosulfan Endosulfan has been found to marginally increase (P = 0.05) the total number of tumor* and the pulmonary ^enomas in mice given the compound orally1. Endosulfan has been found to be non-mutagenic in three different E. Coli mutagen tests'. In a national Cancer Institute study3, endosulfan was found to be non-carcinoger.ic 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, Teratcconic, and Mutagenic Activ ities of Selected Pesticides and Industrial Chemicals', National Technical Information Service NurJbor PB -11)159, 1168. *PahrUtF 'Coe^arttii*^ Mtftlgehic Studies with Pesticides* in Chemical Carcinogen Essays. iajc Sci. Pub. No. 10, 1974. National oncer Institute Draft Furr urion of Bioass vy Fe-uor.s', Chepi 4 fee*. Rep. 1 (If)1161*1^09 a 1178. 61 |* (MhfCiaHSe ftA(t<V'lce*P6HAti4r'*< I MONS 021977 Endrin Endrin (CAS No. 72-20-9) has been reported to cause chromosome breakage in cells1. Endrin was non-mutagenic by a S.typhimurium test using mouse liver micronomes and has tested negative on se"eral E. coli tests5. Rat feeding studies (up to 100 ppm) showed no increase in tumor incidence1*. Endrin will be considered a probable non-carcinogen for this project. Grant, W. F., "Cytological Effects of Environmentr 1 MutacensPesticides," Mutat, Res. 2 (4), 221,222, 1973. Van DVfck, P. and Van de Yoorde, H., "Mutagenicity Versus Carcinogenicity of Organochloride Inpectacidcs", Meded. Fac. Landbouwwet., Rijksuniv, Gent., 1 (2), part 2, 1491-1498, 1976. 7r'ahrig, R., 'Comparative Mutagenicity Studies with Pesticides", in IARC Sci. Pub..No, 10, 161-181, 1974. ''"Endrin" in IARC Monographs on the Evaluation of Carcinogenic Risk of ChemicalsitoiMan* Volume S, 157-171, 1974. 65 I ItdtAANtCS RESEARCH c6a>6ATI$nJ Jf HONS 021978 Epichlorohydrin Epichlorohydrin (chloromethy1 oxirane, l-chloro-2,3-epoxypropane, CAS No. 106-89-8) has been reported to be carcino genic in mice by subcutaneous injection and active as an initi ator in a t\vo-3tage skin carcinogenesis study in mice1. Epichlo.'Ohydrin is also a typhimuriun causing chromosome aberrations, mutatinuS. typhimuriun in a host mediated assay and E. coli, and Neurospera crassa?. It will be considered a probable carci nogen for this proKrt. Production and Persistance It is estimated that 2.2 x 10' Kg is emitted per year'. Pro duction in 1973 was estimated1*- *' to be 1.6 x 10- Kg, 1.5 x 10s Kg and 8.2 x Kg on another recent estimate- of 2.2 x 10s Kg. The production : * expected to grow 4-51 a year". In the atmosphere epoxides have a half life of 3 to 11 hours'. Epichlorohydrin has a boiling point of 117"c and a vapcr pressure of 12 rut at 2I'CC' . 1"Epichlorohydrin" in IASC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to M.an, Volume 11, 131-139. 1976. -Allport. J-, ct al., "A Study cf Industrial Data or. Candidate Chemicals for Testing", National Technical Information Service Number PB 274 254, 1977. :.HRC Source Assessment Data Base, July 1977. 'Raddinc, S. B., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. *Fuller, B., et al.f "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number Pi C6C 442, 1976. 6Verachueren, X., Handbook of Environmental Data on Organic \ iVai .Nitr*nd.Heiohold.Co* . N. Y. . 1977. 66 pEst^iacoppio6>a-ioe MONS 021979 Eptam Eptam (ethyl di-n-propylthiocarbamate, CAS No. 759-94-4) waa negative in a bone marrow chromosomal aberration test when fed to rots at 1/5 LD50 (LD50 If30 mg/Kg)1. Eptam may have had an effect on Vicia faba2. It 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 agent"*. Neither of these primary references could be found on Cancer)ine, 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. Kurmnyi, A. I., "Mutagenic Activity of Seme Pesticides, Derivatives of Urea, Carbamic and Thiocarbamic Acids", Tsitol. Scr.ot. H (4 ), 357-359, 1977. Hakeok, H. and Shehab, A,, "Cytolocical Effects of Eptam and Cotoran on Vicia Faba", Egypt. J. aot., 16 (1-3), 303-311, 1974. -- Jurek, A.-, "Carcinogenicity of Pesticides", Roczn. Panstw. Zakl. (5), f6}-576, 1974. Dongan, J., sc al., "Preliminary Scoring of Selected Air Pollutants, Appendix! IV* National Technical. Information Servige Number 1JB 1976 67 4 4i<**<t<ltes#i4cHcO'tPOf4t>Ore4 HONS 021980 Ethanol Much has b^on written about the mutagenicity or carcinogenicity of ethanol (87 references in Toxline) with both positive2 and negativg results. It has been tested extensively in animal systems . In general it is considered a non-carcinogen and non-wut;gen 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 SXerfuing, S., "The toxicity of Ethar.ol. A Tentative RisX Evaluation," Adv. Exp. Med. Biol., 85B, 403-419. 1977. (57 references' ^Braun, R. and Schoeneick, 7. "Influences of Ethanol and Carbon Tetrachloride on the Mutagenic selectivity of Cyclophosphamide m the Host-Mediated Assay* with Salmonella Tvphimurium," Mutat, Res. 31 (3), 191-194, 1975. * 3Charbey, R.C., et al.f "Evaluation of the Effect of Ethanol on the Frequency of Miar6mlei *in the Bone Marrow of .Swiss, Mice, * Mutat. Res. 43 <3). 441,444, 1977. '`Survey of Compounds Which have Been Tested for Carcinogenic Activity, >NHj MSrl*t ^oUoesi i. 1 3. 3. 4..a,. 6,: *nd 7. SB J 4o1*4t*> fefcKRM <fo*oMr|>* HONS 021981 Ethyl Benzene No data have been found to indicate that ethyl benzene is a muta gen or a carcinogen. A review of its use as a fracrance is noted1. Ethyl benzene has been found non-carcinogenic to rats, guinea pig, rabbit and monkey by inhalation and to rats orally?. it is negative on the viral enhancement of hamster cell transformation'. It is therefore classified as a non-carcinogen for this project. 'Opdyke, Dl. L., "Monographs on Fragrance Raw Materials Ethyll^enzene'y Qpod Coapet. Toxicol. 1_3, Suppl., 801-334, 1975. `Brown, S. D., et el., "Research Program on Hazard Priority Nanking pfManufactured Chemicalf', National Technical InforigationSaruice Number. PS 203 161, 19^3. ^terfcdnkl cdimfirbcationl from '31 C? ,ct$ton on-9 Februarv 1374. 69 xftfpkhTa ESAR4ict>ifpoAr>e* > ; MONS 021982 Ethylene No data was fourri 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 MONS 021983 Ethylene Dibromide Ethylene dibromide (1,2-dibromoethane, ethylene bromide, CAS No. 106-93-4) has been found to produce squamous-cell carcino mas of the forestomach in mice and rats after its oral adminstration*. It has also been reported to be mutagenic in Salmonella typhimurium, Escherichia coli, Neurospora crassa, Saccharomyces cerevisiao, Tradescantia, serratia narcescens, and Drosophila melanogaster test systems2<3> u . Ethylene dibromide will be considered a probable carcinogen for this project. Production and Persistance It is estimated that 8.9 x 105 Kg of ethylene dibromide is emitted per year from stationary sources-. Another reference cites a production of 1.'43 x 10' Kg with 1.38 x 109 Kg released''. Other references cite production of 1.5 x 109 Kg (1974 ) '> , 1.4 x 10' Kg; , and 1.5 x 103 Kg, 1.2 x i09 Kg for 1974 and 1975-. The use of ethylene dibromide in gasoline 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 abo''e animal studies-. Its air pollution potential has been assessed". 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 mm at 25C'. "Ethylene Dibromide", in IARC Monographs or. the Evaluation of the Carcinogenic Risk of Chemicals to Man, Volume 15, 195-209, 19'7. Ailport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testina", National Technical Information Service Number PB 274 264, 1577. :Fishbein, b., "Industrial Mutagens and Potential Mutagens I. !(a iogenated Aliphatic Derivatives", Mutat. Res. 3_2, 267-308 , 1976. "Johns, R., "Air Pollution Assessment of Ethylene Dibromide", National Technical Information Service Number PB 256 736, 1976. -MRC Source Assessment Data Base, July 1977. 6Brown, .L. L- , et al., ^ResearchjHroqram on Hazard Priority Ranking of Manufactured Chemical^1 .National Technical -Infor mation Service Number PB 263 161, 1975. 7 Padding, S., B.:, at al. , ,"Reviewjdf the.Environmental Fate rof Selected Chproijcalfsf , National jTfAhlcal unfornwtion Service .Vuinbe r * PB 17 1977.' n HONS 021984 Ethylene Dibromide References - Continued 'ruller, B., et al., 'Preliminary Scoring of 'Organic Air Pollutants", National Technical information Service Number BB 264 442,. 1976. 12 i<QNSAti-co|nrv4Rcti coneoRTioa MONS 021985 Ethylene Dlchlori.de 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 flies2 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 irJ Kg released1', 4.2 x 10? Kg (1973) : produced, and production of 4.2 x 10' Kg, 3.6 x 10? Kg, and 3.6 x 10- Kg in 1974, 1975, and 1976r . An air pollution assessment of ethylene dichloride has been made". Ethylene dichlortde reacts slowly with provides with a half life of 1000 days and is resistant to photochemical degradation-. The HO reaction half life has bee.", estimated to be 2 34 hours". It has a boiling point of 83.5C and a vapor pressure of 61 mm at 20C9. '"New Findings on Two Carcinogens Reported to Subcommittee by NIOSH", OccuDational Safety & Health Reporter 7 (35) 1331, 1978. ' " `Johns, R., "Air Pollution Assessment of Ethylene Dichloride", National Technical Information Service Number PB 256 733, 1976. }MRC Source Assessment Data Base, July 1977. "Brown, S. L., et al., "Research Program on Ha.ard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. 50origcn, J., et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 274 264, 197". 6Radding`, S, B., et al., "Review of the Environmental Fate of Selected Cheai^aljp? 4 National Technical Information Service Number PB 26? 121* 1?77. 'vovschuoren, K., Handbook of Environmental Data on Organic Chemicals; .VanA Ngfet4a#d fleinfold Co.7 N. V., 1977. 73 P4s<Ata<lHldb'{pb4Afr'M 021986 mons Although ethylene glycol (1,2-ethanediol) has been reported to give neoplastic effects at 4 gm/kg on mouse skin1, no other con firming reports of carcinoqenicity or mutagenicity have been found. Many reports indicate that ethylene qlycol 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 sults- . Mori' recently, tests eluding subcutaneous and inhalation tests monkey". It is also All in all, ethylene for this project. have been negative for ethylene glycol3 in rat tests'", subcutaneous newborn mice tests3 using rat, guinea pig, rabbit, doq, and negative in the Salmonella test for mutagens glycol will be considered a non-carcinogen a ' teller, B. et al., "Preliminary Scoring of Ormnic Air Pollutants", National Technical Information Service Number PB 264 444, 1976. Hartwell, J. L,., "Survey of Compounds Which ikive Been Tested for Carcinogenic Activity", National Technical Informational Service Number TB 216 478, Page 36, 1951. 'Horburgor, F., "Carcinogenicity of Several Compounds", National Technical Information Service Number PB 183 027, 26 pp., 1968. "Mason, 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. ' Dorse, P. H. , "Injection of Newborn Mice with Sever. Chemical Ad juvants to Help Determine Their Safety", National Technical In formation Service Number PB 195 153, 135 pp., 1969. *Coon, R. , et al., "Animal Inhalation Studies on Ammonia, Ethylene Glycol, Formaldehyde, Dimethylamine, and Ethanol", Toxicol. Appl. Pharmacol. 1_6 C3> , 646-645, 1970. 7McCann, J., et al., ."Detection of Carcinogens as Mutagens in the Salmonella/Microsom* Teat: Assay of 300 Chemicals", Proc. Nat. /\cad., Sci. (USA) 72 .(12), 5173-5139, 1975. *Ap.lpojrt,f^, at 41A , l"A jStudv - if jlndusttrlal, Dat4 on Candidate phem- ijrf lsj fo|Jte^ti , rfJadipnaJ. |T($n(caJ Jn formation Sfceviee, jujnber. ..... ^ WOHSHtTOitlSfAllCHaOSPBRAriOia * . HONS 02198? Ethylene Oxide Ethylene oxide (oxirane, 1,2-epoxyethane, CAS No. 75-21-8) has been found negative on akin 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 oxide*. Ethylene oxide is a mutagen in Salmonella tvphimurium, Neurospora crassa and Drosphila melanogaster tests^':. It will be considered a possible carcinogen for this project based on the in t'i; mutagenicity data. Production and Persistance It is estimated that 4.5xl0*kg ethylene oxide is omitted per year from stationary sources*3.** 5 *Other estimates of production includes 1,8x10' kg produced with 4.5xl07 kg released1", 1.8xl0?kg produced, 1.8xL03 kg produced in 1974*, 1.9xl0? kc produced in 1973 , and 1.8xl03 and 2.0xl0? produced in 1974 and 1975-. its primary use as an intermediate is expected to grow at 4.7-3.2' per year until 1980:. Dispersed in the atmosphere, epexides would be oxidized by HO radicals with a 3-11 hour naif life ; Its reaction with HO radicals has also been estimator to give half iifes of 1.6 days'* and 23 hours". It has a boilina point of il'C and a vapor pressure of 1095 mm at 20"C ', "Ethylene Oxide" in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 11, 157-167, 1976 . ' Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing," National Technical Information Service Number PD 274 264, 1977. J 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. 5 Dorigan, J., et al.s Preliminary ScoringfofISelelbtJd organic Air Pollutants," National Technical Information Service Number PB 264 444, 1976 .75 > iMbNS^Nird *es*Aftc*coiiPO'*lKj* HONS 021988 Ethylene Oxide _ References - CbritllftieS "Radding, S. L., et el., "Review of the Environmental Fate of selected Chemicals,* National Technical Information Service Number Pi 2*7 121, 1977. 'verecnuersnj *,, Handbook of Environmental Data on oagadlc Chemicals, Van Nosferand Reinhcld Co., N. Y., 1977. 76 iriOisaKTO KESCAhoedOSWRAfi-ipii MONS Ethylenlmlne t'thylenimine (Aziridine, CAS No. 151-56-4) is well documented as being a potent mutaqen, and is used as a mutagen in many plant studies (533 references on Toxline to its use as a mutagen or carcinogen). It lias also been 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 rats*. It is considered a probable carcinogen for this project. Production and Persistance It is estimated that 3.7 x 10" Kg is released to the environment per year'. Estimates of production are 2.3 x 10*5 * *K*g, 1.4 x 106 K::, 2.2 x lO" Kg ( 1 9 74), and 2.3 x 106 Kg per year'/-'. Ethylenirr.mo infinitely soluble m water\ basic, and polar, and could therefore be expected to bo very slow to escape from water to the atmosphere'. Its reaction with HO in the atmosphere has toon found to have ,i half-life of 1.5 days', 47 hours' and 56 hours'. It has a belling point of 56I>C and a /apor pressure of 160 nm at 2 0 C . "Aziridine" in. I ARC Monographs on the Evaluation of Carcino genic Risk of Chemistry to Man, Volume 9, 37-4$, 1976. Brown, s. L. et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 164, 1975. 5Allport, .T. et al., "A Study of Industrial Data on Candidate Chemicals for Testinq", National Technical Information Service Number PB 274 264, 1977. u Radtiiifg, |Sl ff., et al., ".Review of , the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 121, 1977. 5rilte4,i ^.leti al`., "PrelSmidar* tec<4rii}g|of Organic Aic Pollutants" Utmorial rrlchnicini Infot^atldn|^r4ifc4 Iluiqberf EB 2641 442: 197.6. ,7& .fdoIisMTt 3*fsHh|tT7Jc|s<foJ4'ifc>fc HONS 021990 Fluoranthene Fluoranthene (CAS No. 206-44-0) was tested for carcinogencity in 1935 and 1938 on mice by skin (0.3% in benzene for 501 days) and oral (10 mg for 18 months) routes of administration with negative results '. 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 mice1, 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 TA98, 100 and 1537 strains of S. typhimurium for mutagencityu. It is considered a probable non-carcinogen for this project. 'Survey of Compounds Which Have Been Tested for Carcinogenic Activity, nci, phs-hs, VOlUJae 1. - 2Arcos, J. C. and Argus, M. F., Chemical Induction of Cancer, .Volume IIA, Academic Press, New York, 1974 , pp. 26, TTT~. JHoffman, D., et al., J. Natl. Cancer Inst. 2, 1165-1175, 1972. "Rao, V. K., et alt, "Environmental Mutagenesis of EnergyRelattdi Ellf lueits#, p^netics, 8_3, $60, 1976. 7ft {K&lfANlOlRfcSEAftFH CCtftPCSpAtlOfi/ MOMS 021991 Ftarmldehyde Formaldehyde (methanal, formalin, methyl aldehyde, CAS No. 50-00-0) has been tested for carcinogenicity with negative results on many animal species in short termlusually less than a year) test's1. However, 1300 mgAg (65 weeks) caused neoplastic effects in rats2 and 1 ml of 0.4% formaldehyde solution caused spindle cell sarcomas and fibrosarcomas at the injection site of 4/10 rats evaluated at least 649 days1. Formal dehyde has been shewn to be a mutagen in Drosophila melanogaster, E. coli, barley, Vicia faba, yeast, and viral transformation enhancement tests'**'6, but negative on the mouse dominant lethal test7. For this project formaldehyde will be aor.sideiod a possible carcinogen. Production and Persistance It is estimated that 4.1xl07 kg formaldehyde is emitted per year frem stationary sources with 82' of this being from charcoal ranufactun. and catalytic cracking in petroleum refining1. Other estimates of production include 2.6x10' kg produced anc 2.4xl0~ kg released2, 2.6xl0:" kg produced and 6.4x10 kg released",_2.6xl9 * kg produced (1974) and 2.9x10' kg ad 2.6x10 kg produced in 19/3 and 1975 The production of formaldehyde projected to grow by 4-5 j,or year in the next five years-. In solution it is essentially non-volataie, but in the air it will react with HO radical with a half life of 2.6 hours * or 1.2 hours'*. As a gas it has a boiling point of -21'C and a vapor pressure of 1946 nri at 25'C: Its environmental fate, biological, a.-d er.vi roirrental effects have been studied 1 \ -S'-rvey of Chemicals Which Have Bc-or. Tested for Carcinogenic Activity, National Cancer Institute, PHS-149, Voi-.rres 1, 2, 3, 4, and 5. Dcrigan, J., et al., "Preliminary Socrim of Selected Organic Air Pollutant," National Technical Information Service Nunber PB 264 445, 1976. 3Watanabe, F., et al., Gann 5, 451-452, 1954. (From Survey of Chemicals ... - Reference 1, Volume 3) 'Brown,S. L., et al., "Research Program on Hazard Priority Ranking of Manu factured Chemicals," National Technical Information Service Number PB 263 164, 19752 5Sawicki, E., "Chemical (imposition and Potential Genotoxic Aspects of Polluted Atmosphere," in IAIC Sci. Pub. No. 16, 127-157, 1977. 'Personal Ccrrnumcaticn wit)) 3.:C. Casto on 9 February 1978. 79 Es4efctCCtM>ot*4TloK HONS 021992 Formaldehyde References - Continued Epstein, S. S., et al., "Detection of Chemical Mutagens by the Dominant lethal Assay in the Mouse," Toxicol. Appl. Pharmacol. 23. 299-325, 1972. `MRC Source Assessment Data Base, July 1977. 'Radding, S. L., et al., "Review of the Environmental Fate of Selected Chemicals," .National Technical Information Service Number PB 267 121, 1977. ! kllport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Tasting," National Technical Information Service Nurber PB 274 264, 19?7. 1 'Atlantic Research Corp., "Investigation of Selected Potential Environ mental Contaminants: Formaldehyde" (Prepared for EPA), National T^hntcsli Information Service (Timber PB 256 839, 1976. < SC , eONSANTDHse^ClGO|f*Riinpt i MONS 021993 Guthion Guthion has been found to be mutagenic in that it induced chromo some breaks in Wl-38 cells and in HE -2 cells1. Guthion also in creased mitotic recombination in S. cerevisiae2. However, it did not prove to be a mutagen in S. typhimurium assays2 or in E. coli or B.subtil is systems2 and did not induce dominant lethal effects in mice5. For this project it is considered a non-carcinogen. `Alam, M. T. and Kasatiya, S. S. , "Cytological Effects of an Organic Phosphate Pesticide on Human Cells in vitro," Can. J. Genet. Cytol. lji (4), 665-671, 1976 . 2Simmon, V. F., et fl-r "in I'itrj Mutagenic Studies of Twenty Pesticide*", Toxicol. A*ppl. Pharmacol. 32 ID 1976. 'Jorgenson, T. A., PIT IF., '"In Vive Mutagenesis Investigations of `Sen Conmercial pesticides", Toxicol. Appl. Pharmacol. 37 (1) KM i. 1*7*. i 81 c a^mA.ndHiccFOArictac HONS 021994 Heptachlor The IARC monograph on heptachlor (heptachloro-tstrahydro methanoindene, 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 transformation2. Recent NCI tests5 with rats and mice remonstrated 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 Persistance It is estimated that 1.1 x 101* Kg heptachlor is emitted per year from stationary sources4. Estimates of production include 2.7 x 106 Kg (1971) 1 and 2.7 x 106 Kg produced'-. It has a melting point of 95C and a vapor pressure of 3 x 10-4 mm at 25C 1 . 1"Heptachlor" in IARC Monograph on the Evaluation o: Carcino genic Risk of Chemicals to Man", Volume 5, 1~ 3- 191, 1974. Personal communications with B. C. Casto on 9 February 1978. -'"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 445b 1976. 17 <T MOKSAKnO SE4RCH 0B>T0*AT|5N 4 MONS 021995 Hexachlorobenzen* Hexaehlorobenzene (benzene hexachloride, CAS No. 118-74-1) induces microsomal enzymes1, is only slightly teratogenic 1 and tests positive/negative 3 and negative2 on the dominant lethal test in cats. When fed to rats it was non-carc inogenic1*, ard by S. typhimur1 im tests (using mouse liver microsomes) it was negative 5. Hexaehlorobenzene 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 is therefore considered a possible carcinogen for this project. Production and Persistance It has a ti/2 ^ 2 days in the air reacting with OH to form pentachlorophenal. Its production is estimated to be 1.3 x 10* 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 10* pounds released8. It has a boiling point of 322-326l'C:>. Dybing, E. and Aune, T., "Hexaehlorobenzene induction of 2,4Diaminoamide Mutagenicity in Vitro", Acta Pharmacol Toxicol. 40 (5), 575-583, 1977. ;Khera, K. S., "Hexachlorobenzene: Teratogenicity and Dominant Lethal Studies in Rats", Toxical. Appl. Pharmacol. 29 (1), 109, 1974. 3Fpstein, S. S., et al., "Detection of Chemical Mutagenes by the Dominant Lethal Assay in the .Mouse", Toxical. Appl. Pharmacol. 23, 288-325, 1972. "Boyland, E., et al., "Kidney Tumors in Rats Following Treatment with 2-Acetylaminofluorene, Tryptophan and 14-Saccharolactone and the Failure of Substances which Cause Porphyrinuria to Induce Tumors", pp. 58-59 in British Empire Cancer Campaign 1963 - Part 2: Scientific Report, 707 pp., 196 3. 5 Van Dijck, P. and Van de Voorde, H., "Mutagenicity versus Carcinogenicity of Organochloride Insecticides", Meded. Fac. Landbouvjvet. , Rijksuniv. Cent, 4_1 .(2) part 2, 1491-1498, 1976. *Guerzoni, M. E.( et al., "Mutagenic Activity of Pesticides", fcLvi 4ei.; Tecnol. Alimenti Nutr. Un. (Ital) 6 (3), 161-165, 1*7$ 4 a3 5 K tAR<lHlCOftPOAAlOfl HONS 021996 Hexachloroben2ene References - Continued 7Cabral, J. R. P., et al., "Carcinogenic Activity of Hexachlorobenzene in Hamsters", Nature 269 (5628), 510-511, 1977. *Brown, S. L., et al.. "Research Program on Hazard Priority Ranking of Manufactured Chemicals", National Technical fInfoaMliiin #exar|ce*NuaU>er PB 263 161, 197S. , *Verschueren,j K., Handbook of Environmental Data on Organic Clvamlcal.lVahlNp4trfnd,ReinholdCo., New York,. 1977. a MtNSAXIO RESEARCH CORPORATION > | MONS 021997 HexachiorpbutJdlene Hexachlorobutadiene injected I.P. in mice apparently caused no lung adenomas1 . A two year study with rats on diets contain ing hexachlorobutadiene showed no effects at 0.2 mg/kg/day or lass, but renal tubular adenomas and adenocarcinomas at 2 and 20 m<i/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'. NIO.SII 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 10* pounds is produced in tha USA with 7. 3 x IP1' po'-ruis betnq released per year . It reacts with OH and Ot with a ti/2 of less than one day jnd has a low watersol uabi1ityr. The boiling point of hexachlgrobutadiene is 210 C with a vapor pressure of 22 mm at 100'C' . :Test for Carcinogenicity of Organic Contaminants of United States Drinking Waters by Pulmonary Tumor Response in a Strain of Mice," Cancer Res. 22 27)7,2720, 1977 Results of a Two-year Chronic Toxicity Study with Hexa chlorobutadiene in Rats (Meeting Abstract) Toxical. Appl. Pharnagol. 4J. (1), 204,1977. Kouiba, R. J., et 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. 30 (2), 255-265, 1974. ^Brown, S. L., et al." Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Infor mation Service Number PB 26i 161, 1975. (Verschuern, K., Handbook of Environmental Data on Organic Chemical*. Van Noatrand Reinhold Co.., N.Y., 1977. f5- MONS 021998 He xame thy lcnetetramine Hexamethylenetetramine (CAS No. 100-97-0) has been extensively tested in both rats and mice1. Almost all of these tests show that this chemical is non-carcinogenic when given either orally (up to of drinking water) or subcutaneously (25 gm/Kg)2. It has oeen tested on E. coli differential growth (pol A) test witn 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 interperitonea1 mouse dominant lethal test, and positive on a chromosomal aberra- ation test in cultured lyphocytes". Hexamethylenetetramine will bo considered a non-carcinogen (with some, positive data) for this project because of the extensive negative animal data. "Survey o: Compounds Which Have 3oen 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. Delia Porta, C. , et ai., "Nor.-Carcinogenicitv of Hexamethylenete tramine in Mice and Rats", rood Cosmet. Toxicol., 6 (6), 707 715, 1968. 3Fluc!., 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, 197fiu ``Allport, J. et it., "K Study of Industrial Data on Candidate Chemicals for Testing", National Technical Infprmation Service Number .PB.274 .264.1 7.' 36 4o#sa*td hssespchii*a* >&&*. MQNS 021999 Hydrazine Hydrazine (diamine, CAS No. 302-01-2) has been shown to be carcinogenic in mice after oral and inberperitoneal administration and in rats following oral administration1. It was negative in hamsters after oral administra tion1. Hydrazine i3 considered a probable carcinogen for this project. Production and Persistence It is estimated that 3.5xl03kg hydrazine is emitted per year7. 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 1.4x10* kg and 1.7xI07 kg in i974 ?'V The demand for hydrazine is expected to increase 15-17% a year until 19854. Hydrazine is polar, non volatile and water soluable suggesting mat it will not transfer to the atmosphere at significant rates1. Oxidation by HO radicals in the gas phase is reported to be rapid with a half life of less than one hour3. It has a boiling point of 113 c and a vapor pressure of 16 nnt at 20C'. '"Hydrazine" in IAfC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 3, 127-136, 1974. MJt Source Assessrent Data Base, Jbly 1977. 'Radding, S. B., etal., "Review of the Environmental Fate of Selected Chemicals," National Technical information Service Number PB 267 121, 1977. 'Allport, J., etal., "A Study of Industrial Data on Candidate Chemicals for Testing,* National.Technical Information Servioe Number PB 274 264, 1977. Verson1.*-run, K., Handbook of Er.-. iro;-cental Data c-:i Organic Chemicals, .Van Nostrandj Reinbold Co. N. SY. , 1977. 81 bdNfA'Nf0( CORPORAtidN' M0NS 022000 Hydroguinonc Hydroquinone is listed on the NI0S1I Suspected Carcinogen list, but it is apparently there by mistake. The 1955 reference cited1 shows 20 mg of hydroquinone applied to the skin of mice (in benzene) developed only one tumor out of 22 surviving mice as compared with ono 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 12% tumors vs. 12% for the cholesterol control2. Hydroquinone is said to be an inhibitor of 3,4-benzpyrene carcinogenesis3, in active as a promoter1*, and slightly active as a promoter6 of carcinogenesis. Hydroquinone has been reporter! as more toxic to repair deficient E. coli (pol A ) indicating that it may induce DNA damage'-, but negative in inducing antibiotic resistance in micrococcus pyrogens6. Chromosome aberrations have been noted in several plant systems after treatment with hydroculnone' . Those 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 considers i a probable non-carcinocer. (with some significant positive data' for this pro-ect. Roe, F. J. C. and Salaman, :l. , "Further Studies on Incomplete Carcinogenesis", British J. of Cancer, 9, 17?-.103 , 1955. Boyland, E. et al., "Further Experiments on Implantation of Materials into the Urinary Bladder of Mice", British J. of Cancer, ^fl, 575-581, 1964. 'Van Duuren, B. L. and Goldschmidt, B. M., "Cocarclnocenic and Tumor-Promoting Agents in Tobacco". J. Nat`1. Cancer Inst., 56, 1237-1242, 1976. ' '- ""Study of Tobacco Carcinogenesis. XIII. Tumor-Promotino Sub fractions of the Weakly Acidic Fraction", Toxline. interacti'on between Hydroquinone and Cigarette Smoke Condensate in Short-Term'Skin Ttfete foriCarcinoqenicity", Toxline. 6Allport, J., et el., "A Study of Industrial Data on Candidate Chemicals for Testing"f National Technical Information Service Number ?B 274.264, l\77, SQb MQNS 022001 Kelthane Kelthane has been found non-mutagenic to E. coli bacteria in the wp2 TYR to prototrophy test1. It is considered a probable non-carcinogen for this project. Ashwood-Smith, <M. id.! i"MUtac{etiicJLtvt o f Dichlorvos'j Nature. 240 , 413-419} 1972'. 8$ 4 MofcjAN-floInl'CArfci) fc|*pc$*>Tlc*u' HONS 022002 Mo lathion Malathion has been demonstrated not to be a teratogen1 and Ames et.al consider it not to be a mutagen2. It has been found to be a non-mutaqomc in four test systems5, and a study by the National Cancer Institute found it to be non-carcinogenic to rats and noncarcinoqenic to mice1*. Malathion was found non-mutagenic by a dominant lethal test in mices but was a slight promoter in rats when given with dimethvlbenz (a) anth>:acineU For this project Malathion is classed as a probable non-carctnogen. Kimbrough, H. D. ar.d dames, T. 13., "Effect of ''name Phos phorous Comoour.ds ar.d Ukvlatmg Aoents o:-. the Pat Fetus", Arch. Environ, health, ]J>", 305-808 ,' 1968. McCann, J., et al., "Detection of Carcinogens as Mutagens in the Sal monel la/M: crosom.e Test: Assay of 300 Chemicals", Proc. Vat. Acad. Sc;. USA), ~2. 3135-5139', 1975 . Fahrm, R. , "Comparative Mut acenicitv Studies with Pesticides", in Chemical Carcinoeencsis Essays, International Agency for Research on Cancer-Sclent:fic Publication Vo. 13, o. 161-181, 1971. " ' Na t: o.-.a 1 Cancer Institute Draft Summaries of Bioassav Reports", Chen,". Peg. Rep. I (451, 1597-161 8 , 1978. " Jorconsen, T. A., et al., Mutagenesis Investigations of Ten Commercial Pesticides", Toxicol. Appl. Pharmacol. 22 (1) , 109 , 1976. Silinskas, K. C., and Okey, A. B., ^Protection by DDT Against Mammary Tumors and Leukemia During Prolonged Feeding of 7;12-Dimethvlbenz (a) anthracene to Female Rats", J. Nat'l. Cancer Inst., 55 <3), 653-658. 1975. 90 '.MONSANTO PeSEAflCHlClpnFll^AJIpN * MONS 022003 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 . `Dickens, F. and Jones, H. E. H., "Further Studies on the Carcinogenic and Growth-Inhibitory Activity of Lactones and .Related. Substances''., British J- irn.al of Cancer, i7, `10-!08, 1963. 91 i fcONSANTOf RESEARCH CORPORATION; MONS 022004 Mercaptobenzothlazole Mercaptobenzothiazole (2-benzothiazolethiol, Captax, CAS No. 149-30-4) was one of the 80 chemicais evaluated as having the greatest potential for environmental effects1. The study they cite is a negative mice feeding study' in which two qroups 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 study' it was given orally and subcutaneously at 100 and 215 mg/kg respectively to two mouse strains 136 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 mctagenicitv and teratogenic activity but the results are unclear'-. Because of the limited tests hus far conducted, more !>: r data might change :ts classification, but it will be considered a possible carcinogen for this project. Production and Pers i s tar.ee The production o: .-.e-rcap tober.zuthiazole is estimated at 6x10 pounds per year wit.-, trie release of 6x10" pounds per year-. It is reactive towards RO (tS = 8 davs) , ilO (tS = l day) and 03 (t'i = 9.6 hrs. > . " `Brown, S. L. et al., "Research Program, or. hazard Priority Rank ing of Manuracturou Chemicals," National Technical Information Service Number PB 263 151, 1975. Innes, J. R. , .-t al., J. Nat. Cancer Inst. 4_2, 1101-1114, 1969. (From PUS-149; Survey of Compounds Which Have Been Evaluated for Carcinogenic Activity.) '"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 PB22& 161, 1968.' 42 S MftwsXNto Research tconpoRAtiON[*i MONS 022005 Mercaptobenxothiaxola References - Continued 5"Evaluation of Carcinogenic, <TeratoaeniC(and Mutagenic Acti vities of Selected Pesticide* arid?Industrial Chemicals,Volume ii." National Technical information Service Number PB 223 160, 1968. 93 a eoNSAN-aoiRESEAFca EaRpaRi-ivqM.r i MGNS 022006 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. 'Ehrenberg, L., 'et*al., "On the Reaction (Kine&ics and Mutagenic Activity of Methylating and Beta-Halogenoethylating Gasoline Additives", Radiat. Bot. 14 (3), 185-194, 1974. 94 . MONSANTO .RCSEARCHi OOBROBATfc>B MGNS 022007 Methyl Chloride No data have been found indicatinq that methyl chloride (chloromethane, CAS No. 74-87-1) is a carcinogen (e.g. Toxline, Cancer line Survey of Compounds). However, it does appear to be a muta gen to Salmonella typhimurium1. Because of the close correlation between mutaqens and carcinogens, methyl chloride has been placed on the possible carcinogen list. Product:on and Persistance 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 iO Kg produced in 1974, 1975, and 1976, with a pro jected nrowth of 6% per year"`. Reaction in the atmosphere with the HO radical is slow with a half-life of about one year3. It takes 27 minutes for 50^ of a 1 ppm water solution to evapor ate at 25C'. Methyl chloride has a boiling point of -24,,C and a vapor Pressure of 380C mm (5 atm) at 20C and 2150 mm (2.83 atm) at 25C<'. Andrews, A. w. et al., "A Comparison of the Mutagenic Properties cf Vmvl Chloride and Methvl Chloride", Mutat. Res. 40 (3), 273-275, 1976. ` ~ MRC Source Assessment Data 3ase, July 1977. Brmvr., S. b. et al., "Research Program on Hazard Priority Rank- n.: of Manufactured Chemicals", National Technical Information Service Nuniber PB 26 3 164 , 19 75 . 'Don-ian, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 445, 1976. Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nost ran3 ' Re irfhoT Co. , New York, 1 9 77 . 95 lUDNSprfTP PESEARC* COfn}Ofc4Tlo|l ^ HONS 02200S Methyl Ethyl Ketone Methyl ethyl ketone (MEX, 2-butanono) is included on the NIOSH Suspected Carcinogen liat because of a teratogenic reference and as a priority pollutant. MEK does appear to be embryotoxic, fetotoxic, and perhaps teratogenic when tested at high concentrations (1000-3000 ppm)1*'. Rat feeding studies conducted in 1939 and 1940 were negative3'1*. Mouse skin application tests in 1965 of mixtures containing MEK were generally negative in the absence of benzo(a)pyrenes. MEK has also boon tested on TA 1535, 1536, 1537, and 1538 strains of S. typhimuriurr 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. ;Schwetz, 9. A., et ai., "Embryo-and Fetctoxicity of Inhaled Carbon Tetrachloride, 1,1-Dichloroethane and Methyl Ethyl Ketone in Rats", Toxicol. Appl. Pharmacol. 28 (3), 452-464, 1974. -- -Embryo Toxicity and Feto Toxicity cf Inhaled Carbon Tetrachlor ide, 1,1-Dichlorcethane, and Methyl Ethyl Ketone in Rats", Toxicol. Appl. Pharmacol. 2^ (l), 123, 1974. Nakahara, W. and Mori, K., Proc. l.-np. Acad., Japan, 15, 278 281, 1939. (From Survey of Chemical Which das Been Evaluated for Carcinogenic Activity). ``Nakahara, w. and Mori, K. , Proc. Imp. Acad., Japan, Gann 34, 143-145, 1940. (From Survey of Chemicals Which Have Been Evaluated for Carcinogen Activity). sHorton, A. W., et al., Cancer Research 25^, 1759-1763, 1965. (From uryey of Chemicals Which Have Been Evaluated for Car cinogenic! Activity) *Shirasu, if.,, et al. , Mutagenicity Screening of Pesticides in It 4*ofesi*T F4stAF4Hlcp4PO*iATiO>* HONS 022009 Methyl Methacrylate Methyl methacrylate is on the NIOSH Suspected Carcinogen list because of a paper which shows that 0.25 mg/kg of the compound (1/5 ld50) 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 thi9 project. Singh, A. R. et al., "Embryonic-Fetal Toxicity find Teratogenic Effects of a Grouo ofi Methacrylate Esteiis ini Rais"., ,J. Dental Besearph, 51,, 16 32-1J6&8 ,( 1972 . 97 ifcfoasikNTb MsAnHjaD*p-ii>*r HONS 022010 4,4'-Methylene Bis(2-ChIorojni1 ine) 4,4'-Methylene bis(2-chloroaniline) or MOCA (CAS No. 101-14-4) has been found to be a carcinogen in mice and rats 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 is considered a probable carcinogen for this project Production and Persist.mei It is estimated that 4.5 x IT4 Kg is emitted uer year from a 3 x 10& Kg production3. Other estimates of roduction a re 1.52.3 x 10^ Kg in 19703 and 1.5 x 10^ Kg in 19 "'1/4,5 1 he re action with the HO radical in the atmosp. here is estimated to yield a half-life of 12 hour: 1'4 or one day3' while the O3 haiflife is one day and the RCb half-life is 39 days3. It is said to have a meltinu coin*, or I. O'C* and a nealicrble vapor pressure^. "4 , 4'-.Methylene Bi s(2-Chloroani 1 ine) " in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 4. 5- 7 IT 1974. --------- ---------------------------------------------- OSHA Compliance Guide, 29 CFR Part 1910, 19~3. ?Brown, S. L. , et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Service Number PB 263 162, 1975. 'Radding, S. B., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Number PB 267 127., 1977. -Dorigan, J., et al., "Preliminary Scoring of Selected Organic Air Ppllutanta", National Technical Information Service Number PBi264 445, 1976 .. 9B # MdNSAHTiO RfSE4RCH *O.RfJORATlON 6 HONS 022011 Methylene Chloride There are no positive data on methylene chloride (dichloromethane) in Toxline'or Cancerline . Interim resul ts of carcinogenic tests in a two-year inhalation study involving nearly 2,000 animals ex posed to concentrations of methylene chi oride as high as 3500 ppm were negative1. One recent report cites methylene chloride as being a positive in the Ames test2. Met hylene chloride is still considered a non-carcinogen for this pro ject until further testing is completed because of the negative NCI animal data. Methvl 'no Chloride Passes Early Tests", Them. Eng. News., 5_5 (19), 6, '.9 7'. Mutati '-n Research, Volume 53, January 1 978 . 99 It0>**tc**ee|u|c| c **>$* T'<fN I HONS 022012 Methylenedlaniline The IARC monograph1 on methylenedianiline (4,4-diaminodiphenyl methane, bis(p-aminopheny 1) methane, CAS No. 101-77-9) 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 methylenediani1ino is on the NIOSH sefety alert list (this list has been requested from NIOSH) and because of significant positive results12'3 * 5it can at least be considered a possible carcinogen. Production and Persistence It is estimated that 2.6 x 10' Kg is emitted per year from sta tionary sources". The production has beep estimated to be 5 x 10' Kg, 7 x 19 Kg, and 1 x 10f Kg in 1965, 1966, a n d i 9 7 2 . It has a melting point of 93C and a boiling point of 231C at 11 nr.'. 1IARC' Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man - Volume 4, 79-85, 1974. 2Schoental, R. , "Carcinogenic and Chronic Effects of 4,4'Di aminodioheny lnethane , an F.poxvresin Hardner" , nature 219 , li62-1 16 3`, 1568. 5!3teinhoff, D. and Grundmann, E. , "Zur Cancerocenen Wirkunc von 4,41-Diaminodiphsnylmethan und 2,4 *-Diaminodiphenylmethan' Naturioissenschaften 5_7, 247-248, 1970. IfitC feource Assessment Data Base, -July1977. sVerschueren, K., Handbook of Environmental Data on Orqanic Chemical s, Van Nostrand Keirnolri Co~ New VorjT, n`~7. 10Q 1 MOIISANTP .RgSEAACti qOBPOpAT ipff MONS 022013 Methylstyrene One reference cited in the NIOSH Suspected Carcinogen list shows methylstyrene to be a teratogen1. Permissible exposure limits have been determined for methylstyrene*2. Application of methyl styrene to rabbit5 inhalation or rat skin3**^ demonstrated only a reversible1' 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, 2i 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", Fad. 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 Putadiene and Alpha-Methylstyrene", Mater. Nauch. Sess., Posoyashck. 50-Letiyu Obrazov. SSSR, Omsk. Gas, Med. Inst.; p. 871-873, 1972. 5Effect of Isopropylbenzene and Alpha-Methylstyrene on Leucopoiesis" Farmakol|Toksikol, 35^ (4), 49L-492, 19 72 . '"Effect of the Wastes from Phenol Production on Housefly Larvas" Mater, Kbnf. Molodykh, Uch.i Sfeud., Posvyashch. SQt-L^tiyu* SSSR; p. 3.75-377,.. 19 73. 101 jMONS4n.TO SESSAPOllCOSPORATlOM' * HONS 022014 Morpholine Morpholine (chethyleneijiude oxide, !etrnhydro-l, 4-isoxazine, CAS No. 110 91-8) is cited in one reference as causing neoplastic effects in the mouse after oral administration of 6.33 <?Vkg over 28 weeks1. This refers to a study (with no control animals) in which 40 swiss mice (20M.20F! were given neutralized morpholine in their food:. After 40 weeks, 5 malignant lynpbcmas and 5 lung adenomas were found in the surviving 39 animals. (When given in combination with sodiun nitrite, many more tutors were found.) In another atudy, 100 gAg morpholine as 0.5% of the diet for rats produced no tumors, but 0.5% sodiun nitrite added gate 7 tutors '. Many other studies have been conducted with sodiun nitrite add to produce r.itrosanorpholine Ln Russian studies, morpholine in the air in 0.008 0.07 mg/1 concentrations for four months caused mitagenic chrcmoscmal aberrations in bone narrow cells ir. rats" and guinea pics'. The future classification of morpholine requires more data, but for this project it will be considered a possible carcinogen. Production and Persistence It is estimated tiiat 1 n 10' y : .: r _ :uc,:` J .ini 5.5 x 13^ K :: is era t ted ter year ;. Dor:con, J., a al., "Preliruruiry Scoring c: Selectee Ir.cmic Air Pollu tants. Appendix III.," National Technical Information Service Number PB 264 44 a", 1976. -Greenblatt, M., et al., J. National Cancer Inst. 46 (5>, 1029-1034, 1971. (Fran P5IS-149; Survey of Ccnpounds Which Have Beer. Tested for Carcinogenic Activity) '.harder. J. and Bunkle, G., .7. Kreosforsch 7_j ;i) , 54-66, 1969 (Prcm PHS149) uFomenko, V. N. and Strekalova, E. K., "Mutagenic Action of Seme Industrial Poisons as a Function of Concentration and Exposure Time," Ttoksikol. Nov. Prom.Khun. Vcshchescv. h3, 51-57, 1973. (G\ 79, 14 3228) -'Migukina, N. V., "Evaluation of tne Danger of Morpholine During Chronic Action," TioksDcol.1 ffcv.lPrcm.Khim. Voshehestv. n, 92-100, 1973. (CA 79, 14 3 345) 132 * .*>NS4NJO RESEARCH iCORf>QRA'II0N|l MONS 022015 Ilaptha Naptha (coal tar naptha) was f^und in the report "Preliminary Scoring of Organic Air Pollutants" (PB 264 446) cited as a recognized carcinogen. Actually napthas vary in composition de pending on their source with coal tar naptha being mainly benzene and its homologs!. From other sources nantha could be principally paraffins, methanol and acetone, or gasoline1. 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. HYpurl diptliogary. 053 |*$h$A>4TCj HONS 022016 1 -fi'aph t !i t .rmino 1-Naphthylamine (aliJha-naphthylamine, CAS No. 134-32-7) had no carcinogenic effect when given orally to hamsters and both oral and subcu taneous tests with mice give inconclusive results1. In dogs, it was demonstrated that l-naphtlr'lnmine, if carcinogenic at all, was less so than the 2-isomer1. Other tests on dogs;, hamsters, mice rats, and rabbits-1 show that 1-naphthylamine may be carcin ogenic and also it is generally contaminated with the 2-isomer which is a potent carcinoqcn1`. It is an OSHA regulated car cinogen (Code of Federal Reaulations 29 CFR 1910.1004) whether or not it is truly a carcinogen'. It is also a positive on the >. typhimurium test', and an enhancement of viral t ran s fc rr.a t ion test For these reasons, it is considered a possible carcinogen for this project. . Production and Persistance Production has been estimated to he : x 1 O' :<-i in : 46 3" and 3._ x lO1 Kg m 1974 '. It reacts with oxidicmc materials : r. the atmosphere17 * a* n4d5 * reacts with the HO radical m air with a 12 hour half-life1. It has a he: line point :? 300.3 C arid a vapor pressure of 1 in at 104.3*0'. 1 "1-Naphthylamine" in I ARC Monographs or. the Fvalnation of Car cinogenic Risk of Chemicals to Mar. ,~~'o 1 u.v.e 4, 87-96, 19 /4. 'Hartwell, J. L. , "Survey of Compounds Which Have Been Tested for Carcinogenic Activity, Second Edition", National Technical Information Service Number T9 216 4`3, 1951. JShubik, P. , et al., "Survey cf Compounds Which Have 3eer, Tested for Carcinogenic Activity, Supplement I", National Technical Information Service Number PB 216 248, 1957. 4OSHA CompliancejGujde, 29 CFR Part 1910, P. 298-300, 1978. 5McCann, J. et al.t "Detection of Carcinogens as Mutagens in the iSalmoneAla/fcicrosome Test", Proc. Nat. Acad. Sci. (USA) J2. (J. 21, 5135-31 191 1975 " 10 4 SEAKC8 CqR8QR|T)|0|li>4 MONS 022017 1-Napthlamine References - Continued Personal communication with B. C. Casto on 9 February 1978. 'Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number PB 264 445, 1976. qRaddig, S. B., et al., "Review of the Environmental Fate of Selected Chemical*", National Technical Information Service Niutoea Pft 267j 1211 1977. U)5 fc (MewMNi'o *esgARCH|ct>rtet>A1,ribff < MONS 022018 Napthalene Napthalene (CAS No. 91-20-3) has generally been negative when qiven 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 animals'. 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 1537'. Napthalene is considered 3 probable non-carcinogen for this project. !Survey of Compounds Which Have Been Tested for Carcinogenic Activity, NCI, ms--149, Volumes 1, Fi T, and 4. :Arccs, J. C. and Argus, M. F., Chemical Induction of Cancer, Volume IIA, Academic Press, New York, 1974, ?joes 1^4, 237, and 7W.--------------------------- ' 3Kraemer, M. et al,, "S. Typhimurium and E. Coli to Detect Chemical Mutagens", Naunyn Schmiedebergs Arch Pharmakol, 284, 46R; 1974. ``McCann, J. et al., "Detection of Carcinogens as Mutagens in the Salmonella/Microsomo Test: Assay of 300 Chemicals", Proc. Nat. Ac&d.lScii (USf\) ,t 72 (12) 51*5-4139,. 1975. 105 ..MONSANTO HeSEAflCHtCORPORATiON d MONS 022019 Napthoquinone Napthoquinone is on the NIOSH 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 skin cancers and 1/46 papillomas for benzene alone on mice surviving 200 days. 8-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* IN.| "9*4 the Cajrcinogenic Action-of Certain Quinones", Proc. Imparill Acad' (Tokyo) 1, 309-3f2, J194(X. 1'07 afMfe'JS'lNrO ESSAUCHlCbrfPbHAtl&f'l * MQNS 02202Q 1-Napthftl Mcthylcarbamate The primary reference to this compound carcinogenic potential frv-m a Russian journal has not been obtained. Another Russian reference from the same year' declares that 2-napthyl methylcarbamate is carcinogenic while 1-napthyl methyl carbamate is non-carcinogenic. 1-Napthyl methylcarbamate tested on male and female mice of two strains was found to be non-carcinogenic-1. 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 reported-'. It is probably a non-carcinogen based on the available literature. ' Zabezhmskiy, M. A., "Investigations on Possible Carcinogenic Effects of Beta-Sevin", Vopr. Onkol. ^6 (11), 106-107, 1970. 2"Evaluation of Carcinogenic, Teratogenic, and Mutagenic Act ivities of Selectfea Ast^.id4s and Industrial Chemicals), National Technic'.a Information)Service Number PB-223 159, 1968. -'Survey of .Compounds Whicli lilave Been Tested for Carcinogenic *e**|vify,iNCI,! Prtstf4| WluJies|5| and 6. SOJ a MaN**STi>nEse*nc)4cofiP/oiiAa'ioft MOMS 022021 Nitrobenzene Although on structural basis nitrobenzene (CAS No. 98-95-3) has been predicted to be a carcinogen, there was no positive indi cation from actual tests of the chemical cited in "Air Pollution Assessment of Nitrobenzene"1 or on Cancerline or Toxline. it has been reported to induce sex-linked recessive lethal mutations in Drosophila melanogaster when administered as a vapor for 8-10 days*2, with only one in vitro positive test reported, nitro benzene will be considered a non-carcinogen (with some positive data) for this project. 'Dorigan, J. and Hushon, J., "Air Pollution Assessment of Nitro benzene", National Technical Information Service Number P9-257 776, May.1976. 2Allport, J., et al,, "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number EB. 27.4 264. 1977. 1*09 IMDN3&NT PEStARSHCOBPlOf'NriOl * HONS 022022 Nitropheno No data on the carcinoqcnicity of nitrophenols could be found on Cancerline or Toxline but p-nitrophenol has been found to be mutagenic by one test system and non-mutagenic by five other test systems*. When comparing S. typhimurium test results with other .systems, Ames classified nitrophenol as a non-mutagen*2. For this project, nitrophenols will be classed as probable non carcinogens . '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. 2>lcCanri, J. et' 41.t "Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300 Chemicals", Proc. Nat. Acad. Sci* (USJ|) gl, 5135-5139, 1975. HO 1 MdNSANTOfRjESEA^CM CORPqRATlOtl MQNS 022023 Nitrosodimethylamine There arc much data showing nitrosodimethylamine (dimethylnitrosamine) to be a potent carcinogen1. It has, therefore, been placed on the probable carcinogen list for this project, in the final selection of carcinogens, however, it may not be advantageous to select this -.ompound. This is because nitrosodimethylamine rapid ly decomposes in sunlight2, 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 system1. Production and Persistence Nitrosodimethylamine is emitted in less than 100 Kg/year quan tities from the dimethylhydrazine stationary sources'. One esti mate of production is less than 450 Kg/year*. Photolysis of nitrosodimethylamine is reported to be rapid with a half life of less than one hour5. It has a boiling point of 152 c . 'IARC Monographs: Evaluation of the Carcinogenic Risk of Chemicals to Man - Volume 1, 95-106, 1972. 2Bretschneider, K. and Matz, J., "Occurrence and Analysis of Nitrosamines in Air", in Environmental N-Nitroso Compound;, Analysis and Formation, IARC Sci. Pub. No. 355-399, I?76. 3 Fine, D. H. et al., "N-Nitroso Compounds in Air and Water", in Environmental N-Nltroso Compounds, Analysis and Forma tion, IARC Sci. Pub. No. 14. 401-408, 1976. ^ "MRC Source Assessment Data Base, July 1977. 5Radding, S. B., et al., "Review of the Environmental Fate of Selected Chemicals", National Technical Information Service Nupy^eri iFBJ2l 12U. 1977. f Verschtiersn, , Handbook of Environmental Data on Organic * Chemicals, ` Va n Nostrand Re'-tholdifCo! , New York , L9 7 7 ". ft *0NS4Nr<* e*aAB<*<igp|P|>n*2fn f HONS 022024 Nitrochlorobenzenr Nitrochloroben2ene (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 appendix7. For this project it will be con sidered a possible carcinogen. Production and Persistance It is estimated that 3 x 10? Kg nitrochlorobenzene is emitted per year from stationary sources'. An estinate of production is 6.4 x 107 Kg, produced of each of the isomers in 19677. Nitro chlorobenzene reacts with oxidizing materials in the atmosphere''. In the soil, microflora decomposes this chemical in 64 days'. The m,p, and 0-isomers have boiling points of 23b, 242, and 2 4 5 C with a vapor pressure of 10 mm at 25C:. Tardiff, R. G., et al., "Ha locenated Organics in Tap Water: A Toxicoloqica1 Evaluation" m The Environmental Impact of Water chlorination. National Technical Information Service Number COST 751096, p. 213-228, 1976. Fuller, B., et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number ?3 264 441, 1976. MRC Source Assessment Data Base, July 1977. ' Verschuren, K., Handbook of Environmental Data on Organic Chemicals, Van Npstrand fteinhold Co., New York, TfTTT- lid |%upH5AbCO rtESEAjeh ' MONS 022025 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 beinq a slight teratogen only when given in sufficient quantity as to cause toxic poisioning to be appar ent in the dams*. It has been found to be non-mutagenic by several different in r-'.rr tests', but does cause an antimitotic action in cells.3 It is therefore classified as a probable noncarcinogcn for this proiect. K1 mb rough, R. D. and Games, T. 3., "Effect of Organic Phosphorus Compound? and Alkvlatine Agents on the Rat Fetus", Arch. Environ. Health, 16, 805 -`808, 1968. Fahrxg, ft., "Comparative Mutagenic studies with Pesticides"', fin Chemical Carpino^en(Essays, IARC Scientific Publication |lo4 1974 . 1 Irar.t, w. F.. "Cytoloqical Effects of Environmental Mutaaensi- 5osticidje|">|fut4t. (Reg.; 21 (4.) 721-2*2,1197 1U mphs^nio jse**chico>v'<aiioni : HONS 022026 Pentane Although n-pcntane 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-carcinogensJ. For this project pentane will be considered a non-carcinogen. 'Fuller, B. et al., "Preliminary Scoring of Organic Air Pollutants', National Technical Information Service Number PB 2 64 442. 1976k `Sawicki, E., "Chemical Composition and Potential Genotoxic Aspects of Polluted Atmospheres", IARC Sci. Pub. No. 16, 127-157, 1977. i'H 10i MNSAH lBESE*HCM COBBORATtON l MONS 022027 Pentachlorophenol Pentachlorophenol (CAS No. 87-86-5) has been fcund negative in some rel atively short studies on rabbit skin and orally in rats, and cats1. More recently it has been found negative in two strains of mice both orally and subcutaneously'. Pentachloropher.o 1 is also negative in Drosophila tests , in a host-mediated assay in mice1' and other microbial systems". Some authors consider pentachlorophenol a known mutagen0, and there are other positive as well as negative short term tests reported . It is also positive at the 100 ,,g level in the hamster embryo adenovirus enhancement assay'. For these reasons pentachlorophenol will be considered a possible carcinogen for this project for the f;rst round of evaluations. Prodiction and Persistence One estimate of production is 2.1 x lO'.kg (1969 capacity) and a con sumption of 2.3 x 10' Kg in 1975. In the soil it decrades completely in >72 days10. it has a boiling point of 310C and a vapor oressure of 1.1 x 10~" mm at 208C10. ' Deichman, et al., (1911) in Survey of Compounds Which Have Been Tested for Carcinogenic Activity, J. 1. Hartwell, editor, Nat ional Technical Information Service Number PB 216 478, 1951. "Evaluation of Carcinogenic, Teratogenic, and Mutagenic Activities of Selected Pesticides and Industrial Chemicals", National Technical Information Service Number Fa 223 159, 1968. 1Vogel, E. and Chandler, J. L. R., "Mutagenicity Testing of Cyclamate and Some Pesticides in Drosophila Melanogaster", Experientia _3C) (6), 621-623, 1974 . ' Buselmaier, W., et al., "Comparative Investigations on the Mutaoenicity of Pesticides in Mammalian Test Systems", Mutat. Res. '21 (1 ) , 25-26 , 1 973. ^Anderson, K. J., et al., "Evaluation of Herbicides for Possible Mutagenic Properties", J. Agr. Focal Chem. 20 (3), 649-656, 1972. 6Daugherty, R. C. and Piotrowska, K., "Screening by Negative Chemical Ionization Mass Spectrometry for Environmental Con tamination with Toxic Residues: Application to Human Urines", Proc. NaTtl. Acad. Sci 22 16) J fl777-17Bl, 1976. ?Fahfig, Jt., "Comparative Mutagenicity Studies with Pesticides", J'n Chemical C ire ir.ogvnesis Essays, Binrrw. IARC Sci. Pub. No. 10, 161- 115 fcON$A*Tc*MEjeHcii MONS 022028 Pentachlorophenol References - Continued ^Personal communications with Dr. Bruce Casto, 2/17/78. 9Dorigan, J. ec al., "Preliminary Scoring of Selected Organic Air PbMutants", National Technical Information Service Number PB 264 446, 1976. 10ViichiMrin, X., Handbook of Environmental Data on Organic Chytyals, Van Noatrand Reinhold Co., New York, 1$71. lit tft>6sMrO PESdAfccHlC04PDRAXl0fa4 MONS 022029 Phenol Phenol (hydroxybenzene, CAS No. 108-95-2) has been reported to give rise to papillomas after administration on mouse skin'*2. Phenol has also been reported negative by injection and negative on the skin of mice3. It has recently been given in combination with other chemicals3. In mutagenicity tests, phenol has been found to be mutagenic t.o Drosophila, revert E. coli to streptomycin independence, and induce chromosome breakage in the root tip of Allium cepa while beinq 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 pcresol and phenol) produced by gut bacterial metabolism of tyro sine' . 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 intro tests are with systems which have not been extensively evaluated. Although it is a borderline chemical, phenol will be considered a probable noncarcmogen (with some positive data) for this project. ; Sula man, M. if. and Cl vn-ienn :ns, 0. M. , 9rit. J . Cancer, n, 4 34 444, 1957. Boutwo 11 , R. K. and Bcsch, D. K., Cancer Research 1_9 , 41 3-424 , 1959. ' . "Survey of Compounds Which Have Been Tested for Carcinogenic Ac; .'.'it y, NIH, PHS-149, Volumes 3,4,5,6, and 7. -Ailoort, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testinq", National Technical Information Service Number P3 274 264, 1977. 'Brown, S. L. et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 164, 1975. Bone, E. S., et al., "The Production of Urinary Phenols by Human Cut Bacteria" (Mee.tinq Abstract). J. Med. Microbiol. 9 (2), p. vi, 1976. ?Hossak, D. lJ. and Richardson, J. C., "Examination of the Potential Mutagenicity of Hair Dye Constituents Using the Micronucleus Test , Expenertti4,i 33| (3 , <372-378, 11977. 10I I fcdNiANlolrtESEAFfcfl CdRPdRA'mOfc'a HONS 022030 Polychlorinated Biphonyln Polychlorinated biphenyls (PCB, chlorinated <liphenyls, Aroclora, Kanechlors) have been cited extensively in the literature as carcinogens'7. Or. close inspection, many of the carcinogeni city studies on PCB's have been questionable^'- or negative5 and the increase in cancer among PCB workers has been ques tioned5. 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. Production and Persistence It is estimated that 1.8x10" kg is emitted per yearp. Other estimates of production are 1.4x10' kg, 2.5x10' kg, and 1.8x10" kg (1974) '~:l Production of PCB's 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 be important1. Reaction with HO radical predicts a half life of 26 days'. They have a boiling oint of 363-390C and a vapor pressure less than 1 mm at 5C * 1 . `"Polychlorinated Biphenyls" in IARC Monographs on the Evalua tion of Carcinogenic Risk of Chemicals to Man, Volume 7, 261 289, 1971 . Lloyd, J. W., et al., "Polychlorinated Biohe.nvls", J. Occup. Med, 1J (2), 109-113, 1976. `' "Andrews, E. J., et al., "PCB Diet" Science _i_80 (4083), 255 257,- 1973. "Survey of Compounds Which Have Been Tested for Carcinogenic Activity, National Cancer Institute, PHS-149, 1972-1973 edition. Number 325. 51 to* N., et al., "Histopathological Studies on Liver Tumorigenesis in Rats Treated w/thfpolychiorinated Biphenyls,'" Gann, 65 (6), 545-549, 1974. ^Lawcence, iG., |"rcu? and Melanoma". (Letter to the Editor) , N. Snfet 4>) (IIS 12)1 .lb$-l|9r,|il977. 11* * cqepqpiTiCjh ; MONS 022031 Polychlorinated Biphenyls References - Continued 7NIOSH Suspected Carcinogens, 1976 edition. '''IRC 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 263 162, 1975. 'borigan, J., et al., "Preliminary Scoring of Selected Organic Air Pollutants," National Technical Information Service Number. PB" 264 446, 1976. 1'Redding, . B., et al., "Review of the Environmental Fate of Selected Chemicals," National Technical Information Service Numberi Pft 267,121 , 1977 . 119 >Jo*sasto RfcE*ac*dOR(fc>e/*r(py.a MONS 022032 Propanol In 1939 and 1940, propanol (propyl alcohol, CAS No. 71-23-8) was found non-carcinoqenic in rat feeding studies1'5. The only cur rent references which could be found were by Gibel et al. who re fer to tumor formation after oral (5 Otg/ Mg) and subcutaneous (6qm/ Kg) administration of propanol to rats3 and an E. coli test1*. Tf. ' studies which have been conducted on isopropancl have been negative5. Propanol will be considered a probable non-carcinogen (with some significant positive data) for this project. ;Na)cahara, W. and Mori, K. , Proc. Ire. Acad., Japan 1 5 , 278-281, 1939. ` 'Nakahara, w. and Mori, K., Gann 3, 143-145, 1940. 'Gibel, W., et al., "Experimental Study on Caneorogenic Activity of Propanol-1, 2-Methylpropanol-l and 3-Methylbutanol", Arch. Geschwulstforsch 5 (1), 19-24, 1975. "'Gibel, W. , et al., "Studies on the Toxicity and Mutagenicity of Single Fusel Oil Componsents on E. Coli", Acta 3iol. Med. Ger. 2, 843-852, 1969. ""Isopropyl Alcohol hnd Isopropyl Oils" in IARC Monographs on the Evaluation of the Carcinogenic Sisk of Chemicals to Man, Volume 15, 223-243,t1977. 120 t)ES*A|'CHf CO'tPpftAl-'ONt . MQNS 022033 Propylene Oxide Propylene oxide (methyloxirane , 1,2-epoxypropane, CAS No. 75-56 9) 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 inha 1lation 1* By tests, transformation of hamster cells' occurred at 250 mj/ ml1*. It is also reported to cause reversion to adenine, pro totrophy in Neurospora crassa and cause recessive lethal mutation in Drosophila melanogaster'. For this project it will be considered a possible carcinogen. Production and Persistence - It is estimated that 4.4xl0`' kg propylene oxide is emitted per year'. Other production estimates include 7.5x10 kg per year', 8.0x10' kg (1974)', 8.0x10 kg (1975)', and 7.0-10 kg (1973) with 0. S. consumption predicted to grow by 9-10.5% a year from 1 975 to I960' . If dispersed in the atmosphere, epoxides would be oxidized by HO radicals with a half life of 3-11 hoursThe 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 o: 596 ~.r. at 25C?. "Propylene Oxide" i:-. IARC Monographs on the F.valuation of Carcinogenic Risk of Chemicals to Man, Volume 11, 191-199, 1976 Rowe, L. K., et al.. "Toxicity of Propylene Oxide Determined on Experimental Animals," Arch. Industr. Hlth., 13, 228-236, 1956. Casco, R. C., et al., "Assay of Industrial Chemicals in Syrian Hamster Cells for Enhancement of Viral Transformation" (Meeting Abstract), Proc. Am. Assoc. Cancer Res., 18, 155, 1977. 'Pcrsc-nai communication with B. C. Casto on 9 February, 1978. Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing," National Technical Information Service Number PB 274 264, 1977. VMRC Source Assessment Data Base, July 1977. 7Dorigan J., et al., "Preliminary Scoring of Selected Air Pollutants," National Technical Information Service Number PB >264 446, 1916 . 1:21 kJols^NTf) MsfcARfcd (Jofrpofcyi-feJ , MONS 022034 Propyldhe Oxide References - Continued ^Redding, S. B., et al., "Rfeview of the Environmental Fate of Selected Chemicals," National Technical Information Service Number PB 267 121, 1977. ,12? 4 IONIANCORPORATION HONS 022035 Pyrene Pyren* (CAS No. 129-00-0) has generally been tested on mouse skin with negative results'. It has also been reported negative on mouse skin followed by croton oil or preceded by benzo(a)pyrene1. It is usually considered to be non-carcinogenic:> 3 and has been reported as non-mutagenic to S. Typhimurium strains TA 98, 100, 1 535 and 1 5 3 7 3 . it is considered a non-carcinogen for this pro ject. :Survey of Compounds Which Have Been Tested for Carcinogenic Activity, NCI, PHS-149, Volumes 1, T~, T7 5~ and 7. Arcos, J. C. and Argus, M. F. , Chemical Induction of Cancer, volume IIA, Academic Press, New York, 1974, pages 210 and 237. 3McCa"nnf JJ etfal.., "Detection offCarcinqgens asf Mutagens in the Salmonalla/Microsome Tests Assay oif 300 Chemicals", Proc. Nat. Acad. ici. ,<USA), 72 (12), 5135-5139, 1975. . 1*1 .f rtcfclAiUDMESfe***:* E<]nr4R'ac*r* MQNS 022036 Sorbic Acid Sorbic Acid (2,4-hexadienoic acid, CAS No. 110-44-1) Is a widely used food perservative. In 1966 and 1968, Dickens et al. re ported several rat studies with sorbic acid. In these tests (using 6-12 rats) 3orbic acid injected subcutaneously at 2 mg/ injection in oil or water sometimes caused local fibrosarcomas at the injection site1-1. Given in the drinking water at 0.1 gm/1, no effects were seen3. 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, rats1* and mice'' (groups of\100 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 response . Several >. tests (eg B. subtilis) have been negative for sorbic acid but.positive for reaction products of sorbic acid and sodium nitrite'. Better subcutaneous tests should be conducted on sorbic acid, but the negative results on the recent large scale feeding tests and negative :> results suggest that sorbic acid should be considered a non- caramogen at the present time.* * * * 5 6 Dickens, F., et al., Brit. J. Cancer 20, 134-144, 1966. ;Dickens, F. and Wayforth, H. B., Brit. Emp. Cane. Camp. ^6, 108, 1968. -:Dickens, F., et al., Brit. J. Cancer, 22, 762-768, 1968. "Grant, I. F., et al., "Long-Term Toxicity of Sorbic Acid in the Rat," Food Cosmet. Toxicol. 13 (1), 31-45, 1975. 5Hendy, R. J., et al., "Long-Term Toxicity Studies of Sorbic Acid in Mice," Food Cosmet. Toxicol. 14 (5), 381-386, 1976. 6Mason, P. L., et al., "Long-Term Toxicity of Parasorbic Acid in.Rats," Food.Cosmet. Toxicol. 14 (5), 387-394, 1976. 7Ksds, T.t and Carcinogenicity|S^:reening of Food Additives by th* Rfc-Assay and Reversion'Procedures," IARC Sci. Pub. NO. J05-115, 1976. 124 4*ac**AitO|RESfe/iRCli ccfeOft4?iot b MONS 022037 Styrene Styrene (vinyl benzene, CAS No. 100-42-5) has been found to be both positive5 and negative1 on the Salmonella typhimurium mutagen test after activation with S-9 microsomes. Without S-9 activation it has been found negative by this test1'3. In other systems, styrene was found positive on a host-mediated forward 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 tests1'. 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 Persistance It is estimated that 5.6 x 10" Kg styrene is emitted per year from stationary sources'. Another source estimate 2.0 x 109 Kg (1975) produced7. It has a 1.28 relative chemical reactivity in the atmosphere (where methane is zero, butane is 1.27, 2-pentane is 1.58 and 2-butene is 15.5) ,1-. Styrene has a 145.2C boil ing point and a vapor pressure of 5 mm at 20C-.* * 3 :DeMeester, C. et al., "Mutagenic Activity of Styrene and Styrene Oxide", Arch. Int. Physiol. Biochim., 85 (2), 398-399, 1977. ~ -Vainio, H., et al., "A Study on the Mutagenic Activity of Styrene and Styrene Oxide", Scand. J. Work Environ. Health, 2(3), 147-151, 1976. " 3Stolr, D. R., "Mutagenicity Testing of Styrene and Styrene Epoxide in Salmonella Typhimurium", Bull. Environ. Contain. Toxicol.,. 17, (6), 739-742, 1977. ~ "Loprieno, N., et al., "Mutagenicity of Industrial Compounds: .Syrni and tits JPo4si>alf tfetaboli.te Styrene iCfcida" ,4 Hutet.lResi (40 (4) , ,317-324, {1976. 125 MN|A|lTO(F<fejEkHC& jCORpORj^lOM. HONS 022038 Styrene References Continued 'Allport, J. et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PD 274 264, 1977. Personal communication with 3. C. Casto or. 9 February 1979. MRC Source Assessment Dat3 3ase, July 1977. 'Fuller, 3. et al., "Preliminary Scoring of Organic Air Pollu tants", National Technical Information Service Number P3 264 442, 1976. -Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co., N. Y., 1977. 15eung, C. K. K. and Phillips, C. R., "Estimated of Physiological Smog Sympton Potential from Chemical Reactivity of Hydrocarbons", Atm.. Environ. 7, 19 73. 1*26 kQNS/ftaotflfcsetvl Cone<V'4Tiop HONS 022039 Sulfolane Sulfolane (tetrlhydrotbiophene,-1-dioxide, CAS No. 126 33-0} was one of the eighty chemicals selected as having the greatest potential environmental effects 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. J.t is considered a probable non-carcinogen for this project. 'Brown, S. U,. et al. "Research Program on Hazard Priority Ranking, oJS Manufactured Chemicals," National Technical .Information Service Number PB 263 161, 1575. 12? MANfo*stEAmct< MONS 022040 Tetrabromoethane Tetrabromoethane (CAS No. 79-27-6) was one of eighty chemicals having potential for environmental effects1. It has tested negative in some short term {92 day), limited exposure {15 min./ day) tests on rats, mice, rabbits and guinea pigs2. It has tested positive in a E. coli (pol A+, pol A -) differential growth mutagen test but negative in S. typhimurium strains TA1530 and TA 1535 3'1*. With only one in vitro positive test (which has not been extensively validated) tetrabromoethane will be considered a probable non-carcinoqen for this project. 'Brown, S. L., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Infor mation Service Numbers PB 263 162, 1975. 2Cray, A. W. A., Arch. Ind. Hyg., 2. 407-419, 1950. {from PHS149: Survey of Compounds Which Have Been Tested for Carcino genic Activity) 3Brem, li., et al., "The Mutagenicity and DNA-Modifying Effect of .Haloalkanes, " Cancer. Res. 2i-, 2576-2579, 1974 . 'Rosenkranz, H. S., "Mutagenicity and DNA-Modifying Activity: A compariaon of .Two Microbial Assays," Mutat. Res. 41 (1), 61-70 1976. -- 138 poneopATjON W . MONS 022041 Tetrachloroetha no 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 1535 strains1. It has been cited as a carcinogen based on a Na tional Cancer Institute bioassay12 where it was found to be a car cinogen for mice but not for rats3.* 5 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) Evaporation of 50' from a 1 ppm solution of water at 25"C will occur in 56 minutes'. It has a boiling point of 146.4C and a vapor pressure of 5 mm at 2oCs. water solubility is 2.9 gm/1 at 2 0 BC ' . 1 Brem, H., Stein, A. R., and Rosenkranz, H. S., "The Mutagenicity and DNA-Modifying Effect of Haloalkanes", Cancer Res. 3, 3576-2579, 1974. Kraybi11, H. F., "Origin, Classification and Distribution of Chemicals in Drinking Water with an Assessment of their Carcin ogenic Potential", m The Environmental Impact of Water Chlorination, Oak Ridge National Laboratory, National Technical Information Service Numbei CONF 751096, p. 229, 1976. Chemical Regulation Reporter 1^ (51), 1961 , 1978. ``MRC Source Assessment Data Base, July 1977. 5Verschueren, K., Handbook of Environmental Data on Organic Chemicals, Van Nostrjfnd Re inhold Co., New York, 1978. Il29 *! MOfciAaTtJlntsfc'fnfcH fcORfo'RatJon [ f MONS 022042 Tot rachloroe thylone Tha NTIS document "Air Pollution Assessment of Tetrachloroethylene " 1 cites ext ensive toxicological data but reports no evidence of car cinogenicity, mutaaenici tv or teratoaenicitv for tetrachloroethylene (perchlorocthy1ene, CAS No. 127-19-4) in humans. Also no difference in the incidence of tumors were observed between con trol and experimental rats exposed to 100 or 600 ppm of tet.rachloroethylene. A recent report by NCI however, has shown tetrachloroethylene to be a liver carcinogen in B6C3F1 of both sexes. Tetrachloroethylene has, therefore, been assigned to the PROVABLE carcinogen list. Production and Persistance It is estimated that 7.9 x 13 Ko tetrachloroethylene is emitted per year from stationary sources with solvent evaporation from degreasing operations accounting for better than 99 of that quantity'. Other estimates of production are 3.0 x 103 Kg (19"5) 3.3 x 10" Kcj produced and 2.6 x ! 3 " Kg released , and production of 3.3 x 10" Kg, 3.1 v in- k and 3.6 x 13` Kc : n 1-774 , 1373, and 1 9 76" . A 1 9 76 forecast yr ; ;ected a yearly rrovth of 3-4 but in light of the NC! carcinocen study, lower standards for occu pational exposure from NIPSH, and a decrease in. fluorocarbon use, the production of tot rachloroothy 1 : n.e is expected to decrease' . It is not photoactive and. has an expected HO radical reaction half-life of 8 days'. Another reference cites phetodecradation with a halt-life of 2 days'. Kvaioration of 30; from a 1 ppm water solution at 27c will ta<e only 24-28 minutes'. It has a boiling point of 121.2*C and a vapor pressure cf 14 nr. at 20C . 'Fuller, B. B., "Air Pollution Assessment of Tetrachloroethylene", National Technical Information Service, Number PB-256 731 , 99 pages, 1976. z"Bioassay of Tetrachloroethylene for Possible Carcinogenicity CAS Ho. 127-18-4", National Technical Information Service .Number P? 272 940/ 3L. 130 JldNjAflTOl AESEARCh C3A?ORfT)Oh > HONS 022043 Tetrachloroethylene References - Continued MRC Source Assessment Data Base, July 1977. "Dongan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Nuirtber PB 264 446, 1976. :Brown, s. L. et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. fAllporfr, J. et al., "A Study of Industrial Data on Candidate Chemicals for Testing^*, National Technical Information Service Number: PB'2?74 36*,f 1*77 7Verschuerer* K,;, Hapdbpok of Environmental Data on Organic Cheipicylsj nj Nr^pirand Roinhold Co., 1?I7. nai MO*W10|AESeA*CM COaPORlirttiH* HONS 022044 Tetraethyl Load Tetraethyl lead (tetraethyl plumbane, CAS No. 78-00-2) has been found to induce lymphomas when injected subcutaneously into neo natal mice1 although the significance nf this test has been ques tioned7. Oral doses were not found to be teratogenic-' and an epidemiological study found no health hazard from occupational exposureu . ' Tetraethyl lead has been found to cause ONft fragmentation and to enhance viral transformation in hamster embryo at the 12.5 ..q level'. Tetraethyl lead is considered a possible carcinogen for this project. Production and :lersistance One estimate of release to the environment is 1.3 x 10; K; per year'-' from a production of 1.4 x 10' The release figure notes that most of this is through use : r. casoline where it is converted to lead halides and =or.o lead phosphates". Another set or fi mires cites a release of 6.6 x 1?' from a production of 1.6 x 10 Km in 1 9 7 3 . The 19~1 production has been estimated to be 2.4 x 10" Kg'. The production :f tetraethyl lead is ex pected to decrease rapidly from these figures because of rerj- lati.cns requiring less lead in gasoline . In the air it has a_ half-life of 2-3 days from reactions w;t.t :;C and Ox radicals ' . It has a bcilinc point of 200C (deccm: oses) ar.d a vaorr ores sure of 3.15 met. at 20C > 7. ' '' 'Epstein, S. S. and Mantel, N., "Carcinogenicity of Tetraethyl bead: , Exper ler.tia, 2_4 (6), 580-531, 1983. "Tetraetnyl anc Te trams thy 11 e ad" , l r. XASC Monographs o-. thu Evaluation of Carcinogenic Risk of Chemicals to Man. Volume 2, 150-160, 1373. `Kennedy, C. L., at al . , "Teratogenic Evaluation of Lead Compounds in Mi.ce and Rate", Food .Cosmet. Toxical. 3 (6), 629-632 , 1 975. uRobinson, f. R., "Healfclf, iow Clin !lt Be Measured", HEW Publ/. (MIOSH), 76 134, 114, 30, 1976. Personal jeommu:\igationj Hith Dc I Bruce C. Casto 2/17/18. 131 . IdoIsfittrO-^SsfAlKjMrcriPf^Atii^^ HONS 022045 Tatra*tKylT* ad References - Continued 4Brown, S. L., et al., "Research Program on Hazard Priority Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 165, 1975, 7Dorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number :PB '264 {446;, '1976 . r Ve rschue ren, K. , Handbook of Environmental Cat a or. Organic Chemicals, Van Sostrand Rei.nhold Co., New To r k , 1 5 77 . U3 iMOeSAHTO aSSEAflCH CJOaPpiJATipN MONS 022046 Toluene An extensive search of Cancerlino and Toxlino along with the NTIS 'ocument "Air Pollution Assessment of Toluene"1 and the Stanford Research Institute hazard priority ranking* failed to find data which would indicate that toluene is a carcinogen, it tested negative1 in a differential growth mutauen test using E. colt (pol. A) and will be considered a non-carcinogen for this project 'walker, P. , "Air Pollution Assessment of Toluene", National Technical Information Service Number PB 256 735, 1976. *Brown, S. L. et al., "Research Procram on hazard Priority Kan.-;ing of Manufactured Chemicals", National Technical Information Servite Number PB 263 161. 197a. 3 Pluck, &, R. et-al., "Evaluation of a ON A Polymer'ane-De ficient Mutant of E. Coli for the Rapid Detection of Carcinogens", Chem. BiplM Interact., 15, 219-231, 1976. 1234 4oMA*TOinesEARCH corporvtioi , HONS 022047 Toluene Dlisocyanate There is no data on Toxline or Cancorline to indicate that toluene diisocyanate is a mutagen or a carcinogen. 135 MOrlslHT.i fc&fARflHrdDSPOBATiC* MONS 022048 Toluenediamine To 1uencdiamine (toluene-2,4-diamine, CAS Ho* 95-80-7), generally used as a hair dye, has been fouid by several studies to be non-carcinogenic when applied to the skin of mice1*2 and rats5 although the same data can be interpreted to show increased lung tumors and total tumors in the test groups1*. Toluenodiamino has been reported to produce hepatomas in rats when fed at 9.1 percent of diet for 33 weeks' or 11 gm/kg for 36 weeks". In rats, 280 ma/Kg (35 weeks) subcutaneously is reported to cause neoplasms'. It has also oven found to casue morpohologica1 transformation in primary Syrian hamster embryo cells. It also mutates Salmonella t yph l n i n:r l um strains TA 15 3 9 and TA 99 at 0.5 uq/ml when acti vated with the S9 microsomcs'i*. with positive and m tests, toluene-diamine will be considered a probable carcinogen for this project. Production and Persistence One estimate of production is 2.9 x 107 Kg per year with 0.015 as a (rictm of production loss7. It has a boiling point of 292C and a vapor pressure of 1 mm at 106.5C7. : i 1 o s , A. . , et a 1 . . "Dermal Carcinogenicity Stud/ by v--se- Sxim Pu.Mirg with 2 ,4 - To 1 ue ned l air. l ne Alone or ir. Si; :cio:.jiivc Hair Dye i'urmulations", J . Toxical . invito r.. Healer. 1 . : , 4 3: 4 4 C , 1 9" . . Burner'.. C . , t al . , "Lor.g-Terr Toxicity Studies on x i d i ; c. Hair Dyes", ,-ood Cosmet. Toxicol. 1_3 (3 ), 3 5 3- 35 ', 1 ?' 3 . r.: r. e 1 , H. . and Holinar.ri, 5., "study of Long-Tern i' e r u * a r. e o u s Toxicity and .arcir.osenicity cf Hair Lyes (Oxidicins Dy-. s' ir. sdlS" , rood Cosmet. Toxicol. 1_1 (4 ), 641-64B, 1973. Bridges, 3. A. and Dreen. M. H., "Carcinogenicity of Hair Dyes by Skin Painting in Mice" (letter to Editor), J. Toxicol. Environ. Health 2 i 1 ) , 251-252, 1976. Shah, >'.. J. et al., "Comparative Studies of Bacterial Mutation an d H a r ; t r Cell Transformation Induced by 2,4-To!ui-:.e diamine" Meeting Abstract), Proc. Am. Assoc. Cancer Res. 13, 22. 1977. 'Cancer Research 2_9, 1137, 1969. ?Dorigan, J. et al., "Preliminary Scoring of Organic Air Pollutants", National Technical Information Service Number PB 264 446, 1976. Pienta, R. J. et al., "Correlation <Jf Bfcte'rlal Mutagenicity and Hamster Cell Transformations with Tumor i`ga n i c i ty Induced by 2, 4-Toluenadiamine" / Cancer Lett, {Amsterdam), 3 (A/2), 45- 52 , 197 7. Ii6 VQNJAMTOIRESEARCH ecfttORXTIoIl MONS 022049 Toxaphene No significant data were found to indicate that toxaphene is a mutagen or a carcinoqen. It tests negative on the dominant lethal test for mice'. It has been placed on the probable non carcinogen list for this project. `Epstein, S. S. et al., "Detection of Chemical Mutagens by the Dominant .Lethal Assay in the Mouse", Toxicol. Appl. Pharmacol. 137 * i)on4a4to {research corporation t MOMS 022050 Trichlorfon Trichlorfon has been found to be carcinogenic to mice, rata, and cats given orally, subcutaneously, cutaneously, 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 Kg/yenr of trichlorfon is emitted from stationary sources'. ]MRC Source Assessment Data Base, July 1977. E38 WnIsInt# Rs^ARCtf<t;cpfVsoty^i<}N| 022051 MQNS Trlchloroethane 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. :"3ioassay of 1.1,1-Trichloroethane'for Possible Carcinogenidity' Carcinog. Tech. Rep. Ser. - Nat'l. Cancer Inst. (U.S.); ISS NCI-CG-TR-3^, ,70 jap. 1975. . ?ers.o(ialj cojraiunicatijon Iwitjhlg'J Cjfasto bi 9 JFe&rjuary, 1>198 i! WONS*NTd FlESdMctl COFCPOPtf* hqns 022052 I'cichJ oroethylone Trichloroethylene (trIchloroethene, TCE, 'CAS N0CT79UOI-6) has been found to induce a high incidence of hepatocellular carcino ma in B6C3F1 mice of both sexes by NCI It has also been found to be weekly mutagenic in E. coli and to TA100 strain of S. typhimurium (0.8-2.01 vapor dose response when exposed one hour) in the presence of activated microsomes2. A review of the production, uses and environmental effects has been compiled by Fishbein \ TCE is considered a probable carcinogen for this projec t . Ptpiuction and Pcrs istance it is estimated that 1.6x10' kg of TCE is emitted per year with 9 5 , of that coming from solvent evaporation in degreasm-i operations -. Another estimate is a production of 1.93x10"' kg with 1.95x10" kg released-. Other production estimates' ' include 1.8x10' kg (1974) and 1.3x10' kg/year, with about 60 of the production released to the environment'. Production has also been reported to bo 1.8x10' kg ( 1974), 1 . 3X10 ' (1 9 75) and 1.4x10" kg (1976) with a 11 deciinq predicted for future years . Since that prediction, OSHA has lowered the standard for occupational exposure and NCI found that TCE causes turners m mice which will mean a much greater decline in the expected production-. TCE has a high atmospheric photodecredat icr. rate with a half life of 0.3 days at sea level". Other sources predict atmospheric reaction with the HO radical with a halt life of 36 .hours' or less than 50 hours'. Kith its high volatility and low water soluability it is expected to fairly rapidly migrate into the atmosphere. In^fact 504 of a i ppm solution wii: evaporate f^om water at 25 C in 19-24 minutes '. Its boiling point is 86.7'c and it has a vapor pressure of 6 0 mm jt 20'C '. ' "Carcinosenesis Bioassay of Trichloroethylene, CAS No. 79-01t" Natl anal Cancer Institute Carcinogcnesis Technical Report Services, Number 2, February 1976 (SCI-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. 3 Fishbein, L., "Industrial Mutagens and Potential Mutagens I. Halogenated Aliphatic Derivatives," MufcatJ R^sf 3C, 267-308, 1976. ~ iH monMnjo 8e5QAftCHjcoF(r4'4Al>4Ni*l HONS 022053 Trichloroethylene References - Continued "MRC Source Assessment Data Base, July 1977. Brown, S. L,., et al., "Research Program on Hazard Priority Ranking of Manufactured Chemicals," National Technical Infor mation Service Number PB 263 161, 1975. *Radding, S. L-, et al., "Review of the Environmental Fate of Selected Chemicals," National Technical Information Service Number 267 121, 1977. Fuller,.B., et al., "Preliminary Scoring of Organic Air Pollutants," National Technical Information Service Number PB 264 ]4jl2,> 1976. eFuller, B. B., "Air Pollution Assessment of Trichloroethylene," tf.t!on4U Technical! In/ormation Service Number PB 2S6 730, 1976. mi HfcndbOoklEnvironmental ,Datal on{ Organic Chemicals. nhpl4 lo.l Nl Y.' 141 B*Oi<54NT<I RCJSARdH CORPO^ATH}K| MONS 022054 Trichlorofluoromethane In mice, trichlorofluoromethane (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-carcinogenic-1-. 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 activation2-. Preliminary results from an NCI bioassay shows no difference between control and treated male or female rats?. It is probably not a carcinogen. " 'Epstein, s. s., et al., "Synergistic Toxicity and Carcinogenicity of 'Freons1 and Piperonyl Butoxide", Nature 214, 526-528, 1967. JUehleke, H., et al., "Metabolic Activation of Haloalkanes and Tests in vitrc for Mutagenicity", Xenobiotica 7 (7), 393-400, 1977. " 3flCI preliminary !datal ont trichlorofluoromethane, Nov. 27, -19 76. 142 \' V l4NS<to|fsEju?ci) corPqr4t(cn MONS 022055 Trichlorophenol Trichlorophenol (2,4,6-trichlorophendl,"Dovfeide 2s, CAS No. 88 06-2) has been found to be a carcinogen in mice when given orally but not subcutaneously1'2. 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 plants'. 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 Pe rsistance It is estimated that 5 x 10' Kg trichlorophenol is emitted from stationary sources per year1*. Since this is used as a pesticide, non-stationary sources (or total production) should be considered. It completely disappears in soil suspensions in 5 days5. Trichlorophenol (2,4,6) has a boiling point of 244.5C and a solubil ity of 800 mg/1 at 25C5. ^valuation of Carcinogenic, Teratogenic, and Mutaqenic Activities of Selected Pesticides and Industrial Chemicals", National Tech nical Information Service Number PB 223 159, 1968. innes, J. R. M., et al., "J. Nat. Cancer Inst., 2, 1101-1114, 1969. ~ ' "Cytological Effects of Pesticides. V. Effects of Some Herbicides on vicia Faba", Cytologia 39. 663-643, 1974 . *MRC Source Assessment Data Base, Jujy .197,7, verschueren, K., Handbook of Environmental Data Chemicals, Van Nostranai Keinhold Cpu , *Jew Yorjc, u on Organic 1977. ^ONSVJTOt HESEJURCF |:0f<>l3RA^ONl. HONS 022056 Urethane* Urethane (ethyl carbamate, CAS No. 51-79-6) has been ehown 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 Per3istance The only production data which could be found cited production from one US company with data not given and production below 454 Kg from a second company'. It has a boiling point of 183C and sublimes at 102C at 54 mm Mg, and is volatile at room temperature:. *The name urethane is sometimes applied to hiqh molecular weight polyurethanes used as forms, elastomers and coatings. Such products are not made from the chemical urethane and do not generate it or. decomposition. J"Urethane" in I ARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 7, 111-140, 1974. ' 144 MPNSfHTO FESSACtCHlCO'V'QRAllQN MONS 022057 vinyl Acatata vinyl acetate (CAS No. 108-05-4) has-been found to be non-car- cino'ii'iiif in rats at 2,500 ppm for 4 hrs./day for 12 months by C. M.i I t on i 1 . It has also been found negative on mouse skin?, mouse sebaceous glands5, and S. typhimurium tests'*'6, Both commercial vinyl acetate' and repeated tests of purified vinyl acetate" have been found to be mutagenic at a level of 150 ug/ml in viral r-ans format ion, vinyl acetate will be considered a possible carcinogen for this project for the first round of evalu.it ions. . P roduc t_i_on and Persistance It is estimated that 6.8 x in Kg is emitted per year from stationary sources'. Another estimate is a release of 7.8 x 10^ Kg from a production of 5.5 x 10' Kg-. Tt reacts with oxidizing , materials in the a tnosphore , and has a boiling point ot 73C and a vapor pressure of 83 mm at 20C'. "Survey of Compounds \h i i*.v Boer. Tested for Carcmoqenic Activity, 1572 - l)'l Vr1irv", V. S. Department of Health, I'.duca t ; on and Welfare, DHK\ Publication No. (Nil!) 75, Public He 3 : h Hervi co Publication No. 14 9. Garibyan, * . and rapoyar., - -3., "Study of the 31astcm~genir Activity 'f Certain Cher.i.:.t'. Substances C'sir.g a Minh-Spee.! Test Me*, hot!", Gig. Sanit. ?, ~4-7'', it'". ^Garibyan, D. K. and Papoyar., 5. A., "Use of Sebaceous Gland Reactions as a Test for Rapid Determination of Carcinogenic Activity of Chemicals", Nc-:c* . ttoci Izuch. Zagryaz.nen iva Vnesh. Srery K.instserogen, Voschostojir.i : 1 12- 115 , 1972. McCann, I. et ai., "Detection cf Carcinogens as Mutagens in the Sa1 none 11 a/Microsomc Test", Proc. Nat. Acad. Sci . (USA) 7 2(12) , 51 35- 5 11.', 1975. 'itartsen, II., et al., "Alkylating and Mutagenic Metabolites of llalogon.tted Olefins Produced by Human and Animal Tissues", Proc. Am. Assoc. Cancer Res. 1_7, 1 7, 1976. 6Bartsch, H. et el., "The Predictive Value of Tissue - Mediated ^ Mutagenicity Assays to Assess the Carcinogenic Risk of Chemicals , XARC Sci. Pub. No. 12, 467-491, 1976. 145i i (ONSANTO( RESEARCH COBPOBSlhON MONS 022058 Vinyl Acetate References - Continued 7Casto, 3. C. et al., "Assay of Industrial Chemicals m Syrian Hamster Cells for Enhancement of Viral Transformation", (Meeting Abstract), Proc. Am. Assoc. Cancer Res. 1_9, 155, 1977. 7Porsonal Communication with ?. C. Casto on > Pebruary 1978. ?MRC Source Assessment Data Base, July 1977. 1JDorigan, J. et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service Number P9 364 446, 1976.11 11Verschueren, K., Handbook of Environmental Data on Organic Chemicals. Van Nostrand Reinhold Co., New York, TT7TI 146 ft MONSANTO-RfcSMRCM CORPORATION MONS 022059 Vinyl Bromide 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 typhimurium 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 first phase of this project. Production and Persistance It is estimated that 4x101 kc/year of vinyl bromide is emitted from stationary sources.? 1Bartsch, H. et al., "Alkylating and Mutagenic Metabolites of Halegenated Olefins Produced by Human and Animal Tissues," Proc. Am. Assoc. Cancer Res. 1_7, 17, 1976 . :Barbin, A., et al., "Liver-Microsome-Mediated Formation of Alkylating Agents fror Vinyl Bromide and Vinyl Chloride," Biochem. Biophys. Res. Comm. 7 (2), 596-603, 1975. 3>MRC Soutce*Assessment Data Base, July 197!7. 14 T * **ONSANTp J*ESEARCHlCOBfOR*TlON MONS 022060 VinVl Chlorido 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, zymbal 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. typhimurium (Ames test)' and in enhancement of viral transformation3. Production and Persistance It is estimated that 1.4x10' kg is emitted per year*. The 1973 production of vinyl chloride was 2.4xl03 kg in the United States of which 97^ was used for production of polyvinyl chloride1. A 1974 EPA estimate was 9xl07 kg released to the atmosphere1. Other estimates of.production are 2.5xl03 kg (1974) 5 and 2.5x10' kg, 1.9xl0? kg and 2.6xl03 kg in 1974, 1975, and 1976'. The demand for PVC is expected to increase at an annual rate of 8-10?. through 1981' . 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 mm at 25'C . I "Vinyl Chloride" m IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Volume 7, 291-105, 1974. - Bartsch, !!., et al., "The Predictive Value of Tissue - Mediated Mutaqenicity Assays to Assess the Carcinocenic Risk of Chem icals, : IARC Sci.'Publ No. 12, 467-491, 1976. 3 Verschueren, X.,Handbook of Environmental Data on Organic Chemicals, Van Nostrand Reinhold Co., N. Y., 1977. II Personal communication with B. C. Casto on 9 February 1978. 51 MRC Source Assessment Data Base, July 1977. * Radaing, S. B., et al., "Review of the Environmental Fate of Selected Chemicals," National Technical Information Service Number PB 267 121, 1977. 7 Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for,Testing,* National Technical Information Ser vice Number P8 274 264, 1977. 149 tMOf<S4N?9ftSe,Ai4clk corporation?* MGNS 022061 Vinylidene Chloride Vinylidene chloride '(1,1-dichloroethylene,' CAS No. 75-35-4*) has been found to be mutagenic in the Salmonella typhimurium testl-J and in a metabolizing -itro system with E. coli K12". !t has also been reported to be carcinogenic in rats and rabbits' 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 lively to pose a significant risk to the general population7. Vinylidene chloride has been placed on the probable carcinogen list for this project. Production and Persistance It is estimated that 2.1 x 10r Kg are emitted a year from stationary services, with 70% of this coming from the oxychlorination of ethylene dichloride6. Other estimates of production and release are production of 2.7 x 107 Kg with 4.1x10" Kg released9, production of 1.2 x 108 Kg with 1.4 - 1.8 x 10c emitted and a 5 - 10% growth rate predicted7, 1.2 x 10' Kg produced with 1.1 x 10- Kg released'*', 7.7 x lO'.Kg produced from 1973 - .1975 with a 7 growth predicted :, and 2.7 x 10* Kg produced in 1972'-'. The 03 and HO reactions are estimted to gi\e less than a nr.-?-da' 1'.alf life!" while another reference cites HO half life of 26 hours *. Evapora tion of 50* from a 1 ppm solution at 25C will occur in 22 minutes1'. It has a vapor pressure of 617 mm at 25C and a boiling point of 37'C'*. Bartsch, II., et al., "Alkylating and Mutagenic Metabolites of Halogenated Olefins Produced by Human and Animal Tissue", Proc. Am. Assoc. Cancer Res. i_7, 17, 1976. "IARC, "Information Bulletin on the Survey of Chemicals being Tested for Carcinogenicity", International Agency for Research on Cancer, Lyon, Bulletin No. 5, July 1975. ?Bartsch, II., 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. uGreim, H. C. . et al., "Mutagenicity ir, o:,:rs and Potential Carcinogenicity of Chlorinated Ethylenes as a Function of Metabolic Oxdrane Formation", Biochem. Pharmacol., 2_4, 2013 2017, 1975. 149 ) kpfSAlfTp f*SE*Cl* gORIJOR VP* MONS 022062 Vinylidene Chloride References - Continued `JAnon, "Food Additives, Packaging Material for Use During Irradiation of Pre-Packaged Foods", Fed. Register, 33, 4659, 1968. 6Caputo, A., et al., "Oncogenicity of Vinyl Chloride at Low Concentrations in Rats and Rabbits, IRCS, 2, 1582, 1974. ~Hushcn, J. and Kornreich, M., "Air Pollution Assessment of Vinylidene Chloride", National Technical Information Service Number PB 256 738, 1976. -MRC Source Assessment Data Base, July 1977. `Brown, S. L. , et al., "Research Program or. hazard Priority Ranking of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. ;0Dorigan, J., et al., "Preliminary Scoring of Selected Organic Air Pollutants", National Technical Information Service No. PB 264 446, 1976. 1'Allport, J., et al., "A Study of Industrial Data on Candidate Chemicals for Testing", National Technical Information Service Number PB 274 264, 1977. 12Radding, S. 3., 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 cHeimicala, Van Nostrand Reinhold Co., N. Y., 1977. 150 B MON5ANIO. MVAVtt CORPORATION HONS 022063 Xyldhe Some literature suggests that xylenes are non-carcinogenic irritants1'*. Other literature indicates that all of tho xylenes cause neoplasms on mice after dermal application1. This may re fer to the same study where an increased number of unspecified tumors were observed in the mouse upon dermal application of mixed xylene after the use of croton oil or methane1*. The results of this study are considered equivocal" and would at most suggest that xylenes are promoters. The old xylene carcinogen liter ature is negative after skin painting mice5 and xylene is considereda non-carcinogen for this project. Pound, A. W. , "Induced Cell Proliferation and the Initiation of Skin Tumor Fornvtion in Mice by Ultraviolet Liaht", Pathology 2(4), 269-275, 1970. '' ' Listgarten, M. A., et al., "Ultrastructural Alterations in Hamster Cheek Pouch Epithelium ir> Response -c a Carcinogen", Arch. Oral Biol. 8 (2), 145-165, 3Fulier, 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 Rank ing of Manufactured Chemicals", National Technical Information Service Number PB 263 161, 1975. ( 5Survey of Chesdcals Which Have Been Tested for Carcinogenic Activity! $ICIf PhS-149 ,? VotOmefl* isa * ( M0NSA}T{O"lffSE(L':ff JORpOpATJON MQNS 022064 t Monsanto 9WS COPY t MSC/EASC - Dayton tOOL/DlVJlMrrTLOCATKMI Analysis imi or Moim received .REPORT CL O h 2 < a. > z a: < t k u. v> j s < to h < 2 ob. hz t--o Zh to O >J < u fi zu < Q- P REPORT NO.: MDA-012 JOB/PROJECT NO. 4 08.0540 DATE: . - i ' -.-a MONSANTO-OJVTON r. MTPAL TITLE: ANALYSIS OF WATER SAMPLES FROM THE KEARNY PLANT FOR PC9 CONTENT authors: Arthur J. Wright ABSTRACT: -phis report gives the results of the analysis of four water samples from the Kearny Plant for PCB content. *r too 4^~ Approved Donald^J. Dahm, Manager Environmental Analytical Sciences center Approval date: Restricted Distribution (see over) HIFT.NO.: M D A -012 AUTHORS: A . J . W r ig h t HONS 022065 COMPANY CONFIDENTIAL This document is the property ot Monsanto Company snd th# rsdpient is responses for its safskseping snd disposition. It- contains CONFIDENTIAL INFORMATION which must not bat rsproducad. revsaled to unauthorised persons or sent outside the Company without proper authorisation. DISTRIBUTION COPY number 3 D, M. Widdows 4 H. L. Williams 5 D. J. Dahm/W. M. Haynes 6 D. G. Glasgow 7 R. L. Maute/F. N. Hodgson 8 A. J . Wright 9 D. B . Nelson 10 Central Files 11 Technical Reports Library Kearny Dayton Dayton Dayton Dayton Dayton Dayton Davton St. Louis ABSTRACT ONLY R. K, Flitcraft Dayton Note: Distribution of this report is restricted. Requests for additional copies should be made through the principal contact at the Monsanto location involved or the Manager, Environmental Analytical Sciences Center, Dayton Laboratory, Dayton, Ohio COMPANY CONFIDENTIAL When no longer naadad. or upon request, return this report to Central Files, Dayton. MQNS 022066 ;> COMPANY CONFIDENTIAL INTRODUCTION Samples of water taken from four aitea in the area of the Kearny Plant of Monsanto Industrial Chemicals Company were analyzed for PCB content. RESULTS The PCB concentrations found are presented below. Sample Identification PCB Concentration, ppb Ground well River above plant River at plant River below plant 0.06 0.11 2.7 0.48 EXPERIMENTAL METHOD The samples were worked up following the procedure of ASTM D-3304, Analysis of Environmental Materials: Polychlorinated Biphenyls. Analysis of the extracts obtained following workup were done by electron capture gas chromatography under the following conditions: GC Mode 1: Column: Column Temperature: Injection Temperature: Detector Temperature: Carrier Gas: PCB's Screened For: Varian Model 3700 6' x ' glass packed with 4% XE-60 200*C 220*C 350*C N2 at 45 ral/min Aroclor 1254 and Aroclor 1242 PCB's were identified by comparing the sample chromatograms to standard chromatograms for Aroclor 1242 and 1254, two PCB's that have been used widely. The PCB concentration was then deter mined from the calibration curve for the appropriate standard. 1 COMPANY;CONFIDENTIAL MONSANTO RESEARCH CORPORATION HONS 022067