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MICROTIA AND HEARING DEFICITS IN CD-1 MICE FOLLOWING GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS)
Citation:
Tarka, D. K., G R. Klinefelter, D W. Herr, AND J M. Rogers. MICROTIA AND HEARING DEFICITS IN CD-1 MICE FOLLOWING GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS). Presented at Teratology Society Meeting, Montreal, Quebec, Canada, June 23-28, 2001.
Description:
TARKA1,2, D.K., G.R. KLINEFELTER1,2, D.W. HERR3, and J.M. ROGERS 1,2. 1University of North Carolina, School of Medicine, Curriculum in Toxicology, Chapel Hill, North Carolina; and USEPA, NHEERL, 2Reproductive Toxicology Division and 3Neurotoxicology Division, Research Triangle Park, North Carolina. Microtia and hearing deficits in CD-1 mice following gestational exposure to ethane dimethanesulfonate (EDS).
Microtia, including small external ears, poses considerable therapeutic and reconstructive challenges for clinicians. Here we report that CD-1 mice exhibit microtia following gestational exposure to ethane dimethanesulfonate (EDS), an alkylating agent and well-known Leydig cell toxicant. Initially, time-pregnant dams were dosed with 0, 25, and 50 mg/kg/day on gestation days (GD) 11-17. Ear size, estimated by calculating the semi-circular area of the external ear, was measured on postnatal days 4, 8, 18, and 28. All treated offspring exhibited small external ears. Compared to controls, high-dose offspring were more severely affected, with an approximate 75% decrease in size, than the 30% decrease observed with low-dose exposures. Additionally, dosing between GD 11-13 produced smaller ears than GD 9-11, 13-15, or 15-17, but not as small as the GD 11-17 regimen, even when the dosage was increased to 100 mg/kg/day. Single dose exposures on GD 10 or 11, when the ear begins to develop, did not produce microtia. Preliminary brainstem auditory evoked response (BAER) testing revealed a decreased percentage of affected adult offspring responding to tones. When presented with a rarefaction click, or 4, or 16 kHz tone pips, the percent of high-dose responders ranged from 57-85% as compared to a 100% response in controls. If treated mice are hearing-impaired, EDS could become a model compound to induce hearing deficits. Current studies are underway to elucidate the pathogenesis of the microtia. (This abstract does not necessarily reflect EPA policy) DKT; Training Agreement CT827206.