Safety Testing

Question 1

Who regulates the drugs before being able to sell them?

Answer 1

EPA

Question 2

What are the three types of general tests in toxicology?

Answer 2

Acute toxicity
Subchronic toxicity
Chronic toxicity

Question 3

What are the six special tests in toxicology?

Answer 3

Repro and fertility
Teratogenicity
Mutagenicity
Carcinogenicity
Skin, eye, or muscle irritation
Hemolysis

Question 4

Which animals are most commonly used in safety testing?

Answer 4

Rats and dogs

Others include mice, rabbits, guinea pigs, hamsters, gerbils, swine and primates sometimes

Question 5

True or False. Cost is not an important factor in safety testing.

Answer 5

False.

Question 6

Target species

Answer 6

The species that will be exposed to the compound

Question 7

Describe what a qualities a tested compound should have.

Answer 7

• 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

Question 8

What are the three levels used in dosages?

Answer 8

High dose- produces clinical signs
Mid-dose that produces clinical signs
Low dose- largest dose that does not produce toxicosis

Question 9

How often should you observe in safety testing? And what are you looking for?

Answer 9

Daily; detailed clinical signs and postmortem findings

Question 10

What type of experiment is used in acute toxicity?

Answer 10

An acute LD50 or LC50 depending on species

Question 11

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.

Answer 11

False. Can be single or multiple exposures in 24 hours; the observation period is one day or sometimes up to 14 days.

Question 12

Which species is usually used in acute toxicity tests?

Answer 12

More than one species of rodent

Question 13

How long is the period of exposure in a subchronic toxicity test?

Answer 13

More than one day to 90 days

Question 14

How is the subchronic test set up? What is the size of each group?

Answer 14

• 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)

Question 15

What two tests are run at intervals during a subchronic toxicity test?

Answer 15

Hematologic and biochem analyses

Question 16

At the end of the subchronic test, a PM exam is performed, but what other data is collected throughout the test?

Answer 16

Weekly BW
Feed and water consumption
Clinical signs

Question 17

What is the difference between chronic toxicity testing and subchronic testing?

Answer 17

Period of exposure is 90 days or more

Usually up to 18 months in mice, 24 months in rats, dogs, or primates

Question 18

What does the repro and fertility test measure?

Answer 18

The effects of toxicants on any stage of reproduction

Question 19

Explain the repro and fertility test.

Answer 19

• 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

Question 20

What are the parameters recorded during the repro and fertility tests?

Answer 20

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

Question 21

What is a teratogen?

Answer 21

Any substance that produces nonlethal structural or functional abnormalities in the fetus

Question 22

Embyrotoxic or fetotoxic

Answer 22

Any substance that causes death of the embryo or fetus

Question 23

What species is terotogenicity testing performed on?

Answer 23

Rats, mice, or rabbits

Question 24

Explain the teratogenicity test.

Answer 24

• 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

Question 25

Mutagenesis

Answer 25

Induction of chromosomal chances

Question 26

What types of tests screen for mutagenicity?

Answer 26

Dominant lethal test, Cytologic tests

Host-mediated microbial assay

Question 27

How is a carcinogenicity test run?

Answer 27

• 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

Question 28

How do you run an eye irritation test?

Answer 28

• 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

Question 29

Explain a skin irritation test.

Answer 29

• test compound is applied on as shaved area of the skin of an albino rabbit
• response is scored at periodic intervals

Question 30

Other injection irritation tests

Answer 30

Drugs that are IM, SC, or intramammary are tested for tissue irritation by evaluating inflammation or necrosis

Question 31

Explain hemolysis tests.

Answer 31

• 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