p-xylene

Specific investigations: other studies

Description of key information

Several repeated-dose ototoxicity studies in rats have been conducted with exposure via inhalation to individual xylene isomers or mixed xylenes .

These studies have demonstrated that ototoxicity occurs following exposure to p-xylene or mixed xylenes. The NOAEC for p-xylene (6 hours/day, 5 days/week for 13 weeks) is 450 ppm (1954 mg/m³). Human data provide limited evidence that xylenes may induce decrements in human hearing, although the underlying exposure assessment was weak (cumulative xylene exposure was based on a single determination of methyl hippuric acid coupled with self-reported duration of exposure) making it unclear if these changes were temporary or permanent.

Additional information

Several repeated-dose ototoxicity studies in rats have been conducted with exposure via inhalation to individual xylene isomers or mixed xylenes. These studies have demonstrated that ototoxicity occurs following exposure to p-xylene or mixed xylenes (Gagnaire et al, 2001, 2005; Maguinet al, 2006). Ototoxicity has been demonstrated using electrophysiological, behavioural and morphological techniques and is characterised by shifts in auditory thresholds and loss of outer hair cells in the cochlea. No evidence of recovery from such effects was seen following an 8 week recovery period and effects are considered to be permanent (Gagnaire et al, 2001). The NOAEC for p-xylene (6 hours/day, 5 days/week for 13 weeks) was shown to be 450 ppm (1954 mg/m³); the NOAEC for m-xylene and o-xylene was 1800 ppm (7817 mg/m³).

p-Xylene induced ototoxicity has been shown to occur within 3 weeks using inhalation exposures of 1800 ppm (6 hours/day, 5 days/week; Maguin et al, 2006).

The NOAEC for mixed xylenes is affected by the relative proportions of the constituents and, in particular the presence of ethylbenzene (a common impurity in mixed xylenes) (Gagnaire and Langlais, 2005). Brainstem auditory-evoked responses were recorded following 4, 8 and 13 wk of exposure to two samples of mixed xylenes and again after an 8 wk recovery period. Cytocochleograms (total hair cell counts) were made at the end of the recovery period. The results demonstrated an irreversible, functional loss of hearing (as assessed from auditory evoked response) in male rats with a NOAEC of 500 ppm for mixed xylene no. 1 and a NOAEC of 1000 ppm for mixed xylene no. 2. Microscopic examination of the organ of Corti and basilar membrane demonstrated clear reductions in hair cells with a LOAEC of 250 ppm and a NOAEC of 500 ppm for the two samples, respectively.

A study of auditory function in medical laboratory workers (15 males and 15 females) exposed to a mixture of xylene isomers (mean airborne concentration 36.5 mg/m³) while working in a histology laboratory was reported by Fuente et al. (2013). A group of 30 non-exposed workers (matched for gender, age, and educational level) served as controls. Neither group was exposed to noise levels above 85 dBA time-weighted average, The xylene-exposed participants showed significantly worse pure-tone thresholds in comparison with the non-exposed participants, and demonstrated significantly worse results for the pitch pattern sequence test, dichotic digit test, speech recognition in noise test, and auditory brainstem response. A significant correlation was reported between the concentrations of methyl hippuric acid in urine and binaural average hearing level (2 to 8kHz) in xylene-exposed workers. The authors identified several weakness in the study (noise and xylene exposure levels were measured in a cross-sectional manner; cumulative xylene exposure was based on a single determination of methyl hippuric acid coupled with self-reported duration of exposure; testing in the exposed group occurred only 16 hr after the last exposure). Overall the results provide limited evidence that xylenes may induce decrements in human hearing, and it was unclear if these changes were temporary or permanent.