Toxicology 1: Intro Flashcards
Toxins are normally what kind of situation?
Emergency
Definitionof Toxicology
The study of the adverse effects of xenobiotic compounds, including their chemical properties, biological effects and treatments
Toxin definition
A poisonous substance that is a specific product of the metabolic activities of living organism
-antigenic poison or venom of plant of animal origin
-subset of toxicants
Toxicant is?
Synonym for poison/toxic agent
Factors determining toxicity
Dose
Duration/Frequency of Exposure
Route of Exposure
ADME
Physiological Factors
Dose
defintion?
EF50?
LD50
LC50
Amount of drug, toxin or toxicant that reaches the site or sites of action in an animal
ED50: Dose producing a therapeutic response in 50% of the population
LD50: Dose causing death in 50% of the population
LC50: Concentration of a toxin/toxicant that will cause death in 50% of the population
We use these values to compare relative toxicities and estimate potency
Bromethalin
LD50 variation in species
Rodenticide
- sold as bait blocks, pellets, bars, and ‘worms’
- single feeding–> just one bite!
- sudden death, vengeance, trounce, assault
What is the Toxicokinetics of Bromethalin
rapidly absorbed
peaks in plasma in 4h
N-dethylated in liver (CYP450)
Uncouples oxidative phosphorylation
Depletion of ATP depletion of ATP disrupt Na+/K+ pimp
ADD*
Which animal is most sensitive to toxicity from bromethalin?
CATS 0.54mg/kg
Which animal is the least sensitive to bromethalin?
Guiene pig
Selenium whats the big deal?
Prevents free radical damage in tissues
Maintains proper immune, muscle, heart function
Selenoproteins in skeletal muscle help cells
sequester calcium
What can cause selenium deficiency’s?
1) Selenium deficient soils
2) Feed mixing errors
Skeletal muscle cannot
sequester Ca+ -> calcification
of tissue
White muscle disease
Cardiomyopathy
death
What happens if you give too much Selenium?
Lethargy, tachycardia, sweating, teeth grinding
Hair loss, nail discoloration, hoof lesions
lameness, emaciation, death
Zinc what is the big deal (small animal)?
Cofactor for enzymes/proteins
involved in cell division and growth
Maintain proper immune system, skin protectant
What can cause zinc deficiency?
1) Zinc deficient diets
2) Genetic predisposition causing
malabsorption of zinc from GI
Inhibition of RBC enzymes-> oxidative damage
Zinc-responsive dermatitis
Alopecia
Susceptible to skin infections
Duration/Frequency of Exposure
4 ranges
Acute exposure
Subacute exposure
Subchronic exposure
Chronic exposure
Acute exposure
Exposure to a chemical for less than 24 hours
Usually a single dose occurring from a single incident
-Iron overdoses in pigs
-Insecticide ingestion in animals
Subacute exposure
Exposure to a chemical for one month or less
Repeated doses
-Dogs eating aflatoxin contaminated food for 4 weeks
Subchronic exposure
copper toxicity in sheep and dogs
Exposure to a chemical for 1 to 3 months
Repeated doses
Chronic exposure
copper toxicity in sheep and dogs
Exposure to a chemical for > 3 months
to years
Repeated doses
Aflatoxins
exposure?
sources?
Acute –> Subacute Exposure
Sources:
-Ingestion of contaminated food
- Aflatoxins are produced by Aspergillus spp. fungus
- Predisposition of Aspergillus spp. to grow in hot, dry weather
Mechanism of toxicity for Aflatoxin B1
Aflatoxicosis has what kind exposure?
ALL
Acute and Subacute more common
Route of exposure
what are the 4 ways
Oral
-GI
Dermal
-skin
Inhalation
-lungs
Parental
-IV
-Intraperitoneal
-IM
-SQ
What is the most common route of toxins in animals is?
ORAL
requires nearly all of the dose to pass through liver before reaching systemic circulation
Some examples of toxic ingestions for large animals?
Some examples of toxic ingestions for small animals?
Dermal toxicity is most common is?
Anti flea and tick for dogs on cats
Inhalation toxicity is seen in which species more commonly?
Birds
-lungs have large surface area, increased absorption
-Avoids liver first pass effect
- metabolism can occur in lungs (p450 enzymes)
What is Teflon fume fever?
Teflon Fumes:
-Overheating Teflon-coated pans forming toxic particulates/gases (polytetrafluoroethylene)
- Flu-like symptoms in humans
Clinical SignsClinical Signs:
-Acute pulmonary distress & dyspnea, somnolence, convulsions, death
NecropsyNecropsy:
-Acute, severe to massive, hemorrhagic pulmonary necrosis, edema
Parenteral routes for toxicity?
