Chronic toxicity and oncogenicity bioassay of inhaled ethyl acrylate in Fischer 344 rats and B6C3F1 mice.

Male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 25 or 75 ppm (0, 0.10 or 0.31 mg/l) ethyl acrylate vapors, 6 hours per day, 5 days per week, for a total of 27 months. Additional rats and mice were exposed to 225 ppm (0.92 mg/l) for 6 months and then held for 21 additional months post-exposure. Histopathologic changes in olfactory portions of the nasal mucosa were present in animals in all of these three exposure groups. These microscopic exposure-related changes were concentration-dependent, primarily in terms of distribution of the lesions within the nasal cavity. Generally those areas of the nasal mucosa normally lined by olfactory epithelium were altered, while the regions lined by respiratory epithelium were relatively unaffected. There was no indication of an oncogenic response in any organ or tissue in either rats or mice. A follow-up study in which Fischer 344 rats and B6C3F1 mice were exposed to 5 ppm (0.02 mg/l) for 24-months revealed no treatment-related changes in the nasal mucosa.

Pharmacokinetic and toxicological evaluation of dogs fed 1,2,4,5-tetrachlorobenzene in the diet for two years.

1,2,4,5-Tetrachlorobenzene (TCB), an intermediate in several industrial processes, was administered in the diet to dogs at 5 mg/kg . d for 2 yr, followed by a 20-mo recovery phase. The animals were examined periodically for toxicity; the concentration of TCB in the plasma and fat was measured during the 2 yr of exposure and 20 mo of recovery. After 18 mo of exposure, all clinical chemistry parameters were normal; however, after 24 mo, serum alkaline phosphatase activity and total bilirubin levels were slightly elevated in the dogs dosed with TCB. Both clinical chemistry parameters returned to normal levels within 3 mo of the cessation of exposure. After the 20-mo recovery, gross and histopathologic examination of tissues revealed no morphological changes considered related to the ingestion of TCB. At the end of 2 yr of exposure, TCB had reached 98 and 97% of the calculated steady-state concentrations in fat and plasma, respectively. TCB was eliminated from the fat and plasma with half-life values of 111 and 104 d, respectively. Although there were only small differences in the approach to steady state, differences in the rate of elimination of TCB from fat and plasma resulted in dramatic changes in the fat/plasma ratio of TCB throughout the entire study.

Chronic toxicity and reproduction studies of hexachlorobutadiene in rats.

Hexachlorobutadiene (HCBD), while not produced commercially in the United States, may be encountered as an unwanted by-product of certain processes associated with the chlorination of hydrocarbons. Studies were conducted to assess the potential long-term toxicity of HCBD. In a reproduction study conducted in rats, dose levels of 20 or 2.0 mg/kg-day of HCBD induced slight maternal toxicity (primarily of the kidney) but caused no adverse effects on reproductive parameters-percent pregnancy and neonatal survival/development. A decreased neonatal body weight was noted at the highest dose level of 20 mg/kg-day of HCBD. No toxicologic effects were observed among the adults at a dose level of 0.2 mg/kg-day or among the neonates at dose levels of 0.2 or 2.0 mg/kg-day of HCBD. In a chronic toxicity study in rats, ingestion of 20 mg/kg-day for up to 2 years caused multiple toxicologic effects, primarily of the kidney, including the development of renal tubular adenomas and adenocarcinomas. Ingestion of the intermediate dose level of 2 mg/kg-day caused lesser degrees of toxicity, but no evidence of neoplasia. Ingestion of the lowest dose level of 0.2 mg/kg-day of HCBD caused no effects that could be attributed to treatment. These data indicate a dose-response relationship for HCBD-induced toxicity affecting primarily the kidney. HCBD-induced neoplasms occurred only at a dose level higher than that causing discernible renal injury.

Results of a two year chronic toxicity study with hexachlorobutadiene in rats.

Lifetime ingestion by rats of 0.2 mg/kg/day of hexachlorobutadiene caused no discernible ill effects. Slight degrees of primarily renal toxicity occurred with 2 mg/kg/day; 20 mg/kg/day caused multiple toxic effects, including renal tubular neoplasms.