Risk Assessment
 Elmhurst College
 Chemistry Department
   Virtual ChemBook


Click for larger image 

Risk Assessment and Analysis

INTRODUCTION:

Adapted from: "Chemical Risk: A Primer", American Chemical Society, 1984.

Scientifically, many of the same questions are asked repeatedly. What tests are being used and what do they determine? How are the test results interpreted? What assumptions are made and how complete and accurate are the data? What are the risks to the general public, and to particularly sensitive individuals such as children and the elderly? How do exposure to these chemicals compare with other risks that we take everyday? What is acceptable risk?

Risk:

People take risks every day, in many forms - crossing the street, smoking, drinking alcohol, driving a car, the list is endless. Somehow we catalog all of these risks, deciding some are acceptable, others are not, and not even considering others. Every risk involves a combination of these two factors: (1) the probability of an undesirable occurrence and (2) the severity of that occurrence.

A chemical risk assessment consists of an estimation of the probability of harm and the severity of the consequence as measured by some adverse health effect caused by a certain level of exposure to a chemical for a certain length of time. These two factors, although simple to state, are frequently difficult to determine. Exposure estimates of a food additive or a drug, require careful analysis of the products containing them, and an estimation of the consumption patterns by different populations. This analysis may provide information about the degree of risk, but not whether the chemical is "safe", which is an individual judgment.

 Toxicity Estimation Techniques:

Clinical Human Studies
provide the strongest evidence of human toxicity to a chemical by observing the actual acute toxic effects experienced by individuals. Scientists can determine cause and effect by comparison of control groups (those not exposed to the chemical) to those that are exposed to the chemical. Various doses of the chemical may also be given in this type of study to determine the minimum effect dose, as well as, the toxic dose. However, obvious moral and ethical reasons limit the toxicity testing that can be directly performed on humans.

Epidemiological Studies are used to gather data from various populations on the incidence and distribution of disease or ill effects associated with chemical exposures in real life situations. There are many problems associated with determining exposures, proper controls, limiting other factors which may be responsible. For example these studies were carried out for many years before smoking was found to cause lung cancers.

Animal Studies are used to determine under controlled laboratory conditions, the dose of the chemical in question that will produce toxic effects in an animal. This is then used to help predict what may occur in humans, however animals and humans may not have the same response to a toxic chemical.

Estimating Chemical Toxicity:

The fundamental question of any chemical risk assessment is whether a chemical substance will reach a target individual and a target organ in a large enough concentration to cause damage. Toxicity (acute - short term or chronic - long term) is the likelihood a specific concentration of a substance to cause harm to living organism when ingested, inhaled, are absorbed through the skin. The specific type of damage is determined by the concentration or level of exposure. For example a small amount of salt is beneficial to most people, however chronic effects of salt may cause kidney problems. Drinking an excess of sea water (3 % salt solution) (acute dose) will cause death.

Chemical Analysis:

A necessary procedure in chemical risk assessment is to determine the chemical properties of the substance in relation to biological processes. These properties include: chemical structure - the arrangement of atoms and form; solubility in water (polar) and lipids (non-polar) in various biological compartments such as the stomach, intestines, blood, cells, brain, etc.; bioaccumulation in various tissues or non retention in the body; transformation of the chemical from one form to another by biological processes.


Click for larger image 

 High Dose to Low Dose Extrapolation:

An important step in the estimation of chemical toxicity is generating a dose response curve. This is a graphic representation of the data showing adverse effects at particular dose levels as depicted by the red line. The data in the red line area are generated by giving relatively high doses to a fairly small number of test animals.

If low doses are given to the animals, no adverse effects may show up in a small sample of test animals. Sometimes risk effects which should be regulated need to be observed at a level of one case in a million cases. Since this is not possible with small samples of test animals, the high doses are used. The high doses themselves may cause problems in interpreting the data.

Linear Extrapolation Theory: Once the high dose data is obtained and plotted as in the red line, an extrapolation to low does is made. A straight line, linear extrapolation may be used, which then assumes that even a very tiny dose may cause some adverse effect.

Threshold Theory: According to the threshold theory of toxicity, a toxic substance must be present in an organism at some threshold concentration before any adverse effects are evident. Below this concentration, no such adverse effects are observed. By using this theory it is assumed that tiny doses of a toxic substance will not cause any adverse effects.

Scientists do not agree which theory provides the correct answer concerning low dose effects of toxic substances. A further complication is the fact that animal data is then extrapolated to human effects, which may not provide the correct answer either, a human is not a "giant rat".

 

TOXICITY TESTING EXPERIMENTAL DESIGN

Controlled Experiments
are designed to consider some of the following: amount of chemical to be tested, route of administration, the effect and organ to be observed, the length of time for the test, and the possible use of animals.

See graphic on the left

According to the Toxicity Threshold Theory , a toxic substance must be present in an organism at some "threshold" concentration before any toxic effects are evident. Therefore exposing test animals to large doses of potentially toxic chemicals almost certainly will elicit a toxic response.

High to Low Dose Extrapolation using a dose-response curve is an important step in any estimation of chemical toxicity. The dose-response curve is a graphic representation of the quantitative relationship between the level of exposure and the intensity or occurrence of a resulting adverse health effect. The effects at high exposure levels are extrapolated to low exposure levels. The problem is that scientists disagree on the method of extrapolation - whether linear to the zero point (any tiny dose may have some effect) or whether there is a threshold limit (small doses have no toxic effects).

Estimation of Risk is usually quantified as a number after all the test results are evaluated. The risk may be one in a million, one in 100,000, or 1 in 1000. This number is still uncertain (as much as 100 times greater or smaller) and of little value unless compared to a more familiar risk. The final determination of acceptable risk is a social decision, not a scientific one. No absolute answer can be provided to the question of, "How safe is safe enough?"