Regulatory Implications of Cumulative Risk for Perchlorate as an Iodide Uptake Inhibitor

Abstract

This research applies aggregate and cumulative risk assessment considerations to intakes of compounds acting through the sodium-iodide symporter mechanism to produce iodide uptake inhibition into the thyroid. Four approaches to setting regulatory limits considered here based on NOELs/LOELs yield the following estimates of the safe levels of perchlorate in water (when perchlorate in water is the sole intake) or total goitrogens (PEC) acting through the same mechanism: 1) Approach 1: 18 μg/L; 2) Approach 2: 400 μg/L (50% required inhibition) or 38 μg/L (5% required inhibition); 3) Approach 3: 338 μg/L (without serum half-life correction) or 573 μg/L (with serum half-life correction); 4) Approach 4: 737 μg/L (without serum half-life correction) or 973 μg/L (with serum half-life correction) for 50% required inhibition; 375 μg/L (without half-life) or 735 μg/L (with half-life) for 5% required inhibition. Where water is not the sole route of exposure and perchlorate is not the sole goitrogen acting through the sodium-iodide symporter mechanism, the results of Approaches 3 and 4 can be applied to mixtures of compounds that produce these values as PECs. Results of the analysis suggest that compound-by-compound regulatory limits may be better dealt with through a change to risk-based management strategies that are built around the concept of focusing limited regulatory resources on the main contributors to risks induced by the mechanism considered here.