The prevalence of hearing loss ≥ 25 dB was much greater in the toluene plus noise group (86.2%) than in the noise-only (44.8%) and administrative (5.0%) groups in model 1, when 0.5 kHz was included in the measure- ment (p < 0.001) (Table 2). The prevalence rate dropped approximately 20% for the toluene plus noise group when 0.5 kHz was excluded (model 2), but the difference in prevalence of hearing loss at ≥ 25 dB between these two groups remained large (67.2% vs. 32.8%, p < 0.001). Compared with the administrative clerks, the age-adjusted OR for hearing loss at ≥ 25 dB for all toluene plus noise–exposed workers was 7.7 and 4.2 times greater than that for the noise-only group in models 1 and 2, respectively. The OR of hear- ing loss at ≥ 25 dB among workers exposed to toluene plus noise increased as the toluene and noise level increased in model 1; however, the relationship was reversed in model 2. When we calculated the mean hearing thresholds at the measured pure-tone frequen- cies for each group, results showed a reversed J-shape with a turning point at the frequency of 2 kHz (Figure 1). Poorer hearing thresholds were observed at both low and high frequen- cies in the exposure groups, with the poorest at 4 and 6 kHz in both the toluene plus noise group and the noise-only group. The mean thresholds at higher frequencies were similar between the subgroup of toluene plus ≥ 85 dB and the noise-only group. The effects at 3 and 4 kHz were less for the subgroup of toluene plus < 85 dB. However, as for the 1 kHz fre- quency, workers in the toluene plus noise group had poorer thresholds than did those exposed to noise only. Figure 2 shows the prevalence rates of hearing loss with the inclusion of 0.5 kHz (model 1) and with the toluene plus noise group being stratiﬁed into quintile groups by 1 2 Frequency (kHz) 3 4 6 Administrative Noise-only exposure Toluene + < 85 dB Toluene + ≥ 85 dB 0 10 ) L H20 B d ( d l o h rse30 h T 40 50 Figure 1. Group mean hearing thresholds [decibel hearing level (dBHL)] at frequencies between 1 and 6 kHz for administrative, noise-only, and toluene plus noise groups. Environmental Health Perspectives • VOLUME 114 | NUMBER 8 | August 2006 the CEI of toluene. Hearing loss at 25–39 dB was most prevalent for the toluene plus noise group, with a peak prevalence at the CEI of 176–430 year-ppm toluene. The average hearing loss increased to a peak of 32.6 dB for those with exposures of 1,521–2,265 year- ppm toluene. After controlling for age, smoking tobacco, drinking alcohol, and hearing protector use, the multivariate logistic regression analysis demonstrated an overall OR of 140 (95% CI, 32.1–608) for hearing loss in workers exposed to both toluene and noise in model 1 (0.5 kHz included) (Table 3). This analysis stratified the toluene plus noise group into four levels using the CEI of toluene. The hearing loss prevalence was 100% for workers with the CEI exposure of 201–530 year-ppm: the ORs showed a V-shape with an extreme risk at this toluene exposure level. The overall Toluene and hearing loss estimated risk for hearing loss dropped greatly to an OR of 29.1 (95% CI, 9.3–91.4) when 0.5 kHz was not used in the risk measure (model 2). The risk of hearing loss remained at a peak value at the exposure of 200–530 year-ppm but was much smaller (OR = 55.6; 95% CI, 9.7–317). Discussion Previous human studies on the ototoxic effect of toluene from occupational exposure are not conclusive. Since the ototraumatic interaction between solvent and noise exposure was sug- gested by Barregard and Axelsson (1984), the effects have been assumed to be dependent on the exposure dose and period. A series of ani- mal studies have demonstrated clear evidence of ototoxic effects with a very high level of toluene exposure over a short period of time (Johnson et al. 1990; Lataye and Campo < 25 dB 25–39 dB 40–54 dB ≥ 55dB Mean ± SD 45 40 35 30 25 20 15 10 5 0 ) B d ( s s o l g n i r a e H nb 5 19 39 9 9 11 10 18 38 7 24 36 3 32 24 7 8 55 Model 2a OR (95% CI) 1.0 5.0 (1.7–15.1) 29.1 (9.3–91.4) 48.0 (9.2–252) 55.6 (9.7–317) 30.4 (6.3–146) 14.3 (3.5–58.3) 1.0 2.4 (0.9–6.2) 2.4 (0.5–11.1) 1.0 0.5 (0.2–1.2) 1.4 (0.3–7.3) 1.0 1.4 (0.6–3.2) 1.1 (0.3–3.4) 1.0 0.7 (0.2–2.6) 1285 100 s90 s lo80 g in70 r a e60 h ith50 w t 40 n e rc30 e P20 10 0 Administrative Noise only < 175 176–430 431–1,520 1,521–2,265 ≥ 2,266 Figure 2. Comparison of hearing loss among the administrative, noise-only, and toluene plus noise groups by exposure and toluene CEI using model 1. Table 3. Multivariate logistic regression analyses showing ORs (95% CIs) of hearing loss of ≥ 25 dB for toluene plus noise and noise-only groups. Variable Administrative Noise-only Toluene by CEI (year-ppm) < 200 200–530 531–2,000 ≥ 2,001 Age (years) < 40 40–49 ≥ 50 Smoking tobacco No Yes Quit Drinking alcohol No Yes Quit Use hearing protection Yes No Sample size 60 58 58 13 12 15 18 62 99 15 57 110 9 86 69 21 15 161 nb 3 26 50 10 12 13 15 25 46 8 27 49 3 40 26 13 12 67 aPure tone of 0.5 kHz was excluded. bNumber of persons with hearing loss ≥ 25 dB. Toluene CEI (year-ppm) Model 1 OR (95% CI) 1.0 12.8 (3.4–47.6) 140 (32.1–608) 104 (15.2–713) > 1,080 (313 to > 9,999) 102 (14.2–739) 92.8 (15.1–572) 1.0 2.2 (0.8–6.1) 1.3 (0.2–7.3) 1.0 0.6 (0.2–1.6) 1.1 (0.2–6.5) 1.0 1.2 (0.4–3.1) 3.7 (0.9–14.8) 1.0 0.3 (0.1–1.4)