Associations of uric acid with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers

Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects.     

Associations of patella lead with polymorphisms in the vitamin D receptor, delta-aminolevulinic acid dehydratase and endothelial nitric oxide synthase genes

A cross-sectional analysis was performed to evaluate associations of polymorphisms in the vitamin D receptor (VDR), delta-aminolevulinic acid dehydratase (ALAD), and endothelial nitric oxide synthase (eNOS) genes with patella lead concentrations in 652 lead workers in the Republic of Korea. There was a wide range of patella lead (from below detection limit to 946 microg Pb/g bone mineral), with a mean (standard deviation) of 75.2 (101.0). There were no associations of ALAD or eNOS genotypes with patella lead, but workers with the VDR B allele had significantly (P value < 0.05) higher patella lead (on average, 25% or approximately 6.6 microg Pb/g bone mineral) than lead workers with the VDR bb genotype. There was evidence that the relation between age and patella lead was modified by both the VDR and eNOS genotypes.     

Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers

Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.     

Associations of lead biomarkers and delta-aminolevulinic acid dehydratase and vitamin D receptor genotypes with hematopoietic outcomes in Korean lead workers.

OBJECTIVES: This study compares and contrasts associations of dimercaptosuccinic acid (DMSA)-chelatable lead, tibia lead, and blood lead with five hematopoietic outcomes and evaluates the effect modification of these relations by polymorphisms in the delta-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes. METHODS: A cross-sectional study of 798 lead workers and 135 unexposed referents was performed. RESULTS: The DMSA-chelatable lead, tibia lead, and blood lead levels ranged in the lead (Pb) workers from 4.8 to 2103 g, -7 to 338 g Pb/g bone mineral, and 4 to 86 g/dl, respectively. The mean of the hemoglobin, hematocrit, zinc protoporphyrin (ZPP), and urinary (ALAU) and plasma (ALAP) delta-aminolevulinic acid levels of the lead workers were 14.2 (SD 1.4) g/dl, 42.4 (SD 4.4)%, 80.2 (SD 63.5) g/dl, 2.1 (SD 3.7) mg/l, and 17.7 (20.6) g/ml, respectively. After adjustment for the covariates, tibia lead was associated with all five hematopoietic outcomes, while blood lead and DMSA-chelatable lead were associated only with ZPP, ALAP, and ALAU. A comparison of the regression coefficients, total model adjusted R2 values, and delta R2 values revealed that blood lead was the best predictor of ZPP, ALAP, and ALAU. Only tibia lead was significantly associated with hemoglobin and hematocrit levels, but the additional variance explained by tibia lead was (<1%). No clear effect modification of the relations between the lead biomarkers and hematopoietic outcomes studied was caused by ALAD or VDR genotype. CONCLUSIONS: Lead must have a chronic, cumulative effect on hemoglobin and hematocrit levels, and any speculated mechanism cannot merely involve short-term plasma or target organ lead levels.     

Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes

Evidence suggests that lead and selected genes known to modify the toxicokinetics of lead--namely, those for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD)--may independently influence blood pressure and hypertension risk. We report the relations among ALAD and VDR genotypes, three lead dose measures, and blood pressure and hypertension status in 798 Korean lead workers and 135 controls without occupational exposure to lead. Lead dose was assessed by blood lead, tibia lead measured by X-ray fluorescence, and dimercaptosuccinic acid (DMSA)-chelatable lead. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele, and there were no ALAD(2) homozygotes; 11.2% (n = 89) had at least one copy of the VDR B allele, and 0.5% (n = 4) had the BB genotype. In linear regression models to control for covariates, VDR genotype (BB and Bb vs. bb), blood lead, tibia lead, and DMSA-chelatable lead were all positive predictors of systolic blood pressure. On average, lead workers with the VDR B allele, mainly heterozygotes, had systolic blood pressures that were 2.7-3.7 mm Hg higher than did workers with the bb genotype. VDR genotype was also associated with diastolic blood pressure; on average, lead workers with the VDR B allele had diastolic blood pressures that were 1.9-2.5 mm Hg higher than did lead workers with the VDR bb genotype (p = 0.04). VDR genotype modified the relation of age with systolic blood pressure; compared to lead workers with the VDR bb genotype, workers with the VDR B allele had larger elevations in blood pressure with increasing age. Lead workers with the VDR B allele also had a higher prevalence of hypertension compared to lead workers with the bb genotype [adjusted odds ratio (95% confidence interval) = 2.1 (1.0, 4.4), p = 0.05]. None of the lead biomarkers was associated with diastolic blood pressure, and tibia lead was the only lead dose measure that was a significant predictor of hypertension status. In contrast to VDR, ALAD genotype was not associated with the blood pressure measures and did not modify associations of the lead dose measures with any of the blood pressure measures. To our knowledge, these are the first data to suggest that the common genetic polymorphism in the VDR is associated with blood pressure and hypertension risk. We speculate that the BsmI polymorphism may be in linkage disequilibrium with another functional variant at the VDR locus or with a nearby gene.     

Amyotrophic lateral sclerosis,lead, and genetic susceptibility: polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin D receptor genes

Previous studies have suggested that lead exposure may be associated with increased risk of amyotrophic lateral sclerosis (ALS). Polymorphisms in the genes for delta-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) may affect susceptibility to lead exposure. We used data from a case-control study conducted in New England from 1993 to 1996 to evaluate the relationship of ALS to polymorphisms in ALAD and VDR and the effect of these polymorphisms on the association of ALS with lead exposure. The ALAD 2 allele (177G to C; K59N) was associated with decreased lead levels in both patella and tibia, although not in blood, and with an imprecise increase in ALS risk [odds ratio (OR) = 1.9; 95% confidence interval (95% CI), 0.60-6.3]. We found a previously unreported polymorphism in ALAD at an Msp1 site in intron 2 (IVS2+299G>A) that was associated with decreased bone lead levels and with an imprecise decrease in ALS risk (OR = 0.35; 95% CI, 0.10-1.2). The VDR B allele was not associated with lead levels or ALS risk. Our ability to observe effects of genotype on associations of ALS with occupational exposure to lead or with blood or bone lead levels was limited. These findings suggest that genetic susceptibility conferred by polymorphisms in ALAD may affect ALS risk, possibly through a mechanism related to internal lead exposure.     

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.     

Associations of lead biomarkers with renal function in Korean lead workers

Aims: To compare associations of lead biomarkers with renal function in current and former lead workers.     

Associations among lead dose biomarkers, uric acid, and renal function in Korean lead workers

Recent research suggests that both uric acid and lead may be nephrotoxic at lower levels than previously recognized. We analyzed data from 803 current and former lead workers to determine whether lead biomarkers were associated with uric acid and whether previously reported associations between lead dose and renal outcomes were altered after adjustment for uric acid. Outcomes included uric acid, blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-ss-d-glucosaminidase (NAG) and retinol-binding protein. Mean (+/- SD) uric acid, tibia lead, and blood lead levels were 4.8 +/- 1.2 mg/dL, 37.2 +/- 40.4 microg/g bone mineral, and 32.0 +/- 15.0 microg/dL, respectively. None of the lead measures (tibia, blood, and dimercaptosuccinic-acid-chelatable lead) was associated with uric acid, after adjustment for age, sex, body mass index, and alcohol use. However, when we examined effect modification by age on these relations, both blood and tibia lead were significantly associated (ss = 0.0111, p < 0.01 and ss = 0.0036, p = 0.04, respectively) in participants in the oldest age tertile. These associations decreased after adjustment for blood pressure and renal function, although blood lead remained significantly associated with uric acid (ss = 0.0156, p = 0.01) when the population was restricted to the oldest tertile of workers with serum creatinine greater than the median (0.86 mg/dL). Next, in models of renal function in all workers, uric acid was significantly (p < 0.05) associated with all renal outcomes except NAG. Finally, in the oldest tertile of workers, associations between lead dose and NAG were unchanged, but fewer associations between the lead biomarkers and the clinical renal outcomes remained significant (p less than or equal to 0.05) after adjustment for uric acid. In conclusion, our data suggest that older workers comprise a susceptible population for increased uric acid due to lead. Uric acid may be one, but not the only, mechanism for lead-related nephrotoxicity.     

Association of renal function and delta-aminolevulinic acid dehydratase polymorphism among Vietnamese and Singapore workers exposed to inorganic lead

Objectives

To investigate the effect of δ‐aminolevulinic acid dehydratase (ALAD) polymorphisms on the association between blood lead and renal function among Vietnamese and Singaporean workers who were exposed to low to medium levels of inorganic lead, and to study the distribution of ALAD polymorphism among Vietnamese, Chinese, Malays and Indians.

Methods

A total of 459 male and female workers were studied. Blood and urine were collected for each worker in order to determine ALAD genotype, blood lead, and urinary δ‐aminolevulinic acid (ALAU). Renal function tests included urine albumin (Ualb), urine β2 microglobulin (Uβ2m), urinary α1 microglobulin (Uα1m), N‐acetyl‐glucosaminidas (NAG), and urine retinol blinding protein (RBP). A multiple regression model with interaction term was applied to fit the entire data and to explore the modifying effect of ALAD polymorphism on the relation of blood lead to each renal function parameter.

Results

ALAD1‐1 was the predominant genotype for all the ethnic groups while ALAD2‐2 was the rarest. The frequency of ALAD2 allele was higher among Malays (8.8%) and Indians (10.6%) compared to the Chinese (5.0%) and Vietnamese (4.3%). The geometric mean of blood lead for all workers was 19.0 μg/dl. The models for Uβ2m, Uα1m, and NAG showed that the ALAD1‐2/2‐2 group had higher β coefficients than the ALAD1‐1 group. Corresponding to 10 μg/dl blood lead, ALAD1‐1 homozygotes had an increment of 1.288 μg/g Cr, 1.175 mg/g Cr, and 1.995 U/g Cr for Uβ2m, Uα1m, and NAG, respectively. ALAD1‐2/2‐2 subjects had higher increments of 3.802 μg/g Cr, 2.138 mg/g Cr, and 3.89 U/g Cr for Uβ2m, Uα1m, and NAG, respectively.

Conclusion

The frequency of the ALAD2 allele is as low in Vietnamese workers as in Chinese. Workers with the ALAD2 allele appeared more susceptible to the effects of lead (especially at higher levels) on renal function.     

Associations of tibial lead levels with BsmI polymorphisms in the vitamin D receptor in former organolead manufacturing workers

We evaluated associations of tibial lead levels with polymorphisms in the vitamin D receptor (VDR) in 504 former organolead manufacturing workers with past exposure to lead. In this cross-sectional study, we measured tibial lead by (109)Cd K-shell X-ray fluorescence. Tibial lead was evaluated in subjects with different VDR genotypes defined using the BsmI restriction enzyme, adjusting for confounding variables. Study participants had a mean age +/- SD of 57.4 +/- 7.6 years. A total of 169 (33.5%) subjects were homozygous for the BsmI restriction site (designated bb), 251 (49.8%) were heterozygous (Bb), and 84 (16.7%) were homozygous for the absence of the restriction site (BB). Among all of the study subjects, tibial lead concentrations were low, with a mean +/- SD of 14.4 +/- 9.3 microg Pb/g bone mineral. There were only small differences in tibial lead concentrations by VDR genotype, with mean +/- SD tibial lead concentrations of 13.9 +/- 7.9, 14.3 +/- 9.5, and 15.5 +/- 11.1 in subjects with bb, Bb, and BB, respectively. In a multiple linear regression model of tibial lead concentrations, the VDR genotype modified the relation between age and tibial lead concentrations; subjects with the B allele had larger increases in tibial lead concentrations with increasing age (0.37, 0.48, and 0.67 microg/g per year of age in subjects with bb, Bb, and BB, respectively; the adjusted p-value for trend in slopes = 0.04). The VDR genotype also modified the relation between years since last exposure to lead and tibial lead concentrations. Subjects with bb evidenced an average decline in tibial lead concentrations of 0.10 microg/g per year since their last exposure to lead, whereas subjects with Bb and BB evidenced average increases of 0.03 and 0.11 microg/g per year, respectively (the adjusted p-value for trend in slopes = 0.01). Polymorphisms in the vitamin D receptor modified the relations of age and years since the last exposure to lead with tibial lead concentrations. Although controversy remains on the influence of the VDR genotype on bone mineral density, the data suggest that variant VDR alleles modify lead concentrations in bone, either by influencing lead content or calcium content or both.     

Relationship between delta-aminolevulinic acid dehydratase genotypes and heme precursors in lead workers

BACKGROUND: The objective of this study was to investigate the relationships between genotypes of delta-aminolevulinic acid (ALA) dehydratase (ALAD) and disturbances in the heme biosynthetic pathway by lead exposure. METHODS: The subjects were 192 male lead workers and 125 control subjects. Blood lead concentrations (Pb-B), plasma ALA concentrations (ALA-P), and ALAD genotypes were determined for all subjects. In lead workers, ALAD activity, ALA in urine (ALA-U), and erythrocyte zinc protoporphyrin (ZP) were also determined. RESULTS: The frequency of ALAD2 (minor type of ALAD allele) was calculated to be 0.087 in all subjects. No significant relationship was found between ALAD2 frequency and Pb-B levels in lead workers. ALAD1 homozygotes showed significantly higher levels of ZP and ALA-P in comparison with those of ALAD2 carriers at Pb-B levels more than 20 microg/dL and 40 microg/dL, respectively. CONCLUSIONS: ALAD1 homozygotes might be more susceptible than ALAD2 carriers to disturbances in heme metabolism caused by lead exposure.     

Associations of patella lead and other lead biomarkers with renal function in lead workers

OBJECTIVE: We sought to compare associations of patella lead, which may represent a unique cumulative and bioavailable lead pool, with other lead measures in models of renal function. METHODS: Renal function measures included blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, and urinary N-acetyl-beta-D-glucosaminidase (NAG) and retinol-binding protein. RESULTS: In 652 lead workers, mean (SD) blood, patella, and tibia lead were 30.9 (16.7) microg/dL, 75.1 (101.1) and 33.6 (43.4) microg Pb/g bone mineral, respectively, and were correlated (Spearman's r = 0.51-0.74). Patella lead was associated (P < 0.05) with NAG in all lead workers. In models of effect modification by age, higher patella lead also was associated with higher serum creatinine in older participants. Similar associations were observed for blood and tibia lead. CONCLUSIONS: Associations between patella lead and adverse renal outcomes were not unique; this may be due, in part, to high correlations among the lead biomarkers in this study.     

Polymorphism of delta-aminolevulinic acid dehydratase and its effect on blood lead levels in Thai workers

To determine the prevalence of delta-aminolevulinic acid dehydratase (ALAD) polymorphism and its effects on blood lead levels (BLLs) in Thai workers, the authors performed a cross-sectional analysis of 389 Thai workers who were exposed to lead in a battery plant. The authors collected blood for BLLs and genotypic study, and they found that the allele frequencies of ALAD1 and ALAD2 were 0.98 and 0.02, respectively. They made a comparison of BLLs between genotype by dividing the levels into 2 categories of lead exposure (high and medium magnitude of exposure) and using length of employment as a covariance. Their results showed no significant difference of BLLs between the ALAD1-1 and ALAD1-2/ALAD2-2 groups in both levels of exposure. The frequency of ALAD2 in Thai workers was low; the authors found that ALAD polymorphism had a small or only modest effect on BLLs.     

Different behaviors of erythrocyte delta-aminolevulinic acid dehydratase. A comparison study between lead workers and normals.

Different characteristics of erythrocyte delta-aminolevulinic acid dehydratase (ALA-D1) between the workers with the history of occupational lead exposure and normals are described. In the blood of lead workers, when the hemolysates are heated at 60 C for five minutes, the activity of the erythrocytes ALA-D increases up to about 3.6-fold of an initial level, and as a result of heating the optimum in pH-activity curvee changes from pH 6.0 to pH 6.6, which is similar to the optimum pH of normal ALA-D. On the contrary, in normal blood, the optimum in the pH-activity curve is but little changed, even though the erythrocyte ALA-D activity is increased up to about 1.3-fold of the initial level by heating the hemolysates at 60 C for five minutes.     

Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers.

The gene that encodes gamma-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (CPU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 microg/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 micromol/ml; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations >/= 40 microg/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration.     

Blood lead and erythrocyte delta-aminolevulinic acid dehydratase levels in Manchester taxi drivers.

Among 40 Manchester taxi drivers the mean blood lead was 1.10 mumol/1 (22.8 mug per 100 ml). The mean erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity among 34 of them was 30.1 units. No significant association was found between the blood lead levels and erythrocyte ALAD activity in these 34 men. No significant association was found between either blood lead elvels or erythrocyte ALAD activity and duration of service or weekly mileage as a taxi driver or with drinking or smoking habits, or age. The mean blood lead of those with homes in the north east quadrant of the city was higher than of those living elsewhere but the difference was not statistically significant. Although there was no correlation between blood lead levels and the source of domestic water, the mean blood lead of those with lead domestic plumbing was appreciably higher than the level of those with copper plumbing. There was no indication that, by virtue of their occupation, the taxi drivers were liable to greater lead absorption than their fellow-citizens.