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1. To examine the bioequivalence of an isotope-labelled tracer to study toxicant disposition, we conducted 33 controlled human exposures to a mixture of 50 ppm 1H8-toluene and 50 ppm 2H8-toluene for 2 h, and measured concentrations in blood and breath, and metabolite levels in urine for 100 h post-exposure. 2. A physiologically based kinetic (PBK) model found that compared with 1H8-toluene, 2H8-toluene had a 6.4+/-13% (mean+/-SD) lower AUC, a 6.5+/-13% higher systemic clearance (1.46+/-0.27 versus 1.38+/-0.25 l/h-kg), a 17+/-22% larger terminal volume of distribution (66.4+/-14 versus 57.2+/-10 l/kg) and a 9.7+/-26% longer terminal half-life (38+/-12 versus 34+/-10 h) (p < 0.05 for all comparisons). 3. The higher 2H8-toluene clearance may have been due to an increased rate of ring oxidation, consistent with the 17% higher observed fraction of 2H5- versus 1H5-cresol metabolites in urine. 4. The larger terminal volume and half-lives for 2H8-toluene suggested a higher adipose tissue/blood partition coefficient. 5. Observed isotope differences were small compared with interindividual differences in 1H8-toluene kinetics from previous studies. 6. The PBK model allowed us to ascribe observed isotope differences in solvent toxicokinetics to underlying physiologic mechanisms.

1. The rate of conjugation of benzoic acid with glycine was measured in the homogenates of 110 specimens of human liver and in 67 specimens of human renal cortex. 2. The assay for the formation of benzoyl glycine consisted of measuring the formation of benzoyl glycine from (14C) benzoic acid and glycine in the presence of coenzyme A and ATP. 3. In human liver, the mean (+/- SD) and coefficient of variation for the formation rate of benzoyl glycine were 254 +/- 90.5 nmol min-1 per g liver and 36%, respectively. There was a weak, but significant, negative correlation (r = -0.339, p < 0.001) between the rate of formation of benzoyl glycine and the liver donor's age. 4. In the human kidney, the rate of benzoyl glycine formation was normally distributed. The mean (+/- SD) and coefficient of variation were 321 +/- 99.3 nmol min-1 per g kidney and 31%, respectively. 5. These in vitro results are consistent with the view that the in vivo rate of conjugation of carboxylic acid with glycine varies among subjects and is normally distributed.

1. A rapid and sensitive semi-micro method for the determination of hippuric acid formation by tissue samples in vitro is described and applied to the determination of the post-mortem survival of hippuric acid formation in rat and human cadaver tissue samples. 2. Hippuric acid formation survived in rat and human cadaver liver for at least 72 h when corpses were stored at 4 degrees. 3. Hippuric acid formation was detected in human cadaver liver and kidney samples and was absent from brain, intestine, heart and lung. 4. Post-mortem liver samples from a case of acute pancreatitis failed to form hippuric acid as did kidney samples from a case of systemic lupus erythematosus with renal involvement.

1. 4-Nitrobenzoic acid was metabolized by the marmoset to amino derivatives to the extent of 18.8% (p.o.) and 11.4% (i.p.) of the dose. 2 Reduction of 4-nitrobenzoic acid was significantly decreased by antibiotic pretreatment; the mean decrease in reduction was 81% for animals doses orally and 73% for intraperitoneally dosed marmosets. 3. 4-Nitrohippuric acid was the major metabolite of 4-nitrobenzoic acid, accounting for 30.6% and 49.6% of p.o. and i.p. doses respectively. 4. Antibiotic pretreatment affected the marmosets' normal capacity to reduce 4-nitrobenzoic acid for many weeks after the initial administration. 5. Maximum radioactivity in the blood, after an oral dose, was reached in 30-40 min; the average half-life for the elimination of 4-nitro[carboxy-14C]benzoic acid and its metabolites was 30.4 +/- 3 min after an intramuscular dose. 6. Radioactivity of 4-nitro[carboxy-14C]benzoic acid representing 3.4% of the dose was excreted in rat bile in 24 h.

The urinary metabolites of a single dose (1 g) of salicylic acid were investigated in black Nigerian subjects (78 females 44 males). Qualitatively, the major metabolites were the glycine and glucuronic acid conjugates. Quantitatively, there was a statistically significant difference in the level of these metabolites between female and male subjects (P less than 0.001) (using Student's t-test). The results of the present study compared with earlier published data show a statistically significant quantitative difference between black Nigerians and Caucasians (P less than 0.001). The results suggest possible racial and sex differences in the metabolism of salicylic acid.