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FIPRONIL
of the second stage of the review programme referred to in Article 8(2)
of Council Directive 91/414/EEC
January 2005
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B.7.8 Livestock feeding studies
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B.7.8.1 Dairy cattle
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(Byrd. J.W.; 1994a)
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Study 1 (Byrd. J.W. 1994a ):
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Eleven animals were dosed orally, once per day with encapsulated fipronil for 35 consecutive days. Two
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animals served as untreated control. The nine others were divided into 3 groups that were treated at the
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nominal level of 0.04 – 0.12 and 0.40 mg/kg feed/day respectively (dry matter basis). The actual average
daily doses calculated on the feed intake (dry weight basis) and the animal body weights were:
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- Group I: 0.04 mg/kg feed d.m./day (equivalent to 0.0011 mg/kg b.w./day)
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- Group II: 0.13 mg/kg feed d.m./day (equivalent to 0.0031 mg/kg b.w./day)
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- Group III 0.43 mg/kg feed d.m./day (equivalent to 0.0101 mg/kg b.w./day)
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Based on a maximum residue intake by animal of 0.01 mg/kg d.m./day as calculated in section B.7.12.3,
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these doses have to be considered as an 4X, 16X and 43X dose levels respectively.
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The animals were milked twice daily (morning/evening) throughout the study. The morning and evening
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milk samples were composited and sub samples were taken for residue analysis. Plateau level of fipronil
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in cow was established by monitoring the fipronil derived residue level in milk. Once the residue plateau
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level in milk was achieved. the animals were slaughtered and the tissues sent for analysis.
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The milk and tissue samples were analysed for fipronil, MB46136 (sulfone) and MB45950 (sulfide).
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Residues of fipronil and its metabolites were extracted from samples with acetonitrile/acetone and the
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extracts cleaned on florisil/silica gel/activated carbon column prior CG/ECD analysis. The recoveries of
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the fortifications performed on milk and tissues were in the range of 84% to 114%. Triplicate analyses
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were performed on each milk and animal tissues. The limit of quantification was 0.010 mg/kg.
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This additional study was performed in order to provide supplemental data on:
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- the rate of fipronil residue decline in milk following the termination of dosing
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Three lactating dairy cows were administered fipronil daily at a rate equivalent to 1.0 mg/kg in the feed
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(actual daily dose: 1.04 mg/kg feed d.m./day. equivalent to 0.0402 mg/kg b.w./day). A fourth cow served
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as control. The cows were treated orally each day following the morning milking. The oral fipronil
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administration lasted for 20 days. Milk samples were collected on day 14, 16, 18 and 20 prior to the
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termination of the dosing and on day 1, 2, 4, 7 and 19 following the termination of dosing. Milk fat was
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separated from whole milk collected on the last day of dosing only. Milk samples were analysed for fipronil.
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MB45950 and MB46136. Apart milk, no other tissues were analysed in this study.
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Findings: Table B.7.8.1a below summarised the residue level observed in milk from day 0 to day 34
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(study 1) and from day 14 to day 39 (study 2). each figure being the mean of three values and assuming
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Table B.7.8.1a: Summary of fipronil and metabolite residues in whole milk (mg/kg)
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Fipro. 45950 46136 Fipro. 45950 46136 Fipro. 45950 46136 Fipro. 45950 46136
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0 ND ND ND ND ND ND ND ND ND
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a b
ND=No detectable residue : mean day 3 to 34 : maximum of individual value
c
: mean of 24 data. of which 14 <0.010 mg/kg taken as equal to 0.010 mg/kg
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For the 0.04 and 0.13 ppm dose levels, residues in milk remained very low throughout the dosing period
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and no transfer of fipronil and MB45950 were observed in milk samples (individual values reported mostly
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as not detectable). Metabolite sulfone MB46136 was the sole compound detected with a maximum value
as
of 0.018 mg/kg.
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At the high dose level (0.43 ppm), residues in milk were high enough to ascertain that a steady state was
on
reached after 4 weeks of dosing. The residue was predominantly comprised of MB46136 with trace
amount of fipronil (<0.010) and insignificant amount of MB45950 (reported mostly as not detectable). On
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the basis of these data, where steady state concentration is reached after 4 weeks, fipronil is to be
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considered as a substance for which the residue reaches a plateau slowly.
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In the 1.04 ppm dose group, a decline of the fipronil derived residue was observed following the cessation
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of the dosing in the second study. The decline was about 66% after one week and MB46136 residues
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were only found at approximately 0.005 mg/kg after nineteen days. The estimated half-life of MB46136 in
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milk was calculated as 5.2 days.
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In the milk fat sample obtained on the last day of dosing (day 20) MB46136 was also the major
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component of the total residue. A transfer factor of fipronil derived residue (mainly MB46136) from whole
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milk to milk fat was calculated as 14 indicating that the residues concentrated in milk fat.
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Table B.7.8.1b: Transfer factor Whole milk / fat milk
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Milk Sample Residue (mg/kg)
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(day 20) fipronil MB45950 MB46136
Whole milk <0.003 <0.003 0.037
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iso
In animal tissues (table B.7.8.1c) the highest fipronil derived residue was observed for fat samples as
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expected from the lipophilic character of the molecule. At the three dose levels, negligible amounts of
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MB45950 were found in all animal matrices. As for milk sample, the residue was almost entirely
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comprised of MB46136. Fipronil was only observed at significant level in the fat sample only.
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Sample 0.04 mg/kg dose 0.13 mg/kg dose 0.43 mg/kg dose
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ND = No detectable residue
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The residues observed in milk and in animal tissues appeared to be strictly linearly related to the residue
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dose levels in animals feed. Linear regressions are shown in the figure B.7.8.1 overleaf, the calculation
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- Residues were expressed as “sum of fipronil and sulfone” only (MB45950 not taken into account),
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Figure B.7.8.1: Linear regression between residue levels in feed and residue levels in dairy cattle tissues
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Re sidue s in tissue s
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0,60
(mg/kg)
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Fat
as
y = 1,1365x + 0,0144
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0,50 Fat
R2 = 0,9988
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Liver
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Milk
0,40
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Muscle
Kidne y
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Kidney y = 0,0707x + 0,0042
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0,30 R2 = 0,9737
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Milk
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y = 0,1325x + 0,0002
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0,20 R2 = 0,9996
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Muscle
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y = 0,1030x - 0,0029
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0,10 R2 = 0,9956
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Live r
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y = 0,3035x + 0,0038
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0,00
R2 = 0,9936
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0,000 0,100 0,200 0,300 0,400 0,500
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Dose le ve l (mg/kg b.w./day)
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Table B.7.8.1c hereafter gives the transfer factors (TF) for each tissue, calculated as the ratio of the total
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residue in the animal tissue over the residue content in the feed. The mean transfer factors were
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calculated using the mean of triplicate analyses performed on each milk and tissue samples and the
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maximum transfer factor, using the maximum individual value. Total fipronil derived residues (fipronil +
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- For any residue values reported as not detectable, the residue value was taken as zero.
- For residue value reported as below the LOQ (<0.010 mg/kg), the value was assumed to be equal to
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0.005 mg/kg.
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Fat
Maxb 0.069 1.70 0.223 1.72 0.588 1.37
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Liver
Maxb 0.012 0.30 0.061 0.47 0.160 0.37
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Meana
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ND: No detectable residue NA: Not applicable (a reliable TF cannot be derived from concentrations <0.01 or ND)
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a b
: calculated with the mean of 3 individual analyses : calculated with the maximum out of 3 individual analyses
to
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Conclusions: MB46136 was the major component of the total residue whatever the investigated
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matrices. Due to the lipophilic nature of the compound, the highest residue was found in fat. Fipronil
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parent compound was observed at significant level in fat only. MB45950 was reported as non-detectable
or
in most of the animal tissues/milk (except in one case at the high dose level for milk and for fat where it
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The residues observed in milk and in animal tissues appeared to be strictly linearly related to the residue
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dose levels in animal feed. Maximum and mean transfer factors in milk and animal tissues were
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B.7.8.2 Laying hens feeding study
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(Byrd J.W.; 1994)
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Forty laying hens were chosen for this study and dosed orally once per day with encapsulated fipronil for
42 consecutive days. The animals were divided into 3 groups treated at the nominal dose level
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corresponding to 0.01 - 0.03 and 0.10 mg/kg in feed (dry matter basis) respectively and an additional control
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group. The actual average daily dose rate calculated on the mean feed intake (98 – 90 and 109 g d.m. for
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each group respectively) and the mean animal body weights (1.464 – 1.629 and 1.676 kg) were:
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- Group I: 0.010 mg/kg feed d.m./day (equivalent to 0.0007 mg/kg b.w./day)
- Group II: 0.031 mg/kg feed d.m./day (equivalent to 0.0017 mg/kg b.w./day)
ed
- Group III 0.103 mg/kg feed d.m./day (equivalent to 0.0067 mg/kg b.w./day)
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Based on a maximum residue intake by animal of 0.0019 mg/kg d.m./day as calculated in section
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B.7.12.3, these doses have to be considered as a 5X, 16X and 54X dose levels.
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Eggs were collected twice daily (morning and evening). The egg samples were combined and sent for
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residue analysis. Plateau level of fipronil-derived residues in hens was monitored through the residue
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analysis in eggs. Once the residue plateau level in eggs was achieved, the animals were slaughtered and
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the tissues sent for analysis. The tissue samples were analysed for fipronil, MB45950 and MB46136 using
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similar analytical method such as described previously in the dairy cow study. Triplicate analyses were
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performed on each animal tissue and the limit of quantification was 0.010 mg/kg in all animal tissues.
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Findings: The residue levels in eggs and poultry tissues are reported in tables B.7.8.2a&b, each figure
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being the mean of three values. Apart from sporadic findings of traces of MB46136, no significant residues
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were observed in eggs at the low dose level. Data obtained on eggs from the medium and high dose levels
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indicate that a plateau level had been reached after 3-4 weeks of feeding.
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iso
Study 0.010 mg/kg dose 0.031 mg/kg dose 0.103 mg/kg dose
d
Day Fipronil 45950 46136 Fipronil 45950 46136 Fipronil 45950 46136
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0 ND ND ND ND ND ND ND ND ND
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1 ND ND ND ND ND ND ND ND ND
tb
3 ND ND <0.010 ND ND ND ND ND <0.010
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a
: maximum of individual value
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On the basis of the data obtained on eggs at the medium and high doses, where steady state
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At all dose levels, no MB45950 was found in the egg samples (reported as not detected). Trace amounts
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of fipronil, if any, were observed at the high dose level only (the highest residue found to be
to
<0.010 mg/kg). MB46136 was found to be the major component of the total residue with maximum
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individual residue levels of 0.036 and 0.116 mg/kg at day 34 and 25 for the medium and high dose levels
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respectively.
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Residues observed in tissues are detailed in table B.7.8.2b hereafter. MB45950 was not observed at any
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dose level (only 1 value was reported as below 0.010 mg/kg at medium level and none for the high dose
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group). Negligible amounts of fipronil were observed at the medium and high doses, although these
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amounts could be qualified as trace since they were below 0.010 mg/kg at the most. The highest residue
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content was found in the skin with adhering fat, no matter the dose level, and was comprised mostly of
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MB46136.
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Table B.7.8.2b : Summary of fipronil and metabolites residues (mg/kg) in hen tissues
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Sample 0.010 mg/kg dose 0.031 mg/kg dose 0.103 mg/kg dose
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Fipronil 45950 46136 Fipronil 45950 46136 Fipronil 45950 46136
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Muscle ND ND <0.010 ND ND <0.010 ND ND 0.012
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Liver ND ND <0.010 ND ND 0.020 <0.010 ND 0.069
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Skin with fat ND ND 0.013 <0.010 ND 0.054 <0.010 ND 0.191
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on
As previously for dairy cattle, residues in eggs and tissues indicated a strict linear relationship with the
residue dose levels in animals feed. Linear regressions are shown in the figure B.7.8.2, the calculation
ed
being performed as follow:
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- residues were expressed as “sum of fipronil + sulfone” only (MB45950 not taken into account),
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- ND residues were assumed to be equal to zero,
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- residues at LOQ (<0.010 mg/kg) were assumed to be equal to 0.005 mg/kg.
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Figure B.7.8.2: Linear regression between residue levels in feed and residue levels in laying hen tissues
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Re sidue s in tissue s Skin fat
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0,20
(mg/kg) y = 1,9510x - 0,0043
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R2 = 0,9993
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Skin fat
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0,15
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Eggs
Liver Eggs
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y = 1,1662x + 0,0007
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Muscle
lat R2 = 0,9998
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0,10
in
Live r
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y = 0,7440x - 0,0027
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R2 = 0,9999
tb
0,05
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Muscle
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y = 0,0972x + 0,0020
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Mean and maximum transfer factor (TF) presented in the following table were calculated as previously for
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dairy cattle, assuming that values reported as ND were taken as zero and value below LOQ as equal to
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0.005 mg/kg.
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Table B.7.8.2c Transfer factor (TF) for fipronil+sulfone residues in eggs and hen tissues
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at
ND: No detectable residue NA: Not applicable (a reliable TF cannot be derived from concentrations <0.01 or ND)
tf
a b
en
: calculated with the mean of 3 individual analyses : calculated with the maximum of 3 individual analyses
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Conclusions: Negligible amounts of fipronil were observed in all the investigated poultry tissues (egg
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included). MB45950 was reported as non-detectable in all of the poultry tissues. The sulfone metabolite
MB46136 was the major component of the total residue, irrespective of the nature of the animal tissues.
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as
Due to the lipophilic nature of the compound, the highest residue was found in skin with adhering fat, up
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to 0.20 mg/kg in the high level group.
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on
The residues observed in egg and in poultry tissues appear to be strictly linearly related to the residue
dose levels in animal feed. Maximum and mean transfer factors in egg and poultry tissues were
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calculated as well as, linear regressions.
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B.7.8.3 Pigs
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No feeding study is required for pig for the following reasons:
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- the metabolic pattern do not differ significantly in the rat as compared to ruminant (goat. hen)
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therefore no metabolism study in the pig was triggered
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- the fipronil-derived residue estimated in the pig diet is very low (0.003 mg/kg of dry feed).
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tb
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B.7.9 Residues in succeeding or rotational crops
s
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(Jesudason & Mackie S.J.W. 1995a)
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Material and Methods: The study was performed on a sandy loam soil contained in trays kept outside
under a plastic roof. 14C-fipronil solution was applied to the soil as a single uniform band application over
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as
the entire surface at a rate equivalent to 163 g/ha, which corresponds to 1.6 times the maximum
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application rate supported as representative use for maize in Europe. The soil was then covered with a 3-
th
5 cm of untreated soil to simulate sub-surface soil treatment. The soil was allowed to age for 30 days
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after treatment and incorporated before each planting interval. The treated soil was subsequently planted
with the following crops at three times periods:
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- after 30 days : sowing of lettuce, carrot and sorghum
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- after 153 days : sowing of lettuce, radish. and wheat
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- after 365 days : sowing of lettuce, radish and sorghum.
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Plant samples were harvested at maturity; additionally wheat and sorghum were also sampled as green
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plants (approximately half maturity). The Total Radioactive Residues (TRR) were determined for each
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crop part at each rotational interval by combustion followed by liquid scintillation counting. The limit of
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quantification ranged from 0.002 ppm to 0.010 ppm.
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Samples containing total residues in excess of 0.010 mg/kg were extracted with acetonitrile, then with a
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mixture of acetonitrile and water (1/1). Additional extractions were performed on wheat straw with
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0.1N HCl in acetonitrile/water (1/1) and finally by refluxing in 3N HCl in methanol. Extractable residues
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were then processed through partition between water and organic solvents. The extracted residues were
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characterised and identified. Identification of organosoluble residues was confirmed by mass
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spectrometry (LC/MS/MS).
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iso
Findings: The table B.7.9a summarises the total radioactive residues found in the crops at the three
in
rotational intervals. The highest total residue (0.172 mg/kg) was observed in straw from wheat sown after
d
5 months. All other samples were found to contain residues in much smaller amounts (from 0.003 mg/kg
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to 0.036 mg/kg, with higher levels generally found in drier crop parts).
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tb
Table B.7.9a: Total Radioactive Residues in rotational crops treated with 14C-fipronil
no
Crop Commodity
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The extractability of residues from samples where the TRR value was greater than 0.010 mg/kg is
sp
summarised in table B.7.9b hereafter. The extraction procedures employed enabled the dissolution of a
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major portion of total residues (at least 75 % for sorghum and more than 90 % for the other plant
or
matrices). Upon partition between water and organic solvents, extractable residues were characterised as
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mostly organosoluble. The samples containing the highest hydrosoluble residues were wheat and
en
sorghum grains, accounting for 17% and 25% of the total residue respectively. The total recovery and
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accountability of radioactive residues was greater than 88% of the TRR in all of the analysed matrices at
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the three rotational intervals. The non-extractable residues were all below 0.01 ppm.
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Table B.7.9b: Extraction efficiency of TRR in rotational crops treated with [14C]-fipronil
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TRR Organo-Soluble Water-soluble Total extractable Non-extractable Total Recovered
t
Crop Matrix
of
mg/kg mg/kg %TRR mg/kg %TRR mg/kg %TRR mg/kg %TRR mg/kg %TRR
is
as
30 DAT
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Carrot Leaf 0.021 0.019 90 nq nq 0.019 90 0.001 5 0.020 95
th
Carrot Root 0.016 0.017 106 nq nq 0.017 106 0.001 6 0.018 112
on
Sorghum Forage 0.028 0.024 86 nq nq- 0.024 86 0.001 4 0.025 90
edt
Sorghum Stover 0.036 0.027 75 0.004 11 0.031 86 0.008 22 0.039 108
an
gr
153 DAT
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Wheat Forage 0.017 0.014 82 nq nq- 0.014 82 0.001 6 0.015 88
ot
Wheat Straw 0.172 0.204 119 0.002 1 0.206 120 0.011 6 0.215 125
tn
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Wheat Grain 0.012 0.010 83 0.002 17 0.012 100 0.001 8 0.013 108
m
365 DAT
n
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Sorghum Forage 0.014 0.011 79 nq nq 0.011 79 0.002 14 0.013 93
t
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st
Sorghum Stover 0.024 0.019 80 0.003 12 0.022 92 0.005 21 0.027 113
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Sorghum Grain 0.016 0.009 56 0.004 25 0.013 81 0.004 25 0.017 106
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nq: not quantified, below LOQ
n.
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Compounds characterised in the samples from the rotational crop studies are summarised in the table
iso
B.7.9c below. Fipronil parent compound and its oxidation derivative sulfone (MB46136) were observed in
most samples, as opposed to the reduction derivative MB45950 that was generally not detected (except
in
TRR Fipronil 200761 200766 46136 46513 105320 45950 104615 105048 Unknown
ld
Pyrazole 4 position SOCF3 SOCF3 SOCF3 SO2CF3 CF3 SO2CF3 SCF3 SO3H CF3
ou
sh
30 DAT
an
153 DAT
at
Root 0.003 na na na na na na na na na na
EC
Straw 0.172 0.020 0.015 0.067 0.044 (0.019*) 0.012 ** ** 0.003 0.007
fa
365 DAT
sp
Root 0.003 na na na na na na na na na na
tf
en
a
sd
The concentration of RPA 200761 and RPA 104615 together and not individually na: not analysed (TRR <001 mg/kg)
* = Identity questionable (see text ). Extracted only after acidic refluxing and no confirmed by GC/MS. **= Not Detected
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Most samples were also found to contain degradation products resulting from the modification of the
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nitrile moiety, the major one being the amide RPA200766 (found at levels <0.01 mg/kg except in wheat
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straw where it accounts for 0.067 mg/kg and 40% of TRR).
is
as
That same wheat straw sample is the only one found to contain detectable amounts (0.019 mg/kg) of the
eb
desulfinyl metabolite MB46513. Nevertheless, Mass Spectrometry did not confirm this compound.
th
Furthermore, MB46513 is known as a photometabolite of fipronil and has been observed only after foliar
on
or soil surface application without incorporation. It is usually easily extractable under mild conditions, as
opposed to the component of the residue in wheat straw tentatively identified as MB46513, which could
ed
be extracted only by means of refluxing in 3N HCl in methanol. Thus the finding of MB46513 as a residue
t
an
in wheat straw seems artefactual in character.
gr
be
Minor quantities of RPA200761 (the corresponding carboxylic acid to the amide RPA200766) were
ot
observed in wheat straw, wheat grain and sorghum (forage, stover and grain), together with minor
tn
quantities of RPA104615 in carrot leaf and sorghum forage and stover. The metabolite RPA105048 was
us
only detected in wheat straw at the very low level of 0.003 mg/kg and a number of very minor unknowns
m
were detected each less than 0.01 mg/kg. A summary of the total toxic residue in each crop part is given
n
in Table B.7.9d.
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Table B.7.9d: Residues (mg fipronil equiv./kg) in plants grown in soil previously treated with [14C]fipronil
st
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Time between fipronil application and sowing
Re
Part
Plant 30 days 153 days 365 days
n.
analysed
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TRR Toxic residuea TRR Toxic residuea TRR Toxic residuea
lat
Lettuce
iso
foliage 0.003 ND 0.006 ND 0.009 ND
foliage 0.021 0.006
in
Carrot
d
grain 0.012 NF
d
an
a
p
= Toxic residue = sum of fipronil and metabolites sulphide + sulfone and for wheat straw + desulfinyl derivative
ta
ND : not determined (samples with total residues less than 0.01 mg/kg were not subjected to residue characterisation)
da
Conclusion: The total radioactive residue observed in rotational crops was mainly comprised of fipronil
at
alu
and its sulfone (MB46136) as well as of the non-toxicologically relevant metabolites RPA200766 (amide)
and RPA200761 (carboxylic acid). The presence of the photometabolite MB46513 in wheat straw was not
ev
confirmed and was assumed to be artefactual. Therefore, the plant residue definition proposed for plants
EC
in section B.7.3.1 (sum fipronil + sulfone) also applied to the residues observed in rotational crops. The
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metabolism pathway established for this study is consistent with the established degradation and plant
fa
As far as relevant residues are concerned, the level of 0.010 mg/kg was exceeded in only one item
sp
intended for human food (carrot roots) and in only one crop part used for animal feed (wheat straw).
m
Unfortunately information on the expected residue levels in rotational crops is incomplete since for carrots
or
tf
and wheat, data were provided for a single sowing date only (30 and 153 days respectively).
en
um
Moreover, it is a common agricultural practice to have a sequence of two maize crops over two
successive years in the same plot. Such a practice has to be taken into account and additional data on
oc
cumulative applications over two years are requested in order to conclude that no significant residues are
sd
expected in rotational crops (especially in root crops such as carrot and in cereal crops such as wheat).
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B.7.10 Proposed pre-harvest intervals for envisaged uses, or withholding periods and
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justification
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- Preharvest interval on each relevant crop
eb
Not applicable since fipronil is applied prior to or at time of sowing the crops, the PHI is therefore
th
automatically defined as the time between sowing and harvest. As indicative values, this time can be:
on
80-120 days for maize silage
120-180 days for maize grain
ed
120-150 days for sunflower seed.
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an
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- Re-entry period for livestock to areas to be grazed
ot
No re-entry period needs to be established as the representative crops are not grazed.
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us
m
- Re-entry period for man to crops, buildings or spaces treated
n
In the representative uses, fipronil is applied in furrow with subsequent incorporation at planting. Because
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of this and considering that there is no need to re-enter the field shortly after sowing, the potential
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exposure of man is negligible and no re-entry period needs to be defined.
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n.
- Withholding period for animal feedingstuffs
io
Fipronil is not being used as a post harvest treatment for animal feedingstuffs and no quantifiable
lat
residues are present at harvest, therefore no specific withholding period is necessary.
iso
in
d
- Waiting period between last application and sowing or planting the crops to be protected
ea
Fipronil is intended to be used at the sowing stage therefore there is no need for a specific waiting period
er
For the representative crops considered in this dossier, treatment is made in the soil at planting and
sh
therefore no dislogeable residue would be expected. So, there is no need to specify a waiting period
d
m
cu
do
s
t hi
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B.7.11 Community MRLs and MRLs In EU Member States
is
as
No EU MRLs have been set for fipronil. MRLs in EU member states are detailed in the following table.
eb
Generally values were set at the LOQ level (0.01 to 0.03 mg/kg) and the residue defined as “sum of
th
fipronil and sulfone expressed as fripronil”.
on
Table B.7.11: fipronil MRLs in EU Member States
ed
Crop Belgium &
t
Commodity Luxembourg France Italy Spain
an
groups
gr
fruits banana 0.02 0.01 - -
be
wheat 0.02 0.01 - -
rice 0.02 0.01 - -
ot
tn
rye 0.02 0.01 - -
cereals triticale 0.02 0.01 - -
us
maize 0.02 0.01 0.01 0.01*
m
silage maize 0.02 - 0.02 0.01*
n
io
sweet corn 0.02 - - -
t
sorghum 0.02 - 0.01 -
ra
st
Oil seed sunflower 0.02 0.01 0.01 0.01*
gi
Roots beet 0.02 0.01 0.02 -
Re
Potatoes potato 0.02 - 0.03 0.01*
n.
Fruiting tomato 0.02 - 0.01 -
io
vegetables eggplant - - 0.01 -
Others tobacco fresh - - 0.01lat -
iso
tobacco dry - - 0.05 -
in
d
ea
B.7.12 Proposed MRL and justification for the acceptability of those residues
er
tb
The residue data reported in sections B.7.6.1 indicated that residue trials were performed using four
ld
ou
application scenarios:
sh
- the seed treatment using an application rate of 250 - 1500 g/100 kg seeds
(equivalent to 50 – 300 g/ha on the basis of 20 kg seeds/ha).
d
an
- the granule soil incorporation using an application rate of 177 to 400 g/ha
ka
- the soil spraying with incorporation using an application rate of about 200 g/ha
ac
p
- In maize grain at harvest, fipronil and metabolites residues were always below the analytical limits of
ta
quantification that gradually improved from 0.010-0.020 mg/kg for the residue trials performed prior to
da
In view of the large number of trials performed, all showing residues below LOQ, it is proposed to derive
alu
the MRL and STMR from the data obtained with the most sensitive analytical method (0.001 and
ev
0.002 mg/kg per analyte). Moreover, since the maximum application rate supported by the cGAP is
100 g/ha (see point B.7.5) it is also proposed to take only into account the trials performed with and
EC
On these bases, the residue data suitable for MRL and STMR setting on maize grain are the following,
the residue being expressed as “sum fipronil + sulfone”.
ar
sp
All trials 75-420 g/ha 26x <0.004 mg/kg and 1x 0.005 mg/kg
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Based on the 26 data below the LOQ (<0.004 mg/kg) and on the fact that the 0.005 mg/kg value (0.003 +
s
hi
<0.002 mg/kg) was obtained for an exaggerated dose rate of 200 g/ha, an MRL of 0.005 mg/kg is
t
of
proposed for maize grain. This MRL also applied for sweet corn since the above-mentioned results
included 5 trials performed on this crop with a dose rate of about 200 g/ha (see trials n°10 to 14 in table
is
as
B.7.6.1c).
eb
th
- MRL maize grain 0.005 mg/kg
on
- MRL sweet corn 0.005 mg/kg
ed
Since no residues were detected for a limit of quantification of 0.004 mg/kg in 13 trials performed with and
t
an
exaggerated dose rate equal or higher than 200 g/ha (more than two times the maximum supported rate
gr
of 100 g/ha), an STMR equal to half the LOQ is proposed for maize grain.
be
ot
- STMR maize grain <0.002 mg/kg
tn
us
- For silage (green plant), as previously for grain, no residues were observed but many trials were
m
conducted prior to 1993 with an LOQ of 0.010 or 0.020 mg/kg per analyte. The trials performed with an
n
LOQ of less than 0.005 mg/kg (per analyte) and with an application rate equivalent or higher than 75 g/ha
io
t
(critical rate -25%) are the following, the residue being expressed as “sum fipronil + sulfone”.
ra
st
gi
Seed treatment 75 g/ha 6x <0.010 mg/kg
Re
Granule in furrow 153-156 g/ha 2x <0.010 mg/kg
n.
400 g/ha 2x <0.004 mg/kg
io
Soil treatment 188-197 g/ha 2x <0.004 mg/kg
200 g/ha 8x <0.010 mg/kg
lat
iso
All trials 75-400 g/ha 16x <0.010 mg/kg and 4x <0.004 mg/kg
in
d
Since no residues were observed, even in the 4 trials performed with a dose rate of about 200 to 400 g/ha
ea
and with an LOQ of 0.004 mg/kg, an STMR of 0.004 mg/kg is proposed for maize silage.
er
tb
Due to the limited number of trials carried out on maize silage with an LOQ of 0.004 mg/kg, it seems
ou
difficult to propose, as for grain, an STMR value of 0.002 mg/kg for silage. Additional residue data
sh
performed with a lower LOQ are needed to reduce the STMR value used for silage in the livestock
d
No residues were observed in the 12 trials performed on sunflower. As previously for maize, it is
ta
da
proposed to derive the LMR and STMR from the trials performed with the more sensitive analytical
method (LOQ 0.002 mg/kg per analyte) and with and application rate equivalent or higher than 375
n
io
g/100 kg seed (critical rate -25%). These trial results are the following, the residue level being expressed
at
The 0.002 mg/kg STMR is supported by the fact that no residues were detected in the 3 trials performed
tf
m
cu
do
s
hi
B.7.12.3 Food of animal origin
t
of
- Calculation of livestock dietary burden.
is
as
The calculation was performed according to the EU guidance document 7031/VI/95. Nevertheless, the
eb
20% dry matter content mentioned for silage (clover and grasses) is not relevant for maize silage where a
th
value of 30-40% appears to be more appropriate. Therefore, a 35% dry matter content was used for
on
maize silage in the calculations below.
ed
The livestock feeding studies have shown fipronil to reach a plateau slowly in milk and eggs (after 3-4
t
an
weeks). Hence, the STMR values calculated for maize and sunflower were used, according to the 1997
gr
JMPR instructions summarised in the following table.
be
ot
Table B.7.12.3a: Guidance on the estimation of pesticide dietary intakes by animals (1997, JMPR Report)
tn
MRL for STMR for
us
animal commodity animal commodity
m
Feed item residue level STMR STMR
n
Feed incorporation rates maximum maximum
io
Feeding study residue levela highest mean
t
ra
a
To be understood as "residue level in animal commodity observed in the feeding study at the relevant dosing level".
st
gi
Re
The livestock dietary burden calculated as specified above, are summarised in the four following tables.
n.
io
Table B.7.12.3b: Dairy cattle daily intake (550 kg body weight, maximum daily feed intake 20 kg DM)
Maximum Dry matter Intake as STMR lat
Residue Intake on
Commodity
iso
intake (%) Content (%) fresh (kg) (mg/kg) Intake (mg) diet 100%
maize silage 100% 35% 57 0.004 0.229 0.229
in
0.228 mg/animal/day
0.0004 mg/kg b.w./day
tb
Table B.7.12.3c: Beef cattle daily intake (350 kg body weight, maximum daily feed intake 15 kg DM)
ou
intake (%) Content (%) fresh (kg) (mg/kg) Intake (mg) diet 100%
d
0.171 mg/animal/day
ac
Table B.7.12.3d: Chicken daily intake (1.9 kg body weight, maximum daily feed intake 0.120 kg DM)
n
0.00023 mg/animal/day
0.00012 mg/kg b.w./day
n
fa
Table B.7.12.3e: Pig daily intake (75 kg body weight, maximum daily feed intake 3 kg DM)
ar
sp
0.009 mg/animal/day
0.0001 mg/kg b.w./day
oc
m
cu
do
Concentrations of residues in livestock feed calculated in the above tables are smaller than the lowest
s
hi
dosing levels observed in the livestock feeding studies summarised in Section B.7.8 (0.04 and 0.01 mg/kg
t
of
feed d.m./day for cattle and hen respectively). Nevertheless, for the determination of residue levels in
food of animal origin, it is proposed to proceed by extrapolation, since there is clear evidence from the
is
as
livestock feeding studies that the residues in edible animal tissues are linearly related with the dose levels
eb
in feed.
th
on
Such extrapolation will be made by means of the transfer factors (ratio of residue level in the
tissue/residue level in the feed) and also by means of the regression curve equations.
ted
an
For each animal tissue (milk included), the transfer factor for fipronil derived residue is taken from the
gr
livestock feeding dose which is the closest to the level of estimated residue exposure in the animal diet. If
be
no meaningful transfer factor could be calculated at the selected dose because of residues in tissues
ot
below the LOQ, then the transfer factor will be taken from the next higher dose.
tn
- The STMR values in animal tissues (milk included) are calculated by applying the mean transfer
us
factor to the estimated animal residue burden.
m
- The MRL proposals in animal tissues (milk included) are calculated by applying the maximum
n
transfer factor to the actual estimated animal residue burden. MRL proposals are also calculated using
tio
the linear regression curve equation calculated in section 7.8.
ra
st
gi
Details of the calculations are shown in the table B.7.12.3f thereafter.
Re
Table B.7.12.3f: STMR and MRL calculations for fipronil in animal products
n.
io
Residue STMR calculation LMR Calculation
in Mean lat
Maximum Basis for Regression MRL
Animal Commodity
iso
Animal diet transfer STMR transfer MRL curve proposals
(mg/kg DM/d) factor (mg/kg) factor proposal calculation
in
Poultry 0.0019 Muscle 0.12 0.0002 0.14 0.0003 0.0020 not necessary
ou
The various calculations in above table show that for most of the animal products, the estimated values
da
are close or below 0.001 mg/kg, especially in milk, poultry and pig products. For these commodities it
n
At the opposite, some estimated values for ruminant fat, liver and kidney and pig fat are higher than
ev
0.005 mg/kg and the following MRL proposals are made for these commodities:
EC
maize silage and sunflower grain were globally below the limit of quantification and the residue intakes by
sp
animals were not based on actual residue levels observed in plants, but were derived from the lowest
m
LOQ achieved in the residue trials. For maize silage, residues (fipronil + sulfone) were assumed to be
or
0.004 mg/kg, since the lowest LOQ in trials performed with an exaggerated rate was 0.002 mg/kg per
tf
analyte.
en
um
Additional data on maize silage performed with a lower LOQ (<0.001 mg/kg) would probably confirm a
oc
“no residue situation” in maize silage, and the fact that it is no necessary to set MRLs in animal products.
sd
hi
:T
NG
NI
AR
W
m
cu
do
s
hi
B.7.13 Proposed EU Import tolerances and justification for acceptability of those residues
t
of
is
No relevant since no import tolerances have been claimed.
as
eb
th
B.7.14 Basis for differences in conclusion reached having regard to CAC MRLs
on
Fipronil was evaluated by the 2001 JMPR meeting. The following draft MRLs have been proposed at
ed
step 3 of the Codex procedure and submitted for comments.
t
an
gr
Table B.7.14: Fipronil Codex MRL proposal (JMPR 2001)
be
Crop group Commodity MRL Residue definition
ot
Fruits Banana 0.005
tn
Brassica Cabbages, head 0.02
us
Flowerhead brassicas 0.02
m
Wheat 0.002*
n
Barley 0.002*
io
Oats 0.002*
t
ra
Cereals Rye 0.002*
st
Triticale 0.002* fipronil
gi
(parent compound only)
Re
Rice 0.01
a
Rice straw and fodder, dry 0.2
n.
Maize 0.01
io
Maize forage 0.1a lat
0.1a
iso
Maize fodder
Oil seed Sunflower seed 0.002*
in
Eggs 0.02
an
- Plant products: In comparison to the present evaluation, the main difference is that for plant products
p
the residue definition for monitoring proposed by the Codex is limited to the parent compound fipronil
ta
only, taking into account that the sulfone metabolite was never detected in the field residue trials.
da
Thereby, the MRL for sunflower seed is proposed on the basis of the lowest LOQ of 0.002 mg/kg for a
n
io
single analyte. This MRL is consistent with the 0.005 mg/kg value proposed at EU and level and based on
at
At the opposite, the MRL of 0.010 mg/kg proposed for maize is not supported by the residue trails
EC
provided at EU level, where no residues were detected in grain even in the trials performed with an
exaggerated rate, up to 4 times the maximum dose rate supported in the cGAPs.
n
fa
to
The proposal to include the sulfone metabolite in the residue definition for monitoring as well as for risk
ar
- Sulfone MB46136 is a toxicological relevant metabolite for which the low ADI value of 0.0002 mg/kg
m
b.w./d applied,
or
- Fipronil and sulfone are analysed with the same analytical method, both compounds can be
tf
- In the plant metabolism studies the sulfone metabolite was generally observed at harvest in higher
um
proportions than the parent compound itself as summarised in the table overleaf.
oc
sd
hi
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NG
NI
AR
W
m
cu
do
s
hi
Table B.7.14b: Fipronil and sulfone proportions in plant metabolism studies
t
of
Metabolism Plant TRR fipronil sulfone Ratio
study part (mg/kg) (%TRR) (%TRR) sulfone/fipronil
is
as
Maize 1 fodder 3.70 12% 38% 2.3
eb
Maize 2 fodder 0.51 12% 16% 1.3
Sunflower leaves 1.43 37% 17% 0.5
th
Cotton foliage 2.33 0.3% 7% 23.0
on
Sugar beet Leaves 0.66 ND 31% >30.0
ed
roots 0.06 14% 64% 4.5
t
an
Wheat grain 0.02 18% ND <0.2
gr
Except in wheat grain and in sunflower leaves, in the other crop matrices sulfone was always detected
be
in higher proportion than fipronil. Therefore sulfone appears to be a better indicator than fipronil of the
ot
presence of residues in plant. For a compound affected with such a low ADI, the inclusion of this
tn
“better indicator” in the residue definition appears to be necessary.
us
m
- Animal products: In contrast with the plant residue definition, there is an agreement concerning the
n
io
residue definition for animal products. Both definitions include the parent and the sulfone. Globally, Codex
t
ra
MRLs are significantly higher than those proposed in this monograph, especially for fat. Moreover, MRLs
st
are defined for milk and eggs whereas no values were proposed at EU level.
gi
Re
The milk MRL Codex value of 0.020 mg/kg is not acceptable since the TMDI is 156%, 1002% and 553%
n.
of the ADI for child, infant and toddler respectively with PDS/UK chronic exposure model and, 1137% and
io
lat
835% for the French one, these calculations being performed with the milk and milk products
iso
consumption data solely. It is not possible to conclude that a milk controlled with such a residue level is
save for children.
in
d
ea
B.7.15 Estimates of potential dietary exposure through diet and other means
er
tb
Calculations of potential intakes of fipronil residues in food have been carried out using the three following
ou
models:
sh
- The WHO/FAO model based on the GEMS/food regional diet (WHO/FSF/FOS/98.3, may 1998) for a
60 kg body weigh adult and for the European population.
d
an
- The UK/PSD model for four subgroups (adult, school children, toddler and infant).
ge
- The French model for three subgroups (adult, toddler and infant)
ka
ac
These estimates were made using the proposed ADI of 0.0002mg/kg b.w./day and the following data:
p
- when MRLs were not proposed for animal products (milk, egg, poultry meat, …) the residue values
ta
estimated by linear regression were used in the TMDI calculation (see table B.7.12.3e).
da
- the animal product STMRs calculated with the mean transfer factors in table B.7.12.3e were used for
n
io
- The meat residue level was calculated assuming a fat content of 20% and a muscle content of 80%.
alu
ev
EC
n
fa
to
ar
sp
m
or
tf
en
um
oc
sd
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NG
NI
AR
W
m
cu
do
s
hi
Table B.7.15.1a: Adult (60 kg) TMDI and IEDI calculations based on the WHO/FAO European diet
t
of
WHO/GEMS MRL or
Commodity consumption Estim. level a TMDI STMR IEDI
is
as
(g/person/day) (mg/kg) (µg/commodity/d) (mg/kg) (µg/commodity/d)
eb
Maize (grain) 8.8 0.005 0.044 0.002 0,018
th
Sunflower seed 0.0 0.005 0.000 0.002 0,000
on
Sunflower oil 8.5 0.005 0.043 0.002 0,010
ed
Sweet corn 14.5 0.005 0.073 0.002 0,058
t
0.0017a
an
Milk & milk products 340.8 0.579 0.001 0,443
gr
Cattle meat 63.3 0.006 0.380 0.0037 0,076
be
Cattle liver 0.4 0.01 0.004 0.0032 0,002
ot
Cattle kidney 0.2 0.01 0.002 0.0011 0,000
tn
Cattle fat 0.0 0.03 0.000 0.0146 0,000
us
Pig meat 75.8 0.006 0.455 0.0010 0,023
m
Pig fat and lard 7.4 0.03 0.222 0.040 0,030
n
io
Poultry meat 53 0.002a 0.106 0.0007 0,021
t
ra
Poultry offal (liver) 0.4 0.02a 0.008 0.0013 0,001
st
Egg 37.6 0.003a 0.113 0.0012 0,090
gi
Re
Total (µg/person/day) : 2.028 0.772
n.
Total (µg/kg b.w./day) : 0.034 0.013
io
% ADI : 17% lat 6%
a
: linear regression estimated value
iso
in
Table B.7.15.1b: TMDI and IEDI calculations for adult, infant and toddler based on French model
d
ea
LMR or Adult (60 kg) Infant (8.8 kg) Toddler (10.6 kg)
er
a
Commodity Estim. level STMR Diet TMDI IEDI Diet TMDI IEDI Diet TMDI IEDI
tb
(mg/kg) (mg/kg) (g/p./d) (µg/d) (µg/d) (g/p./d) (µg/d) (µg/d) (g/p./d) (µg/d) (µg/d)
no
sweet corn 0,005 0,002 0.0 0,000 0,000 0,2 0,001 0,000 0,7 0,004 0,001
ld
sunflower oil 0,005 0,002 7,9 0,040 0,016 0,1 0,001 0,000 0,7 0,004 0,001
ou
sh
offals 0,01 0,0032 3,5 0,035 0,011 0,3 0,003 0,001 1,3 0,013 0,004
cattle & sheep meat 0,006 0,0041 116 0,696 0,429 5,1 0,031 0,019 14,2 0,085 0,053
d
an
pig meat 0,006 0,0011 17,6 0,106 0,018 0,6 0,004 0,001 3,5 0,021 0,004
ge
other meat 0,006 0,0041 9,3 0,056 0,034 46,7b 0,280 0,173 93,3b 0,560 0,345
ka
milk &milk products 0,0017a 0,001 480,4b 0,817 0,480 772b 1,312 0,772 796,7b 1,354 0,797
ac
other milk products 0,0017a 0,001 1,3 0,002 0,001 227 0,385 0,227 84,9 0,144 0,085
p
0,002a 123b
ta
poultry meat 0,0006 0,246 0,086 5 0,010 0,004 8,9 0,018 0,006
da
egg 0,003a 0,0012 18 0,054 0,022 3,9 0,012 0,005 10,8 0,032 0,013
n
water 0,0001 0,0001 1000 0,100 0,100 109 0,011 0,011 245 0,025 0,025
io
at
a
: linear regression estimated value
b th
: 97;5 percentile intakes for two commodities, mean intakes for other food.
n
fa
to
ar
sp
m
or
tf
en
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Table B.7.15.1c: TMDI and IEDI calculations for adult, infant and toddler based on UK/PSD Model
s
hi
MRL or Adult (70.1 kg) Child (43.3 kg) Infant (8.7 kg) Toddler (14.5 kg)
t
of
Commodity Estim. STMR Diet TMDI IEDI Diet TMDI IEDI Diet TMDI IEDI Diet TMDI IEDI
is
(mg/kg) (mg/kg) (g/p./d) (µg/d) (µg/d) (g/p./d) (µg/d) (µg/d) (g/p./d) (µg/d) (µg/d) (g/p./d) (µg/d) (µg/d)
as
eb
sweet corn 0,005 0,002 2,7 0,014 0,005 1,0 0,005 0,002 0,5 0,003 0,001 1,5 0,008 0,003
oilseed total 0,005 0,002 32,5 0,163 0,065 29,3 0,147 0,059 5,2 0,026 0,010 12,6 0,063 0,025
th
on
maize (corn meal) 0,005 0,002 1,0 0,005 0,002 2,2 0,011 0,004 5,6 0,028 0,011 2,1 0,011 0,004
a b b b b
milk-cow 0,0017 0,001 665,9 1,132 0,666 674,5 1,147 0,675 871,9 1,482 0,872 801,7 1,363 0,802
ed
b b b b
t
meat (ex poultry) 0,006 0,0037 205,0 1,230 0,759 133,9 0,803 0,495 38,5 0,231 0,142 86,9 0,521 0,322
an
meat fat 0,03 0,0146 0,0 0 0 0,1 0,003 0,001 0,0 0 0 0,0 0 0
gr
be
kidney 0,01 0,0011 0,7 0,007 0,001 0,8 0,008 0,001 0,2 0,002 0,000 0,0 0 0
liver 0,01 0,0032 3,7 0,037 0,012 2,9 0,029 0,009 0,8 0,008 0,003 0,4 0,004 0,001
ot
tn
a
egg 0,003 0,0012 22,0 0,066 0,026 18,2 0,055 0,022 12,1 0,036 0,015 10,0 0,030 0,012
us
a
poultry meat 0,002 0,0007 19,9 0,040 0,014 10,4 0,021 0,007 3,4 0,007 0,002 8,4 0,017 0,006
m
Total (µg/person/day) : 2,693 1,550 2,228 1,276 1,823 1,057 2,016 1,175
n
io
Total (µg/kg b.w./day) : 0,038 0,022 0,051 0,029 0,210 0,121 0,139 0,081
t
ra
% ADI : 19% 11% 26% 15% 105% 61% 70% 41%
st
a
: linear regression estimated value
gi
b th
: 97;5 percentile intakes for two commodities, mean intakes for other food.
Re
n.
The TMDI and EIDI calculations performed with the different models and for several subgroups of
io
population are summarised in the following table. For children, the relative high consumption values for
lat
milk explain that some TMDI are over 100% of the ADI. Nevertheless, these evaluations must be
iso
considered as an overestimate since the calculated residue levels in milk are not based on a transfer of
in
actual residues from maize silage, but on default value set at the lowest LOQ (0.004 mg/kg).
d
ea
Model
Adult child Infant toddler Adult child Infant toddler
no
WHO/FAO 17% - - - 6% - - -
ld
Based on these data, it is concluded that representative use of fipronil on maize and sunflower do
an
The acute exposure was performed using the consumption data from UK acute exposure model for adult
ta
and toddler. The calculations presented in the table below were performed using an Acute Reference
da
Dose (ARfD) of 0.009 mg/kg b.w./day and a very conservative default variability factor of 10 for sweet
n
io
corn. The meat residue level was calculated assuming a fat content of 20%.
at
alu
Table B.7.15.2: NESTI calculation for adults and toddlers (UK Acute exposure model)
ev
a
Commodity Estim. level bility Portion Intake % Portion Intake %
n
(mg/kg) Factor (g/p./day) (µg/kg bw/d) ARfD (g/p./day) (µg/kg bw/d) ARfD
fa
Meat (ex. poultry) 0,006 - 301 0,026 0,3 136 0,056 0,6
um
a
: linear regression estimated value
hi
:T
NG
NI
AR
W
m
cu
do
The NESTI value represents less than 5% of the ARfD. Based upon these data, it is concluded that
s
hi
representative uses of fipronil on maize and sunflower do not present an unacceptable acute risk for the
t
of
consumer.
is
as
eb
B.7.15.3 Exposure via water
th
on
Consumption from drinking water is based on the WHO approach. This approach is to allocate one tenth
ed
of the ADI to water and this allocation is converted to a Maximum Acceptable Concentration (MAC) in
t
water as follows:
an
gr
ADI x body weight x P
be
C
ot
tn
where: body weight = 60 kg (adult)
us
P = fraction of the ADI allocated to drinking water (i.e. 1/10)
m
C = daily consumption of water (2 litters)
n
io
Therefore, with an ADI of 0.0002 mg/kg/day (0.2 µg/kg/day), the MAC for fipronil is
t
ra
st
0.2 x 60 x 0.1= 0.6 µg/l
gi
Re
2
n.
Due to the low ADI, the calculated maximum acceptable concentration in water is only 6 times the
io
maximum acceptable concentration in drinking water of 0.1 µg/l. lat
iso
in
d
ea
er
tb
no
ld
ou
sh
d
an
ge
ka
pac
ta
da
n
io
at
alu
ev
EC
n
fa
to
ar
sp
m
or
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en
um
oc
sd
hi
:T
NG
NI
AR
W
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B.7.16 Summary and evaluation of residue behaviour
s
t hi
of
Fipronil is an insecticide active by contact and ingestion on many pests. It interferes with the passage of
chloride ions through the Gamma-Aminobutyric Acid (GABA) regulated chloride channel. Fipronil is active
is
as
against many insects including soil insects (lepidopterae, coleopterae) present during larval stage, such
eb
as wireworm, able to damage plant root system.
th
on
Representative uses of fipronil are only soil incorporated. The active substance is used as a soil
insecticide in many types of formulations applied at sowing by spaying of WG or by spreading of granular
ed
and as a seed treatment. Some foliar uses registered in European states are no longer supported by the
t
an
notifier.
gr
be
ot
- Plant metabolism
tn
The metabolism of fipronil has been investigated on five different crops using soil applications or seed
us
treatment. These crops are representative of the following plant groups:
m
- Cereals (wheat and corn)
n
- Pulses and oilseed (sunflower, cotton)
io
t
- Roots and tubers (sugar beet)
ra
Due to the structure of the molecule, metabolism studies were performed with 14Cf-fipronil labelled on the
st
gi
phenyl ring only.
Re
n.
Metabolism in plants following soil application or seed treatment is characterised by the low uptake (Less
io
than 5% of the applied radioactivity) and low translocation of radioactive residues in sunflowers, corn,
wheat and to a lesser extent sugar beet.
lat
iso
in
For soil incorporated or seed treatment uses, the plant metabolism studies carried out for maize,
d
sunflower, sugar beet and wheat indicate that a common metabolic pathway could be defined for these
ea
- by hydrolysis of the nitrile moiety to yield the amide RPA200766, which hydrolyses to the carboxylic
no
acid RPA200761
ld
ou
Fipronil, metabolites MB46136 (sulfone) and RPA200766 were found to be the major compounds
sh
detected in the different plant parts, accounting for about 14-40%, 12-64% and 13-60% of the total
d
radioactivity (TRR) respectively. Additional metabolites were characterised but generally observed at low
an
levels (<10% TRR) with the exception of metabolites RPA105320 in sugar beet leaves (18% TRR) and
ge
RPA200761 in maize forage and wheat grain (11% and 37% TRR respectively). In all these plant
ka
At least, only fipronil, metabolite MB46136 (sulfone) and metabolite RPA200766 (amide) appeared to be
ta
da
major metabolites in plants. However, since metabolite RPA200766 was not found to be active at the
GABA receptor nor found to be acutely toxic to rats (a single dose of 2000 mg/kg did not lead to any
n
io
mortality of sign of neurotoxicity), it was proposed to limit the residue definition in plants to the parent
at
- Animal metabolism
to
The metabolism of fipronil has been investigated in lactating goats and laying hens using 14C-fipronil
ar
labelled on the phenyl ring. Fipronil was administrated for 7 and 28 consecutive days to goats and hens,
sp
respectively at the nominal dose levels of 0.05 - 2.0 and 10.0 mg/kg feed dry matter/day.
m
or
- Lactating goat: The results from the 2 ppm dosed goat were considered as abnormal since total
tf
recovery was very low (50%) and the no-proportional dose response was not in accordance with the
en
results from other dosed goats and from the feeding study where a clear relationship between the
um
residue levels in feed and the residues in tissues was observed. Thus, conclusions are mainly based
oc
m
cu
do
Approximately 83% and 77% of the total administered dose was recovered at the low, and high dose
s
hi
levels respectively. The majority of the radioactivity was observed in the faeces (ca 65%)
t
of
demonstrating an extensive excretion of fipronil material. The radioactivity found in urine, milk and
tissues indicated a minimum absorption of 15-19%. Small amount of radioactivity (<5% TRR) was
is
as
observed in milk whatever the dose regimen, with a maximum level of 0.001 mg/kg for the 0.05 ppm
eb
dosed goat. At 10 ppm, radiolabelled fipronil derived material partitioned in milk with residue level
th
increasing over study duration and a maximum value of 0.166 mg/kg. Consistent with the lipophilic
on
nature of the compound and its metabolites, fipronil derived residues were preferentially observed in
fat matrices (omental/renal).
ed
t
an
Parent fipronil and metabolite MB46136 (sulfone) were found to be the major components in milk,
gr
muscle, omental fat and renal fat, accounting for 60–75% and ca 20% of the TRR respectively.
be
MB46136 was also major in kidney and liver (50-75 % TRR).
ot
tn
Laying hen: A large proportion of the administered dose was eliminated and recovered in the faeces
us
(ca. 28% to 42%). As evidenced by the lipophilic nature of the compound, a low radioactivity was
m
found in the lean tissues (muscle, liver) whereas a larger proportion of it was observed in the fat
n
matrices (skin, fat, egg yolk). The metabolite MB46136 was also reported to be the major constituent
io
t
of the fipronil derived residues in any of the investigated tissues, accounting for more than 95% of the
ra
total radioactivity.
st
gi
Re
These two metabolism studies demonstrate that fipronil and metabolite MB46136 are the major
n.
components of the various investigated matrices, both accounting for more than 70% of the TRR.
io
Therefore the residue definition proposed for animal products is:
lat
iso
- Residue trials
ea
Extensive residue data have been generated for maize and sunflower following soil incorporated
er
applications or seed treatment. In order to fulfil the European requirements, field trials were conducted
tb
both in southern and northern Europe and in compliance with the GLP requirements. These field residue
no
trials were conducted over several growing seasons, from 1990 to 2001. Although residue in plants was
ld
defined as “sum of fipronil and sulfone (MB46136)”, the metabolites MB45590, MB46513 and
ou
RPA200766 have been monitored in most of the residue trials in order to ascertain that these compounds
sh
would not be found at levels greater than the limit of quantification (LOQ). The analytical limits of
d
quantification gradually improved over the duration of these studies. It decreased from 0.010-0.020 mg/kg
an
for the residue trials performed prior to 1994 to 0.001-0.002 mg/kg for the more recent ones (for each
ge
individual compound).
ka
ac
Maize: 70 residue studies were carried out for soil-incorporated uses (in furrow/overall), seed
p
treatment and bait applications. These trials were performed according to the following practices:
ta
da
- In furrow granular application with incorporation 156 to 420 g a.i./ha (23 studies)
at
Extensive trials were conducted at exaggerated dose rates of 150 to 420 g/ha, up to four times the
EC
maximum dose rate of 100 g/ha supported as representative uses for maize. Globally, no residue
above the limit of quantification was ever observed in the grain and silage portions (at harvest), for any
n
fa
of the investigated soil uses. Residue data on sweet corn confirmed the absence of quantifiable
to
Sunflower: Residue data in sunflower were generated for seed treatment only. Trials were carried out
m
at the supported dose rate of 15 - 30 g/ha (equivalent to 100 - 375 g a.i./100 kg of seed) as well as at
or
exaggerated doses (1000 - 1500 g a.i./100 kg seed). The residues were determined in raw agricultural
tf
These field trials demonstrated the absence of residue above the limit of quantification (<0.002 mg/kg
oc
per analyte) in seed, flower head and processed fractions. Residue studies performed with seed
sd
m
cu
do
s
hi
Information provided by the residues trials was sufficient to propose MRLs for maize grain, sweet corn
t
of
and sunflower.
is
as
- Storage stability
eb
Freezing storage stability of fipronil and its metabolites has been investigated on maize, cottonseed and
th
their processed commodities (pressed cake, oils, starch, silage…) stored frozen at less than -10°C and
on
on potato and lettuce stored at –20°C. Globally, no significant degradation was observed and fipronil,
metabolites MB46136, MB45950, MB46136, RPA200766 and RPA105048 were stable in every substrate.
ed
t
an
Storage stability studies were also performed on meat and milk of lactating cow and on meat and eggs of
gr
laying hens. Fipronil and metabolites MB46136, MB45950 were stable in the samples stored frozen -10°C
be
over a period of 3 months.
ot
tn
These storage period stabilities correspond to the time interval between the sampling dates and the
us
analyses of the plant and animal samples in the corresponding residue trials and livestock studies.
m
n
- Effect of processing
io
t
Model hydrolysis studies were performed separately for fipronil and its sulfone metabolite MB46136. The
ra
experimental conditions (pH: 4-6; temperature: 90°C - 120 °C) were chosen as to mimic typical industrial
st
gi
processing such as backing, boiling, brewing and sterilization. Such studies demonstrated that under
Re
these hydrolytic conditions, the formation of a degradation/transformation product in significant proportion
n.
(greater than 10%) was never observed. For fipronil, only minor amount (5%) of the non-toxicologically
io
relevant metabolite RPA200766 was observed under conditions simulating the sterilization process (pH 6,
lat
120°C). Study conducted with the metabolite MB46136 lead to the same conclusion. No significant
iso
degradation of MB46136 was observed in any of the processing studies. The formation of the product
in
RPA105320, in minor proportion (8%), was only found under the sterilization conditions. Therefore the
d
processing of raw agricultural commodities containing either fipronil and/or its metabolite MB46136 would
ea
Additionally, processing studies were performed on sunflower and maize. Nevertheless, these studies
no
were conducted using grains with residue levels below the limit of quantification so that, no transfer
ld
Fipronil livestock feeding studies were carried out for dairy cows and laying hens. Daily oral doses of
an
fipronil were administered for several consecutive days to the cows (35 days) and hens (42 days).
ge
Lactating cows and laying hens were fed at dose levels corresponding to:
ka
Once a residue plateau was achieved, the animals were slaughtered and tissue samples collected for
ta
da
residue analysis.
n
io
Fipronil was found to be a compound reaching a plateau slowly in the milk (4 weeks) and egg (3 weeks).
at
The sulfone metabolite MB46136 was the major component in any of the animal tissues in contrast with
alu
the parent compound fipronil that was observed in negligible amounts in the various investigated animal
ev
Due to the lipophilic character of the molecule, fipronil derived residues were preferentially located in fat
n
fa
matrices (cow fat, skin fat with adhering fat for poultry). The residues observed in milk, egg and animal
to
tissues were found to be strictly linearly related to the residue dose levels in animal feed. Maximum and
ar
mean transfer factors were calculated for every tissues as well as, linear regressions.
sp
m
A confined rotational crop study has been performed using [14C]-fipronil labelled on the phenyl ring and a
tf
dose rate of 163 g/ha (1.6X). Following an ageing period of 30 days, the treated soil was planted with
en
crops belonging to different crop groups (cereal, root and leafy vegetable):
um
m
cu
do
s
hi
Residue analyses were performed on crops at maturity as well as at half maturity for sorghum and wheat.
t
of
Of the total extractable residues, fipronil, MB46136 and RPA200766 were the major constituents.
Therefore, the plant residue definition derived from the plant metabolism studies (sum fipronil + sulfone)
is
as
also applied to the residues observed in rotational crops
eb
th
Apart from the residue observed in the wheat straw (0.172 mg/kg at 153 days), the total radioactive
on
residues found in the crops, at various rotational intervals, were very low (from 0.003 mg/kg to
0.36 mg/kg). Toxicological relevant residues above 0.010 mg/kg were only observed in one item intended
ed
for human food (carrot roots) and in only one crop part used for animal feed (wheat straw). Unfortunately
t
an
information on these crops was incomplete since data were provided for a single sowing date only.
gr
be
Moreover, it is a common agricultural practice to have a sequence of two maize crops over two
ot
successive years in the same plot. Such a practice has to be taken into account and additional data on
tn
cumulative applications over two years have to be requested in order to conclude that no significant
us
residues are expected in rotational crops (especially in root crops such as carrot and in cereal crops such
m
as wheat).
n
io
t
- Proposed MRLs
ra
MRLs are proposed on the basis of the following residue definition for plant and animal products:
st
gi
Sum fipronil (parent compound) + sulfone metabolite MB46136 expressed as fipronil
Re
n.
Plant products: Globally, no fipronil parent compound residues nor sulfone residues were never
io
detected in the supervised residue trials performed on maize and sunflower even in those conducted
lat
with an exaggerated rate, up to 4 times the maximum dose rate of 100 g/ha. Thereby, the following
iso
MRLs are proposed for maize and sunflower on the basis of the lowest LOQ of 0.004 mg/kg (sum
in
A STMR of 0.002 mg/kg is proposed for these commodities, since no residues were detected for a
ou
limit of quantification of 0.004 mg/kg in trials performed with an exaggerated dose rate equal or higher
sh
No values are proposed for processed commodities (oil, floor, cake, …), since no residues were
ge
observed in the processing studies performed on maize and sunflower treated with and exaggerated
ka
dose rate.
ac
p
Animal products: MRLs for animal products were based on the maximum transfer factors and linear
ta
da
regression curves elaborated in the feeding studies. The calculation shows that for most of the animal
products the estimated residues were close or below 0.001 mg/kg, especially in milk, egg, poultry and
n
io
pig products. For these commodities no MRL value are proposed. At the opposite, some estimated
at
values for ruminant fat, liver, kidney and pig fat were higher than 0.005 mg/kg and the following MRLs
alu
are proposed:
ev
EC
These proposals have to be considered as an overestimate. Residues in maize grain, maize silage
ar
and sunflower grain were globally below the limit of quantification and the residue intakes by animals
sp
were not based on actual residue levels detected in plants, but were derived from the lowest LOQ
m
achieved in the residue trials (0.004 mg/kg). Providing of additional data on maize silage performed
or
with a lower LOQ (<0.001 mg/kg) would probably lead to the conclusion that it is not necessary to set
tf
STMRs were also calculated using the mean transfer factors proposed in the feeding studies. These
oc
m
cu
do
- Preharvest interval on each relevant crop
s
hi
Not applicable since fipronil is applied prior to or at time of sowing the crops, the PHI is therefore
t
of
automatically defined as the time between sowing and harvest. As indicative values, this time can be
- 80-120 days for corn silage,
is
as
- 120-180 days for corn grain,
eb
- 120-150 days for sunflower seed.
th
on
- Exposure through diet and other means
ed
t
an
Chronic exposure: Calculations of potential intake of fipronil residues in food have been carried out using
gr
the 3 following models:
be
- WHO/FAO model using the mean consumption data as given by GEM/food panel for Europe.
- UK/PSD model using the UK national consumption data (mean/97.5th percentile) for the 4 main
ot
tn
subgroups (adult, school child, toddler and infant).
us
- French model using the French national consumption data (mean/97.5th percentile) for the 3 main
m
subgroups (adult, toddler and infant).
n
io
t
TMDI calculations were performed including the proposed MRLs for plant and animal products and the
ra
estimated residue levels calculated by linear regression for the other animal commodities for which no
st
gi
MRLs were proposed (milk, egg, poultry meat…). STMR values elaborated for plant and animal
Re
commodities were used for IEDI evaluation. TMDI and IEDI calculations, expressed as % of the ADI
n.
(0.0002 mg/kg b.w./d) are summarised in the above table.
io
lat
TMDI calculation IEDI calculation
iso
Model
Adult child Infant toddler Adult child Infant toddler
in
WHO/FAO 17% / / / 6% / / /
d
For children, the relative high consumption values for milk explains that some TMDI are over 100% of the
no
ADI. Nevertheless, these evaluations must be considered as an overestimate since the residue levels in
ld
milk are not based on a transfer of actual residues that are present in maize silage, but on default value
ou
equal to the lowest LOQ (0.004 mg/kg). IEDI values are always below 100% of ADI.
sh
d
Acute exposure: Calculation has been performed with the UK/PSD acute exposure model using the 97.5th
an
consumption data for the British adult and toddler population. The NESTI value calculated for sweet corn
ge
and animal products (milk, egg, meat,…) is always less than 5% of the ARfD (0.009 mg/kg b.w./d).
ka
ac
Based upon these data, it is concluded that representative uses for fipronil do not lead to an unacceptable
p
m
cu
do
B.7.17 References relied on
s
t hi
of
Title / Source
Author(s) Dossier Year Company report no Data Owner
is
protection
as
file No. GLP / GEP status
eb
Published
th
Plant metabolism studies
on
ed
Yenne S.P., Annex II, 1994a Metabolic Fate and Distribution of 14C-Fipronil Yes BASF
t
Stone J.L. 6.1.1/01 (M&B46030) in Corn (171-4 Nature of the Residue -
an
Plants)
gr
Generated by: Rhone-Poulenc Ag Company, USA
be
Document No: R010630
ot
14 Sepytember 1994
tn
GLP / GEP Yes
us
un-published
Metabolic Fate and Distribution of 14C-Fipronil in Corn
m
Yenne S.P., Annex II, 1995a Yes BASF
n
Jesudason P. 6.1.1/02 Generated by: Rhone-Poulenc Ag Company, USA
io
Document No: R010634
t
ra
18 December 1995
st
GLP / GEP Yes
gi
un-published
Re
Bellett J., Annex II, 1993a Insecticides: Fipronil: Metabolism in Sunflowers Yes BASF
n.
French N.P., 6.1.1/03 Generated by: Rhone-Poulenc Agriculture Ltd.
io
Humphreys Document No: R010624
S.P., Maycey 26 February 1993
lat
iso
Yenne S.P., Annex II, 1995a 14C-Fipronil: Distribution and Metabolic Fate in Cotton Yes BASF
d
ea
un-published
ou
Oliver R.G., Annex II, 1993a Fipronil-14C: Metabolism in Sugarbeet (Final Report) Yes BASF
sh
P. 01 March 1993
ge
un-published
(14C)-Fipronil: Metabolism in wheat following
ac
22 June 2001
at
un-published
ev
EC
England
m
11 August 1994
tf
un-published
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
(14C)-M&B46,030: Distribution, Metabolism and
as
Stewart F.P. Annex II, 1994a Yes BASF
eb
6.2.1.2/01 Exretion following Multiple Oral Administration to the
Laying Hen
th
Generated by: Rhone-Poulenc Agriculture
on
Document No: R010220
ed
19 May 1994
t
GLP / GEP Yes
an
un-published
gr
be
Residue trials in maize
ot
tn
Baudet L., Annex II, 1999 Fipronil and metabolites - Formulation EXP60720A Yes BASF
us
Yslan F. 6.3.1.2.1/01 (WG) - South / Spain / 1998 - 2 Harvest trials:
m
Residues in maize (grain).
Generated by:
n
io
Rhone-Poulenc Secteur Agro, Lyon, France;
t
ra
Document No: R009971
st
10 August 1999
gi
GLP / GEP Yes
Re
un-published
n.
Richard M., Annex II, 1998a Fipronil and metabolites (MB45950, MB46136, Yes BASF
io
Maestracci M. 6.3.1.2.1/02 MB46513, RPA200766) - Formulation EXP60720A
lat
(WG) - Trials / France /1997: Residues in maize (cob,
iso
green plant, grain).
Generated by: Rhone-Poulenc
in
23 September 1997
er
Souvignet I. Annex II, 2001a Fipronil; MB 46030 and its metabolites MB 45950; MB Yes BASF
no
05 April 2001
ge
Gateaud L. Annex II, 2001e Residues in sweet corn (plant and cob) South / Yes BASF
ac
EXP60720A (WG)
Generated by: Aventis CropScience S.A., FRA
n
io
05 April 2001
alu
un-published
Gateaud L. Annex II, 2000b Residues in sweet corn (plant and cob) South / Yes BASF
EC
Generated by:
to
15 December 2000
m
un-published
tf
en
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Muller M.A: Annex II, 1996a Fipronil and Metabolites (MB45950, MB46136, Yes BASF
eb
6.3.1.2.2/04 MB46513, RPA200766) - Formulation EXP60166B
(GR) - Trials Italy 1995 - Residues in maize (shoot and
th
grain)
on
Generated by: Rhone-Poulenc;
ed
Document No: R010750
25 March 1996
t
an
GLP / GEP Yes
gr
un-published
be
Muller M.A. Annex II, 1995b Fipronil and metabolites (MB45950, MB46136, Yes BASF
ot
6.3.1.2.2/05 RPA200766) - Formulation EXP60166B (GR) - Greece
tn
1994 - Residues im maize (silage, grain)
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
us
France
m
Document No: R010736
n
io
05 October 1995
t
ra
GLP / GEP Yes
st
un-published
gi
Richard M., Annex II, 1994g Fipronil and Metabolites (MB45950, MB46136 and Yes BASF
Re
Muller M.A. 6.3.1.2.2/06 RPA200766) - Formulation EXP60166B (GR) - Greece
n.
1993 - Residues in Corn (green plant and cob)
io
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
France lat
iso
Document No: R010700
16 November 1994
in
un-published
ea
Richard M., Annex II, 1994e Fipronil et Metabolites (MB45950 - MB46136 - Yes BASF
er
21 December 1994
sh
Richard M., Annex II, 1994f Fipronil et Metabolites (MB45950, MB46136 et Yes BASF
Muller M.A. 6.3.1.2.2/08 RPA200766) - Formulation EXP60166B (GR) - Essai
ge
grain)
ac
France
ta
da
un-published
alu
Claviere B., Annex II, 1991b MB46030 et ses principaux Metabolites Formulation Yes BASF
ev
Muller M.A. 6.3.1.2.2/09 EXP60166 (GR) Essais France 1990 residus dans le
Mais pour ensilage
EC
20 February 1991
to
un-published
sp
Dupont C., Annex II, 1991b MB46030 et ses principaux Metabolites Formulation Yes BASF
m
Muller M.A. 6.3.1.2.2/10 EXP60166 (GR) - Essais France 1991 - Residus dans
or
le Mais ensilage
tf
25 November 1991
GLP / GEP Yes
oc
un-published
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Claviere B., Annex II, 1991a MB46030 et ses Principaux Metabolites - Formulation Yes BASF
eb
Muller M.A. 6.3.1.2.2/11 EXP60166 (GR) - Essais France 1990 - Residus dans
le Mais Grain
th
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
on
France
ed
Document No: R010638
13 June 1991
t
an
GLP / GEP
gr
un-published
be
Muller M.A. Annex II, 1996a FIPRONIL ET METABOLITES (MB45950, MB46136, Yes BASF
ot
6.3.1.2.2/12 MB46513, RPA200766) - ALDICARBE ET
tn
METABOLITES (sulfoxyde et sulfone) - Formulation
EXP61071A (GR) - Essais France 1995 - Residus
us
dans le mais (ensilage et grain)
m
Generated by: Rhone-Poulenc
n
io
Document No: R010780
t
ra
21 June 1996
st
GLP / GEP Yes
gi
un-published
Re
Maestracci M. Annex II, 1996a Fipronil and Metabolites (MB45950, MB46136, Yes BASF
n.
6.3.1.2.2/13 MB46513, RPA200766) - Formulation EXP80415A
io
(FS) - Trials Spain 1995 - Residues in Maize (grain
and straw) lat
iso
Generated by: Rhone-Poulenc
Document No: R010788
in
09 December 1996
d
un-published
er
Richard M., Annex II, 1995b Fipronil et metabolites (MB45950, MB46136 et Yes BASF
tb
France;
sh
Muller M.A. Annex II, 1994e Fipronil et ses metabolites - Formulation Yes BASF
ka
le mais (grain)
p
France
Document No: R010686
n
io
01 July 1994
at
un-published
ev
Muller M.A. Annex II, 1994h Fipronil et ses metabolites - Formulation Yes BASF
6.3.1.2.2/16 EXP80415A(FS) - Essais France 1993 - Residus dans
EC
le mais ensilage
n
France
to
22 July 1994
sp
un-published
or
tf
en
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Muller M.A. Annex II, 1994d Fipronil et ses metabolites - Formulation Yes BASF
eb
6.3.1.2.2/17 EXP80415A(FS) - Essai France 1993 - Residus dans
le mais doux
th
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
on
France
ed
Document No: R010685
01 July 1994
t
an
GLP / GEP Yes
gr
un-published
be
Muller M.A. Annex II, 1994g Fipronil et ses metabolites - Formulation EXP80415A Yes BASF
ot
6.3.1.2.2/18 (FS) - Essai France 1993 - Residus dans le mais
tn
(Etude de decroissance)
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
us
France
m
Document No: R010688
n
io
22 July 1994
t
ra
GLP / GEP Yes
st
un-published
gi
Muller M.A. Annex II, 1994i Fipronil et ses Metabolites - Formulation Yes BASF
Re
6.3.1.2.2/19 EXP80415A(FS) - Essai France 1993 - Residus dans
n.
le mais ensilage
io
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
France lat
iso
Document No: R010684
24 July 1994
in
un-published
ea
Muller M.A. Annex II, 1993b Fipronil et Metabolites - Formulation EXP80415A (FS) Yes BASF
er
France
ld
27 Octobre 1995
sh
Klein E. H.-J. Annex II, 2002c Decline of residues in flint corn European Union Yes BASF
6.3.1.2.2/21 (Southern zone) 2000 Fipronil granular bait (GB) 0.5
ge
(EXP61829A)
ac
un-published
alu
Klein E. H.-J. Annex II, 2002b Decline of residues in sweet corn European Union Yes BASF
ev
(EXP61829A)
n
18 March 2002
sp
un-published
or
tf
en
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Richard M., Annex II, 1998a Fipronil and metabolites (MB45950, MB46136, Yes BASF
eb
Maestracci M. 6.3.1.3.1/01 MB46513, RPA200766) - Formulation EXP60720A
(WG) - Trials / France /1997: Residues in maize (cob,
th
green plant, grain).
on
Generated by: Rhone-Poulenc
ed
Document No: R009957
23 September 1998
t
an
GLP / GEP Yes
gr
un-published
be
Souvignet I. Annex II, 2001a Fipronil; MB 46030 and its metabolites MB 45950; MB Yes BASF
ot
6.3.1.3.2/01 46136; MB 46513 formulation EXP 60720A wg north
tn
France 2000 1 harvest trial south France 2000 2
harvest trials residues in sweet corn
us
Generated by: Aventis CropScience S.A., FRA
m
Document No: C012489
n
io
05 April 2001
t
ra
GLP / GEP Yes
st
un-published
gi
Muller M.A. Annex II, 1996a FIPRONIL ET METABOLITES (MB45950, MB46136, Yes BASF
Re
6.3.1.3.2/02 MB46513, RPA200766) - ALDICARBE ET
n.
METABOLITES (sulfoxyde et sulfone) - Formulation
io
EXP61071A (GR) - Essais France 1995 - Residus
lat
dans le mais (ensilage et grain)
iso
Generated by: Rhone-Poulenc
Document No: R010780
in
21 June 1996
d
un-published
er
Claviere B., Annex II, 1991b MB46030 et ses principaux Metabolites Formulation Yes BASF
tb
Muller M.A. 6.3.1.3.2/03 EXP60166 (GR) Essais France 1990 residus dans le
no
Generated by:
ou
Claviere B., Annex II, 1991a MB46030 et ses Principaux Metabolites - Formulation Yes BASF
ka
Muller M.A. 6.3.1.3.2/04 EXP60166 (GR) - Essais France 1990 - Residus dans
ac
le Mais Grain
p
France
Document No: R010638
n
io
13 June 1991
at
GLP / GEP
alu
un-published
ev
Dupont C., Annex II, 1991a Residus dans le mais vert Etude de decroissance Yes BASF
Muller M.A. 6.3.1.3.2/05 Essai / France / 1991 Formulation EXP60166 (GR)
EC
29 November 1991
ar
un-published
m
Claviere B., Annex II, 1990a Residus dans le mais Etude de decroissance Essai / Yes BASF
or
Generated by:
um
18 December 1990
sd
un-published
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Muller M.A. Annex II, 1994e Fipronil et ses metabolites - Formulation Yes BASF
eb
6.3.1.3.2/07 EXP80415A(FS) - Essais France 1993 - Residus dans
le mais (grain)
th
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
on
France
ed
Document No: R010686
01 July 1994
t
an
GLP / GEP Yes
gr
un-published
be
Muller M.A. Annex II, 1994h Fipronil et ses metabolites - Formulation Yes BASF
ot
6.3.1.3.2/08 EXP80415A(FS) - Essais France 1993 - Residus dans
tn
le mais ensilage
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
us
France
m
Document No: R010687
n
io
22 July 1994
t
ra
GLP / GEP Yes
st
un-published
gi
Muller M.A. Annex II, 1993b Fipronil et Metabolites - Formulation EXP80415A (FS) Yes BASF
Re
6.3.1.3.2/09 - Essais France 1992 - Residus dans le Mais (Grain)
n.
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
io
France
Document No: R010675 lat
iso
27 October 1993
GLP / GEP Yes
in
un-published
d
Klein E. H.-J. Annex II, 2002d Decline of residues in flint corn European Union Yes BASF
ea
(EXP61829A)
no
18 March 2002
GLP / GEP Yes
d
an
un-published
Klein E. H.-J. Annex II, 2002a Decline of residues in sweet corn European Union Yes BASF
ge
(EXP61829A)
p
18 March 2002
at
un-published
ev
Muller M.A. Annex II, 1994c Fipronil et ses metabolites - Formulation Yes BASF
fa
le tournesol (graine-huile-tourteau)
ar
France
m
01 July 1994
tf
un-published
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Maestracci M. Annex II, 1997g Fipronil and Metabolites (MB45950, MB46136, Yes BASF
eb
6.3.2.2/02 MB46513, RPA200766) - Formulation EXP80415A
(FS) - Trials Spain 1996 - Residues in Sunflower
th
(seed, pressed cake, oil)
on
Generated by: Rhone-Poulenc
ed
Document No: R010826
26 August 1997
t
an
GLP / GEP Yes
gr
un-published
be
Muller M.A. Annex II, 1995a Fipronil et ses Metabolites (MB45950, MB46136, Yes BASF
ot
6.3.2.2/03 RPA200766) - Formulation EXP80415A (FS) - Essai
tn
Espagne 1994 - Résidus dans le Tournesol (graine,
huile, tourteau)
us
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
m
France
n
io
Document No: R010747
t
ra
08 December 1995
st
GLP / GEP Yes
gi
un-published
Re
Muller M.A. Annex II, 1993a Fipronil et Metabolites - Formulation EXP80415A (FS) Yes BASF
n.
6.3.2.2/04 - Essais France 1992 - Residus dans le Tournesol
io
(Graine)
lat
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
iso
France
Document No: R010670
in
25 October 1993
d
un-published
er
Muller M.A. Annex II, 1994c Fipronil et ses metabolites - Formulation Yes BASF
tb
le tournesol (graine-huile-tourteau)
ld
France
sh
Muller M.A. Annex II, 1993a Fipronil et Metabolites - Formulation EXP80415A (FS) Yes BASF
ka
(Graine)
p
France
Document No: R010670
n
io
23 October 1993
at
un-published
ev
Muller M.A. Annex II, 1994c Fipronil et ses metabolites - Formulation Yes BASF
6.5.2.1/01 EXP80415A(FS) - Essais France 1993 - Residus dans
EC
le tournesol (graine-huile-tourteau)
n
France
to
01 July 1994
sp
un-published
or
tf
en
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
Muller M.A. Annex II, 1995a Fipronil et ses Metabolites (MB45950, MB46136, Yes BASF
eb
6.5.2.1/02 RPA200766) - Formulation EXP80415A (FS) - Essai
Espagne 1994 - Résidus dans le Tournesol (graine,
th
huile, tourteau)
on
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
ed
France
Document No: R010747
t
an
08 December 1995
gr
GLP / GEP Yes
be
un-published
ot
Maestracci M. Annex II, 1997g Fipronil and Metabolites (MB45950, MB46136, Yes BASF
tn
6.5.2.1/03 MB46513, RPA200766) - Formulation EXP80415A
(FS) - Trials Spain 1996 - Residues in Sunflower
us
(seed, pressed cake, oil)
m
Generated by: Rhone-Poulenc
n
io
Document No: R010826
t
ra
26 August 1997
st
GLP / GEP Yes
gi
un-published
Re
n.
Storage stability studies
io
Upalawanna Annex II, 1994d lat
Storage stability of fipronil and its metabolites in field Yes BASF
iso
S. 6.0/01 corn substrates and corn processed fractions
Generated by: Rhone-Poulenc Secteur Agro, Lyon,
in
France;
d
ea
23 Novembere 1994
GLP / GEP Yes
tb
un-published
no
Eng S. Annex II, 1996b Fipronil: Freezer Storage Stability of Fipronil and Its Yes BASF
ld
un-published
Eng S. Annex II, 1997a Fipronil: Freezer Storage Stability of Fipronil and its Yes BASF
ka
05 November 1997
GLP / GEP Yes
n
io
un-published
at
Plaisance Annex II, 1998a Storage Stability Study of Fipronil and Its Metabolites Yes BASF
alu
10 June 1998
n
un-published
to
Eng S. Annex II, 1996a Storage Stability Study of Fipronil and its Metabolites Yes BASF
ar
18 September 1996
tf
un-published
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
Title / Source
s
hi
Author(s) Dossier Year Company report no Data Owner
t
file No. GLP / GEP status protection
of
Published
is
as
eb
Industrial processing studies
th
Metcalf D., Annex II, 2001a (14C)-Fipronil - Investigation of the nature of the Yes BASF
on
McMillan- 6.5.1/01 potential residue in the products of industrial
ed
Staff S., processing or household preparation
t
Knight S. Generated by: Aventis CropScience UK
an
Document No: C016240
gr
08 November 2001
be
GLP / GEP Yes
ot
un-published
tn
Kowite W.J. Annex II, 1993a Fipronil: Magnitude of Residues in Corn processing Yes BASF
us
6.5.2.2/01 Fractions Resulting from Ground Applications of
m
Granular Formulated Product (1992)
Generated by: Rhone-Poulenc Ag Company, USA
n
io
Document No: R010663
t
ra
19 August 1993
st
GLP / GEP Yes
gi
un-published
Re
n.
Livestock feeding studies
io
Byrd J.W. Annex II, 1994a
lat
Fipronil: Magnitude of Residues in Meat and Milk of Yes BASF
iso
13 September 1994
er
un-published
Byrd J.W. Annex II, 1994b Fipronil: Magnitude of Residues in Meat and eggs of Yes BASF
no
15 September 1994
d
un-published
ge
Byrd J.W. Annex II, 1994a Fipronil: Magnitude of Residues in Meat and Milk of Yes BASF
ka
13 September 1994
da
Tew E.L. Annex II, 1999a Fipronil: Residue Decline in Dairy Cow Milk and Yes BASF
at
27 September 1999
GLP / GEP Yes
n
un-published
fa
Byrd J.W. Annex II, 1994b Fipronil: Magnitude of Residues in Meat and Eggs of Yes BASF
to
15 september 1994
or
un-published
en
um
oc
sd
hi
:T
NG
NI
AR
W
m
cu
do
s
t hi
of
Succeeding crop study
is
Fipronil (14C-phenyl ring labeled) sub-surface soil
as
Jesudason Annex II, 1995a BASF
eb
P.A., Mackie 6.6.1/01 treatment: Accumulation study on confined rotational
S.J.W. crops.
th
Generated by: Rhone-Poulenc
on
Document No: R010589
ed
14 December 1995
t
GLP / GEP Yes
an
un-published
gr
be
ot
tn
us
m
n
io
t
ra
st
gi
Re
n.
io
lat
iso
in
d
ea
er
tb
no
ld
ou
sh
d
an
ge
ka
ac
p
ta
da
n
io
at
alu
ev
EC
n
fa
to
ar
sp
m
or
tf
en
um
oc
sd
hi
:T
NG
NI
AR
W