||Effect of Dose on Di-Isodecyl Phthalate Disposition in Rats with Cover Letter.
||General Motors Corp., Warren, MI.;Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
||18 Aug 1983
Organ tissues ;
Gastrointestinal tract ;
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||Di-isodecyl phthalate (DIDP) is a plasticizer used extensively in polyvinyl chloride materials. Being low in acute toxicity, DIDP is many times administered at extremely high doses to produce the documented end-point effects. Dose-related alterations in disposition were therefore investigated as a potential mechanism contributing to the reported exposure effects. Dawley rats were administered (carboxyl-1 C) DIDP perorally in corn oil at 0.1, 11.2 and 1000 mg/Kg. At each treatment level, 99% of administered 14 C was recovered in excreta within 72 hr. The percent of total administered 14 C recovered in feces increased with increasing dose (3, 66, and 82%) and in extracts analyzed by HPLC, 30% of 14 C at the low dose and 60% at the high dose were identified as DIDP, the remainder as metabolites. Excretion in urine was biphasic and there was not an apparent dose effect on the rates of elimination. Metabolites in urine included phthalic acid (PA) and a group of mono-isodecyl phthalate derivatives. The proportions of PA in urine were 38 and 40% after 0.1 and 11.2 mg/Kg respectively and decreased to 18% after 1000 mg/Kg. In major organ tissues, the percent of the dose retained after 72 hr was not dose dependent. Therefore, gastrointestinal absorption is limited with increasing dose and distribution to tissue is proportional. There is evidence suggesting partial saturation or inhibition of Metabolism but it was not an apparent factor in clearance capacity.
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