title: Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats.
abstract: Diisononyl phthalate (DINP) is a plasticizer abundantly used in consumer products as a substitute for other plasticizers prohibited in certain products due to reproductive toxicity. As anti-androgenic effects of DINP are suspected, DINP effects on reproduction and sexually dimorphic behavior were studied. Pregnant Wistar rats were gavaged from gestation day 7 to postnatal day (PND) 17 with vehicle, 300, 600, 750 or 900 mg DINP/kg bw/day. In fetal testes histopathological effects typical of phthalates were observed. In male offspring, DINP caused increased nipple retention, reduced anogenital distance, reduced sperm motility and increased sperm count. DINP affected spatial learning as female offspring performed better than controls and similarly to control males in the Morris Water Maze, indicating masculinization of behavior in DINP exposed females. These results show that DINP causes anti-androgenic effects on reproductive development, though less potent than DEHP, DBP and BBP, and further safety evaluation of DINP appears warranted.
authors.affiliation: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark. jubo@food.dtu.dk
authors.forename: Julie
authors.initials: J
authors.lastname: Boberg
authors.forename: Sofie
authors.initials: S
authors.lastname: Christiansen
authors.forename: Marta
authors.initials: M
authors.lastname: Axelstad
authors.forename: Thuri Seidler
authors.initials: TS
authors.lastname: Kledal
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Vinggaard
authors.forename: Majken
authors.initials: M
authors.lastname: Dalgaard
authors.forename: Christine
authors.initials: C
authors.lastname: Nellemann
authors.forename: Ulla
authors.initials: U
authors.lastname: Hass
mesh_terms: D000726:Androgen Antagonists; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007774:Lactation; D007858:Learning / Q000187:drug effects; D008297:Male; D009558:Nipples / Q000187:drug effects; D010795:Phthalic Acids / Q000008:administration & dosage / Q000633:toxicity*; D010968:Plasticizers / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology; D013737:Testis / Q000187:drug effects / Q000196:embryology
chemical_list: D000726:Androgen Antagonists; D010795:Phthalic Acids; D010968:Plasticizers; C012125:diisononyl phthalate