Kluwe W M, McConnell E E, Huff J E, Haseman J K, Douglas J F, Hartwell W V
Environ Health Perspect. 1982 Nov;45:129-33. doi: 10.1289/ehp.8245129.
Five phthalate ester and related compounds (phthalic anhydride, phthalamide, di(2-ethylhexyl) phthalate, di(2-ethylhexyl) adipate and butyl benzyl phthalate) have been tested for carcinogenic effects in standard lifetime rodent feeding studies. Groups of 50 male and female rats and mice were fed diets containing various concentrations of the test chemicals for 102-106 consecutive weeks. The dietary concentrations were estimated to be maximally tolerated doses and half maximally tolerated doses. All animals that died during the study and all survivors at the end of two years were examined grossly and microscopically for the presence of tumors. The incidences of animals with tumors at a specific anatomic site in the treated groups and the controls were compared statistically. Neither phthalamide nor phthalic anhydride increased tumor incidences in rats or mice. Di(2-ethylhexyl) phthalate increased the incidences of liver tumors in rats and mice of both sexes, while di(2-ethylhexyl) adipate caused liver tumors in male and female mice, only. Butyl benzyl phthalate did not cause tumors in male or female mice, but the incidence of myelomonocytic leukemia in butyl benzyl phthalate-treated female rats was significantly greater than that in the controls. Chemically induced early deaths in the butyl benzyl phthalate-treated male rats precluded an evaluation of carcinogenic potential in this sex. Under the conditions of these tests, di(2-ethylhexyl) adipate was considered to be carcinogenic in both rats and mice and di(2-ethylhexyl) adipate was considered to be carcinogenic in mice. The evidence for carcinogenic effects of butyl benzyl phthalate in female rats was judged to be equivocal because of the variable nature of the incidence of myelomonocytic leukemia in Fischer 344 rats. Phthalamide and phthalic anhydride did not exhibit carcinogenic effects in these studies.
已在标准的终生啮齿动物喂养研究中对五种邻苯二甲酸酯及相关化合物（邻苯二甲酸酐、邻苯二甲酰胺、邻苯二甲酸二（2-乙基己基）酯、己二酸二（2-乙基己基）酯和邻苯二甲酸丁苄酯）的致癌作用进行了测试。将50只雄性和雌性大鼠及小鼠分成若干组，连续102 - 106周喂食含有不同浓度受试化学物质的饲料。日粮浓度估计为最大耐受剂量和半数最大耐受剂量。对研究期间死亡的所有动物以及两年结束时的所有存活动物进行大体和显微镜检查，以确定是否存在肿瘤。对处理组和对照组中特定解剖部位出现肿瘤的动物发生率进行统计学比较。邻苯二甲酰胺和邻苯二甲酸酐均未增加大鼠或小鼠的肿瘤发生率。邻苯二甲酸二（2-乙基己基）酯增加了雌雄大鼠和小鼠肝脏肿瘤的发生率，而己二酸二（2-乙基己基）酯仅在雌雄小鼠中引发肝脏肿瘤。邻苯二甲酸丁苄酯未在雄性或雌性小鼠中引发肿瘤，但经邻苯二甲酸丁苄酯处理的雌性大鼠中骨髓单核细胞白血病的发生率显著高于对照组。经邻苯二甲酸丁苄酯处理的雄性大鼠因化学诱导的早期死亡而无法评估该性别中的致癌潜力。在这些测试条件下，己二酸二（2-乙基己基）酯被认为在大鼠和小鼠中均具有致癌性，邻苯二甲酸二（2-乙基己基）酯被认为在小鼠中具有致癌性。由于Fischer 344大鼠中骨髓单核细胞白血病发生率的变化性质，邻苯二甲酸丁苄酯对雌性大鼠致癌作用的证据被判定为不明确。在这些研究中，邻苯二甲酰胺和邻苯二甲酸酐未表现出致癌作用。
