title: Developmental toxicity interactions of methanol and radiofrequency radiation or 2-methoxyethanol in rats.
abstract: This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. 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 RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hour intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. These results point out that interactions in developmental toxicology, such as those of RF radiation, 2ME, and methanol that we have studied, are complex, and such interactions cannot be fully understood or predicted without more research. It is important that combined exposure effects be considered when developing both physical agent and chemical agent exposure guidelines and intervention strategies.
authors.affiliation: National Institute of Occupational Safety and Health, Cincinnati, Ohio 45226, USA. bknelson@cdc.gov
authors.forename: B K
authors.initials: BK
authors.lastname: Nelson
authors.forename: D L
authors.initials: DL
authors.lastname: Snyder
authors.forename: P B
authors.initials: PB
authors.lastname: Shaw
mesh_terms: D000014:Abnormalities, Drug-Induced; D000016:Abnormalities, Radiation-Induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects / Q000528:radiation effects; D007035:Hypothermia / Q000139:chemically induced; D000432:Methanol / Q000633:toxicity*; D011247:Pregnancy; D011846:Radio Waves / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D005026:Ethylene Glycols; D012997:Solvents; D013723:Teratogens; C005219:methyl cellosolve; D000432:Methanol