DINOCAP JMPR 1974
Explanation
Dinocap was evaluated at the Joint Meeting in 1969 (FAO/WHO,
1970) at which time neither an acceptable daily intake nor tolerances
could be established because the data were insufficient. Further
information was required on the compounds included in dinocap, on the
nature of terminal residues and on residues in countries other than
the USA. Assurance of a standardized technical product was also
required.
Since the 1969 meeting, some additional experimental work has
been reported.
IDENTITY
Composition of Technical Product
Data on the composition of two dinocap products, Karathane
Technical and Karathane WD, from the same manufacturer have been
reported (Kurtz et al., 1970). Data were presented on the GLC analysis
of Karathane Technical samples over the period December 1963 to May
1969. Karathane Technical contained approximately 74% (range 72.0
- 76.7%) of 2,4- and 2,6-dinitro-octylphenyl crotonates and
approximately 6% of mixed nitro-octylphenyls, 0.54 - 0.86%
mononitro-octylphenols and 4.0 - 6.9% dinitro-octylphenols.
Non-volatile material accounted for 6 - 13%. Infra-red and biological
examination of the non-volatile fraction indicated that the material
was a complex polymeric mixture, inactive against mildews and fungi
and not phytotoxic.
GLC analysis of the technical dinitro-octylphenols showed that
ortho-octyl isomers (2,4-dinitro-6-octylphenols) and the para-octyl
isomers (2,6-dinitro-4-octylphenols) made up 65.6 - 69.3 and
30.7 - 34.4% respectively of the dinitro-octylphenols in the
formulation.
Analysis of four Karathane WD samples showed 16.8 - 17.7%
2,4- and 2,6-dinitro-octylphenyl crotonates, 2.4 - 3.1%
dinitro- octylphenols and 0.19 - 0.21% mononitro-octylphenols giving
a total active ingredient content of 19.4 - 20.7%, which is in good
agreement with the declared content.
The foregoing data demonstrated that the composition of Karathane
Technical was relatively constant over the period 1963-1969. The
limited data on Karathane WD showed good agreement between the total
active ingredient found and the value to be expected from the assay of
Karathane Technical.
Data were not available to the Meeting to evaluate the
composition of other manufacturers' products.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
This compound was reconsidered by the 1974 Joint Meeting on the
basis of two new metabolism studies (Rohm and Haas, 1970; Graham and
Bornak, 1972). These studies, however, did not meet Joint Meeting data
requirements (FAO/WHO, 1970) for an ADI. The Meeting emphasized that
additional studies with a larger number of ducks at various dose
levels were needed to establish the exact dosage of dinocap which does
not produce cataracts.
Significant data were not available to allocate an ADI for man.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Studies with 14C-dinocap fed to rats and cows are described in
detail in the following section. Rats fed 10 mg per day for seven days
followed by a four-day withdrawal period showed low levels of
radioactivity in the tissues, the highest being in the liver and
kidney and corresponding to about 3.5 mg/kg, calculated as dinocap.
Lactating cows fed up to 1 ppm in the diet had no detectable residues
in milk or tissues. Although the feeding levels were low, they
reflected those likely to be encountered in practice.
FATE OF RESIDUES
In Animals
One adult female and one adult male albino rat were each dosed
for 7 consecutive days with 14C-dinocap, labelled uniformly in the
aromatic ring (Rohm and Haas, 1970). The dosing period was followed by
a four-day withdrawal period prior to slaughter. The daily dose was
10 mg/animal or 500 ppm in the daily diet. The results of this study,
summarized in Table 1, showed that virtually all of the dinocap and/or
its metabolites was quickly excreted in the faeces and urine, about
equally by each route. Only approximately 0.3% of the administered
dinocap and/or metabolites remained in the tissues or organs. The
tissue and organ residue data, Table 2, show that there was no
tendency for residues to concentrate in any particular tissue or
organ. The highest levels of radioactivity were in the kidney and
liver, where they were equivalent to about 3.5 mg/kg calculated as
dinocap.
Dinocap, uniformly 14C-labelled in the aromatic ring was
administered to 3 lactating Holstein dairy cows at dosing levels of
0.1, 0.3 and 1.0 ppm based on the total daily diet (Graham and Bornak,
1974). The sensitivity of detection of radioactivity was 0.004 mg/kg
in milk and urine, 0.05 mg/kg in fat and 0.04 mg/kg in other tissues.
Dinocap and/or its metabolites were eliminated almost entirely in the
faeces with only small quantities in the urine. No radioactive
residues above control levels were found in either the milk or the
tissues at any of the dosing levels. Recovery of all the administered
dinocap in the excreta was satisfactory.
TABLE 1. 14C-dinocap material balance in rate fed 14C-dinocap
in the diet
Percent Recovery of
Total Administered Dose
Sample Female Rat Male Rat
Urine 38.4 50.8
Faeces 63.5 49.5
Cage Wash 2.4 2.5
CO2 0.2 0.2
Tissues and Organs 0.3 0.3
TOTAL 104.8 103.3
TABLE 2 Residue data and recovery of radioactive residues in tissues
and organs of rats fed 14C-dinocap in the diet
FEMALE MALE
mg/kg Recovery mg/kg Recovery
Organ average %1 average %1
Kidneys 3.48 0.007 2.76 0.006
Liver 3.31 0.034 3.79 0.044
Stomach and Intestine 2.21 0.044 1.12 0.025
Skin and Hair 2.14 0.080 2.66 0.110
Blood 1.34 0.003 0.83 0.004
Fat 0.98 0.002 0.58 0.001
Carcass 0.92 0.160 0.51 0.080
Adrenals 0.82 0.000 0.83 0.000
TABLE 2 (Cont'd.)
FEMALE MALE
mg/kg Recovery mg/kg Recovery
Organ average %1 average %1
Spleen 0.73 0.001 0.67 0.001
Lung 0.73 0.001 0.63 0.001
Heart, Aorta, and Thymus 0.68 0.001 0.49 0.001
Trachea and Esophagus 0.68 0.000 0.52 0.000
Gonads - - 0.25 0.002
Ovaries and Oviduct 0.65 0.000 - -
Submaxillary Lymph Nodes 0.49 0.001 0.44 0.000
Skeletal (Bone, Muscle) 0.42 0.001 0.25 0.001
Brain, Spinal Cord,
Pituitary 0.13 0.000 0.16 0.000
1 Recovery is based on total administered dose of 1.44 × 107
DPM × 7 = 1.01 × 108 DPM.
METHODS OF RESIDUE ANALYSIS
Colorimetric methods of residue analysis described in the 1969
monograph (FAO/WHO, 1970) determine the dinitrophenol moiety. These
methods are nonspecific since they would include residues of
dinitrophenols arising from other sources. Such methods are suitable
to determine residues in samples from supervised trials but not for
regulatory purposes. Similar concerns were discussed in the 1969
monograph (FAO/WHO, 1970) on binapacryl where colorimetric methods
suggested for binapacryl will also determine its metabolite,
2-sec-butyl-4,6-dinitrophenol (dinoseb) which also has uses as a
pesticide. Other pesticides such as dinoprop, dinosam, dinoterbon,
DNOC, etc., would also interfere with or be determined by the
colorimetric methods for dinocap. The development and evaluation of a
specific residue method for dinocap suitable for regulatory purposes
is required.
EXAMPLES OF NATIONAL TOLERANCES REPORTED TO THE MEETING
Tolerance
Country Commodity (mg/kg)
Australia Apples, apricots, beets, carrots,
citrus, corn, cucumbers, grapes,
melons, onions, peaches, pears,
peppers, plums, potatoes,
tomatoes 7
Belgium Apples, apricots, beets, carrots,
citrus, corn, cucumbers, grapes,
melons, onions, peaches, pears,
peppers, plums, potatoes,
tomatoes 1
Canada Apples, cucumbers, grapes,
melons, peas, squash NR1
Federal Rep. Apples, apricots, beets, carrots,
of Germany citrus, corn, cucumbers, grapes,
melons, onions, peaches, pears,
peppers, plums, potatoes,
tomatoes 1
Netherlands Apples, apricots, beets, carrots,
citrus, corn, cucumbers, grapes,
melons, onions, peaches, pears,
peppers, plums, potatoes,
tomatoes 1
Switzerland Apples, apricots, citrus,
cucumbers, grapes, melons,
peaches, pears, plums 0.1
U.S.A. Dried apple pomace 0.32
Apples, apricots, cantaloupes,
cucumbers, grapes, honeydew
melons, muskmelons, nectarines,
peaches, pears, pumpkins,
squash (summer and winter),
watermelons 0.12
1 Negligible residues (< 0.05 ppm).
2 Including related nitro-octylphenols (principally dinitro, calculated
as the ester).
APPRAISAL
Data presented to the Meeting concerning dinocap technical
material (Karathane Technical from one manufacturer) indicated that
this material was of relatively constant composition. This was
confirmed by analyses of a formulation from the same manufacturer.
Information was not available on technical materials or formulations
from other manufacturers.
Dinocap administered to animals is rapidly excreted. Residues
were not detected in the milk or tissues of cows given 14C-dinocap in
their diet at levels likely to be encountered in crop materials fed to
cows. Colorimetric methods discussed in the 1969 Monograph (FAO/WHO,
1970) would be adequate for the determination of residues of the
parent compounds in samples from supervised trials but not suitable
for regulatory purposes. Data are not available on the metabolism or
degradation of dinocap.
National tolerances are in effect in a number of countries.
RECOMMENDATIONS
The residue data from the 1969 monograph (FAO/WHO, 1970) were
reviewed together with new information on technical material and
animal studies. Since no ADI was established, no recommendations for
tolerances could be made. However, provided good agricultural practice
is observed, the following levels of dinocap and related
nitro-octylphenols, expressed as dinocap, need not be exceeded.
GUIDELINE LEVELS 1
Crops mg/kg
Apples, apricots, blackberries, boysenberries,
cantaloupes, cucumbers, grapes, honeydew
melons, muskmelons, peaches, pears, pumpkins,
raspberries, squash, strawberries 0.1 2
1 Recommended guideline levels are based on following
pre-harvest intervals: cantaloupes, cucumbers, honeydew melons,
muskmelons, pumpkins, squash - 7 days; blackberries,
boysenberries, raspberries - 14 days; apples, apricots, peaches,
pears, strawberries - 21 days; grapes - 28 days.
2 At or about the limit of determination.
FURTHER WORK OR INFORMATION
REQUIRED
1. Information on the nature of dinocap residues.
2. Residue data from countries other than the U.S.A. and Canada.
3. The development and evaluation of a specific residue method
suitable for regulatory purposes.
REFERENCES
FAO/WHO. (1970) 1969 Evaluations of some pesticide residues in food.
FAO/PL/1969/M/17/1; WHO/Food Add./70.38.
Graham, W.H. and Bornak, W.E. (1974) A study to determine residue
levels in milk and tissues from cows fed C14-Karathane. Report No.
23-49. Rohm and Haas Company, Philadelphia, USA. (Unpublished).
Kurtz, C.P., Baum, H. and Swittenbank, C. (1970) Gas chromatographic
determination of total active ingredient content of Karathane
Technical and Karathane WD. I. Development of the method. J. Ass. off.
analyt. Chem., 53:887-895.
Rohm and Haas. (1970) A material balance study in rats using
C14-Karathane uniformly labelled in the aromatic ring. Report No.
23-27. Rohm and Haas Company, Philadelphia, USA. (Unpublished).
See Also:
Toxicological Abbreviations
Dinocap (FAO/PL:1969/M/17/1)
Dinocap (Pesticide residues in food: 1989 evaluations Part II Toxicology)
Dinocap (JMPR Evaluations 1998 Part II Toxicological)