Lecture 22 - Endocrine Disrupting Chemicals Flashcards
A community downstream of a gas work in Sarnia
Has bad health, many more girls than boys
Is caused by chemicals
No resolution in Sarnia
Birthrates starting to normalize
Scott Grant - former Ontario Minister of Education
Whistleblower reports about Sarnia air conditions in 2009, 2014, and 2019
Benzene leak in spring 2018
23x safe level, 12x safe level for 9 months
Linked to leukemia and altered reproductive function
Unclear if modifies endocrine function
Cryderman discovered elevated DDT, PBCs, HCBs and mercury in Aamjiwnaang residents compared to Canadian/US averages
Endocrine disrupting chemicals (EDCs)
Change to the normal function of endocrine glands and hormone action imposed by external compounds
Modify activity at hormone receptors – either augment or block
Confusing results….
Some do both!!
Global Assement of EDCs from 2002
Change in wildlife exposed to certain chemicals
Altered genitalia, sex ratios, reproductive capacity, and evidence for cancer
Limited evidence for causal connections
Valid hypothesis but not enough proof to draw conclusions
Challenging to link specific chemical to outcome for a number of reasons
Warrants follow up
Found it!
Evidence on EDCs 2002-2012
Many more potential EDCs and hormones affected
Windows of exposure :
- During development
- In adulthood
- Transgenerational effects
Low dose and non-monotonic dose response (makes it harder to investigate)
Increasing biodiversity threats
Accumulation of more compelling evidence
Histological studies – chemical effects occur through endocrine mode of actions (mechanism)
Chemicals with endocrine disrupting properties linked to disease outcomes in lab
Observations of endocrine-related effects in wildlife populations
The rate of incidence of many endocrine-related diseases or disorders in humans
Reason for concern
Speed of increases in disease incidence in recent decades rules out genetic factors as the sole explanation.
Environmental factors outside EDCs (nutrition, age of mother, viral diseases) also at play
Despite potential confounds some EDC-health associations are apparent.
Might in fact be underestimated
EDCs now associated with:
Female reproductive health Male reproductive health Sex ratio in humans Thyroid related disorders and diseases Neurodevelopment in children and wildlife Hormone related cancers Adrenal disorders in humans and wildlife Immune function, immune diseases and disorders Metabolic disorders Wildlife population sustainability loss
EDCs: Expanding risk
EDCs & potential EDCs are everywhere
primarily include human-made chemicals
present in food, daily objects, air, etc…
Increasing number of EDCs & potential EDCs
exposed to far more EDCs than just organic pollutants
only a fraction of potential EDCs understood.
Action is variable
Developmental stage and dose important
Developmental susceptibility
Endocrine systems key in physical and psychological development
Disruption alters development – permanent change in organs and brain
Critical windows for different systems
Timing of exposure will determine systems affected and magnitude of affect
Sex specific effects
It is possible for a chemical to have different effects depending on the life stage you encounter it in
Non-monotonic dose response
Expect magnitude of effect to increase proportional to dose
Not true for EDCs
Sometimes exposure has an effect, sometimes doesn’t….
Effects occur at such low doses toxicology not currently assessing
Typically an experiment might use a higher dose but sometimes lower doses are worse
In addition to linear, dose-response curves could be:
Biphasic (two peaks, low and high with lower effects in the middle)
U shaped
Inverted U shaped
Effects of EDCs: Reproduction
Reproductive health decreased over the past 50yrs
Correlates with increase in use of EDCs
Males:
Lower sperm count and quality
Increased hypospadias and cryptorchidism
Increased testicular cancer
Females:
Multi-ova follicles, PCOS, altered cycle
Early menopause
Increased breast and rare cervicovaginal cancers
Effects of EDCs: Obeisity
Some EDCs act as obesogens – contributing to the diabetes and obesity epidemic
PPAR-γ: regulates fatty acid storage and adipocyte differentiation
Binding can lead to adipogenesis
Promiscuous receptor so many EDCs may activate
Phthalates: class of chemicals
Plasticizers, solvents and additives
Vinyl flooring, food containers, cosmetics
Experiment
Expose males to one phthalate from childhood to adulthood (day 20-120)
Oral gavage in olive oil (10ml/kg)
Collected blood and examined cells of the testis
Decrease in testicle size relative to body, sperm count, and motility
Phthalate under these conditions reduces male fertility
Saw a response at how and high levels (not medium)
Parental exposure to DEHP induces obesity in mice
Pregnant mice given 3 doses of DEHP for 8 days of pregnancy and 7 days following birth
Effect on male and female offspring
Only the moderate dose (0.25mg/kg) had effect
0.05mg/kg trend towards significance
Female and male offspring: weigh more, greater fat deposits, elevated blood markers of obesity
DEHP increases PPAR-y: could explain increased adipose deposits
Bisphenol A: staple of food containers
BPA key ingredient in many food containers
Makes plastic pliable, can bend and compress without breaking
BPA – bad rap ~ 10 years ago
Many things no longer contain BPA because established EDC
BPA replaced with BPS – evidence it is an EDC too
Illegal in products for kids in Canada
Parental exposure to bisphenol (low dose) affects body weight - rats
Pregnant rats: 0.1mg/kg or 1.2mg/kg BPA via water for 14 days of pregnancy and 20 days breast feeding
Offspring weight, and female estrous cycle
Increased weight in all offspring
In females only low dose caused weight increase
Decreased cyclicity and reduced LH following BPA exposure in utero
Weight gain and loss of reproductive function following BPA
Effects similar to T exposure
EDCs: Transgenerational Effects?
Rodents studies: epigenetic transgenerational inheritance
Effects observed in grandchildren (3rd generation)
Pesticides can affect reproductive function in male rats
Deficits in sperm volume and quality for 4 generations
Only see when pesticide exposure during critical period for F1
Other EDC effects also reported as transgenerational
No evidence for this in humans to date
Don’t even need to be personally exposed
EDCs: where do we go from here
Need further studies to ID classes of chemicals, levels of exposure, and critical windows
Understand discrepant findings
Demonstrate same effects in humans as animal species
Understand biological mechanisms to aid in treatment development/harm reduction
Work towards understanding effects in pregnant
mothers and infants
Hard population but most vulnerable
EDCs: hopefully not too late
Efforts to reduce EDC use result in decreased levels in the environment
Decreased levels in animals (including humans)
Decreased negative effects of these chemicals
Critical to reduce use as fast as possible
Rare to get DDT now, DDE is a breakdown product
Dropped years back, now more osprey nests occupied
Shows nature can recover
