ARDS- Diafenthiuron May 2003

Diafenthiuron is registered in Australia for use on cotton to control two-spotted mite and cotton aphid. Details of the registered use pattern can be found on the approved labels of registered products containing diafenthiuron as the active constituent. This Animal Residue Data Sheet provides information on the possible residues in feed commodities obtained from crops treated with diafenthiuron, 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 diafenthiuron in food and animal feed commodities, as listed in Table 1 and Table 4 of the MRL Standard (as of April 2003 ) are shown below. The residue definition of diafenthiuron is the sum of diafenthiuron; N-[2,6-bis(1-methylethyl)- 4-phenoxyphenyl]-N'-(1,1-dimethylethyl)urea; and N-[2,6-bis(1-methylethyl)-4-phenoxyphenyl]- N'-(1,1-dimethylethyl)carbodiimide, expressed as diafenthiuron.

Code		Food	MRL, mg/kg
Food Commodities
SO	0691	Cotton seed	0.2

Animal commodities
MO	0105	Edible offal (mammalian)	*0.02
MM	0095	Meat (mammalian)[in the fat]	*0.02
ML	0106	Milks	*0.02

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 diafenthiuron are summarised below.

Species	MFL, ppm in diet	Equivalent DDIL, mg/kg bw	Equivalent intake of diafenthiuron, mg/animal/day
Cattle^a	2.4	0.096	48
Sheep^b	2.3	0.096	5.75
Pig^c	2.3	0.096	5.75
Poultry^d	N/A
^a Based on a 500 kg animal consuming 20 kg DM/day, extrapolated from sheep MFL. ^b Based on sheep feeding study ^c Based on a 60 kg animal consuming 2.5 kg DM/day, extrapolated from sheep MFL. ^d N/A= not applicable. No poultry data available. Cotton seed meal and hulls should not be fed to poultry.

Detailed information

All feed commodities

Feed commodities that may contain residues of diafenthiuron are listed in the table below. The theoretical maximum proportion of the diet that the commodity can compose, when residues are present at the MRL, without the significant risk of animal commodity MRLs being violated is also given. In this instance, cotton commodities (seed, meal and hulls) may be fed to livestock at 100 % of the theoretical dietary intake with minimal risk of violating the animal commodity MRLs. Calculations for cotton trash have been included to demonstrate that only small amounts may be used as animal feed without impacting upon the animal commodity MRLs. However, as the cotton industry practice recommends, cotton trash should not be used as an animal feed commodity. 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	STMR (mg/kg)^d	Maximum intake of diafenthiuron from commodity (mg/animal/day)^e	Theoretical maximum proportion of diet (%)^f
Cattle (Based on a 500 kg animal consuming 20 kg DM/day)
Cotton seed	30	6	0.06	0.36	100
Cotton seed meal	30	6	0.06	0.36	100
Cotton seed hulls	20	4	0.06	0.24	100

Sheep (Based on a 60 kg animal consuming 2.5 kg DM/day)
Cotton seed	30	0.75	0.1	0.15	100
Cotton seed meal	20	0.50	0.1	0.15	100
Cotton seed hulls	20	0.50	0.1	0.15	100

Pigs (Based on a 60 kg animal consuming 2.5 kg DM/day)
Cotton seed	30	0.75	0.06	0.045	100
Cotton seed meal	30	0.75	0.06	0.045	100
Cotton seed hulls	20	0.50	0.06	0.030	100

^a The feed commodities that may contain residues of diafenthiuron, 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 STMR (Supervised trial Median Residue) for each feed commodity (correction for dry weight basis where required) ^e The maximum intake of diafenthiuron when the commodity is fed at the maximum assumed level (Column 1) in the absence of other sources of diafenthiuron. ^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 diafenthiuron 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. For example: a cow consumes 10 kg of grain containing 10 mg/kg of diafenthiuron and 10 kg of apple pomace containing 5 mg/kg of diafenthiuron. The total intake of diafenthiuron is 150 mg in 20 kg of feed. This is equivalent to 7.5 ppm in the feed [150÷20].

STMR: The Supervised Trial Median Residue. The highest residue that livestock are likely to be exposed to in practice when fed the commodity over a prolonged period.

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. As shown below, cotton trash data has been considered separately. It is not considered good agricultural practice to use cotton trash as an animal feed commodity.

Cattle

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	STMR, mg/kg	% DM^b	Intake of diafenthiuron, mg/animal/day^c
Oilseeds	Cotton seeds	30	6	0.06	-	0.36
Plant protein meals	Cotton seed meal	30	6	0.06	-	0.36

Total		100				1.2
^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:	0.72	mg/animal/day
equivalent to:	0.00144	mg/kg bw
equivalent to:	0.036	ppm in the diet

MFL (Based on the sheep feeding data (Attachment 2):	2.4	ppm in the diet
equivalent DDIL:	0.096	mg/kg bw

Sheep

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	STMR, mg/kg	% DM^b	Intake of diafenthiuron, mg/animal/day^c
Oilseeds	Cotton seeds	30	0.75	0.06	-	0.045
Plant protein meals	Cotton seed meal	20	0.50	0.06	-	0.030

Total		100				0.075
^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:	0.075	mg/animal/day
equivalent to:	0.00125	mg/kg bw
equivalent to:	0.03	ppm in the diet

MFL (Based on the sheep feeding study (Attachment 2):	2.3	ppm in the diet
equivalent DDIL:	0.096	mg/kg bw

Pigs

Feed group	Feed commodity	% in the diet	Feed intake, kg/animal/day^a	STMR, mg/kg	% DM^b	Intake of diafenthiuron, mg/animal/day^c
Oilseeds	Cotton seed	30	0.75	0.06	-	0.045
Plant protein meals	Cotton seed meal	30	0.75	0.06	-	0.075

Total		100%				0.12
^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:	0.12	mg/animal/day
equivalent to:	0.002	mg/kg bw
equivalent to:	0.048	ppm in the diet

MFL (Based on the sheep feeding study (Attachment 2):	2.3	ppm in the diet
equivalent DDIL:	0.096	mg/kg bw

Attachment 2: Residue data

Introduction

The residue definition of diafenthiuron is the sum of diafenthiuron; dimethylethyl urea (CGA 177960) and carbodiimide (CGA 140408), expressed as diafenthiuron. A conversion factor of 1.044 is required to express dimethylethyl urea as parent equivalents.

Selected animal transfer data

Sheep Study

Reference: George B. and Adams, S., The Accumulation and depletion of diafenthiuron in Sheep, Ciba-Geigy Crop Protection Technical Report No. 96/6/1527, 1996.

In the sheep study, animals were dosed at 20 mg ai/animal for 56 days. The dose was equivalent to 20 ppm in the feed, assuming 1 kg dry matter is consumed per day. The mean body weight of the sheep used in the study was 34.9 kg. Groups of animals were slaughtered at 14, 28, 42 and 56 days of feeding and at 56 days feeding plus 14 days withdrawal. Samples of blood, plasma, muscle, liver, kidney, omental fat, renal fat and subcutaneous fat were analysed for residues. In metabolism studies, the diimide metabolite is the predominant compound present in animal tissues. The results of the diimide metabolite (CGA 177960) are shown in the table below.

Table 1: Residues of diafenthiuron diimide in sheep tissues at various times after dosing.

Days of	Residues diafenthiuron diimide (mg/kg)
dosing	Muscle	Kidney	Liver	Omental fat	Renal fat	Subcutaneous fat
14	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	0.05, <0.02	<0.02, <0.02
28	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02
42	nd	nd	nd	0.03, 0.03	0.03, 0.04	<0.02, <0.02
56	<0.02, <0.02, <0.02, <0.02	<0.02, <0.02, <0.02, <0.02	<0.02, <0.02, <0.02, <0.02	0.04, 0.04, 0.03, 0.11	0.05, 0.05, 0.05, 0.12	<0.02, <0.02, <0.02, <0.02
56 + 14	nd	nd	nd	<0.02, <0.02	0.02, 0.05	<0.02, <0.02

Nd = not determined. Limit of determination = 0.02 mg/kg for all tissues.

The data show that feeding at levels equivalent to 20 ppm in the feed result in non-detectable residues in muscle, kidney, liver and subcutaneous fat, but finite residues in omental and renal fat. If the dosing level is scaled in relation to the likely exposure from treated cotton seed (0.1 mg/kg), non-detectable residues would be expected in all tissues, including omental and renal fats. Based on the sheep feeding study, the MRLs of *0.02 mg/kg for meat (mammalian) [in the fat] and edible offal (mammalian) were established.

In order to calculate the Maximum Feed Level (MFL) for sheep, the feeding level in the sheep study is scaled to the estimated feed level where resides are expected to be below 0.02 mg/kg. Thus, when a factor of 6 is applied, a maximum feed level of 3.33 ppm is likely to result in residues at or about the LOQ of 0.02 mg/kg in all tissues, including fat. The MFL has been "normalised" to an animal of 60 kg and having a daily intake of 2.5 kg of DM. This equates to an MFL of 2.3 ppm for sheep.

The sheep MFL has been extrapolated to calculate MFL for cattle and pigs, assuming the transfer factor is equivalent in all species. However it is noted that in JMPR 2002, extrapolation between species is generally not supported. Data indicates that the transfer factor of residues for sheep, goats and pigs is approximately the same for cattle, if not lower. Conversely, the transfer factor may be higher in cattle when extrapolating from sheep/ goats. Accordingly, unless there is animal feeding data available from cattle, the MFL for cattle may be underestimated. When extrapolating the MRL for cattle, it has been scaled to an animal of 500 kg with a daily intake of 20 kg. This calculates to an equivalent MFL of 2.4 ppm for cattle. In a similar fashion, the MFL for pigs is 2.3 ppm.

Goat Study

Reference: R. Rümbeli, The nature of metabolites in urine, faeces, milk and tissue extracts of lactating goats after multiple oral administration of 2-[2-14C]isopropyl CGA 106630, Project 92RR01, Report 19/93, Switzerland, 13 August 1993.

A goat was dosed with14C-diafenthiuron at equivalent to 5 ppm in the diet for four days. Pooled milk and tissue results expressed in ¹⁴C equivalent (mg/kg) are tabulated below.

TRR (mg/kg equivalents)

Milk

0-24 hr

Milk

24-48 hr

Milk

48-72 hr

Milk

72-81 hr

Liver

Kidney

Muscle

Fat

0.013

0.018

0.021

0.029

0.60

0.03

0.01 (mean)

0.15 (mean)

In the goat metabolism study, the maximum total radioactive residue (TRR) of 0.029 mg/L was found in milk over a 4 day dosing period. If the dose level is scaled in relation to the exposure likely from treated cotton seed (0.1 mg/kg), residues in milk are likely to be below the limit of quantitation of 0.02 mg/kg. Based on the limits of quantitation in other tissues, an MRL of *0.02 mg/kg was established for milk. It is noted that residue level in milk had not stabilised at the end of the study, maximum 0.029 mg/kg TRR at day 4. However, it is unlikely that residues would be significant to impact upon the milk MRL.

Selected residue data for animal feed commodities

Cotton

Diafenthiuron is registered for use on cotton at 300 or 400 g ai/ha. Relevant residue data from trials conducted in Australia, Israel, South Africa and Spain are tabulated below. In order to account for different application rates used in the trials, the total residue level has been scaled proportionately to the maximum Australian rate of 400 g ai/ha. In cases where the total residue was less than the limit of detection, the total (scaled) residue level was not adjusted. To sum the total residue level, a conversion factor of 1.044 was applied to express CGA 177960 as parent equivalents (only when there were finite levels present).

Cotton seed and oil:

Trial Site	Application			Sample	DAT	Residues (mg/kg)
Year, Report No.	Rate (g ai/ha)	Interval (days)	No.			Diafenthiuron	CGA 140408	CGA 177960	Total	Total (scaled)
Moree, NSW, 1993	400	24	2	seed	37	<0.02, <0.02, <0.02, 0.04	<0.02, <0.02, <0.02, <0.02	<0.02, <0.02, <0.02, <0.02	<0.06, <0.06, <0.06, <0.06	<0.06, <0.06, <0.06, <0.06
93/7/1418	800	24			37	<0.02, <0.02, <0.02, <0.02	<0.02, <0.02, <0.02, <0.02	<0.02, <0.02, <0.02, <0.02	<0.06, <0.06, <0.06, <0.06	<0.06, <0.06, <0.06, <0.06
Moree, NSW,	400	22	2	seed	34	0.04, 0.03	<0.02, <0.02	0.04, 0.04	0.102, 0.092	0.102, 0.092
1994, 96/1/1515	800	22	2	seed	34	<0.02, 0.03	<0.02, <0.02	0.03, 0.05	0.071, 0.102	0.036, 0.051
Melrose, Qld,	400	20	2	seed	36	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
1995, 96/1/1515				oil		<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
	800	20	2	seed	36	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
				oil		<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
Israel, 1127/89	500	3	9	Seed (dehulled)	30	<0.04	0.04	0.04	0.122	0.097
South Africa, 1005/88	300	3	7- 8	Seed (dehulled)	35	nd	0.03	<0.04	0.07	0.09
South Africa, 1006/88	400	3	7- 8	Seed (dehulled)	35	<0.03	0.03	<0.04	0.07	0.07
South Africa, 1007/88	300	3	8	Seed (dehulled)	35	<0.03	0.02	<0.04	0.09	0.12
South Africa, 1008/88	400	3	7- 8	Seed (dehulled)	35	nd	0.04	<0.04	0.08	0.08
Spain, 1157/87A2	400	5	7	Seed (delinted)	42	nd	<0.03	<0.035	0.07	0.07
Spain, 1156/87B2	400	5	7	Seed (delinted)	35	nd	<0.03	<0.035	0.07	0.07
Spain, 1158/87A2	400	4	7	Seed (delinted)	42	nd	<0.03	<0.035	0.07	0.07
Spain, 1158/87B2	400	5	7	Seed (delinted)	35	nd	<0.03	<0.035	0.07	0.07

Median cotton seed residue = <0.06 mg/kg

Average cotton seed residue = 0.07 mg/kg

Maximum cotton seed residue = 0.12 mg/kg

Cotton Seed Hulls:

Trial Site	Application			Sample	DAT	Residues † (mg/kg)
Year, Report No.	Rate (g ai/ha)	Interval (days)	No.			Diafenthiuron	CGA 140408	CGA 177960	Total	Total (scaled)
Melrose, Qld,	400	20	2	hulls	36	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
1995, 96/1/1515	800	20	2	hulls	36	<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
South Africa, 1006/88	400	3	7- 8	Hulls	35	<0.03	0.09	<0.03	0.15	0.15
South Africa, 1007/88	300	3	7- 8	Hulls	35	<0.02	0.08	<0.03	0.13	0.173

Median cotton hull residue = <0.06 mg/kg

Average cotton hull residue = 0.09 mg/kg

Maximum cotton hull residue = 0.175 mg/kg

Cotton Seed Meal:

Trial Site	Application			Sample	DAT	Residues (mg/kg)
Year, Report No.	Rate (g ai/ha)	Interval (days)	No.			Diafenthiuron	CGA 140408	CGA 177960	Total	Total (scaled)
Melrose, Qld,	400	20	2	meal		<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06
1995, 96/1/1515	800	20	2	meal		<0.02, <0.02	<0.02, <0.02	<0.02, <0.02	<0.06, <0.06	<0.06, <0.06

Median cotton seed meal residue = <0.06 mg/kg

Average cotton seed meal residue = <0.06 mg/kg

Maximum cotton seed meal residue = <0.06 mg/kg