Bisphenol A (BPA) is a chemical that is commonly used in the manufacturing of polycarbonate plastics and epoxy resins. It is a carbon- based synthetic compound that has the chemical formula (CH?)?C(C?H?OH)?. It is part of the group diphenylmethane derivatives and bisphenols. It contains two hydroxyphenyl groups. The effect that BPA has on humans and the environment has been brought into question because it is a reproductive, developmental and systemic toxicant for animals.
It is also slightly estrogenic. People are predominantly exposed to BPA through food packaging that is made using BPA, but it is also found in everyday objects including toys, medical equipment and dental monomers. Over 1 million pounds of BPA are released into the environment each year.
Standardized toxicity tests have been administered globally and have indicated that the levels that were found in humans and the environment were below levels that could cause potentially adverse effects. Several studies focusing on low doses have found subtle effects in laboratory animals at low concentrations. This is concerning for the environment because some of the concentration levels found during the experiment are close to the current environmental levels, which puts sensitive aquatic organisms at a high risk of adverse effects. This has led to many studies on the effects of BPA and methods of removal of BPA from the environment. In mammals, estrogen receptors modulate many physical processes. Chemicals that have features similar to those of estrogens can interact with estrogen receptors and create biological responses that are similar to those caused by natural estrogens in the body. BPA is a structural analogue of estrogen and has the ability to bind to estrogen receptors. BPA can be detoxified by the body and does not typically accumulate.
It is a topic of debate whether or not serum concentrations of BPA in humans can be high enough to affect the normal estrogen related functions. One study found that most BPA concentrations are orders of magnitude less than what could be measured by modern analytical methods. They also found that BPA concentrations were below those required to occupy more than 0.0009% of Type II Estrogen Binding Sites, GPR30, ER? or ER? receptors. These results found limited to no potential for estrogenicity in humans. They also questioned the reports of measurable BPA in human serum, stating that an accurate analysis of BPA in serum is almost unachievableIn one study conducted in 2005 by the Center for Disease Control (CDC), the researchers found BPA in 95 % of urine samples that were collected from 394 American adults and were tested using isotope dilution GC-MS. Other studies focused on the exposure level to children. Researchers studied the potential exposures at home and at daycare for nine children and found that the average BPA exposure level for the young children was 42.
98 ng/kg/day. Another study focused on 257 preschool children and found that BPA was detected in more than 50% of indoor air, hand wipe, and food samples. They found that 99% of the exposure for the children was due to diet, about 52-74 ng/kg/day. Health Effects of BPA on Adults In other studies the researchers focused on the health effects of BPA on adults, given that studies of the health effects of BPA on humans are very limited. Detectable BPA levels in the blood have been associated in women with conditions including obesity, endometrial hyperplasia, recurrent miscarriages, abnormal karyotypes and polycystic ovarian syndrome.
Three separate studies found connections between higher BPA exposure and health related impacts that could lead to chromosomal abnormalities. One study found that women carrying fetuses with abnormal karyotypes had higher BPA serum than those carrying fetuses with normal karyotypes. The only caveat about this study is the fact that maternal age was not controlled. Serum BPA Levels and Recurrent Miscarriages In a different study it was found that there is an association between serum BPA levels and recurrent miscarriages. In 45 women with a history of three or more consecutive first trimester miscarriages, they found mean BPA levels that were more than three times as high as the 32 women without fertility problems. Among 35 of the women that then became pregnant, there was some evidence of lower BPA in the women who had successful pregnancies as compared to the women who miscarried again. It is important to note that the median exposure levels of the two groups was identical and there were only a few women with high exposure levels.
Epidemiological studies like those have several limitations. The studies used small sample sizes, had limited detail relating to the subject selection criteria and limited control for potential confounders. Also, because of the design of the experiments it was impossible to determine if the BPA metabolism was a secondary effect due to the conditions that were examined in the studies. The impact of BPA is especially concerning in children. UDP glucuronosyltransferase is the primary phase 2 BPA metabolizing enzyme.
It is not present in the human fetus until after birth. This is concerning because during the fetal development and early postnatal life through adolescence, there are critical periods of organ development. Exposure to endocrine disrupting chemicals during this time could have permanent adverse effects. Although not tested on humans, it was found through rodents, primates and other species that unconjugated BPA easily diffuses across the placenta from the mother’s circulation and into the fetus. One study looked at the effects of BPA on CYP19 or aromatase, which is highly expressed in placental cells.
CYP19 catalyzes the conversion of estrogen from its precursors. In the study they focused on the effect of BPA in the transcription of CYP19 in JEG-3 cells. JEG-3 cells are human choriocarcinoma cells that have a long lifespan and high proliferation activity.
They found that the cells treated with BPA had reduced aromatase activity. Real time PCR was used to show that 5 µM of BPA significantly reduced the mRNA expression in the cells. The proximal promoter region of exon I.1 in placental cells controls the activity of the CYP19 gene. The promoter activity of the gene fragment and exon-I.
1 spliced mRNA abundance were also elevated. These results showed that BPA repressed the transcriptional control of promoter I.1.
The study found that BPA could potentially reduce estrogen synthesis by down regulating CYP of placental cells Another study took place to test omen with a history of infertility are at increased risk of impaired glucose tolerance during pregnancy. Studies suggest higher urinary bisphenol A (BPA) concentrations are associated with diabetes in nonpregnant populations, but the association between BPA and glucose levels among pregnant women is unclear. The purpose of the study is to assess trimester-specific urinary BPA concentrations in relation to blood glucose levels among subfertile women. The design for the study was: Environment and Reproductive Health Study, an ongoing prospective cohort study. The study took place at a fertility center in a teaching hospital. Patients: A total of 245 women contributed at least one urine sample during first and/or second trimesters, delivered a singleton or twin pregnancy, and had available blood glucose data (2005 to 2015). Main outcome measure: Blood glucose levels after a nonfasting 50-g glucose challenge test at 24 to 28 weeks of gestation.Results: The specific gravity-adjusted geometric mean urinary BPA concentrations during first and second trimesters were 1.
39 and 1.27 µg/L, respectively. Second-trimester BPA concentrations were positively associated with blood glucose (P, trend = 0.01). Specifically, the adjusted mean glucose levels (95% confidence interval) for women in the highest quartile of second-trimester BPA concentrations was 119 (112, 126) mg/dL compared with 106 (100, 112) mg/dL for women in the lowest quartile. No associations were observed between first-trimester BPA concentrations and glucose levels. Conclusion being: BPA exposure during the second trimester may have adverse effect on blood glucose levels among subfertile women.
As the findings represent the first report suggesting a potential etiologically relevant window for BPA and glucose in humans, further studies are needed.The purpose of another study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. This study was conducted in a fertility center in a teaching hospital. The study evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake.
The outcome was to measure live birth rates per every initiated treatment cycle measured. In the study, they found that soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03).
The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. In conclusion, it is safe to say that soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations.
Many other adverse health effects have been linked to exposure to BPA. Research on mice has found that prenatal exposure to BPA could potentially change the gross ovarian anatomy with a reduced number of corpora lutea. It could also lead to an increase in unilateral or bilateral blood filled ovarian bursae. This is particularly concerning since BPA has been found in the serum of maternal and fetal plasma. It has also been detected in placental tissue and breast milk. Other researchers have found that BPA exposure increases the aneuploidy in oocytes or meiotic disturbances in mice. Also, aneuploidy of the ovum has been connected to miscarriages.
This connection has also been seen in humans. One study involved the effect of BPA exposure in the reproduction of sheep. The study found that prenatal BPA treatment induced reproductive neuroendocrine defects, including Luteinizing Hormone (LH) excess and dampened LH surge as well as perturbed early ovarian gene expression. During ovulation an LH surge causes the egg to move through the ovary wall and begin to move down the fallopian tube for fertilization within 24-36 hours of the LH surge. They used three different BPA doses on pregnant sheep and found that none of the doses had an effect on the corpora lutea, progestogenic cycles, and mean number or duration of ovulatory or anovulatory follicles.
Differences were found in the follicular count trajectories in all three follicle size classes of the prenatal BPA treated animals as compared to the controls. In the prenatal BPA-treated group, the number of follicular waves tended to be more variable, ranging from 2-5 follicular waves per cycle. The control group had 3 to 4 waves per cycle.
The changes in the ovarian follicular dynamics paired with the defects in the time interval between estradiol rise and preovulatory LH release could likely lead to a subfertility in prenatal BPA- treated females. One such study focused on using multifunctional biocapsules to remove phenol and BPA from an environment. This method uses a biocapsule with an immobilized enzyme with a layer by layer configuration. The BPA is removed by enzymatically oxidizing the BPA and then the reaction product is bound onto a chitosan core biopolymer. This technique has several functions including the enzymatic breakdown of BPA, the use of the core material to absorb the degraded compound, colorimetric quantification and potential magnetic capabilities. These capsules have the capability to remove 5.
6 ppm of BPA and up to 10 ppm of phenol within 15 hours.Another method developed to detect phenolic compounds such as BPA found that nickel nanoparticles can be used to construct electrochemical enzyme sensors. They used the nickel nanoparticles as an enzyme immobilization platform and electrode material and createda screen printing enzyme biosensor to detect the presence of BPA. The nickel biosensors were compared to the performance of the sensors based on iron oxide and gold nanoparticles. The three configurations were compared by their reproducibility, stability of more than 100 assays, and a wide linear range. Nickel was found to have a better detection limit and sensitivity than iron oxide or gold nanoparticles Another experiment was conducted on fathead minnows (Pimephales promelas), a species of freshwater fish. Bisphenol A (BPA), a high-volume chemical used to make polycarbonate plastic, epoxy resins, and other chemicals has been reported to be weakly estrogenic. To investigate the effects of long-term exposure to Bisphenol A, a multi-generation study was conducted in which the fathead minnows were exposed to water concentrations of BPA in the range from 1 to 1280 ?g/L.
This specific experiment shows the growth and reproductive effects of BPA on sexually mature adults in the F0 generation and the effects on hatchability in the F1 generation. Mean measured concentrations of BPA in the water for all doses, over a 164-d exposure period, were between 70% and 96% of nominal. An inhibitory effect of BPA on somatic growth (length and weight) occurred in adult male fish exposed to 640 and 1280 ?g/L (after 71 and 164 d). BPA induced vitellogenin synthesis (VTG; a biomarker for estrogen exposure) in males at concentrations of 640 and 1280 ?g/L after 43 d and 160 ?g/L after 71 d. In females, plasma VTG concentrations were elevated above controls only after 164-d exposure to 640 ?g/L.
Inhibition of gonadal growth (as measured by the gonadosomatic index) occurred in both males and females at concentrations of 640 and 1280 ?g/L after 164 d. In males, a concentration of 16 ?g/L altered the proportion of sex cell types in the testis, suggesting inhibition of spermatogenesis. Concentrations of BPA that induced VTG synthesis and affected gonadal development were lower than those that resulted in discernible effects on reproductive output. Egg production was inhibited at a BPA concentration of 1280 ?g/L, and hatchability in the F1 generation was reduced at a BPA concentration of 640 ?g/L (there were not enough eggs spawned in the 1280 ?g/L group for hatchability studies to be conducted). The results demonstrate that BPA acts as a weak estrogen to fish when administered via the water, with effects on breeding at and above 640 ?g/L.
Another study which talks studies the BPA in pregnant women and the its effect on the offspring. Phthalates and BPA are endocrine disrupting chemicals (EDCs) widely used in consumer products. Evidence suggests that phthalate and BPA exposure alters steroid hormone levels in adults, while in utero exposure has been associated with altered fetal reproductive development in boys. However, the impact of exposure during distinct critical windows of in utero development on hormone concentrations and sexual maturation during the pubertal transition has not been examined. The objective of this study was to assess trimester-specific in utero phthalate and BPA exposure in relation to measures of reproductive development among peripubertal boys in a Mexico City birth cohort. The methods used to come to a probably conclusion was that they measured maternal urinary phthalate metabolites and BPA during the first, second, and third trimesters of pregnancy. They measured serum levels of testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG), and assessed sexual maturation (Tanner staging and testicular volume) among male children at age 8-14 years (n = 109). Linear and logistic regression were used to investigate trimester-specific in utero exposure as predictors of peripubertal hormone levels and sexual maturation, respectively.
In sensitivity analyses they evaluated estimated exposure at 7 weeks gestation and rates of change in exposure across pregnancy in relation to outcomes. The results of the study was exposure to phthalates during the third trimester was associated with reduced odds of having a Tanner stage >1 for pubic hair development (e.g. MBzP OR = 0.18 per interquartile range (IQR) increase; 95% CI:0.
03-0.97) and higher peripubertal SHBG levels (e.g. MBzP 15.
2%/IQR; 95% CI:3.2-28%), while first and second trimester phthalates were not. In contrast, exposure to DEHP during the first trimester was associated with higher estradiol (11%/IQR; 95% CI:1.5-22%), while second or third trimester DEHP exposure was not. Sensitivity analyses yielded similar findings. So in conclusions associations between in utero phthalate and BPA exposure and peripubertal measures of male reproductive development are dependent on the timing of that exposure during gestation. These findings suggest that future epidemiological studies relating in utero EDC exposure to pubertal outcomes should consider windows of susceptibility.
Another study involves investigating the increasing prevalence of thyroid nodular disease (TND) which has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to thyroid-disrupting chemicals may contribute to TND and altered thyroid function. They investigated the association between exposures to bisphenol A (BPA), its chlorinated derivatives (Clx BPA), and bisphenol F (BPF) with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212) was conducted, where cases were those with thyroid nodules (diameter >3mm), and controls without nodules. Serum TSH and free thyroxine and urinary levels of BPA, BPF and Clx BPA were measured using immunoassays and tandem mass spectrometry, respectively. The association between exposures to BPA compounds and TND, adjusting for age, BMI, thyroid hormones and urinary iodine was assessed using logistic regression.
Linear regression was used to explore associations between urinary BPA, BPF and ClxBPA and serum thyroid hormones. With the exception of a chlorinated BPA compound (30%), the rest of bisphenols were quantified in 100% of urine samples. A positive and significant (p<0.05) association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or Clx BPA.
A larger study would be justified.Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.
05 and 0.5 ?g/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 ?g/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year.
The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA.The endocrine disruptor bisphenol A (BPA) and the pharmaceutical 17?-ethinyl estradiol (EE) are synthetic chemicals with estrogen-like activities. Despite ubiquitous human exposure to BPA, and the widespread clinical use of EE as oral contraceptive adjuvant, the impact of these estrogenic endocrine disrupting chemicals (EDCs) on the immune system is unclear. Here they report results of in vivo dose response studies that analyzed the histology and microstructural changes in the spleen of adult male and female CD-1 mice exposed to 4 to 40,000??g/kg/day BPA or 0.02 to 2??g/kg/day EE from conception until 12-14 weeks of age. Results of that analysis indicate that both BPA and EE have dose- and sex-specific impacts on the cellular and microanatomical structures of the spleens that reveal minor alterations in immunomodulatory and hematopoietic functions.
These findings support previous studies demonstrating the murine immune system as a sensitive target for estrogens, and that oral exposures to BPA and EE can have estrogen-like immunomodulatory effects in both sexes.It has been found that BPA has the potential to have a wide range of health effects on humans and other organisms, especially involving reproductive health. There is still a lot of research to be done to determine what levels of BPA are safe for adults, children, and animals as well as the environment.
Research also needs to be done on how to best detect and remove BPA from everyday products, especially related to food packaging and preparation. Lastly, it is important to find the best method to remove BPA from the environment.