NTP Toxicology and Carcinogenesis Studies of Pentachloronitrobenzene (CAS No. 82-68-8) in B6C3F1 Mice (Feed Studies).
Toxicology and carcinogenesis studies of pentachloronitrobenzene (99% pure), a fungicide, were conducted by administering diets containing 0, 2,500, or 5,000 ppm pentachloronitrobenzene to groups of 50 B6C3F1 mice of each sex for 103 weeks. These doses were selected because, in 13-week studies in which the chemical was administered in feed at doses up to 20,000 ppm in male mice and up to 40,000 ppm in female mice, body weight gain depression was observed at 10,000 ppm and above in males and female and deaths occurred at 40,000 ppm in females. The National Cancer Institute had conducted 2-year (diet) studies in B6C3F1 mice and Osborne-Mendel rats (See TR-61 reported in 1978). Survival among male mice was low, not all livers were examined from dosed female mice, and the size of the control group was considered to be small. For these reasons, the NCI decided to conduct additional 13-week and 2-year studies in B6C3F1 mice. Under the conditions of the NCI studies, pentachloronitrobenzene was not carcinogenic in either Osborne-Mendel rats or B6C3F1 mice. In the studies reported in this Technical Report, the survival of male mice was comparable among control and dosed groups (control, 35/50; low dose, 31/50; high dose, 32/50). Final mean body weights of low dose and high dose male mice were 96% and 90% that of the controls. All groups of female mice showed evidence of bacterial infection. At week 84, survival in dosed and control female mice was 38/50; 34/50; 30/50; after week 84, survival in dosed groups decreased, with the final survival being 30/50; 20/50; 15/50. The mean body weight of high dose female mice was more than 10% lower than that of the control group after week 20 and was 21% lower than controls at week 104. The mean body weight of low dose female mice was within 10% that of the control group until week 88 and was 18% lower than controls at week 104. No compound-related neoplastic lesions were seen in either male or female mice. The nonneoplastic lesions observed in female mice were considered to be secondary to bacterial infection (primarily Klebsiella) and included hematopoiesis of the liver (9/50; 21/50; 23/50) and spleen (14/50; 23/48; 27/50), plasma cell hyperplasia of the mediastinal lymph nodes (1/44; 4/47; 9/45), and ovarian abscesses (12/49; 22/50; 29/50). Pentachloronitrobenzene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of Aroclor 1254-induced male Syrian hamster or male Sprague-Dawley rat liver S9 when tested according to the preincubational protocol. Pentachloronitrobenzene was not mutagenic at the TK+/- locus of L5178Y mouse lymphoma cells in the presence or absence of Aroclor 1254-induced F344/N rat liver S9. In cultured Chinese hamster ovary cells, pentachloronitrobenzene did not induce sister-chromatid exchanges but did induce chromosomal aberrations both with and without Aroclor 1254-induced male Sprague-Dawley rat liver S9. An audit of the experimental data was conducted for the 2-year studies of pentachloronitrobenzene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenicity for either male or female B6C3F1 mice receiving 2,500 or 5,000 ppm of pentachloronitrobenzene. Infection is considered to have decreased survival of the female mice and thus reduced the sensitivity for determining the presence or absence of a carcinogenic response. Synonyms or Trade Names: Avicolreg.; PCNB; quintozene; Botrilexreg.; Brassicolreg.;Folosanreg.; PKhNB; Tilcarexreg.; Terraclorreg.; Tritosanreg.