Abstract  The report by Cholakis et al. (1980) presents methods and results of a total of nine toxicology studies with RDX. As per instructions, the acute toxicity studies and the two genotoxicity studies (Ames test and Dominant lethal mutation test) were not considered in this review. Overall, the tests, which were carried out during the period 1978-1980, can be considered acceptable even at the light of specific guidelines (from EPA and OECD) which were published about a decade later. Minor omissions in experimental design, testing or reporting are indicated below in the answers to the posed questions. In a few instances reporting and/or interpretation of findings is unclear.

Abstract  The U.S. Environmental Protection Agency’s (EPA) National Center for Environmental Assessment (NCEA) is currently developing a human health assessment of 1,3,5-trinitro-1,3,5-hexahydrotriazine (RDX) CAS No. 121-82-4. The study reports by Levine et al. (1983) entitled “Determination of the Chronic Mammalian Toxicological Effects of RDX: Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-trinitro-1,3,5- triazine (RDX) in the Fischer 344 Rat,” and Crouse et al. (2006) entitled “Subchronic Oral Toxicity of RDX in Rats” are being considered for the development of an oral toxicity value for RDX. Additionally, the study report by Lish et al. (1984) entitled “Determination of the Chronic Mammalian Toxicological Effects of RDX: Twenty-Four Month Chronic Toxicity/ Carcinogenicity Study of Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in the B6C3F1 Hybrid Mouse” is being considered in the development of a cancer assessment for RDX in conjunction with a reevaluation of the incidence of hepatocellular adenomas and carcinomas (Parker et al. 2006). The reports of Levine et al. (1983) and Lish et al. (1984) are on the effects from chronic oral (dietary) exposure to RDX in Fischer 344 (F344) rats and B6C3F1 mice. Crouse et al. (2006) describe effects from a 90-day gavage exposure to RDX in F344 rats. The primary reports and the associated necropsy and histopathology reports have not been subjected to a formal peer review process. Such a peer review process is important in establishing the appropriateness, validity, robustness of the study design, conduct, and findings of the reported investigation. The purpose of the requested peer review was for EPA to receive written comments from individual experts.