Solvent ototoxicity in the rat and guinea pig.
There is clear evidence that aromatic solvents can disrupt the auditory system in humans and animals. As far as animal models are concerned, solvent-induced hearing loss seems to be species-dependent. Indeed, most published data have been obtained with the rat, which shows mid-frequency cochlear deficits, whereas the guinea pig does not show any permanent hearing loss after solvent exposure. In the current investigation, the effects of two solvents, toluene (600 ppm) and styrene (1000 ppm), were studied in both Long-Evans rats and pigmented guinea pigs exposed 6 h/day for 5 consecutive days. Cochlear function was tested by using distortion product otoacoustic emissions (DPOAE) measured prior to the solvent exposure, 20 min after the end of the exposure and successively at 2 and 4 weeks post-exposure. In addition to cochlear testing, solvent concentrations in blood and urinary metabolites were measured. A cochlear histological analysis was performed at the end of the experiment. No decrease in DPOAE amplitude was observed in the guinea pig, even immediately following the end of exposure. The rat model showed severe disruption of auditory function and cochlear pathology, whereas the guinea pig had no disruption of DPOAE or cochlear pathological alterations. Therefore, the vulnerability of the cochlear function was strictly dependent on the species. As expected, an important difference in the styrene concentration in blood was observed: the solvent concentrations were fourfold higher in the rat than in the guinea pig. Therefore, it is clear that a pharmacokinetic or an uptake difference might explain the difference in susceptibility observed between the two species. Moreover, the metabolism pathways of the solvents were different depending on the species. Attempts to explain differences of vulnerability between the rat and guinea pig are addressed in the present paper.
Lataye
Robert
R
Institut National de Recherche et de Sécurité, Laboratoire de Neurotoxicité, Avenue de Bourgogne, PO Box 27, 54501 Vandoeuvre, France.
Campo
Pierre
P
Pouyatos
Benoît
B
Cossec
Benoît
B
Blachère
Véronique
V
Morel
Georges
G
D000818:Animals; D001299:Audiometry; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006038:Glyoxylates / Q000097:blood; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000503:physiopathology; D006626:Hippurates / Q000097:blood; D008297:Male; D008333:Mandelic Acids / Q000097:blood; D008854:Microscopy, Electron; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020058:Styrene / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D014050:Toluene / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*
D006038:Glyoxylates; D006626:Hippurates; D008333:Mandelic Acids; C012482:phenylglyoxylic acid; D014050:Toluene; D020058:Styrene; C037938:mandelic acid; C030514:hippuric acid