Lowney Yvette W, Wester Ronald C, Schoof Rosalind A, Cushing Colleen A, Edwards Melanie, Ruby Michael V
Exponent, Boulder, CO, USA.
Toxicol Sci. 2007 Dec;100(2):381-92. doi: 10.1093/toxsci/kfm175. Epub 2007 Sep 13.
Regulatory agencies have relied on dermal absorption data for soluble forms of arsenic as the technical basis for specific absorption values that are used to calculate exposure to arsenic in weathered soil. These evaluations indicate that percutaneous absorption of arsenic from soil ranges from 3.2 to 4.5% of the dermally applied dose, based on studies of arsenic freshly mixed with soil. When this value is incorporated into risk assessments and combined with other assumptions about dermal exposures to soil, the conclusion is often that dermal exposure to arsenic from soil may contribute significantly to overall exposure to arsenic in soil. Prior characterization research has indicated that the solubility of arsenic in soil varies, depending on the provenance of the soil, the source of the arsenic, and the chemical interaction of arsenic with other minerals present within the soil matrix. Weathering produces forms of arsenic that are more tightly bound within the soil and less available for absorption. Our research expands on prior in vivo studies to provide insights into the potential for dermal absorption of arsenic from the more environmentally relevant substrate of soil. Specifically, two soils with very high concentrations of arsenic were evaluated under two levels of skin hydration. One soil, containing 1400 mg/kg arsenic, was collected adjacent to a pesticide production facility in New York. The other soil, containing 1230 mg/kg arsenic, was collected from a residential area with a history of application of arsenical pesticides. Although the results of this research are constrained by the small study size dictated by the selection of an animal research model using monkeys, the statistical power was optimized by using a "crossover" study design, wherein each animal could serve as its own comparison control. No other models (animal or in vitro) were deemed adequate for studying the dermal absorption of soil arsenic. Our results show dermal absorption of soluble arsenic in solution to be 4.8 +/- 5.5%, which is similar to results reported earlier for arsenic in solution (and used by regulatory agencies in recommendations regarding dermal absorption of arsenic). Conversely, absorption following application of arsenic in the soil matrices resulted in mean estimated arsenic absorption of 0.5% or less for all soils, and all individual estimates were less than 1%. More specifically, following application of arsenic-bearing soils to the abdomens of monkeys, urinary arsenic excretion could not be readily distinguished from background. This was true across all five soil-dosing trials, including application of the two dry soils and three trials with wet soil. These findings are consistent with our understanding of the environmental chemistry of arsenic, wherein arsenic can be present in soils in complexed mineral forms. This research addresses an important component involved in estimating the true contribution of percutaneous exposures to arsenic in soil relative to exposures via ingestion. Our findings suggest that dermal absorption of arsenic from soil is truly negligible, and that EPA's current default assumption of 3% dermal absorption of arsenic from soils results in significant overestimates of exposure.
监管机构一直将可溶形式砷的皮肤吸收数据作为特定吸收值的技术依据,这些吸收值用于计算风化土壤中砷的暴露量。这些评估表明,根据对新鲜混合土壤中砷的研究,经皮肤从土壤中吸收的砷占经皮施用剂量的3.2%至4.5%。当将该值纳入风险评估并与其他关于皮肤接触土壤的假设相结合时,通常得出的结论是,经皮肤接触土壤中的砷可能对砷的总体暴露有显著贡献。先前的特征研究表明,土壤中砷的溶解度各不相同,这取决于土壤的来源、砷的来源以及砷与土壤基质中其他矿物质的化学相互作用。风化会产生在土壤中结合更紧密、吸收性更低的砷形态。我们的研究在先前体内研究的基础上进行拓展,以深入了解从更具环境相关性的土壤基质中经皮肤吸收砷的可能性。具体而言,对两种砷浓度极高的土壤在两种皮肤水合水平下进行了评估。一种含砷量为1400毫克/千克的土壤是从纽约一家农药生产设施附近采集的。另一种含砷量为1230毫克/千克的土壤是从一个有施用含砷农药历史的居民区采集的。尽管这项研究的结果受到使用猴子作为动物研究模型所决定的样本量较小的限制,但通过使用“交叉”研究设计优化了统计功效,即每只动物都可作为自身的对照。没有其他模型(动物或体外模型)被认为足以研究土壤中砷的皮肤吸收。我们的结果表明,溶液中可溶砷的皮肤吸收为4.8±5.5%,这与先前报道的溶液中砷的结果相似(监管机构在关于砷的皮肤吸收建议中采用了该结果)。相反,在土壤基质中施用砷后的吸收导致所有土壤的平均估计砷吸收量为0.5%或更低,且所有个体估计值均小于1%。更具体地说,在将含砷土壤施用于猴子腹部后,尿砷排泄量与背景值难以区分。在所有五项土壤给药试验中都是如此,包括施用两种干燥土壤和三项湿润土壤试验。这些发现与我们对砷的环境化学的理解一致,即砷在土壤中可能以络合矿物形式存在。这项研究解决了估算经皮接触土壤中砷相对于经口接触砷的真实贡献所涉及的一个重要组成部分。我们的研究结果表明,经皮肤从土壤中吸收砷实际上可忽略不计,而且美国环境保护局目前默认的土壤中砷经皮肤吸收3%的假设导致对暴露量的显著高估。