U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

WHO Guidelines on Protecting Workers from Potential Risks of Manufactured Nanomaterials. Geneva: World Health Organization; 2017.

Cover of WHO Guidelines on Protecting Workers from Potential Risks of Manufactured Nanomaterials

WHO Guidelines on Protecting Workers from Potential Risks of Manufactured Nanomaterials.

Show details

6Specific Recommendations

6.1. Assess Health Hazards of MNMs

  • Recommendation 1: The GDG recommends assigning hazard classes to all MNMs according to the Globally Harmonized System (GHS) of Classification and Labelling of Chemicals for use in safety data sheets. For a limited number of MNMs this information is made available in these guidelines (Table 2) (STRONG, moderate quality evidence).
  • Recommendation 2: The GDG recommends updating safety data sheets with MNM-specific hazard information, or indicating which toxicological end-points did not have adequate testing available (STRONG, moderate-quality evidence).
  • Recommendation 3: For the respirable fibres and granular biopersistent particles’ groups, the GDG suggests using the available classification of MNMs given in Table 2 for provisional classification of nanomaterials of the same group (CONDITIONAL, low-quality evidence).
Table 2. Classification of Hazardous Properties of Nanomaterials (MNMs) That have an Existing OECD Dossier.

Table 2

Classification of Hazardous Properties of Nanomaterials (MNMs) That have an Existing OECD Dossier.

A list of selected nanomaterials and their up-to-date hazard classes, according to the GHS and as assigned by the systematic review team, is available in Table 2. The most common hazard classes assigned to MNMs are:

  • specific target organ toxicity after repeated exposure
  • carcinogenicity
  • germ cell mutagenicity
  • serious eye damage
  • respiratory or skin sensitization.

From evidence to recommendation

Evidence

The animal and genotoxicity studies, as collected and reviewed by the OECD and reported in the specific nanomaterial dossiers, formed the evidence for the assignment of hazard classes to the various MNMs. In addition to the OECD data, the evidence for carcinogenic properties was based on assessment of a limited number of MNMs by the International Agency for Research on Cancer (IARC). Based on an assessment of study limitations, the quality of the evidence was rated as moderate to high for the various MNMs.

Recommendation 3 to bridge the hazard classes from specific materials within a group to other materials within that same group, is based on low-quality evidence that the respirable fibres or GBP materials have similar toxicological properties (see Best practice, Classification of MNMs, section 5.1).

Benefits and harms

The benefits of having MNMs properly classified and labelled according to their hazards, in terms of focus on risk and control measures, clearly outweigh the possible harm that the classification might be overly cautious given the lack of information about the hazards of MNMs in general. In some cases, the classification system could also result in underestimation of the hazard.

Values and preferences

The hazard classification forms the basis for labelling products according to their hazards. In many countries, this is legally binding. This information is also included in the SDS informing workers and employers about the safety and hazards of the products they use. Even though the GHS might not be optimal for MNMs, and is being continually developed, it is a systematic approach that is generally recognized globally.

Grouping MNMs with similar properties is important, especially in the absence of information on the hazards of many new materials.

Net benefits worth the costs

Assigning hazard classes to MNMs is not a very costly procedure if data from studies are available.

Strength of the recommendation

Based on the above considerations, the GDG makes a strong recommendation for the assignment of hazard classes to MNMs. For bridging from specific materials within the same group, the recommendation is conditional.

Summary of findings: MNMs and hazard class assignment

Systematic review question: Which hazard classes can be assigned to specific MNMs according to the UN GHS and making use of MNM-specific dossiers as developed by the OECD? The MNM dossiers compiled by the OECD give an overview of the available toxicological data for a number of specific MNMs.

Evidence summary

The systematic review was undertaken by Lee et al. (2017) (26) and was published by WHO.

Number of studies and participants

There were 11 OECD dossiers containing toxicity testing information. These were used by the systematic review team to assign one or more hazard classes, according to the GHS, to the following nanomaterials: fullerene, single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT), silver, gold, silicon dioxide, titanium dioxide, cerium dioxide, dendrimer, nanoclay and zinc oxide in nanoparticle form. For the assessment of carcinogenicity, the review team also used the evidence summaries compiled by IARC on SWCNTs, MWCNTs and titanium dioxide.

Data in the dossiers

Dossiers mostly contained results of in vivo animal studies and in vitro genotoxicity studies supplied by member countries and nongovernmental organizations such as the Business and Industry Advisory Committee to the OECD.

Risk of bias in the included dossiers

The main limitations to the studies included in the dossiers were that they did not fulfil the OECD criteria for good methodological quality, such as being published in a peer-reviewed journal and complying with good laboratory practice (GLP). For some studies, the GLP test data were not fully disclosed because of the company’s intellectual property rights. Studies were classified at low risk of bias if they were in the OECD category 1 or 2, complied with GLP, were based on test guidelines and resulted in a peer-reviewed publication; at medium risk of bias if the above applied but there was no compliance with GLP; and at high risk of bias if none of the above applied.

Classification of MNMs

The MNMs were classified as having a specific hazard according to the GHS, having no hazard according to the available studies, or as having no data when these were not available for classification. “No hazard” does not necessarily imply that there is no hazard but only that this was not found in the studies used in the OECD dossiers.

For fullerene, there was evidence that there is no hazard for acute toxicity, skin-, eye- or respiratory damage, germ cell mutagenicity or specific target organ toxicity after repeated exposure but, for the other hazard classes, data were missing.

For SWCNT, there was evidence of a hazard for germ cell mutagenicity (Cat 2) and specific organ toxicity after repeated exposure (Cat 1). For reproductive toxicity no clear hazard could be established based on the available data. There was also evidence of no hazard in acute toxicity, skin damage, respiratory/skin sensitization, or reproductive toxicity. For specific target toxicity after single exposure, there were no data. For carcinogenicity there were no data but there is an IARC classification 3, meaning not classifiable.

For MWCNT, there was evidence of a hazard for eye damage (Cat 2), germ cell mutagenicity (Cat 2), carcinogenicity (Cat 2, IARC 2B/3) and specific organ toxicity after repeated exposure (Cat 1). There was also evidence of no hazard in acute toxicity, skin damage, respiratory/skin sensitization, or reproductive toxicity. For specific target toxicity after single exposure, there were no data.

For silver nanoparticles, there was evidence of a hazard for respiratory/skin sensitization (Cat 1B) and specific target organ toxicity after repeated exposure (Cat 1☒2). For acute toxicity, skin corrosion, eye damage, germ cell mutagenicity and reproductive toxicity there was evidence of no hazard. For carcinogenicity and specific target organ toxicity after single exposure, there were no data.

For gold nanoparticles, there was evidence for specific target organ toxicity after repeated exposure (Cat 1). There were no data for the other classes.

For silicon dioxide, there was evidence for specific target organ toxicity after repeated exposure (Cat 2), but no hazard for acute toxicity, skin or eye damage, respiratory or skin sensitization, germ cell mutagenicity and reproductive toxicity. For carcinogenicity and specific organ toxicity after single exposure, there were no data.

For titanium dioxide, there was evidence for possible carcinogenicity ((IARC Cat 2B), reproductive toxicity (Cat 1), and specific organ toxicity after repeated exposure (Cat 1), but also evidence of no hazard for acute toxicity, skin or eye damage, respiratory or skin sensitization or germ cell mutagenicity. There were no data for specific organ toxicity after single exposure.

For cerium dioxide, there was evidence of specific target organ toxicity after repeated exposure (Cat 1), but also evidence of no hazard for acute toxicity. There were no data for the other hazard classes.

For dendrimer and nanoclay, there were no animal toxicity or genotoxicity data to use for classification.

For zinc oxide, there was evidence for specific organ toxicity after repeated exposure (Cat 1) but also evidence of no hazard for acute toxicity, skin or eye damage, germ cell mutagenicity and reproductive toxicity. There were no data for respiratory/skin sensitization, carcinogenicity and specific organ toxicity after single exposure.

For physical hazards, there was evidence that silicon dioxide and titanium dioxide were not flammable or explosive. There was no evidence for the other MNMs.

Quality of the evidence

The evidence was rated as high quality if there was at least one study at low risk of bias; as moderate quality if there was at least one moderate-quality study; and as low quality if there were only studies at high risk of bias. The quality of the evidence for all but one of the classifications of hazards was in the moderate or high category (Table 2).

Implementation guidance, research recommendation

Implications for research

There is high to moderate-quality evidence for 11 specific MNMs to be classified according to the GHS. This exercise should also be undertaken for other MNMs not mentioned here. Where data are available, they should be used for the development of SDS.

6.2. Assess Exposure to MNMs

  • Recommendation 4: The GDG suggests assessing workers’ exposure in workplaces with methods similar to those used for the proposed specific OEL value of the MNM (CONDITIONAL, low-quality evidence).
  • Recommendation 5: Because there are no specific regulatory OEL values for MNMs in workplaces, the GDG suggests assessing if workplace exposure exceeds a proposed OEL value for the MNM. A list of proposed OEL values is provided in Annex 1 of these guidelines. The chosen OEL should be at least as protective as a legally mandated OEL for the bulk form of the material (CONDITIONAL, low-quality evidence).
  • Recommendation 6: If specific OELs for MNMs are not available in workplaces, the GDG suggests a stepwise approach for inhalation exposure with, first an assessment of the potential for exposure; second, conducting a basic exposure assessment and third, conducting a comprehensive exposure assessment such as proposed by OECD or CEN (CONDITIONAL, moderate-quality evidence). For dermal exposure assessment, there was insufficient evidence to recommend one method of dermal exposure assessment over another.

Knowledge about exposure and subsequent risk assessment forms the basis for measures to control exposure. However, without an exposure level that can serve as a benchmark or guideline level that indicates a risk for adverse health effects, it will be difficult to make decisions about control measures.

There are several alternative ways to measure MNM exposure such as the number concentration or the mass concentration of an MNM, where it is unclear which method is best for assessing health risks. Therefore, the GDG recommends using the same method as has been used for proposed OEL values. This determines the measurement method and at the same time enables a comparison with a benchmark level that probably indicates a safe exposure level.

Only when no proposed OEL is available for an MNM does the GDG recommend using a more generic exposure assessment that consists of a tiered approach. In the first tier, a qualitative assessment is made of possible absence or presence of exposure. In the second tier, called a basic measurement, a quantitative assessment is made of the exposure concentration. In the third tier, called a comprehensive measurement, the size distribution, morphology and chemical composition of particles is characterized.

The recommendations are based on the evidence compiled in two systematic reviews on the quality of exposure assessments in studies and on OELs proposed for various MNMs.

A comprehensive and up-to-date list of proposed OEL values for MNMs is available in Annex 1, Table A.1.1. The values proposed come from a wide range of institutions and countries. Some authors propose one value for all MNMs (general approach), others propose one value for a group of MNMs (categorical approach), but most propose a value for one specific MNM (specific approach).

The user should be aware that these OELs do not imply a safe level below which adverse health effects do not occur, because they are all based on extrapolation from animal research, or other fields such as air pollution, since there are only very limited data available on long-term human-health effects. Users should make their own choice of the best applicable OEL value. This is similar to the selection of OELs for bulk materials, where a range of values may be available and the user has to make a choice.

Deveau et al. provide a practical framework for how to find the best applicable OEL for a particular problem from a list of varying OELs for one chemical. This approach can also be used for the list of OELs for MNMs (27).

The exposure assessment and measurement strategy as proposed by OECD and the Comité Européen de Normalisation (European Committee for Standardization: CEN) distinguishes the following three levels of assessment that can be used as stand-alone modules or embedded in a harmonized tiered approach (28).

  • The initial assessment provides information on the likelihood of MNMs being released during an activity or process, and usually does not comprise any measurements.
  • The basic assessment, using hand-held or personal devices or samplers, measures exposure as particle number concentration(s) or as respirable mass, or both, in the breathing zone or the workstation air and in the background air. These measurements are supported by laboratory analysis of the samples to characterize the MNM(s) either by chemical composition or morphology.
  • In addition to the basic assessment, the comprehensive assessment provides a characterization of the aerosols in the breathing zone that enables, for example, estimation of the dose of MNMs that is deposited in the gas-exchange region of the lung.

From evidence to recommendation

Evidence

The evidence for these recommendations is based first on a systematic review of all available proposed OELs (29). Since there is no consensus on a valid way of deriving OELs for MNMs, the GDG could not take the quality of the evidence into account and therefore has only formulated conditional recommendations.

Second, the recommendation is informed by a systematic review of exposure measurement methods that shows there is moderate-quality evidence that basic and comprehensive inhalation exposure assessment methods are feasible in practice (30). There was only very low-quality evidence about feasibility of measurements for dermal exposure assessment.

Benefits and harms

The benefits of OELs are that they can constitute a benchmark against which local measurements can be compared. The drawback is that many associate the OEL with a safe level below which no adverse health effects will occur. Since both measurements and adverse health effects are uncertain, the OELs can give a false sense of security. However, balancing the two, the GDG decided that the benefits outweigh the harms.

Comprehensive assessment can be time consuming and requires expert knowledge and instrumentation. Many countries would struggle to carry out comprehensive exposure assessments and few companies would be able to pay for such assessments, especially small and medium-sized enterprises (SMEs). Therefore, the GDG recommended the tiered approach.

Values and preferences

The OEL is a familiar concept to stakeholders and widely used for assessing bulk materials. The same holds for the exposure assessment approach, which is used in general for chemicals.

Net benefits and costs

The costs of derivation of an OEL depend on the method, but it is not necessarily expensive. The GDG considers the measurement of MNMs and comparison with OELs to be an important strategy and its costs to be a useful investment in prevention.

The costs for the measurement instruments are considerable – at least several thousand dollars for hand-held particle measurement devices. However, in many countries it is possible to rent the equipment for short periods. The benefit of measuring is that it enables comparison with an OEL and evaluation by means of a before–after comparison to determine whether measures to control exposure are successful.

Strength of the recommendation

Given the difficulty of establishing the quality of the OELs, the recommendation for using them is conditional. Given the complexities and the costs of measurements, the GDG makes a conditional recommendation for the assessment of exposure.

Summary of findings: systematic review of proposed OELs

Systematic review question: Which specific OEL values that should protect workers are proposed for workers or workplaces with potential exposure to an MNM or a group of MNMs based on studies that proposed a value underpinned with empirical research or arguments.

Evidence summary

The systematic review by Mihalache et al. (2017) was published as a journal article (29).

Number of studies and participants

Twenty studies from a wide range of countries and institutes that proposed 56 OEL values were included in the systematic review. Of these, two proposed one value for all MNMs, 14 proposed one value for a group of MNMs and 40 proposed a value for a specific MNM.

OELs in studies

All studies that considered inhalation exposure proposed OELs for chronic exposure. One study proposed OELs for dermal and oral exposure for CNTs and fullerenes and two studies derived OELs for acute/peak exposure.

In 15 of the studies the exposure values were derived by extrapolation from animal studies. Two studies derived the OEL from the background level or from an environmental exposure limit. Six studies used a bridging approach to derive an OEL for a group of MNMs, arguing that the risks will similarly apply to members of the whole group (fibres, GBPs, MNMs with specific toxic bulk material with an OEL, soluble MNMs and non-biopersistent MNMs).

Two studies proposed limits for all MNMs. Six studies proposed OELs for a group of MNMs. The rest proposed OELs for specific MNMs: seven for titanium dioxide (TiO2) nanoparticles, six for CNTs, three for fullerenes, three for silver nanoparticles and one study each for silicon dioxide nanoparticles, low-toxicity dust consisting of GBP, nanocellulose fibres and nanoclays.

Risk of bias in the included studies

One of the study limitations was that the authors did not always give sufficient information about the specific MNM or group of MNMs and the way the OELs were derived. Also, it was unclear if the proposed OELs, especially the number-based OELs for primary nanoscale particles, can be matched with measurements at the workplace where mostly micro-sized agglomerates of MNMs are assessed.

Proposed OELs that are publicly available

Four studies proposed the asbestos OEL of 0.01 fibres/cm3 for nanofibres.

Four studies proposed values for GBP, of which two studies each had two proposals. One study proposed 500 µg/m3 and 1250 µg/m3 for the respirable fractions dependent on whether particles exhibited specific toxicity or not. In the other study, the proposals for metal and metal oxide nanoparticles are 20 000 particles/cm3 and 40 000 particles/cm3 dependent on particle density.

One study proposed the same OEL for non-biopersistent material as for their bulk material.

For carbonaceous material, proposed OELs ranged from 0.67 µg/m3 for MWCNT to 390 µg/m3 for fullerenes.

For nanosilver there are six proposals varying from 0.098 µg/m3 up to 50 µg/m3.

There are 10 proposals for TiO2 nanoparticles from the lowest, 17 µg/m3, to the highest, 2000 µg/m3.

Some variations in reported OELs for nanomaterials that are chemically the same are due to different models used to derive OELs and some are due to different physicochemical properties including specific toxicity of nanomaterials.

Quality of the evidence

The GDG did not consider the limitations in the studies because there is no generally accepted way of deriving OELs. There were multiple studies with consistent proposals for fibres only. For all other MNMs there was considerable variation. Therefore, the GDG considered the quality of the evidence as low.

Implementation guidance, research recommendation

Implications for practice

Workplace exposure studies indicate that in most situations, exposure exceeds the majority of the proposed OELs. This should be a strong incentive for exposure control measures.

Implications for research

More studies are needed to derive OELs for specific MNMs. Harmonization of OELs requires agreement about interspecies and intraspecies’ adjustment factors and exposure values.

Summary of findings: systematic review on exposure assessment and measurement

Systematic review question: In workers potentially exposed to MNMs or workplaces with exposure to MNMs, which exposure measurement techniques to assess MNMs are feasible based on studies that assessed and measured exposure?

Evidence summary

The systematic review was published by Boccuni et al. (2017) as a journal article (30).

Number of studies and participants

The systematic review included papers on exposure through inhalation and dermal absorption. There were no papers identified on exposure through ingestion. The systematic review identified 59 articles that described 53 measurement techniques. Among these, four papers analysed both inhalation and dermal exposure. Three studies of dermal exposure were conducted in the workplace and one in the laboratory setting. These papers reported very poor data on specific techniques for dermal exposure measurements. Therefore, systematic review conclusions were focused on measurements of exposures through inhalation.

Measurements in studies

There were 53 descriptions of a basic measurement technique and of these there were 13 additional descriptions of a comprehensive technique to assess the presence or absence of MNMs in workplace air. All 53 techniques measured exposure by inhalation; of these, four studies also considered exposure by dermal absorption.

Outcomes in studies

The studies used either a basic assessment technique or a comprehensive technique.

Risk of bias in the included studies

The basic exposure assessment was rated as moderate quality in 40 studies and as high quality in two studies.

The comprehensive exposure measurement was rated as moderate quality in 11 studies and as high quality in two studies.

Exposure measurements carried out

A basic exposure measurement that assesses the presence or absence of MNMs in the workplace air was demonstrated in 53 studies.

A comprehensive exposure measurement was demonstrated in 13 studies.

Comprehensive measurement techniques are more expensive than basic measurement techniques.

Quality of the evidence

The quality of the evidence is moderate for both basic and comprehensive assessments because the majority of the studies demonstrate at least a moderate-quality exposure assessment. There was very low quality and inconsistent evidence on specific techniques of dermal exposure measurement.

Implementation guidance, research recommendation

Implications for practice

The GDG concludes that there is moderate-quality evidence that both basic and comprehensive measurement techniques are feasible in the workplace.

Implications for research

Studies to validate basic and comprehensive measurement techniques including techniques to assess dermal exposure are needed.

6.3. Control Exposure to MNMs

6.3.1. Focus on prevention of inhalation of MNMs

  • Recommendation 7: Based on a precautionary approach, the GDG recommends focusing control of exposure on preventing inhalation exposure with the aim of reducing it as much as possible (STRONG, moderate-quality evidence).
  • Recommendation 8: The GDG recommends reduction of exposures to a range of MNMs that have been consistently measured in workplaces especially during cleaning and maintenance, collecting material from reaction vessels and feeding MNMs into the production process. In the absence of toxicological information, the GDG recommends implementing the highest level of controls to prevent any exposure of workers. When more information is available, the GDG recommends taking a more tailored approach (STRONG, moderate-quality evidence).

Sometimes, specific types of MNMs are processed in a specific way, such as in an open or closed system during synthesis, and thus this determines the likelihood of exposure. The GDG recommends that under these circumstances, the distinctive processes related to the type of MNM are taken into account in the evaluation of workers’ likelihood of exposure and the routes of exposure.

The GDG further notes that there is a need to perform high-quality evaluations of worker exposures to nanomaterials in LMI countries.

From evidence to recommendation

Evidence

The evidence for these recommendations is based on two systematic reviews of studies that measured exposure to specific MNMs in the work environment. One review assessed what the most likely routes of exposure were and during which tasks these exposures occurred. This review was published by Basinas et al. (2017) (31). The other review assessed the levels of exposure to MNMs, how well the exposures were measured and during which tasks the exposures occurred. This review by Debia et al. (2016) was published as a journal article (32). The studies on inhalation were considered of high quality, but those on dermal and ingestion exposure contained assumptions that reduced the quality of the evidence. The studies on workplace exposure measurements mostly used well elaborated exposure assessment strategies and were rated as high-quality studies.

Benefits and harms

To be able to implement an effective control strategy, it is important to know if there is exposure to MNMs and what the most important route of uptake is. The recommendation aims at preventing potential harmful effects of MNMs through a focused control strategy.

Values and preferences

The routes of uptake form an important part of the occupational hygiene strategy to reduce exposure to chemicals. There are no specific values or preferences connected to this issue.

Net benefits and costs

It is important to know the routes of exposure. For inhalation exposure, the methods of measurement are well-defined, but for dermal and ingestion exposure this is more complicated and not yet standardized. Certainty about the dermal route of exposure would imply more specific exposure assessment and involve considerably more work and cost.

Strength of the recommendation

For inhalation exposure, based on the above considerations, the recommendation is strong. For dermal exposure, the quality of evidence is low and thus the recommendation is conditional.

Summary of findings: routes of exposure to MNMs

Systematic review question: In workers with potential exposure to MNMs, what are the most likely routes of exposure for specific MNMs and during specific tasks based on workplace measurements of MNMs?

Evidence summary

The systematic review was published by Basinas et al. (2017) (31).

Number of studies and participants

There were 107 studies reporting a total of 424 exposure assessment situations, i.e. combinations of activity and type of MNM with workers’ potential exposure to MNMs and sufficient data to allow assessment of the likelihood of exposure by route.

Exposures in studies

The exposure assessment situations related to potential workers’ exposure to CNTs and CNFs (N = 63), Si-based (N = 42), TiO2 (N = 43), other metal oxides (N = 77), metals (N = 38), and other nanomaterials (N = 61).

Outcomes in studies

For every exposure assessment situation, the likelihood of a route of exposure was assessed by applying specific criteria. For inhalation exposure, an adapted set of criteria was used based on the CEN Standard (PREN 17058) Workplace exposure – Assessment of inhalation exposure to nano-objects and their agglomerates and aggregates (33). Dermal exposure was based on an established source-to-reception model. For each combination of activity and type of MNM, the likelihood of exposure by a particular route was derived by aggregating across the relevant individual assessments.

Risk of bias in the included studies

The main limitations of the studies are listed below:

  • The data that were available from studies included in the review comprised measurement in small and research scale-productions and therefore may not adequately represent the exposure conditions in industrial workplaces.
  • For the inhalation route, there was a lack of harmonized methods to measure personal exposure at the workers’ breathing zone. Most of the evaluated exposure assessments were based on stationary sampling, not necessarily representative of workers’ exposure via inhalation.
  • For the dermal route only, there were limited indirect measurement data available that resulted from the analysis of collected surface samples.
  • No measurement data are available on ingestion exposure.
  • Protection provided by PPE was not considered in the review because it is not relevant to determine the route and form of exposure.

Results

There is high-quality evidence that, in general, the form and route of exposure depends mainly on the activity (i.e. process and operational conditions), rather than just on the type of MNM handled (Annex 3).

There is also high-quality evidence that the likelihood of exposure is affected by the presence of risk management measures and the scale of production. In principle, both inhalation and dermal exposure are less likely when the process is enclosed. For example, CNTs, Si-based and various metal oxides are processed within enclosed reaction vessels, which makes exposure unlikely during production. Other materials such as TiO2 and metals can be synthesized with flame pyrolysis and mechanical reduction in a not fully enclosed process, which makes exposure more likely to occur.

When a worker can possibly inhale MNMs, potential for dermal exposure also exists. However, for some forms (e.g. when an MNM is in suspension/liquid form), dermal exposure or ingestion exposure can be possible even when inhalation exposure is unlikely.

For the following situations and MNMs, exposure was unlikely:

For CNTs and CNFs, there is high-quality evidence that inhalation exposure usually does not occur in the reaction phase of synthesis and handling and transfer of liquids. There is high-quality evidence that dermal exposure does not occur in the reaction phase of synthesis.

For Si-based nanomaterials, there is high-quality evidence that inhalation and dermal exposure do not occur in the reaction phase of synthesis.

For other metal oxides and mixtures, there is high-quality evidence that inhalation and dermal exposure do not occur in the reaction phase of synthesis.

For other MNMs, there is high-quality evidence that inhalation and dermal exposure do not occur in the reaction phase of synthesis.

Quality of the evidence

Quality of the studies was dependent on the methods used to quantify release and the applicability or not of the adapted set of criteria described in the CEN Standard (PREN 17058) Workplace exposure – Assessment of inhalation exposure to nano-objects and their agglomerates and aggregates (33).

Conclusions reached using the adapted CEN criteria and both off-line and online data, were considered to be based on high-quality data. For some MNMs there is an established exposure assessment method based on chemical analysis, e.g. for CNT and TiO2. When this chemical analysis was used to quantify the release, the quality was considered high even if no online measurements were available or if the available online measurements for the activity involving MNMs were not considerably higher than background.

For dermal exposure, evidence was considered as high quality if surface contamination was clearly established and/or if release was confirmed through both online and off-line measurements and a transparent description of the process and operational conditions was provided.

Implementation guidance, research recommendation

Implications for practice

The GDG concludes that there is high-quality evidence for workers’ inhalation exposure and low-quality evidence for dermal exposure to MNMs in general.

There is also high-quality evidence that in some situations inhalation exposure is unlikely, such as for CNTs and CNFs during handling and transfer of liquid intermediaries and ready-to-use products, and high-quality evidence that dermal exposure does not occur during the reaction phase of synthesis for most MNMs.

There were no studies of ingestion exposure. However, established conceptual models imply that where dermal exposure occurs, ingestion exposure is likely.

Implications for research

There is a need to conduct more representative studies to better estimate workers’ inhalation exposure by assessing MNMs at the personal breathing zone, rather than in the near-field. Studies that directly measure dermal and ingestion exposure of workers to MNMs are needed. For all routes of exposure more measurements are needed under real industrial production conditions. More research should be conducted to characterize exposures to nanomaterials in a broad range of industries where nanomaterials are used.

Summary of findings: workplace exposures to MNMs

Systematic review question: In workplaces where MNMs are in use according to the OECD list, does comprehensive measurement of exposure lead to confirmation of exposure to MNMs and if so during which tasks? Any study type in which exposure to MNMs was comprehensively measured was included.

Evidence summary

The systematic review was published by Debia et al. (2016) as a journal article (32).

Number of studies and participants

Over the reviewed period (January 2000–January 2015), 50 studies in 72 workplaces with 306 exposure situations were eligible and included in the review. Studies were mainly located in the Republic of Korea and the United States, but none in LMI countries. Most studies (62.5%) were in research laboratories or pilot plants.

Exposures in the studies

Exposures to carbonaceous and metallic nanomaterials and nanoclays were evaluated in the studies.

Outcomes in studies

Authors reported weight-based concentrations (mass concentration), count-based concentrations (number concentration) and off-line qualitative analysis.

Risk of bias in the included studies

The main limitations in the studies were that the exposure measurements were not real breathing zone sampling and not as comprehensive as would be advisable.

Confirmed exposure

Of the 306 exposure situations, there was confirmed exposure in 233 (76%) ranging from 100% for nanoclays, 83% for carbonaceous MNMs and 73% for metallic MNMs.

In 233 of the exposure situations, confirmed workers’ exposure was mainly confined to microsized agglomerated MNMs with only a few studies reporting the sampling of nanoscale airborne MNMs.

Exposures to carbonaceous MNMs ranged from not detected to 910 µg/m3 of elemental carbon (EC) with local engineering controls and from not detected to 1000 µg/m3 EC without controls.

Carbon nanofibre exposure ranged from not detected to 1.6 CNF structures/cm3 with local engineering controls and from 0.09 CNF structures/cm3 to 193 CNF structures/cm3 without controls.

Titanium dioxide nanoparticle exposure ranged from 0.24 to 0.43 µg/m3 with local engineering controls and from 0.09 to 33 µg/m3 without controls.

Aluminium oxide nanoparticle exposure was not detected with local engineering controls and ranged from not detected to 0.157 µg/m3 without controls.

Silver nanoparticle exposure ranged from 0.09 to 4.99 µg/m3 during dry synthesis with no controls (only general ventilation) and from 0.38 to 0.43 µg/m3 during wet synthesis (with fume hood). Reactor cleaning activities yielded the highest exposure, up to 33 µg/m3 (with local exhaust ventilation).

Iron nanoparticle exposure ranged from 32 µg/m3 with local engineering controls to 335 µg/m3 without controls.

In 231 of the exposure situations, workers were exposed to micro-sized agglomerated MNMs and in two of the exposure situations to nanoscale MNMs.

Quality of the evidence

GRADE had to be considerably adapted to fit the type of studies reviewed. Consistent results in several studies with comprehensive measurements were considered high-quality evidence. The GDG judged that given the comprehensiveness of the measurements and the consistency of the results, there was overall high-quality evidence that workers are exposed to micro-sized agglomerated MNMs in workplaces during production and use of products. For the same reasons, the evidence for handling tasks was rated as high quality.

Implementation guidance, research recommendation

Implications for practice

The GDG concludes that there is high-quality evidence that workers are exposed to micro-sized agglomerated nanoparticles and that exposure occurs mostly during handling tasks, cleaning operations and machining of products. There was low-quality evidence of exposure to nanoscale primary airborne nanoparticles in workplaces. There were no studies, and therefore there was no evidence of exposures in LMI countries.

Implications for research

Longitudinal studies evaluating workers’ exposure over time are needed. Studies of workers’ exposure in LMI countries are also needed.

6.3.2. Use controls to reduce the level of exposure

  • Recommendation 9: The GDG recommends taking control measures based on the principle of hierarchy of controls, meaning that the first control measure should be to eliminate the source of exposure before implementing control measures that are more dependent on worker involvement, with PPE being used only as a last resort. According to this principle, engineering controls should be used when there is a high level of inhalation exposure or when there is no, or very little, toxicological information available. In the absence of appropriate engineering controls PPE should be used, especially respiratory protection, as part of a respiratory protection programme that includes fit-testing (STRONG, moderate-quality evidence).
  • Recommendation 10: The GDG suggests preventing dermal exposure by occupational hygiene measures such as surface cleaning and the use of appropriate gloves (CONDITIONAL, low-quality evidence).
  • Recommendation 11: When assessment and measurement by a workplace safety expert is not available, the GDG suggests using control banding for nanomaterials to select exposure control measures in the workplace. Owing to a lack of studies, the GDG cannot recommend one method of control banding over another (CONDITIONAL, very low-quality evidence).

The GDG considered that in the absence of toxicological information on MNMs, the most stringent control measures should be applied to prevent workers from being exposed. This is also called a no-exposure policy.

Control banding is an approach to risk management for SMEs that can be applied to prevent worker exposures in cases of incomplete information about a nanomaterial. Control-banding strategies are often found in toolkits with categories, or bands, of health hazards, that are combined with exposure scenarios to determine the desired controls. This approach allows users to make meaningful inferences about likely exposures and to make decisions about necessary controls, reducing the exposures within four or five hazard bands (34).

When there is only limited toxicological information available for MNMs, or when analogies can be made with hazard properties of similar materials in broad groups, this should lead to control banding. When full toxicological information is available, this should lead to full risk assessment. The GDG therefore notes that control banding does not replace risk assessment, but it can still be beneficial for communication and better risk management.

From evidence to recommendation

Evidence

The evidence for these recommendations is based on two systematic reviews, both of which were published as journal articles. The first, by Myojo, Nagata & Verbeek (2017), reviewed the effects of control measures (35). The other, by Eastlake, Zumwalde & Geraci (2016), assessed the effects of the control-banding approach (36). For the control measures varying levels of evidence were found and therefore parts of the recommendation are conditional. Overall the risk of bias across studies was low but precision was unclear. For PPE the quality of the evidence was further downgraded because of indirectness, meaning that there were only laboratory studies and no field studies. For control banding there were only two studies, with a high risk of bias.

Control-banding tools such as those listed in the systematic review (36) can be used proactively as a low-cost intervention to reduce exposures to nanomaterials in the workplace.

Benefits and harms

There are clear benefits of preventing and decreasing exposure by engineering controls.

Values and preferences

The hierarchy of controls is a generally accepted concept in occupational hygiene, in which increased value is given to what are known as “more preventive” solutions (see Hierarchy of controls). Control banding is an approach that is well understood by employers and employees and seems feasible with bulk materials (37).

Net benefits and costs

The costs for full enclosure or process change can be considerable but decrease with the hierarchy of controls. The GDG attaches much weight to more preventive solutions. Control banding requires training but no considerable investments (38).

Strength of the recommendation

Based on the above considerations, the GDG makes a strong recommendation for control measures for inhalation exposure but a conditional recommendation for full body protection to prevent dermal exposure and a conditional recommendation for control banding.

Evidence summary of controls to reduce exposure to MNMs

Systematic review question: In workers or workplaces with exposure to MNMs, what is the effect of workplace ventilation, PPE or organization of work aimed at reducing exposure, on the level of exposure to MNMs compared to no controls or protective equipment based on studies that compared a situation with the intervention to a situation without the intervention?

The effect of the controls was expressed as the protection factor (PF), which is defined as the ratio of exposure level (either mass-based or particle-based) without the controls divided by the exposure level with the controls. If the PF is >1 controls reduce exposure. A PF of 10 indicates that controls reduce exposure by 90%.

Evidence summary

The systematic review by Myojo and Nagata (2017) was published as a journal article (35).

Number of studies and participants

There were 50 studies with 55 workplaces/participants. Of these studies, 27 were before–after comparisons.

Controls evaluated in studies

There were 14 studies with 27 workplaces that evaluated ventilation, 19 studies with 23 participants evaluated PPE, 16 studies evaluated other control strategies: five on suppression with fluids, two on automation of a process with five workplaces, eight on other organizational strategies, and one on the use of SDS. All studies were about MNM exposure and 15 of these were on exposure to carbon nanotubes.

Outcomes in studies

All outcomes were expressed as a PF.

Risk of bias in the included studies

The main limitations were no control group for the studies on engineering controls and no fieldwork for the respiratory protection studies. Risk of bias in the studies was 2 to 3 on a scale that ranged from −3 to 3, in which −3 meant a very high risk of bias and +3 a very low risk of bias.

Effects of exposure

For engineering controls, enclosure achieved the highest PFs of > 100 (seven cases).

For ventilation, PFs varied from 0.12 to 55 (20 cases) with 15 cases providing PFs >3. For ventilation of fume cupboards, the PF was influenced by the face velocity of the air and the movements of workers. Face velocity is the inward airflow velocity measured in several specific locations across the plane of the fume cupboard sash opening.

For process automation, the PFs varied between 2.5 and 8.2 (five cases) but, owing to interruption of the process by handling material, one case yielded a PF of 0.073. The studies on dustiness and fluid-dust suppression did not provide before–after measurements and did not allow for a PF calculation.

For respiratory protection, masks rated at the protection level of N95 respirators provided a PF of more than 10 in 11 cases. Higher rated P100 respirators provided higher PFs of around 100. One study evaluated a cloth mask which yielded a PF of 1.1 to 1.35. One study reported on a loose-fitting powered air-purifying respirator with PFs over 1.1 million. Most studies were performed in the laboratory under ideal conditions with exposure to sodium chloride as a proxy for MNM because of its size. However, it is unclear whether these results can be extrapolated to mask performance in real workplaces.

Quality of the evidence

Risk of bias in the studies was low. Except for the respiratory protection studies the evidence was direct. The results were consistent across studies. Precision of the effects was unclear because the authors did not provide estimates of statistical precision. Publication bias can be expected, but could not be assessed owing to a lack of data.

The rating of the evidence was defined as low quality at the outset because all studies were non-randomized and non-controlled. The evidence was not upgraded or downgraded.

Implementation guidance, research recommendation

Implications for practice

The GDG concludes that there is only low-quality evidence that exposure to MNMs can be decreased with engineering controls such as enclosure and ventilation, when the specific exposure situations are taken into consideration. There is also only low-quality evidence that respiratory protection can considerably decrease exposure, if the proper type is used and fit-testing is performed for each wearer.

Implications for research

Field studies that evaluate dust control techniques, such as modification and suppression are needed. In addition, studies on the effectiveness of respiratory protection under real workplace conditions are needed.

Evidence summary: control banding for safe handling of manufactured nanomaterials

Systematic review question: In workers or workplaces with potential exposure to MNM, what is the effect of the use of a control-banding tool on controls in place or level of exposure compared to no risk assessment tool or an alternative risk assessment tool based on any type of controlled study?

Evidence summary

The full review was published by Eastlake, Zumwalde & Geraci (2016) as a journal article (36).

Number of studies and participants

There were two studies that evaluated 32 different exposure situations. One study was conducted in two MNM research laboratories with exposure to metal and ceramic nanoparticles and CNTs in the United States. The other study reported an additional 27 cases of potential exposure to a variety of MNMs, but did not provide details of the geographical location or the worksite.

Interventions in studies

Both studies were about evaluating potential exposure to a variety of MNMs using the control-banding nanotool developed by Paik, Zalk & Swuste (38).

The use of the control-banding nanotool was compared to assessments performed by an experienced occupational hygienist.

Outcomes in studies

The outcome in both studies was the recommendation of an engineering control.

Risk of bias in the included studies

The main limitations were that there was only a qualitative analysis and no exposure measurements. One of the studies did not provide details of the work situations.

Effects of exposure

In the two studies, the recommendations provided using the control-banding nanotool concurred with those of the occupational hygienist in 59% (19/32) of cases. The control-banding nanotool recommended a lower level of control than the occupational hygienist in 28% (9/32) of cases. The control-banding nanotool recommended a higher level of control than the occupational hygienist in 13% (4/32) of cases.

No exposure assessment data were provided to verify that engineering controls recommended by the occupational hygienist reduced exposure potential.

Quality of the evidence

According to GRADE, observational studies start as low-quality evidence, unless they can be upgraded. Based on the limitations of the studies (qualitative analysis, no exposure assessment data, no details about workplaces), the evidence found in this systematic review was downgraded to very low quality.

Implementation guidance, research recommendation

Implications for practice

The GDG concludes that there is only very low-quality evidence that use of the control-banding nanotool leads to similar control measures to those an experienced occupational hygienist would recommend. Professionals, employers and workers would all need training to be able to use the tool.

Implications for research

The low quality of evidence on the effectiveness of control-banding approaches to reduce worker exposure to nanomaterials to safe levels, suggests that more research needs to be conducted in this area. Specifically, effectiveness of control banding to reduce exposures to MNMs should be evaluated by carrying out measurements selected through the use of control-banding tools (against more comprehensive risk assessment and risk management approaches). Control-banding tools should be further evaluated for use with MNMs. Control-banding tools should be calibrated against exposure measurements and guidance for selection of the appropriate tool for specific situations should be developed.

6.4. Health Surveillance

The GDG cannot make a recommendation for targeted MNM-specific health surveillance programmes over existing health surveillance programmes that are already in use, due to the lack of evidence.

The GDG further notes that existing occupational health surveillance systems could be implemented to monitor health outcomes possibly associated with MNM exposure where there are health concerns. Given that knowledge of MNMs and their adverse health effects is increasing rapidly, this recommendation should be updated in five years to take into account new findings.

From evidence to recommendation

Evidence

The evidence for this recommendation is based on a small number of non-randomized studies at high risk of bias that did not show the benefits of health examinations.

Benefits and harms

The benefits of health examinations could not be assessed. Setting up a health surveillance system for workers exposed to MNMs would be costly. In addition, it would be difficult, with the current lack of knowledge, to ascribe adverse health effects to MNM exposure.

Values and preferences

It is well known that general health examinations are highly valued by consumers and this is probably also the case for workers (39).

Net benefits and costs

Since the GDG could not assess any benefits of health examinations that are specific for MNMs, only considerable costs remain.

Strength of the recommendation

Based on the above considerations, there is no recommendation for specific health examinations.

Summary of findings: health examinations of workers exposed to MNMs

Systematic review question: In workers exposed to MNMs, what is the effect of health surveillance on any adverse health outcome compared to no health surveillance or an alternative form of health surveillance based on any study that described or evaluated health surveillance?

The systematic review was published by Gulumian et al. (2016) as a journal article (40).

Number of studies and participants

There were seven studies of which six compared health indicators between exposed and unexposed workers, with 1278 participants. One study described a programme, but did not report any health outcomes. Studies showed that workers were exposed to a mixture of MNMs (3), CNTs (2), nanosilver (1) and TiO2 (1).

Health examinations in studies

Studies reported on biomarkers from exhaled breath condensate, blood and urine such as markers of oxidative stress and antioxidant enzymes; early health effects such as pulmonary and neurobehavioural test results; and self-reported health outcomes.

Risk of bias in the included studies

The main limitations were that there were no controlled studies with a longitudinal design; all of them were cross-sectional.

Effects of exposure

Two studies found biomarker levels (exhaled breath condensate concentrations of malondialdehyde, 4-hydroxy hexenal (4-HHE) and n-hexanal/aldehyde) elevated in exposed groups compared to unexposed groups.

Early health indicators (lung function parameters) did not deviate from physiologically normal parameters or did not differ between groups.

The prevalence of allergic dermatitis and sneezing was higher among workers exposed to MNMs in one study.

Quality of the evidence

According to GRADE, observational studies start as low-quality evidence unless they can be upgraded. The evidence found in this systematic review was further downgraded because of limitations in study design. There were no reasons to upgrade the evidence.

Implementation guidance, research recommendation

Implications for practice

The GDG concludes that there is only very low-quality evidence on whether targeted nanomaterial health surveillance might reveal early signs of adverse health effects. There was no evidence on specific items that should be included in a surveillance programme.

Implications for research

More research needs to be conducted to (i) identify biomarkers specific to nanomaterial exposures; (ii) identify potential early signs predicting potential long-term adverse health effects, and (iii) validate current medical tests for use in asymptomatic nanomaterial-exposed workers. It is important to emphasize to workers participating in health surveillance that these programmes at this point are research efforts with unproven benefit and health significance to participants.

Exposure registry studies, based on which workers can be followed over time to validate candidate biomarkers, are needed.

6.5. Training and Involvement of Workers

The GDG considers training of workers and worker involvement in health and safety issues to be best practice, but cannot recommend one form of training of workers over another, or one form of worker involvement over another, owing to the lack of studies available.

The GDG commissioned a systematic review to answer the question “what training should be provided to workers?”. The question was reformulated to look at the effects of additional training and education on workers potentially exposed to MNMs. The systematic review by von Mering & Schumacher (2017) was published by WHO (41). The GDG also conducted preliminary searches to answer the question about worker participation in the workplace risk assessment and management of MNMs. However, no studies were found on this topic.

Summary of findings: training and involvement of workers

Systematic review question: In workers exposed to MNMs, does specific training or education on safe handling of MNMs have an effect on the level of exposure to MNMs or on the level of controls (including PPE) implemented compared to no training, or an alternative form of training?

Evidence summary

The systematic review did not locate any studies on the effects of worker training. There were no studies that established specific workers’ training needs related to MNMs.

Research recommendation

Implications for research

The GDG recommends evaluating the effect of worker and employer training on the level of MNM exposure and the installation of controls compared to alternative forms of training, preferably with a controlled before–after design. Similarly, the GDG recommends evaluating the effect of different forms of worker involvement on level of exposure and implementation of controls.

© World Health Organization 2017.

Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/licensing.

Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user.

Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).

Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”.

Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization.

Bookshelf ID: NBK525045
Contents

Views

In this Page

Other titles in this collection

Recent Activity

ClearTurn OffTurn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...