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Event: 959

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, Free serum thyroxine (T4)

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increased, Free serum thyroxine (T4)
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Biological Context

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Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
blood

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
thyroxine increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Transthyretin interference KeyEvent Kristie Sullivan (send email) Under Development: Contributions and Comments Welcome Under Development
TH displacement from serum TTR leading to altered amphibian metamorphosis KeyEvent Jonathan Haselman (send email) Under development: Not open for comment. Do not cite
TH displacement from serum TBG leading to altered amphibian metamorphosis KeyEvent Jonathan Haselman (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
African clawed frog Xenopus laevis NCBI
rat Rattus norvegicus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
During development and at adulthood High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

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Following displacement of T4 from its binding site on TTR by some competitive ligand (like EMD 21388, etc.), the T4 joins the small pool of free hormone found in serum. This increases the amount of free T4 and has been demonstrated in animal models following administration of a xenobiotic competitive ligand.

Kohrle et al (1989) administered 2 umol of EMD 21388 per 100g BW in a single ip injection to euthyroid adult male Sprague-Dawley rats. Rat serum was analyzed for T3 and T4 content via species-adapted RIA and percent free TH was determined via equilibrium dialysis. Serum T4 decreased significantly following 1 hr or administration and remained low for several hours, while % free T4 increased significantly at 1 hr and remained elevated. {insert Figure 5} Previously, both in vitro and in vivo electrophoretic data showed complete inhibition of radiolabeled T4 binding to TTR. Administration of EMD 21388 to rats did not impact T3 concentrations or deiodinase activity.

Lueprasitsakul et al (1990) also administered EMD 21388 to euthyroid adult male Sprague-Dawley rats as a single 2 umol ip injection with additional time points as well as a single injection of 0.3 umol. In addition, one treatment group were exposed to varying doses from 0.2 to 2 umol EDM21388 per 100 g BW. Significant decreases in radiolabeled T4 bound to TTR were found within 3 minutes, reaching a maximum at 10 minutes. A simultaneous increase in % free T4 was noted at 3 minutes and reached a maximum at 10 minutes. {insert Figure 3} These effects were observed for both the high dose of 2 umol and the low dose of 0.3 umol; however, it was noted that % T4 bound to TTR recovered to almost control levels after 3 hours at the low dose. The authors concluded that EMD 21388 administration increased both the free T4 concentration as well as the albumin-bound T4 (which is available in serum and can play a greater role in transport when needed).

Mendel et al (1992) performed additional kinetic studies with radiolabeled T4 and albumin using Sprague-Dawley rats receiving a single ip injection of 2 umol EMD 21388. To overcome the dilution effect found with equilibrium dialysis, ultrafiltration of undiluted serum was employed to measure the % free T4. The % free T4 increased significantly at 20 minutes and the compensatory response of albumin appears to have been saturated after 20 minutes, as shown by the plasma disappearance curve for radiolabeled albumin. {insert Figures 2 and 3} The authors concluded that these data did not confirm TTR is a major carrier of T4 from plasma to liver and other tissues; however, these data also did not distinguish between whether transfer in vivo could be via albumin or from the free pool of T4 in serum.

Chanoine et al (1992) administered low (0.3 umol) and high dose (2 umol) EMD 21388 to Sprague-Dawley rats via single ip injection and a second treatment group had radiolabeled T4 injected 15 minutes following the EMD 21388 adminisatration. Both doses produced a similar significant increase to free T4 in serum within 15 minuteas of administration. {insert Figure 1} Binding of T4 to albumin in serum increased an order of magnitude in both high and low dose treatments. The low dose had no effect on the %T4 bound to TTR in the choroid plexus or the cerebrospinal fluid; however, the high dose did significantly decrease this. {insert Figure 2}

Pedraza et al (1996)

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

Total T4 is most often measured using a serum-based diagnostic kit; however, free T4 is considered a more reliable measure of thyroid dysfunction and the only direct measurements for unbound thyroid hormone are equilibrium dialysis and ultrafiltration (Zoeller et al 2007). Large volumes of serum must be used to capture the very low concentrations of free THs and this requires pooling in non-adult animals.

Total T4 is most often measured using human serum based diagnostic kits, but free T4 (and T3) is only directly measured through equilibrium dialysis and ultrafiltration (Midgley 2001). Large volumes of serum must be used due to the very low concentrations of free T4 normally found (0.1% of total T4), which requires pooling of samples taken from fetus or pup. Some researchers have tried to “micronize” this process through combining RIA to measure total TH and dialysis to estimate the free fraction (Zoeller et al 2007).  Extracted materials can also be quantified by HPLC. The reference range for free T4 is 9.8 to 18.8 pM/L (Dirinck et al 2016).

T3 is found in similar plasma concentrations to T4 (i.e. 5-10 pM) with < 0.4% being in the unbound state. Measuring free serum T3 is labor intensive and requires equipment not available in many clinical reference laboratories and thus ultrafiltration is often used (Abdalla and Bianco 2014). Immunoassays and MS/MS are also used.

Measuring displacement of T4 from serum transport proteins is done mainly via one of three in vitro methods: radioligand binding assay, plasmon resonance-based biosensor, or fluorescence displacement.

Radioligand binding assays, using [125I]-T4 as a label, were developed to demonstrate affinity for xenobiotics to human or rat TTR and TBG (Brouwer and van den Berg 1986, Lans et al 1994).  The most commonly used method was first published by Somack et al 1982 and adapted by Hamers et al 2006, Lans et al 1993 and Ucan-Marin et al 2010. Similar assays have been developed using [125I]-T3 as a label for affinity to chicken and bullfrog TTR (Yamauchi et al 2003).  Radioligand methods suffer from having to use heavily regulated isotopes and lower throughput to provide free T4 measurements (due to the extra wash/separation procedure needed). The most well-known protocol uses TTR purified from human serum (which may not be as stable as recombinant) and performed in a pure aqueous solution, which may not be as stable for lipophilic compounds (Chauhan et al 2000 is an example using PCBs).

Purkey et al 2001 published a binding assay using polyclonal TTR antibodies covalently bound to sepharose resin which is then mixed with plasma pre-treated with compound of interest, washed and analyzed via HPLC.

Marchesini et al 2006 reported on the development of two surface plasmon resonance(SPR)-based biosensor assays using recombinant TTR and TBG, validated with known thyroid disruptors and structurally related compounds including halogenated phenols, polychlorinated biphenyls, bisphenols and a hydroxylated PCB metabolite (4-OH-CB 14).  TH is covalently bound to a gold-layered chip and a mixture of the compound of interest and transport protein are injected in a flow cell passing over the bound TH.  The authors found that these biosensor methods were more sensitive (IC50 of 8.6 ± 0.7 nM for rTTR), easier to perform and more rapid that radioligand binding assays and immunoprecipitation-HPLC.

Marchesini et al 2008 applied their biosensor-based screen to 62 chemicals of public health concern and found that hydroxylated metabolites of PCBs (particularly para-hydroxylated ones) and PBDEs (BDEs 47, 49 and 99) displayed the most potent binding to TBG and TTR, confirming many other previous studies.  The authors conclude their optimized assays are suitable for high-throughput screening for potential thyroid disruption.

Cao et al 2010, Cao et al 2011 and Ren and Guo 2012 developed the FLU-TTR, based on a protein-binding fluorescent probe (ANSA, or 8-anilo-1-naphthalenesulfonic acid ammonium salt) that becomes highly fluorescent after binding to T4. When the compound of interest is introduced and displaces the ANSA-thyroxine probe, this fluorescence is reduced.  This allows generation of binding constant (K) data as opposed to past efforts that generated IC50 values.  Cao et al 2011 developed a fluorescent microtiter method for pTTR and TBG tested with bisphenol A.

Montano et al 2012 developed a competitive T4-TTR fluorescence displacement assay in a 96-well format, modified from the original method (Nilsson and Petersen 1975) and using a new selective method to extract hydroxylated metabolites while reducing fatty acid interference (modified from Hovander et al 2000).

Aqai et al 2012 described a rapid and isotope-free (13C6-T4) screening of thyroid transport protein ligands, using a competitive binding assay for rTTR using fast ultrahigh performance LC-electrospray ionization triple-quadrupole MS. The method involves the use of immunomagnetic beads followed by screening with flow cytometry and UPLC-MS. The high-throughput screening mode is capable of detecting T4 in water at the part-per-trillion level and in the part-per-billion level in urine.

Relevant Phase II enzymes that are responsible for TH metabolism include UGT1A1, UGT1A6 and SULT2A1 while relevant cellular import/export transport proteins include MCT8, OATP1A4 and MRP2. All contribute towards systemic clearance of TH and conjugates from serum whether increasing biliary excretion or moving TH into tissues and across the placenta and BBB.  Enzyme induction can only be measured via in vitro cell-based assays and since these enzymes are all controlled by specific nuclear receptors, assays targeting these receptors might act as surrogate measurement (Murk et al 2013). Several methods measuring expression of UGT or SULT mRNA have been published; however, there have been limited efforts to develop higher-throughput methods.  The EPA ToxCast Phase I efforts used quantitative nuclease protection assays (qNPA) to screen several hundred chemicals for UGT1A1 and SULT2A1 (Rotroff et al 2010, Sinz et al 2006).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Data in humans focusing on the thyroid disruption potential of hydroxylated PCBs and PBDEs is scarce, the data are conflicting and suffer from differing analytical and reporting methods. 

Hagmar et al 2001a and 2001b examined 4-OH-CB107 and 4-OH-CB187 in adult females and male fishermen from the Baltic Sea and found no associations. Similarly, Bloom et al 2009 found no associations between PFOS and TH in a small study of New York anglers.

Athanasiadou et al 2008 assessed PBDEs in pooled serum samples from 11-15 year old children living near an urban municipal waste site as well as mothers who consume fish from a rural location in Nicaragua.  BDE-47 was the most abundant congener found in samples, followed by BDEs 99, 100 and 153. This study was the first to confirm that hydroxylated metabolites (OH-PBDEs) accumulate in human serum, identifying 19 OH-PBDEs – at least six (6) of which were also found and retained in rat serum following exposure to an artificial PBDE mixture (Malmberg et al 2005).  The dominant congeners were 4-OH-BDE17 and 4’-OH-BDE-49.  These data support the concept that residential exposure to PBDEs is strongly influenced by inhalation and ingestion of house dust rather than consumption of contaminated food.

Dalliare et al 2009 looked at the relationship between TH status and exposure to PCB-153, pentachlorophenol, hexachlorobenzene and hydroxylated PCBs in pregnant Inuit women and their infants. PCB-153 was the most predominant congener found to be elevated most in pregnant women, followed by infant and cord plasma levels.  OH-PCB results were a sum of 11 major congeners and found to be higher in pregnant women than cord blood, but highly intercorrelated.  Overall, the results suggest that the compounds measured in serum were not significant predictors of TH or TSH concentrations in this population.  The strongest results were found for PCP, which was negatively associated with free T4 in neonate cord blood, suggesting PCP reduces the transfer of T4 across the placenta.

Dallaire et al 2009b examined the relationship between TH status and TBG and exposure to 41 different contaminants, including PCBs and metabolites, PBDEs, PFOS, organochlorine pesticides and dioxin-like compounds, in over 500 Inuit adults. Negative associations were reported between rT3 and 14 PCBs, 7 hydroxylated metabolites, methylsulfonyl metabolites and 2 pesticides.  Negative associations were also reported between free T4 and hexachorobenzene as TBG concentrations were inversely related to 8 PCBs, 5 hydroxylated metabolites and three pesticides. This was the first large study to examine the effect of PFOS on TH homeostasis in exposed human adults, observing a significant negative associations with TSH, total T3 and TBG while observing a positive association with free T4.

Chevrier et al 2010 measured concentrations of 10 PBDE congeners and TH in 270 pregnant Californian (CHAMACOS cohort) women during the 27th week of gestation. This study reported significant inverse associations between TSH and serum concentrations of BDEs 28, 47, 99, 100 and 153 but did not observe an association between PBDEs and free T4.

Eskenazi et al 2013 measured PBDEs in maternal prenatal and child serum samples and examined the association between blood concentration and attention, motor functioning and cognition at ages 5 and 7 in an ongoing large California cohort (CHAMACOS).  They observed weak correlations between cognition, motor function and attention and PBDE concentration in maternal prenatal and child blood at age 7 and the authors claim it largely supporting previous findings in smaller cohorts exposed to both PDBEs and PCBs.

Eguchi et al 2015 measured PCBS, OH-PCBs, PBDEs, methoxylated PBDEs, OH-PBDEs and bromophenols and TH in the serum of Vietnamese cohort composed of human donors from an e-waste recycling site and a rural site.  In general, PCBs, OH-PCBs, PBDEs and bromophenols were higher in sera from the recycling site; however, the concentrations of methoxylated PBDEs were higher at the rural site.  Positive associations between PCBs and OH-PCBs concentrations and total and free T4 and T3, as well as a negative association with TSH, among females.

Dirinck et al 2016 examined the relationship between PCBs (n=29) and serum hydroxylated PCBs (n=18) and clinically available markers of thyroid function (TSH, free T4) in 180 subjects recruited upon visitation to the Antwerp University Hospital Department of Endocrinology from 2009 to 2012. The combined regression model for both PCBs and hydroxylates identified PCBs 95 and 99 and 3-OH-CB180 as significant predictors of free T4 , while the model run for just serum hydroxylate identified 3-OH-CB118 and 3-OH-CB180 as major predictors of free T4.  The former is a product of metabolizing PCBs 107, 118 and 126 while the latter comes from PCBs 172 and 180.

References

List of the literature that was cited for this KE description. More help

Abdalla, S.M. and A.C. Bianco. (2014) Defending plasma T3 is a biological priority.  Clin. Endocrinol. (Oxf)  81(5): 633-641.

Alshehri, B., D’Souza, D. G., Lee, J. Y., Petratos, S., & Richardson, S. J. (2015). The Diversity of Mechanisms Influenced by Transthyretin in Neurobiology: Development, Disease and Endocrine Disruption. Journal of Neuroendocrinology, 27(5), 303–323. http://doi.org/10.1111/jne.12271

Andrea, T.A., R.R. Cavalieri, I.D. Goldfine and E.C. Jorgensen (1980) Binding of thyroid hormones and analogues to the human plasma protein prealbumin. Biochemistry  19(1): 55-63.

Aqai, P., C. Fryganas, M. Mizuguchi, W. Haasnoot and M.W. Nielen. (2012) Triple bioaffinity mass spectrometry concept for thyroid transporter ligands.  Anal. Chem.  84(15): 6488-6493.

Athanasiadou, M., S.N. Cuadra, G. Marsh, A> Bergman, and K. Jakobsson. (2008) Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua.  Environ. Health Perspect. 116(3): 400-408.

Barter, R.A. and C.D. Klaassen. (1994) Reduction of thyroid hormone levels and alteration of thyroid function by four representative UDP-glucuronosyltransferase inducers in rats.  Toxicol. Appl. Pharmacol.  128(1): 9-17.

Blake, C.C., J.M. Burridge and S.J. Oatley. (1978) X-ray analysis of thyroid hormone binding to prealbumin. Biochem Soc. Trans. 6(6): 1114-1118.

Bloom, M.S., J.E. Vena, J.R. Olson and P.J. Kostyniak.  (2009)  Assessment of polychlorinated biphenyl congeners, thyroid stimulating hormone, and free thyroxine among New York state anglers.  Int. J. Hyg. Environ. Health  212(6): 599-611.

Branchi, I., E. Alleva and L.G. Costa.  (2002)  Effects of perinatal exposure to a polybrominated diphenyl ether (PBDE 99) on mouse neurobehavioural development.  Neurotoxicology  23(3): 375-384.

Brouwer, a, & van den Berg, K. J. (1986). Binding of a metabolite of 3,4,3’,4'-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin. Toxicology and Applied Pharmacology, 85(3), 301–312.

Calvo, R.M., E. Jauniaux, B. Gulbis, M. Asuncion, C. Gervy, B. Contempre and G. Morreale de Escobar.  (2002)  Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development.  J. Clin. Endocrinol. Metab.  87(4); 1768-1777.

Cao, J., L.H. Guo, B. Wan and Y. Wei. (2011) In vitro fluorescence displacement investigation of thyroxine transport disruption by bisphenol A.  J. Environ Sci, (China)  23(2): 315-321.

Cao, J., Y. Lin, L.H. Guo, A.Q. Zhang, Y. Wei and Y. Yang. (2010) Structure-based investigation on the binding interaction of hydroxylated polybrominated diphenyl ethers with thyroxine transport proteins.  Toxicology  277(1-3): 20-28.

Chan, S.Y., J.A. Franklyn, H.N. Pemberton, J.N. Bulmer, T.J. Visser, C.J. McCabe and M.D. Kilby.  (2006)  Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction.  J. Endocrinol.  189(3): 465-471.

Chan, S., S. Kachilele, C.J. McCabe, L.A. Tannahill, K. Boelaert, N.J. Gittoes, T.J. Visser, J.A. Franklyn and M.D. Kilby.  (2002)  Early expression of thyroid hormone deiodinases and receptors in human fetal cerebral cortex.  Brain Res. Dev. Brain Res.  138(2): 109-116.

Chang, S.C., J.R. Thibodeaux, M.L. Eastvold, D.J. Ehresman, J.A. Bjork, J.W. Froehlich, C. Lau, R.J. Singh, K.B. Wallace and J.L. Butenhoff. (2008) Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS).  Toxicology  243(3): 330-339.

Chanoine, J.-P., Alex, S., Fang, S. L., Stone, S., Leonard, J. L., Kohrle, J., & Braverman, L. E. (1992). Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid and the brain. Endocrinology, 130(2), 933–938.

Chauhan, K. R., Kodavanti, P. R. S., & McKinney, J. D. (2000). Assessing the Role of ortho-Substitution on Polychlorinated Biphenyl Binding to Transthyretin, a Thyroxine Transport Protein. Toxicology and Applied Pharmacology, 162(1), 10–21. http://doi.org/10.1006/taap.1999.8826

Cheek, A.O., K. Kow, J. Chen and J.A. McLachlan. (1999) Potential mechanisms of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin.  Environ. Health Perspect.  107(4): 273-278.

Chevrier, J., K.G. Harley, A. Bradman, M. Gharbi, A. Sjodin and B. Eskenazi.  (2010)  Polybrominated diphenyl ether (PBDE) flame retardants and thyroid hormone during pregnancy.  Environ. Health Perspect.  118(10) : 1444-1449.

Chopra, I.J., P. Taing and L. Mikus. (1996) Direct determination of free triiodothyronine (T3) in undiluted serum by equilibrium dialysis/radioimmunoassay (RIA).  Thyroid  6(4): 255-259.

Costa, L.G., R. de Laat, S. Tagliaferri and C. Pellacani.  (2014)  A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity.  230(2): 282-294.

Dallaire, R., G. Muckle, E. Dewailly, S.W. Jacobson, J.L. Jacobson, T.M. Sandanger, C.D. Sandau and P. Ayotte. (2009a)  Thyroid hormone levels of pregnant inuit women and their infants exposed to environmental contaminants.  Environ. Health Perspect.  117(6): 1014-1020.

Dallaire, R., E. Dewailly, D. Pereg, S. Dery and P. Ayotte.  (2009b)  Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults.  Environ. Health Perspect.  117(9): 1380-1386.

Darnerud, P.O., D. Morse, E. Klasson-Wehler and A Brouwer.  (1996)  Binding of a 3,3', 4,4'-tetrachlorobiphenyl (CB-77) metabolite to fetal transthyretin and effects on fetal thyroid hormone levels in mice.  Toxicology  106(1-3): 105-114.

De Escobar, G.M., M.J. Obregon and F.E. del Rey.  (2004)  Maternal thyroid hormones early in pregnancy and fetal brain development.  Best Pract. Res. Clin. Endocrinol. Metab.  18(2): 225-248.

Dirinck, E., A.C. Dirtu, G. Malarvanna, A. Covaci, P.G. Jorens and L.F. Van Gall. (2016) A Preliminary Link between Hydroxylated Metabolites of Polychlorinated Biphenyls and Free Thyroxin in Humans.  Int. J. Environ. Res. Public Health  13(4): 421.

Eguchi, A., K. Nomiyama, N. Minh Tue, P.T. Trang, P. Hung Viet, S. Takahashi and S. Tanabe.  (2015)  Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels.  Environ. Res.  137: 440-449.

Emerson, C.H., J.H. Cohen III, R.A Yung, S. Alex and S.L. Fang. (1990) Gender-related differences of serum thyroxine-binding proteins in the rat. Acta Endocrinol. (Copenh)  123(1): 72-78.

Erratico, C.A., A. Steitz and S.M. Bandiera. (2013) Biotransformation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) by human liver microsomes: identification of cytochrome P450 2B6 as the major enzyme involved.  Chem. Res. Toxicol.  26(5): 721-731.

Erratico, C.A., S.C. Moffatt and S.M. Bandiera. (2011) Comparative oxidative metabolism of BDE-47 and BDE-99 by rat hepatic microsomes.  Toxicol. Sci.  123(1): 37-47.

Eskenazi, B., J. Chevrier, S.A. Rauch, K. Kogul, K.G. Harley, C. Johnson, C. Trujillo, A. Sjodin and A. Bradman.  (2013)  In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study.  121(2) : 257-262.

Feo, M.L., M.S. Gross, B.P. McGarrigle, E. Eljarrat, D. Barcelo, D.S. Aga and J.R. Olson. (2013) Biotransformation of BDE-47 to potentially toxic metabolites is predominantly mediated by human CYP2B6.  Environ. Health Persepct.  121(4): 440-446.

Ferguson, R.N., H. Edelhoch, H.A. Saroff, J. Robbins and H.J. Cahnmann (1975) Negative cooperativity in the binding of thyroxine to human serum prealbumin. Preparation of tritium-labeled 8-anilino-1-naphthalenesulfonic acid.  Biochemistry  14(2): 282-289.

Friesema EC, Jansen J, Jachtenberg JW, Visser WE, Kester MH, Visser TJ 2008 Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Molecular endocrinology (Baltimore, Md 22:1357-1369

Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH 2006 Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Molecular endocrinology (Baltimore, Md 20:2761-2772

Friesma, E.C., J. Jansen and T.J. Visser. (2005) Thyroid hormone transporters.  Biochem. Soc. Trans.  33(part 1): 228-232.

Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ 2003 Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 278:40128-40135

Grimm, F. a., Lehmler, H. J., He, X., Robertson, L. W., & Duffel, M. W. (2013). Sulfated metabolites of polychlorinated biphenyls are high-affinity ligands for the thyroid hormone transport protein transthyretin. Environmental Health Perspectives, 121(6), 657–662.

Gutshall, D.M., G.D. Pilcher and A.E. Langley. (1989) Mechanism of the serum thyroid hormone lowering effect of perfluoro-n-decanoic acid (PFDA) in rats. J. Toxicol. Environ. Health   28(1): 53-65.

Hagenbuch, B. (2007)  Cellular entry of thyroid hormones by organic anion transporting polypeptides.  Best Pract. Res. Clin. Endocrinol. Metab.  21(2): 209-221.

Hagenbuch B, Meier PJ 2004 Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch 447:653-665

Hagmar, L., L. Rylander, E. Dyremark, E. Klasson-Wehler and E.M. Erfurth. (2001a).  Plasma concentrations of persistent organochlorines in relation to thyrotropin and thyroid hormone levels in women.  Int. Arch. Occup. Environ. Health  74(3): 184-188.

Hagmar, L., J. Bjork, A. Sjodin, A. Bergman and E.M. Erfurth. (2001b) Plasma levels of persistent organohalogens and hormone levels in adult male humans.  Arch. Environ. Health  56(2): 138-143.

Hallgren, S., T. Sinjari, H. Hakansson and P.O. Darnerud. (2001) Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice.  75(4): 200-208.

Hallgren, S. and P.O. Darnerud. (2002) Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects.  Toxicology  177(203): 227-243.

Hamers, T., J.H. Kamstra, E. Sonneveld, A.J. Murk, M.H. Kester, P.L. Andersson, J. Legler and A. Brouwer. (2006) In vitro profiling of the endocrine-disrupting potency of brominated flame retardants.  Toxicol. Sci.  92(1): 157-173.

Hamers, T., Kamstra, E. Sonneveld, A.J. Murk, T.J. Visser, M.J. Van Velzen, A. Brouwer and A. Bergman. (2008) Biotransformation of brominated flame retardants into potentially endocrine-disrupting metabolites, with special attention to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47).  Mol. Nutr. Food Res.  52(2): 284-298.

Harley, K.G., A.R. Marks, J. Chevrier, A. Bradman, A. Sjodin and B. Eskenazi.  (2010)  PBDE concentrations in women's serum and fecundability.  Environ. Health Perspect.  118(5): 699-704.

Henneman, G., R. Docter, E.C. Friesma, M. de Jong, E.P. Krenning and T.J. Visser.  (2001)  Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability.  Endocr. Rev.  22(4): 451-476.

Heuer, H.  (2007)  The importance of thyroid hormone transporters for brain development and function.  Best Pract. Res. Clin. Endocrinol. Metab.  21(2):  265-276.

Hood, A. and C.D. Klaassen. (2000a) Differential effects of microsomal enzyme inducers on in vitro thyroxine (T(4)) and triiodothyronine (T(3)) glucuronidation.  Toxicol. Sci.  55(1): 78-84.

Hood, A. and C.D. Klaassen.  (2000b)  Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues.  Toxicol. Appl. Pharmacol.  163(3): 240-248.

Hovander, L., M. Athanasiadou, L. Asplund, S. Jensen and E.K. Wehler. (2000). Extraction and cleanup methods for analysis of phenolic and neutral organohalogens in plasma.  24(8): 696-703.

Hume, R., J. Simpson, C. Delahunty, H. van Toor, S.Y. Wu, F.L. Williams, T.J. Visser et al.  (2004) Human fetal and cord serum thyroid hormones: developmental trends and interrelationships.  J. Clin. Endocrinol. Metab.  89(8): 4097-4103.

Inoue, K., F. Okada, R. Ito, S. Kato, S. Sasaki, S. Nakajima, A. Uno, Y. Saijo, F. Sata, Y. Yoshimura, R. Kishi and H. Nakazawa. (2004) Perfluorooctane sulfonate (PFOS) and related perfluorinated compounds in human maternal and cord blood samples: assessment of PFOS exposure in a susceptible population during pregnancy.  Environ. Health Perspect.  112(11): 1204-1207.

Kato, Y., K. Haraguchi, M. Onishi, S. Ikushiro, T. Endo, C. Ohta, N. Koga, S Yamada and M. Degawa. (2014) 3,3',4,4'-Tetrachlorobiphenyl-mediated decrease of serum thyroxine level in C57BL/6 and DBA/2 mice occurs mainly through enhanced accumulation of thyroxine in the liver.  Biol. Pharm. Bull.  37(3) 504-509.

Kato, Y., M. Onishi, K. Haraguchi, S. Ikushiro, C. Ohta, N. Koga, T. Endo, S. Yamada and M. Degawa. (2013) A possible mechanism for 2,3',4,4',5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level in mice.  Biol. Pharm. Bull.  36(10): 1594-1601.

Kato, Y., S. Tamaki, K. Haraguchi, S. Ikushiro, M. Sekimoto, C. Ohta, T. Endo, N. Koga, S. Yamada and M. Degawa. (2012) Comparative study on 2,2',4,5,5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice.  Toxicol. Appl. Pharmacol.  263(3): 323-329.

Kato, Y., M. Onishi, K. Haraguchi, S. Ikushiro, C. Ohta, N. Koga, T. Endo, S. Yamada and M. Degawa. (2011) A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice.  Toxicol. Appl. Pharmacol.  254(1): 48-55.

Kato, Y., K. Haraguchi, M. Kubota, Y. Seto, S. Ikushiro, T. Sakaki, N. Koga, S. Yamada and M. Degawa. (2009) 4-Hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl-mediated decrease in serum thyroxine level in mice occurs through increase in accumulation of thyroxine in the liver.  Drug Metab. Dispos.  37(10): 2095-2102.

Kato, Y., S. Ikushiro, R. Takiguchi, K. Haraguchi, N. Koga, S. Uchida, T. Sakaki, S. Yamada, J. Kanno and M. Degawa. (2007) A novel mechanism for polychlorinated biphenyl-induced decrease in serum thyroxine level in rats.  Drug Metab. Dispos. 35(10) : 1949-1955.

Kato, Y., S. Ikushiro, K. Haraguchi, T. Yamazaki, Y. Ito, H. Suzuki, R. Kimura, S. Yamada, T. Inoue and M. Degawa. (2004) A possible mechanism for decrease in serum thyroxine level by polychlorinated biphenyls in Wistar and Gunn rats.  Toxicol. Sci.  81(2): 309-315.

Kato, Y., K. Haraguchi, T. Yamazuki, Y. Ito, S. Miyajima, K. Nemoto, N. Koga, R. Kimura and M. Degawa. (2003) Effects of polychlorinated biphenyls, kanechlor-500, on serum thyroid hormone levels in rats and mice.  Toxicol. Sci.  72(2): 235-241.

Kim, S.Y., E.S. Choi, H.J. Lee, C. Moon and E. Kim.  (2015)  Transthyretin as a new transporter of nanoparticles for receptor-mediated transcytosis in rat brain microvessels.  Colloids Surf B Biointerfaces  136: 989-996.

Kim do K, Kanai Y, Matsuo H, Kim JY, Chairoungdua A, Kobayashi Y, Enomoto A, Cha SH, Goya T, Endou H 2002 The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics 79:95-103

Kohrle, J., S.L. Fang, Y. Yang, K. Irmscher, R.D. Hesch, S. Pino, S. Alex, and L.E. Braverman. (1989). Rapid effects of the flavonoid EMD 21388 on serum thyroid hormone binding and thyrotropin regulation in the rat. Endocrinoloy 125: 532-537

Koopman-Essenboom, C., D.C. Morse, N. Weisglas-Kuperus, I.J. Lutkeschipholt, C.G. Van der Paauw, L.G. Tuinstra, A. Brouwer and P.J. Sauer.  (1994)  Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants.  Pediatr. Res.  36(4): 468-473.

Lans, M. C., Klasson-Wehler, E., Willemsen, M., Meussen, E., Safe, S., & Brouwer, A. (1993). STRUCTURE-DEPENDENT, COMPETITIVE INTERACTION OF HYDROXY-POLYCHLOROBIPHENYLS, -DIBENZO-p-DIOXINS AND -DIBENZOFURANS WITH HUMAN TRANSTHYRETIN. Chemico-Biological Interactions, 88, 7–21.

Lans, M. C., Spiertz, C., Brouwer, a, & Koeman, J. H. (1994). Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs. European Journal of Pharmacology, 270(2-3), 129–136. http://doi.org/10.1016/0926-6917(94)90054-X

Larsson, M., Pettersson, T., & Carlström, a. (1985). Thyroid hormone binding in serum of 15 vertebrate species: isolation of thyroxine-binding globulin and prealbumin analogs. General and Comparative Endocrinology, 58(3), 360–375.

Loubiere, L.S., E. Vasilopoulou, J.N. Bulmer, P.M. Taylor, B. Stieger, F. Verrey, C.J. McCabe, J.A. Franklyn, M.D. Kilby and S.Y. Chan. (2010)  Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction.  Placenta  31(4): 295-304.

Lueprasitsakul, W., Alex, S., Fang, S. L., Pino, S., Irmscher, K., Köhrle, J., & Braverman, L. E. (1990). Flavonoid administration immediately displaces thyroxine (T4) from serum transthyretin, increases serum free T4, and decreases serum thyrotropin in the rat. Endocrinology 126 (6)

Lupton, S.J., P. McGarrigle, J.R. Olson, T.D. Wood and D.S. Aga. (2010) Analysis of hydroxylated polybrominated diphenyl ether metabolites by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.  Rapid Commun. Mass. Spectrom.  24(15): 2227-2235.

Lupton, S.J., B.P. McGarrigle, J.R. Olson, T.D. Wood and D.S. Aga. (2009)  Analysis of hydroxylated polybrominated diphenyl ether metabolites by liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.  22(11): 1802-1809.

Malmberg, T., M. Athanasiadou, G. Marsh, I. Brandt and A. Bergman.  (2005) Identification of hydroxylated polybrominated diphenyl ether metabolites in blood plasma from polybrominated diphenyl ether exposed rats.  39(14): 5342-5348.

Marchesini, G.R., E. Meulenberg, W. Haasnoot, M. Mizuguchi and H. Irth.  (2006) Biosensor recognition of thyroid-disrupting chemicals using transport proteins.  Anal. Chem.  78(4): 1107-1114.

Marchesini, G.R., A. Meimaridou, W. Haasnoot, E. Meulenberg, F. Albertus, M. Mizuguchi, M. Takeuchi, H. Irth and A.J. Murk. (2008) iosensor discovery of thyroxine transport disrupting chemicals.  Toxicol. Appl. Pharmacol.  232(1): 150-160.

Martin, L.A., D.T. Wilson, K.R> Reuhl, M.A. Gallo and C.D. Klaassen. (2012) Polychlorinated biphenyl congeners that increase the glucuronidation and biliary excretion of thyroxine are distinct from the congeners that enhance the serum disappearance of thyroxine.  Drug Metab. Dispos.  40(3): 588-595.

Martin, L. and C.D. Klaassen. (2010) Differential effects of polychlorinated biphenyl congeners on serum thyroid hormone levels in rats.  Toxicol. Sci.  117(1): 36-44.

Meerts, I.A., Y. Assink, P.H. Cenjin, J.H. Van Den Berg, B.M. Weijers, A. Bergman, J.H. Koeman and A. Brouwer. (2002) Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat.  Toxicol. Sci. 68(2): 361-371.

Meerts, I.A., J.J. van Zanden, E.A. Lujiks, I. van Leeuwen-Bol, G. Marsh, E. Jakobsson, A. Bergman and A. Brouwer. (2000) Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro.  Toxicol. Sci.  56(1): 95-104.

Mendel, C. M. (1989). Modeling thyroxine transport to liver : rejection of the “enhanced dissociation” hypothesis as applied to thyroxine. Am J Physiol, 257(Endocrinol Metab 20), E764–E771.

Mendel, C. M., Cavalieri, R. R., & Kohrle, J. (1992). Thyroxine (T4) transport and distribution in rats treated with EMD 21388, a synthetic flavonoid that displaces T4 from transthyretin. Endocrinology, 130(3), 1525–1532.

Midgley, J. E. (2001) Direct and indirect free thyroxine assay methods: theory and practice.  Clin. Chem.  47(8): 1353-1363.

Miksys, S. and R.F. Tyndale. (2004) The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics.  Drug Metab. Rev.  36(2): 313-333.

Montano, M., E. Coccco, C. Guignard, G. Marsh, L. Hoffmann, A. Bergman, A.C. Gutleb and A.J. Murk. (2012) New approaches to assess the transthyretin binding capacity of bioactivated thyroid hormone disruptors.  Toxicol. Sci.  130(1): 94-105.

Morse, D.C., E.K. Wehler, W. Wesseling, J.H. Koeman and A. Brouwer.  (1996)  Alterations in rat brain thyroid hormone status following pre- and postnatal exposure to polychlorinated biphenyls (Aroclor 1254).  Toxicol. Appl. Pharmacol.  136(2): 269-279.

Morse, D.C., D. Groen, M. Veerman, C.J. van Amerongen, H.B. Koeter, A.E. Smits van Proojie, T.J. Visser, J.H. Koeman and A. Brouwer.  (1993)  Interference of polychlorinated biphenyls in hepatic and brain thyroid hormone metabolism in fetal and neonatal rats.  Toxicol. Appl. Pharmacol.  122(1) :27-33.

Munro, S.L., C.F. Lim, J.G. Hall, J.W. Barlow, D.J. Craik, D.J. Topliss and J.R. Stockigt (1989) Drug competition for thyroxine binding to transthyretin (prealbumin): comparison with effects on thyroxine-binding globulin. J. Clin. Endocrinol. Metab.  68(6): 1141-1147,

Nishimura M, Naito S 2008 Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies. Drug Metab Pharmacokinet 23:22-44

Pedraza, P., Calvo, R., Obregón, M. J., Asuncion, M., Escobar Del Rey, F., & Morreale De Escobar, G. (1996). Displacement of T4 from transthyretin by the synthetic flavonoid EMD 21388 results in increased production of T3 from T4 in rat dams and fetuses. Endocrinology, 137(11), 4902–4914. http://doi.org/10.1210/en.137.11.4902

Purkey, H.E., M.I. Dorrell and J.W. Kelly. (2001) Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma.  Proc. Natl. Acad. Sci. USA  98(10): 5566-5571.

Refetoff, S., N.I. Robin and V.S. Fang. (1970) Parameters of thyroid function in serum of 16 selected vertebrate species: a study of PBI, serum T4, free T4, and the pattern of T4 and T3 binding to serum proteins.  Endocrinology  86(4): 793-805.

Refetoff, S. (2015) Thyroid Hormone Serum Transport Proteins. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

Ren, X.M., L.H. Guo, Y. Gao, B.T. Zhang and B. Wan. (2013) Hydroxylated polybrominated diphenyl ethers exhibit different activities on thyroid hormone receptors depending on their degree of bromination.  Toxicol. Appl. Pharamacol.  268(3): 256-263.

Ren, X. M., & Guo, L. H. (2012). Assessment of the binding of hydroxylated polybrominated diphenyl ethers to thyroid hormone transport proteins using a site-specific fluorescence probe. Environmental Science and Technology, 46(8), 4633–4640. http://doi.org/10.1021/es2046074

Rerat, C. and H.G. Schwick (1967) [Crystallographic data of blood plasma prealbumin]. [Article in French] Acta Crystallogr.  22(3): 441-442.

Richardson, S. J. (2007). Cell and molecular biology of transthyretin and thyroid hormones. International Review of Cytology, 258(January), 137–93. http://doi.org/10.1016/S0074-7696(07)58003-4

Richardson, S. J., Wijayagunaratne, R. C., D’Souza, D. G., Darras, V. M., & Van Herck, S. L. J. (2015). Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters. Frontiers in Neuroscience, 9(March), 1–8.

Rickenbacher, U., McKinney, J. D., Oatley, S. J., & Blake, C. C. (1986). Structurally specific binding of halogenated biphenyls to thyroxine transport protein. Journal of Medicinal Chemistry, 29(5), 641–648.

Ritchie, J.W. and P.M. Taylor.  (2001)  Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta.  Biochem. J.  356(Part 3); 719-725.

Riu, A., J.P. Cravedi, L. Debrauwer, A. Garcia, C. Canlet, I. Jouanin and D. Zalko. (2008) Environ. Int. 34(3): 318-329.

Roberts LM, Woodford K, Zhou M, Black DS, Haggerty JE, Tate EH, Grindstaff KK, Mengesha W, Raman C, Zerangue N 2008 Expression of the thyroid hormone transporters MCT8 (SLC16A2) and OATP14 (SLCO1C1) at the blood-brain barrier. Endocrinology 149:6251-6261

Rotroff, D.M., B.A. Wetmore, D.J. Dix, S.S. Ferguson, H.J. Clewell, K.A. Houck, E.L. Lecluyse, M.E. Anersen, R.S. Judson, C.M. Smith, M.A. Sochaski, R.J. Kavlock, F. Boellmann, M.T. Martin, D.M. Reif, J.F. Wambaugh and R.S. Thomas. (2010) Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening.  117(2): 348-358.

Sato, K., J. Sugawara, T. Sato, H. Mizutamari, T. Suzuki, A. Ito, T. Mikkaichi, T. Onogawa, M. Tanemoto, M. Unno, T. Abe and K. Okamura.  (2003)  Expression of organic anion transporting polypeptide E (OATP-E) in human placenta.  Placenta  24(2-3): 144-148.

Schreiber, G. (2002). The evolutionary and integrative roles of transthyrein in thyroid hormone homeostasis. Journal of Endocrinology, 175(1), 61–73. http://doi.org/10.1677/joe.0.1750061

Schroder van der Elst, J.P., D. van der Heide, H. Rokos, G. Morreale de Escobar and J. Kohrlre. (1998) Synthetic flavonoids cross the placenta in the rat and are found in fetal brain.  Am. J. Physiol.  274(2 Psrt 1): E253-E256.

Schroder van der Elst, J.P., D. van der Heide, H. Rokos, J. Kohrle and G. Morreale de Escobar. (1997)  Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat.  Endocrinology  138(1): 79-84.

Schuur, A.G., F.M. Boekhorst, A. Brouwer and T.J. Visser. (1997) Extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on thyroid hormone turnover in male Sprague-Dawley rats.  Endocrinology  138(9): 3727-3734.

Sinjari, T. and P.O. Darnerud. (1998) Hydroxylated polychlorinated biphenyls: placental transfer and effects on thyroxine in the foetal mouse.  Xenobiotica  28(1): 21-30.

Sparkes, R.S., H. Sasaki, T. Mohandas, K. Yoshioka, I. Kilsak, Y. Sasaki, C. Heinzmann and M.I. Simon. (1987) Assignment of the prealbumin (PALB) gene (familial amyloidotic polyneuropathy) to human chromosome region 18q11.2-q12.1. Hum. Genet.  75(2): 151-154.

Stapleton, H.M., S.M. Kelly, R. Pei, R.J. Letcher and C. Gunsch.  (2009) Metabolism of polybrominated diphenyl ethers (PBDEs) by human hepatocytes in vitro.  Environ. Health Perspect.  117(2): 197-202.

Tohyama K, Kusuhara H, Sugiyama Y 2004 Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology

Ucan-Marin, F., A. Arukwe, A.S. Mortensen, G.W. Gabrielsen and R.J. Letcher. (2010) Recombinant albumin and transthyretin transport proteins from two gull species and human: chlorinated and brominated contaminant binding and thyroid hormones.  Environ. Sci. Technol.  44(1): 497-504.

Van Birgelen, A.P., E.A. Smit, I.M. Kampen, C.N. Groeneveld, K.M. Case, J. Van der Kolk, H. Poiger, M. Van den Berg, J.H. Koeman and A. Brouwer. (1995) Subchronic effects of 2,3,7,8-TCDD or PCBs on thyroid hormone metabolism: use in risk assessment.  Eur. J. Pharmacol.  293(1) : 77-85.

Van den Berg, K. J. (1990). Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin. Chemico-Biological Interactions, 76(1), 63–75.

Van den Berg, K. J., Van Raaij, J. a G. M., Bragt, P. C., & Notten, W. R. F. (1991). Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo. Archives of Toxicology, 65(1), 15–19.

Viberg, H., A. Fredriksson and P. Eriksson. (2002) Neonatal exposure to the brominated flame retardant 2,2',4,4',5-pentabromodiphenyl ether causes altered susceptibility in the cholinergic transmitter system in the adult mouse.  Toxicol. Sci. 67(1): 104-107.

Viollon-Abadie, C., D. Lassere, E. Debruyne, L. Nicod, N. Carmichael and L. Richert. (1999) Phenobarbital, beta-naphthoflavone, clofibrate, and pregnenolone-16alpha-carbonitrile do not affect hepatic thyroid hormone UDP-glucuronosyl transferase activity, and thyroid gland function in mice.  Toxicol. Appl. Pharmacol.  155(1) 1-12.

Visser, T.J. and R.P. Peeters. (2012) Metabolism of thyroid hormone.  In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-.

Visser, T. J. (2010). Cellular Uptake of Thyroid Hormones. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-.

Visser, T.J. (1996) Role of sulfate in thyroid hormone sulfation.  Eur. J. Endocrinol.  134(1): 12-14.

Visser, T.J., E. Kaptein, J.A. van Raaij, C.T. Joe, T. Ebner and B. Burchell. (1993)

Multiple UDP-glucuronyltransferases for the glucuronidation of thyroid hormone with preference for 3,3',5'-triiodothyronine (reverse T3).  FEBS Lett.  315(1): 65-68.

Weiss, J.M., P.L. Andersson, M.H. Lamoree, P.E. Leonards, S.P. van Leeuwen and T. Hamers. (2009) Competitive binding of poly- and perfluorinated compounds to the thyroid hormone transport protein transthyretin.  Toxicol. Sci.  109(2): 206-216.

Weiss, J. M., Andersson, P. L., Zhang, J., Simon, E., Leonards, P. E. G., Hamers, T., & Lamoree, M. H. (2015). Tracing thyroid hormone-disrupting compounds: database compilation and structure-activity evaluation for an effect-directed analysis of sediment. Analytical and Bioanalytical Chemistry, 5625–5634. http://doi.org/10.1007/s00216-015-8736-9

Yamauchi, K., A. Ishihara, H. Fukazawa and Y. Terao.  (2003) Competitive interactions of chlorinated phenol compounds with 3,3',5-triiodothyronine binding to transthyretin: detection of possible thyroid-disrupting chemicals in environmental waste water.  Toxicol. Appl. Pharmacol.  187(2): 110-117.

Yen, P. M. (2001). Physiological and molecular basis of thyroid hormone action. Physiological Reviews, 81(3), 1097–1142.

Zhang, J., J.H. Kamstra, M. Ghorbanzadeh, J.M. Weiss, T. Hamers and P.L. Andersson. (2015) In Silico Approach To Identify Potential Thyroid Hormone Disruptors among Currently Known Dust Contaminants and Their Metabolites.  Environ. Sci. Technol.  49(16): 10099-10107.

Zoeller, R. T., Tan, S. W., & Tyl, R. W. (2007). General background on the hypothalamic-pituitary-thyroid (HPT) axis. Critical Reviews in Toxicology, 37(1-2), 11–53.

Zoeller, R.T. and J. Rovet.  (2004)  Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings.  J. Neuroendocrinol.  16(10): 809-818.