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Ninety Day Toxicity and Toxicokinetics of Fluorochloridone after Oral Administration in Rats

Author

Listed:
  • Suhui Zhang

    (School of Public Health, Fudan University, Shanghai 200032, China)

  • Xiaoqin Cheng

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Yu Wang

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Junpei Fan

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Rui Li

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Su Zhou

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Shihong Liu

    (School of Public Health, Fudan University, Shanghai 200032, China)

  • Jingmin Shi

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Jie Sun

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Yue Hu

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Chaojin Xu

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Chunhua Wu

    (School of Public Health, Fudan University, Shanghai 200032, China)

  • Xiuli Chang

    (School of Public Health, Fudan University, Shanghai 200032, China)

  • Liming Tang

    (Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China)

  • Zhijun Zhou

    (School of Public Health, Fudan University, Shanghai 200032, China)

Abstract

The ninety day toxicity and toxicokinetics of fluorochloridone (FLC) were accessed in Wistar rats. Animals were gavaged with FLC at doses of 31.25 mg/kg, 125 mg/kg and 500 mg/kg for ninety days, followed by thirty days for recovery. On the 1st, 60th, 75th and 90th days of the dosing phase, plasma of ten animals of all groups treated with FLC was collected for toxicokinetic analysis of FLC by an UPLC-MS/MS method. Numerous changes in body weight, hematology, serum chemistry, and organ weight ratios were observed by the 45th and 90th dosing day. Most changes in groups treated with FLC were absent on the last recovery day. Testis and epididymis lesions were consistently seen in histopathological observations on the 45th, 90th dosing day and the last recovery day. Repeated administration of FLC increased the level of testosterone in serum in male rats on the 90th dosing day. FLC plasma concentrations could be detected in all animal drug-treated groups during the dosing phase, and a dose proportional relationship was seen between FLC dose and AUC or C max . This study will support future studies on the mechanism of FLC-induced toxicity.

Suggested Citation

  • Suhui Zhang & Xiaoqin Cheng & Yu Wang & Junpei Fan & Rui Li & Su Zhou & Shihong Liu & Jingmin Shi & Jie Sun & Yue Hu & Chaojin Xu & Chunhua Wu & Xiuli Chang & Liming Tang & Zhijun Zhou, 2015. "Ninety Day Toxicity and Toxicokinetics of Fluorochloridone after Oral Administration in Rats," IJERPH, MDPI, vol. 12(5), pages 1-25, May.
    • Handle: RePEc:gam:jijerp:v:12:y:2015:i:5:p:4942-4966:d:49220
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    References listed on IDEAS

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    1. Svenja Rieke & Sophie Koehn & Karen Hirsch-Ernst & Rudolf Pfeil & Carsten Kneuer & Philip Marx-Stoelting, 2014. "Combination Effects of (Tri)Azole Fungicides on Hormone Production and Xenobiotic Metabolism in a Human Placental Cell Line," IJERPH, MDPI, vol. 11(9), pages 1-20, September.
    2. Don Lotter, 2015. "Facing food insecurity in Africa: Why, after 30 years of work in organic agriculture, I am promoting the use of synthetic fertilizers and herbicides in small-scale staple crop production," Agriculture and Human Values, Springer;The Agriculture, Food, & Human Values Society (AFHVS), vol. 32(1), pages 111-118, March.
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    Cited by:

    1. Fen Zhang & Zhijing Ni & Shuqi Zhao & Yanna Wang & Xiuli Chang & Zhijun Zhou, 2022. "Flurochloridone Induced Cell Apoptosis via ER Stress and eIF2α-ATF4/ATF6-CHOP-Bim/Bax Signaling Pathways in Mouse TM4 Sertoli Cells," IJERPH, MDPI, vol. 19(8), pages 1-12, April.
    2. Howard W. Mielke, 2016. "Editorial: Lead Risk Assessment and Health Effects," IJERPH, MDPI, vol. 13(6), pages 1-3, June.
    3. Hongyan Zhu & Rui Li & Su Zhou & Suhui Zhang & Yu Wang & Shihong Liu & Qingwen Song & Xiuli Chang & Yubin Zhang & Luqing Liu & Liming Tang & Zhijun Zhou, 2019. "The Oral NOAEL of Flurochloridone in Male Wistar Rats in Ninety-Day Subchronic Toxicity Test Was 3mg/kg/day," IJERPH, MDPI, vol. 16(4), pages 1-7, February.

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