TABLE 4.

Summary of Pb ototoxicity findings from twenty-four human study

PAPER	FINDINGS
Baloh, R. (1979)	• No significant differences between control and Pb group (baseline to study below).
Spivey, G. (1980)	• No significant changes from previous audiometric results (above) (Baloh et al. 1979) after 12 to 18 months of BLL monitoring and follow-up testing.
Holdstein, Y. (1986).	• Normal hearing threshold levels. • Significant difference between exposed and control IPL I-III with stimulus delivered at 10/s and 55/s. • A negative correlation between BLL and IPL for wave III-V was significant.
Lille, F. (1988)	• All BAEP results were found to be within normal ranges aside from one patient. • One Pb-exposed alcoholic participant was found to have an increased I-V interpeak latency of 4.7 ms.
Araki, S. (1992)	• Auditory ERP P300 component was prolonged significantly in Pb workers compared to control. • Auditory ERP P300 latency in Pb workers was correlated (Pearson’s product moment correlation coefficient) significantly with BLL, UPb (not shown). • Controls had significantly lower BLL, plasma Zn, and plasma Cu.
Discalzi, G. L. (1992)	• No significant correlation for linear regression was found between 3-year BLL, BLL, or Pb exposure duration and BAEP latencies (I, III, and V). • All BAEP latencies and interpeak latency differences were significantly different in Pb workers compared to controls. • When comparing 21 Pb working participants with an average 3-year BLL above 50 μg/dL to 28 participants below 50 μg/dL, a significantly longer I-V interpeak latency was observed.
Discalzi, G. L. (1993).	• Greater I-V mean IPL between controls and workers. • Greater I-V mean IPL in workers with Pb levels over 50 μg/dL and those under 50 μg/dL.
Hirata, M. (1993).	• Latency of peak III-V was increased significantly in the Pb-exposed. • Latencies for individual peaks I and III were significantly longer in the unexposed workers.
Murata, K. (1993)	• All BAEP latencies (I, III, and V) were not significantly different between Pb workers and controls. • BAEP latency I-V and V were significantly correlated with packed cell volume in 20 workers. • Auditory ERP P300 latencies were significantly longer in Pb workers compared to controls. • Auditory ERP P300 latencies was significantly correlated (simple correlation coefficient) in 22 workers with BLL, urinary Pb, years of employment, urinary Zn, and age.
Murata, K. (1995)	• No significant differences in BAEP latencies (I, I-III, or I-V) were found between Pb workers and controls.
Farahat T. M. (1997).	• 8 kHz was significantly different between workers with BLL < 30 μg/dL and those ≥ 30 μg/dL. • Threshold at 2, 4, and 8 kHz were significantly different in workers and controls. • A significant positive correlation was observed at 8 kHz between BLL and threshold.
Forst, L. S., (1997)	• High frequency HL was evident in cohort. • Significant Spearman correlation with threshold and BLL at 4 kHz. • Trend tests were not significant.
Fujimura, Y. (1998)	• BAEP latency V was significantly different than expected values for Pb smelter #1. • Auditory ERP P300 latency was significantly different from control for Pb smelter #1.
Buchanan, L. (1999)	• Two of five participants reported noise exposure histories. One participant with history of noise exposure had thresholds of 110 dB at 6 kHz in one ear. • Range of mean hearing thresholds were 9.5 dB at 2 kHZ to 32 dB at 6 kHz. • At high frequencies mean DPOAE amplitudes show lowered levels consistent with noise exposure. • No significant associations between DPOAE and BLLs were observed.
Wu, T. (2000)	• Age was correlated with HL. • Long-term Pb exposure metric was significantly associated with HL, though correlated with age. • Increasing thresholds were noted when groups were stratified by BLL (25-40, 41-60, and over 60 μg/dL); however the lowest group (below 25 μg/dL) did not fit this relationship.
Counter, S. A. (2002)	• More HL in men than women. • Four case profiles with high Pb levels described. • No significant relationship between BLL and thresholds. • Those with hearing loss displayed longer (non-significant) absolute wave latencies, but normal IPL.
Yokoyama K. (2002)	• No significant differences between Pb workers and controls were observed in BAEP latencies (I, I-III, and III-V). • BAEP latencies were not found to correlate with BLLs.
Bleecker M. L. (2003)	• Peak I & V latency significantly correlated with Integrated Pb exposure, BLL and TWA. • Peak III latency correlated significantly only with TWA, and integrated Pb exposure. • When stratifying by BAEP pathology, the group with longest wave I latency and I-V IPL had significantly higher BLL and TWA than the group with normal wave I latency and normal I-V IPL.
Chuang H.-Y. (2007)	• Age was associated with HL. • Increasing selenium levels were protective against HL. • An increase of 0.1 μg/dL of log-transformed BLL significantly associated with a 7 dB increase in HL.
Hwang, Y.-H. (2009)	• Higher BLLs increased risk of HL in high frequencies of 3, 4, 6, and 8 kHz. • Higher BLLs were significantly correlated with hearing loss at 0.5, 2, 3, 4, 6, and 8 kHz as well as the average noise and maximum noise levels. • Levels above 7 μg/dL were significantly associated with hearing thresholds above 25 dB (odds ratios 3.06–6.26) in logistic models adjusting for noise and age.
Park, S. K. (2010)	• Odds of HL significantly increased with bone (patella) Pb levels. • A positive interaction was found between bone (tibia) Pb levels and time in the linear mixed effects model showing a faster elevation of thresholds with increasing levels of Pb. • Effect modification analysis showed non-linear dose-response for threshold changes and low, medium, and high occupational noise.
Choi, Y-H. (2012)	• Age-adjusted BLLs were higher in participants who were older, less-educated, smokers, those with high occupational noise exposures, those with a BMI over 30, and those without diabetes. • Participants with HL had significantly higher age-adjusted geometric mean BLL (0.46 to 0.40 μg/dL). • BLL were significantly correlated with blood cadmium levels. • Highest BLL quintiles had 18.6 % (95 % CI: 7.4, 31.1 %) higher average thresholds than those in the lowest quintiles. • Models showed the average thresholds trended across all quintiles significantly with BLL before and after adjusting for occupational and recreational noise exposures. • In logistic models (using a yes or no for hearing loss defined as an average of thresholds at four frequencies over 25 dB) BLL was found as a significant predictor of HL, however it was no longer significant when noise exposure was adjusted for.
Saunders, J. E. (2013)	• No meaningful significant relationships found in the group as a whole after Bonferroni corrections. • DPOAE at 3 kHz, 4 kHz, and the mean of all DPOAE frequencies were significantly correlated with BLL before Bonferroni corrections. • Three case reports of workers with high metals exposure and hearing loss.
Huh, D-A, (2016)	• Risk of hearing loss (defined as pure-tone average at or over 25 dB) increased for participants with BLLs above the mean OR = 1.14 (95 % CI: 0.42, 3.13). • Increasing levels of Pb significantly trended with increasing hearing loss in a fully adjusted model – controlling for age, sex, smoking status, monthly income, education levels, body mass index, occupational noise exposure, loud noise exposure, firearm noise exposure, hypertension, and diabetes mellitus. A 43 % higher odds of hearing loss (95 % CI: 1.03–2.00) was shown in this model for every 1 μg/dL increase in BLL. • The highest quintile of BLL (2.9–26.5 μg/dL) showed significant increased risk for hearing loss across two other models adjusting for fewer variables. However the trend across quintiles in these other models was not significant.

Table Abbreviations: BLL – blood lead levels; CI – confidence interval; HL – hearing loss; IPL – interpeak latency; OR – odds ratio; Pb – lead; TWA – time weighted average.