Appendix B
Agents with Potential Carcinogenic Activity and Their Occurrence in the Diet

This appendix is a compilation of all agents classified by IARC as known (1), probable (2A), or possible (2B) human carcinogens, or by the NTP as known or reasonably anticipated to be carcinogenic to humans. The appendix is subdivided into four tables in terms of dietary occurrence as follows:

  • Table B-1: Agents That Might Be Encountered in U.S. Diets
  • Table B-2: Agents Formerly Encountered in U.S. Diets
  • Table B-3: Agents Rarely or Accidentally Encountered in U.S. Diets
  • Table B-4: Agents Unlikely to Have Ever Been Present in U.S. Diets

Caveats and Disclaimers

The classification of these agents as potential carcinogens is based on epidemiological data in only 20% of the cases. In most cases, the classification is based on findings in high-dose animal experiments, usually conducted in more than one species. The IARC 2B classification typically signifies sufficient evidence of carcinogenicity from animal studies. Limited evidence in animals, without other highly suggestive data from human or mechanistic studies would not result in a 2B rating. The committee relied on IARC and NTP classifications of potential carcinogens as a means of obtaining a large set of agents of potential concern that have been systematically and rigorously evaluated by the same criteria.



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--> Appendix B Agents with Potential Carcinogenic Activity and Their Occurrence in the Diet This appendix is a compilation of all agents classified by IARC as known (1), probable (2A), or possible (2B) human carcinogens, or by the NTP as known or reasonably anticipated to be carcinogenic to humans. The appendix is subdivided into four tables in terms of dietary occurrence as follows: Table B-1: Agents That Might Be Encountered in U.S. Diets Table B-2: Agents Formerly Encountered in U.S. Diets Table B-3: Agents Rarely or Accidentally Encountered in U.S. Diets Table B-4: Agents Unlikely to Have Ever Been Present in U.S. Diets Caveats and Disclaimers The classification of these agents as potential carcinogens is based on epidemiological data in only 20% of the cases. In most cases, the classification is based on findings in high-dose animal experiments, usually conducted in more than one species. The IARC 2B classification typically signifies sufficient evidence of carcinogenicity from animal studies. Limited evidence in animals, without other highly suggestive data from human or mechanistic studies would not result in a 2B rating. The committee relied on IARC and NTP classifications of potential carcinogens as a means of obtaining a large set of agents of potential concern that have been systematically and rigorously evaluated by the same criteria.

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--> The carcinogenic risk posed by a substance is a function of its exposure and potency, which in some cases can differ dramatically for different routes of exposure. Listings in this table should not be interpreted as indicating that the actual risk to humans is significant. In some cases, it is possible that there is no risk under the conditions of human exposure. Definitive conclusions regarding human risk are difficult to reach, as discussed in Chapter 5. The primary purpose of this table is to provide a collection of substances that form the basis for the risk comparisons made in Chapter 5. For the majority of agents listed, the IARC monographs, FDA tabulations, NRC reports, and assistance from several groups provided enough information to unequivocally assign agents to one of the four tables. In a few cases, the assignment of agents to a given table was difficult (e.g., agents with past exposures, several dyes, drugs, and chemical intermediates). For example, before passage of the first Food and Drug Act of 1906, many unevaluated substances, many of them harmful, found their way into the food supply. Table B-2 (Agents Formerly Encountered in U.S. Diets), therefore, covers only the period since 1906. Even today, occurrences of exposure to trace levels of chemical intermediates and dyes used in food packaging are difficult to establish. A food packaging component often can be regarded as an indirect additive. A component is virtually never used in all types of packaging. Constituents that are used in the manufacture of food packaging components are generally present, if at all, as unwanted impurities, typically at very low levels. Also, veterinarians have considerable latitude in prescribing drugs in treating livestock and poultry. Thus, parallel problems are encountered with drug residues and with pesticide residues as well. The number of all these is large, and establishing exposure with any accuracy to a quantitatively minor substance in our complex food supply entails major problems of surveillance, sampling, and analysis. Inadvertent accidental exposures can be difficult to anticipate or

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--> recognize. The PBB contamination of animal feed and resulting human exposure in Michigan is an obvious case that the committee noted. However, other cases suggest that our assessment of such exposures may be too limited, and thus the list in Table B-3 might well be inappropriately short. These include the use of phenobarbital to increase the metabolic elimination of chlordane in cattle feeding on contaminated pineapple leaves, illegal use of anabolic steroids in European meat production (Daeseleire, 1992), and related precautionary notes of Truhaut et al. (1985). Td01 Estimation As indicated by the TD01 values listed, the carcinogenic activity of these substances spans at least eight orders of magnitude, and human exposures perhaps even a wider range, starting in some cases at infinitesimal levels. Thus, although TD01 values and related risk numbers present the appearance of accuracy, it is inappropriate in general to treat the results as providing for actual predictions of health risks. TD01 values are derived from cancer potency or unit risk values available from U.S. EPA or Cal/EPA, using the approximation TD01 = 0.01 · qhuman where qhuman is an upper bound estimate of the slope of the cancer dose-response curve in humans. In general, an upper confidence limit on the value qhuman estimates was obtained by fitting the multistage model to dose-response data from animal cancer bioassays, thereby providing a lower confidence limit on the TD01. This procedure included corrections for differences in pharmacokinetics at high and low doses, study length, and animal body size. Time-dependent forms of the multistage model were used for cases of poor survival in some study groups, provided sufficient data were

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--> available. In a few cases, the estimate of potency was derived directly from human data. For a large number of agents, potency was derived by systematically applying the data selection criteria of regulatory agents to the Canrcinogenic Potency Database (CPDB) of Gold and colleagues. These criteria have been described by Hoover et al. (1995) and Cal/EPA (1992) and are highlighted below: Data sets showing statistically significant dose-related increases in cancer incidence were used, unless the CPDB indicated that the authors considered the results unrelated to exposure to the carcinogen. Data sets were excluded from consideration if the end point was specified as all tumor bearing animals or combined unrelated tumors. When several studies were available, the highest quality study was selected. The quality of the study was judged on the basis of such factors as the numbers of animals, dose selection, duration, etc. Where there were multiple studies of similar quality conducted in the most sensitive species, the geometric mean of potencies derived from these studies was calculated. When both sexes of the same species/strain were tested under the same laboratory conditions, and no other adequate studies were available for that species, the data set for the more sensitive sex was selected. Potency was derived from data sets for malignant tumors, combined malignant and benign tumors, or tumors that would have likely progressed to malignancy. In a few cases, the committee derived cancer potency values directly from bioassay data using the data selection criteria and techniques described above.

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--> Table B-1 Agentsa That Might Be Encountered in U.S. Diets Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) A-alpha-C (2-Amino-9H-pyrido[2,3-b]indole) 2B N: Derived (cooking) 2.50E-02 Acetaldehyde 2B N: Constitutive, derived and added. Also S (synthesized for food additive use) Carcinogenicity by oral route uncertain Acrylamide 2A S: Tap water; constituent of food packaging 2.22E-03 Acrylonitrile 2A S: constituent of food packaging; pesticide 1.00E-02 Aflatoxins 1 N: Acquired (mycotoxin)   Aflatoxin B1 1 N: Acquired (mycotoxin) 2.17E-04 Aflatoxin M1 2B N: Acquired (mycotoxin)   Alcoholic beverages 1 N and S   p-Aminoazobenzene 2B S: food color trace impurity   4-Aminobiphenyl 1 S: food color impurity 4.76E-04 Amitrole 2B S: pesticide 1.06E-02 Androgenic (anabolic) steroids 2A N: Constitutive S: veterinary product and food residue   Aramite 2B S: pesticide 3.33E-01 Arsenic 1 N: Pass-through. Also, indirect additive from tap water and previously through pesticidal use 1.89E-03

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) Asbestos 1 N: Added through tap water. Carcinogenicity by oral route uncertain Atrazine 2B S: pesticide   Benz(a)anthracene 2A N: Derived (cooking) 5.00E-04 Benzene 1 N: Constitutive; derived (cooking); added (food packaging constituent, tap water) 1.00E-01 Benzidine 1 S: trace food color impurity 2.00E-05 Benzo(b)fluoranthene 2B N: Derived (cooking); pass-through 5.56E-04 Benzo(j)fluoranthene 2B N: Derived (cooking); pass-through 1.30E-03 Benzo(k)fluorathene 2B N: Derived (cooking); pass-through   Benzo[a]pyrene 2A N: Derived (cooking); pass-through 8.33E-04 Beryllium and beryllium compounds 2A N: Pass-through and added (tap water)   Betel quid with tobacco 1 N: Direct   Bracken fern 2B N: Direct; a food   Bromodichloromethane 2B S: In tap water; N: Present in marine microalgae (non-food occurrence) 7.69E-02 1,3-Butadiene 2A S: Food packaging constituent 5.56E-03 Butylated hydroxyanisole 2B S: Direct and indirect food additive 5.00E+01 Cadmium and cadmium compounds 1 N: Pass-through and added (tap water) Carcinogenicity by oral route uncertain

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--> Caffeic acid 2B N: Constitutive 5.88E-01 Captafol 2A S: pesticide 6.67E-02 Carbon tetrachloride 2B S: Pesticide; tap water contaminant 5.56E-02 Chlordane 2B S: pesticide 7.69E-03 Chlordecone (Kepone) 2B S: pesticide 6.25E-04 Chlorinated paraffins (Ave. chain length C12; approx. 60% chlorine by weight) 2B S: General industrial use 1.12E-01 -Chlorinated toluenes 2B S:pesticides   Chloroform 2B S: insecticide; tap water contaminant 3.23E-01 3-Chloro-2-methylpropene   S: plastics and pesticides intermediate 7.14E-02 Chlorophenols 2B S: general industrial use   2,4,6-Trichlorophenol 2B S: pesticide 1.43E-01 p-Chloro-o-toluidine and its strong acid salts 2A S: pesticide 3.70E-02 Chromium (VI) compounds 1 N: Pass-through and added (tap water) 2.44E-01 Citrus Red No. 2 2B S: orange skin colorant   Cobalt and cobalt compounds 2B N: Constitutive (essential in B12); pass-through. Also indirect additive   Coffee (urinary bladder) 2B N: Traditional food beverage   p-Cresidine 2B S: food color intermediate 6.67E-02

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) Danthron (Chrysazin; 1,8-Dihydroxyanthraquinone) 2B N: plant constituent drug; S: Synthesized for use as drug 1.32E-01 DDD   S: persistent lipophilic pesticide 2.94E-02 DDE   S: Metabolite of DDT 2.94E-02 DDT 2B S: persistent lipophilic pesticide 2.94E-02 2,4-Diaminotoluene 2B S: food packaging constituent 2.50E-03 Dibenz(a,h)acridine 2B N: Derived (cooking)   Dibenz(a,j)acridine 2B N: Derived (cooking)   Dibenz(a,h)anthracene 2A N: Derived (cooking); pass-through (plant uptake fuel combustion byproducts) 2.44E-03 7H-Dibenzo(c,g)carbazole 2B N: Derived 1.32E-05 Dibenzo(a,e)pyrene 2B N: Derived   Dibenzo(a,h)pyrene 2B N: Derived 3.23E-05 Dibenzo(a,i)pyrene 2B N: Derived 3.45E-05 Dibenzo(a,l)pyrene 2B N: Derived and added (tap water)   1,2-Dibromo-3-chloropropane 2B S: pesticide; persistent in groundwater 1.43E-03 p-Dichlorobenzene 2B S: indirect additive (pesticide and other) 2.50E-01 1,2-Dichloroethane (Ethylene dichloride) 2B S: pesticide fumigant; general industrial use 1.43E-01 Dichloromethane 2B S: used in food processing; fumigant 7.14E-01

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--> 1,3-Dichloropropene 2B S: soil fumigant 2.33E-01 Dichlorvos (DDVP) 2B S: insecticide 3.45E-02 Di(2-ethylhexyl)phthalate 2B S: plasticizer 1.19E+00 Diethylstilbesterol 1 S: growth promoter in cattle production 2.86E-05 Diethyl sulfate 2A S: general industrial use 1.03E-02 Dimethylformamide 2B S: food packaging constituent   Dimethyl sulfate 2A S: indirect food additive 7.69E-04 1,6-Dinitropyrene 2B S: Diesel combustion; assume uptake by food plants 2.22E-04 1,8-Dinitropyrene 2B S: Diesel combustion; assume uptake by food plants 1.32E-04 1,4-Dioxane 2B S: food packaging constituent 3.70E-01 Epichlorohydrin 2A S: food packaging constituent 1.25E-01 Estrogen, non-steroidal 1     Estrogen, steroidal 1 N: Constitutive and added (drug residues)       S: synthetic growth promoters   Estradiol 17 (and esters) 2B N: Constitutive and added (drug residues) 2.56E-04 Estrone (and estrone benzoate) (Steroidal estrogens, group 1; estrone - sufficient in animals) N: Constitutive  

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) Ethinyl estradiol (Steroidal estrogens, group 1; ethinyl estradiol - sufficient in animals) S: Added (meat residues)   Ethyl acrylate 2B N: Constitutive; S: Food packaging constituent; added flavoring ingredient   Ethylene oxide 1 S: fumigant 3.23E-02 Ethylene thiourea 2B S: pesticidal breakdown product 2.22E-01 Formaldehyde 2A N: Derived and added (preservative in defoaming agent; in food packaging). Carcinogenicity by oral route uncertain Glu-P-1 (2-Amino-6-methyldipyrido[1,2-a:3',2'-d]-imidazole 2B N: Derived (cooking) 2.08E-03 Glu-P-2 (2-Aminodipyrido[1,2-a:3',2'-d]-imidazole) 2B N: Derived (cooking) 7.14E-03 Glycidaldehyde 2B N: Derived   Heptachlor 2B S: pesticidal contaminant, in food chain 2.22E-03 Hexachlorobenzene 2B S: pesticidal contaminant, in food chain 5.56E-03 Hexachlorocyclohexanes (HCH) 2B S: pesticidal contaminant, in food chain   alpha isomer 2B S: pesticidal contaminant, in food chain 3.70E-03 beta isomer 3 S: pesticidal contaminant, in food chain 6.67E-03

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--> gamma isomer 3 S: pesticidal contaminant, in food chain 9.09E-03 technical grade 2B S: pesticidal contaminant, in food chain 2.50E-03 Hot mate (Ilex paraguariensis) 2A N: Added   Indeno(1,2,3-cd)pyrene 2B N: Pass-through; derived   Isoprene 2B N: Constitutive   IQ (2-Amino-3-methylimidazo[4,5-f]quinoline) 2A N: Derived (cooking) 7.14E-03 Lead and lead compounds, inorganic 2B N: Pass-through   Me-A-alpha-C (2-Amino-3-methyl-9H-pyrido-[2,3-b]indole) 2B N: Derived (cooking) 8.33E-03 Medroxyprogesterone acetate 2B S   MeIQ 2B N: Derived (cooking) 4.76E-03 MeIQx 2B N: Derived (cooking) 2.94E-03 Mestranol (Steroidal estrogens, group 1; mestranol - sufficient in animals) S: Estrogen steroid used in meat production   5-Methoxypsoralen (in the presence of UVA) 2A N: Constitutive   8-Methoxypsoralen (xanthotoxin) plus UV radiation 1 N: Constitutive (excluding UV radiation)  

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) N-Nitrosodiethanolamine 2B S: Impurity in herbicide atrazine; contaminant in cutting fluids and some cosmetics 3.57E-03 N-Nitrosomethyl-vinylamine 2B N: Derived 6.25E-05 N-Nitroso-N-methylurethane 2B N: Derived 9.09E-05 Polybrominated biphenyls 2B S: was flame retardant; now minimal and localized food chain contaminant 3.33E-04 Ponceau MX 2B S: Was drug and cosmetic color in US; used as a food colorant elsewhere 2.22E+00 beta-Propiolactone 2B S: Industrial use 7.14E-04 Reserpine 3 N: Indirectly added veterinary drug 9.09E-04 o-Toluidine 2B S: Chemical intermediate (e.g., pesticides, dyes); N: constitutive 5.56E-02 o-Toluidine hydrochloride (2B) S 7.69E-02 a Agents identified by IARC as known (1), probable (2A), or possible (2B) human carcinogens or by the NTP as known or reasonably anticipated to be carcinogens (NTP K or NTP R, if the agent has not been classified as 1, 2A, or 2B by IARC). b For definition of terms and overall evaluations, see Preamble, pp.28-29 (IARC 1993). c Where possible, synthetic agents (S) are distinguished from naturally occurring (N) (as defined in Chapter 1). Naturally occurring agents are subclassified into constitutive, derived, acquired, or added (as defined in Chapters 1 and 2). d The TD01 is the chronic dose in mg/kg/day causing a 1% increase in tumors in experimental animals.

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--> Table B-4 Agentsa Unlikely to Have Ever Been Present in U.S. Diets Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) 2-Acetylaminofluorene (NTP R) S: was intended for pesticidal use but never marketed 2.63E-03 Adriamycin 2A N: Antibiotic; also S (synthesized for use)   AF-2 (2-(2-furyl)-3(5-nitro-2-furyl)acrylamide] 2B S: Food additive previously in Japan 4.17E-02 2-Aminoanthraquinone 3 (NTP R) S: dye and pharmaceutical intermediate 3.03E-01 0-Aminoazotoluene 2B S: dye 2.63E-03 1-Amino-2-methylanthraquinone 3(NTP R) S: dye intermediate 6.67E-02 2-Amino-5-(5-nitro-2-furyl)-1,3,4-thiadiazole 2B S: drug 6.25E-04 0-Anisidine 2B S: dye intermediate; water pollutant 7.14E-02 0-Anisidine hydrochloride (2B) S: dye intermediate 9.09E-02 Azaserine 2B N: mycotoxin. S (synthesized) drug. 9.09E-04 Azacytidine 2A N: antibiotic (drug)   Azathioprine 1 S: drug 5.56E-03 Benzidine based dyes 2A S: dyes   Benzotrichloride 2B S: Dye and herbicide intermediate 7.69E-04

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) Bischloroethyl nitrosourea (BCNU) 2A S: drug   Bis(chloromethyl)ether 1 S: chemical intermediate 2.17E-04 Bischloromethyl methyl ether 1 S: chemical intermediate   Bleomycins 2B N: antibiotic; drug   beta-Butyrolactone 2B S: chemical intermediate 1.00E-02 Carrageenan, degraded 2B S: produced synthetically from seaweed.   Ceramic fibres 2B S: used in thermal insulation   Chlorambucil 1 S: drug 2.27E-05 Chlorendic acid 2B S: chemical intermediate 1.10E-01 Chlornaphazine 1 S: drug   1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea 2A S: drug   1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea 1 S: drug   Chloromethyl methyl ether (technical grade) 1 S: chemical intermediate 4.17E-03 4-Chloro-0-phenylenediamine 2B S: dye intermediate 6.25E-01 Chlorozotocin 2A S: drug 4.17E-05 C.I. Acid Red 114 2B S: dye   C.I. Basic Red 9 monohydrochloride (NTP R) S: dye 4.00E-02

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--> C.I. Direct Blue 15 2B S: dye   Cisplatin 2A S: drug   Coal-tars 1 S: used in various pharmaceutical, cosmetic, and biocidal preparations   Cupferron (NTP R) S: chemical reagent 4.55E-02 Cyclophosphamide (anhydrous) 1 S: drug 1.64E-02 Cyclophosphamide (hydrated) 1 S: drug 1.75E-02 Cyclosporin (Ciclosporin) 1 N: antibiotic. Drug.   Dacarbazine 2B S: drug 2.04E-04 Danthron (Chrysazin; 1,8-Dihydroxyanthraquinone) 2B N: plant constituent drug. S: Synthesized for use as drug. 1.32E-01 Daunomycin 2B N: antibiotic. drug.   N,N'-Diacetylbenzidine 2B S: dye intermediate   2,4-Diaminoanisole 2B S: dye intermediate 4.35E-01 2,4-Diaminoanisole sulfate (2B) S: dye intermediate 7.69E-01 4,4'-Diaminodiphenyl ether (4,4'-Oxydianiline) 2B S: chemical intermediate 7.14E-02 3,3'-Dichlorobenzidine 2B S: dye intermediate; curing agent 8.33E-03 3,3'-Dichlorobenzidine dihydrochloride (2B) S: dye intermediate; curing agent   3,3'-Dichloro-4,4'-diaminodiphenyl ether 2B S: may not be commercially used   Diepoxybutane 2B S: chemical intermediate, curing agent   1,2-Diethylhydrazine 2B S: an experimental rocket fuel  

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) Diglycidyl resorcinol ether (DGRE) 2B S: used as or in epoxy resins 5.88E-03 Diisopropyl sulfate 2B S: chemical intermediate   3,3'-Dimethoxybenzidine (o-Dianisidine) 2B S: dye and chemical intermediate 2.04E-03 3,3'-Dimethoxybenzidine dihydrochloride (2B) S: dye and chemical intermediate 2.70E-03 trans-2-[(Dimethylamino)-methylimino]-5-[2-(5-nitro-2-furyl)vinyl]-1,3,4-oxadiazole 2B S: possibly used in pharmaceutical 2.27E-02 2,6-Dimethylaniline (2,6-Xylidine) 2B N: present in tobacco leaves; S: chemical intermediate 1.75E+00 3,3'-Dimethylbenzidine (o-Tolidine) 2B S: dye intermediate 1.33E-04 3,3'-Dimethylbenzidine dihydrochloride (2B) S: dye intermediate 1.79E-04 Dimethylcarbamoyl chloride 2A S: pesticide intermediate 7.69E-04 1,2-Dimethylhydrazine 2B S: experimental rocket fuel 1.82E-05 Dimethylvinylchloride (NTP R) S: chemical intermediate 2.22E-01 Direct Black 38 (technical grade) 2A S: dye 1.35E-03 Direct Blue 6 (technical grade) 2A S: dye 1.35E-03 Direct Brown 95 (technical grade) 2A S: dye 1.49E-03 Erionite 1 N: Natural zeolite   Ethyl methanesulfonate 2B S: No evidence of commercial use  

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--> Formaldehyde 2A N: pyrolysis product S: many industrial uses 5.56E-01 2-(2-Formylhydrazino)-4-(5-nitro-2-furyl)thiazole 2B S: No evidence of commercial use 4.35E-03 Griseofulvin 2B N: antibiotic. S/N (acquired): occasional veterinary drug 7.14E-01 HC Blue 1 2B S: in hair dyes 1.96E-01 Hydrazine 2B S: rocket fuel 5.88E-04 Hydrazine sulfate 2B S: used in metal refining 3.33E-03 Hydrazobenzene (1,2-Diphenylhydrazine) 3 (NTP - R) S: colorant of waxes, resins, soaps, fats 1.15E-02 Iron dextran complex 2B S: drug   Lasiocarpine 2B N: Acquired (contamination of cereal grains in Asia) 1.28E-03 Lead acetate 2B S: general industrial uses. Was used in medicine and hair dyes 3.57E-02 Lead phosphate 2B S: limited industrial use   Lead subacetate 2B S: analytical reagent. Astringent in lotions. 2.63E-01 Magenta (containing CI Basic Red 9) 2B S: dye   Melphalan 1 S: cancer drug 7.69E-05 Merphalan 2B S: cancer drug   2-Methylaziridine (Propyleneimine) 2B S: chemical and pharmaceutical intermediate 3.85E-04

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--> Agent IARC Classificationb Occurencec TD01d (mg/kg-d) 4,4'-Methylene bis(2-chloroaniline) 2A S: curing agent for polyurethane prepolymers 6.67E-03 4,4'-Methylene bis(N,N-dimethyl)benzeneamine 3 (NTP - R) S: dye intermediate; antioxidant in grease and oil 2.17E-01 4,4'-Methylene bis(2-methylaniline) 2B S: dye intermediate 1.09E-02 Methyl methanesulfonate 2B S: commercial use unknown 1.01E-01 2-Methyl-1-nitroanthraquinone (of uncertain purity) 2B S: dye intermediate 2.33E-03 Metronidazole 2B S: human drug; some veterinary use. 5.00E-02 Michler's ketone (NTP R) S: dye intermediate 1.16E-02 Mitomycin C 2B N: antibiotic 1.22E-06 Monocrotaline 2B N: Constitutive in bush teas; not believed consumed in US 1.00E-03 MOPP and other combined chemotherapy including alkylating agents 1 S: cancer drug   Mustard gas (sulfur mustard) 1 S: cancer drug   Myleran (1,4-butanediol dimethylsulfonate) 1 S: cancer drug   Nafenopin 2B S: experimental drug  

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--> 2-Naphthylamine (beta-Naphthylamine) 1 N: pyrolysis product (will clarify). S: dye intermediate 5.56E-03 Niridazole 2B S: drug   5-Nitroacenaphthene 2B S: dye intermediate not commercially used in US 7.69E-02 1-[(5-Nitrofurfurylidene)-amino]-2-imidazolidinone 2B S: antibacterial agent, reported used to treat urinary tract infections 5.56E-03 Nitrogen mustard 2A S: vesicant in chemical warfare. potential cancer drug.   Nitrogen mustard hydrochloride (NTP - R) S: antineoplastic and immunosuppressant in human and veterinary medicine   Nitrogen mustard N-oxide 2B S: cancer drug and chemical sterilant   N-Nitroso-N-ethylurea 2A S: No known commercial use. Environmental occurrence unknown 3.70E-04 3-(N-Nitrosomethyl-amino)propionitrile 2B N: Derived   4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) 2B N: Derived   N-Nitroso-N-methylurea 2A S: No known commercial use. Environmental occurrence unknown 8.33E-05 N-Nitrosomorpholine 2B S: No evidence of commercial use. Impurity in methylene chloride and chloroform 1.49E-03 N'-Nitrosonornicotine 2B N: Derived 7.14E-03

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) Noresthisterone 2B S: human drug   Oxymethalone (NTP R) S: human drug   Panfuran S (containing dihdroxymethyl-furatrizine) 2B S: human drug   Phenacetin 2A S: human and veterinary analgesic and antipyretic 4.55E+00 Phenazopyridine 2B S: human drug 5.88E-02 Phenazopyridine hydrochloride 2B S: human drug 6.67E-02 Phenobarbital 2B S: human and veterinary sedative and anticonvulsant 2.17E-02 Phenoxybenzamine 2B S: human drug 3.23E-03 Phenoxybenzamine hydrochloride 2B S: human drug 3.70E-03 Phenytoin 2B human and veterinary anticonvulsant   Procarbazine (2A) S: cancer drug 7.14E-04 Procarbazine hydrochloride 2A S: cancer drug 8.33E-04 1,3-Propane sultone 2B S: chemical intermediate 4.17E-03 Rockwool 2B S: thermal and acoustic insulant   Selenium sulfide 3 (NTP R) S: topical drug in human and veterinary medicine   Slagwool 2B S: thermal and acoustic insulant  

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--> Solar radiation 1 N   Streptozotocin 2B N: antibiotic 9.09E-05 Talc containing asbestiform fibres 1 N   Tetranitormethane (NTP R) S: diesel and rocket fuel additive 7.69E-04 Thioacetamide 2B S: previously used with mercury as mordant 1.64E-03 4,4'-Thiodianiline 2B S: dye intermediate 6.67E-04 Thorium dioxide (NTP K) N: limited commercial use. was radio-opaque for x-ray imaging.   Treosulfan 1 S: cancer drug   Trichlormethine (Trimustine hydrochloride) 2B S: cancer drug   Tris (1-aziridinyl)phosphine sulfide (Thiotepa) 1 S: cancer drug 8.33E-04 Tris(2,3-dibromopropyl)phosphate 2A S: flame retardant 4.35E-03 Trypan blue 2B S: biological stain   Ultraviolet radiation A 2A N   Ultraviolet radiation B 2A N   Ultraviolet radiation C 2A N   Uracil mustard 2B S: cancer, immunosuppressive, antiviral and antibacterial drug   Vinyl bromide 2A S: general industrial use 1.85E-02

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--> Agent IARC Classificationb Occurrencec TD01d (mg/kg-d) 4-Vinylcyclohexene 2B S: Byproduct of chemical production processes   4-Vinylcyclohexene diepoxide 2B S: General industrial use   a Agents identified by IARC as known (1), probable (2A), or possible (2B) human carcinogens or by the NTP as known or reasonably anticipated to be carcinogens (NTP K or NTP R, if the agent has not been classified as 1, 2A, or 2B by IARC). b For definition of terms and overall evaluations, see Preamble, pp.28-29 (IARC 1993). c Where possible, synthetic agents (S) are distinguished from naturally occurring (N) (as defined in Chapter 1). Naturally occurring agents are subclassified into constitutive, derived, acquired, or added (as defined in Chapters 1 and 2). d The TD01 is the chronic dose in mg/kg/day causing a 1% increase in tumors in experimental animals.