Midterm 3 Flashcards

1
Q

MOA of Atrazine

A

Imbalance in steroid levels

Alters LH and FSH so effecting hypothalamus/pituitary hormone secretion

Adverse effects (gonad development)

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2
Q

Why is Atrazine used? What is the concentrations in BC?

A

Broadleaf weed control on crops (corn, blueberries…)

Detected in 71-75% waterways in BC

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3
Q

Where is Atraine banned? Why? Maximum concentrations of pesticides in water?

A

EU banned Atrazine due to persistent groundwater contamination.
Maximum level of 0.1 ug/L

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4
Q

Concentrations of Atrazine in Canada vs US

A

Canada: 5 ug/L

US: 3 ug/L

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5
Q

What is Endocrinology?

A

The study of the endocrine glands and their secretions (hormones)

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6
Q

What are endocrine glands?

A

Ductless glands that secrete hormones into the blood

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7
Q

Expanded Definition/Funciton of Hormones

A
  1. Hormones are not necessarily produced by ductless glands - hormones can be secreted by small groups of cells or even by individual cells
  2. Secretion from an endocrine gland or cell is not uni-hormonal - multiple active chemicals are produced by a cell
  3. Most hormones have multiple production sites
  4. Hormones are not only secreted into the bloodstream - they are not always blood borne - they can be released into lymph or extracellular fluids
  5. Hormone action cannot by stereotyped - it vaires according to the state of the target site. This may be determined by the receptors expressed in the target cell/ Action dependent on the state of the target - must be a receptor on the cell.
  6. Hormones do not always act on distant target sites - they can have paracrine or autocrine effects
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8
Q

Necessity of Multicellular Organisms for Hormones

A

The evolution of multicellular organisms made it necessary to have coordinating systems to regulate and integrate the function of different cells

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9
Q

Mechanisms of Water Soluble Hormone Action

A

(All amino acid-based hormones except thyroid hormone)

  • Cannot enter target cells
  • Act on plasma membrane receptors
  • Coupled by G proteins to intracellular second messengers that mediate the target cell’s response
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10
Q

Mechanisms of Lipid Soluble Hormone Action

A

(Steroid and Thyroid Hormones)

- Act on intracellular receptors that directly activare genes

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11
Q

Mechanism of Xenobiotic Disruption of Endocrine Systems

A
  1. Hormone action exerted via Binding Receptors:
    - Can be initiated by chemicals if able to bind to receptor and generate hormone response
    - Can by blocked by chemical if binds and blocks receptor site without induction of hormone
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12
Q

Other Mechanisms or Xenobiotic Disruption of Endocrine System

A

Hormone synthesis, secretion, transport, or elimination

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13
Q

Consequences of Receptor-Mediated Signalling

A
  • Hormones act at low levels
  • Largest effect at lower doses
  • Saturation of receptors and thus effect at high doses
  • Desensitization and down-regulation of receptors at high-hormone levels (bind to gene decreases transcription levels - decrease hormonal effects)
  • EDCs act via receptors are subject to same conequences
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14
Q

How is Hormonal action Life-Stage Specific

A
  1. Low doses matter
  2. Effects at high dose does not predict effects at low dose
  3. Early life exposure produce adverse effects in adulthood
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15
Q

Traditional Toxicology Concepts

A
  • The higher the dose, the more toxic

- Endpoints: gene mutations, weight loss, death, and tested at high levels

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16
Q

Chemicals with Endocrine Activity Act Via Principles of Endocrinology and thus:

A
  • May act at low doses
  • Should by expected to have non-monotonic dose responses
  • Will have tissue specific and time specific effects
  • Will show different effects and dose responses during development relative to adults
  • WIll likely NOT have a threshold
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17
Q

Evidence of EDC Effects in Wildlife and Humans

A

Mammals: reproductive and immune function Baltic Seals (organochlorines - PCB)

Birds: egg shell thinning (DDT)

Reptiles: Apopka alligators gonadal and devel. abnormalities (organochlorines)

Fish: ALtered steroid levels, gonad size, and reproduction (industrial and municipal effluents)

Invertebrates: Masculinization of marine gastropods (TBT)

Humans (controversial) - reproductive effects (sperm count, puberty, cancers)

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18
Q

3 Lines of Evidence Fuel Concerns over Endocrine Disruptors

A
  1. Increase trends of many endocrine-related disorders in humans
  2. Observations of endocrine-related effects in wildlife populations
  3. Lab studies linking chemicals with endocrine effects to disease outcomes
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19
Q

BPA as Developmentally Inducing Human Disease

A
  1. Reproductive/ Endocrine System - breast or prostate cancer, endometriosis, infertility, diabetes, early puberty, obesity
  2. Pulmono-cardiovascular System - heart disease, hypertension, stroke
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20
Q

How Many Endocrine Axes Disrupted by Environmental Contaminants?

A

Reproductive axis: Estrogenic/ anti-estrogenic and Androgenic/ anti-androgenic

Stress Axis: Anto-adrenal

Thyroid Axis: thyroidogenic/ anti-thyroidogenic

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21
Q

Definition of EDS

A

A substance that has the ability to disrupt the synthesis, secretion, transport, binding, action or elimination of hormones in an organism or its progent that is responsible for the maintenance of homeostasis, reproduction, development, or behaviour of an organism

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22
Q

3 Testing and Assessment Strategies

A

Mammalian

Ecotoxicity tests

Non-animal tests

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23
Q

EDTA Task Force replaced by EDTA Advisory Group to:

A

Begin assessment of endocrine disruptors

Examine case reports from OECD countries

Review conceptual framework

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24
Q

OECD Tests to Identify EDS

A

In vitro: estrogen and androgen receptor binding affinity, human estrogen receptor transcriptional activation, androgen or thyroid transactivation

In vivo: Uterotrophic and Hershberger (rats), amphibian metamorphosis assay…

In vivp (extended/ transgenerational) - rodent, fish, frog, bird, invertebrates

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25
Q

Countries Implementing EDS Testing

A

US, Japan, EU require information about the endocrine disrupting effects of chemicals

Canada: No mandatory testing strategy and OECD test guidelines

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26
Q

Pulp Mill Effluent Effects

A

Fish downstream of pulp and paper mill effluent -> sex steroids (decrease gonad size and delayed sexual maturity)

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27
Q

MOA for Hormone Mimic/Blocker

A

Brain (Telencephalon and hypothalamus) -> Pituitary (GnRH) -> Gonad (FSH and LH) -> Estradiol Testosterone

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28
Q

Pulp Mill Effluent Monitorinf Program

A

Based on Fisheries Act: Protect fish, fish habitat and the use of fisheries resources (Environment Canada)

Sublethal toxicity testing every three years, but if no effects every 6 years

29
Q

Biological Monitoring of Pulp Mill Effluent

A

Reference vs Mill Site: Liver, Somatic Index, Gonadal Somatic Index)

  • Fish survey (condition factors, LSI, GSI)
  • Benthic invertebrate community survey
30
Q

FIndings of Pulp Mill Effluent

A

Effects on reproduction still prevalent shown by OECD fish test

  • ____ out of 12 effluents tested inhibited egg production in 5 day fathead minnow
  • Higher correlations with organic extracted phases
31
Q

Bisphenol A

A

A ubiquitous plasticizer present in food and beverage plasitc, medical devies, cleaners, personal care products, dental fillings…

32
Q

Effects of Bisphenol A

A

Low dose animal and bio monitoring studies show BPA is estrogenic in multiple animal models, weak in early studies but equipotent to endogenous estrogen (*mER) membrane

33
Q

Relationship between BPA and Negative Trends in Human Health

A

Abnormal penile/ urethra development in males

Early sexual maturation in females

Increased neurobehaviour problems like ADHD and autism

Increased childhood obesity

Sperm count

34
Q

Presence of BPA in Canadians; Why is it Effective

A

90% of Canadians’ urine
- GM = 1.16 ug/L

Although excreted rapidly, ubiquitous and continuous exposure!!

35
Q

Steps of Gonadal Determination and Differentiation

A
    • SRY products results in sex determination (bipotential gonad into testis)
  1. Differentiation into different cell types of testis
  2. Production of testosterone and MIF from testis results in male genitalia

(Female differentiation is the default setting)

36
Q

Standardized Endpoints of Screening Assay

A
Survival
Secondary sex characteristics
Vitellogenin
GSI
Gonad histopathology
Spawning success
E and T concentrations
37
Q

What is Linuron? Its water quality guideline?

A

Ureic based herbicide

Water quality guideline: 7 ug/L

38
Q

Found effects of Linuron on Hormone Levels

A
  • Did NOT affect tubercle development, no androgenic impacts

THEREFORE
Linuron may not be a pure anti-androgen but have multiple MOAs that affect vertebrate reproduction

39
Q

US EPA findings of Linuron

A

Estrogen receptor/estrogenic effects in vitro, not observed in vivo

40
Q

Definition of Pharmaceuticals

A

Prescription, over the counter vetrinary therapeutic drugs to prevent or treat human and animal diseases

41
Q

Response and Responsible Compounds of PPCPs

A

Response: Increase vitellogenin in males, alter testis development

Responsible compounds: Estradiol, estrone, ethynyl estradiol

42
Q

3 Stages of Ethynyl Estradiol as Biomarker to Population Level Effects

A

Vitellogenin -> Gonad histopathology -> Population crash

43
Q

Canada’s Water Quality Guideline for Municipal Effluent Constituents

A

17 a-ethinylestradiol (EE2) = 0.5 ng/L

Nonynphenol and ethoxylates (industral surfactant) = 1 ug/L

44
Q

Canadian Municipal Effluent Monitoring

A

No mandatory sub-lethal effects monitoring

Currently chronic exposure for aquatic wildlife

45
Q

OECD EDS testing strategy for complex effluent

A

Use relevant endpoints to detect endocrine system dysfunction based on OECD EDS tests to establich NOECs

46
Q

What is a Keystone Species?

A

A species that has a disproportionately large effect on the communitires in which it occurs

47
Q

How do keystone species maintain local biodiversity within a community by:

A
  1. Controlling populations of other species that would otherwise dominate the community

Or

  1. By providing critical resources for a wide range of species
48
Q

What is Community Structure?

A

Reductions/ increases in community structure (relative abundance of multiple species within a community)

Biodiversity changes (# of species/ community)

49
Q

Classification of Metal Mines in Canada

A

Base metals (copper, zinc, lead, nickel)

Precious metals (gold, platinum group metals, silver)

Uranium

Iron ore

Other metals like titanium, tantalum, magnesium…

50
Q

Environment Canada requires an environmental impact assessment during the Modern Mine Life cycle. What is this assessment?

A

EIA = ER + Physical Stressors

51
Q

3 Parts of Modern Mine Life Cycle

A
  1. Planning and construction (clearing/ blasting)
  2. Operations (wastewater and tailings management)
  3. Closure (site clean-up, maintenance, monitoring)
52
Q

Metal Mining Effluent Regulations (MMER) Summary

A

2002 Fisheries Act

Includes provisions to allow the discharge of metal mine effluent into fish-frequented water bodies, subject to certain requirements regarding:

  • Discharge limits
  • Acute lethality
  • Environmental effects on fish, fish habitat, and fisheries resources
53
Q

Overall goal of MMER

A

To minimize the effect of mine effluent on waters frequented by fish

54
Q

Mines that are subject to MMER may deposit an effluent that contains a deleterious substance if:

A

A) the concentration of the deleterious substance in the effluent does not exceed the authorized limits

B) the pH of the effluent = 6.0-9.5

C) the effluent is not acutely lethal

55
Q

The effluent is not acutely lethal IF

A

Effluent is deemed non-acutely lethal if it kills less than 50% of the trout subjected to it at 100% concentration over 96 h period

Tested monthly 96 h rainbow trout toxicity assay (standard) but additional testing of cause and effect if fails

56
Q

Authorized Limits for Deleterious Substances (Monthly Means) summarizes…

A

The monthly mean concentration limits in mg/L or in becquerel per L (Bq/L) for the deleterious substances listed in MMER

57
Q

Environmental Effects Monitoring

A

Sublethal toxicity testing of effluent
(Fish health)

Field surveys (biological monitoring of benthic invertebrate community structure)

Water quality and effluent monitoring every 3 years (6 if no effect)

58
Q

5 Endpoints of Fish Health

A
  1. LSI
  2. GSI
  3. Growth/ weight
  4. Reproduction
  5. Behaviour
59
Q

Britannia Mine Case Study: Recovering from:

A

Pollution from industry: lumber processing (present) and metal mining, pulp mill, chlor-alkali

60
Q

Contaminants discharged in Industrial Effluents

A

Organochlorines (dioxins and furans)
Metals (copper, zinc and iron)
Sulphuric acid
Mercury

61
Q

What is Acid Mine Drainage?

A

The natural mineralization at Britannia contains metal sulphides which when exposed to air and water react to form (oxidation) a sulphuric acid solution containing dissolved metals. This mixture is known as Acid Rock Drainage or Acid Mine Drainage and can be very toxic to aquatic life.

62
Q

What is eDNA?

A

DNA released into the environment, collects via water, sediment or soil. Isolated and analyze DNA for target taxa; eDNA for environmental assessments

63
Q

3 Reasons for eDNA

A
  1. Regulatory
  2. Conservation
  3. Invasive species
64
Q

Why eDNA; regulatory?

A

Environmental RA
Commercial, recreational, aboriginal fish protection
Species at Risk Act
BC endangered species act
Metal and Diamond Mining Effluent Regulations

65
Q

Conservation reasons for eDNA

A

Species inventory

Habitat mapping

66
Q

Invasive Species reasons for eDNA

A

Early detection

Confirm erradication

67
Q

Advantages of eDNA

A
Less invasive
More sensitive
Time saving
Cost effective
Accurate
Reduced observer bias
Retroactive testing
Ease of access
Expanded survey window
68
Q

Limitations of eDNA

A

Only detects presence of target DNA (alive or dead? Age? Size? Gender? Specific location?)
Detect/non-detect result - cannot determine number
eDNA degradation