Trichloroethylene Inhibits Uptake of 3H‐5‐Hydroxytryptamine but not Uptake of 3H‐Zimeldine or 3H‐Propranolol in Isolated Perfused Rat Lungs

Hede, A; Berglund, Bengt G.; Post, Claes

doi:10.1111/j.1600-0773.1987.tb01791.x

Cited by 2 publications

(1 citation statement)

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“…dose of 3,000 mg/kg on day 17 of pregnancy (19). In vitro, TCE has been reported to inhibit 5-hydroxytryptamine uptake in the isolated perfused rat lung (22,23).…”

Section: Lung Cancer In Animalsmentioning

confidence: 99%

Pulmonary toxicity and carcinogenicity of trichloroethylene: species differences and modes of action.

Green

2000

Environ Health Perspect

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Trichloroethylene (TCE) is both acutely toxic and carcinogenic to the mouse lung following exposure by inhalation. In contrast, it is not carcinogenic in the rat lung and is markedly less toxic following acute exposure. Toxicity to the mouse lung is confined almost exclusively to the nonciliated Clara cell and is characterized by vacuolation and increases in cell replication. Chloral, a metabolite of TCE that accumulates in Clara cells and has been shown to be the cause of the toxicity, also causes aneuploidy in some test systems. Cytotoxicity, increased cell division, and aneuploidy are known risk factors in the development of cancer and provide a plausible mode of action for TCE as a mouse lung carcinogen. All acute and chronic effects of TCE on the mouse lung are believed to be a direct consequence of high cytochrome P450 activity and impaired metabolism of chloral in Clara cells. Comparisons between species suggest that the ability of the human lung to metabolize TCE is approximately 600-fold less than that in the mouse. In addition, the human lung differs markedly from the mouse lung in the number and morphology of its Clara cells. Thus, the large quantitative differences between the metabolic capacity of the mouse lung and the human lung, together with the species differences in the number and morphology of lung Clara cells, suggest that the risks to humans are minimal and that other tumor sites should take precedent over the lung when assessing the potential risks to humans exposed to TCE. Key words: carcinogenicity, lung, mode of action, species comparisons, toxicity, TCE, trichloroethylene. - (1). Consequently, the pulmonary airways are exposed to this chemical irrespective of the route of administration, and at high dose levels both toxicity and cancer have been observed in laboratory animals. The effects are species specific; the mouse is far more sensitive to the acute toxicity of TCE than the rat and is also the only species in which an increased incidence of lung tumors has been seen. As a result of this difference in sensitivity between laboratory animals, a number of investigators have sought to explain the mechanistic basis of the both toxicity and carcinogenicity in mice and the relevance of these data to humans exposed to this chemical. In this article the effects of TCE on the lung are reviewed together with proposed modes of action for both acute toxicity and cancer. Lung Cancer in AnimalsIncreases in pulmonary adenomas and adenocarcinomas have been observed in two studies in which mice were exposed to TCE by inhalation. Fukuda et al. (2) reported an increase in both pulmonary adenomas and adenocarcinomas following exposure of female CD-1 mice (males were not tested) to 150 and 450 ppm TCE (6 hr/day, 5 days/week for 104 weeks) and, in a shorter study, Maltoni et al. (3,4) reported an increase in pulmonary adenomas in male Swiss and female B6C3F1 mice exposed to 600 ppm, 7 hr/day, 7 days/week for 78 weeks. In contrast to the inhalation studies, lung tumor incidences were not increased in B6...

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“…dose of 3,000 mg/kg on day 17 of pregnancy (19). In vitro, TCE has been reported to inhibit 5-hydroxytryptamine uptake in the isolated perfused rat lung (22,23).…”

Section: Lung Cancer In Animalsmentioning

confidence: 99%