Final Flashcards
What is the MOA for atrazine and its main adverse effects?
- targets endocrine axis (pituitary/hypothalamus and reproductive)
- increases activity of aromatase (converts more testosterone into estrogen)
- impairs male gonad development/causes development of female gonads in males
- affects LH/FSH production (US Tier 1 findings)
What is atrazine and what regulations currently exist?
- herbicide that blocks photosynthesis
- FW WQG in EU - 0.1 ug/L
in CA - 1.8 ug/L
in USA - 10 ug/L
Describe the debate around atrazine
- independent reviews used traditional risk assessment methods and found reproductive disruptive effects
- reviews funded by Syngenta used their own assessment methods and vaguely stated findings
- US EPA findings found some connections between atrazine and chronic effects in amphibians but concluded concentrations in some places were insufficient
Define what a hormone is
molecules that are capable of signalling and triggering biological responses
What are some characteristics of a hormone?
- can have multiple modes of actions
- are secreted by either glands, tissues or individual cells
- can be blood borne or released into extracellular fluids
- responses vary by target site and receptors available
- can have paracrine or autocrine results
What is the difference between agonistic and antagonistic hormones?
agonist = mimics hormone and can trigger the same or amplified response
antagonist = blocks hormone from binding to site and stops response
What effects can xenobiotic hormones have in humans and animals?
humans = reduced fertility, reduced sperm quality, affects brain development
animals = affects or delays growth and development, lowers reproductive success
How can one hormone have a non-monotonic response?
low and high doses can have adverse effects while balanced concentrations may be harmless, or low and high doses may be safe and middle concentrations harmful
i.e deficiency and excess both can cause adverse effects
Why are new screening methods needed for endocrine disruptors?
need methods that will cover low dose responses in order to capture any non-monotonic effects
How did DDT affect alligators in Lake Apopka?
- disrupted the reproductive endocrine axis (pituitary gland/blood/liver/gonad complex)
- altered gonad development
- affected sex hormone (LH/FSH) concentrations
- caused egg and embryo abnormalities
What life stage is most vulnerable to endocrine disruptors and why?
developmental stage because low doses can cause a stronger adverse effect than in adults and can create health concerns into adulthood
Define an endocrine disrupting chemical
substances that disrupt the creation of, release, transport, binding, response or elimination of hormones in an individual or its offspring
How does OECD test for endocrine disrupting chemicals?
multiple in vivo + in vitro tests with multigenerational responses as well
How do pulp mills affect fish?
- lowers sex hormone concentrations (affects secondary sex characteristics and gametogenesis)
- decreases gonad size
- delays sexual maturity and reproductive interactions
What is Environmental Effects Monitoring (EEM)?
- 3 year testing at pulp mills according to Fisheries Act guidelines
- tests chronic effects on fish development, algae, invertebrates
- compares downstream + upstream effects of liver (metabolism) and gonadosomatic (reproductive) indexes (ratio to total fish size) in fish
What were some pulp mill EEM findings and why are they still inconclusive?
- found reproductive effects in fish from pulp mill effluents (i.e inhibited egg production in minnow)
- unknown which components in effluents is responsible
What is bisphenol A (BPA) and what disruption does it cause?
- plasticizer found in many daily goods and products (food plastics, medical devices, personal care products)
- found in 90% of Canadians
- short term exposure is less harmful (excreted quickly) but long term exposure can cause adverse effects
- mimics estrogen and can affect membrane estrogen receptors
Name some effects BPA causes in humans
- abnormal male sex organ development
- lowers age of maturity in females
- increases occurances of neurobehavioural issues (autism, ADHD)
- can cause childhood obesity and adult diabetes
- reduces sperm count in males
What are regrettable substitutes?
substances that are less known to science but are used to replace a known toxic substance, and can also end up to be toxic
What endpoints are included in the OECD’s 21 day fish assay?
- survival
- secondary sex characteristics
- vitellogenin
- gametosomatic index
- spawning success
- concentrations of estrogen + testosterone
- 7 day egg survival + deformity
- ovary estrogen gene expression
What is vitellogenin?
proteins produced in the liver that are precursors for egg yolk production
ovary produces estrogen (testosterone aromatase conversion) which signals to liver to produce vitellogenin
What is linuron?
- herbicide
- WQG = 7 ug/L
- is an anti-androgen (reduces spiggin production in male sticklebacks, affected accessory sex gland development in rats)
What were the results of the linuron experiment on sticklebacks? What did EPA find in their Tier 1 tests?
- did not decrease tubercles in males or increase in females
- no effect on gametosomatic index or body weight
- results suggest it may not be a pure androgen and could have multiple MOAs
- may inhibit testosterone production
- needs Tier 2 testing
Describe the lifestyle of fathead minnows
- spawns 2 months early during the summer
- male parental care
- sexual maturity and max reproduction in year 2 of 4 year lifespan, typically die after year 2
- populations expected to crash if there are 2 straight years of reproductive failure
