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Study Reviews - PCB effects on the Thyroid
Study Review #1
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altered thyroid hormones have been consistently seen in human
populations at background levels of PCB exposure
Global contamination by a variety of anthropogenic persistent
organic chemicals, such as dioxins and PCBs, has resulted in human exposure
throughout all phases of development. Detectable concentrations of PCBs
and dioxins have been found in amniotic fluid, placenta and foetal tissue
samples while infants who are breast-fed can obtain blood levels greater
than those of their mother's. In two separate food poisoning episodes where
infants were exposed in utero to elevated levels of heat-degraded PCBs
(PCBs, PCQs, PCDFs), a variety of adverse mental and physical developmental
abnormalities have been observed. In additional human cohorts where
exposure could be considered as environmental or background, more subtle
effects, including lower birth weights, alterations in thyroid hormones
and lymphocyte subpopulations and detriments in neurological development,
have been consistently seen. In most instances, negative associations were
made between in utero exposure to contaminants compared with lactational.
Although the observed neurodevelopmental deficits have been described as
subtle, there could be unknown consequences related to future intellectual
functionality. Current regulatory efforts should focus on identification
and control of environment and food chain contamination as in utero exposure
is a direct consequence of the accumulated maternal body burdens. (Feeley
et al, 2000)
Study Review #2
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PCBs bear a striking structural resemblance to thyroid hormones
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PCBs act as agonists, antagonists, and partial agonists to
thyroid hormones (PCBs interfere)
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inappropriate levels of thyroid hormones at key moments can
produce permanent brain damage
Thyroid hormones regulate neuronal proliferation, migration,
process outgrowth, synaptic development, and myelin formation in specific
brain regions. Because brain development occurs during discrete windows
of time, inappropriate levels of thyroid hormones in definitive periods
can produce permanent damage, the nature of which depends upon the timing
and magnitude of the insult. Thyroid hormones cross the placenta and enter
the brain primarily as thyroxine (T4); therefore, conditions selectively
lowering serum T4 levels alter brain hormone availability. Triiodothyronine
(T3) is the predominant form of the hormone that binds to the receptor.
T3 is produced from T4 in the brain by the enzyme type II, 5'-deiodinase.
Polychlorinated biphenyls (PCBs) are synthetic environmental toxicants
that bear a striking structural resemblance to the active thyroid hormones
and can, depending upon the species, dosage, and congener used, act
as agonists, antagonists, and partial agonists to thyroid hormones.
(Porterfield et al, 1998)
Study Review #3
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PCBs and dioxins are structurally similar to thyroid hormones
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PCBs and dioxins have binding characteristics similar to
thyroid hormones
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PCBs and dioxins can either decrease or mimic the biological
action of the thyroid hormones
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deficient or excessive thyroid hormones can cause irreversible
neurological damage in the womb or infancy
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mothers or children with existing thyroid disorders could
experience greater harm even at low PCB levels which leave others unharmed
Neurologic development follows orderly patterns that can
be severely disturbed when thyroid hormones are deficient or excessive.
Should this occur at appropriate development periods, irreversible neurologic
damage can result. The nature of the deficits depends upon the specific
development period and the severity of the thyroid disturbance. PCBs
and dioxins are structurally similar to the thyroid hormones. Their
binding
characteristics are similar to those of thyroid hormones and all three
groups bind to the cytosolic Ah receptor, the thyroid hormone receptor
and the serum thyroid hormone binding protein transthyretin. Depending
upon the dose of toxin and the congener used, the toxins either decrease
or mimic the biological action of the thyroid hormones. Either effect,
if occurring during brain development, can have disastrous consequences.
Children and animals exposed to PCBs or dioxins in utero and/or as infants
can exhibit varying degrees of behavioral disorders. These disorders resemble
those seen in children exposed to thyroid hormone deficiencies in utero
and/or in infancy. The mechanism of developmental neurotoxicity of PCBs
and dioxins is not known but data suggest it could be partially or entirely
mediated by alterations in availability and action of thyroid hormones
during neurological development. It is possible that transient exposure
of the mother to doses of toxins presently considered nontoxic to the mother
could have an impact upon fetal or perinatal neurological development.
If the toxins act via their effect on thyroid hormone action, it is
possible that doses of toxins that would normally not alter fetal development,
could become deleterious if superimposed on a pre-existing maternal/or
fetal thyroid disorder. (Porterfield, 1994)
Study Review #4
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PCB exposed adults with existing thyroid disorders may face
greater risk of developing brain, motor, or metabolic dysfunction
Alterations in thyroid hormone level or responsivity to thyroid
hormone have significant neurologic sequelae throughout the life cycle.
During fetal and early neonatal periods, disorders of thyroid hormone may
lead to the development of motor and cognitive disorders. During childhood
and adult life, thyroid hormone is required for neuronal maintenance as
well as normal metabolic function. Those with an underlying disorder
of thyroid hormone homeostasis or mitochondrial function may be at greater
risk for developing cognitive, motor, or metabolic dysfunction upon exposure
to substances which alter thyroid hormone economy. Polychlorinated
biphenyls (PCBs) and dioxins have been argued to interfere with thyroid
hormone action and thus may affect the developing and mature brain. Animal
models provide useful tools for studying the effects of thyroid hormone
disorders and the effects of environmental endocrine disruptors. The congenitally
hypothyroid, hyt/hyt, mouse exhibits abnormalities in both the cognit (incomplete
abstract) (Sher et al, 1998)
Study Review #5
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evidence is increasing that PCBs impair learning, memory
and attentional processes in children
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such neurodevelopmental effects may be linked to alterations
in hormone binding to the thyroid hormone receptor
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thyroid hormones are essential for normal behavioral, intellectual,
and neurological development
Thyroid hormones are essential for normal behavioral, intellectual,
and neurological development. Congenital hypothyroidism, if not treated,
can result in irreversible mental retardation, whereas thyroid diseases
with more moderate impairment of thyroid function, such as resistance to
thyroid hormone, cause less severe intellectual and behavioral abnormalities,
including attention deficit hyperactivity disorder. There is increasing
evidence that exposure to certain synthetic compounds, including dioxins
and polychlorinated biphenyls (PCBs), during the perinatal period
can also impair learning, memory, and attentional processes in offspring.
Animal and human studies suggest that exposure to these environmental toxicants
impair normal thyroid function. Although the precise mechanisms of action
of the adverse effects these toxicants have on neurodevelopment have not
yet been elucidated, it is possible that they are partially or predominantly
mediated by alterations in hormone binding to the thyroid hormone receptor.
The convergence of studies that examine the neurodevelopmental consequences
of moderate impairment of thyroid function, such as is found in resistance
to thyroid hormone, with those studies that demonstrate the adverse behavioral
and cognitive effects of perinatal exposure to dioxins and PCBs serves
to generate new hypotheses to test in a research setting. Such studies
may provide new insights into the basic pathogenesis of developmental
neurotoxicity following exposure to thyroid-disrupting synthetic compounds.
(Hauser et al, 1998)
Study Review #6
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PCBs alter serum thyroid hormone levels in humans
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hydroxylated PCBs compete with thyroid hormones for binding
sites
Organochlorine compounds, particularly polychlorinated biphenyls
(PCBs), alter serum thyroid hormone levels in humans. Hydroxylated organochlorines
have relatively high affinities for the serum transport protein transthyretin,
but the ability of these compounds to interact with the human thyroid receptor
is unknown. Using a baculovirus expression system in insect cells (Sf9
cells), we produced recombinant human thyroid receptor ss (hTRss). In competitive
binding experiments, the recombinant receptor had the expected relative
affinity for thyroid hormones and their analogs. In competitive inhibition
experiments with PCBs, hydroxylated PCBs (OH-PCBs), DDT and its metabolites,
and several organochlorine herbicides, only the OH-PCBs competed for binding.
The affinity of hTRss for OH-PCBs was 10,000-fold lower (Ki = 20-50 microM)
than its affinity for thyroid hormone (3,3',5-triiodothyronine, T3; Ki
= 10 nM). Because their relative affinity for the receptor was low, we
tested the ability of OH-PCBs to int (incomplete abstract) (Cheek et al,
1999)
Study Review #7
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PCBs and dioxins can alter human thyroid hormone status
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thyroid hormone alterations have been observed in mothers
and infants exposed to background levels of PCBs
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thyroid hormones stimulate development of the central nervous
system in embryos
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the thyroid system is linked to other important body systems
that use similar biochemical signals
Polychlorinated biphenyls (PCBs), PCDDs and PCDFs (summarized
as dioxins) are potentially toxic compounds which occur widely in the environment.
They are presently a pollution problem because they are resistant to either
chemical or biologic degradation and they accumulate in the food chain.
Perinatal PCB/dioxin exposure may affect neurodevelopmental and behavioral
outcome in accidentally as well as in background prenatal exposed children,
suggesting that the developing human brain is particularly sensitive to
these compounds. Data regarding the potential immunotoxic effects of PCBs
and dioxins in human beings remain scarce. Adult humans are less susceptible
than perinatally exposed infants. Perinatal exposure to PCBs and dioxins
at a high level may affect primary antibody response. Prenatal background
exposure to PCBs and dioxins may result in changes in the T-cell population
without effect on the health status of the infant nor on humoral immunity.
In most studies a relation between PCB exposure and birthweight have been
found. PCBs and dioxins provide inter- or intra-cellular signals that alter
growth, differentiation and function of cells in a tissue-, stage-, or
cell-specific manner. They have the potential to disrupt the endocrine
system of animals as well as humans. Perinatal exposure to chemicals that
mimics natural steroidal hormones can have a profound impact on later development
of the reproductive system. Elevated levels of dioxins and PCB can also
alter the human thyroid hormone status. Relatively subtle thyroid hormone
alterations have been observed in pregnant mothers and their infants exposed
to background levels of PCBs and dioxins. Thyroid hormones are needed to
stimulate neuronal and glial proliferation and differentiation of the central
nervous system. Androgens and estrogens can also alter the development
of the central nervous system. The brain-pituitary-reproductive and thyroid
Axis and the brain-thymus-lymphoid axis are linked by an array of internal
mechanisms of communication that use similar signals (neurotransmitters,
peptides, growth factors, hormones) acting on similar recognition targets.
The construction of the physiological systems of the pituitary/hypothalamic
region of the brain takes place in utero. At that time endocrine disruptors
may be the most threatening, leading to changes in the endocrine, immune,
and nervous systems and hypothalame function that do not respond to normal
hormonal and neurotransmitter messages in the usual manner throughout life.
In this presentation the key data concerning the effects of perinatal exposure
to PCBs and dioxins on the endocrine, reproductive, immune and central
nervous system in human infants and children will be described. The strengths
and weakness of our current understanding and conflicting study data about
the interaction between neural, immune and endocrine processes will be
discussed. (Weisglas-Kuperus, 1996)
Study Review #8
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PHAHs [which include PCBs] can disrupt the thyroid hormone
system at a multitude of interaction sites, which may have a profound impact
on normal brain development
Several classes of environmental contaminants have been claimed
or suggested to possess endocrine-disrupting potency, which may result
in reproductive problems and developmental disorders. In this paper the
focus is on the multiple and interactive mechanisms of interference of
persistent polyhalogenated aromatic hydrocarbons (PHAHs) [a class of chemicals
which includes PCBs] and their metabolites with the thyroid hormone system.
Evidence suggests that pure congeners or mixtures of PHAHs directly
interfere with the thyroid gland; with thyroid hormone metabolizing enzymes,
such as uridine-diphosphate-glucuronyl transferases (UGTs), iodothyronine
deiodinases (IDs), and sulfotransferases (SULTs) in liver and brain; and
with the plasma transport system of thyroid hormones in experimental animals
and their offspring. Changes in thyroid hormone levels in conjunction
with high PHAH exposure was also observed in captive as well as free ranging
wildlife species and in humans. Maternal exposure to PHAHs during pregnancy
resulted in a considerable fetal transfer of hydroxylated PHAHs, which
are known to compete with thyroxine (T4) for plasma transthyretin (TTR)
binding sites, and thus may be transported to the fetus with those
carrier proteins that normally mediate the delivery of T4 to the fetus.
Concomitant changes in thyroid hormone concentrations in plasma and in
brain tissue were observed in fetal and neonatal stages of development,
when sufficient thyroid hormone levels are essential for normal brain development.
Alterations
in structural and functional neurochemical parameters, such as glial fibrillary
acidic protein (GFAP), synaptophysin, calcineurin, and serotonergic neurotransmitters,
were observed in the same offspring up to postnatal day 90. In addition,
some changes in locomotor and cognitive indices of behavior were
observed in rat offspring, following in utero and lactational exposure
to PHAHs. Alterations in thyroid hormone levels and subtle changes in neurobehavioral
performance were also observed in human infants exposed in utero and through
lactation to relatively high levels of PHAHs. Overall these studies indicate
that persistent PHAHs can disrupt the thyroid hormone system at a multitude
of interaction sites, which may have a profound impact on normal brain
development in experimental animals, wildlife species, and human infants.
(Brouwer et al, 1998)
Study Review #9
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thyroid hormone alterations
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adverse effects may occur within the range of current background
human body levels of PCBs in the general population
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use of the dioxin Toxic Equivalency Factor (TEF) may underestimate
risk of neurodevelopmental effects
A scientific evaluation was made of functional aspects of
developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated
dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in
experimental animals and in human infants. Persistent neurobehavioral,
reproductive and endocrine alterations were observed in experimental animals,
following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The
lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral
and reproduction endpoints, based on body burden of TCDD-toxic equivalents
(TEQs) in animals, are within the range of current background human
body burdens. Relatively subtle adverse effects on neurobehavioral
development and thyroid hormone alterations have also been observed
in infants and children exposed to background levels. Exclusive use of
the
toxic equivalency factor (TEF) approach may underestimate the risk of neurodevelopmental
effects, because both Ah receptor dependent and independent mechanisms
may be involved in these effects. The use of marker congeners and/or
bioassays based on Ah receptor mediated mechanisms are rapid, low cost
pre-screening alternatives for expensive and time consuming gas chromatographic-mass
spectrometric analysis. (Brouwer et al, 1995)
Study Review #10
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hyper- and hypothyroidism can be caused by PCBs and dioxins
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the hypothalamic-pituitary-ovarian-axis can be damaged directly
by contaminants, but also indirectly through changes in thyroid hormone
secretion.
Contaminants can influence female fertility at every phase
of reproduction. Fluctuation in the neurotransmitters of the brain can
be detrimental to the pulsatile secretion of the gonadotropin-releasing
hormone (GnRH). Numerous contaminants can be stored in the pituitary (eg,
mercury), causing a change in the gonadotropin production. Other substances
(eg, mercury and chloro-organic compounds), are deposited in the adrenal
cortex, being high in fat content. This can lead to inhibition of various
enzymatic systems and as a result higher androgen levels in the blood as
well as partial insufficiency of the adrenal cortex. Hyper- and hypothyroidism
can be caused by dioxins, polychlorinated biphenyls (PCB), cadmium
or lead. Thus the hypothalamic-pituitary-ovarian-axis can be damaged
directly by contaminants, but also, indirectly through changes caused in
prolactin, adrenal steroid and thyroid hormone secretion. Contaminants
stored in the ovary can influence the production of estradiol and progesterone.
Toxins can inhibit the normal development of the oocyte and in certain
cases can cause chromosomal aberrations. Numerous contaminants also have
an adverse effect on the production of male semen. This is shown by a deficient
number of sperms with normal motility, in reduced fertilization capability
as well as in morphological and chromosomal aberrations in the spermatogenesis,
which leads to abortion, stillbirth and congenital malformation. Even if
conception occurs in spite of increased parental contamination, these pregnancies
have a higher risk of abortion, congenital malformation, placental insufficiency
and premature birth. (Gerhard, 1993)
Study Review #11
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thyroid effects can be highly relevant to prenatal and postnatal
development
Endocrine disrupting chemicals (EDCs) may affect mammalian
development either indirectly (by impairing implantation, placental development,
lactation, etc.) or directly, altering the maturation of target tissues.
Current regulatory tests for reproductive or developmental toxicity should
be carefully evaluated with regard to risk assessment of EDCs, considering
hazard identification (are relevant endpoints being assessed?) and dose-response
assessment (are sensitive NOEL/dose-response curves being provided?). Many
in vitro and in vivo assays for sex steroid disruption are available; provided
that the metabolic capacities of the assays are defined, they could be
integrated in a sensitive battery for early detection of steroid-disrupting
potentials. The screening battery should address further regulatory in
vivo tests (e.g. what specific parameters have to be investigated). As
regards dose-response, qualitative differences may be observed between
lower and higher exposures, showing primary hormone-related effects and
frank embryotoxicity, respectively. Other problems concern (a) the identification
of critical developmental windows, according to hormone concentrations
and/or receptor levels in the developing target tissues; (b) the potential
for interactions between chemicals with common mechanism/target (e.g. xenoestrogens);
(c) most important, besides sex steroids more attention should be given
to other mechanisms of endocrine disruption, e.g., thyroid effects,
which can be highly relevant to prenatal and postnatal development. (Mantovani
et al, 1999)
Study Review #12
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Toxic Equivalency Factors (TEFs) are inappropriate for estimating
PCB thyroid effects
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only certain types of PCBs affect thyroid hormone levels
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more research is needed
The methods used to evaluate the toxicological effects of
PCBs in animals have been reviewed. The data show that Toxic Equivalency
Factors (TEFs) could be developed to assess the potential toxicity of PCB
mixtures for certain specific target organ effects (such as the liver and
immune system) but would be inappropriate for other effects (e.g. thyroid
function and neurochemical effects). More data on a wider range of
individual PCB congeners and a method for systematically balancing toxicodynamic
and toxicokinetic data are required before the TEF approach can be fully
evaluated. With the exception of the teratogenic effects seen in mice and
the anti-oestrogenic effects reported in in vitro studies, there are insufficient
data on individual PCB congeners to evaluate the structure-activity relationships
for the effects of PCBs on reproduction. The data also show that individual
PCBs may have opposing effects on a particular aspect of reproduction (for
example individual PCB congeners may have either oestrogenic or anti-oestrogenic
effects). Studies with individual PCB congeners have shown both enhancement
and antagonism of the teratogenic effects of 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin
(TCDD) in the mouse. It is not possible to use TEFs to evaluate the reproductive
effects of PCBs. The mechanism(s) responsible for the effects of PCBs on
postnatal neurobehavioural development in rodents and monkeys have not
been elucidated. At least two groups of PCBs which might be responsible
for the observed effects have been identified in this review, one affecting
the dopaminergic system and the other group affecting thyroid hormone levels.
Considerably more research would be required before the TEF approach could
be applied to the effects of PCBs on postnatal neurobehavioural development.
This would include research on an appropriate animal model to determine
whether the critical toxicological mechanism is mediated through the Ah
receptor. The reproductive toxicity of complex PCB mixtures such as those
found in foods will depend on the identifies and relative proportions of
individual PCB congeners in the mixture. It is not possible to give an
accurate estimate of a NOAEL or LOAEL from the reproduction studies using
commercial PCB mixtures which could be readily applied to the safety assessment
of PCBs present as contaminants in food. It is concluded that the data
presented in this paper support the hypothesis that there is no satisfactory
method derived from the available studies in laboratory animals for evaluating
the potential risk of adverse effects on reproduction posed by contamination
of foods with PCBs. (Battershill, 1994)
Study Review #13
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PCBs in concentrations commonly found in humans can induce
significant increases in the levels of free thyroxine in the serum by competing
with the thyroid hormone binding proteins present in the serum --- leading
to hypothyroidism
The relationship between the presence of residue levels of
polychlorinated biphenyls (PCBs) in human blood and the occurrence of mild
hypothyroidism was reviewed. A model to estimate the effects of PCBs on
the levels of free thyroid hormones in the plasma was examined and the
validity of the equilibrium hypothesis for explaining the apparent biological
findings was contemplated. Calculations carried out on the basis of published
experimental data revealed that PCBs in concentrations commonly found
in humans can induce significant increases in the levels of free thyroxine
in the serum by competing with the thyroid hormone binding proteins present
in the serum. Available experimental data were shown to support the
hypothesis that antagonist binding of PCBs to serum thyroid binding proteins
could result in the occurrence of hypothyroidism. The author concludes
that the biological findings are compatible with the hypothetical redistribution
of the thyroid hormone between the specific and nonspecific binding proteins
in the serum. (McKinney, 1987)
Study Review #14
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PCB commercial mixtures (Aroclors) have been shown to produce
thyroid alterations
Aroclors appear to have a low order of acute lethality. Data
for non- Aroclor PCB mixtures and specific PCB isomers suggest that mice
and guinea pigs are more sensitive than rats. Aroclors are lethal at much
lower total doses when administered subchronically or chronically than
acutely, indicating that PCBs bioaccumulate to concentrations that are
toxic. Animal studies have shown that the liver and cutaneous tissues are
the major target organs for Aroclors. Aroclors have also been shown to
produce stomach and thyroid alterations, immunosuppressive effects,
and porphyria in animals. Animals are sensitive to repeated exposures to
Aroclors as a result of rapid bioaccumulation to toxic levels. Monkeys
are particularly sensitive to the toxic effects of Aroclors. Toxic effects
have not been documented in humans who were exposed to Aroclors via the
environment. Occupational exposure to Aroclors has been associated with
reversible skin lesions and subclinical alterations in serum enzymes that
are suggestive of liver enzyme induction and possible hepatocellular damage.
More serious health effects were observed in humans who consumed rice oil
that had been contaminated with Kaneclors in Japan ("Yusho" incident) and
Taiwan ("Yu Cheng" incident). Aroclors appear to be fetotoxic but not teratogenic
in various species of animals, including rats, mice, rabbits, and monkeys,
but the possibility that contaminants (e.g. PCDFs) may be responsible for
the effects should be recognized. Slight decreases in birth weight, gestational
age, and/or neonatal behavioral performance have been reported in infants
born to mothers who had environmental or occupational exposure to PCBs.
These effects are inconclusive and not definitely attributable to PCBs.
Oral exposure to Aroclors produced deleterious effects on reproduction
in monkeys, mink, and, at higher doses, rodents. PCBs have produced generally
negative results in vitro and in vivo mutagenic assays. Feeding studies
in laboratory animals demonstrated the carcinogenicity of several PCB mixtures,
but it is not clear which components of the mixture or metabolites are
actually carcinogenic. The liver is the primary target of PCB carcinogenicity.
(Anon. ATSDR, 1989)
Study Review #15
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even low doses of PCBs interact with the thyroid system
This article addresses issues related to the characterization
of endocrine-related health effects resulting from low-level exposures
to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive
review of the literature but reflects workshop discussions. "The Characterizing
the Effects of Endocrine Disruptors on Human Health at Environmental Exposure
Levels," workshop provided a forum to discuss the methods and data needed
to improve risk assessments of endocrine disruptors. This article contains
an overview of endocrine-related (estrogen and thyroid system) interactions
and other low-dose effects of PCBs. The data set on endocrine effects includes
results obtained from mechanistic methods/ and models (receptor based,
metabolism based, and transport protein based), as well as from (italic)in
vivo(/italic) models, including studies with experimental animals and wildlife
species. Other low-dose effects induced by PCBs, such as neurodevelopmental
and reproductive effects and endocrine-se (incomplete abstract) (Brouwer
et al, 1999)
Study Review #16
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dioxins are linked to subcutaneous sarcomas and tumors of
the thyroid (cancer) --- (certain PCBs are dioxin-like)
Studies involving polychlorinated biphenyls (PCBs) are reviewed.
PCBs are a class of halogenated aromatic compounds, including halogenated
biphenyls, naphthalenes, dibenzodioxides, and dibenzofurans. PCBs persist
in the environment and are retained in tissue because they are lipid soluble.
They affect reproduction, suppress the immune system, cause tumors in laboratory
rodents, cause hepatic porphyria, and cause chick edema in chickens. Cell
mediated immunity is impaired by PCB, although the degree of impairment
is determined by the type of isomers present. PCBs are not teratogenic,
but they are fetotoxic, producing cleft palates, subcutaneous edema, and
hemorrhage. PCBs are passed to mammalian offspring in the milk. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin
(1746016) (TCDD) is known to cause hepatocellular carcinomas and squamous
carcinomas of the oropharynx and lungs. Subcutaneous sarcomas and tumors
of the thyroid are also noted. The primary source of PCB exposure to
the general United States population is fish from contaminated water. Serum
cholesterol levels in humans are directly proportional to PCB levels. The
concentration of PCB in human milk is particularly high. There is no clear
evidence of harm to humans from PCB, but research is inconclusive. The
author concludes that PCB may be a cancer promoter, but additional studies
on exposed human cohorts, such as fishermen, must be done before any conclusions
about the effects of PCB on humans can be reached. (Kimbrough, 1985)
Study Review #17
Toxic effects in animals and humans of polychlorinated biphenyls
(PCBs), polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins
(PCDDs), including in-vitro assays, carcinogenicity and teratogenicity,
and occurrence in human tissue, were reviewed, along with data on species
sensitivity and mechanism of action. Distinctions were made between studies
on purified compounds, their specific isomers, and mixtures of compounds.
Effects of accumulation of PCBs in adipose tissue in rats and mice were
noted for various compounds, including some in the Aroclor, Clophen, and
Kanechlor series, where the liver was established as a major site for PCB
carcinogenic effects, although little if any mutagenicity was noted. Studies
of PCB teratogenic and reproductive effects were summarized for various
rodent species and for rhesus-monkeys. Other pathological effects discussed
were hepatic porphyria, chloracne, thyroid toxicity, and immunotoxicity.
Other topics reviewed were PCB pharmacokinetics, metabolism, and species
sensitivity. PCDFs were reviewed in terms of occurrence, acute toxicity,
and teratogenicity. In-vitro assays of aryl-hydrocarbon-hydroxylase (AHH)
induction and receptor binding were also noted, with a table of these values
for various PCDF isomers and analogs. Included too were studies on PCDF
metabolism and accumulation in animals as well as humans. PCDDs, synthetic
compounds occurring as contaminants in chlorophenols and in waste from
chlorophenol production, were reviewed for carcinogenicity, teratogenic
and reproductive effects, and immunotoxicity, with distinctions made where
possible among the various isomers. Also described were studies on metabolism
and tissue distribution of PCDDs in rodents and humans, including bioavailability
to humans. Studies on the mechanism of actions of these compounds were
reviewed, with emphasis on induction of various microsomal cytochrome-P450
enzymes and AHH, receptor binding, and data on their environmental occurrence
and presence in human tissue and milk. Calculation of toxicity for setting
regulatory standards was discussed. (Iverson et al, 1991)
Study Review #18
Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants
that have been intensively investigated for three decades. They are broad-acting
toxicants occurring in complex mixtures and accurate risk assessment has
proven to be elusive. Focusing on a limited set of end points and emphasizing
a fixed set of congeners have led to more streamlined data sets that are
meant to expedite hazard characterization and risk assessment for the most
potent congeners--aryl hydrocarbon receptor (AhR) agonists. Unfortunately,
this has made it impossible to confirm or deny significant contributions
from the more prevalent components of the mixtures. PCBs may be only coincidentally
present, rather than causal, in some diseases. Still, attempts to determine
associations with incomplete residue data may lead to erroneous conclusions
and make accurate risk assessment even more elusive. Responses not mediated
through the AhR are presented and emphasize large data gaps. Dissimilar
analytical reports emphasize that s (incomplete abstract) (Hansen, 1998)
Study Review #19
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PCBs exhibit hormonal activity and bind transthyretin, a
thyroid hormone binding protein
Organochlorine industrial compounds, combustion products
and pesticides have been widely identified in the environment and residues
have been detected in extracts prepared from fish, wildlife, human tissues
as well as human milk and serum. Many of these compounds possess sex steroid
activities and therefore have the potential to disrupt endocrine-regulated
homeostasis. Organochlorines which exhibit hormonal activity include: (i)
polychlorinated
biphenyls (PCBs), hydroxylated PCBs, o,p'-DDT, and other organochlorine
insecticides which exhibit estrogen receptor (ER) agonist activities; (ii)
p,p'-DDE, a ligand for the androgen receptor which exhibits antiandrogen
activity; (iii) PCBs, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD),
and related aromatic hydrocarbons which bind the aryl hydrocarbon (Ah)
receptor and exhibit tissue-specific antiestrogenic activity; and (iv)
hydroxylated
aromatics which bind transthyretin, a thyroid hormone binding protein.
Although, it has been suggested that the estrogenic ac (incomplete abstract)
(Safe et al, 1997)
Study Review #20
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PCBs are thyroid disrupting
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PBBs (polybrominated biphenyls) may also affect thyroid hormone
status
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hydroxylation (metabolic conversion) of PCBs or PBBs may
play an important role
Brominated flame retardants such as polybrominated diphenyl
ethers (PBDEs), pentabromophenol (PBP), and tetrabromobisphenol A (TBBPA)
are produced in large quantities for use in electronic equipment, plastics,
and building materials. Because these compounds have some structural resemblance
to the thyroid hormone thyroxine (T(4)), it was suggested that they may
interfere with thyroid hormone metabolism and transport, e.g., by competition
with T(4) on transthyretin (TTR). In the present study, we investigated
the possible interaction of several brominated flame retardants with T(4)
binding to TTR in an in vitro competitive binding assay, using human TTR
and 125 I-T(4) as the displaceable radioligand. Compounds were tested in
at least eight different concentrations ranging from 1.95 to 500 nM. In
addition, we investigated the structural requirements of these and related
ligands for competitive binding to TTR. We were able to show very potent
competition binding for TBBPA and PBP (10.6- and 7.1-fold stronger
than the natural ligand T(4), respectively). PBDEs were able to compete
with T(4)-TTR binding only after metabolic conversion by induced rat liver
microsomes, suggesting an important role for hydroxylation. Brominated
bisphenols with a high degree of bromination appeared to be more efficient
competitors, whereas chlorinated bisphenols were less potent compared
to their brominated analogues. These results indicate that brominated
flame retardants, especially the brominated phenols and tetrabromobisphenol
A, are very potent competitors for T(4) binding to human transthyretin
in vitro and may have effects on thyroid hormone homeostasis in vivo
comparable to the thyroid-disrupting effects of PCBs. (Meerts et al,
2000)
Study Review #21
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hydroxylated PCBs (metabolized) are potent inhibitors of
T2 (diiodothyronine) and probably T3 (triiodothyronine)
-
inhibition of T3 may cause developmental neurotoxicity (brain
damage)
In this study we investigated the possible inhibitory effects
of hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) on iodothyronine
sulfotransferase activity. The results indicate that OH-PCBs are potent
inhibitors of this activity in vitro, with IC50 concentrations in the low
micro molar range. Inhibition of sulfotransferase activity towards 3,3'-diiodothyronine
(T2) was similar to that towards 3,3',5-triiodothyronine (T3) in this in
vitro assay, therefore, T2 can be used as the model substrate for the active
hormone T3. An important structural requirement for T2 sulfotransferase
inhibition is a hydroxyl group on the para or meta position of the OH-PCBs.
Since T3 is the active hormone, playing a very important role in somatic
and brain development and since hydroxylated PCBs can accumulate in fetuses,
inhibition of T3 sulfation could be a possible mechanism for the developmental
neurotoxicity of PCBs.(Gerlienke-Schuur et al, 1998)
Study Review #22
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two models indicate a structural relationship between some
PCBs and thyroid hormones
-
PCBs are reactive with thyroxine (T4)
Structure activity relationships of polychlorinated biphenyls
(PCBs) were discussed. The physicochemical and toxicological properties
of PCBs were considered. The skin and liver are the apparent target organs,
although toxic effects have occurred in other organ systems. The toxicological
properties of PCBs are frequently congener specific, showing a significant
dependence on the number and position of their chlorine substituents. Because
of this, the pattern of chlorine substitution has been used to discriminate
PCB congeners according to their toxicity. The toxic effects of PCBs appear
to involve at least three basic mechanisms: reversible binding to specific
molecular sites of action such as receptors and enzymes, irreversible covalent
binding to macromolecules such as DNA and proteins, and accumulation in
lipid rich tissues. Physicochemical properties of PCBs that could influence
their reactivity in biological systems were discussed. These include coplanarity
of the aromatic ring and its relation to chlorine atom substitution, cleft
type interactions and their dependence on lateral chlorine substitution,
and the availability of unsubstituted vicinal positions in the molecule
for oxidative metabolism. Reactivity models that have been used to predict
PCB toxicity in biological systems were considered. These include a stacking
model approach based on the aromatic rings, a cleft type model approach
based on lateral chlorine atom substitution, and an estrogen active analog
model. The stacking model predicts that non ortho substituted (coplanar)
PCBs will show dioxin like properties, whereas ortho substitution is usually
not associated with dioxin like toxicity. Both the stacking and cleft
type models have indicated a structural relationship between some PCBs
and thyroid hormones. Some hydroxylated ortho substituted PCBs, which
are frequent PCB metabolites, show estrogen like activity in that they
can bind to estrogen receptors. Possible relationships between PCB structures
and their toxic endpoints were discussed and compared with those of chlorinated
diphenyl ethers. The reactivity of PCBs in terms of thyroxine and
estradiol equivalency was discussed. (McKinney et al, 1994)
Study Review #23
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PCBs are accumulated in the thyroid gland
Organic mercury compounds, polychlorobiphenyls, organochlorines
were examined as representative of hazardous substances which will attack
infants in different ways than adults. Although PCBs are not used directly
in connection with foodstuffs, like DDT, they are accumulated and concentrated
in the environment. Attention was first drawn to PCBs after 1,000 cases
of intoxication resulted from contamination of a cooking oil following
an industrial mishap. PCBs are found in the highest concentrations in the
sea, and are transferred gradually through the food chain. The safety dose
for man is 5 mug/kg/day, calculated with a safety factor of 100, the lowest
reported toxic dose was 14 times this amount. PCBs are accumulated primarily
in the fat, skin, adrenals, thyroids, and liver. Toxic inorganic mercurials
can be converted into more highly toxic methyl mercury by biological processes.
Repeated biological concentration has produced the relatively high concentrations
of mercury in ocean fish. The total body mercury content is correlated
with the concentrations in hair, blood, and erythrocytes, and much of the
methyl mercury accumulates in the erythrocytes. The minimum toxic level
in Minamata disease was calculated as 5 mug/kg, indicating that man is
more sensitive to mercury than monkeys. Uptake below the range of elimination
(half life, 70-74 days) will not result in Minamata disease. Complete recovery
of toxic metals from waste water is necessary. (Ito, 1977)
Study Review #24
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hydroxylated PCBs may decrease thyroid hormone levels
-
60% of 65 other industrial chemicals (mostly pesticides)
also interfered with thyroid hormones (so humans face combined impacts)
Previous results in experimental systems have suggested that
hydroxylated PCBs may decrease thyroid hormone levels through associative
interaction with transthyretin. In the present paper it was investigated
whether this property was also shared by various industrial chemicals,
mainly pesticides. In total, 65 compounds from 12 chemical groups were
analyzed for direct interference with the T4 binding site of transthyretin
using a competitive binding assay. Sixty per cent of the compounds were
competitive at a concentration level of 100 muM. Relatively strong interactions
were observed by several chlorophenols, chlorophenoxy acids and nitrophenols,
as well as by individual compounds such as hexachlorobenzene, dicofol,
bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups,
e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil,
also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased
plasma TT3 levels. The resu (incomplete abstract) (Van Den Berg et al,
1991)
Study Review #25
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subclinical effects may be present in the background population
of humans
The developmental effects of polyhalogenated aromatic
hydrocarbons (PHAHs) were reviewed. Several mechanisms of action of
PHAHs have been reported. These have included enzyme induction or inhibition,
interaction with cellular receptors, and metabolic alterations. One of
these actions, binding to the cellular arylhydrocarbon (Ah) receptor resulting
in protein induction and altered gene expression, has received particular
attention. Ah receptor binding is also characteristic of hormones as well
as tetrachloro-dibenzo-p-dioxin (TCDD) which has been known to mimic, block,
and modulate hormonal actions. TCDD as well as other Ah receptor ligands
have been reported to be potent developmental toxicants. In addition, TCDD
has been found to impair reproduction and fertility. Evidence has suggested
that these effects of TCDD as well as those of other polychlorinated
biphenyls appear to be mediated via the Ah receptor. Several effects
reported to be associated with exposure to PHAHs have recently been linked
to changes in thyroid hormone levels. Epidemiological studies have suggested
that dioxin has adverse effects in highly exposed populations and that
subclinical
effects may be present as well in the background population. The author
concludes that the developmental toxicity of dioxin and related compounds
appears to be related to a complex series of alterations involving multiple
endocrine systems. (Birnbaum, 1995)
Study Review #26
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organochlorine compounds (such as PCBs) are associated with
abnormal thyroid function
The developmental effects of endocrine system disrupting
chemicals in the environment on wildlife and humans were discussed. Numerous
endocrine system disrupting chemicals have been released into the environment
since World War II. Exposure to these chemicals has been associated with
abnormal
thyroid function in birds and fish; decreased fertility in birds, fish,
shellfish, and mammals; decreased hatching success in fish, birds, and
turtles; demasculinization and feminization of male fish, birds, and mammals;
defeminization and masculinization of female fish, gastropods, and birds;
and alterations of immune function in birds and mammals. The effects of
DDT and polychlorinated biphenyls on the reproductive system of bald-eagles
were mentioned as examples of these effects. The diethylstilbestrol (DES)
syndrome was discussed as an example of the consequences of environmental
exposure to estrogenic chemicals in humans. DES exposed humans provide
a model for exposure during early life to estrogenic chemicals, including
environmental pollutants, that are estrogen agonists. Daughters of women
who took DES in the 1960s have suffered reproductive organ dysfunction,
abnormal pregnancies, increased infertility, immune system disruption,
and depression. When they reached adulthood, they sustained a significant
increase in the incidence of vaginal clear cell adenocarcinomas. The general
characteristics of endocrine system disrupting chemicals were discussed.
Such chemicals include a number of polychlorinated biphenyls, dioxins,
DDT, other organochlorine compounds, and industrial chemicals. Most of
them are not mutagenic or acutely toxic at concentrations typically encountered
in the environment. The adverse effects stem from exposure during prenatal
or early postnatal life and the ability of the chemicals to be stored in
the body fat until being mobilized during egg laying or pregnancy and lactation.
(Colburn et al, 1993)
Study Review #27
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PCBs, dioxins and furans are associated with disease of the
thyroid
The mechanisms of various industrial toxins in causing disease
of the thyroid, testes, ovary and pancreas are reviewed. Toxins
include: polyhalogenated biphenyls, polyhalogenated dibenzodioxins
and dibenzofurans, organochlorine pesticides, polycyclic aromatic hydrocarbons,
hydroxyphenols and hydroxy pyridines, phthalates, lithium, iodine and radiation.
The importance of medical surveillance in the workplace is emphasized in
the light of the increasing numbers of women in industry and the associated
potential reproductive risks. (Barsano, 1992)
Study Review #28
-
thyroid hormones may play a role in oxidative DNA damage
which leads to cancer
-
PCBs are implicated in tumor (cancer) induction as an indirect
result of oxidative DNA damage
The importance of oxidative DNA damage in inducing tumors
following exposure to tumor promoting agents was examined in this review.
Intracellular reactive oxygen species that have been identified as the
most probable causes of oxygen stress were explored and studies on the
nature and properties of the products of DNA oxidation were reviewed. Single
and double strand breaks, modified bases, and the formation of deoxyribose
radicals have all been described following exposure to genotoxic substances.
The role of oxidative damage in the actions of presumed nongenotoxic carcinogens
such as transition metal ions, metabolic products of lipids, natural processes,
radiation, polyhydroxyphenols and quinones, and peroxisome proliferators
was discussed. Reports have implicated natural processes such as inflammation,
metals such as chelated iron (7439896), trivalent chromium (7440473), magnesium
(7439954) ion, and miscellaneous agents such as high energy radiation,
polyhydroxyphenols and quinones, alcohol, 4-nitroquinoline-1-oxide (56575),
choline deficiency, methapyrilene (91805), and Aroclor (PCBs) in
tumor induction as an indirect result of oxidative DNA damage. Similarly,
it has been proposed that the induction of oxidative DNA damage may be
involved in the actions of known tumor promoters. Studies have also supported
the role of products of lipid metabolism in inducing proliferation of hepatic
peroxisomes and the enhancement of peroxisomal and mitochondrial enzymes
as well as a direct action of peroxisome proliferators in inducing oxidative
DNA damage. In addition, evidence exists that thyroid hormones may play
a role in oxidative DNA damage mediated carcinogenesis. The authors
conclude that oxidative DNA damage plays a role in the development of cancer
in humans and animals. (Clayson et al, 1994)
Study Review #29
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common food poisoning symptoms include thyroid function changes
As compounds, nitrites, polychlorinated biphenyls -PCBs,
food additives, sodium glutamate, harmful metals contained in food containers,
N-nitrosoamines and radiation contained in processed foodstuffs mostly
affect humans. The most common food poisoning symptoms include decreased
appetite, anemia, skin rash and pigmentation, diarrhea, blood pressure
changes, nausea, headache and liver and thyroid function changes.
(incomplete abstract) (Miyaki et al, 1973)
Study Review #30
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new legislation requires EPA to test chemicals for anti-thyroid
activities and effects on steroid/thyroid hormone synthesis
Anthropogenic chemicals that disrupt endocrine function during
critical stages of development can produce profound reproductive alterations
in both wildlife and humans. Of the tens of thousands of chemicals in existence,
few have been tested for their ability to disrupt the endocrine system.
Newly enacted legislation requires that the USEPA develop a chemical screening
and testing program for endocrine effects. At present, the Endocrine Disrupters
Screening and Testing Advisory Committee (EDSTAC) is considering a screening
battery (Tier 1) to detect (anti)estrogenic (E) (anti)androgenic (A) and
antithyroid
activities using in vivo and in vitro assays. In addition, the battery
should detect alterations of hypothalamic-pituitary function,
steroid/thyroid
hormone synthesis as well as receptor-mediated effects in mammals and
other taxa. Chemicals positive in Tier 1 should be labeled as potential
endocrine disrupters and subjected to testing (Tier 2). The present discussion
(incomplete abstract) (Gray, 1998)
Study Review #31
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dioxin in breast milk may affect infants’ thyroid function
The developmental effects of dioxin are important because
of the high sensitivity of mammals as well as the irreversibility and longevity
of the effects. In animal experiments, exposure to dioxin during pregnancy
and lactation induce various functional effects on offspring at very low
doses. In humans, even if there is no exposure to dioxin after birth, there
might be effects on thyroid function in infants exposed to dioxin from
breast milk. In this report, low-dose developmental effects of dioxins
on offspring in animal experiments and human studies were reviewed. In
terms of risk assessment, methods to describe dosimetry, models to describe
dose-response and approaches to express health risk are discussed. (Yonemoto,
2000)
Study Review #32
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more studies of thyroid functionality are needed, because
human exposure to PCBs is inevitable
Studies involving endocrine effects in humans and experimental
animals resulting from the exposure to dioxin-like (non-ortho-substituted
PCBs, PCDDs/PCDFs) and nondioxin-like (PCBs, OC pesticides) compounds (DLCs
and NDLCs) were presented. A variety of reproductive and hormonal parameters,
including androgen status, sexual differentiation, and thyroid functionality,
were discussed. As in utero and lactational exposure of the human fetus/neonate
to these environmental contaminants is inevitable, continued research to
identify sensitive biomarkers of effect and susceptibility, as well as
to define dose-response relationships, is required. (Feeley 1995)
Study Review #33
-
alterations in neurotransmitter systems and thyroid function
may underlie behavioral dysfunction
Nine participants outlined findings in the area of neurobehavioral
effects of dioxin-like compounds and presented plans for new studies. Neurobehavioral
effects are among the most sensitive and well studied toxicity end points
for this class of compounds. A focus of the workshop was presentation of
designs for major new studies in human populations outside the United States
that are intended to extend and clarify the results of two previous large-scale
studies in populations in Michigan and North Carolina. Improved methods
for exposure assessment and more focused approaches to understanding specific
neurobehavioral deficits were highlighted. Animal studies and in vitro
mechanistic studies are emphasizing the importance of alterations in
neurotransmitter systems and thyroid function that may underlie behavioral
dysfunction. There is continuing improvement in analytical and study
design methods to identify the most active congeners of PCB mixtures in
the environment. These diverse studies will contribute to effective response
of public health and regulatory groups to this continuing problem. (Golub
et al, 1995)
Study Review #34
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hexachlorobenzene correlates with thyroid cancer --- [hexachlorobenzene
is closely related to certain PCBs]
Unusually high levels of hexachlorobenzene (HCB) were detected
in the air and in sera of volunteers of a village located in the vicinity
of an organochlorinated-compounds factory (Flix, Catalonia, Spain). A significant
increase for specific causes of death was obtained only for neoplasms of
unknown origin. However, an excess of incident cases was observed for thyroid
neoplasms, soft-tissue sarcoma and brain neoplasms in men. These descriptive
findings are in agreement with previously reported associations between
soft-tissue sarcoma and human exposure to organochlorinated compounds,
as well as with animal experiments relating HCB and thyroid cancer,
and add new information on the possible relation between organochlorinated
compounds, and particularly HCB, and cancer. (Grimalt et al, 1994)
Study Review #35
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PCBs and dioxins reduce circulating thyroid hormone levels
Polychlorinated biphenyls (PCBs) and dioxins are widespread
environmental contaminants that are suspected of causing cognitive deficits
in children exposed in utero. Very little is known about which of the PCB
and dioxin congeners present in the environment are responsible for the
changes in cognitive function or about the mechanisms through which these
chemicals affect the central nervous system (CNS). Because both PCBs
and dioxins reduce circulating thyroid hormone levels, it has been
proposed that these chemicals may affect CNS function indirectly by reducing
the availability of thyroid hormone to the brain during development Thyroid
hormones play a critical role in brain development, and spatial learning
and memory is one of the behavioral functions most severely affected by
neonatal hypothyroidism. In the studies reviewed here, we investigated
the effects of three ortho-substituted PCBs, two coplanar PCBs and 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) on spatial le (incomplete abstract) (Schantz et al, 1997)
Study Review #36
-
PCBs cause blood-level alterations and affect the circadian
rhythm
This paper reviews endocrine effects of chemicals and physical
agents in man, in laboratory animals and in in vitro experiments. Effects
on the hypothalamus, pituitary, pineal gland, thyroid, parathyroid
and calcium metabolism, adrenal glands and glucose metabolism are discussed.
Metals (lead, manganese, cadmium, organotin compounds), solvents (benzene,
dioxane, styrene, tetrachloroethylene, toluene), organochlorine compounds
(PCB, TCDD) and physical agents were shown to cause blood-level
alterations and affect the circadian rhythm. Diabetes mellitus might
arise as a result of occupational exposure or heighten the susceptibility
to occupational diseases. (Baccarelli, 1999)
Study Review #37
-
thyroid function is detrimentally impacted by chemical exposures
Many environmental and occupational agents have been shown
to cause detrimental effects on endocrine function and growing scientific
evidence supports the hypothesis that such alterations may produce serious
consequences for health. Although those chemicals mimicking (or contrasting)
estrogenic or androgenic actions have raised great concern, the relevance
of disruption of other hormonal pathways is not negligible. This article
reviews the effects of chemical and physical agents on the hypothalamus-pituitary
unit, pineal gland, thyroid, parathyroid and calcium metabolism,
adrenal glands, and glucose metabolism. Metals (Pb, Mn, Cd, organotin compounds),
solvents (benzene, dioxane, styrene, tetrachloroethylene, toluene), organochlorines
(PCBs, TCDD), and physical agents have been shown in human, animal
or in vitro studies to cause alterations of the blood levels, and of the
activity or circadian rhythm of pituitary hormones. Melatonin has been
proposed as the link between environmental/occupational fac (incomplete
abstract) (Baccarrelli, 1999)
Study Review #38
-
thyroid function is adversely affected by certain man-made
chemicals
Reports of decreased semen quality and increased rates of
developmental abnormalities of the male reproductive tract along with increasing
incidence of testicular cancer have focused attention on man-made chemicals
as potential causative factors. A biologically plausible hypothesis has
been advanced which suggests that man-made chemicals act as endocrine disruptors
through interaction with the estrogen receptor resulting in altered development
of the reproductive tract. Available evidence suggests that this mechanism
may play only a minor role in the purported adverse effects described to
date. Man-made chemicals, however, may induce adverse health effects through
mechanisms independent of the estrogen receptor. Indeed, man-made chemicals
have been shown to induce adverse effects on thyroid function and
androgen-dependent processes in animal studies. Hence the focus on estrogenic
mimics may be too simplistic and alternate mechanisms could be more relevant
due to target gland exposure levels and potency of the toxicant. Before
it can be concluded that man-made chemicals pose little or no risk to the
development of the reproductive tract in the fetus and children it will
be necessary to, at the very least, insure that: 1) exposure scenarios
include the most sensitive developmental stage, 2) all endocrine targets
have been evaluated for potential effects, and 3) the role of environmentally
and biologically relevant levels of chemical mixtures in adverse health
outcomes have been evaluated. Due to potential for exposure, sensitivity
of the developing reproductive tract, suggestive evidence of a possible
role of man-made chemicals in developmental abnormalities of the reproductive
tract, and the many outstanding research questions, it is concluded that
there is sufficient cause for concern. (Foster, 1998)
Study Review #39
-
PCBs have known or suspected adverse effects on the human
thyroid
-
need to investigate the potential harm posed by these factors
in the quantities commonly encountered (1981)
Chronic ingestion of modest doses of dietary iodine, radiation,
and polyhalogenated biphenyls (PCB's and PBB's) are environmental
factors with known or suspected adverse effects on the human thyroid.
Iodine consumption in the United States is approaching 1 mg daily for a
large segment of the population. Data are reviewed which support the need
for concern regarding the long-term adverse effects of dietary iodine on
thyroid function, particularly in certain susceptible individuals. Environmental
sources of radiation pose a significant risk of thyroid cancer and hypothyroidism
under certain circumstances which may be intentional, inadvertent, or accidental.
Exposure to polyhalogenated biphenyls during manufacture or as industrial
pollutants are hazardous to man and to wildlife in moderate or large quantities
and perhaps also in small amounts. The need to investigate the potential
harm posed by these factors in the quantities commonly encountered
is emphasized. (Barsano, 1981)
Study Review #40
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Current evidence has not suggested that PCB exerts an important
influence on thyroid function. (1974)
PCBs are produced in the United States under the trade names
of Aroclor 1232, 1242, 1248, 1254, and 1260, and in Japan under the names
Kanechlor-200, -300, -400, -500, and -600. PCBs are transported in the
environment in several ways including dumping, vaporization, and leakage.
Residue levels in various species in Europe, North America, the Caribbean,
Japan, and the southern hemisphere are discussed; substrates include plankton;
fish; sea birds such as herring gulls and brown pelican; marine mammals
such as the ringed seal, harp seal, hooded seal, grey seal, bearded seal,
harbor seal, bottle-nosed dolphin, common dolphin, surinam dolphin, harbor
porpoise, sea lion, finback whale, and pilot whale; birds of prey; and
humans and human food. The physiological effects of PCBs are considered
mainly on a class-by-class basis. Acute toxicity is considered for mammals,
birds, fish, and insects. Liver morphological changes have been studied
extensively. A widely studied effect of organochlorine compounds is the
induction of hepatic microsomal enzymes in mammals. The effects of these
chemicals on mammalian reproduction are reviewed. Avian reproduction is
considered in the light of eggshell thickness, egg production and hatchability,
specific effects on the male of the species, and teratogenic effects. The
geometric similarity of DDT and PCBs to the synthetic estrogen, stilbestrol,
has led to examination of the possibility that chlorinated hydrocarbons
could act as synthetic estrogens. Current evidence has not suggested
that PCB exerts an important influence on thyroid function. DDT has
caused an increase in liver vitamin A levels, but comparable studies with
PCBs are not available. Carcinogenic studies are as yet very few. Some
effects of PCBs on immunosuppressive mechanisms have been reported. Hydropericardium
and generalized edema, porphyria, inhibition of adenosine triphosphatase,
physiological effects on microorganisms, and the effects on non-human primates
are also reviewed. (Peakall, 1975)
Study Review #41
The PCBs are members of the halogenated hydrocarbon class
of environmental chemicals that includes the dibenzofurans and dioxins.
The PCBs were used over a period of 40 years for number of industrial purposes.
Their appearance in the ecosystem and biological samples from wildlife,
as well as documented cases of accidental poisoning led to the banning
of their manufacture in 1977. The PCBs continue to be of concern to environmental
toxicologists because of their persistence in the environment and reports
that exposure to relatively low levels may be associated with subtle behavioral
and neurological deficits, particularly if exposure occurs during development.
Developmental neurotoxicity of PCBs has been reported in humans and confirmed
in several laboratory animal species, including non-human primates. During
the last 20 years, there has been an attempt to understand the cellular
bases of PCB-induced behavioral and neurological effects in animal models.
Exposure of adul (incomplete abstract) (Tilson et al, 1997)
Study Review #42
As part of an epidemiologic study on exposure to a toxic
waste incineration plant we investigated whether blood concentrations of
polychlorinated biphenyls (PCBs), lead, and cadmium, as well as concentration
of mercury in 24-hr urine samples were associated with thyroid hormone
status. As an indication of status, we determined levels of thyroid-stimulating
hormone (TSH), free thyroxine (FT(4)), and free triiodothyronine (FT(3))
in children living in households where [less than/equal to] 10 cigarettes
were smoked per day. Eight PCB congeners (PCBs 101, 118, 138, 153, 170,
180, 183, and 187) were measured in whole blood samples. Of these, seven
congeners (PCB 101 was not detected in any sample) and the sum of all PCB
congeners were analyzed as predictors for thyroid hormone status in separate
linear regression models adjusted for potential confounders. In addition,
the possible effects of cadmium, lead, and mercury on levels of thyroid
hormones were examined. Blood concentrations and information on que (incomplete
abstract) (Osius et al, 1999)
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