Chapters 1 & 2 - Intro Toxicology & The Action of Poisons Flashcards
Definition of poison
Any solid, liquid or gas that, through either oral or topical routes, can interfere with life processes of cells of the organism.
This interference occurs by the inherent qualities of the poison without mechanical action and irrespective of temperature.
Another term for poison
Toxicant
What does the term ‘toxic’ describes?
The effects of a poison on living systems.
What does the term ‘toxicosis’ describes?
The disease state that results from exposure to a poison (often used interchangeably with poisoning and intoxication)
Definition of toxicity and how it is usually expressed.
The amount of a poison that, under a specific set of conditions, causes toxic effects or results in detrimental biologic changes.
It is usually expressed as milligrams (mg) of toxicant per kilogram (kg) or body weight.
Definition of dosage (as in toxicity)
Amount of toxicant per unit of animal weight
Definition of dose (as in toxicity)
Total amount of toxicant received per animal
What is threshold dose of a toxic or adverse reaction?
The threshold above which detrimental effects can be measured.
What is the lethal concentration (LC) and how it is expressed?
The lowest concentration of compound in feed or water that causes death.
Expressed as milligrams of compound per kilogram of feed and water.
What is the acute lethal toxicity (expressed as LC50)?
Concentration of compound in feed or water that will kill 50% of animals exposed.
Terms used to define toxicity (6)?
- Highest nontoxic dose (HNTD)
- Toxic dose-low (TDL)
- Toxic dose-high (TDH)
- Lethal dose (LD)
- Median lethal dose (MLD)
- Effective Dose 50 (ED50)
What is the highest nontoxic dose (HNTD)?
The largest dose that does not result in clinical or pathologic drug-induced alterations.
What is the toxic dose-low (TDL)?
The lowest dose that will produce alterations; administration of twice this dose is not lethal.
What is the toxic dose-high (TDH)?
The dose that will produce drug-induced alterations and administration of twice this dose is lethal.
What is the lethal dose (LD)?
The lowest dose that causes death in 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) or 100% (LD100).
What is the median lethal dose (MLD)?
Equivalent to LD50: The lowest dose that causes death in 50% of animals.
What is the Effective Dose 50 (ED50)?
The dosage of a drug or therapeutic agent that produces the desired effect in half of a population.
Expression of safety for drugs (2) ?
Expressions of safety for drugs are given by comparisons of LD50 to the ED50:
- Therapeutic index (TI)
- Standard Safety Margin (SSM)
What is the therapeutic index (TI)?
It is an expression of safety for drugs and is defined by the ratio of the LD50 to the ED50:
TI = LD50 / ED50
What is the standard safety margin (SSM)?
It is an expression of safety for drugs and is defined by the ratio of the LD1 to the ED99 (more conservative than the TI).
SSM = LD1 / ED99
Which of the expressions of safety for drugs is more conservative: Therapeutic Index (TI) or Standard Safety Margin (SSM)?
Standard Safety Margin (SSM) is more conservative than the Therapeutic Index (TI)
Ranking to classify the relative toxicities of compounds (6)
Classification Toxicity
- 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
What is acute toxicity?
Term that describes the effects of a single dose or multiple doses during a 24-hour period
What is acute LD50?
Patterned toxicity study designed to compare the most reproducible part of the dose-response curve for different chemicals under closely defined conditions of exposure.
Definition of LD50
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.
Characteristics of LD50
- The LD50 value does not pertain to the severity of clinical signs observed or the characteristic changes caused by the toxicant.
- The LD50 value bears no relationship to adverse effects such as chronic toxicity, reproductive hazard or cancer risk.
- The LD50 is based on a ‘quantal’ (all-or-none) response of a population of animals and is the cumulative response to increasing dosage. It is a sigmoid graph when plotted on linear coordinates. Response is nearly linear at the LD50 and is most rapidly and reliably affected by dosage in this area.
- The LD50 can be transformed to a straight line on semilogarithmic or probit paper.
- The slope of the dose-response curve defines the margin between minimal and maximal toxic response.
What does the slope of the (log)dose-response curve in LD 50 represents?
Defines the margin between minimal and maximal toxic response.
What is subacute toxicity?
It refers to repeated exposure and effects observed for 30 days or less.
What is subchronic toxicity?
Is the study of exposure and effects for 1 to 3 months.
Studies of 3 months are considered adequate to express all forms of toxicosis except carcinogenic effects and multigenerational (reproductive) effects.
What is chronic toxicity?
It is produced by prolonged exposure for 3 months or longer.
Compounds that are rapidly metabolized have about the same / greater / smaller chronic LD50 than single-dose LD50?
Have about the same chronic LD50 as the single-dose LD50, because the rapidly excreted compound has little opportunity to accumulate in the body.
What is the chronicity factor?
It is the ratio of the acute LD50 to chronic (90-day) LD50.
Chronicity Factor = Acute LD50 / 90-day LD50
Compounds with cumulative effects have a high chronicity factor.
Threshold Chronicity factor that indicates a relatively cumulative toxicant?
Chronicity factor greater than 2 indicates a relatively cumulative toxicant.
Rank these species by Daily Dry Food Intake (% Body Weight):
Cat (adult, young), dog (adult, young), finishing cattle, dairy cow (gestating, lactating), ewe (lactating, nonlactating), pig (sow, feeder, finishing), mature horse
- Cat (kitten) = small puppy – 8% body weight
- Feeder pig (15kg) – 7%
- Dog (adolescent) – 6%
- Finishing pig (70kg) – 4.5%
- Ewe (lactating) = Lamb (30kg) = Cat (adult) – 4%
- Sow (lactating) – 3-4%
- Dog (adult) – 3%
- Dairy cow (lactating) = Horse = Ewe (nonlactating) – 2-3%
- Dairy cow (gestating) – 1.8%
- Finishing cattle (600 kg) – 1.5%
How many ppb are in 1 ppm?
1 ppm = 1,000 ppb
1 ppm = X ppb = X ppt?
1 ppm = 103 ppb = 106 ppt
How many grams in:
- Megagram
- kilogram
- miligram
- microgram
- nanogram
- picogram
- femtogram
- Megagram (M) = 106 gram
- kilogram (kg) = 103 gram
- miligram (mg) = 10-3 gram
- microgram (µg) = 10-6 gram
- nanogram (ng) = 10-9 gram
- picogram (pg) = 10-12 gram
- femtogram (fg) = 10-15 gram
How many mg/kg are in 1 ppm?
1 ppm = 1 mg/kg = 1 µg/g
How many acres and square meters are in 1 hectare?
1 hectare = 2,471 acres = 10,000 m2
How many inches are in 1 meter (m)?
1 m = 39.37 inches
How many square feet are in 1 acre?
1 acre = 43,560 square feet
How many grams are in 1 ounce (oz)?
1 g = 28.35 grams