The surge of applications for engineered nanomaterials (ENMs) across multiple industries raises safety concerns regarding human health and environmental impacts. ENMs can be hazardous through various mechanisms, including, particle dissolution and shedding of toxic metal ions, surface reactivity and perturbation of cellular membranes, lysosomal membrane damage, activation of inflammation pathways (e.g., NLRP3 inflammasome), etc. The aim of this review is therefore to discuss practical approaches for the safer design of ENMs through modification of their physicochemical properties that can lead to acute and/or chronic toxicity. This is premised on our understanding of how different ENMs induce toxicity within various biological systems. We will summarize studies that have investigated nanomaterial toxicity both in vitro and in vivo to understand the underlying mechanisms by which nanoparticles can cause inflammation, fibrosis, and cell death. With this knowledge, researchers have identified several design strategies to counter these mechanisms of toxicity. In particular, we will discuss how metal doping, surface coating and covalent functionalization, and adjustment of surface oxidation state and aspect ratio of ENMs could reduce their potential adverse effects. While these strategies might be effective under certain experimental and exposure scenarios, more research is required to fully apply this knowledge in real life applications of nanomaterials.

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Historically, formaldehyde was used as a preservative in personal care products to extend product shelf-life; however, given its skin sensitization potential it has been phased out of use and replaced with formaldehyde-releasing preservatives, such as Dimethyloldimethyl hydantoin (DMDMH). A relationship has been established between positive patch test results following exposure to DMDMH and previous sensitization to formaldehyde. Upon direct contact with the skin, formaldehyde can react with skin proteins and cause an acute inflammatory reaction, which may progress to skin sensitization following repeated exposure. This quantitative risk assessment (QRA) aimed to assess the risk of skin sensitization induction following use of shampoo products containing the maximum allowable concentrations of DMDMH in formulation (1% w/v), translating to a free formaldehyde concentration of 0.02%. To determine a margin of safety (MOS) for exposure to DMDMH from use of shampoo products, consumer exposure levels (CEL) were estimated based on typical use scenarios and then benchmarked against an acceptable exposure level (AEL). The AEL was derived using a weight of evidence approach where a range of no expected sensitization induction levels (NESILs) was utilized. The MOS values for a shampoo product containing 1% DMDMH (.02% formaldehyde) was above 1 for the typical use scenario indicating a low likelihood of skin sensitization induction among healthy individuals. Thus, it can be concluded that shampoo products containing DMDMH at or below current allowable concentrations are not expected to increase the risk of skin sensitization induction.