Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development

Regulatory Toxicology and Pharmacology

Volumn 58, Issue 1, 2010, Pages 79-99

  Goodman, Julie E ^a   Kerper, Laura E ^a   Boyce, Catherine Petito ^a   Prueitt, Robyn L ^a   Rhomberg, Lorenz R ^a  

^a GRADIENT   (United States)

Author keywords

Background exposure; Dioxin; Epidemiology; PCB; Thyroid; Thyroid stimulating hormone; Thyroid binding globulin; Thyroxine; Triiodothyroxine

Indexed keywords

DIOXIN; LIOTHYRONINE; POLYCHLORINATED BIPHENYL; POLYCHLORINATED DIBENZODIOXIN; POLYCHLORINATED DIBENZOFURAN; THYROGLOBULIN; THYROTROPIN; THYROXINE;

AGE; ARTICLE; CHILD DEVELOPMENT; CORRELATION ANALYSIS; DEVELOPMENTAL STAGE; ENVIRONMENTAL EXPOSURE; HUMAN; OUTCOMES RESEARCH; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RISK ASSESSMENT; THYROID FUNCTION; THYROID HORMONE BLOOD LEVEL; TOXICITY TESTING; UMBILICAL CORD BLOOD;

BENZOFURANS; BIOLOGICAL MARKERS; DIOXINS; ENVIRONMENTAL EXPOSURE; HUMANS; INFANT, NEWBORN; POLYCHLORINATED BIPHENYLS; THYROID GLAND; THYROID HORMONES; THYROTROPIN;

EID: 77955925172     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2010.04.008     Document Type: Article

References (54)

1. Alcock, R.E., Jones, K.C., 1996. Dioxins in the environment: a review of trend data. Environ. Sci. Technol. 30, 3133-3143. Available from: (accessed 23.01.09). http://pubs.acs.org/doi/pdf/10.1021/es960306z.
2. Alvarez-Pedrerol M., Ribas-Fito N., Torrent M., Carrizo D., Garcia-Esteban R., Grimalt J.O., Sunyer J. Thyroid disruption at birth due to prenatal exposure to beta-hexachlorocyclohexane. Environ. Int. 2008, 34(6):737-740.
3. Alvarez-Pedrerol M., Ribas-Fito N., Torrent M., Carrizo D., Grimalt J.O., Sunyer J. Effects of PCBs, p,p'-DDT, p,p'-DDE, HCB and beta-HCH on thyroid function in preschool children. Occup. Environ. Med. 2008, 65(7):452-457.
4. Baccarelli A., Giacomini S.M., Corbetta C., Landi M.T., Bonzini M., Consonni D., Grillo P., Patterson D.G., Pesatori A.C., Bertazzi P.A. Neonatal thyroid function in Seveso 25years after maternal exposure to dioxin. PLoS Med. 2008, 5(7):e161.
5. Brucker-Davis F. Effects of environmental synthetic chemicals on thyroid function. Thyroid 1998, 8(9):827-856.
6. Chevrier J., Eskenazi B., Bradman A., Fenster L., Barr D.B. Associations between prenatal exposure to polychlorinated biphenyls and neonatal thyroid-stimulating hormone levels in a Mexican-American population, Salinas Valley, California. Environ. Health Perspect. 2007, 115:1490-1496.
7. Chopra I.J., Sabatino L. Nature and sources of circulating thyroid hormones. Werner & Ingbar's the Thyroid: A Fundamental and Clinical Text 2000, 121-135. Lippincott Williams & Wilkins, Philadelphia. eighth ed. L.E. Braverman, R.D. Utiger (Eds.).
8. Darnerud P.O., Lignell S., Glynn A., Aune M., Tornkvist A., Stridsberg M. POP levels in breast milk and maternal serum and thyroid hormone levels in mother-child pairs from Uppsala, Sweden. Environ. Int. 2009, 10.1016/j.envint.2009.11.001.
9. Giacomini S.M., Hou L., Bertazzi P.A., Baccarelli A. Dioxin effects on neonatal and infant thyroid functions: routes of perinatal exposure, mechanisms of action and evidence from epidemiology studies. Int. Arch. Occup. Environ. Health 2006, 79:396-404.
10. Gray G.M., Baskin S.I., Charnley G., Cohen J.T., Gold L.S., Kerkvliet N.I., Koenig H.M., Lewis S.C., McClain M.R., Rhomberg L.R., Snyder J.W., Weekley L.B. The Annapolis accords on the use of toxicology in risk assessment and decision-making: an Annapolis Center workshop report. Toxicol. Methods 2001, 11(3):225-231.
11. Green W.L. The thyroid gland. Textbook of Physiology 1989, vol. 2:1480-1500. W.B. Saunders Co., Philadelphia, PA. 21st ed.
12. Greene J.F., Hays S., Paustenbach D. Basis for a proposed reference dose (RfD) for dioxin of 1-10pg/kg-day: a weight of evidence evaluation of the human and animal studies. J. Toxicol. Environ. Health B Crit. Rev. 2003, 6(2):115-159.
13. Herbstman J., Sjodin A., Apelberg B.J., Witter F.R., Halden R.U., Patterson D.G., Panny S.R., Needham L.L., Goldman L.R. Birth delivery mode modifies the association between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels. Environ. Health Perspect. 2008, 116:1376-1382.
14. Hübner U., Englisch C., Werkmann H., Butz H., Georg T., Zabransky S., Herrmann W. Continuous age-dependent reference ranges for thyroid hormones in neonates, infants, children and adolescents established using the ADVIA® Centaur™ analyzer. Clin. Chem. Lab. Med. 2002, 40(10):1040-1047.
15. Ilsen A., Briet J.M., Kopper J.G., Pluim H.J., Oosting J. Signs of enhanced neuromotor maturation in children due to perinatal load with background levels of dioxins. Follow-up until age 2 years and 7 months. Chemosphere 1996, 33(7):1317-1326.
16. Kaminski N.E., Faubert Kaplan B.L., Holsapple M.P. Toxic responses of the immune system. Casarett & Doull's Toxicology: The Basic Science of Poisons 2008, 485-556. McGraw Hill. seventh ed. C.D. Klaassen (Ed.).
17. Kimbrough R.D., Krouskas C.A. Polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans and birth weight and immune and thyroid function in children. Regul. Toxicol. Pharmacol. 2001, 34:42-52.
18. Klein R.Z., Mitchell M.L. Hypothyroidism in infants and children. Werner & Ingbar's the Thyroid: A Fundamental and Clinical Text 2000, 973-988. Lippincott Williams & Wilkins, Philadelphia. eighth ed. L.E. Braverman, R.D. Utiger (Eds.).
19. Koopman-Esseboom C., Morse D.C., Weisglas-Kuperus N., Lutkeschipholt I.J., Van Der Paauw C.G., Tuinstra L.G.M.T., Brouwer A., Sauer P.J.J. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr. Res. 1994, 36:468-473.
20. LaKind J.S., Berlin C.M., Sjodin A., Turner W., Wang R.Y., Needham L.L., Paul I.M., Stokes J.L., Naiman D.Q., Patterson D.G. Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning. Environ. Health Perspect. 2009, 117(10):1625-1631.
21. Lans M.C., Spiertz C., Brouwer A., Koeman J.H. Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs. Eur. J. Pharmacol. 1994, 270(2-3):129-136.
22. Larsen P.R., Davies T.F. Hypothyroidism. Williams Textbook of Endocrinology 2002, 423-455. WB Saunders, Philadelphia. 10th ed. P.R. Larsen (Ed.).
23. Lopez-Espinosa M.A., Vizcaino E., Murcia M., Fuentes V., Garcia A.M., Rebagliato M., Grimalt J.O., Ballester F. Prenatal exposure to organochlorine compounds and neonatal thyroid stimulating hormone levels. J. Exp. Sci. Environ. Epidemiol. 2009, 10.1038/jes.2009.47.
24. Maervoet J., Vermeir G., Covaci A., Van Larebeke N., Koppen G., Schoeters G., Nelen V., Baeyens W., Schepens P., Viaene M.K. Association of thyroid hormone concentrations with levels of organochlorine compounds in cord blood of neonates. Environ. Health Perspect. 2007, 115(12):1780-1786.
25. Matsuura N., Uchiyama T., Tada H., Nakamura Y., Kondo N., Morita M., Fukushi M. Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan - the second report from research on environmental health. Chemosphere 2001, 45:1167-1171.
26. Morse D.C., Groen D., Veerman M., van Amerongen C.J., Koëter H.B., Smits van Prooije A.E., Visser T.J., Koeman J.H., Brouwer A. Interference of polychlorinated biphenyls in hepatic and brain thyroid hormone metabolism in fetal and neonatal rats. Toxicol. Appl. Pharmacol. 1993, 122(1):27-33.
27. Nagayama J., Iida T., Hirakawa H., Matsueda T., Okamura K., Hasegawa M., Sato K., Ma H.Y., Yanagawa T., Igarashi H., Fukushige J., Watanabe T. Effects of lactational exposure to chlorinated dioxins and related chemicals on thyroid functions in Japanese babies. Organohalogen Compd. 1997, 33:446-450.
28. Nagayama J., Kohno H., Kunisue T., Kataoka K., Shimomura H., Tanabe S., Konishi S. Concentrations of organochlorine pollutants in mothers who gave birth to neonates with congenital hyperthyroidism. Chemosphere 2007, 68(5):972-976.
29. Nagayama J., Okamura K., Iida T., Hirakawa H., Matsueda T., Tsujid H., Hasegawa M., Sato K., Maf U.-Y., Yanagawa T., Igarashi H., Fukushige J., Watanabe T. Postnatal exposure to chlorinated dioxins and related chemicals on thyroid hormone status in Japanese breast-fed infants. Chemosphere 1998, 37(9-12):1789-1793.
30. National Research Council (NRC), 2006. Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment. Committee on EPA's Exposure and Human Health Reassessment of TCDD and Related Compounds. National Academies Press, Washington, DC, 199p.
31. Ness D.K., Schantz S.L., Moshtaghian J., Hansen L.G. Effects of perinatal exposure to specific PCB congeners on thyroid hormone concentrations and thyroid histology in the rat. Toxicol. Lett. 1993, 68(3):311-323.
32. Nishimura N., Yonemoto J., Miyabara Y., Sato M., Tohyama C. Rat thyroid hyperplasia induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Endocrinology 2003, 144:2075-2083.
33. Osius N., Karmaus W., Kruse H., Witten J. Exposure to polychlorinated biphenyls and levels of thyroid hormones in children. Environ. Health Perspect. 1999, 107:843-849.
34. Otake T., Yoshinaga J., Enomoto T., Matsuda M., Wakimoto T., Ikegami M., Suzuki E., Naruse H., Yamanaka T., Shibuya N., Yasumizu T., Kato N. Thyroid hormone status of newborns in relation to in utero exposure to PCBs and hydroxylated PCB metabolites. Environ. Res. 2007, 105(2):240-246.
35. Pluim H.J., de Vijlder J.J.M., Olie K., Kok J.H., Vulsma T., van Tijn D.A., van der Slikke J.W., Koppe J.G. Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations. Environ. Health Perspect. 1993, 101:504-508.
36. Ribas-Fito N., Sala M., Cardo E., Mazon C., De Muga M.E., Verdu A., Marco E., Grimalt J.O., Sunyer J. Organochlorine compounds and concentrations of thyroid stimulating hormone in newborns. Occup. Environ. Med. 2003, 60(4):301-303.
37. Rice R.H., Mauro T.M. Toxic responses of the skin. Casarett and Doull's Toxicology: The Basic Science of Poisons 2008, 741-760. McGraw-Hill Companies, Inc. seventh ed. C.D. Klaassen (Ed.).
38. Robbins J. Thyroid hormone transport proteins and the physiology of hormone binding. Werner & Ingbar's the Thyroid: A Fundamental and Clinical Text 2000, 105-120. Lippincott Williams & Wilkins, Philadelphia. eighth ed. L.E. Braverman, R.D. Utiger (Eds.).
39. Sandau C.D., Ayotte P., Dewailly E., Duffe J., Norstrom R.J. Pentachlorophenol and hydroxylated polychlorinated biphenyl metabolites in umbilical cord plasma of neonates from coastal populations in Quebec. Environ. Health Perspect. 2002, 110(4):411-417.
40. Sauer P.J., Huisman M., Koopman-Esseboom C., Morse D.C., Smits-van Prooije A.E., van de Berg K.J., Tuinstra L.G.M.T.H., van der Paauw C.G., Boersma E.R., Weisglas-Kuperus N., Lammers J.H.C.M., Kulig B.M., Brouwer A. Effects of polychlorinated biphenyls (PCBs) and dioxins on growth and development. Hum. Exp. Toxicol. 1994, 13:900-906.
41. Schecter A., Cramer P., Boggess K., Stanley J., Papke O., Olson J., Silver A., Schmitz M. Intake of dioxins and related compounds from food in the U.S. population. J. Toxicol. Environ. Health 2001, 63:1-18.
42. Seo B.W., Li M.H., Hansen L.G., Moore R.W., Peterson R.E., Schantz S.L. Effects of gestational and lactational exposure to coplanar polychlorinated biphenyl (PCB) congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone concentrations in weanling rats. Toxicol. Lett. 1995, 78(3):253-262.
43. Startin J.R., Rose M.D. Dioxins and dioxinlike PCBs in food. Dioxins and Health 2003, 89-136. John Wiley & Sons, Inc., Hoboken, New Jersey. second ed. A. Schecter, T.A. Gasiewicz (Eds.).
44. Takser L., Mergier D., Baldwin M., de Grosbois S., Smargiassi A., Lafond J. Thyroid hormones in pregnancy in relation to environmental exposure to organochlorine compounds and mercury. Environ. Health Perspect. 2005, 113:1039-1045.
45. ten Tusscher G.W., Guchelaar H.J., Koch J., Ilsen A., Vulsma T., Westra M., van der Slikke J.W., Olie K., Koppe J.G. Perinatal dioxin exposure, cytochrome P-450 activity, liver functions and thyroid hormones at follow-up after 7-12years. Chemosphere 2008, 70(10):1865-1872.
46. US EPA, 2003a. Exposure and Human Health Risk Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds. Part II: Health Assessment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds (NAS Review Draft) [Dioxin Reassessment]. National Center for Environmental Assessment (NCEA), Washington, DC, December 2003.
47. US EPA, 2003b. Exposure and Human Health Risk Reassessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds. Part III: Integrated Summary and Risk Characterization for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds (NAS Review Draft) [Dioxin Reassessment]. National Center for Environmental Assessment (NCEA), Washington, DC, December 2003.
48. US EPA, 2004. Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds, National Academy of Sciences (NAS) Review Draft. EPA/600/P-00/001Cb. Available from: http://www.epa.gov/ncea/pdfs/dioxin/nas-review.
49. US EPA, 2008. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Dose-Response Studies: Preliminary Literature Search Results and Request for Additional Studies. EPA/600/R-08/119. Available from: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=199923.
50. US EPA, 2009. Recommended Toxicity Equivalency Factors (TEFs) for Human Health Risk Assessments of Dioxin and Dioxin-like Compounds, External Review Draft. Prepared by the Risk Assessment Forum. Available from: (accessed 01.09.09). http://www.epa.gov/OSA/raf/files/hhtef_draft_090109.pdf.
51. Van den Berg M., Birnbaum L.S., Denison M., De Vito M., Farland W., Feeley M., Fiedler H., Hakansson H., Hanberg A., Haws L., Rose M., Safe S., Schrenk D., Tohyama C., Tritscher A., Tuomisto J., Tysklind M., Walker N., Peterson R.E. The 2005 World Health Organization re-evaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol. Sci. 2006, 93:223-241.
52. Van den Berg M., Birnbaum L., Bosveld A.T., Brunstrom B., Cook P., Feeley M., Giesy J.P., Hanberg A., Hasegawa R., Kennedy S.W., Kubiak T., Larsen J.C., van Leeuwen F.X., Liem A.K., Nolt C., Peterson R.E., Poellinger L., Safe S., Schrenk D., Tillitt D., Tysklind M., Younes M., Waern F., Zacharewski T. Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environ. Health Perspect. 1998, 106(12):775-792.
53. Wang S.L., Su P.H., Jong S.B., Guo Y.L., Chou W.L., Papke O. In utero exposure to dioxins and polychlorinated biphenyls and its relations to thyroid function and growth hormone in newborns. Environ. Health Perspect. 2005, 113(11):1645-1650.
54. Wilhelm M., Wittsiepe J., Lemm F., Ranft U., Kramer U., Furst P., Roseler S.C., Greshake M., Imohl M., Eberwein G., Rauchfuss K., Kraft M., Winneke G. The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24months. Mutat. Res. 2008, 659(1-2):83-92.