Creating a Project Budget

BOS 4201, Toxicology 1

Course Learning Outcomes for Unit VI Upon completion of this unit, students should be able to:

7. Discuss the objectives of toxicity testing. 7.1 Explain the objectives of toxicity testing. 7.2 Assess the endpoints for toxicity testing.

Course/Unit Learning Outcomes

Learning Activity

7.1 Unit Lesson, Unit Readings

7.2 Unit Lesson, Unit Readings

Reading Assignment Chapter 21: Toxicity Testing

Unit Lesson There are thousands of new chemicals introduced every year by manufacturers, and the health risks from any potential exposure need to be assessed for both the occupational and environmental issues. Toxicity Testing Toxicity testing is performed to assess the health risks of exposure. One purpose of the testing is to determine a dose-effect, and the other is to determine the toxicity relative to other known chemicals. There are two common methods used for this; one uses laboratory animals, and the other uses in vitro testing. Other methods for testing include human data from exposures and non-biological models. The objectives of toxicity testing are to determine any adverse effects. Exposure durations are an important factor for toxicity testing. The categories of exposure duration include acute, subacute, subchronic, and chronic. The outcomes include the severity, if the effects are reversible or irreversible, and if the effects are immediate or delayed. The extent and complexity of the testing are dependent on the type of chemical hazard, how the chemical is being used, the projected level of exposure, and the extent of the release into the environment. The objective is to predict the human health outcomes as a result of the route of exposure and dose. A toxicity test must include the following components:

 a biological model,

 an endpoint that can be measured, and

 a well-developed protocol (Richards & Bourgeois, 2014, p. 368). Endpoints to toxicity testing include the following indicators:

 inflammation,

 necrosis,

 lipid peroxidation,

 receptor interaction, and

 immunosuppression (Richards & Bourgeois, 2014, p. 197). Toxicity testing on animals is used to make inferences on human health. The data obtained from animal testing is used to estimate human risk for both acute and chronic exposures. In addition, the toxicity studies

UNIT VI STUDY GUIDE

Toxicity Testing

BOS 4201, Toxicology 2

UNIT x STUDY GUIDE

Title

using laboratory animals provide an understanding of how a chemical may produce an adverse response in humans. They also provide a range of exposure levels from no effect to highly toxic, and they are a justification for public health risk assessments (Richards & Bourgeois, 2014). The most common animals used are rats and mice as well as guinea pigs and rabbits. The Society of Toxicology (2006) has a public policy that states that research on animals is necessary and reliable to predict toxic properties. The Society of Toxicology (2006) adopted a public policy statement concerning the use of animals for toxicological studies, which has been summarized below.

 Research involving laboratory animals is necessary to ensure and enhance human and animal health and protection of the environment.

 In the absence of human data, research with experimental animals is the most reliable means of detecting important toxic properties of chemical substances and for estimating risks to human and environmental health.

 Research animals must be used in a responsible manner.

 Scientifically valid research designed to reduce, refine, or replace the need for laboratory animals is encouraged (Richards & Bourgeois, 2014, p. 371).

The endpoints of the toxicological tests must be quantifiable and repeatable. It includes anything from irritation to death. There are standardized tests to determine such things as acute toxicity, dermal toxicity, chronic toxicity, reproductive toxicity, and neurotoxicity (Richards & Bourgeois, 2014). Using death as an endpoint in toxicity testing is common, and the results are expressed as LD50, the lethal dose given in which 50% of the animals tested die. The LD50 does not provide any information on the chronic effects. The route of exposure for the LD50 is usually oral. For exposure where inhalation is the route of exposure, the LC50 (lethal concentration) value is referenced, and it also indicates that 50% of the test animals died. Richards and Bourgeois (2014) stated, “It must be recognized that the LD50 acute toxicity testing is a poor indicator of human health effects because death is the least desirable measure of toxicity” (p. 374). Efficacy and the therapeutic index are two measures that actually provide information on doses that will safely utilize a chemical for treatment. Quantitatively measured, the ED50 measures the efficacy, or the lowest effective dose, that is evident in 50% of the population (Richards & Bourgeois, 2014). The therapeutic index (TI) indicates the safety of the drug. The higher the therapeutic index, the safer the drug (Richards & Bourgeois, 2014). A small therapeutic index indicates that there is a small margin between the lethal/toxic dose and effective dose. In other words, there is a higher risk of overdosing versus treating a condition with drugs that have a very small therapeutic index. However, drugs with a high therapeutic index have a large margin between the lethal/toxic dose and the effective dose, and, therefore, they hold less of a risk in overdosing with a dose that is effective for treatment of the condition. Human studies are another method of determining the toxicity of a substance. Unfortunately, people have to be exposed and experience the health effects before a health effect is verified. There are a number of sources for toxicity information from human studies, case reports, clinical studies, and epidemiological studies. Epidemiological studies are indicated when there are questions regarding the relationship between an exposure and disease. The results of an epidemiological study show through numbers whether a relationship exists and whether the results represent a relative risk. For example, a smoker would be 20 times more likely to develop lung cancer than a nonsmoker. Although epidemiological studies offer obvious advantages over laboratory studies, there are some notable disadvantages, which are listed below.

 Tests are not cost effective.

 It is difficult to quantify exposures.

 A large number of individuals are needed for statistical evaluation.

 A controlled environment is not possible, allowing other factors to question accuracy of results.

 Extended periods of time are needed to complete studies and publish results (Richards & Bourgeois, 2014, p. 384).

BOS 4201, Toxicology 3

UNIT x STUDY GUIDE

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Any new chemical being introduced needs to be tested for potential toxicity to human health and to the environment. Both the acute and chronic effects must be known to protect the health of those exposed. The LD50 and the LC50 are important concepts in assessing the endpoints of toxicity. Animals are used in the testing of chemical toxicity, and there should be more methods introduced to reduce or eliminate the distress caused by the tests. Alternatives to animal testing were proposed to overcome some of the drawbacks associated with animal experiments and to avoid the unethical procedures. The 3 Rs strategy is being applied, which stands for reduction, refinement, and replacement of laboratory use of animals. Alternatives to animal testing, such as tissue and cell cultures and computer modeling, offer limited data in some cases but may be utilized as a replacement for some types of animal testing. Alternative methods are growing in popularity. Computer modeling can provide information on alternatives. Researchers are encouraged to replace the animal with another test, reduce the total number of animals used, and refine the study in order to reduce the distress of laboratory animals (Richards & Bourgeois, 2014). The computer models can help predict the toxicity from the parent compound and the metabolites; this is especially important for any substances that have not been tested yet. In vitro tests can be utilized to perform some endpoint toxicity tests such as the ones listed below:

 mutagenicity and chromosome damage,

 tumor promotion,

 cytotoxicity,

 eye irritation,

 cardiac muscle toxicity,

 nephrotoxicity,

 hepatotoxicity,

 endocrine toxicity,

 respiratory toxicity,

 reproductive toxicity, and

 ecological toxicity (Richards & Bourgeois, 2014, pp. 387–390).

References Richards, I. S., & Bourgeois, M. M. (2014). Principles and practice of toxicology in public health (2nd ed.).

Burlington, MA: Jones & Bartlett Learning. Society of Toxicology. (2006). Animals in research: The importance of animals in the science of toxicology.

Retrieved from https://www.toxicology.org/pubs/docs/air/AIR_Final.pdf

Suggested Reading Click here to access the Chapter 21 PowerPoint presentation. Click here to access a PDF version of the presentation.