Lead exposure in the environment has decreased markedly with the elimination of lead from gasoline and paint, but there are still substantial numbers of US workers exposed. There were approximately 3 million lead-exposed workers in the 1980s, based on NIOSH data. Data from a NIOSH-sponsored lead surveillance program in 37 states in 2005 showed 130,000 workers under surveillance, which is likely to be a fraction of the number exposed. Adult lead exposure may increase risk of several chronic diseases. IARC has classified lead as a 'probable' carcinogen, primarily based on stomach and lung cancer associations. Lead exposure has been associated with increased blood pressure. Very high levels of lead can cause renal failure; increasing literature indicates that sub-clinical effects, which may lead to renal failure, can be seen at lower levels. Under a previous grant from NIOSH, we have assembled and followed a cohort of 58,000 men with documented blood lead levels for mortality and end-stage renal disease incidence (ESRD), through 2010. These men were in a NIOSH-sponsored state-based surveillance program (ABLES). Our ABLES cohort had a mean 12 years of follow-up, with 3300 deaths and 302 cases of ESRD. Half had only one blood test; the median number was 4. Workers were categorized by highest blood lead level. There was a strong healthy worker effect in this young cohort (all cause SMR=0.69). The highest BL category (>40 ?g/dl) had elevated lung and larynx cancer SMRs (1.20, 95% CI: 1.03-1.39, n=174, and 2.11, 95% CI: 1.05-3.77, n=11, respectively). The lung cancer SMR in the highest BL category with 20+ years follow-up was 1.35 (0.92-1.90). Among those with race information, the standardized ESRD incidence ratio (SIR) in the highest BL category (>51?g/dl) was 1.47 (0.98-2.11), increasing to 1.56 (1.02-2.29) for those followed 5+ years. For the entire cohort (race imputed), the SIR in the highest category was 1.36 (0.99-1.73), increasing to 1.43 (1.01- 1.85) with 5+ years follow-up. RRs in internal analyses increased by blood lead category (test for trend p=0.003). ESRD risks were highest in non-whites. Our data suggest that current occupational blood lead standards may not be strict enough. In this new R01 application, we now propose to follow this same ABLES cohort an additional 6 years for mortality and ESRD, increasing our power to detect associations as the healthy worker effect wears off. We expect 3570 new deaths, including 302 new lung cancer deaths. We expect 200 new ESRD cases. We also propose to measure bone lead (a measure of cumulative exposure) among a sub-sample of 200 men to determine the correlation of bone-based rankings with our prior ranking of subjects based on blood lead. We will also measure renal function in these men, enabling analysis of sub-clinical disease in relation to both bone and blood lead; sub-clinical disease is important as it may progress to clinical disease.
The objective of this grant proposal is add six years follow-up to our prior study of 58,000 male lead- exposed workers from 11 states, who have been in a lead surveillance program (the NIOSH-backed ABLES program). In that work we found excess lung cancer mortality and end-stage renal disease, among those with the highest blood lead levels. This proposal will provide us with increased statistical power to detect new associations, confirm old ones, and will enable us to evaluate the adequacy of the current occupational lead standard. We also seek to determine the correlation of our prior exposure rankings, based on one or a few past blood lead measurements, with measurements of bone lead (a measure of cumulative exposure) among a sub-sample of 200 members of the cohort, and to study sub-clinical kidney function in this same sub-sample (which may lead to clinical disease).