Possibilities to group nanomaterials across different substances - A case study on organic pigments

Grouping concepts to reduce the testing of NFs have been developed for regulatory purposes for different forms of the same substance. Here we explore possibilities to group nanomaterials across different substances for nonregulatory applications, using the example of 16 organic pigments from six chemical classes. Organic pigments are particles consisting of low-molar-mass organic molecules, and rank by tonnage among the most important substances manufactured in nanoform (NF). Tiered testing strategies relevant to the inhalation route included Tier 1 (deposition, dissolution, reactivity, inflammation) and if available Tier 3 data (in vivo). A similarity assessment of the pigment NF data was conducted in a quantitative (Tier 1 and Tier 3 in vivo potency) or qualitative (Tier 3 in vivo effects) manner. We observed that chemical similarity of organic pigments was predictive for their similarity of reactivity and dissolution, but that additional NF descriptors such as surface area or size, modulate the similarity in inflammation or cytotoxicity. We applied the concept of biologically relevant ranges to crop the values of the Tier 1 data matrix before applying similarity algorithms. The Tier 3 assessment by in vivo inhalation confirmed the IATA methodical choices and IATA assessment criteria as consistent and conservative. We suggested limits of acceptable similarity for Tier 1 data and demonstrated their application to support the grouping of some candidate NFs (subsequently confirmed by Tier 3 data). Four candidate NFs exceeded the limits of acceptability for Tier 1 and were escalated from Tier 1 to Tier 3, but were then included in the group, demonstrating the conservative Tier 1 criteria. The resulting group of low-solubility, low-reactivity materials included both NFs and non-NFs of various substances, and could find use for risk management purposes in the occupational handling of pigment powders.

Automated summary

This study explores the possibility of grouping nanomaterials across different substances and uses organic pigments as an example. The results show that chemical similarity predicts reactivity and dissolution of pigments, while other nanomaterial descriptors influence inflammation and cytotoxicity. The concept of biologically relevant ranges and similarity algorithms can support the grouping of candidate nanomaterials.