20 endocrine disruptors

Question 1

what are the stories on the history of endocrine disruptors?

Answer 1

Question 2

what is the story of DDT?

Answer 2

-highly effective insecticide
-helped controlling and ultimately eradicating malaria in North America in the late 40s and 50s
-nobel prize to paul Mueller who identified the insecticidal activity of DDT (1948)

Question 3

what is the problem with DDT?

Answer 3

-bioaccumulative
-linked to disappearing bird populations in the US in the 1950s->Silent Spring
-motivated Rachel Carson’s book silent spring
-causes eggshell thinning through affecting prostaglandin-regulated calcium metabolism

Question 4

what is the story of DES?

Answer 4

diethylstilbestrol
-one of the most famous chemicals resulting in severe human impact was DES
-initial developed as a livestock food additive
-1941-1971 chemical was prescribed to pregnant women in the US as it was hypothesized to prevent miscarriage

Question 5

what was the problem with DES?

Answer 5

-in 1971, DES was banned for use in humans due to its potential to cause a rare vaginal cancer (cervical clear cell carcinoma) in girls and young women of mothers that were given DES during pregnancy (high risk of 1:1000)
-other risks included genital tract abnormalities, infertility, ectopic pregnancy (8.6x more likely), spontaneous abortion (1.8x), premature birth (4.7x), etc.
-affects estrogen-responsive tissue (estrogen receptor potential mechanism); generational effects (epigenetics)

Question 6

what is the story of TBT?

Answer 6

tributyl tin
-in the 1980s, dwindling mollusc populations along main shipping routes
-was shown to cause phenomenon called “imposex”: masculization of female snails
-the impact of TBT on oyster colonies in the Bay of Arcathon (france) resulted in ban of TBT on vessels <25m long
-potential mechanisms through nuclear retinoid-X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPAPgamma)

Question 7

what is the story of municipal effluents?

Answer 7

-in the early 1990s, british scientists found severely changed gonadal phenotypes in male fish downstream of municipal wastewater treatment plants
-these phenotypes manifested as the occurrence of female tissues in testes, termed “intersex”
-in some cases, up to 100% of fish showed intersex phenotypes

Question 8

what was the problem of municipal effluent?

Answer 8

-severely feminized male roach (rutilus rutilus) from a british river have reduced fertility
-similar phenomena were shown in fishes in other countries in north america and europe
-effects were thought to be mediated through estrogens in effluents

Question 9

what is the story of semen quality/quantity impacts?

Answer 9

Question 10

what is the story of plasticizers?

Answer 10

-other chemicals that gained notoriety were plasticizers such as bisphenol A (BPA) and phthalates
-used since the 1950s as a hardener for plastics
-6 billion pounds per year used in consumer products, including baby bottles and infant toys

Question 11

what is the problem with plasticizers?

Answer 11

-due to its ubiquity concerns rose regarding the potential effects of BPA in humans and wildlife
-initial studies suggested reproductive effects such as polycystic ovary syndrome (PCOS) based on studies with rats
-BPA was shown to act as a weak estrogen
-Canada was one of the first countries to ban BPA in baby bottles and other infant products (note: no full risk assessment was conducted, and the evidence continues to be highly controversial)

Question 12

what are some other chemicals for which similar effects were reported?

Answer 12

Question 13

what do these stories have in common?

Answer 13

-effects discussed in the previous case studies all appear to be mediated or associated with endocrine processes/hormonal regulation
-most health outcomes were related to reproduction
-outcomes have potential severe impacts on fitness (wildlife) and/or individual health (humans)
-causative chemicals appear to be ubiquitous in the environment

Question 14

what is the background of the endocrine system?

Answer 14

Question 15

what is the example of the endocrine system?

Answer 15

Question 16

what are the key hormone groups in the endocrine system?

Answer 16

a) thyroid hormones
b) growth hormones
c) adrenal cortex hormones
d) reproductive hormones (sex steroids, gonadotropins)

Question 17

what is the importance of thyroid hormones?

Answer 17

-growth
-metabolism
-development
-other (e.g. cardiovascular)

Question 18

what is the importance of growth hormones?

Answer 18

-stimulates growth and cell reproduction
-protein synthesis

Question 19

what is the importance of adrenal hormones?

Answer 19

1. adrenal cortex
   -aldosterone: electrolytes
   -cortisol: stress
   -androgens: reproduction, other
2. medulla
   -sympathetic nervous system control
   -EPI and NEPI: fight or flight

Question 20

what is the importance of reproductive hormones?

Answer 20

1. reproduction/mating behavior
2. secondary sex characteristics
3. formation of reproductive organs
   -gonads
   -brain

Question 21

what are the four classes of hormones?

Answer 21

Question 22

how do hormones work?

Answer 22

Question 23

what is the WHO-IPCS definition of endocrine disruption?

Answer 23

”.. 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”

Question 24

what is the concept of dose-response?

Answer 24

Question 25

why are we concerned with endocrine disruption?

Answer 25

increasing concern about the possible impacts of chemicals in the environment on endocrine and reproductive systems in humans and wildlife because: 1. endocrine active chemicals (especially those with hormone-like properties) can be biologically active at very low levels, sometimes in the ng/L range 2. interaction with processes that may affect crucial physiological functions 3. ubiquitous (found everywhere)

Question 26

how do endocrine disruptors interact with the endocrine system?

Answer 26

Question 27

what are considered the two endpoints for assessment?

Answer 27

of the four main mechanisms of endocrine toxicity, only two are considered in current endocrine disruptor assessments

Question 28

what are the endpoints?

Answer 28

Question 29

what is the case study of estrogens in the environment?

Answer 29

-we will take a closer look at one specific type of EDCs, estrogens -focus on the main "pill" ingredient ethinylestradol (EE2), a potent synthetic estrogen (90% of the pill and other pharmaceuticals get excreted in our wastewater stream) -estrogens have been shown to affect the reproductive system of male fish and amphibians and are suspected to be responsible for environmental phenomena such as intersex fish

Question 30

what are the global estrogen levels in municipal effluents?

Answer 30

Question 31

what is the endocrine disruption in fish (estrogenicity) in the case study)?

Answer 31

-UK studies suggested that municipal effluents pose a significant risk to wild fish populations due to exposure to estrogenic chemical -since, there has been additional evidence from studies around the world including the US, canada, europe and asia that municipal effluents may pose a significant risk to wild fishes

Question 32

how did they answer the question "is the birth control pill an effective form of contraception for wild fish?"

Answer 32

-58 designated research lakes in ontario -whole ecosystem experiment at the experimental lakes area, canada (lake 260) -added the "pill", which is EE2 (ethinylestradiol)

Question 33

how much of the "pill" was added?

Answer 33

Question 34

what happened in fathead minnow?

Answer 34

-massive induction of the yolk protein precursor vitellogenin in males -significant histological changes

Question 35

what was the population structure of fathead minnows?

Answer 35

complete population decline

Question 36

but what happened to the population after?

Answer 36

population fully recovered 2 years after EE2 addition stopped

Question 37

what were the results in lake trout?

Answer 37

-induction of vitellogenin -no marked histological changes -small decrease in population after 3 years-> probably due to collapse of fathead minnow population (food source)

Question 38

what were the conclusions?

Answer 38

-significant population-relevant impacts of commonly found environmental concentrations of estrogen on select fish species -"the pill" is as effective for fathead minnow as for humans (>99%) -longer term effects on other species (e.g. lake trout) likely linked to trophic cascade (fathead minnow primary diet) good news: -after removal of estrogens from ecosystem fish populations recovered -other evidence from UK studies on areas with high proportions of intersex fish did not find any effects on populations

Question 39

what are the national and international policies and regulatory perspectives?

Answer 39

due to the significant concerns pertaining to the potentially high toxicological risks posed by EDCs, several national and international programs have been established or amended to prioritize endocrine disruption in chemical screening and risk assessment: a) USA: endocrine disruptor screening program (EDSP) b) EU: reach program (registration, evaluation, authorization and restriction of chemical substances) c) japan: EXTEND (extended tasks on endocrine disruption; former SPEED [strategic program on environmental endocrine disruptors]) d) OECD: conceptual framework for the testing and assessment of EDCs

Question 40

what is the current model of risk assessment of endocrine disruptors?

Answer 40

Question 41

what are the CF and OECD test guidelines for detection of EDCs?

Answer 41

Question 42

what is the summary?

Answer 42

endocrine disruption is of significant ecotoxicological concern because: a) endocrine active chemicals (especially those with hormone-like properties) can be biologically active at very low levels b) interaction with processes that may affect crucial physiological functions c) ubiquitous -most studies conducted to date focus on reproduction; however, endocrine disruption can have effects on diverse biological functions including growth/development, osmoregulation, metabolism, etc.

Question 43

what is still controversial?

Answer 43

there is significant remaining controversy regarding the ecological (and in some cases human health) impacts of endocrine active chemicals in the environment 1. estrogenic effects in fish: there are no demonstrated declines in wild populations even in populations with high incidences of intersex 2. several follow up studies on sperm counts and sperm quality could not confirm global trends claimed by initial danish studies 3. most chemicals shown to be endocrine active in the lab are very weak EDCs, especially those that were claimed to be estrogenic (e.g. BPA) 4. concern about this hyper-focus distracting from other "contaminants of real concern"