Airway particle exposure and developmental toxicity: From potential link to inflammation to within-laboratory reproducibility challenges

Research within nanotoxicology has revealed inhalation of particles can interfere with fetal development. Our research group has contributed knowledge on several aspects of developmental toxicity of manufactured nanomaterials. In some cases, the same batch of particles were examined in more than one mouse study. The present review evaluates whether our findings are within-laboratory reproducible and furthermore examines the potential relationships between induced maternal lung inflammation as a potential mediator of developmental toxicity, irrespectively of particle type. Our results ranged from fully reproducible (lack of effects on gestational and litter parameters, on germline mutations in females, irrespective of particle type, and on daily sperm production in F1 males of mothers exposed to carbon black; and depression of immune system function after maternal exposure to multiwalled carbon nanotubes) to not reproducible (transplacental genotoxicity and daily sperm production in the F2 generation of mothers exposed to carbon black and behavioral measures in general). Delineation of the relationship between maternal lung inflammation and developmental effects was somewhat hampered by differences time span from exposure termination to assessment of lung inflammation. At the observed levels, lung inflammation was however not associated with changes in gestational nor litter parameters, and did not seem to play a role in transplacental genotoxicity. In conclusion, this review reveals both consistency and variability in outcomes across studies. The results underscore the complexity of effects of nanoparticle exposure in developmental toxicology and reproducibility of results and warrants future research to focus on reproducibility and elucidate specific mechanisms underlying the observed toxicological effects.