PASSIVE TRANS-CHORIONIC TRANSPORT OF TOXICANTS TOPICALLY TREATED JAPANESE MEDAKA (ORYZIAS-LATIPES) EGGS

Seven chemicals were evaluated for their trans-chorionic permeability or permeability factor (PF) using the medaka embryo-larval assay (MELA) topical treatment procedure. Eggs were treated employing the standard MELA protocol, but were immediately extracted following treatment. Extraction was carried out through homogenization, and subsequent filtration or centrifugation, with non-polar solvent. Analysis was performed employing gas chromatographic techniques with multiple specific detectors. The PF values for the seven chemicals ranged from 10.5% to 82.9%. These results indicate that even in the presence of membrane permeable DMSO carrier, passive transport is taking place. The amount of toxicant penetrating the egg is apparently controlled by the lipid solubility of the chemical, which is established by the properties of that chemical, and not by the solubility in, or penetrability of, the DMSO, The PF data were regressed against the n-octanol-water partition coefficient (K-ow) for each chemical to determine if there was a relationship between the PF and this physico-chemical coefficient of lipid affinity. The data correlated well, with an R(2) of 0.96 for the regression line PF = 11.1 log K-ow + 3.97. These findings suggest that, using this or a similar equation, it may be possible to predict an appropriate MELA topical dose to represent a given ambient water concentration.