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EC number: 200-826-3 | CAS number: 74-97-5
Frequency and severity of changes after a single dose: No significant changes were noted after administration of 500 mg/kg of the test substance. After a single dose of 3,000 and 4,500 mg/kg, fatty degeneration of the liver and the kidney was slight or absent in mice that died three or four hours later, was usually severe in the mice killed twenty-four hours later, but was generally not found in those surviving forty-eight hours or longer. Twelve of fifty mice that died or were killed within forty-eight hours showed subcapsular necrosis of the liver, and 5 showed some hydropic liver cells; slight similar changes were seen in one of five mice killed ninety-six hours after receiving the compound. Eight of 32 mice that were killed or died within twenty-four hours after administration of the compound showed hemoglobin casts in a few renal tubes; 7 of these mice received 4,500 mg/kg, and 1 of the 7 showed epithelial necrosis in a few scattered convulted renal tubules. Slight cardiac fatty degeneration was found in only 1 mouse, which died within twenty-four hours after a dose of 3,000 mg/kg. The few adrenal glands examined showed indications of transient lipoid deplation of the cortex.
Frequency and severity of changes after consecutive daily doses: In the series of mice given multiple doses of 3000 mg/kg, the lesions were more frequent, severe and prolonged than after a single dose. 24 to 48 hours after the initial dose, fatty degeneration occurred in the liver, the kidney and less frequently in the heart. It was slight or absent after eighty hours. Twenty-three of 32 mice that died or were killed within seventy-two hours after the initial dose showed subcapsular necrosis of the liver, 8 showed hydropic degeneration and 8 showed a slight to moderate increase of mononuclear cells periportally. Such changes were infrequent after three days and were not seen in mice killed more than five days after the initial dose. One mouse killed nine days after the initial dose showed a few focal and centrolobular areas of coagulation necrosis of the liver cells. Hemoglobin casts were seen in this series in only 1 animal, which died in forty-eight hours, shortly after the third daily dose. Another mouse, which died twenty-four hours after the sixth daily dose, showed extensive tubular necrosis of the inner cortical zone of the kidney. Slight pneumonitis was found in nearly all groups. Cloudiness of the eyes was observed in only 2 of 11 mice that died six hours after the second dose and in 3 of 8 mice that died shortly after the third daily dose of 3,000 mg/kg. It was found in 2 of 8 mice that died after a second daily dose of 4,500 mg/kg.
A single gavage and 10 day repeated dose toxicity study was performed with the test substance bromochloromethane. 50% of bromochloromethane in olive oil was administered by stomach tube to several series of white Swiss mice. Three series of mice were given a single dose of 500, 3,000 and 4,500 mg/kg, respectively, and a fourth series was given 3,000 mg/kg on one to ten consecutive days. The control group received olive oil only. Several representative mice from each series were killed for histologic examination and some of the mice that died were also examined. Fatty degeneration of the liver and kidney, as well as focal necrosis and hydropic degeneration of the liver was observed in the 3,000 and 4,500 groups after single oral dose. Changes were most severe after 24 hours and were reversible in mice surviving 48 hours. No effects were noted at 500 mg/kg. In the series of mice given multiple doses of 3000 mg/kg, the lesions were more frequent, severe and prolonged than after a single dose. The oral LD50 in mice was determined to be 4300 mg/kg bw.
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