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

► Rats were exposed to diisononyl (DiNP) and dibutyl phthalate (DBP) in the diet from GD 12 to PND 14. ► 7600ppm DBP caused increased number of permanent malformations of the male reproductive tract. ► 3800–11,400ppm DiNP induced temporary effects on testes (PND 2) and anogenital distance (PND 14). ► DiNP did not significantly increase permanent reproductive tract malformations. Male rat sexual development was evaluated after dietary administration of 0, 760, 3800, 11,400ppm diisononyl phthalate (DiNP) and 7600ppm 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 11,400ppm DiNP. Pup weight was reduced on PND 2 and 14 at 11,400 and 3800ppm DiNP. DBP induced multinucleated germ cells (MNGs) and Leydig cell aggregates (LCAs) in PND 2 testes. 7600ppm DBP reduced anogenital distance (AGD) on PND 2 and 14, and increased nipple retention and reproductive tract malformations on PND 49. DiNP induced MNGs (3800ppm) and LCAs (11,400ppm) on PND 2, and reduced AGD (11,400ppm) 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.