Sng, Judy MMed; Quee, David Koh Soo PhD; Yu, Liya E. PhD; Gunaratnam, Saravanan MSc
The National University of Singapore (NUS) has seen a steady increase in the number of research projects involving nanomaterials over recent years. There are currently more than hundred projects dealing with nanomaterials, with even more expected over the next few years. The types of nanomaterials used range widely from simple substances such as zinc oxide to highly complex functional molecules. Table 1 lists some of the most commonly encountered nanomaterials within NUS research laboratories.
There is concern that researchers handling nanomaterials in free form may be at high risk of exposure, with as yet unknown long-term health consequences. A recent online survey by Balas et al1 among various university-based and public laboratories around the world revealed that many researchers did not use any type of protection, even among those who recognized the possibility of the nanomaterials becoming airborne. Results of toxicity research to date points to potential adverse health outcomes from exposure to some nanomaterials.2
National University of Singapore has a comprehensive occupational safety and health program currently in place that includes a standard operating procedure for safe handling of nanomaterials; but at present, there are no environmental or health surveillance requirements specifically for people handling nanomaterials that are not composed of regulated chemicals. The challenge is to build a comprehensive database that adequately accounts for the great diversity in nanomaterials types and handling methods, while at the same time maintaining convenience, acceptability, and sustainability over the long term.
Result of Survey of NUS Researchers Handling Nanomaterials
During a nanomedicine and nanotoxicology workshop for researchers held in February 2010, we conducted a self-administered questionnaire survey on the researchers' perceptions of nanomaterials-related risk. Forty-four of 85 individuals who attended the workshop responded (52% response rate), 39 (89% of respondents) of whom were currently working with nanomaterials.
Of those who responded, only 5% agreed with the statement that working with nanomaterials posed no health risk at all, while 60% disagreed and 35% were unsure. A total of 73% agreed that all nanomaterials should be treated as hazardous until proven safe (18% unsure, 9% disagreed). Most (72%) were aware of a code of practice on safe handling of nanomaterials in their laboratory (16% unsure, 12% disagree). More than half (52%) did not think that the same safety data sheet could be used for the bulk chemical and their nanomaterial derivatives (25% unsure, 23% thought it could).
Developments in Singapore Labor Legislation
In the 2006 revision of Singapore's labor law, there were new requirements for employers and stakeholders to take “reasonably practicable measures” to reduce occupational health risks at source to ensure that their employees are not at risk of adverse health effects.3 The identification of such measures is through a process of activity based risk assessment. With the pressing need for occupational health care for our nanomaterials laboratory researchers and the new labor legislations in mind, a multidisciplinary project team was established in NUS. The team consists of occupational health, environmental monitoring, and laboratory safety specialists from the Department of Epidemiology and Public Health, Department of Civil & Environmental Engineering, and the Office of Safety, Health and Environment, respectively.
Thus, in this project, we aim to
1. characterize typical exposures in our research laboratories by assessing
a. concentration and physical properties of airborne nanoparticulate levels and
b. potential for dermal exposure and the likely significance.
2. Develop a health surveillance protocol for persons working with nanomaterials in NUS, building on the existing occupational safety and health risk assessment systems.
All persons working with nanomaterials in NUS laboratories will be included. As there is at present no clear exposure definitions or limits for nanosized particles, any individual working directly with nanomaterials or working in the same room where processes involving nanomaterials are ongoing will be classified as potentially exposed.
The basic registry structure consists of two main elements: detailed exposure assessments and health surveillance.
At present, the university requires all principal investigators involved in laboratory-based research projects to submit risk assessment details to the Office of Safety, Health and Environment for approval before commencement of work via an online project risk assessment system.
In addition to routine laboratory project risk assessment details, the nanomaterials research laboratory database will collect information on the chemical and physical form of the nanomaterials being handled, as well as details on the work processes that take place. This would include information on the types of benchwork being carried out such as mixing, pouring, centrifuging; and also whether the processes take place in a fume hood or on open bench tops.
Environmental monitoring will be conducted in all laboratories handling nanomaterials. Measurements will be taken before, during, and after experiments (or selected activities) to allow for correction for background airborne nanomaterial levels, which consist of naturally occurring nanomaterials from sources such as resuspension of airborne particles due to activities not directly involving engineered nanomaterials.
Two main aspects will be studied—(1) monitoring and detection of airborne nanomaterial concentrations in the laboratories and (2) characterization of chemical and physical properties of airborne nanomaterials.
A handheld condensation particle counter will provide concentration counts of airborne particles, which will be complemented with chemical measurements of airborne nanoparticles collected in various size stages such as using inductively coupled plasma mass spectrometry.
Analysis of the deposition of nanosized particles on surfaces such as gloves and possibly bench tops will also be conducted to assess the potential for dermal exposure.
By studying the types of materials used, the processes involving nanomaterials in the laboratories with the accompanying environmental measurement data, we hope to stratify the laboratories into several levels of risk for inhalation and risk of skin exposure—the two main routes through which nanomaterials are currently thought to enter the body. This is akin to the control banding concept4,5 and will form the initial basis for a job exposure matrix, which may prove a useful tool in subsequent epidemiologic studies on nanomaterials workers.6 Environmental monitoring data will also be used to research the effectiveness of current control measures used within the laboratories.
At present, researchers in contact with known hazards (based on chemical composition and regardless of particle size) are already under regular statutory medical surveillance by occupational health professionals from the Office of Safety, Health and Environment. To streamline processes and maximize acceptability, this component of the project will build on the existing NUS health surveillance program.
Prescribed hazardous chemical exposures for which medical surveillance is required:
a. Fumes, dust, or vapor for arsenic and its compounds
b. Asbestos dust
c. Benzene fumes/vapor
d. Cadmium and its compounds
e. Fumes, dust, or vapor for Lead and its compounds
f. Fumes, dust, or vapor for manganese and its compounds
g. Fumes, dust, or vapor for mercury and its compounds
h. Organophosphates fumes/vapor
i. Perchloroethylene fumes/vapor
j. Silica dust
k. Tar, pitch, bitumen, and creosote
l. Trichloroethylene fumes/vapor
m. Vinyl chloride monomer fumes/vapor
Researchers handling nanomaterials containing any of the 13 chemicals in the list would already be required to undergo statutory medical surveillance. One such group would be those using cadmium-containing quantum dots. During the health surveillance visits, focused physical examination and laboratory tests specific to the exposure and its known health effects will be conducted. For example, persons working with cadmium would be specifically screened for renal, respiratory, and bone problems. Laboratory tests for them would include blood cadmium level and urine beta-2 microglobulin. Typically, exemption from statutory medical surveillance is allowed only when environmental monitoring shows levels to be consistently below 10% of permissible exposure limits (PELs). However, there is evidence to suggest that some nanomaterials may exert toxic effects at levels far below permissible exposure limits,7 highlighting the need to review the relevance of PELs for nanosized materials.
Materials which are relatively nonreactive in bulk form have also been shown to exert toxic effects at the nano level (such as gold,8 zinc oxide9). The aim of the project is thus to encompass all persons handling any form of nanomaterials in NUS, regardless of quantity. This will be achieved in stages, the first of which is extending the health surveillance program to include those handling nanomaterials in the prescribed hazards list at levels below the 10% PEL threshold for bulk materials.
The next group to be targeted for health surveillance would be researchers handling nanomaterials, where there is strong suspicion of possible adverse health effects—such as carbon nanotubes, where animal studies have linked exposure to asbestos-like pathogenicity.10 Other examples are nano-gold8 and zinc oxide.9 The protocol for health surveillance will be regularly reviewed and revised, as new evidence on health effects become available. For example, if in the future, some nanomaterials were to be confirmed as nonhazardous to human health, health surveillance for persons only handling these could be deemed unnecessary.
Currently, there are no official guidelines or consensus on the specific types of health surveillance programs nanomaterial-exposed employees should undergo. Thus, the health surveillance component of our project will initially follow the occupational health program that is already in place in the University. This encompasses basic health information such as prior or present medical problems or symptoms; history of cigarette smoking; and general physical examination and investigations such as blood counts, liver and renal function, chest x-ray, spirometry, and specific toxicology tests if necessary (eg, blood cadmium level, urine mercury level).
By collecting detailed information on exposure and baseline health status and eventually expanding the registry to include other research and educational institutions both locally and internationally, we hope that in time there will be an adequate base for a cohort study that can provide good data on the exposure characteristics and health outcomes of nanomaterial-exposed persons.
1. Balas F, Arruebo M, Urrutia J, Santamaria J. Reported nanosafety practices in research laboratories worldwide (published ahead of print January 31, 2010). Nat Nanotechnol. 2010;5:93–96.
2. Trout DB, Schulte PA. Medical surveillance, exposure registries, and epidemiologic research for workers exposed to nanomaterials. Toxicology. 2010;269:128–135.
4. Schulte P, Geraci C, Zumwalde R, Hoover M, Kuempel E. Occupational risk management of engineered nanoparticles. J Occup Environ Hyg. 2008;5:239–249.
5. Paik SY, Zalk DM, Swuste P. Application of a pilot control banding tool for risk level assessment and control of nanoparticle exposures. Ann Occup Hyg. 2008;52:419–428.
6. Schulte PA, Geraci CL, Schubauer-Berigan MK, Zumwalde R, Mayweather C, McKernan JL. Issues in the development of epidemiologic studies of workers exposed to engineered nanoparticles. J Occup Environ Med. 2009;51:323–335.
7. Shvedova AA, Kisin ER, Mercer R, et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol. 2005;289:L698–L708.
8. Li JJ, Zou L, Hartono D, Ong C-N, Bay B-H, Lanry Yung L-YL. Gold nanoparticles induce oxidative damage in lung fibroblasts in vitro. Adv Mater. 2008;20:138–142.
9. Deng X, Luan Q, Chen W, et al. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotechnology. 2009;20:115101.
10. Pacurari M, Castranova V, Vallyathan V. Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans? J Toxicol Environ Health A. 2010;73:378–395.