Endocrine toxicology: history, characteristics and concepts for endocrine disrupting compounds

Question 1

what is an endocrine-disrupting compound

Answer 1

-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)ppulations

Question 2

what is some evidence that suggests endocrine disruptor issues

Answer 2

-the main evidence suggesting that exposure to environmental chemicals can lead to the disruption of endocrine function comes from changes seen in wildlife species (reported in molluscs, crustacea, fish, etc around the world)
-some evidence in humans that adverse endocrine-mediated effects have followed either intentional or accidental exposures to high levels of particular chemicals

Question 3

what are some examples of endocrine-disrupting chemicals (EDCs)

Answer 3

-natural hormones from any animal, released into the environment, and chemicals produced by one species that exert hormonal action on another
-natural chemicals, including toxins produced by components of plants
-synthetically produced pharmaceuticals that are intended to be highly hormonally active
-man-made chemicals and by-products released into the environment

Question 4

history of endocrine disruption

Answer 4

-disruption is not a new concept
-ancients were familiar with herbal preparations
-farmers observed repro issues with sheep
-1908-10->first hormone discovered
-1930s-> Chemicals were known to interact with hormone receptors
-1940s-> Steroid compounds used in livestock industry
-development of the pill

Question 5

diethystilbestrol (DES)

Answer 5

-synthetic non-steroid estrogenic chemical
-approved in 1947 and given intentionally to woman in the 1950-1970s to prevent miscarriage
-in the us an estimated 5-10 million woman and children were exposed
-exposure moderately elevated the risk of breast cancer later in life in mothers that took the drug
-1st generation offspring: exposure caused a suite of reproductive abnormalities

Question 6

effects of DES

Answer 6

females
-2.5x increase in breast cancer risk
-greatly elevated risk for uterine cancer (age 20-40)
males
-elevated risk of epididymal cysts
-sometimes led to abnormal testicular development
-20x increased chance of hypospadia
-there was studies shown that DES did not reduce the chance of miscarrage

Question 7

an important first step in governing exposure to chemicals with EDC properties is

Answer 7

the identification of their ability to cause harm

Question 8

what does grouping chemicals by key characteristics (KCs) do

Answer 8

-is provides a basis for searching, organizing and evaluating mechanistic evidence to support the identification of EDCs
-authors of the paper identified 10 KCs for comprise the properties of all hormone systems

Question 9

what are the 10 KCs

Answer 9

-receptor ligand or agonist
-receptor antagonist
-receptor expression
-signal transduction
-epigenetic alteractions
-hormone synthesis
-hormone transport
-hormone distribution of circulating hormone levels
-hormone break down or clearece
-fate