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

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 15; no. 2; pp. 153 - 169
• Main Authors: Hushka, Leslie J., Waterman, Stacey J., Keller, Laura H., Trimmer, Gary W., Freeman, James J., Ambroso, Jeffrey L., Nicolich, Mark, McKee, Richard H.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-03-2001; Elsevier
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Body Weight - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Developmental landmarks; Di-isodecyl phthalate; DIDP; Diet; diisodecyl phthalate; Female; Fertility - drug effects; Kidney - drug effects; Kidney - pathology; Litter Size - drug effects; Liver - drug effects; Liver - pathology; Male; Maternal Exposure - adverse effects; Medical sciences; Multigeneration; No-Observed-Adverse-Effect Level; Offspring survival; Organ Size - drug effects; Paternal Exposure - adverse effects; Phthalic Acids - administration & dosage; Phthalic Acids - toxicity; Plasticizer; Plasticizers - administration & dosage; Plasticizers - toxicity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Reproduction; Reproduction - drug effects; Sexual Maturation - drug effects; Toxicology; Two-generation; Various organic compounds; DIDP; Reproduction; Plasticizer; Multigeneration; Di-isodecyl phthalate; Two-generation; Offspring survival; Developmental landmarks; Rat; Toxicity; Rodentia; Oral administration; Multigeneration study; Sterility; Vertebrata; Mammalia; Fertility; Animal; Development; Teratogen; Male genital diseases
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/S0890-6238(01)00109-5

Di-isodecyl phthalate (DIDP) is a commercial plasticizer with low toxicity in many animal studies. The effects of dietary DIDP administration on fertility and developmental parameters were assessed in Sprague-Dawley rats utilizing two generation reproductive toxicity studies generally consistent with current regulatory guidelines. Dietary levels ranged from 0.02 to 0.8% (or approximately 15 to 600 mg/kg/day). In the reproductive studies, there were no effects on fertility, but there were decreases in adult body weight along with corresponding increases in liver and kidney weights and histopathologic changes indicative of peroxisomal proliferation. There were no effects on live birth index, but reduced offspring survival was observed at postnatal days 1 to 4. This reduced survival was more pronounced in the F
2 generation in which statistical significance was achieved at levels of 0.2% DIDP and greater. There were also transient decreases in offspring body weights prior to weaning, corresponding to rapid offspring growth, and high levels of food consumption. There were no notable alterations in developmental landmarks. Overall, these studies provided experimentally defined No-Observed-Adverse-Effect Levels (NOAELs) of 0.06% (approximately 50 mg/kg/day) for F
2 offspring survival and 0.8% (approximately 600 mg/kg/day) for fertility, other measures of reproductive function, and developmental landmarks. Statistical 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 reduced F
2 offspring survival.