Ototoxicity in rats exposed to ortho-, meta- and para-xylene vapours for 13 weeks.
Male Sprague-Dawley rats were exposed to ortho-, meta- or para-xylene by inhalation (450, 900 and 1,800 p.p.m., 6 hr/day, 6 days/week for 13 weeks) and sacrificed for morphological investigations 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Among the three isomers studied, only para-xylene produced moderate to severe ototoxicity in rats exposed at 900 and 1,800 p.p.m. Increased auditory thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 1800 p.p.m. para-xylene. The auditory threshold shifts (35 to 38 dB) did not reverse after 8 weeks of recovery Moderate and severe losses of outer hair cells of the organ of Corti occurred in animals exposed to 900 and 1800 p.p.m. para-xylene respectively. Thus, the no observed effect level of para-xylene was 450 p.p.m. based on the loss of outer hair cells observed by light and electron microscopy.
Gagnaire
F
F
Department of Pollutants and Health, National Institute for Research and Safety, Vandoeuvre, France. gagnaire@inrs.fr
Marignac
B
B
Langlais
C
C
Bonnet
P
P
D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001299:Audiometry; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000187:drug effects*; D007536:Isomerism; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D014992:Xylenes / Q000008:administration & dosage / Q000633:toxicity*
D014992:Xylenes