2 spectrum of toxic effects Flashcards
what is the spectrum categories of toxic effects?
- local vs systemic
- reversible vs irreversible
- immediate (acute) vs delayed (chronic)
- morphological, functional and biochemical effects
- allergic vs idiosyncratic reactions
- graded (continuous) vs quantal (all or none) responses
what are local effects?
-uncommon compared to systemic
-corrosive chemicals on skin (ex: strong acids and bases such as battery acid)
-irritating gases and vapours in respiratory tract (ammonia and chlorine gas cause build up of fluid in lungs)
what are systemic effects?
-xeno must be distributed into systemic circulation and distributed to organs/tissues
-many xenos preferentially cause toxic effect in one or few specific organs (target organs)
-target organ may not always have the highest xeno conc
what are reversible effects?
-effects disappear after exposure ends
-usually short-term and/or low dose exposures
-ex: drinking on a weekend, effects eventually go away
what are irreversible effects?
-effects persists or even worsen after exposure ends
-ex carcinomas, teratogenic effects, neuronal damage, liver cirrhosis
-usually long-term and/or high dose exposures
-ex: ethanol when decades of alcoholism cause liber cirrhosis)
what are immediate (acute) effects?
-timeframe minutes to days
-ex: cyanide (can’t produce ATP) and carbon monoxide poisoning (high affinity for Hb than O so can’t produce ATP)
what are delayed (chronic) effects?
-timeframe months to years
-ex: cancer develops 10-20 years after exposure, both in individuals and also potentially their offspring (recall diethylstilbestrol (DES) rare reproductive cancer in daughters)
-illustrates the need to conduct long-term toxicological studies and transgenerational toxicological studies
what are morphological effects?
-gross or microscopic effects on tissues; commonly irreversible
-ex: thalidomide teratogenicity (gross: missing limbs)
-ex: histopathological effects on liver cells (microscope view of cells differ with liver cirrhosis)
what are functional effects?
-ex: liver or kidney function, reproduction
-generally reversible effects
what are biochemical effects?
-virtually all toxic effects are initiated by an alteration in biochemical processes (ex: receptor binding, enzyme inhibition, interaction with DNA)
-such biochemical effects are often used as biochemical markers or “biomarkers” that serve as early indicators or “markers” of toxic effects
-note than such biochemical effects are reversible and do not necessarily indicate an adverse morphological or functional effect
what are allergic effects?
a) hypersensitivity reactions: require prior exposure; xeno can react with protein to produce antigen, antibodies are produced and illicit immune response
-ex: bee venoms and nuts can cause a severe allergic reaction
-ex: perfumes, multiple chemical allergy syndrome, “sick building syndrome”
b) autoimmune reactions: xenos can initiate autoimmune diseases such as systemic lupus erythematosus (fairly rare)
what are idiosyncratic effects?
-genetically based abnormal reactivity to a xeno with no known cause
-ex: certain drugs can produce rare, idiosyncratic reactions
what are graded effects?
-continuous (infinite number) responses
-ex: effects on body weight, food consumption, enzyme activity
what are quantal effects?
-all or none responses (yes or no)
-ex: mortality, cancer
why are certain organs targets of xenobiotics?
-generally due to greater susceptibility or higher xeno conc (depends on kinetics, dynamics and dose defines the poison), although the explanation is not always clear
