Environmental exposure to heavy metal mixture of lead (Pb), cadmium (Cd), and mercury (Hg) would induce hazardous health effects. However, there is a paucity of data on how exposure to heavy metal mixture alters the metabolic dynamics of individual metals. Considering that the dose plays a key role in determining the toxicity of heavy metals, we performed a factorial design with three heavy metals (Pb, Cd, and Hg) at low exposure levels. Female rats were exposed to Pb, Cd, and (or) Hg from successful mating until pup weaning. Their concentrations in maternal blood, breast milk, and postnatal day 0 (PND0) and PND21 offspring blood and whole brain were measured. Using ANOVA analysis, Pearson correlation, and structural equation model, we demonstrated the complex interactions among heavy metals during their absorption, mother-offspring transport, and target organ accumulation. Among all the explored samples, almost all the highest Pb, Cd, and Hg levels were observed in their respective single heavy metal exposure groups. In addition, Hg was found could antagonize the transport of Pb or Cd, when they cross the placental barrier and blood-brain barriers (BBB). However, the effect of Hg no longer presented when they are absorbed through the digestive system. The antagonistic effect of Pb on Cd was observed when they cross the placental barrier. In addition, Cd was also found to compete the transport pathway of Pb when they cross the BBB after birth. Compared to Pb and Hg, we found that the transport efficiency of Cd in the digestive system was lower, whereas the chelation of Cd by the placental barrier was better. This preliminary information may help researchers to explore the mechanism underlying the hazardous effects of heavy metal mixture exposure, or for regulatory agencies to revise guidelines for heavy metal exposure.
Keywords: Cadmium; Factorial design; Heavy metal mixture; Lead; Mercury; Metabolic dynamic.
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