REPRODUCTIVE EFFECTS OF 4 PHTHALIC-ACID ESTERS IN THE MOUSE

REPRODUCTIVE EFFECTS OF 4 PHTHALIC-ACID ESTERS IN THE MOUSE
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DOI:
10.1016/0041-008x(87)90011-1
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发表时间:
1987-04-01
影响因子:
3.8
通讯作者:
REEL, JR
REEL, JR
中科院分区:
医学3区
文献类型:
--
作者:
LAMB, JC;CHAPIN, RE;REEL, JR

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这些研究通过连续繁殖方案比较了四种邻苯二甲酸盐的生殖毒性。给小鼠喂食含有邻苯二甲酸二乙酯(DEP)(0.0、0.25、1.25或2.5%)、邻苯二甲酸二正丁酯(DBP)(0.0、0.03、0.3或1.0%)、邻苯二甲酸二正己酯(DHP)(0.0、0.3、0.6或1.2%)或邻苯二甲酸二(2-乙基己基)酯(DEHP)(0.0、0.01或0.3%)的饲料。雄性和雌性CD-1小鼠在同居前和同居期间分别给药7天和98天。在同居期间,通过测量每对幼鼠的产仔数和每窝活仔数、幼鼠体重和后代存活率来评估生殖功能。暴露于DEP的动物的生殖功能没有明显的影响,尽管对体重增加和肝脏重量有显著影响。暴露于DBP导致每对幼鼠的产仔数和每窝幼鼠的活仔数以及在1.0%剂量下出生的活仔比例减少,但在较低剂量水平下则没有。一项交叉交配试验表明,雌性小鼠受到DBP的影响,而雄性小鼠则没有受到DBP的影响,表现为可育对百分比、每窝活仔数、活仔出生比例和活仔体重显著下降。饲粮中DHP含量分别为0.3、0.6和1.2%时,对每对幼鼠的产仔数、每窝幼鼠的活仔数以及幼鼠出生活仔率产生了剂量相关的不利影响。一项跨界交配研究表明,两性都受到影响。DEHP(0.1和0.3%)导致繁殖能力和幼崽出生存活数量和比例呈剂量依赖性下降。一项交叉交配试验表明,两性都受到DEHP暴露的影响。这些数据表明,连续育种方案能够区分活性较高和较低的同系物的定性和定量生殖效应,以及由于邻苯二甲酸酯烷基取代的细微变化而导致的生殖毒性的巨大差异。
These studies compared the reproductive toxicity of four phthalates by a continuous breeding protocol. Mice were given diets with diethyl phthalate (DEP) (0.0, 0.25, 1.25, or 2.5%), di-n-butyl phthalate (DBP) (0.0, 0.03, 0.3, or 1.0%), di-n-hexyl phthalate (DHP) (0.0, 0.3, 0.6, or 1.2%), or di(2-ethylhexyl) phthalate (DEHP) (0.0, 0.01, or 0.3%). Both male and female CD-1 mice were dosed for 7 days prior to and during a 98-day cohabitation period. Reproductive function was evaluated during the cohabitation period by measuring the numbers of litters per pair and of live pups per litter, pup weight, and offspring survival. There was no apparent effect on reproductive function in the animals exposed to DEP, despite significant effects on body weight gain and liver weight. DBP exposure resulted in a reduction in the numbers of litters per pair and of live pups per litter and in the proportion of pups born alive at the 1.0% amount, but not at lower dose levels. A crossover mating trial demonstrated that female mice, but not males, were affected by DBP, as shown by significant decreases in the percentage of fertile pairs, the number of live pups per litter, the proportion of pups born alive, and live pup weight. DHP in the diet resulted in dose-related adverse effects on the numbers of litters per pair and of live pups per litter and proportion of pups born alive at 0.3, 0.6, and 1.2% DHP in the diet. A crossover mating study demonstrated that both sexes were affected. DEHP (at 0.1 and 0.3%) caused dose-dependent decreases in fertility and in the number and the proportion of pups born alive. A crossover mating trial showed that both sexes were affected by exposure to DEHP. These data demonstrate the ability of the continuous breeding protocol to discriminate the qualitative and quantitative reproductive effects of the more and less active congeners as well as the large differences in reproductive toxicity attributable to subtle changes in the alkyl substitution of phthalate esters.