veterinary drug residues and food safety

Question 1

what is clenbuterol classified as

Answer 1

B1 and B2 agonist

Question 2

what do B1 and B2 agonists cause

Answer 2

tachycardia, bronchodilation, tocolytic, repartitioning agents

Question 3

what is the concern to people with chloramphenicol residues

Answer 3

aplastic anemia

Question 4

what is the concernt o people with diethystilbestrol residues

Answer 4

bone marrow toxicity and carcinogen

Question 5

what is the concern to people with metronidazole residues

Answer 5

carcinogen and teratogen

Question 6

what is the concern to people with nitrofurazone residues

Answer 6

carcinogen

Question 7

what is the concern to people with phenylbutazone residues

Answer 7

blood dyscrasias, possible carcinogen

Question 8

what is the concern to people with sulfonamide residues

Answer 8

hypersensitivity and thyroid tumors

Question 9

what is the concernt o people with penicillin residues

Answer 9

hypersensitivity

Question 10

what are the concerns regarding antimicrobial use in food animals

Answer 10

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

Question 11

why is antibiotic resistance in commensal enteric bacteria of food animals a concern

Answer 11

those bacteria can spread to people

Question 12

which enteric commensal bacteria are we concerned about resistance occuring in

Answer 12

E. coli, salmonella, campylobacter

Question 13

who does the veterinary drugs directorate work under

Answer 13

health products and food branch of health canada

Question 14

what is the VDDs function

Answer 14

approve drugs for veterinary use in Canada (does not regulate drug use) and performs human health risk assessments

Question 15

what is the CFIAs role in veterinary drugs

Answer 15

tests for drug residues in food and approves biologics (vaccines, antibodies)

Question 16

what legislation does inappropriate drug use fall under

Answer 16

provincial

Question 17

what is involve in the pre-market approval of veterinary drugs

Answer 17

human safety, clinical efficacy, safety in intended species, safety to environment, manufacturing/quality control, labelling

Question 18

what is involved in looking at human safety of food animal drugs

Answer 18

toxicology and pharmacology, microbiology, drug residues and metabolism

Question 19

who takes care of examing drugs for quality control

Answer 19

analytical chemists

Question 20

what is done to measure clinical efficacy and safety in intended species for a drug

Answer 20

clinical evaluation

Question 21

what 3 types of studies are done to evaluate tox/pharm regarding human safety of a food animal drug

Answer 21

subchronic toxicity studies; chronic oral toxicity studies; special studies

Question 22

what species are used for subchronic toxicity studies

Answer 22

2 species of lab animals; one rodent (rat) and one non-rodent (rabbit)

Question 23

how is the drug administered in subchronic toxicity studies and why

Answer 23

orally (because people will be ingesting residues)

Question 24

how is the drug administered in subchronic toxicity studies and why

Answer 24

orally (because people will be ingesting residues)

Question 25

how long do subchronic toxicity studies last

Answer 25

3-12 months

Question 26

how many different dose groups are used for subchronic toxicity studies

Answer 26

low, medium and high (3)

Question 27

minimum number of animals for subchronic toxicity studies

Answer 27

20 (10 of each sex) per group

Question 28

what are chronic oral toxicity studies

Answer 28

same as subchronic but longer -- 12 months up to 2 years

Question 29

what are examples of special studies

Answer 29

carcinogenicity, reproductive and teratogenicity studies; genetic toxicity (mutagenicity) tests, immunotoxicity, neurotoxicity and endocrine changes

Question 30

what do carcinogenicity tests look for

Answer 30

increased incidence of tumors; required if drug is a suspected carcinogen or if chronic toxicity studies show histopathology

Question 31

what methods of testing do special studies use

Answer 31

lab animals or in vitro tests

Question 32

what do reproductive studies look for

Answer 32

if the drug causes spermatogenesis/estrus cycling/conception/parturition problems

Question 33

what do teratogenicity studies look for

Answer 33

if the drug affects fetal development

Question 34

how are genetic toxicity studies done

Answer 34

in vitro to look for DNA damage

Question 35

when will immunotoxicity, neurotoxicity or endocrine studies be required

Answer 35

depends on family of drug, structure and relationship

Question 36

what areas are evaluated regarding microbiology of food animal drugs (specifically antimicrobials)

Answer 36

spectrum of activity (MIC), antimicrobial resistance (AMR), effect on target species gut flora, effect on human gut flora

Question 37

what pathogens are considered regarding antimicrobial spectrum of activity

Answer 37

target animal pathogens, food-borne pathogens and commensal bacteria (esp. with oral antimicrobials)

Question 38

what areas are looked at when evaluating AMR

Answer 38

mechanism of AMR, mechanism of AMR transfer, rates of AMR development, cross-resistance to other antimicrobials

Question 39

what areas are looked at when evaluating effect on target species gut flora of antimicrobials

Answer 39

do zoonotic pathogens increase, are there changes in fecal shedding (enteric flora changes are usually transient)

Question 40

what areas are evaluated regarding microbiology of food animal drugs (specifically antimicrobials)

Answer 40

spectrum of activity (MIC), antimicrobial resistance (AMR), effect on target species gut flora, effect on human gut flora, impact on human medicine

Question 41

what areas are looked at when evaluating effect on target species gut flora of antimicrobials

Answer 41

do zoonotic pathogens increase, are there changes in fecal shedding (enteric flora changes are usually transient)

Question 42

what is looked at when evaluating effect of food animal antimicrobial on human gut flora

Answer 42

do residues of drug in food cause changes in human gut flora; if so, what concentration of drug is required

Question 43

what is the concern regarding impact on human medicine with antimicrobials

Answer 43

if AMR to this drug would directly effect human medicine

Question 44

what does acceptable daily intake mean (ADI)

Answer 44

amount of drug that can be consumed by a human over a lifetime (every day for whole life) with no adverse effects

Question 45

how is ADI determined

Answer 45

toxicology and microbiology data

Question 46

what is the "no observable effect level" (NOEL)

Answer 46

highest dose in the most susceptible species that does not cause any adverse effects

Question 47

toxicological ADI

Answer 47

= NOEL/safety factor

Question 48

what is the usual safety factor

Answer 48

100 (10x for intra species variability and 10x for inter species variability)

Question 49

what is the safety factor if there are special toxicity concerns

Answer 49

can be up to 1000x

Question 50

when is the microbiological ADI used

Answer 50

for antimicrobials only

Question 51

what is the microbiological ADI

Answer 51

must be lower than the lowest concentration of drug that can cause changes in human gut flora (can be lower than toxicological ADI)

Question 52

what does maximum residue limit determine (MRL)

Answer 52

how much drug residue is allowed in food (maximum amount of drug marker residue allowed in tissue)

Question 53

how is MRL determined

Answer 53

by the total residue limit allowed

Question 54

what is the calculation for total residue limit

Answer 54

ADI/food consumption factor

Question 55

what can the marker residue be

Answer 55

either parent compound or metabolite (or combination)

Question 56

what are withdrawal periods

Answer 56

period of time from last treatment until an animal can be slaughtered or milk/eggs used for consumption

Question 57

who determines withdrawal periods and how

Answer 57

determined by the Drug Residues and Metabolism team using MRLs

Question 58

what does the withdrawal period equal

Answer 58

amount of time for marker residue concentration in the 99th percentile (slowest) animal treated with the drug to fall below the MRL

Question 59

what does the withdrawal period equal

Answer 59

amount of time for marker residue concentration in the 99th percentile (slowest) animal treated with the drug to fall below the MRL

Question 60

the withdrawal period is exceptionally conservative if what occurs

Answer 60

drug label is followed (proper species, dose, route, health status)

Question 61

what makes a carcass a "suspect" carcass to be tested for residues

Answer 61

injection site lesions, evidence of pathology or illness

Question 62

what are processing plants residue limits for milk

Answer 62

if they can detect it, it's not acceptable (even if residue is BELOW the MRL) -- processing plants set different standards

Question 63

what safety factors are applied to determining the MRL

Answer 63

minimum of 100X safety factor for calculating ADI and very high food consumption values assumed