Multi-omics inhalation toxicity assessment of urban soil dusts contaminated by multiple legacy sources of lead (Pb).

Although animal studies have evaluated lead (Pb) toxicity, they are limited to soluble forms, such as Pb-acetate, which do not reflect the range found in the exposome. Recent studies on Pb speciation of residential soils in urban areas revealed that the initial Pb sources are not persistent and are extensively repartitioned into adsorbed forms of Pb rather than insoluble phosphates. We investigated the inhalation and neurological toxicity of dusts generated from a surficial soil sample collected from a residential site with an exposomic mixture of various Pb species, both adsorbed phases (Fe and Mn oxide, humate bound Pb) and mineral phases (Pb hydroxycarbonate, pyromorphite, galena). Mice inhaled East Chicago dust (ECD) generated from a composite soil sample for 4 h/day, 7 days/week, for 4 weeks. Mice were necropsied immediately, 1, 14 and 30 days post exposure to evaluate both toxicity and recovery. Exposure to ECD caused changes in memory and spatial learning in the Morris Water Maze test. RNAseq analysis of the hippocampus region revealed multiple differentially expressed genes and impacts on pathways involved in ion channel complexes, and neuron-to-neuron synapse. Metabolomics analysis of plasma highlighted significant alterations in metabolic processes immediately after exposure that resolved after 14 days of rest.