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toxicology > 1. intro, history, definitions > Flashcards

1. intro, history, definitions Flashcards

1
Q

What is toxicology?

A
  • study of the harmful interactions between chemicals and biological systems
  • regulation of how we produce, store, transport and use chemicals
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2
Q

chemistry of toxicants

A

molecular structures

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3
Q

biochemistry of how poisons affects biological molecules

A

impacts on enzyme function, binding to cellular receptors

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4
Q

physiology of these effects on tissues, organs and whole organisms

A

impacts on growth, development reproduction

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5
Q

ecological effects of the toxins in the environment

A

environmental toxicology, ecotoxicology

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6
Q

toxon

A

bow

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7
Q

toxikon

A

a poisonous substance into which arrowheads were dipped

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8
Q

logos

A

the study of

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9
Q

ebers papyrus

A

One of the earliest written medical (toxicology) documents. Directions for the collection, preparation and administration of over 800 medicinal and poisonous recipes.

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10
Q

origin of toxicology

A

from the use of poisons in murder and suicides

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11
Q

poisoning in ancient greece

A
  • so common they began developing antidotes

- sometimes testing poisons and antidotes on criminals

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12
Q

hippocrates

A
  • added poisons and clinical toxicological principles to medical therapy
  • treat the poisoning by influencing the absorption
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13
Q

socrates

A

was sentenced to death for corrupting the youth and chose hemlock poisoning

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14
Q

dioscorides

A

classified poisons as animal, plant or mineral, recognizing this as imporatant for treating poisonings

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15
Q

poisonings among romans

A

epidemic proportions in the 4th century BC

-sulla

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16
Q

Sulla

A

issued the first low against poisoning 82bc

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17
Q

paracelsus

A
  • german physician-alchemist and son of physician
  • formulated views that remain part of modern toxicology, pharmacology, and therapeutics –> considered treating disease with chemicals
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18
Q

paracelsus’ principles

A

1• Experimentation is essential in the examination of responses to
chemicals
2• One should make distinction between the therapeutic and toxic properties of chemicals
• e.g., Warfarin used to treat heart conditions, also a rodenticide…
• e.g., Niclosamide used to help tissue regeneration, also a mollusciside…
3• These properties are sometimes but not always distinguishable except by dose
• “All substances are poisons, there are none that is not a poison. The right dose differentiates a poison and a remedy.”
4• One can ascertain a degree of specificity of chemicals and their therapeutic or toxic effects
• These led to the notion of dose-response relationships in toxicology.

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19
Q

mathieu orfila

A

1787-1853

  • Spanish physician in french court
  • used autopsy material and chemical analysis to provide legal proof of poisoning
  • father of forensic toxicology
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20
Q

king edward 1

A

1306
-first environmental law
• Londoners had cut down all the surrounding forest and began burning more coal
• This led to horrible smog due to particulate matter, sulphur dioxide and nitrogen oxides in the air
• Decreed that anyone burning coal will be put do death when he visited London

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21
Q

Pierre- Marie-Alexis Millardet

A

1850s
-first modern pesticide
He sprayed grapes with a mixture of copper sulfate and lime (calcium hydroxide) to make the grapes bitter
• Sprayed grapes had fewer “powdery mildew” fungal infestations
• Led to development of “Bordeaux mixture” as a fungicide in orchards
• It is still used today as an ‘organic’ pesticide
• Can be harmful to fish, livestock, earthworms and humans…

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22
Q

The rise of the chemical industry in the 20th century

A

The number of chemicals produced by industry exploded and many were used without toxicity testing or environmental impact assessments (because these regulations were not always around!)

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23
Q

Xenobiotics

A 
substances foreign to life (“xeno” = foreign; “biotic” = relating to life)
Human-made substances which did not exist in nature before being synthesized in the laboratory
-For example...
• Agricultural pesticides
• Industrial chemicals
• Food additives
• Flame retardants
• etc.
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24
Q

DDT (dichloro-diphenyl-trichloroethane)

A

A synthetic insecticide developed in the 1940’s
• First used to prevent insect-borne human diseases (e.g., malaria)
• Then widely used to treat livestock, crops, gardens and in cities (e.g., mosquitoes in Winnipeg…)
Very persistent in the environment
• Persistent Organic Pollutants (POPs)
• Legacy Pollutants
• No longer used, but still around
Travels long distances in the upper atmosphere.
• Atmospheric deposition (scary)
• Polar bears in Arctic
• Penguins in Antarctica

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25
Q

Rachel Carson (1907-1964)

A

• Beginning of the environmental movement in the 1960s - widely regarded as the inspiration
-• Wrote “Silent Spring” (1962) on the dangers of pesticides
• One of the most important contributions to environmental toxicology
• Showed link between egg-shell thinning in birds from industrially synthesized pesticides
• Spurred a national policy on pesticides in US and later led to ban on DDT (in 1972) and other organochloride pesticides

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26
Q

economic ‘externality’

A

In the early days of industry, companies simply dumped waste chemicals into waterways.
• This is called an economic ‘externality’ (a cost of production is externalized by the company to be carried by society).

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27
Q

Endocrine Disrupting Compounds (EDCs)

A

in the 1990’s
• Chemicals that can mimic or disrupt hormone function (e.g., testosterone, estrogens, thyroid hormones)
• Vast majority of EDCs mimic estrogen in the body
• e.g., Bisphenol A (BPA) and Bisphenol S (BPS)
• Colborn, T., Dumanoski, D. and Myers, J.P., 1996. Our Stolen Future: Are We Threatening Our Fertility, Intelligence and Survival? A Scientific Detective Story.

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28
Q

Nanoparticles

A

2000s
• Found in more than 1,300 commercial products including medical equipment, textiles, fuel additives, cosmetics, plastics, etc.

29
Q

Pharmaceuticals and Personal Care Products (PPCPs)

A

2000s

• Drugs we take and smells (the stink) we put on our bodies

30
Q

Microplastics

A

2000s, find them everywhere

31
Q

Since the 2000s, significant research has gone into, microplastics, ppcps, nanoparticles

A

Moral is that before we even know how to deal with one problem, several more are discovered…

32
Q

a large portion of knowledge of toxicology

A

has become known only in the past 4-5 decades.

33
Q

• Toxicant:

A

a substance capable of producing a toxic effect when in contact with a living organism at a sufficiently high concentration

34
Q

contaminant

A

in the place of toxicant • Substance that pollutes, spoils or poisons something.

35
Q

• Toxin:

A

a toxicant produced by a living organism (microbe, plant, or animal)
• i.e., a naturally produced toxicant

36
Q

Poisonous animal

A

must be touched by you

37
Q

Venomous animal

A

injects toxin into you

38
Q

Teratogen

A

substance capable of causing malformation during the development of the fetus (e.g., Thalidomide, late 50’s early 60’s).

39
Q

Thalidomide

A

was prescribed to pregnant women for morning sickness. It was found to be a teratogen that causes phocomelia (limbs close to the trunk or severely underdeveloped).

40
Q

Dr. Frances Kelsey

A

a Canadian physician working for the USA Food and Drug Agency (FDA), prevented the licencing of thalidomide in the USA.

41
Q

Mutagens:

A

physical or chemical agents that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level.
- UV and radioactive substances

42
Q

Benzopyrene

A

mutagen
(in green) is in tobacco smoke(!) and can mess up base-pairing in a DNA strand by forming an DNA adduct. When repaired by the cell, a different nucleotide base (mutation) can be accidentally used to fix DNA strand.

43
Q

carcinogen

A

is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer

44
Q

Carcinogen exposure

A

increases the risk of developing cancer. The risk is higher for some carcinogens than others. For example, benzopyrene, it is
high…

45
Q

radionuclide

A

is a big atom which can decay and release radiation

46
Q

mutagens aren’t necessarily

A

carcinogens, and carcinogens aren’t necessarily mutagens!!!

47
Q

Mechanistic toxicology

A
  • Focuses on understanding specific chemical, biochemical and molecular mechanisms by which toxicants have their effects.
  • Adverse Outcome Pathways
48
Q

• Descriptive toxicology

A
  • Focuses on the toxicity testing of chemicals
  • Provides information for safety evaluation and regulatory requirements
    * Acute lethal toxicity
  • Bioassays
  • Animal testing…
49
Q

Clinical toxicology

A 
Concerns diseases (usually human) caused by or uniquely associated with toxicants
Usually a specialization of medical doctors
50
Q

Forensic toxicology

A

Focuses on the medical and legal aspects of toxicants on humans and animals
Asks “why did they die?”

51
Q

Reproductive toxicology

A

Studies the occurrence of adverse effects of toxicant exposure on the male or female reproductive system
70% of global amphibian populations are in decline. In part, due to xenobiotic toxicants messing with their reproduction.
One study has shown that over 18 years the average sperm counts fell by a third in 26,000 human men.

52
Q

Developmental toxicology

A

Studies life-long adverse effects of toxicants arising from exposures:
• Before conception
• During prenatal development • Teratogens…
• Fetal Alcohol Syndrome…
• Postnatal to puberty • EDCs…

53
Q

Occupational toxicology

A

Focuses on toxicological hazards occurring in workplace, with objective of preventing adverse effects in workers

In the 1770s, Percival Potts made the first occupational toxicology observation: chimney sweeps had higher incidences of cancer from exposure to soot.

9/11 Firefighters – high rates of cancer due to exposure to smoke and other carcinogens
http://www.freshairenvironmental.ca/

54
Q

Environmental toxicology

A

Focuses on detecting compounds and impacts in the natural environment

55
Q

Ecotoxicology

A

Impacts on animals and populations in a natural ecosystem

56
Q

Regulatory toxicology

A

Work focuses on the risk decision-making based on data from mechanistic and descriptive toxicology
• Set standards for “safe” exposure

57
Q

toxicants differ in how they react with?

A

water

58
Q

Hydrophilic (water loving):

A

Dissolve in water, polar.

59
Q

Hydrophobic (water hating):

A

Do not dissolve in water, non- polar. If ingested, will be stored in fat tissue so often called lipophilic.

60
Q

Octane

A
  • Non-polar (no partial charge)
  • Cannot form hydrogen bonds
  • Can form Van der Wall bonds
61
Q

Octanol

A
  • The hydroxyl (OH) end is polar
  • The rest isn’t
  • Thus is amphiphatic
62
Q

Water molecule

A
  • Polar (partial charge across molecule)

- Can form hydrogen bonds

63
Q

Toxicologists and environmental chemists (in North America…) often use the

A

‘parts per’ system.
ppm = ‘parts per million’ = 1 g of substance in 1 million g other substance
• 1 mL of substance in 1000 L of water • 1mg/L
• 1 g of substance in 1000 kg of soil
• 32 seconds out of a yea

64
Q

ppb

A

‘parts per billion’.
• 1g of substance in1,000,000L of water • 1μg/L
• Three seconds out of a century

65
Q

ppt

A

‘parts per trillion’. Eg:
• 1gofsubstancein1,000,000,000Lofwater • 1ng/L
• Threesecondsoutofa1000centuries

66
Q

We can now measure compounds in these trace amounts.

A

We find trace amounts of toxicants pretty much everywhere. Are these trace amounts biologically relevant??
Ecotoxicologists are trying to answer this question!

67
Q

We find trace amounts of toxicants pretty much everywhere.

A

– Our food, water, blood…
– But remember, animals are virtually never exposed to
just a single toxicant at a time • Generally in complex mixtures

68
Q

Toxicants Are Different Sizes

A

Because these have vastly different properties due to their various size and chemical compositions, the way we detect and quantify toxicants can vary greatly! Some commonly-used methods are:
Atoms: Atomic absorption spectroscopy
Small molecules: High Performance Liquid Chromatography (HPLC) and Gas Chromatography (GC)
Proteins: Enzyme-Linked Immunosorbent Assay (ELISA)

toxicology (10 decks)

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