Bisphenol A and Phthalates Exhibit Similar Toxicogenomics and Health Effects

Bisphenol A and Phthalates Exhibit Similar Toxicogenomics and Health Effects

Sumaya Hassan (University of Kashmir, India), Rohaya Ali (University of Kashmir, India), Durdana Shah (University of Kashmir, India), Nasreena Sajjad (University of Kashmir, India) and Jasfeeda Qadir (University of Kashmir, India)
DOI: 10.4018/978-1-5225-9452-9.ch014


Bisphenol A and phthalates are most frequently detected organic pollutants found in our surroundings because of their regular use as plasticizers in daily use polymeric products. BPA is used in manufacturing baby feeding bottles, water pipes, canned food linings, and food packaging materials. Phthalates are used in polyvinyl chloride products including clothing, toys, medical devices, and food packaging. These chemicals are not bound to the matrix and leach out into the surroundings on slight change in the environment, like alteration in pH, temperature, and pressure. Humans are continuously exposed to these chemicals through skin contact, inhalation, or ingestion when the leachates enter food, drinks, air, water, or soil. The Comparative Toxicogenomics Database (CTD) revealed that Bisphenol A has 1932 interactions with genes/proteins and few frequently used phthalates (DEHP, MEHP, DBP, BBP, and MBP) showed 484 gene/protein interactions. Similar toxicogenomics and adverse effects of Bisphenol A and phthalates on human health are attributed to their 89 common interacting genes/proteins.
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Plastic Pollution

Plastics, being essential materials in modern civilization, are used widely, almost everywhere in the world. Plastics and many products manufactured from them promote risks to human health and environment (Thompson et al., 2009). Plastics contain many hazardous substances including Bisphenol A, pthalates, brominated flame retardants and poly-fluorinated chemicals, etc. that causes various human health issues like respiratory problems, liver dysfunction, vision failure, skin diseases, cancers, lungs problems, dizziness, headache, reproductive problems, birth defects, cardiovascular and gastrointestinal troubles (Proshad et al.,2018). BPA and phthalates are found in many widely used products including medical devices, perfumes, flooring materials, food packaging, toys, cosmetics, computers and CDs and hence, represent a considerable component of plastic (Meeker &Ferguson, 2012).

Bisphenol A

Bisphenol A (BPA, 2,2-bis (4-hydroxyphenyl)propane) is a monomer that was developed in 1890s as a synthetic estrogen. Later in 1930s, it was reported to have stimulatory effects on the female reproductive system of rats as that of estrone (Dodds, 1936). BPA has also been used in various consumer products, like polycarbonate plastic, PVC, dental sealants and food packaging. Humans are usually exposed to BPA through via their diet, inhalation and dermal route (Vandenberg et al., 2012). In 2008, it was estimated that 2.8 million metric tons of BPA were produced and subsequently 5.5 million metric tons were expected in 2011 (Bailin et al., 2008). BPA is an identified endocrine disruptor as it binds to estrogen receptors and hence produces estrogenic effects. Although BPA has a lower affinity for nuclear estrogen receptors as compared to 17-beta estradiol (E2) (Figure 1A), its estrogenic strength is equal to that of E2 for responses that are mediated by non-nuclear estrogen receptor (Vinas et al., 2012). BPA can also act as an anti-estrogen by blocking the estrogenic response while competing with endogenous estradiol (Richter et al., 2007; Bonefeld-Jorgensen et al., 2007). BPA directly bind to androgen receptors, and hence, possibly acts as anti-androgenic by blocking the endogenous androgen activity (Sohoni et al., 1998; Wetherill et al., 2007). BPA has also been found to bind thyroid receptors possessing both agonistic and antagonistic effects on thyroid function (Moriyama et al., 2002). BPA also interacts with CNS, pancreas and immune system (Wetherill et al., 2007). Various in vitro, in vivo and epidemiologic studies have shown that BPA is associated with several diseases, including coronary heart disease (Melzer et al., 2010), cardiovascular disease (Magliano and Lyons, 2013), diabetes (Shankar and Teppala, 2011) and obesity (Wang et al., 2012). It has also been employed as a model for determining the low dose and non-monotonic nature of hormones that regulate our endocrine system (Vandenberg et al., 2012). BPA has been reported to have significant effects at low doses, which may not be present at higher doses used in toxicology studies (Vandenberg et al., 2012). Since most of us are exposed to low doses of BPA regularly, it becomes necessary to determine the health effects of BPA on humans. There are ample studies that link BPA with various adverse health effects in mammalian and non-mammalian models (Richter et al., 2007; Bonefeld-Jorgensen et al., 2007; Saal et al., 2007; Crain et al., 2007). The results are obviously worrying as humans are ubiquitously exposed to BPA. The exposure to BPA starts in the womb itself as it is detected in the follicular and amniotic fluid, placental tissue, cord blood and human fetal liver (Ikezuki et al., 2002; Schonfelder et al., 2002; Nahar et al., 2012). BPA is also detected in urine samples of adults and children, serum of pregnant women and breast milk (Schonfelder et al., 2002; Calafat et al., 2005; Kuruto-Niwa et al., 2007; Braun et al., 2011).

Figure 1:

Structure of β-estradiol (A) and Bisphenol A (B)


Key Terms in this Chapter

Gene Ontology: Gene ontology (GO) is a bioinformatics tool used to unify the representation of gene/gene product attributes across all the species.

Epigenetic Modifications: Epigenetic modifications alter the genomic expression and its effects without altering the actual DNA sequence. These include DNA methylation, histone modification and microRNA-mediated genetic silencing.

Plasticizers: Plasticizers are the chemical additives thatincrease the elasticity of plastic. Plasticizers tend to soften the plastic in order to make it more flexible and bendable.

Comparative Toxicogenomics Database: The Comparative Toxicogenomics Database (CTD) is a research tool that provides curated scientific data describing the relationship between various chemicals, genes/proteins, diseases, phenotypes, pathways, and interaction components.

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