氟氯西林低剂量会影响雄性大鼠的生殖系统，但不会影响生育能力和早期胚胎发育。
Low dose of flurochloridone affected reproductive system of male rats but not fertility and early embryonic development.
机构信息
School of Public Health/MOE Key Laboratory for Public Health Safety/NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, 200032, China.
Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai, 201203, China.
出版信息
Reprod Biol Endocrinol. 2019 Aug 6;17(1):64. doi: 10.1186/s12958-019-0508-5.
BACKGROUND
Fluorochloridone (FLC) is a widely used herbicide, and its target organs are testes and epididymides. The Globally Harmonized System of Classification and Labelling of Chemicals classified FLC as Level 2-possibly cause fertility or fetal damage (no relevant data support). The maximum residue levels of FLC in processed crops have been reviewed in the latest European Food Safety Authority (EFSA) report in 2018. However, the toxic effect of FLC on fertility and early embryonic development is limited, and the health risk assessment of FLC needs further consideration. This study investigated the potential effects of FLC on fertility and early embryonic development in rats.
METHODS
One hundred rats of each sex were divided into four groups including three FLC-treated groups at doses of 2 mg/kg, 5 mg/kg and 15 mg/kg, and a vehicle control group (0.5% (w/v) sodium carboxymethyl cellulose). Male and female rats were dosed for 9 and 2 consecutive weeks, intragastrically, prior to cohabitation and lasted throughout the mating period for males and continued until Gestation Day 7 (GD7) for females. Parameters such as weights and coefficients of reproductive organs, epididymal sperm number and motility, indexes of copulation, fecundity and fertility indexes, mating period, estrous cycle, corporalutea number, implantations, live, dead and resorbed fetuses, preimplantation loss rate, and postimplantation loss rate were observed in this study.
RESULTS
Obvious toxicity of male reproductive system was found at the dose of 15 mg/kg including decreases in testicular and epididymal weight, also in sperm motility rate. Whereas the increase in sperm abnormality rate was observed. However, no significant effects of FLC were found on lutea count, implantations count, fetuses count and weight, live fetuses count (rate), dead fetuses count (rate), resorbed fetuses count (rate), placentas weight, fetuses gender, preimplantation loss (rate) and postimplantation loss (rate). Furthermore, FLC had no adverse effects on fertility and early embryonic development in rats.
CONCLUSION
The no-observable-adverse-effect level (NOAEL) of FLC on fertility and early embryonic development in rats was considered to be 5 mg/kg/day.
背景
氟氯草酮（FLC）是一种广泛使用的除草剂，其靶器官是睾丸和附睾。全球化学品统一分类和标签制度将 FLC 归类为 2 级-可能对生育能力或胎儿造成损害（没有相关数据支持）。2018 年，欧洲食品安全局（EFSA）的最新报告审查了加工作物中 FLC 的最大残留水平。然而，FLC 对生育能力和早期胚胎发育的毒性作用有限，需要进一步考虑 FLC 的健康风险评估。本研究调查了 FLC 对大鼠生育能力和早期胚胎发育的潜在影响。
方法
100 只雌雄大鼠分为四组，包括三个 FLC 处理组，剂量分别为 2mg/kg、5mg/kg 和 15mg/kg，以及一个载体对照组（0.5%（w/v）羧甲基纤维素钠）。雌雄大鼠连续 9 周和 2 周灌胃给药，在合笼前和整个交配期给药，持续至雄性大鼠的交配期，持续至雌性大鼠的妊娠第 7 天（GD7）。本研究观察了体重和生殖器官系数、附睾精子数量和活力、交配指数、受孕指数和生育指数、交配期、动情周期、 corpora lutea 数、植入数、活胎、死胎和吸收胎、着床前损失率和着床后损失率等参数。
结果
在 15mg/kg 剂量下，雄性生殖系统出现明显毒性，包括睾丸和附睾重量下降，精子活力下降。然而，观察到精子畸形率增加。然而，FLC 对黄体数、植入数、胎儿数和体重、活胎数（率）、死胎数（率）、吸收胎数（率）、胎盘重量、胎儿性别、着床前损失（率）和着床后损失（率）没有显著影响。此外，FLC 对大鼠的生育能力和早期胚胎发育没有不良影响。
结论
FLC 对大鼠生育能力和早期胚胎发育的无观察不良效应水平（NOAEL）被认为是 5mg/kg/天。
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