Two-generation reproduction studies in rats fed di-isodecyl phthalate

Di-isodecyl phthalate (DIDP) is a commercial plasticizer with low toxicity in many animal studies. The effects of dietary DIDP administration on ferti lity and developmental parameters were assessed in Sprague-Dawley rats util izing two generation reproductive toxicity studies generally consistent wit h current regulatory guidelines. Dietary levels ranged from 0.02 to 0.8% (o r approximately 15 to 600 mg/kg/day). In the reproductive studies, there we re no effects on fertility, but there were decreases in adult body weight a long with corresponding increases in liver and kidney weights and histopath ologic changes indicative of peroxisomal proliferation. There were no effec ts on live birth index, but reduced offspring survival was observed at post natal days 1 to 4. This reduced survival was more pronounced in the F-2 gen eration in which statistical significance was achieved at levels of 0.2% DI DP and greater. There were also transient decreases in offspring body weigh ts prior to weaning, corresponding to rapid offspring growth, and high leve ls of food consumption. There were no notable alterations in developmental landmarks. Overall, these studies provided experimentally defined No-Observ ed-Adverse-Effect Levels (NOAELs) of 0.06% (approximately 50 mg/kg/day) for F, offspring survival and 0.8% (approximately 600 mg/kg/day) for fertility , other measures of reproductive function, and developmental landmarks. Sta tistical evaluation of the data from both studies identified 108 mg/kg/day with a 95% lower bound value of 86 mg/kg/day as a theoretical NOAEL for red uced F-2 offspring survival. (C) 2001 Elsevier Science Inc. All rights rese rved.