Urinary system toxic responses

It is noteworthy that the styrene reference concentration (RfC) in the Integrated Risk Information System is based on the biomarker-response relationship found in workers (Mutti et al. 1984 EPA 1998). The Environmental Protection Agency (EPA) used the relationship of urinary biomarker to ambient-air concentration of workers to develop an RfC that was adjusted for the difference in exposure time between the workplace and the general population. That is a valid approach because it derives a workplace concentration-toxicity relationship in workers, which can then be adjusted for the general population to account for differences in exposure time and can take uncertainty factors into account. It is different from direct adjustment of the styrene BEI to evaluate human population biomonitoring data on styrene metabolites in urine, which would have the uncertainties described above and in Chapter 5. 

Numerous studies have examined the relationship of urinary tract sofids to toxicity and to bladder cancer in humans (Burin et al. 1995 Cohen et al. 2000 La Vecchia et al. 1991 RBCWG 1995). The evidence suggests that lumary amorphous precipitate and urinary crystals of any kind are not associated with cytotoxicity or deleterious effects in humans. Crystalliuia in hmnans is not associated with any toxicological response (McPherson et al. 2006 Pearle and Lotan 2007). In some instances it can be an indication of the propensity of the individual to form calculi from these substances, such as calcium oxalate, or occasionally it can be an indication of systemic metabolic disturbances, such as gout, oxalosis, or hypercalcemia. 

The hepatic monooxygenase system is primarily responsible for oxidation of tetrachloroethylene. Thus, compounds that stimulate or induce tetrachloroethylene metabolism could influence the toxicity associated with exposure to this chemical. Results of experiments that have investigated possible enhancement of tetrachloroethylene-induced toxicity by increasing tetrachloroethylene metabolism have been equivocal. Pretreatment of rats with ethanol (Cornish and Adefrrin 1966 Klaassen and Plaa 1966) and phenobarbital (Cornish et al. 1973 Moslen et al. 1977) failed to enhance tetrachloroethylene hepatic toxicity. Pretreatment with polychlorinated biphenyls (PCBs), on the other hand, increased urinary excretion of tetrachloroethylene metabolites in rats and enhanced tetrachloroethylene-induced hepatotoxicity (Moslen etal. 1977). 

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