Heindel J J, Gulati D K, Mounce R C, Russell S R, Lamb J C
Developmental and Reproductive Toxicology Group, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1989 Apr;12(3):508-18. doi: 10.1016/0272-0590(89)90024-9.
A continuous breeding protocol was utilized to examine the reproductive toxicity of three phthalate esters. CD-1 mice were given diets with either di-n-propyl phthalate (DPrP: 0.0, 1.25, 2.5, or 5.0%), di-n-pentyl phthalate (DPP: 0.0, 0.5, 1.25, or 2.5%), or di-n-octyl phthalate (DOP: 0.0, 1.25, 2.5, or 5.0%). Both male and female mice (20 pairs per treatment group, 40 pairs of control animals) were dosed for 7 days prior to and during a 98-day cohabitation period. Reproductive function was evaluated during the cohabitation period by measuring number of litters per pair, live pups per litter, and pup weight. There was no apparent effect on reproductive function in the animals exposed to DOP at dose levels sufficient to cause a significant increase in liver weight. Both DPP and DPrP were toxic to the reproductive system as evidenced by a complete inhibition of fertility at 1.25 and 2.5% DPP or 5.0% DPrP, and reduced fertility (litters/pair and live pups/litter, 0.5% DPP; live pups/litter, 2.5% DPrP). Toxicity of DPP had a strong male component and female component, whereas DPrP was more toxic to the female than the male reproductive system. DPP and DPrP treatment was associated with decreased body weight, increased liver weight, decreased testis and epididymis weights, decreased epididymal sperm concentration, and elevated seminiferous tubule atrophy. A comparison of seven phthalate esters tested using this continuous breeding protocol indicates the relative order of reproductive toxicity as diethylhexyl, dihexyl, dipentyl, dibutyl, dipropyl; diethyl and dioctyl are nontoxic.
采用连续繁殖方案来检测三种邻苯二甲酸酯的生殖毒性。给CD-1小鼠喂食含有以下成分的日粮：邻苯二甲酸二正丙酯（DPrP：0.0%、1.25%、2.5%或5.0%）、邻苯二甲酸二正戊酯（DPP：0.0%、0.5%、1.25%或2.5%）或邻苯二甲酸二正辛酯（DOP：0.0%、1.25%、2.5%或5.0%）。在为期98天的同居期之前及期间，对雄性和雌性小鼠（每个处理组20对，40对对照动物）给药7天。在同居期通过测量每对小鼠的产仔数、每窝活仔数和仔鼠体重来评估生殖功能。在足以导致肝脏重量显著增加的剂量水平下，接触DOP的动物的生殖功能未出现明显影响。DPP和DPrP对生殖系统均有毒性，表现为在1.25%和2.5%的DPP或5.0%的DPrP时生育能力完全受到抑制，以及生育能力降低（每对产仔数和每窝活仔数，0.5%的DPP；每窝活仔数，2.5%的DPrP）。DPP的毒性有很强的雄性和雌性成分，而DPrP对雌性生殖系统的毒性比对雄性更大。DPP和DPrP处理与体重减轻、肝脏重量增加、睾丸和附睾重量减轻、附睾精子浓度降低以及生精小管萎缩增加有关。使用该连续繁殖方案测试的七种邻苯二甲酸酯的比较表明，生殖毒性的相对顺序为二乙基己基、二己基、二戊基、二丁基、二丙基；二乙基和二辛基无毒。
