Safety Testing Flashcards
Who regulates the drugs before being able to sell them?
EPA
What are the three types of general tests in toxicology?
Acute toxicity
Subchronic toxicity
Chronic toxicity
What are the six special tests in toxicology?
Repro and fertility Teratogenicity Mutagenicity Carcinogenicity Skin, eye, or muscle irritation Hemolysis
Which animals are most commonly used in safety testing?
Rats and dogs
Others include mice, rabbits, guinea pigs, hamsters, gerbils, swine and primates sometimes
True or False. Cost is not an important factor in safety testing.
False.
Target species
The species that will be exposed to the compound
Describe what a qualities a tested compound should have.
- pure or commercially produced
- a vehicle should be inert and does not alter the properties of the tested compound
- a control vehicle should be used
What are the three levels used in dosages?
High dose- produces clinical signs
Mid-dose that produces clinical signs
Low dose- largest dose that does not produce toxicosis
How often should you observe in safety testing? And what are you looking for?
Daily; detailed clinical signs and postmortem findings
What type of experiment is used in acute toxicity?
An acute LD50 or LC50 depending on species
True or False. During acute toxicity tests, it is only a single exposure during a 24 hour period and the observation period is only one day.
False. Can be single or multiple exposures in 24 hours; the observation period is one day or sometimes up to 14 days.
Which species is usually used in acute toxicity tests?
More than one species of rodent
How long is the period of exposure in a subchronic toxicity test?
More than one day to 90 days
How is the subchronic test set up? What is the size of each group?
- Rats and dogs are usually used at 3 different dosage levels plus a control group
- rats= 30-40 (equally divided by sex)
- dogs= 6-10 (equally divided by sex)
What two tests are run at intervals during a subchronic toxicity test?
Hematologic and biochem analyses
At the end of the subchronic test, a PM exam is performed, but what other data is collected throughout the test?
Weekly BW
Feed and water consumption
Clinical signs
What is the difference between chronic toxicity testing and subchronic testing?
Period of exposure is 90 days or more
Usually up to 18 months in mice, 24 months in rats, dogs, or primates
What does the repro and fertility test measure?
The effects of toxicants on any stage of reproduction
Explain the repro and fertility test.
- usually 2-3 successive generations of rats are used for this experiment
- adult males and females are dosed for 60 days before mating
- females are also treated during gestation and lactation
- offspring are dosed from weaning until lactation
- parameters recorded at each step
What are the parameters recorded during the repro and fertility tests?
Fertility index Length of gestation period Live births Stillbirths Survival at 5 days and at weaning Number of each sex Body weight Gross abnormalities Microscopic exam of selected offspring
What is a teratogen?
Any substance that produces nonlethal structural or functional abnormalities in the fetus
Embyrotoxic or fetotoxic
Any substance that causes death of the embryo or fetus
What species is terotogenicity testing performed on?
Rats, mice, or rabbits
Explain the teratogenicity test.
- females are exposed to the tested compound during the period of organogenesis (organ development)– 6-15 days of preg in rats and mice; 6-18 days of preg in rabbits
- fetuses are removed surgically one day before the expected day of parturition
- fetuses are examined for gross changes, number of live and dead, number of resorptions, BW, sex, and any external malformation
- then examined for skeletal and visceral malformations
Mutagenesis
Induction of chromosomal chances
What types of tests screen for mutagenicity?
Dominant lethal test, Cytologic tests
Host-mediated microbial assay
How is a carcinogenicity test run?
- done on rats and mice
- exposure to the tested compound is for the life of the animal and starts from weaning
- animals are necropsied and the incidence of tumors is compared between the treated and controlled
How do you run an eye irritation test?
- drug is instilled in the conjunctival sac of one eye of an albino rabbit and the other serves as a control
- tissue response is scored at period intervals of 72 hours
Explain a skin irritation test.
- test compound is applied on as shaved area of the skin of an albino rabbit
- response is scored at periodic intervals
Other injection irritation tests
Drugs that are IM, SC, or intramammary are tested for tissue irritation by evaluating inflammation or necrosis
Explain hemolysis tests.
- required for compounds administered IV route
- drug is administer IV and the Hb content of a plasma sample one min after injection is compared with that of a sample before injection
