1 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 o nitrotoluene
The NTP Report on Carcinogens, Twelfth Edition (RoC) (NTP, 2011) identified o nitrotoluene as “ reasonabl y 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 , p eer
- reviewed technical reports of human and laboratory studies to evaluate whether substances are possible human carcinogens. T he NTP RoC does not present a quantitative assessment of the risks of cancer associated with a given chemical. Rather, it indicate s 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 C ancer G uidelines reference the NTP criteria for assessing individual stud ies 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 acc ep tability 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 of2 carcinogenicity in hum ans”. 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 listin g o - nitrotoluene on the Toxics Release Inventory, to conclude that o - nitrotoluene can reasonabl y 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 o

Toluidine 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 Triang le 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 Tr iangle 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 H ealth 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.