veterinary drug residues and food safety Flashcards
what is clenbuterol classified as
B1 and B2 agonist
what do B1 and B2 agonists cause
tachycardia, bronchodilation, tocolytic, repartitioning agents
what is the concern to people with chloramphenicol residues
aplastic anemia
what is the concernt o people with diethystilbestrol residues
bone marrow toxicity and carcinogen
what is the concern to people with metronidazole residues
carcinogen and teratogen
what is the concern to people with nitrofurazone residues
carcinogen
what is the concern to people with phenylbutazone residues
blood dyscrasias, possible carcinogen
what is the concern to people with sulfonamide residues
hypersensitivity and thyroid tumors
what is the concernt o people with penicillin residues
hypersensitivity
what are the concerns regarding antimicrobial use in food animals
resistance in both target bacteria and in commensal bacteria (enteric), changes in food animal normal flora (increased enteric pathogens), drug residues that can effect human enteric flora
why is antibiotic resistance in commensal enteric bacteria of food animals a concern
those bacteria can spread to people
which enteric commensal bacteria are we concerned about resistance occuring in
E. coli, salmonella, campylobacter
who does the veterinary drugs directorate work under
health products and food branch of health canada
what is the VDDs function
approve drugs for veterinary use in Canada (does not regulate drug use) and performs human health risk assessments
what is the CFIAs role in veterinary drugs
tests for drug residues in food and approves biologics (vaccines, antibodies)
what legislation does inappropriate drug use fall under
provincial
what is involve in the pre-market approval of veterinary drugs
human safety, clinical efficacy, safety in intended species, safety to environment, manufacturing/quality control, labelling
what is involved in looking at human safety of food animal drugs
toxicology and pharmacology, microbiology, drug residues and metabolism
who takes care of examing drugs for quality control
analytical chemists
what is done to measure clinical efficacy and safety in intended species for a drug
clinical evaluation
what 3 types of studies are done to evaluate tox/pharm regarding human safety of a food animal drug
subchronic toxicity studies; chronic oral toxicity studies; special studies
what species are used for subchronic toxicity studies
2 species of lab animals; one rodent (rat) and one non-rodent (rabbit)
how is the drug administered in subchronic toxicity studies and why
orally (because people will be ingesting residues)
how is the drug administered in subchronic toxicity studies and why
orally (because people will be ingesting residues)
how long do subchronic toxicity studies last
3-12 months
how many different dose groups are used for subchronic toxicity studies
low, medium and high (3)
minimum number of animals for subchronic toxicity studies
20 (10 of each sex) per group
what are chronic oral toxicity studies
same as subchronic but longer – 12 months up to 2 years
what are examples of special studies
carcinogenicity, reproductive and teratogenicity studies; genetic toxicity (mutagenicity) tests, immunotoxicity, neurotoxicity and endocrine changes
what do carcinogenicity tests look for
increased incidence of tumors; required if drug is a suspected carcinogen or if chronic toxicity studies show histopathology
what methods of testing do special studies use
lab animals or in vitro tests
what do reproductive studies look for
if the drug causes spermatogenesis/estrus cycling/conception/parturition problems
what do teratogenicity studies look for
if the drug affects fetal development
how are genetic toxicity studies done
in vitro to look for DNA damage
when will immunotoxicity, neurotoxicity or endocrine studies be required
depends on family of drug, structure and relationship
what areas are evaluated regarding microbiology of food animal drugs (specifically antimicrobials)
spectrum of activity (MIC), antimicrobial resistance (AMR), effect on target species gut flora, effect on human gut flora
what pathogens are considered regarding antimicrobial spectrum of activity
target animal pathogens, food-borne pathogens and commensal bacteria (esp. with oral antimicrobials)
what areas are looked at when evaluating AMR
mechanism of AMR, mechanism of AMR transfer, rates of AMR development, cross-resistance to other antimicrobials
what areas are looked at when evaluating effect on target species gut flora of antimicrobials
do zoonotic pathogens increase, are there changes in fecal shedding (enteric flora changes are usually transient)
what areas are evaluated regarding microbiology of food animal drugs (specifically antimicrobials)
spectrum of activity (MIC), antimicrobial resistance (AMR), effect on target species gut flora, effect on human gut flora, impact on human medicine
what areas are looked at when evaluating effect on target species gut flora of antimicrobials
do zoonotic pathogens increase, are there changes in fecal shedding (enteric flora changes are usually transient)
what is looked at when evaluating effect of food animal antimicrobial on human gut flora
do residues of drug in food cause changes in human gut flora; if so, what concentration of drug is required
what is the concern regarding impact on human medicine with antimicrobials
if AMR to this drug would directly effect human medicine
what does acceptable daily intake mean (ADI)
amount of drug that can be consumed by a human over a lifetime (every day for whole life) with no adverse effects
how is ADI determined
toxicology and microbiology data
what is the “no observable effect level” (NOEL)
highest dose in the most susceptible species that does not cause any adverse effects
toxicological ADI
= NOEL/safety factor
what is the usual safety factor
100 (10x for intra species variability and 10x for inter species variability)
what is the safety factor if there are special toxicity concerns
can be up to 1000x
when is the microbiological ADI used
for antimicrobials only
what is the microbiological ADI
must be lower than the lowest concentration of drug that can cause changes in human gut flora (can be lower than toxicological ADI)
what does maximum residue limit determine (MRL)
how much drug residue is allowed in food (maximum amount of drug marker residue allowed in tissue)
how is MRL determined
by the total residue limit allowed
what is the calculation for total residue limit
ADI/food consumption factor
what can the marker residue be
either parent compound or metabolite (or combination)
what are withdrawal periods
period of time from last treatment until an animal can be slaughtered or milk/eggs used for consumption
who determines withdrawal periods and how
determined by the Drug Residues and Metabolism team using MRLs
what does the withdrawal period equal
amount of time for marker residue concentration in the 99th percentile (slowest) animal treated with the drug to fall below the MRL
what does the withdrawal period equal
amount of time for marker residue concentration in the 99th percentile (slowest) animal treated with the drug to fall below the MRL
the withdrawal period is exceptionally conservative if what occurs
drug label is followed (proper species, dose, route, health status)
what makes a carcass a “suspect” carcass to be tested for residues
injection site lesions, evidence of pathology or illness
what are processing plants residue limits for milk
if they can detect it, it’s not acceptable (even if residue is BELOW the MRL) – processing plants set different standards
what safety factors are applied to determining the MRL
minimum of 100X safety factor for calculating ADI and very high food consumption values assumed
