(511b) Risk Characterization of Cadmium Based on Human Biomonitoring Data

The purpose of this study was to describe and evaluate forward integrated exposure model for Cadmium (Cd). This included the construction and analysis of exposure scenarios in order to calculate expected relevant biomarker levels (e.g cadmium concentration in urine and blood), which were directly compared with real life human biomonitoring (HBM) data. Towards this goal, exposure estimates for cadmium were calculated using the integrated exposure modelling platform INTEGRA and were later validated with HBM data. The assessment of Cd intake included major exposure pathways such as diet water, inhalation, dust and soil ingestion. Diet mostly corresponded to meat and edible offal food category, fish and seafood, vegetables and vegetables products, grains and drinking water. The HBM data, collected in the framework of several studies and facilitated by the HBM4EU consortium in an effort to cover a large part of EU Member states, were aggregated and age differentiated. HBM data were accompanied by detailed exposure related to environmental emissions data, food items residues concentration in dust and in soil, concentration in ambient and indoor air, were used as ancillary data for exposure reconstruction, describing multi-pathway and multi-route exposure.

Exposure reconstruction, a process of corresponding HBM data to external exposure, uses deterministic methods such as the intake mass balance and stochastic methods such as exposure conversion factor and Bayesian approach. This methodology is able to approximate the daily intake and to address complex exposure scenarios, dynamic in time. The HBM data have been selected since they pose a very good approximation of aggregate exposure, providing an integrated overview of the body burden to xenobiotics that an individual is exposed to. For the exposure reconstruction of cadmium, toxicokinetic properties were based on previous well validated models. According to those, cadmium metal and cadmium salts are not well absorbed. Approximately 1% of the dose is absorbed following inhalation, oral or dermal exposure. Absorption of cadmium is affected by properties such as absorption efficiency of each route. After absorption, cadmium is widely distributed throughout the body. Moreover, cadmium does not undergo any direct metabolic reaction, such as oxidation, reduction or alkylation, leading to very slow excretion of absorbed cadmium (almost 0.01% of the body burden per day). As a consequence, as it is also reflected by the biomonitored levels (urine, blood), cadmium accumulates through lifetime.

The results of the study can be considered representative for the general population in the EU from newborns to the elderly. They showed that diet is the main source of Cd exposure and it is mostly related to items highly consumed by adults. The daily intake for all age groups ranges between 0.2 and 1 μg/kg_bw/d. Adults are also susceptible to Cd exposure through smoking which has been proved to be the second most prevalent exposure pathway. The daily intake contribution of smoking found to be 0.02 μg/kg_bw/d. The average daily intake estimate remains constant independently on the biological matrix in which the HBM data was reported in the first place (blood-urine). Regarding to HBM data, the levels of Cd in blood and urine are in the range of 0.1 to 1 mg/L. Moreover, the expected biomonitored levels are not directly related to the daily intake patterns, but to the accumulation through aging. These observations are highly corroborated with the indicative measure levels, confirming the robustness of the estimates and provide increased confidence when using it to compare with regulatory thresholds based on the toxicological properties of Cd in humans. Lastly, the analysis indicated that individuals that are highly exposed to cadmium are close to the EFSA tolerable week intake of 2.5 μg/kg_bw. Internal dose was calculated based on reconstructed intakes calculated by HBM data of cadmium in urine. In most of the studies it found to be 0.1 and 1 μg/g. This is the result of cadmium’s high accumulation in the kidneys, due to its very slow elimination.

Exposure reconstruction and internal dose assessment offer unique opportunities regarding the interpretation of HBM data, quantitatively associating them with exposure pathways contribution in the overall intake. In order to carry out exposure reconstruction, a minimum of information regarding the toxicokinetic behavior of the compound of interest is required. This allows the translation of the biomarker levels measured at a given point in time, to long-term daily intake patterns. Thus, the level of confidence regarding the intake estimates or the exposure levels of a specific pathway and route (e.g. identification of contribution of smoking over diet regarding Cd exposure) requires more detailed information regarding the daily activity pattern and microenvironments encountered, dietary habits and consumer products use. This in turn requires the use of individual HBM data, accompanied by ancillary information that would shed light on the mechanistic link between exposure dynamics and observed HBM data.