Animal Residue Data Sheet - Tebufenozide

Tebufenozide is registered or approved for use in Australia on avocado, blueberry, citrus fruits, custard apples, kiwifruit, longan, lychee, macadamia nuts, apples and pears, and grapes. Details of the registered use patterns can be found on the approved labels of registered products containing tebufenozide as the active constituent. This Animal Residue Data Sheet provides information on the possible residues in feed commodities obtained from crops treated with tebufenozide, to provide assistance in the formulation of animal diets that should not result in the violation of animal commodity MRLs.

Current MRLs

The Australian MRLs for tebufenozide in food and animal feed commodities, as listed in Table 1 and Table 4 of the MRL Standard [as at 19 June 2003] are shown below. The residue definition of tebufenozide is the parent compound per se.

Code	Food	Current MRL, mg/kg
Food Commodities
FI 0326	Avocado	0.5
FC 0001	Citrus fruits	1
SB 0716	Coffee beans	T0.05
FI 0332	Custard apple	0.3
DF 0269	Dried grapes	4
FB 0269	Grapes	2
FI 0341	Kiwifruit	2
FI 0343	Litchi	2
FI 0342	Longan	2
TN 0669	Macadamia	0.05
FS 0245	Nectarines	T1
FS 0247	Peaches	T1
FT 0307	Persimmon, Japanese	T1
FP 0009	Pome fruits	1
Animal commodities
MO 0105	Edible offal (mammalian)	*0.02
MM 0095	Meat (mammalian) [in the fat]	*0.02
ML 0106	Milk	*0.01
Animal feed commodities
AB 0269	Grape pomace, dry	10
	Pome fruit pomace, dry	10

Summary of maximum feeding levels and livestock dietary intakes

The Maximum Feeding Level (MFL, the feeding level at which the MRLs are based), the equivalent Daily Dietary Intake For Livestock (DDIL) and the equivalent daily intake of tebufenozide are summarised below.

Species	MFL, ppm in diet	Equivalent DDIL, mg/kg bw	Equivalent intake of tebufenozide, mg/animal/day
Cattle^a	6	0.28	132
Sheep^b	6	0.25	15
Pig^c	6	0.25	15
^a Based on actual feeding study data ^b Based on a 60 kg animal consuming 2.5 kg DM/day ^c Based on a 60 kg animal consuming 2.5 kg DM/day

Detailed information

All feed commodities

Feed commodities that may contain residues of tebufenozide are listed in the table below. The theoretical maximum proportion of the diet that the commodity can comprise, when residues are present at the MRL, without the significant risk of animal commodity MRLs being violated is also given. It should be noted that the feeding levels assumed by the NRA when setting animal commodity MRLs are theoretical values, and they should not be taken as recommendations of appropriate rations for livestock.

Commodity^a	Assumed Maximum proportion of diet (%)^b	Feed intake (kg/animal/day)^c	MRL (mg/kg)^d	Maximum intake of tebufenozide from commodity (mg/animal/day)^e	Theoretical maximum proportion of diet (%)^f
Cattle (Based on a 500 kg animal consuming 20 kg DM/day)
Pome fruit pomace, dry	20	4	10	40	69
Grape pomace, dry	20	4	10	40	69
Citrus pulp	20	4	1	4	100
Sheep (Based on a 60 kg animal consuming 2.5 kg DM/day)
Pome fruit pomace, dry	20	0.5	10	5	69
Grape pomace, dry	20	0.5	10	5	69
Citrus pulp	20	0.5	1	0.5	100
Pigs (Based on a 60 kg animal consuming 2.5 kg DM/day)
Pome fruit pomace, dry	20	1	10	10	69
Grape pomace, dry	20	1	10	10	69
Citrus pulp	20	1	1	1	100
Poultry (Based on a 2 kg animal consuming 150 g DM/day)
Pome fruit pomace, dry	5	0.0075	10	0.075	100
Grape pomace, dry	5	0.0075	10	0.075	100
Citrus pulp	5	0.0075	1	0.0075	100
^a The feed commodities that may contain residues of tebufenozide, and may form more than 20% of an animals diet. ^b The maximum % of the diet that the commodity is assumed to comprise for the purposes of setting MRLs, based on Stockfeed Information Document 1 ^c The equivalent amount of feed for an animal of designated weight and feed intake that is assumed for the purposes of setting MRLs ^d The MRL for each feed commodity (correction for dry weight basis where required) ^e The maximum intake of tebufenozide when the commodity is fed at the maximum assumed level (Column 1) in the absence of other sources of tebufenozide. ^f The maximum % of the diet at which the commodity could theoretically be fed without significant risk of exceeding animal commodity MRLs. It is assumed that the residue in the feed commodity is present at the MRL (or dry weight equivalent) and other dietary sources of tebufenozide are absent.

Abbreviations and definitions

DM: Dry matter. The feed consumption for livestock and the residue levels in feed commodities are expressed on a dry matter basis.

DDIL: Daily Dietary Intake for Livestock. The level of dietary exposure for a specified chemical in a specified species that should not result in exceedance of the relevant animal commodity MRLs. Expressed in mg chemical/kg bodyweight.

MFL: Maximum Feeding Level. The level of dietary exposure for a specified chemical in a specified species that should not result in exceedance of the relevant animal commodity MRLs. Expressed in terms of ppm in the feed.

MRL: The concentration of a chemical residue, in units of mg/kg, that is legally permitted in or on a food or food commodity.

ppm in the feed: Parts per million in the feed. An alternate way of expressing the level of dietary exposure for a chemical. The level of chemical intake is calculated as though it were present uniformly in the total feed intake. The ppm in the feed is calculated using the following formula: DDIL (mg chemical/kg bw) _ body weight (kg) ¸ daily feed intake (kg). For example: a cow consumes 10 kg of grain containing 10 mg/kg of Chemical X and 10 kg of apple pomace containing 5 mg/kg of Chemical X. The total intake of Chemical X is 150 mg in 20 kg of feed. This is equivalent to 7.5 ppm in the feed [150÷20].

Attachment 1: Anticipated maximum dietary exposure

The following calculations outline the theoretical diet used to calculate the maximum anticipated dietary exposure, maximum feeding level (MFL) and the daily dietary intake for livestock (DDIL) for cattle, sheep, pigs and poultry.

Cattle

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	MRL, mg/kg	% DM^b	Intake of tebufenozide, mg/animal/day^c
Fruit by-products [2040% maximum]	Pome fruit pomace, dry	4020	84	10	-	8040
Fruit by-products [2040% maximum]	Grape pomace, dry	4020	84	10	-	8040
Total		4020	84			8040
^aBased on assumed feed consumption of 20 kg dry matter/day ^bEstimate of percentage dry matter. Applied to MRLs expressed on a fresh weight basis ^cBased on assumed bodyweight of 500 kg

Maximum anticipated dietary exposure:	80 40 mg/animal/day
equivalent to:	0.160.08 mg/kg bw
equivalent to:	42 ppm in the diet

MFL (Based on the available animal feeding data (Attachment 2)):	6 ppm in the diet
equivalent DDIL:	0.28 mg/kg bw*

* Based on actual doses and body weights in feeding study

Sheep

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	MRL, mg/kg	% DM^b	Intake of tebufenozide, mg/animal/day^c
Fruit by-products [4020% maximum]	Pome fruit pomace, dry	4020	1	10	-	105
Fruit by-products [4020% maximum]	Grape pomace, dry	4020	1	10	-	105
Total		4020	1			105
^aBased on assumed feed consumption of 2.5 kg dry matter/day ^bEstimate of percentage dry matter. Applied to MRLs expressed on a fresh weight basis ^cBased on assumed bodyweight of 60 kg

Maximum anticipated dietary exposure:	10 5 mg/animal/day
equivalent to:	0.170.08 mg/kg bw
equivalent to:	4 2 ppm in the diet

MFL (Based on the cattle feeding data (Attachment 2)):	6 ppm in the diet
equivalent DDIL:	0.25 mg/kg bw

Pigs

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	MRL, mg/kg	% DM^b	Intake of tebufenozide, mg/animal/day^c
Fruit by-products [20% maximum]	Pome fruit pomace, dry	20	0.5	10	-	5
Fruit by-products [20% maximum]	Grape pomace, dry	20	0.5	10	-	5
Total		20	0.5			5
^aBased on assumed feed consumption of 2.5 kg dry matter/day ^bEstimate of percentage dry matter. Applied to MRLs expressed on a fresh weight basis ^cBased on assumed bodyweight of 60 kg

Maximum anticipated dietary exposure:	5 mg/animal/day
equivalent to:	0.08 mg/kg bw
equivalent to:	2 ppm in the diet

MFL (Based on the cattle feeding data (Attachment 2)):	6 ppm in the diet
equivalent DDIL:	0.25 mg/kg bw

Attachment 2: Residue data

The residue definition of tebufenozide in Australia is the parent compound per se.

Selected residue data for animal feed commodities

Residue data for various crops including pome fruits, grapes and various subtropical fruits (inedible peel) were reviewed (Mimic Insecticide, product number 48462). Residues of tebufenozide in pome fruits and grapes are also reviewed in the 1996 JMPR, at:

http://www.fao.org/WAICENT/FAOINFO/AGRICULT/AGP/AGPP/Pesticid/JMPR/Download/96/tebufen2.pdf .

Selected animal transfer data and metabolism studies

Laying hens —tissues and eggs

Six groups of 10 hens each were dosed with three radiolabelled versions of tebufenozide for 7 days at a dose level of about 30 ppm in the diet. Actual doses were approximately 3.3 mg/day administered in a gelatin capsule. Hens weighed approximately 1.5 kg on average and feed consumption was approximately 110 g feed/day. The doses correspond to around 2.2 mg/kg bw/day. Another 10 birds served as untreated controls. ¹⁴C labels were on the ethylbenzoyl (A label), 3,5-dimethyl benzoyl (B label) and tert-butyl (T label) portions of the molecule. Tissues collected within 24 hours of sacrifice.

Results

Sample type	¹⁴C-Residues (mg equiv/kg)
	A-label	B-label	T-label
Liver	0.13	0.18	3.95
Fat	0.13	0.06	0.16
Thigh muscle	0.02	0.01	0.07
Breast muscle	0.006	0.000	0.03
Kidney	0.13	0.12	0.97
Eggs Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7	0 0.02 0.03 0.04 0.06 0.06 0.07	0 0 0.01 0.04 0.02 0.03 0.03	0 0.03 0.05 0.04 0.09 0.11 0.13

Average residues of tebufenozide parent compound in eggs (labels A, day 5 eggs, label B and T, day 7 eggs) from the three groups was 0.005 mg/kg. Tebufenozide was not detected in muscle or liver and average residues in fat were 0.018 mg/kg.

The feed level used in the metabolism study was approximately 60 times higher than the estimated maximum daily exposure of 0.5 ppm in the diet from Australian use patterns. Residues in poultry tissues and eggs are expected to be non-detectable at the estimated exposure level of 0.5 ppm and no analytical methods were available for poultry matrices therefore no poultry MRLs are considered necessary.

Lactating cows — milk and tissues

Lactating dairy cows were dosed orally by capsule with tebufenozide for 28 consecutive days at approximately 0, 6, 18 and 60 ppm in feed. The feed levels correspond to ca. 0.28, 0.79 and 2.51 mg/kg bw/day. Animals were withdrawn from dosing for 3 days and residues were determined in milk and tissues.

Tebufenozide residues in milk following 28 consecutive daily doses

Days of dosing	Average residues in milk at each dose level
	6 ppm	18 ppm	60 ppm
-1	0	0	0
0	0	(0.002)	(0.004)
3	0	(0.005)	0.025
6	0	(0.004)	0.021
9	0	(0.006)	0.024
13	0	(0.006)	0.017
16	(0.002)	(0.007)	0.026
20	(0.002)	(0.009)	0.028
23	(0.003)	(0.007)	0.019
27	0	(0.004)	0.015
30 (+3)	0	0	0

0 indicates less than the limit of detection or <0.003 mg/kg. The limit of quantitation was reported as 0.01 mg/kg. Results between LOD and LOQ are shown in parentheses.

Tebufenozide residues in tissues following daily dosing for 28 days

Matrix	Dose level	Days of	Residues (mg/kg)
	(ppm)	dosing	(Tebufenozide)
Liver	6	27	0.014, 0.008, 0.009
		30	<LOD
	18	27	0.041, 0.014, 0.026
		30	<LOD
	60	27	0.061, 0.101, 0.066
		30	<LOD
Kidney	6	27	<LOD (3)
		30	<LOD
	18	27	0.007, <LOD (2)
		30	<LOD
	60	27	0.007, 0.043, 0.006
		30	<LOD
Muscle	6	27	<LOD (3)
		30	<LOD
	18	27	0.022, <LOD (2)
		30	<LOD
	60	27	<LOD, 0.056, 0.028
		30	<LOD
Fat	6	27	0.029, 0.011, 0.011
		30	0.007
	18	27	0.109, <LOD, 0.063
		30	0.005
	60	27	0.063, 0.380, 0.23
		30	0.016

Day 30 of dosing = 3 days withdrawal. LOD 0.003 mg/kg (milk), 0.006 mg/kg (liver, muscle, kidney).