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鱼类对有机化学品经皮吸收的基于生理学的毒代动力学模型。

A physiologically based toxicokinetic model for dermal absorption of organic chemicals by fish.

作者信息

Nichols J W, McKim J M, Lien G J, Hoffman A D, Bertelsen S L, Elonen C M

机构信息

Mid-Continent Ecology Division-Duluth, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Minnesota 55804, USA.

出版信息

Fundam Appl Toxicol. 1996 Jun;31(2):229-42. doi: 10.1006/faat.1996.0095.

Abstract

A physiologically based toxicokinetic model was developed to describe dermal absorption of waterborne organic chemicals by fish. The skin was modeled as a discrete compartment into which compounds diffuse as a function of chemical permeability and the concentration gradient. The model includes a countercurrent description of chemical flux at fish gills and was used to simulate dermal-only exposures, during which the gills act as a route of elimination. The model was evaluated by exposing adult rainbow trout and channel catfish to hexachloroethane (HCE), pentachloroethane (PCE), and 1,1,2,2-tetrachloroethane (TCE). Skin permeability coefficients were obtained by fitting model simulations to measured arterial blood data. Permeability coefficients increased with the number of chlorine substituent groups, but not in the manner expected from a directly proportional relationship between dermal permeability and skin:water chemical partitioning. An evaluation of rate limitations on dermal flux in both trout and catfish suggested that chemical absorption was limited more by diffusion across the skin than by blood flow to the skin. Modeling results from a hypothetical combined dermal and branchial exposure indicate that dermal uptake could contribute from 1.6% (TCE) to 3.5% (HCE) of initial uptake in trout. Dermal uptake rates in catfish are even higher than those in trout and could contribute from 7.1% (TCE) to 8.3% (PCE) of initial uptake in a combined exposure.

摘要

建立了一个基于生理学的毒代动力学模型,以描述鱼类对水中有机化学物质的皮肤吸收情况。皮肤被建模为一个离散的隔室,化合物根据化学渗透性和浓度梯度扩散到其中。该模型包括对鱼鳃处化学通量的逆流描述,并用于模拟仅经皮肤暴露的情况,在此期间鳃作为消除途径。通过将成年虹鳟鱼和沟鲶暴露于六氯乙烷(HCE)、五氯乙烷(PCE)和1,1,2,2-四氯乙烷(TCE)来评估该模型。通过将模型模拟结果与实测动脉血数据拟合,获得皮肤渗透系数。渗透系数随氯取代基数量的增加而增加,但并非以皮肤渗透性与皮肤-水化学分配之间成正比关系所预期的方式增加。对虹鳟鱼和沟鲶皮肤通量的速率限制进行评估表明,化学物质的吸收更多地受皮肤扩散的限制,而非皮肤血流量的限制。来自假设的皮肤和鳃联合暴露的建模结果表明,在虹鳟鱼中,皮肤摄取量可能占初始摄取量的1.6%(TCE)至3.5%(HCE)。沟鲶的皮肤摄取率甚至高于虹鳟鱼,在联合暴露中可能占初始摄取量的7.1%(TCE)至8.3%(PCE)。

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