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Bisc 308 > Midterm 3 > Flashcards

Midterm 3 Flashcards

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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
Countries Implementing EDS Testing
US, Japan, EU require information about the endocrine disrupting effects of chemicals Canada: No mandatory testing strategy and OECD test guidelines
26
Pulp Mill Effluent Effects
Fish downstream of pulp and paper mill effluent -> sex steroids (decrease gonad size and delayed sexual maturity)
27
MOA for Hormone Mimic/Blocker
Brain (Telencephalon and hypothalamus) -> Pituitary (GnRH) -> Gonad (FSH and LH) -> Estradiol Testosterone
28
Pulp Mill Effluent Monitorinf Program
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
Biological Monitoring of Pulp Mill Effluent
Reference vs Mill Site: Liver, Somatic Index, Gonadal Somatic Index) - Fish survey (condition factors, LSI, GSI) - Benthic invertebrate community survey
30
FIndings of Pulp Mill Effluent
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
Bisphenol A
A ubiquitous plasticizer present in food and beverage plasitc, medical devies, cleaners, personal care products, dental fillings...
32
Effects of Bisphenol 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
Relationship between BPA and Negative Trends in Human Health
Abnormal penile/ urethra development in males Early sexual maturation in females Increased neurobehaviour problems like ADHD and autism Increased childhood obesity Sperm count
34
Presence of BPA in Canadians; Why is it Effective
90% of Canadians’ urine - GM = 1.16 ug/L Although excreted rapidly, ubiquitous and continuous exposure!!
35
Steps of Gonadal Determination and Differentiation
1. + SRY products results in sex determination (bipotential gonad into testis) 2. Differentiation into different cell types of testis 3. Production of testosterone and MIF from testis results in male genitalia (Female differentiation is the default setting)
36
Standardized Endpoints of Screening Assay
``` Survival Secondary sex characteristics Vitellogenin GSI Gonad histopathology Spawning success E and T concentrations ```
37
What is Linuron? Its water quality guideline?
Ureic based herbicide Water quality guideline: 7 ug/L
38
Found effects of Linuron on Hormone Levels
- 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
US EPA findings of Linuron
Estrogen receptor/estrogenic effects in vitro, not observed in vivo
40
Definition of Pharmaceuticals
Prescription, over the counter vetrinary therapeutic drugs to prevent or treat human and animal diseases
41
Response and Responsible Compounds of PPCPs
Response: Increase vitellogenin in males, alter testis development Responsible compounds: Estradiol, estrone, ethynyl estradiol
42
3 Stages of Ethynyl Estradiol as Biomarker to Population Level Effects
Vitellogenin -> Gonad histopathology -> Population crash
43
Canada’s Water Quality Guideline for Municipal Effluent Constituents
17 a-ethinylestradiol (EE2) = 0.5 ng/L | Nonynphenol and ethoxylates (industral surfactant) = 1 ug/L
44
Canadian Municipal Effluent Monitoring
No mandatory sub-lethal effects monitoring | Currently chronic exposure for aquatic wildlife
45
OECD EDS testing strategy for complex effluent
Use relevant endpoints to detect endocrine system dysfunction based on OECD EDS tests to establich NOECs
46
What is a Keystone Species?
A species that has a disproportionately large effect on the communitires in which it occurs
47
How do keystone species maintain local biodiversity within a community by:
1. Controlling populations of other species that would otherwise dominate the community Or 2. By providing critical resources for a wide range of species
48
What is Community Structure?
Reductions/ increases in community structure (relative abundance of multiple species within a community) Biodiversity changes (# of species/ community)
49
Classification of Metal Mines in Canada
Base metals (copper, zinc, lead, nickel) Precious metals (gold, platinum group metals, silver) Uranium Iron ore Other metals like titanium, tantalum, magnesium...
50
Environment Canada requires an environmental impact assessment during the Modern Mine Life cycle. What is this assessment?
EIA = ER + Physical Stressors
51
3 Parts of Modern Mine Life Cycle
1. Planning and construction (clearing/ blasting) 2. Operations (wastewater and tailings management) 3. Closure (site clean-up, maintenance, monitoring)
52
Metal Mining Effluent Regulations (MMER) Summary
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
Overall goal of MMER
To minimize the effect of mine effluent on waters frequented by fish
54
Mines that are subject to MMER may deposit an effluent that contains a deleterious substance if:
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
The effluent is not acutely lethal IF
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
Authorized Limits for Deleterious Substances (Monthly Means) summarizes...
The monthly mean concentration limits in mg/L or in becquerel per L (Bq/L) for the deleterious substances listed in MMER
57
Environmental Effects Monitoring
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
5 Endpoints of Fish Health
1. LSI 2. GSI 3. Growth/ weight 4. Reproduction 4. Behaviour
59
Britannia Mine Case Study: Recovering from:
Pollution from industry: lumber processing (present) and metal mining, pulp mill, chlor-alkali
60
Contaminants discharged in Industrial Effluents
Organochlorines (dioxins and furans) Metals (copper, zinc and iron) Sulphuric acid Mercury
61
What is Acid Mine Drainage?
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
What is eDNA?
DNA released into the environment, collects via water, sediment or soil. Isolated and analyze DNA for target taxa; eDNA for environmental assessments
63
3 Reasons for eDNA
1. Regulatory 2. Conservation 3. Invasive species
64
Why eDNA; regulatory?
Environmental RA Commercial, recreational, aboriginal fish protection Species at Risk Act BC endangered species act Metal and Diamond Mining Effluent Regulations
65
Conservation reasons for eDNA
Species inventory | Habitat mapping
66
Invasive Species reasons for eDNA
Early detection | Confirm erradication
67
Advantages of eDNA
``` Less invasive More sensitive Time saving Cost effective Accurate Reduced observer bias Retroactive testing Ease of access Expanded survey window ```
68
Limitations of eDNA
Only detects presence of target DNA (alive or dead? Age? Size? Gender? Specific location?) Detect/non-detect result - cannot determine number eDNA degradation

Bisc 308 (2 decks)

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