Bisphenol A
Kimberly Neild
142 Main Street
Broad Brook, CT 06016
(860) 627-8316
Banner ID# 01128276
Paper written for BIO122: General Biology II
Professor Pamela McManus
17 April 2008
Bisphenol A
INTRODUCTION
Bisphenol A [BPA; HO-C6H4-C(CH3)2-C6H4-OH] is a monomer that was
originally synthesized as a synthetic estrogen, but was later found to be valuable because
of its cross-linking abilities with other chemicals. Today, BPA is used to manufacture
plastic polymers and epoxy resins mostly for use in food and beverage containers and
dental sealants (Alonso-Magdalena et al. 2006). It is one of the most abundant chemicals
produced worldwide and had a global capacity in 2003 of greater than 6.4 billion pounds
with a 6-10% growth expected per year (vom Saal et al. 2005).
Because of the widespread use of BPA in polycarbonate plastics as well as in the
linings of cans, humans are continually exposed to this chemical, especially in developed
countries (Calafat et al. 2005). This is significant for two reasons. First, contact with
foods and beverages, especially those that are acidic or basic or have been heated, has
been shown to cause leaching of BPA (vom Saal et al. 2005). Second, BPA is a known
endocrine-disrupter (vom Saal et al. 1998), meaning that it has the ability to interfere with
many of the functions that our endocrine system performs because it can mimic estrogen.
It has been demonstrated in numerous studies that BPA causes adverse effects in
laboratory animals even at very low doses (vom Saal et al. 2005). Based on this
knowledge, it is reasonable to assume that BPA is capable of causing damage to the
normal balance within the human body, as well. Here I present the evidence concerning
the presence of bisphenol A in our environment; how it enters our bodies and why; and
the effects on the reproductive systems of mice that it has been linked to.
Migration
The movement of a chemical from one substance into another that it has come in
contact with is called migration. It is well known that when plastic is manufactured using
bisphenol A as a monomer, the ester bonds created in the polymer are vulnerable to
hydrolysis, especially under certain conditions. This means that the plastic begins to
break down, leaving the monomers of BPA to accumulate in the substance that the plastic
is in contact with (vom Saal et al 2005). There have been several experiments done
recently that have tested the concentration of BPA in baby bottles, food storage cans, and
water bottles (both for use by people and laboratory animals) (Brede et al. 2003;
Consumers Union 1999; Goodson et al. 2004; Howdeshell et al. 2003). In general, the
experiments were performed with a goal of testing if the migration level of BPA
increased, decreased or remained the same if the environmental conditions were altered.
It has been found that the migration levels of bisphenol A into food and water
increased with high heat, acidic or basic contents, and increased age and usage of the
plastic products (Brede et al. 2003; Consumers Union 1999; Goodson et al. 2004;
Howdeshell et al. 2003; Kang et al. 2003). These findings are significant because of the
widespread usage of products containing BPA. It is found in the plastic linings of food
and beverage cans, in dental sealants, and in any polycarbonate plastic, including
Nalgene water bottles and clear plastic baby bottles (Calafat et al. 2005). In most cases,
if a plastic is labeled as a number “7” on the bottom, it is a polycarbonate plastic which
contains BPA.
Exposure to bisphenol A
Given that bisphenol A is found widely throughout the environment of developed
countries, it is no surprise that it can be found in measurable concentrations in our bodies.
One study conducted in the United States found BPA in 95% of the urine samples that
were tested (Calafat et al. 2005). According to this same study, these levels corresponded
with previous studies done in other countries, including Japan and Southeast Asia. These
findings confirm that BPA is leaching into our food and water.
Another study has shown that BPA is metabolized in the body and is excreted in
urine within 24 hours after being administered (Volkel et al. 2002). This knowledge,
combined with the more recent urine testing, has led scientists to believe that our
exposure to BPA is greater than we realized previously (vom Saal et al. 2005). In order
for BPA to be detected reliably in human urine, we must be ingesting it regularly from
multiple sources.
Endocrine-disrupting chemicals
Bisphenol A is one of many chemicals known to interfere with the endocrine
system of humans and other animals. They are collectively referred to as “endocrinedisrupting” or “hormonally active” chemicals, meaning that they attach to the same
receptor sites as normally produced hormones in our bodies (vom Saal et al. 1998). This
means that if an endocrine-disrupting chemical is present in the body, it will bind to the
receptor sites, causing the effects of a hormone release. Except that it was not produced
from our own internal signals.
Specifically, bisphenol A is an endocrine-disrupting chemical that is able to bind
to estrogen receptors in the body. In adults, this characteristic of BPA is not as
detrimental as it is for a developing fetus or juvenile. Hormonal imbalances in an adult
can be noticeable and will certainly effect the functioning of certain processes, but only
while the endocrine-disrupting chemical is present in the body. In contrast, an animal
that is undergoing a key developmental period, such as while in the womb, is much more
susceptible to changes in the hormonal balance (vom Saal et al. 1998).
Effects of bisphenol A
In a study performed by researchers at the University of Missouri-Columbia to
determine the effects of bisphenol A on the reproductive organs of laboratory mice,
pregnant females were given two different doses of BPA (either 2 ppb or 20 ppb) for 7
days. After birth, the offspring were allowed to mature, and then the males were isolated
and randomly selected for testing (vom Saal et al. 1998).
It was found that the two doses had different effects on the mature male
offspring’s reproductive ability. The 2 ppb dose of BPA permanently increased the size
of the preputial glands by 35% in the mice; the preputial glands are responsible for the
sociosexual behaviors exhibited by males, specifically urine marking and aggressiveness
towards other males. Conversely, the same dose reduced the size of the epididymides, an
organ that stores sperm in male mice until maturation. It also decreased the size of the
seminal vesicles which contribute fluid to the ejaculate, and which have previously been
shown to be important to fertility in male mice. A possible explanation for this difference
is that these two organs develop from different embryonic tissues in mice. The
epididymides and seminal vesicles both develop from Wolffian ducts, while the preputial
glands develop from tissues in the embryonic urogenital sinus and perineum (other
organs which develop from these tissues include the prostate, penis, and scrotum). Both
the Wolffian ducts and the urogenital sinus and perineum contain estrogen receptors
during prenatal development in mice, and can therefore be affected by any abnormal
amounts of estrogen (vom Saal et al. 1998).
The 20 ppb dose of BPA significantly decreased the efficiency of sperm
production by 20% compared to the control group of males. In previous studies by the
same group of scientists, the prostate glands of male mice that were exposed prenatally to
either the 2 ppb or 20 ppb dose of BPA were increased by 30% compared to a control
group of males (vom Saal et al. 1998). Both of these results are significant when
compared with the effects of BPA concentration at 2 ppb because it proves that varying
the dosage also varies the effect on reproductive organs in male mice. It is not
necessarily true that the higher the dose, the worse the effect.
Traditionally, toxicology studies have been done based on what level of a
chemical causes gross abnormalities in a fetus. This level, once determined, would serve
as a starting point for finding the no-observed-adverse-effect-level (NOAEL). Once the
NOAEL was found, no studies were required to be done on lower doses (vom Saal et al.
1998). So even if a toxin is having an effect on normal embryonic development, as long
as we don’t observe those effects, there is nothing more to be done to regulate the
chemical. The amounts of BPA tested on the mice (2 ppb and 20 ppb) were much lower
than previous toxicology studies done, and the lowest dose of 2 ppb was lower than the
amount of bisphenol A that can migrate out of a dental sealant immediately following
application to the teeth in an adult human (vom Saal et al. 1998).
The findings of this study on bisphenol A’s effects on the reproductive organs of
male mice leads to the conclusion that if an endocrine-disrupting chemical that can mimic
estrogen enters the body, it can bind to estrogen receptors and interfere with normal
embryonic development. However, the results of this study are not ones that would be
apparent by observation of adult male mice. It was only through methodical testing in a
controlled environment that the effects on their reproductive organs were discovered. It
is highly possible that human infant development may be affected by BPA, but we
haven’t been able to measure it yet.
It is also important to note that even minor changes to the phenotypes of
individuals within a population can cause significant repercussions (vom Saal et al.
1998). Traits that are not in the best interests of the individuals will be selected against
over time, but this does not normally include changes caused by chemicals. A toxin that
does not differentiate between genotypes threatens the entire population and can affect
survivability and the ability to reproduce. In addition, as the population evolves over
time, it may no longer be able to survive in its environment. Tampering with natural
selection in any population can lead to trouble for the individuals and the entire
population. This is true for mice, humans, and all other creatures.
CONCLUSIONS
While the effects of bisphenol A continue to be researched and debated, the fact
remains that it is present in our environment. BPA migrates out of polycarbonate plastics
and can linings, and it has been detected in the urine samples of a majority of Americans
tested. It is a known endocrine-disrupter, and it has been shown to have negative effects
on the reproductive organs of mice. Other studies not covered in this paper indicate that
exposure to BPA is related to ovarian disease in women, prostate cancer in men, and
altered immune system function, just to name a few (vom Saal et al. 2005). Most of these
studies were done with lower doses of BPA than is considered a harmful level of BPA by
the U.S. Environmental Protection Agency.
The European Union has taken steps to protect its citizens by setting a “tolerable
daily intake” level of BPA, which directly affects plastic and food manufacturers. Food
manufacturers must prove that any plastic that comes in contact with foods does not
exceed the mandated migration limit of BPA (Brede et al. 2003). While this is not a
solution to the problem, it is acknowledging the danger to some extent. More studies will
need to be done to assess the effects of BPA on people and animals, but in the mean time,
it is better to err on the side of caution. The “safe dose” level of BPA that is acceptable
according to the U.S. EPA has not been adjusted to reflect the current research on BPA
(vom Saal et al. 2005). The U.S. EPA should follow the European Union’s example and
lower the “safe dose” level of BPA and begin widespread testing of food and beverages
manufactured and packaged in the United States. These steps are the minimum that we
can do to protect children while more research is done on the low dose effects of BPA.
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