title: Ninety day toxicity and toxicokinetics of fluorochloridone after oral administration in rats.
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 Cmax. This study will support future studies on the mechanism of FLC-induced toxicity.
authors.affiliation: School of Public Health, Fudan University, Shanghai 200032, China. 12111020016@fudan.edu.cn.
authors.forename: Suhui
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. cxq19850429@aliyun.com.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. ohyue@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. 13761243089@126.com.
authors.forename: Junpei
authors.initials: J
authors.lastname: Fan
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. lirui200901@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. hello-world-zhou@163.com.
authors.forename: Su
authors.initials: S
authors.lastname: Zhou
authors.affiliation: School of Public Health, Fudan University, Shanghai 200032, China. 13211020060@fudan.edu.cn.
authors.forename: Shihong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. sjabcd1983@163.com.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. sjabcd1983@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. huyue86816@hotmail.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. ratxu1972@126.com.
authors.forename: Chaojin
authors.initials: C
authors.lastname: Xu
authors.affiliation: School of Public Health, Fudan University, Shanghai 200032, China. chwu@shmu.edu.cn.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Public Health, Fudan University, Shanghai 200032, China. xlchang@shmu.edu.cn.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chang
authors.affiliation: Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. tangliming@smda.gov.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Tang
authors.affiliation: School of Public Health, Fudan University, Shanghai 200032, China. zjzhou@fudan.edu.cn.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D009929:Organ Size; D011760:Pyrrolidinones / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D013733:Testicular Diseases / Q000139:chemically induced; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000378:metabolism
chemical_list: D011760:Pyrrolidinones; D013739:Testosterone; C077976:raiser