The systemic toxic effects of di-isononyl phthalate (DINP) were evaluated in a 4-wk study in male Sprague-Dawley rats. The animals were administered DINP intravenously at dosages of 125, 250, and 500 mg/kg every other day for 4 wk. The control and the positive control group were administered vehicle (egg yolk phosphatides plus glycerol solutions) and 500 mg/kg di(2-ethylhexyl) phthalate (DEHP), respectively. Clinical signs were observed immediately after administration and consumption of food, and mean body weight was recorded once a week for 4 wk. The absolute and relative organ weights, hematology, clinical chemistry, and pathological changes were evaluated at the end of the study.
No adverse effects nor death were observed in any animal in the DINP-treated groups. Food consumption, mean body weight, and absolute and relative organ weights of DINP-treated rats were not significantly different from those of the control group. Hematological parameters (LYMPH%, NEU%, and NEU#) in the 500 mg/kg DINP-treated group increased significantly, whereas no treatment-related changes in clinical chemistry parameters were observed in any DINP-treated animals. Lesions were observed in the liver and testis of rats treated with 500 mg/kg. In this 4-wk study, the no observed adverse effect level (NOAEL) of DINP was 250 mg/kg, based on the pathological changes in the liver and testis and the significant changes in hematology observed in the 500 mg/kg DINP-treated group.
Treatment related abnormalities, consisting of obvious pathological changes in the liver, kidney and testis, increases in hematological parameters, and increases in clinical chemistry parameters, were observed in the 500 mg/kg DEHP-treated group, which served as the positive control.