title: Developmental toxicity of methoprene and several degradation products in Xenopus laevis.
abstract: Methoprene is an insect juvenile growth hormone mimic, which inhibits pupation and is used for the control of emergent insect pests such as mosquitoes. Researchers have hypothesized that methoprene use in US may be a contributing factor to the recent increase in malformed amphibians. However, little is known concerning the developmental toxicity of methoprene and its degradation products in amphibians. In these studies, the aqueous stability and developmental toxicity of methoprene and several degradation products (methoprene acid, methoprene epoxide, 7-methoxycitronellal, and 7-methoxycitronellic acid) were examined. Xenopus laevis embryos (stage 8) were exposed to the test chemicals for 96 h. Assays were conducted under static renewal (24 h) conditions and chemical concentrations in water were measured at the beginning and end of the renewal periods. Methoprene exposure did not result in developmental toxicity at concentrations up to 2 mg/l, which is slightly higher than its water solubility. Methoprene acid, a relatively minor degradation product, produced developmental toxicity when concentrations exceeded 1.25 mg/l. Methoprene epoxide and 7-methoxycitronellal caused developmental toxicity at concentrations of 2.5 mg/l and higher. 7-Methoxycitronellic acid was not developmentally toxic at a test concentration as high as 30 mg/l. The five test chemicals had differential stability in aqueous solution that was in some instances affected by the presence of test organisms. These data indicate that methoprene and its degradation products are not potent development toxicants in X. laevis. This, in combination with the fact that field applications of sustained-release formulations of methoprene result in methoprene concentrations that do not typically exceed 0.01 mg/l, suggests that concerns for methoprene-mediated developmental toxicity to amphibians may be unwarranted.
authors.affiliation: US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804-2595, USA. degitz.sigmund@epa.gov
authors.forename: Sigmund J
authors.initials: SJ
authors.lastname: Degitz
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Durhan
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tietge
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kosian
authors.forename: Gary W
authors.initials: GW
authors.lastname: Holcombe
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000196:embryology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects; D047108:Embryonic Development; D004781:Environmental Exposure / Q000009:adverse effects; D006728:Hormones / Q000378:metabolism / Q000633:toxicity; D007301:Insect Hormones / Q000378:metabolism / Q000633:toxicity; D008726:Methoprene / Q000378:metabolism / Q000633:toxicity*; D013723:Teratogens; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*; D014982:Xenopus laevis / Q000002:abnormalities* / Q000196:embryology* / Q000378:metabolism
chemical_list: D006728:Hormones; D007301:Insect Hormones; D013723:Teratogens; D014874:Water Pollutants, Chemical; D008726:Methoprene