DERMAL ABSORPTION OF PHTHALATE DIESTERS IN RATS
DERMAL ABSORPTION OF PHTHALATE DIESTERS IN RATS
复制标题
DOI：
10.1016/0272-0590(89)90063-8
复制
发表时间：
1989-01-01
期刊：
影响因子：
--
通讯作者：
SIPES, IG
中科院分区：
文献类型：
--
作者：
ELSISI, AE;CARTER, DE;SIPES, IG
本研究检查了一系列邻苯二甲酸二酯在大鼠中的经皮吸收程度。这些测试是二甲基，二乙基，正丁基，二异丁基，二己基，二（2-乙基己基），二异癸基，和苄基丁基邻苯二甲酸酯。从雄性F344大鼠背部的皮肤区域（直径1.3cm）剪下毛发，以157 μ mol/kg的剂量施用[14 C]邻苯二甲酸二酯，并且用穿孔帽覆盖施用区域。将大鼠圈养在代谢笼中7天，代谢笼允许单独收集尿液和粪便。每24小时收集一次尿和粪便，并将14 C排泄量作为经皮吸收的指标。在24 h时，邻苯二甲酸二乙酯的排泄量最大（26%）。随着烷基侧链长度的增加，在前24小时内排泄的14 C的量显着下降。邻苯二甲酸二乙酯、邻苯二甲酸三丁酯和邻苯二甲酸二异丁酯在7天内排泄的累积剂量百分比最大，约为所用14 C的50-60%;邻苯二甲酸二甲酯、邻苯二甲酸苄丁酯和邻苯二甲酸二己酯的累积剂量百分比居中（20-40%）。除邻苯二甲酸二异癸酯外，尿液是所有邻苯二甲酸二酯的主要排泄途径。该化合物吸收不良，几乎无尿排泄。7天后，残留在体内的每种邻苯二甲酸酯的剂量百分比极小，并且未显示出特定的组织分布。大部分未排泄的剂量留在给药区域。这些数据表明，邻苯二甲酸二酯的结构决定了皮肤吸收的程度。邻苯二甲酸二乙酯的吸收最大化，然后随着烷基侧链长度的增加而显著降低。
This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the [14C]phthalate diester was applied in a dose of 157 .mu.mol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of 14C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of 14C excreted in the first 24 hr decreased significantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied 14C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal and showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased.