Skip to main content

Currently Skimming:

7 Respiratory Tract Toxicity and Cancer
Pages 233-245

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 233...
... . In keeping with the committee's charge, the chapter focuses on hazard characterization and the mode of action for trichloroethylene toxicity, assessing the available information from in vitro, animal, and human studies.
From page 234...
... Recent studies of recombinant (r) cytochrome P-450s and rodent and human lung microsomes revealed that rat and human rCYP2E1, rCYP2F, and rCYP2B1 were all capable of mediating trichloroethylene metabolism to chloral hydrate (Forkert et al.
From page 235...
... 7-1 for bioactivation of trichloroethylene within the Clara cells, predominantly involving CYP2F2, that correlates with bronchiolar cytotoxicity. The rates of chloral hydrate production in human lung microsomes were low and were detected in only three of eight subjects (Forkert at al.
From page 236...
... However, the blood-gas partition coefficient in humans is 1.5- to 2.5-fold lower than that in mice and rats, respectively, which suggests that delivery of trichloroethylene to the circulatory system for translocation to target organs may be significantly less efficient in humans. This factor should be taken into account when using animal data in risk assessment analysis for trichloroethylene (Sato et al.
From page 237...
... RESPIRATORY TRACT TOXICITY AND CANCER 23 mouse lung after exposure by inhalation, it is not carcinogenic in the rat lung and is markedly less toxic after acute exposure (Stewart et al. 1979; Fukuda et al.
From page 238...
... 238 ASSESSING THE HUMAN HEALTH RISKS OF TRICHLOROETHYLENE TABLE 7-1 Animal Carcinogenicity Studies of Trichloroethylene Reference Animals (Sex) Exposure Route Stabilizers Fukuda ICR mice (F)
From page 239...
... 0, 100, 300, 600 ppm 90/group Excess lung tumors in both strains; liver tumors in male Swiss mice. 0, 100, 500 ppm 30/group No increase in any tumors, except increase in lymphomas in female mice.
From page 240...
... 240 ASSESSING THE HUMAN HEALTH RISKS OF TRICHLOROETHYLENE weeks. No pulmonary tumors were observed, but the study was considered inadequate because of chemical toxicity and early mortality in the rats.
From page 241...
... RESPIRATORY TRACT TOXICITY AND CANCER 241 TABLE 7-2 Epidemiologic Data on Lung Cancer and Exposure to Trichloroethylene Exposed Estimated Relative Risk Reference Study Population Cases (95% confidence interval) Cohort Studies -- Incidence Raaschou-Nielsen Workers in Denmark et al.
From page 242...
... 1994 assembly workers, ever exposed Wilcosky et al. 1984 White male rubber-industry 11 0.64 workers in Ohio, cumulative exposure of more than 1 yr ABBREVIATIONS: NA, not available; TCE, trichloroethylene; U-TCA, urinary trichloroacetic acid.
From page 243...
... RESPIRATORY TRACT TOXICITY AND CANCER 243 tumor formation in mice. Trichloroethylene is not mutagenic but some of its metabolites are.
From page 244...
... . Studies with recombinant cytochrome P-450s have revealed that, although rat and human rCYP2E1, rCYP2F, and rCYP2B1 were all capable of mediating trichloroethylene metabolism to chloral hydrate, the rat rCYP2E1 exhibited greater affinity than rat rCYP2F4 and rCYP2B1 and human rCYP2E1 (Forkert et al.
From page 245...
... Thus, pulmonary cancer is does not appear to be a critical end point in assessing human health risks of trichloroethylene.


This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.