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Lecture

CHEM 1500 Lecture Notes - Endocrine Disruptor, Nerve Growth Factor, Testicular Cancer


Department
Chemistry
Course Code
CHEM 1500
Professor
d

Page:
of 3
Chapter 9: Environmental Endocrine Disruption:
Some chemicals unintentionally interfere with hormone function in animals and in
some cases in humans.
A wave of interdisciplinary research over the past few years has been demonstrated
that chemicals in our environment can interfere with endocrine function.
In adults the endocrine system exhibits the ability to recover from fairly significant
perturbations, in the fetus even minor change in hormone levels can result in
lifelong effects.
Historical background:
A study in laboratory animals have demonstrated that estrogenic properties of a
number of industrial chemicals including bisphenol A, now widely used in plastics,
resins and dental sealants.
Hormonally active chemicals are widely used for beneficial medical purposes, but
adverse effects also occur.
Diethylstilbestrol (DES) daughters have an increased risk of reproductive and
immunological abnormalities, while sons are at risk of genital anomalies and
abnormal spermatogenesis.
Examples of DES indicate that fetus rather than the adult may be most at risk from
adverse effects of hormonal disruption.
Mechanisms of Action and Fetal Vulnerability:
Some pesticides and other industrial checmicals can directly bind to or block
hormone receptors, thereby initiating or blocking receptor-activated gene
transcription—the production of protentis from genetic information.
Other environmental chemical act indirectly on hormonal balance by altering
hormone production, hormone transport on hormonal balance by altering hormone
production, hormone transport on binding proteins, receptor numbers on target
organs or hormone metabolism.
Polychliroinated biphenyls (PCBs) interfere with thyroid function by a variety of
mechanism, including increased metabolism of the thyroid hormone T4., interfere
with T4 delivery to the developing brain by displacement from the carrier protein
and interfere with the conversion of T4 to the active form of thyroid hormone
known as T3.
During development, the fetus is more sensitive to hormonal fluctuation.
Low level exposure to hormones or toxicants may result in permanent physiological
changes not seen in adults exposed at similar levels.
Subtle hypothyroidism during fetal and neonatal life causes disruption of
neurotransmitters, nerve growth factors, nerve cell growth and normal energy
production in the developing brain, altering cognitive and neuromotor development.
Potential Health implications:
Reported abnormalities in labortoary animals and wildlife exposed to endocrine-
disrupting chemicals include feminization of males, abnormal sexual behaviour,
birth defects, altered sex ratio, lower sperm density, decreased testis size, altered
time to puberty, cancers of the mammary glands or testis, reproductive failure, and
thyroid dysfunction.
Epidemiological studies have found associations between exposure to specific
pesticides or industrial chemicals and thyroid stimulating hormone, testosterone and
prolacting levels in adults.
Some of these studies have also found signifincant association with other relevant
endpoints including diminished sperm quality, impaired sexual function, and
testicular cancer.
Numerous studies have found associations between occupational solvent or
pesticide exposure and subfertility or adverse effects on offspring but its not clear if
its because of endocrine mechanism.
Some case control studies have shown increased risk of cryptorchidism
undescended testicles and hypospadias ( a birth defect of the penis) among the
songs of the farmers and of women gardeners exposed to pesticides.
Hormones and neurobehavioural effects:
Exposure to certain environmental pollutants has been associated with learning and
behavioural abnormalities following parental or early postnatal exposures
Beyond endocrine distruption: other signalling pathways:
The structural and functional development of the brain is dependent on integration
of the actions of hormones, neurotransmitters, neurotrophins and locally produced
steroids.
Recent study has demonstrated that in the developing brain, neurotransmitters
perform frwoth regulatory functions.
Policy implications:
Detecing health effects due to exposure to endocrine distrupting chemicals is
difficult and will continue to pose substantial challenges.
The international Joint commission and the POPs Treaty:
The internnaional joint commission IJC has taken a leadership in defining a
“persistent toxic substance” and targeting such chemicals for elimination.
IJC advocated a weight of evidence approach to the indentification of substances
that may cause harm.
The commission linked persistent toxic substances, particularly organochorlines, in
the great lakes to injury disease and death in variety of life forms including humans.
The science advisory board SAB of the IJC found tht the class of chlorinated
organics tends to exhibit persistence and toxicity and that evaluating and regulating
these substances on a chemical by chemical basis is impractical and unscientific.
The SAB recommended, therefore that organochlorines be treated as a class and be
subject to phaseout, expect in individuals cases in which the weight of evidence
supports the view that a chemical does not threaten health and the integrity of
ecosystem.
Framework recognizes that the effects of chemicals on health and ecosystem is
complex, that cause and effect relationship are often difficult to establish with
certinity, but that incontrovertible proo of causual link between indivudal chemicals
and indivudal effect is not a reasonable standard since the substances exist as
mixutues in the environment and produce complex effects.
The
IJC has laid out an approach intended to protect human health and environment
from harm, while recognizing the limits of science and acknowledgeing the
difficulties inherent in reducing scientific uncertnitiny in complex systems.
The Stockholm convention is an important part of the effort to reduce human
exposures to endocrine distrupting chemicals.
Screening, testing and tracking:
The U.S envrionemtnal protection agency and the organization for economic
cooperation and development are developing screening and testing programs to
evaluate the effects of a variety of environmental chemicals on estrogen, androgen
and thyroid hormone function.
Improved monitoring of disease and exposure is essential for tracking trends in
subtle, delayed effects of environmental exposures.
A science based prectionary approach is a traditional part of medicine and public
health.
Public health practitioners have historically worked to prevent adverse health
effects through education and practical exposure reduction whenever feasible.
Because many endocrine distruptors are environmentally persistent and can travel
great distances in air and water currents an international perspective is cirtical to
success.