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Volunteer subjects were exposed to m-xylene 6 h/d over five successive days under the following types of environmental conditions: exposure type I: constant xylene concentration in air, subjects performed periodic ergometer exercise at 100 W; exposure type II: varying xylene concentration in air with peak levels coinciding with periodic ergometer exercise; and exposure type III: constant xylene concentration in air, subjects sedentary. The three types of exposure were identical in that the time-weighted averages of the xylene concentrations in the air inhaled over the whole day were about the same (in most cases 4.1 mmol/m3). Nevertheless, the daily xylene uptakes proved to be somewhat different, while the maximum rates of xylene uptake occurring in the three exposure types were markedly different. In exposure types I and II the main part of the day's xylene uptake took place during the repeated short exercise sessions and resulted, partly due to an altered distribution of organ blood flow, in a greater distribution of xylene to tissues with slow elimination characteristics (and a greater cumulation of xylene) than in exposure type III. Although relatively high pulmonary uptake rates of xylene (about 150-300 micromol/min) were estimated to have occurred over 15-min periods at a time, no signs of saturation kinetics were noted. The relative contributions of the two biotransformation pathways of m-xylene (side-chain oxidation and aromatic oxidation) were not markedly altered by the different environmental conditions, but aromatic oxidation, producing 2,4-xylenol, tended to increase slightly over the five exposure days. The blood xylene levels attained under stable near-equilibrium conditions and under conditions of greatly increased uptake appeared to be directly related to the rate of xylene uptake, whereas no such relation existed in the phase of decreasing xylene uptake.

Occupational xylene exposure in the breathing zone of 15 painters was measured during three consecutive workdays. The applicability of the use of different biological samples was tested by the monitoring of xylene concentrations in blood and exhaled air, and urinary methylhippuric acid excretion as well. The best relation to the time-weighted average of xylene exposure was obtained for urinary methylhippuric acid concentration at the end of the workday; an amount of 665 mg/g of creatinine corresponded to 50 ppm of xylene. The amount of methylhippuric acid in a morning sample at the end of the work week, on the other hand, correlated to the mean exposure of the three preceding days. Xylene concentrations in exhaled air and blood sampled after the workday correlated poorly to the exposure of the preceding day. The urinary elimination of methylhippuric acid after the finished work week showed two distinct phases of excretion, with different biological half-times (1.9-5.3 h for the first 10 h after exposure and 16.5-48.4 h for the next two days).

Gas chromatographic methods have been developed for the urinalysis of metabolic products of ethylbenzene. "Minor" metabolites were emphasized in this process. The methods were worked out so that simultaneous determination of several compounds could be achieved with one method. On the whole, four assays are described, which together allow 12 different compounds to be measured. Since one of the methods presented can be applied to determine "minor" metabolites of xylene as well, methodological data for these are also reported. The methods described have successfully been used in metabolic studies of ethylbenzene in rat and man.