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680076 
Journal Article 
Developmental and reproductive toxicity Of di-isoheptyl phthalate in rodents 
Mckee, RH; Pavkov, KL; Trimmer, GW; Keller, LH; Stump, DG 
2005 
1 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
TOX/5000409 
84 
1S 
57 
English 
Di-isoheptyl phthalate (DIHP) is a branched, 7-carbon phthalate ester. Since some phthalates of similar structure have been shown to produce developmental and/or reproductive effects in rodents, an assessment of the potential for DIHP to produce developmental and reproductive toxicity was conducted. In a developmental toxicity study, female rats were given DIHP by oral gavage on gestational days 6-20. There were significant reductions in uterine weight, increased resorptions, and reduced fetal weights in the high dose group (750 mg/kg). Fetal examination revealed malformations and variations of both the skeletal system and the viscera including ectopic testes. The intermediate dose, 300 mg/kg/day, was the no effect level. In a two-generation reproductive toxicity study, DIHP was administered in the diet at 1000, 4500, and 8000 ppm. There were significant effects on indicators of male reproductive development in the high dose group. In the first (F1) generation, anogenital distance was reduced, time to balanopreputial separation was increased, there was a significant increase in thoracic nipples and testicular abnormalities; weights of testes and accessory reproductive organs were significantly reduced. Testicular sperm counts and daily sperm productions were significantly reduced. Fertility was reduced in the high dose group. In the second (F2) generation, anogenital distance was significantly reduced, and there was evidence of reduced weight gain during lactation. The overall no effect level (NOEL) in the reproductive toxicity study was in the range of 64 - 168 mg/kg/day (gestation - lactation periods). By comparison, estimated exposures in the general human population are in the range of < 1 ug/kg/day. 
Rats; Animals; Female; Pregnancy; Reproduction/*DRUG EFFECTS; Teratogens/*TOXICITY; Phthalic Acids/*TOXICITY; Body Weight/DRUG EFFECTS; Dose-Response Relationship, Drug; Abnormalities, Drug-Induced; Administration, Oral; Testis/ABNORMALITIES; Nipples/ABNORMALITIES; Fertility/DRUG EFFECTS; No-Observed-Adverse-Effect Level; Male; NO CAS RN