ZnO nanoparticles and organic chemical UV-filters are equally well tolerated by human immune cells

Abstract

An important part of assessing the toxic potential of nanoparticles for specific applications should be the direct comparison of biological activities with those of alternative materials for the same application. Nanoparticulate inorganic ultraviolet (UV) filters, such as zinc oxide (ZnO), are commonly incorporated into transparent sunscreen and cosmetic formulations. However, concerns have been raised about potential unwanted effects, despite their negligible skin penetration and inherent advantages over organic chemical UV-filters. To provide useful application-relevant assessments of their potential hazard with/without UVA co-exposure, we directly compared cytotoxic and immune response profiles of human THP-1 monocytic cells to ZnO nanoparticles (30 nm) with bulk ZnO particulates (200 nm) and five conventional organic chemical UV-filters – butylmethoxydibenzoylmethane (avobenzone), octylmethoxycinnamate, octylsalicylate, homosalate and 4-methylbenzylidene camphor. High exposure concentrations of both organic and particulate UV-filters were required to cause cytotoxicity in monocyte and macrophage cultures after 24 h. Co-exposure with UVA (6.7 J/cm²) did not alter cytotoxicity profiles. Particle surface area-based dose responses showed that ZnO NPs were better tolerated than bulk ZnO. Organic and particulate UV-filters increased apoptosis at similar doses. Only particulates increased the generation of reactive oxygen species. Interleukin-8 (IL-8) release was increased by all particulates, avobenzone, homosalate and octylsalicylate. IL-1β release was only increased in macrophages by exposure to avobenzone and homosalate. In conclusion, direct effects were caused in monocytes and macrophages at similar concentrations of both organic UV-filters and ZnO nanoparticulates – indicating that their intrinsic cytotoxicity is similar. With their lower skin penetration, ZnO nanoparticles are expected to have lower bioactivity when used in sunscreens.

Keywords:

• Cytokine release
• cytotoxicity
• ROS
• sunscreen
• UVA

Acknowledgements

We wish to thank Victoria Coleman at the National Measurement Institute, Sydney, Australia for use of the disc centrifuge, and Micronisers Australasia Pty. Ltd. and Baxter Laboratories Pty. Ltd. for the supply of ZnO and organic chemical samples, and for helpful discussions.

Declaration of interest

This work has been supported by the Advanced Manufacturing Cooperative Research Centre (AMCRC), The Victorian Centre for Advanced Materials Manufacturing Ltd (VCAMM) and the National Health and Medical Research Council (NHMRC, Australia) project grant #616621. TWT is also Chief Technical Officer and a Director of Micronisers Australasia Pty. Ltd., a manufacturer and supplier of ZnO mainly for industrial and agricultural purposes, and also provided the ZnO samples used in this study. BNF is also Senior Scientist at Baxter Laboratories, a formulator of sunscreens containing both metal oxide and organic chemical UV-filters, and also provided the organic UV-filter samples used in this study. The other authors declared no competing interests.

Supplementary material available online