Exam 3: Lecture 9, Intro to Toxicology Flashcards

1
Q

Important concept of Toxicology?

A

Dose makes the poison

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2
Q

Toxicology definition?

A

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

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3
Q

Tox substances:

A

Toxins = naturally occurring

Toxicants = synthetic chemicals with different intended purposes

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4
Q

Hazard is

A

ability of substance to cause damage, inherent propery

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5
Q

Risk is…

A

chance/probability of toxicity from exposure

risk assessment - estimate potential effect on human health

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6
Q

LD50

A

Lethal dose, at which half subjects die

the Higher it is, the less toxic something is

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7
Q

Idosyncratic reactions are…

A

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

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8
Q

Reversible Toxicity

A

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

Live and GI have high ability to regenerate

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9
Q

Irreversible Toxicitiy

A

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

cancers and birth defects cause by chemical exposures

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10
Q

Local Toxicity

A

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

produced by ingestion of toxic substances or inhalation of irritant materials

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11
Q

Systemic Toxicity

A

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

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12
Q

Most chemicals usually elicit major toxicity in…

A

only 1 or 2 organs and not all organs

not always site of highest conc
target organs of toxicity

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13
Q

Additive effect

A

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

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14
Q

Synergistic effect

A

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

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15
Q

Potentiation

A

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

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16
Q

Antagonism

A

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

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17
Q

Receptor antagonism

A

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

18
Q

Chemical antagonism or inactivation

A

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

19
Q

Dispositional antagonism

A

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

20
Q

Functional antagonism

A

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

21
Q

Tolerance

A

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

22
Q

Dispositional tolerance

A

amount of chemical reaching site of action decreases over time

23
Q

Chemical or cellular tolerance

A

lower availability of receptors and/or mediators

24
Q

Species Differences

A

different doses can cause different effects in different species

25
Factors affecting toxicity?
``` Genetics Age Gender Diet Lifestyle Disease state Medication ```
26
Desirable drugs
Optimal safety optimal PK/ADME Optimal Formulation Optimal Potency/Selectivity
27
Two principal concepts underlie animal toxicity testing which are not true
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
28
When extrapolating high to low doses across species it is important to...
consider molecular, biochemical and cellular mechanisms responsible for toxicological responses
29
S4
Toxicity Testing
30
S9
Anticancer pharmaceuticals
31
Acute toxicity Testing
aim to approximate the LD50
32
Subacute (Repeated-Dose) Toxicity Testing
performed after 3/4 repeated admin aid to establish doses for sub chronic studies
33
Subchronic Toxicity Testing
Establish a no observed adverse effect level (NOAEL) 90 days (13 weeks) is the most common test duration
34
Chronic Toxicity testing
usually 6 month - 2 yr in rodent | over 1 yr in non rodents
35
Developmental and Reproductive Toxicity Testing
study adverse effects on developing organism occurring anytime during life span study of occurrence of adverse effects on male/female repro system
36
Mutagenicity
Ames Test
37
Carcinogenicity testing
Mice: 18 month - 2 yr rodents 2 - 2.5 yrs most expensive, to evaluate carcinogenic potential of chemicals
38
Neurotoxicity Assessment
Hard to ases
39
Immunotoxicity Assessment
xenobiotic exposure can alter immune system
40
Eye and Skin Irritation and corrosion
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