Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland.
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.
D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D007774:Lactation / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008321:Mammary Glands, Animal / Q000187:drug effects*; D008892:Milk / Q000187:drug effects / Q000378:metabolism*; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D008055:Lipids; D010795:Phthalic Acids; D004051:Diethylhexyl Phthalate; D002332:Carnitine O-Acetyltransferase; D010170:Palmitoyl-CoA Hydrolase