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PHAR 303 > L21. Environment & Occupational Toxicology > Flashcards

L21. Environment & Occupational Toxicology Flashcards

1
Q

What are the different ecozones in Canada and what are their challenges?

A
  • Agricultural & urban-based regions: drinking water quality, urban congestion, air pollution, loss of wildlife habitat and farmland
  • Coasts: declining fish stocks, forestry practices, land-based pollution
  • Arctic: managing impacts of resource development in a fragile ecosystem, reducing contamination of traditional food sources by toxic substances emitted from distant sources. Impact of climate change
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2
Q

What is “environmental chemodynamics”?

A
  • The properties of a chemical influence its behaviour in the environment
  • We can predict how a chemical will partition between environmental compartments:
    • Air (atmosphere)
    • Water (hydrosphere)
    • Soil (lithosphere)
    • Biological systems
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3
Q

What are the major factors that influence the impact of environmental chemicals?

A
  • Persistence
  • Bioaccumulation and Biomagnification
  • Toxicity
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4
Q

Name 6 different contaminants along with their half life, the media they accumulate in, and what they are used for.

A
  1. DDT has a half life of 10 years. Its media is soil. And it is an insecticide.
  2. TCDD has a half life of 9 years. Its media is soil. And it is a contaminant of herbicide/defoliant.
  3. Atrazine has a half life of 25 months. Its media is water (pH 7.0) and it is a herbicide.
  4. Benzoperylene has a half life of 14 months. Its media is the soil and it results from incomplete combustion of fossil fuels and tobacco.
  5. Phenanthrene (PAH: polycyclic aromatic hydrocarbon) has a 138 day half life. Its media is soil and it is used In the fabrication of dyes, plastics, drugs, pesticides and from burning of coal, wildfire, and waste.
  6. Carbofuran has a 45 day half life. Its media is water (pH 7.0) and it is a pesticide.
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5
Q

How long does it take for a compound to be removed from the environment?

A

4 half lives.

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6
Q

What is bioaccumulation? When does it apply?

A
  • Accumulation of contaminants from the environment & food
  • Positively correlated with lipophilicity: Bioaccumulative substances are hydrophobic and fat-soluble
    (high octanol-water partition coefficient; KOW)
  • It applies to plants, animals, and people.
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7
Q

Explain an example of the relationship between lipids and bioaccumulation.

A

Lipid concentration of organisms living in in Lake Ontario (fish, etc) has a direct correlation with bio accumulation and increase of PCBs. So organisms with lipids will bioacccumnulate PCBs to increase the amount of PCBs above the amount thats already in Lake ontario.

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8
Q

What is biomagnification? Give an example.

A

Due to food digestion & absorption the concentration of ingested chemicals in gastrointestinal tract causes an increase in chemical concentration in organisms with increasing trophic level. The higher you are in the food chain the more concentrated the chemical is.
- Ex: DDE, a metabolite of DDT, is present in water so it biomagnifies up the food chain starting at small fish, then bigger fish, then becomes even more concentrated in fish-eating birds.

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9
Q

What is toxicity hazard identification? What is the approach?

A

Characterization of the Innate Adverse Toxic Effects of Agents: Weight-of-evidence approach.

  • Structure-Activity Relationships
  • In vitro and short term tests
  • Animal bioassays
  • Epidemiologic data
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10
Q

What is the Stockholm convention on persistent organic pollutants (POPS)?

A
  • POPS are persistent, bioaccumulate/magnify, and are toxic
  • The text of the convention was adopted in Stockholm in 2001 and entered into force in 2004. Canada is part of it, the US is not.
  • Goal: to eliminate or significantly reduce the release of POPS into the environment such as:
    Polychlorinated biphenyls (PCBs) and Dichlorodiphenyldichloroethylene (DDE) (metabolite of DDT).
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11
Q

How has the Stockholm convention affected PCBs and POPS in the environment?

A
  • In 2005, 1 year later, the blubber of polar bears from the canadian arctic was measured for the chemicals. Still a lot of PCBs and DDEs
  • There were a lot of PCBs in mothers and infants in Nunavik because they eat polar bears.
  • There was an association between PCBs in Inuit preschoolers and behavioural problems such as anxiety -> affects neurodevelopment of these children.
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12
Q

If you agree to the Stockholm convention, what categories can the POPS fall into?

A

You can either:

  • Annex A (Elimination): Agree to eliminate the POPS
  • Annex B (Restriction): You can restrict them because some of the countries deemed they were essential, usually countries who have issues with malaria because it can protect from that.
  • Annex C (Unintentional production): hard to get rid of and due to byproducts in the industry & hard to find substitutes.
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13
Q

What is Tetrabromodiphenyl ether and pentabromodiphenyl ether?

A

They are POPS used as flame retardants. They are not approved for use in Canada and are being gradually replaced with alternatives.
Listed in Annex A

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14
Q

What is PFOS and PFOSF (perfluorooctane sulfonic acid, its salts and perfluorooctane sulfonyl fluoride)?

A

They are POPS and are gradually being replaced.
Again, the replacements may also have adverse effects. A lot of the replacements have shorter chains and are also ending up being toxic.
Listed in Annex B

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15
Q

What are the uses of PFOS and PFOA?

A
  • Industrial surfactants, dispersants
  • Waterproofing
  • Fire-fighting foam
  • Teflon coated pans
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16
Q

How do we get exposed to PFOS and PFOA?

A
  • Oral: food (fish), drinking water
  • Inhalation: dust
  • PFOA in serum: 7 ng/mL – 690 ng/mL
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17
Q

What is the half life of PFOS and PFOA?

A
  • Humans: Average of 2.7 years (persistent)

* Groundwater: 5-15 years

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18
Q

Where does PFOA and PFOS accumulate?

A

Whatever we do here in the urban centres, due to the distribution through winds and currents, it all ends up in the arctic. -> it is really a global issue. It is not something only one country can address. Biomagnification in the water in the arctic

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19
Q

What toxicity has been shown for PFOA in animal studies?

A
  • Reproductive toxicity
  • Developmental toxicity
  • Liver
  • Kidney
  • Immunological
  • Tumorogenesis
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20
Q

What toxicity has been shown for PFOA in epidemiological studies?

A
  • Increased Cholesterol
  • Low infant birth weight
  • Immunological
  • Cancer
  • Thyroid hormone disruption
  • Endocrine disruption
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21
Q

Explain a case of PFOA toxicity.

A
  • Personal injury cases against DuPont for contaminating drinking water in Ohio and West Virginia: thyroid disease, high cholesterol, ulcerative colitis, kidney cancer, preeclampsia, and testicular cancer.
  • Jan 22, 2021: DuPont, Chemours and Corteva announced a cost-sharing agreement worth $4 billion to settle lawsuits involving the historic use of the highly
    toxic “forever chemicals” (because they stay in the environment for a long time) known as PFAS.
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22
Q

What can be done in order to combat occupational toxicology?

A
  • Application of the principles and methods of toxicology toward chemical and biological hazards encountered at work.
  • The objective is to prevent adverse health effects in workers arising from their work environment.
23
Q

Explain the toxicological evaluation of occupational agents and its challenges.

A
  • Must establish causality through:
    1. In vitro assays
    2. Animal toxicology studies
    3. Human challenge studies 4. Case reports
    5. Epidemiology studies
  • Challenges:
  • we don’t necessarily have access to the factories etc. So we have the CSST in Qc.
  • Many of the workers are often unionized and the researchers can go through the union to put pressure on the companies to allow them to conduct their research.
24
Q

What organizations in the USA set the occupational exposure limits? What values do they set?

A

ACGIH – American Conference of Governmental Industrial Hygienists
OSHA – Occupational Safety and Health Administration
Values:
TLVs – threshold limit values
TLV-TWA (time weighted average) for 8-h/d, 5-d/w
TLV-STEL (short term exposure limit) – 15-min
TLV-C - ceiling
PELs – permissible exposure limits
RELs – recommended exposure limits

25
Q

What is the history of the discovery of workplace exposures?

A
  • Agricola (1494-1555) Toxic nature of exposures
  • Paracelsus (1492-1541) In mining, smelting and metallurgy.
  • Ramazzini (1633 – 1714) Hazards to miners, chemists, metal workers, tanners, pharmacists, grain sifters, stonecutters, sewage workers and even corpse bearers
26
Q

What are the challenges in occupational toxicology?

A

Difficult to establish a causal link between illness and job:

  1. Equivalence of occupationally-induced vs. non-occupational disease.
  2. Protracted latent interval between exposure and expression of disease. Its hard to prove that the kind of disease that you have is linked to your exposure 10-20 yrs ago. For asbestos it was a bit easier because you could actually see the fibre in the lungs
  3. Multi-factorial nature of diseases of occupational origin.
27
Q

What are the control/prevention approaches for occupational hazards?

A
  • Change the process to use or produce less hazardous compounds
  • Automate and enclose the process to isolate the compounds. ex: increase ventilation
  • Implement admin. and work practice controls to reduce duration/intensity of exposure
  • Install or upgrade local exhaust system and dilution exhaust
  • Institute a comprehensive program for personal protective equipment use when necessary
28
Q

What are pesticides and what are the different classifications based on use?

A

Pesticides are chemicals designed to kill, reduce, or repel pests.

  • Can be used for insects: insecticides and insect repellants
  • Can be used for weeds: herbicides
  • Can be used for moulds: fungicides and wood preservatives
  • Can be used for rats, mice, moles: rodenticides
  • Fumigants can be used for all of the above
29
Q

Rank the pesticides in order of most to least used.

A

Herbicides > fungicides > insecticides > Other

30
Q

Name 2 types of herbicides.

A

Glyphosate and Triazines.

31
Q

What are the problems with aerial application of pesticides?

A
  • Very difficult to avoid drift or overspray.
  • Even under correct conditions (low wind, accurate application) trailing vortices generated by winds can disperse pesticides to untargeted areas.
32
Q

How can humans be exposed to pesticides?

A

Humans absorb them dermally from literally anywhere on the skin.

33
Q

Describe the movement of pesticides (and chemicals) in the environment.

A
  • Depends on: physical & chemical properties of the chemical
  • They can come down in rain water due to evaporation, in runoff into rivers, etc.
  • Diffusion very fast in air.
  • Can get into soil, into water….
  • If you treat your crops with pesticides they will end up in our food.
34
Q

When assessing the properties of pesticides, what needs to be considered?

A
  • Bioaccumulation—particularly important for fat soluble compounds
  • Degradation—what amount is left over time. Can it be degraded by cooking?
  • Toxicity—acute, chronic, aquatic, terrestrial
  • Carcinogenicity—to fish, mice, rats (surrogates for human toxicity)
35
Q

What is the testing approach used for testing pesticides? Describe it.

A
  • The tiered testing approach.
    • Tier 1: 1-2 years of acute tests (e.g., using oral doses to rats) to determine potential human toxicity
    • Tier 2: 2-4 years of chronic tests using mammals, birds, fish, invertebrates
    • Tier 3: about 2 years of simulated field tests using micro- or mesocosms (large enclosed water-based ecosystem/pond/tanks with multispecies from plankton to fish)
36
Q

What is important to figure out when analyzing a pesticide?

A
  • Its mechanism of action:
    What are the target and non-target organisms of the pesticide? Do they hit the target organism? Does it specifically affect the plant? Or is it gonna affect other organisms in the field including the people? So some are more targeted and specific
    Therefore, you need to optimize the specificity for the target species.
37
Q

How long does it take to register a pesticide for use? How much does it cost? Who does it for the government of Canada? What needs to be done?

A
  • Usually takes 6-10 years to register a pesticide
  • Cost approximately $1,000,000/year
  • The Pest Management Regulatory Agency (PMRA), under the Minister of Health, administers the Pest Control Products Act for the Government of Canada.
  • Pesticide manufacturers have to provide a list of data to get an approval to be able to use the pesticide. Also give you the maximum limit of exposure. So if you have to get up to the limit amount in order for he herbicide to be useful, then the farmer probably won’t use it.
38
Q

What are the occupations at risk of herbicide exposure?

A
  • Golf course maintenance
  • Sports and field turf management
  • Agricultural workers
  • Garden nursery employees
  • Professional gardeners
  • Agriculture & viticulture staff
  • Landscaping professionals
  • Local and state maintenance
  • Horticulture experts
  • Lawn and care maintenance
  • Parks and forest employees
  • Avid home gardeners
    (not important to memorize all of these, i just put these so we have an idea)
39
Q

What is Glyphosate?

A

It is the main ingredient for RoundUp, one of the world’s most used herbicides.

40
Q

What is the main use of RoundUp/Glyphosate?

A

Roundup: use was increased when genetically modified crops became available. They genetically modified corn to make it glyphosate tolerant so the corn is not affected by this herbicide but the weeds are. So it will kill everything (except for the corn) that is competing for the crop.
Cotton, soybean, corn are all genetically modified crops.

41
Q

What is the problem with the use of RoundUp & genetically modified crops?

A
  • Problem: even more use of this herbicide now.
  • The Canadian Food Inspection Agency found trace amounts of glyphosate in roughly 30% of food products it tested, and residue levels above the recommended limits in nearly 4% of grain products.
  • The amount of Glyphosate found in Quebec rivers is also increasing
42
Q

What is the mechanism of action of glyphosate?

A

Glyphosate inhibits a plant enzyme that is involved in the production of phenylalanine, tyrosine and tryptophan (amino acids) which are essential to their growth. Because of this the weeds or anything that hasn’t been genetically modified to be resistant will be killed.

43
Q

What is the classification of the safety of glyphosate by different organizations?

A
  • International Agency for Research on Cancer (IARC): Glyphosate is classified as “probably carcinogenic in humans” (category 2A), based on epidemiological studies, animal studies, and in vitro studies.
  • European Chemicals Agency (ECHA) Risk Assessement Committee (March 15, 2017): Glyphosate may cause serious eye damage and be toxic to aquatic life. However, it was not found to be implicated as a carcinogen, a mutagen, or toxic to reproduction.
  • State of California in 2017: Glyphosate was listed as “known to cause cancer”.
  • Nothing is simple. Every state/country/region will make their own decisions based on the info
44
Q

Explain a case study on RoundUp exposure and what came of it.

A
  • In a US Superior Court: In June 2018, Dewayne Johnson, a 46-year-old former California school groundskeeper who was dying of non- Hodgkin lymphoma, took Monsanto (company that makes RoundUp) (which had been acquired by Bayer earlier that month) to trial in San Francisco County superior court, alleging that it had spent decades hiding the cancer-causing dangers of its Roundup herbicides. The judge ordered that jurors be allowed to consider both scientific evidence related to the cause of Johnson’s cancer and allegations that Monsanto suppressed evidence of the risks, with possible punitive damages. In August 2018, the jury awarded Johnson US$289 million in damages.
  • By April 2019, manufacturers were required to update commercial labels for products containing glyphosate to include statements such as:
  • Re-entry into the sprayed areas should be restricted to 12 hours after its application in agricultural areas.
  • The product is to be applied only when the potential to spread to areas of human activity, such as houses, cottages, schools and recreational areas, is minimal.
  • Instructions for buffer zones to protect areas beyond those targeted as well as aquatic habitats.
45
Q

What is MAC and what is the MAC of Glyphosate in Canada’s drinking water?

A

MAC: maximum acceptable concentration

MAC in canada: 280 ug/L

46
Q

What is Atrazine?

A
  • Broad leaf herbicide
  • 100s of million pounds used annually in the U.S.
  • Photosynthesis inhibitor
  • Used a lot, especially in corn
47
Q

What happens (short term and long term) if you are exposed to atrazine above the MCL? What is the MCL of Atrazine?

A
  • MCL (maximum contaminant level): 3 ppb
  • Short-term: congestion of heart, lungs and kidneys; low blood pressure; muscle spasms; weight loss; damage to adrenal glands.
  • Long-term (lifetime exposure): weight loss, cardiovascular damage, retinal and some muscle degeneration; cancer
48
Q

Explain the experiment done on Xenopus laevis with Atrazine.

A
  • Atrazine-Induced Gonadal Malformations in
    Xenopus laevis (frogs)
  • Treatment with 0.1ppb (μg/L) atrazine (which is below the MCL)
  • This frog has ovaries and testes: multiple messed up reproductive systems. Hermaphrodite: gonads are not differentiating into either ovaries or testes but rather both.
  • MCL was set at 3 ppb by the EPA: correspond to 1,000 times higher than the level found to produce no negative effects in laboratory studies
49
Q

What is the proposed mechanism of Atrazine?

A
  • Normally Testosterone is converted to estradiol via aromatase.
  • Atrazine induces this process even more which decreases T and increases E. It therefore demasculinizes and feminizes amphibians.
  • We also have this enzyme, will it do the same to us?
50
Q

Does Atrazine have an impact on humans?

A
  • The months of increased risk of a birth defect (April-July) and increased levels of nitrates, atrazine and other pesticides in surface water were significantly associated.
  • Pesticide use also correlates with poor semen quality
  • Tricky because you are not getting a direct measure of exposure. There are other pesticides, etc. Correlation NOT causation. Hard to have conclusive data.
51
Q

What is the canadian drinking water quality guideline for atrazine? What about in the EU?

A
  • MAC Canada: 0.005 mg/L
  • The EU banned atrazine in 2003. It was re-approved for use in Canada in 2017 but is listed for special review in Q4 (2021-2022).
52
Q

What is the CSST? What do they enforce? What are some examples?

A
  • Commission de la santé et de la sécurité du travail.
  • Un travailleur a le droit de refuser d’exécuter un travail qui présente un danger pour lui ou pour une autre personne (Workers have the right to refuse to do a job that presents a danger to themselves or to another person).
  • Examples provided: asbestos, beryllium, demolition, snow removal from roof, CO, work in the cold.
53
Q

What needs to be done if you work in a mcgill lab or other specialized area?

A
  • Need to go through Workplace safety WHMIS training
    •What are the hazards of this product?
    •How do you work safely with this hazardous product (controls, specific personal protective equipment, storage, disposal, etc.)?
    •How do you deal with an emergency, including an unexpected exposure or spill?
    •Where do you get more information about this product?

PHAR 303 (21 decks)

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