Animal Residue Data Sheet - Methoprene

Last updated J June 2002

Methoprene is registered in Australia for use on cereal grains. Details of the registered use patterns can be found on the approved labels of registered products containing methoprene as the active constituent. This Animal Residue Data Sheet provides information on the possible residues in feed commodities obtained from crops treated with methoprene. It also provides information on the anticipated maximum dietary exposure of animals fed treated commodities, which should not result in the violation of animal MRLs.

Current MRLs

The Australian MRLs for methoprene in food and animal feed commodities, as listed in Table 1 and Table 4 of the MRL Standard [as at 7 June 2002] are shown below. The residue definition of methoprene is methoprene, sum of cis- and trans-isomers.

Code	Food	MRL, mg/kg
Food Commodities
GC 0080	Cereal grains	2
CM 0654	Wheat bran, unprocessed	5
CF 1210	Wheat germ	10

Animal commodities
ML 0812	Cattle Milk	0.1
MO 0105	Edible offal (mammalian)	*0.01
MM 0095	Meat [mammalian][in the fat]	0.3

Animal feed commodities
There are no current animal feed commodity Table 4 entries

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 methoprene are summarised below. Please note that poultry MRLs have not been established.

Species	MFL, ppm in diet	Equivalent DDIL, mg/kg bw	Equivalent intake of methoprene, mg/animal/day
Cow (milk)	2	0.08	40
Cattle^a	2	0.08	40
Sheep ^b	2	0.08	5
Pig ^c	2	0.08	5
Poultry^d	None determined	None determined	-
^a Based on a 500 kg animal consuming 20 kg DM/day ^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 ^d Based on a 2 kg animal consuming 150 g DM/day

Detailed information

All feed commodities

Feed commodities that may contain residues of methoprene 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. For instance, were apple pomace to be fed to cattle at 50% of the diet, the remainder of the diet would need to be free of residues of methoprene to minimise the risk of cattle commodity MRLs being violated. 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. Please note that no calculations were undertaken for wheat germ as it is not normally fed to animals.

Commodity^a	Assumed Maximum proportion of diet (%)^b	Feed intake (kg/animal/day)^c	MRL (mg/kg)^d	Maximum intake of methoprene from commodity (mg/animal/day)^e	Theoretical maximum proportion of diet (%)^f
Cattle (Based on a 500 kg animal consuming 20 kg DM/day)
Cereal grains	100	20	2	40	100
Wheat bran, unprocessed	40	8	5	40	40
Wheat germ	Nil	-	10	-	-

Sheep (Based on a 60 kg animal consuming 2.5 kg DM/day)
Cereal grains	100	2.5	2	5.0	100
Wheat bran, unprocessed	Nil	-	5	-	-
Wheat germ	Nil	-	10	-	-

Pigs (Based on a 60 kg animal consuming 2.5 kg DM/day)
Cereal grains	100	2.5	2	5.0	100
Wheat bran, unprocessed	40	1.0	5	5.0	40
Wheat germ	Nil	-	10	-	-

Poultry (Based on a 2 kg animal consuming 150 g DM/day)
Cereal grains	100	0.15	2	0.3	100
Wheat bran, unprocessed	40	0.06	5	0.3	40
Wheat germ	Nil	-	10	-	-

^a The feed commodities that may contain residues of methoprene, 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 methoprene when the commodity is fed at the maximum assumed level (Column 2) in the absence of other sources of methoprene. ^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 methoprene 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) x body weight (kg) ÷ by daily feed intake (kg).

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 methoprene, mg/animal/day^c
Grain	Cereal grains	100	20	2	-	40
Processed grain fractions	Wheat bran, unprocessed	Nil
Total		100	20			40
^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:	40 mg/animal/day
equivalent to:	0.08 mg/kg bw
equivalent to:	2 ppm in the diet

MFL (Based on the available animal feeding data (Attachment 2)):	2 ppm in the diet
equivalent DDIL:	0.08 mg/kg bw

Sheep

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	MRL, mg/kg	% DM^b	Intake of methoprene, mg/animal/day^c
Grain	Cereal grains	100	2.5	2	-	5.0
Processed grain fractions	Wheat bran, unprocessed	Nil
Total		100	2.5	2		5.0
^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 cattle data, as no sheep feeding data available):	2 ppm in the diet
equivalent DDIL:	0.08 mg/kg bw

Pigs

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	MRL, mg/kg	% DM^b	Intake of methoprene, mg/animal/day^c
Grain	Cereal grains	100	2.5	2	-	5.0
Processed grain fractions	Wheat bran, unprocessed	Nil
Total		100	2.5			5.0
^a)Based on assumed feed consumption of 2.5 kg dry matter/day ^b)Estimate of percentage dry matter. Applied to MRLs expressed on a fresh weight basis ^c)Based 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 cattle data, as no pig feeding data available):	2 ppm in the diet
equivalent DDIL:	0.08 mg/kg bw

Poultry

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	MRL, mg/kg	% DM^b	Intake of methoprene, mg/animal/day^c
Grain	Cereal grains	100	0.15	2	-	0.3
Processed grain fractions	Wheat bran, unprocessed	Nil
Total		100	0.15			0.3
^aBased on assumed feed consumption of 0.150 kg dry matter/day ^bEstimate of percentage dry matter. Applied to MRLs expressed on a fresh weight basis ^cBased on assumed bodyweight of 2 kg

Maximum anticipated dietary exposure:	0.3 mg/animal/day
equivalent to:	0.15 mg/kg bw
equivalent to:	2 ppm in the diet

MFL:	No relevant data has been considered by the NRA that would allow the recommending of either MRLs or MFLs.
equivalent DDIL:	NA

Attachment 2: Residue data

The residue definition of methoprene in Australia is the sum of cis- and trans-isomers of methoprene.

Selected residue data for animal feed commodities

Methoprene residues in grains

Grain	Country of trial	Treatment rate (g/t)	Methoprene residue (mg/kg) at months (m) after treatment
Grain	Country of trial	Treatment rate (g/t)	0-1.9m	2-5.9m	6-8.9m	> or equal to 9m
Maize	USA	1.1				0.16
Wheat	Australia	0.83	0.66	0.65	0.61	0.72
		0.86	0.75	0.58	0.59	0.53
		0.97	0.55	0.54	0.54
		0.98	0.71	0.86	0.63
		1.0	0.38
		1.0	0.65
		1.0	0.78
		1.0	0.47
		1.0	0.5	0.3	0.3	0.3
		1.0	0.45
		1.0	1.95
		1.0	0.55
		1.0	0.96
		1.0	0.68	0.64	0.73	0.62
		1.0	0.7	0.6	0.8	0.7
		1.0	0.53	0.53	0.56	0.63
		1.0	1.93	0.53	0.61	0.69
		1.0	0.64	0.48	0.64	0.74
		1.02	1.09	1.14	0.83	0.66
		1.1	0.59	0.55	0.57	0.70
Rice	Australia	0.9	0.45	0.33
	Thailand	1.0		0.66
	USA	1.0	0.42
	USA	1.0	0.39
Sorghum	Australia	1.0	0.8	0.98
Sorghum	Australia	1.0	0.93	0.78
Barley	Australia	1.0	0.65
		1.0	0.34
		1.0	0.63
		1.0	0.50
		1.0	0.60	0.56	0.55	0.51
		1.0	0.72	1.1	0.91	0.93
Oats	Australia	1.0	0.77
		1.0	0.51
		1.0	0.96
		1.0	0.65
		1.0	1.0	0.58	0.65	0.94
		1.0	0.74	0.53	0.96	1.02

Data demonstrating the distribution of methoprene in grain fractions is shown below:

Grain	Treatment rate (g/t)	Storage (months)	Methoprene residue (mg/kg)
Grain	Treatment rate (g/t)	Storage (months)	Grain	Bran	Pollard
Wheat	1.0	13	0.7	1.2	1.5
	1.0	9	0.60	1.8	2.4
	1.0	9	0.61	1.4	2.3
Rice	0.93	3	0.35	0.99	1.8 (hulls)
Rice	0.93	4.5	0.31	0.90	1.4 (hulls)

Selected animal transfer data

Lactating cows — milk

Lactating cows were dosed orally for 28 days with methoprene, at average dosages of 1.53, 4.07 and 14.8 mg/cow/day (equivalent to 0.1, 0.3 and 1.0 ppm in feed). Milk samples were taken daily.

Animal No.	Approximate dose rate in the diet (ppm)	Methoprene residues in whole milk (mg/kg) at sampling day
Animal No.	Approximate dose rate in the diet (ppm)	2	4	8	12	16	20	24	28
36	0.1 (0.0027 mg/kg bw)	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
99	0.1	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
111	0.1	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
121	0.1	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
18	0.3 (0.0078 mg/kg bw)	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
102	0.3	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
116	0.3	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
218	0.3	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
37	1.0 (0.028 mg/kg bw)	<0.01	<0.01	0.012	<0.01	<0.01	<0.01	<0.01	<0.01
107	1.0	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
120	1.0	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
124	1.0	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01

A 1986 JMPR review of the milk residue data for methoprene has indicated that the mean residue in the milk of three cows after 28 day feeding at approximately 1.5 ppm in the feed were 0.014 mg/kg and the highest residue level for an individual cow was 0.03 mg/kg. Consequently, JMPR recommended an MRL of 0.05 mg/kg for Cattle milk.

Taking into account that cattle can be fed at a higher rate (MRL of 2 mg/kg for cereal grains) than the feeding rate of 1.5 ppm in the diet, the recommended MRL of 0.1 mg/kg for Cattle milk is considered appropriate and the maximum feeding level 2 ppm.

A radiolabelled study indicated that residues in milk decline with a half-life of approximately 45 hours. The data is available on file at the NRA.

Cattle - tissues

Cattle were dosed daily by capsule for 7-21 weeks with methoprene at 0.016, 0.048 and 0.16 mg/kg bw, equivalent to 0.5, 2 and 5 ppm in the feed. Residue levels of methoprene found in omental fat by biopsy from two animals from each treatment group are as follows:

Samples taken on week	Maximum methoprene residues in omental fat (mg/kg)
Samples taken on week	0.5 ppm	2 ppm	5 ppm
1	0.05	0.12	0.32
2	0.16	0.14	0.30
3	<0.01	0.01	0.15
4	0.07	0.16	0.38
5	0.06	0.12	0.36
6	0.06	0.14	0.31
7	0.05	0.17	0.21
14			0.41
21			0.29

Residues of methoprene (mg/kg) found in tissues of the cattle at 7 weeks following slaughter were:

Dosage group (mg/kg b.w)	ppm methoprene in the diet	Methoprene residues (mg/kg)
Dosage group (mg/kg b.w)	ppm methoprene in the diet	Omental fat	Renal fat	Subcut. fat	Liver	kidney	fore quarter muscle	hind quarter muscle	back muscle
0.014	0.46	0.05	0.05	0.04	<LOQ	<LOQ	<LOQ	<LOQ	<LOQ
0.014	0.46	NA	0.04	0.03	<LOQ	<LOQ	<LOQ	<LOQ	<LOQ
0.057	1.88	0.17	0.15	0.09	<LOQ	<LOQ	<LOQ	<LOQ	<LOQ
0.048	1.58	0.09	0.11	0.12	<LOQ	<LOQ	<LOQ	<LOQ	<LOQ
0.048	1.58	0.14	0.17	0.12	<LOQ	<LOQ	<LOQ	<LOQ	<LOQ
0.153	5.0	0.21	0.39	0.28	<LOQ	<LOQ	<LOQ	0.03	0.07
0.143	4.7	0.21	0.40	0.29	<LOQ	<LOQ	<LOQ	<LOQ	<LOQ

For cattle tissues, the maximum feeding level at which the residue in fat would comply with the MRL of 0.3 mg/kg was 2 ppm.

Cattle - decline of residues

Cattle were fed methoprene at 0.028mg/kg bw for 28 days and single animals slaughtered at 7 and 14 days post treatment. Residues occureed in live (0.016 and 0.021 mg/kg) at the end of feeding and these were ,0.01 mg/kg Methoprene 7 days later. Residues found in fat are shown following:

Withdrawal period (days)	Methoprene residues (mg/kg)
Withdrawal period (days)	Omental fat	Renal fat	Subcutaneous fat
0	0.079	0.02	0.2
7	0.036	0.04	0.01
14	0.027	0.03	0.02

Cattle were fed methoprene at either 0.033 or 0.1 mg/kg bw for 7 weeks followed by slaughter at 0-3 weeks later. Results in the fat were as follows:

Dosage rate (mg/kg bw)	Withdrawal period (days)	Methoprene residues (mg/kg)
Dosage rate (mg/kg bw)	Withdrawal period (days)	Omental fat	Renal fat	Subcut. fat
0.033	0	0.13	0.14	0.11
	7	0.06	0.06	0.11
0.01	0	0.21	0.40	0.28
	7	0.22	0.28	0.28
	14	0.22	0.12	0.22
	21	0.17	0.12	0.12

Poultry

JMPR reported that when chickens were given feed treated with methoprene at 0, 25, 50 and 100 ppm for 14-63 days, residues in poultry meat and eggs were less than 0.1 mg/kg.

Published data (Quistad et al 1976; Ag Food Chem 24(3): 644-648) indicated that a residue of 8.03 mg/kg occurred in egg white at a dose rate of 77 mg/kg bw, and residues of 0.056 mg/kg occurred in egg yolk at a dose rate of 0.6 mg/kg bw. No detectable residues of methoprene occurred in muscle or liver, but a residue of 2.1 mg/kg was found in chicken fat when dosed at 59 mg/kg bw. No MFL or MRLs could be recommended from the data.