Nanotoxicology: characterizing the scientific literature, 2000–2007
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Understanding the toxicity of nanomaterials and nano-enabled products is important for human and environmental health and safety as well as public acceptance. Assessing the state of knowledge about nanotoxicology is an important step in promoting comprehensive understanding of the health and environmental implications of these new materials. To this end, we employed bibliometric techniques to characterize the prevalence and distribution of the current scientific literature. We found that the nano-toxicological literature is dispersed across a range of disciplines and sub-fields; focused on in vitro testing; often does not specify an exposure pathway; and tends to emphasize acute toxicity and mortality rather than chronic exposure and morbidity. Finally, there is very little research on consumer products, particularly on their environmental fate, and most research is on the toxicity of basic nanomaterials. The implications for toxicologists, regulators and social scientists studying nanotechnology and society are discussed.
KeywordsNanotoxicology Exposure pathway Literature review Environment Health and safety EHS
Understanding the toxicity of nanomaterials and nano-enabled products is important for human and environmental health and safety as well as public acceptance. The scientific literature is a primary source of information about nanomaterial toxicology and thus plays a role in the emerging dialogue about the safety of nano-enabled products.
What is the relative distribution of published nanotoxicological research across the areas of human health and the environment?
Within each of these research domains, what emphases have emerged thus far?
Which materials and exposure pathways have been researched and which have not?
Which stages of the nanomaterial life-cycle have been addressed in toxicological research?
In this commentary, we use the above questions to determine base-line measures for the current state of knowledge about nanomaterial toxicity. We highlight apparent gaps in the ongoing nano-toxicological literature that could have significant implications for experts, regulators, and the public.1 Assessing the scientific literature is important at this juncture as the toxicology of nanomaterials has increasingly become the subject of regulatory and media attention.2
To characterize the peer-reviewed literature on nanotoxicology, we utilized two complementary bibliometric strategies. First SciFinder Scholar, a search engine for scientific literature across the Physical, Biomedical, and Natural Sciences utilizing the CAS (Chemical Abstracts Service) and MEDLINE (U.S. National Library of Medicine) databases were used.3 To construct a comprehensive population of journal and review articles in English for the period between 2000 and 2007, we used a modified search term strategy from a list developed by the International Council on Nanotechnology (ICON) at Rice University for their database of research on environmental health and safety (EHS) of nanomaterials.4 The search terms included: safety, environmental health, human health, animal health, toxic, nano, nanomaterial, nanoparticle, nanotechnology, Buckyball, fullerene, quantum dot, and ultrafine. We also utilized the ICON EHS database to examine the types of studies that have been researched (e.g., in vivo vs. in vitro) and to compare across nanomaterial types (e.g., carbon, semiconductor, metal, etc.). The selection and categorization of nanomaterial types (e.g., oxides, carbon, etc.) was consistent with that of the ICON database, which categorizes primarily on a chemical basis.
Peer-reviewed research on nanomaterials and their toxicology has grown nearly 600 percent since the year 2000, increasing almost exponentially across the 7-year period. As noted by Lubick (2008), the scholarly literature is dispersed across a wide range of disciplines and journals. Our search of SciFinder Scholar produced approximately 900 total articles in about 58 different journals. The journals with the greatest number of relevant articles had 18 articles at most and are spread across Chemistry, Biology, Physics and Engineering fields. This is consistent with the interdisciplinarity of nanotechnology, showing that if one is to stay current on the published literature, it requires maintaining a knowledge base from a variety of different sciences.
Comments and conclusion
The nano-toxicological literature is dispersed across a range of disciplines and sub-fields. Most of the published research has focused on in vitro testing and does not take into account the complexity of in vivo interactions. Most research has not specified exposure pathway(s) and has focused on acute toxicity and mortality rather than chronic exposure and morbidity. There is very little research on consumer products, particularly on their environmental fate, and most research is on the toxicity of nanomaterials followed by intermediates. This focus on basic materials can be explained by lack of basic understanding, as the nanotechnology field is in its infancy. For example, the differences in behaviors of single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNT) remain unclear—especially in a biological environment—and CNTs are among the best studied nanomaterials.
The lack of publicly available research on the toxicity of nano-enabled consumer products and the product end life has implications for public acceptance of nanotechnology. A survey of industrial practices suggests that industrial nanotoxicological testing of consumer products is limited (Conti et al. 2008). It is likely that companies such as DuPont who developed their own nanomaterial testing guidelines6 are doing in-house testing. However, the results of such studies may not be published in the peer-reviewed literature characterized here. We would point to a significant risk to the nanotechnology enterprise if hazard data are to come only from industry. The US public is unlikely to trust and accept such assurances, and indeed, such assurances from an un-trusted source are likely to amplify public perception of risk (Poortinga and Pidgeon 2004).
These initial results have significant implications for toxicologists, regulators, and social scientists studying nanotechnology and society. The diffuseness of the scholarly literature may challenge the abilities of the public and civil society to stay informed about the toxicological implications of nanomaterials, as keeping up to date with the literature requires subscription to a proprietary database and not just access to a single or a few journals. It may also make it more difficult to communicate realistic expectations about health and safety to consumers. As described by Hutchison (2008), unknown toxicity of consumer products may pose serious problems for public acceptance of nano-enabled products. With its database, ICON has provided a valuable service in making the references to the scientific literature publicly available; however, a larger, coordinated effort in clearinghouse construction seems to be called for, as access to the journals themselves is necessarily limited to those in academia or industry with collective resources. Maynard et al. (2006) elaborates further by urging for systematic risk research to emerge in all facets, government, industry, academia, and with other stakeholders if nano-industries are to thrive, from nano-materials to nano-enabled products.
This research provides measures for the claims in previous reports on nanomaterial toxicology, demonstrating significant gaps in the emerging field of nanotoxicology. Are these merely the result of the newness or infancy of the field that will be remedied over time as more attention and funding are dedicated to nanotoxicological research? Or, are such gaps the result of specific challenges posed by “nano-scale” materials to established toxicological approaches? Addressing these questions will require additional research, the accessible dissemination of which will contribute to the comprehensive development of the nanotoxicology field.
We are a research team in a NSF center, the Center for Nanotechnology in Society at University of California at Santa Barbara, which is charged with both understanding and engaging with different interest groups, including the US public. Nanotoxicity questions figure prominently in such engagement; we aimed to see how difficult it is for educated non-specialists to locate and assess the extant literature.
It precedes the roll-out of a NSF and EPA sponsored national Center for Environmental Implications of Nanotechnology, intended to more systematically address and integrate research on the toxicological and ecological effects of nanotechnology. The program solicitation is available at: http://www.nsf.gov/pubs/2007/nsf07590/nsf07590.htm.
The SciFinder Scholar search tool is a product of the CAS division of the American Chemical Society. Information and access to the database is available at: http://www.cas.org/SCIFINDER/SCHOLAR/index.html.
The ICON database is available through Rice University at: http://icon.rice.edu/resources.cfm?doc_id=8597. Last accessed March 2008.
Available at Evident Technologies, http://www.evidenttech.com/.
The Nano Risk Framework, developed by DuPont and the Environmental Defense Fund, available at http://www.nanoriskframework.com/.
This research at the CNS-UCSB is funded by the National Science Foundation under cooperative agreement #SES 0531184. Any opinions, findings, and conclusions are those of the authors and do not necessarily reflect the views of the National Science Foundation. The authors thank Milind Kandlikar, Trish Holden, and Kristin Kulinowski for helpful discussions during preparation of the manuscript.
- Lubick N (2008) Risks of nanotechnology remain uncertain. In: Environmental Science & Technology Online News. Available at http://pubs.acs.org/subscribe/journals/esthag-w/2008/feb/science/nl_nanorisks.html. Accessed 20 Feb 2008