pietroiusti2014

Occupational Medicine 2014;64:319–330 doi:10.1093/occmed/kqu051 In-depth review Engineered nanoparticles at the workplace: current knowledge about workers’ risk A. Pietroiusti and A. Magrini Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy Correspondence to: Antonio Pietroiusti, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy Tel: +39 06 2090 2204; fax: +39 06 2090 2212; e-mail pietroiu@uniroma2.it Aims To perform an in-depth review of the state of art of nanoparticle exposure at work Methods Original articles and reviews in Pubmed and in principal databases of medical literature up to 2013 were included in the analysis In addition, grey literature released by qualified regulatory agencies and by governmental and non-governmental organizations was also taken into consideration Results There are significant knowledge and technical gaps to be filled for a reliable evaluation of the risk posed for workers by ENPs Evidence for potential workplace release of ENPs however seems substantial, and the amount of exposure may exceed the proposed occupational exposure limits (OELs) The rational use of conventional engineering measures and of protective personal equipment seems to mitigate the risk Conclusions A precautionary approach is recommended for workplace exposure to ENPs, until health-based OELs are developed and released by official regulatory agencies Key words Engineered nanoparticles; health effects; metrics; occupational exposure limit; workplace exposure Introduction Nanotechnology is a recognized cross-cutting technology, whose products, called engineered nanoparticles (ENPs), are characterized by a size range between and 100 nm At this dimension, the material acquires novel physicochemical properties, which are very useful for industrial and biomedical purposes A growing number of workers are estimated to be involved in work processes directly or indirectly linked with ENPs, and according to a recent projection, million workers will be potentially exposed to ENPs in 2020 [1] The European Commission (EC), aiming to set a clear definition for nanomaterials for legislative purposes, recently defined nanomaterials as ‘natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm–100 nm [2]’ This definition has implications both for classifying exposed people (i.e those managing or processing materials with ≥50% ENPs) and for the assessment of exposure (in fact, knowledge of number concentration is needed to establish exposure) As emphasized by the EC, the definition has legislative purposes; therefore, health effects may occur even when nanoparticle percentage is 300 nm CPC counts particles >10 nm with an upper limit of about 1000 nm CPC is useful for detecting particles in the nano-sized range, but it does not provide a size distribution by separating particles into size range When OPC and CPC are used together, there is an overlap of the two instruments in the range 300–1000 nm, making possible an indirect evaluation of particles 100 nm in their lowest dimension, were dominant in the aerosol Control of exposure There is preliminary inference that ENPs follow the classical laws of aerosol physics, fluid dynamics and filtration theory and that enclosure of the process with efficient ventilation may be an effective means to reduce exposure [59] In fact, during nanometal oxide reactor cleanout, the average percent reduction in airborne particulate was close to 100% by use of local exhaust ventilation and custom-fitted flange [61,62] In a laboratory case study, the use of benchtop enclosures prevented the release of carbon nanoparticles during the procedure of dispersion in a liquid [63] The enclosure was placed on a ventilated benchtop (100 ft/min) Before installation of exposure controls, airborne multi-walled carbon nanotubes bundles were observed by transmission electron microscope, and none were detected in the samples collected after the enclosure was installed A study of laboratory fume hoods showed that the hood design affects the nanoparticle release, and an aircurtain hood design (with a different airflow pattern) significantly reduced workers’ exposures [64] As far as personal exposure protective equipment is concerned, a study of the filtration performance of a NIOSH N95 respirator showed that it meets the NIOSH respirator certification criteria (>95% filtration efficiency), although the most penetrating particle size was 50 nm in diameter (~2% filter penetration) [65] A more recent investigation of the same group showed that a mechanical filter would offer a relatively higher filtration performance for nanoparticles than an electrostatic counterpart rated for the same filter efficiency [66] Thus, it seems that traditional engineering control measures may remove ENPs as effectively as they fine particles However, further confirmatory data are needed Downloaded from http://occmed.oxfordjournals.org/ at University of Hawaii at Manoa Library on August 17, 2014 Three literature reviews on ENPs occupational exposure have been published by Kaluza et al [3], Brouwer et al [45] and Kuhlbusch et al [17] The most recent review took into account 25 studies covering a wide range of ENPs, including the majority of those prioritized by the OECD However, most examined studies not refer to OELs or to NEAT, making interpretation of the data difficult in terms of workers risk After the publication of the above mentioned reviews, 21 workplace surveys regarding possible workplace exposure to 26 ENPs have been published Some of these articles refer to proposed OELs or to NEAT and are listed in Table 2 The present analysis shows that under certain circumstances (maintenance activity, open gas-phase production process, open handling of nanopowders) a release of ENPs may occur Although the possible exposure to 26 ENPs was analysed, CNTs/carbon nanofibres were by far the most frequently studied ENPs, a finding in keeping with previous reviews Personal exposure was evaluated in seven studies regarding nine ENPs, whereas no information on this detection technique was available in previous reports Some of the reviewed surveys explicitly refer to proposed OELs Once again, no such information was available in previous reviews The following considerations are elicited by the analysis of these surveys: This fact raises the possibility that workers’ exposure to ENPs is actually an exposure to the bulk form, therefore exempt from the possible peculiar toxic effects linked to their size On the other hand, ENPs may undergo de-agglomeration processes once they come into contact with pulmonary cells [60], so local and systemic size-related effects are possible (v) Traditional engineering processes (chemical fume hoods, enclosed production processes, custommade gloveboxes and high-efficiency particulate air-filtered vacuums) generally allowed good control of workers’ exposure, although in some cases their improper use (or non use) has led to workers’ exposure exceeding the proposed OELs (vi) The pattern of exposure is generally characterized by transient high peaks, linked to specific operations The recently proposed limits for short-term exposure are therefore of great relevance in this context 326  Occupational Medicine Table 2.  ENPs, methods and main findings of the analysed workplace surveys No of reports Personal sampling Metrics No of reports showing exposure Remarks References CNTs/CNFs 12 4/12 NC: 12/12 MC:8/12 SAC:2/12 9/12 Transient high peaks of mainly aggregated ENPs Titanium dioxide 2/5 NC: 5/5 MC:3/5 SAC:1/5 4/5 Low-level exposure, in all cases below the proposed OELs Silver 2/4 3/4 Silicon 0/2 Silica 1/2 Transient high peaks of single (non-aggregated) ENPs in one case Transient peaks of both aggregated and nonaggregated ENPs Transient high peak in one case Aluminium 0/2 NC: 4/4 MC: 2/4 SAC: 0/4 NC: 2/2 MC: 0/2 SAC: 0/2 NC: 2/2 MC: 1/2 SAC: 0/2 NC: 2/2 MC: 0/2 SAC: 0/2 Lee et al [19], Birch et al [22], Dahm et al [27], Lee et al [28], Morawska et al [36], Debia et al [46], Fleury et al [47], Ling et al [48], Methner et al [49], Ogura et al [50], Ogura et al [51], Ogura et al [52] Curwin and Bertke [21], van Broekhuizen et al [24], Morawska et al [36], Yang et al [53], Koivisto et al [54] Lee et al [26], Lee et al [28], Ling et al [48], Zimmermann et al [55] Zimmermann et al [55], Wang et al [56] Copper 0/2 NC: 2/2 MC: 0/2 SAC: 0/2 2/2 Nanocellulose 0/1 1/1 Zinc oxide 0/1 Nanoclays 0/1 Cerium oxide 0/1 Chromium 0/1 Cobalt 0/1 Aluminium oxide 1/1 Zinc 0/1 Germanium 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 1/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 1/1 SAC: 1/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 2/2 2/2 2/2 Transient high peaks of single (non agglomerated) ENPs in one case Transient high peaks of single (nonagglomerated) ENPs in one case Very slight increase van Broekhuizen et al [24], Tsai et al [57] Debia et al [46], Zimmermann et al [55] Debia et al [46], Zimmermann et al [55] Vartiainen et al [58] 1/1 Slight increase, well below proposed OELs Ling et al [48] 1/1 Transient high peaks Morawska et al [36] 1/1 Transient high peaks of aggregated ENPs Leppänen et al [59] 1/1 Transient high peaks of single (non-aggregated) ENPs Transient high peaks of single (non-aggregated) ENPs Transient peaks of aggregated ENPs, below proposed OELs Transient high peaks of single (non-aggregated) ENPs Transient high peaks of single (non-aggregated) ENPs Zimmermann et al [55] 1/1 1/1 1/1 1/1 Zimmermann et al [55] Curwin and Bertke [21] Zimmermann et al [55] Zimmermann et al [55] Downloaded from http://occmed.oxfordjournals.org/ at University of Hawaii at Manoa Library on August 17, 2014 ENPa A Pietroiusti and A. Magrini: Engineered Nanoparticles at the Workplace  327 Table 2.  (Continued) ENPa No of reports Personal sampling Metrics No of reports showing exposure Remarks References NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 1/1 SAC: 1/1 NC: 1/1 MC: 1/1 SAC: 1/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 1/1 SAC: 0/1 NC: 1/1 MC: 0/1 SAC: 0/1 NC: 1/1 MC: 1/1 SAC: 1/1 NC: 1/1 MC: 1/1 SAC: 1/1 1/1 Transient high peaks of single (non-aggregated) ENPs Transient high peaks of single (non-aggregated) ENPs Transient peaks of aggregated ENPs, below proposed OELs Transient peaks of aggregated ENPs, below proposed OELs Transient high peaks of single (non-aggregated) ENPs Transient peaks of aggregated ENPs Zimmermann et al [55] 0/1 Nickel 0/1 Calcium oxide 1/1 Iron oxide 1/1 Platinum 0/1 Carbon black 0/1 Calcium carbonate 0/1 Magnesium oxide 1/1 Yttrium oxide 1/1 1/1 1/1 1/1 1/1 1/1 1/1 1/1 1/1 Transient high peaks of single (non-aggregated) ENPs Transient peaks of aggregated ENPs, below proposed OELs Transient peaks of aggregated ENPs, below proposed OELs Zimmermann et al [55] Curwin and Bertke [21] Curwin and Bertke [21] Zimmermann et al [55] Tsai et al [57] Tsai et al [57] Curwin and Bertke [21] Curwin and Bertke [21] CNTs/CNFs, carbon nanotubes/carbon nanofibres; NC, number concentration; MC, mass concentration; SAC, surface area concentration; OEL, occupational exposure level Several ENPs were sometimes concomitantly analysed in the same study a Health surveillance Occupational health surveillance consists of hazard surveillance and medical surveillance and can occur at the workplace or at population level At the current stage of knowledge, hazard surveillance would involve collecting information on which ENPs are being manufactured or handled and where in the workplace exposure might occur This determination is mostly a matter of management judgment, supplemented by environmental measurements and worker input Assessing the health of nanomaterial workers is a critical component of responsible development of the technology, and both exposure registries and development of epidemiological studies are recommended [67] Exposure registers involve the enrolment of workers to collect information about their exposure so that research can eventually be conducted and timely and targeted risk communication, intervention or advice can be provided Exposure registers may serve as the basis for conducting prospective studies of workers exposed to ENPs However, carrying out epidemiologic studies of nanotechnology workers will be difficult because of the diversity of the workplaces and types of ENPs In spite of these limitations, NIOSH recently began a study of US workers in facilities that produce or use engineered carbon nanoparticles [68,69] Collected data include respirable particle mass, number and active surface area; personal fullshift daily exposure and targeted sampling of the tasks associated with the highest exposures A similar study is being developed in France [70] Currently, it is not clear that, beyond hazard surveillance and routine medical surveillance, there is any specific medical testing that is warranted for workers potentially exposed to ENPs According to the American College of Occupational and Environmental Medicine [71], it is uncertain whether screening methods commonly used in medical surveillance, such as spirometry, will have the sensitivity and specificity to detect potential early adverse effects from exposure to nanoparticles Other more sensitive tests, such as cytokine measurements might be more reliable However, specific biological markers of exposure or response to ENPs suitable for surveillance have not been identified A  promising approach may come from the utilization of ‘omics’ which consist of the mapping of Downloaded from http://occmed.oxfordjournals.org/ at University of Hawaii at Manoa Library on August 17, 2014 Gold 328  Occupational Medicine Conclusions Uncertainties still exist regarding several aspects of the risk posed by ENPs for workers The main grey areas are the development of reliable and easy-to-use instruments for their measurement in the workplace, the possibility of obtaining personal exposure evaluations and the quantification of the additional health risk they may pose to workers in comparison with the bulk form of the same material In spite of these limitations, provisional OELs have been developed by non-official organizations Although different limits have been proposed in different countries, they may nevertheless provide a good reference to check the reliability of existing engineering and personal protective measures for exposed workers In fact, available data coming from workplace surveys indicate that substantial exposure may occur whenever the implementation of protective measures is inappropriate or neglected Key points •• Release of engineered nanoparticles may occur in the workplace of exposure is still far from optimal, given the uncertainties in metrics and the relatively poor performance of currently available instruments •• More severe adverse health effects than those caused by larger particles may be expected, although no evidence of this is yet available in humans •• A precautionary approach, possibly based on provisional occupational exposure levels, is probably the best way to minimize the risk in potentially exposed workers •• Assessment Funding The authors are supported, in part, by the European Commission (FP7-MARINA: grant agreement 263215; FP7 NANoREG: grant agreement 310584) and the Italian Ministry of Health (“Finalizzato Salute” project RF-2009-1536665) Conflicts of interest None declared References Roco MC The long view of nanotechnology development: the National Nanotechnology Initiative at 10 years Journal Nanopart Res 2011;13:427–445 EC Commission Recommendation of 18 October 2011 on the 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