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Proposed Suite of Models for Estimating Dose Resulting from Exposures by the Dermal Route (SETAC)
Citation:
Fisher, H., E. Hubal, M. Evans, A. Bunge, A. Jarabek, AND Dan Vallero. Proposed Suite of Models for Estimating Dose Resulting from Exposures by the Dermal Route (SETAC). The Society of Environmental Toxicology and Chemistry (SETAC) North America 41st Annual Meeting, RTP, NC, November 15 - 19, 2020. https://doi.org/10.23645/epacomptox.13503201
Impact/Purpose:
Poster presented to the Society of Environmental Toxicology and Chemistry (SETAC) North America Annual Meeting November 2020. To predict dose and potential risk associated with dermal exposures, understanding of contaminant fate and transport in skin is required. A suite of models is presented for use in characterizing and quantifying dosimetry of toxic agents absorbed by the dermal route in order to incorporate mechanistic information into risk characterization through chemical case studies. This research area will further develop quantitative, objective, flexible and transparent, tools and approaches to assess chemical exposures – esp. improved estimates of exposure and dose for a range of indoor contaminants. The results of these efforts will be of direct benefit to program and regional offices as well as the greater scientific community.
Description:
Dermal absorption may be an important pathway for exposure to chemicals in the residential environment that may lead to toxic effects at the portal of entry or systemically. To predict dose and potential risk associated with dermal exposures, understanding of contaminant fate and transport in skin is required. Drivers for absorption and transport in skin will be a function of exposure duration, chemical properties, and metabolism. A suite of models is presented for use in characterizing and quantifying dosimetry of toxic agents absorbed by the dermal route in order to incorporate mechanistic information into risk characterization. These range from a distributed parameter model that only considers resistance in the stratum corneum to a model that treats the entire skin system as one well-stirred compartment. The model suite provides the flexibility required to evaluate dosimetry on a variety of compounds by including the required level of resolution to incorporate rate limiting components. The suite is demonstrated through a case study involving three phthalates: Diethylhexyl phthalate (DEHP), Diethyl phthalate (DEP), and Benzyl butyl phthalate (BBzP). Within the suite, the simple models, those that do not rely on diffusion mechanics, for a given compartment are best suited for scenarios with large time scales, determined by the exposure time for the stratum corneum and the metabolism in the viable epidermis. We also found that the molecular weight and octanol to water partition coefficient (Kow) had a significant effect on the relative speed of diffusion through each compartment and, therefore, the best choice of models. Large chemicals with a high Kow, such as DEHP, were able to easily cross compartment boundaries but diffused through each compartment at a significantly slower rate. This behavior is better modeled by the diffusion-based compartment models. DEP, on the other hand, is smaller and has a lower Kow, leading to relatively more time spent crossing the compartment boundaries, as opposed to diffusing through the compartment, which lends itself better to the simpler models within the suite. Combined with models to describe transfer of compounds from air and surfaces in the residential environment, this suite of models will enable improved estimates of exposure and dose for a range of indoor contaminates. This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication.
URLs/Downloads:
DOI: Proposed Suite of Models for Estimating Dose Resulting from Exposures by the Dermal Route (SETAC)
SETAC_FISHER_DERMAL_MODEL.PDF (PDF, NA pp, 466.589 KB, about PDF)