Histopathological lesions

Moderate but prolonged exposure of rats to TBT and TPhT acetate at subchronic levels (< 20 mg/kg OTC) brought about histopathologic lesions in lungs, liver, intestines and kidneys besides reduction in lymphocyte count at higher concentrations37. 

There were no treatment-related gross or histopathological lesions of the skeletal muscle or bone in rats, guinea pigs, dogs, or quail exposed to 0, 15, 48, or 260 ppm hexachloroethane 6 hours/day, 5 days/week for 6 weeks (Weeks et al. 1979). 

Both oral and inhalation exposures to high concentrations of hexachloroethane were associated with hyperactivity, ataxia, convulsions, and/or prostration in rats, sheep, and dogs. The mechanism for these neurological effects is not clear since there were no apparent histopathological lesions in the brains of the affected animals. Neurological effects were only noted with the high-dose exposures. 

In contrast, no reproductive effects were observed in male Sprague-Dawley rats exposed to 500 ppm -hexane 22 hours a day for 6 months (IRDC 1981). No treatment-related lesions were noted in any of the reproductive tissues examined (seminal vesicles, prostate, testis, epididymis). Similar results were reported in both sexes of weanling Fischer 344 rats exposed to up to 10,000 ppm -hexane 6 hours a day, 5 days a week for 13 weeks (Cavender et al. 1984). No treatment-related histopathologic lesions were present in any of the following reproductive tissues ovaries, uterus, oviducts, vagina, cervix, seminal vesicles, prostate, testis, or epididymis. 

Histopathologic lesions of the liver have been demonstrated in several oral studies in rodents dosed at higher levels of 1,4-dichlorobenzene. Cloudy swelling and centrilobular necrosis were observed in the livers of rats that received 1,4-dichlorobenzene at 500 mg/kg/day for 4 weeks (Hollingsworth et al. 1956). Thirteen-week studies have resulted in degeneration and necrosis of hepatocytes in rats that received doses of 1,200 mg/kg/day and above and in mice, hepatocellular degeneration was observed at... 

Gastrointestinal Effects. Intermediate-duration (30-148 days) exposure did not cause treatment-related histopathological lesions in the esophagus, stomach, small intestines, or large intestines in rats exposed to hexachlorobutadiene at dose levels up to 20 mg/kg/day (Schwetz et al. 1977) or levels up to 100 mg/kg/day (Kociba et al. 1971). Lifetime exposure at dose levels of 20 mg/kg/day (Kociba et al. 1977a) did not result in any effect on this system. 

In the same study, serum biochemical parameters (aspartate aminotransferase activity and total bilirubin) were increased at doses of 20 mg/kg/day. Urinary excretion of coproporphyrin increased at dose levels of 20 mg/kg/day in lifetime studies however, histopathological lesions were not found (Kociba et al. 1977a). 

Cardiovascular Effects. Inhalation and oral studies in humans and animals have not revealed any treatment-related histopathological lesions of heart tissue, or impairment of cardiac functions, even at dose levels causing severe liver and kidney damage (Adams et al. 1952 Stewart et al. 1961 Umiker and Pearce 1953). It is possible that high-level carbon tetrachloride exposure may produce cardiac arrhythmias by sensitization of the heart to catecholamines (Reinhardt et al. 1971). Accordingly, there is some concern for cardiovascular toxicity following substantial exposure to carbon tetrachloride. 

Immunological Effects. Oral lifetime exposure to 2,3-benzofuran caused no histopathological lesions in lymphatic tissues of rats or mice (NTP 1989). This provides limited evidence that the immunological system may not be a major target for 2,3-benzofuran toxicity, but more definitive conclusions are not possible without further studies. 

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