Structure-Activity Relationships and the Classification of Chemicals

Haz-Map has been published on the National Library of Medicine (NLM) website since 2002. In 2003, there were 1237 chemicals in Haz-Map, including all regulated by OSHA and published in Documentation of the TLVs and BEIs, 7th Ed. by ACGIH (American Conference of Governmental Industrial Hygienists). Since 2006, the author has been contracted by the US Department of Labor to work full-time to add chemicals to Haz-Map. The count was 5723 in 2010 and is currently 7438. At current rates for completing profiles, the count by the end of this year will be 11,480.

Haz-Map can be seen as a research project to explore what we know and don't know about the thousands of chemicals to which workers are exposed, with application to environmental toxicology as well. In adding chemicals to Haz-Map, the structures of new chemicals are compared to the structures of well-known chemicals already in the database. Most of the new chemicals added can be classified as members of a class. There are now 250 classes (Categories) of chemicals in Haz-Map under 12 Major Categories. It is basic logic that members of a class inherit the properties of that class.

In summary, Haz-Map is a research project to publish the established occupational health effects of hazardous chemicals and to study the structure-activity relationships of workplace chemicals. Such research can help to classify chemicals for the prevention of occupational and environmental diseases.

With Sufficient Force, Something Happens

In toxicology and pharmacology, the most important factor is the dose. The impact of a poison or drug depends upon its mass and how quickly it is absorbed and excreted. Without sufficient dose, there is no adverse effect (toxicology) or no therapeutic effect (pharmacology).

Paracelsus (1493-1541) was the first physician to understand this concept based on his experiments, "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison, and a remedy." In his experiments, he plotted what we call today "dose-response relationships." Such experiments determine the percentage of organisms or systems that respond to chemicals at increasingly higher doses. Below a certain threshold dose, no adverse effects or therapeutic effects are observed.

The existence of a dose-response relationship strengthens the evidence for a causal relationship between the chemical and the disease. This is fairly simple to do for acute effects like carbon monoxide poisoning. With increasing doses above the threshold dose, increasing number of experimental animals have adverse effects. The dose-response relationship is also important in determining causality in chronic diseases, for example, the fact that moderate smokers have intermediate risks for lung cancer compared with nonsmokers and heavy smokers.