Module 5 Flashcards
(25 cards)
What are endocrine disrupting compounds?
1 pt
An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations.
What is evidence of endocrine disruptors?
2 pt
- The main evidence suggesting that exposure to environmental chemicals can lead to disruption of endocrine function comes from changes seen in wildlife species.
- Reported effects in molluscs, crustacea, reptiles, birds and mammals in various parts of the world. - Some evidence in humans that adverse endocrin-mediated effects have followed either intentional or accidental exposure to high levels of particular chemicals
- Clearest example is diethylstilbestrol (DES), a prescribed estrogen given to pregnant women to prevent miscarriage
- Accidental release of chemicals
What are some examples of EDCs?
4 pt
Chemicals with hormonal activity, i.e. potential endocrine disruptors, include:
1. Natural hormones from any animal, release into the environment, and chemicals produced by one species that exert hormonal actions on other animals
2. Natural chemicals including toxins by components of plants
3. Synthetically produced pharmaceuticals that are intended to be highly hormonally active
4. Man-made chemicals and by-products released into the environment
What are some anthropogenic or man-made EDCs?
5 pt
- PCBs
- Mathoxychlor
- o,p’-DDT
- 2,6-cis-Diphenylhexamethyl-cyclotetrasioxane
- Bisphenol A
Xenobiotic endocrine modulators
What are some naturally-derived EDCs?
8 pts
Flavonoids
* Kaempferol (Flavone)
* Naringenin (Flavenone)
* Daidzen (Isoflavone)
* Phloretin (Chalcone)
* Coumestrol (Coumestan)
* Genistein
Other phyto-estrogens
* B-Sitosterol
* Enterolactone (Lignan)
Oestrogenic and anti-oestrogenic compounds from plants
What are some sources of EDCs in the environment?
6 pt
- Chemical Production
- Emissions to the atmosphere
- Incorporation into consumer products - Industrial discharges
- Untreated wastewater
- Treated wastewater
- Biosolids application
- Emissions to rivers, lakes and oceans - Sewage system to treatment facility
- Emissions to the atmosphere
Are animals and humans exposed to EDCs in different ways?
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How are domestic animals implicated in environmental endocrine disruption?
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How are domestic animals used in environmental endocrine disruption?
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How are domestic animals exposeed to or affected by endocrine disrupting chemicals?
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What are some examples of chemicals that are implicated in disruption of reproduction in domestic animals?
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What is the history of endocrine disruption?
5 pt
Endocrine disruption is not a ‘new’ concept
* ancients were familiar with herbal preparations
* farmers observing reproductive problems with sheep
* 1930s - chemicals were known to interact with hormones receptors
* 1940s - steroid compounds used in livestock industry
* development of the birth control pill
What is diethylstilbestrol (DES)?
1 pt
Synthetic non-steroid estrogenic chemical
* Approved in 1947 and given intentionally to women in the 1950s - 1970s to prevent miscarriage during pregnancy
* In the US, an estimated 5 - 10 million women and children were exposed to DES between 1947 - 1971
* DES exposure moderately elevated the risk of breast cancer later in life in mothers that took the drug
* 1st generation offspring: DES exposure caused a suite of reproductive abnormalities
What are the effects of DES?
6 pt
Females:
* 2.5x increase in breast cancer risk
* greatly elevated risk of uterine cancer (during ages 20 - 40)
* abnormal urogenital development
Males:
* elevated risk of epidydimal cysts
* sometimes led to abnormal testicular development
* 20x increased chance of hypospadia
By 1952, at least 4 studies had found that DES did not reduce the chance of miscarriage
* subsequent work showed DES actually elevated the chance of miscarriage
What are the mechanisms of endocrine disruption?
4 pt
- They may mimic the biological activity of a hormone by binding to a cellular receptor, leading to an unwarranted response by initiating the cell’s normal response to the naturally occuring hormone at the wrong time or to an excessive extent (agonistic effect)
- They may bind to the receptor but not activate it. Instead the presence of the chemical on the receptor will prevent binding of the natural hormone (antagonistic effect)
- They may bind to transport proteins in the blood, thus altering the amounts of natural hormones that are present in the circulation.
- They may interfere with the metabolic processes in the body, affecting the synthesis or breakdown rates of the natural hormones.
What are the key characterics (KCs) of EDCs?
3 pt
- An important key first step in governing exposures to chemicals with EDC properties is the identification of their ability to cause harm
- Grouping chemicals by key characteristics (KCs) provides a basis for searching, organizing and evaluating mechanistic evidence to support theidentification of EDCs
- Authors of the paper identified 10 KCs for EDCs to comprise the properties of all hormone systems
What is the dose-response relationships for chemicals?
1 pt
The central dogma in toxicology is often considered to be “the dose makes the poison”
* all chemicals are toxic AND the adverse effect of a toxin is proportional to the dose
Also assumed that there are no effects at exposures below the lowest observed adverse effect level (LOAEL)
How do EDCs mess with the assumptions we have of dose-relationships with chemicals?
2 pt
In a** monotonic response**, the observed effects may be linear or nonlinear, but the slope does not change sign.
Dose-response relationships with EDCs can be non-monotonic, which have been reported in hundreds of studies
* the same is common for hormones themselves
What is a non-monotonic dose-response curve (NMDRC)?
2 pt
- U-shaped: with maximal responses of the measured endpoint observed at low and high doses
- Inverted U-shape: with maximal responses observed at intermediate doses
What are the dose ranges for effects of EDCs?
3 pt
Specific effects of EDCs can be categorized as occuring in the:
1. physiological dose range
* the amount of freee endogenous hormone that the EDC is mimicking or antagonizing
2. toxicological dose range
* identified by some measure of toxicity, such as death, decrease in body weight, or malformations
3. environmentally relevant dose range
* established for chemicals where there is information concering levels monitored in air, food, or water
What are the future needs for EDC research?
4 pt
A large number of non-communicable diseases havde their origin during development
Environmental factors interact with our genetic background to increase susceptibility to a variety of diseases and disorders
Research needs:
* Strengthening knowledge of EDCs
* Improved testing for EDCs
* Reducing exposures and thereby vulnerability to disease
* Identifying endocrine active chemicals
What is endocrine toxicity testing?
4 pt
National andninternational programs have been initiated to develop new guidelines for the screening and testing of potential EDCs in vertebrates
* USA: Endocrine Disruptor Screening Program (EDSP)
* EU: REACH Program (Registration, Evaluation, Authorisation and Restriction of Chemical substances)
* Japan: SPEED (Strategic Program on Environmental Endocrine Disruptors)
* OECD: Concceptual Framework for the Testing and Assessment of EDCs
What is a tiered screening system?
2 pt
Tier 1 assays
* screen large numbers of substances
* intended to provide some mechanistic data for single known pathways (estrogenic, androgenic, thyrogenic)
* in vivo assays capture multiple modes of action
Tier 2 assays
* determine longer term effects on organisms and the dose required to obtain the effects
compounds deemed positive in Tier 1 will undergo Tier 2 testing to characterize hazards and develop data for risk assessment
What is the flow of a tiered screening system?
3 pt
In vitro assessment of oestrogen, androgen and thyroid activity (inexpensive, rapid, sensitive and simple asssays of ED potential)
* priority setting
* mechanism of action
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Short-term* in vivo tests (Effects on development in neonatal and prepubertal animals)
* development of organs
* in utero exposures
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Multigenerational in vivo* studies (Effects on reproduction and development in subsequent generations)
* species differennces in sensitivity and critical periods
* dose response effects that cover potential range of exposure
* route of exposure
