Estimation of benchmark dose for bone damage and renal dysfunction in a Chinese male population occupationally exposed to lead.
OBJECTIVE
The aim of this study was to examine a possible relationship between lead nephropathy and its effects on the skeleton in male population occupationally exposed to lead in China.


METHODS
One hundred and fifty-five lead-exposed male workers in a storage battery plant in Shanghai were selected as the exposed subjects while the 36 healthy male officers in the plant who were not occupationally exposed to lead were treated as the control. Blood lead (BPb) and urine lead were used as biomarkers for exposure. Z score, urine hydroxyproline (HYP), serum alkaline phosphatase (bone isoenzyme) (BALP) and serum osteocalcin (BGP) were used as biomarkers for bone effects. Urine N-acetyl-beta-D-glucosaminidase (UNAG) and urine albumin (UALB) were applied as biomarkers of renal tubular and glomerular dysfunction. Bone mineral density was measured by the monophoton absorptiometry (SPA-4).


RESULTS
It was found that there were linear correlate relationships between lead exposure and NAG, ALB, BALP, BGP, HYP, Z score (P < 0.01), after controlling confounders such as age and work year. NAG, ALB, BALP, BGP and HYP would increase with the increase of lead exposure. Z score would decrease with the increase of lead exposure. Of 21 subjects with osteoporosis, nine subjects were suffering from renal dysfunction. The prevalence of renal dysfunction (42.86%) was significantly higher in the subjects with osteoporosis than in those without osteoporosis (17.65%) (chi(2) = 7.310, P = 0.007). The prevalence of osteoporosis had relationship with renal tubular damage, but not with renal glomerular damage. This showed that glomerular dysfunction plays a smaller role than tubular dysfunction in the causation of bone damage. Benchmark dose in terms of BPb was calculated using Benchmark Dose Software Version 1.3.2 software. The benchmark dose lower limit of a one-sided 95% confidence interval (BMDL) for 10% excess risk was also determined. It was found that BMDL(-05) for BALP, UNAG, BGP, HYP, Z score and UALB of BPb increased sequentially. The BMDL values for UNAG (10.13 microg dL(-1)) were lower than those of Z score (14.17 microg dL(-1)).


CONCLUSIONS
The present study has thus demonstrated the combined adverse effects (osteoporosis and renal dysfunction) caused by occupational exposure to lead. There was a dose-response relationship between lead exposure and prevalence of osteoporosis, renal dysfunction and bone metabolism. The renal dysfunction might develop earlier than osteoporosis. Osteoporosis caused by lead was related to the change of bone metabolism and renal dysfunction, which was especially to tubular damage but not to glomerular damage.
Department of Occupational Health, School of Public Health, Fudan University, Shanghai 200032, China.
Yi
Y
Sun
Donghong
D
Sun
Zhijun
Z
Zhou
Guoying
G
Zhu
Lijian
L
Lei
Haiying
H
Zhang
Xiuli
X
Chang
Taiyi
T
Jin
D000328:Adult; D015519:Bone Density / Q000187:drug effects; D004784:Environmental Monitoring / Q000379:methods; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D007854:Lead / Q000032:analysis / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced*; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis; D010024:Osteoporosis / Q000139:chemically induced*
D007854:Lead