Kinetics of m-xylene in man: General features of absorption, distribution, biotransformation and excretion in repetitive inhalation exposure.

Sedentary volunteer subjects were exposed to an m-xylene concentration of about 3.9 mmol/m3 over five successive days, 6 h/d. It was noted that about 60% of the inhaled xylene was retained in the lungs. The estimated daily uptake of xylene was recovered nearly quantitatively as methylhippuric acid in the urine. Other pathways of xylene excretion played a minor role. The rate of 2,4-xylenol excretion shortly after a day's exposure was about 1-2% of that for methylhippuric acid excretion, and pulmonary excretion of unchanged xylene amounted to about 4% of the estimated uptake. In the blood, xylene was mainly associated with serum proteins, and only small amounts resided in the cells. Postexposure excretion of xylene in expired air and the urinary excretion of methylhippuric acid were initially rapid (elimination half-time about 1 h), and after an intermediate phase it attained, some 6-16 h after the exposure, a slow phase of elimination (half-time about 20 h). These observations are congruent with the concept that xylene is distributed to at least two main tissue compartments in the body. The slow elimination takes place from tissues with a high xylene solubility and a small perfusion, for example, adipose tissue; in this compartment cumulation of xylene occurs over repeated exposures. Under the conditions studied no signs of saturation of the metabolic pathways or renal excretion were noted.