Appendix C

Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens

In support of the assessment of styrene, the National Toxicology Program (NTP) searched PubMed, Scopus, and Web of Science by using substance-specific terms (the substance name, major synonyms, and major metabolites) and topic-specific terms (see Table C-1). The results underwent a first level of review, during which titles and abstracts were screened for relevance. In a second level of review, the full text of references were reviewed for their relevance and substance. In the second level of review, 986 references were considered. Seventy additional references were recommended to NTP by an expert panel (Phillips et al. 2008 a,b). In total, 551 references were cited in the final background document (NTP 2008). The date on which the searches were run and the specific search strings used for each database were not provided to the committee. The committee found that providing more detail on the search strategies and the inclusion and exclusion criteria would have improved transparency of the methods that NTP used to identify and evaluate relevant literature related to styrene exposure. Similar observations about clear and concise descriptions of literature searches have been made by previous committees of the National Academies (IOM 2011; NRC 2011, 2014), and approaches that ensure greater transparency in literature search and review are being initiated by the US Environmental Protection Agency’s Integrated Risk Information System (EPA 2013) and NTP’s Office of Health Assessment and Translation (NTP 2013).

The final background document for styrene (NTP 2008) summarizes the literature up to the date of the peer review of the background document (July 2008), and the substance profile (NTP 2011) summarizes literature up to the date of the peer review by the Board of Scientific Counselors (February 2009) (Bucher et al. 2013). (See Figure 1-1 for a schematic of the 12th Report on Carcinogens process.) After peer review, both the background document and the substance profile were updated to reflect peer-review and public comments. NTP periodically reviewed the scientific literature up to the release of the 12th Report on Carcinogens (June 2011) “for any new studies that would warrant a re-review of the NTP’s preliminary recommendations to the [Health and Human Services] Secretary” (Bucher 2013).

TABLE C-1 Topic-Specific Search Terms Used in the National Toxicology Program’s Literature Searches

*The asterisk, sometimes referred to as a wild card, represents a truncation and is used to find all terms that begin with the given text string. Abbreviations: ADME, absorption, distribution, metabolism, and excretion; MeSH, medical subject headings. Source: Bucher 2013.

REFERENCES

Bucher, J.R. 2013. Follow-up Questions. Material submitted by the NAS Committee on Review of the Formaldehyde Assessment in the NTP 12^th RoC and the NAS Committee on Review of the Styrene Assessment in the NTP 12^th RoC, April 2, 2013.

EPA (U.S. Environmental Protection Agency). 2013. Part 1. Status of Implementation of Recommendations. Materials Submitted to the National Research Council, by Integrated Risk Information System Program, U.S. Environmental Protection Agency, January 30, 2013 [online]. Available: http://www.epa.gov/iris/pdfs/IRIS%20Program%20Materials%20to%20NRC_Part%201.pdf [accessed Jan. 13, 2014].

IOM (Institute of Medicine). 2011. Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: National Academies Press.

NRC (National Research Council). 2011. Review of the Environmental Protection Agency’s Draft IRIS Assessment of Formaldehyde. Washington, DC: National Academies Press.

NRC (National Research Council). 2014. Review of EPA’s Integrated Risk Information System (IRIS) Process. Washington, DC: National Academies Press.

NTP (National Toxicology Program). 2008. Report on Carcinogens Background Document for Styrene, September 29, 2008. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, Research Triangle Park, NC [online]. Available: http://ntp.niehs.nih.gov/NTP/roc/twelfth/2010/FinalBDs/Styrene_Final_508.pdf [accessed Aug. 14, 2013].

NTP (National Toxicology Program). 2011. Styrene. Pp. 383-392 in Report on Carcinogens, 12th Ed. U.S. Department of Health and Human Services, National Toxicology Program, Research Triangle Park, NC [online]. Available: http://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/Styrene.pdf [accessed Aug. 14, 2013].

NTP (National Toxicology Program). 2013. Draft OHAT Approach for Systematic Review and Evidence Integration for Literature-Based Health Assessments. U.S. Department of Health and Human Services, National Institute of Health, National Institute of Environmental Health Sciences, Division of National Toxicology Program, Office of Hazard Assessment and Translation, February 2013 [online]. Available: http://ntp.niehs.nih.gov/NTP/OHAT/EvaluationProcess/DraftOHATApproach_February2013.pdf [accessed Jan. 13, 2014].

Phillips, D., S. Snedeker, S. Eustis, M. Stone, P. Infante, E.M. Ward, G. Matanoski, G.S. Yost, S.S. Que Hee, L. Zeise, and T.J. Smith. 2008. Part A – Peer Review of the Draft Background Document on Styrene. Styrene Expert Panel Report [online]. Available: http://ntp.niehs.nih.gov/NTP/roc/twelfth/2008/ExpertPanelMtgs/Styrene_PanelReportPartA_508.pdf [accessed July 17, 2013].

Phillips, D., S. Snedeker, S. Eustis, M. Stone, P. Infante, E.M. Ward, G. Matanoski, G.S. Yost, S.S. Que Hee, L. Zeise, and T.J. Smith. 2008. Part B – Recommendation for Listing Status for Styrene and Scientific Justification for the Recommendation. Styrene Expert Panel Report [online]. Available: http://ntp.niehs.nih.gov/NTP/roc/twelfth/2008/ExpertPanelMtgs/Styrene_PanelReportPartB_508.pdf [accessed July 17, 2013].