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烷基二甲基苄基氯化铵和双十烷基二甲基氯化铵在 CD 大鼠和新西兰白兔体内的产前发育毒性。

Prenatal developmental toxicity of alkyl dimethyl benzyl ammonium chloride and didecyl dimethyl ammonium chloride in CD rats and New Zealand White rabbits.

机构信息

Toxicology Regulatory Services, Charlottesville, Virginia, USA.

出版信息

Birth Defects Res. 2021 Jul 15;113(12):925-944. doi: 10.1002/bdr2.1889. Epub 2021 Mar 21.

Abstract

The prenatal developmental toxicity potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) was evaluated in regulatory-compliant studies. Pregnant female CD rats (25/group) and New Zealand White rabbits (16/group) were administered ADBAC (0, 10, 30, or 100 mg/kg/day and 0, 1, 3, or 9 mg/kg/day, respectively), or DDAC (0, 1, 10, or 20 mg/kg/day and 0, 1, 3, or 10 mg/kg/day, respectively), by oral gavage on gestation days (GD) 6-15 for rats and GD 6-18 for rabbits. At scheduled termination (GD 21 for rats; GD 29 for rabbits), maternal necropsies were conducted and live fetuses were weighed and examined for external, visceral, and skeletal malformations and variations. Clinical signs of maternal toxicity were observed in rats and rabbits dosed with ADBAC, resulting in no-observed-adverse-effect levels (NOAELs) of 10 and 3 mg/kg/day, respectively. Despite the treatment-related maternal toxicity of ADBAC, the NOAEL for prenatal developmental toxicity was 100 and 9 mg/kg/day for rats and rabbits, respectively, the highest doses evaluated. Repeated oral doses of DDAC resulted in maternal toxicity in both species at the top two doses, with 25% mortality noted in rabbits at 10 mg/kg/day. No teratogenic effects were observed at any dose for either species. However, increased incidence of dead fetuses per litter and decreased fetal body weights were observed in rabbits at the maternally lethal dose of 10 mg/kg/day. The NOAEL for maternal toxicity of DDAC was 1 mg/kg/day for both species and the NOAEL for prenatal developmental toxicity was 20 and 3 mg/kg/day, for rats and rabbits, respectively.

摘要

在符合监管要求的研究中评估了烷基二甲基苄基氯化铵(ADBAC)和双十烷基二甲基氯化铵(DDAC)的产前发育毒性潜力。妊娠雌性 CD 大鼠(每组 25 只)和新西兰白兔(每组 16 只)分别经口给予 ADBAC(分别为 0、10、30 或 100mg/kg/天和 0、1、3 或 9mg/kg/天)或 DDAC(分别为 0、1、10 或 20mg/kg/天和 0、1、3 或 10mg/kg/天),给药时间为大鼠妊娠第 6-15 天,兔子妊娠第 6-18 天。在预定的处死时间(大鼠妊娠第 21 天;兔子妊娠第 29 天),对母体进行尸检,并对活胎进行称重和检查,以评估其是否存在外部、内脏和骨骼畸形和变异。ADBAC 处理的大鼠和兔子出现了母体毒性的临床症状,导致无观察到不良影响水平(NOAEL)分别为 10 和 3mg/kg/天。尽管 ADBAC 存在与母体毒性相关的作用,但大鼠和兔子的产前发育毒性的 NOAEL 分别为 100 和 9mg/kg/天,为评估的最高剂量。DDAC 重复口服剂量在两种物种的最高两个剂量下均导致母体毒性,在兔子中观察到 10mg/kg/天剂量时 25%的死亡率。在任何剂量下,两种物种均未观察到致畸作用。然而,在兔子的母体致死剂量 10mg/kg/天,死胎发生率增加,胎仔体重降低。DDAC 的母体毒性的 NOAEL 为 1mg/kg/天,DDAC 的产前发育毒性的 NOAEL 为 20 和 3mg/kg/天,分别为大鼠和兔子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1361/8359997/210203984147/BDR2-113-925-g008.jpg

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