Thank you for the question.
When we use the animal models, in a lot of cases, to do what we call hazard identification, it's basically an internationally recognized standard, as I mentioned earlier. There are specific guidelines and interpretations that are internationally recognized by all the various countries, including the EU, Australia, and so on.
When we expose animals to certain chemicals and ask how is that going to be related to humans—and I agree with you—what we do is take the precautionary approach, and we actually apply what we call the uncertainty factor, or safety factors, which means we are not sure; therefore, we build in a certain margin of error or margin of translation from animal to human. So that builds in that so-called uncertainty in linking it from animal data, then, to the human environment. That is usually a factor of about 100 times, just to build in that uncertainty or that precautionary approach that we take.
Secondly, when we look at the risk assessment or the hazard identification, we also look at the end point or the level at which there is a certain effect being observed in animals or in rats. Also, as I mentioned, it's not only dealing with just one species. We look at more than one species. For example, we could do it in rats; we could do it in mice, or sometimes in dogs. So we look at the variability among the various species as well in the pre-market scenario.
From that we look at whether there is any concern about the age variation within the lifetime of the animals. Is there something that's more sensitive or obvious for the older animals? Is there anything of concern when they are reaching the later stage of their lifetime, or for pregnant women, and so on and so forth? When we identify those potential health concerns, we tack on another uncertainty factor of margin of safety, which is the margin where we say, okay, in order to be protective—that is, applying the precautionary approach again—we tack another uncertainty factor onto that.
By accumulating all this uncertainty, or the safety margin, if we want to call it that, including what we call the entire species in the sense that animal to human may be different, and when we talk about intra-species, within a population, let's say within the human populations, because of the various ages, races, and all that sort of stuff, there may be variability, so we apply that protective factor in addition to that.
By doing all this, we actually build in enough of what we call the margin of safety, but you can call it a margin of uncertainty, taking the precautionary approach to build in that comfort zone in order to develop what we call the acceptable daily intake.
