Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure.

Amanda Bullert, Xueshu Li, Chunyun Zhang, Kendra Lee, Casey F Pulliam, Brianna S Cagle, Jonathan A Doorn, Aloysius J Klingelhutz, Larry W Robertson, Hans-Joachim Lehmler
Author Information
  1. Amanda Bullert: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  2. Xueshu Li: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  3. Chunyun Zhang: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  4. Kendra Lee: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  5. Casey F Pulliam: Interdisciplinary Program in Human Toxicology, University of Iowa, Iowa City, IA 52242, USA.
  6. Brianna S Cagle: Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, IA 52242, USA.
  7. Jonathan A Doorn: Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52242, USA.
  8. Aloysius J Klingelhutz: Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
  9. Larry W Robertson: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  10. Hans-Joachim Lehmler: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.

Abstract

The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis identified PCB 52 in all tissues investigated. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry (Nt-LCMS), were primarily found in the serum and liver of rats exposed to 100 mg/kg BW. Metabolomic analysis revealed minor effects on L-cysteine, glycine, cytosine, sphingosine, thymine, linoleic acid, orotic acid, L-histidine, and erythrose serum levels. Thus, the metabolism of PCB 52 and its effects on the metabolome must be considered in toxicity studies.
Highlights: PCB 52 was present in adipose, brain, liver, and serum 3 weeks after PCB exposureLiver and serum contained hydroxylated, sulfated, and methylated PCB 52 metabolitesMetabolomics analysis revealed minor changes in endogenous serum metabolitesLevels of dopamine and its metabolites in the brain were not affected by PCB 52.

References

  1. Environ Sci Technol. 2020 Sep 15;54(18):11443-11452 [PMID: 32816464]
  2. Sci Total Environ. 2022 Oct 10;842:156490 [PMID: 35667425]
  3. Environ Toxicol Pharmacol. 2008 Mar;25(2):241-6 [PMID: 18452002]
  4. Toxicology. 2001 Feb 21;159(1-2):11-21 [PMID: 11250051]
  5. Toxicology. 2015 Dec 2;338:59-68 [PMID: 26463278]
  6. Environ Toxicol Chem. 2018 May;37(5):1409-1419 [PMID: 29334126]
  7. Environ Sci Pollut Res Int. 2014 Jan;21(2):998-1009 [PMID: 23852585]
  8. Environ Toxicol Chem. 2008 Feb;27(2):299-305 [PMID: 18348647]
  9. Bull Environ Contam Toxicol. 1979 Sep;23(1-2):36-43 [PMID: 115519]
  10. Toxicol Sci. 2012 Feb;125(2):496-508 [PMID: 22094459]
  11. J Pharm Sci. 1977 Apr;66(4):497-501 [PMID: 404418]
  12. Int J Hyg Environ Health. 2013 Nov;216(6):755-62 [PMID: 23571136]
  13. Environ Sci Technol. 2013;47(21):12184-92 [PMID: 24060104]
  14. Toxicol Appl Pharmacol. 2001 Sep 1;175(2):176-83 [PMID: 11543650]
  15. Int J Biochem. 1991;23(12):1427-37 [PMID: 1761152]
  16. Science. 1967 Sep 29;157(3796):1524-30 [PMID: 6038165]
  17. Neurotoxicology. 2021 Sep;86:59-68 [PMID: 34265337]
  18. Toxicology. 1994 Jan 26;86(1-2):71-87 [PMID: 8134924]
  19. Environ Pollut. 2020 Nov;266(Pt 1):115233 [PMID: 32712482]
  20. Environ Pollut. 2021 Jan 1;268(Pt A):115726 [PMID: 33032095]
  21. Environ Sci Technol. 2011 Oct 1;45(19):8298-305 [PMID: 21863805]
  22. Cell Rep. 2019 Sep 3;28(10):2608-2619.e6 [PMID: 31484072]
  23. Environ Sci Pollut Res Int. 2014 Oct;21(20):11951-72 [PMID: 24943885]
  24. Environ Sci Technol. 2016 Aug 2;50(15):8290-5 [PMID: 27379686]
  25. Environ Sci Technol. 2015 Jan 6;49(1):616-25 [PMID: 25420130]
  26. Biochem Biophys Res Commun. 1979 Nov 28;91(2):475-83 [PMID: 42397]
  27. Chem Res Toxicol. 2021 Apr 19;34(4):988-991 [PMID: 33734669]
  28. Toxicol Lett. 2017 Jul 5;276:100-107 [PMID: 28552772]
  29. Metabolomics. 2018 Mar 20;14(5):54 [PMID: 30830328]
  30. Environ Health Perspect. 1994 Aug;102(8):676-9 [PMID: 7895708]
  31. Pharmacol Ther. 2010 Feb;125(2):260-85 [PMID: 19931307]
  32. Environ Sci Technol. 2022 Feb 1;56(3):1780-1790 [PMID: 34994547]
  33. Environ Toxicol Chem. 2002 Nov;21(11):2264-9 [PMID: 12389902]
  34. Chem Res Toxicol. 2015 Sep 21;28(9):1774-83 [PMID: 26271003]
  35. Environ Sci Technol. 2012 Oct 16;46(20):11393-401 [PMID: 22974126]
  36. Environ Sci Technol. 2022 Jul 5;56(13):9515-9526 [PMID: 35658127]
  37. Nature. 1974 Dec 20;252(5485):698-9 [PMID: 4215979]
  38. Int J Hyg Environ Health. 2023 Jan;247:114056 [PMID: 36395656]
  39. Chem Res Toxicol. 2000 Aug;13(8):710-8 [PMID: 10956058]
  40. Environ Toxicol Pharmacol. 2018 Mar;58:196-201 [PMID: 29408762]
  41. IARC Monogr Eval Carcinog Risks Hum. 2016;107:9-500 [PMID: 29905442]
  42. Environ Sci Technol. 2015 Jan 20;49(2):1156-64 [PMID: 25510359]
  43. Chem Res Toxicol. 2021 Sep 20;34(9):1948-1952 [PMID: 34491731]
  44. Toxicol Sci. 2004 Jul;80(1):54-9 [PMID: 15056809]
  45. Chem Res Toxicol. 1996 Jan-Feb;9(1):158-64 [PMID: 8924585]
  46. Environ Health Perspect. 2010 Apr;118(4):479-84 [PMID: 20064788]
  47. Toxicol In Vitro. 2023 Jun;89:105568 [PMID: 36804509]
  48. Environ Sci Technol. 2020 Oct 6;54(19):12345-12357 [PMID: 32910851]
  49. Environ Health Perspect. 2010 Jun;118(6):796-802 [PMID: 20146964]
  50. Toxicol Sci. 2006 Aug;92(2):490-9 [PMID: 16702228]
  51. Chem Res Toxicol. 2008 Jul;21(7):1359-67 [PMID: 18549251]
  52. Chem Res Toxicol. 2020 Jun 15;33(6):1328-1338 [PMID: 31403789]
  53. Arch Toxicol. 2017 Feb;91(2):749-760 [PMID: 27318803]
  54. Chem Res Toxicol. 2006 Nov;19(11):1420-5 [PMID: 17112228]
  55. J Great Lakes Res. 2011 Jun;37(2):359-364 [PMID: 23538476]
  56. Toxicol Sci. 2017 Jul 1;158(1):101-115 [PMID: 28431184]
  57. Arch Environ Contam Toxicol. 2002 Jan;42(1):105-17 [PMID: 11706375]
  58. Environ Res. 2023 Mar 1;220:115148 [PMID: 36580985]
  59. J Chromatogr A. 2008 Dec 19;1214(1-2):37-46 [PMID: 19019378]
  60. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1993 May;105(1):95-106 [PMID: 8101795]
  61. J Agric Food Chem. 1975 Sep-Oct;23(5):851-3 [PMID: 1159182]
  62. J Public Health Policy. 2018 Nov;39(4):463-540 [PMID: 30401808]
  63. Crit Rev Toxicol. 2015 Mar;45(3):245-72 [PMID: 25629923]
  64. J Biochem Mol Toxicol. 2022 Oct;36(10):e23161 [PMID: 35822628]
  65. Int J Hyg Environ Health. 2019 Sep;222(8):1109-1114 [PMID: 31444116]
  66. Toxicol Appl Pharmacol. 2000 Jan 1;162(1):10-21 [PMID: 10631123]
  67. Environ Sci Technol. 2022 May 17;56(10):6537-6547 [PMID: 35500099]
  68. Environ Sci Technol. 2018 May 15;52(10):6000-6008 [PMID: 29659268]
  69. Chem Res Toxicol. 2019 Apr 15;32(4):727-736 [PMID: 30729780]
  70. Pharm Res. 2019 Dec 23;37(1):12 [PMID: 31873819]
  71. Environ Int. 2016 Feb;87:13-9 [PMID: 26638015]
  72. J Biol Chem. 1983 May 10;258(9):5967-76 [PMID: 6304102]
  73. Environ Sci Technol. 2019 Apr 2;53(7):3948-3958 [PMID: 30821444]
  74. Growth Dev Aging. 1996 Autumn-Winter;60(3-4):131-43 [PMID: 9007564]
  75. Int J Mol Sci. 2020 Feb 04;21(3): [PMID: 32033061]
  76. Environ Toxicol Pharmacol. 2021 Nov;88:103757 [PMID: 34688910]
  77. Drug Metab Dispos. 2009 May;37(5):1065-72 [PMID: 19196841]
  78. Drug Metab Dispos. 2016 Dec;44(12):1899-1909 [PMID: 27625140]
  79. Chemosphere. 2016 Mar;147:389-95 [PMID: 26774304]
  80. Toxicology. 2005 Mar 30;208(3):377-87 [PMID: 15695023]
  81. Environ Sci Pollut Res Int. 2014 May;21(10):6334-45 [PMID: 23636595]
  82. Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494 [PMID: 29762782]
  83. Toxicol Appl Pharmacol. 1990 Oct;106(1):136-44 [PMID: 2123577]
  84. Environ Toxicol Pharmacol. 2018 Sep;62:69-78 [PMID: 29986280]
  85. Chem Res Toxicol. 2014 Aug 18;27(8):1411-20 [PMID: 24988477]
  86. Environ Sci Technol. 2006 Aug 1;40(15):4633-8 [PMID: 16913117]
  87. Environ Sci Pollut Res Int. 2022 Jan;29(3):3463-3473 [PMID: 34386925]
  88. J Nutr Biochem. 1990 Jul;1(7):350-4 [PMID: 15539224]
  89. Toxicol Sci. 2019 Oct 1;171(2):406-420 [PMID: 31268529]
  90. Toxicol Appl Pharmacol. 2019 Aug 15;377:114620 [PMID: 31195005]
  91. Environ Sci Technol. 2020 Sep 15;54(18):11386-11395 [PMID: 32786554]
  92. Toxicol Sci. 2013 Dec;136(2):500-13 [PMID: 24014653]
  93. Environ Toxicol. 2014 Aug;29(8):876-83 [PMID: 22996836]
  94. Environ Sci Technol. 2010 Apr 15;44(8):2822-7 [PMID: 19957996]
  95. Environ Res. 2023 Apr 1;222:115354 [PMID: 36709868]
  96. Toxicol Sci. 2002 Aug;68(2):361-71 [PMID: 12151632]
  97. Neurotoxicol Teratol. 2020 May - Jun;79:106880 [PMID: 32259577]
  98. J Agric Food Chem. 2003 Sep 10;51(19):5607-11 [PMID: 12952408]
  99. Toxicology. 2018 Feb 1;394:93-101 [PMID: 29233657]
  100. Environ Sci Technol. 2015 Jul 07;49(13):8087-95 [PMID: 26046945]
  101. Environ Sci Technol. 2017 Jul 18;51(14):7853-7860 [PMID: 28656752]
  102. Eur J Epidemiol. 2021 Aug;36(8):861-872 [PMID: 34420151]
  103. Int J Hyg Environ Health. 2014 Sep;217(7):765-74 [PMID: 24951400]
  104. Environ Int. 2016 Sep;94:538-545 [PMID: 27352881]
  105. Toxicol Lett. 1997 Apr 28;91(2):99-104 [PMID: 9175845]
  106. Ann N Y Acad Sci. 1979 May 31;320:436-48 [PMID: 110197]
  107. Environ Sci Technol. 2018 May 1;52(9):5154-5160 [PMID: 29667399]
  108. Toxicol Ind Health. 2016 Nov;32(11):1825-1847 [PMID: 26056131]
  109. Environ Sci Technol. 2022 Sep 6;56(17):12460-12472 [PMID: 35994059]

Grants

  1. P30 ES005605/NIEHS NIH HHS
  2. R01 ES031098/NIEHS NIH HHS
  3. T32 CA078586/NCI NIH HHS
  4. P42 ES013661/NIEHS NIH HHS
  5. R01 ES014901/NIEHS NIH HHS

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