Determination of a guidance value for the communication of individual-level biomonitoring data for urinary arsenic.

BACKGROUND: Available guidance values to interpret individual-level biomonitoring data (ILBD) for the sum of urinary inorganic-related arsenic species (SUIAS) are generally based on population statistical descriptors and not on a predetermined exposure level that should not be exceeded. The objective of this study was thus to propose a range of SUIAS concentrations, reflecting an exposure corresponding to WHO's provisional guideline value (PGV) for arsenic in drinking water (10 µg/L), within which an exposure-based biomonitoring guidance value can be identified. METHOD A comprehensive literature review was carried out in order to identify studies that were relevant to the determination of a guidance value. Drinking water arsenic exposure and urinary biomonitoring concentrations obtained from selected studies were used to conduct a structural equation modeling meta-analysis, from which regression coefficients were obtained to derive an interpretative guidance range. RESULTS Individuals exposed to the arsenic background level comparable to North American and European countries and to a water source contaminated at the WHO's PGV, would have, on average, urinary SUIAS between 9 and 20 µg/L, with the most probable value being 15 µg/L. To address the associated uncertainty, the final guidance value selection within this range may be based on a targeted sensitivity and specificity towards detecting overexposed individuals. Indeed, spans of sensitivity of 60-82%, and of specificity of 58-85%, were estimated for the proposed range based on drinking water exposure raw data from the literature. CONCLUSION The range of guidance values obtained appears suitable for interpreting and communicating ILBD in any population biomonitoring studies in which background exposure is comparable to the North American and European context. Before selecting a single value within the proposed range, it will be important for Public Health officials to assess the possible consequences of this selection on the management and communication of the biomonitoring results.

Biological monitoring of exposure to rare earth elements and selected metals in the Inuit population of Nunavik, Canada.

In Nunavik (Northern Quebec, Canada), some mining projects are envisioned, that could increase the contamination of the environment by various chemicals, including rare earth elements (REEs), and implicitly Inuit population exposure. The objective of this study was to determine the baseline biological exposure of the population to these elements, before the potential mining development occurs. In the framework of the 2017 Qanuilirpitaa? Inuit health survey, urine samples were obtained from a representative sample of the adult Nunavik population, which were used to constitute 30 pooled samples according to age, sex and Nunavik subregions. Pooled samples were analyzed using sensitive and accurate methods involving ICP-MS platforms to quantify urinary concentrations of 17 REEs and 7 elements of interest in Nunavik (arsenic, antimony, chromium, cobalt, nickel, thallium and uranium). REEs were mostly not detected in pooled samples from this population. Detectable concentrations were found in some samples for cerium (range: 0.5-0.7 nmol/L; 27% > method detection limit (MDL) and lanthanum (range: 0.2-0.4 nmol/L; 33% > MDL). As for the other elements of interest, antimony, arsenic, cobalt and thallium were detected in 100% of the samples, whereas chromium and nickel were detected in 83% and 80% of the samples, respectively. Concentrations of arsenic (geometric mean (GM) = 0.5 µmol/L) and cobalt (GM = 5.2 nmol/L) were greater than in the general Canadian population; the opposite was observed for nickel (GM = 8.9 nmol/L). Arsenic concentrations increased significantly with age, whereas the opposite trend was observed for nickel and thallium. In this first biomonitoring study focusing on REEs and carried out in a representative sample of the Nunavik population, we found no evidence of significant exposure from pooled samples analysis. These results could eventually be used as baseline values in future studies aiming to assess temporal trends of exposure to REEs.

A probabilistic toxicokinetic modeling approach to the assessment of the impact of daily variations of lead concentrations in tap water from schools and daycares on blood lead levels in children.

The aim of this study was to assess the impact of exposure to tap water lead concentration ([Pb]TW) occurring in schools or daycares on blood lead level (BLL) of attending children. Given the potentially wide variations in space and time of ([Pb]TW) documented in the literature, a simple probabilistic toxicokinetic (STK) model that allows the simulation of the time-varying evolution of BLL in response to these variations was developed. Thus, basic toxicokinetic equations were assembled to simulate BLL in a typical infant, toddler and pupil. The STK model's steady-state BLL predictions showed good correspondence when validated against Integrated Exposure and Uptake BioKinetic model predictions for comparable [Pb]TW values. Exposures to three distributions of [Pb]TW in specific sets of Canadian schools and daycares documented in the scientific literature were simulated probabilistically with Monte Carlo simulations. For the highest distribution of [Pb]TW simulated (median, 90th percentile = 24, 412 µg/L), average annual BLL (median, 97.5th percentile) varies between 1.5 and 6.4 µg/dL in infant and 1.1 and 3 µg/dL in pupils. Toddler's results were midway between those from the infants and pupils. Under this exposure scenario, the infant may present BLL > 5 µg/dL for a significant number of days over the course of the academic year (median; 97.5th: 17; 227 days). However, peak exposure may remain unnoticed if rare and drowned out by the background BLL. In conclusion, even if they may be sparse, peak exposure episodes to [Pb]TW in schools and daycares may suffice to increased BLL in attending individuals. This finding emphasizes the need for further characterization of [Pb]TW in schools and daycares in order to identify potentially problematic institutions and therefore avoid undesirable exposures for the children attending them.

Deriving A Drinking Water Guideline for A Non-Carcinogenic Contaminant: The Case of Manganese.

Manganese is a natural contaminant of water sources. It is an essential oligo-element, which may exert toxicity at high doses, particularly via inhalation. Its toxicity by the oral route is less known, but epidemiological and experimental studies tend to support its neurodevelopmental toxicity in infants and children. This paper describes the method used by a middle-size public health institution to derive a Drinking Water Guideline (DWG) for manganese. After reviewing the work done by major public health institutions, authors confirmed the use of experimental data to derive a point-of-departure (POD) of 25 mg of manganese/kg/day, based on neurodevelopmental effects on pup rats. Then, a total uncertainty factor of 450 was applied to calculate a Toxicological Reference Value (TRV) of 55 µg/kg/day. The final DWG proposed for manganese is 60 µg/L and is based on a relative source contribution (RSC) of water of 20% and an infant drinking scenario of 182 mL/kg of body weight (BW) of water (95th percentile of the ingestion rate distribution for 0⁻6 months). Despite its limitations, e.g., starting with the work done by other agencies, such an approach demonstrates in a transparent way the rationale and challenging choices made by regulators when deriving a DWG.

Human health risk assessment on the consumption of fruits and vegetables containing residual pesticides: A cancer and non-cancer risk/benefit perspective.

Pesticide residues in food is a public health concern. This study aimed to evaluate health risk and benefit associated with chronic consumption of fruits and vegetables (F&V) containing residual pesticides in the province of Quebec, Canada. Based on a representative sample of Quebecers (n=4727, aged 1-79) enrolled in the Canadian nutrition survey, population's mean chronic dietary exposure through consumption of F&V was evaluated for 169 different pesticide active ingredients (PAI), including 135 for which toxicological reference values (TRV) were available in the literature. Total lifetime cancer risk was estimated to be 3.3×10-4 considering the 28 substances for which an oral slope factor was also available. Non-cancer risk quotients greater than 1 were obtained at the 95th percentile of children's exposure for 10 of the 135 PAIs, and considering the most severe pesticide-specific TRV. Dithiocarbamates and imazalil are the authorized PAI that contribute the most to cancer and non cancer risk; they are therefore identified as "priority" PAI. For each estimated case of cancer triggered by PAI exposure, at least 88 cases were deemed prevented by the consumed F&V, based on the population's etiological fraction of the cancer risk that F&V prevent. Concluding, chronic health risks investigated are low and health benefits of F&V consumption by far outweigh the PAI-related risk. However, risk estimates are not negligeable and uncertainties remain. Thus, reducing PAI exposure through F&V consumption with a particular focus on "priority" PAI mentionned above, while maintaining an abundant and varied F&V diet, is desirable.

Lung cancer and mesothelioma risk assessment for a population environmentally exposed to asbestos.

Asbestos-related cancer risk is usually a concern restricted to occupational settings. However, recent published data on asbestos environmental concentrations in Thetford Mines, a mining city in Quebec, Canada, provided an opportunity to undertake a prospective cancer risk assessment in the general population exposed to these concentrations. Using an updated Berman and Crump dose-response model for asbestos exposure, we selected population-specific potency factors for lung cancer and mesothelioma. These factors were evaluated on the basis of population-specific cancer data attributed to the studied area's past environmental levels of asbestos. We also used more recent population-specific mortality data along with the validated potency factors to generate corresponding inhalation unit risks. These unit risks were then combined with recent environmental measurements made in the mining town to calculate estimated lifetime risk of asbestos-induced lung cancer and mesothelioma. Depending on the chosen potency factors, the lifetime mortality risks varied between 0.7 and 2.6 per 100,000 for lung cancer and between 0.7 and 2.3 per 100,000 for mesothelioma. In conclusion, the estimated lifetime cancer risk for both cancers combined is close to Health Canada's threshold for "negligible" lifetime cancer risks. However, the risks estimated are subject to several uncertainties and should be confirmed by future mortality rates attributed to present day asbestos exposure.