15 species sensitivity Flashcards
what are the factors that influence toxicity?
why is it important to know species differences in response to toxicants?
-extrapolate results from toxicity studies (from model organisms)
-choosing appropriate test species (dont test on whales, humans or endangered species)
-understanding evolution of detoxification/resistance mechanisms
-“designing” drugs/chemicals
can you think of examples where selective toxicity for one species over another is beneficial?
-pesticides (selectively toxic)
-invasive species
-antibiotics (kill bacteria)
what is often wanted in ecotoxicology?
we often want to identify the concentration of a substance in the environment below which adverse effects are unlikely to occur
what is the species sensitivity distribution (SSD)?
SSD approach is used when the toxicity of a chemical has been studied on a broader range of species representing multiple species categories (for ex, fish, invertebrates, plants)
-used to infer a concentration that will be protective of a desired proportion of species in a hypothetical community
species differences in toxicity are usually attributable to differences in:
ADME (toxicokinetics)
what is absorption?
-plays an important role in affecting toxicity
-for ex: DDT is more readily absorbed across the skeletal chitin of insects than the skin of humans
what is metabolism?
-rate of metabolism is often the biggest influence on toxicity
-primarily in the liver (some in the intestine and kidneys)
-products of metabolism= metabolites
-two types of metabolism: detoxification (less toxic metabolite) and bioactivation (more toxic metabolite)
what is an example of metabolism?
what are metabolizing enzymes in different species?
-chemical and drug metabolism can occur in the cells that line the intestine
-CYP enzymes are among the most important
-the levels of various CYP450 enzymes differ across species (ex: rat, dog, monkey and humans)
what is distribution (and storage)?
-ultimately determines the sites where toxicity occurs
-blood (and lymph) are main avenues for distribution
-many toxicants are also stored in the body
-fat tissue, liver, kidney and bone are the most common storage deposits
what is elimination?
-kidney is the primary excretory organ
-gastrointestinal tract, and the lungs (for gases)
-other ways include lactation, crying, sweating
what is toxicity testing?
-early 20th century-> need for toxicity testing grew
-several animal models were developed
-such testing had obvious advantages+disadvantages
what is the case study in this lecture?
thalidomide
-synthesized in Germany in 1940s
-subjected to animal testing in hamsters and species of mice
-results indicated that it appeared relatively safe under the regulatory approaches used in some countries
-prescribed in canada, europe, australia and asia (not US)
when was thalidomide prescribed and what are the effects?
-a sleep and anti-nausea aid prescribed to pregnant women
-critical time period of exposure was around gestation days (GD) 35-50
common effects include:
-amelia (absence of limbs)
-phocomelia (absence of most of the arm with hands extending flipper-like from the shoulders)
-dysmelia (malformation, missing or extra limbs)
-bone hypoplasticity (incomplete development of cells)
what was thalidomide research?
-over 2000 research papers and the proposal of approx. 15 plausible (possible) mechanisms of action
-inhibition of angiogenesis (critical during limb development of the fetus) is one theory; loss of newly formed blood vessels leads to limb malformation
