Exogeneous arsenic exposure estimation from urinary arsenic species measurements and prenatal exposure threshold for asthma in children

Exposure to inorganic arsenic (iAs, arsenite As³⁺ and arsenate As⁵⁺) is associated with many adverse health effects, such as skin lesions, cancer, and developmental and neurotoxicity. Using urinary measurement of iAs as an exposure metric may not be precise, as the levels of iAs and its metabolites excreted in urine are disproportionate to external exposure. We aimed to retrospectively estimate exogeneous exposures to iAs, monomethylated (MMA) and demethylated (DMA) from their urinary measurements, and to derive prenatal exposure threshold for asthma in children. Based on prior information obtained from previous pharmacokinetic studies, we employed a Bayesian Markov chain Monte Carlo simulation procedure to solve the corresponding pharmacokinetic equations for the unknown excretion and conversion parameters. We reanalyzed the arsenic urine measurements from 323 pregnant women in a previous study to estimate their exogeneous iAs exposure and its association with asthma incidence in 132 children from mother‒infant pairs at 8, 11, and 14 years of age. In contrast to the results obtained with urinary iAs, the exogeneous iAs estimates was significantly associated with asthma incidence in children. The derived BMDL_0.1 (lower bound of the benchmark dose with an extra risk of 0.10) ranged from 0.25 to 0.29 μg/kg_bw/day, which was slightly higher than the BMDL₀₅ of 0.06 μg/kg_bw/day for skin cancer as recommended by the EFSA. Approximately 25 % of the studied pregnant women exceeded this level. The retrospective exposure estimation for arsenicals may have applications in epidemiological studies and health risk assessment. Further studies to reduce prenatal exposure to iAs are recommended.