Caractérisation de la toxicocinétique de l’octylphénol chez le rat en vue d’une meilleure analyse de risque toxicologique des perturbateurs endocriniens
p-tert-Octylphenol is a degradation product of alkylphenol ethoxylates that can be found in the environment. It has been reported to act as a weak estrogenic compound by binding to the estrogen receptor. This study was undertaken to 1) develop a sensitive method for the determination of octylphenol in blood and various tissues using gas chromatography coupled with detection by mass spectrometry, 2) characterize the blood and tissues toxicokinetics of octylphenol in male and female Sprague-Dawley rats and 3) develop a physiologically-based toxicokinetic model for octylphenol that can describe/predict unchanged blood and tissues octylphenol concentrations in rats. Male and female Sprague-Dawley rats were given a single dose of octylphenol either by oral gavage, intravenous injection or subcutaneous injection. In a repeated dosing experiment, rats were given octylphenol (oral) daily for 35 days (female) or 60 days (male). Blood and tissue samples were collected at various time following the onset of exposure and analyzed for octylphenol content using a method developed in our laboratory. These results showed that blood and tissues octylphenol concentrations were generally higher in female than male rats. Experiments done with rat liver microsomes confirmed that these differences were related to octylphenol metabolism. The results of the repeated exposure study indicate that there is no bioaccumulation of octylphenol at these exposure levels. A physiologically-based pharmacokinetic model for octylphenol was developed and validated using the data obtained in female and male rats. The model simulates adequately blood and tissues octylphenol concentrations following oral, intravenous or subcutaneous exposure. In conclusion, this study provided essential data on the toxicokinetics of octylphenol. These data are essential to predict the relationship between the internal and the external dose of octylphenol and will facilitate the risk assessment of octylphenol in humans.
Toxicology Endocrine disruptor p-tert-Octylphenol Analytical method Toxicokinetic Toxicokinetic modeling Sprague-Dawley rats