Development of risk-based nanomaterial groups for occupational exposure control

Abstract

Given the almost limitless variety of nanomaterials, it will be virtually impossible to assess the possible occupational health hazard of each nanomaterial individually. The development of science-based hazard and risk categories for nanomaterials is needed for decision-making about exposure control practices in the workplace. A possible strategy would be to select representative (benchmark) materials from various mode of action (MOA) classes, evaluate the hazard and develop risk estimates, and then apply a systematic comparison of new nanomaterials with the benchmark materials in the same MOA class. Poorly soluble particles are used here as an example to illustrate quantitative risk assessment methods for possible benchmark particles and occupational exposure control groups, given mode of action and relative toxicity. Linking such benchmark particles to specific exposure control bands would facilitate the translation of health hazard and quantitative risk information to the development of effective exposure control practices in the workplace. A key challenge is obtaining sufficient dose-response data, based on standard testing, to systematically evaluate the nanomaterials' physical-chemical factors influencing their biological activity. Categorization processes involve both science-based analyses and default assumptions in the absence of substance-specific information. Utilizing data and information from related materials may facilitate initial determinations of exposure control systems for nanomaterials.

Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity, apoptosis, oxidative stress, and inflammation

“…Physico-chemical properties of nanomaterials that have been recognized to influence their inhalability, deposition efficiency, and toxicology are their airborne and hydrodynamic size, size distribution, shape (and aspect ratio), their state of agglomeration, surface properties and functionalization (surface area, porosity, charge, reactivity, chemistry/ coatings, contaminants), as well as solubility and crystallinity (Kuempel et al, 2012;Nel et al, 2013a;Oberdörster, 2009;Oberdörster et al, 1994;Rodriguez-Yanez et al, 2013;Zhu et al, 2013). Also in in vitro cytotoxicity assays, particle size, surface chemistry and coating, as well as chemical composition have been recognized as key determinants of nanoparticle adverse effects (Feltis et al, 2012;Horev-Azaria et al, 2011;Kroll et al, 2011).…”

“…Also in vivo, ZnO NM effects are reported being caused by dissolved ions (Kuempel et al, 2012), as recorded by increased LDH levels in the bronchoalveolar fluid (BALF; Kao et al, 2012). Klein et al (2012) found short-term inhalation exposure to 2.5 and 12.5 mg/m 3 Z-COTE® HP1 to increase inflammatory parameters in the BALF in a concentrationdependent manner.…”

“…For TiO 2 NMs, dose metrics related to adverse effects are surface area, volume, mass or number (by particle size fraction), with the dose-response relationship possibly being non-linear at low doses (Kuempel et al, 2012). In a rat short-term inhalation study (STIS; 5-day exposure period, 6-hour exposure/day), both nanoscaled (70% anatase/ 30% rutile, 20-30 nm, TEM; test substance concentration 100 mg/m 3 ) and pigmentary (non-nano) TiO 2 (200 nm, DLS; test substance concentration 250 mg/m 3 ) induced reversible mild neutrophilic inflammation and activation of macrophages in the lung (van Ravenzwaay et al, 2009).…”

Overview of Risk Management for Engineered Nanomaterials

“…determining the health risk). The banding strategies developed for nanomaterials have been recently reviewed [20], and approaches to link quantitative risk assessment with exposure control banding schemes (for categorical decision-making and validation) have been described [21].…”

“…It is unlikely that it will be possible to assess toxicologically (using animal studies) all the ENMs in, or entering, commerce [21,36,37]. Therefore, it may be necessary to screen materials individually or as categories and assign them to hazard and control categories (based on physical-chemical parameters).…”