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We summarized the findings of reproductive and developmental toxicity studies on carbon-based nanomaterials (CNMs). Placental transfer of fullerenes in rats and single-walled (SW) and multi-walled (MW) CNTs in mice was shown after intravenous injection. SWCNTs appeared to be embryolethal and teratogenic in mice when given by intravenous injection and induced death and growth retardation in chicken embryos. In mice-administered MWCNTs, fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offspring after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported. Oral gavage of MWCNTs had no developmental toxicity in mice and rats. MWCNTs produced morphological defects, developmental arrest, and death in zebrafish embryos. Intratracheal instillation of carbon black (CB) induced testicular toxicity in adult mice. Maternal airway exposure to CB in gestation had testicular toxicity and altered postnatal behavior, renal development, immune and genotoxic responses, and brain morphology in mouse offspring. Nanodiamonds and graphite nanoparticles inhibited vasculogenesis and/or angiogenesis in chicken embryos. Graphene oxide (GO) induced malformations in zebrafish embryos. Intravenous injection of reduced GO during late gestation caused maternal death and abortion in mice. Oral administration of GO during lactation caused growth retardation of offspring. Overall, the available data provide initial information on the potential reproductive and developmental toxicity of CNMs. However, confirmatory studies using well-characterized CNMs, state-of-the-art study protocol and appropriate route of exposure, are required to clarify the findings and provide information suitable for risk assessment.

Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after a single intratracheal instillation in rats. The diameter and median length of the MWCNTs used in this study were approximately 60 nm and 1.5 μm, respectively. Groups of male Sprague-Dawley rats were intratracheally instilled with 0.04, 0.2, or 1 mg/kg of the individually dispersed MWCNT suspension. After instillation, the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers, and the lung, liver, kidney, spleen, and cerebrum were histopathologically evaluated at 3-day, 1-week, 1-month, 3-month, and 6-month post-exposure. Transient pulmonary inflammatory responses were observed only in the lungs of the group of rats exposed to 1 mg/kg of MWCNTs. Morphology of the instilled MWCNTs in the lungs of rats was assessed using light microscopy and transmission electron microscopy (TEM). Light microscopy examination revealed that MWCNTs deposited in the lungs of the rats were typically phagocytosed by the alveolar macrophages and these macrophages were consequently accumulated in the alveoli until 6-month post-exposure. The 400 TEM images obtained showed that all MWCNTs were located in the alveolar macrophages or macrophages in the interstitial tissues, and MWCNTs were not located in the cells of the interstitial tissues. There was no evidence of chronic inflammation, such as angiogenesis or fibrosis, induced by MWCNT instillation. These results suggest that MWCNTs were being processed and cleared by alveolar macrophages.