Ariane Leroyer

Renal and Neurologic Effects of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple Interactions at Environmental Exposure Levels

Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children’s health is little known. We studied their effects on two main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and β2-microglobulin were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> 55 μg/L; mean, 78.4 μg/L). The urinary excretion of retinol-binding protein, Clara cell protein, and N-acetyl-β-d-glucosaminidase was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children’s renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals.

Biomarkers of Renal Effects in Children and Adults with Low Environmental Exposure to Heavy Metals

The health effects of chronic exposure to heavy metals such as lead, cadmium, and mercury are widely documented, yet few data exist about the renal impact of low environmental exposure to these metals, particularly in children. The aim of this study was to assess renal parameters in children and adults living in an environment known for its past heavy metal contamination around two nonferrous smelters in northern France (Noyelles-Godault and Auby) and to compare their results with age and gender-matched controls living in neighboring municipalities with unpolluted soil (total: 400 children, 600 adults, sex ratio = 1). The integrity of renal function was assessed by measuring the urinary excretion levels of total protein, albumin, transferrin, g 2 -microglobulin, retinol-binding protein, brush border antigen, and the enzyme N-acetyl- g -D-glucosaminidase (NAG). The mean blood concentrations of lead (Pb-B, children h 42.2 w /L, adults h 71.3. w /L) and of cadmium (Cd-B, children h 0.52 w g/L, adults 0.86 w g/L) were all relatively low, indicating a low uptake of these heavy metals from the environment despite relatively high levels in soil (between 100 and 1700 ppm for lead and 0.7 to 233 ppm for cadmium). Pb-B levels were, however, significantly increased in boys, girls, and women--but not men--living in the polluted area. Boys, men, and women living in the polluted area had also on average higher Cd-B levels. The concentrations of mercury in urine (Hg-U) were by contrast similar in control and exposed groups. None of the renal parameters studied showed a significant difference between control and exposed groups. The influence of heavy metals on renal parameters was further assessed by stepwise multiple regression, testing Pb-B, Cd-B, Hg-U, age, gender, body mass index (BMI), urinary creatinine levels, and area of residence as predictors in both children and adults, including first-order metal interaction terms, smoking habits, and alcohol consumption in adults. The only positive correlation was found between the urinary excretion of NAG activity (standardized for BMI and urinary creatinine) and Cd-B levels when taking the whole children population, indicating that even low cadmium burdens may produce subtle effects on the proximal tubule in children, although deleterious consequences are unlikely should exposure not increase. However, in the absence of other positive findings even after studying the smaller subgroups with higher levels of heavy metals, these results are clearly indicative of the minimal renal impact of living around nonferrous smelters that are currently complying with pollution regulations, even when soil contamination is still high.

Environmental lead exposure in a population of children in northern France: Factors affecting lead burden

BACKGROUND This study is part of the assessment of a site in northern France polluted by lead from industrial emissions. Our objectives were to look for the factors that influence lead burden in children aged 8-11 years. METHODS A cross-sectional population-based study took place in 1996-97 and included 400 children (200 of whom lived on the metal-polluted site). RESULTS The geometric mean of the blood-lead levels of children living on the polluted site was 39.5 microg/l (95% CI = 36.3-43.1); that of the non-exposed children was 30.6 microg/l (95% CI = 27.8-33.6) (P < 0.0001). Analysis of the variations in the mean blood-lead levels showed associations with: distance from the smelting plants (mean blood-lead level fell by a factor of 1/1.3 (95% CI = 1/1.2-1/1.4) for each km from the smelter over the range of 1-3 km and was constant thereafter) and consumption of tap water (when the water pipes were made of lead, the mean blood-lead level of children who drank tap water was twice as high (95% CI = 1.2-3.4) as that of children who did not). CONCLUSIONS The childrens blood-lead levels were essentially linked to two factors: proximity to the smelters and drinking tap rather than bottled water.

Environmental exposure to lead in a population of adults living in northern France: lead burden levels and their determinants

As part of the assessment of a site in northern France polluted by metals from two smelters (in particular, lead, cadmium and mercury), a cross-sectional study was carried out which intended to estimate the levels of the lead burden of the adult population living on the site and the factors associated with these levels. The exposed zone included 10 municipalities in the Nord-Pas de Calais region, located in the vicinity of two non-ferrous metal smelters. The soils in these municipalities contained between 100 and 1700 ppm of lead. The non-polluted zone contained 20 municipalities from the same region, drawn randomly from those in the region of comparable size but free from any industrial lead exposure. The adult study population (301 men and 300 women) was stratified according to age, sex, employment status and exposure level. The inclusion criteria required subjects who were aged between 20 and 50 years and had been living in the exposed zone for at least 8 years; the exclusion criteria were pregnancy, cancer, kidney disease and diabetes. No more than 10% of the subjects participating could work at one of the two smelters. Data collection took place at home; visiting nurses interviewed subjects to complete a questionnaire and also took blood samples. The lead assay was performed by atomic absorption spectrometry. The geometric mean of the blood-lead levels was 74 microg/l, 95% CI = 69-80 among men and 49 microg/l, 95% CI = 46-53 among women. Blood-lead levels exceeding 100 microg/l were found among 30% of men and 12% of women. Several factors were associated with variation of the mean blood-lead level: the blood-lead level was significantly higher among the men for subjects living less than 1 km from the smelters (geometric mean x 1.3, 95% CI = 1.1-1.6), for those who drink alcoholic beverages (x 1.1, 95% CI = 1.0-1.2 for consumption of 30 g/day), those who smoke (x 1.2, 95% CI = 1.0-1.3 for 20 cigarettes/day), and for subjects with occupational exposure; among the women, for subjects living less than 1 km from the smelters (geometric mean x 1.5, 95% CI = 1.2-1.7), for those who drink alcohol (x 1.1, 95% CI = 1.1-1.2 for a daily consumption of 10 g), and for women living in a building constructed before 1948 (x 1.2, 95% CI = 1.0-1.4).

Urinary homovanillic acid and serum prolactin levels in children with low environmental exposure to lead

Current evidence suggests that the neurotoxic effects of lead may partially be mediated through interference with the dopaminergic system. The aim of this study was to assess the levels of two peripheral dopaminergic markers- serum prolactin (Pro-S) and urinary homovanillic acid (HVA-U) - in children living around two lead smelters, who are presumed to be exposed to high environmental lead pollution (n = 200), and compare their results with 200 age- and sex-matched controls living in an area unpolluted by heavy metals, giving a total of 400 children (200 boys and 200 girls). The influence of lead exposure on HVA-U and Pro-S was assessed by stepwise multiple regression, testing lead concentrations in blood (Pb-B), age, sex and area of residence as predictors. Though lead levels were significantly higher in boys and in the lead-polluted environment, mean Pb-B values were relatively low, indicating a low uptake of lead in the contaminated environment (39.5 μg l-1, range 4.6-165μgl-1, n = 200), and no significant correlation could be found with either Pro-S or HVA-U. However, when the subgroup of 121 children with Pb-B levels above 50 μg l-1 were considered, a weak positive correlation was found between Pb-B and HVA-U (r2 = 0.04, p = 0.03), whilst in the even smaller subgroup of 15 children with Pb-B levels above 100 μg l-1, Pro-S appeared to be positively correlated with Pb-B, though the numbers of children were too small for the correlation to reach statistical significance (p = 0.095). These weak associations, probably not important in biological terms, indicate that Pro-S and HVA-U are not useful biomarkers at present exposure levels to lead in the environment. Nevertheless, the finding of subtle biochemical alterations in the dopaminergic system at Pb-B levels of around 100μgl-1 supports the recommended setting of the action level at this value.

Long-term occupational trajectories and suicide: a 22-year follow-up of the GAZEL cohort study

Objective Most suicides occur among individuals of working age. Risk is elevated in some occupational groups, however relations between long-term occupational trajectories and suicide are not well known. We describe career-long occupational trajectories and examine their influence on suicide. Methods Data come from GAZEL, a French cohort study set among employees of a large national utilities company. Occupational grade was obtained from company records from the time of hiring (1953‒1988). Group-based trajectory models were used to define occupational trajectories over a mean time period of 25.0 (standard deviation 6.5) years. Causes of mortality, coded using the International Classification of Diseases, were recorded from 1993‒2014 and studied using Cox regression models. Results Of the 20 452 participants included in the study, 73 died by suicide between 1993‒2014. Results suggested an increased risk of suicide [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.08-6.15] among participants with persistently low occupational grade compared to those with higher occupational grade and career development. After adjustment for all covariates, especially psychological factors, this association was reduced and no longer statistically significant (HR 2.02, 95% CI 0.82-4.95). Conclusions Persistently low occupational grade could be related to an elevated risk of suicide. This association partly reflects psychological and health characteristics, which can influence occupational trajectories and be reinforced by unfavorable work conditions.

Exposition aux solvants organiques dans l’industrie de chaussures à Sfax (Tunisie)

IntroductionMalgre l’importance de l’utilisation des solvants organiques dans l’industrie de la chaussure, les donnees d’exposition des salaries a ces solvants sont quasi absentes en Tunisie. L’objectif de cette etude est d’instaurer une surveillance biotoxicologique d’exposition dans les entreprises de fabrication de chaussures dans le cadre d’une etude pilote afin de la generaliser dans tous les secteurs industriels de la metropole de Sfax.

Case Study: Occupational Assessment of Exposure to Organic Solvents in an Adhesive Producing Company in Sfax, Tunisia

The Ontario Ministry of the Environment (MOE) sets science-based ambient air quality criteria, or AAQCs, to evaluate regional air quality data. An AAQC is a desirable concentration of a contaminant in air that is unlikely to adversely affect human health or the environment. The term “ambient” is used to reflect general air quality independent of location or source of a contaminant. AAQCs are most commonly used in environmental assessments, special studies using ambient air monitoring data, assessment of general air quality in a community and annual reporting on air quality across the provinceS fax, the second largest city in Tunisia, is considered one of the main industrial and agricultural pillars of the country’s economy. At the industrial level, adhesive producing companies are known for their great consumption of organic solvents. Chemical risks caused by organic solvents encountered in this sector occupy, by far, first place in terms of health hazards.(1,2) In spite of the large quantity of solvents used, there is little information on exposure of workers to these chemical reagents and on their health effects. Prevention of occupational hazards, and more specifically of chemical risks, rests on regulatory procedures.(3,4) The Tunisian regulation on health impact,(5–7) however, does not require employers to carry out air concentration measurements or to assess biological exposure indexes (BEI) in working areas. This investigation on solvent exposure levels was conducted in an adhesive producing company with the participation of a group of volunteer workers. The main solvents used in the studied company are acetone, cyclohexane, n-hexane, methylethylketone, toluene, and trichloroethylene. Assessment of the occupational exposure to this mixture of solvents was based on atmospheric measurements and analysis of workers’ urine.