Hazard and risk assessment strategies for nanoparticle exposures: how far have we come in the past 10 years?

David B Warheit

doi:10.12688/f1000research.12691.1

Abstract

Nanotechnology is an emerging, cross-disciplinary technology designed to create and synthesize new materials at the nanoscale (generally defined as a particle size range of ≤10 -9 meters) to generate innovative or altered material properties. The particle properties can be modified to promote different and more flexible applications, resulting in consumer benefits, particularly in medical, cosmetic, and industrial applications. As this applied science matures and flourishes, concerns have arisen regarding potential health effects of exposures to untested materials, as many newly developed products have not been adequately evaluated. Indeed, it is necessary to ensure that societal and commercial advantages are not outweighed by potential human health or environmental disadvantages. Therefore, a variety of international planning activities or research efforts have been proposed or implemented, particularly in the European Union and United States, with the expectation that significant advances will be made in understanding potential hazards related to exposures in the occupational and/or consumer environments. One of the first conclusions reached regarding hazardous effects of nanoparticles stemmed from the findings of early pulmonary toxicology studies, suggesting that lung exposures to ultrafine particles were more toxic than those to larger, fine-sized particles of similar chemistry. This review documents some of the conceptual planning efforts, implementation strategies/activities, and research accomplishments over the past 10 years or so. It also highlights (in this author’s opinion) some shortcomings in the research efforts and accomplishments over the same duration. In general, much progress has been made in developing and implementing environmental, health, and safety research-based protocols for addressing nanosafety issues. However, challenges remain in adequately investigating health effects given 1) many different nanomaterial types, 2) various potential routes of exposure, 3) nanomaterial characterization issues, 4) limitations in research methodologies, such as time-course and dose-response issues, and 5) inadequate in vitro methodologies for in vivo standardized, guideline toxicity testing.

Highlights

Nanotechnology continues to be an emerging multidisciplinary science platform that is often defined as creating products and applications based primarily upon the synthesis of molecules in the nanoscale (10-9 meter) size range
The results demonstrated that aerosol exposures of rats to 0.54 (4.9 f/cc), 2.5 (56 f/cc), and 25 (252 f/cc) mg/m3 of VGCFTM-H produced concentration-related small, detectable accumulation of extrapulmonary fibers with no adverse tissue effects outside of the lungs
In conclusion, this mini-review has focused on select hazard and risk assessment strategies and research efforts that have been proposed or conducted during the past decade with the intention of better estimating potential adverse health effects following nanoparticle exposures

Summary

Introduction

Nanotechnology continues to be an emerging multidisciplinary science platform that is often defined as creating products and applications based primarily upon the synthesis of molecules in the nanoscale (10-9 meter) size range. A study design and the implementation of a subchronic (13-week) inhalation toxicity study with CNFs in rats are described This discussion serves to demonstrate and emphasize the difficult challenges, time dependency, expenses, and toxicological complexity that are required to generate meaningful data and provide accurate perspectives on the issues related to developing adequate risk assessments for the variety of nanomaterial types that currently exist in commerce and to which workers and consumers are exposed. With respect to the hazard component of the framework with a new material, the hazard findings of a base set of toxicity tests on a newly developed, well-characterized, ultrafine rutile-type TiO (uf-TiO ) particle type were reported by Warheit et al.[15] These hazard assessments were composed by focusing upon general potential routes, including acute lung instillation studies, oral toxicity tests, dermal irritation and sensitization investigations, acute ocular (eye) irritation tests, genetic toxicology assessments, and screening aquatic toxicity guideline studies. It was noteworthy that the biodistribution and biokinetics of nanoscale TiO2 exposures following pulmonary and gastrointestinal routes were relatively similar but distinctly different from the intravenous route of administration

Conclusions

10. National Research Council

Findings

14. Warheit DB