Use of Benchmark Doses in Estimating Non-Cancer Effects

As we saw in chapter 7, toxicity factors used to evaluate non-cancer effects are primarily based on no-observed adverse effect levels (NOAELs) from animal studies. 

Uncertainty factors are incorporated into the NOAEL to develop a reference dose that represents a threshold dose below which adverse effects should not occur. This dose can be considered a safe dose. However, this approach suffers from several limitations, including the following  

By definition, the NOAEL is a level at which no adverse effects occur. However, all levels below the threshold will be NOAELs. The goal of animal studies is to identify the highest dose that causes no effect. This is the threshold dose, and is the most relevant dose upon which to base safe concentrations. The NOAEL approach rarely allows for use of this dose in most situations the investigator cannot know what the highest NOAEL is because it would require testing of too many different doses. 

In the 1980s, an approach was introduced that used the entire dose-response relationship for the chemical in establishing what were referred to as benchmark doses. This approach has gained favor over the past several years, especially for chemicals with developmental or reproductive effects. This approach eliminates the need to identify a NOAEL, and generally reduces the uncertainty associated with developing a safe level. However, it requires more data than the NOAEL approach, and therefore more time and money. 

Similar to cancer dose-response relationships (figure 10.1), the best-fit curve steepness and location are uncertain. Therefore, a 95UCL curve is identified based on the variability of the laboratory data. An EDjg is also identified from this 95UCL curve. This lower (e.g., more health-protective) EDjo is then selected as the BMD. This is shown in figure 10.3. 

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