Cancer mortality and chemical exposure in a retrospective zinc and lead smelter cohort: A 48-year follow-up.

INTRODUCTION: Very few studies to date have investigated cancer mortality in non-ferrous metal smelters. Existing studies mainly focus on lead exposure and have reported inconsistent results. The aim of this study was to investigate the risk of excess cancer mortality in the employees of a lead and zinc smelter located in the north of France by 1) comparing mortality in this cohort of employees with that of the regional population; 2) studying the associations between occupational exposure and cancer deaths. METHODS: The study cohort was composed of male workers, born in France, who had been employed by the company in question for at least 365 consecutive days. A company-specific job-exposure matrix was produced in order to calculate a cumulative exposure index for 15 toxic agents. Deaths of smelter employees which occurred between January 1, 1968 and December 31, 2015 were compared to those in the regional population (standardized mortality ratio, SMR). The relationships between the cumulative exposure indexes and mortality by cancer site were studied using Cox regression models with age and the 20-year lagged cumulative exposure index as time-dependent variables. RESULTS: Vital status was found for 2177 of the employees in the cohort (98%). Median follow-up was 34.8 years (interquartile interval = 24.3-44.8), totaling 74,437 person-years. Compared to the regional population, no excess risk of all-cause mortality (n = 913, SMR = 0.96, 95%CI:0.90-1.02), nor of cancer mortality (n = 338, SMR = 0.97, 95%CI:0.87-1.08) was found. An overall significant excess risk of cancer mortality was found for employees who worked in this non-ferrous metal smelter for a period of between 15 and 29 years (n = 139, SMR = 1.23, 95%CI:1.04-1.45). Asbestos exposure was found to be associated with an increased risk of mortality for all cancer sites (p = 0.0012), lip-oral cavity-pharynx malignant neoplasms (MN) (p = 0.0141) and trachea-bronchus-lung MN (p = 0.0018); lead exposure was associated with the same risk for lip-oral cavity-pharynx (p = 0.0378) and liver MN (p = 0.0155); aromatic amine exposure with bladder MN (p = 0.0002); chromium exposure with colon-rectum-anus MN (p = 0.0057) and colon MN (p = 0.0315); bismuth exposure with rectal MN (0.0011) and sodium hydroxide vapor exposure with laryngeal MN (0.0150). CONCLUSION: Including occupational exposure to numerous toxic agents other than lead in this study of smelter mortality has made it possible to identify associations between different toxic agents and cancers, opening up new avenues for future research.

Bioaccessibility of trace elements as affected by soil parameters in smelter-contaminated agricultural soils: a statistical modeling approach.

An investigation was undertaken to identify the most significant soil parameters that can be used to predict Cd, Pb, and Zn bioaccessibility in smelter-contaminated agricultural soils. A robust model was established from an extended database of soils by using: (i) a training set of 280 samples to select the main soil parameters, to define the best population to be taken into account for the model elaboration, and to construct multivariate regression models, and (ii) a test set of 110 samples to validate the ability of the regression models. Total carbonate, organic matter, sand, P(2)O(5), free Fe-Mn oxide, and pseudototal Al and trace element (TE) contents appeared as the main variables governing TE bioaccessibility. The statistical modeling approach was reasonably successful, indicating that the main soil factors influencing the bioaccessibility of TEs were taken into account and the predictions could be applicable for further risk evaluation in the studied area.

Assessing Cd, Pb, Zn human bioaccessibility in smelter-contaminated agricultural topsoils (northern France).

The extractability of Cd, Pb, and Zn was investigated in contaminated agricultural topsoils located in an area highly affected by the past atmospheric emissions of two smelters in northern France in order to assess their mobility and human bioaccessibility. The determination of Cd, Pb, and Zn bioaccessibility (Unified Barge Method, in vitro test) was made to evaluate the absolute trace element (TE) bioavailability. The results highlighted differences in bioaccessibility between Cd, Pb, and Zn (Cd > Pb > Zn). The mean values of the bioaccessible fractions of Cd, Pb, and Zn during the gastric phase were 82, 55, and 33%, respectively, of the pseudototal concentrations, whereas during the gastrointestinal phase, the bioaccessible fractions of metals decreased to 45, 20, and 10%, respectively. Stepwise multiple regression analysis showed that human bioaccessibility was affected by various physicochemical parameters (i.e., sand, carbonates, organic matter, assimilated P, free Al oxides, and pseudototal Fe contents). Sequential extractions were performed as an indication of the TE availability in these soils. Cadmium occurred in the more available fractions, Pb was mostly present as bound by oxides, and a significant contribution to the pseudototal Zn concentration was defined as the unavailable residual form related to the crystalline structures of minerals. The concepts of bioavailability and bioaccessibility are important for quantifying the risks associated with exposure to environmental pollutants and providing more realistic information for human health.

1-Hydroxypyrene and 3-hydroxybenzo[a]pyrene as biomarkers of exposure to PAH in various environmental exposure situations.

OBJECTIVE: To evaluate the utility of urinary 3-hydroxybenzo[a]pyrene (3-OH-B[a]P) as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs) in various environmental exposure scenarios alongside the more usually studied 1-hydroxypyrene (1-OH-Pyr). METHODS: Two groups of 15 and 10 non smoking, healthy men and women, were exposed for approximately 6h to ambient air at two outdoor locations close to metallurgical industries, and at one indoor location in an urban setting. Atmospheric measurements of 16 "priority" PAHs were carried out during each exposure. Urinary 1-OH-Pyr and 3-OH-B[a]P were also analysed, samples being taken the morning before exposure, at the end of exposure, then 4 and 15 h after the end of exposure. Urinary 1-OH-Pyr and 3-OH-B[a]P were analysed using high performance liquid chromatograph with fluorescence detection. Limits of detection (LOD) were 0.092 nmol/L and 0.28 pmol/L for 1-OH-Pyr and 3-OH-B[a]P respectively. RESULTS: Average ambient air concentrations varied from 0.27 to 2.87 ng/m(3) for pyrene, 0.04 to 1.20 ng/m(3) for B[a]P, and from 70.0 to 910.6 ng/m(3) for the sum of the 16 PAH (SigmaPAHs). Concentrations of 1-OH-Pyr were not correlated with atmospheric concentrations of PAHs to which subjects were exposed, nor with the concentrations of 3-OH-B[a]P. Nearly 80% of measurements of 3-OH-B[a]P were lower than the LOD and no relationship between atmospheric concentrations and urinary metabolites was observable. However, the percentage of post-exposure values of 3-OH-B[a]P greater than the LOD increased significantly with the median of atmospheric concentrations of Pyr, B[a]P and SigmaPAH at the different sites (test of linear trend, p<0.02 in all cases). CONCLUSION: Although we used very sensitive techniques for the measurements of urinary metabolites, especially for 3-OH-B[a]P, neither 1-OH-Pyr nor 3-OH-B[a]P were an unequivocal biomarker of exposure to atmospheric PAHs in environmental exposure scenarios relevant to the general population. It would be interesting to investigate other urinary monohydroxy PAH metabolites in this context.