Engineered nanoparticles are smaller than 100 nm and designed to improve or achieve new physico-chemical properties. Consequently, also toxicological properties may change compared to the parent compound. We examined developmental and neurobehavioral effects following maternal exposure to a nanoparticulate UV-filter (UV-titan L181).

This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about the implications for embryo-fetal development and health later in life. Clearly, the potential for hazard remains to be characterized. Considering the increased production and application of nanomaterials and related consumer products a testing strategy for NP should be established. Due to large gaps in data, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis.

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.

Titanium dioxide nanoparticles (nanoTiO₂) are used in various applications including in paints. NanoTiO₂ inhalation may induce pulmonary toxicity and systemic effects. However, the underlying molecular mechanisms are poorly understood. In this study, the effects of inhaled surface‐coated nanoTiO₂ on pulmonary global messenger RNA (mRNA) and microRNA (miRNA) expression in mouse were characterized to provide insight into the molecular response. Female C57BL/6BomTac mice were exposed for 1 hr daily to 42.4 ± 2.9 (SEM) mg surface‐coated nanoTiO₂/m³ for 11 consecutive days by inhalation and were sacrificed 5 days following the last exposure. Physicochemical properties of the particles were determined. Pulmonary response to nanoTiO₂ was characterized using DNA microarrays and pathway‐specific PCR arrays and related to data on pulmonary inflammation from bronchial lavages. NanoTiO₂ exposure resulted in increased levels of mRNA for acute phase markers serum amyloid A‐1 (Saa1) and serum amyloid A‐3 (Saa3), several C‐X‐C and C‐C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more than 1.2‐fold (adjusted P‐value < 0.05) following exposure. Real time polymerase chain reaction confirmed the upregulation of miR‐1, miR‐449a and revealed dramatic induction of miR‐135b (60‐fold). Thus, inhalation of surface‐coated nanoTiO₂ results in changes in the expression of genes associated with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011.

Effects of maternal pulmonary exposure to carbon black (Printex 90) on gestation, lactation and DNA strand breaks were evaluated. Time-mated C57BL/6BomTac mice were exposed by inhalation to 42 mg/m³ Printex 90 for 1 h/day on gestation days (GD) 8–18, or by four intratracheal instillations on GD 7, 10, 15 and 18, with total doses of 11, 54 and 268 μg/animal. Dams were monitored until weaning and some offspring until adolescence. Inflammation was assessed in maternal bronchoalveolar lavage (BAL) 3–5 days after exposure, and at weaning. Levels of DNA strand breaks were assessed in maternal BAL cells and liver, and in offspring liver. Persistent lung inflammation was observed in exposed mothers. Inhalation exposure induced more DNA strand breaks in the liver of mothers and their offspring, whereas intratracheal instillation did not. Neither inhalation nor instillation affected gestation and lactation. Maternal inhalation exposure to Printex 90-induced liver DNA damage in the mothers and the in utero exposed offspring.

Lead (Pb) is a ubiquitous environmental pollutant and a potent toxic compound. Humans are exposed to Pb through inhalation, ingestion, and skin contact via food, water, tobacco smoke, air, dust, and soil. Pb accumulates in bones, brain, liver and kidney. Fetal exposure occurs via transplacental transmission. The most critical health effects are developmental neurotoxicity in infants and cardiovascular effects and nephrotoxicity in adults. Pb exposure has been steadily decreasing over the past decades, but there are few recent exposure data from the general European population; moreover, no safe Pb limit has been set. Sensitive biomarkers of exposure, effect and susceptibility, that reliably and timely indicate Pb-associated toxicity are required to assess human exposure-health relationships in a situation of low to moderate exposure. Therefore, a systematic literature review based on PubMed entries published before July 2019 that addressed Pb exposure and biomarkers of effect and susceptibility, neurodevelopmental toxicity, epigenetic modifications, and transcriptomics was conducted. Finally included were 58 original papers on Pb exposure and 17 studies on biomarkers. The biomarkers that are linked to Pb exposure and neurodevelopment were grouped into effect biomarkers (serum brain-derived neurotrophic factor (BDNF) and serum/saliva cortisol), susceptibility markers (epigenetic markers and gene sequence variants) and other biomarkers (serum high-density lipoprotein (HDL), maternal iron (Fe) and calcium (Ca) status). Serum BDNF and plasma HDL are potential candidates to be further validated as effect markers for routine use in HBM studies of Pb, complemented by markers of Fe and Ca status to also address nutritional interactions related to neurodevelopmental disorders. For several markers, a causal relationship with Pb-induced neurodevelopmental toxicity is likely. Results on BDNF are discussed in relation to Adverse Outcome Pathway (AOP) 13 ("Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities") of the AOP-Wiki. Further studies are needed to validate sensitive, reliable, and timely effect biomarkers, especially for low to moderate Pb exposure scenarios.