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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.
Representative terms from entire chapter:
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