Dostal L A, Weaver R P, Schwetz B A
National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Toxicol Appl Pharmacol. 1987 Dec;91(3):315-25. doi: 10.1016/0041-008x(87)90054-8.
Five daily oral doses of di(2-ethylhexyl) phthalate (DEHP) (2 g/kg) given to rats on Days 2-6, 6-10, or 14-18 of lactation caused significant decreases in body weight and increases in hepatic peroxisomal enzymes palmitoyl CoA oxidase and carnitine acetyltransferase in the dams and their suckling pups. Plasma cholesterol and triglyceride levels were decreased in the lactating dams. Decreased food consumption, as indicated by pair-fed rats, accounted for the decreased body weight in the pups but not the increases in enzyme activities. To determine whether DEHP and mono(2-ethylhexyl) phthalate (MEHP) were transferred through the milk, milk and plasma were collected from lactating rats 6 hr after the third dose of DEHP. The milk contained 216 +/- 23 micrograms/ml DEHP and 25 +/- 6 micrograms/ml MEHP (mean +/- SE), while the plasma contained less than 0.5 micrograms/ml DEHP and 75 +/- 12 micrograms/ml MEHP. The high milk/plasma ratio for DEHP (greater than 200) indicates efficient extraction of DEHP from the plasma into the milk. DEHP dosing during lactation also caused a decrease in mammary gland weight and a decrease in mammary gland RNA content which reflects synthetic activity. The water content of the milk was reduced, which probably accounted for the increase in lipid in the milk. Milk lactose was decreased in DEHP-treated and pair-fed rats, consistent with the decrease in milk production. The results show that exposure to high doses of DEHP during lactation in rats can result in changes in milk quality and quantity and can lead to DEHP and MEHP exposure in the suckling rat pups.
在哺乳期的第2 - 6天、6 - 10天或14 - 18天，给大鼠每日口服五次邻苯二甲酸二（2 - 乙基己基）酯（DEHP）（2 g/kg），导致母鼠及其哺乳幼崽体重显著下降，肝脏过氧化物酶体酶棕榈酰辅酶A氧化酶和肉碱乙酰转移酶增加。哺乳期母鼠的血浆胆固醇和甘油三酯水平降低。如配对喂养的大鼠所示，食物摄入量减少是幼崽体重下降的原因，但不是酶活性增加的原因。为了确定DEHP和单（2 - 乙基己基）邻苯二甲酸酯（MEHP）是否通过乳汁转移，在第三次给予DEHP 6小时后，从哺乳期大鼠收集乳汁和血浆。乳汁中含有216±23微克/毫升的DEHP和25±6微克/毫升的MEHP（平均值±标准误），而血浆中DEHP含量低于0.5微克/毫升，MEHP含量为75±12微克/毫升。DEHP的乳汁/血浆比率很高（大于200），表明DEHP能有效地从血浆中提取到乳汁中。哺乳期给予DEHP还导致乳腺重量减轻以及反映合成活性的乳腺RNA含量降低。乳汁的含水量降低，这可能是乳汁中脂质增加的原因。DEHP处理组和配对喂养组大鼠的乳汁乳糖减少，这与乳汁分泌量减少一致。结果表明，大鼠在哺乳期接触高剂量DEHP可导致乳汁质量和数量发生变化，并可导致哺乳幼崽接触DEHP和MEHP。
