Humans ; Occupational Health ; Occupational Health Services ; World Health Organization

Anniversaries and Special Events ; Education, Medical ; history ; History, 20th Century ; History, 21st Century ; Occupational Medicine ; history

Cadmium ; adverse effects ; Dose-Response Relationship, Drug ; Environmental Exposure ; adverse effects ; Humans ; Occupational Exposure ; adverse effects ; Risk Assessment

Cadmium ; pharmacology ; Cells, Cultured ; Heat-Shock Proteins ; biosynthesis ; Humans ; Metallothionein ; biosynthesis ; Ubiquitin ; biosynthesis

Animals ; Cells, Cultured ; Male ; Phenols ; toxicity ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; drug effects ; metabolism ; Steroidogenic Factor 1 ; genetics ; metabolism

Animals ; Benchmarking ; methods ; statistics & numerical data ; Dose-Response Relationship, Drug ; Humans ; Models, Statistical ; No-Observed-Adverse-Effect Level ; Risk Assessment ; methods ; statistics & numerical data ; Toxicology ; methods

China ; Health Occupations ; legislation & jurisprudence ; Health Personnel ; Humans ; Occupational Health ; legislation & jurisprudence ; Preventive Health Services ; legislation & jurisprudence ; Risk Factors

Animals ; Cadmium Chloride ; toxicity ; Dose-Response Relationship, Drug ; Estradiol ; toxicity ; Female ; Organ Size ; drug effects ; Rats ; Rats, Sprague-Dawley ; Uterus ; drug effects ; pathology

Toxicology ; Translational Medical Research

OBJECTIVETo use the data of occupational epidemiology to estimate the benchmark dose (BMD) of renal dysfunction induced by lead.

METHODSBlood lead was considered as an exposure biomarker, while urinary total protein (TP), urinary beta(2)-microglobulin (beta(2)-MG) and urinary N-Acetyl-beta-D-glucosaminidase (NAG) were considered as effect biomarkers reflecting the damage of renal function. The dichotomized (binary) data was used as effect endpoints. The BMD and BMD lower limit (BMDL) of blood lead were estimated at the 10% benchmark response using BMDS version 1.3.1.

RESULTSThere was an increased prevalence of hyper-TP-uria, hyper-beta(2)-MG-uria and hyper-NAG-uria with an increasing blood lead concentration. There was obviously dose-response relationship between blood lead and TP, beta(2)-MG and NAG, respectively. The BMD and BMDL of blood lead affecting renal function were estimated to be 323.6 - 754.3 microg/L and 274.2 - 541.5 microg/L. The BMDL of blood lead was ranged from low to high as NAG, TP and beta(2)-MG. The urinary NAG activity might be served as a sensitive biomarker in detecting early renal dysfunction.

CONCLUSIONIt should be feasible to use the BMD approach to set up the reference dose (RfD) and reference concentration (RfC). BMD approach might provide a new and better way for setting up the RfD/RfC.

Acetylglucosaminidase ; urine ; China ; epidemiology ; Clinical Chemistry Tests ; methods ; standards ; Humans ; Lead ; blood ; Lead Poisoning ; blood ; epidemiology ; urine ; Occupational Exposure ; analysis ; Prevalence ; Proteinuria ; urine ; beta 2-Microglobulin ; urine