Suggestions for topics for next week is an elaboration on the Ames and Gold article, "Paracelsus to parascience: the environmental cancer distraction." I'm interested in the 'industry's' take on the article's premises and any action the EPA is considering. I would also assume that some of the same ideas expressed for carcinogens may be applicable for non-carcinogens.
When we say "industry" we often think of major industrial producers of pollution. However when considering the notion of carcinogens, the agriculture industry and food and drug industry are very concerned and involved as well.
Let's review concept of mutations and cancer, then expound on the concept of threshold.. Mutations to the DNA of cells cause cancer. So chemicals that cause mutations cause cancer. But, some chemicals (and things) that do not cause mutations, like asbestos, also cause cancer. (And some things, known to cause mutations in standard tests, do not cause cancer in whole animals.) Since no mutations in our somatic cells are beneficial, most people would believe that all mutations are harmful. (Mutations to the germ tissue are also almost always harmful, but one mutation in a gillion will be beneficial to the progeny, and from that stem changes that lead to better adaptation of species to their environment and eventually to new species.) Conventional wisdom is that 6 to 8 mutations in key locations of a cell's geome are required for cancer. I know of no science that refutes that notion.
In dose-response testing and analysis, a threshold is the dose, below which there is no response, or at least no observable response. The dose at which the effect is zero. Most non-carcinogens are assumed to have a threshold, and that is the starting point of the derivation of the RfD. We might describe the threshold as the NOEL, NOAEL, which is somewhere below the LOAEL. But is this true? For example, I apply a organophosphate insecticide, but feel just fine. I go to my annual physical and the doctor says I'm just fine. Do the 'cides I am exposed to have no effect? At the "clinical" level they did not, because they did not result in "disease." At the social level they did not, because I keep my job and do not make an insurance claim. How about at the molecular and cellular level? The ACh inhibitors keep me from sweating normally. If I work in a hot climate, my body may produce new sweat glands or the old ones may hypertrophy. Thus there is an effect, although in that example not an "adverse" effect. I suspect, that if we had a molecular microscope, we'd see that almost everything has some effect on almost everything else. But often the effect is not noticeable or not worth thinking about.
From that we might speculate about two aspects of the high to low dose extrapolation. First, that a chemical that causes mutations at a high dose might not cause mutations at a low dose. For example, the body may have protective mechanisms that prevent chemical adducts from forming, as long at the dose is below a certain level. Second, as a practical matter, the amount of mutations might be so low that they are inconsequential or immeasurably small, at least compared with other sources of mutations, and hence are not worth talking about. Ames and Gold then introduce a third concept, again from the practical side, that avoiding these chemicals might lead to more harm. For example, pesticide-free fruits and vegetables cost more so people eat less of them. Another example of this is the use of subsistence (traditional) foods. The conflict being (besides the weak link between chemicals in those foods and disease) is that the traditional foods have certain beneficial nutrients (polyunsaturated fats), which the likely replacement foods lack. Here is a summary and full report.
For a full overview of cancer risk assessment from the EPA's viewpoint, read Proposed Guidelines for Carcinogen Risk Assessment.
Module 13 Index