DIOXATHION JMPR 1972
Explanation
Dioxathion was evaluated at the Joint Meeting in 1968 and further
information was required by 30 June 1972 (FAO/WHO, 1969b). Since the
previous evaluation, some new experimental work on residues in food
has been reported and the information filed with FAO in 1968 was
reviewed.
IDENTITY
Other information on identity and properties
Technical dioxathion contains a minimum of 68% of the cis and
trans isomers of 2,3-p-dioxanedithiol-S, S-bis (O,O-diethyl
phosphorodithioate). The remainder consists of related compounds
described by Arthur and Casida (1959) as:
1. 10% ethyl phosphorothioates and ethyl phosphorodithioates.
2. 1% bis (diethoxyphosphinothioyl) disulfide.
3. 5% 2-p-dioxenethiol-S-(O,O-diethylphosphorodithioate).
4. Diethylphosphorothioic acid, diethylphosphorodithioic acid
and their salts and oxygen analogues of the cis and
trans isomers of the principal component and of (3) above.
O,O,O-triethyl phosphorothioate and O,O,S-triethyl
phosphorodithioate have been identified as the specific compounds
occurring in (1) above (Hercules Inc., 1968).
An effort has been made to synthesize, isolate and identify the oxygen
analogues of dioxathion and of the dioxene component (3 above).
Initial attempts to isolate these compounds in pure form using various
chromatographic techniques were not successful because of their
relative instability. Recently, a new approach employing column
chromatography on silica gel packing has been successfully used to
isolate the four possible oxygen analogues of dioxathion and the
oxygen analogue of 2-p-dioxenethiol S-(O,O-diethyl
phosphorodithioate). These are shown in Figure 1.
The identities of these products have been confirmed by phosphorus NMR
and by infrared and mass spectroscopy. Each of the four isolated
oxygen analogues of dioxathion yield glyoxal osazone in the
cleavage-hydrolysis step of the dioxathion residual method, and hence
would be measured by that procedure provided they were not removed or
destroyed by the clean-up technique. It has been shown that the
isolated oxygen analogues of dioxathion do not pass through the
alumina column used for clean-up in the current residue method.
Because of their instability, it is probable that the oxygen analogues
occur in technical dioxathion in very small amounts, if at all. NMR
measurements have demonstrated that the oxygen analogue content of
technical dioxathion is less than 1-2%, which is the limit of
detection. A more precise measurement is planned using more sensitive
pulsed Fourier transform NMR techniques. Additional work is also
underway to determine whether amounts of oxygen analogues are present
in dioxathion residues on plants.
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERNS
Dioxathion is registered and used in many countries principally for
treating livestock, citrus fruit, pome fruit, grapes and stone fruit.
Dioxathion products are used on livestock principally cattle in the
U.S.A., Australia, East and South Africa, South and Central America,
France and Italy. Countries using these products on citrus fruit
include the U.S.A., Africa, Japan, Turkey and Italy. There is
significant use on pome fruit in the U.S.A., France, United Kingdom,
South America and Italy. Use on grapes extends to the U.S.A., Germany,
France and Italy.
In some countries use on cattle precludes application to dairy cattle.
However, in countries where ticks are a serious problem and frequent
dipping is needed, dairy cows must be treated as well as beef cattle.
RESIDUES RESULTING FROM SUPERVISED TRIALS
In animals
Hurwood (1966) as part of a study of the excretion of pesticides in
milk following dermal application of several organophosphorus
acaricides to dairy cattle studied the uptake and excretion of
dioxathion. When cows were sprayed with the officially recommended
concentration (0.075%) of dioxathion emulsion, the maximum level of
residues in milk were found at the third milking (29 hours) after
spraying. The level of residue in milk fell rapidly and was not
detectable (>0.005 ppm) 70 hours after spraying.
Three dairy cows were sprayed with commercial dioxathion cattle spray,
9 litres of spray (0.075%) being applied to each. Samples of milk were
taken before treatment and twice daily for 5 days thereafter.
Dioxathion was determined by the method of Dunn (1958). The results
are given in Table 1.
Studies reported by Watts (1968) showed that cows sprayed with 0.075%
dioxathion emulsion gave milk containing a maximum (mean of six cows)
of 2.25 ppm in fat of milk three hours after treatment. The range of
residue levels reported was 1.13 to 3.33 ppm. The level of dioxathion
residues in the milk of three treated animals did not decline very
rapidly. At 45 hours post treatment (the fourth milking) the mean
residue level was 1.27 ppm (with a range of 0.92 to 1.53 ppm) in the
fat of milk.
TABLE 1 Residues of dioxathion in butterfat and milk following spray
treatment of daily cattle with 0.075% dioxathion
Time after Dioxathion in butterfat and total excretion at each milking
treatment COW 7 COW 8 COW 9 MEAN
(h) In fat Excretion In fat Excretion In fat Excretion In fat Excretion
(ppm) per (ppm) per (ppm) per (ppm) per
milking milking milking milking
(mg) (mg) (mg) (mg)
Pre -1 - - - - - - -
5 3.33 534 2.30 204 1.13 261 2.25 358
21 1.00 669 1.21 363 1.61 599 1.24 544
29 1.29 797 2.22 612 3.18 982 2.23 797
45 0.92 508 1.37 472 1.53 805 1.27 600
53 0.08 33 - - - - - -
69 - - - - - - - -
77 - - - - - - - -
1 Represents a value less than the minimum detectable residue.
In plants
For a number of years dioxathion has been used as a dormant spray on
apricots, cherries, peaches, plums and prunes when the material is
applied at the rate of 4 kg/ha. It has been shown that these uses do
not give rise to detectable residues of dioxathion in the fruit at
harvest, when using analytical procedures specific to dioxathion and
its metabolites, which are capable of determining levels of less than
0.1 ppm (Hercules Inc., 1970).
FATE OF RESIDUES
General comments
Dioxathion residues are confined to peel of citrus fruit, the skin of
apples and the fat of meat. It is believed that the residue on grapes
is also confined to the skin. The cis and trans isomers of
dioxathion, the most biologically active major components, are also
the most stable components of residues. Only drastic conditions will
significantly alter the nature or quantity of the residues originally
present. Therefore, under storage conditions normal for fresh fruit
and meat, residues will remain relatively constant in amount and
composition. Removal of the peel of citrus fruit and the skin of
apples in commercial processing or for culinary purposes in the home
will remove all of the dioxathion residue present on the whole fruit.
No significant amount passes into citrus fruit juice. There is
evidence that when grapes are pressed only trace amounts will occur in
the juice. Similarly, the removal of fat from meat cuts by trimming
prior to sale and the loss of fat during cooking will materially
reduce dioxathion residues in the meat. The amount consumed will be
low in comparison with the amount in raw products.
Distribution of dioxathion residues
Apples
Dioxathion residues are confined to the skin of apples. The pulp
contained 0.3 ppm dioxathion with a residue concentration in the peel
of 36.8 and 77.2 ppm dioxathion (Hercules Inc., 1961).
Citrus fruit
Dioxathion residues are confined to the peel of the fruit; no more
than an apparent 0.03 ppm was found in the edible portion. No
significant cholinesterase inhibiting materials can be extracted from
the pulp with hexane or chloroform (Hercules Inc., 1958; Gunther
et al., 1958).
Any conversion of dioxathion, by oxidation or other means, to a
metabolite not responding to the specific analytical method must occur
rather slowly, since dioxathion disappears from the peel at a slow
rate. Testing of the pulp from lemons sampled 71 days after the
application of the highest approved dosage (1.5 lb/100 gal) showed a
barely detectable inhibition of cholinesterase by a test which would
have detected less than 0.01 ppm dioxathion-oxon.
Grape
Because of solubility characteristics, it is believed that the residue
on grapes is also confined to the skin (Hercules Inc., 1960). Trials
in California demonstrated the persistence of dioxathion residues on
grapes and the relationship between rate of application, stage of
growth and residue level. Residues declined slowly after the first
week, and were only about half the original level after 8 weeks.
Allowance for dilution by growth indicated a very slow loss.
Meat
Dioxathion residues are confined to the fat of meat of animals sprayed
or dipped in dioxathion (Hercules Inc., 1960). Cattle, sheep, pigs and
goats all showed the same distribution pattern. Studies using
dioxathion labelled with 32P showed that cattle treated with
dioxathion eliminate considerable quantities in faeces and in urine.
Much of the applied dose is, however, first transferred to fatty
tissues. These studies showed that the material concentrated in fat is
only dioxathion (Chamberlain et al., 1960). In another study in
which 32P-labelled dioxathion was applied to the skin of a steer it
was shown that fatty tissues accumulated small amounts of the
insecticide. No detectable residues were found in meat samples (Plapp
et al., 1960).
Claborn et al., (1960) showed that when dioxathion was applied to
cattle, sheep, goats and pigs the residue is found only in fatty
tissue. No residues were found in any muscular tissue.
Nature and stability of dioxathion residues
Studies of dioxathion residues on fruit show a slow rate of decline
under natural conditions. The average half-life of dioxathion residues
on citrus fruit from three different tests was 84 days, for California
grapes 45 days and for apples 56 days (Gunther et al., 1958;
Hercules Inc., 1961). Casida and Ahmed (1959) established that the
cis and trans isomers are the most persistent components of
dioxathion residues on plant surfaces. Loss by volatilization was
least for the cis and trans isomers with half-lives of 19-27 days.
Hydrolysis does not occur readily on plant surfaces and is primarily
confined to absorbed materials. The cis and trans isomers
hydrolyse more slowly than other components both on plant surfaces and
when subjected to strong alkali in vitro. Low volatility and
resistance to hydrolysis appear to account for their long residual
persistence.
The work of Casida and Ahmed (1959) also shows that, after application
to the surface of cotton leaves, the dioxene fraction and the cis
and trans isomer fractions of dioxathion form more polar and more
potent anticholinesterase agents; those formed from the dioxene
fraction are very rapidly dissipated (0.2 day); those from the cis
and trans isomers are somewhat more stable but decline to 10-20% of
initial activity within 3 days. In other work, using radioactive
dioxathion, it was established that the amount of unhydrolysed, but
more polar materials, in aged plant residues, was a small fraction
(10% on cabbage; 1% on beans) of the unchanged cis and trans
isomers. This work indicates that only relatively small amounts of
more polar metalbolites are formed and that they are subject to rapid
hydrolysis once formed.
Casida and Ahmed (1959) also established that the ratio of cis and
trans isomers to each other is unchanged after application to
plants. Therefore, no conversion of one isomer to the other occurs.
Information on the effect of processing on dioxathion residues was
obtained in connection with the production of dried citrus pulp and
apple pomace. In the manufacture of dried citrus pulp for cattle feed
from the peel, rag and seed remaining after the extraction of juice
from citrus fruit, the dioxathion residue is reduced 63-80%.
Destruction of dioxathion occurs in both the liming-filtration steps
and the drying operation in which the limed material is processed in a
rotary kiln at a gas temperature of about 310°F for 13 minutes. Drying
moist apple pomace in a rotary kiln using an inlet air temperature of
500°F caused a 60% loss of dioxathion residue.
Pyrolytic experiments by Diveley et al. (1959) showed that, when
dioxathion was slowly heated to 135° - 140°C in vacuo, the trans
isomer pyrolyzed completely, whereas the cis isomer remained intact.
The products formed from the trans isomer were O,O-diethyl
hydrogen phosphorodithioate and 2-p-dioxenethiol S(O,O-diethyl
phosphorodithioate). Continued pyrolysis of the trans and cis
isomers at 160° - 165°C resulted in the decomposition of both isomers
to O,O-diethyl hydrogen phosphorodithioate and 2-p-dioxenethiol
S(O,O-diethyl phosphorodithioate).
Evidence of residues in food in commerce or at consumption
Dioxathion residues were not reported to have been found in any of the
wide range of commodities examined by the U.S. Food and Drug
Administration during the six years 1963-69 (Duggan et al., 1971).
Neither was the presence of dioxathion reported in total diet samples
in U.S.A. (Corneliussen, 1970).
The most intensive use of dioxathion on plants occurs in California
and Florida. Advice from the Departments of Agriculture in both states
indicates practically no incidence of dioxathion residues in fruit in
either state. In 1970, 150 samples of citrus were analysed in
California but only one of these was found to contain dioxathion. No
residue was reported on 329 samples of other fruit on which the use of
dioxathion is permitted. In 1970, 357 citrus samples and in 1971, 394
samples were screened in Florida by analytical methods which would
detect dioxathion. No dioxathion residues were detected.
During 1971, the New South Wales Department of Agriculture analysed
1437 samples of internal fat from cattle slaughtered within the cattle
tick quarantine area (Snelson, 1972). It was found that 320 (23%)
contained dioxathion at levels ranging from 0.01 to 2.14 ppm, 4
samples having residues above 1 ppm. Thus the incidence of dioxathion
residues in fat from cattle had increased from the 13.8% reported
during 1970.
Of the 1439 cattle dips maintained by the New South Wales Government,
713 (50%) were charged with dioxathion in 1971. A total of 1063
samples of butter were collected from commercial butter factories in
the cattle tick quarantine areas during 1971 and analysed by the
laboratories of the Board of Tick Control. Of these, 382 (36%)
contained dioxathion residues at levels ranging from 0.01 to 1.02 ppm.
In the previous year (1970) the incidence was 18.6%.
METHODS OF RESIDUE ANALYSIS
The colorimetric method of Dunn (1958) is still regarded as specific
and sensitive for the determination of dioxathion residues in plant
and animal products. The multi-residue detection methods (Storherr
et al., 1971; Abbott et al., 1970) have been used to determine
dioxathion residues in plant and animal products and appear entirely
satisfactory for regulatory purposes.
APPRAISAL
The 1968 Joint Meeting (FAO/WHO, 1969a and 1969b) recommended an ADI
of 0.0015 mg/kg body-weight. Temporary tolerances were recommended for
residues in citrus fruits, pome fruits, grapes and meat. Further
information was required on (a) the composition of technical
dioxathion, (b) disappearance of residues in storage and processing
and (c) residue levels in products in commerce.
Technical dioxathion contains a minimum of 68% of the cis and
trans isomers of 2,3-p-dioxanedithiol S,S-bis (O,O-diethyl
phosphorodithioate). The remaining related compounds include 10% ethyl
phosphorothioates and ethyl phosphorodithioates. Results of studies
confirm the identity and relative instability of the oxygen analogues.
Studies of dioxathion residues on fruit show a slow rate of decline
under natural conditions. The average half-life of residues on citrus
fruits, grapes and apples was determined to be 84 days, 45 days and 56
days, respectively. The cis and trans isomers have been shown to
be the most persistent components. Loss by volatilization was least
for these isomers. Hydrolysis does not take place readily on plant
surfaces but does occur with those fractions which are absorbed into
plant tissues.
The ratio of cis and trans isomers to each other is unchanged
after application to plants.
Information derived from the processing of citrus pulp and apple
pomace shows that 60-80% of the residues are lost during the drying
operation.
Data available from Australia showed the incidence and level of
dioxathion residues in the fat of meat of cattle and in dairy produce.
These indicate that the tolerance in the fat of meat of cattle does
not require amendment. The occurrence of dioxathion residues in milk
and milk products as a result of the dipping of cattle for tick
control indicates the need for a tolerance for dioxathion residues in
milk and milk products.
Reports from the California Department of Agriculture indicated that
only 1 of 150 citrus samples examined in 1970 contained dioxathion
residues. No dioxathion residues were found on 124 samples of apples,
81 samples of pears or 124 samples of grapes. Dioxathion was not
reported to be found in any commodities analysed in the U.S.A. over
the period 1963 - 1969. Neither does it appear in the results of total
diet studies reported from U.S.A.
Due to the stability of dioxathion residues, no appreciable decline in
levels is to be expected during normal storage of any of the
commodities mentioned above after harvest, slaughter, etc.
Questions referred by the Sixth Session of the Codex Committee on
Pesticide Residues were considered. In the light of the available
information there was little likelihood that dioxathion residues could
occur in the juice of apples and grapes. The strong affinity of the
residue for the skin and the fact that residues in plant juices are
readily degraded were noted.
Examination of original data showed that the class "pome fruits"
included apples, pears and quinces. Since the residues in animal
tissues and milk, resulting from the direct treatment of animals, is
partitioned preferentially into fatty tissues and milk fat,
opportunity has been taken to clarify this fact in the tolerance
previously recommended for "meat".
RECOMMENDATIONS
TOLERANCES
The tolerances recommended in 1968 have been confirmed as no longer
temporary. The following tolerances are based on residues likely to be
found at harvest in the case of plant products and at slaughter in the
case of meat. The limit proposed for milk and milk products are given
on the assumption that blending will take place before milk enters
commercial channels.
ppm
Apples, pears, quinces 5
Grapes 2
Citrus fruit 3
Fat of meat of cattle,
sheep, goats and pigs 1
Milk and milk products
(fat basis) 0.2
Apricots, cherries,
peaches, plums and prunes 0.1*
* at or about the limit of determination
FURTHER WORK OR INFORMATION
None
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