Toxicokinetics of p-tert-octylphenol in male and female Sprague-Dawley rats after intravenous, oral, or subcutaneous exposures.
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.
Hamelin
G
G
Departement de Sante Environnementale et Sante au Travail, Universite de Montreal, Montreal, Quebec.
Charest-Tardif
G
G
Krishnan
K
K
Cyr
D
D
Charbonneau
M
M
Devine
P J
PJ
Haddad
S
S
Cooke
G M
GM
Schrader
T
T
Tardif
R
R
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013501:Surface-Active Agents / Q000493:pharmacokinetics* / Q000633:toxicity*
D010636:Phenols; D013501:Surface-Active Agents; C105260:4-tert-octylphenol