Reference

Absorption, bioavailability, and metabolism of para-nonylphenol in the rat

Absorption, bioavailability, and metabolism of para-nonylphenol in the rat. Green, Trevor; Swain, Cindy; Van Miller, John P.; Joiner, Ronald L. ( Syngenta Central Toxicology Laboratory, Macclesfield SK10 4TJ, UK). Regulatory Toxicology and Pharmacology, 38(1), 43-51 (English) 2003 Elsevier Science. CODEN: RTOPDW. ISSN: 0273-2300. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) To better interpret the responses to para-nonylphenol (NP; CASRN84852-15-3) in in vivo toxicity studies, including estrogen-like activity, the bioavailability of 14C-radiolabeled NP has been detd. in male and female CD rats following either single oral doses of 10 and 100 mg/kg, single i.v. doses of 10 mg/kg, or repeated daily oral doses of 10 mg/kg for up to 14 d. Up to 80% of an oral dose of NP was rapidly absorbed, the remainder being excreted unchanged in feces. Excretion was largely complete within 24 h of dosing. Following absorption, NP was metabolized in the liver, with the majority of the metabolites excreted in bile, mainly as glucuronide conjugates. Unchanged NP was found only in bile and urine from female rats given a 100 mg/kg dose, indicating that metabolic satn. occurred. Following repeated dosing, steady state was reached within 7 d. There was no evidence of significant accumulation into tissue compartments nor of a significant change in clearance or the metabolite profiles in urine. These data suggest that the estrogen-like effects obsd. in toxicity studies with female rats at oral NP doses of approx. 50 mg/kg/d and greater are a result of the increased bioavailability of NP which occurs following metabolic satn.