Ninety day toxicity and toxicokinetics of fluorochloridone after oral administration in rats

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...

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Bibliographic Details
Published in:International journal of environmental research and public health 2015-05, Vol.12 (5), p.4942-4966
Main Authors: Zhang, Suhui, Cheng, Xiaoqin, Wang, Yu, Fan, Junpei, Li, Rui, Zhou, Su, Liu, Shihong, Shi, Jingmin, Sun, Jie, Hu, Yue, Xu, Chaojin, Wu, Chunhua, Chang, Xiuli, Tang, Liming, Zhou, Zhijun
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Body Weight
Dose-Response Relationship, Drug
Drug Administration Schedule
Kinetics
Male
Organ Size
Plasma
Pyrrolidinones - pharmacokinetics
Pyrrolidinones - toxicity
Rats
Rats, Wistar
Rodents
Tandem Mass Spectrometry
Testicular Diseases - chemically induced
Testis - drug effects
Testis - pathology
Testosterone - metabolism
Toxicity
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Summary: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 Cmax. This study will support future studies on the mechanism of FLC-induced toxicity.
ISSN:1660-4601
1661-7827
1660-4601
DOI:10.3390/ijerph120504942