# Risk Assessment of Bisphenol A in the Korean General Population
## 4 Risk Characterization of BPA  
In a domestic epidemiological study using the Korean National Environmental Health Survey 2016, urinary BPA among 922 adolescents aged 12-17 years did not show a significant relationship with the lifetime prevalence of asthma and serum IgE levels [12]. The mean urinary BPA for these participants was 0.67-0.86 ug/g creatinine for 478 males and 1.37-1.03 ug/g creatinine for 422 females. Compared to the EFSA's new TDI, exposure of these subjects translates into an immunological risk with adverse health effects. Therefore, determining the risk characterization of BPA using the current approach of comparing TDI and exposure levels to determine BPA safety is confusing. BPA does not show a typical classical dose-response relationship at low-dose exposure. However, assessment methods for this non-monotonic dose-response relationship, such as U-shape or inverted U-shape, have not yet been developed. Since the health effects of BPA in humans are related to exposure in low doses, a new TDI could be established if a method for evaluating the dose-response relationship at low-dose exposure in human was proposed. Therefore, this study performed risk characterization using the margin of exposure (MOE) approach, which compared the exposure amount and point of departure (POD) of critical effects in this study. The MOE approach is a tool used to consider possible safety concerns arising from the substances in food which are both non-threshold genotoxic carcinogens or without TDI [62]. Generally, MOEs are not used to assess the safety of regulated substances such as food additives or food contact materials. Use of MOEs can help support risk managers in defining possible actions required to keep exposure to such substances as low as possible. BPA can be used in the manufacture of polycarbonate and other plastic products and epoxy resin-based food can liners that are not genotoxic and are regulated in various exposure sources [16; 19]. Given the uncertainty in hazard characterization, the MOE approach was deemed appropriate for assessing the potential human health risks of low-dose exposure to BPA. Firstly, three points of departure (PODs) from epidemiological and animal studies were selected for their critical effects. Previous sub-chronic and multigenerational studies using rodents first identified a no observed adverse effect level of toxicity (NOAEL) of 5 mg/kg bw/day for systemic toxicity [47; 48]. Available pharmacokinetic data and comparisons between ages and species further support the use of this NOAEL as a very conservative tool in extrapolating data to humans. This NOAEL was also used as a POD in the establishment of current TDI by several agencies. Secondly, the lowest toxicity value was selected, which was one of 19 BMDL values for 10 endpoints by EFSA [19]. The lowest value was BMDL\({}_{20}\) (60 ng/kg bw/day) for an immunotoxic effect, which was assigned a likelihood level of likely at a weight of evidence approach by EFSA. Finally, an estimated daily intake based on blood BPA level (cut point in blood 0.979 ng/mL) in a Korean case-control study was selected [63]. The relationship between urinary BPA concentration and thyroid function was not confirmed; however, a relationship between serum BPA and thyroid cancer was reported [63]. The T3 group had a higher prevalence of thyroid cancer compared to the T1 group. The urinary mean BPA value of the T3 group (1.38 ug/g creatinine) was close to the 75 th percentile of urinary BPA levels (range: 1.29-3.21 ug/g creatinine) in the Korean general population (Figure 2). Although there are limitations of the case-control study, it was selected as a POD because it presented statistically significant results as a domestic epidemiological study. The estimated daily intake was calculated as 0.5 ug/kg bw/day using the blood BPA level that was not correlated with thyroid cancer [63].