The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
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Thyroid Hormone-like Activity of Metribuzin as a Endocrine Disruptor in Rats and HeLaTRE Cell Culture

내분비장애물질로서 Metribuzin의 랫드와 HeLaTRE Cell 중 갑상선 호르몬활성 영향

  • You, Are-Sun (Division of Pesticide Safety Evaluation, Department of Crop Life Safety, National Academy of Agricultural Sciences) ;
  • Jeong, Mi-Hye (Division of Pesticide Safety Evaluation, Department of Crop Life Safety, National Academy of Agricultural Sciences) ;
  • Lee, Je-Bong (Division of Pesticide Safety Evaluation, Department of Crop Life Safety, National Academy of Agricultural Sciences) ;
  • Park, Yoen-Ki (Division of Pesticide Safety Evaluation, Department of Crop Life Safety, National Academy of Agricultural Sciences) ;
  • Shin, Jin-Sup (Division of Pesticide Safety Evaluation, Department of Crop Life Safety, National Academy of Agricultural Sciences) ;
  • Park, Kyung-Hun (Division of Reclaimed land agriculture Research, Department of Rice and Winter, National Institute of Crop Science)
  • 유아선 (국립농업과학원 농산물안전성부 농약평가과) ;
  • 정미혜 (국립농업과학원 농산물안전성부 농약평가과) ;
  • 이제봉 (국립농업과학원 농산물안전성부 농약평가과) ;
  • 박연기 (국립농업과학원 농산물안전성부 농약평가과) ;
  • 신진섭 (국립농업과학원 농산물안전성부 농약평가과) ;
  • 박경훈 (국립식량과학원 벼맥류부 간척지농업과)
  • Published : 2008.12.31
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Abstract

This study was carried out to investigate the suitability of the pubertal assay and the enhanced TG 407 as methods for detection of endocrine-mediated effects. Thyroid function was also considered. Male and female Sprague-Dawley rats were gavaged daily with 0, 25, 50, 100 mg/kg metribuzin in corn oil during 30 days. The effects of metribuzin on thyroid gland, the genital organs and thyroid hormone were measured in male and female rats. Dose of metribuzin 50 mg/kg/day increased relative weight of testis, prostate, and seminal vesicle in male rats but relative weight of thyroid gland was not significantly different from control group. Dose of metribuzin 25 mg/kg/day decreased relative weight of thyroid gland in female rats. Another purpose of this study was to investigate the effects of endocrine-disruptors as like thyroid hormone in vitro. Luciferase activity was measured to detect reaction of test chemicals and thyroid hormone response elements in HeLaTRE cell. Dose of metribuzin from 1 to 1,000 nM increased to 106-122% of luciferase activity.

최근 내분비장애 추정물질의 분류를 위해 많은 시험법이 연구되고 있으며 미국 EPA와 OECD에서는 시험법을 설정하려고 노력하고 있다. 추후 기등록농약에 대한 자료요구 또는 신규 등록농약 적용 등록기준의 추가 등을 고려하여 내분비계장애 추정물질 관련 OECD와 EPA에서 권장하는 시험법을 확립하고자 본 연구를 수행하였다. 시험약제를 30일간 경구 투여하여 조사한 결과, metribuzin 투여 수컷에서 부고환, 전립선, 정낭의 중량이 증가하였고 갑상선에서는 유의한 중량변화가 나타나지 않았다. 암컷에서는 갑상선의 중량 감소가 나타난 반면에 생식장기 중량에는 유의적인 변화가 없었다. Metribuzin 투여수컷에서 testosterone이 100 mg/kg/day 처리수준에서 감소하였고 FT4가 50, 100 mg/kg 수준에서 증가하였다. 암컷에서는 T3가 50, 100 mg/kg/day 수준에서 증가하여 갑상선 호르몬에 영향이 나타나는 것을 볼 수 있었다. 시험세포를 이용한 시험결과, 시험약제를 1 nM에서 1,000 nM까지 처리하였을 때 음성대조군과 비교할 때 metribuzin은 106-122%의 영향을 나타내어 세포이용시험에서는 metribuzin이 갑상선 호르몬성 영향을 보인 것으로 나타났다. 항갑상선 호르몬성 영향 시험에서는 시험약제 100 nM과 T4의 혼합 처리시 metribuzin은 양성 대조군과 비교하여 감소하여 항갑상선 호르몬성 영향을 나타내었다. 본 시험을 통하여 OECD TG 407과 EDSTAC에서 권고하는 pubertal assay와 수의과학 검역원에서 제조한 HeLaTRE cell을 이용한 in vitro 시험이 갑상선 호르몬성 영향 검색 시험으로 활용될 가능성이 있는 것으로 사료되었다.

Keywords

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