LEARNING OBJECTIVES & STUDY GUIDE (weeks 1-5)
Week 1 (Risk Assessment and Toxicology)
• Define key terms and concepts (e.g., NOAEL, LOAEL, LD50, RfD, slope factor, etc.)
o NOAEL: the highest exposure at which there
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LEARNING OBJECTIVES & STUDY GUIDE (weeks 1-5)
Week 1 (Risk Assessment and Toxicology)
• Define key terms and concepts (e.g., NOAEL, LOAEL, LD50, RfD, slope factor, etc.)
o NOAEL: the highest exposure at which there are no discernable negative biological effects of a certain chemical.
o LOAEL: lowest observable adverse effect level: lowest dose administered that does produce an adverse effect
o LD50: the dose at which one half of the test group dies in a certain period of time. LD stands for “lethal dose”
o TD50: toxic dose at which 50% of individuals show toxicity
o LC50: for air; lethal concentration where 50% of individuals die
o TC50: for air; toxic concentration for which 50% of individuals show toxicity
o Reference dose (RfD): a level of daily oral exposure to a chemical, such as a pesticide, that has no apparent adverse effect on humans; the RfD is used in setting regulatory guidelines.
o Slope factor
o Toxicology: A field of science dedicated to the study of the adverse effects of chemicals on biological systems.
o Tolerance: An EPA-set limit on the amount of residual pesticide that can be present in foods and consumer goods.
o Exposure vs. Dose
Exposure deals with things like the air that we breathe, the water we drink, and dermal contact. Some portion of the chemicals that are in the air, water, or soil can enter the body, or all or none of it enters the body. It depends on you and the type of chemical.
Dose refers to the quantity that is taken into the body. There are two types:
• Administered dose—quantity taken into the body (e.g., chemicals ingested like a pill)
• Absorbed dose—the quantity that traverses a biological barrier like the lining of your small intestines or your lung linings to enter the body
o First-pass effect: everything that is absorbed from the GI tract goes directly to the liver first; the liver metabolizes food, drugs, and toxins.
• Explain how toxic agents are identified and characterized – differentiate between acute and chronic toxicity and tests for each
o Toxicant: A synthetic compound that exerts notable adverse effects on a biological system
Regulatory toxicology: The subspecialty that focuses on the use of laboratory and epidemiological data to guide the development and enforcement of laws aimed at protecting consumers and the environment from chemicals.
o Characterization
Toxicity tests are costly, so many chemicals are not well tested (a lot of the toxicology data is uncertain)
Significant differences between humans and animals cause conflicting results. Even among humans, we are all quite different in how we respond to environmental exposures. With current testing techniques, it is unlikely we will be able to fully understand all risks from all chemicals.
If the subject is hydrophobic, it fears water, so more of the chemical will be found in the body's fat tissue
If the substance is hydrophilic, it loves water, so more of the chemical will be found in the body's bloodstream (blood is water based)
o Time: acute vs. chronic
o Location: local vs. systemic
o Acute toxicity: Sudden onset of toxic effect, minutes, hours, or days
Acute does NOT mean severe
E.g., irritants, chlorine gas
o Chronic toxicity: Toxic effect after long periods of exposure, usually many months or years
E.g., cancer, liver damage, lung fibrosis
o Local toxicity: toxic effect occurs at the site of exposure
E.g., pulmonary edema, acid on skin, asbestosis
o Systemic toxicity: requires absorption of the toxicant into the body, then distribution of the toxicant (usually by the bloodstream) to susceptible organs, which is where the toxic effect occurs
E.g., liver damage, kidney damage
o Paracelsus – “dose makes the poison”
Identification (EPA Pesticide Labels by dose that results in LD50)
• Category I: 50 0-50 ug/kg (FATAL IF SWALLOWED)
• Category II: 50-500 ug/kg
• Category III: 500-5000 ug/kg (Harmful if swallowed)
• Category IV: >5000 ug/kg (caution)
• Describe chemical absorption, distribution, metabolism and excretion
o Absorption: the movement of a chemical across a biologic barrier, such as skin, intestinal lining or alveoli
o Distribution: the movement of a chemical throughout the body.
o Metabolism: the processing of chemicals within the body; it can involve activation, inactivation, breakdown, or conjugation with other constituents.
o Excretion: how we get rid of things
Feces: food, chemicals, indigestible materials that go through the GI tract but are never taken up into the body, so they just pass right on through
Expired air: a breathalyzer test measures the amount of alcohol on your exhaled breath. This accurately correlates to the amount of alcohol in your blood. So we eliminate some volatile chemicals (chemicals that easily go from a liquid to a gas/vapor state) through exhaled air.
Urine: this is the way most chemicals are excreted from the body. The body must get rid of things like ammonia created during normal functions, as well as environmental chemicals that inadvertently enter the body. Generally speaking, the liver prepares chemicals for excretion and the kidneys actually excrete. In a way, the liver and kidneys work as a team.
• Characterize the primary routes of human exposure (oral, inhalation, dermal)
o Oral/Ingestion: the introduction of a compound into the digestive tract via the mouth.
o Inhalation: The introduction of a as or particle into the lungs via the airway
o Dermal exposure: The process by which a chemical gains entry into the body via the skin.
• Define the four steps of risk assessment
o Hazard identification: recognize when a hazard might cause an undesirable health effect
Hazard index = (average daily intake)/RfD
• If <1, no clean up
Cancer risk = average daily intake x slope factor
• If ≥ 10-3, then hazardous/cancerous effect/requires cleanup
o Dose-response assessment: Toxicology/epidemiology (how bad is it?)
Animal studies and accidental human exposure allows us to figure out the health response to a given dose
We might feed a rat with a varying dose of a chemical to observe potential health responses.
Limitations of epidemiology in dose-response assessment Usually retrospective; can discover associations but rarely causation; subject to bias; often high-dose occupational studies or accidents; women and children are underrepresented
o Exposure assessment: Magnitude and duration of exposure are major factors
What is the probability that people will come into contact with this chemical?
o Risk characterization: lets us quantitatively measure all the steps together to estimate the magnitude of risk.
Environmental risks are characterized by chronic exposures at very low doses
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