Mbm 432 Applied molecular toxicology

Question 1

Human chemical carcinogenesis

Answer 1

A multistage process that leads to cancer, caused by exposure to certain chemicals in a human’s environment.

Most of these chemicals do not cause DNA damage directly but are converted into electrophilic carcinogens by the body’s toxin neutralization processes. The electrophiles are then attracted to neutrophiles in the cells (DNA and protein) and bind to them covalently, causing damage. Still, some of these chemicals act directly.

The degree of carcinogenesis caused by these chemicals vary from person to person.

Question 2

Toxicogenomics

Answer 2

A field that studies the effects of toxins on an organisms’ cells at the genetic level.
It is based on collection, interpretation and storage of information about gene expression and protein activity of cells in response to toxic substances.

Question 3

Genotoxicity

Answer 3

A property of substances, characterized by their ability to cause genetic damage. This damage may lead to cancer and other genetic diseases.

Question 4

Mutagenicity

Answer 4

A property characterized by the causation of mutations in the genetic material of an organism.

Used interchangeably with genotoxicity, although all genotoxic substances are mutagenic but not all mutagenic substances are genotoxic.

Question 5

Epigenetics

Answer 5

The study of how the environment shapes genetic expression.
Unlike mutations, epigenetic changes are reversible and do not change DNA structure.

Question 6

Toxicological risk assessment

Answer 6

The systematic analysis of potential health risks from exposure to hazardous substances or conditions.

Question 7

What is risk

Answer 7

The tendency of something to lead to adverse effects

Question 8

What is risk management?

Answer 8

A set of actions, chosen to reduce risk

Question 9

5 Objectives of risk assessment

Answer 9

To protect human and ecological health from toxic substances

Balance risks and benefits of substances like pesticides

To establish limits for exposure to toxic substances

Establishes a hierarchy of risk, for regulatory agencies to prioritize handling the most risky exposuresfirst.

Estimation of residual risk after risk reduction steps have been taken

Question 10

Toxins

Answer 10

Poisonous substances produced through biological activity

Question 11

Toxicants

Answer 11

Any toxic substance. Includes toxins and poisonous chemicals

Question 12

Toxic

Answer 12

Poisonous

Question 13

Toxicity

Answer 13

Describes the degree to which a substance is poisonous.

Question 14

4 factors Toxicity depends on

Answer 14

Dose,
duration and route of exposure
Shape and structure of the toxic substance
Individual human factors

Question 15

Dose

Answer 15

Amount of substance actually administered. Does not account for the size and weight of the animal.
10mg of a drug.

Question 16

Dosage

Answer 16

refers to the amount per body weight of the individual.
10 mg/kg of body weight.

Question 17

Total dosage

Answer 17

Considers duration of exposure.
A dosage of 10 mg/kg per day for 10 days translates to a Total Dosage of 100 mg/day / kg

Question 18

Efficacy of an agent

Answer 18

A measure of the maximum effect the agent can have on a system, relative to the ideal effect. can be quantified in a range of 0 to 1, with one being the ideal effect.

Question 19

Potency

Answer 19

The amount of agent required to produce an intended effect.

Usually stated (in determining toxicant potency) as amount (mg, concentration or total dosage) required to produce half the maximum effect (0.5 efficacy).

A drug that produces this half maximum effect at a lower dose is said to be more potent than one that requires more of it.

Question 20

Toxication

Answer 20

An instantaneous toxic action resulting from the action of a toxic agent at a given moment in time.

Question 21

Intoxication

Answer 21

Refers to the effects that occur from being exposed to a toxic substance. Could be instantaneous or not.

Question 22

Toxicology

Answer 22

The study of poisons, chemical, physical, biological e.t.c.
and their effects on organisms

Question 23

What is a poison?

Answer 23

A poison is a chemical or physical agent that produces adverse responses in biological organisms, capable of disturbing the normal physiological homeostasis of the exposed body.

Question 24

What is the significance of the concept of poison being quantitative?

Answer 24

The concept of poison being quantitative means that any substance can be harmful at some doses but may have no harmful effect at lower doses.

There is a range of possible effects between these two limits, from subtle long-term chronic toxicity to immediate lethality.

Question 25

Provide two examples of substances that demonstrates the quantitative nature of poison?

Answer 25

Vinyl chloride: A potent hepatotoxicant at high doses, a carcinogen with a long latent period at lower doses, and apparently without effect at very low doses. Aspirin: safe at recommended doses but can cause gastric mucosa damage and is fatal at a dose of about 0.2 to 0.5 g/kg.

Question 26

Why is measuring toxicity complex?

Answer 26

Toxicity measurement is complex because it may be acute or chronic and can vary from one organ to another, as well as with factors like age, genetics, gender, diet, physiological condition, or the health status of the organism.

Question 27

What makes classifying a substance as a toxicant complex (2 things)

Answer 27

Due to genetic variation. What is toxic to one organism/species/strain may be harmless to another. Also some substances are poisonous when combined with others but harmless alone

Question 28

5 importance of toxicology

Answer 28

Facilitate the development of more selective toxicants like anticancer drugs and pesticides. To understand how exposure to certain chemicals cause acute and chronic illnesses. To understand physiology and pharmacology by using toxic agents as chemical probes For the recognition, Identification and quantification of hazards from occupational exposure to chemicals. For the development of standards and regulations to protect humans and the environment from adverse effects of toxic chemicals.

Question 29

3 classifications of toxicity of a substance based on duration and frequency of exposure

Answer 29

Acute: Single or short term dosing causes toxicity Sub-acute: Repeated applications for a duration less than half-life expectancy of the organsim, causes toxicity Chronic: Toxicity is shown only after repeated exposure to the substance for a time greater than half the life-expectancy of the organism

Question 30

3 examples of toxic pesticides and their effects

Answer 30

Organochlorines: Hypersensitivity to light, sound and touch, causes tremors, dizziness, nausea and confusion Organophosphates and carbamates: Causes nausea, diarrhea, muscle weakness and fatigue Pyrethroids: May be carcinogenic and affect the reproductive and endocrine system

Question 31

3 possible sites of toxic actions

Answer 31

Local (non-systemic): Affects wherever it comes in contact with. e.g acids, alkalis Remote (systemic): Affects a part of the body, far from its entry point Local and Remote: Can both act locally and remotely. e.g Oxalic acid.

Question 32

3 sources of toxic substances. Give examples

Answer 32

Chemical: Most common. e.g drugs corrosives Plants: Cocaine Animals: least common, most dangerous. e.g Scorpions, spiders, snakes, wasps e.t.c.

Question 33

4 examples of toxic solvents and vapours with their effects

Answer 33

Benzene: Carcinogenic. At low concentrations, may cause dizziness, headache and loss of appetite. High exposure causes irregular heart beat which leads to death. Toluene: Neurotoxin Methyl Chloride: Affects reproductive health. n-hexane: Neurotoxin

Question 34

6 branches of Toxicology

Answer 34

Mechanistic Forensic Clinical Environmental Food Regulatory

Question 35

6 examples of toxic plants and their effects

Answer 35

Cashew: Allergic dermatitis Grasses: Allergic rhinitis Lilies: Affects the GI tract Mushrooms: Affects the nervous system Fugus that grows on peanuts: Liver cancer Legumes: Affects reproductive system

Question 36

7 types of toxic agents

Answer 36

Heavy metals Solvents and vapours Radiation and radioactive materials Dioxin/Furans Pesticides Plant Toxins Animal Toxins

Question 37

8 classifications of toxic agents

Answer 37

According to the target organ they act on e.g hepatotoxic, nephrotoxic According to their use e.g. drugs, pesticides According to their source e.g. chemical, animal of plant According to their effects e.g. Carcinogen, mutagen According to their physical state e.g gas, liquid According to their chemistry e.g. Amine, hydrocarbon According to their poisoning potential e.g. slightly toxic, extremely toxic According to their biochemical mechanism of action e.g alkylating agent

Question 38

Definition of the clinical branch of toxicology

Answer 38

Has to do with the treatment of poisonings and injuries caused by xenobiotics

Question 39

Definition of the Environmental branch of toxicology

Answer 39

A branch that deals with environmental pollutants and their effects on flora and fauna

Question 40

Definition of the food branch of toxicology

Answer 40

Studies adverse effects of food components, both natural and processed

Question 41

Definition of the Forensic branch of toxicology

Answer 41

A branch that has to deal with identifying the role of toxic substances in an individual's death

Question 42

Definition of the mechanistic branch of toxicology

Answer 42

A branch that deals with the molecular and cellular mechanisms by which chemicals use to bring about toxic responses

Question 43

Four examples of heavy metals and their effects

Answer 43

Cadmium: Carcinogenic. Smokers are more exposed so lung cancer Lead: Damage the brain and Kidneys, leading to death. Causes miscarriage and in main damages organs that produce sperm. Mercury: High levels damage brain, kidneys and foetuses Selenium: Oral exposure to high levels causes selonosis, characterized by hair loss, brittle nails and neurological issues. Short-term exposure to high levels in air can cause respiratory tract irritation and stomach pain. Longer-term exposure leads to worsening of these symptoms

Question 44

Definition of the regulatory branch of toxicology

Answer 44

Assigns risk to substances of commercial importance

Question 45

Short and long term effects of Dioxin/Furans

Answer 45

Short term: Skin lesions and altered liver function Long term: Impairment of the immune, nervous, endocrine and reproductive system

Question 46

Short and long term effects of exposure to radiation

Answer 46

Short term: Acute radiation syndrome (ARS). Symptoms include nausea, vomiting, headache and diarrhea Long term: Cancer, Abnormal foetuses, Poor mental health

Question 47

Two examples of toxic animals and their toxic effect

Answer 47

Scorpions: Produces neurotoxin Snakes: Produce neurotoxin

Question 48

Types of toxic mechanisms

Answer 48

Direct: The poison itself causes adverse effects e.g. corrosives Indirect: Toxicity results from interacton of the poison with biological activity, leading to a negative change e.g effects on DNA, Interferenct with enzymatic actions

Question 49

What is exposure in terms of toxicology

Answer 49

The concentration of chemical involved and frequency of its interaction with people

Question 50

What is excessive exposure

Answer 50

The degree of exposure that leads to injury or adverse effects

Question 51

4 ways humans may be exposed to toxicants

Answer 51

Accidental poisoning Intentional poisoning Occupational exposure General environmental exposure

Question 52

4 Routes of exposure

Answer 52

Skin and mucuous membranes Lungs (inhalation) Ingestion Eyes

Question 53

2 chemicals that can be absorbed through the skin

Answer 53

Aniline Hydrogen cyanide

Question 54

Exposure through the lungs depends on

Answer 54

The size and shape of the particle

Question 55

Effect of exposure to a toxicant of large size via the lung

Answer 55

Particles >10 micro-meters lodge in brochi/bronchioles. It is cleared by mucociliary activity and moves via the oesophagus into the gut.

Question 56

Effect of exposure to a toxicant of small size via the lung

Answer 56

Anything less than 2 micro meter persists in the alveoli and causes harm e.g Asbestos Macrophages in the lungs attempt engulfing it but are damaged instead. This leads to hydrolytic enzyme leak from the damaged macrophages, causing local tissue damage and fibrosis.

Question 57

The presentation of adverse effects that occur from ingestion of toxicants could be

Answer 57

Local Systemic Both local and Systemic e.g Allergic reaction Accumulatory: Either harmless (some pesticides like organophosphates accumulate in adipose tissue) or harmful (death of nerve cells following repetitive exposure)

Question 58

4 factors that affect the degree of adverse effect a toxicant produces at any given moment after ingestion

Answer 58

Balance between absorption and excretion Balance between injury and repair Immediate or delayed effect Reversible or irreversible

Question 59

3 outcomes interacting chemicals could cause

Answer 59

Additive effect (1+1= 2) Synergistic effects (1+1 = 4) Antagonist (1 + 5 = 2)

Question 60

Define tolerance to a chemical

Answer 60

A decrease in sensitivity to that chemical. Usually after an initial period of exposure

Question 61

Define resistance to a chemical

Answer 61

Complete insensitivity towards a chemical

Question 62

What is meant by the word toxicodynamics

Answer 62

The term encompasses the mode of action of a toxicant on a living organism that ultimately leads to the adverse effects it produces

Question 63

What is the toxicodynamics of liver cirrhosis caused by excessive alcohol

Answer 63

Excessive ethanol injures the liver by blocking metabolism of fat and carbohydrate, leading to the accumulation of fat in the liver cells, a condition known as fatty liver disease (FLD). Ethanol is converted to acetaldehyde. Acetaldehyde is a key toxin that can cause cellular damage, inflammation, and fibrosis, which contributes to the development of cirrhosis.