1932

Abstract

Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal–fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed.

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2023-01-20
2024-04-19
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Literature Cited

  1. 1.
    Simon AK, Hollander GA, McMichael A. 2015. Evolution of the immune system in humans from infancy to old age. Proc. Biol. Sci. 282:182120143085
    [Google Scholar]
  2. 2.
    Wild CP. 2005. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomark. Prev. 14:81847–50
    [Google Scholar]
  3. 3.
    Wild CP. 2012. The exposome: from concept to utility. Int. J. Epidemiol. 41:124–32
    [Google Scholar]
  4. 4.
    Pristner M, Warth B. 2020. Drug-exposome interactions: the next frontier in precision medicine. Trends Pharmacol. Sci. 41:12994–1005
    [Google Scholar]
  5. 5.
    Rackaityte E, Halkias J. 2020. Mechanisms of fetal T cell tolerance and immune regulation. Front. Immunol. 11:588
    [Google Scholar]
  6. 6.
    Perez-Muñoz ME, Arrieta M-C, Ramer-Tait AE, Walter J. 2017. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5:48
    [Google Scholar]
  7. 7.
    Tanaka M, Nakayama J. 2017. Development of the gut microbiota in infancy and its impact on health in later life. Allergol. Int. 66:4515–22
    [Google Scholar]
  8. 8.
    Dugershaw BB, Aengenheister L, Hansen SSK, Hougaard KS, Buerki-Thurnherr T. 2020. Recent insights on indirect mechanisms in developmental toxicity of nanomaterials. Part. Fibre Toxicol. 17:31
    [Google Scholar]
  9. 9.
    Mathiesen L, Buerki-Thurnherr T, Pastuschek J, Aengenheister L, Knudsen LE. 2021. Fetal exposure to environmental chemicals; insights from placental perfusion studies. Placenta 106:58–66
    [Google Scholar]
  10. 10.
    Al-Enazy S, Ali S, Albekairi N, El-Tawil M, Rytting E 2017. Placental control of drug delivery. Adv. Drug Deliv. Rev. 116:63–72
    [Google Scholar]
  11. 11.
    Roth M, Obaidat A, Hagenbuch B. 2012. OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br. J. Pharmacol. 165:51260–87
    [Google Scholar]
  12. 12.
    Daud ANA, Bergman JEH, Bakker MK, Wang H, Kerstjens-Frederikse WS et al. 2015. P-glycoprotein-mediated drug interactions in pregnancy and changes in the risk of congenital anomalies: a case-reference study. Drug Saf. 38:7651–59
    [Google Scholar]
  13. 13.
    Han LW, Gao C, Mao Q. 2018. An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus. Expert Opin. Drug Metab. Toxicol. 14:8817–29
    [Google Scholar]
  14. 14.
    Mathias AA, Hitti J, Unadkat JD. 2005. P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages. Am. J. Physiol.-Regul. Integr. Comp. Physiol. 289:4R963–69
    [Google Scholar]
  15. 15.
    Caserta D, Pegoraro S, Mallozzi M, Di Benedetto L, Colicino E et al. 2018. Maternal exposure to endocrine disruptors and placental transmission: a pilot study. Gynecol. Endocrinol. 34:111001–4
    [Google Scholar]
  16. 16.
    Li L-X, Chen L, Meng X-Z, Chen B-H, Chen S-Q et al. 2013. Exposure levels of environmental endocrine disruptors in mother-newborn pairs in China and their placental transfer characteristics. PLOS ONE 8:5e62526
    [Google Scholar]
  17. 17.
    Zhang X, Li X, Jing Y, Fang X, Zhang X et al. 2017. Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China. Environ. Pollut. 222:267–75
    [Google Scholar]
  18. 18.
    Yin S, Zhang J, Guo F, Zhao L, Poma G et al. 2019. Transplacental transfer of organochlorine pesticides: concentration ratio and chiral properties. Environ. Int. 130:104939
    [Google Scholar]
  19. 19.
    Woo CSJ, Partanen H, Myllynen P, Vähäkangas K, El-Nezami H. 2012. Fate of the teratogenic and carcinogenic ochratoxin A in human perfused placenta. Toxicol. Lett. 208:192–99
    [Google Scholar]
  20. 20.
    Partanen HA, El-Nezami HS, Leppänen JM, Myllynen PK, Woodhouse HJ, Vähäkangas KH. 2010. Aflatoxin B1 transfer and metabolism in human placenta. Toxicol. Sci. 113:1216–25
    [Google Scholar]
  21. 21.
    Warth B, Preindl K, Manser P, Wick P, Marko D, Buerki-Thurnherr T. 2019. Transfer and metabolism of the xenoestrogen zearalenone in human perfused placenta. Environ. Health Perspect. 127:10107004
    [Google Scholar]
  22. 22.
    Sayyari A, Uhlig S, Fæste CK, Framstad T, Sivertsen T. 2018. Transfer of deoxynivalenol (DON) through placenta, colostrum and milk from sows to their offspring during late gestation and lactation. Toxins 10:12E517
    [Google Scholar]
  23. 23.
    Muoth C, Aengenheister L, Kucki M, Wick P, Buerki-Thurnherr T. 2016. Nanoparticle transport across the placental barrier: pushing the field forward. ! Nanomedicine 11:8941–57
    [Google Scholar]
  24. 24.
    Bongaerts E, Nawrot TS, Van Pee T, Ameloot M, Bové H. 2020. Translocation of (ultra)fine particles and nanoparticles across the placenta; a systematic review on the evidence of in vitro, ex vivo, and in vivo studies. Part Fibre Toxicol. 17:56
    [Google Scholar]
  25. 25.
    Hartmann NB, Baun A. 2010. The nano cocktail: ecotoxicological effects of engineered nanoparticles in chemical mixtures. Integr. Environ. Assess. Manag. 6:2311–13
    [Google Scholar]
  26. 26.
    Naasz S, Altenburger R, Kühnel D. 2018. Environmental mixtures of nanomaterials and chemicals: the Trojan-horse phenomenon and its relevance for ecotoxicity. Sci. Total Environ. 635:1170–81
    [Google Scholar]
  27. 27.
    Ezekiel CN, Abia WA, Braun D, Šarkanj B, Ayeni KI et al. 2022. Mycotoxin exposure biomonitoring in breastfed and non-exclusively breastfed Nigerian children. Environ. Int. 158:106996
    [Google Scholar]
  28. 28.
    Braun D, Eiser M, Puntscher H, Marko D, Warth B. 2021. Natural contaminants in infant food: the case of regulated and emerging mycotoxins. Food Control 123:107676
    [Google Scholar]
  29. 29.
    Anderson HA, Wolff MS. 2000. Environmental contaminants in human milk. J. Expo. Anal. Environ. Epidemiol. 10:6 Pt. 2755–60
    [Google Scholar]
  30. 30.
    Haddad S, Ayotte P, Verner M-A. 2015. Derivation of exposure factors for infant lactational exposure to persistent organic pollutants (POPs). Regul. Toxicol. Pharmacol. 71:2135–40
    [Google Scholar]
  31. 31.
    Lehmann GM, Verner M-A, Luukinen B, Henning C, Assimon SA et al. 2014. Improving the risk assessment of lipophilic persistent environmental chemicals in breast milk. Crit. Rev. Toxicol. 44:7600–17
    [Google Scholar]
  32. 32.
    Morishita Y, Yoshioka Y, Takimura Y, Shimizu Y, Namba Y et al. 2016. Distribution of silver nanoparticles to breast milk and their biological effects on breast-fed offspring mice. ACS Nano 10:98180–91
    [Google Scholar]
  33. 33.
    World Health Organ 2021. Infant and young child feeding Fact Sheet, World Health Organ. Geneva: https://www.who.int/news-room/fact-sheets/detail/infant-and-young-child-feeding
  34. 34.
    Adaku Chilaka C, Mally A 2020. Mycotoxin occurrence, exposure and health implications in infants and young children in sub-Saharan Africa: a review. Foods 9:111585
    [Google Scholar]
  35. 35.
    Juan C, Raiola A, Mañes J, Ritieni A. 2014. Presence of mycotoxin in commercial infant formulas and baby foods from Italian market. Food Control 39:227–36
    [Google Scholar]
  36. 36.
    Zhang K, Flannery BM, Oles CJ, Adeuya A. 2018. Mycotoxins in infant/toddler foods and breakfast cereals in the US retail market. Food Addit. Contam. B 11:3183–90
    [Google Scholar]
  37. 37.
    Lehmann GM, LaKind JS, Davis MH, Hines EP, Marchitti SA et al. 2018. Environmental chemicals in breast milk and formula: exposure and risk assessment implications. Environ. Health Perspect. 126:996001
    [Google Scholar]
  38. 38.
    Liao C, Liu F, Kannan K. 2013. Occurrence of and dietary exposure to parabens in foodstuffs from the United States. Environ. Sci. Technol. 47:83918–25
    [Google Scholar]
  39. 39.
    Fujii Y, Yan J, Harada KH, Hitomi T, Yang H et al. 2012. Levels and profiles of long-chain perfluorinated carboxylic acids in human breast milk and infant formulas in East Asia. Chemosphere 86:3315–21
    [Google Scholar]
  40. 40.
    Westerhoff P, Atkinson A, Fortner J, Wong MS, Zimmerman J et al. 2018. Low risk posed by engineered and incidental nanoparticles in drinking water. Nat. Nanotechnol. 13:8661–69
    [Google Scholar]
  41. 41.
    Stroustrup A, Bragg JB, Busgang S, Andra S, Curtin P et al. 2020. Sources of clinically significant neonatal intensive care unit phthalate exposure. J. Expo. Sci. Environ. Epidemiol. 30:1137–48
    [Google Scholar]
  42. 42.
    Frederiksen H, Skakkebaek NE, Andersson A-M. 2007. Metabolism of phthalates in humans. Mol. Nutr. Food Res. 51:7899–911
    [Google Scholar]
  43. 43.
    Demirel A, Çoban A, Yıldırım Ş, Doğan C, Sancı R, İnce Z. 2016. Hidden toxicity in neonatal intensive care units: phthalate exposure in very low birth weight infants. J. Clin. Res. Pediatr. Endocrinol. 8:3298–304
    [Google Scholar]
  44. 44.
    Jenkins R, Tackitt S, Gievers L, Iragorri S, Sage K et al. 2019. Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study. Pediatr. Nephrol. 34:81413–24
    [Google Scholar]
  45. 45.
    Stark A, Smith PB, Hornik CP, Zimmerman KO, Hornik CD et al. 2022. Medication use in the neonatal intensive care unit and changes from 2010 to 2018. J. Pediatr. 240:66–71.e4
    [Google Scholar]
  46. 46.
    Toma M, Felisi M, Bonifazi D, Bonifazi F, Giannuzzi V et al. 2021. Paediatric medicines in Europe: the paediatric regulation—Is it time for reform?. Front. Med. 8:54
    [Google Scholar]
  47. 47.
    Iszatt N, Janssen S, Lenters V, Dahl C, Stigum H et al. 2019. Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month. Microbiome 7:34
    [Google Scholar]
  48. 48.
    Oliveira M, Duarte S, Delerue-Matos C, Pena A, Morais S. 2020. Exposure of nursing mothers to polycyclic aromatic hydrocarbons: levels of un-metabolized and metabolized compounds in breast milk, major sources of exposure and infants’ health risks. Environ. Pollut. 266:115243
    [Google Scholar]
  49. 49.
    Lee S, Kim S, Park J, Kim H-J, Choi G et al. 2018. Perfluoroalkyl substances (PFASs) in breast milk from Korea: time-course trends, influencing factors, and infant exposure. Sci. Total Environ. 612:286–92
    [Google Scholar]
  50. 50.
    Zhu H, Kannan K. 2019. Occurrence of melamine and its derivatives in breast milk from the United States and its implications for exposure in infants. Environ. Sci. Technol. 53:137859–65
    [Google Scholar]
  51. 51.
    Rawn DFK, Sadler AR, Casey VA, Breton F, Sun W-F et al. 2017. Dioxins/furans and PCBs in Canadian human milk: 2008–2011. Sci. Total Environ. 595:269–78
    [Google Scholar]
  52. 52.
    Urbancova K, Lankova D, Sram RJ, Hajslova J, Pulkrabova J. 2019. Urinary metabolites of phthalates and di-iso-nonyl cyclohexane-1,2-dicarboxylate (DINCH)—Czech mothers’ and newborns’ exposure biomarkers. Environ. Res. 173:342–48
    [Google Scholar]
  53. 53.
    Frederiksen H, Kuiri-Hänninen T, Main KM, Dunkel L, Sankilampi U. 2014. A longitudinal study of urinary phthalate excretion in 58 full-term and 67 preterm infants from birth through 14 months. Environ. Health Perspect. 122:9998–1005
    [Google Scholar]
  54. 54.
    Navaranjan G, Takaro TK, Wheeler AJ, Diamond ML, Shu H et al. 2020. Early life exposure to phthalates in the Canadian Healthy Infant Longitudinal Development (CHILD) study: a multi-city birth cohort. J. Expo. Sci. Environ. Epidemiol. 30:170–85
    [Google Scholar]
  55. 55.
    Urbancova K, Dvorakova D, Gramblicka T, Sram RJ, Hajslova J, Pulkrabova J. 2020. Comparison of polycyclic aromatic hydrocarbon metabolite concentrations in urine of mothers and their newborns. Sci. Total Environ. 723:138116
    [Google Scholar]
  56. 56.
    Drage DS, Harden FA, Jeffery T, Mueller JF, Hobson P, Toms L-ML. 2019. Human biomonitoring in Australian children: Brominated flame retardants decrease from 2006 to 2015. Environ. Int. 122:363–68
    [Google Scholar]
  57. 57.
    Gyllenhammar I, Benskin JP, Sandblom O, Berger U, Ahrens L et al. 2018. Perfluoroalkyl acids (PFAAs) in serum from 2-4-month-old infants: influence of maternal serum concentration, gestational age, breast-feeding, and contaminated drinking water. Environ. Sci. Technol. 52:127101–10
    [Google Scholar]
  58. 58.
    Calafat AM, Weuve J, Ye X, Jia LT, Hu H et al. 2009. Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ. Health Perspect. 117:4639–44
    [Google Scholar]
  59. 59.
    Blake MJ, Castro L, Leeder JS, Kearns GL. 2005. Ontogeny of drug metabolizing enzymes in the neonate. Semin. Fetal Neonatal Med. 10:2123–38
    [Google Scholar]
  60. 60.
    Zane NR, Chen Y, Wang MZ, Thakker DR. 2018. Cytochrome P450 and flavin-containing monooxygenase families: age-dependent differences in expression and functional activity. Pediatr. Res. 83:2527–35
    [Google Scholar]
  61. 61.
    Ezekiel CN, Abia WA, Braun D, Šarkanj B, Ayeni KI et al. 2022. Mycotoxin exposure biomonitoring in breastfed and non-exclusively breastfed Nigerian children. Environ. Int. 158:106996
    [Google Scholar]
  62. 62.
    Sánchez EM, Diaz GJ. 2019. Frequency and levels of aflatoxin M1 in urine of children in Bogota, Colombia. Mycotoxin Res. 35:3271–78
    [Google Scholar]
  63. 63.
    Chen G, Gong YY, Kimanya ME, Shirima CP, Routledge MN. 2018. Comparison of urinary aflatoxin M1 and aflatoxin albumin adducts as biomarkers for assessing aflatoxin exposure in Tanzanian children. Biomarkers 23:2131–36
    [Google Scholar]
  64. 64.
    Badée J, Qiu N, Collier AC, Takahashi RH, Forrest WF et al. 2019. Characterization of the ontogeny of hepatic UDP-glucuronosyltransferase enzymes based on glucuronidation activity measured in human liver microsomes. J. Clin. Pharmacol. 59:Suppl. 1S42–55
    [Google Scholar]
  65. 65.
    Bhatt DK, Mehrotra A, Gaedigk A, Chapa R, Basit A et al. 2019. Age- and genotype-dependent variability in the protein abundance and activity of six major uridine diphosphate-glucuronosyltransferases in human liver. Clin. Pharmacol. Ther. 105:1131–41
    [Google Scholar]
  66. 66.
    Buratti FM, Darney K, Vichi S, Turco L, Di Consiglio E et al. 2021. Human variability in glutathione-S-transferase activities, tissue distribution and major polymorphic variants: meta-analysis and implication for chemical risk assessment. Toxicol. Lett. 337:78–90
    [Google Scholar]
  67. 67.
    Vyskočilová E, Szotáková B, Skálová L, Bártíková H, Hlaváčová J, Boušová I. 2013. Age-related changes in hepatic activity and expression of detoxification enzymes in male rats. Biomed. Res. Int. 2013:408573
    [Google Scholar]
  68. 68.
    Xu S, Hou D, Liu J, Ji L 2018. Age-associated changes in GSH S-transferase gene/proteins in livers of rats. Redox Rep. 23:1213–18
    [Google Scholar]
  69. 69.
    Coughtrie MWH. 2016. Function and organization of the human cytosolic sulfotransferase (SULT) family. Chem. Biol. Interact. 259:Pt. A2–7
    [Google Scholar]
  70. 70.
    Stanley EL, Hume R, Coughtrie MWH. 2005. Expression profiling of human fetal cytosolic sulfotransferases involved in steroid and thyroid hormone metabolism and in detoxification. Mol. Cell. Endocrinol. 240:132–42
    [Google Scholar]
  71. 71.
    Dubaisi S, Caruso JA, Gaedigk R, Vyhlidal CA, Smith PC et al. 2019. Developmental expression of the cytosolic sulfotransferases in human liver. Drug Metab. Dispos. 47:6592–600
    [Google Scholar]
  72. 72.
    Leonetti CP, Butt CM, Stapleton HM. 2018. Disruption of thyroid hormone sulfotransferase activity by brominated flame retardant chemicals in the human choriocarcinoma placenta cell line, BeWo. Chemosphere 197:81–88
    [Google Scholar]
  73. 73.
    van den Dries MA, Keil AP, Tiemeier H, Pronk A, Spaan S et al. 2021. Prenatal exposure to nonpersistent chemical mixtures and fetal growth: a population-based study. Environ. Health Perspect. 129:11117008
    [Google Scholar]
  74. 74.
    Roell KR, Reif DM, Motsinger-Reif AA. 2017. An introduction to terminology and methodology of chemical synergy—perspectives from across disciplines. Front. Pharmacol. 8:158
    [Google Scholar]
  75. 75.
    Van Der Ven LTM, Van Ommeren P, Zwart EP, Gremmer ER, Hodemaekers HM et al. 2022. Dose addition in the induction of craniofacial malformations in zebrafish embryos exposed to a complex mixture of food-relevant chemicals with dissimilar modes of action. Environ. Health Perspect. 130:447003
    [Google Scholar]
  76. 76.
    Heindel JJ, Newbold R, Schug TT. 2015. Endocrine disruptors and obesity. Nat. Rev. Endocrinol. 11:11653–61
    [Google Scholar]
  77. 77.
    Pearce JL, Neelon B, Bloom MS, Buckley JP, Ananth CV et al. 2021. Exploring associations between prenatal exposure to multiple endocrine disruptors and birth weight with exposure continuum mapping. Environ. Res. 200:111386
    [Google Scholar]
  78. 78.
    Ferguson KK, McElrath TF, Meeker JD. 2014. Environmental phthalate exposure and preterm birth. JAMA Pediatr. 168:161–67
    [Google Scholar]
  79. 79.
    Braun JM. 2017. Early-life exposure to EDCs: role in childhood obesity and neurodevelopment. Nat. Rev. Endocrinol. 13:3161–73
    [Google Scholar]
  80. 80.
    Sifakis S, Androutsopoulos VP, Tsatsakis AM, Spandidos DA. 2017. Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems. Environ. Toxicol. Pharmacol. 51:56–70
    [Google Scholar]
  81. 81.
    Viñas R, Jeng Y-J, Watson CS. 2012. Non-genomic effects of xenoestrogen mixtures. Int. J. Environ. Res. Public Health 9:82694–714
    [Google Scholar]
  82. 82.
    Lee H-R, Jeung E-B, Cho M-H, Kim T-H, Leung PCK, Choi K-C. 2013. Molecular mechanism(s) of endocrine-disrupting chemicals and their potent oestrogenicity in diverse cells and tissues that express oestrogen receptors. J. Cell. Mol. Med. 17:11–11
    [Google Scholar]
  83. 83.
    Bouskine A, Nebout M, Brücker-Davis F, Benahmed M, Fenichel P. 2009. Low doses of bisphenol A promote human seminoma cell proliferation by activating PKA and PKG via a membrane G-protein-coupled estrogen receptor. Environ. Health Perspect. 117:71053–58
    [Google Scholar]
  84. 84.
    Bocato MZ, Ximenez JPB, Hoffmann C, Barbosa F. 2019. An overview of the current progress, challenges, and prospects of human biomonitoring and exposome studies. J. Toxicol. Environ. Health B 22:5–6131–56
    [Google Scholar]
  85. 85.
    Yu M, Tu P, Dolios G, Dassanayake PS, Volk H et al. 2021. Tooth biomarkers to characterize the temporal dynamics of the fetal and early-life exposome. Environ. Int. 157:106849
    [Google Scholar]
  86. 86.
    Gorrochategui E, Jaumot J, Lacorte S, Tauler R. 2016. Data analysis strategies for targeted and untargeted LC-MS metabolomic studies: overview and workflow. TrAC Trends Anal. Chem. 82:425–42
    [Google Scholar]
  87. 87.
    Vitale CM, Price EJ, Miller GW, David A, Antignac J-P et al. 2021. Analytical strategies for chemical exposomics: exploring limits and feasibility. Exposome 1:1osab003
    [Google Scholar]
  88. 88.
    Jamnik T, Flasch M, Braun D, Fareed Y, Wasinger D et al. 2022. Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development. Nat. Commun. 13:2653
    [Google Scholar]
  89. 89.
    Chen L, Zhong F, Zhu J. 2020. Bridging targeted and untargeted mass spectrometry-based metabolomics via hybrid approaches. Metabolites 10:9348
    [Google Scholar]
  90. 90.
    Hu X, Walker DI, Liang Y, Smith MR, Orr ML et al. 2021. A scalable workflow to characterize the human exposome. Nat. Commun. 12:5575
    [Google Scholar]
  91. 91.
    Ren J-L, Zhang A-H, Kong L, Wang X-J. 2018. Advances in mass spectrometry-based metabolomics for investigation of metabolites. RSC Adv. 8:4022335–50
    [Google Scholar]
  92. 92.
    Misra BB, Langefeld C, Olivier M, Cox LA. 2019. Integrated omics: tools, advances and future approaches. J. Mol. Endocrinol. 62:1R21–45
    [Google Scholar]
  93. 93.
    Bian Y, Bayer FP, Chang Y-C, Meng C, Hoefer S et al. 2021. Robust microflow LC-MS/MS for proteome analysis: 38 000 runs and counting. Anal. Chem. 93:83686–90
    [Google Scholar]
  94. 94.
    Bian Y, Zheng R, Bayer FP, Wong C, Chang Y-C et al. 2020. Robust, reproducible and quantitative analysis of thousands of proteomes by micro-flow LC-MS/MS. Nat. Commun. 11:157
    [Google Scholar]
  95. 95.
    Fitz V, Berger D, Abiead YE, Koellensperger G. 2022. Systematic investigation of LC miniaturization to increase sensitivity in wide-target LC-MS-based trace bioanalysis of small molecules. Front. Mol. Biosci. 9:857505
    [Google Scholar]
  96. 96.
    Schmidt A, Schmidt A, Markert UR. 2021. The road (not) taken—placental transfer and interspecies differences. Placenta 115:70–77
    [Google Scholar]
  97. 97.
    Pattillo RA, Gey GO. 1968. The establishment of a cell line of human hormone-synthesizing trophoblastic cells in vitro. Cancer Res 28:71231–36
    [Google Scholar]
  98. 98.
    Li H, van Ravenzwaay B, Rietjens IMCM, Louisse J. 2013. Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds. Arch. Toxicol. 87:91661–69
    [Google Scholar]
  99. 99.
    Gauster M, Huppertz B. 2010. The paradox of caspase 8 in human villous trophoblast fusion. Placenta 31:282–88
    [Google Scholar]
  100. 100.
    Wolfe MW. 2006. Culture and transfection of human choriocarcinoma cells. Placenta and Trophoblast: Methods and Protocols, Vol. 1 MJ Soares, JS Hunt 229–39 Totowa, NJ: Humana
    [Google Scholar]
  101. 101.
    Vargas A, Moreau J, Landry S, LeBellego F, Toufaily C et al. 2009. Syncytin-2 plays an important role in the fusion of human trophoblast cells. J. Mol. Biol. 392:2301–18
    [Google Scholar]
  102. 102.
    Evseenko DA, Paxton JW, Keelan JA. 2006. ABC drug transporter expression and functional activity in trophoblast-like cell lines and differentiating primary trophoblast. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290:5R1357–65
    [Google Scholar]
  103. 103.
    Aengenheister L, Keevend K, Muoth C, Schönenberger R, Diener L et al. 2018. An advanced human in vitro co-culture model for translocation studies across the placental barrier. Sci Rep. 8:5388
    [Google Scholar]
  104. 104.
    Levkovitz R, Zaretsky U, Gordon Z, Jaffa AJ, Elad D. 2013. In vitro simulation of placental transport: part I. Biological model of the placental barrier. Placenta 34:8699–707
    [Google Scholar]
  105. 105.
    Huang X, Lüthi M, Ontsouka EC, Kallol S, Baumann MU et al. 2016. Establishment of a confluent monolayer model with human primary trophoblast cells: novel insights into placental glucose transport. Mol. Hum. Reprod. 22:6442–56
    [Google Scholar]
  106. 106.
    Myllynen P, Vähäkangas K. 2013. Placental transfer and metabolism: an overview of the experimental models utilizing human placental tissue. Toxicol. Vitro 27:1507–12
    [Google Scholar]
  107. 107.
    Muoth C, Wichser A, Monopoli M, Correia M, Ehrlich N et al. 2016. A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment. Nanoscale 8:3917322–32
    [Google Scholar]
  108. 108.
    Turco MY, Gardner L, Kay RG, Hamilton RS, Prater M et al. 2018. Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature 564:7735263–67
    [Google Scholar]
  109. 109.
    Haider S, Meinhardt G, Saleh L, Kunihs V, Gamperl M et al. 2018. Self-renewing trophoblast organoids recapitulate the developmental program of the early human placenta. Stem Cell Rep. 11:2537–51
    [Google Scholar]
  110. 110.
    Lee JS, Romero R, Han YM, Kim HC, Kim CJ et al. 2016. Placenta-on-a-chip: a novel platform to study the biology of the human placenta. J. Matern. Fetal Neonatal Med. 29:71046–54
    [Google Scholar]
  111. 111.
    Blundell C, Tess ER, Schanzer ASR, Coutifaris C, Su EJ et al. 2016. A microphysiological model of the human placental barrier. Lab. Chip 16:163065–73
    [Google Scholar]
  112. 112.
    Blundell C, Yi Y-S, Ma L, Tess ER, Farrell MJ et al. 2018. Placental drug transport-on-a-chip: a microengineered in vitro model of transporter-mediated drug efflux in the human placental barrier. Adv. Healthc. Mater. 7:21700786
    [Google Scholar]
  113. 113.
    Mandt D, Gruber P, Markovic M, Tromayer M, Rothbauer M et al. 2018. Fabrication of biomimetic placental barrier structures within a microfluidic device utilizing two-photon polymerization. Int. J. Bioprint. 4:2144
    [Google Scholar]
  114. 114.
    Schuller P, Rothbauer M, Kratz SRA, Höll G, Taus P et al. 2020. A lab-on-a-chip system with an embedded porous membrane-based impedance biosensor array for nanoparticle risk assessment on placental Bewo trophoblast cells. Sens. Actuators B 312:127946
    [Google Scholar]
  115. 115.
    Kreuder A-E, Bolaños-Rosales A, Palmer C, Thomas A, Geiger M-A et al. 2020. Inspired by the human placenta: a novel 3D bioprinted membrane system to create barrier models. Sci. Rep. 10:15606
    [Google Scholar]
  116. 116.
    Hutson JR, Garcia-Bournissen F, Davis A, Koren G 2011. The human placental perfusion model: a systematic review and development of a model to predict in vivo transfer of therapeutic drugs. Clin. Pharmacol. Ther. 90:167–76
    [Google Scholar]
  117. 117.
    Miller RK, Genbacev O, Turner MA, Aplin JD, Caniggia I, Huppertz B. 2005. Human placental explants in culture: approaches and assessments. Placenta 26:6439–48
    [Google Scholar]
  118. 118.
    Valero L, Alhareth K, Gil S, Simasotchi C, Roques C et al. 2017. Assessment of dually labelled PEGylated liposomes transplacental passage and placental penetration using a combination of two ex-vivo human models: the dually perfused placenta and the suspended villous explants. Int. J. Pharm. 532:2729–37
    [Google Scholar]
  119. 119.
    Juch H, Nikitina L, Reimann S, Gauster M, Dohr G et al. 2018. Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in early human placental explants and reduce hCG secretion. Nanotoxicology 12:290–103
    [Google Scholar]
  120. 120.
    Lacconi V, Massimiani M, Paglione L, Messina A, Battistini B et al. 2022. An improved in vitro model simulating the feto-maternal interface to study developmental effects of potentially toxic compounds: the example of titanium dioxide nanoparticles. Toxicol. Appl. Pharmacol. 446:116056
    [Google Scholar]
  121. 121.
    Boos JA, Misun PM, Brunoldi G, Furer LA, Aengenheister L et al. 2021. Microfluidic co-culture platform to recapitulate the maternal-placental-embryonic axis. Adv. Biol. 5:8e2100609
    [Google Scholar]
  122. 122.
    Schymanski EL, Bolton EE. 2022. FAIRifying the exposome journal: templates for chemical structures and transformations. Exposome 2:1osab006
    [Google Scholar]
  123. 123.
    Tamayo-Uria I, Maitre L, Thomsen C, Nieuwenhuijsen MJ, Chatzi L et al. 2019. The early-life exposome: description and patterns in six European countries. Environ. Int. 123:189–200
    [Google Scholar]
  124. 124.
    Apel P, Rousselle C, Lange R, Sissoko F, Kolossa-Gehring M, Ougier E. 2020. Human biomonitoring initiative (HBM4EU)—strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment. Int. J. Hyg. Environ. Health 230:113622
    [Google Scholar]
  125. 125.
    Huhn S, Escher BI, Krauss M, Scholz S, Hackermüller J, Altenburger R. 2021. Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive. Environ. Sci. Eur. 33:17
    [Google Scholar]
  126. 126.
    IARC Work Group Eval. Carcinog. Risks Hum 2002. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene Lyon, Fr: IARC
  127. 127.
    Rocha O, Ansari K, Doohan FM. 2005. Effects of trichothecene mycotoxins on eukaryotic cells: a review. Food Addit. Contam. 22:4369–78
    [Google Scholar]
  128. 128.
    IARC Work. Group Eval. Carcinog. Risks Hum 1993. Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins Lyon, Fr: IARC
  129. 129.
    Rai A, Das M, Tripathi A. 2020. Occurrence and toxicity of a fusarium mycotoxin, zearalenone. Crit. Rev. Food Sci. Nutr. 60:162710–29
    [Google Scholar]
  130. 130.
    IARC Work. Group Eval. Carcinog. Risks Hum 2012. Plants Containing Aristolochic Acid Lyon, Fr: IARC
  131. 131.
    Guo Y, Xiao D, Yang X, Zheng J, Hu S et al. 2019. Prenatal exposure to pyrrolizidine alkaloids induced hepatotoxicity and pulmonary injury in fetal rats. Reprod. Toxicol. 85:34–41
    [Google Scholar]
  132. 132.
    Kwakye GF, Jiménez J, Jiménez JA, Aschner M. 2018. Atropa belladonna neurotoxicity: implications to neurological disorders. Food Chem. Toxicol. 116:346–53
    [Google Scholar]
  133. 133.
    Green BT, Lee ST, Panter KE, Brown DR. 2012. Piperidine alkaloids: human and food animal teratogens. Food Chem. Toxicol. 50:62049–55
    [Google Scholar]
  134. 134.
    Chenchen W, Wenlong W, Xiaoxue L, Feng M, Dandan C et al. 2014. Pathogenesis and preventive treatment for animal disease due to locoweed poisoning. Environ. Toxicol. Pharmacol. 37:1336–47
    [Google Scholar]
  135. 135.
    Lone Y, Koiri RK, Bhide M. 2015. An overview of the toxic effect of potential human carcinogen Microcystin-LR on testis. Toxicol. Rep. 2:289–96
    [Google Scholar]
  136. 136.
    Friedman MA, Fernandez M, Backer LC, Dickey RW, Bernstein J et al. 2017. An updated review of ciguatera fish poisoning: clinical, epidemiological, environmental, and public health management. Mar. Drugs 15:372
    [Google Scholar]
  137. 137.
    IARC Work. Group Eval. Carcinog. Risks Hum 2010. Some Non-Heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures Lyon, Fr: IARC
  138. 138.
    IARC Work. Group Eval. Carcinog. Risks Hum 2018. Some Industrial Chemicals Lyon, Fr: IARC
  139. 139.
    Zong C, Hasegawa R, Urushitani M, Zhang L, Nagashima D et al. 2019. Role of microglial activation and neuroinflammation in neurotoxicity of acrylamide in vivo and in vitro. Arch Toxicol 93:72007–19
    [Google Scholar]
  140. 140.
    Park J-S, Samanta P, Lee S, Lee J, Cho J-W et al. 2021. Developmental and neurotoxicity of acrylamide to zebrafish. Int. J. Mol. Sci. 22:73518
    [Google Scholar]
  141. 141.
    IARC Working Group Eval. Carcinog. Risks Hum 1995. Dry Cleaning, Some Chlorinated Solvents and Other Industrial Chemicals Lyon, Fr: IARC
  142. 142.
    de Conti A, Kobets T, Escudero-Lourdes C, Montgomery B, Tryndyak V et al. 2014. Dose- and time-dependent epigenetic changes in the livers of Fisher 344 rats exposed to furan. Toxicol. Sci. 139:2371–80
    [Google Scholar]
  143. 143.
    Liu H, Nie F-H, Lin H-Y, Ma Y, Ju X-H et al. 2016. Developmental toxicity, oxidative stress, and related gene expression induced by dioxin-like PCB 126 in zebrafish (Danio rerio). Environ. Toxicol. 31:3295–303
    [Google Scholar]
  144. 144.
    Paul R, Moltó J, Ortuño N, Romero A, Bezos C et al. 2017. Relationship between serum dioxin-like polychlorinated biphenyls and post-testicular maturation in human sperm. Reprod. Toxicol. 73:312–21
    [Google Scholar]
  145. 145.
    Brun NR, Panlilio JM, Zhang K, Zhao Y, Ivashkin E et al. 2021. Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish. Commun. Biol. 4:11129
    [Google Scholar]
  146. 146.
    IARC Work. Group Eval. Carcinog. Risks Hum 2018. DDT, Lindane, and 2,4-D Lyon, Fr: IARC
  147. 147.
    Naughton SX, Terry AV. 2018. Neurotoxicity in acute and repeated organophosphate exposure. Toxicology 408:101–12
    [Google Scholar]
  148. 148.
    Yu L, Lam JCW, Guo Y, Wu RSS, Lam PKS, Zhou B. 2011. Parental transfer of polybrominated diphenyl ethers (PBDEs) and thyroid endocrine disruption in zebrafish. Environ. Sci. Technol. 45:2410652–59
    [Google Scholar]
  149. 149.
    Zhang H, Yang X, Li X, Cheng Y, Zhang H et al. 2020. Oxidative and nitrosative stress in the neurotoxicity of polybrominated diphenyl ether-153: possible mechanism and potential targeted intervention. Chemosphere 238:124602
    [Google Scholar]
  150. 150.
    Fenton SE, Ducatman A, Boobis A, DeWitt JC, Lau C et al. 2021. Per- and polyfluoroalkyl substance toxicity and human health review: current state of knowledge and strategies for informing future research. Environ. Toxicol. Chem. 40:3606–30
    [Google Scholar]
  151. 151.
    Qian Y, Shao H, Ying X, Huang W, Hua Y. 2020. The endocrine disruption of prenatal phthalate exposure in mother and offspring. Front. Public Health 8:366
    [Google Scholar]
  152. 152.
    Qian X, Li J, Xu S, Wan Y, Li Y et al. 2019. Prenatal exposure to phthalates and neurocognitive development in children at two years of age. Environ. Int. 131:105023
    [Google Scholar]
  153. 153.
    Vo TTB, Yoo Y-M, Choi K-C, Jeung E-B. 2010. Potential estrogenic effect(s) of parabens at the prepubertal stage of a postnatal female rat model. Reprod. Toxicol. 29:3306–16
    [Google Scholar]
  154. 154.
    Rubin BS. 2011. Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J. Steroid Biochem. Mol. Biol. 127:1–227–34
    [Google Scholar]
  155. 155.
    IARC Work. Group Eval. Carcinog. Risks Hum 2019. Some Chemicals That Cause Tumours of the Urinary Tract in Rodents Lyon, Fr: IARC
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