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Mixtures enzyme induction

In a second experiment rats were pre-exposed to the mixture of all 10 chemicals (50 ppm each) 4 h a day for 3 consecutive days. On day four the rats were once more exposed and the kinetics of the compounds followed in blood. There seemed to be a systematic decrease (although not statistically significant) in blood concentrations indicative of greater metabolism due to enzyme induction. [Pg.391]

The enzyme induction properties of PBDEs have been less studied than for other structurally similar chemicals, but the existing information suggests that they can be classified as mixed-type inducers of hepatic microsomal monooxygenases (Damerud et al. 2001 de Wit 2002 Hardy 2002b). Few studies have examined the structure-induction relationships for PBDEs. Chen et al. (2001) examined the ability of 12 PBDE congeners and 3 commercial mixtures to induce EROD activity in chick and rat hepatocytes, in liver cell lines from rainbow trout, rat, and human, and in a human intestinal cell line. The number of... [Pg.226]

Metals have been shown to dramatically alter CYP concentrations, but there have not been any studies examining the effects on pesticide biotransformation. In contrast, several studies have examined the effects of enzyme induction on pesticide biotransformation. Pre-exposure of channel catfish to the PCB mixture Aroclor 1254 failed to alter the biotransformation of chlorpyrifos or parathion81. As mentioned above, the fungicide propioconizole induced the activation of parathion to the oxon in fathead minnow53. [Pg.184]

Hepatic Effects. The hepatotoxic potential of PCB mixtures is well-documented in animals by oral and other routes of exposure. The spectrum of possible hepatic effects in animals is broad and includes microsomal enzyme induction, liver enlargement, increased serum levels of liver enzymes and lipids, and histopathologic alterations that progress to fatty and necrotic lesions and tumors. The findings of human studies, however, are not as obvious. Many of the human studies involving worker and other populations with high body burdens of PCBs report associations between PCBs and hepatic indices such as liver... [Pg.41]

The lowest reported hepatic effect levels in intermediate-duration oral studies are NOAELs for microsomal enzyme induction in rats (Bruckner et al. 1974,1977 Litterst et al. 1972). Liver microsomal nitroreductase and demethylase were induced in rats that were fed 6.03 mg/kg/day (lowest tested dose) Aroclor 1242, 1248,1254, or 1260 for 4 weeks (Litterst et al. 1972). All of these PCB mixtures also caused increased relative liver weight at 2.5 mg/kg/day and increased liver triglycerides at 25 mg/kg/day however, histology was not evaluated. The effects were generally dose-related among... [Pg.137]

Li MH, Hansen LG. 1996b. Enzyme induction and acute endocrine effects in prepubertal female rats receiving environmental PCB/PCDF/PCDD mixtures. Environ Health Perspect 104(7) 712-722. [Pg.778]

In order to use PBTK modeling in the assessment of mixtures, Cassee et al. (1998) suggest that one of the components is first modeled and regarded as the prime toxicant being modified by the other components. Based on in vitro data on the other components, effects of, e.g., inhibition or induction of specific biotransformation isoenzymes can be incorporated in the model. Effects of competition between chemicals in a mixture for the same biotransformation enzymes may also be incorporated by translating the effects into effects on the Michaelis-Menten parameters that are then incorporated into the model. [Pg.377]


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