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.
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
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).
Td01Estimation
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
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.
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 |
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 |
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 |
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 |
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 |
|
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 |
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) |
|
Agent |
IARC Classificationb |
Occurrencec |
TD01d (mg/kg-d) |
5-Methylchrysene |
2B |
N: Pass-through (assume food plant uptake) |
7.69E-05 |
Methylmercury compounds |
2B |
N: Derived |
|
N-Methyl-N'-nitro-N-nitrosoguanidine |
2A |
N: Derived |
1.20E-03 |
Mirex |
2B |
S: pesticidal contaminant, in food chain |
5.56E-04 |
5-(Morpholinomethyl)-3-[(5-nitrofurfurylidene-amino]-2-oxalolidione |
2B |
S: veterinary drug |
2.56E-03 |
Nickel, metallic |
2B |
N: Pass-through |
|
Nickel compounds |
1 |
N: Pass-through |
|
Nitrilotriacetic acid, and its salts |
2B |
S: Industrial use |
1.89E+00 |
Nitrilotriacetic acid, trisodium salt monohydrate |
(2B) |
S: Industrial use |
1.00E+00 |
6-Nitrochrysene |
2B |
S: byproduct of fuel combustion; assume uptake by food plants |
2.50E-05 |
Nitrofen (technical grade) |
2B |
S: herbicide |
1.22E-01 |
2-Nitrofluorene |
2B |
S: byproduct of diesel fuel combustion Assume deposition on food plants |
1.28E-03 |
2-Nitropropane |
2B |
S: used in adhesives which contact food |
3.70E-01 |
1-Nitropyrene |
2B |
N: incomplete combustion detected in grilled chicken; S: in diesel and gasoline exhaust particulates |
9.09E-03 |
4-Nitropyrene |
2B |
S: byproduct of fuel combustion; assume deposition on food plants |
4.00E-04 |
N-Nitroso-N-dibutylamine |
2B |
N: Derived |
9.09E-04 |
N-Nitrosodiethylamine |
2A |
N: Derived |
2.78E-04 |
N-Nitrosodimethylamine |
2A |
N: Derived (also constitutive in plant not consumed in US) |
6.25E-04 |
N-Nitrosodi-N-propylamine |
2B |
N: Derived; also S (pesticidal impurity) |
1.43E-03 |
N-Nitrosomethylethylamine |
2B |
N: Derived |
4.55E-04 |
N-Nitrosopiperidine |
2B |
N: Derived |
1.06E-03 |
N-Nitrosopyrrolidine |
2B |
N: Derived |
4.76E-03 |
N-Nitrososarcosine |
2B |
N: Derived |
7.14E-02 |
Ochratoxin A |
2B |
N: Acquired (mycotoxin) |
4.76E-04 |
Pentachlorophenol |
2B |
S: wood perservative and herbicide, in food chain |
5.56E-01 |
Phenyl glycidyl ether |
2B |
S: Food-packaging constituent |
7.14E-02 |
o-Phenylphenate, sodium |
2B |
S: fungicide |
3.33E+00 |
PhIP (2-Amino-1-methyl-6- phenylimidazo[4,5-b]pyridine |
2B |
N: Derived (cooking) |
2.00E-03 |
Pickled vegetables (traditional in China) |
1 |
N and S |
|
Agent |
IARC Classificationb |
Occurrencec |
TD01d (mg/kg-d) |
Polychlorinated biphenyls |
2A |
S: General industrial use, in food chain |
1.30E-03 |
Polychlorinated biphenyls (> 60% chlorine by weight) |
2A |
S: General industrial use, in food chain |
2.00E-03 |
Potassium bromate |
2B |
S: Flour bromination; low residue |
2.04E-02 |
Progestins |
2B |
N: Constitutive S: synthetic hormones |
|
Progestrone |
|
N: Constitutive and added (drug residues) |
|
Propylene oxide |
2A |
S: food product and package sterilant; used in food starch production |
4.17E-02 |
Propylthiouracil |
2B |
S |
1.00E-02 |
Radon and its decay products |
1 |
N: Added through tap water |
|
Saccharin |
2B |
S: Non-nutritive sweetening agent; was used as preservative |
7.69E+01 |
Safrole |
2B |
N: Constitutive and added |
4.55E-02 |
Salted fish (Chinese style) |
1 |
N: Direct; a food |
|
Silica, crystalline |
2A |
N: Added |
Carcinogenicity by oral route uncertain |
Sodium o-phenylphenate |
2B |
S: Fungicide and antibacterial agent |
|
Sterigmatocystin |
2B |
N: Acquired (mycotoxin) |
2.86E-04 |
Styrene |
2B |
N: Constitutive and added; (S: food-packaging constituent) |
|
Styrene oxide |
2A |
S: food-packaging constituent |
6.25E-02 |
Sulfallate |
2B |
S: herbicide |
5.26E-02
|
Testosterone |
(Androgenic steroid, group 2A; testosterone sufficient in animals) |
N: constitutive and added (drug residue) |
|
Tetrachlorodibenzo-p-dioxin |
2B |
S: Widespread environmental contaminant in food chain |
7.69E-08 |
Tetrachloroethylene |
2B |
S: General industrial use; contaminant of food and water |
1.96E-01 |
Toluene diisocyanate |
2B |
S: Food-packaging constituent |
2.56E-01 |
Toxaphene (polychlorinated camphenes) |
2B |
S: Pesticidal contaminant of food and water |
8.33E-03 |
Toxins derived from Fusarium monilforme |
2B |
N: Acquired (mycotoxin) |
|
Trp-P-1 (Tryptophan-P-1) |
2B |
N: Derived |
3.85E-04 |
Trp-P-2 (Tryptophan-P-2) |
2B |
N: Derived |
3.13E-03 |
Urethane (Ethyl carbamate) |
2B |
N: Derived |
1.00E-02 |
Vinyl chloride |
1 |
S: Food-packaging constituent |
3.70E-03 |
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 TD01 is the chronic dose in mg/kg/day causing a 1% increase in tumors in experimental animals. |
This page in the original is blank. |
Table B-2 Agentsa Previously But No Longer Encountered in U.S. Diets
Agent |
IARC Classificationb |
Occurrencec |
TD01d (mg/kg-d) |
Benzyl violet 4B |
2B |
S:Was direct food color additive |
5.00E-01 |
Carbon black extracts |
2B |
S: Use of food colorant 'channel black' disapproved in 1976. Note IARC listing of extracts, not carbon black |
|
Chloramphenicol |
2A |
N: Antibiotic, in soil. S: synthetically produced antibiotic; meat residues. |
|
Chlorphenoxy herbicides |
2B |
S: All uses in food production cancelled by 1974. |
|
Diethylstillbesterol |
1 |
S: growth promoter in cattle production |
2.86E-05 |
Dihydrosafrole |
2B |
S: was food flavorant (35 years ago) |
2.27E-01 |
4-Dimethylaminoazo-benzene |
2B |
S: Was food colorant in U.S. prior to 1918 |
2.17E-03 |
1,1-Dimethylhydrazine (UDMH) |
2B |
S: agricultural chemical breakdown product |
3.57E-03 |
Ethylene dibromide |
2A |
S: was widely used fumigant. Currently a groundwater contaminant in a few locations |
4.00E-02 |
Agent |
IARC Classificationb |
Occurrencec |
TD01d (mg/kg-d) |
Methylthiouracil |
2B |
S: Was growth promoter in meat production (swine and sheep) |
2.50E-02 |
N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide |
2BS: used in veterinary applications6.67E-03 |
|
|
Oil Orange SS |
2B |
S: General food colorant until 1956 |
|
Ponceau 3R |
2B |
S: Food color delisted in 1961 |
6.25E-01 |
Thiourea |
2B |
N: Indirect additive (was citrus fungicide, chemical intermediate for pesticide production); is constitutive for nonfood plants. |
1.39E-01 |
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. Values derived from epidemiologic data are indicated in bold face. |
Table B-3 Agentsa Rarely or Accidentally Encountered in U.S. Diets
Agent |
IARC Classificationb |
Occurrencec |
TD01d (mg/kg-d) |
Acetamide |
2B |
N: Derived (constitutive in a non-food plant) |
1.43E-01 |
Antimony trioxide |
2B |
N: metallic compound; uses include as glassware constituent |
|
Auramine |
2B |
S: may have been food dye in some countries |
1.14E-02 |
p-Chloroaniline |
2B |
S: intermediate; pesticide degradant |
|
Cycasin |
2B |
N: Constitutive |
|
Danthron (Chrysazin; 1,8-Dihydroxyanthraquinone) |
2B |
N: plant constituent drug; S: synthesized for use as drug. |
1.32E-01 |
Glasswool |
2B |
S: Use in food processing |
|
Hexamethylphosphor-amide |
2B |
S: General industrial use |
1.61E-04 |
Methylazoxymethanol acetate |
2B |
N: Constitutive (of cycasin) |
|
4,4'-Methylenedianiline |
2B |
S: Indirect food additive through use as curing agent in resins used to coat large containers in alcoholic beverage production |
6.25E-03 |
4,4'-Methylenedianiline dihydrochloride |
(2B) |
S: See cell above |
8.33E-03 |
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. |
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 |
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 |
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 |
|
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 |
|
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 |
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 |
|
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 |
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 |
|
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 |
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. |