Differential developmental toxicities of di-n-hexyl phthalate and dicyclohexyl phthalate administered orally to rats.
The objective of this study was to evaluate the developmental toxic potential of di-n-hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague-Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg(-1) per day, by gavage, on gestational days (GD) 6-20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg(-1) per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg(-1) per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg(-1) per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg(-1) per day. DCHP produced fetal growth retardation at 750 mg kg(-1) per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg(-1) per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP.
Saillenfait
Anne-Marie
AM
Institut National de Recherche et de Sécurité, Rue du Morvan, CS, 60027, 54519 Vandoeuvre Cedex, France. anne-marie.saillenfait@inrs.fr
Gallissot
Frédéric
F
Sabaté
Jean-Philippe
JP
D000284:Administration, Oral; D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005327:Fetal Resorption / Q000139:chemically induced*; D005865:Gestational Age; D007536:Isomerism; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D036401:Toxicity Tests, Chronic
D010795:Phthalic Acids; D010968:Plasticizers; C027387:di-n-hexyl phthalate; C036042:dicyclohexyl phthalate