Towards health-based nano reference values (HNRVs) for occupational exposure: Recommendations from an expert panel

Our plain-English summary of Towards health-based nano reference values (HNRVs) for occupational exposure: Recommendations from an expert panel, by M. Visser, I. Gosens, D. Bard, et al (NanoImpact, 2022).

The study

• Authors: M. Visser, I. Gosens, D. Bard, P. van Broekhuizen, G. Janer, E. Kuempel, M. Riediker, U. Vogel, S. Dekkers
• Journal: NanoImpact
• Published: 2022;26:100396
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Unique physicochemical characteristics of engineered nanomaterials (ENMs) suggest the need for nanomaterial-specific occupational exposure limits (OELs). Setting these limits remains a challenge. Therefore, the aim of this study was to set out a framework to evaluate the feasibility of deriving advisory health-based occupational limit values for groups of ENMs, based on scientific knowledge. We have used an expert panel approach to address three questions: 1) What ENM-categories should be distinguished to derive advisory health-based occupational limit values (or health-based Nano Reference Values, HNRVs) for groups of ENMs? 2) What evidence would be needed to define values for these categories? And 3) How much effort would it take to achieve this? The panel experts distinguished six possible categories of HNRVs: A) WHO-fiber-like high aspect ratio ENMs (HARNs), B) Non-WHO-fiber-like HARNs and other non-spheroidal ENMs, C) readily soluble spheroidal ENMs, D) biopersistent spheroidal ENMs with unknown toxicity, E) biopersistent spheroidal ENMs with substance-specific toxicity and F) biopersistent spheroidal ENMs with relatively low substance-specific toxicity. For category A, the WHO-fiber-like HARNs, agreement was reached on criteria defining this category and the approach of using health-based risk estimates for asbestos to derive the HNRV. For category B, a quite heterogeneous category, more toxicity data are needed to set an HNRV. For category C, readily soluble spheroidal ENMs, using the OEL of their molecular or ionic counterpart would be a good starting point. For the biopersistent ENMs with unknown toxicity, HNRVs cannot be applied as case-by-case testing is required. For the other biopersistent ENMs in category E and F, we make several recommendations that can facilitate the derivation of these HNRVs. The proposed categories and recommendations as outlined by this expert panel can serve as a reference point for derivation of HNRVs when health-based OELs for ENMs are not yet available.

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

In plain English

This article reported an expert panel's recommendations, not a new study of workers or animals. A nine-member core panel held four online discussion rounds in 2020; a 24-member review panel gave written comments. They considered setting advisory health-based limits (HNRVs) for groups of engineered nanomaterials. The panel proposed six categories, A to F. Category A covered biopersistent 'WHO-fiber-like' nanomaterials longer than 5 μm with a length-to-width ratio of at least 3:1. Here asbestos served as the benchmark, with fiber number as the preferred measure. Using earlier rat data on Mitsui-7 carbon nanotubes, the authors calculated that a Health Council of the Netherlands limit of 400 fibers per cubic metre for amphibole asbestos corresponded to an excess risk of about 1 in 500,000. They noted no human data existed on mesothelioma or lung cancer from such nanomaterials. Category B mostly needed more toxicity data and category D case-by-case testing; for category C, the ionic or molecular counterpart's limit was considered sufficient, and for E and F the panel outlined approaches. The authors concluded that their categories could serve as a reference point.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Expert panel recommendation paper: expert panel discussions supported by relevant literature. It was not a systematic review and not an original study of workers or animals.
• Who was studied: An expert panel from toxicology, epidemiology, occupational health and exposure sciences. A core panel of nine members (the main authors, including three technical writers) took part in four rounds of online discussion meetings in 2020. A review panel of 24 members provided written comments on the project proposal, the discussion topics and the draft publication.
• Exposure: Occupational exposure to engineered nanomaterials. Asbestos was used as the benchmark material for deriving a limit value for WHO-fiber-like high aspect ratio nanomaterials, such as certain carbon nanotubes.
• Main results:
  • The panel distinguished six categories of nanomaterials (A to F) for health-based nano reference values.
  • Category A (WHO-fiber-like HARNs) was defined as nanomaterials with a length of more than 5 μm and an aspect ratio of at least 3:1 length to width that can be considered biopersistent.
  • The panel also considered agglomerates or aligned bundles of HARNs to be WHO-fiber-like HARNs when they had a diameter under 3 μm and a length over 5 μm.
  • The article noted that, according to the IFA GESTIS database, national occupational exposure limits for asbestos range from 2000 to 300,000 fibers per cubic metre.
  • The authors used rat data on Mitsui-7 carbon nanotubes from an earlier study (Kasai et al., 2016). On that basis, they considered the Health Council of the Netherlands' recommended limit of 400 fibers per cubic metre for amphibole asbestos sufficiently worst-case to use as the value for category A. That limit corresponds to an excess risk level of approximately 1 in 500,000.
  • For category A, the panel agreed that fiber number is the preferred dose metric. The authors noted that the WHO optical microscopy method for counting asbestos fibers is not applicable to fibers thinner than 200 nm.
  • For category B (non-WHO-fiber-like HARNs and other non-spheroidal nanomaterials), the panel considered it not possible at the moment to derive a value because toxicological data are insufficient. The exception was carbon-based materials, for which existing carbon nanotube limits could be used.
  • For category C (readily soluble spheroidal nanomaterials), the panel considered the occupational exposure limit of the ionic or molecular counterpart sufficient.
  • For category D (biopersistent spheroidal nanomaterials with unknown toxicity), HNRVs cannot be applied and case-by-case testing is needed.
  • For category E (biopersistent spheroidal nanomaterials with substance-specific toxicity), the panel recommended that values may be derived by applying an assessment factor to the occupational exposure limit of the larger-scale counterpart.
  • For category F (biopersistent spheroidal nanomaterials with relatively low substance-specific toxicity), the experts were of the opinion that existing data, for example on carbon black, ultrafine particles and diesel exhaust particles, could be combined in a weight-of-evidence approach to arrive at a general value.
• The authors' conclusion: The authors concluded that the proposed categories and recommendations can serve as a reference point for future derivation of health-based nano reference values. They stated that more work is needed to fill data gaps, including a harmonized method to count nanofibers for category A.
• Limitations the authors state:
  • Only a quick literature screening was done before each meeting; no systematic literature review was performed.
  • There are no human data on mesothelioma or lung cancer from exposure to WHO-fiber-like nanomaterials. The category A estimate relies on rat data for one type of carbon nanotube.
  • The GRACIOUS project's recommendations on biopersistence cut-offs were not yet published at the time of the discussions and were not discussed. As a result, the category A definition includes no cut-off for biopersistence.
  • How national regulators would set and implement these limits was outside the scope of the study.

Topics

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Aspect Ratio (Length-to-diameter ratio).

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