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An assessment of the use of dimethyl sulfoxide as a solvent for hydrophobic chemicals in a Drosophila-based developmental toxicity prescreen.

Toxicologist 2002 Mar; 66(1-S):236
Dimethyl sulfoxide (DMSO) is routinely used in toxicity testing to solubilize hydrophobic chemicals; however, the potential of DMSO to induce developmental toxicity in the Drosophila-based prescreen has not been well characterized. The purpose of this study was to investigate this toxicity and to determine a maximum concentration of DMSO which can be used. Three separate experiments were conducted with DMSO (CAS# 67-68-5; Sigma D-5879, 99.5%) at concentrations ranging from 0.05 - 150 l/vial. Drosophila were exposed throughout development (egg through third instar larva) in culture vials to medium containing DMSO. A mated, untreated, Oregon-R wild-type female was added to each vial and allowed to oviposit for 20 hours, then removed. Emerging offspring were collected over 10 days, and examined microscopically (25x) for bent humeral bristles and wing blade notches; morphological defects shown to occur with an increased incidence in flies exposed to developmental toxicants. In each experiment, the incidence of the two defects at each concentration was compared to the concurrent controls using chi-square. Where replicate data were available at a given concentration, incidence data were also pooled and compared to the pooled controls. No flies emerged at concentrations greater than 50 g/vial. In the first experiment the incidence of bent humeral bristles was significantly increased at 25 l/vial, 64/246 (p< 0.001) and at 50 l/vial, 2/2 (p< 0.001); in the second experiment bristle defects were increased only at 50 l/vial, 5/8 (p< 0.001); in the third experiment bristle defects were increased at 1.0 l/vial, 5/155 and 5.0 l/vial 5/146 (both p< 0.05). These results indicate that higher concentrations of DMSO can increase the incidence of bristle defects in developing flies. However, based on the lack of a statistically significant increase in defects at lower concentrations in the pooled data across 3 experiments, the data suggest that DMSO at a concentration of 10 l/vial can be used to evaluate hydrophobic chemicals in this assay.
Toxic-materials; Morphology; Insects; Solvents; Hydrophobic-bonds; Maximum-permissible-concentrations; Mutagenicity; Reproductive-effects; In-vivo-study
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The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee