In 1987, the International Agency for Research on Cancer (IARC) in Lyon, France, upgraded styrene’s classification from a Group 3 “not classifiable” to a Group 2B “possibly carcinogenic to humans.” This reclassification resulted from revisions to IARC’s classification scheme and considerations of styrene oxide, an intermediate formed during styrene metabolism. No new data from human epidemiology or long-term animal studies prompted the reclassification.
SIRC disagrees with this conclusion. An upgrade in classification to “probably carcinogenic to humans” is inconsistent with the most current styrene health effects data. Although there is a large volume of data on human and animal cancer, no consistent or definitive conclusions are provided, and, hence, SIRC believes a conclusion that styrene is probably carcinogenic to humans is not supported. SIRC assumes this change in classification is due in part to changes made to the technical guidelines IARC uses to assess data. SIRC will not be able to fully analyze IARC’s upgrade until the full monograph report is published in 2019.
IARC classifications are based on hazard assessments and not risk assessments. IARC classifications are not indicators of real world potential risk. The mere presence of, or exposure to, a chemical is not an indication of risk or potential harm.
In 1993, Health Canada, co-administrator with Environment Canada of the Canadian Environmental Protection Act (CEPA), completed an exhaustive assessment of styrene’s possible health and environmental effects. Their review  concluded that styrene is “non-toxic,” and as such does not require regulation under CEPA. Health Canada, after examining all aspects of human and environmental health—including a full assessment of styrene’s carcinogenic potential—found that “… styrene is not entering the environment in quantities or under conditions that may constitute a danger to the environment on which human life depends, or to human life or health.” Also, as part of its internal evaluation, Health Canada’s classification structure required that styrene be classified as a Class III possible human carcinogen, largely following the IARC conclusion.
Additionally, the CEPA Priority Substances List Styrene Assessment Report shows that the evaluators were well aware of the complexity and shortcomings of the database on styrene. Canada’s classification scheme does not drive its regulatory programs to the same extent as the EPA’s does in the United States; when real-life exposures were factored in, the final Canadian decision was that styrene did not warrant regulatory consideration.
For many years, substances on priority lists developed by European authorities were required to undergo an in-depth risk assessment covering the potential risks posed by the substance to humans (including workers, consumers, and humans exposed via the environment) and the environment (including the terrestrial, aquatic and atmospheric ecosystems, and accumulation through the food chain).
Styrene was assessed by the United Kingdom’s Health Safety Executive (UK-HSE) as the member state Rapporteur:
- The draft for publication  of the RAR for the human health part was released by the UK-HSE in June 2008, but was not published by the European Commission because it had not completed the Existing Substances Regulation’s (ESR’s) adoption process by the time REACH was adopted (see below).
In December 2006, the European Parliament and the European Council replaced the earlier system (including the ESR) when it adopted Regulation (EC) No. 1907/2006, Registration, Evaluation, Authorisation and Restriction of Chemicals, or REACH. This regulation established the European Chemicals Agency (ECHA). The operational requirements began to be applied a year later, in 2008.
As styrene is produced in and/or imported into Europe in quantities greater than one metric ton per year, REACH required that it be registered in a central database managed by ECHA (“Registration”). Therefore, the European Chemical Industry Association (Cefic) established a “REACH Consortium” to prepare and submit the registration documents. Styrene’s registration was completed in December 2010.
For substances, like styrene, that had not completed the risk assessment process under the earlier law, REACH required the submittal of an “Annex XV Transitional Report”  which the UK-HSE submitted to ECHA. This report included both the 2002 styrene RAR (environmental part) and the 2008 RAR draft for publication (human health part).
The transitional dossier confirmed that there should be no classification for carcinogenicity and mutagenicity (as agreed by the relevant expert committee under the ESR legislative framework). In addition, as no agreement had been reached as of December 2008 regarding styrene’s reproductive toxicity classification, completing the discussion of this endpoint became the responsibility of ECHA.
In 2011, Denmark submitted a proposal to the Risk Assessment Committee (RAC) of ECHA so that the styrene dossier could be completed. In late 2012, the RAC adopted an opinion  in which the RAC recommended that styrene should have a “Category 2” designation for reproductive toxicity (“suspected of damaging the unborn child”), hazard code H361d, under the CLP Directive and a “Category 3” designation (“toxic to reproduction”), hazard code R63 (development), under the DSD regulation. The committee also recommended a specific target organ toxicity classification of STOT-RE1 (causes damage to the hearing organs through prolonged or repeated exposure), hazard code H372 under the CLP directive and specific target organ (Xn) hazard code R48/20 under DSD.
These actions were adopted by the European Commission in 2014 and became effective Dec. 1, 2016.
- IARC 2002, International Agency for Research on Cancer (IARC), “Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene,” IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, v. 82, pp. 437-550, 2002; http://monographs.iarc.fr/ENG/Monographs/vol82/mono82-9.pdf.↵
- CEPA 1993, Priority Substances List Assessment Report, Styrene, Canadian Environmental Protection Act (CEPA), Environment Canada & Health Canada, Government of Canada, 1993, http://www.hc-sc.gc.ca/ewh-semt/alt_formats/hecs-sesc/pdf/pubs/contaminants/psl1-lsp1/stryene/styrene-eng.pdf.↵
- EU Styrene RAR 2002, European Union Risk Assessment Report, CAS No. 100-42-5, EINECS No. 202-851-5, styrene Part 1, environment, 1st Priority List, v. 27, European Chemicals Bureau, Final Report, 2002, 98 p.; http://echa.europa.eu/documents/10162/a05e9fc2-eaf7-448e-b9b2-d224d28173c0.↵
- EU Styrene RAR 2008, European Union Risk Assessment Report, Styrene, CAS No. 100-42-5, EINECS No. 202-851-5, Draft for Publication, prepared by the UK rapporteur on behalf of the European Union, June 2008, 448 p.; http://echa.europa.eu/documents/10162/13630/trd_rar_uk_styrene_en.pdf.↵
- ECHA 2009, “Styrene, CAS No: 100-42-5, EINECS No: 202-851-5,” Annex XV Transitional Report Documentation of the work done under the Existing Substance Regulation (EEC) No 793/93 and submitted to the European Chemicals Agency according to Article 136(3) of Regulation (EC) No 1907/2006, 134 p., 2009; http://echa.europa.eu/documents/10162/13630/trd_uk_styrene_en.pdf.↵
- ECHA 2012, “Opinion proposing harmonised classification and labelling at EU level of Styrene, EC number: 202-851-5, CAS number: 100-42-5,” Committee for Risk Assessment (RAC), European Chemicals Agency, 14 p., adopted 28 Nov 2012; http://echa.europa.eu/documents/10162/d96caf76-f7fe-40cb-acd1-7859a4d3071d.↵