ToxSci Advance Access originally published online on February 14, 2007
Toxicological Sciences 2007 97(1):189-195; doi:10.1093/toxsci/kfm016
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Estimation of Benchmark Dose for Pancreatic Damage in Cadmium-Exposed Smelters
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* Department of Occupational Health, School of Public Health, Fudan University, Shanghai 200032, China
Environmental Medicine; Department of Public Health and Clinical Medicine, Umeå University, SE-90187 Umeå, Sweden
Institute of Environmental Medicine, Karolinska Institutet, SE-171 77, Stockholm, Sweden
1 To whom Correspondence should be addressed. Fax: +86-21-64178160. E-mail: tyjin{at}shmu.edu.cn.
Received November 20, 2006; accepted December 13, 2006
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Abstract |
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The aim of this study was to estimate the benchmark dose (BMD) for pancreas dysfunction caused by cadmium (Cd) exposure in smelters. Smelter workers who had been exposed to Cd for more than 1 year and matching nonoccupationally exposed subjects were asked to participate in this study. Urinary cadmium (UCd) was used as a biomarker for exposure, serum insulin and amylase were used as biomarkers for pancreatic effects. In this study, serum insulin and amylase were lower in the smelter workers than in the nonoccupationally exposed subjects. A significant dose-response relationship with UCd was displayed. BMDs in terms of urinary Cd corrected for creatinine were calculated by use of BMDS (version 1.3.2). The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that the BMDL10 for serum insulin and serum amylase was 3.7 and 5.3 µg/g Cr, respectively. Compared to the BMDL for renal damage caused by Cd exposure, identified by the effect biomarkers urinary ß2-microglobulin, urinary N-acetyl-ß-glucosaminidase, and urinary albumin (UALB), it was shown that BMDL10 for serum insulin is the lowest among all values and UALB gave the highest value (5.8 µg/g Cr). This study indicates that Cd exposure can result in pancreatic dysfunction and the effect appears at lower urinary Cd level than renal dysfunction. The endocrine function of the pancreas was affected at lower urinary levels of Cd, compared to the exocrine function, which was seen at higher urinary levels of Cd than those giving rise to renal tubular dysfunction.
Key Words: cadmium exposure; benchmark dose; pancreas; biomarker; renal; endocrine.