Risk Assessment From In Vitro Testing: Staggeringly Complex or Just Impossible?
In vitro testing has been proposed as a way to clear out the backlog of toxicity testing on thousands of chemicals currently in use. It's quicker and cheaper and lab animals needn't be "sacrificed". The plan is to use the results to estimate the dose response curve in humans so that regulatory agencies can regulate accordingly. Too bad it won't be that easy.
In this month's Environmental Health Perspectives, Kenny Crump et al discuss the daunting task of using data from in vitro testing to set reasonably safe exposure limits. See (free): "The Future Use of In Vitro Data in Risk Assessment to Set Human Exposure Standards".
The problem of course is that it's not a matter of exposing some cells in a petri dish to the chemical of interesting and watching what happens. There are multiple pathways and multiple feedback mechanisms involving multiple types of cells that define the pathways to toxicity, not to mention any that work to offset and fix the ill effects. How many might there be and in how many ways might they interact? A model of how E. coli protects against heat shock "consists of a set of 31 differential-algebraic equations with 27 kinetic parameters, data for many of which are not yet available." Just finding these pathways will be a huge undertaking and billions of dollars in funding are being sought over the next decade to find and elucidate them.
Nevertheless, the authors conclude: "Use of in vitro data in risk assessment has great promise toward allowing chemicals to be tested more quickly and cheaply and for reducing or eliminating the need for subjecting animals to toxic insults. It is our hope that the bar for accepting approaches based on in vitro data will not be set too high. In view of the numerous serious limitations of current approaches, results from these methods based on whole-animal data should not be held up as gold standards. This point is particularly important considering that almost all whole-animal data are obtained from high doses that may operate through different sets of [toxicity pathways] than do low doses."
That last sentence is the key. We're entering a whole new world of toxic torts. One in which many heretofore innocuous chemicals will be claimed to be toxic at very low doses.
