# Risk Assessment of Bisphenol A in the Korean General Population
## 2 Literature Search for Safety Levels of BPA  
In principle, epidemiological studies are considered first for dose-response assessment to establish a level of safety such as TDI. However, when these studies are insufficient, the results of animal tests are used to set a safety level. Therefore, it is important to determine whether the observed adverse effects in animals are relevant in humans. Because of the gap between the health effects observed from epidemiological evidence and the endpoint of animal testing, controversy still continues over the biological significance of many of the more sensitive endpoints in humans through exposure to BPA, and whether studies that have assessed only conventional endpoints are adequate for the detection of all potentially relevant effects. Over the past decades, many epidemiological studies have suggested associations between BPA exposure and human health effects [34; 35; 36; 37; 38; 39]. However,no dose-response assessment has yet been attempted based on epidemiological studies. Many regulatory authorities around the world reviewing these low-dose studies have generally concluded that they are insufficient for use in risk assessment because of a variety of flaws in some of the study designs, scientific uncertainty concerning the relevance of the reported effects to health, and the inability of other researchers to reproduce the effects in standardized studies [16; 40; 41; 42; 43; 44]. There is an extensive literature on the evaluation of the health effects of BPA in animal models [19]. BPA has consistently been found to cause several adverse effects in rats and mice at doses of 50 mg/kg bw per day and above. However, these amounts (3 g/day for 60 kg adult) are difficult to identify in humans. Over the past 20 years, many studies have provided evidence that considerably lower dose levels (range 0.002-0.2 mg/kg bw/day) of BPA induce some health effects in animals following exposure during gestation and/or lactation [40; 45; 46]. However, these studies have limitations in applying dose-response modeling because of experimental design, such as the use of only one or two dose levels, non-oral route of administration, and lack of data on internal dosimetry. In addition, the systematic review of these studies suggests many limitations, including the lack of independent confirmation of the findings and scientific consensus on whether the changes observed would result in impairment of functional capacity or the ability to compensate for additional stresses. The safety levels of BPA for humans established by different risk assessment authorities show disparities with respect to the range of exposure. The BPA safety level for agencies other than EFSA fell within a range of similarly derived values (from a TDI of 0.005 ug/kg bw/day to a TDI of 0.5 ug/kg bw/day). Many agencies have accepted the study of [PERSON] et al. [47; 48] as a good statistical and methodological study to establish safe levels of BPA. Table 1 summarizes the safety levels of BPA by international organizations. U.S. EPA and the National Sanitation Foundation (NSF International) have determined the appropriate NOAEL for BPA to be 5 mg/kg bw/day, and the two agencies have set the chronic oral safety level of BPA as 0.05 mg/kg bw/day [42; 49] and 0.016 mg/kg bw/day [50], respectively. The U.S. Food and Drug Administration (US FDA) and Japan have proposed three safe levels for each critical endpoint [41; 51]. A provisional tolerable daily intake (pTDI) of 25 ug/kg bw/day was established in 1996 and 2008 by the Food Directorate of Health Canada [43; 44]. Meanwhile, the FAO/WHO did not establish the TDI of BPA due to a lack of toxicological data suitable for human risk assessment [40].