title: Deleterious effects in reproduction and developmental immunity elicited by pulmonary iron oxide nanoparticles.
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 4mg/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 4mg/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 4mg/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 2mg/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.
authors: Myunggok Eye Research Institute, Konyang University, 685, Gasuwon-dong, Seo-Gu, Daejeon 302-718, South Korea. Electronic address: pejtoxic@hanmail.net.
authors: Eun-Jung
authors: EJ
authors: Park
authors: Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, South Korea.
authors: Uiseok
authors: U
authors: Jeong
authors: Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, South Korea.
authors: Younghun
authors: Y
authors: Kim
authors: Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon, South Korea.
authors: Byoung-Seok
authors: BS
authors: Lee
authors: College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors: Myung-Haing
authors: MH
authors: Cho
authors: Genome Application Division, Macrogen Inc., Seoul, South Korea.
authors: You-Seok
authors: YS
authors: Go
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity*; D007113:Immunity, Innate / Q000187:drug effects*; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D012098:Reproduction / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D005290:Ferric Compounds; C000499:ferric oxide
keywords: Immunotoxicity; Iron oxide nanoparticles; Mortality; Reproduction; Sex ratio