Annexes

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

Annex 1. Summary of JECFA evaluations of veterinary drug residues from the 32nd meeting to the present

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

Annex 2. Recommendations on compounds evaluated by the 47th JECFA

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 B_la.

	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.