Toxic Tuesdays

Dealing with Uncertainty When Evaluating Toxicity​

Toxic Tuesdays

CHEJ highlights several toxic chemicals and the communities fighting to keep their citizens safe from harm.

Dealing with Uncertainty When Evaluating Toxicity

In a recent issue, we discussed the many challenges in evaluating the adverse health effects that result from exposure to a mixture of toxic chemicals. Despite this, scientists still estimate and assess risks by attempting to compensate for these uncertainties.

This is done by assigning an uncertainty factor (UF) to the different uncertainties. How well these uncertainty factors fill in the gap in what we do not know is a matter of controversy and opinion. Especially when you acknowledge that we only have good toxicity information on about 1% of the more than 80,000 chemicals that are in use.

Consider just a few of the uncertainties. The first step in assessing risks is to determine what substances a person was exposed to, at what concentration and for how long. Rarely is this information ever available, so assumptions need to be made to estimate this critical information. Sometimes, there is limited air, soil or water data. This data is often collected for a different purpose, such as to evaluate the need for remediation as opposed to evaluating public health risks. There are also uncertainties in how the samples were collected, the accuracies of and precision of the analytical measurements and the thoroughness of the sampling (were the samples taken at the right places, analyzed for the right substances and at relevant concentrations). At times, modeling is used to estimate how much of a chemical a person was exposed to (usually after making assumptions about even what kind of chemicals a person was exposed to), how long they were exposed and at what concentration.

The next step is to evaluate the toxicity information available on the chemical in question. This would include information from animal studies, clinical trials and epidemiological studies involving people. Since most of the data that exists is from animal studies, this step already creates enormous uncertainties. These uncertainties include extrapolating results in animals to people; the variability in response among people; the sensitivity in response among people; estimating acute or short-term responses in people when the only data you have is from chronic or long-term exposure, and vice versa. These examples just touch the surface of the many uncertainties in our understanding of how chemicals affect a person’s health. 

Another factor that comes into play is the health status of the individual who was exposed. People who are generally healthy and without pre-existing conditions respond differently to toxic chemicals than people with prior exposures, poor immune or nutritional status, or pre-existing health problems.

To address these many uncertainties, scientists have developed what were originally called safety factors, but now are referred to simply as uncertainty factors (UF). These uncertainty factors can range from 1 to 10 and often are multiplied together to yield a composite uncertainty factor that can be as high as 100 (10 x 10). These UFs are included in the estimate of the risks a person or group of people face.

Scientists give an UF to each specific uncertainty trying to compensate for the uncertainty. Doing this requires making many assumptions about areas of knowledge that very little is known about. These assumptions are made by “scientific experts” who very quickly become convinced that they “know” the health risks that a person or a group of people face. Of course, they do not really know. Instead, what they have is an opinion based on multiple assumptions, typically for a single substance.

What compounds this process is that the people who make these risk assessment estimates are scientific experts, and do not include the people who have to bear the risks of the chemical exposures. That’s not right! The people who bear the risks need to be involved in the risk assessment and health evaluation process because of the many uncertainties that exist in estimating exposures and in extrapolating what little data exist to evaluate adverse health effects resulting from exposures to low level mixtures of toxic chemicals.

For more about uncertainties when evaluating the adverse effects from chemical exposures, see Environmental Decisions in the Face of Uncertainty, by the Institute of Medicine of the National Academies, 2013.

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