A cohort mortality study of lead-exposed workers in the USA, Finland and the UK.

OBJECTIVES: To investigate further whether inorganic lead is a carcinogen among adults, or associated with increased blood pressure and kidney damage, via a large mortality study. METHODS: We conducted internal analyses via Cox regression of mortality in three cohorts of lead-exposed workers with blood lead (BL) data (USA, Finland, UK), including over 88 000 workers and over 14 000 deaths. Our exposure metric was maximum BL. We also conducted external analyses using country-specific background rates. RESULTS: The combined cohort had a median BL of 26 µg/dL, a mean first-year BL test of 1990 and was 96% male. Fifty per cent had more than one BL test (mean 7). Significant (p<0.05) positive trends, using the log of each worker's maximum BL, were found for lung cancer, chronic obstructive pulmonary disease (COPD), stroke and heart disease, while borderline significant trends (0.05≤p≤0.10) were found for bladder cancer, brain cancer and larynx cancer. Most results were consistent across all three cohorts. In external comparisons, we found significantly elevated SMRs for those with BLs>40 µg/dL; for bladder, lung and larynx cancer; and for COPD. In a small subsample of the US cohort (n=115) who were interviewed, we found no association between smoking and BL. CONCLUSIONS: We found strong positive mortality trends, with increasing BL level, for several outcomes in internal analysis. Many of these outcomes are associated with smoking, for which we had no data. A borderline trend was found for brain cancer, not associated with smoking.

Environmental lead exposure and cognitive function in community-dwelling older adults.

OBJECTIVE: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. METHODS: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p

Past adult lead exposure is linked to neurodegeneration measured by brain MRI.

OBJECTIVE: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes. METHODS: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as microg lead per gram of bone mineral (microg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated. RESULTS: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 5 vs < 5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula. CONCLUSIONS: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.

Predictors of DMSA chelatable lead, tibial lead, and blood lead in 802 Korean lead workers.

OBJECTIVES: To examine the interrelations among chelatable lead (by dimercaptosuccinic acid, DMSA), tibial lead, and blood lead concentrations in 802 Korean workers with occupational exposure to lead and 135 employed controls with only environmental exposure to lead. METHODS: This was a cross sectional study wherein tibial lead, DMSA chelatable lead, and blood lead were measured. Linear regression was used to identify predictors of the three lead biomarkers, evaluating the influence of age, job duration, sex, education level, alcohol and tobacco use, creatinine clearance rate, and body mass index. RESULTS: DMSA chelatable lead concentrations ranged from 4.8 to 2102.9 microg and were positively associated with age, current smoking, and creatinine clearance rate. On average, women had 64 microg less DMSA chelatable lead than men. When blood lead and its square were added to a model with age, sex, current smoking, body mass index, and creatinine clearance rate, blood lead accounted for the largest proportion of the variance and sex became of borderline significance. Tibial lead concentrations ranged from -7 to 338 microg/g bone mineral and were positively associated with age, job duration, and body mass index. Women had, on average, 9.7 microg/g less tibial lead than men. Blood lead concentrations ranged from 4.3 to 85.7 microg/dl and were positively associated with age and tibial lead, whereas current smokers had higher blood lead concentrations and women had lower blood lead concentrations. CONCLUSIONS: The data suggest that age and sex are both predictors of DMSA chelatable lead, blood lead, and tibial lead concentrations and that tibial lead stores in older subjects are less bioavailable and may contribute less to blood lead concentrations than tibial lead stores in younger subjects. Although blood lead concentrations accounted for a large proportion of the variance in DMSA chelatable lead concentrations, suggesting that measurement of both in epidemiological studies may not be necessary, the efficacy of each measure in predicting health outcomes in epidemiological studies awaits further investigation.

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.

Predictors of dimercaptosuccinic acid chelatable lead and tibial lead in former organolead manufacturing workers.

OBJECTIVES: To identify predictors of tibial and dimercaptosuccinic acid (DMSA) chelatable lead in 543 organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: In this cross sectional study, tibial lead (by 109Cd K-shell x ray fluorescence), DMSA chelatable lead (4 hour urinary lead excretion after oral administration of 10 mg/kg), and several exposure measures were obtained on study participants, mean (SD) age 57.6 (7.6) years. RESULTS: Tibial lead concentrations ranged from -1.6 to 52.0 micrograms lead/g bone mineral, with a mean (SD) of 14.4 (9.3) micrograms/g. DMSA chelatable lead ranged from 1.2 to 136 micrograms, with a mean (SD) of 19.3 (17.2) micrograms. In a multiple linear regression model of tibial lead, age (p < 0.01), duration of exposure (p < 0.01), current (p < 0.01) and past (p = 0.05) cigarette smoking, and diabetes (p = 0.01) were all independent positive predictors, whereas height (p = 0.03), and exercise inducing sweating (p = 0.04) were both negative predictors. The final regression model accounted for 31% of the variance in tibial lead concentrations; 27% was explained by age and duration of exposure alone. DMSA chelatable lead was directly associated with tibial lead (p = 0.01), cumulative exposure to inorganic lead (y.microgram/m3, p = 0.01), current smoking (p < 0.01), and weight (p < 0.01), and negatively associated with diabetes (p = 0.02). The final model accounted for 11% of the variance in chelatable lead. When blood lead was added to this model of DMSA chelatable lead, tibial lead, cumulative exposure to inorganic lead, and diabetes were no longer significant; blood lead accounted for the largest proportion of variance (p < 0.001); and the total model r2 increased to 19%. CONCLUSIONS: The low proportions of variance explained in models of both tibial and chelatable lead suggest that other factors are involved in the deposition of lead in bone and soft tissue. In epidemiological studies of the health effects of lead, evaluation of associations with both these measures may allow inferences to be made about whether health effects are likely to be recent, and thus potentially reversible, or chronic, and thus possibly irreversible. The data also provide direct evidence that in men the total amount of lead in the body that is bioavailable declines with age.

Lead poisoning.

Lead poisoning is the most common disease of environmental origin in the United States today. Adult lead poisoning results primarily from exposure by inhalation in the workplace. Pediatric lead poisoning results principally from the ingestion of lead from environmental media, including paint chips, dust, soil, drinking water, ceramics, and medications. Lead is toxic to many organ systems, among them developing erythrocytes, the kidneys, and the nervous system. Lead-induced toxicity to the central nervous system causes delayed development, diminished intelligence, and altered behavior. In young children, this effect has been demonstrated convincingly to occur at blood lead levels between 10 and 20 micrograms per dl. The Centers for Disease Control and Prevention has recommended that a blood lead level of 10 micrograms per dl or higher be considered evidence of increased lead absorption, and the National Academy of Sciences has concurred in that recommendation. Unresolved issues in need of further study include the frequency of screening young children for lead, the question of whether women should be offered screening for lead before conceiving a pregnancy, the role of x-ray fluorescence analysis in assessing lead in bone, and the appropriate legislative response of the United States government to lead-based paint abatement.

Residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, childhood lymphoma, and childhood nervous system tumors: systematic review, evaluation, and meta-analysis.

In 1979, Wertheimer and Leeper reported an increased risk of cancer mortality among children living near 'electrical wiring configurations' suggestive of high current flow. Since then, numerous, often inconclusively small, investigations with conflicting results have studied the possible association between exposure to electric and magnetic fields (EMF) and health effects. The high prevalence of exposure to EMF has drawn attention to the issue of carcinogenesis. We report here the results of a meta-analysis of 13 epidemiologic studies of residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, lymphoma, and nervous system tumors. The combined relative risks for leukemia, lymphoma, and nervous system tumors are 1.49 (95 percent confidence interval [CI] = 1.11-2.00); 1.58 (CI = 0.91-2.76); and 1.89 (CI = 1.34-2.67) respectively. The reports of the primary studies were evaluated for epidemiologic quality and adequacy of exposure assessment. We found no statistically significant relation between combined relative risk estimates and 15 indicators of epidemiologic quality. Assessment of EMF exposure in the primary studies was found to be imperfect and imprecise. Additional high quality epidemiologic research, incorporating comprehensive assessments of EMF exposure collected concurrently with surrogate measures of exposure, is needed to confirm these results.

A pilot study using 99mTc to measure lead and platinum in the human kidney.

A pilot study has been conducted to investigate the hypothesis that the chemotherapeutic drug, cisplatinum, can mobilize skeletal lead. In vivo measurements of lead and platinum in the kidney of chemotherapy patients were performed with the technique of x-ray fluorescence, using 99mTc in a backscatter geometry. The results of the pilot study were inconclusive; the majority of patients exhibited no evidence of kidney lead at the level of system sensitivity, and negligible blood and urine lead levels.

In vivo X-ray fluorescence of lead in bone using K X-ray excitation with 109Cd sources: radiation dosimetry studies.

Independent experiments have been performed at two centers, to evaluate the dosimetric properties of their respective 109Cd K X-ray fluorescence (XRF) bone lead measurement systems. Measurements were made of the dose to several points on the skin on the lower leg, at the surface of the tibia, in the red marrow tibia cavity, at the midcalf, and in the abdominal region occupied by the conceptus. Overall agreement between the two data sets was found. Similarities and differences are discussed. The effective dose values for an in vivo measurement of tibia lead concentration in 1-, 5-, and 10-year-old and adult subjects were calculated from one data set to be 1100, 420, 190, and 34/38 (male/female) nSv, respectively, for an in vivo median precision (one standard deviation) of 4.9 micrograms Pb (g bone mineral)-1 for a 30-min adult measurement.