BISPHENOL ABy Samuel OkorieEOH 555 April 27, 2016

https://pubs.acs.org/cen/coverstory/89/8923cover2.html

What is Bisphenol A (BPA)?

http://www.thyromend.com/thyroid_hormones.html

BPA exposure

http://www.dimensionsofdentalhygiene.com/2013/11_November/Features/Minimize_BPA_Exposure.aspx

Diethylstilbestrol (DES)

http://www.yalescientific.org/2009/02/determining-the-effects-of-desplex/

History of BPAIn the 1940s, diethylstilbestrol (DES) was synthesized from BPA.

Epoxy resins were first discovered in 1950. They discovered polycarbonates in 1957.

In 1958, FDA started regulating industries BPA ‘s use.

In 1980s, FDA refined the regulation of BPA (Dose dependence)

In 1988, FDA adopted the first safety standard BPA (50µg/kg per body MW).

In 1993, BPA was branded an endocrine disruptor.

In 2008, FDA vs Science committee ; BPA controversies.

Since 2009, FDA has issued a ban on BPA use.

Scope of the research

• The highest exposure of BPA was found to be in baby bottle formulas. Fetuses, infants, and children are the main concern, however, BPA affects all ages.

• 2341 out of 2517 urine samples collected from persons six years and older showed detectable levels of BPA in their urine.

• Animal studies on infants revealed that exposure of BPA can lead to harmful health effects.

• Epigenetic effects on studies’ interpretation of data led to disagreements amongst scientists about the BPA exposure and safety.

• 92% of U.S. population has detectable BPA levels in their serum, and there is no accepted standard for BPA.

Mechanism of BPA

Carchia, E., Porreca, I., Almeida, P. J., D'Angelo, F., Cuomo, D., Ceccarelli, M., . . . Ambrosino, C. (2015). Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity. Cell Death Dis, 6, e1959. doi:10.1038/cddis.2015.319

Toxicological Studies • In Japan, Scientists conducted a study to examine BPA activity

on thyroid system. • Their hypothesis stated that BPA could affect or disrupt

thyroid hormone action by transcriptional inhibition. • BPA inhibits transcription by diminishing the binding of

triiodothyronine (T3) to nuclear thyroid receptors (NTRs) and compressors (N-CoRs) to thyroid receptors (TRs) respectively.

• TRα and TRβ are the encoding genes for NTRs isoforms.• Both TRα and TRβ have similar ligand binding domains. • They grew a culture containing hepato-blastoma cells

(HepG2).

Thyroid Hormone regulation

http://www.animalendocrine.info/2011/08/confirming-diagnosis-of-hyperthyroidism_30.html

Toxicological Studies Continued…

• They cultured NTRs from rat livers using iodine-125 T3 (about 122MBq).

• NTR were incubated with BPA in 5mM dithiothreitol 4 degree and left overnight.

• TRβ3 genes are ubiquitous and their expressions begin in early development.

TRα

TRα1 TRα2

TRα3

TRΔαs

TRβ

TRβ1 TRβ2

TRβ3

TRΔβs

Results

(Moriyama, 2002)

Toxicological results continued…

(Moriyama, 2002)

Toxicological Studies Conclusion• BPA disrupts the signaling pathway of T3 at the ligand binding

domain. • At high concentration, BPA reduced transcriptional activities

mediated by TRα1 and TRβ1. • Based on effects of BPA TSHα promoter, BPA increased

transcription in the presence of TRβ1 and TRβ2 expressed I the pituitary and hypothalamus.

• Concentration increase of T3 decreased the protein activation; however, BPA effect on the domains remained unconstrained.

Epidemiological and Exposure Studies • BPA has been associated with increased blood pressure (BP). • BPA exposure is primary from canned foods. A randomized

trial study was conducted to demonstrate the effects of BPA on the cardiovascular system.

• n=60 and µ≥60 years old • They provided the participants two servings of canned

beverages in three different combination. • Two cans (CC), two glass bottles (GG), or one can, one bottle

(CG). • It was a blinded study, where they blinded the researchers

that measured the BPs.

Exposure ResultsTable 1. Basic Characteristics of the Participants

Variable Parameter n 60 Age, y mean±SD 73.1±4.2 Sex, female, n, % 58 (93.3) Weight, kg, mean±SD 57.9±7.6 Hypertension, n, %

Yes, with treatment 26 (43.3) Yes without treatment 1 (1.7) No 33 (55.0) Diabetes mellitus, n, %

Yes, with treatment 9 (15.0) Yes without treatment 0 (0.00) No 51 (85.0) Drinker, n, %

Yes 13 (21.7) No 47 (78.3) Smokers, n, %

Yes 3 (3.50) No 57 (95.0) Average sleep time, n, %

≤5 h/d 17 (28.3) 6-7 h/d 20 (33.3) 7-8 h/d 15 (25.0) 8-9 h/d 6 (10.0) ≥10 h/d 2 (3.4)

Completed trial, n, % 60 (100.0)

(Bae, 2014)

CONCLUSION • Because of the species to species differences between humans

and animals, scientists have difficulties establishing cause-effect relationships between BPA exposure and health effects from animal studies.

• BPA half-life ranges from 4 to 43 hours. The body instantly excretes BPA through urination because of its short half-life.

• BPA exposure can only be measure effectively every 2 hours in the urine.

• At very low levels of BPA, other chemicals can act synergistically with BPA, or indirectly affect other systems in response to other chemicals.

CONCLUSION continued…• Since there is no established standard for BPA, but a ban, to

protect fetuses, infants, and young children from BPA exposure, I propose we enforce the current ban by creating more programs to educate mothers on the effects of BPA.

• By educating the mothers, the political decisions weighing on BPA exposures for infants will gain momentum.

• Since most political decisions are merely based on public opinions, having the mothers on my side with help enforces the ban against manufacturers of plastic derivatives.

• Note that the current ban by the FDA is zero use of BPA in manufacturing of plastics.

References

1. Bae, S., & Hong, Y.-C. (2015). Exposure to Bisphenol A From Drinking Canned Beverages Increases Blood Pressure: Randomized Crossover Trial. Hypertension, 65(2), 313-319. doi:10.1161/HYPERTENSIONAHA.114.04261

2. Carchia, E., Porreca, I., Almeida, P. J., D'Angelo, F., Cuomo, D., Ceccarelli, M., . . . Ambrosino, C. (2015). Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity. Cell Death Dis, 6, e1959. doi:10.1038/cddis.2015.319

3. Moriyama, K., Tagami, T., Akamizu, T., Usui, T., Saijo, M., Kanamoto, N., . . . Nakao, K. (2002). Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab, 87. doi:10.1210/jc.2002-020209