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Variation in dissolution behavior among different nanoforms and its implication for grouping approaches in inhalation
Johannes G Keller1, Michael Persson2, Philipp Müller1
1BASF SE, Dept. Experimental Toxicology and Ecology, Dept. Material Physics, 67056 Ludwigshafen, Germany.
Nanoimpact
|May 13, 2022
Summary
Biodissolution rates of nanoforms (NF) impact inhalation toxicity assessments. Understanding NF dissolution helps group similar nanomaterials for regulatory REACH registration, reducing animal testing.
Area of Science:
- Environmental Science
- Toxicology
- Materials Science
Background:
- Nanoform (NF) registration under REACH requires data for each substance.
- Similarities in physiological interactions, like biodissolution, can enable read-across for NF groups, reducing animal testing.
- Inhalation toxicity is a key endpoint for NF safety assessment.
Purpose of the Study:
- To investigate how physical parameters of 17 nanoforms (NFs) of silica and pigments affect dissolution rates and transformations.
- To compare dissolution behavior under lung lining (pH 7.4) and lysosomal (pH 4.5) conditions.
- To establish numerical rules for grouping NFs based on dissolution similarity for regulatory purposes.
Main Methods:
- Assessed dissolution rates, half-times, and structural transformations of 17 NFs (silica, organic/inorganic pigments) in simulated lung and lysosomal fluids.
- Benchmarked dissolution against TiO2, BaSO4, and ZnO nanomaterials.
- Utilized automated image evaluation for structural transformation analysis.
Main Results:
- Dissolution rates varied significantly, with structural transformations observed between 0.1 to 10 ng/cm²/h.
- Dissolution half-times spanned five orders of magnitude, influenced by substance, fluid, and NF-specific differences.
- A biologically relevant dissolution range (1 hour to 1 year) was proposed, with ZnO, Ag, SiO2, and BaSO4 NFs falling within it.
- Numerical rules for pairwise similarity were proposed, grouping colloidal silica NFs based on Al-doping, not shape or surface treatment.
Conclusions:
- Dissolution behavior is a critical factor for grouping NFs and reducing animal testing for REACH registration.
- The proposed numerical rules and biologically relevant time scales aid in grouping NFs for inhalation toxicity assessment.
- Subtle differences in NFs can significantly modulate dissolution, but substance and simulant fluid are primary drivers.
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