With tobacco smoking, diet is the main source of cadmium (Cd) exposure in the general population. The carcinogenic and estrogenic activities of Cd make it a contaminant of potential concern for hormone-dependent cancers including breast cancer. Postmenopausal women represent the most appropriate population to investigate the possible impact of exogenous factors with potential estrogenic activity on breast cancer as, after menopause, their estrogenic influence is predominant. We systematically reviewed available studies on the association between dietary exposure to Cd and breast cancer focusing on postmenopausal women. A meta-analysis combining the risk estimators was performed and potential sources of between studies heterogeneity were traced. Studies were searched from MEDLINE through 31 January 2015 and from the reference lists of relevant publications. Six eligible studies published between 2012 and 2014 were identified and relative risk estimates were extracted. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect models. Meta-analyses were performed on the whole set of data and separate analyses were conducted after stratification for study design, geographic location, use of hormone replacement therapy (HRT), tumor estrogen receptor status (ER+ or ER-), progesterone receptor status (PGR+ or PGR-), body mass index (BMI), smoker status, zinc or iron intake. No statistically significant increased risk of breast cancer was observed when all studies were combined (mRR=1.03; 95% confidence interval [CI]: 0.89-1.19). Several sources of heterogeneity and inconsistency were identified, including smoker status, HRT use, BMI, zinc and iron intake. Inconsistency was also strongly reduced when only considering ER-, PGR-, tumors subgroups from USA and from Japan. The risks were, however, not substantially modified after stratifications. No evidence of publication bias was found. The present study does not provide support for the hypothesis that dietary exposure to Cd increases the risk of breast cancer in postmenopausal women. Misclassification in dietary Cd assessment in primary studies could have biased the results towards a finding of no association.

Inhalation exposure to cadmium at the workplace has been associated with an increased risk of lung cancer and non-cancer respiratory effects. To ensure levels of cadmium remain below effect levels, air quality is monitored and regulations specifying an air limit value are implemented. The EU Carcinogens and Mutagens Directive of 2019 recommended values for the inhalable fraction and the respirable fraction but the latter only for a transitional period. Cadmium exposure has also been associated with systemic effects, following its storage in the kidneys and due to its long half-life. The accumulation of cadmium occurs via different exposure routes and from different sources, including workplace dust and fumes, food, and smoking. Biomonitoring (in blood, urine) has been identified as the most appropriate method to follow up cumulative exposure and total cadmium body burden, as it conveniently reflects intakes by all routes. However, it is not systematically implemented. This paper has a double objective: first, proposing a possible limit value for the respirable fraction, using an approach integrating epidemiological data. Secondly, demonstrating that the implementation of both air and biological limit values is key to protecting workers’ health in occupational settings. The paper summarizes the current knowledge on cadmium health effects and how biomarkers reflect those. It presents an approach to derive a respirable value, using recent human data, and describes how the combination of air monitoring and biomonitoring is applied by the EU industry to protect the workforce. While a respirable fraction value helps protect workers against local respiratory adverse health effects, air monitoring alone is not sufficient to protect workers against systemic effects of cadmium. Therefore, complementary biomonitoring and the implementation of a biological limit value is recommended.

Zinc sulphide is a widely used inorganic powder, and its production has reached quantities greater than 1000 t/year. Therefore, in accordance with OECD guideline 436, an acute inhalation test was implemented to provide more accurate data. This study is crucial for ensuring the safety of workers exposed to zinc sulphide dust and complying with regulatory requirements for REACH. Due to particle-specific properties, the maximum attainable concentration of zinc sulphide for an inhalation study was not certain. Two dry dispersion systems were used to aerosolize the zinc sulphide powder, and the generated aerosol was supplied to a nose-only inhalation exposure system. The results showed a maximum attainable concentration of 0.82 mg/L at an MMAD of 1.5 µm over a 4 h exposure. In the inhalation study, all six rats showed no specific symptoms and good health status and survived a post-exposure observation period of up to 14 days. From the results observed, the status of Not classified was derived according to CLP. Based on the experimental results, an LC50 was not determined but is considered to be higher than 0.82 mg/L (the maximum achievable aerosol concentration). These findings highlight the importance of documenting efforts to achieve aerosol conditions when concentrations required by OECD test guidelines cannot be reached.