Lloyd J. Sullivan

Metabolism of bisphenol A in the rat

Summary A study has been made of the metabolic fate of an orally administered dose of bisphenol A-C14 in the rat. Over an 8-day period, 28% of the C14 was excreted in the urine and 56% in the feces. No C14O2 could be detected in respiratory CO2, and at the end of 8 days no C14 residues could be detected in the carcass. Corollary information was obtained by gas chromatography and infrared spectroscopy. The metabolic products appearing in the urine were examined by ion exchange and gas chromatography. The results show that bisphenol A is primarily excreted as the glucuronide. Less than 1% of the material present in urine was free bisphenol A. No evidence was found for the existence of ethereal sulfates. The metabolites appearing in the feces were extracted and examined by gas chromatography. Some 35% of this material was identified as free bisphenol A, while an additional 35% was identified as a hydroxylated product of bisphenol A. The remaining 30% could not be chromatographed and was probably present as a conjugate. Comparison of these results with literature studies on other diphenols are in agreement that these compounds are excreted as glucuronides, not as ethereal sulfates.

Excretion of certain polyethylene glycol ether adducts of nonylphenol by the rat.

A nonylphenol polyethylene glycol ether (Tergitol TP-9) containing an average of 9 moles of ethylene oxide per mole of nonylphenol was separately labeled with ethylene-1,2-14C oxide and nonylphenol-14C (uniformly labeled aromatic ring) and chracterized on thin-layer chromatoplates. In 7 days, the rat excreted 39% of an oral dose (67 mg/kg) of ethylene oxide-labeled TP-9 in urine, 52% in feces, and 1.2% as 14CO2, while over the same time interval the rat excreted 20% of the nonylphenol-labeled TP-9 in urine, 78% in feces, and none as 14CO2. Nonylphenol-14C per se was found to be excreted in a similar manner. The 7-, 10-, 12-, and 15-mole adducts of nonylphenol were isolated by column chromatography from ethylene oxidelabeled TP-9 and administered individually to rats. The 12- and 15-mole adducts were excreted to a greater extent in the feces than were the 7- and 10-mole adducts, while the reverse situation occurred in urine. Free TP-9 per se was found in urine to the extent of 1.0% of the dose. The 14- and 15-mole adducts were present in the highest concentration. Ion exchange chromatographic studies of the urinary metabolites of ethylene-14C oxide TP-9 and nonylphenol-14C TP-9 indicate that the principal metabolites of TP-9 are the mono- and dicarboxylic acids of polyethylene glycol and the glucuronic acid conjugates of nonylphenol.

Metabolism of 2-ethylhexyl sulfate by the rat and rabbit

Abstract A study has been made of the metabolic fate of an orally administered dose of C 14 - or S 35 -labeled 2-ethylhexyl sulfate in the rat. In 4 days the rat excreted 77.5% of the C 14 -labeled compound in urine, 6.6% in feces, and 7.1% as respiratory CO 2 . In the case of the S 35 -labeled compound, 80.4% of the S 35 was excreted in the urine and 2.4% in the feces over 3 days. No C 14 or S 35 residues (less than 0.1% of dose) could be detected in animal carcasses after 4 days. The urinary metabolites of 2-ethylhexyl-C 14 sulfate in the rat were identified as 2-ethylhexyl sulfate (60%) and 2-ethyl 2,3-dihydroxyhexanoic acid (30%). Small quantities of 2-ethylhexanol (1%) and 2-ethylhexanoyl glucuronide (5%) were also present. Evidence for the loss of inorganic sulfate-S 35 was obtained with 2-ethylhexyl sulfate-S 35 . Separation and partial identification of metabolites was achieved by ion exchange and gas chromatography, while studies involving infrared and nuclear magnetic resonance spectroscopy aided in the identification. Identical products were obtained with the rabbit.

Metabolism of Carbaryl by Kidney, Liver, and Lung from Human Postembryonic Fetal Autopsy Tissue

Metabolic profiles of carbaryl in human postembryonic fetal autopsy tissue were determined using an in vitro tissue-maintenance technique. 1-Naphthyl-14C or N-methyl-14C-carbaryl was applied to growth medium containing explants of the tissue. Each mixture was incubated for 18 hr and the medium analyzed by DEAE-cellulose column chromatography. Fetal liver performed the metabolic processes of demethylation, hydrolysis, hydroxylation, and oxidation, followed by conjugation, as was found with adult liver. However, the anionics from fetal liver amounts to 20% of those found with adult liver. The kidney made naphthyl glucuronide and naphthyl sulfate, whereas the lung produced naphthyl sulfate from carbaryl. The metabolic activities of the fetal kidney and lung were close to the corresponding human adult tissues based upon the anionic metabolites found and the amount of unmetabolized carbaryl in the medium after 18 hr of incubation. Silica gel chromatography of ether-extractable neutral fractions from DEAE-cellulose revealed 3,4, and 9 ether-extractable metabolites from lung, kidney, and liver, respectively. The present study shows that the in vitro technique is capable of semiquantitatively demonstrating the metabolic activities of specific organs from the human fetus.