Lin L I
Toxicol Ind Health. 1987 Jun;3(2):25-48. doi: 10.1177/074823378700300204.
This paper contains statistical evaluations of the effect of 9 different plasticizers on rat hepatic peroxisome proliferation. There were 9 21-day feeding studies with one plasticizer in each study. The plasticizers are: di(2-ethylhexyl)phthalate (DEHP), butyl benzyl phthalate (BBP), 711 phthalate (711P), di(n-butyl)phthalate (DBP), di(undecyl)phthalate (DUP), di(isodecyl)phthalate (DIDP), di(isononyl)phthalate (DINP), 610 phthalate (610P), and di(ethylhexyl)adipate (DEHA). For each plasticizer, several dosage (as % of diet) groups, plus a negative control group (0%) and a reference control group (1.2% DEHP) were included. There were 5 males and 5 females, approximately 5 weeks old, per group per plasticizer, for a total of 470 animals. For each animal, body weight and food intake were measured prior to treatment and twice a week during the treatment period. Animals were necropsied at the end of the 21-day treatment period. Selected organs and blood samples of each animal were collected for measuring hepatic enzymes, proteins, fat stains, organ weights and serum fats. The endpoints included electron microscopy examination of liver peroxisome proliferation and liver histological abnormalities. The statistical evaluation utilized a multivariate approach that condensed a complex phenomenon into certain meaningful and simple endpoints for quantitative comparisons. The dose of each plasticizer that would protect 99% and 99.9% of rats against peroxisome proliferation (xx% statistically predicted dose, or xx% SPD) was estimated. Marked differences were seen in the ability of the 9 test compounds to cause hepatic peroxisome proliferation in rats. The graphic ranking of overall potency is, in order from most potent to least potent: DEHP, DIDP, DINP, DBP, DEHA, DUP, BBP, 711P and 610P. The ranking in terms of 99.9% SPD is: DEHP, DINP, DIDP, DBP, 610P, DUP, DBP, 711P and DEHA. It was also found that the histological findings of reduced basophilia or increased eosinophilia were highly correlated with peroxisome proliferation (r = 0.94). The other histological findings were incidental observations for specific plasticizers.
本文包含对9种不同增塑剂对大鼠肝脏过氧化物酶体增殖影响的统计评估。共有9项为期21天的喂养研究，每项研究使用一种增塑剂。这些增塑剂分别是：邻苯二甲酸二（2-乙基己基）酯（DEHP）、邻苯二甲酸丁苄酯（BBP）、711邻苯二甲酸酯（711P）、邻苯二甲酸二正丁酯（DBP）、邻苯二甲酸二（十一烷基）酯（DUP）、邻苯二甲酸二异癸酯（DIDP）、邻苯二甲酸二异壬酯（DINP）、610邻苯二甲酸酯（610P）和己二酸二（2-乙基己基）酯（DEHA）。对于每种增塑剂，设置了几个剂量（占饮食的百分比）组，外加一个阴性对照组（0%）和一个阳性对照组（1.2% DEHP）。每种增塑剂的每组有5只雄性和5只雌性大鼠，约5周龄，总共470只动物。对于每只动物，在处理前以及处理期间每周两次测量体重和食物摄入量。在21天处理期结束时对动物进行剖检。收集每只动物的选定器官和血液样本，用于测量肝脏酶、蛋白质、脂肪染色、器官重量和血清脂肪。终点指标包括肝脏过氧化物酶体增殖的电子显微镜检查和肝脏组织学异常。统计评估采用多变量方法，将复杂现象浓缩为某些有意义且简单的终点指标进行定量比较。估计了能保护99%和99.9%的大鼠免受过氧化物酶体增殖影响的每种增塑剂的剂量（xx%统计预测剂量，或xx% SPD）。在9种受试化合物引起大鼠肝脏过氧化物酶体增殖的能力方面观察到显著差异。总体效力的图形排名从最强到最弱依次为：DEHP、DIDP、DINP、DBP、DEHA、DUP、BBP、711P和610P。按照99.9% SPD的排名为：DEHP、DINP、DIDP、DBP、610P、DUP、DBP、711P和DEHA。还发现嗜碱性降低或嗜酸性增加的组织学结果与过氧化物酶体增殖高度相关（r = 0.94）。其他组织学结果是特定增塑剂的偶然观察结果。
