Comparing semiconductor nanocrystal toxicity in pregnant mice and non-human primates

Abstract

Rationale: Despite growing use of engineered nanomaterials (ENM) in applications from electronics to medicine, the potential risk to human health remains a critical concern within clinical use. ENM exposure during pregnancy can potentially cause reproductive toxicity even at levels that produce no measurable harm to animals in normal conditions. Methods: Phospholipid micelle-encapsulated CdSe/CdS/ZnS semiconductor nanocrystals with an average hydrodynamic diameter of 60 nm were intravenously injected during pregnancy in both rodent and nonhuman primate animal models. Cadmium concentration levels and maternal haematological and biochemical markers were determined, along with histopathological examination of major organs. Results: Nanocrystals were found to have crossed the placenta from mother to fetus in both rodents and nonhuman primates. However, the animal models display different responses with respect to reproductive toxicity. In the rodent model, toxicity symptoms are absent in treated subjects, with no observed gestational or fetal abnormalities and complications. A significantly higher miscarriage rate of 60% is recorded for macaques after prenatal nanoparticle administration. There was a miscarriage rate of 15% in the general population despite only ~0.16% of the initial cadmium dose present in the fetus. Blood and biochemical markers of treated macaques indicate acute hepatocellular injury within a week after nanoparticle administration. Histology of major organs of the miscarried macaque fetuses show no abnormalities. Conclusion: The potential of nanomaterials to cross the placenta and impact fetal survival in primates suggest the necessity of precautionary measures to prevent gestational exposure of ENMs.