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MEMORANDUM

TO: Larry Reisman

Chief 

Analytical Support Branch 

CC: Daniel Bushman, Ph.D.

Analytical Support Branch

FROM: Martin Gehlhaus

Toxicologist 

Analytical Support Branch 

DATE: June 30, 2011

SUBJECT: Review of National Toxicology Program (NTP) Cancer Classification Data for onitrotoluene

The NTP Report on Carcinogens, Twelfth Edition (RoC) (NTP, 2011) identified onitrotoluene as “reasonably anticipated to be a human carcinogen.” The NTP RoC summary 

profile for o-nitrotoluene (NTP, 2011), the NTP RoC background document for o-nitrotoluene

(NTP, 2008), the primary NTP studies (NTP, 2002, 1996, 1992), and other supporting 

documents cited in the NTP RoC summary profile have been reviewed.

Consistent with the EPA Guidelines for Carcinogen Risk Assessment, the NTP RoC 

evaluates the scientific literature and publicly available, peer-reviewed technical reports of 

human and laboratory studies to evaluate whether substances are possible human carcinogens. 

The NTP RoC does not present a quantitative assessment of the risks of cancer associated with a 

given chemical. Rather, it indicates the potential hazard associated with chemicals but do not 

establish the exposure conditions that would pose cancer risks to individuals.

Inconsistencies between how the data were interpreted by the NTP and how that same 

data would be interpreted under EPA’s Guidelines for Carcinogen Risk Assessment (U.S. EPA, 

2005) were not identified. The EPA Cancer Guidelines reference the NTP criteria for assessing 

individual studies in the assessment of carcinogenicity, stating “(c)riteria for the technical 

adequacy of animal carcinogenicity studies have been published and should be used as guidance 

to judge the acceptability of individual studies, e.g., NTP, 1984...” (pg. 2-16).

NTP and EPA use similar criteria for listing chemicals as “reasonably anticipated to be a 

human carcinogen” or “likely to be carcinogenic to humans”, respectively. The EPA 

Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005) specifically detail “likely to be 

carcinogenic to humans” as a comparable weight of evidence term to the NTP classification 

“reasonably anticipated to be a human carcinogen” (pg. 2-53). Supporting data for an agent 

listed with this EPA descriptor includes “an agent that has tested positive in animal experiments 

in more than one species, sex, strain, site, or exposure route, with or without evidence of 
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carcinogenicity in humans”. Based on the available data, the NTP RoC background document 

and summary have identified o-nitrotoluene as “reasonably anticipated to be a human 

carcinogen,” as an increased incidence of tumors was observed in experimental animals at 

multiple sites in multiple species.

The conclusions of the NTP RoC for o-nitrotoluene were consistent with how the Agency 

would consider the carcinogenicity data available for o-nitrotoluene. Therefore, it would be 

appropriate for the Agency, for the purposes of listing o-nitrotoluene on the Toxics Release 

Inventory, to conclude that o-nitrotoluene can reasonably be anticipated to cause cancer in 

humans. 

References

National Toxicology Program (NTP). (1992). Toxicity Studies of o-, m-, and p-Nitrotoluenes 

Administered in Dosed Feed to F344/N Rats and B6C3F1 Mice. Toxicity Report Series No. 23. 

NIH Publication No. 93-3346. Department of Health and Human Services, Public Health 

Service, Research Triangle Park, NC. 

NTP. (1996). NTP Comparative Toxicity and Carcinogenicity Studies of o-Nitrotoluene and oToluidine Hydrochloride (CAS Nos. 88-72-2 and 636-21-5) Administered in Feed to Male 

F344/N Rats. Toxicity Report Series No. 44. Department of Health and Human Services, Public 

Health Service, Research Triangle Park, NC. 

NTP.(2002). Toxicology and Carcinogenesis Studies of o-Nitrotoluene (CAS no. 88-72-2) in 

F344/N Rats and B6C3F1 Mice (Feed Studies). Technical Report Series No. 504. Department of 

Health and Human Services, Public Health Service, Research Triangle Park, NC.

NTP. (2008). Report on Carcinogens Background Document for o-Nitrotoluene. Department of 

Health and Human Services, Public Health Service, Research Triangle Park, NC.

NTP. (2011). Report on Carcinogens, Twelfth Edition. Department of Health and Human 

Services, Public Health Service, Research Triangle Park, NC.

U.S. EPA. (2005) Guidelines for carcinogen risk assessment. Risk Assessment Forum, 

Washington, DC; EPA/630/P-03/001F.