toxicological testes and end points of toxicity Flashcards
characteristics of acute experimental toxicity-lethality
- Experimental toxicology
- Single dose toxicity testing
- LD50
- Cumulative dose-effect
- curves
- Yes/no response
- Traditional 1st classification
- and dose-range finding
discuss acute clinical toxicology
- A toxic effect that is directly
- related to exposure
- The chocolate dog!
- Generally pharmacological
- active substances at a high dose: interaction with a target (enzyme, receptor)
discuss Acute toxicity (LD50 vs
TC50) in vivo
- Typical animal species:
- Rodents:
- Rats and mice
- Hamsters
- Chickens
- they are Descriptive tests: dose range findings
- n.b what kills the animal and what doesnt
discuss Acute toxicity (LD50 vs
TC50) in vitro
- Concentration dependent toxicity
- testing in different cell-types:
- Direct cytotoxicity (dead cells):
- Fibroblast type cells
- HepG2 cells (liver derived)
- Neuro 2A cells (neuroblastoma)
- Caco cells (colon carcinoma)
discuss Subacute experimental toxicity
- repetitive dose
- Defined protocol, 7-10 repetitive doses to different dosage groups Clinical observation,
- postmortem (gross) pathology
- Substance characherisation
- –are there behavioral changes. do animals get sick
discuss Subacute clinical toxicology
- Not defined, but common in daily practice as the time between 1st exposure, onset of clinical symptoms and reporting
- n.b if u see the cs right away then its acute but if u see the cs aftwer a day or 2 then it is subacute
discuss the 90 day toxicity testing in rats
- 90 days = ⅛ of the life span of the animal - at least 3 differentdoses (male and female groups)
- Daily exposure should induce all possible toxic effects
- Generally oral application (in drug-testing application according to the intended clinical use where possible)
- Extended protocol: daily clinical (including behavioral studies when appropriate), urine and blood sampling, total (histo-) pathology
- Defines NO(A)EL (mg/kg BW): the tested dose without any effect (no-observable (adverse) effect level)
- Defines LOEL: the lowest dose that induces a measurable effect: lowest observable effect level
discuss regulatory toxicology in 90 days rodent toxicity test
- determines NOAEL
- determines ADI (acceptable daily intake)
- n.b it helps u know how much residue is in a drug or food that is acceptable for consuption
- how much residue can be in the meat without anybody getting sick
discuss 90 day rodent toxicity test in vet. toxicology
- Qualitative information
- Steepness of the dose response curve (NOAEL -LOEL)
- Organ-specific effects (target structures)
- Reversibility of the effects(prognosis)
- tells u more about pxe.g nsaid reversible as long as there is no perforation
- ADI-MRL
formula for acceptable daily intake (ADI0
ADI =NO(A)EL (mg/kg) * 65 kg BW
UF (10 * 10)
formula for MRI
MRL =NO(A)EL (mg/kg) * 65 kg BW
UF * FF
what do we get from mri
withdrawal period
all vet products hav gone thru this process
how long does spermatogenesis lasts in a boar
3 9 days
how long is spermatogenesis in human and horse
75 days
if there are defects, they occured 75 days ago
which mycotoxin has transgenerational toxicity in pigs
- zearalenone
- effects seen in f1
- leads to infertility
- no effects on sons
- Agonists/antagonists of ER receptors regulating transcription
- Substrate for enzymes regulating the synthesis & inactivation of endogenous hormones
- effects seen at puberty
