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PPT- Paul Flashcards

(54 cards)

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1
Q

What does conventional toxicity studies provide indications of?

A

Appropriate dose range
Probable adverse effect
Target organ or system
Special toxicity

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2
Q

How is knowledge of toxicity primarily obtained?

A

Study and observation of people during normal use of a substance or from accidental exposure
Experimental studies using animals or plants under controlled conditions (in vivo)
Using cells, sub cellular fractions or single-celled organisms to the chemical (in vitro)

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3
Q

How is knowledge of xenobiotics to humans derived?

A

Clinical investigations
Epidemiological studies
Adverse reactions

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4
Q

What are examples of testing performed during short and long term studies?

A

Haematological
Biochemical
Urine analysis
Neurological and physical changes
Post mortem examination

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5
Q

What is acute toxicity?

A

The harmful effect that will bring mortality over a short term exposure toxicants at relatively high concentrations
(96 hours)h

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6
Q

What is chronic toxicity?

A

The harmful effect that will bring mortality over a long term exposure of toxicants at relatively low concentrations

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7
Q

What is lethal dose (LD50)?

A

The dose of the pollutant which will result in mortality of half the subject population

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8
Q

Why do we perform testing on animals?

A

Animal testing generates histopathological, clinical and biochemical data

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9
Q

What do the most common gene mutation tests involve?

A

Microorganisms-culture systems
Mammalian cells-
Fruit flies-sex linked recessive lethal mutations
Mice

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10
Q

What is the Ames test?

A

A biological assay to assess the mutagenic potential of chemical compounds.

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11
Q

What is the exposure phase?

A

The moment at which the toxic substance comes into contact with the body

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12
Q

What is the toxicokinetic phase?

A

The description of what rate a chemical will enter the body and what happens to it once it is the body

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13
Q

What is the toxicodynamic phase?

A

Forms the interactions of toxic ants with the organisms causing harmful effects

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14
Q

What does ADME stand for?

A

Absorption, distribution, metabolism and elimination

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15
Q

Dose meaning?

A

Concentration or amount of toxin that enters the living organism at a given time

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16
Q

Exposure dose?

A

Dose present in environment

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17
Q

Absorbed dose?

A

Proportion of exposure dose that enters the living organisms

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18
Q

3 main routes of absorption

A

Gastrointestinal tracts
Lungs
Skin

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19
Q

Main site of absorption through lungs?

A

Alveoli

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20
Q

Bio transformation phase 1 metabolic enzymes

A

Oxidative process- cytochrome P-540 and NADPH cytochrome P 450
Reduction process- reverse reaction of alcohol dehydrogenase
Hydrolysis

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21
Q

Types of storage

A

Adipose tissue- lipophilic compounds
Bones- chemicals similar to calcium, fluorine, lead and strontium
Blood- plasma proteins
Liver and kidneys- higher capacity for binding chemicals

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22
Q

Excretion

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A

Kidney- water soluble compounds in the urine
Lungs- volatile compounds, gaseous metabolites
Liver- bile, fat soluble compounds
Other routes- hair, nails, skin, sweat and milk

23
Q

Dose amount

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A

A measure of the magnitude of the dose

24
Q

Dose frequency

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A

How often exposure occurs

25
Dose duration
Over what period of time the dose occurs
26
Toxic effect calculation
Dose x exposure
27
Monotonic curve
May be linear or non linear but the slope never reversed from positive to negative or vice versa
28
Non monotonic curve
Changes sign, from positive to negative or vice versa
29
Biologically relevant nonmonotonic curve
U-shaped or inverted U-shaped dose-response relationship
30
What is paracetamol?
A synthetic non-opioid analgesic and antipyretic
31
Bioavailability of paracetamol
60% after 500mg and 90% after 1000mg ingested
32
Plasma half life of paracetamol
1.25- 3 hours
33
How does the binding of chemicals to plasma proteins effect its availability?
The less bound a drug is, the more efficiently it can diffuse across cell membranes. Reduces biologically effective dose delivered to the target organ Blood proteins that drugs bind are albumin, lipoprotein, glycoprotein
34
What is cytochrome P-540?
Enzymes that predominantly catalyse oxidation reactions in association with NADPH Found in the endoplasmic reticulum Molecular weight of 40-60kDa
35
From which site would you expect a weak acid toxicant to be absorbed?
The stomach as they are in their non-ionised form
36
How are dose response curve is used to evaluate toxicity
Slope indications how much the response changes as the dose changes
37
4 mechanisms for the transport of toxicant through biological membranes
Passive diffusion Active transport Facilitated diffusion Endocytosis
38
Factors that affect the absorption of toxic substances across the cell membrane
Concentration gradient across membrane Lipid solubility of xenobiotic Electrical change of xenobiotic
39
How does the size of particles influence their absorption from the lungs?
>10um do not enter respiratory tract <0.01um are likely to be exhaled 0.01-10um are deposited in various parts of the respiratory tract
40
How does phagocytosis enable xenobiotics to enter cells?
Plasma membrane surrounds particles and then engulfs them
41
What role does pinocytosis play in toxicokinetics?
Water soluble chemicals are transported via pinocytosis in the lining of lumen in the small intestine Lipid droplets/solutes in extracellular fluid
42
What attribute of the skin limits the rate of absorption?
Keratin- cohesive protein filaments found in the outer layer of the skin which forms a chemically resistant barrier
43
What characteristics of the small intestine account for toxicant absorption?
Large surface area for xenobiotics to passively diffuse Intestine supported by extensive vascular system close to the villi/microvilli to facilitate absorption. Long transit time and therefore increased opportunity for absorption Higher pH facilitates the absorption of weak bases. Bile acids emulsify fats in order to increase absorption of lipid soluble toxicants.
44
What is a dose-response curve?
Defines potency of a chemical Describes how a chemical’s effects changes as exposure increases
45
What is chemical distribution?
Toxicity is reduced by concentrating the chemical in an organ other than the target organ. Blood flow through an organ Ease of chemical transfer across the capillary wall and cell membrane Affinity of the components of the organ for the chemical Lipid solubility (Blood brain barrier)
46
How does Adipose tissue affect availability of toxicants?
It is served as storage, holding toxicants Losing weight fast can mobilize toxicant and release to the blood stream and site of action Increase toxicity as a result of bioaccumulation.
47
Why are newborn and infants more susceptible to some toxicants?
Newborn, infants and toddlers are more susceptible to the toxicity of an agent (at same dose equivalent) than an adult due to inefficiency of enzymes pathways responsible for biotransformation. Reduced blood brain barrier Increased uptake of some toxicants e.g. in the lungs
48
How does bone increase half life of toxicants?
Serves as storage for toxicants, as such performs a detoxicification role until toxicant released into the system, usually happens slowly e.g. fluoride, lead and strontium. e.g. T½ of lead for 20 years
49
List 3 factors that affect the toxicology of a substance
Route of exposure Duration of exposure Frequency of exposure
50
What is a xenobiotic?
Xenobiotic is a foreign chemical substance found within an organism that is not normally naturally produced by or expected to be present within that organism. It can also cover substances which are present in much higher concentrations than are usual.
51
How is necrosis differentiated from apoptosis?
A form of cell death that is distinguishable from apoptosis in that it is not controlled and orderly
52
What is the NOAEL?
No Observe Adverse Effect Level Highest dose at which a significant adverse effect could not be found
53
What is bioactivation?
The process by which a xenobiotic may be converted to more reactive or toxic forms
54
In toxicity testing name 3 tests that are routinely performed and give the rationale for inclusion of these tests.
Haematology e.g. rbc, wbc, plts, retics. Biochemistry – Liver function tests, renal function tests. Neurological tests – cognitive behaviour, spatial recognition

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