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Benchmark dose for cadmium-induced renal effects in humans

Suwazono, Yasushi; Sand, Salomon; Vahter, Marie; Filipsson, Agneta Falk; Skerfving, Staffan LU ; Lidfeldt, Jonas LU and Akesson, Agneta (2006) In Environmental Health Perspectives 114(7). p.1072-1076
Abstract
OBJECTIVES: Our goal in this study was to explore the use of a hybrid approach to calculate benchmark doses (BMDs) and their 95% lower confidence bounds (BMDLs) for renal effects of cadmium in a population with low environmental exposure. METHODS: Morning urine and blood samples were collected from 820 Swedish women 53-64 years of age. We measured urinary cadmium (U-Cd) and tubular effect markers [N-acetyl-beta-D-glucosaminidase (NAG) and human complex-forming protein (protein HQ in 790 women and estimated glomerular filtration rate (GFR; based on serum cystatin Q in 700 women. Age, body mass index, use of nonsteroidal anti-inflammatory drugs, and blood lead levels were used as covariates for estimated GFR. BMDs/BMDLs corresponding to an... (More)
OBJECTIVES: Our goal in this study was to explore the use of a hybrid approach to calculate benchmark doses (BMDs) and their 95% lower confidence bounds (BMDLs) for renal effects of cadmium in a population with low environmental exposure. METHODS: Morning urine and blood samples were collected from 820 Swedish women 53-64 years of age. We measured urinary cadmium (U-Cd) and tubular effect markers [N-acetyl-beta-D-glucosaminidase (NAG) and human complex-forming protein (protein HQ in 790 women and estimated glomerular filtration rate (GFR; based on serum cystatin Q in 700 women. Age, body mass index, use of nonsteroidal anti-inflammatory drugs, and blood lead levels were used as covariates for estimated GFR. BMDs/BMDLs corresponding to an additional risk (benchmark response) of 5 or 10% were calculated (the background risk at zero exposure was set to 5%). The results were compared with the estimated critical concentrations obtained by applying logistic models used in previous studies on the present data. RESULTS: For both NAG and protein HC, the BMDs (BMDLs) of U-Cd were 0.5-1.1 (0.4-0.8) mu g/L (adjusted for specific gravity of 1.015 g/mL) and 0.6-1.1 (0.5-0.8) mu g/g creatinine. For estimated GFR, the BMDs (BMDLs) were 0.8-1.3 (0.5-0.9) mu g/L adjusted for specific gravity and 1.1-1.8 (0.7-1.2) mu g/g creatinine. CONCLUSION: The obtained benchmark doses of U-Cd were lower than the critical concentrations previously reported. The critical dose level for glomerular effects was only slightly higher than that for tubular effects. We suggest that the hybrid approach is more appropriate for estimation of the critical U-Cd concentration, because the choice of cutoff values in logistic models largely influenced the obtained critical U-Cd. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
renal tubular dysfunction, glomerular dysfunction, renal, human, environmental exposure, benchmark dose, continuous data, urinary cadmium, risk assessment
in
Environmental Health Perspectives
volume
114
issue
7
pages
1072 - 1076
publisher
National Institute of Environmental Health Science
external identifiers
  • pmid:16835061
  • wos:000239035100039
  • scopus:33745802345
ISSN
1552-9924
DOI
10.1289/ehp.9028
language
English
LU publication?
yes
id
29053d1a-0642-4969-8065-7e06c737bf9a (old id 402243)
date added to LUP
2007-10-19 15:30:02
date last changed
2018-09-16 04:10:12
@article{29053d1a-0642-4969-8065-7e06c737bf9a,
  abstract     = {OBJECTIVES: Our goal in this study was to explore the use of a hybrid approach to calculate benchmark doses (BMDs) and their 95% lower confidence bounds (BMDLs) for renal effects of cadmium in a population with low environmental exposure. METHODS: Morning urine and blood samples were collected from 820 Swedish women 53-64 years of age. We measured urinary cadmium (U-Cd) and tubular effect markers [N-acetyl-beta-D-glucosaminidase (NAG) and human complex-forming protein (protein HQ in 790 women and estimated glomerular filtration rate (GFR; based on serum cystatin Q in 700 women. Age, body mass index, use of nonsteroidal anti-inflammatory drugs, and blood lead levels were used as covariates for estimated GFR. BMDs/BMDLs corresponding to an additional risk (benchmark response) of 5 or 10% were calculated (the background risk at zero exposure was set to 5%). The results were compared with the estimated critical concentrations obtained by applying logistic models used in previous studies on the present data. RESULTS: For both NAG and protein HC, the BMDs (BMDLs) of U-Cd were 0.5-1.1 (0.4-0.8) mu g/L (adjusted for specific gravity of 1.015 g/mL) and 0.6-1.1 (0.5-0.8) mu g/g creatinine. For estimated GFR, the BMDs (BMDLs) were 0.8-1.3 (0.5-0.9) mu g/L adjusted for specific gravity and 1.1-1.8 (0.7-1.2) mu g/g creatinine. CONCLUSION: The obtained benchmark doses of U-Cd were lower than the critical concentrations previously reported. The critical dose level for glomerular effects was only slightly higher than that for tubular effects. We suggest that the hybrid approach is more appropriate for estimation of the critical U-Cd concentration, because the choice of cutoff values in logistic models largely influenced the obtained critical U-Cd.},
  author       = {Suwazono, Yasushi and Sand, Salomon and Vahter, Marie and Filipsson, Agneta Falk and Skerfving, Staffan and Lidfeldt, Jonas and Akesson, Agneta},
  issn         = {1552-9924},
  keyword      = {renal tubular dysfunction,glomerular dysfunction,renal,human,environmental exposure,benchmark dose,continuous data,urinary cadmium,risk assessment},
  language     = {eng},
  number       = {7},
  pages        = {1072--1076},
  publisher    = {National Institute of Environmental Health Science},
  series       = {Environmental Health Perspectives},
  title        = {Benchmark dose for cadmium-induced renal effects in humans},
  url          = {http://dx.doi.org/10.1289/ehp.9028},
  volume       = {114},
  year         = {2006},
}