Chapter 3Chapter 3

Environmental Toxicology

Learning ObjectivesLearning ObjectivesBy 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 Basic Assumption of ToxicologyToxicology

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

Definition of ToxicologyDefinition of Toxicology• Toxicology is defined as “the study of the adverse

effects of chemicals on living organisms.”

History of Toxicology History of Toxicology Paracelsus •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.

Paracelsus (1493–1541)

What is a Toxicologist?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 ToxicologyFields within Toxicology• Regulatory• Forensic• Clinical

• Environmental• Reproductive • Developmental

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

Toxicology TermsToxicology TermsThe spectrum of toxic dose describes the range of hazards that are related to exposure to a particular chemical.Poison•“defined as any agent capable of producing a deleterious response in a biological system.”Toxic Agent•Very general term to describe a material or factor that can be harmful to biological systems.Toxicity•Refers to “the degree to which something is poisonous.”•Related to a material’s physical and chemical properties

Toxicology TermsToxicology TermsToxicants•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. •Some toxic plants include:

o Some mushrooms (e.g., Amanita phalloides, “death cap”)o Poison hemlocko Foxgloveo Poison oak/poison ivyo Rhubarb, especially the leaves, which have high levels of oxalateso Some houseplants such as dieffenbachia

Examples of Toxic PlantsExamples of Toxic Plants

DoseDose• Refers to “the amount

of a substance administered at one time.”

Lethal Dose 50 (LDLethal Dose 50 (LD5050))

• 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-ResponseDose-ResponseRelationshipRelationship

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

• This relationship can help establish:o Casual association between a toxin and biological effectso Minimum dosages needed to produce a biological effecto Rate of the accumulation of harmful effects

Dose-Response CurveDose-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 are:o One for the responses of an individual to a chemicalo One for a population

Figure 3-2 Figure 3-2 Individual dose–response Individual dose–response curve.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 Figure 3-3 A population dose–response A population dose–response

curve. 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 Figure 3-4 The threshold of a dose–response The threshold of a dose–response

curve.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.

ThresholdThreshold

Factors That Affect the Factors That Affect the Concentration and Toxicity of a Concentration and Toxicity of a

ChemicalChemical• 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 Most Frequent Sites of Exposure to Environmental ChemicalsEnvironmental Chemicals

Gastrointestinal tract• Ingestion (e.g., consumption

of contaminated food or drink)Respiratory System• InhalationSkin• Injections into the

bloodstream• Contact with the surface of

the skin (topical mode)

Length and Duration of ExposureLength and Duration of ExposureAcute – Usually a single exposure for less than 24 hoursSubacute – Exposure for one month or lessSubchronic – Exposure from one to three monthsChronic – Exposure for more than three months

Effects of Chemical MixturesEffects of Chemical MixturesExposures to chemicals in the real world are usually to multiple chemicals, not just one.

•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.

• Potentiation happens when one chemical that is not toxic causes another chemical to become more toxic.

• Colative interaction exists when several non-toxic components mix and produce a toxic effect.

• Antagonism means that “two chemicals administered together interfere with each other’s actions or one interferes with the action of the other.”

Effects of Chemical MixturesEffects of Chemical Mixtures

Individual ResponsesIndividual ResponsesResponses to toxic substances can very greatly due to many variables such as:

o age, sex, weight, health condition, genetic background, use of medication or alcohol, allergies, and/or pregnancy

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.

LatencyLatency• 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. o 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 ToxicityTesting for Toxicity• The subjects used for testing the toxicity of

chemicals include the following:o Volunteers who have had normal or accidental exposures

o Animals exposed purposively (in vivo experiments)

o Cells derived from human, animal, or plant sources (in vitro experiments)

Risk AssessmentRisk 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. (Figure 3-5)

Risk AssessmentRisk Assessment

Process of Risk AssessmentProcess of Risk Assessment

1. Hazard identification2. Dose-response assessment3. Exposure assessment4. Risk characterization

Hazard IdentificationHazard Identification• Definition: hazard

o “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 AssessmentDose-Response Assessment• Measures “the relationship between the amount of

exposure and the occurrence of the unwanted health effects.”

Exposure AssessmentExposure 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 AssessmentExposure Assessment• 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?

Risk CharacterizationRisk Characterization• Develops “estimates of the number of excess

unwarranted health events expected at different time intervals at each level of exposure.”

Risk ManagementRisk 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.”