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Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens (2014)

Chapter: Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens

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Suggested Citation:"Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens." National Research Council. 2014. Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens. Washington, DC: The National Academies Press. doi: 10.17226/18725.
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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).

Suggested Citation:"Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens." National Research Council. 2014. Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens. Washington, DC: The National Academies Press. doi: 10.17226/18725.
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TABLE C-1 Topic-Specific Search Terms Used in the National Toxicology Program’s Literature Searches

Human Cancer Animal Tumors Genotoxicity ADME/Mechanisms
MeSH terms MeSH terms MeSH terms MeSH terms
Case reports Adenocarcinoma Aneuploidy Absorption
Case–control studies Adenoma Cell transformation, neoplastic Biotransformation
Cohort studies Carcinogens Chromosome aberrations Metabolism
Epidemiology Carcinoma Cytogenic analysis Pharmacokinetics
Epidemiologic studies Neoplasms DNA adducts Cytochrome P-450 enzyme
Mortality Precancerous condition DNA damage system
Neoplasms Sarcoma DNA repair
Occupational exposure Animals Germ-line mutation Text words
Prospective studies Micronuclei Activation
Retrospective studies Text words Mutagens Bioactivation
Manpower Cancer Foci Mutagenesis Mutation Clearance Detoxif*
Text words Malignan* Oncogenes Distribution
Case-referent Mice Polyploidy Excretion
Cancer Oncogenic* Sister-chromatid exchange Kinetics
Carcinogenic Rats SOS response Mechanism
Epidemiolog* Tumor Metabolite
Tumor Tumorigenic* Text words
Workers Chromosom*
Clastogen*
Genetic toxicology
Strand break
Unscheduled DNA synthesis

*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.

Suggested Citation:"Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens." National Research Council. 2014. Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens. Washington, DC: The National Academies Press. doi: 10.17226/18725.
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REFERENCES

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

Suggested Citation:"Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens." National Research Council. 2014. Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens. Washington, DC: The National Academies Press. doi: 10.17226/18725.
×
Page 165
Suggested Citation:"Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens." National Research Council. 2014. Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens. Washington, DC: The National Academies Press. doi: 10.17226/18725.
×
Page 166
Suggested Citation:"Appendix C: Review of the Literature Search Used in the National Toxicology Program 12th Report on Carcinogens." National Research Council. 2014. Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens. Washington, DC: The National Academies Press. doi: 10.17226/18725.
×
Page 167
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Many people in the United States are exposed to styrene. Sources of environmental exposure included food (from migration of styrene from polymer packaging materials), cigarette smoke, vehicle exhaust and other forms of combustion and incineration of styrene polymers. Occupational exposure to humans can occur during the industrial processing of styrene. It is used to create a broad spectrum of products, including latex paints and coatings; synthetic rubbers; construction materials, such as pipes, fittings, and lighting fixtures; packaging; household goods, such as synthetic marble, flooring, and molded furnishings; and automotive parts. In 2011, the National Toxicology Program (NTP) listed styrene as "reasonably anticipated to be a human carcinogen" in its 12th Report on Carcinogens, marking the first time that the substance was listed. Congress directed the Department of Health and Human Services to arrange for the National Academy of Sciences to independently review the substance profile of styrene and it listing in the NTP report.

Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens concurs with the NTP determination that there is limited but credible evidence that exposure to styrene in some occupational settings is associated with an increase in the frequency of lymphohematopoietic cancers. Additionally, the NRC report authoring committee independently reviewed the scientific evidence from studies in humans, experimental animals, and other studies relevant to the mechanisms of carcinogenesis and made level-of-evidence conclusions. Based on credible but limited evidence of carcinogenicity in traditional epidemiologic studies, on sufficient evidence of carcinogenicity in animals, and on convincing evidence that styrene is genotoxic in exposed humans, this report finds that compelling evidence exists to support a listing of styrene as, at a minimum, "reasonably anticipated to be a human carcinogen."

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