Bisphenol A: A Scientific Evaluation

Michael A. Kamrin, PhD

Disclosures
In This Article

What Are the Risks of BPA in Humans?

To assess the risk of BPA to humans, it is necessary to compare the doses required to cause adverse effects with the doses to which people are exposed. The ratio of these 2 values is a measure of whether toxicity is likely to occur and, if not, what the margin of safety is. When this ratio is higher, it is less likely that humans are at risk.

The absence of convincing effects of BPA at low doses suggests that the high-dose rodent studies are the most appropriate ones to use in estimating the minimum exposure that will cause toxicity in humans. The results of the 1982 NTP study mentioned previously[9] suggest that the lowest dose at which effects were observed is 50 mg/kg bw/day. This value is consistent with the results from the more recent 3-generation study by Tyl and coworkers.[11] This recent study also showed a "no-effect" level (NOEL) of 5 mg/kg bw/day. (It is important to note that these "lowest effect" levels are for reduction in body weight and are not related to reproductive or developmental toxicity.)

It is not possible to directly translate these NOELs in rodents into corresponding levels in humans because of incomplete knowledge of the biology of both types of organisms. As a result, a variety of assumptions are made in performing this extrapolation. In general, such extrapolations are performed by government agencies as part of activities aimed at reducing any human risk from likely levels of exposure. Because the aim is to be protective rather than scientifically accurate, the assumptions used are designed to overstate toxicity. Thus, the resultant values are acceptable daily intakes rather than NOELs and, as such, are lower than NOELs that may be generated with the best science.

On the basis of this approach, the US Environmental Protection Agency (EPA) has calculated its human acceptable daily-intake level, known as the Reference Dose (RfD), by dividing the rodent "lowest effect" level of 50 mg/kg bw/day by 1000. This calculation is based on the assumption that humans may be up to 10 times more sensitive than rodents to BPA exposure; that a sensitive human may be up to 10 times more sensitive than a typical human; and that significant scientific uncertainties about the effects of BPA remain due to limitations in available studies. Thus, the US EPA RfD, published in its Integrated Risk Information System, is 50 mcg/kg bw/day or .050 mg/kg bw/day.[18]

The European Commission Scientific Committee on Food[2] based its assessment on the rodent NOEL (from the 3-generation study) rather than the "lowest effect" level from the NTP study, ie, 5 mg/kg bw, and made a different assumption about the magnitude of the uncertainty factor needed to account for data gaps. As a result, it arrived at a tentative, acceptable daily-intake value, known in Europe as the Tolerable Daily Intake (TDI), of 10 mcg/kg bw/day or .010 mg/kg bw/day. It should be noted that this TDI considers effects on very young animals and is therefore applicable to young children.

As indicated previously, metabolic studies suggest that contrary to one of the fundamental assumptions that are part of the approach to calculate RfDs and TDIs, humans are likely to be less, rather than more, sensitive to BPA effects than rodents. Incorporating the results of these studies into the assessment would very likely lead to a significantly higher acceptable level of daily exposure.

As discussed in detail in the section on exposure, using the best available scientific data leads to a range of .001-.1 mcg/kg bw/day as a reasonable estimate of daily exposure. Comparing the high end of this range, .1 mcg/kg bw/day, with the RfD and TDI, it can be seen that human exposures are 100-1000 times lower than the acceptable levels calculated by government agencies. The ratio of the acceptable daily intake to the high end of the exposure-dose range is 100 for the TDI and 500 for the RfD. This value is often described as a margin of safety or a margin of exposure and in this case it is 100 or 500, depending on whether the TDI or RfD is used.

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