Toxicity Testing

Question 1

What was the Thalidomide/Contergan disaster?

Answer 1

• Thalidomide was a drug marketed as a treatment for nausea and morning sickness in pregnant women
• Thousands of infants were born with limb malformations after their mothers took Thalidomide during the first trimester of pregnancy
• The drug had passed safety tests in animals but was not tested on pregnant animals
• The incident led to the withdrawal of the drug from the market in 1961

Question 2

What is teratogenicity?

Answer 2

• Teratogenicity refers to the ability of a substance to cause birth defects or congenital anomalies
• Today, toxicity testing includes the evaluation of teratogenicity to ensure the safety of new drugs

Question 3

Why is there a drive towards animal-free alternatives in toxicity testing?

Answer 3

• The Thalidomide/Contergan disaster led to the argument for extensive animal-based toxicity testing prior to marketing a new drug
• However, there is currently a major drive towards the development and usage of animal-free alternatives to test novel drugs and chemicals
• Animal-free alternatives can reduce the reliance on animal testing while still ensuring the safety of new drugs.

Question 4

What is product authorization?

Answer 4

• Product authorization is the process of evaluating and approving new drugs for sale
• It involves factors such as manufacturing, method of sales, dosage, indications for usage, warnings, and contraindications

Question 5

Why is toxicity testing important in product authorization?

Answer 5

• to ensure that new drugs do not cause harm or adverse effects
• a drug must be tested for toxicity to obtain a license for sale

Question 6

What organizations play a role in setting standards for drug development and approval?

Answer 6

• The World Health Organization (WHO)
• The National Drug Advisory Board

Question 7

What is the purpose of toxicity testing?

Answer 7

The purpose of toxicity testing is to ensure that new drugs are safe for use

Question 8

What is the purpose of full toxicological evaluation in animals for drugs?

Answer 8

To evaluate the safety and potential harmful effects of the drug in animals before testing it on humans.

Question 9

What are the potential harmful effects of drugs?

Answer 9

Drugs can cause side effects or toxicity that can harm the patient or lead to adverse reactions, including death.

Question 10

What is tissue-specific toxicity?

Answer 10

It is when a test substance causes toxicity in specific biological systems.

Question 11

Why are biological considerations important in toxicity testing?

Answer 11

Because the choice of test species, sex, metabolic and physiological similarities to human body, modulatory effects due to immune response, route of administration, diet, duration of testing and number of test animals can affect the results.

Question 12

What are the physico-chemical properties of a test substance?

Answer 12

They are the properties of the substance that are related to its physical and chemical characteristics.

Question 13

What are some examples of physico-chemical properties that can affect toxicity testing?

Answer 13

Structure (chemistry of functional groups), vapour pressure, pKa, solubility (water vs fat), melting point, and purity.

Question 14

Why is it important to consider the physico-chemical properties of a test substance in toxicity testing?

Answer 14

Because they can affect how the substance interacts with biological systems and influence its toxicity

Question 15

Is research with laboratory animals necessary?

Answer 15

Yes, it is the most reliable way to detect toxic properties of chemical substances and estimate risks to human and environmental health

Question 16

How should we use laboratory animals in research?

Answer 16

Responsibly and with scientifically-valid research designs.

Question 17

What are the alternatives to using laboratory animals?

Answer 17

The development and use of alternative methods.

Question 18

Is reducing the number of animals used for research and testing important?

Answer 18

Yes, when scientifically appropriate and valid

Question 19

What factors does toxicity testing depend on?

Answer 19

It depends on the type of substance, regulations of particular countries, and the use of the test agent.

Question 20

What is the major toxicity testing-related question for drugs?

Answer 20

Whether the drug is new or previously tested, whether it is given as a single dose or repeat doses, what is the route of administration, what is the age group and gender of patients, and whether it is used in child-bearing age group

Question 21

What is the purpose of full toxicological evaluation in animals for drugs?

Answer 21

To evaluate the safety and potential harmful effects of the drug in animals before testing it on humans.