Studies by the National Toxicology Program on di(2-ethylhexyl)phthalate

Area of Science:

• Toxicology
• Environmental Health
• Carcinogenesis

Background:

• The plasticizer di(2-ethylhexyl)phthalate (DEHP) is a widespread environmental contaminant.
• Previous studies by the National Toxicology Program (NTP) indicated DEHP induces hepatocellular neoplasms in rats and mice.

Purpose of the Study:

• To investigate the genotoxicity, dermal absorption, reproductive and developmental toxicity, and biochemical mechanisms of DEHP.
• To assess the role of peroxisome proliferation in DEHP-induced hepatocarcinogenesis.

Main Methods:

• Genotoxicity assays (bacterial mutagenicity, mouse lymphoma assay, chromosomal aberration, sister chromatid exchange).
• Dermal absorption study in rats.
• Reproductive and developmental toxicity studies in mice and rats.
• Biochemical analysis of hydrogen peroxide (H2O2) production and degradation in rat liver homogenates.

Main Results:

• DEHP was not mutagenic or clastogenic but caused a marginal increase in sister chromatid exchanges in CHO cells.
• DEHP showed poor dermal absorption in rats.
• DEHP was a reproductive toxicant in mice and caused developmental toxicity in mice at low doses, but not in rats.
• Increased H2O2 levels in rat liver homogenates correlated with DEHP's carcinogenic potential, suggesting peroxisome proliferation involvement.

Conclusions:

• DEHP is not genotoxic but exhibits reproductive and developmental toxicity in mice.
• Peroxisome proliferation may play a role in DEHP-induced liver cancer.
• Species-specific differences in toxicity and mechanism warrant further investigation.