Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene Natalie L.M. Cappaert a,b, * , Sjaak F.L. Klis a , Hans Muijser b , Beverly M. Kulig b , Luco C. Ravensberg b , Guido F. Smoorenburg a a Hearing Research Laboratories, Room G.02.531, University Medical Center, Heidelberglaan 100, NL-3584 CX, Utrecht, The Netherlands b TNO Food and Nutrition Research, Utrechtseweg 48, NL-3704 HE, Zeist, The Netherlands Received 25 September 2000; accepted 31 January 2002 Abstract The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2 ± 0.8-mg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8 ± 0.1 mg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Guinea pig; Rat; Ethyl benzene; Outer hair cell; Ototoxicity; Electrocochleography 1. Introduction Some organic solvents are known to affect the auditory system in mammals. Several studies reported that humans who were occupationally exposed to organic solvents like toluene [15], styrene [14,17] and trichloroethylene [16] can develop hearing deficits. Animal experiments have con- firmed that several organic solvents do affect the auditory system and have shown that the auditory periphery is the main target for these solvents. Rats exposed to toluene [3,20], styrene [3,21], trichloroethylene [3,9] or xylene [3,21] showed hearing loss predominantly in the mid- frequency region, which is from 8 to 20 kHz in the rat. However, organic solvent ototoxicity seems to be species dependent. Guinea pigs did not show any ototoxic effects or only mild acute effects as a result of exposure to solvents known to be ototoxic in rats. To our knowledge, five ototoxicity studies with organic solvents were performed on guinea pigs. The first organic solvent study with this species was published in 1983 [24]. Four groups of albino guinea pigs were exposed to 0, 6000, 12,000 and 17,000 ppm of trichloroethylene, 4 h/day for 5 days. The compound action potential (CAP) in response to a 7-kHz tone and the cochlear microphonics (CM) at 4 kHz were recorded. Neither potential differed significantly between the control group and all three exposed groups. Pregnant guinea pigs were exposed to toluene [19]. During the exposure period, the toluene concentration was increased from 500 to 2000 ppm. Hearing impairment in either mothers or their offspring was not observed. Subsequently, the male offspring was exposed to further increasing toluene vapor concentra- tions (2000–4000 ppm over a 21-day period). Again, no hearing loss was detected 1 – 2 days after the exposure. In an acute study [7], pigmented guinea pigs were exposed to 500 or 1200 ppm of styrene for 7 h. The CAP and CM in response to tone bursts from 2 to 40 kHz were assessed 18–22 h after the end of the exposure. No differences were 0892-0362/02/$ – see front matter D 2002 Elsevier Science Inc. All rights reserved. PII:S0892-0362(02)00208-8 * Corresponding author. Hearing Research Laboratories, Room G.02.531, University Medical Center, Heidelberglaan 100, NL-3584 CX Utrecht, The Netherlands. Tel.: +31-30-2507564; fax: +31-30-2541922. E-mail address: n.l.m.cappaert@kmb.azu.nl (N.L.M. Cappaert). www.elsevier.com/locate/neutera Neurotoxicology and Teratology 24 (2002) 503 – 510