A harmonized occupational biomonitoring approach.

Biomonitoring has been widely used in assessing exposures in both occupational and public health complementing chemical risk assessments because it measures the concentrations of chemical substances in human body fluids (e.g., urine and blood). Biomonitoring considers all routes and sources of exposure. An occupational biomonitoring guidance document has been elaborated (OECD Occupational Biomonitoring Guidance) within the OECD framework and specifically, the Working Parties on Exposure and Hazard Assessment by scientific experts from 40 institutes and organizations representing 15 countries. The guidance provides practical information for assessing chemical exposures in occupational settings including the three common routes of exposure: inhalation, skin absorption and ingestion due to hand to mouth contact. The elaborated stepwise approach for conducting biomonitoring is tailored for occupational health professionals, scientists, risk assessors, and regulators. It includes methods for selecting appropriate biomarkers, devising sampling strategies, and assessing laboratories for validated analytical methods for the biomarker of interest, and ensuring timely feedback of results. Furthermore, it describes procedures for setting up efficient biomonitoring programs based on the Similar Exposure Group (SEG) approaches. Derived health-based human exposure biomarker assessment values called Occupational Biomonitoring Levels (OBLs) are proposed for use in occupational exposure and risk assessment. It also helps with the interpretation of biomonitoring results routinely collected and procedures for communicating biomonitoring results at individual, collective, and workplace levels. Ethical considerations associated with biomonitoring are also discussed. The ultimate goal of this biomonitoring approach is to promote harmonized application and interpretation of biomarkers as well as evidence-based occupational risk management measures.

Human Biomonitoring Initiative (HBM4EU): Human Biomonitoring Guidance Values Derived for Dimethylformamide.

Within the European Joint Program on Human Biomonitoring HBM4EU, human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GVGenPop) or for occupationally exposed adults (HBM-GVWorker) are derived for prioritized substances including dimethylformamide (DMF). The methodology to derive these values that was agreed upon within the HBM4EU project was applied. A large database on DMF exposure from studies conducted at workplaces provided dose-response relationships between biomarker concentrations and health effects. The hepatotoxicity of DMF has been identified as having the most sensitive effect, with increased liver enzyme concentrations serving as biomarkers of the effect. Out of the available biomarkers of DMF exposure studied in this paper, the following were selected to derive HBM-GVWorker: total N-methylformamide (tNMF) (sum of N-hydroxymethyl-N-methylformamide and NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine. The proposed HBM-GVWorker is 10 mg·L-1 or 10 mg·g-1 creatinine for both biomarkers. Due to their different half-lives, tNMF (representative of the exposure of the day) and AMCC (representative of the preceding days' exposure) are complementary for the biological monitoring of workers exposed to DMF. The levels of confidence for these HBM-GVWorker are set to "high" for tNMF and "medium-low" for AMCC. Therefore, further investigations are required for the consolidation of the health-based HBM-GV for AMCC in urine.

Human biomonitoring initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) derived for cadmium and its compounds.

AIMS: The methodology agreed within the framework of the HBM4EU project is used in this work to derive HBM-GVs for the general population (HBM-GVGenPop) and for workers (HBM-GVWorker) exposed to cadmium (Cd) and its compounds. METHODS: For Cd, a significant number of epidemiological studies with dose-response relationships are available, in particular for kidney effects. These effects are described in terms of a relation between urinary Cd (U-Cd) or blood Cd (B-Cd) levels and low molecular weight proteinuria (LMWP) markers like beta-2-microglobulin (ß2M) and retinol-binding protein (RBP). In order to derive HBM-GVs for the general population and workers, an assessment of data from evaluations conducted by national or international organisations was undertaken. In this work, it appeared relevant to select renal effects as the critical effect for the both groups, however, differences between general population (including sensitive people) and workers (considered as an homogenous population of adults who should not be exposed to Cd if they suffer from renal diseases) required the selection of different key studies (i.e. conducted in general population for HBM-GVGenPop and at workplace for HBM-GVWorker). RESULTS AND CONCLUSIONS: For U-Cd, a HBM-GVGenPop of 1 µg/g creatinine (creat) is recommended for adults older than 50 years, based on a robust meta-analysis performed by EFSA (EFSA, 2009a). To take into account the accumulation of Cd in the human body throughout life, threshold or 'alert' values according to age were estimated for U-Cd. At workplace, a HBM-GVWorker of 2 µg/g creat is derived from the study of Chaumont et al., (2011) for U-Cd, and in addition to this recommendation a HBM-GVworker for B-Cd of 5 µg/L is also proposed. The HBM-GVWorker for U-Cd is similar to the biological limit value (BLV) set by the new amendment of the European Carcinogens and Mutagens Directive in June 2019 (2 µg/g creat for U-Cd).

Risk of lung cancer associated with occupational exposure to mineral wools: updating knowledge from a french population-based case-control study, the ICARE study.

OBJECTIVES: To assess the risk of lung cancer associated with exposure to mineral wools (MWs), while taking into account smoking, asbestos, and crystalline silica exposures. METHODS: The analyses were restricted to men (1350 cases and 1912 controls). Lifelong occupational history was collected. MWs and asbestos exposures were assessed, using task-exposure matrices and silica exposure, a job-exposure matrix. RESULTS: We observed consistent not-significant increased risks of lung cancer of the same order of magnitude among workers exposed to high levels of MWs (odds ratio, 1.4; 95% confidence interval: 0.9 to 2.2; for highest quartile of the Cumulative Exposure Index). CONCLUSIONS: These results do not allow to draw firm conclusion about a carcinogenic effect of MWs on the lung, but they cannot exclude it. Given the high number of potentially exposed workers, it will be necessary to replicate them in a future further removed from the asbestos ban.

Night work and breast cancer: a population-based case-control study in France (the CECILE study).

Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population-based case-control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99-1.64]). Odds ratios were 1.35 [1.01-1.80] in women who worked on overnight shifts, 1.40 [1.01-1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01-2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13-3.35] in women employed in night work for >4 years before their first full-term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full-term pregnancy.

Breast cancer risk by occupation and industry: analysis of the CECILE study, a population-based case-control study in France.

BACKGROUND: It has been suggested that certain occupational exposures may play a role in breast cancer etiology. The recognition of high-risk occupations may give clues about potential mammary carcinogens in the work place. METHODS: We conducted a population-based case-control study in France including 1,230 breast cancer cases and 1,315 population controls with detailed information on lifetime work history. Odds ratios for women ever employed in an occupation or industry were adjusted for well-established risk factors for breast cancer. RESULTS: Adjusted odds ratios were marginally increased in some white-collar occupations, as well as in textile workers (2.4; 95% CI [0.9-6.0]), rubber and plastics product makers (1.8; 95% CI [0.9-3.5]), and in women employed for more than 10 years as nurses (1.4; 95% CI [0.9-2.1]) and as tailors/dressmakers (1.5; 95% CI [0.9-2.6]). The incidence of breast cancer was increased among women employed in the manufacture of chemicals, of non-metallic mineral products, and decreased among women in agriculture. CONCLUSIONS: These findings suggest a possible role of occupational exposures in breast cancer, including night-shift work, solvents and endocrine disrupting chemicals and require further studies with detailed assessment of occupational exposures.