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Organophosphate Esters: Are These Flame Retardants and Plasticizers Affecting Children’s Health?

  • Synthetic Chemicals and Health (A Zota and T James-Todd, Section Editors)
  • Published:
Current Environmental Health Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Organophosphate esters (OPEs) are applied to a variety of consumer products, primarily as flame retardants and plasticizers. OPEs can leach out of products over time and are consequently prevalent in the environment and frequently detected in human biomonitoring studies. Exposure during pregnancy is of particular concern as OPEs have recently been detected in placental tissues, suggesting they may be transferred to the developing infant. Also, studies have now shown that children typically experience higher exposure to several OPEs compared with adults, indicating they may be disproportionately impacted by these compounds. This review summarizes the current literature on reproductive and child health outcomes of OPE exposures and highlights areas for future research.

Recent Findings

Experimental animal studies demonstrate potential for OPEs to adversely impact health, and a limited number of epidemiologic studies conducted in adult cohorts suggest that OPEs may interfere with the endocrine system. Neurodevelopment is perhaps the most well studied of children’s health endpoints, and several studies indicate that prenatal and early life OPE exposures impact both cognitive and behavioral development. Associations have also been reported with reproductive outcomes (e.g., fertilization and pregnancy loss) and with the timing of parturition and preterm birth. Cross-sectional studies also demonstrate associations between OPEs and respiratory health outcomes, allergic disease, and measures of adiposity.

Summary

An expanding body of research demonstrates that OPEs are associated with adverse reproductive health and birth outcomes, asthma and allergic disease, early growth and adiposity, and neurodevelopment. Still, additional research is urgently needed to elucidate the full impact of OPEs on children’s health.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dodson RE, Rodgers KM, Carey G, Cedeno Laurent JG, Covaci A, Poma G, et al. Flame retardant chemicals in college dormitories: flammability standards influence dust concentrations. Environ Sci Technol. 2017;51(9):4860–9.

    Article  CAS  PubMed  Google Scholar 

  2. Dodson RE, Perovich LJ, Covaci A, Van den Eede N, Ionas AC, Dirtu AC, et al. After the PBDE phase-out: a broad suite of flame retardants in repeat house dust samples from California. Environ Sci Technol. 2012;46(24):13056–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Stapleton HM, Sharma S, Getzinger G, Ferguson PL, Gabriel M, Webster TF, et al. Novel and high volume use flame retardants in US couches reflective of the 2005 PentaBDE phase out. Environ Sci Technol. 2012;46(24):13432–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. van der Veen I, de Boer J. Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis. Chemosphere. 2012;88(10):1119–53.

    Article  PubMed  CAS  Google Scholar 

  5. Reemtsma T, Quintana J, Rodil R, Farcia-Lopez M, Rodriguez I. Organophosphorus flame retardants and plasticizers in water and air occurrence and fate. Trends Anal Chem. 2008;27(9):727–37.

    Article  CAS  Google Scholar 

  6. ATSDR. Toxicological profile for phosphate ester flame retardants. U.S. DHHS. 2012.

  7. Wei GL, Li DQ, Zhuo MN, Liao YS, Xie ZY, Guo TL, et al. Organophosphorus flame retardants and plasticizers: sources, occurrence, toxicity and human exposure. Environ Pollut. 2015;196:29–46.

    Article  CAS  PubMed  Google Scholar 

  8. Stapleton HM, Klosterhaus S, Eagle S, Fuh J, Meeker JD, Blum A, et al. Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ Sci Technol. 2009;43(19):7490–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Marklund A, Andersson B, Haglund P. Screening of organophosphorus compounds and their distribution in various indoor environments. Chemosphere. 2003;53(9):1137–46.

    Article  CAS  PubMed  Google Scholar 

  10. Abbasi G, Saini A, Goosey E, Diamond ML. Product screening for sources of halogenated flame retardants in Canadian house and office dust. Sci Total Environ. 2016;545–546:299–307.

    Article  PubMed  CAS  Google Scholar 

  11. Carlsson H, Ulrika N. C O. Video display units: an emission source of the contact allergenic flame retardant triphenyl phosphate in the indoor environment. Environ Sci Technol. 2000;2000(34):3885–9.

    Article  CAS  Google Scholar 

  12. Hoffman K, Butt CM, Chen A, Limkakeng AT Jr, Stapleton HM. High exposure to organophosphate flame retardants in infants: associations with baby products. Environ Sci Technol. 2015;49(24):14554–9.

    Article  CAS  PubMed  Google Scholar 

  13. Li J, Zhao L, Letcher RJ, Zhang Y, Jian K, Zhang J, et al. A review on organophosphate Ester (OPE) flame retardants and plasticizers in foodstuffs: levels, distribution, human dietary exposure, and future directions. Environ Int. 2019;127:35–51.

    Article  CAS  PubMed  Google Scholar 

  14. Gomes G, Ward P, Lorenzo A, Hoffman K, Stapleton HM. Characterizing flame retardant applications and potential human exposure in backpacking tents. Environ Sci Technol. 2016;50(10):5338–45.

    Article  CAS  PubMed  Google Scholar 

  15. Keller AS, Raju NP, Webster TF, Stapleton HM. Flame retardant applications in camping tents and potential exposure. Environ Sci Technol Lett. 2014;1(2):152–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mendelsohn E, Hagopian A, Hoffman K, Butt CM, Lorenzo A, Congleton J, et al. Nail polish as a source of exposure to triphenyl phosphate. Environ Int. 2016;86:45–51.

    Article  CAS  PubMed  Google Scholar 

  17. Bergh C, Torgrip R, Emenius G, Ostman C. Organophosphate and phthalate esters in air and settled dust-a multi-location indoor study. Indoor Air. 2011;21(1):67–76.

    Article  CAS  PubMed  Google Scholar 

  18. Betts KS. Exposure to TDCPP appears widespread. Environ Health Perspect. 2013;121(5):a150.

    PubMed  PubMed Central  Google Scholar 

  19. He R, Li Y, Xiang P, Li C, Zhou C, Zhang S, et al. Organophosphorus flame retardants and phthalate esters in indoor dust from different microenvironments: bioaccessibility and risk assessment. Chemosphere. 2016;150:528–35.

    Article  CAS  PubMed  Google Scholar 

  20. Wu M, Yu G, Cao Z, Wu D, Liu K, Deng S, et al. Characterization and human exposure assessment of organophosphate flame retardants in indoor dust from several microenvironments of Beijing. China. Chemosphere. 2016;150:465–71.

    Article  CAS  PubMed  Google Scholar 

  21. Zhou L, Hiltscher M, Gruber D, Puttmann W. Organophosphate flame retardants (OPFRs) in indoor and outdoor air in the Rhine/Main area, Germany: comparison of concentrations and distribution profiles in different microenvironments. Environ Sci Pollut Res Int. 2017;24(12):10992–1005.

    Article  CAS  PubMed  Google Scholar 

  22. Castorina R, Butt C, Stapleton HM, Avery D, Harley KG, Holland N, et al. Flame retardants and their metabolites in the homes and urine of pregnant women residing in California (the CHAMACOS cohort). Chemosphere. 2017;179:159–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kim JW, Isobe T, Sudaryanto A, Malarvannan G, Chang KH, Muto M, et al. Organophosphorus flame retardants in house dust from the Philippines: occurrence and assessment of human exposure. Environ Sci Pollut Res Int. 2013;20(2):812–22.

    Article  CAS  PubMed  Google Scholar 

  24. Meeker JD, Cooper EM, Stapleton HM, Hauser R. Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations. Environ Health Perspect. 2013;121(5):580–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Meeker JD, Stapleton HM. House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parameters. Environ Health Perspect. 2010;118(3):318–23.

    Article  CAS  PubMed  Google Scholar 

  26. Tajima S, Araki A, Kawai T, Tsuboi T, Ait Bamai Y, Yoshioka E, et al. Detection and intake assessment of organophosphate flame retardants in house dust in Japanese dwellings. Sci Total Environ. 2014;478:190–9.

    Article  CAS  PubMed  Google Scholar 

  27. Cao Z, Xu F, Covaci A, Wu M, Yu G, Wang B, et al. Differences in the seasonal variation of brominated and phosphorus flame retardants in office dust. Environ Int. 2014;65:100–6.

    Article  CAS  PubMed  Google Scholar 

  28. Yang F, Ding J, Huang W, Xie W, Liu W. Particle size-specific distributions and preliminary exposure assessments of organophosphate flame retardants in office air particulate matter. Environ Sci Technol. 2014;48(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  29. Bradman A, Barr DB, Claus Henn BG, Drumheller T, Curry C, Eskenazi B. Measurement of pesticides and other toxicants in amniotic fluid as a potential biomarker of prenatal exposure: a validation study. Environ Health Perspect. 2003;111(14):1779–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fromme H, Lahrz T, Kraft M, Fembacher L, Mach C, Dietrich S, et al. Organophosphate flame retardants and plasticizers in the air and dust in German daycare centers and human biomonitoring in visiting children (LUPE 3). Environ Int. 2014;71:158–63.

    Article  CAS  PubMed  Google Scholar 

  31. Carignan CC, McClean MD, Cooper EM, Watkins DJ, Fraser AJ, Heiger-Bernays W, et al. Predictors of tris(1,3-dichloro-2-propyl) phosphate metabolite in the urine of office workers. Environ Int. 2013;55:56–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cequier E, Sakhi AK, Marce RM, Becher G, Thomsen C. Human exposure pathways to organophosphate triesters-a biomonitoring study of mother-child pairs. Environ Int. 2015;75:159–65.

    Article  CAS  PubMed  Google Scholar 

  33. Dodson RE, Van den Eede N, Covaci A, Perovich LJ, Brody JG, Rudel RA. Urinary biomonitoring of phosphate flame retardants: levels in California adults and recommendations for future studies. Environ Sci Technol. 2014;48(23):13625–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hou R, Xu Y, Wang Z. Review of OPFRs in animals and humans: absorption, bioaccumulation, metabolism, and internal exposure research. Chemosphere. 2016;153:78–90.

    Article  CAS  PubMed  Google Scholar 

  35. • Phillips AL, Hammel SC, Hoffman K, Lorenzo AM, Chen A, Webster TF, et al. Children’s residential exposure to organophosphate ester flame retardants and plasticizers: Investigating exposure pathways in the TESIE study. Environ Int. 2018;116:176–85 This work demonstrates that hand-to-mouth contact and dermal absorption may be important pathways of OPE exposure, especially for young children.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hughes MF, Edwards BC, Mitchell CT, Bhooshan B. In vitro dermal absorption of flame retardant chemicals. Food Chem Toxicol : an international journal published for the British Industrial Biological Research Association. 2001;39(12):1263–70.

    Article  CAS  Google Scholar 

  37. Liu X, Yu G, Cao Z, Wang B, Huang J, Deng S, et al. Occurrence of organophosphorus flame retardants on skin wipes: insight into human exposure from dermal absorption. Environ Int. 2017;98:113–9.

    Article  CAS  PubMed  Google Scholar 

  38. Makinen MS, Makinen MR, Koistinen JT, Pasanen AL, Pasanen PO, Kalliokoski PJ, et al. Respiratory and dermal exposure to organophosphorus flame retardants and tetrabromobisphenol A at five work environments. Environ Sci Technol. 2009;43(3):941–7.

    Article  CAS  PubMed  Google Scholar 

  39. Schreder ED, Uding N, La Guardia MJ. Inhalation a significant exposure route for chlorinated organophosphate flame retardants. Chemosphere. 2016;150:499–504.

    Article  CAS  PubMed  Google Scholar 

  40. Sundkvist AM, Olofsson U, Haglund P. Organophosphorus flame retardants and plasticizers in marine and fresh water biota and in human milk. J Environ Mon : JEM. 2010;12(4):943–51.

    Article  CAS  Google Scholar 

  41. Li J, Yu N, Zhang B, Jin L, Li M, Hu M, et al. Occurrence of organophosphate flame retardants in drinking water from China. Water Res. 2014;54:53–61.

    Article  PubMed  CAS  Google Scholar 

  42. Cooper EM, Covaci A, van Nuijs AL, Webster TF, Stapleton HM. Analysis of the flame retardant metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP) in urine using liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2011;401(7):2123–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lynn RK, Wong K, Garvie-Gould C, Kennish JM. Disposition of the flame retardant, tris(1,3-dichloro-2-propyl) phosphate, in the rat. Drug Metab Dispos: the biological fate of chemicals. 1981;9(5):434–41.

    CAS  Google Scholar 

  44. Nomeir AA, Kato S, Matthews HB. The metabolism and disposition of tris(1,3-dichloro-2-propyl) phosphate (fyrol FR-2) in the rat. Toxicol Appl Pharmacol. 1981;57(3):401–13.

    Article  CAS  PubMed  Google Scholar 

  45. Sasaki K, Suzuki T, Takeda M, Uchiyama M. Metabolism of phosphoric acid triesters by rat liver homogenate. Bull Environ Contam Toxicol. 1984;33(3):281–8.

    Article  CAS  PubMed  Google Scholar 

  46. Van den Eede N, Maho W, Erratico C, Neels H, Covaci A. First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions. Toxicol Lett. 2013;223(1):9–15.

    Article  PubMed  CAS  Google Scholar 

  47. Wang G, Du Z, Chen H, Su Y, Gao S, Mao L. Tissue-specific accumulation, depuration, and transformation of triphenyl phosphate (TPHP) in adult zebrafish (Danio rerio). Environ Sci Technol. 2016;50(24):13555–64.

    Article  CAS  PubMed  Google Scholar 

  48. Minegishi K, Kurebayashi H, Nambaru S, Morimoto K, Takahashi T, Yamaha T. Comparative studies on absorption, distribution, and excretion of flame retardants halogenated alkyl phosphate in rats. Eisei Kagaku. 1988;34(2):102–14.

    Article  CAS  Google Scholar 

  49. Su G, Crump D, Letcher RJ, Kennedy SW. In vitro metabolism of the flame retardant triphenyl phosphate in chicken embryonic hepatocytes and the importance of the hydroxylation pathway. Environ Sci Technol. 2015;48(22):13511–9.

    Article  CAS  Google Scholar 

  50. Butt CM, Congleton J, Hoffman K, Fang M, Stapleton HM. Metabolites of organophosphate flame retardants and 2-ethylhexyl tetrabromobenzoate in urine from paired mothers and toddlers. Environ Sci Technol. 2014;48(17):10432–8.

    Article  CAS  PubMed  Google Scholar 

  51. Butt CM, Hoffman K, Chen A, Lorenzo A, Congleton J, Stapleton HM. Regional comparison of organophosphate flame retardant (PFR) urinary metabolites and tetrabromobenzoic acid (TBBA) in mother-toddler pairs from California and New Jersey. Environ Int. 2016;94:627–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ding J, Xu Z, Huang W, Feng L, Yang F. Organophosphate ester flame retardants and plasticizers in human placenta in Eastern China. Sci Total Environ. 2016;554–555:211–7.

    Article  PubMed  CAS  Google Scholar 

  53. Feng L, Ouyang F, Liu L, Wang X, Wang X, Li YJ, et al. Levels of urinary metabolites of organophosphate flame retardants, TDCIPP, and TPHP, in pregnant women in Shanghai. J Environ Public Health. 2016;2016:9416054.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Hoffman K, Butt CM, Webster TF, Preston EV, Hammel SC, Makey C, et al. Temporal trends in exposure to organophosphate flame retardants in the United States. Environ Sci Technol Lett. 2017;4(3):112–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hoffman K, Daniels JL, Stapleton HM. Urinary metabolites of organophosphate flame retardants and their variability in pregnant women. Environ Int. 2014;63:169–72.

    Article  CAS  PubMed  Google Scholar 

  56. Hoffman K, Lorenzo A, Butt CM, Adair L, Herring AH, Stapleton HM, et al. Predictors of urinary flame retardant concentration among pregnant women. Environ Int. 2017;98:96–101.

    Article  CAS  PubMed  Google Scholar 

  57. Liu LY, He K, Hites RA, Salamova A. Hair and nails as noninvasive biomarkers of human exposure to brominated and organophosphate flame retardants. Environ Sci Technol. 2016;50(6):3065–73.

    Article  CAS  PubMed  Google Scholar 

  58. Liu LY, Salamova A, He K, Hites RA. Analysis of polybrominated diphenyl ethers and emerging halogenated and organophosphate flame retardants in human hair and nails. J Chromatogr A. 2015;1406:251–7.

    Article  CAS  PubMed  Google Scholar 

  59. Su G, Letcher RJ, Yu H, Gooden DM, Stapleton HM. Determination of glucuronide conjugates of hydroxyl triphenyl phosphate (OH-TPHP) metabolites in human urine and its use as a biomarker of TPHP exposure. Chemosphere. 2016;149:314–9.

    Article  CAS  PubMed  Google Scholar 

  60. Van den Eede N, Heffernan AL, Aylward LL, Hobson P, Neels H, Mueller JF, et al. Age as a determinant of phosphate flame retardant exposure of the Australian population and identification of novel urinary PFR metabolites. Environ Int. 2015;74:1–8.

    Article  PubMed  CAS  Google Scholar 

  61. •• Ospina M, Jayatilaka NK, Wong LY, Restrepo P, Calafat AM. Exposure to organophosphate flame retardant chemicals in the US general population: data from the 2013–2014 National Health and Nutrition Examination Survey. Environ Int. 2018;110:32–41 Provides an assessment of a range of OPEs in a large, representative U.S. population.

    Article  CAS  PubMed  Google Scholar 

  62. Sasaki K, Takeda M, Uchiyama M. Toxicity, absorption and elimination of phosphoric acid triesters by killifish and goldfish. Bull Environ Contam Toxicol. 1981;27(6):775–82.

    Article  CAS  PubMed  Google Scholar 

  63. Romano ME, Hawley NL, Eliot M, Calafat AM, Jayatilaka NK, Kelsey K, et al. Variability and predictors of urinary concentrations of organophosphate flame retardant metabolites among pregnant women in Rhode Island. Environ Health : a global access science source. 2017;16(1):40.

    Article  CAS  Google Scholar 

  64. Hoffman K, Garantziotis S, Birnbaum LS, Stapleton HM. Monitoring indoor exposure to organophosphate flame retardants: hand wipes and house dust. Environ Health Perspect. 2015;123(2):160–5.

    Article  CAS  PubMed  Google Scholar 

  65. •• Carignan CC, Minguez-Alarcon L, Butt CM, Williams PL, Meeker JD, Stapleton HM, et al. Urinary concentrations of organophosphate flame retardant metabolites and pregnancy outcomes among women undergoing in vitro fertilization. Environ Health Perspect. 2017;125(8):087018 This work evaluates preconception OPEs and associations with pregnancy outcomes. Inverse associations between the sum of three OPE metabolites (BDCIPP, ip-PPP, and DPHP) and proportions of fertilization, implantation, clinical pregnancy, and live birth are reported.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Wang Y, Li W, Martinez-Moral MP, Sun H, Kannan K. Metabolites of organophosphate esters in urine from the United States: concentrations, temporal variability, and exposure assessment. Environ Int. 2019;122:213–21.

    Article  CAS  PubMed  Google Scholar 

  67. • Zhao F, Chen M, Gao F, Shen H, Hu J. Organophosphorus flame retardants in pregnant women and their transfer to chorionic villi. Environ Sci Technol. 2017;51(11):6489–97 This work measured several OPEs and their metabolites in human chorionic villi and deciduae. Findings indicate potential maternal-fetal transfer in early gestation, prior to the development of a mature placenta.

    Article  CAS  PubMed  Google Scholar 

  68. Baldwin KR, Phillips AL, Horman B, Arambula SE, Rebuli ME, Stapleton HM, et al. Sex specific placental accumulation and behavioral effects of developmental Firemaster 550 exposure in Wistar rats. Sci Rep. 2017;7(1):7118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Phillips AL, Chen A, Rock KD, Horman B, Patisaul HB, Stapleton HM. Transplacental and lactational transfer of Firemaster(R) 550 components in dosed Wistar rats. Toxicol Sci : an official journal of the Society of Toxicology. 2016;153(2):246–57.

    Article  CAS  Google Scholar 

  70. He C, Toms LL, Thai P, Van den Eede N, Wang X, Li Y, et al. Urinary metabolites of organophosphate esters: concentrations and age trends in Australian children. Environ Int. 2018;111:124–30.

    Article  CAS  PubMed  Google Scholar 

  71. • Gibson EA, Stapleton HM, Calero L, Holmes D, Burke K, Martinez R, et al. Differential exposure to organophosphate flame retardants in mother-child pairs. Chemosphere. 2019;219:567–73 This work found that children had higher levels of two of six assessed OPEs measured in urine than their mothers.

    Article  CAS  PubMed  Google Scholar 

  72. Chen Y, Fang J, Ren L, Fan R, Zhang J, Liu G, et al. Urinary metabolites of organophosphate esters in children in South China: concentrations, profiles and estimated daily intake. Environ Pollut. 2018;235:358–64.

    Article  CAS  PubMed  Google Scholar 

  73. He C, English K, Baduel C, Thai P, Jagals P, Ware RS, et al. Concentrations of organophosphate flame retardants and plasticizers in urine from young children in Queensland, Australia and associations with environmental and behavioural factors. Environ Res. 2018;164:262–70.

    Article  CAS  PubMed  Google Scholar 

  74. Cooper EM, Kroeger G, Davis K, Clark CR, Ferguson PL, Stapleton HM. Results from screening polyurethane foam based consumer products for flame retardant chemicals: assessing impacts on the change in the furniture flammability standards. Environ Sci Technol. 2016;50(19):10653–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ginsberg G, Hattis D, Sonawane B. Incorporating pharmacokinetic differences between children and adults in assessing children’s risks to environmental toxicants. Toxicol Appl Pharmacol. 2004;198(2):164–83.

    Article  CAS  PubMed  Google Scholar 

  76. Makri A, Goveia M, Balbus J, Parkin R. Children’s susceptibility to chemicals: a review by developmental stage. J Toxicol Environ Health B Crit Rev. 2004;7(6):417–35.

    Article  CAS  PubMed  Google Scholar 

  77. Selevan SG, Kimmel CA, Mendola P. Identifying critical windows of exposure for children’s health. Environ Health Perspect. 2000;108(Suppl 3):451–5.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. 2000;108(Suppl 3):511–33.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Soubry A, Hoyo C, Butt CM, Fieuws S, Price TM, Murphy SK, et al. Human exposure to flame-retardants is associated with aberrant DNA methylation at imprinted genes in sperm. Environ Epigenetics. 2017;3(1):dvx003.

    Article  CAS  Google Scholar 

  80. •• Carignan CC, Minguez-Alarcon L, Williams PL, Meeker JD, Stapleton HM, Butt CM, et al. Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization. Environ Int. 2018;111:232–8 Findings from this work indicate that female partner exposure may be more important in pregnancy outcomes than male partner OPE exposures.

    Article  CAS  PubMed  Google Scholar 

  81. •• Ingle ME, Minguez-Alarcon L, Carignan CC, Butt CM, Stapleton HM, Williams PL, et al. The association between urinary concentrations of phosphorous-containing flame retardant metabolites and semen parameters among men from a fertility clinic. Int J Hyg Environ Health. 2018;221(5):809–15 Findings from this work suggest that odds of having a low sperm count decrease with increasing BDCIPP concentrations Associatiosn with other OPE metabolites were weak and inconsistent.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. •• Messerlian C, Williams PL, Minguez-Alarcon L, Carignan CC, Ford JB, Butt CM, et al. Organophosphate flame-retardant metabolite concentrations and pregnancy loss among women conceiving with assisted reproductive technology. Fertil Steril. 2018;110(6):1137-44 e1 This work evaluated preconception OPEs and pregnancy loss Findings suggest that higher DPHP and summed OPE metabolites are associated with greater risk of pregnancy loss.

    Article  CAS  Google Scholar 

  83. Hoffman K, Hammel SC, Phillips AL, Lorenzo AM, Chen A, Calafat AM, et al. Biomarkers of exposure to SVOCs in children and their demographic associations: the TESIE study. Environ Int. 2018;119:26–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. •• Boyle M, Buckley JP, Quiros-Alcala L. Associations between urinary organophosphate ester metabolites and measures of adiposity among US children and adults: NHANES 2013–2014. Environ Int. 2019;127:754–63 This cross-sectional assessment reports inverse associations between DBUP and the indicators of adiposity and reports that BCEP is associated with increased prevalence odds of being overweight vs. normal weight among children.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Araki A, Saito I, Kanazawa A, Morimoto K, Nakayama K, Shibata E, et al. Phosphorus flame retardants in indoor dust and their relation to asthma and allergies of inhabitants. Indoor Air. 2013;24(1):3–15.

    Article  PubMed  CAS  Google Scholar 

  86. Canbaz D, van Velzen MJ, Hallner E, Zwinderman AH, Wickman M, Leonards PE, et al. Exposure to organophosphate and polybrominated diphenyl ether flame retardants via indoor dust and childhood asthma. Indoor Air. 2016;26(3):403–13.

    Article  CAS  PubMed  Google Scholar 

  87. •• Araki A, Bastiaensen M, Bamai YA, Van den Eede N, Kawai T, Tsuboi T, et al. Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children. Environ Int. 2018;119:438–46 In this work, TDCIPP in house dust, and metabolites of TDCIPP TBOEP and TCIPP in urine were associated with children’s allergic symptoms.

    Article  CAS  PubMed  Google Scholar 

  88. Bi C, Maestre JP, Li H, Zhang G, Givehchi R, Mahdavi A, et al. Phthalates and organophosphates in settled dust and HVAC filter dust of U.S. low-income homes: association with season, building characteristics, and childhood asthma. Environ Int. 2018;121(Pt 1):916–30.

    Article  CAS  PubMed  Google Scholar 

  89. •• Castorina R, Bradman A, Stapleton HM, Butt C, Avery D, Harley KG, et al. Current-use flame retardants: maternal exposure and neurodevelopment in children of the CHAMACOS cohort. Chemosphere. 2017;189:574–80 Prenatal samples of maternal urine were assessed for OPEs and child neurodevelopment was assessed in this work. OPE metabolites were positively associated with worse scores on the WISC-IV (particularly the Working Memory scale), and higher scores on the BASC-2 Hyperactivity scale.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. • Lipscomb ST, McClelland MM, MacDonald M, Cardenas A, Anderson KA, Kile ML. Cross-sectional study of social behaviors in preschool children and exposure to flame retardants. Environ Health : a global access science source. 2017;16(1):23 Using silicone wristbands to assess exposure cross-sectionally, children with higher ΣOPFR were rated as having less responsible behavior and more externalizing behavior problems.

    Article  Google Scholar 

  91. •• Doherty BT, Hoffman K, Keil AP, Engel SM, Stapleton HM, Goldman BD, et al. Prenatal exposure to organophosphate esters and behavioral development in young children in the Pregnancy, Infection, and Nutrition Study. Neurotoxicology. 2019;73:150–60 Results of this work suggest associations between prenatal exposure to OPEs (i.e., BDCIPP and DPHP) and attention problems, withdrawal, and hyperactivity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. •• Doherty BT, Hoffman K, Keil AP, Engel SM, Stapleton HM, Goldman BD, et al. Prenatal exposure to organophosphate esters and cognitive development in young children in the Pregnancy, Infection, and Nutrition Study. Environ Res. 2019;169:33–40 Worse cognitive assessment scores were associated with higher prenatal ip-PPP in maternal urine samples in this assessment.

    Article  CAS  PubMed  Google Scholar 

  93. Preston EV, McClean MD, Claus Henn B, Stapleton HM, Braverman LE, Pearce EN, et al. Associations between urinary diphenyl phosphate and thyroid function. Environ Int. 2017;101:158–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Xu T, Wang Q, Shi Q, Fang Q, Guo Y, Zhou B. Bioconcentration, metabolism and alterations of thyroid hormones of tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in zebrafish. Environ Toxicol Pharmacol. 2015;40(2):581–6.

    Article  CAS  PubMed  Google Scholar 

  95. Wang Q, Liang K, Liu J, Yang L, Guo Y, Liu C, et al. Exposure of zebrafish embryos/larvae to TDCPP alters concentrations of thyroid hormones and transcriptions of genes involved in the hypothalamic-pituitary-thyroid axis. Aqua Toxicol (Amsterdam, Netherlands). 2013;126:207–13.

    Article  CAS  Google Scholar 

  96. Wang Q, Lam JC, Han J, Wang X, Guo Y, Lam PK, et al. Developmental exposure to the organophosphorus flame retardant tris(1,3-dichloro-2-propyl) phosphate: estrogenic activity, endocrine disruption and reproductive effects on zebrafish. Aqua Toxicol (Amsterdam, Netherlands). 2015;160:163–71.

    Article  CAS  Google Scholar 

  97. Wang Q, Lai NL, Wang X, Guo Y, Lam PK, Lam JC, et al. Bioconcentration and transfer of the organophorous flame retardant 1,3-dichloro-2-propyl phosphate causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish larvae. Environ Sci Technol. 2015;49(8):5123–32.

    Article  CAS  PubMed  Google Scholar 

  98. McGee SP, Konstantinov A, Stapleton HM, Volz DC. Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor. Toxicol Sci : an official journal of the Society of Toxicology. 2013;133(1):144–56.

    Article  CAS  Google Scholar 

  99. Liu X, Jung D, Jo A, Ji K, Moon HB, Choi K. Long-term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio). Environ Toxicol Chem. 2016;35(9):2288–96.

    Article  CAS  PubMed  Google Scholar 

  100. Liu X, Ji K, Choi K. Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN cell lines and in zebrafish. Aqua Toxicol (Amsterdam, Netherlands). 2012;114–115:173–81.

    Article  CAS  Google Scholar 

  101. Kim S, Jung J, Lee I, Jung D, Youn H, Choi K. Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines. Aqua Toxicol (Amsterdam, Netherlands). 2015;160:188–96.

    Article  CAS  Google Scholar 

  102. Moser VC, Phillips PM, Hedge JM, McDaniel KL. Neurotoxicological and thyroid evaluations of rats developmentally exposed to tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloro-2-ethyl)phosphate (TCEP). Neurotoxicol Teratol. 2015;52(Pt B):236–47.

    Article  CAS  PubMed  Google Scholar 

  103. Kassotis CD, Kollitz EM, Hoffman K, Sosa JA, Stapleton HM. Thyroid receptor antagonism as a contributory mechanism for adipogenesis induced by environmental mixtures in 3T3-L1 cells. Sci Total Environ. 2019;666:431–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Farhat A, Crump D, Chiu S, Williams KL, Letcher RJ, Gauthier LT, et al. In ovo effects of two organophosphate flame retardants--TCPP and TDCPP--on pipping success, development, mRNA expression, and thyroid hormone levels in chicken embryos. Toxicol Sci : an official journal of the Society of Toxicology. 2013;134(1):92–102.

    Article  CAS  Google Scholar 

  105. Liu X, Ji K, Jo A, Moon HB, Choi K. Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio). Aqua Toxicol (Amsterdam, Netherlands). 2013;134–135:104–11.

    Article  CAS  Google Scholar 

  106. Schang G, Robaire B, Hales BF. Organophosphate flame retardants act as endocrine-disrupting chemicals in MA-10 mouse tumor leydig cells. Toxicol Sci : an official journal of the Society of Toxicology. 2016;150(2):499–509.

    Article  CAS  Google Scholar 

  107. Meeker JD. Exposure to environmental endocrine disruptors and child development. Arch Pediatr Adolesc Med. 2012;166(10):952–8.

    Article  PubMed  Google Scholar 

  108. Ely DM, Driscoll AK, Mathews TJ. Infant mortality by age at death in the United States, 2016. NCHS Data Brief No 326. 2018.

  109. Patisaul HB, Roberts SC, Mabrey N, McCaffrey KA, Gear RB, Braun J, et al. Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster(R) 550 in rats: an exploratory assessment. J Biochem Mol Toxicol. 2013;27(2):124–36.

    Article  CAS  PubMed  Google Scholar 

  110. Crump D, Chiu S, Kennedy SW. Effects of tris(1,3-dichloro-2-propyl) phosphate and tris(1-chloropropyl) phosphate on cytotoxicity and mRNA expression in primary cultures of avian hepatocytes and neuronal cells. Toxicol Sci : an official journal of the Society of Toxicology. 2012;126(1):140–8.

    Article  CAS  Google Scholar 

  111. McGee SP, Cooper EM, Stapleton HM, Volz DC. Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure. Environ Health Perspect. 2012;120(11):1585–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Welsh JJ, Collins TF, Whitby KE, Black TN, Arnold A. Teratogenic potential of triphenyl phosphate in Sprague-Dawley (Spartan) rats. Toxicol Ind Health. 1987;3(3):357–69.

    Article  CAS  PubMed  Google Scholar 

  113. Fu J, Han J, Zhou B, Gong Z, Santos EM, Huo X, et al. Toxicogenomic responses of zebrafish embryos/larvae to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) reveal possible molecular mechanisms of developmental toxicity. Environ Sci Technol. 2013;47(18):10574–82.

    Article  CAS  PubMed  Google Scholar 

  114. •• Hoffman K, Stapleton HM, Lorenzo A, Butt CM, Adair L, Herring AH, et al. Prenatal exposure to organophosphates and associations with birthweight and gestational length. Environ Int. 2018;116:248–54 This work finds associations between several OPE metabolites and gestational duration The results suggest associations differ based on the infant sex.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Wade MG, Kawata A, Rigden M, Caldwell D, Holloway AC. Toxicity of flame retardant isopropylated triphenyl phosphate: liver, adrenal, and metabolic effects. Int J Toxicol. 2019;38(4):279–90 1091581819851502.

    Article  CAS  PubMed  Google Scholar 

  116. Thomas MB, Stapleton HM, Dills RL, Violette HD, Christakis DA, Sathyanarayana S. Demographic and dietary risk factors in relation to urinary metabolites of organophosphate flame retardants in toddlers. Chemosphere. 2017;185:918–25.

    Article  CAS  PubMed  Google Scholar 

  117. Poma G, Sales C, Bruyland B, Christia C, Goscinny S, Van Loco J, et al. Occurrence of Organophosphorus flame retardants and plasticizers (PFRs) in Belgian foodstuffs and estimation of the dietary exposure of the adult population. Environ Sci Technol. 2018;52(4):2331–8.

    Article  CAS  PubMed  Google Scholar 

  118. Babich MA. Preliminary risk assessment of flame retardant (FR) chemicals in upholstered furniture foam Bethesda, MD 20814: U.S. Consumer Product Safety Commission 2006.

  119. Camarasa JG, Serra-Baldrich E. Allergic contact dermatitis from triphenyl phosphate. Contact Dermatitis. 1992;26(4):264–5.

    Article  CAS  PubMed  Google Scholar 

  120. Carlsen L, Andersen KE, Egsgaard H. Triphenyl phosphate allergy from spectacle frames. Contact Dermatitis. 1986;15(5):274–7.

    Article  CAS  PubMed  Google Scholar 

  121. Wang Q, Lam JC, Man YC, Lai NL, Kwok KY, Guo Y, et al. Bioconcentration, metabolism and neurotoxicity of the organophorous flame retardant 1,3-dichloro 2-propyl phosphate (TDCPP) to zebrafish. Aqua Toxicol (Amsterdam, Netherlands). 2015;158:108–15.

    Article  CAS  Google Scholar 

  122. Jarema KA, Hunter DL, Shaffer RM, Behl M, Padilla S. Acute and developmental behavioral effects of flame retardants and related chemicals in zebrafish. Neurotoxicol Teratol. 2015;52(Pt B):194–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Noyes PD, Haggard DE, Gonnerman GD, Tanguay RL. Advanced morphological-behavioral test platform reveals neurodevelopmental defects in embryonic zebrafish exposed to comprehensive suite of halogenated and organophosphate flame retardants. Toxicol Sci : an official journal of the Society of Toxicology. 2015;145(1):177–95.

    Article  CAS  Google Scholar 

  124. Oliveri AN, Bailey JM, Levin ED. Developmental exposure to organophosphate flame retardants causes behavioral effects in larval and adult zebrafish. Neurotoxicol Teratol. 2015;52(Pt B):220–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Dishaw LV, Hunter DL, Padnos B, Padilla S, Stapleton HM. Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio). Toxicol Sci : an official journal of the Society of Toxicology. 2014;142(2):445–54.

    Article  CAS  Google Scholar 

  126. de Esch C, Slieker R, Wolterbeek A, Woutersen R, de Groot D. Zebrafish as potential model for developmental neurotoxicity testing: a mini review. Neurotoxicol Teratol. 2012;34(6):545–53.

    Article  PubMed  CAS  Google Scholar 

  127. Bailey J, Oliveri A, Levin ED. Zebrafish model systems for developmental neurobehavioral toxicology. Birth Defects Res C Embryo Today. 2013;99(1):14–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Grandjean P, Landrigan PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014;13(3):330–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hammel SC, Hoffman K, Webster TF, Anderson KA, Stapleton HM. Measuring personal exposure to organophosphate flame retardants using silicone wristbands and hand wipes. Environ Sci Technol. 2016;50(8):4483–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. •• Gibson EA, Stapleton HM, Caler L, Holmes D, Burke K, Martinez R, et al. Flame retardant exposure assessment: findings from a behavioral intervention study. J expo Sci Env Epid. 2019;29(1):33–48 This case-crossover study suggests that hand washing and cleaning may be effective means of reducing exposure to OPEs.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology, Geisel School of Medicine Dartmouth College, Lebanon, NH, 03756, USA

    Brett T. Doherty

  2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Brett T. Doherty & Julie L. Daniels

  3. Nicholas School of the Environment, Duke University, 9 Circuit Drive, Box 90328, Durham, NC, 27708, USA

    Stephanie C. Hammel, Heather M. Stapleton & Kate Hoffman

  4. Children’s Health and Discovery Initiative, Duke School of Medicine, Durham, NC, 27708, USA

    Heather M. Stapleton & Kate Hoffman

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  1. Brett T. Doherty
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Doherty, B.T., Hammel, S.C., Daniels, J.L. et al. Organophosphate Esters: Are These Flame Retardants and Plasticizers Affecting Children’s Health?. Curr Envir Health Rpt 6, 201–213 (2019). https://doi.org/10.1007/s40572-019-00258-0

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