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A human corneal epithelial cell line, 10.014 pRSV-T (HCE-T cells), has been used to develop a three-dimensional in vitro model of the human comeal epithelium (HCE-T model). HCE-T cells form a stratified culture when grown at the air-liquid interface on a collagen membrane in serum-free medium. This model served as the basis for assays which supported the ocular irritancy assessment of water-soluble test substances. In vitro assays used were transepithelial permeability to sodium fluorescein (TEP) and transepithelial electrical resistance (TER). These measured alterations in the barrier function of this comeal epithelial equivalent Barrier function is a well-developed property in the HCE-T model that supports the mechanistic relevance of these assays. In vitro data, averaged from replicate assays, were compared to respective Drake rabbit eye irritation data from the publicly available ECETOC and CTFA databases using linear regression with Pearson's correlation analysis. For chemicals, Pearson's correlation coefficients, r, from comparisons of Draize maximum average scores (MAS) to TEP and TER data were 0.71 and 0.55, respectively. For product formulations, Pearson's correlation coefficients from comparisons of Draize MAS to TEP and TER data were 0.86 and 0.80, respectively. Data indicated that barrier function alterations in the HCE-T model correlated with ocular irritancy and comeal toxicity. While the irritancy of the chemicals tested was effectively assessed only by the TEP assay,

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The distribution, excretion, and possible metaboism of 14C-and/or 74As-cacodylic acid, an organoarsenical herbicide, was studied in rats following a single intravenous injection, intratracheal instillation or oral gavage. Male Sherman rats were dosed at levels ranging from 200 mg/kg to 120 ,g/kg. The extent and rate of lung absorption was greater than gastrointestinal absorption. Concentrations in the liver and whole blood were higher after peroral dosing than intravenous administration. Levels observed in plasma and other tissues were similar after all three routes following the absorptive phase. The percent dose found in the whole blood, red blood cells, and plasma was similar for all doses given by these routes. Less than 0.1½ of the administered dose was recovered as "4CO2 by any route at 24 hr after administration. Twenty-four hours after intravenous, intratracheal, and peroral administration, 71, 60, and 25%, respectively, was excreted in the urine. After intravenous administration of 200 mg/kg, sufficient 14C-cacodyllc acid was recovered in bile to account for the small amount excreted in the feces. Cacodylic acid is probably not metabolized to inorganic arsenic since the disposition of 14C and 74As-cacodylic acid were identical.Kinetic analyses of the plasma curve for 14C-cacodylic acid (high dose) yielded three half-times; 0.014, 0.214 and 3.42 hr with an apparent volume of distribution of 15.3 ml. Highest initial concentrations were found in the whole blood, muscle, kidney, liver and lung.Levels in all tissues decreased rapidly, but remained high in whole blood. The red blood cells were found to be the major site of body burden of cacodylic acid.