Harry A. Roels

Environmental exposure to cadmium and risk of cancer: a prospective population-based study

BACKGROUNDnCadmium is a ubiquitous environmental pollutant, which accumulates in the human body such that 24-h urinary excretion is a biomarker of lifetime exposure. We aimed to assess the association between environmental exposure to cadmium and cancer.nnnMETHODSnWe recruited a random population sample (n=994) from an area close to three zinc smelters and a reference population from an area with low exposure to cadmium. At baseline (1985-89), we measured cadmium in urine samples obtained over 24 h and in the soil of participants gardens, and followed the incidence of cancer until June 30, 2004. We used Cox regression to calculate hazard ratios for cancer in relation to internal (ie, urinary) and external (ie, soil) exposure to cadmium, while adjusting for covariables.nnnFINDINGSnCadmium concentration in soil ranged from 0.8 mg/kg to 17.0 mg/kg. At baseline, geometric mean urinary cadmium excretion was 12.3 nmol/day for people in the high-exposure area, compared with 7.7 nmol/day for those in the reference (ie, low-exposure) area (p<0.0001). During follow-up (median 17.2 years [range 0.6-18.8]), 50 fatal cancers and 20 non-fatal cancers occurred, of which 18 and one, respectively, were lung cancers. Overall cancer risk was significantly associated with a doubling of 24-h cadmium excretion (hazard ratio 1.31 [95% CI 1.03-1.65], p=0.026. Population-attributable risk of lung cancer was 67% (95% CI 33-101) in the high-exposure area, compared with that of 73% (38-108) for smoking. For lung cancer, adjusted hazard ratio was 1.70 (1.13-2.57, p=0.011) for a doubling of 24-h urinary cadmium excretion, 4.17 (1.21-14.4, p=0.024) for residence in the high-exposure area versus the low-exposure area, and 1.57 (1.11-2.24, p=0.012) for a doubling of cadmium concentration in soil.nnnINTERPRETATIONnHistorical pollution from non-ferrous smelters continues to present a serious health hazard, necessitating targeted preventive measures.

Exposure To Lead By the Oral and the Pulmonary Routes of Children Living in the Vicinity of a Primary Lead Smelter

Abstract Yearly from 1974 to 1978, a medical survey was carried out among 11-year-old children attending schools situated less than 1 and 2.5 km from a lead smelter. Age-matched control children from a rural and urban area were examined at the same time. The blood lead levels (PbB) of the children living in the smelter area (mainly those attending schools located less than 1 km from the smelter) were higher than those of rural and urban children. The mean PbB levels were usually lower in girls than in boys, especially in the smelter area. Despite a slightly decreasing trend in the annual mean airborne lead concentration at less than 1 km (mean PbA: from 3.8 μg/m3 in 1974 to 2.3 μg/m3 in 1978) the PbB levels there did not improve, whereas 2.5 km from the plant a significant tendency to normalization of PbB became apparent. Therefore, in the third survey, the medical examination was combined with an environmental study which demonstrated that lead in school-playground dust and in air strongly correlated. Lead on the childrens hands (PbH) was also significantly related to lead in air or lead in dust. Less than 1 km from the factory boys and girls had on the average 436 and 244 μg Pb/hand, respectively, vs 17.0 and 11.4 μg Pb/hand for rural boys and girls, respectively. Partial correlations between PbB, PbA, and PbH indicated that in the smelter area the quantitative contribution of PbA to the childrens PbB is negligible compared to that of PbH. Thus, the control of airborne lead around the lead smelter is not sufficient to prevent excessive exposure of children to environmental lead. In view of the importance of lead transfer from dust and dirt via hands to the gastrointestinal tract remedial actions should be directed simultaneously against the atmospheric emission of lead by the smelter and against the lead particulates deposited on soil, dust, and dirt.

Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders

Background: Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore-processing and ferroalloy production, the risks among welders with lower exposures are less well understood. Methods: Confined space welding in construction of a new span of the San Francisco–Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose–effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (nu200a=u200a43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. Results: The mean time weighted average of Mn-air ranged from 0.11–0.46 mg/m3 (55% >0.20 mg/m3). MnB >10 µg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV1/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose–effect relationships with CEI and/or MnB were found for IQ (p⩽0.05), executive function (p⩽0.03), sustaining concentration and sequencing (p⩽0.04), verbal learning (p⩽0.01), working (p⩽0.04) and immediate memory (p⩽0.02), even when adjusted for demographics and years of welding before Bay Bridge. Symptoms reported by the welders while working were: tremors (41.9%); numbness (60.5%); excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%); toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose–effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05), depression (p<0.01) and headache (p<0.05) were statistically significant. Conclusions: Confined space welding was shown to be associated with neurological, neuropsychological and pulmonary adverse health effects. A careful enquiry of occupational histories is recommended for all welders presenting with neurological or pulmonary complaints, and a more stringent prevention strategy should be considered for Mn exposure due to inhalation of welding fume.

Epidemiological survey of workers exposed to cadmium.

Pulmonary ventilatory function and various biological indices have been investigated in three groups of workers exposed to cadmium dust (women with less than 20 years’ exposure [E1], men with less than 20 years’ exposure [E2], and men with more than 20 years’ exposure [E3]) and in three matched control groups. The current airborne Cd dust concentration in the workrooms was below the actual American threshold limit value (200μg/cu m). A slight but significant reduction in forced vital capacity, in forced expiratory volume in one second, and in peak expiratory flow rate was found in E3 workers. Kidney damage was more prevalent than pulmonary ventilatory changes, since excessive proteinuria was observed in 15% of E2 workers and in 68% of E3 workers. The electrophoretic pattern of the urinary proteins suggests that the lesion is first glomerular and later becomes predominantly tubular (mixed proteinuria).

Bone resorption and environmental exposure to cadmium in women: A population study

Background Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction. Objective We sought evidence for a direct osteotoxic effect of cadmium in women. Methods We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density. Results In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, –0.009 g/cm2 (p = 0.055) for proximal forearm bone density, and –16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were –0.01223 g/cm2 (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, –9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 μg/day). Conclusions In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones.

Cadmium-Related Mortality and Long-Term Secular Trends in the Cadmium Body Burden of an Environmentally Exposed Population

Background Few population studies have reported on the long-term changes in the internal cadmium dose and simultaneously occurring mortality. Objective We monitored blood cadmium (BCd), 24-hr urinary cadmium (UCd), and mortality in an environmentally exposed population. Methods Starting from 1985, we followed BCd (until 2003), UCd (until 1996), and mortality (until 2007) among 476 and 480 subjects, randomly recruited from low- exposure areas (LEA) and high-exposure areas (HEA). The last cadmium-producing plant in the HEA closed in 2002. Results From 1985–1989 to 1991–1996, BCd decreased by 40.3% and 18.9% in the LEA and HEA, respectively (p < 0.0001 for between-area difference). From 1991–1996 until 2001–2003, BCd remained unchanged in the HEA (+ 1.8%) and increased by 19.7% in the LEA (p < 0.0001). Over the entire follow-up period, the annual decrease in BCd averaged 2.7% in the LEA (n = 258) and 1.8% in the HEA (n = 203). From 1985–1989 to 1991–1996, UCd fell by 12.9% in the LEA and by 16.6% in the HEA (p = 0.22), with mean annual decreases of 2.7% (n = 366) and 3.4% (n = 364). Over 20.3 years (median), 206 deaths (21.5%) occurred. At baseline, BCd (14.6 vs. 10.2 nmol/L) and UCd (14.1 vs. 8.6 nmol/24-hr) were higher in deaths than in survivors. The risks (p ≤ 0.04) associated with a doubling of baseline UCd were 20% and 44% for total and noncardiovascular mortality, and 25% and 33% for a doubling of BCd. Conclusions Even if zinc–cadmium smelters close, historical environmental contamination remains a persistent source of exposure. Environmental exposure to cadmium increases total and noncardiovascular mortality in a continuous fashion without threshold.

Environmental exposure to cadmium and renal function of aged women in three areas of Belgium

Abstract The relationship between environmental cadmium pollution and prevalence of signs of renal disturbance was investigated. Women over 60 years of age who had spent the major part of their life in a cadmium-polluted area in Belgium (Liege, n = 60) and who had never been occupationally exposed to cadmium constituted the “exposed” group. Women living in two areas less polluted by cadmium (Charleroi, n = 70, and Brussels, n = 45) served as “control” groups. The group of aged women from the Liege area has on the average a higher cadmium body burden, as reflected by an increased excretion of cadmium in urine, than the groups of aged women in the two other areas. The parameters selected for evaluating renal function (urinary excretion rates of total protein, amino acids, β 2 -microglobulin, albumin) follow the same trend. Furthermore, a statistically significant correlation was found between the urinary excretion rate of cadmium and that of total protein, amino acids, β 2 -microglobulin, and albumin. The results suggest that environmental pollution by cadmium as found in some industrialized areas in Europe may exacerbate the age-related decline of renal function in population groups nonoccupationally exposed to heavy metals.

Impact of Environmental Cadmium Pollution on Cadmium Exposure and Body Burden

The body burden of cadmium, as estimated from 24-h urine cadmium levels, was determined in 1,523 subjects who were not occupationally exposed and who lived in five areas of Belgium. Urinary cadmium levels differed significantly with place of residence. These differences persisted after standardization for the other significant determinants (i.e., age, body mass index, smoking habits, social class, alcohol consumption, and menopause). The highest 24-h urine cadmium levels were found in subjects who lived in areas that contained cadmium-polluted soils. The body burden overload has been attributed mainly to the consumption of locally grown vegetables and the use of contaminated well water for cooking and drinking. Blood cadmium levels were also dependent on place of residence. However, the geographical differences in blood cadmium did not parallel those of urine cadmium. Blood cadmium is more influenced by recent exposure; therefore, this latter observation might reflect the recent implementation of preventive measures in some areas.

Response of free erythrocyte porphyrin and urinary ? -aminolevulinic acid in men and women moderately exposed to lead

SummaryThe responses of various biological parameters of the haem biosynthesis pathway in a group of adult male and female workers moderately exposed to inorganic lead have been compared. The identical range of blood lead levels in both groups indicates a similar degree of exposure. Women, however, exhibit a larger increase in free erythrocyte porphyrin (FEP) and in urinary δ-aminolevulinic acid (ALA-U) than men.The earlier response in women is probably not due to a relative degree of anaemia (menstrual blood loss) as compared to men, since there is no significant correlation between haemoglobin (Hb) and FEP or ALA-U, and consequently standardization for the same Hb-content does not modify the independent effect of lead on the FEP and ALA-U responses. A greater susceptibility to Pb of the haem biosynthesis pathway in women has therefore been confirmed by the results of the present epidemiological survey among workers of both sexes.A preliminary and limited survey on children (11 to 12 years old) of schools situated at less than 1 km from a Pb-processing plant revealed increased FEP and blood lead concentrations and demonstrated that like women children exhibit an earlier biological response to Pb-B than adult men.

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.