Annex 1. Summary of JECFA evaluations of veterinary drug residues from the 32nd meeting to the present
Annex 2. Recommendations on compounds evaluated by the 47th JECFA
The attached table summarizes the veterinary drug evaluations conducted by JECFA at the 32nd (1987), the 34th (1989), the 36th (1990), the 38th (1991), the 40th (1992), the 42nd (1994), the 43rd (1994), 45th (1995) and 47th (1996) Meetings. These meetings were devoted exclusively to the evaluation of veterinary drug residues in foods. Please see Reports of those meetings, published in WHO Technical Report Series.
Some notes regarding the Table:
· The "Status" column refers to the ADI and indicates if "No" ADI was established, if a full ADI was given, or if the ADI is Temporary (TE).· Where an MRL is temporary, it is so indicated by "TE".
· Several compounds have been evaluated more than once. The data given is for the most recent evaluation.
Substance |
ADI (m g/kg bw) |
ADI status |
JECFA |
MRL (m g/kg) |
Tissue |
Species |
Marker residue (MR) |
Abamectin |
0-11 |
Full |
47 (1996) |
100 |
Muscle, fat |
Cattle |
Avermectin Bla
|
50 |
Kidney |
||||||
Albendazole |
0-50 |
Full |
34 (1989) |
1002 |
Muscle, fat, milk |
Cattle, sheep |
2-Aminobenzimidazole sulfone, MR in milk needs to be identified |
50002 |
Liver, kidney |
||||||
Azaperone |
0-3 |
TE |
43 (1994) |
60 TE |
Muscle, fat |
Pigs |
Sum of azaperone and azaperol |
100 TE |
Liver, kidney |
||||||
Benzylpenicillin |
30 m g/person/day |
Full |
36 (1990) |
50 |
Muscle, liver, kidney |
All species |
Parent drug |
4 |
Milk |
||||||
BST |
Not specified |
Full |
40 (1992) |
Not specified |
Muscle, liver, kidney, fat, milk |
Cattle |
|
Carbadox |
Limited acceptance |
Full |
36 (1990) |
30 |
Liver |
Pigs |
Quinoxaline-2-carboxylic acid |
5 |
Muscle |
||||||
Carazolol |
0-0.1 |
Full |
43 (1994) |
53 |
Muscle, fat/skin |
Pigs |
Parent drug |
25 |
Liver, kidney |
||||||
Ceftiofur |
0-50 |
Full |
45 (1995) |
200 |
Muscle |
Cattle, pigs |
Desfuroylceftiofur |
2000 |
Liver |
||||||
4000 |
Kidney |
||||||
600 |
Fat |
||||||
100 m g/l |
Milk |
Cattle |
|||||
Chloramphenicol |
None |
No |
42 (1994) |
No MRL |
|
|
|
Chlorpromazine |
None |
No |
38 (1991) |
No MRL |
|
|
|
Chlortetracycline, oxytetracycline & tetracycline |
0-3 (Group ADI) |
Full |
45 (1995) |
|
|
|
|
47 (1996) |
100 |
Muscle |
Cattle, pigs, sheep, poultry |
Parent drugs, singly or in combination |
|||
300 |
Liver |
Cattle, pigs, sheep, poultry |
|||||
600 |
Kidney |
||||||
200 |
Eggs |
Poultry |
|||||
100 |
Milk |
Cattle, sheep |
|||||
1004 |
Muscle |
Fish, Giant prawn |
|||||
Clenbuterol |
0-0.004 |
Full |
47 (1996) |
0.2 |
Muscle, fat |
Cattle, horses |
Parent drug |
0.6 |
Liver, kidney |
||||||
0.05 |
Milk |
Cattle |
|||||
Closantel |
0-30 |
Full |
36 (1990) |
|
|
|
|
40 (1990) |
1000 |
Muscle, liver |
Cattle |
Parent drug |
|||
3000 |
Kidney, fat |
||||||
1500 |
Muscle, liver |
Sheep |
|||||
5000 |
Kidney |
||||||
2000 |
Fat |
||||||
Cypermethrin |
0-50 |
Full |
47 (1996) |
200 TE |
Muscle, liver, kidney |
Cattle, sheep, chickens |
Parent drug |
1000 TE |
Fat |
||||||
100 TE |
Eggs |
Chickens |
|||||
50 TE |
Milk |
Cattle |
|||||
a -Cypermethrin |
0-20 |
Full |
47 (1996) |
100 TE |
Muscle, liver, kidney |
Cattle, sheep, chickens |
Parent drug |
500 TE |
Fat |
||||||
50 TE |
Eggs |
Chickens |
|||||
25 TE |
Milk |
Cattle |
|||||
Dexamethasone |
0-0.015 |
Full |
42 (1992) |
0.5 TE |
Muscle, kidney |
Cattle, horses, pigs |
Parent drug |
43 (1994) |
2.5 TE |
Liver |
|||||
0.3 m g/l TE |
Milk |
Cattle |
|||||
Diclazuril |
0-20 |
TE |
45 (1995) |
500 TE |
Muscle |
Sheep, rabbits & poultry |
Parent drug |
3000 TE |
Liver |
||||||
2000 TE |
Kidney |
||||||
1000 TE |
Fat |
||||||
Dihydrostreptomycin & streptomycin |
0-30 (Group ADI) |
TE |
43 (1994) |
500 TE |
Muscle, liver, fat |
Cattle, pigs, chickens, sheep |
Sum of dihydrostreptomycin and streptomycin |
1000 TE |
Kidney |
||||||
200 m g/l TE |
Milk |
Cattle |
|||||
Dimetridazole |
None |
No |
34 (1989) |
No MRL |
|
|
|
Diminazene |
0-100 |
Full |
42 (1994) |
500 |
Muscle |
Cattle |
Parent drug |
12000 |
Liver |
||||||
6000 |
Kidney |
||||||
150 m g/l |
Milk |
||||||
Doramectin |
0-0.5 |
Full |
45 (1995) |
105 |
Muscle |
Cattle |
Parent drug |
100 |
Liver |
||||||
30 |
Kidney |
||||||
150 |
Fat |
||||||
Enrofloxacin |
0-0.6 |
TE |
43 (1994) |
No MRL |
|
|
|
Estradiol-17b |
Unnecessary |
Full |
32 (1987) |
Unnecessary |
|
Cattle |
|
Febantel |
0-4 6 |
TE |
45 (1995) |
100 TE |
Muscle, kidney, fat |
Cattle, sheep, pigs |
Sum of fenbendazole, oxfendazole, and oxfendazole sulfone, expressed as oxfendazole sulfone equivalents |
500 TE |
Liver |
||||||
100 m g/l TE |
Milk |
Cattle |
|||||
Fenbendazole (see febantel) |
|
|
|
|
|
|
|
Flubendazole |
0-12 |
Full |
40 (1992) |
10 |
Muscle, liver |
Pigs |
Parent drug |
200 |
Muscle |
Poultry |
|||||
500 |
Liver |
||||||
400 |
Eggs |
||||||
Flumequine |
None |
No |
42 (1994) |
No MRL |
|
|
|
Furazolidone |
None |
No |
40 (1992) |
No MRL |
|
|
|
Gentamicin |
0-4 |
TE |
43 (1994) |
100 TE |
Muscle, fat |
Cattle, pigs |
Parent drug |
200 TE |
Liver |
||||||
1000 TE |
Kidney |
||||||
100 m g/l TE |
Milk |
Cattle |
|||||
Ipronidazole |
None |
No |
34 (1989) |
No MRL |
|
|
|
Isometamidium |
0-100 |
Full |
40 (1992) |
100 |
Muscle, fat, milk |
Cattle |
Parent drug |
500 |
Liver |
||||||
1000 |
Kidney |
||||||
Ivermectin |
0-1 |
Full |
40 (1992)
|
100 |
Liver |
Cattle |
H2Bla |
40 |
Fat |
||||||
36 (1990) |
15 |
Liver |
Other species |
||||
20 |
Fat |
||||||
Levamisole |
0-6 |
Full |
42 (1992) |
10 |
Muscle, kidney, fat |
Cattle, sheep, pigs and poultry |
Parent drug |
100 |
Liver |
||||||
Metronidazole |
None |
No |
34 (1989) |
No MRL |
|
|
|
Moxidectin |
0-2 |
Full |
45 (1995) |
|
|
|
|
47 (1996) |
207 |
Muscle |
Cattle, deer 8 |
Parent drug |
|||
507 |
Muscle |
Sheep |
|||||
100 |
Liver |
Cattle, sheep, deer 8 |
|||||
50 |
Kidney |
||||||
500 |
Fat |
||||||
Neomycin |
0-60 |
Full |
47 (1996) |
500 |
Muscle, liver, fat |
Cattle, chickens, ducks, goats, pigs, sheep, turkeys |
Parent drug |
10000 |
Kidney |
||||||
500 |
Eggs |
Chickens |
|||||
500 m g/l |
Milk |
Cattle |
|||||
Nitrofurazone |
None |
No |
40 (1992) |
No MRL |
|
|
|
Olaquindox |
Limited acceptance |
TE |
42 (1994) |
No MRL but 4 m g/kg of MQCA (TE) is consistent with GVP |
Muscle |
Pigs |
MQCA |
Oxfendazole (see febantel) |
|
|
|
|
|
|
|
Oxolinic acid |
None |
No |
43 (1994) |
No MRL |
|
|
|
Oxytetracycline (see chlortetracycline) |
|
|
|
|
|
|
|
Progesterone |
Unnecessary |
Full |
32 (1987) |
Unnecessary |
|
Cattle |
|
Propionylpromazine |
None |
No |
38 (1991) |
No MRL |
|
|
|
Ractopamine |
None |
No |
40 (1992) |
No MRL |
|
|
|
Ronidazole |
Withdrawn |
No |
42 (1994) |
No MRL |
|
|
|
Spectinomycin |
0-40 |
Full |
42 (1994) |
300 TE |
Muscle |
Cattle, pigs, and chicken |
Parent drug |
2000 TE |
Liver |
||||||
5000 TE |
Kidney |
||||||
500 TE |
Fat |
||||||
200 m g/l TE |
Milk |
||||||
Spiramycin |
0-50 |
Full |
43 (1994) |
|
|
|
|
47 (1996) |
200* |
Muscle |
Cattle, chickens |
*Sum of spiramycin and neospiramycin **Expressed as spiramycin equivalents(antimicrobially active residues) |
|||
200** |
Muscle |
Pigs |
|||||
600* |
Liver |
Cattle, chickens |
|||||
600** |
Liver |
Pigs |
|||||
300** |
Kidney |
Cattle |
|||||
300** |
Kidney |
Pigs |
|||||
800* |
Kidney |
Chickens |
|||||
300* |
Fat |
Cattle, chickens |
|||||
300** |
Fat |
Pigs |
|||||
100 m g/l* |
Milk |
Cattle |
|||||
Streptomycin (see dihydrostreptomycin) |
|
|
|
|
|
|
|
Sulfadimidine |
0-50 |
Full |
42 (1994) |
100 |
Muscle, liver, kidney, fat |
Cattle, sheep, pigs and poultry |
Parent drug |
25 m g/l |
Milk |
Cattle |
|||||
Sulphthiazole |
None |
No |
34 (1989) |
No MRL |
|
|
|
Testosterone |
Unnecessary |
Full |
32 (1987) |
Unnecessary |
|
Cattle |
|
Tetracycline (see chlortetracycline) |
|
|
|
|
|
|
|
Thiamphenicol |
0-6 |
TE |
47 (1996) |
40 TE |
Muscle, liver, kidney, fat |
Cattle, chickens |
Parent drug |
Tiabendazole |
0-100 |
Full |
40 (1992) |
100 |
Muscle, liver, kidney, fat |
Cattle, pigs, goats and sheep |
Sum of tiabendazole and 5-hydroxytiabendazole |
100 |
Milk |
Cattle, goats |
|||||
Tilmicosin |
0-40 |
Full |
47 (1996) |
100 |
Muscle, fat |
Cattle, pigs, sheep |
Parent drug |
1000 |
Liver |
Cattle, sheep |
|||||
1500 |
Liver |
Pigs |
|||||
300 |
Kidney |
Cattle, sheep |
|||||
1000 |
Kidney |
Pigs |
|||||
50 TE |
Milk |
Sheep |
|||||
Trenbolone acetate |
0-0.02 |
Full |
34 (1989) |
2 as MR |
Muscle |
Cattle |
a -Trenbolone |
10 as MR |
Liver |
b -Trenbolone |
|||||
Triclabendazole |
0-3 |
Full |
40 (1992) |
200 |
Muscle |
Cattle |
5-Chloro-6-(2',3'-dichlorophenoxy)-benzimidazole-2-one |
300 |
Liver, kidney |
||||||
100 |
Fat |
||||||
100 |
Muscle, liver, kidney, fat |
Sheep |
|||||
Tylosin |
None |
No |
38 (1991) |
No MRL |
|
|
|
Xylazine |
None |
No |
47 (1996) |
No MRL |
|
|
|
Zeranol |
0-0.5 |
Full |
32 (1987) |
2 |
Muscle |
Cattle |
Parent drug |
10 |
Liver |
1 The ADI for abamectin was established by the 1995 Joint Meeting on Pesticide Residues (JMPR)2 Parent drug equivalents
3 The Committee noted that the concentration of carazolol at the injection site may exceed the ADI which is based on the acute pharmacological effects of carazolol
4 Oxytetracycline only
5 The Committee noted the high concentration of residues at the injection site during the 35-day period after parenteral administration of the recommended dose
6 Group temporary ADI for febantel, fenbendazole and oxfendazole
7 At the 45th meeting the Committee noted the very high concentration and great variation in the level of residues at the injection site over a 49-day period after dosing cattle
8 Temporary
b -Adrenoceptor blocking agents
Clenbuterol
Acceptable daily intake (ADI): 0-0.004 m g per kg of body weight
Recommended maximum residue limits (MRLs)1
1 MRLs are expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
0.2 |
0.6 |
0.6 |
0.2 |
|
0.05 |
Horses |
0.2 |
0.6 |
0.6 |
0.2 |
|
|
Xylazine
The Committee was unable to establish an ADI for xylazine because it concluded that a metabolite, 2,6-xylidine, is genotoxic and carcinogenic. The Committee was unable to establish MRLs for xylazine because of the lack of information on metabolism and residue depletion in edible tissues.
The following information would be required for further review:
· Data on xylazine metabolism in target species sufficient to identify a suitable marker residue and target tissues.· Additional data on residue depletion of xylazine and its metabolites in target species. These data should include evidence to show, in particular, whether 2,6-xylidine is present at the recommended withdrawal times.
· A suitable analytical method for determining the marker residue in target tissues.
Anthelminthic agents
Abamectin
ADI: 0-1 m g per kg of body weight 1
1 This ADI, which applies to the parent drug abamectin, was established by the 1995 Joint FAO/WHO Meeting on Pesticide Residues (JMPR; FAO Plant Production and Protection Paper 133, 1996).
Recommended maximum residue limits (MRLs) 2
2 MRLs are expressed as avermectin Bla.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
|
100 |
50 |
100 |
|
|
Moxidectin
ADI: 0-2 m g per kg of body weight1
1 This ADI was established at the forty-fifth meeting of the Committee.
Recommended maximum residue limits (MRLs)2
2 MRLs are expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
20 |
100 |
50 |
500 |
|
|
Sheep |
503 |
100 |
50 |
500 |
|
|
Deer 4 |
20 |
100 |
50 |
500 |
|
|
3 This MRL was established at the present meeting. All other MRLs were established at the forty-fifth meeting of the Committee. At that meeting the Committee noted the high concentration and great variation in the level of residues at the injection site over a 49-day period after dosing cattle.4 Temporary MRLs (see the report of the forty-fifth meeting of the Committee).
Antimicrobial agents
Chlortetracycline, oxytetracycline and tetracycline ADI: 0-3 m g per kg of body weight 1
1 This ADI was established at the forty-fifth meeting of the Committee.
Recommended maximum residue limits (MRLs)2
2 MRLs are expressed as the parent drug, singly or in combination.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
100 |
300 |
600 |
|
|
100 |
Pigs |
100 |
300 |
600 |
|
|
|
Sheep |
100 |
300 |
600 |
|
|
100 |
Poultry |
100 |
300 |
600 |
|
200 |
|
Giant prawn (Penaeus monodon) |
1003 |
|
|
|
|
|
Fish |
1003 |
|
|
|
|
|
3 This MRL applies only to oxytetracycline.
Neomycin
ADI: 0-60 m g per kg of body weight
Recommended maximum residue limits (MRLs)1
1 MRLs are expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
500 |
500 |
10000 |
500 |
|
500 |
Pigs |
500 |
500 |
10000 |
500 |
|
|
Sheep |
500 |
500 |
10000 |
500 |
|
|
Goats |
500 |
500 |
10000 |
500 |
|
|
Chickens |
500 |
500 |
10000 |
500 |
500 |
|
Ducks |
500 |
500 |
10000 |
500 |
|
|
Turkeys |
500 |
500 |
10000 |
500 |
|
|
Spiramycin
ADI: 0-50 m g per kg of body weight 1
1 The ADI was established at the forty-third meeting of the Committee.
Recommended maximum residue limits (MRLs)
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle 2 |
200 |
600 |
300 |
300 |
|
100 |
Pigs 3 |
200 |
600 |
300 |
300 |
|
|
Chickens 2 |
200 |
600 |
800 |
300 |
|
|
2 MRLs are expressed as the sum of spiramycin and neospiramycin.3 MRLs are expressed as spiramycin equivalents (antimicrobially active residues).
Thiamphenicol
ADI: 0-6 m g per kg of body weight 1
1 Temporary ADI.
Recommended maximum residue limits (MRLs)2
2 Temporary MRLs, expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
40 |
40 |
40 |
40 |
|
|
Chickens |
40 |
40 |
40 |
40 |
|
|
The following information is required for evaluation in 1999:
· Detailed reports of the carcinogenicity study in rats on which the summary report was available at the present meeting and the range-finding study used to establish dose levels in that study.· Residue depletion studies with radiolabelled and unlabelled thiamphenicol for identification of the marker residue and target tissues in non-ruminant cattle, chickens and pigs.
Tilmicosin
ADI: 0-40 m g per kg of body weight
Recommended maximum residue limits (MRLs)1
1 MRLs are expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
100 |
1000 |
300 |
100 |
|
|
Pigs |
100 |
1500 |
1000 |
100 |
|
|
Sheep |
100 |
1000 |
300 |
100 |
|
502 |
2 Temporary MRL. The results of a study in lactating sheep with radiolabelled drug for estimation of the relationship between total residues and parent compound in milk are required for evaluation in 1999.
Insecticides
Cypermethrin
ADI: 0-50 m g per kg of body weight
Recommended maximum residue limits (MRLs)1
1 Temporary MRLs, expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
200 |
200 |
200 |
1000 |
|
50 |
Sheep |
200 |
200 |
200 |
1000 |
|
|
Chickens |
200 |
200 |
200 |
1000 |
100 |
|
The following information is required for evaluation in 2000:
· The results of radiodepletion studies that extend beyond the recommended withdrawal times using the drug in its topical formulation. The study should determine the depletion of the total residues and the parent drug in target species.· Evidence to verify that no interconversion of isomeric forms occurs during metabolism in the target species.
· Further information on the validation of analytical methods, particularly data on the derivation of the limits of determination and limits of quantification.
alpha-Cypermethrin
ADI: 0-20 m g per kg of body weight
Recommended maximum residue limits (MRLs)1
1 Temporary MRLs, expressed as the parent drug.
|
Muscle (m g/kg) |
Liver (m g/kg) |
Kidney (m g/kg) |
Fat (m g/kg) |
Eggs (m g/kg) |
Milk (m g/l) |
Cattle |
100 |
100 |
100 |
500 |
|
25 |
Sheep |
100 |
100 |
100 |
500 |
|
|
Chickens |
100 |
100 |
100 |
500 |
50 |
|
The following information is required for evaluation in 2000:
· The results of radiodepletion studies in sheep and chickens that extend beyond the recommended withdrawal times using the drug in its topical formulation. The study should determine the depletion of the total residues and the parent drug.· The radiodepletion study submitted for cattle should be reassessed to determine the depletion of the total residues and the parent drug.
· Evidence to verify that no interconversion of the cis-isomeric forms to the trans-isomeric forms occurs during metabolism in the target species.
· Further information on the validation of analytical methods, particularly data on the derivation of the limits of determination and limits of quantification.