L1. Intro to Toxicology Flashcards
Poison: Toxicant
any solid, liquid, or gas when introduced into a biologic system can interfere with the life processes of the cells of that organism by its own inherent properties.
Poison: Mechanism of Action
Attack common receptors
compete for metabolites
Damage membranes
Alter nucleic acid synthesis
Toxin
Poison from a biological process
Biotoxin
general
Zootoxin
insect / reptile
Mycotoxin
fungal
Phytotoxin
plant
Phycotoxin
Algea
Toxic
refers to adverse effects
Arsenic is toxic to the GIT and kidney
Toxicosis
Disease state of being poisoned
Arsenic toxicosis = acute onset of vomiting progressing to hemorrhagic diarrhea
Toxicity
Essentially the dose
the acute toxicity of Arsenic is 5mg/kg BW
LD50
lethal dose 50
Quantal response of a group
Straight line on semi log or probit paper
Lethal to 50% of animals defined conditions
Does not address severity/clinical characteristics
No relationship to chronic toxicity or other effects
ED50
effective dose 50
NOEL
No Observed Effect Level
NOAEL
No Observed Adverse Effect Level
HNTD
Highest Non-Toxic Dose
Dose-Response
Fundamental relationship in Toxicology
Paracelsus: “All things are poison and nothing is without poison; only the dose makes a thing not a poison”
dose makes the poison
Analytical capabilities are better than our interpretive abilities
Assumptions
- Response is due to the poison
- may only be “associated with”
- Magnitude of the response is dose-related
- higher dose = bigger response
- Quantifiable method of measuring response
- related to molecular events caused by the agent
- Secondary biomarkers
- AChE, AST
- Clinical Response
“Agent”
Poison/toxicant
Chemical - of chemical origin
Xenobiotic - any foreign compound
Toxin - biological origin
Elements - lead, selenium, copper
Pharmaceuticals - Antimicrobial, physiologic drugs
Nutrients - Protein, fat
Response:
What
clinical signs, lesions, sub-clinical
Response:
where
Local, systemic, organ-specific
Response:
When
Acute, Chronic
Response:
Why
Sources, intended
Response:
How
Access, route of exposure
Dose-Response Curves:
No effect
Dose-Response Curve:
No threshold
Dose-Response Curve:
Threshold
Therapeutic Index
TI=LD50/ED50
Standard Safety Margin
SSM = LD1/ED99
Chronicity Factor
Acute LD50/90 day LD50
measure of cumulative toxicity
Risk
The likelihood fo Poisoning occurring under the conditions of normal use
Risk Ratio compares toxiticy to use
Factors Affecting Outcome:
Physiological:
Species
Nitrate poisoning in ruminants vs. monogastrics
Factors Affecting Outcome:
Physiological:
Breed
Ivermectin toxicosis in collies
Factors Affecting Outcome:
Physiological:
Age
neonates and geriatrics are generally more susceptible
Factors Affecting Outcome:
Physiological:
Sex
Gossypol can cause infertility in males
Factors Affecting Outcome:
Physiological:
Pregnancy
Abortive agents
Factors Affecting Outcome:
Physiological:
Lactation
ergot alkaloids can inhibit lactation
Factors Affecting Outcome:
Physiological:
Nutritional status
Healthy vs. malnutrition
Factors Affecting Outcome:
Physiological:
Health status
Healthy vs. chronically ill
Factors Affecting Outcome:
Environmental
Seasonal - blue-green algea
Transportaion - Copper toxicosis in sheep
Water quality and quantity
Factors Affecting Outcome:
dose
how much toxin did the patient ingest
Factors Affecting Outcome:
Route
IV vs, inhalation
Factors Affecting Outcome:
Physical Nature of Agent
pellet vs. powder
Factors Affecting Outcome:
Solubility
Changes adsorption/metabolism
Factors Affecting Outcome:
Chemical Interactions
Alters ADME within biological system
4 Types
- Additive: 2+4=6
- Synergistic: 2+4=12
- Potentiation: 0+4=6
- Antagonistic: 3+6=7
Diagnosing Intoxications
Overview of Diagnostic Strategy:
History is crucial
Clinical Sings and progression
Clinical Pathology
Analytical toxicology
Necropsy findings
Histopathology
Managing Intoxications
“Treat the patient not the poison”
- Each patient and toxicant are unique
- General guidelines
- stabilize airway, breathing, circulation
- Get more history and re-evaluate
- Prevent further absorption
- Give specific antidote in available
- Enhance elimination
Calculations:
Essential units to commit to memory:
Part Per Million (PPM)
1 ppm = 1mg/kg = 1microgram/g
1 penny in $10,000
Calculations:
Essential units to commit to memory:
Part Per Billion (PPB)
1 PPB = 1ug/kg = 1ng/g
1 penny in $10,000,000
1 second in 32 years
Conversions:
Active ingredient
Active ingredient often reported as %
Exposure data in PPM
Conversion is easy
Look at the pic for math.
“MOVE DECIMAL 4 PLACES”
1 PPM = 0.0001%
1% = 10,000 PPM
Conversions:
Feeds
Ingredients often lbs/ton or g/ton
Remeber feed and water intake are extremely vairiable
Feed Concentration to Dosage
Feed tags report inclusion concentration
Toxicity data in mg/kg dosages
Need to Know:
Concentration of compound in feed
Animal weight
Amount of feed consumed (estimate as %BW)