A PHYSIOLOGICALLY-BASED TOXICOKINETIC MODEL FOR DERMAL ABSORPTION OF ORGANIC-CHEMICALS BY FISH

A physiologically based toxicokinetic model was developed to describe dermal absorption of waterborne organic chemicals by fish. The skin wa s 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 g ills and was used to simulate dermal-only exposures, during which the gills act as a route of elimination. The model was evaluated by exposi ng adult rainbow trout and channel catfish to hexachloroethane (HCE), pentachloroethane (PCE), and 1,1,2,2-tetrachloroethane (TCE). Skin per meability coefficients were obtained by fitting model simulations to m easured arterial blood data. Permeability coefficients increased with the number of chlorine substituent groups, but not in the manner expec ted from a directly proportional relationship between dermal permeabil ity and skin:water chemical partitioning. An evaluation of rate limita tions on dermal flux in both trout and catfish suggested that chemical absorption was limited more by diffusion across the skin than by bloo d flow to the skin. Modeling results from a hypothetical combined derm al and branchial exposure indicate that dermal uptake could contribute from 1.6% (TCE) to 3.5% (HCE) of initial uptake in trout. Dermal upta ke rates in catfish are even higher than those in trout and could cont ribute from 7.1% (TCE) to 8.3% (PCE) of initial uptake in a combined e xposure. (C) 1996 Society of Toxicology