DICHLOFLUANID JMPR 1977
Explanation
The Joint Meeting evaluated dichlofluanid in 1969 and 1974 (FAO/WHO,
1970, 1975). A temporary ADI was established in 1974, when further
information was required on the absorption, distribution and excretion
of dichlofluanid and on the pharmacokinetics of the
dichlorofluoromethylthio moiety. Further information was recorded as
desirable on the fate of the fluorine-containing moiety of the
molecule in and on plants, on residues resulting from supervised
trials on various specified crops, on residues in raw agricultural
products moving in commerce and on the suitability of Becker's
analytical method for regulatory purposes.
Some of the required information has been provided, and is reviewed
below.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Absorption, distribution, biotransformation and excretion
Groups of rats received a single oral dose of 14C-dichlofluanid (0.1,
5 or 20 mg/kg b.w.) in order to establish the excretion rate and
distribution over various organs. The 14C-label was incorporated in
the dichlofluoromethylthio moiety and thus, activities reflect the sum
of the unchanged compound and some of its metabolites. 40-60% of the
dose was eliminated in urine and 20-30% in faeces, while 22% was
exhaled within the first 48 hr. In 24 hr the elimination through bile
following an intraduodenal injection (0.5 mg/kg b.w.) was 7% of the
initial activity. From these data it was calculated that 70-80% of
orally administered dichlofluanid was absorbed.
The distribution over various organs was measured during the 10 days
following oral administration of 5 mg dichlofluanid/kg b.w.
In a period from 2 hr to 2 days after injection, about a ten-fold
decrease in the amount of labelled substances in the whole body was
observed. After 10 days a residue of 1% was measured. Similar
decreases were found in pancreas, spleen, lungs, brain, testes,
muscle, skin, perirenal fat, erythrocytes and plasma, while liver,
kidneys and adrenals showed somewhat higher residues. A dissimilar
pattern was found in the thyroid. The maximal concentration was
reached after 1 day (compare e.g., plasma, 1.5 hr) and at each time of
measurement a relative concentration about 50 times that in the whole
body was observed (Weber et al., 1977).
COMMENTS
Adequate information on absorption, distribution, excretion and
pharmacokinetics of the dichlorofluoromethylthic moiety has been
provided. Within 2 days about a ten-fold decrease in the amount of
labelled dichlofluanid was observed in most of the organs. After 10
days a residue of 1% of the dose was present. The consequence of
relatively high residues of this organic fluorine compound in the
thyroid was of some concern and should be further investigated.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 1500 mg/kg in the diet, equivalent to 75 mg/kg bw
Dog: 1000 mg/kg in the diet, equivalent to 25 mg/kg bw
ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR HUMANS
0-0.3 mg/kg bw
RESIDUES IN FOOD AND THEIR EVALUATION
RESIDUES RESULTING FROM SUPERVISED TRIALS
Some of the trials data requested in 1974, together with data on some
other crops, were supplied (Table 1). Residues were below the
following levels (mg/kg): 15 in blackberries, 7 in gooseberries and
onion leaves, 2 in paprika, 1 in dried hops, 0.5 in wheat straw and
0.1 in wheat grain and onions (bulbs). In addition, residues resulting
from supervised trials on eggplants and gherkins were at or below 1
mg/kg and on potatoes below 0.1 mg/kg. New residue data for currants,
beans with pod, strawberries (under glass), cucumber, lettuce (under
glass) and tomatoes were below the limits recommended by the 1974
Joint Meeting.
No information was provided on residue levels in loganberries,
mulberries, raspberries, leaf brassicas, melons, kohlrabi or barley.
FATE OF RESIDUES
In soil
Different types of soil were field-treated with 15 kg
dichlofluanid/ha; 2-3 months after application, residues of
dichlofluanid + dimethylphenylsulphamide (DMSA) in the upper layers
(0-10 cm depth) were below 0.1 mg/kg. Columns containing 30 cm layers
of sand or sandy loam were treated with dichlofluanid at a rate
corresponding to 2.5 kg/ha and leached to simulate a rainfall of 200
mm. Less than 1% of the applied dose (as dichlofluanid + DMSA) was
found in the leachate (Bayer, 1975/77).
In Japan, volcanic ash, diluvial and alluvial soils treated 1-3 times
each with 2 mg dichlofluanid/kg soil, contained < 0.03-0.4 mg/kg 7-11
days after the last application; 27 days after the last of 4-5
applications, residues were < 0.03-1.4 mg/kg (Takase and Terada,
1976).
In processing
Field-treated strawberries with original levels of 8.6 and 5.1 mg
dichlofluanid + DMSA/kg contained 1.9 and 1.5 mg/kg respectively after
washing. After canning, residues declined to 1.3 and 1.0 mg/kg. 08
mg/kg was found in jam made from the strawberries (Wrieden, 1976).
RESIDUES IN FOOD MOVING IN COMMERCE
In 1976 a total of 449 samples of 19 fruits and vegetables (especially
strawberries, currants and blackberries) moving in commerce were
analysed for dichlofluanid (including DMSA calculated as the parent
compound) in the Netherlands (Food Inspection Services, 1976). Only 15
of the samples, all of strawberries, currants or raspberries, had
residues above 2mg/kg of which three samples of strawberries contained
residues higher than 5 mg/kg (5.4, 14.5 and 20 mg/kg). In 189 samples,
the residues were at or below 0.1 mg/kg. Residue levels (except in two
samples of strawberries) were well below the limits recommended by the
Joint Meeting.
METHODS OF RESIDUE ANALYSIS
A gas-chromatographic method has been developed which determines
dichlofluanid + DMSA (Vogeler, 1975/77). After extraction with
water/acetone and dichloromethane, dichlofluanid is saponified and the
total DMSA determined by a flame photometric detector in the sulphur
mode. The lower limit of determination is at or about 0.1 mg/kg
expressed as dichlofluanid. The method is less suitable for regulatory
purposes than the multi-residue method of Becker.
The Becker method was studied collaboratively by 4 laboratories
(Thier, 1977). 16 species of fruit and vegetables were spiked within a
range of 0.01-15 mg dichlofluanid/kg and analysed. Recoveries were
between 71 and 106% with an average of about 90%. The method of Becker
is suitable for regulatory purposes.
APPRAISAL
Residue data requested by the 1974 Joint Meeting confirmed that the
temporary maximum residue limits recommended then for beans,
cucumbers, currants, lettuce, strawberries and tomatoes were
appropriate. They also provided a basis for the new temporary limits
recommended below.
Dichlofluanid was shown not to be readily leached from soil. Residues
in soil after field application were below 0.5 mg/kg after one month
and below 0.1 mg/kg after 2-3 months.
Residues in strawberries were reduced to about 20-30% of the original
level by washing, 15-20% by canning and 10-15% by jam making.
TABLE Residues of dichlofluanid + dimethylphenylsulphamide (DMSA) expressed as dichlofluanid on different crops from
supervised trials
Crop Country1/ Dose kg No. of Days after Residue (mg/kg) References
a.i./ha applications last appl.
blackberries D 2.0 5 0 11.6 - 47.0 Bayer, 1975/77
4 8.4 - 22.5
7 7.0 - 7.2
14 3.1 - 5.2
21/22 1.0 - 3.2
beans, green, D 1.3 5 0 1.6 -2.6 Bayer, 1975/77
with pods 4-7 0.4 -0.8
14-28 0.1 -0.3
cucumber D 1 8 0-10 <0.1 -0.1 Bayer, 1975/77
J 1.5-2 10 1-7 <0.1 2/ Nitokuno, 1971/74
cucumber, D 0.6-2 10 0-1 0.5 - 3.2
under glass 3-10 0.3 - 1.8
currants D 2.0 3 0 11.1 - 18.7 Bayer, 1975/77
(black) 4 7.0 - 8.9
7 3.6 - 3.9
14 2.7 - 2.8
21 0.6 - 0.9
eggplant J 4 1-2 0-1 <0.1 - 1.0 2/ Nitokuno, 1971/74
3-7 0.1 - 0.5 2/
gooseberries D 2.0 4 0 5.2 - 7.9 Bayers 1975/77
4 4.1 - 6.7
7 2.7 - 6.1
14-21 0.7 - 2.2
TABLE (Continued)
Crop Country1/ Dose kg No. of Days after Residue (mg/kg) References
a.i./ha applications last appl.
gherkins, D 1.2 10 0-1 0.5 - 0.8 Bayer, 1975/77
under glass 3-10 0.3 - 0.6
hops J 5.0-5.8 3 21 0.42 Nitokuno, 1971/74
26 0.041
lettuce J 2 4-9 2-10 <0.1-0.1 2/ Nitokuno, 1971/74
lettuce, D 0.6 6 0 31
under glass 14-28 0.1-2.4 Bayer, 1975/77
onions, D 1.0 6 0 12.3 - 19.0 Bayer, 1975/77
leaves 4 3.7 - 7.9
7 3.0 - 6.9
14 1.8 - 3.4
21-28 0.3 - 2.1
bulbs D 0-28 <0.1
bulbs J 0.8-1.3 7-14 7-20 <0.1 Nitokuno, 1971/74
peppers, D 1 6 0-1 1.3 - 3.5 Bayer, 1975/77
sweet 3-14 <0.1 - 0.8
potatoes D 0.6 6 7 <0.1 Bayer, 1975/77
strawberries, J 2.5-3 2-4 1-10 0.3 - 4.6 2/ Nitokuno, 1971/74
under glass
tomatoes D 1.2 6 0-7 0.3 - 1.0 Bayers 1975/77
J 1.5-4 1-10 0-7 <0.1 - 0.3 2/ Nitokuno, 1971/74
TABLE (Continued)
Crop Country1/ Dose kg No. of Days after Residue (mg/kg) References
a.i./ha applications last appl.
tomatoes, D 1.2 6 0-7 0.1 - 0.5 Bayer, 1975/77
under glass
wheat grain D 1 1 42 <0.1 - 0.1 Bayer, 1975/77
wheat 0 14.1 - 23.4
ears/straw 14 1.5 - 2.9
28-35 0.1 - 0.3
1/ D = Federal Republic of Germany
J = Japan
2/ analysed for dichlofluanid only
The gas-chromatographic multi-residue analytical method of Becker has
been validated for regulatory purposes by collaborative study. A
method for determining both dichlofluanid and dimethylphenylsulphamide
(DMSA) by gas chromatography has been developed, but is less suitable
for regulatory analysis.
RECOMMENDATIONS
The following temporary maximum residue limits are recommended in
addition to those proposed in 1974. They refer to dichlofluanid only.
Commodity Limit, mg/kg Pre-harvest interval (days) on
which recommendation is based
Blackberries 15 3-7
Gooseberries 7 0-7
Sweet peppers 2 1-3
Eggplants,
hops (dried) 1 0-1
Wheat straw 0.5 28
Onions, bulb 0.1 0-28
Potatoes 0.1 0-21
Raw grain
(barley, oats,
rye, wheat) 0.1 42
FURTHER WORK OR INFORMATION
REQUIRED (by July 1979)
1. Studies to elucidate the accumulation seen in the thyroid.
2. Results from current studies on the pathways of degradation,
especially the fate of the fluorine-containing moiety of the molecule
in or on plants.
DESIRABLE
1. Further residue data on dichlofluanid residues (parent compound)
resulting from supervised trials especially on melons and leaf
brassicas.
REFERENCES
Bayer, A.G. 1975/77 Pflanzenschutzmittel-Rückstände, Dichlofluanid
(Euparen); Leverkusen, Federal Republic of Germany (unpublished).
Food Inspection Services; 1976 Information from the Netherlands on
pesticides included in the priority lists. Dichlofluanid. Ref: CL
1977/15; Oct. 20, 1977.
Nitokuno Institute; 1971/74 Analytical Test Results on Residues,
Dichlofluanid (Euparen), Nihon Tokushu Noyaku Seizo K.K., Japan
Takase, I. and Terada, H. 1976 Residues of Euparen and Morestan in
Upland Soils after Multiple Treatment. Nihon Tokushu Noyaku Seizo
K.K., Agric. Chemicals Inst., Japan; Report No. 1043; 30 March 1976.
Thier, H.-P. 1977 Arbeitsgruppe zur Rückstandsanalytik der Pestizide
in Lebensmitteln. Unpublished
Vogeler, K. 1975-7 in Bayer A.G., 1975-77, reference above
Weber, H., Patschke, K., Wegner, L.A. Dichlofluanid - 14C
(EuparenR-Wirkstoff); Biokinetische Untersuchungen an Ratten. Bayer
AG Bericht Nr. 7081. Submitted to the WHO (1977) (unpublished report)
Wrieden, J. 1976 Untersuchungen von Fungizidrückständen (EUPAREN) in
Erdbeeren nach deren Verarbeitung zu Marmelade und Obstkonserven.
Diplomarbeit, Inst. f. spezielle Lebensmitteltechnologie, Univ.
Hohenheim; Fed. Rep. Germany.
FAO/WHO, 1970 1969 evaluations of some pesticide residues in food.
FAO/PL:1969/M/17/1; WHO/Food Add./70.38.
FAO/WHO 1975 1974 evaluations of some pesticide residues in food. AGP:
1974/M/11; WHO Pesticide Residues Series, No. 4.