Impairments of Endocrine Functions: Causes and Consequences - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 198

protein). Among these compounds, PCBs, brominated flame retardants [polybrominated
diphenyl ether (PBDEs) and tetrabromobisphenol (TBBPA) in particular], perchlorates, or
alkylphenols are frequently found in the environment.
In rodents, PCB exposure is associated with a decreased T4 level. In a study on wild fish
in San Francisco Bay, Brar et al. (2010) have shown that T3 and T3/T4 ratio are correlated
with PCB exposures. Biological effects of PBDEs in animals seem to be similar to those of
PCBs. In rodents, amphibians ( Xenopus laevis ), and fish ( Pimephales promelas ), decreased
T4 levels have been reported (Kudo et al. 2006; Kuriyama et al. 2007; Lema et al. 2008). It
has been reported that PBDEs during prenatal exposure of rats cause long-term changes
in motor activity (hyperactivity) and disrupt performance in learning and memory tests
(Kuriyama et al. 2005). A recent study (Park et al. 2011) on tetrabromoethylcyclohexane, a
potential substitute for PBDEs hexabromocyclodecane has shown a significant reduction
in total plasma thyroxin and a significant increase in mean thyroid epithelial cell height in
the juvenile brown trout Salmo trutta .
The brominated flame retardant TBBPA has biological effects observed across many
species (Darnerud 2003; Saegusa et al. 2009). In amphibians, marked molecular effects
were observed in vivo on TH signaling (Fini et al. 2007). TBBPA could affect TH binding
to thyroid receptors and the transport of TH by the TH-binding protein, transthyretin
(Kitamura et al. 2005). In rodents, TBBPA induces neurobehavioral effects (Nakajima et
al. 2009). Long-term exposure of European flounder ( Platichthys flesus) ) to TBBPA increased
levels of the TH thyroxin (T4) in correlation with internal concentrations of the test com-
pound. The authors indicated a possible competition of TBBPA for plasma protein binding.
Triiodothyronin (T3) levels were not affected, and histology showed no signs of altered
thyroid gland activity (Kuiper et al. 2007).
Perchlorates are chemicals with well-known antithyroidal effects (Bernhardt et al. 2011; Li
et al. 2011; Boas et al. 2012). They inhibit thyroidal iodine uptake in all vertebrates, because
they have a greater affinity for NIS than iodine, and the structure of the symporter is largely
conserved in all vertebrates (Carr and Patiño 2010). In teleosts and amphibians, it has been
widely demonstrated that perchlorates decrease T4 concentration in blood and tissue, cause
thyroid histopathological alterations, and induce trouble in growth and metamorphosis fail-
ure (Carr and Patiño 2010). In fish, more precisely zebrafish, perchlorate induced hypothyroid-
ism, which causes a halt to spawning (Mukhi and Patiño 2007). Another class of chemicals,
nonylphenols, induced a significant decrease of thyroxin levels in fish, whereas no effect on
triiodothyronine concentrations was detected, thus inhibiting the TH balance (Zaccaroni et
al. 2009). No histopathological changes were detected in the thyroid. Other organic chemicals
and also metals have been described or suspected to cause thyroid disruption (Brucker-Davis
1998; Brown et al. 2004; Miller et al. 2009; Pearce and Braverman 2009; Carr and Patiño 2010).
Thyroid disruption properties can be detected with in vitro cellular tests. Jugan et al.
(2007) have developed a cellular assay (PC-DR-LUC) that can be used to identify com-
pounds that have thyromimetic or TH-antagonistic effects on thyroid receptors. Kitamura
et al. (2005) showed a thyromimetic effect of TBBPA on in vitro cellular test using a GH3
pituitary cell line. In vitro bioassays indicate that some of polycyclic aromatic hydrocarbon
derivatives have agonist or potentiation activity with thyroid receptors and have a strong
TTR-binding activity (Bekki et al. 2009). Fini et al. (2007) have developed an in vivo test for
the detection of thyroid receptor agonists and for the determination of effects of TH pro-
duction inhibitors, including inhibitors of TH synthesis, antagonists acting at the receptor,
and deiodinase inhibitors.
Real-life exposure of humans and wildlife to a wide spectrum of synthetic chemicals
makes it difficult to prove the causative thyroid effect of one single agent. Therefore, it is