Hypothesis-driven weight of evidence evaluation indicates styrene lacks endocrine disruption potential

References

• Afarinesh MR, Shafiei F, Sabzalizadeh M, Haghpanah T, Taheri M, Parsania S, Golshan F, Sheibani V. 2020. Effect of mild and chronic neonatal hypothyroidism on sensory information processing in a rodent model: a behavioral and electrophysiological study. Brain Res Bull. 155:29–36.
   PubMed Web of Science ®Google Scholar
• Andrews P, Freyberger A, Hartmann E, Eiben R, Loof I, Schmidt U, Temerowski M, Folkerts A, Stahl B, Kayser M. 2002. Sensitive detection of the endocrine effects of the estrogen analogue ethinylestradiol using a modified enhanced subacute rat study protocol (OECD Test Guideline no. 407). Arch Toxicol. 76(4):194–202.
   PubMed Web of Science ®Google Scholar
• Beliles RP, Butala JH, Stack CR, Makris S. 1985. Chronic toxicity and three-generation reproduction study of styrene monomer in the drinking water of rats. Fundam Appl Toxicol. 5(5):855–868.
   PubMedGoogle Scholar
• Biegel LB, Flaws JA, Hirshfield AN, O'Connor JC, Elliott GS, Ladics GS, Silbergeld EK, Van Pelt CS, Hurtt ME, Cook JC, et al. 1998. 90-Day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol. Toxicol Sci. 44(2):116–142.
   PubMed Web of Science ®Google Scholar
• Borgert CJ, Mihaich EM, Ortego LS, Bentley KS, Holmes CM, Levine SL, Becker RA. 2011. Hypothesis-driven weight of evidence framework for evaluating data within the US EPA’s Endocrine Disruptor Screening Program. Regul Toxicol Pharmacol. 61(2):185–191.
   PubMed Web of Science ®Google Scholar
• Borgert CJ, Mihaich EM, Quill TF, Marty MS, Levine SL, Becker RA. 2011. Evaluation of EPA’s Tier 1 Endocrine Screening Battery and recommendations for improving the interpretation of screening results. Regul Toxicol Pharmacol. 59(3):397–411.
   PubMed Web of Science ®Google Scholar
• Borgert CJ, Stuchal LD, Mihaich EM, Becker RA, Bentley KS, Brausch JM, Coady K, Geter DR, Gordon E, Guiney PD, et al. 2014. Relevance weighting of Tier 1 Endocrine Screening endpoints by rank order. Birth Defects Res B Dev Reprod Toxicol. 101(1):90–113.
   PubMedGoogle Scholar
• Borgert CJ, Becker RA, Carlton BD, Hanson M, Kwiatkowski PL, Sue Marty M, McCarty LS, Quill TF, Solomon K, Van Der Kraak G, et al. 2016. Does GLP enhance the quality of toxicological evidence for regulatory decisions? Toxicol Sci. 151(2):206–213.
   PubMed Web of Science ®Google Scholar
• Borgert CJ, Fuentes C, Burgoon LD. 2021. Principles of dose-setting in toxicology studies: the importance of kinetics for ensuring human safety. Arch Toxicol. 95(12):3651–3664.
   PubMed Web of Science ®Google Scholar
• Borgert CJ, Matthews JC, Baker SP. 2018. Human-relevant potency threshold (HRPT) for ERα agonism. Arch Toxicol. 92(5):1685–1702.
   PubMed Web of Science ®Google Scholar
• Browne P, Judson RS, Casey WM, Kleinstreuer NC, Thomas RS. 2015. Screening chemicals for estrogen receptor bioactivity using a computational model. Environ Sci Technol. 49(14):8804–8814.
   PubMed Web of Science ®Google Scholar
• Chamkhia N, Sakly M, Rhouma KB. 2006. Male reproductive impacts of styrene in rat. Toxicol Ind Health. 22(8):349–355.
   PubMed Web of Science ®Google Scholar
• Cruzan G, Cushman JR, Andrews LS, Granville GC, Johnson KA, Bevan C, Hardy CJ, Coombs DW, Mullins PA, Brown WR. 2001. Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks. J Appl Toxicol. 21(3):185–198.
   PubMed Web of Science ®Google Scholar
• Cruzan G, Cushman JR, Andrews LS, Granville GC, Miller RR, Hardy CJ, Coombs DW, Mullins PA. 1997. Subchronic inhalation studies of styrene in CD rats and CD-1 mice. Fundam Appl Toxicol. 35(2):152–165.
   PubMedGoogle Scholar
• Cruzan G, Cushman JR, Andrews LS, Granville GC, Johnson KA, Hardy CJ, Coombs DW, Mullins PA, Brown WR. 1998. Chronic toxicity/oncogenicity study of styrene in CD rats by inhalation exposure for 104 weeks. Toxicol Sci. 46(2):266–281.
   PubMed Web of Science ®Google Scholar
• Cruzan G, Faber WD, Johnson KA, Roberts LS, Hellwig J, Carney E, Yarrington JT, Stump DG. 2005a. Two generation reproduction study of styrene by inhalation in Crl-CD rats. Birth Defects Res B Dev Reprod Toxicol. 74(3):211–220.
   PubMedGoogle Scholar
• Cruzan G, Faber WD, Johnson KA, Roberts LS, Hellwig J, Maurissen J, Beck MJ, Radovsky A, Stump DG. 2005b. Developmental neurotoxicity study of styrene by inhalation in Crl-CD rats. Birth Defects Res B Dev Reprod Toxicol. 74(3):221–232.
   PubMedGoogle Scholar
• Date K, Ohno K, Azuma Y, Hirano S, Kobayashi K, Sakurai T, Nobuhara Y, Yamada T. 2002. Endocrine-disrupting effects of styrene oligomers that migrated from polystyrene containers into food. Food Chem Toxicol. 40(1):65–75.
   PubMed Web of Science ®Google Scholar
• Delclos KB, Weis CC, Bucci TJ, Olson G, Mellick P, Sadovova N, Latendresse JR, Thorn B, Newbold RR. 2009. Overlapping but distinct effects of genistein and ethinyl estradiol (EE(2)) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies. Reprod Toxicol. 27(2):117–132.
   PubMed Web of Science ®Google Scholar
• Endocrine Disruptor Screening and Testing Advisory Committee [EDSTAC]. 1998. Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) final report. Washington (DC): US Environmental Protection Agency.
   Google Scholar
• European Parliament. 2006. Council of the European Union. REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), Regulation (EU) 1907/2006.
   Google Scholar
• European Parliament. 2012. Council of the European Union. BPR (Biocidal Products Regulation), Regulation (EU) 528/2012.
   Google Scholar
• Jarry H, Gamer A, Wuttke W. 2004. Effects of 5-day styrene inhalation on serum LH and testosterone levels and on hypothalamic and striatal amino acid neurotransmitter concentrations in male rats. Inhal Toxicol. 16(4):209–215.
   PubMed Web of Science ®Google Scholar
• Jersey GC, Balmer MF, Quast JF, Park CN, Schuetz DJ, Beyer JE, Olson KJ, McCollister SB, Rampy LW. 1978. Two-year chronic inhalation toxicity and carcinogenicity study on monomeric styrene in rats. Final Report. Dow Chemical Rept MCA NO:STY 1.1-TOX-INH. Midland (MI): Dow Chemical, Health and Environmental Research, Toxicology Research Laboratory.
   Google Scholar
• Kankaanpää JT, Elovaara E, Hemminki K, Vainio H. 1980. The effect of maternally inhaled styrene on embryonal and foetal development in mice and Chinese hamsters. Acta Pharmacol Toxicol. 47(2):127–129.
   PubMedGoogle Scholar
• Katakura Y, Kishi R, Ikeda T, Miyake H. 2001. Effects of prenatal styrene exposure on postnatal development and brain serotonin and catecholamine levels in rats. Environ Res. 85(1):41–47.
   PubMed Web of Science ®Google Scholar
• Khanna VK, Husain R, Hanig JP, Seth PK. 1991. Increased neurobehavioral toxicity of styrene in protein-malnourished rats. Neurotoxicol Teratol. 13(2):153–159.
   PubMed Web of Science ®Google Scholar
• Kishi R, Chen BQ, Katakura Y, Ikeda T, Miyake H. 1995. Effect of prenatal exposure to styrene on the neurobehavioral development, activity, motor coordination, and learning behavior of rats. Neurotoxicol Teratol. 17(2):121–130.
   PubMed Web of Science ®Google Scholar
• Kishi R, Katakura Y, Ikeda T, Chen BQ, Miyake H. 1992. Neurochemical effects in rats following gestational exposure to styrene. Toxicol Lett. 63(2):141–146.
   PubMed Web of Science ®Google Scholar
• Kleinstreuer NC, Ceger P, Watt ED, Martin M, Houck K, Browne P, Thomas RS, Casey WM, Dix DJ, Allen D, et al. 2017. Development and validation of a computational model for androgen receptor activity. Chem Res Toxicol. 30(4):946–964.
   PubMed Web of Science ®Google Scholar
• Klimisch HJ, Andreae M, Tillmann U. 1997. A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul Toxicol Pharmacol. 25(1):1–5.
   PubMed Web of Science ®Google Scholar
• Kuiper GG, van den Bemd GJ, van Leeuwen JP. 1999. Estrogen receptor and the SERM concept. J Endocrinol Invest. 22(8):594–603.
   PubMed Web of Science ®Google Scholar
• Kuwada M, Kawashima R, Nakamura K, Kojima H, Hasumi H, Maki J, Sugano S. 2002. Neonatal exposure to endocrine disruptors suppresses juvenile testis weight and steroidogenesis but spermatogenesis is considerably restored during puberty. Biochem Biophys Res Commun. 295(1):193–197.
   PubMed Web of Science ®Google Scholar
• La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, Guyton KZ, Kortenkamp A, Cogliano VJ, Woodruff TJ, et al. 2020. Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol. 16(1):45–57.
   PubMed Web of Science ®Google Scholar
• Lindbohm ML, Hemminki K, Kyyrönen P. 1985. Spontaneous abortions among women employed in the plastics industry. Am J Ind Med. 8(6):579–586.
   PubMed Web of Science ®Google Scholar
• Marty MS, Borgert C, Coady K, Green R, Levine SL, Mihaich E, Ortego L, Wheeler JR, Yi KD, Zorrilla LM. 2018. Distinguishing between endocrine disruption and non-specific effects on endocrine systems. Regul Toxicol Pharmacol. 99:142–158.
   PubMed Web of Science ®Google Scholar
• Matthews JC. 2021. A mechanistic evaluation of the potential for octamethylcyclotetrasiloxane to produce effects via endocrine modes of action. Crit Rev Toxicol. 51:571–590.
   PubMed Web of Science ®Google Scholar
• Mihaich E, Capdevielle M, Urbach-Ross D, Slezak B. 2017. Hypothesis-driven weight-of-evidence analysis of endocrine disruption potential: a case study with triclosan. Crit Rev Toxicol. 47(4):263–285.
   PubMed Web of Science ®Google Scholar
• Mihaich EM, Borgert CJ. 2018. Hypothesis-driven weight-of-evidence analysis for the endocrine disruption potential of benzene. Regul Toxicol Pharmacol. 100:7–15.
   PubMed Web of Science ®Google Scholar
• Murray FJ, John JA, Balmer MF, Schwetz BA. 1978. Teratologic evaluation of styrene given to rats and rabbits by inhalation or by gavage. Toxicology. 11(4):335–343.
   PubMed Web of Science ®Google Scholar
• National Toxicology Program. 2010. Multigenerational reproductive toxicology study of ethinyl estradiol (CAS No. 57-63-6) in Sprague-Dawley rats. NTP TR 547. Research Triangle Park (NC): National Institutes of Health.
   Google Scholar
• Neal BH, Bus J, Marty MS, Coady K, Williams A, Staveley J, Lamb JC. 2017. Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis. Crit Rev Toxicol. 47:1–57.
   PubMed Web of Science ®Google Scholar
• Ohno K, Azuma Y, Nakano S, Kobayashi T, Hirano S, Nobuhara Y, Yamada T. 2001. Assessment of styrene oligomers eluted from polystyrene-made food containers for estrogenic effects in in vitro assays. Food Chem Toxicol. 39(12):1233–1241.
   PubMed Web of Science ®Google Scholar
• Ohtani H, Ichikawa Y, Iwamoto E, Miura I. 2001. Effects of styrene monomer and trimer on gonadal sex differentiation of genetic males of the frog Rana rugosa. Environ Res. 87(3):175–180.
   PubMed Web of Science ®Google Scholar
• Organisation for Economic Co-operation and Development [OECD]. 2012. Guidance document on standardised test guidelines for evaluating chemicals for endocrine disruption. ENV/JM/MONO(201222. Paris: OECD/IOMC.
   Google Scholar
• Rotroff DM, Dix DJ, Houck KA, Knudsen TB, Martin MT, McLaurin KW, Reif DM, Crofton KM, Singh AV, Xia M, et al. 2013. Using in vitro high throughput screening assays to identify potential endocrine-disrupting chemicals. Environ Health Perspect. 121(1):7–14.
   PubMed Web of Science ®Google Scholar
• Ruiz P, Ortiz-Zarragoitia M, Orbea A, Theron M, Le Floch S, Cajaraville MP. 2012. Responses of conventional and molecular biomarkers in turbot Scophthalmus maximus exposed to heavy fuel oil no. 6 and styrene. Aquat Toxicol. 116-117:116–128.
   PubMed Web of Science ®Google Scholar
• Ruiz P, Ortiz-Zarragoitia M, Orbea A, Vingen S, Hjelle A, Baussant T, Cajaraville MP. 2014. Short- and long-term responses and recovery of mussels Mytilus edulis exposed to heavy fuel oil no. 6 and styrene. Ecotoxicology. 23(5):861–879.
   PubMed Web of Science ®Google Scholar
• Santini F, Mantovani A, Cristaudo A, Rago T, Marsili A, Buselli R, Mignani A, Ceccarini G, Bastillo R, Taddei D, et al. 2008. Thyroid function and exposure to styrene. Thyroid. 18(10):1065–1069.
   PubMed Web of Science ®Google Scholar
• Sawaki M, Noda S, Muroi T, Mitoma H, Takakura S, Sakamoto S, Yamasaki K. 2003. Evaluation of an in utero through lactational exposure protocol for detection of estrogenic effects of ethinyl estradiol on the offspring of rats: preliminary trial. Reproductive Toxicology. 17(3):335–343.
   PubMed Web of Science ®Google Scholar
• Schneider K, Schwarz M, Burkholder I, Kopp-Schneider A, Edler L, Kinsner-Ovaskainen A, Hartung T, Hoffmann S. 2009. “ToxRTool”, a new tool to assess the reliability of toxicological data. Toxicol Lett. 189(2):138–144.
   PubMed Web of Science ®Google Scholar
• Slikker W, Andersen ME, Bogdanffy MS, Bus JS, Cohen SD, Conolly RB, David RM, Doerrer NG, Dorman DC, Gaylor DW, et al. 2004. Dose-dependent transitions in mechanisms of toxicity. Toxicol Appl Pharmacol. 201(3):203–225.
   PubMed Web of Science ®Google Scholar
• Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO. 1995. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 103:113–122.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Seth PK, Srivastava SP. 1992a. Effect of styrene on testicular enzymes of growing rat. Indian J Exp Biol. 30(5):399–401.
   PubMedGoogle Scholar
• Srivastava S, Seth PK, Srivastava SP. 1992b. Biochemical and morphological studies in testes of rat offspring of mothers exposed to styrene during lactation. Pharmacol Toxicol. 70(4):314–316.
   PubMedGoogle Scholar
• Srivastava S, Seth PK, Srivastava SP. 1989. Effect of styrene administration on rat testis. Arch Toxicol. 63(1):43–46.
   PubMed Web of Science ®Google Scholar
• Takao T, Nanamiya W, Nazarloo HP, Asaba K, Hashimoto K. 2000. Possible reproductive toxicity of styrene in peripubertal male mice. Endocr J. 47(3):343–347.
   PubMed Web of Science ®Google Scholar
• Tatarazako N, Takao Y, Kishi K, Onikura NA, Arizono K, Iguchi T. 2002. Styrene dimers and trimers affect reproduction of daphnid (Ceriodaphnia dubia). Chemosphere. 48(6):597–601.
   PubMed Web of Science ®Google Scholar
• U.S. EPA. 2009a. Endocrine Disruptor Screening Program: Tier 1 screening order issuing announcement. 74 FR 54422, Oct. 21, 2009.
   Google Scholar
• U.S. EPA. 2009b. Final contaminant candidate list 3 chemicals: Screening to a PCCL. EPA 815-R-09-007.
   Google Scholar
• U.S. EPA. 2011. Weight-of-evidence: evaluating results of EDSP Tier 1 screening to identify the need for Tier 2 testing. EPA-HQ-OPPT-2013-0275-0004. Washington, DC: USEPA, Office of Chemical Safety and Pollution Prevention.
   Google Scholar
• U.S. Public Law 114-182. 2016. Frank R. Lautenberg Chemical Safety for the 21st Century Act, 15 U.S.C. § 2601 et. seq. 15 U.S.C. 2603, Sec. 4. Testing of Chemical substances and Mixtures.
   Google Scholar
• World Health Organization [WHO], International Program on Chemical Safety [IPCS]. 2002. Global assessment of the state-of-the-science of endocrine disruptors. WHO/PCS/EDC/02.2. Geneva: World Health Organization; p. 1–188.
   Google Scholar