LAUSR

Abstract With the extensive application of iron oxide nanoparticles (FeNPs), attention about their potential risks to human health is also rapidly raising, particularly in sensitive subgroups such as pregnant women and babies. In this study, we a single instilled intratracheally FeNPs (1, 2, and 4 mg/kg) to the male and female parent mice, mated, then assessed reproductive toxicity according to the modified OECD TG 421. During the pre‐mating period (14 days), two female parent mice died at 4 mg/kg dose, and the body weight gain dose‐dependently decreased in male and female parent mice exposed to FeNPs. Additionally, iron accumulation and the enhanced expression of MHC class II molecules were observed in the ovary and the testis of parent mice exposed to the highest dose of FeNPs, and the total sex ratio (male/female) of the offspring mice increased in the groups exposed to FeNPs. Following, we a single instilled intratracheally to their offspring mice with the same doses and evaluated the immunotoxic response on day 28. The increased mortality and significant hematological‐ and biochemical‐ changes were observed in offspring mice exposed at 4 mg/kg dose, especially in female mice. More interestingly, balance of the immune response was shifted to a different direction in male and female offspring mice. Taken together, we conclude that the NOAEL for reproductive and developmental toxicity of FeNPs may be lower than 2 mg/kg, and that female mice may show more sensitive response to FeNPs exposure than male mice. Furthermore, we suggest that further studies are necessary to identify causes of both the alteration in sex ratio of offspring mice and different immune response in male and female offspring mice. HighlightsFeNPs were single instilled intratracheally to the male and female parent mice.Two female parent mice died at 4 mg/kg dose during pre‐mating period.The body weight gain dose‐dependently decreased in male and female parent mice.Iron accumulation was observed in the ovary and the testis of FeNP‐treated parent mice.The total sex ratio of the offspring mice increased in FeNP‐treated parent group.