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Hormonally
Active Agents (HAAs) is the name the committee gave to the class
of chemicals that were covered in the report. The committee focused
its attention on synthetic chemicals found to have hormonal activities
such as estrogens, antiestrogens and antiandrogens. These are chemicals
that have been reported to induce reproductive and developmental
defects, neurobehavioral abnormalities, immunologic deficits, carcinogenesis
and ecologic effects.
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- In
its report, the NRC sought to identify chemicals with hormonal
activity. Hormone disruptors include chemicals that act
by other pathways, or for which the mechanism is unknown.
- The
panel's review was largely limited to the sex steroid hormones,
estrogen and testosterone. The committee chose not to report
on chemicals that interfered with other hormonal systems
(such as the thyroid or adrenals), primarily because the
literature on these effects was quite limited when the committee
began its review in 1994. Increasingly, however, it has
become clear many other hormone systems are vulnerable to
disruption by HAAs.
- The
committee noted that a lack of knowledge about how a chemical
affects humans and wildlife does not mean that a reported
effect is unconfirmed or unimportant
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The
NAS committee was not able to consider most of the literature that
was published after June 1997 even though its report was not published
until August 1999. This was unfortunate, because many
new and revealing studies were published during that period. Among
other advances, literature that appeared in recent years suggests
that currently used pesticides, as well as chemicals commonly used
in consumer products (such as phthalates, phenols and flame retardants)
are also HAAs. |
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What
does the report say about exposure of humans and wildlife to HAAs?
Wildlife and people in most of the world carry contaminants at levels
known to produce effects in the laboratory.
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- The
report states that, "Many of the HAAs are relatively persistent
chemicals, and therefore, exposure to one or several of
them is virtually guaranteed for most organisms".
- Moreover,
humans are almost universally exposed. In fact, the report
continues, "More than 95% of all the U.S. population had
detectable concentrations of PCBs, regardless of age, sex,
race or geographic location." "Although the concentrations
were found to be greatest in older people, even children
were not immune from exposure" "5.1% had concentrations
greater than 3 ppm."
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What
does the report say about effects on wildlife? The report demonstrates
clear evidence from wildlife showing endocrine disrupting effects:
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- As
the report states, "Many wildlife studies show associations
between reproductive and developmental anomalies and exposure
to environmental contaminants, some of which are HAAs"
- These
demonstrable, replicated effects include impacts on reproduction,
behavior and immune system function. "Reported reproductive
disorders in wildlife have included morphologic abnormalities,
eggshell thinning, population declines, impaired viability
of offspring, altered hormone concentrations, and changes
in sociosexual behavior."
- Overall,
the NAS committee concluded, "Laboratory studies illustrate
that exogenous exposure to several HAAs (e.g., DDT, methoxychlor,
PCBs, dioxin, bisphenol A, octylphenol, BBP, DBP, chlordecone
and vinclozolin) during critical periods of development
can interfere with normal reproductive development."
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What
does the report say about HAAs and human cancer? The cancer risk
to humans from HAAs has been studied for only a few chemicals. Moreover,
except for DES, extensive human cancer studies have been limited to
adult exposures. This leaves the questions of how these chemicals
may affect children, or how they affect adults who were exposed in
the womb, still unanswered. This is a huge gap in the research literature,
because of the DES experience and because of the possibility for several
cancers that errors in cell replication laying the groundwork for
cancers later in life actually take place during fetal differentiation,
i.e., in the womb.
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- "No
studies have been conducted to examine associations between
risk of any cancer and exposure to any HAAs during development,
particularly during fetal life." Until sampling is done
throughout development, the associations between HAAs and
cancer in humans cannot be ruled out.
- The
report notes, "The data that exist for evaluating the postulated
relationships between HAAs and human cancers are mostly
limited to studies involving exposure to DDT, DDE, TCDD
, and various PCBs. Other compounds with potential hormonal
activity have received little attention. Furthermore, exposure
to HAAs and their possible effects during susceptible periods
such as fetal life or pregnancy and transgenerational effects
have not been evaluated in human studies."
- "The
committee agreed that lack of evidence could not be taken
as an indication that a proposed process does not operate."
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What
does the report say about other health effects? Research on human
health effects is still in its infancy, but studies are beginning
to reveal effects as well as trends in human health data that are
consistent with predictions based upon laboratory experiments with
HAAs in animals.
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- For
example decreased ano-genital distance in exposed animals
predicted an increased risk of the birth defect hypospadias
in humans. The
rate in humans was found to have doubled over the past
twenty years. (Hypospadias is a malformation of the penis
in which the opening of the urethra is found on the underside
instead of at the tip.)
- PCBs
have been shown to influence neurological development in
animals. The report found consistent correlations in people
between prenatal exposure to PCBs and cognitive deficits.
"Studies of cognitive
development .show consistent correlations between prenatal
exposure to PCBs and deficits at up to 11 years of age."
- PCBs
in the maternal diet have been linked to developmental effects,
in particular, birth weight and growth.
- The
report notes that multinational
trend studies support a downward trend in mean sperm
concentration. The report goes on to note that this may
be confounded by local geographic variation.
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How
are these findings likely to affect policy makers and regulators?
The report contains several important conclusions that will present
significant challenges to risk assessment as it is currently practiced:
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- Effects
of HAAs in wildlife and laboratory animals have been shown
to occur at levels that are millions of times lower than
the traditional range at which toxicological studies are
conducted.
- "Endogenous
hormones can be active at concentrations as low as picograms
per milliliter in the blood." Only recently has the technology
permitted scientists to measure contaminants at these levels.
- Laboratory
data suggest that higher doses do not necessarily result
in greater effects. Some chemicals do not behave as traditional
toxicology would predict; their dose-response curves are,
in fact, nonlinear. In other words, the report says, "Biological
responses to some HAAs might be greater at lower doses than
at higher doses."
- For
the developing fetus, there is no safe dose. The report
notes the unique risks to the developing fetus and addresses
effects related to the timing of prenatal exposures.
- People
experience HAAs in complex mixtures, but few mixtures have
been studied. The report states; "The committee recognizes
that wildlife and humans are exposed to complex mixtures
of chemicals and that interactions between chemicals in
mixtures cannot always be predicted by examining each chemical
individually."
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