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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
Rachel Carson (1907-1964)
• 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
26
economic ‘externality’
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).
27
Endocrine Disrupting Compounds (EDCs)
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.
28
Nanoparticles
2000s • Found in more than 1,300 commercial products including medical equipment, textiles, fuel additives, cosmetics, plastics, etc.
29
Pharmaceuticals and Personal Care Products (PPCPs)
2000s | • Drugs we take and smells (the stink) we put on our bodies
30
Microplastics
2000s, find them everywhere
31
Since the 2000s, significant research has gone into, microplastics, ppcps, nanoparticles
Moral is that before we even know how to deal with one problem, several more are discovered...
32
a large portion of knowledge of toxicology
has become known only in the past 4-5 decades.
33
• Toxicant:
a substance capable of producing a toxic effect when in contact with a living organism at a sufficiently high concentration
34
contaminant
in the place of toxicant • Substance that pollutes, spoils or poisons something.
35
• Toxin:
a toxicant produced by a living organism (microbe, plant, or animal) • i.e., a naturally produced toxicant
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Poisonous animal
must be touched by you
37
Venomous animal
injects toxin into you
38
Teratogen
substance capable of causing malformation during the development of the fetus (e.g., Thalidomide, late 50’s early 60’s).
39
Thalidomide
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
Dr. Frances Kelsey
a Canadian physician working for the USA Food and Drug Agency (FDA), prevented the licencing of thalidomide in the USA.
41
Mutagens:
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
Benzopyrene
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
carcinogen
is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer
44
Carcinogen exposure
increases the risk of developing cancer. The risk is higher for some carcinogens than others. For example, benzopyrene, it is high...
45
radionuclide
is a big atom which can decay and release radiation
46
mutagens aren’t necessarily
carcinogens, and carcinogens aren’t necessarily mutagens!!!
47
Mechanistic toxicology
* Focuses on understanding specific chemical, biochemical and molecular mechanisms by which toxicants have their effects. * Adverse Outcome Pathways
48
• Descriptive toxicology
* Focuses on the toxicity testing of chemicals * Provides information for safety evaluation and regulatory requirements * Acute lethal toxicity * Bioassays * Animal testing...
49
Clinical toxicology
``` Concerns diseases (usually human) caused by or uniquely associated with toxicants Usually a specialization of medical doctors ```
50
Forensic toxicology
Focuses on the medical and legal aspects of toxicants on humans and animals Asks “why did they die?”
51
Reproductive toxicology
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
Developmental toxicology
Studies life-long adverse effects of toxicants arising from exposures: • Before conception • During prenatal development • Teratogens... • Fetal Alcohol Syndrome... • Postnatal to puberty • EDCs...
53
Occupational toxicology
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/
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Environmental toxicology
Focuses on detecting compounds and impacts in the natural environment
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Ecotoxicology
Impacts on animals and populations in a natural ecosystem
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Regulatory toxicology
Work focuses on the risk decision-making based on data from mechanistic and descriptive toxicology • Set standards for “safe” exposure
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toxicants differ in how they react with?
water
58
Hydrophilic (water loving):
Dissolve in water, polar.
59
Hydrophobic (water hating):
Do not dissolve in water, non- polar. If ingested, will be stored in fat tissue so often called lipophilic.
60
Octane
- Non-polar (no partial charge) - Cannot form hydrogen bonds - Can form Van der Wall bonds
61
Octanol
- The hydroxyl (OH) end is polar - The rest isn’t - Thus is amphiphatic
62
Water molecule
- Polar (partial charge across molecule) | - Can form hydrogen bonds
63
Toxicologists and environmental chemists (in North America...) often use the
‘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
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ppb
‘parts per billion’. • 1g of substance in1,000,000L of water • 1μg/L • Three seconds out of a century
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ppt
‘parts per trillion’. Eg: • 1gofsubstancein1,000,000,000Lofwater • 1ng/L • Threesecondsoutofa1000centuries
66
We can now measure compounds in these trace amounts.
We find trace amounts of toxicants pretty much everywhere. Are these trace amounts biologically relevant?? Ecotoxicologists are trying to answer this question!
67
We find trace amounts of toxicants pretty much everywhere.
– Our food, water, blood... – But remember, animals are virtually never exposed to just a single toxicant at a time • Generally in complex mixtures
68
Toxicants Are Different Sizes
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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