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Publication : Reevaluation of a twenty-four-month chronic toxicity/carcinogenicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in the B6C3F1 hybrid mouse.

First Author  Parker GA Year  2006
Journal  Int J Toxicol Volume  25
Issue  5 Pages  373-8
PubMed ID  16940009 Mgi Jnum  J:125775
Mgi Id  MGI:3759914 Doi  10.1080/10915810600846245
Citation  Parker GA, et al. (2006) Reevaluation of a twenty-four-month chronic toxicity/carcinogenicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in the B6C3F1 hybrid mouse. Int J Toxicol 25(5):373-8
abstractText  Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been widely used as an explosive in U.S. army munitions formulations since World War II. Two-year carcinogenicity studies revealed RDX to be noncarcinogenic in two strains of rats, but a 2-year carcinogenicity study in B6C3F1 mice revealed an increased incidence of hepatocellular neoplasms in females. Based on results of the study in B6C3F1 mice, RDX has been classified as a possible carcinogen. The authors reevaluated the archived histological sections from the B6C3F1 mouse study, using current histopathologic diagnostic criteria and interpretations. The earlier evaluation showed a statistically significant increase in the incidence of hepatocellular adenoma/carcinoma in female mice from the three highest dose groups (7, 35, and 175/100 mg/kg/day). The revaluation yielded a slightly lower incidence at each of the dose levels in female mice. The reduced number of hepatocellular neoplasms was largely due to reclassification of hepatocellular adenomas as foci of cytoplasmic alteration, in compliance with current diagnostic criteria. The reevaluation was reviewed by a pathology working group (PWG), which arrived at a consensus classification of each lesion. Based on the consensus diagnoses of the PWG, only one female group (35 mg/kg/day) showed a significant increase when compared to controls. The incidence of hepatocellular neoplasms for all groups, including the 35 mg/kg/day group, was within the reported incidence range for spontaneous hepatocellular neoplasms in female B6C3F1 mice. The increased incidence of hepatocellular neoplasms in female mice given RDX at 35 mg/kg/day was interpreted as equivocal evidence of a carcinogenic effect.
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