There are two types of information the risk assessor must gather in order to determine the potential of an agent to cause adverse health effects: types of injury and conditions of exposure. An adverse effect is defined by the US Environmental Protection Agency as "..any biochemical, physiological, anatomical, pathological, and/or behavioral change that results in functional impairment that may affect the performance of the whole organism or reduce the ability of the organism to respond to an additional challenge."
The types of injury and conditions of exposure characterize the 'inherent toxicity' of the substance in question.
Types of Injury
The types of injury from exposure to a toxicant can be either systemic or contact. Examples of systemic injury include liver and kidney damage, reproductive toxicity, developmental toxicity affecting the fetus, and cancer. Contact injuries include skin irritation, rash, blisters or other injury at the site of contact with the agent.
Conditions of Exposure
The conditions of exposure describe the conditions under which the various types of injury occur and are based on duration of exposure.
Sources of Information
Assessors have access to numerous databases, which are compiled with hazard information from research studies on a vast array of substances. The types of studies include:
The most pertinent and best quality studies are pooled together and analyzed to give a portrait of the agent.
Epidemiological studies are considered the best source of information because they are based on human exposures. The best epidemiological studies will give a clear and direct link between exposure and adverse effects.
Relative Risk (RR) is an expression frequently used to describe the results of any given epidemiological study.
Relative Risk = Incidence of Death or Disease Among the Exposed vs. Unexposed Population
Epidemiological studies are limited because there is often no data for new substances, it can be difficult for the epidemiologist to discount factors such as smoking or other exposures which cause disease or health effects, and it is often difficult to obtain accurate exposure data.
In the absence of human data it is assumed that effects observed in animals have the potential to occur in humans. This is the purpose of the animal study. Some animals exhibit a specific type of response that is very similar to humans. For example developmental studies are conducted on rats and rabbits, not on mice. The types of animal studies conducted are based on exposure duration and dose range:
Acute: A single dose of the substance with 14 days observation. This type of study is generally to determine a lethal dosage; an LD50 . LD50 is defined as the dose at which 50% of the study population experiences death as the adverse effect. Unpleasant as it may seem, it is necessary to determine the lethal dose for an average individual in order to rate the danger of this substance relative to other substances. All substances, even sugar and water are lethal at large enough dosages. Substances that are lethal at very low doses will generally not be allowed on the market for the general public and may be unlawful to possess.
Subchronic: This type of study lasts for 5-90 days with smaller doses given at a regular interval. The purpose of this type of test may be to obtain the Maximum Tolerated Dose (MTD), No Observed Effects Level (NOEL), or Lowest Observed Effects Level (LOEL). MTD is defined as the highest dose that the test species can tolerate without causing excessive toxicity other than tumor formation.
Chronic: This study lasts for 1-2 years and may be used for determining the long term NOEL, LOEL or cancer formation (oncogenicity).
Any of the above studies can be conducted via an oral, dermal or inhalation route of exposure with a minimum of three groups of animals.
The effects of the substance are then determined based on clinical signs of toxicity such as loss of balance, loss of body weight and other obvious clinical signs, organ tissue damage, developmental and reproductive damage, immunotoxicity, as well as tumor formation.
This page was prepared by Theresa L. Pedersen, UCD EXTOXNET FAQ Team. September, 1997. I would like to thank Nu-may Ruby Reed, PhD for allowing me to draw freely from her lectures on Health Risk Assessment, which are the backbone of this page. Her lectures were conducted at the University of California, Davis in the fall quarter of 1996. Thanks again Ruby!