EVE 489/589 Toxicology

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Berniece Stafford
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1 EVE 489/589 Toxicology Lecture #3 1. Video: Toxicology of pollution 2. Case study review 3. Toxic Responses 4. Case study Part II Review of Mary Beth 1. Any new questions/concerns for Mary Beth? 2. Any new data sources? 3. Possible explanations for water color? Things that are clear so far All chemicals have the potential to produce toxicity only the dose permits something not to be poisonous Toxicity any adverse health effect that is causally linked to a chemical exposure Range of Effect Minor irritation Immediate death 1

2 Some Manifestations of Toxicity Enzyme inhibition Death cap mushrooms (LD 50 = 30g) Antiretroviral HIV drugs Inflammation (local or widespread) EC and airway inflammation Necrosis (tissue death) Rattlesnake and brown recluse venoms Some Manifestations of Toxicity, cont. Lipid peroxidation (free radical oxidation of fatty acids leading to cellular injury or death) Immune-mediated hypersensitivity Hay fever, seafood allergies (anaphylaxis) Immunosuppression PAHs at Superfund sites Mutagenic Aflatoxins in peanut butter Spectra of Adverse Effects Detoxification? Adverse effects may involve different levels in the body DNA Cells Tissues Organs Direct vs. Indirect damage Direct injury describes adverse intracellular activities Indirect injury is produced through alteration of extracellular regulatory mechanisms Reversible vs. Nonreversible 2

3 Spectra of Adverse Effects, cont. The level of toxicity depends on the concentration of the toxicant at the site of action and is influenced by Rate of absorption (octanol-to-water ratio) MBE terminology: input rate Access to the target cell Rate of biotransformation or bioactivation MBE terminology: Rate of elimination MBE terminology: Spectra of Adverse Effects, cont. Other factors that influence toxicity: Chemical and physical properties of the compound Corrosive, reactive, etc. Method and duration of exposure Route of entry; acute vs. chronic Overall health of the organism exposed Normal vs. susceptible Spectra of Adverse Effects, cont. Potential outcomes to toxic chemical exposure: Cells and tissues repair sufficiently to resume normal function Binge drinking the hangover couple days later Incomplete repair is only sufficient to resume some function Chronic alcoholism liver damage Complete death of an organ or the organism occurs Alcohol poisoning 3

Exposure Necrosis Can dead tissue be replaced?

body/organ may be able to adapt and resume some level of function Using the

by replacement of cells, structural repair ensues.

4 Exposure Necrosis Can dead tissue be replaced? If minimal damage, function likely not compromised If extensive damage, body/organ may be able to adapt and resume some level of function Using the liver as an example: When complete functional repair cannot be accomplished by replacement of cells, structural repair ensues. Too much cellular repair leads to cirrhosis The result is scarring and diminished function. Normal Liver Cirrhosis of the Liver 4

Factors That Modify Toxicity Age Fetuses especially vulnerable due to rapid growth Thalidomide Infants and children Lead Elderly Decreased renal functions Gender Reproductive toxicity Teflon, Gor-Tex

5 Factors That Modify Toxicity Age Fetuses especially vulnerable due to rapid growth Thalidomide Infants and children Lead Elderly Decreased renal functions Gender Reproductive toxicity Teflon, Gor-Tex and low sperm counts Agricultural chemicals and gestational problems. Hormones Body fat Blood alcohol percentages Factors That Modify Toxicity, cont d Disease Impaired liver/kidney function Suppressed immune function Lifestyle and Diet Residence in Beijing, Mexico City, Cairo, etc. Cigarette smoke Mercury in fish, shellfish Genetics A drug may be therapeutic for some, toxic for others Toxicology + Genetics = Toxicogenomics 5

6 IPCS and CSAFs In 2001, guidance from the International Programme on Chemical Safety (IPCS) called for the replacement of default uncertainty factors with chemical specific adjustment factors (CSAFs). Variable CSAFs based on: age sex genetic predispositions Better CSAFs lead to improved risk assessment Case Study #1 Mary Beth Refer to the handout provided (Part II). Questions: 1. Coal dust is an established toxicant. What is the dose, route of exposure and mechanism of action that causes black lung disease? 2. Is coal dust a chemical or physical toxicant? Explain. 3. Is coal dust a targeted or systemic toxicant? Explain. 6

Chapter 3. Toxicity and the Factors That Modify Toxic Responses

Chapter 3. Toxicity and the Factors That Modify Toxic Responses Chapter 3 Toxicity and the Factors That Modify Toxic Responses Cellular Basis of Toxicity All chemicals have the potential to produce toxicity. Toxicity may be generally defined as any adverse effect of