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Toxicokinetics of p-tert-octylphenol in male and female Sprague-Dawley rats after intravenous, oral, or subcutaneous exposures. 2009

G Hamelin, and G Charest-Tardif, and K Krishnan, and D Cyr, and M Charbonneau, and P J Devine, and S Haddad, and G M Cooke, and T Schrader, and R Tardif
Departement de Sante Environnementale et Sante au Travail, Universite de Montreal, Montreal, Quebec.

This study was undertaken to characterize the toxicokinetics of p-tert-octylphenol (OP), a weak estrogenic compound, in male and female rats. Male and female Sprague-Dawley rats were given a single dose of OP either by oral gavage (50, 125 or 250 mg/kg), by intravenous (iv) injection (2, 4, or 8 mg/kg), or by subcutaneous (sc) injection (125 mg/kg). In a repeated dosing experiment, rats were given OP (oral) daily (25, 50, or 125 mg/kg) for 35 d (female) or 60 d (male). Blood and tissue samples were collected and analyzed for OP content using gas chromatography with detection by mass spectrometry. Blood OP concentrations were generally higher in female than male rats following a single oral or sc administration but were similar following a single iv injection. Tissue OP concentrations were also higher in female than male rats following oral exposure, consistent with the faster metabolism of OP observed in male rat liver microsomes. After subchronic administration, blood OP concentrations were higher at the end of exposure for female (33 d) (2.26-fold, not significant) and male (57 d) (3.47-fold) rats than single dosing but there was no change in the tissue OP concentrations. Gender differences in tissue OP concentrations may contribute, in part, to gender differences in the toxicity of OP in rats. The fact that OP was found in all reproductive tissues confirms its potential for direct endocrine-like effects.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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