CHRONIC TOXICITY AND CARCINOGENIC EVALUATION OF DIISONONYL PHTHALATE IN RATS

Groups of 110 Fischer 344 rats/sex were fed diisononyl phthalate (DINP ) at dietary levels of 0, 0.03, 0.3, and 0.6 wt% for periods up to 2 y ears. Interim sacrifices of 10 predesignated rats/sex/dose were at 6, 12, and 18 months with surviving animals sacrificed at 24 months. At s tudy termination, survival was in excess of 60% for every group. At th e mid or high dose, the following biological effects were noted: sligh t decreases in food consumption and body weight; slight increase in mo rtality; a dose-related increase in relative organ weights of liver an d kidney; and some slight effects on urinalysis, hematologic, and clin ical chemistry parameters. No peroxisome induction was observed in liv ers of treated rats compared with controls. No clear treatment-related nonneoplastic or neoplastic lesions were found. However, mononuclear cell leukemia (MNCL) and changes known to be associated with an increa sed incidence of MNCL were seen in the mid-dose and high-dose groups. A literature review suggests that MNCL is a common finding in aging F3 44 rats and that this increased incidence in rats treated with DINE is not relevant to man. A clear no-observed-effect level was demonstrate d for all biological end points at a dietary level of 0.03 wt% or appr oximately 17 mg/kg/day of (C) 1997 Society of Toxicology.