Nanotechnology, i.e., the science and technology of matter on the nanometer scale, is a fast-growing industry that includes the production and handling of engineered nanomaterials (ENMs). Data from the 2012 Second Regulatory Review on Nanomaterials estimated that direct employment in nanotechnology amounted to 300,000–400,000 jobs in the European Union [1
]. Their increased market-oriented production and handling can yield exposure with the potential for unforeseen negative health effects. In particular, workers in companies producing and handling nanomaterials are likely to have higher exposures to these materials than the general population.
Biomonitoring (BM) is an important tool to survey individuals’ internal exposure, i.e., the body burden of chemicals and/or their metabolites known as exposure biomarkers that accumulate from different sources of exposure, and the early biological effects known as effect biomarkers, highlighting, e.g., oxidative stress or inflammation [2
]. The relevance of BM can be for the purpose of exposure assessment, risk management, and health surveillance [4
]. Occupational BM programs are thus of particular interest during primary and secondary manufacturing of ENMs [6
], i.e., processes identified as being at-risk of ENM exposure with unknown toxicity in humans [8
]. Yet, despite the broad employment in the field of nanotechnology, biomonitoring programs for ENM-handling workers are limited in number and scope [11
]. A systematic review identified seven BM programs measuring oxidative stress, inflammation, cardiovascular and genotoxicity biomarkers in the blood, urine, and exhaled-breath condensates (EBCs) of ENM-handling workers for the period 2000–2015; only one took place in Europe [15
]. Reasons behind the scarcity of such programs include scientific, methodological, political, and regulatory challenges, as examined by Guseva Canu and colleagues, who concluded that lack of political and regulatory support are currently the most salient issues [16
A recent questionnaire survey highlighted that a lack of legal enforcement, in addition to a lack of BM guidance values and limited toxicokinetic information, currently constituted the most cited obstacles for using BM data in risk assessment [3
]. This survey targeted risk assessors, but not the issue of BM acceptance among managers and workers, and practical aspects affecting its feasibility. Addressing these issues is crucial when deciding how to best design a BM program in such occupational settings; ignoring it would result in failure during implementation due to insufficient adherence of participants, unexpected logistical constraints, and ineffective communication. Therein, our survey aimed at identifying factors influencing participation acceptance in a BM program in companies producing and/or handling ENMs. It was conducted in the framework of the European-funded NanoExplore project, which aims at building an integrated approach for exposure and health effect monitoring of engineered and incidental nanoparticles in various workplaces.
A total of 43 companies provided an answer to our survey, which represents a 2.42% response rate. Of these 43 companies, six declared not to be involved with any ENM-related activity. Nineteen companies provided an answer without completing the questionnaire, yet seven of them provided confirmation of ENM-related activity. Our analysis and discussion are based on the 18 completed managers’ questionnaires. We do not provide separate analysis by respondents’ position for this questionnaire (13 completed by managers and five by H&S specialists) because of the small number of respondents. Additionally, five workers completed the second questionnaire and qualitative results are reported below.
3.1. General Company Characteristics
Most of the respondent companies were located in Europe (n
= 9; 51%), but some were located overseas (n
= 4; 22%). The main activities involving ENMs were R&D activities (n
= 12; 67%), nano-safety and industrial hygiene (n
= 6; 35%), and production (n
= 6; 35%). In half of the companies, the number of workers involved in ENM-related processes was 10 or less (n
= 9; 50%), and three companies (17%) reported employing between 10 and 49 workers for ENM-related activities. Detailed values are reported in Table 1
3.2. ENM Characteristics and Handling Specificities
The majority of companies reported having their employees work with ENM-related processes during 15 min to 1 h or 1 to 4 h per day (both n
= 5; 28%; Figure 2
A), for 2 or 3 days per week (n
= 9; 50%; Figure 2
B). Most companies indicated producing or using less than 1 kg of ENM per year (n
= 8; 44%; Figure 2
C), in majority in solid form (n
= 14; 78%) or dispersed in a liquid (‘liquid’; n
= 12; 67%; Figure 2
D). The most commonly manufactured and/or handled ENMs were titanium dioxide (TiO2
= 11; 61%), multi-walled carbon nanotubes (MWCNT; n
= 8; 44%), and silicon dioxide (SiO2
) and graphene (both n
= 7; 39%; Figure 2
3.3. Health and Safety Plan and Practice
Thirteen companies (72%) reported having a nanomaterial-specific H&S plan (‘No’: n
= 1; 6%; ‘Not provided’: n
= 4; 22%), yet only two companies (11%) indicated following an ENM exposure monitoring program (‘No’: n
= 12; 67%; ‘Not provided’: n
= 4; 22%). Fifteen companies (83%) confirmed using engineering controls; local exhaust ventilation (LEV) and recycled air systems with high-efficiency particulate air (HEPA) or ultra-low particulate air (ULPA) being the most frequent (n
= 8; 44% and n
= 4; 22%, respectively; Figure 3
A, left panel). LEV types were, in six out of eight (75%) companies, laboratory fume hoods and/or glove boxes (Figure 3
A, right panel).
The use of PPE was widely reported. Single-use chemical protection gloves (n
= 16; 89%), laboratory coats or woven fabric or cotton coveralls (n
= 14; 78%), and goggles (n
= 9; 50%) were the most frequently reported PPEs overall. Disposable self-filtering masks or respirators were reported by companies as the most frequently used type of respiratory PPEs (n
= 8; 44%; Figure 3
B). H&S specialists employed by the respondent companies were both occupational physicians and H&S specialists (engineer and technicians) (n
= 6; 33%; and n
= 10; 56%, respectively). Strategies used to manage the risk uncertainty related to ENM exposure were mostly based on an application of H&S procedures already in place for other substances (n
= 5; 28%). Four companies (22%) reported reviewing the state of research regularly and updating their H&S procedures accordingly.
3.4. Managers’ Participation Acceptance and Study Practical Feasibility
A majority of the respondent companies (n
= 15; 83%) had participated in a research study or a scientific partnership in the past (‘No’: n
= 1; 6%; ‘Not provided’: n
= 2; 11%). Thirteen companies (72%) confirmed that they would consider participating in a research study evaluating ENM exposure and possible impact on workers’ health, whereas three (17%) responded negatively (Figure 4
A, left panel). Reasons for refusing participation were concerns about data protection and confidentiality (n
= 1; 33%), or that in-house H&S specialists already had sufficient ENM information (n
= 1; 33%). The main reasons for favorably considering participating in a research study were the improvement of workers’ workers (n
= 9; 69%), an increased knowledge about ENM-related H&S practice, and help in developing specific ENM-related H&S procedures and practice (both n
= 8; 62%). Four managers also indicated that such a study would provide useful data to fulfil obligations under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation [25
] (Figure 4
A, right panel). According to managers and H&S specialists, the main reasons for their workers to participate would be the acquisition of individual exposure and biological results (n
= 6; 33%), assessment of their health during the project (n
= 5; 28%) and indirect health benefits to other workers in the sector (n
= 5; 28%; Figure 4
Regarding practical aspects of ENM research, several managers and H&S specialists indicated that they would be comfortable with ENM exposure measurements (n
= 7; 37%), and sampling of biological media for their workers (n
= 5; 28%; Figure 5
A, left and middle panels, respectively). One of the practical hurdles of BM studies conducted in occupational settings is whether adequate space is available inside or near the working premises. This is specifically the case when EBC sampling is part of the study. Yet, only two companies (11%) confirmed the availability of an in-house room for biological sampling, and 14 of them (78%) did not know or did not provide a response (Figure 5
A, right panel). Recognizing that participation in research programs can be time-consuming for companies, we also asked about expectations regarding acceptable duration and frequency of research campaign(s). Most managers reported preferring a study condensed in one campaign (n
= 5; 28%) that would last 7 days maximum (n
= 3; 17%), and require an hour per day or less of participants’ time (Figure 5
B, upper panels). In general, managers reported spring and fall as being the most suitable periods to accommodate a research campaign (Feb.–March: n
= 6; 33%; Apr.–May–June: n
= 3; 17% and Sept.–Oct.–Nov.: n
= 4; 22%; Figure 5
B, lower left panel). Around the New Year period (Dec.–Jan.: n
= 5; 28%) and summer months (July–Aug.: n
= 3; 17%) were considered as the worst periods due to reporting workload and holiday time, respectively (Figure 5
B, lower middle panel). All managers but one (n
= 7; 39%) agreed on study procedures being conducted during employees’ working hours (Figure 5
B, lower right panel).
3.5. Workers’ Participation Acceptance and Study Practical Feasibility
Five workers completed the worker’s questionnaire. Three workers from three companies reported being employed with a permanent contract and having worked for the company for 3 to 5 years, and the other two workers were either self-employed for more than 5 years or working under a short-term (3 months or less) contract. All workers confirmed that ENMs were produced and/or handled in the company, and that they handled ENMs at their workplace. Additionally, these workers indicated having received training regarding health effects and safety of ENMs.
These five workers unanimously reported willingness to participate in a study of ENM exposure and impact on their health. Furthermore, workers reported that acquisition of their individual results would be the main reason for participating, in accordance with what managers reported. Indirect benefits from such a study to the general population (including consumers) and to co-workers or other workers in the sector, and funding of the research study by a public institution, were also indicated as valuable reasons to consider participation.
All five workers confirmed that there was sufficient space for an ambient air-monitoring device at the workstation(s) where ENMs were produced and/or handled. Most workers confirmed feeling comfortable completing a questionnaire addressing their lifestyle habits and medical history, either administered face-to-face by a health professional or self-administered on a personal electronic device such as a tablet. When asked about biological sampling procedures, all workers reported feeling comfortable with exhaled air sampling; three of five workers were similarly comfortable with either one of the other procedures listed, i.e., exhaled breath condensate, urine, and buccal cell sampling. Workers unanimously stated that their participation in the research study should take place during working hours, in line with managers’ answers. Three workers considered allocating between 15 and 30 min of their time to a research study; the other two preferred either a shorter (15 min or less) or longer period (between 45 and 60 min). Three workers reported a preference for research procedures to take place only once per day, whereas the other two were ready to allocate their time to the research study as often as necessary.
We identified several factors influencing participation for a BM program targeting ENM exposure and possible health effects in companies producing and/or handling ENMs. However, our findings are not generalizable, as the response rate was low, although similar to other surveys [20
]. There could be several reasons for the low response rate. Because the dissemination strategy used in our survey included several intermediary electronic steps that could not be traced, calculation of exact response rates is difficult. Indeed, managers’ responses obtained here actually represent three steps: the invitation to participate was read by the email recipient, then transferred to the manager or H&S specialist, who read the invitation and agreed to participate. Some companies, in particular small companies and start-ups, might also have stopped their ENM-related business. As there is no unique, reliable source identifying such companies in the countries involved in this project, uncertainty remains regarding the number of existing companies actually producing and/or handling ENMs. Overall, 19 questionnaires of the 43 respondent companies were not able to be used. Furthermore, a number of managers or H&S specialists (n
= 7) only opened the questionnaire to provide a confirmation of ENM-related activity; the survey was otherwise empty, thus highlighting the difficulty for researchers to trigger sufficient interest to recruit such companies. The situation with workers is even more complex, as it requests an effective transfer of the information from managers to their workforce, and the effective reception and treatment of this information by workers. Despite our request for managers to inform us if they disseminated the workers’ survey link to their workforce, none contacted us. Consequently, we could not consider the number of responses received from workers to calculate their response rate.
Insufficient interest and limited participation in research are common findings in previous studies conducted in ENM-producing and/or handling facilities. A low response rate was reported in a number of national and international surveys. For instance, the ICOH survey reported a 2.58% response rate despite extensive work to build a solid database of 2029 company contacts and the authority of the ICOH scientific committee “Nanotechnology workers”, which managed this survey [20
]. Another survey conducted in 2012 in Quebec achieved a response rate of 8.4% from industrial companies contacted; however, this required considerable engagement from the study team as they individually called each of the 1181 companies in their database [19
]. A Swiss survey conducted in 2007 provides the only contrasting example in the field [17
]. Their response rate among companies was 58.3%, a figure mostly attributed to the fact that this survey was conducted jointly with the Ministry of Economy and Industry (SECO) and the national insurance provider (SUVA), which provides mandatory insurance, prevention services, and control of occupational H&S in Switzerland. This confirms an already expressed challenge to conduct health research and intervention without political and regulatory support [16
Several lessons can be learnt from this survey. The first relates to the disparity between the number of responses received from managers and workers. The eight-fold lower number of responses from workers compared to managers attests to the challenges of reaching the ENM-handling worker population. Because no survey was previously conducted among workers, we examined the relative numbers of responses in the existing nationwide epidemiological program involving ENM-producing facilities. In a U.S. study of carbon nanotube and nanofiber exposure and health effects, conducted by National Institute for Occupational Safety and Health (NIOSH), the company participation rate was 18%, whereas the workers’ participation rate was 75% [26
]. Similarly, in the French EpiNano program, the company participation rate was 16%, whereas the workers’ participation rate was 99% for a passive epidemiological follow-up and 42% for both passive and active follow-up [27
]. This means that selection is significantly stronger at the company level than at the individual level. Our results confirm the self-selection at the company level but preclude discussion of workers’ selection. The challenge in accessing workers within this survey calls for a revised strategy allowing a facilitated or more direct access to the workers. For this, political and/or regulatory support would be necessary and can include ENM workers’ enrolment through worker unions outside companies.
Finally, our results suggest that respondent companies share a common characteristic not extensively described in the present survey. Indeed, most respondent companies reported having in place a specific H&S plan for working with ENMs, and a significant majority had already participated in other research studies or were involved with a scientific partnership, i.e., highlighting their common interest in and awareness of managing ENM-related issues. This common characteristic could manifest through more questions related to socially oriented traits, with an extensive investigation pertaining to awareness of the precise ENM exposure issue, or on how worker’s health and safety is perceived from the managers’ point of view. In light of the research scarcity in the field, it is particularly important that future studies address this self-selection issue.
The NanoExplore survey aimed to address the participation acceptance in a biomonitoring program targeting ENM exposure, and its practical feasibility in occupational settings among producers and handlers of ENMs. No published study previously addressed our research question, although the question of BM acceptance goes far beyond the field of ENMs. Considering the absolute number of responses and data provided in a field in which some aspects are still under investigation or unknown, our survey, although subject to a non-response concern, is helpful in designing communication strategies aimed at considering managers and workers’ expectations, in order to increase willingness to participate in occupational ENM exposure monitoring and biomonitoring programs. This survey captured a wide range of factors positively or negatively affecting company and individual engagement in ENM research, and provided valuable insights ranging from feelings and expectations regarding such programs to practical aspects regarding availability of space and time, or acceptability of planned BM procedures. Acquisition of individual study results, improvement of workers’ and the general population’s safety, and help in the development of ENM-specific H&S practices were among the most valuable reasons for positively considering participation. Results from this survey will inform further steps of the NanoExplore project (https://www.lifenanoexplore.eu/
(accessed on 8 April 2019)), which consists in designing a harmonized protocol for the BM of occupational ENM exposure and early health effects using biomarkers measured in non-invasive matrices. This survey is available in electronic or printed version, in six languages.