Interactive developmental toxicity of radiofrequency radiation and 2‐methoxyethanol in rats

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Abstract
Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with the microelectronics industry, plastic sealers, and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (RF; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent, 2‐methoxyethanol (2ME), produces enhanced teratogenicity in rats. The present study replicates and extends the previous research investigating the enhanced teratogenicity of combined RF radiation and 2ME exposures. The interactive dose‐related teratogenicity of RF radiation (sham exposure or maintaining colonic temperatures at 42.0oC for 0, 10, 20, or 30 min) and 2ME (0, 75, 100, 125, or 150mg/kg) was investigated by administering various combinations of RF radiation and 2ME to groups of rats on gestation days 9 or 13; gestation‐day 20 fetuses were examined for external, skeletal, and visceral malformations. The results are consistent with and extend our previous research findings. Synergism was observed between RF radiation and 2ME for some treatment combinations, but not for others. The study also clarified which gestational periods, RF radiation exposure durations, and 2ME doses would be most informative in future interaction studies to determine the lowest interactive effect level. Day 9 exposures generally evidenced little effect by 2ME, either by itself or in combination with RF radiation. In contrast, day 13 exposures resulted in highly significant effects from 2ME and RF radiation. The structures showing strong evidence of effects from both 2ME and RF radiation after exposure on gestation day 13 were the forepaw digits, forepaw phalanges, hindpaw digits, hindpaw phalanges, hind limbs, metacarpals, and metatarsals. Statistical analyses did not show a global synergistic effect, but did show evidence for a synergistic effect at intermediate levels of the dose ranges. Future research will address potential interactions at lower doses. © Wiley‐Liss, Inc.