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ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?
Citation:
Bushnell, P., K. Tatum-Gibbs, J. Mckee, P. Evansky, M. Higuchi, M. Lin, W. Oshiro, R. Judson, S. Hester, D. Reif, T. Morozova, T. Mackay, AND W. Boyes. ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals? Presented at Neurobehavioral Teratology Society Meeting, Bellevue, WA, June 28 - July 02, 2014.
Impact/Purpose:
This abstract will be presented at the Neurobehavioral Teratology Society Conference, June 28 - July 2, 2014, Bellevue, WA
Description:
Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adverse outcomes in whole organisms. This study was designed to address these issues using the Drosophila Genetic Reference Panel (DGRP), a set of inbred fruit fly strains with full genome sequences. The goals of the project were to determine whether fruit flies can be used to screen VOCs for acute toxicity, and to identify adverse outcome pathways associated with the VOCs. Phase 1 of this study sought to determine dose-effect functions for three VOCs that differ in their mode of action, using motor activity as a behavioral endpoint. The VOCs selected for Phase 1 included toluene, a CNS narcotic; acrolein, an irritant; and vinyl chloride, a hepatocarcinogen. We used an outbred strain derived from 40 DGRP lines to determine EC20s for the VOCs. Individual flies were placed in 5 mm dia. glass tubes and exposed for 4 hours at various concentrations of the VOCs (n= 16/sex/dose); controls received air. Locomotor activity was recorded in 1 0-minute intervals. Males were generally more active than females. Reliable changes in activity were observed with toluene (150 - 1800 ppm), but not with acrolein (0.5 - 100 ppm) or vinyl chloride (125 - 5000 ppm). Toluene decreased activity in both sexes in a dose-dependent fashion, particularly in the second 2 hours of exposure. Despite differences in activity in air, the sexes did not differ in their sensitivity to toluene: mean (95% CI) EC20 values were 764.9 (672.4 - 870.2) for males and 823.1 (578.5 - 1171.0) ppm for females. In Phase 2, a behavioral response profile across DGRP lines will be determined at the EC20 of toluene, and genetic markers associated with the response to toluene will be identified. The lack of sensitivity to acrolein and vinyl chloride shows that this method is not adequate to screen all types of toxicity attributed to VOCs. The utility of the method for characterizing CNS-based narcotic toxicity pathways remains to be determined. This abstract does not reflect U.S. EPA policy.