| 毒性の概要 | IDENTIFICATION AND USE: 1,2,3-Trichloropropane (TCP) is a colorless liquid with a acrid, unpleasant. It is used as an intermediate in the synthesis of other chemicals (e.g., pesticides) and as a crosslinking agent in the production of polymers, such as polysulfides and hexafluoropropylene. Former uses include a solvent for hydrophobic compounds and resins, as a paint and varnish remover, and as a degreasing agent. HUMAN EXPOSURE AND TOXICITY: Vapors of 1,2,3-trichloropropane were found to be objectionable to subjects at a concentration of 100 ppm because of eye and throat irritation and unpleasant odor. It was noted that vapors of 1,2,3-TCP were acrid at 50 ppm. Acute/subchronic neurotoxic effects of 1,2,3-TCP include CNS damage in humans. Sporadic cases of toxic hepatic injury from 1,2,3-TCP in humans have been reported. In an in vitro micronucleus assay, 1,2,3-TCP did not exhibit mutagenic activity compared to the concurrent control. The DNA breakage capacity and the cytotoxicity was assessed in the alkaline single cell gel electrophoresis test (comet assay) with and without S9-mix in isolated human lymphocytes. 1,2,3-TCP induced DNA breakage. 1,2,3-TCP is a suspected human carcinogen. ANIMAL STUDIES: A dose of 0.5 mL of 1,2,3-TCP applied to the intact skin of rabbits for 4 hr under semi-occlusive and for 24 hr under occlusive dressings produced mild reversible irritation. In contrast to these test results, another study classified 1,2,3-TCP as severely irritating, based on irritation scores from a Draize test on intact and abraded skin of rabbits. After instillation of 0.1 mL of undiluted 1,2,3-TCP, mild to moderate irritation of rabbit eyes was observed, with all effects being reversible within 2-7 days. Symptoms of intoxication in rats and mice included prostration, hypoactivity, ataxia, sedation, dyspnea, convulsions, lacrimation, salivation, irritation of the mucosa of eyes and nose, and liver and kidney damage. Immediate respiratory depression was a frequent cause of death. Delayed deaths (after 7-10 days) were ascribed to liver damage. Three dogs that received intragastic administration of 1,2,3-TCP had CNS depression, within 1-2 hours, and died within 1-2 days. Continuous inhalation of 0.4 and 0.8 mg/cu m of 1,2,3-TCP for 7 days caused hemorrhages in rat lungs with desquamation and destruction of bronchial, bronchiolar & alveolar epithelium. Rats given 113 or 149 mg/kg 1,2,3-TCP in drinking water for 13 weeks developed renal pyknosis, glomerular adhesions, and accumulated protein in the tubular lumen. Intermittent 4-hour exposures for 11 days at 3 ppm of 1,2,3-TCP caused a decreased thickness of olfactory epithelium in rats. A degeneration of the olfactory epithelium was found in rats at 10 ppm or higher concentrations, and inflammation and decreased thickness of the olfactory epithelium were found in mice at 10 to 13 ppm with degeneration at higher concentrations. Among 140 carcinogenic chemicals tested in long-term animal studies, 1,2,3-TCP was among the seven producing uterine neoplasms in mice (spontaneous tumor rate 0.3%). 1,2,3-TCP was evaluated in 2-year toxicology and carcinogenesis studies by the NTP. 1,2,3-TCP induced benign and/or malignant neoplasms at multiple sites in both rats and mice. 15 daily doses of 37 mg/kg 1,2,3-TCP were given by intraperitoneal injection to pregnant rats throughout implantation and organogenesisthere were no fetotoxic or teratogenic effects in the offspring, but maternal toxicity was evident. Male rats given five oral doses of 80 mg/kg/day showed no evidence of testicular toxicity. In a one-generation reproduction study, progeny indices were unaffected by treatment with 1,2,3-TCP. Male rats administered 1,2,3-TCP by gavage at a dosage of 125 mg/kg body weight per day for 120 days showed significant increases in relative testes weights and a significant decrease in relative epididymis weight. However, no effects on sperm count or sperm morphology and no histomorphological changes of testes or epididymis were observed. Impairment of survival rates was observed among pups of treated females that had been mated with untreated males. 1,2,3-TCP is mutagenic in bacterial test systems with Salmonella typhimurium strains TA 97, TA 100, and TA 1535 and E. coli WP2 uvr A in the presence of metabolic activation. 1,2,3-TCP did not induce unscheduled DNA synthesis in primary rat hepatocytes. It induced gene mutation at the thymidine kinase locus in L5178Y mouse lymphoma cells, sister chromatid exchange in Chinese hamster V79 and ovary cells and chromosomal aberrations in Chinese hamster ovary cells, only in the presence of metabolic activation. Additionally, 1,2,3-TCP enhanced the transformation of Syrian hamster embryo cells by simian adenovirus SA7. |
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