Effects of a 13-Week Chloropentafluorobenzene Inhalation Exposure of Fischer 344 Rats and B6C3F1 Mice

Abstract

Chloropentafluorobenzene (CPFB) has been identified as a can didate simulant for nonpersistent chemical warfare agents. Acute toxicity studies have shown that CPFB has limited adverse ef fects on laboratory animals. A 21-day inhalation study of rats and mice to 2.5, 0.8, and 0.25 mg CPFB/liter resulted in re duced weight gain in male and female rats exposed at the high concentration only and identified the liver as a potential target organ. This multiconcentration inhalation study was designed to detect a no-observable-effect level associated with repeated expo sure to CPFB. Male and female rats and mice were exposed to 250, 50, or 10 mg CPFB/m3 (0.25, 0.05, or 0.01 mg CPFB/li ter) for 13 weeks. No treatment-related effects on body weight, clinical chemistries, mortality, absolute or relative organ weight or histopathology were noted.

Evaluation of Chloropentafluorobenzene as an Intake Simulant for Chemical Defense Training

“…The critical effect for evaluation of safe exposure to CPFB is the liver toxicity associated with repeated exposure (Kinkead et al, 1990b). Specifically, hypertrophy and hepatocytomegaly were observed in mice following exposure to 300 ppm CPFB, 6 h/day, for 3 weeks, and the liver-to-bodyweight ratio in rats and female mice was increased in a dose-related fashion.…”

“…Chloropentafluorobenzene does not appear to be mutagenic, either in the presence or absence of metabolic activation, and the questionablc in vitro suggestions of genotoxicity were not borne out by the in vivo studies. In addition, subchronic exposure (Kinkead et al, 1990a) did not produce any of the tissue changes, such as peroxisomal proliferation, which typically accompany promotional carcinogenesis in rodents. Therefore, it is not likely that CPFB would be carcinogenic, even under the conditions of a lifetime bioassay.…”

“…Similarly, assessment of the micronucleated polychromatic and normochromatic erythrocyte populations during the exposures indicated a general absence of genotoxic activity. A PBPK model for CPFB was used to assess the tissue exposure to CPFB during this study (Kinkead et al, 1990b. Based on the modeling, bone marrow tissue exposure to CPFB during the in vivo study was similar to or greater than the concentrations used in the in vitro assays.…”

“…Shortterm exposure to CPFB vapor was shown to pose no serious hazard by the inhalation route when all rats survived a 4-h exposure to an upper limit concentration of 4.84 mg/L (581 ppm), a concentration many orders of magnitude higher than that which is likely to be encountered in the field. Similarly, oral dosing indicates an L') 50 of greater than 5 g/kg, which would classify CPFB as "practically nontoxic" (Kinkead et al, 1990a).…”

“…In order to better evaluate the impact of prolonged or repeated exposure to CPFB, as well as to determine a no-observable-adverse-effect level (NOAEL), a 13-week exposure of rats and mice was carried out at concentrations of 1.2, 6, and 30 ppm (Kinkead et al, 1990a;Kinkead et al, 1991). No treatment-related effects were observed at any concentration in either species.…”