**2. Human exposure to BPA**

The chemical synthesis and industrial conversion of BPA in PC and epoxy resin are shown in

Many food and drink containers are manufactured with PC plastics. On the other side, epoxy resins are normally used as inner liners in food and drink containers; polycarbonate plastics may be encountered in many products, especially in food and drink containers, while epoxy resins are frequently used as inner liners of metallic food and drink recipients with the aim to prevent corrosion. Some thermal paper used in cash registers or similar devices could be a source of BPA. Additionally, BPAs have been used in polyvinylchloride (PVC) industries and

BPA was synthesized for the first time by the Russian chemist A.P. Dianin in 1891, and in the early 1930s, the British biochemist E.C. Dodds tested BPA as an artificial estrogen but found

Dodds eventually developed a structurally similar compound, diethylstilbestrol (DES), which was used as a synthetic estrogen drug [2] in women and in animals until it was banned in 1971 due to its risk of causing cancer. Actually, bisphenol A is used primarily to make plastics, and BPA is contained in products that have been in commercial use since 1957. BPA-based plastic is clear and tough and is made into a variety of common consumer goods, such as water bottles, sports equipment, CDs, and DVDs. Epoxy resins containing BPA are used to line water pipes, as coatings on the inside of many food and beverage cans and in making thermal paper such as that used in sale receipts. In 2015, an estimated 5.4 million tonnes of BPA chemical were produced for manufacturing polycarbonate plastic, making it one of the highest volume of chemicals produced

**Figure 1.** Bisphenol A as a commodity chemical and essential component of two classes of polymers.

**Figure 1**.

76 Bisphenol A Exposure and Health Risks

worldwide.

metal foundries for cast and molding production.

it less effective than estradiol [1].

The human population is primarily exposed to BPA through the diet. Other possible sources of bisphenol A exposure are air, dust, water, and skin contact with thermal paper. From this point of view, most of 50% of BPA exposure account from food and beverages packed and distributed in boxes, bottles, or cans containing BPA. The remaining 50% is coming from thermal paper, or paper in general, in contact with skin. Monomers of BPA are released from slow decay of polymers in contact with food and liquids. BPA release could be accelerated by heating, contact with alkaline or acidic substances, repeated use and exposure to microwaves. In **Table 1**, an overview of typical concentration in food and non-food BPA-containing materials is shown.

BPA may be absorbed in the gastrointestinal tract after ingesting products packed in plastic containers. Like intestinal phenols, BPA is conjugated by glucuronic acid in bowel and liver and excreted in urine as BPA-glucuronide [3].

Levels, normally less than 1 μg/L, measured in human biological fluids indicate a recent exposure to the molecule because of its rapid conjugation and elimination by the liver and gastrointestinal tract in a few hours. Kinetics in vivo study support this hypothesis of rapid plasma clearance of BPA metabolites.

Measured concentrations of BPA in human blood, urine, and other tissues indicated that the majority of the population (91–99%) has detectable levels of BPA-conjugates in their urine, confirming that exposure is widespread in the human population.


**Table 1.** Overview of BPA typical concentration in food and nonfood BPA-containing materials.

The largest scale studies with a consistently high number of enrolled participants (*n* = 2517 and 5476 individuals) spread over a broad range of age were carried out in the USA and Canada, respectively [4–6].

In these studies, the highest BPA levels detected in urine were 3.6 ng/mL for the US and 1.30 ng/mL for the Canadian ones in a subgroup of population within the age group of 6 and 11 years. On the contrary, the adult population had lower BPA urine concentration: 2.6 and 1.16 ng/mL, respectively. Zhang et al. show the same results in a recent study conducted on the Asian population [7].

Mose et al. [8] studied the BPA trans-placental transfer rate in human placentas in ex vivo experiments. Results led the authors to conclude that free BPA can cross the placenta by passive diffusion with a trans-placental transfer rate of 1 (e.g., the concentration in the fetal blood was equal to the concentration in the blood of the mother), as previously demonstrated by Balakrishnan et al. [9].
