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Neuroscience Envrio Toxins and Mental Health > Overview of Toxicology > Flashcards

Overview of Toxicology Flashcards

1
Q

Toxicology

A

A branch of science that studies the adverse effects of chemical, physical or biological agents on living systems and the ecosystem, including the prevention and the amelioration of such adverse effects

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2
Q

Descriptive Toxicology

A
  • Focuses on testing of toxic substances
  • Typically using animals and then correlating finding to humans
  • Provides information for safety evaluation and regulation, such as dose-response information
    E.x., Assessing the reproductive toxicity of BPA
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3
Q

Mechanistic Toxicology

A
  • Identify and understand the mechanisms that underlie the toxic effects of drugs or chemicals on living systems
  • Also identifies whether the effects are genotoxic, teratogenic, carcinogenic, neurotoxic, etc.
    E.x., Study identifying targets of gymnodimines
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4
Q

Regulatory Toxicology

A
  • Assessing whether a drug or chemical poses a risk to human health
  • Uses information gathered from toxicity testing
  • Establishes standards and/or guidelines for safe exposure
    E.x., guidance for the consumption of bitter apricot kernels
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5
Q

Forensic Toxicology

A
  • Concerned with the medico-logical aspects of the harmful effects of toxic substances, environmental chemicals or poisonous products on human animals
    Determines the cause of death in a post-mortem investigation
    E.x., red tide in Florida linked to dolphin deaths
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6
Q

Clinical Toxicology

A
  • Concerned with disease states caused by or associated with toxic substances
  • Usually involves physicians or individuals specialized in emergency medicine and/or poison management
    E.x., New study linked exposure to second-hand tobacco smoke can predict cardiac arrhythmia
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7
Q

Environmental Toxicology

A
  • Concerned with the impact of physical and chemical pollutants in the environment on biological organisms
  • Includes the effects on human health and non-human organisms (such as fish, birds, and terrestrial animals)
    E.x., Micro-plastics in bottled water
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8
Q

Ecotoxicology

A
  • Specialized are within environmental toxicology that is concerned with the impacts of toxic substances on population dynamics in an ecosystem
    -Also evaluate the transport, fate, and interactions of toxic substances in the environment
    E.x., studying the effects of glyphosate (herbicide) on honey bees
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9
Q

Toxins

A

peptides or proteins produced by living cells or organisms

E.x., natural toxins like phytotoxins

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10
Q

Toxicants

A

Substances that are synthetic

E.x., man made things like bisphenol A (BPA)

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11
Q

Poisons

A

Any synthetic or natural substance that is harmful to health

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12
Q

Xenobiotic

A

Foreign substance taken into the body

  • may produce beneficial effects (i.e., pharmaceuticals)
  • may produce toxic effects (i.e., heavy metals)
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13
Q

Toxic Agents

A

Anything that can produce an adverse biological effect

- Can be chemical (cyanide), physical (radiation), or biological (snake venom)

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14
Q

Toxic Substances

A

Any material that has toxic properties

- Can be a discrete toxic chemical (lead) or a mixture of chemicals (gasoline)

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15
Q

Toxicity

A

The degree to which a substance can harm humans or animals

- can be acute, sub-chronic, or chronic

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16
Q

Toxicity can result from?

A

Averse

  • cellular changes (e.x., cell death (cytotoxins))
  • biochemical changes (e.x., elevated liver enzymes(hepatotoxins))
  • Macromolecular changes (e.x., altered insulin signalling (diabetogens))
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17
Q

Acute Toxicity

A
  • Adverse effects occurring in an organism after a single exposure or short-term exposure (<24 hours)
  • Exposure to a large dose (weak toxin) or a small dose (potent toxin)
  • The onset of symptoms is sudden and severe in nature
  • Rapidly changing course of progress
    E.x., Novichok poisoning (inhibits acetylcholinesterase)
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18
Q

Sub-chronic Toxicity

A
  • Due to repeated exposure for several weeks of months
  • The ability of a toxic substance to cause adverse effects for more the lifetime of the exposure organism
    E.x., Warfarin (blood thinner)- internal bleeding
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19
Q

Chronic Toxicity

A
  • The ability of a toxic substance to cause adverse effects over an extended period, usually repeated or continuous exposure, sometimes lasting for the entire life of the exposed organism
  • Cumulative damage
  • Damage becomes so severe that the organ can no longer function as normal
    E.x., Cirrhosis in alcoholics
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20
Q

Toxic response: Local vs Systemic

A

Local: effects at the site of contact (e.x., lungs)
Systemic: effects distant form exposure site (e.x., central nervous system)
- some can be both

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21
Q

Toxic responses: Specific vs Widespread

A

Specific: affects only specific target organs
Widespread: can damage any cell or tissue that it come in contact with
- some can be both

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22
Q

Toxic responses: Immediate vs Delayed

A

Immediate: response minutes to hours after a dingle exposure (e.x., azaspiracides)
Delayed: response days to years after exposure (e.x., PMAA)
- some can be both

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23
Q

Toxic responses: Reversible vs Irreversible

A

Reversible: rapidly regenerating tissue (e.x., liver)
Irreversible: not regenerating or recovery (e.x., carcinogenesis)

Influencing factors

  • tissue involved
  • length of exposure
  • magnitude of toxic
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24
Q

Direct Toxicity

A

substances or their metabolites themselves are toxic (e.x., phthalates)

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25
Q

Indirect Toxicity

A

Some substances may be toxic by indirect modifying an essential biochemical function, interfering with nutrition, or altering a physiological mechanism
(e.x., TiO2 nanoparticles)

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26
Q

Three phases of toxicology

A
  1. Exposure (contact)
    - how an organism come sin contact with a toxin
  2. Toxicokinetic (movement)
    - the study of the movement of the toxin within the body
    - absorption, distribution, metabolism, and excretion (ADME)
  3. Toxicodynamic (effects)
    - the study of what the toxin does to the body
    - physiological, biochemical, molecular (PBM)
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27
Q

Exposure Phase: Sources

A
  • Consumer products,
  • Clothing
  • Residential and other water
  • Indoor and outdoor air, tobacco smoke, household dust
  • Food, beverages, and food packaging
  • Toys
  • Furniture, carpeting, paint, and other building materials
28
Q

Exposure Phase: Route

A
  • oral
  • dermal
  • inhalation
  • injection
29
Q

Exposure Phase: Duration

A
  • Acute (<24 hours)
  • Subacute (<1 month)
  • Sub-chronic (1-3 months)
  • Chronic (>3 months)
30
Q

How to Assess Exposure

A
  • An individuals’ exposed to a substance can be assessed based on the relationship between a person’s body weight and
  • The concentration of the substance
  • Amount of a substance taken into the body
  • Duration and frequency of exposure
  • This will determine the dose of a substance that an individual is exposed to
31
Q

Exposure

A

Any condition which provides an opportunity for an external environment substance to enter the body

32
Q

Dose

A

The amount of a substance actually deposited within the body
- A dose can be affected by route, duration, frequency, amount, concentration as well as body weight, sex, age, time etc.

33
Q

Exposure Units

A

mg/L in water
mg/kg in food
mg/m3 in air

34
Q

Dosage Units

A

Amount of substance per unit weight of the exposed organism

Dosage = mg (dose)/ kg (body weight)/day (duration)

35
Q

Administered Dose

A

The quantity administered to an organism at one time

36
Q

Internal Dose

A

The about of a toxin that stays in an organism’s body

37
Q

Total Dose

A

Sum of all individuals doses

Total dose= concentration X amount X frequency X duration

38
Q

Response (endpoint)

A

The biological response to a substance

Change in structure or function, morbidity or mortality

39
Q

Dose Response Relationship

A

Quantitative analysis or mathematical description of the association between dose (or exposure) and a toxic response (or endpoint)

  • association relationship
  • responses follow normal frequency distribution
40
Q

Normal Distribution

A
  • Graph of individual responses to a substance to show how a population will be affected
  • Response (from mild to severe) along the x-axis
  • # of individuals (few to many) with each type of response along the y-axis
  • If graph the individual responses you end up with a bell-shaped curved (also known as a standard distribution)
  • Largest # of individuals fall within the highest area of the graph (mean response)
  • Standard deviation (SD) is a measure that indicates variation or dispersion of a set of values
  • Greater the SD, the greater the variability within a population
  • SD of 0 means most of the values fall near the mean
  • Indicates majority of responses to a substance are similar within a specific population
  • SD from -1 to 1 accounts for approximately 68% of the individuals
  • SD of -2 to 2 accounts for approximately 95% of the individuals
41
Q

Dose Response Curve

A
  • A quantitative relationship between dose and response can be plotted on a graph
  • Dose (or exposure) on the x-axis – usually in a logarithmic scale (increase by a power of 10)
  • Response (or endpoint) on the y-axis – usually as the percentage of individuals that show a response
  • Dose-response curve normally takes the form of a sigmoid curve shaped like the letter “S”
42
Q

NOAEL

A

No Observed Adverse Effect Level

- highest dose at which no toxic effects observed

43
Q

LOAEL

A

Lowest Observed Adverse Effect Level

- lowest dose at which toxic or adverse effects observed

44
Q

LD50

A

Can extrapolate from dose-response curve

- response vs dose meeting point along the graphed line

45
Q

Toxicokinetic: Absorption

A
  • Normally cells in solid tissues are so tightly compacted that substances cannot pass between them
  • Not going to have a toxic effect if not absorbed readily
  • In order to reach the site where it exerts is toxic effects the substance often has to pass through several membrane barriers
  • Substances that cross the cell membrane use either
  • Passive transfer
  • Facilitated transport (facilitated diffusion, active transportation, and endocytosis)
46
Q

Absorption: Passive Transfer

A
  • Consists of simple diffusion
  • No cellular energy or assistance is required
  • Most common way that toxins cross cell membranes
  • Two factors determine the rate of passive transfer
  • Concentration gradient (high or low)
  • Movement through small pores small pores in membrane or lipophilic interior of the membrane
47
Q

Properties affecting a chemical substance for passive transfer include

A
  • Lipid solubility
  • Molecular size
  • Degree of ionization
48
Q

Absorption: Facilitated diffusion

A

Requires special transport proteins embedded within the cell membrane to facilitate movement of molecules across the membrane

  • Compared to passive transport
  • Faster and can move larger molecules
49
Q

Absorption: Active Transport

A

Some substances are unable to move with diffusion, dissolve in the lipid layer or are too large to pass through aqueous channels or movement may be against the concentration gradient

  • Requires cellular energy (ATP)
  • E.x., sodium transfer pump
50
Q

Absorption: Endocytosis

A

Cell surrounds the substance within a section of its cell wall

51
Q

Toxicokinetic: Distribution

A

Distribution is the process in which an absorbed chemical moves away from the site of absorption to other areas of the body

  • blood can distribute chemicals
  • liver, kidneys, bone can store chemicals
  • barriers are in place for protection (e.x., BBB)
52
Q

Toxicokinetic: Metabolism

A

Conversion of a chemical from one form to another by biological organism
- two types
Detoxification and Bioactivation

53
Q

Metabolism: Biotransformation

A

Something is happening to the compound, either making it more or less toxic
- Phase I reactions
Modify the chemical by adding a functional structure group
- Phase II reaction
Conjugate the modified substance with another substance

54
Q

Toxicokinetic: Detoxification

A

Chemical substance is converted to a less toxic form

Generally speaking lipid-soluble compounds are converted to polar compounds

55
Q

Toxicokinetic: Bioactivation

A

Chemical substance is converted to more reactive or toxic forms
DEHP vs. MEHP

56
Q

Excretion

A

Sites of excretion include the Kidneys (main), GI tract, Lungs, sweat, tears, and breast milk

57
Q

Factors influencing Toxicity

A
  • innate chemical activity of a substance
  • dosage
  • exposure rate
  • absorption
  • species
  • age of organism
  • gender of organism
  • metabolism
  • distribution within the body
  • health status
  • circadian rhythms
  • presence/interaction of other chemicals
58
Q

Interaction: Addictive

A

Effects of two or more chemicals are equal to sum of the effects of each agent given along
2+3=5

59
Q

Interaction: Synergistic Effects

A

Effects of two or more chemicals are greater to sum of the effects of each agent given alone
2+2=20

60
Q

Interaction: potentiation effects

A

Occurs when one chemical that does not normally have toxic effect is added to another chemical, making the second chemical more toxic
0+2=10

61
Q

Interaction: Antagonistic effects

A

Effect of two or more chemicals interfere with each other’s action
Often a desirable effect in toxicology and the basis for most antidotes
- 4+0=1 (one chemical has no effect on its own)
- 4+ (-4) = 0 (one chemical has the opposite effects)
- 4+6=8 (both have toxic effects, less toxic when combined)

62
Q

physiological antagonism

A

Severe drop in blood pressure due to a barbiturate overdose reversed by administration of vasopressor

63
Q

chemical antagonism

A

Mercury toxicity can be reduced by chelating the mercury ions with dimercaprol

64
Q

dispositional antagonism

A

Swallowed poison is absorbed by introducing charcoal into the stomach reducing duration of chemical at target organ

65
Q

receptor antagonism

A

Carbon monoxide poisoning is treated with oxygen to displace the carbon monoxide from the hemoglobin receptors

Neuroscience Envrio Toxins and Mental Health (6 decks)

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