ToxSci Advance Access originally published online on July 22, 2004
Toxicological Sciences 2004 81(2):443-453; doi:10.1093/toxsci/kfh230
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Toxicological Sciences vol. 81 no. 2 © Society of Toxicology 2004; all rights reserved.
Evaluation of the Developmental and Reproductive Toxicity of Methoxychlor using an Anuran (Xenopus tropicalis) Chronic Exposure Model
* Fort Environmental Laboratories, Stillwater, Oklahoma; Product Safety & Environmental Assessment, SC Johnson & Son, Racine, Wisconsin
Received January 13, 2004; accepted July 13, 2004
The chronic toxicity of methoxychlor to the South African clawed frog, Xenopus (Silurana) tropicalis, was evaluated using a life cycle approach. The chronic exposure period ranged from mid-cell blastula stage [NF (Nieuwkoop and Faber, 1994) stage 8] to 90 days of exposure, during which time the organisms generally completed metamorphosis and emerged as juvenile frogs. Methoxychlor concentrations ranged from 1 to 100 µg/l. Methoxychlor concentrations >10 µg/l caused delayed development. Organisms exposed to 10 µg/l methoxychlor for 30 days showed enlarged thyroid glands with follicular hyperplasia. No increase in mortality or external malformation was observed at any of the test concentrations during early embryo-larval development (NF stage 8 to NF stage 46; ca. 2 days exposure). A concentration-dependent increase in external malformations and internal abnormalities of the liver and gonads were noted after 90 days of exposure, however. Skewing of the sex ratio toward the female gender decreased ovary weight and number of oocytes, and increased oocyte immaturity and necrosis were noted at methoxychlor concentrations of 100 µg/l. Reductions in testis weight and sperm cell count were also detected at 100 µg/l methoxychlor. Results from these studies suggested that methoxychlor was capable of altering the rate of larval development, but did not adversely affect early embryo-larval development (2 days of exposure) as manifested in external malformations. Internal malformations, increases in the ratio of phenotypic females, were induced by chronic methoxychlor exposure. In addition, reproductive endpoints, most notably in the female specimens, were adversely affected by methoxychlor exposure. These studies add to the standardization and validation of a useful amphibian test methods capable of evaluating both reproductive and developmental effects of potential endocrine disrupting chemicals over a life cycle exposure.
Key Words: Xenopus tropicalis; life cycle assay; methoxychlor; developmental toxicity; reproductive toxicity.