Exam 3: Lecture 9, Intro to Toxicology

Question 1

Important concept of Toxicology?

Answer 1

Dose makes the poison

Question 2

Toxicology definition?

Answer 2

study of adverse effects of chemical, biological or physical agents on living organisms and the environment

Question 3

Tox substances:

Answer 3

Toxins = naturally occurring

Toxicants = synthetic chemicals with different intended purposes

Question 4

Hazard is

Answer 4

ability of substance to cause damage, inherent propery

Question 5

Risk is…

Answer 5

chance/probability of toxicity from exposure

risk assessment - estimate potential effect on human health

Question 6

LD50

Answer 6

Lethal dose, at which half subjects die

the Higher it is, the less toxic something is

Question 7

Idosyncratic reactions are…

Answer 7

abnormal reactivity of an individual to a chemical based on its genetic, or other individual sensitivity factors with relatively low incidence

can occur in any organ system, skin/liver/hematopoeitic/immune system must affected

Question 8

Reversible Toxicity

Answer 8

largely depends on ability of an injured tissue to adapt, repair and regenerate

Live and GI have high ability to regenerate

Question 9

Irreversible Toxicitiy

Answer 9

CNS has much more limited ability to divide and replace damage neurons

cancers and birth defects cause by chemical exposures

Question 10

Local Toxicity

Answer 10

occur when contact is 1st made by toxicant and the biological system

produced by ingestion of toxic substances or inhalation of irritant materials

Question 11

Systemic Toxicity

Answer 11

require absorption and distribution of toxicant from its entry point to a distance site where the deleterious effects are produced

most substances produce systemic effects except highly reactive

Question 12

Most chemicals usually elicit major toxicity in…

Answer 12

only 1 or 2 organs and not all organs

not always site of highest conc
target organs of toxicity

Question 13

Additive effect

Answer 13

combined responses of two chemicals is equal to cub of responses to each chemical given alone

Question 14

Synergistic effect

Answer 14

combined responses of two chemicals are much greater than the sum of the responses to each chemical given alone

Question 15

Potentiation

Answer 15

one substance does not produce any toxicity on a particular tissue or system but when added to another chemical makes that chemical more toxic

Question 16

Antagonism

Answer 16

Two chemicals administered together interfere with each others actions or one interferes with the action of the other

Question 17

Receptor antagonism

Answer 17

two chemicals bind to same receptor produce less of an effect when given together relative to the addition of their separate effects

Question 18

Chemical antagonism or inactivation

Answer 18

direct chemical interaction between 2 compounds that produce a less toxic effect

Question 19

Dispositional antagonism

Answer 19

disposition is altered such that the conc and or duration of chemical at target organ is reduced

Question 20

Functional antagonism

Answer 20

2 chemicals counter balance each other by producing opposing effects on the same physiological function

Question 21

Tolerance

Answer 21

repeated exposure to a chemical can reduce its pharmacological and/or toxicologic response

Question 22

Dispositional tolerance

Answer 22

amount of chemical reaching site of action decreases over time

Question 23

Chemical or cellular tolerance

Answer 23

lower availability of receptors and/or mediators

Question 24

Species Differences

Answer 24

different doses can cause different effects in different species

Question 25

Factors affecting toxicity?

Answer 25

Genetics
Age
Gender
Diet
Lifestyle
Disease state
Medication

Question 26

Desirable drugs

Answer 26

Optimal safety
optimal PK/ADME
Optimal Formulation
Optimal Potency/Selectivity

Question 27

Two principal concepts underlie animal toxicity testing which are not true

Answer 27

effects produced by compounds in lab animals are applicable to humans

exposure of experimental animal to high doses of chemical is a necessary and valid method of discovering possible hazards in humans

Question 28

When extrapolating high to low doses across species it is important to…

Answer 28

consider molecular, biochemical and cellular mechanisms responsible for toxicological responses

Question 29

S4

Answer 29

Toxicity Testing

Question 30

S9

Answer 30

Anticancer pharmaceuticals

Question 31

Acute toxicity Testing

Answer 31

aim to approximate the LD50

Question 32

Subacute (Repeated-Dose) Toxicity Testing

Answer 32

performed after 3/4 repeated admin

aid to establish doses for sub chronic studies

Question 33

Subchronic Toxicity Testing

Answer 33

Establish a no observed adverse effect level (NOAEL)

90 days (13 weeks) is the most common test duration

Question 34

Chronic Toxicity testing

Answer 34

usually 6 month - 2 yr in rodent

over 1 yr in non rodents

Question 35

Developmental and Reproductive Toxicity Testing

Answer 35

study adverse effects on developing organism occurring anytime during life span

study of occurrence of adverse effects on male/female repro system

Question 36

Mutagenicity

Answer 36

Ames Test

Question 37

Carcinogenicity testing

Answer 37

Mice: 18 month - 2 yr
rodents 2 - 2.5 yrs

most expensive, to evaluate carcinogenic potential of chemicals

Question 38

Neurotoxicity Assessment

Answer 38

Hard to ases

Question 39

Immunotoxicity Assessment

Answer 39

xenobiotic exposure can alter immune system

Question 40

Eye and Skin Irritation and corrosion

Answer 40

eye injury assessed between 3-21 days after app of chemical to rabbits eye

skin testing done by applying patches containing test chemical to shaved section of skin for period of time