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Hydroquinone (HQ) is a high-volume commodity chemical used as a reducing agent, antioxidant, polymerization inhibitor, and chemical intermediate. It is also used in over-the-counter (OTC) drugs as an ingredient in skin tighteners and is a natural ingredient in many plant-derived products, including vegetables, fruits, grains, coffee, tea, beer, and wine. While there are few reports of adverse health effects associated with the production and use of HQ, a great deal of research has been conducted with HQ because it is a metabolite of benzene. Physicochemical differences between HQ and benzene play a significant role in altering the pharmacokinetics of directly administered when compared with benzene-derived HQ. HQ is only weakly positive in in vivo chromosomal assays when expected human exposure routes are used. Chromosomal effects are increased significantly when parenteral or in vitro assays are used. In cancer bioassays, HQ has reproducibly producedrenal adenomas in male F344 rats. The mechanism of tumorigenesis is unclear but probably involves a species-, strain-, and sex-specific interaction between renal tubule toxicity and an interaction with the chronic progressive nephropathy that is characteristic of aged male rats. Mouse liver tumors (adenomas) and mononuclear cell leukemia (female F344 rat) have also been reported following HQ exposure, but their significance is uncertain. Various tumor initiation/promotion assays with HQ have shown generally negative results. Epidemiological studies with HQ have demonstrated lower death rates and reduced cancer rates in production workers when compared with both general and employed referent populations. Parenteral administration of HQ is associatedwith changes in several hematopoietic and immunologic endpoints. This toxicity is more severe when combined with parenteral administration of phenol. It is likely that oxidation of HQ within the bone marrowcompartment to the semiquinone or p-benzoquinone (BQ), followed by cova [ABSTRACT FROM AUTHOR]

Exposure biomarkers, which have long been restricted to the framework of occupational hygiene, currently arouse increasing interest in the field of environmental pollution. To assess their validity, we propose here a conceptual framework that is based on their intrinsic characteristics and on properties related to the procedures for their analysis. The most important criteria are specificity for the toxic substance under consideration and sensitivity, that is, the ability to distinguish contrasted levels of exposure. Their analytic sensitivity and specificity are also important. Fulfilling these criteria is especially important in the context of environmental pollution, because the levels of exposure, and thus the contrasts, are low. This frameworkis used to assess the validity of some biomarkers for polycyclic aromatic hydrocarbons (1-hydroxypyrene and DNA adducts) and for benzene (urinary and serum benzene, trans,trans muconic acid, and S-phenylmercapturic acid). This evaluation shows that the most relevant biomarkers for estimating individual exposure to environmental pollution are 1-hydroxypyrene for polycyclic aromatic hydrocarbons and urinary benzene and S-phenylmercapturic for benzene. [ABSTRACT FROM AUTHOR]

2-Methylpropene (MP) or isobutene is a gaseous chemical used on a large scale in the synthetic rubber industry. The present review coversthe rather scarce literature on MP with respect to its metabolic fate and toxicity in laboratory animals and humans. It has been shown both in vivo and in vitro that MP is metabolized to the primary metabolite 2-methyl-1,2-epoxypropane (MEP) by rodent and human liver tissue.The formation of this reactive epoxide intermediate is catalyzed by CYP2E1, while epoxide hydrolase and glutathione S-transferase appear to be involved in its inactivation. In rats, the capacity to absorb and metabolize MP is saturable. MP is oxidized to compounds that are mainly excreted in urine. Data indicate that rodents can tolerate low levels of MP without apparent toxicity. The primary metabolite MEP, however, is able to produce genetic damage in both prokaryotic and eukaryotic cells in vitro. MP is thus not toxic per se but elicits metabolic activation to become potentially harmful. Consequently, the balance between formation and detoxification of MEP plays a key role in determining the potential toxicity of the parent compound. Obviously, further research, including repeated exposure toxicity studies, is required before an estimation of the risk for man can be made. [ABSTRACT FROM AUTHOR]

1,3-Butadiene is a colorless, volatile gas that has high-volume usage in the synthesis of polybutadiene, styrene-butadiene, and other polymers. Due to its volatile nature, uptake of butadiene occurs almost exclusively by inhalation and absorption through the respiratory system. Sources of exposure include production, transport, and end-use processes in industrial settings or environmental exposures through automotive fuel, fossil fuel combustion, and cigarette smoke. Chronic inhalation studies established that butadiene is carcinogenic in B6C3F1mice and Sprague- Dawley rats, and that mice are considerably more sensitive than rats. For the most part, epidemiologic studies for butadiene have been equivocal, although a recent retrospective follow-up study of styrene-butadiene rubber workers provides the first internally consistent evidence of a relationship between butadiene exposure and leukemia. The mechanism(s) of butadiene-induced carcinogenicity are not entirely understood but are thought to involve covalent interactions of the butadiene epoxide metabolites, epoxybutene and diepoxybutane, with DNA. Species differences in butadiene metabolism are evident. In vitro and in vivo studies clearly reveal that mice have a higher capacity to form reactive epoxides than rats or humans. This is reflected by the very high levels of epoxides in blood and tissues of mice compared with rats exposed to butadiene. These differences in metabolism may explain the greater sensitivity of mice to the carcinogenicity of butadiene. In vitro metabolism data for humans show interindividual variation, but when compared with other species, the data forhumans closely parallel metabolism in the rat, suggesting that the use of mice for quantitative risk assessments overestimates the potency of butadiene in humans. The metabolism findings are corroborated bygenotoxicity studies in laboratory animals and humans occupationallyexposed to butadiene. The use of physiologically based pharmacokinetic m [ABSTRACT FROM AUTHOR]