Systemic uptake of inhaled arsenic in rabbits.

Human occupational exposure to sufficiently high levels of arsenic in air has been associated with lung cancer, but generally not other types of cancer. Thus, a better understanding of the relationship between airborne arsenic exposures and systemic uptake is essential. In this study, rabbits were exposed to one of four levels of arsenic trioxide in air for 8 h/day, 7 days/week, for 8 weeks (0.05, 0.1, 0.22, or 1.1 mg/m3). Plasma levels of inorganic arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured following the last exposure. Although there was a dose-related increase in plasma levels of methylated arsenic metabolites, statistically significant increases in mean inorganic arsenic levels in plasma were observed only in male rabbits exposed to 0.22 mg/m3, and in both males and females exposed to 1.1 mg/m3. Mean inorganic arsenic levels in plasma in males and females exposed to 0.05 and 0.1 mg/m3, and females exposed to 0.22 mg/m3, were not significantly elevated compared to controls. These results suggest that arsenic inhalation has a negligible impact on body burden of inorganic arsenic until air levels are significantly elevated. Based on plasma measurements of inorganic arsenic, the two lowest exposure levels in this study (0.05 and 0.1 mg/m3) are indistinguishable from background.

Estimating dermal transfer from PCB-contaminated porous surfaces.

Health risks posed by dermal contact with PCB-contaminated porous surfaces have not been directly demonstrated and are difficult to estimate indirectly. Surface contamination by organic compounds is commonly assessed by collecting wipe samples with hexane as the solvent. However, for porous surfaces, hexane wipe characterization is of limited direct use when estimating potential human exposure. Particularly for porous surfaces, the relationship between the amount of organic material collected by hexane and the amount actually picked up by, for example, a person's hand touch is unknown. To better mimic PCB pickup by casual hand contact with contaminated concrete surfaces, we used alternate solvents and wipe application methods that more closely mimic casual dermal contact. Our sampling results were compared to PCB pickup using hexane-wetted wipes and the standard rubbing protocol. Dry and oil-wetted samples, applied without rubbing, picked up less than 1% of the PCBs picked up by the standard hexane procedure; with rubbing, they picked up about 2%. Without rubbing, saline-wetted wipes picked up 2.5%; with rubbing, they picked up about 12%. While the nature of dermal contact with a contaminated surface cannot be perfectly reproduced with a wipe sample, our results with alternate wiping solvents and rubbing methods more closely mimic hand contact than the standard hexane wipe protocol. The relative pickup estimates presented in this paper can be used in conjunction with site-specific PCB hexane wipe results to estimate dermal pickup rates at sites with PCB-contaminated concrete.

Implications of arsenic genotoxicity for dose response of carcinogenic effects.

Epidemiological data relating arsenic ingestion and skin and internal cancers strongly suggest a sublinear or threshold relationship. Physiological saturation of methylation-based arsenic detoxification has been proposed as one explanation for a sublinear response. We have evaluated the molecular bases for sublinearity in light of new data and hypotheses regarding arsenic genotoxicity and chemical carcinogenesis. A review of the dose-response relationships observed in arsenic genotoxicity assays is presented. With the exception of sister chromatid exchanges, sublinear dose-response relationships for arsenic-induced chromosomal aberrations were observed repeatedly in different mammalian and human cell systems. Arsenic also enhanced the clastogenicity and mutagenicity of other DNA damaging agents with a sublinear dose response. Consistent with the dose response of arsenic-induced genetic alterations, arsenic also inhibited DNA ligases I and II, enzymes which play a role in DNA repair, with a sublinear dose response. In some cases, protective effects of relatively low exposures to arsenic have been observed, again consistent with sublinearity. We discuss recent theories on the mechanism of arsenic carcinogenicity and the potential implications for dose-response modeling and risk assessment. Overall, based on available arsenic genotoxicity data, we conclude that it is likely that arsenic indirectly induces genetic damage with a sublinear dose response in humans, thus providing a biological basis for a sublinear dose-response relationship for human cancer. Furthermore, these results suggest that linear dose-response modeling from populations experiencing high arsenic exposures is likely to overpredict cancer risks at relatively low arsenic levels.