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ToxSci Advance Access published online on July 22, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh230
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received January 13, 2004
Accepted July 13, 2004

Reproductive and Developmental Toxicology

Evaluation of the Developmental and Reproductive Toxicity of Methoxychlor Using an Anuran (Xenopus tropicalis) Chronic Exposure Model

Douglas J. Fort 1*, John H. Thomas 1, Robert L. Rogers 1, Andra Noll 1, Clinton D. Spaulding 1, Patrick D. Guiney 2, John A. Weeks 2

1 Fort Environmental Laboratories, Stillwater, Oklahoma
2 Product Safety & Environmental Assessment, SC Johnson & Son, Racine, Wisconsin

* To whom correspondence should be addressed. E-mail: djfort{at}fortlabs.com.


  Abstract

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-d 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-d 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-d exposure). A concentration-dependent increase in external malformations and internal abnormalities of the liver and gonads were noted following 90-d exposure, however. Skewing of 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-d 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 method capable of evaluating both reproductive and developmental effects of potential endocrine disrupting chemicals over a life cycle exposure.

Keywords: Xenopus tropicalis; life cycle assay; methoxychlor; developmental toxicity; reproductive toxicity.
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