Possible dose effect relationships in the interaction of radiofrequency (RF) induced hyperthermia and 2-methoxyethanol (109864) (2ME) induced teratogenicity were studied in rats. Pregnant Sprague-Dawley-rats were irradiated with continuous wave 10 megahertz RF radiation of sufficient intensity to increase the animals' colonic temperature (Tc) to 39.0, 40.0, or 41.0 degrees-C and to maintain it at the target values for up to 6 hours (hr) on gestational day 13. Some animals were gavaged with 100mg/kg 2ME. The irradiations were performed in a custom built exposure system in which the 60 hertz electric and magnetic fields varied from 0.17 to 0.20 volts per meter and 0.02 to 0.06 microTesla. All exposures and sham exposures were conducted at an ambient temperature of 24 degrees. The dams were killed on day 20 of gestation and the fetuses were removed, weighed, and examined for external and skeletal malformations. The teratogenic evaluations focused on forepaw digit abnormalities. 2ME consistently reduced fetal body weights across all experimental conditions. 2ME also consistently induced abnormal curvature of the right and left forepaw digits. A significant increase in the incidence of these forepaw anomalies was seen in fetuses from dams treated with 2ME and exposed to RF radiation sufficient to maintain Tc at 41 degrees for 1hr compared to either treatment alone. No consistent interactive effects were seen at lower temperatures or longer durations of RF irradiation at Tc 41 degrees. The authors conclude that RF radiation can interact with 2ME to enhance 2ME developmental toxicity at a relatively low dose in rats. This finding indicates that combined physical and chemical agent interactive effects should be considered when developing guidelines and intervention strategies for combined workplace exposures.
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