**2. Exposure to bisphenol A**

BPA is a chemical compound used to produce polycarbonate plastic and epoxy resins. Therefore, humans are exposed to BPA throughout their life. The predominant source of BPA exposure to general population is ingestion of food and beverages [29, 30]. Humans can also be exposed to BPA through nondietary routes including inhalation [31, 32] and skin contact [33].

### **2.1. Human exposure levels**

BPA levels have been measured in human biological samples due to the widespread use of BPA-containing products. Unconjugated BPA levels in humans were measured as a wide range from 0.2 to 20 ng/ml in serum [32, 34]. BPA also detected in amniotic fluid [35], breast milk [36, 37], and maternal amniotic fluid and fetal plasma [38, 39]. These studies indicate that BPA is able to easily transverse the placental barrier and affect the fetal development.

The estimation of BPA exposure in the general population can be based on the presence of BPA levels in the biological sample and the amount of daily food intake. Based on urinary excretion levels of BPA metabolites, the estimated amounts of BPA in general population are up to 0.16-μg/kg body weight (bw) in the USA and 0.04–0.08 μg/kg bw in Japan [40]. Daily intake levels of BPA to human have been estimated from 0.2-μg/kg bw/day in 3-month-old breasted infants up to 13-μg/kg bw/day in 6-to-12-month-old infants. The estimates of potential dietary exposure in young children and adults were respectively 5.3 and 1.5 μg/kg bw/day based on conservative migration values of BPA and conservative estimates of consumption of commercial foods and beverages [41]. This report shows that infants and children are the highest intake group because they eat, drink, and breathe more than adults and play or bite with the plastic toys.

## **2.2. Metabolism**

system [4–7], immune system [8–10], pituitary gland [11–20], and metabolic system [21–24]. Because, the fetus and neonates are extremely sensitive to perturbation by hormone like chemicals, early life exposure to low dose BPA probably is able to affect the epigenetic mechanism. The epigenetic changes caused by BPA may explain the increased risk of devel-

The mixed exposure to several low-level EDs should be tested because humans are exposed to various EDs simultaneously. Mixture can produce significant adverse effects, even when each chemical is present at low doses that individually do not induce observable effects in reproductive system [4, 25] neuroendocrine system [26], and endocrine

Therefore, this chapter describes the harmful effects on adulthood caused by exposure to low-

BPA is a chemical compound used to produce polycarbonate plastic and epoxy resins. Therefore, humans are exposed to BPA throughout their life. The predominant source of BPA exposure to general population is ingestion of food and beverages [29, 30]. Humans can also be exposed to BPA through nondietary routes including inhalation [31, 32] and skin

BPA levels have been measured in human biological samples due to the widespread use of BPA-containing products. Unconjugated BPA levels in humans were measured as a wide range from 0.2 to 20 ng/ml in serum [32, 34]. BPA also detected in amniotic fluid [35], breast milk [36, 37], and maternal amniotic fluid and fetal plasma [38, 39]. These studies indicate that BPA is able to easily transverse the placental barrier and affect the fetal

The estimation of BPA exposure in the general population can be based on the presence of BPA levels in the biological sample and the amount of daily food intake. Based on urinary excretion levels of BPA metabolites, the estimated amounts of BPA in general population are up to 0.16-μg/kg body weight (bw) in the USA and 0.04–0.08 μg/kg bw in Japan [40]. Daily intake levels of BPA to human have been estimated from 0.2-μg/kg bw/day in 3-month-old breasted infants up to 13-μg/kg bw/day in 6-to-12-month-old infants. The estimates of potential dietary exposure in young children and adults were respectively 5.3 and 1.5 μg/kg bw/day based on conservative migration values of BPA and conservative estimates of consumption of commercial foods and beverages [41]. This report shows that infants and children are the highest intake group because they eat, drink, and breathe more than adults and play or bite

oping adult onset diseases.

128 Bisphenol A Exposure and Health Risks

dose BPA during early life stage.

**2. Exposure to bisphenol A**

**2.1. Human exposure levels**

system [27, 28].

contact [33].

development.

with the plastic toys.

The orally administered BPA could rapidly metabolize to the bisphenol A-glucuronide carried out by the uridine 5′-diphospho-glucuronyl transferase (UGT) in the liver and gut. The metabolic process is called as glucuronidation. Unconjugated parent BPA is converted into other substances such as sulphate conjugate [37]. The conjugated form of BPA does not bind to the estrogen receptors and is excreted in urine [42–44]. It suggests that the conjugates have relatively less estrogenic potency than unconjugated form because of the less binding affinity to nuclear receptors and rapid excretion. The estimated half-life of BPA was about 6 h in the human body [45–47]. In addition, BPA metabolisms in liver cells from rats, mice, and humans showed similar pattern across the species [48].

The metabolic process of BPA is different depending on the route of exposure. The highest concentration of BPA was measured at 1 h after oral or intraperitoneal administration and at 4 h after subcutaneous administration [44]. More than 60% of the glucuronidated BPA were excreted through urine, and unconjugated form of BPA was mainly excreted in the feces [44]. It suggested that the oral route was recommended for appropriated risk assessment of BPA because the predominant exposure route of BPA to human is dietary ingestion [40].

In pharmacokinetic studies, BPA metabolites were measured in human urine and blood after ingestion of 5 mg deuterated (d6)-BPA [46]. Besides, the maximum unconjugated d6-BPA concentration in human serum was detected at 1.6 h after ingestion of the BPA-contained soup [49].

The fetus and newborns are not fully developed in the ability of glucuronidation [50]. In experimental studies, neonates showed higher free BPA levels in blood compared to older animals when given a same level of BPA [50, 51]. Despite the glucuronidation enzymes have not been identified in human, neonates and infants may be vulnerable to BPA exposure compared to adult human.
