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Updated: May 24, 2026
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Using Caenorhabditis elegans for Studying Trans- and Multi-Generational Effects of Toxicants
Published on: July 29, 2019
Two-generation reproduction toxicity study in rats with methoxychlor.
Hiroaki Aoyama1, Hitoshi Hojo, Ken L Takahashi
1Laboratories of Reproductive Toxicology, Toxicology Division, Institute of Environmental Toxicology, Ibaraki, Japan. aoyama@iet.or.jp
Congenital Anomalies
|February 22, 2012
Summary
This study found that methoxychlor, an estrogenic pesticide, caused reproductive toxicity and systemic effects in rats at high doses. Lower doses showed no adverse effects, indicating a potential threshold for toxicity.
Area of Science:
- Toxicology
- Endocrinology
- Reproductive Biology
Background:
- Estrogenic pesticides pose risks to reproductive health.
- Regulatory guidelines aim to predict chemical toxicity.
- Methoxychlor is a known estrogenic pesticide used as a reference compound.
Purpose of the Study:
- To evaluate the sensitivity of current regulatory guidelines for predicting reproductive toxicity.
- To assess the estrogenic and endocrine-disrupting effects of methoxychlor.
- To determine dose-response relationships for methoxychlor toxicity.
Main Methods:
- A two-generation reproduction toxicity study was conducted in Sprague-Dawley rats.
- Rats were exposed to methoxychlor (0, 10, 500, 1500 ppm) in their diet for two generations.
- Systemic toxicity, reproductive parameters, and endocrine effects were evaluated.
Main Results:
- Methoxychlor caused significant systemic toxicity (reduced body weight, weight gain, food consumption) and reproductive toxicity (prolonged estrous cycles, reduced fertility, decreased litter size, altered ovary and uterine weights) in females at 500 and 1500 ppm.
- Males exhibited delayed preputial separation, reduced sperm counts, and decreased reproductive organ weights at higher doses.
- No adverse effects were observed in the 10 ppm group, suggesting a no-observed-adverse-effect level (NOAEL).
Conclusions:
- Current regulatory guidelines appear sensitive enough to detect estrogenic reproductive toxicity.
- Methoxychlor exhibits dose-dependent systemic and reproductive toxicity.
- A threshold exists for methoxychlor toxicity, with no adverse effects observed at 10 ppm.
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