The absorption, metabolism, and excretion of xylenes in man

Summary

Fifteen exposure experiments were carried out, in which four persons each, were simultaneously exposed to a defined concentration of o-, m-, and p-xylene vapors and also to their mixture at a ratio of 1:1:1. The concentrations were in all cases around 0.2 mg/l (Czechoslovakian MAC) or around double the amount. The period of exposure amounted to exactly 8 h.

It was ascertained that the pulmonary retention is practically identical in all persons and in all isomers and amounts to 63.6 ± 4.2%. Its extent does not depend upon inoculation level, nor upon the duration of the exposure. During the period of desaturation the lungs excrete approximately 5% of the total amount retained in the organism. Xylene excretion via urine is quite negligible and amounts to a thousandth of 1%.

The chief metabolites are toluic acids which are excreted in conjugated form with glycine as so-called toluric (=methylhippuric) acids. Free toluic acids, toluylglucuronic acids, and hydroxytoluic acids do not occur in the urine of persons exposed to a reasonable concentration of xylene vapors.

The excreted amounts of toluric acids reach a maximum in the portion of urine collected at the end of exposure; then they decrease rapidly, but trace amounts can be still observed even after 4–5 days. The excretion takes a similar course in different persons and at different intensity of exposure. During the last 2 h of exposure a mean of 23.6% is excreted and in 8 h of exposure 71.7% of the amount excreted within 24 h.

The side metabolites of xylenes are compounds hydroxylated on the aromatic nucleus. After exposure to o-xylene the presence of 2.3- and 3.4-xylenol was observed in urine; after exposure to m-xylene the presence of 2.4 xylenol, and finally after exposure to p-xylene the presence of 2.5-xylenol. The excretion of xylenols reaches a maximum as a rule just after termination of exposure.

It was proved by balance calculation that of the total amount of xylene retained in the organism during exposure, more than 95% is excreted in the form of toluric acid (o-97.1; m-99.2; p-95.1%) and only a small part in form of xylenol (o-0.86; m-1.98; p-0.05%).