A dose response study to assess effects after dietary administration of diisononyl phthalate (DINP) in gestation and lactation on male rat sexual development

Male rat sexual development was evaluated after dietary administration of 0, 760, 3800, 11,400 ppm diisononyl phthalate (DiNP) and 7600 ppm dibutyl phthalate (DBP) from gestation day (GD) 12 to postnatal day (PND) 14. Maternal weight was reduced on GD 20, PND 2 and 14 at 11,400 ppm DiNP. Pup weight was reduced on PND 2 and 14 at 11,400 and 3800 ppm DiNP. DBP induced multinucleated germ cells (MNGs) and Leydig cell aggregates (LCAs) in PND 2 testes. 7600 ppm DBP reduced anogenital distance (AGD) on PND 2 and 14, and increased nipple retention and reproductive tract malformations on PND 49. DiNP induced MNGs (3800 ppm) and LCAs (11,400 ppm) on PND 2, and reduced AGD (11,400 ppm) on PND 14. DiNP did not alter AGD, nipple retention or reproductive tract malformations on PND 49. Global endpoint analysis showed no evidence of a rat “phthalate syndrome” on PND 49 with DiNP administration.

► Rats were exposed to diisononyl (DiNP) and dibutyl phthalate (DBP) in the diet from GD 12 to PND 14.
► 7600 ppm DBP caused increased number of permanent malformations of the male reproductive tract.
► 3800–11,400 ppm DiNP induced temporary effects on testes (PND 2) and anogenital distance (PND 14).
► DiNP did not significantly increase permanent reproductive tract malformations.