2-Methoxyethanol metabolism, embryonic distribution, and macromolecular adduct formation in the rat: the effect of radiofrequency radiation-induced hyperthermia

Exposure of pregnant rats to the solvent 2-methoxyethanol (2ME) and radiofrequency (RF) radiation results in greater than additive fetal malformations (Nelson, B.K., Conover, D.L., Brightwell, W.S.. Shaw, P.B., Werren. D.W., Edwards, R.M., Lary, J.M., 1991. Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxyethanol and radiofrequency radiation in rats. Teratology 43, 621-34; Nelson, B.K., Conover, D.L., Shaw. P.B., Werren, D.W., Edwards, R.M., Hoberman, A.M., 1994. Interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats. Teratology 50. 275-93). The current study evaluated the metabolism of C-14-labeled 2ME and the distribution of methoxyacetic acid (MAA) in maternal and embryonic tissues of pregnant Sprague-Dawley rats either exposed to 10 MHz RF radiation or sham conditions. Additionally, adduct formation For both plasma and embryonic protein was tested as a possible biomarker for the observed 2ME/RF teratogenicity. Rats were administered [ethanol- 1,2-C-14]-2ME (150 mg/kg, 161 mu Ci/rat average) by gavage on gestation day 13 immediately before RF radiation sufficient to elevate body temperature to 42 degreesC for 30 min. Concurrent sham- and RF-exposed rats were sacrificed at 3, 6, 73 or 48 h for harvest of maternal blood, urine, embryos and extra-embryonic fluid. Tissues were either digested for determination of radioactivity or deproteinized with TCA and analyzed by HPLC for quantification of 2ME metabolites. Results show the presence of 2ME and seven metabolites, with the major metabolite. MAA. peaking at 6 h in the tissues tested. MAA, the proximal teratogen: was detectable in maternal serum, urine, embryo and extraembryonic fluid 48 h after dosing. Clearance of total body C-14 was significantly reduced for the RF-exposed animals (P<0.05) for the 24 48 h period. but MAA values for serum, embryos and extraembryonic fluid were similar for both sham- and RF-exposed rats. Additionally, no difference was noted for 2ME metabolite profiles in urine or tissue for sham- or RF-exposed rats, thus eliminating an effect of RF radiation on MAA production as a possible explanation for the reported RF-2ME synergism.