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

Chapter: Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene

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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

Appendix D

Literature Search Strategies Used in Support of the Committee’s Independent Assessment of Styrene

The committee undertook several literature searches to inform its independent assessment of styrene. The general topics of the searches included metabolism, human epidemiology, experimental-animal studies, and mechanisms of carcinogenicity (specifically, genotoxicity, mutagenicity, immunosuppression, and cytotoxicity). Each search was originally run on May 28, 2013, and updated on November 13, 2013.1 The search strategies, exclusion criteria, and number of resulting studies are described below. The committee completed the searches with guidance from NRC (2011), and its work was informed by a recently published case study of applying the principles of systematic review to identify and present mechanistic evidence in human health assessments (Kushman et al. 2013).

METABOLISM

The search strategy used for studies relevant to the metabolism of styrene is presented in Box D-1. The search resulted in 229 papers. National Research Council staff reviewed the titles and abstracts of all 229 results and excluded 184 as not relevant (see Figure D-1). Studies were excluded on the basis of the criteria described in Box D-1. The 45 remaining studies were identified as likely to be relevant or possibly relevant. A committee member reviewed the titles and abstracts and found 27 that could be excluded because they were not focused on styrene; they were focused on urinary biomarkers or on reversible physiologic effects; or they were more pertinent to the consideration of cytotoxicity than of metabolism of styrene. The remaining 18 studies were examined in detail to determine whether they contained information or analysis that should be included as part of the committee’s independent assessment.

_____________________

1The cutoff date for the literature search was chosen to allow the committee time to review the literature within the time constraints of the project schedule.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

BOX D-1 Exclusion Criteria and Search Strategy for Studies of the Metabolism of Styrene

Exclusion Criteria:

 

  • The study was not focused on styrene metabolism or was focused on biomarkers.
  • The publication was already cited in the substance profile of styrene in the NTP 12th RoC.
  • The publication did not contain primary data.
  • The publication did not include information sufficient to determine what experimental methods were used.

Search Strategy:

PubMed: [(“Styrene”[Title/Abstract]) AND (“Cytochrome P-450 Enzyme System”[Mesh] OR “Cytochrome P-450 Enzyme System” OR “Biotransformation”[Mesh] OR “Biotransformation” OR “Metabolism”[Mesh] OR “Metabolism” OR “Pharmacokinetics”[Mesh] OR “Pharmacokinetics”) AND (activation OR bioactivation OR clearance OR detoxif* OR distribution OR excretion OR kinetics OR mechanism OR metabolite)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Medline and Embase: [(styrene.ab. or styrene.ti.) and (Cytochrome P-450 Enzyme System/or Cytochrome P-450 Enzyme System.mp. or Biotransformation/or Biotransformation .mp. or Metabolism/or Metabolism.mp. or Pharmacokinetics or Pharmacokinetics.mp.) AND (activation.mp. OR bioactivation.mp. OR clearance.mp. OR detoxif*.mp. OR distribution.mp. OR excretion.mp. OR kinetics.mp. OR mechanism.mp. OR metabolite.mp.)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Scopus: [(“styrene”) AND (“Cytochrome P-450 Enzyme System” OR “Biotransformation” OR “Metabolism” OR “Pharmacokinetics”) AND (“activation” OR “bioactivation” OR “clearance” OR “detoxif*” OR “distribution” OR “excretion” OR “kinetics” OR “mechanism” OR “metabolite”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Web of Science: [(“styrene”) AND (“Cytochrome P-450 Enzyme System” OR “Biotransformation” OR “Metabolism” OR “Pharmacokinetics”) AND (“activation” OR “bioactivation” OR “clearance” OR “detoxif*” OR “distribution” OR “excretion” OR “kinetics” OR “mechanism” OR “metabolite”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

CANCER STUDIES IN HUMANS

The search algorithms and exclusion criteria used to identify human epidemiology studies are in Box D-2. The initial search yielded 46 articles (see Figure D-2). National Research Council staff reviewed the titles and abstracts of all 46 and excluded 29 as not relevant. The 17 remaining studies were identified as likely to be relevant or possibly relevant. Two committee members reviewed the titles and abstracts and found 13 that could be excluded. The remaining four studies were examined in detail to determine whether they contained information or analysis that should be included as part of the committee’s independent assessment.

EXPERIMENTAL ANIMAL STUDIES

The literature search for publications of animal carcinogenicity bioassays published from January 2008 to November 13, 2013, yielded 118 results. The search terms are described in Box D-3 and a search tree representing the results is depicted in Figure D-3. National Research Council staff reviewed the titles and abstracts of the remaining 118 results and excluded 115 as not relevant. A committee member reviewed the titles and abstracts and found that all three could be excluded. No studies that exposed experimental animals to styrene and evaluated them for the presence of tumors were identified. Thus, the committee’s independent evaluation of the evidence of styrene carcinogenicity in experimental animals relies on studies available to NTP when it conducted its review in 2011.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

BOX D-2 Exclusion Criteria and Search Strategy for Human Studies

Exclusion Criteria:

 

  • The publication did not evaluate ambient or occupational exposures of humans to styrene.
  • The publication did not evaluate health effects related to carcinogenesis or genetic damage.
  • The publication was already cited in the substance profile of styrene in the NTP 12th RoC.
  • The publication did not include primary data.

Search Strategy:

PubMed: [(“Styrene”[Title/Abstract]) AND (“Neoplasms”[Mesh] OR neoplasms OR cancer OR carcinogenic or tumor) AND (“Epidemiology”[Mesh] OR “Epidemiologic Studies”[Mesh] OR epidemiolog* OR case-referent OR “Occupational Exposure”[Mesh] OR workers OR cohort)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Medline and Embase:[ (styrene.ab. or styrene.ti.) and (Neoplasms/ or neoplasms.mp. or cancer.mp. or carcinogenic.mp. or tumor.mp.) and (Epidemiology/ or Epidemiologic Studies/ or epidemiolog*.mp. or case-referent.mp. or Occupational Studies/ or coworkers.mp. or cohort.mp.)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Scopus: [(“styrene”) AND (“neoplasms” OR “cancer” OR “carcinogenic” OR “tumor”) AND (“epidemiology” “epidemiologic studies” OR “epidemiolog*” OR “case-referent” OR “occupational exposure” OR “workers” OR “cohort”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Web of Science: [(“styrene”) AND (“neoplasms” OR “cancer” OR “carcinogenic” OR “tumor”) AND (“epidemiology” OR “epidemiologic studies” OR “epidemiolog*” OR “case-referent” OR “occupational exposure” OR “worker” OR “cohort”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

STUDIES OF MECHANISMS OF CARCINOGENESIS

Genotoxicity and Mutagenicity

The committee identified and evaluated relevant, publicly available, peer-reviewed literature on the genotoxicity and associated mechanistic events that have been associated with exposure to styrene or styrene-7,8-oxide. Exclusion criteria for study relevance were defined and applied to the retrieved literature by reviewing the abstracts of the retrieved publications and then reviewing full

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

text of selected papers. The committee’s exclusion criteria and detailed search terms for studies related to genotoxicity and mutagenicity are presented in Box D-4. Literature trees were used to document identification and selection of the literature evidence (Figure D-4). The selected studies were summarized in evidence tables (see Tables 3-12 to 3-16).

Immunosuppression

The committee undertook a literature search to identify relevant publications on styrene exposure and immunosuppression. Because there was not a specific section in the background document for styrene (NTP 2008) that discussed immunosuppression in detail, the committee undertook a broad search without any date limits (see Box D-5 and Figure D-5). It considered studies relevant if they reported data on changes in basic hematologic measures, such as white blood cell (WBC) count and WBC differential count. The committee included studies that reported such measures as weight of lymphoid organs and expression of functional markers. Efforts were made to identify and include studies that reported effects on local, systemic, innate, and specific immunity in exposed animals or humans. Studies that reported genotoxic measures were excluded from discussion in this section because they are discussed in more detail in the genotoxicity sections of Chapters 2 and 3. The literature search yielded 233 results, 19 of which were relevant articles that were not already cited in the background document for styrene.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

BOX D-3 Exclusion Criteria and Search Strategy for Experimental Animal Studies

Exclusion Criteria:

 

  • The publication did not evaluate styrene exposures in animal models.
  • The publication did not evaluate the incidence of tumors.
  • The publication was already cited in the substance profile of styrene in the NTP 12th RoC.
  • The publication did not include primary data.

Search Strategy:

Pubmed: [(“Styrene”[Title/Abstract]) AND (“Neoplasms”[Mesh] OR “Carcinogen”[Mesh] OR cancer OR Foci OR Malignant* OR Oncogenic* OR Tumor OR Tumorigenic*) AND (“Animals”[Mesh] OR mice OR rats)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Medline and Embase: [(styrene.ab. or styrene.ti.) AND (neoplasms/ or carcinogens/ or cancer.mp. or foci.mp. or malignan*.mp. or oncongenic.mp. or tumor.mp. or tumorgenic*.mp.) AND (animals/ or mice.mp. or rats.mp.)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Scopus: [(“Styrene”) AND (“neoplasms” OR “carcinogens” OR “cancer” OR “foci” OR “malignan*” OR “oncogenic*” OR “tumor” OR “tumorigenic*”) AND (“animals” OR “mice” OR “rats”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Web of Science: [(“Styrene”) AND (“neoplasms” OR “carcinogens” OR “cancer” OR “foci” OR “malignan*” OR “oncogenic*” OR “tumor” OR “tumorigenic*”) AND (“animals” OR “mice” OR “rats”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Cytotoxicity

The committee and National Research Council staff developed a search algorithm to identify relevant cytotoxicity studies that were published in PubMed (see Box D-6 and Figure D-6). The first literature search was run by using selected metabolites as keywords, and a total of 259 references were identified, 12 of which were animal toxicity studies. A second search was undertaken by using styrene in the title or abstract in combination with keywords related to lung toxicity. This search identified 37 references, 14 of which dealt with original research on animal toxicity studies and two of which were reviews. Of the 14, 12 were duplicates of the previous search. On August 8, 2013, a third search was performed by refining the terms used in the first search. In this third search, each metabolite was searched in combination with keywords related to lung toxicity. A total of 12 references were identified, all of which had been identified in

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

the previous search. An additional PubMed search was performed on November 22, 2013. This search identified a total of 217 references, 16 of which addressed animal studies of toxicity of styrene or its metabolites, including two reviews, and all of which had been identified in the previous searches.

BOX D-4 Exclusion Criteria and Search Strategy for Studies of Genotoxicity and Related Mechanisms of Styrene

Exclusion Criteria

 

  • The publication did not evaluate health effects of styrene or its metabolites known to be formed in humans
  • The study evaluated cellular, biochemical, or molecular effects not relevant to the carcinogenesis or the mechanistic event under consideration.
  • The publication did not contain primary data.
  • The publication did not include information sufficient to determine what species were studied or what experimental methods were used.

Search Strategy

PubMed: [(“Styrene”[Title/Abstract]) AND (“Mutation”[Mesh] OR “Cell Transformation, Neoplastic”[Mesh] OR “Cytogenetic Analysis”[Mesh] OR “Mutagens”[Mesh] OR “Oncogenes”[Mesh] OR “Genetic Processes”[Mesh] OR chromosom* OR clastogen* OR “genetic toxicology” OR “strand break” OR “unscheduled DNA synthesis” OR “DNA damage” OR “DNA adducts”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

Medline and Embase: [(styrene.ab. or styrene.ti.) and (1 or 2 or 3 or 4 or 5 or 6 or chromosom*.mp. or clastogen*.mp. or genetic toxicology.mp. or strand break.mp. or unscheduled DNA synthesis.mp. or DNA damage.mp. or DNA adducts.mp.), where the following keywords are: 1) Mutation, 2) Cell Transformation, Neoplastic, 3) Cytogenetic Analysis, 4) Mutagens, 5) Oncogenes, 6) Genetic Processes]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Scopus: [((“Styrene”) AND (“mutation” OR “cell transformation, neoplastic” OR “cytogenetic analysis” OR “mutagens” OR “oncogenes” OR “genetic processes” OR “chromosom*” OR “clastogen* OR “genetic toxicology” OR “strand break” OR “unscheduled DNA synthesis” OR “DNA damage” OR “DNA adducts”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Web of Science: [((“Styrene”) AND (“mutation” OR “cell transformation, neoplastic” OR “cytogenetic analysis” OR “mutagens” OR “oncogenes” OR “genetic processes” OR “chromosom*” OR “clastogen*” OR “genetic toxicology” OR “strand break” OR “unscheduled DNA synthesis” OR “DNA damage” OR “DNA adducts”)]. Search run on 05-28-2013; updated on 11-13-2013; and limited to 01-01-2008 to 11-13-2013.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

BOX D-5 Exclusion Criteria and Search Strategy for Immunosuppression Studies

Exclusion Criteria:

 

  • The publication did not report data on changes in basic hematologic measures after exposure to styrene.
  • The publication did not report measures of lymphoid organs.
  • The publication did not contain primary data.
  • The publication was already cited in the substance profile for styrene in the NTP 12th RoC.
  • The publication did not include information sufficient to determine what species were studied or what experimental methods were used.

Search Strategy:

PubMed: (“styrene”[Title/Abstract]) AND (“lymph node” OR leukopenia OR lymphocyt* OR immunotoxicity OR immunosuppression OR hematologic OR hematopoietic). Search run on 05-28-2013 and updated on 11-26-2013.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

BOX D-6 Exclusion Criteria and Search Strategy for Cytotoxicity Studies

Exclusion Criteria:

 

  • The publication did not contain information on lung cytotoxicity or damage to the lung, liver, or kidney in relation to exposure to styrene or to a metabolite of styrene.
  • The publication did not contain primary data.
  • The publication was already cited in the substance profile for styrene in the NTP 12th RoC.
  • The publication did not include information sufficient to determine what species were studied or what experimental methods were used.

Search Strategies:

PubMed: [(styrene oxide OR vinylphenol OR 4-vinylphenol OR styrene-3,4epoxide OR styrene-7,8-oxide OR epoxyethylbenzene OR mandelic acid OR hydroxymandelic acid OR poly(2-hydroxyethylmethacrylate)]. Search run on 05-09-2013 and limited from 01-01-2010 to 05-09-2013.

PubMed: [(“Styrene”[Title/Abstract]) AND (lung OR pulmonary OR bronchiole OR bronchiolar OR “Clara cell” OR “alveolar type 2 cell”)]. Search run on 05-28-2013 and limited from 01-01-2008 to 05-28-2013.

PubMed: [(lung OR pulmonary OR bronchiole OR bronchiolar OR “Clara cell” OR “alveolar type 2 cell”) AND (styrene oxide OR vinylphenol OR 4-vinylphenol OR styrene-3,4-epoxide OR styrene-7,8-oxide OR epoxyethylbenzene OR mandelic acid OR hydroxymandelic acid OR poly(2-hydroxyethylmethacrylate)]. Search run on 08-08-2013 and limited from 01-01-2010 to 08-08-2013.

Pubmed: [(styrene) AND (lung OR liver OR kidney)]. Search run on 11-22-2013 and limited from 01-01-2008 to 11-22-2013.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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.
×

REFERENCES

IARC (International Agency for Research on Cancer). 1994a. Styrene. Pp. 233-320 in Some Industrial Chemicals. IARC Monographs on the Evaluation of the Carcinogenic Risk to Humans, Vol. 60. Lyon, France: IARC Press [online]. Available: http://monographs.iarc.fr/ENG/Monographs/vol60/mono60.pdf [accessed Feb. 12, 2014].

IARC (International Agency for Research on Cancer). 1994b. Styrene-7,8-oxide. Pp. 321-346 in Some Industrial Chemicals. IARC Monographs on the Evaluation of the Carcinogenic Risk to Humans, Vol. 60. Lyon, France: IARC Press [online]. Available: http://monographs.iarc.fr/ENG/Monographs/vol60/mono60.pdf [accessed Feb. 12, 2014].

IARC (International Agency for Research on Cancer). 2002. Styrene. Pp. 437-550 in Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene. IARC Monographs on the Evaluation of the Carcinogenic Risk to Humans Vol. 82. Lyon, France: IARC Press [online]. Available: http://monographs.iarc.fr/ENG/Monographs/vol82/mono82.pdf [accessed Feb. 12, 2014].

Kushman, M.E., A.D. Kraft, K.Z. Guyton, W.A. Chiu, S.L. Makris, and I. Rusyn. 2013. A systematic approach for identifying and presenting mechanistic evidence in human health assessments. Regul. Toxicol. Pharmacol. 67(2):266-277.

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

Scott, D., and R.J. Preston. 1994. A re-evaluation of the cytogenetic effects of styrene. Mutat. Res. 318(3):175-203.

Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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 175
Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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 176
Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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Suggested Citation:"Appendix D: Literature Search Strategies Used in Support of the Committee's Independent Assessment of Styrene." 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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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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