Pathological Conditons Related to Bisphenols and It' s Compounds

*Geethamani Palanisamy and Divya Palanisamy*

## **Abstract**

Bisphenols (BP) is one of the most important and highest volumes of chemicals produced in the universe. Each year, around 100 tons of bisphenol compounds are released into the atmosphere. In general, bisphenol is most widely used for production of polycarbonate (making plastic bottles like baby bottles and nursing products, dental sealants, CDs, DVDs, eye glasses, medical equipment's, plasticizers etc.) and polymeric resins (epoxy resins, impact resistant safety materials like sports goods etc.). Due to these unavoidable chemicals, human beings are affected by human chronic diseases like obesity, toxicity, neuro disorder, reproductivity disorders, diabetes, cardio related issues, birth defects, metabolic syndrome, breathing issues, digestive related issues, cancer, genetic mutation etc., Children are easily affecting due to the multi dose consumption of packed food containing BP (canned foods) than adults. Women are affecting polycystic ovaries due to the high-level deposition of BP.

**Keywords:** metabolic syndrome, bisphenols, obesity, toxicity, disruption of endocrine, disorders

### **1. Introduction to bisphenol compounds**

The commercial production of Bisphenol compounds (BP) initiated by late 1950's, after the first epoxy resin was developed. A synthetically man-made chemical which is a polymeric monomer named bisphenol (BP) is widely used for the manufacture of plastic things and goods for the usage of daily life need for the human beings (food packages, drink containers, body lotions, playing toys, house hold plastic things, nursing products, decorators and water pipe lines, etc.) and industrial usages. Also, Bisphenol compounds are used for the manufacture of unsaturated polyester, polysulphones and polyetherimide. BP compounds of non-polymer are also used as an additive in flame retardants, thermal papers and brake fluids. The usage of BP is increasing more in more from last few decades in the universe, resulting BP is finding throughout the environment and also in human body [1] through their diet. A huge number of journals published based on the studies of BP and its compounds.

Chemically, BPA has two large phenyl groups with two electron rich hydroxyl group (alcohol and two methyl group). It forms lipophilic (associates with lipids), through the conjugation process, it makes a substance more water soluble. BPA is slightly more hydrophilic (associate with water), found in Adipose tissues and in breast milk too. The hydrophilic form is seen in urine and excrement. From the obtained information [2], BPA has a moderate potential for bioaccumulation and not found that to readily biodegrade.

**Figure 1.** *Structure of BPA.*

### **2. Bisphenol A**

It was discovered by the Chemist A.P.Dianin in the year of 1891. These compounds are basically a carbon based synthesised compound belongs to the group of derivatives of diphenyl methane and bisphenols, which is colourless in nature called polycarbonate and are mostly stable and very strong in nature. The BPA components can withstand up to moderate to very high temperature even it is exposed to oven or furnace. Due to these properties, they can be used to manufacturing safety equipment's components, glassware, bullet proof windows, doors, etc. As one of the main component of epoxy resins in protective coatings or layers of those lining the inner surfaces of plastic tins or cans, BPA supposed to extend the shelf life of food and beverage products. **Figure 1** shows the structure of Bisphenol A. The toughness of BPA plastics has led to their use in medical equipment's like cardiopulmonary (heart-lung) machines, incubators, hemodialyzers (artificial kidneys) and dental sealants and dental fillers and their light weight and optical clarity glasses which has made for eyeglasses [3–5]. Also, the chemicals are found in a variety of other products, including compact discs (CD's) and other paper receipts.

### **3. Adverse health effects**

In 1930s, the first studies indicated that, the BPA to be a weakly estrogenic molecule but later [6] confirmed that it has harmful effects through the animal research. The cancer like breast cancer, prostate cancer, Uro genital abnormalities (in Male babies), early onset of puberty in girls, metabolic disorders like Obesity and type-two diabetics, decreases in semen quality in men and neuro-behaviour problems including attention deficit hyperactivity disorder etc. are the possible diseases and disorder of BPA from the exposures during the critical periods.

### **4. Biological effects of bisphenol A**

During 20th century, it was found it in only plastics even though scientists had developed BFA in 1930's as a man-made estrogens and its cancer causing (Carcinogenic) properties. The American endocrinologist led by his team in the early 1990's, unexpectedly found out, the BPA growth is medium in polycarbonate flask which is used to culture yeast cells. Further, they proceeded to isolate BP samples from the water in the flask and had been autoclaved, where they confirmed the chemical which was found same in the earlier detection (during 1930's). They also confirm that, BPA produced estrogenic effects in cells at the level of 5–10 times lower than who used for safety assessments companies where polycarbonate plastics are manufactured [7].

### *Pathological Conditons Related to Bisphenols and It's Compounds DOI: http://dx.doi.org/10.5772/intechopen.101114*

The leached plastics, resins in tin cans contains BPA products by various conditions including the photochemical break down, exposure of various temperature range (Low to high), maturity of plastics cans and/or resins and the presence of ethanol. In the middle of 1990's, number of studies confirms that, the main adverse effect due to BPA was reproductive system and development in animals by the interfering with their endocrine systems (energy balance and stress response) by the exposure level of BPA (both high and low level). The studies confirm that, due to the accumulation of BPA, it retards sexual behaviour in animals [8–10]. Also, it has been identified that the crossed placental barrier in animals (mammals) like mice and rats has been detected in human beings maternal and fetal serum which was also coincident with in human placental tissues. Thus, Bisphenol compounds found its way into tissues and fluids in the human womb. The chemical reaction attack and its effects in human fetal development is still not-clear. Similarly, the function of the human endocrine system is a matter to discuss. Much more speculation centres on whether BPA is a true endocrine disruptor chemical (EDC) in humans. The substituted Endocrine disruptor like DichloroDiphenylTrichloroEthane (DDT) & diethylstilbestrol, had been combined with birth defects, reduced fertility (infertility), and diseases such as obesity, diabetes, and carcinoma in humans. Derivatives of Bisphenol compounds (BPA, BPS and BPF) are used as alternatives to BPA, are associated with obesity, particularly in children [11, 12].

### **5. BPA with in the environment**

From the industries like chemical, plastics coat and staining manufactures, paper mills or material recycling companies, foundries (casting sand) or any direct or indirect leaching from the above and landfills (waste metal dumping), BPA might enter in to the environment directly. The accumulation of BPA, totally affects the growth, reproduction and life time of aquatic organisms. The United States Environmental Protection Agency (EPA) reported in 2010 that more than 1,000,000 pounds (454,000 kilogrammes) of BPA were released into environmental reservoirs each year, including soil, rivers, lakes, and oceans. Leaching from landfills and release from municipal water supplies, such as those associated with wastewater-treatment plants and paper mills, are the primary sources of environmental contamination. Plastic pollution is a major source of BPA in the world's oceans. Despite the fact that seawater accelerates the breakdown of BPA plastics, the likelihood of leached BPA accumulating in the tissues of marine species is quite low. On the other hand, studies on terrestrial and freshwater species have shown that even low concentrations of the chemical can cause abnormalities when exposed for an extended period of time. BPA exposure, for example, causes an increase in micronuclei in root tip cells, indicating DNA damage in plants. BPA exposure causes sex ratios to become biased toward females in certain species of reptiles whose sex determination is normally influenced by temperature [13–16].

## **6. Effects of BP in human body**

### **6.1 Neurotoxic, neuro behavioural and its effects**

The developmental exposure of BP & BPA are does not appear to affects the sensory system, the spontaneous or Laboratory animals' self-activity or sexual behaviour. At dietary doses below 5 mg/kg bw per day, changes in brain biochemical signalling, morphometric and cellular end-points within sexually dimorphic

### *Bisphenols*

anatomical structures, and neuro-endocrine end-points were described. The most significant restriction is that methodological flaws cause uncertainty in the interpretation of results. Changes in anxiety and convergence of structural brain sex differences were identified as end-points suggestive of effects with possible human relevance based on the available data, although more research is needed to clarify uncertainties [17].

### **6.2 Cardiovascular effects**

The toxicological evidence suggests that BPA has no discernible effect on cardiovascular function. The expert meeting is aware of upcoming cardiovascular function research that will soon inform judgements about cardiac end-points [18].

## **6.3 Metabolic disorders**

Metabolic diseases are a new field of study, and the evidence currently available is insufficient to draw any conclusions about the possible harm to humans. However, the present evidence suggests that more research into the effects of BPA on adiposity, glucose or insulin control, lipids, and other diabetes or metabolic syndrome end-points is needed [19].

## **6.4 Effects on child and infants**

Generally, the conservative assumptions made by the estimated international exposures reported are higher than comparable national estimates. The average and main exposure of exclusively breastfed babies (infants 0–6 months) to BPA was 0.3 μg/kg/day and exposure at the 95% was 1.3 μg/kg/day. When solid foods are introduced, exposure to BPA reduces after 6 months (at 6–36 months). For formulafed newborns, there is a wide range of exposure estimates. Infants (0–6 months) fed liquid formula have a higher exposure than infants fed powdered formula, and infants fed polycarbonate (PC) bottles have a higher exposure than infants fed non PC bottles [20–23].

Infants (0–6 months) who are fed liquid formula out of PC bottles have the highest estimated exposure are 2.4 μg/kg/day and 4.5 μg/kg /day at the 95th percentile. For children older than 3 years, highest exposure estimates did not exceed 0.7 μg/kg / day and 1.9 μg/kg /day at the optimum. For adults, highest exposure estimates did not exceed 1.4 μg/kg/day and 4.2 μg/kg bw/day at the maximum.

For most subgroups evaluated, exposure to BPA through non-food sources is at least one order of magnitude lower than that from food, based on the limited data available. Food, on the other hand, is by far the most significant source of overall BPA exposure in the majority of demographic groups. In addition, possible sources of exposure have been identified (unpackaged food and thermal paper). However, due to a lack of data, researchers were unable to produce exposure estimates. BPA concentrations in unpackaged foods and data on the consumer use patterns for materials and products containing BPA, including specific geographical differences; and the contribution of dermal exposure to overall exposure are furnished from the data over the exposure of BPAs [24–29].

### **6.5 Some studies on BPA and obesity**

The studies of Serbian involve the 103 women aged, 19–50 years measured BPA in first morning urine and the number of anthropometric measures including height, weight, and waist and circumference (WC) were collected. Milosevic et al., *Pathological Conditons Related to Bisphenols and It's Compounds DOI: http://dx.doi.org/10.5772/intechopen.101114*


**Table 1.**

*The diagnosis of obesity (WHO., 2000).*

described a positive suggestion between BPA and obesity [30]. However, limitations of this investigation were cross-sectional sample collection and the quantities of participants were very small. Also, there is no physical activity data were collected. The recent study in USA, involves 977 adult women were conducted; where BPA (urine) were monitored, anthropometric measures were collected (including weight and height). The recent study of BPA (urine) of children and pregnant women were also determined in USA [31]. Of these 408 children were 3 years, 518 children where 5 years were monitored until 7 years of age, along with 369 pregnant women who's between the ages 18 and 35. The anthropometric measures consists of Fat mass index (FMI), body fat (BF) and WC were collected.

The study was to monitor the mothers and their children at different stages of their development. In this investigation, BPA concentration of pregnant women had a positive suggestion with FMI, BF and WC of children at age of 7 but not associated with birth mass and childhood body mass index z-scores (BMIZ) at age of 5 and 7 and there are changes in BMIZ from ages of 5 to 7. The physical activity information of participants was not provided in the limitation of this study. A study in China involving 1326 students aged between 9 and 12 also measured (BPA) urine where anthropometric measures were collected with weight, height, WC, hip circumference and skinfold thickness [32]. From this study, it shows that the BPA had positive relationship with obesity in girls but not in boys.

### **6.6 Obesity diagnosis**

Generally, obesity can be defined by using body mass index (BMI) by WHO to identify the obesity in people. The diagnosis of obesity is represented in the **Table 1.** The child obesity is studied by the nomogram technique. If, BMI equal to or greater than the age- and gender-specific, the 95th percentile is considered as obese (Centre for disease control) [33–35]. An obese person accumulates excess BF in his or her muscle, bone, fat and water. Obese people were facing many health problems at high risk including hypertension, mortality, low high-density lipoprotein cholesterol or high or low-density lipoprotein cholesterol and high levels of triglycerides (dyslipidaemia), coronary heart disease, diabetes (Type II), osteoarthritis, gallbladder disease, stroke and some cancers including endometrial, breast, colon, kidney, and liver cancer and gallbladder [36–40].

### **7. Effects of exposure to BPs**

There is only inadequate information about the adverse effects of non-BPA. However, it is believed that they have similar effects to BPA [41]. In human fluids or tissues including placental tissue, serum, foetal plasma and breast milk, the concentration of BPA has been determined. Many studies have been focussed on children and pregnant women, where high BPA levels were linked with chromosomal abnormalities and miscarriages and infertility in women and abnormal karyotypes in foetuses [42]. The high BPA levels causes to more unilateral or bilateral bloodfilled ovarian bursae in women.

### **7.1 Effect of BPA in biota**

In comparison to non-biotic and biotic environmental compartments, biota contains a small amount of ambient BPA. BPA's published bio-concentration factor (BCF) values are much below 1000, which the US Environmental Protection Agency deems to be the threshold for concern. BCFs for fish exposed to BPA have been reported to be quite low [32].

### **7.2 Effect of BP on wild life**

Numbers of challenges are facing due to the exposure of BPA (high concentration) on wildlife now days. The complexities in the natural system including chemical mixture, spatial varying exposure levels with tropic interactions and related few studies investigated results, the effect of chemical exposure on wildlife in-situ [43]. Many BPA toxicity studies have been used endocrine related measurement endpoints which triggered by other toxicological modes of action that was identifying these mechanisms may/may not be necessary in order to characterise the response to the environmental toxicity [44].

## **8. Relevance of the study to BFA**

BPA metabolism takes place by glucuronidation once in the body, under the catalytic action of the enzymes. While uridine 5-diphospho-glucuronosyltransferase (UGT) catalyses the conversion of BPA-to-BPA glucuronide, sulfotransferase catalyses the conversion of BPA- to the BPA- sulphate. Both metabolites are very soluble and removed from the human body in urine. The biotransformation of BPF and BPS is still unclear, but reactions carried out in vivo and in vitro organisms indicate that BPF metabolism is similar to BPA, while published studies on the biodegradation of BPS are extremely scarce [45].

In response to the same negative health effects of BPA, the US Food and Drug Administration (FDA) banned the use of BPA in baby bottles, sippy cups, and infant formular containers in 2012 [46]. Obesity increases the risk of a number of debilitating and fatal diseases, including diabetes, heart disease, and some cancers (US National Heart, Lung and Blood Institute, 1998). Obesity reduces a person's quality and length of life, raises an individual's healthcare costs, and raises the health costs of a country with a high prevalence of obesity (US National Heart, Lung and Blood Institute, 1998). Obesity is caused by a variety of factors, including lifestyle, genetics, and the consumption of processed foods high in fat, sugar, or carbohydrate; however, BPA and analogues when ingested have been linked to obesity [47–51]. The causes of obesity are plenty, such as lifestyle, genetics, the eating of processed food rich in fat and sugar or carbohydrate; however, BPA and analogues when absorb into the human body play a role in promoting adipogenesis and cause weight gain resulting in obesity especially in adolescent [52–57].
