m-xylene

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

experimental study

Adequacy of study:

supporting study

Applicant's summary and conclusion

Conclusions:

In a group of four human subjects, upon whom repeat exposure experiments with individual xylene isomers or a mixture were performed, urinary excretion was a major and rapid route. The main metabolites for all xylene isomers were toluric acids conjugated to glycine, excreted rapidly via the urine. Subsidiary metabolites were hydroxylated aromatic derivatives - xylenols; these constututed <2% of the total amount excreted for all isomers. 72% of the total amount retained in the body was excreted within 24hr of exposure. Around 5% was excreted from the lungs in exhaled breath.

Executive summary:

For each of o-, m- or p-xylene or a 1:1:1 mixture of all three, four human subjects were exposed to a defined vapour concentration. Concentrations were approx. either 0.2 mg/L or 0.4 mg/L. In total, 15 exposure experiments were carried out for an exposure period of 8hrs. 

Pulmonary retention was similar in all subjects and for all isomers (average 63.6 ± 4.2%) independent of exposure level and duration. At the end of the exposure, 5% of the total amount retained in the body was extracted from the lungs, of which the portion making it to the urine was <0.001%.

The main metabolites were toluic acids, excreted conjugated to glycine as methyl hippuric (toluric) acids. Free toluic acids, hydroxylated or glucuronidated acids are not generally present in the urine of subjects exposed to xylene vapours.

 

Urinary excretion was rapid. Excreted toluric acids reached a peak concentration in urine collected at the end of exposure, then decreased rapidly; however trace amounts were still detected after 4-5 days.

Excretion was similar between subjects and exposure levels. During the last 2 hr exposure, mean 23.6% was excreted and across the 8hr of exposure ad the period following, 71.7% of the total amount was excreted within 24hr.

Subsidiary xylene metabolites were those hydroxylated on the aromatic nucleus group. 

Exposure to o-xylene resulted in the appearance of 2,3- and 3,4- xylenol in the urine; m-xylene in the presence of 2,4-xylenol, and p-xylene the appearance of 2,5-xylenol. Xylenols were also excreted in a peak just after the end of the 8hr exposure.

Balance calculations showed that of the total amount of xylene retained in the human subjects, an average of 95% is excreted as toluric acid (o-xylene 97.1%; m-xylene 99.2%; p-xylene 95.1%)and <2% in the form of xylenols (O-xylene 0.86%; m-xylene 1.98%; p-xylene 0.05%).