Environmental Toxicology Chapter 3 Environmental Toxicology

Learning Objectives By the end of this chapter the reader will be able to: Define the term toxicology Define three important terms used in the field of toxicology State five factors that affect responses to a toxic chemical Discuss the steps involved in risk assessment Describe methods for human exposure assessment

Basic Assumption of Toxicology “All substances are poisons; there is none that is not a poison. The right dose differentiates a poison from a remedy.”

Definition of Toxicology Toxicology is defined as “the study of the adverse effects of chemicals on living organisms.”

History of Toxicology: Paracelsus Paracelsus was one of the founders of modern toxicology. Active during the time of da Vinci and Copernicus (early 16th century). His contributions included the concept of the dose-response relationship and the notion of target organ specificity of chemicals.

History of Toxicology: Mathieu Orfila In the 1800s, he authored a number of significant works, among them Trait des poisons (1813). This work described various types of poisons and their bodily effects, a development that contributed to the foundations of forensic toxicology.

What is a Toxicologist? A scientist who has received extensive training in order to investigate in living organisms “the adverse effects of chemicals . . . (including their cellular, biochemical, and molecular mechanisms of action) and assess the probability of their occurrence.”

Fields within Toxicology Regulatory Forensic Clinical Environmental Reproductive Developmental

Environmental Toxicology Environmental toxicology examines how environmental exposures to chemical pollutants may present risks to biological organisms, particularly animals, birds, and fish.

Poison “defined as any agent capable of producing a deleterious response in a biological system.”

Toxicity Refers to “the degree to which something is poisonous.” Related to a material’s physical and chemical properties

Toxicants Toxic substances that are man-made or result from human (anthropogenic) activity.

Toxin Usually refers to a toxic substance made by living organisms including reptiles, insects, plants and microorganisms.

Examples of Toxic Plants Some mushrooms (e.g., Amanita phalloides, “death cap”) Poison hemlock Foxglove Poison oak/poison ivy Rhubarb, especially the leaves, which have high levels of oxalates Some houseplants such as dieffenbachia

Dose Refers to “the amount of a substance administered at one time.”

Several Ways of Describing a Dose Exposure dose Absorbed dose Administered dose Total dose External dose Internal dose Biologically effective dose

Lethal Dose 50 (LD50) To describe toxic effects, toxicologists use the symbol LD50, which is “the dosage (mg/kg body weight) causing death in 50 percent of exposed animals.” Used to compare the toxicities of different chemicals.

Dose-Response Relationship A type of correlative relationship between “the characteristics of exposure to a chemical and the spectrum of effects caused by the chemical.”

Dose-Response Curve A type of graph used to describe the effect of exposure to a chemical or toxic substance upon an organism such as an experimental animal.

Two Types of Dose-Response Curves One for the responses of an individual to a chemical One for a population

Figure 3-2 Individual dose–response curve. Source: Reprinted with permission from AE Marczewski, M Kamrin. Toxicology for the Citizen. 2nd ed. East Lansing, Mich: Michigan State University, Center for Integrative Toxicology; 1991:5. .

Figure 3-3 A population dose–response curve. Source: Adapted from Guidelines for Ecological Risk Assessment. US Environmental Protection Agency, Risk Assessment Forum. Washington, DC, EPA/630/R095/002F; 1998:81.

Figure 3-4 The threshold of a dose–response curve. Refers to the lowest dose at which a particular response may occur. Source: Reprinted from National Institutes of Health, National Institute of Environmental Health Sciences. Chemicals, the Environment and You: Explorations in Science and Human Health, p. 63. Available at: http://science.education.nih.gov/supplements/nih2/chemicals/guide/pdfs/lesson3.pdf. Accessed February 25, 2010.

Factors That Affect the Concentration and Toxicity of a Chemical Route of entry into the body Received dose of the chemical Duration of exposure Interactions that transpire among multiple chemicals Individual sensitivity

Most Frequent Sites of Exposure to Environmental Chemicals Gastrointestinal tract Respiratory System Skin

Routes of Exposure Ingestion (e.g., consumption of contaminated food or drink) Injections into the bloodstream Contact with the surface of the skin (topical mode) Inhalation

Effects of Chemical Mixtures Additive means that the combination of two chemicals produces an effect that is equal to their individual effects added together. Synergism indicates that the combined effect of exposures to two or more chemicals is greater than the sum of their individual effects.

Effects of Chemical Mixtures (continued) Potentiation happens when one chemical that is not toxic causes another chemical to become more toxic. Antagonism means that “two chemicals administered together interfere with each other’s actions or one interferes with the action of the other.”

Terms That Describe Duration of Exposure Acute - usually a single exposure for less than 24 hours Subacute - exposure for one month or less Subchronic - exposure for one to three months Chronic - exposure for more than three months

Direct Adverse Effects of Exposure to Chemicals Local effects - damage at the site where a chemical first comes into contact with the body. Systemic effects - generalized distribution of the chemical throughout the body by the bloodstream to internal organs. Target organ effects - some chemicals may confine their effects to specific organs.

Latency The time period between initial exposure and a measurable response. The latency period can range from a few seconds (in the case of acutely toxic agents) to several decades for agents that may be carcinogenic.

Carcinogen A chemical (or substance) that causes or is suspected of causing cancer, a disease associated with unregulated proliferation of cells in the body.

Testing for Toxicity The subjects used for testing the toxicity of chemicals include the following: Volunteers who have had normal or accidental exposures Animals exposed purposively (in vivo experiments) Cells derived from human, animal, or plant sources (in vitro experiments)

Risk Assessment Provides a qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences.

Process of Risk Assessment Hazard identification Dose-response assessment Exposure assessment Risk characterization

Hazard Identification Definition: hazard “Inherent capability of an agent or a situation to have an adverse effect.” Hazard identification: “examines the evidence that associates exposure to an agent with its toxicity and produces a qualitative judgment about the strength of that evidence…”

Dose-Response Assessment Measures “the relationship between the amount of exposure and the occurrence of the unwanted health effects.”

Exposure Assessment The procedure that “identifies populations exposed to the toxicant, describes their composition and size, and examines the roots, magnitudes, frequencies, and durations of such exposures.”

Exposure Assessment (continued) Attempts to answer the following questions: Who or what is exposed (e.g., people, aquatic ecosystems)? Does the exposure occur through breathing air, drinking water, skin contact or any other routes? How much exposure occurs? How often and for how long does exposure occur, that is, what is its frequency and duration?

What is an Exposure Assessment? Estimating concentrations in the environment using models Assessing exposures among populations Assessing exposures using monitoring data Assessing exposures using models

Risk Characterization Develops “estimates of the number of excess unwarranted health events expected at different time intervals at each level of exposure.”

Risk Management Oriented toward specific actions and “consists of actions taken to control exposures to toxic chemicals in the environment. Exposure standards, requirements for premarket testing, recalls of toxic products, and outright banning of very hazardous materials are among the actions that are used by governmental agencies to manage risk.”