Di(2-ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre- and postnatally exposed Wistar rats.
Di(2-ethylhexyl) adipate (DEHA) has replaced the phthalates in thin plasticized polyvinyl chloride films used for food packaging, mainly because some phthalates induce testis toxicity and antiandrogenic effects. A dose-range finding study followed by a dose-response/effect study in Wistar rats investigated whether pre- and postnatal DEHA doses of 0, 800, or 1200mg/kg/day body weight and doses of 0, 200, 400, or 800mg/kg/day (main study) elicited developmental toxicity including antiandrogenic effects. In the main study, DEHA induced a prolonged gestation period (800mg/kg/day) and a dose-related increase in postnatal death (400 and 800mg/kg/day). DEHA also induced a permanent decrease in offspring body weight (800mg/kg/day). No antiandrogenic endpoints were affected. We conclude that DEHA induced developmental toxicity and the NOAEL is 200mg/kg. DEHA did not induce antiandrogenic effects similar to those of di(2-ethylhexyl) phthalate even though the chemical structures have similarities and the two chemicals have a common metabolite.
Dalgaard
Majken
M
Institute of Food Safety and Nutrition, Danish Veterinary and Food Administration, 19 Mørkhøj Bygade, 2860, Søborg, Denmark. mac@fdir.dk
Hass
Ulla
U
Vinggaard
Anne Marie
AM
Jarfelt
Kirsten
K
Lam
Henrik R
HR
Sørensen
Ilona K
IK
Sommer
Helle M
HM
Ladefoged
Ole
O
D000726:Androgen Antagonists / Q000633:toxicity*; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005837:Genitalia, Male / Q000187:drug effects / Q000254:growth & development; D006128:Growth / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D013723:Teratogens; D013739:Testosterone / Q000096:biosynthesis; D015430:Weight Gain / Q000187:drug effects
D000726:Androgen Antagonists; D000728:Androgens; D013723:Teratogens; D013739:Testosterone; D004051:Diethylhexyl Phthalate