Chemical toxicity: A matter of massive miscalculation

Published March 1, 2001

An introduction to toxicology

The toxicology testing laboratory dates back to the 1930s, but the science of toxicology in the United States can be traced more realistically to the formation of the Society of Toxicology in 1961. The Society enrolled as members the growing number of scientists involved in testing the effects of environmental pollutants, food additives, drugs, and other chemicals. It was not until the late 1970s and the 1980s that academic departments of toxicology were established at many universities.

Thus, toxicology is a very young discipline. Many of the scientists we call toxicologists have become such through experience rather than formal training. Differing levels of toxicological expertise have contributed to the conflict and uncertainty in the scientific community regarding the toxic effects of a number of chemicals.

Toxicology is a discipline with one principal goal: to understand how chemicals can adversely affect living organisms. Due to the multiplicity of chemicals and our limited understanding of how the human organism works, questions often arise as to whether an adverse effect has actually occurred, even if some biological change can be detected.

Toxicology can provide answers to many questions we wish to address, but those answers must be looked at cautiously. We should not use these data to develop a false sense of what we know and unrealistic expectations for what our actions can accomplish.

We have been taught that science produces certainty. As a result, the public is impatient with scientists who express uncertainty, and tend to believe scientists who express their views without reservations.

In toxicology, the certainty most of us seek is that a particular chemical is safe. Unfortunately, there is no such thing as an absolutely safe chemical: all chemicals can cause toxic effects in large enough amounts. When faced with this reality, most people look for a different certainty: a “safe” amount. They want to know the exact level at which a chemical changes from nontoxic to toxic. Again, this is not a scientifically realistic goal. Human individuals vary tremendously in their responses to their environment, including the chemicals in it, so what is “safe” for one person may not be “safe” for another.

While the government sets “safe” levels for many chemicals, the rationale behind such standards is not entirely scientific. Most people would like to entirely eliminate chemicals identified as highly toxic, but the ubiquitous distribution of many such chemicals makes their elimination unrealistic.

In the minds of the public, however, a single number becomes a dividing line between “safe” and “unsafe.” The amount and quality of scientific evidence behind this number varies from case to case and changes over time, much to the consternation and almost total lack of understanding on the part of the public.

Many levels of toxicity

The acute toxicity of a chemical refers to its ability to do harm as a result of a one-time exposure to the chemical. This exposure is sudden and commonly produces a health emergency. Chronic toxicity, by contrast, refers to the ability of a chemical to do systematic damage as a result of repeated exposures to small quantities or low concentrations of a chemical over long periods of time.

The reactions produced by these two different types of exposure bear no resemblance to one another. The chronic toxic effects of a chemical cannot be predicted from knowledge of that chemical’s acute exposure effects.

Some chemicals have a high acute toxicity but no chronic toxicity. That is to say, small quantities over a long period of time are harmless and, in some cases, are beneficial. Vitamin D and fluoride are two examples. We require small quantities of vitamin D daily for good health, and we know that fluoride is essential for good dental health. The same can be said of sodium chloride, common table salt.

Not surprisingly, some chemicals are chronically toxic but acutely non-toxic. Metallic mercury is one example. A large ingestion of a single dose of metallic mercury will pass through the body without causing significant damage, but a buildup of mercury in small amounts over a lifetime can be lethal.

The dose makes the poison

Although there is little correlation between acute and chronic toxicity, each in its own way is dose-related. The greater the dose, either in small continuous quantities or in a single large quantity, the greater the effect will be.

We ingest many “lethal” doses of a wide variety of compounds that have no effect on us because we spread the dose out over a lifetime. Caffeine in coffee, oxalic acid in spinach, ethanol in scotch, and acetylsalicylic acid in aspirin are just a few examples. Yet even in the face of evidence and common sense, the notion that exposure to trace quantities of foreign chemicals may actually produce beneficial effects is unacceptable to many people who have an anti-chemical bias.

The poor health of people who worked at certain trades was noted by early Greek and Roman physicians. The first monograph on occupational diseases was published in 1567, 26 years after the death of its author, the Swiss physician Paracelus. He set forth one of the basic tenets of modern toxicology when he wrote: “What is it that is not poison? All things are poison and nothing is without poison. It is the dose only that makes a thing not a poison.”

Thresholds are key

The term “threshold” is used in toxicology to describe the dividing line between no-effect and effect levels of exposure. It may be considered as a maximum quantity of a chemical that produces no effect, or the minimum quantity that does produce an effect. It is common for the threshold to vary with the species involved and even with individuals within each species. For purposes of extrapolating animal data to humans, the highest level of exposure that produces no detectable adverse effect of any kind in any test animal is used by toxicologists as the threshold.

A “margin of safety” is an arbitrarily established separation between the threshold of a chemical found by animal experimentation and the level of exposure estimated to be safe for humans. The FDA adopted the convention of a hundredfold margin of safety years ago when it began setting standards for acceptable quantities of food additives.

The assumptions behind the hundredfold margin are that humans are ten times more sensitive to adverse effects of chemicals than are test animals, and that the weak in the human population are ten times more sensitive than the healthy. Compounding the tens, the FDA arrived at the hundredfold margin.

“Safe” levels of a chemical, then, are set by using animal studies to extrapolate the no-effect level for humans, then reducing that quantity by two orders of magnitude for additional safety. Some in the anti-chemical movement have even demanded the government a thousandfold margin, although no more scientific justification for that exists than for the hundredfold margin.

No matter how large the experiment or how great the margin of safety, one can never prove that a chemical–or any other factor in the environment, for that matter–is totally harmless. We can only offer probabilities that there will, in fact, be no harm. Absolute safety is the complete absence of harm . . . and it’s a goal we can never achieve.