General Toxicology Flashcards
Toxicology
Study of poisons - identification of poisons, their chemical properties, their biologic effects as well as the treatments of disease conditions that they cause
Poison
any liquid, solid, or gas (oral or topical) that can interfere with life processes of cells; aka toxicant
Toxin
poisons that originate from biologic processes; classified as biotoxins
Toxic
effects of poison on living system
Toxicosis
Disease state that results from exposure to a poison
Toxicity
The amount of poison that, under a specific set of conditions, causes toxic effects or results in detrimental biologic changes. (Note - in wildlife/aquatics this may be expresses as the concentration of the substance in feed or water; diff from dosage which is directly correlated with concentration when material is freely available)
Threshold Dose
A toxic or adverse reaction to a chemical where above this has detrimental effects that can be measured
Graded response
increase in degree or severity as the amount/dosage of toxicant increases
Dosage
Amount of toxicant per unit of animal weight (typically mg/kg)
Dose
Total amount of toxicant received per animal
Lethal Concentration (LC)
lowest concentration of compound in feed (or water fish) that causes death; mg/kg
Acute lethal toxicity (LC50)
concentration of compound in feed/water that will kill 50% of animals exposed; AKA median lethal dose
Highest Nontoxic Dose (HNTD)
Largest dose that does not result in clinical of pathological
Toxic Dose-Low (TDL)
Lowest dose that will produce alterations; administration of twice this dose is not lethal
Toxic Dose-High (TDH)
dose that will produce drug-induced alterations and administration of twice this dose is lethal
Lethal Dose (LD)
Lowest dose that causes death in any animal during the period of observation. (Various percentages can be attached to the LD value to indicate doses required to kill 1% (LD1), 50% (LD50), 100% (LD100)
Median lethal dose (MLD)
concentration of compound in feed/water that will kill 50% of animals exposed; AKA LD50
Effective Dose 50 (ED50)
dosage of a drug or therapeutic agent that produces the desired effect in half of a population
Therapeutic Index (TI)
TI=LD50/ED50
Standard Safety Margin (SSM)
SSM=LD1/ED99 More conservative estimate than TI
Extremely toxic
<1 mg/kg
Highly Toxic
1-50 mg/kg
Moderately toxic
50-500 mg/kg
Slightly toxic
0.5-5 g/kg
Practically nontoxic
5-15 g/kg
Relatively harmless
> 15 g/kg
Acute toxicity
describes effects of a single dose or multiple doses during a 24-hour period
Subacute Toxicity
refers to repeated exposure and effects observed for 30 days or less
Subchronic Toxicity
Study of exposure and effects for 1-3 months; studies of 3 months are considered adequate to express all forms of toxicosis except carcinogenic effects and multigenerational effects
Chronic Toxicity
Produced by prolonged exposure for 3 months or longer
Lethal Dose 50 (LD50)
a dosage that is lethal to 50% of animals exposed to a specific toxicant under defined conditions, including species, route of exposure, and duration of exposure
Tolerance
due to prolonged exposure to a toxicant, the size of the dose required to produce lethality upon repeated exposure increases
Chronicity factor
ratio of acute to chronic LD50; greater than 2.0 indicates a cumulative factor
Hazard
the probability that a chemical will cause harm under specific conditions of use; aka risk
Toxicokinectics
movement and disposition of toxicants in the organism
Response to chemicals is affected by toxicokinetic influence on?
Rate and amount of absorption
Distribution of chemical within the body
Biotransformation
Rate of excretion
Passive transport
most common toxicant transport; move across membranes along a concentration gradient
Active transport
a specialized form of membrane passage; move against a concentration gradient; metabolic energy required; competitive inhibition can occur
Facilitated diffusion
not common for xenobiotics (foreign chemicals); has some characteristics of both passive diffusion and active transport; compounds move along a concentration gradient; energy not required; transport system can be saturated
Volume of distribution (VD)
the fluid volume in whcih a chemical seems to be dissolved
VD=(weight of chemical distributed in the body)/(Plasma concentration of chemical at equilibrium)
Excretion
typically from kidneys (urine) and liver (bile); can from lungs, intestines, sweat, saliva, and milk
Routes of elimination
Renal (glomerular filtration or active tubular)
Clearance
volume of plasma cleared of a specific xenobiotic each minute
Clearance = (urinary drug concentration (mg/ml) x urine flow rate (ml/min)/(plasma drug concentration (mg/ml)
Rate of elimination
typically exponential and called ‘first-order’ elimination
Half-life
time needed for one-half of a chemical to be eliminated from the body; Cr+Cie^(-kt) ; Cr = concentration remaining; Ci= initial concentration; k=elimination rate constant for a tissue, toxicant and species; t = time in hours or days
