SUPRACIDE(R)/ULTRACIDE(R) Ciba-Geigy (GS 13005)
Other information on properties
Physical state: white crystalline powder
Melting Point: 39-40°C
Vapour Pressure: 1.0 × 10-6 mm Hg at 20°C
Density: 1.495 g/cm3 at 20°C
Solubility: in water 240 ppm = 0.024% at 20°C; slightly
soluble in methanol, acetone and benzene.
Stability: relatively stable in neutral and slightly
acid media; does not change its content
during three days in a phosphate buffer or in
a 0.01 N HCl solution. Stability in alkaline
media is low.
material: minimum 95%
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Absorption, distribution and excretion
Methidathion is well absorbed when administered orally to rats (Esser
et al., 1967) and other mammals but no accumulation occurs in
particular tissues. The activity in all tissues except muscle was
below the detectable level 48 hours after a single oral dose to rats
of about 4 mg/kg of 14C-methidathion (labelled in heterocyclic ring)
(Esser and Müller, 1966). No activity was detected in tissues of rats
eight days after completion of ten consecutive daily oral doses of
about 0.8 mg/kg/day (Dupuis et al., 1971). A total of 34% of
administered activity was recovered from faeces and 24% from urine
after oral administration of 1 mg/kg 14C-methidathion/day for five
days to a lactating cow. The highest tissue level was 0.11 ppm
methidathion equivalents in the liver (Cassidy et al., 1969b).
Traces of methidathion could be detected in the tissues of bull calves
receiving 2.0 mg but not 1.0 mg/kg/day for ten weeks (Polan et al.,
1969a). Rats administered orally about 4 mg/kg of 14C-methidathion
labelled in heterocyclic moiety excreted 80% of the activity in 96
hours, 42.8% in urine, 1.3% in faeces and 36.4% in expired air (Esser
and Müller, 1966). Essentially similar results were found by Dupuis
et al. (1971). One cow excreted 16% of the activity from a 1.7 mg/kg
body-weight oral dose of 14C-methidathion in expired air, 37.9% in
urine, 5.5% in faeces and 1.2% in milk. The animal had received
pre-treatment for 30 days with 1 mg/kg/day of non-labelled
methidathion. Another cow excreted 50.8%, 43.2%, 4.3% and 0.8% by
these routes when given the same dose but without pre-treatment (Polan
and Chandler, 1971).
According to Esser et al., (1969), metabolism in the rat commences
by splitting the P-S bond, the thiol group on the heterocyclic
compound being methylated and then oxidized to the polar sulphoxide.
The greater part of the sulphoxide is oxidized to CO2 after ring
cleavage, excreted directly or oxidized to sulphone, which may itself
be excreted or oxidized to CO2. Three samples of methidathion, each
labelled with 14C in a different position in the molecule, were
administered orally to rats. An identical pattern of excretion was
found with all, up to 36% of the dose being excreted as 14CO2 and up
to 43% as urinary metabolites (Esser and Müller, 1966; Esser et al.,
1967). In experiments in which 90% of administered 14C activity was
recovered, 22-26% of intraperitoneally administered 14C-labelled
methidathion was eliminated as CO2 and 52-58% as urinary metabolites;
71% of 14C-labelled 2-methoxy-delta2-1,3,4-thiadiazolin-5-one,
administered intraperitoneally, was excreted by rats as 14CO2,
showing the heterocyclic moiety is readily cleaved (Bull, 1968). The
same behaviour of 2-methoxy-delta2-1,3,4-thiadiazolin-5-one was
observed in rats after oral administration of carbonyl 14C-labelled
compound with 45% of the label being expired as 14CO2 (Dupuis
et al., 1971). Analysis of urine from rats administered 6 mg/kg
32P-labelled methidathion intraperitoneally showed the presence of
desmethyl methidathion, dimethyl phosphate, dimethyl phosphorothioate,
methyl phosphate and phosphoric acid (Bull, 1968). Of an oral dose of
methidathion 20-25% was excreted in urine by rats as the sulphoxide
and 5-7% as the sulphone derivate of methidathion (Esser et al.,
1967); Dupuis et al., 1971). Traces of sulphoxide and sulphone, but
not of methidathion or its oxygen analogue, were detected in the
tissues of chicken (Kahrs and Mattson, 1969) and in milk from cows
(Polan and Chandler, 1971) administered methidathion. The studies of
Dupuis et al. (1971) on the metabolism of the sulphone and
sulphoxide derivatives confirm the metabolic pathway described by
Esser et al. (1967).
In addition to methidathion, several metabolites have been
demonstrated to occur in treated plants. Dupuis et al. (1971) found
that, in beans and alfalfa, one-third of metabolites liberated
2-methoxy-delta2-1,3,4-thiadiazolin-5-one on hydrolysis. Only trace
amounts of O-[(2-methoxy-5-oxo-delta2-1,3,4-thiadiazolin-4-yl)-methyl],
O,O-dimethyl phosphorothioate and free
2-methoxy-delta2-1,3,4-thiadiazolin-5-one were detected.
Methidathion, its oxygen analogue, phosphate, methyl phosphate,
dimethyl phosphate, dimethylphosphorothioate and desmethyl-methidathion
were demonstrated in treated cotton plants (Bull, 1968).
Special studies on the metabolites
Acute toxicity of metabolites
The acute toxicity of methidathion metabolites have been studied in
the rat and results are summarized in Table 1 (Dupuis et al., 1971).
TABLE 1 Acute toxicity of methidathion metabolites
Substance Cholinesterase Rat LD50
inhibition (AChE) (mg/kg
IC50 - molar body-weight)
Methidathion > 10-4 35
2-methoxy-1,3,4-thiadiazol-5(4H)-one 6 × 10-3 750
Methidathion-oxygen analogue 5.4 × 10-7 10
2-methoxy-4-methylthiomethyl-1,3,4-thiadiazol-5(4H)-One > 10-2 1 110
2-methoxy-4-methylsulphinyl methyl-1,3,4-thiadiazol-5(4H)-one > 10-2 535
2-methoxy-4-methylsulphinyl methyl-1,3,4-thiadiazol-5(4H)-one > 10-2 1 750
Short-term studies on the metabolites
Groups of five male and five female rats were administered by gavage
25, 50, 100, 200 or 400 mg/kg of 2-methoxy-1,3,4-thiadiazolin-5(4H)-
one each day for four weeks. A group of ten male and ten female rats
were fed a control diet for the same period. Three rats died at the
top dosage level and this dose consistently caused convulsions and
hyperirritability. At 200 and 400 mg/kg/day levels, the gain in
body-weight was inhibited. Histological examination indicated
dose-related occurrence of extra medullary haematopoiesis in the
spleen which began to show in the 50 mg/kg group. The no-effect level
was 25 mg/kg/day in this study (Stenger and Roulet, 1965 b).
Two groups of five male and five female rats were fed 0 or 16.2 ppm of
methidathion oxygen analogue in the diet for three weeks. Growth and
behaviour were unaffected but brain and erythrocyte cholinesterase
were inhibited in the test group (Coulston, 1968).
Groups of 25 male and 25 female rats were fed on 0, 2, 6 and 12 ppm of
methidathion-oxygen analogue for three months. Brain cholinesterase
was inhibited above the 2 ppm dietary level; the inhibition of
erythrocyte cholinesterase at this level was of questionable
significance. The behaviour, body-weights, food consumption,
haematological indices, serum chemistry and gross and microscopic
pathology were similar in controls and all test groups (Serrone and
Special studies on neurotoxicity
Four adult hens received four subcutaneous injections of 50 mg
methidathion/kg body-weight (the maximum tolerated dose) at weekly
intervals and they were observed for a further four weeks. The signs
of acute poisoning lasted two to three days each time, but birds
remained in good condition and no paralysis developed.
Neuropathological examinations were not performed (Noakes, 1964).
Five groups of ten adult hens were fed diets containing 0, 16, 52 or
160 ppm methidathion or 316 ppm tri-orthocresylphosphate for 45-47
days. No abnormal neurological signs were found in birds fed
methidathion, but those on tri-ortho-cresylphosphate showed leg
weakness, lack of balance and ataxia during the final week of
treatment. Unequivocal evidence of demyelination of neural tissue was
not found in methidathion or tri-orthocresylphosphate treated animals
Special studies on pharmacology
The effects of atropine and the oxime reactivator, pralidoxime, on the
acute toxic effects of methidathion were investigated in male rats.
Repeated atropine or pralidoxime administration was effective against
one to two times the rat median lethal dose of methidathion, and the
two substances were more effective when given together (Sanderson,
Groups of 20 female rats were administered half the LD50 dose of one
of 15 other organo-phosphorus or carbamate compounds, respectively. If
a potentiating effect was found, decreasing amounts of the combined
insecticidal compounds were given to further groups. Azinphos-methyl,
mevinphos and parathion-methyl had a potentiating effect with ´LD50
doses and carbaryl and fenchlorvos with ¨LD50 doses (Johnston and
Special studies on reproduction
In a three-generation study, three groups of 10 male and 20 female
rats were fed on a diet containing 0, 2 or 16 ppm methidathion for
three weeks, and thereafter on a diet containing 0, 4 or 32 ppm
methidathion. Litters from the second matings were used to provide the
new generations. The F1b litters did not receive test diets until 26
days and the F2b until 22 days after weaning. Fo, F1b and F2b
generations received diets for 27-28 weeks during which they produced
two litters. The number of young surviving at weaning was reduced in
all generations of litters from animals fed 32 ppm methidathion and
the mean liver weight of F3b weanlings of this group was slightly
raised. The body-weight, reproductive capacity and mortality of
parents and the number of litters, litter size, mean birth and weaning
weights of test groups were comparable to controls. The number of
stillbirths and incidence of congenital abnormalities were unaltered
by treatment. No histological damage was found in the organs of the
F3b animals examined. The no-effect level in this study was 4 ppm
methidathion (Lobdell and Johnston, 1966).
Groups of four male and eight female rats were fed for 12 weeks on
diets containing 0 or 50 ppm methidathion and mated, one male being
left with two females for two weeks. No differences from controls were
found with regard to gestation period, fertility, number of young,
survival at weaning or average weight at 25 days of age. No congenital
abnormalities were found in either group (Noakes and Watson, 1964a).
The acute toxicity of methidathion has been studied in several animal
species, and the results are summarized in Table 2.
Three groups of ten male rats received by gavage 8.3, 16.6 or 33.2 mg
methidathion/kg/day on five days a week. None, six and ten animals,
respectively, died within the two-week treatment period (Noakes and
Five groups of ten male rats received by gavage 0, 0.25, 0.83, 2.5 or
8.3 mg methidathion/kg body-weight/day on five days a week for four
weeks. Signs of cholinesterase inhibition occurred during the first
week at the 8.3 mg/kg/day level, but not after in this or other
groups. Dose-related cholinesterase inhibition occurred in RBC and
plasma, the no-effect level being 0.25 mg/kg/day. Plasma
cholinesterase had returned to normal three days after treatment was
stopped but RBC enzyme had not reached normal figures after 21 days
(Noakes and Watson, 1964b).
TABLE 2 Summary of acute oral toxicity of methidathion 1/
Animal Sex LD50 References
Mouse F 17 Noakes and Sanderson, 1964b
Hamster F 30 Ibid.
Rat M & F 20 - 81 Stenger, 1964a, 1964b, 1966a,
1966b; Aeppli, 1969a, 1969b,
1970a, 1970b; Noakes and
Rat M 26 - 65 Ibid., 1964a
Mastri and Keplinger, 1969
Guinea pig F 25 Noakes and Sanderson, 1964b
Rabbit M 80 Ibid.
Dog M & F 200 Sachsse, 1971
Chicken F 80 Noakes and Sanderson, 1964b
1 Formulations calculated as a.i.
Five groups of five male and five female rats received by gavage 0,
2.5, 5.0, 10 and 20 mg methidathion/kg body-weight/day on six days a
week for four weeks. In the 10 and 20 mg/kg groups, four and nine
animals died respectively. Body-weight gain was depressed in all
groups but no relation to dosage was apparent. There was a slight
increase in fat deposition in the liver at 5 mg/kg and at the higher
levels this was more marked (Stenger and Roulet, 1963).
Groups of 24 male and 24 female rats were fed for 22 weeks on diets
containing 0, 1, 4, 16 and 64 ppm methidathion. In a similar study in
the same laboratories groups of 24 male and 24 female rats were fed
for 26 weeks on diets supplying 0, 128 and 256 ppm methidathion. The
rate of body-weight gain was reduced at 64 ppm and above in females
but not in males. Histopathological examination of liver, spleen and
kidneys showed a dose-related increase in fat deposition in the liver
at doses above 64 ppm in both sexes. No abnormalities in
haematological indices or in results of urine analysis were found
(Stenger and Roulet, 1965a).
Groups of 20 male and 20 female rats were fed for six months on diets
containing 0, 0.5, 2, 10, 50 and 250 ppm methidathion. At the 250 ppm
level weight gain was slightly depressed and clinical signs of
cholinesterase inhibition were seen, particularly in females. Plasma
cholinesterase was inhibited in the 250 ppm group and erythrocyte
cholinesterase in groups receiving 10 ppm and above. Experimental
groups were similar to controls with regard to survival, food intake,
weights and microscopic appearance of liver, kidneys, spleen and
testes and the macroscopic appearance of other organs (Noakes and
Four groups of three male and three female beagle dogs received diet
containing 0, 4, 16 and 65 ppm methidathion for two years. The animals
were starved of diet one day each week and received a double ration on
the next day. Administration of methidathion was discontinued from
week 16 to 19.
Erythrocyte cholinesterase was inhibited in the 64 ppm group but brain
cholinesterase was unaffected by treatment. SGPT was markedly elevated
in the 64 and 16 ppm groups and slightly raised in males of the 4 ppm
group. During weeks 16 to 19 these levels fell, but only the 4 ppm
group returned to normal. SGOT levels were not different from controls
at all treatment levels but serum alkaline phosphatase was elevated
and sulphobromophthalein retention increased in the 16 and 64 ppm
groups. The livers of dogs receiving 16 and 64 ppm were pigmented on
macroscopic examination. Microscopically, pigmentation could be seen
in macrophages and hepatic cells (principally centrilobular) in 16 and
64 ppm groups, the intensity of deposit being dose related. The Perl's
reaction showed that the pigment did not contain appreciable
quantities of iron. The kidneys of the 64 ppm group also showed
pigmentation. It was questionable whether the livers of the 4 ppm
group contained excess pigment. Control and test groups were
indistinguishable regarding behaviour, results of clinical tests
including neurological examination, haematological findings, organ
weights and macroscopic and microscopic appearance of organs other
than those mentioned. In addition, two dogs received 64 ppm
methidathion in the diet for four weeks. The SGOT was elevated at two
and four weeks and at autopsy the livers were dark in colour. Moderate
diffuse pigmentation was seen microscopically in the liver of one
animal. The 4 ppm dietary level was considered to be without toxic
effect (Johnston, 1967).
Three Rhesus monkeys were administered by stomach tube individual
doses of methidathion on six days per week. One animal received a
constant dose of 2.56 mg/kg during the entire experimental period (91
days), another monkey received 0.64 mg/kg for 39 days, 5.12 mg/kg for
25 days and 15.26 mg/kg for additional 25 days, the third animal was
given 1.28 mg/kg for 39 days, 3.84 mg/kg for ten days and 7.68 for 40
days. No definite effects were detected using a wide range of toxicity
criteria (Woodward et al., 1965).
Four Rhesus monkeys were administered orally 1 mg methidathion/kg
body-weight/day on six days a week for six months. No changes in
appearance or behaviour were observed, and weight gain, the results of
haematological and serum chemical examinations, the plasma and RBC
cholinesterase activities, brain cholinesterase and gross and
microscopic examination of tissues showed no untoward effect
Three groups of Rhesus monkeys (approximately equal numbers of each
sex) were administered 0, 0.25 and 1.0 mg methidathion/kg
body-weight/day by stomach tube, six days a week for 23 months. Two of
each group were autopsied after 12 months. Plasma and erythrocyte
cholinesterase were inhibited in the 1 mg/kg group but not at the
lower level. Brain cholinesterase was un altered by treatment. Growth,
results of haematological tests, results of chemical analyses of serum
(including for SPGT and alkaline phosphatase) and macro- and
microscopic examination of tissues were similar in control and test
groups (Fabian et al., 1971).
Three groups of two male and two female sheep were fed 0, 15 and 30
ppm methidathion in their diet for 45 days. No abnormalities which
could be attributed to treatment were found when growth, faecal
consistency and gross appearance at autopsy were observed (Murchison,
Four groups of two horses received 0, 10, 20 and 30 ppm of
methidathion in their diet for two weeks. No differences were observed
between control and test animals with respect to appearance, appetite
and results of urine analysis, haematology and serum analysis and
physical and neurological examinations (Watson and Polan, 1967).
Five groups of two male and two female calves aged about seven days
were fed for 87 days on a diet containing 0, 5, 15, 25 and 35 ppm
methidathion. Blood cholinesterase was inhibited after 45 days in the
35 ppm group and after 49 days in the 25 ppm group. Brain
cholinesterase was slightly inhibited in the 35 ppm group. There was
no adverse effect on food intake, body-weight, haematological indices
or the gross and microscopic appearance of tissues (Polan and Libke,
Groups of five ruminating bull calves were administered daily by
capsule 0, 0.5, 1.0 to 2.0 mg methidathion/kg body-weight for ten
weeks. Three animals receiving 2 mg/kg died before the end of the
test. Food intake and body-weight were reduced and blood
cholinesterase inhibited in the 2 and 1 mg/kg groups. The results of
haematological and gross and microscopic tissue examinations were
unremarkable (Polan, 1968).
In order to investigate the long-term toxic effects and possible
carcinogenic action of methidathion, four groups of 25 male and 25
female rats each were fed for three weeks on diets containing 0, 2, 8
or 32 ppm and for a further 101 weeks on diets containing 0, 4, 16 and
64 ppm methidathion. The rate of gain in body-weight was reduced from
week 8 in male animals of the 64 ppm group. After the first year the
rates of gain became erratic in all groups making interpretation of
findings difficult. Female rats on test diets grew at a rate
comparable to controls. Erythrocyte cholinesterase was inhibited in
the 16 and 64 ppm groups while plasma enzyme showed minimal inhibition
at 100 weeks in the 64 ppm group only. Brain cholinesterase was
inhibited in the 64 ppm group with marginal and no reduction in the 16
and 4 ppm groups, respectively. Decreased relative adrenal weights
were found in females of the 16 ppm and 64 ppm groups, and decreased
ovary weights in the 64 ppm groups. The relative kidney weights of
males was increased in the 16 and 64 ppm groups. A greater frequency
of hepatic degenerative changes was noted in rats fed methidathion in
the diet; the high incidence of pulmonary infections in the rats
renders this finding of doubtful toxicological significance. The food
intake, results of haematological investigations and chemical analysis
of serum (including SPGT) and the survival rate were similar in the
test groups and in the control. The incidence of tumours was variable
between groups but was low and not dose-related, and no unusual
tumours were found. The no-effect level in this study was a 4 ppm
methidathion in the diet (Johnston, 1967).
OBSERVATIONS IN MAN
One male subject took 4 mg/day (0.04 mg/kg/day) for 17 days and 8
mg/day (0.08 mg/kg/day) of methidathion for 27 days. No effect was
found on RBC and plasma cholinesterase, the thrombocyte count and
stability or on the clinical condition of the subject (Payot, 1965).
Two groups of eight men received 0.04 and 0.11 mg/kg each day of
methidathion orally in capsules for six weeks. Four men received
placebo capsules. The treatment with methidathion was without effect
on plasma and RBC cholinesterase, SGPT and SGOT, the results of urine
analysis or on the EEG pattern or clinical condition of the subjects
Methidathion is absorbed from the gastrointestinal tract and rapidly
excreted, mainly as CO2 or as low toxicity urinary metabolites. No
tissue accumulation occurs. The oxygen analogue of methidathion is a
transient metabolite in plants but has not been identified in animals;
it is more acutely toxic than methidathion.
Methidathion, a cholinesterase inhibitor, is potentiated with several
other organo-phosphorus compounds, does not cause delayed neurotoxic
effects, is not teratogenic and affects reproductive function only at
a level which is toxic to the adult.
In short-term studies in rats, an increase in the hepatic fat was
observed histologically at high levels. In a two-year feeding study in
dogs, signs of hepatic injury were found at all dietary levels. At the
higher levels evaluated, SGPT, serum alkaline phosphatase and
sulphobromophthalein occurred and pigment deposition was observed
histologically in macrophages and hepatocytes. The nature of the
pigment is not known. Deposition of pigment and signs of liver damage
were not seen in monkeys or rats.
In a long-term study in rats, a greater frequency of hepatic
degenerative changes was noted. There was no evidence of
carcinogenicity. The no-effect level in this study was 4 ppm, based
upon cholinesterase depression. No untoward effects were seen in human
subjects even at 0.11 mg/kg/day taken for six weeks. A no-effect level
was not observed in dogs at 0.1 mg/kg - a lower level than the
no-effect level in other species. However, it was felt that a
temporary ADI could be established on the basis of the data in human
Level causing no toxicological effect
Rats: 4 ppm in diet, equivalent to 0.2 mg/kg
Monkeys: 0.25 mg/kg body-weight/day
Human subjects: 0.11 mg/kg body-weight/day
ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN
0 - 0.005 mg/kg body-weight
RESIDUES IN FOOD AND THEIR EVALUATION
Methidathion was first introduced on a large scale for control of
insects in 1964. It is officially registered and/or approved for use
in the following countries:
Algeria England Netherlands
Angola France Nicaragua
Argentina Greece Pakistan
Australia Germany,Fed.Rep.of Panama
Austria Guatemala Poland
Belgium Iran Senegal
Brazil Israel Somalia Dem.Rep.
Bulgaria Italy South Africa
Chile Jamaica Spain
Costa Rica Japan Switzerland
Cyprus Lebanon Syria
Czechoslovakia Mexico Tunisia
Denmark Morocco Turkey
Dominican Republic Mozambique U.S.A.
Methidathion can be applied against pests in a variety of different
crops, including pome and stone fruits, grapes, citrus, cotton,
potatoes, beet crops, hops, cereals, vegetables, olives and
sugar-cane. The main fields of application are in stone and pome
fruits, citrus and cotton.
The recommended application rates in various crops are given in Table
Methidathion is only recommended for application to growing crops.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Pome fruits, stone fruits, grapes, citrus fruits, vegetables, field
crops and other food plants were treated in field trials with
methidathion 40% ES or WP formulation in concentrations of 20 to 60 g
a.i./100 l spray mixture and in high level dosage trials of up to 300
g a.i./100 l and investigated for residues.
In the residue investigations methidathion was determined by gas
chromatography with a thermionic phosphorus, an electrolytic
conductivity detector or with a microcoulometer, and the two
metabolites GS 13007 and GS 12956 by thin-layer chromatography by
means of fly head-cholinesterase inhibition or silver nitrate.
The limit of detection of the methods is 0.01 ppm. The extraction and
cleanup techniques as well as analytical methods are described in
detail by Eberle and Hörmann. (1971).
Data from residue trials conducted in Australia, France, Germany,
Greece, Indonesia, Israel, Italy, Mexico, Morocco, New Zealand, South
Africa, Spain, Switzerland, United Kingdom and United States of
America were available for evaluation. Copies of the reports of these
trials were filed with FAO.
Eberle and Hörmann (1971) applied statistical tests to show the
possible relationship between the disappearance rate of methidathion
residues and the following parameters: type of formulation,
concentration of a.i. applied, kind and variety of crop.
Using the principles established by these authors it has been possible
to apply the calculations to the extensive data available from many
TABLE 3 Recommended application rates of methidathion
Crop g ai/100 litres g ai/ha
pome fruit 30 - 60
stone fruit 30 - 60
citrus fruit 30 - 60
grapes 30 - 60
potatoes 250 - 800
beets 300 - 600
alfalfa1 600 - 1 200
cereals, millet1 250 - 800
vegetables 250 - 1 000
soya1 250 - 800
groundnuts1 250 - 800
sunflower 400 - 800
maize (corn)1 250 - 800
tobacco, cotton1 250 - 800
sugarcane 50 - 60 300 - 1 500
tea, coffee 30 - 60 250 - 800
palm 40 - 60
banana 50 - 60 250 - 600
1 In these crops it is necessary to adjust the dosage within the
given range to the height and density of the plant.
The degradation of methidathion in apples, grapes, plums, cherries,
oranges and alfalfa is presented using a semi-logarithmic plot (Fig.
1, 2, 3 and 4). The dissipation curves (regression lines) indicate
that methidathion in a rapidly degrading insecticide, the residues of
which decrease exponentially with time. Based on a statistical
analysis of the many residue data obtained in field trials, it is
possible to present the dissipation curves of methidathion on various
crops as regression lines according to the equation log y = a + bx
(Eberle and Hörmann, 1971). These lines are determined by the initial
residue a and the slop b 1; the logarithms of these values are given
in Table 4.
According to Table 4 the initial residue in cherries is log 0.43 = 2.7
ppm. By means of the slope value b = log 0.86 - 1 and an assumed value
for x (time interval), any point on the dissipation curve can be
calculated from the equation log y = a + bx.
On the basis of statistical analysis of the residue results from pome
and stone fruits and grapes (Eberle and Hörmann, 1971), and from
oranges and alfalfa (Hörmann, 1971) the rate of dissipation is not
significantly dependent on the dose or the formulation of the product,
i.e. the rate of dissipation of methidathion in a particular crop does
not change whether the applications are made with 20 or 60 g a.i. per
100 l or whether the EC or the WP formulation is applied.
Pome and stone fruits and grapes
Pome and stone fruits and grapes were treated according to good
agricultural practice in the respective country with 30-60 g a.i./100
l one to five times during a season. In orchards, a spray volume of
2 000 - 2 500 l/ha was applied, in vineyards 1 000 - 1 500 l/ha.
The residues immediately after the final treatment were 1.5 to 3 ppm;
they fell by a half after six to seven days in apples, plums and
grapes and were below 0.15 ppm after 28 days (Fig. 1 and 2).
The methidathion residue in cherries was different from that in the
other fruit types; the initial residues are high (2.5 - 5 ppm) but
these are rapidly reduced by a rapid fruit growth and enzymatic
processes in the cherries; the half-life is only two days, and only 10
to 12 days after the application the residue values were already below
0.3 and 0.15 ppm.
In contrast to stone fruit and grapes the level of residues in apple
can be variety-specific. Thus the residues in the apple variety Golden
Delicious were higher than in other apples, as a result of the high
wax content in the peel of this variety. In Delicious apples the
residue was 0.25 ppm three weeks after the final application; in other
apple varieties a level of 0.12 ppm methidathion was determined at
this stage (Fig. 1).
1 Example of a dissipation curve is shown in Fig. 3.
TABLE 4 Logarithmic values for the initial residue a and the slope b,
calculated from the given number of residue determinations in
Crop a = initial b = slope number of data
residue of the curve evaluated for
apple 0.29 0.95 -1 68
apple 0.79 -1 0.96 -1 130
grapes 0.14 0.94 -1 85
plums 0.33 0.95 -1 20
cherries 0.43 0.86 -1 26
oranges 0.10 0.99 -1 92
alfalfa (fresh) 1.10 0.96 -1 90
alfalfa (dried) 1.19 0.98 -1 39
The two metabolites GS 13007 and GS 12956 are only found in traces in
plant material. The GS 13007 content was determined in apples (in 12
experiments) and in grapes (in three experiments). After the treatment
average levels of 0.04 ppm GS 13007 were found in apples (all
varieties) and 0.15 ppm in grapes (Fig. 1 and 2). Four weeks later the
metabolite GS 13007 had been degraded to lees than 0.02 ppm in both
crops, and after six weeks it was no longer detectable in any of the
samples (limit of detection: 0.01 ppm). The metabolite GS 12956 may
also occur at the same time as GS 13007. As was determined in apples,
grapes and plums, GS 12956 residues after treatment with methidathion
were at no time higher than 0.04 ppm.
In apples residues of 0.02 ppm GS 12956 were found 4 days after
treatment with methidathion. This content was reduced to below 0.01
ppm 10 days after application in all trials.
In apples the residues of methidathion remaining for several weeks
after a treatment are not only in the peel but also penetrate into
the most lipophilic part of the fruit, i.e. the core. This could be
determined in freshly picked apples and apples stored for one year,
dipped for one minute in an emulsion containing 40 g a.i./100 l and
analysed in layers (sample from peel, fruit and core). The active
ingredient content decreases from the peel in the pulp and then
increases in the core. The peel and core contain higher residue
levels compared with the pulp as a result of their higher lipid
content. This analytical result was confirmed by an autoradiogram,
which showed the concentration of methidathion in the peel and core
of a ripe Delicious apple treated 14 days previously with
14C-labelled methidathion (Eberle and Hörmann, 1971).
For scale control in citrus crops it is usually sufficient to apply 60
g methidathion per 100 l; if several applications have to be carried
out the dosage is reduced to 40 g a.i./100 l for each. Trees are
sprayed to runoff at a rate of 20 to 60 l/tree. Addition of oil to the
spray mixture, which is not necessary for a successful application in
citrus crops, leads to an increase of methidathion residues.
In citrus fruits methidathion residues are found exclusively in the
peel. The active ingredient does not penetrate into the fruit pulp.
Analytical data for the whole fruit are calculated by multiplying the
peel value by a factor of 0.28 (= proportion of peel to the whole
In small citrus fruits such as lemons, higher residues are recorded
than in larger fruits, as a result of the difference in surface/weight
ratio. For example, two months after one of two treatments with 60 g
methidathion per 100 l, residues in lemons and limes average 0.70 and
0.61 ppm, in oranges and grapefruits, however, residues are only 0.33
or 0.16 ppm.
The dissipation curve for methidathion in oranges, illustrated in Fig.
31 is a regression line determined from 92 residue values. According
to this, immediately after treatment residues of 1 - 1.5 ppm
methidathion are found in oranges. Reduction of residues is slow;
two-thirds of the initial residues are still present after four weeks
and one-third (0.40 ppm) after 12 weeks (Fig. 3).
Special investigations to determine the oxo-compound GS 13007 and
other metabolites during the breakdown of methidathion in citrus
fruits gave the results shown in Table 5.
TABLE 5 Methidathion metabolites in citrus fruit
metabolite residue in ppm
whole fruit dried fruit pulp
GS 13007 <0.01 <0.01
sulphoxide <0.05 <0.05
sulphone <0.05 <0.05
None of the metabolites listed was detected; the analysis values were
below the limit of detection (Kahrs et al., 1969).
In these crops spray treatments are applied at a rate of 0.3 - 1 kg
Because of the structure of leaf vegetables (lettuce, leek, artichoke,
cabbage), higher residues are found in these than in vegetables with
smooth surfaces (tomatoes or legumes). The residues immediately after
treatment were high (in some cases > 10 ppm), however they fell
rapidly and 14 days later were <1 ppm in leeks, <0.5 ppm in
cabbage and artichokes. In beans and peas the residues were below 0.1
ppm after seven days. In tomatoes even less methidathion was found at
this stage after treatment. Methidathion has a half-life of one day on
Field and forage crops
For control of resistant potato beetles in potatoes, rates of
0.4 - 0.6 kg methidathion/ha are recommended. According to Swiss and
Australian analyses, methidathion residues are found in the foliage
but never in the potato tubers.
In sugar beets no methidathion is detected in the beets.
Maize is free from residues four weeks after two treatments with 1 kg
methidathion per ha or one treatment with 0.8 kg a.i. per ha.
In cotton, rates of 0.3-0.8 kg methidathion per ha are recommended for
the control of various insects and spider mites. Methidathion residues
could be detected in the seeds and in cotton seed oil obtained from
them. Ten and 57 days after five or six applications with 0.5 kg
a.i./ha, residues in the seeds were 0.34 and 0.06 ppm, in crude oil
0.44 and <0.05 ppm, and in refined oil 0.41 and 0.05 ppm.
Alfalfa was investigated after spraying at rates of 0.6-2.8 kg
methidathion per ha. The recommended dose is 0.6 kg a.i. In alfalfa
and pasture crops the residues detected were of the same order. The
level and rate of dissipation of methidathion residues were not
affected by the method of application, so that both aerial and ground
applications, each with 0.6 kg a.i./ha, produced similar initial
residues of 21 and 24 ppm (Mattson and Kahrs, 1969a).
Residue determinations in alfalfa from seven different areas in the
U.S.A. gave the results shown in Table 6 (Mattson and Kahrs, 1969b).
TABLE 6 Methidathion residues in alfalfa
Dose Interval Methidathion residues (ppm)
(kg a.i./ha (days) range average
0.6 0 7.0 - 41.0 24.0
7 0.27 - 5.20 2.3
14 0.08 - 1.10 0.53
21 0.08 - 0.36 0.24
1.1 0 13.0 - 74.0 41.0
7 1.5 - 9.10 6.3
14 0.44 - 3.40 1.5
21 0.19 - 0.64 0.42
The results show that the level of the residues is dependent on the
level of the applied dose; it is independent of the formulation and
the number of applications. Thus similar residues could be detected
after one or after three applications carried out at monthly
intervals. The initial residues on alfalfa and pasture plants are high
(>10 ppm) but fall rapidly even the first day after application (Fig.
Residues of 8.8 ppm found one day after application of 0.6 kg a.i./ha
fell to 1.6 ppm by the seventh day (Nelson, 1967). The half-life for
methidathion on alfalfa was found to be 3´ days (Mattson et al.,
1969). Fahey and co-workers (1970) also confirmed the rapid breakdown
of methidathion, and further determined that the chemical in fresh
alfalfa was considerably reduced by drying. With the help of a
conventional farm drier, the methidathion residues in green alfalfa
were reduced by 8 to 57%.
The following residues of GS 13007, the oxo-analogue of methidathion,
were found in alfalfa and clover (Table 7).
TABLE 7 Residues of the methidathion metabolite GS 13007 in field crops
Dose Interval GS 13007 residues (ppm)
(kg methidathion/ha, (days) alfalfa clover
3 applications) fresh dried fresh dried
0.6 0 0.40 0.08 0.40 0.10
7 0.06 0.04 0.05 0.04
14 <0.01 0.01 0.015 0.03
21 <0.01 0.01 <0.01 0.02
1.1 0 0.40 0.20 0.10 0.40
7 0.10 0.20 0.05 0.26
14 0.02 0.08 0.025 0.05
21 0.01 0.02 0.01 0.07
The proportion of GS 13007 in the total spray residue was about 1% of
the unchanged insecticide. The metabolite was continually degraded
after treatment: its half-life was two to four days on alfalfa and
four to six days on clover (Mattson et al., 1969). This result was
confirmed by Cassidy and co-workers (1969a) by investigations with
14C-labelled methidathion on alfalfa.
The two metabolites GS 28370 and GS 28369, the sulphomide and the
sulphone of methidathion, were not detected during the degradation of
methidathion in alfalfa (Kahrs et al., 1969).
Three weeks after four applications, each with 40 g methidathion per
100 l, residues of 1-2 ppm were found in fresh green hops and 2.3-2.5
ppm on dried hops.
In beer brewed from hops containing 2.4 ppm methidathion, no
methidathion could be detected, with a limit of detection of 0.0001
ppm, which indicates that methidathion residues are completely broken
down during the brewing process.
Tea treated with the recommended level of methidathion (40-60 g
a.i./100 l), contained less than 0.1 ppm a.i. after seven days. After
nine days the values were below the limit of detection of 0.01 ppm.
These analytical results, together with the fact that in the
preparation of tea considerable dilution takes place and only some of
the active ingredient is extracted from the tea leaves, indicated that
methidathion residues are unlikely to be present in brewed tea.
FATE OF RESIDUES
In feeding studies in bull calves using 14C-labelled methidathion it
was shown that a daily dose of 1 mg methidathion per kg body-weight,
administered over ten weeks, left no insecticide residues in the
skeletal musculature or in various organs (heart, kidneys, spleen,
liver, brain). The oxo-compound, GS 13007, did not occur either (Polan
et al., 1969a). It was also shown in studies in milk cows that after
administration of 30, 15 or 7.5 ppm methidathion (corresponding to a
dose of 0.17, 0.35 or 0.18 mg/kg body-weight) for a period of 55 days
neither methidathion (limit of detection 0.005 ppm) nor GS 13007
(limit of detection 0.025 ppm) could be detected in fatty tissue or in
milk (Polan et al., 1969b).
Feeding with alfalfa which has been treated with a normal dose of
methidathion does not lead to active ingredient residues in the milk.
After administration of 1 mg 14C labelled methidathion/kg body-weight
to milk cows for one or five days, only about 1% of the radioactivity
of the administered dose was found in the milk within 4 or 15 days.
This radioactivity was attributable to a small extent only to the
metabolites GS 28370 (sulphoxide) and GS 28369 (sulphone), but mainly
to polar substances which probably originated from the intermediary
metabolism. This is an indication that the thiadiazole ring of the
methidathion molecule is split, and that the resulting C-1 fragments
are utilized for the synthesis of genuine organic substances. No
unchanged methidathion and no GS 13007 (limit of detection 0.01 ppm)
were present in the milk (Cassidy et al., 1969b; Polan and Chandler,
A dose of 1 mg methidathion/kg body-weight which was chosen in most of
the feeding studies is high in comparison with possible insecticide
uptake with treated feed. In order to ingest this dose, a cow for
example must be fed with alfalfa containing residues of 50 ppm
methidathion (Polan et al., 1969a).
These high residues are only occasionally found on alfalfa or grass
after insecticide application, and after one week they are already
dissipated to an average of 3 ppm. In summary, it can be stated with
certainty that no methidathion residues occur in meat or milk products
if the animal has been fed with alfalfa treated with a normal dose of
insecticide under the usual practical conditions.
Since alfalfa is fed to poultry, it was important to clarify whether
methidathion residues remaining for a short time on the feed plants
after an insecticide application affect the poultry in any way or lead
to residues in eggs. Wisman and Young (1969) fed white Leghorn hens
for 30 days with feed containing 10, 50, 100 or 500 ppm methidathion.
Only feed containing 500 ppm impaired feed uptake and laying rate of
the hens. Feed containing 100 ppm had no visible effect. Insecticide
residues were found in the egg yolk after the three higher doses;
after feeding with 100 or 50 ppm the residues were however less than
0.01 ppm methidathion, and six days after the application were below
the limit of detection of 0.002 ppm (for analytical method see Young,
1970). No residues occurred in eggs after ingestion of feed containing
The doses in feed chosen for this trial are - when compared with
residues actually occurring in green feed - again very high. When it
is further taken into consideration that alfalfa forms only about 15%
of chicken feed, the contamination of the eggs with methidathion via
the feed is unlikely.
In plants treated with 14C-labelled methidathion only slight
translocation of the insecticide could be detected. The radioactivity
measured in untreated parts of the plants was generally low and in
most experiments was present in the form of polar metabolites. Traces
of methidathion were only found in alfalfa stems and bean plants one
and two weeks after treatment (about 0.2-0.5% of the applied
radioactivity). Bull (1968), who investigated the translocation of
32P-labelled methidathion after injection into the cotyledons of
cotton plants, also confirmed that methidathion is found in
non-treated parts of the plants in very small proportions only.
Investigations of the metabolism of methidathion in alfalfa and beans
are described in detail and summarized in a paper by Dupuis and
co-workers (1971). The following therefore largely refers to this
paper and is completed by results from investigations described in
As early as 1966 Esser and Müller demonstrated in bean plants and
freshly harvested apples that plants possess the ability to split off
the heterocyclic moiety of the insecticide methidathion and to
metabolize it to CO2.
Dupuis et al. (1971) carried out studies in beans (Phaseous
vulgaris) and alfalfa (Medicago sativa) with 14C-labelled
methidathion to demonstrate CO2 excretion. The product was labelled
as for the metabolic studies on animals, either on the methoxy, the
carbonyl or the methylene group of the molecule. As Fig. 5 shows,
methidathion is degraded to CO2 in both plant species. The lower
percentage proportion of 14CO2 in alfalfa is attributed to the
greater rate of application of methidathion on the leaves of these
plants and not to the difference in plant species.
Degradation to CO2 is independent of labelling, which indicates that
not only the ester compound but also the heterocyclic ring of the
methidathion molecule is split. The quantitative difference in CO2
excretion in bean plants related to the position of labelling is
explained by the number of oxidation processes on the C atom
concerned. By control experiments, in which the stability of
methidathion was tested on glass plates under the same conditions as
in plant experiments, it could be shown that the 14CO2 determined
originated exclusively from metabolic processes in the plant.
After CO2 excretion of treated bean and alfalfa plants was measured
for two weeks, the plants were extracted for further investigation in
an acetone-water mixture; after evaporation of the acetone the extract
was separated by partition into a chloroform and an aqueous phase. The
radioactivity of the non-extracted parts was determined by combustion.
Table 8 (Dupuis et al., 1971) shows the distribution of
radioactivity in the different extraction phases of bean and alfalfa
plants. The high radioactivity in the aqueous phase indicates a
considerable degradation of the insecticide. Unchanged methidathion is
only present in the chloroform phase; the relatively larger proportion
in alfalfa plants two weeks after the treatment is attributed to the
relatively high dose of methidathion applied to these plants.
The metabolite fractions of the chloroform phase can be separated into
a polar and a non-polar fraction by thin-layer chromatography. The
substances in the polar fraction were not analysed further.
The non-polar fraction was rechromatographed using various solvent
systems whereby Rf values corresponding to GS 13007 and GS 12956 were
obtained. Methidathion was found to be the main constituent of the
chloroform phase. Confirmation of the identity of methidathion, GS
13007, and GS 12956 was achieved by co-chromatography with reference
substances in various solvent systems, and by electrophoresis in the
case of GS 12956.
The presence of GS 13007 could also be confirmed by hydrolytic
conversion to GS 12956.
TABLE 8 Distribution of radioactivity in plants after foliar application
plant type of dose days after chloroform phase
labelling (µCi/µl) treatment methidathion GS 13007 GS 12956 polar equeous non- 14CO2
fraction phase extractable
methidathion .............................. percentage of applied dose ........................
beans C = 0 8.3/1 500 71 6.03 0.22 0.66 1.95 20.2 1.55 20.4
beans C = 0 1.39/300 141 <------------------ 6.9 (total) --------> 14.9 12.4 27.4
beans OCH3 1.35/300 161 1.34 0.23 0.55 1.81 47.0 10.65 8.0
beans OH2 6.53/600 131 3.33 0.15 traces 0.15 25.7 10.9 23.3
alfalfa C = 0 7.89/200 141 39.35 0.86 1.00 1.80 32.0 6.4 13.7
alfalfa C = 0 17.1/400 72 53.23 0.33 1.74 0.33 14.5 2.9 -
alfalfa C = 0 17.1/400 132 31.94 0.57 0.48 0.39 17.25 4.9 -
beans C = 0 7.43/400 151 - - 5.4 1.8 55.3 6.7 2.3
1 plants cultivated under laboratory conditions
2 plants cultivated outdoors
3 including 21.5% from yellowed leaves
4 including 9.3% from yellowed leaves
The pattern of metabolites occurring in the chloroform phase is
unrelated to the labelling of the methidathion molecule. The
quantitative distribution of the radioactivity is the result of
different experimental conditions (see Table 8).
The presence of unchanged methidathion, the oxo-analogue GS 13007 and
a further radioactive substance (according to Dupuis et al., 1971,
it is GS 12956) in the chloroform phase was also confirmed by Bull
(1968), and Cassidy and co-workers (1969a). Occurrence of the
metabolite GS 13007 was only transitory during the degradation of the
insecticide and in small quantities, according to Bull (1968) to a
maximum of 1.3% of the applied radioactivity; it is in no way a main
metabolite and is not stored in the plant (Cassidy et al., 1969a).
These laboratory experiments were confirmed by residue determinations
for GS 13007 in alfalfa and clover crops grown under practical
conditions outdoors and treated with methidathion. These trials showed
that residues of the oxo-compound represented 1% of the total amount
of methidathion on the plants (see section on residues in field and
forage crops). Residue determinations were made by thin-layer
chromatography by means of fly head cholinesterase inhibition (Mattson
et al., 1969).
In the aqueous phase at least four metabolic fractions occurred which,
however, could not be satisfactorily separated by thin-layer
chromatography in neutral solution systems. Using solvent systems
containing formic acid or ammonium hydroxide a separation into
distinct zones can be obtained, although this leads to decomposition
of the metabolites. One substance can be determined as the final
product of degradation in the aqueous phase. It can also be liberated
from one-third of the water-soluble radioactivity by acid hydrolysis
of the entire aqueous phase. This substance is GS 12956, whose
identity can be confirmed by co-chromatography with the reference
substance in various solvent systems and by electrophoretic
determination. In addition, it can be converted to GS 26703
(1,3,4-thiadiazolidin-2,5-dione) by acidic cleavage of the methyl
group, a process which Rüfenacht (1968) has described for GS 12956.
To determine whether the metabolic pattern of the aqueous phase is
dependent on the labelling of the methidathion molecule, bean leaves
were treated with differently 14C-labelled samples of the product and
analysed one week later.
The Rf values of the radioactive metabolite fractions of the aqueous
phase, listed in Table 9, indicate that the position of the label has
no significant influence on the metabolite pattern (Dupuis et al.,
As already mentioned, GS 12956 can only be determined in the aqueous
phase after acid hydrolysis (7 N HCl for 24 hours at 23°C) : after
O14CH3-labelling 29.5% of the measured radioactivity is obtained as
14C-GS 12956 and after 14C = 0-labelling 25%. As is to be expected,
after labelling of the methylene group no radioactive GS 12956 is
obtained. If the radioactive fractions of the aqueous phase from zone
1 and zone 2 (see Table 9) are separately hydrolysed with acid, GS
12956 is obtained both from zone 2 and zone 1. This finding indicates
the presence of several metabolites in the aqueous phase; they have
the general structure
and differ from one another only by the radical R.
TABLE 9 Distribution of radioactivity in bean plant after treatment
of leaves with 14C-labelled methidathion
Rf values of radioactive fractions of the
label 0.05 0.351 0.5 0.8
zone 1 zone 2
14CH2 81.5% 18.5%
14C = 0 85.3% 14.7%
O14CH3 83.4% 16.6%
1 main fraction
The instability of zone 2 is an indication of the presence of the
desmethyl conjugate of methidathion, namely O-H-O-methyl-S[2-methoxy-
1,3,4-thiadiazol -5(4H)-onyl-(4)-methyl]-dithio-conjugate is a labile,
rapidly decomposing substance, which contributes some 20% of the
radioactivity of the aqueous phase. The conjugate is metabolized to
water-soluble desmethyl methidathion. From metabolic studies with
14CO-labelled desmethyl methidathion, which was injected into alfalfa
plants, it is known that the conjugate and the desmethyl methidathion,
which arises in the alfalfa plants, are not stable but are converted
to more polar metabolites. As in methidathion the thiadiazole ring is
oxidized to CO2. Desmethyl methidathion does not inhibit
cholinesterase (Simoneaux and Cassidy, 1969).
Contamination of the soil with insecticides may occur either during
the process of application (drainage of the product from the plants,
direct spraying of the soil) or because the treated plants excrete the
insecticide or its metabolites into the soil.
In the soil residues of methidathion were detected after direct
application and also after spraying of apple trees. The active
ingredient content of the upper 5 cm of soil was up to 1.9 ppm, lower
layers from 5-25 cm remained mainly residue-free or contained slight
levels of active ingredient. Initial residues of 1.6-1.9 ppm were
reduced to about 0.25 ppm after two weeks. Methidathion could not be
detected in the soil four weeks after application.
As determined by residue analyses of soil samples, methidathion could
no longer be determined three to five weeks after spray applications
on apple trees or direct application on the soil (Eberle and Hörmann,
1971). The possibility of contamination from treated plants is however
unlikely. According to investigations by Dupuis and co-workers (1971)
bean plants and young apple trees treated with 14C-labelled
methidathion and grown in a nutrient solution excreted only little or
no radioactivity. The radioactivity measured in the nutrient solution
of the bean plants four weeks after treatment was no more than 1-1.5%
of the applied dose. As demonstrated by thin-layer chromatography,
polar substances are involved here. With apple trees no radio-labelled
substances were detected in the nutrient solution (investigation
period: four months; limit of detection: 0.1% of the applied dose). In
two pots, in which young trees were grown in soil, again no
radio-labelled substance was excreted into the soil. These findings
are in accordance with the results of investigation of the
translocation of methidathion in the plant organism. These showed that
radio-labelled methidathion applied on the leaves is translocated in
only very slight quantities to untreated parts of the plants.
As in animal and plant organisms methidathion is metabolized to CO2
in the soil. This is the result of laboratory trials in which Dupuis
and co-workers (1961) treated samples of different soil types with
14CO-labelled methidathion and measured the 14CO2 release at
different times after treatment. The values are summarized in Table
The important role of microorganisms in the breakdown of methidathion
can be seen from the very low release of CO2 from sterilized loam
(2%) and the high level of radioactivity that can be extracted with
acetone from the soil in the form of the unchanged insecticide. In
contrast, the extracted radioactivity (8% from non-sterilized soils)
consists of only one-third of unchanged methidathion. The two
metabolites GS 13007 and GS 12956 do not occur in soil (Eberle and
As for other insecticides, microorganisms are largely responsible for
the degradation of methidathion in soil. According to the
investigations of Getzin and Rosefield (1968) 50% of applied
methidathion is metabolized in a non-sterile loam while only 17 or 29%
is degraded in a loam sterilized by irradiation or heating.
The question of how far methidathion can be washed into the soil has
been tested in the laboratory. Metal columns were filled with
air-dried samples of a sandy loam, a marly loam and a sand containing
5.6%, 3.6% and 2.2% organic components, respectively, treated with
radioactive methidathion (corresponding to a rate of application of 5
kg a.i./ha and artificially watered at a rate of 200 mm during 48
hours). Radioactivity measurements showed that in sandy loam, with the
highest content of organic matter, methidathion can be detected only
in the upper 4 cm, in marly loam and in sandy soil in 8- and 16-cm
deep soil layers. The insecticide content in the 16-cm layer is very
small (1.3% of the applied level). A contamination of underground
water with methidathion is not very likely, since the insecticide,
even in weakly absorbing sand, only penetrated 16 cm into the soil
after 200 mm artificial rain. This assumption has also been confirmed
by the analysis of the rain water, in which methidathion could not be
detected (limit of detection: 0.5% of the applied dose).
TABLE 10 Degradation of 14CO-labelled methidathion
to 14CO2 in soils
Soil type Days after 14CO2 release Radioactivity
treatment (% of applied extracted with
dose) acetone (%)
humus 8 9.6
loam 8 27.9
21 45.0 8
sterilized loam 26 2.0 63
Summary of the metabolism of methidathion
Metabolic studies with radio-labelled material in animals, plants and
soil have shown that the dithiophosphoric ester methidathion
dithiophosphate) is metabolized in all the systems investigated and
largely broken down to C-1 fragments (CO2).
The degradation pathways and the intermediary compounds occurring
during the metabolism in the different systems investigated are shown
in Figure 6. The continuous arrows indicate identified metabolites.
The broken lines indicate the probable but unproven sequence of
metabolites found. The dotted arrow symbolizes a metabolic pathway of
minor importance. The mercaptomethyl compound GS 32978 is placed in
brackets since, although its presence as a primary degradation product
must be assumed, it has not been demonstrated.
In storage and processing
Residue determinations in cooked apples and vegetables
To determine how far methidathion residues would be influenced by the
cooking process, untreated samples of apples, spinach and tomatoes
were fortified with 0.2, 1.0 and 5.0 mg methidathion/kg and cooked for
15, 30 or 45 minutes. Results are shown in Table 11. Residue
determinations were carried out by gas chromatography with a
thermionic phosphorus detector. The limit of detection of this method
is about 0.04 ppm (Blass, 1972).
As can be seen from Table 11 the cooking process leads to a
considerable degradation of the insecticide. After a cooking time of
15 minutes, the added methidathion, which corresponds approximately to
an insecticide residue resulting from an outdoor spray application,
was reduced by at least 90%. After 30 minutes the residue levels, with
the exception of two samples, were below the limit of detection.
In view of the persistence of methidathion residues in the peel of
citrus fruits it was necessary to determine the fate of the residue
when citrus peel is used in the preparation of marmalade. One such
study (Geigy Australasia, 1970) showed that there were no detectable
residues (less than 0.01 ppm) in marmalade prepared from oranges
containing 2 ppm of methidathion in the peel.
Studies show that beer, brewed from treated hops containing 2.4 ppm
methidathion, does not contain methidathion or metabolites at or above
0.0001 ppm. Likewise tea treated with methidathion is unlikely to give
rise to residues in brewed tea.
TABLE 11 Residues of methidathion in apples, spinach and tomatoes
Sample Methidation added Cooking time residues
(ppm) (minutes) (ppm)
0.2 30 <0.04
1.0 30 <0.04
0.2 30 <0.04
1.0 30 0.06
0.2 30 <0.04
1.0 30 <0.04
5.0 30 0.21
METHODS OF RESIDUE ANALYSIS
Residues of methidathion can be determined by specific methods
including gas-liquid chromatography, which are described by Eberle and
The parent compound methidathion is determined in various agricultural
crops and soil by gas chromatography using both sodium thermionic and
electrolytic conductivity detectors with a limit of determination of
0.01 ppm. This gas chromatographic procedure is simple, versatile and
very useful for routine analysis.
The oxo-analogue GS 13007 is detected on thin layer chromatographic
plates by fly head cholinesterase inhibition, and GS 12956, the
heterocyclic moiety of methidathion, by silver nitrate with a
detection limit of 0.01 ppm each.
The various tolerance values established for methidathion in different
countries are shown in Table 12.
TABLE 12 Examples of National Tolerances Reported to the Meeting
Country Tolerance Crop
Australia 2.0 citrus fruit (whole)
0.75 seed oil crops
0.2 pome, fruits (apples, peers)
0.1 vegetables (cauliflower, broccoli
seed vegetables, legumes, tomatoes)
0.01 root vegetables
0.01 cereals, sorghum (grain)
Germany, (Fed. Rep. of) 2.0 citrus fruit
0.3 pome fruits, cabbage
0.2 all other fruits and vegetables
0.21 citrus fruit (without peel)
0.1 other plant products
Belgium 0.2 all fruit and vegetables
Holland 0.2 all fruit and vegetables
Switzerland 0.15 pome fruits, grapes
South Africa 0.5 citrus fruit (whole)
U.S.A. 6.0 alfalfa, clover, grass (fresh and
0.2 cotton seeds
1 provisional tolerance
The withholding periods established for methidathion (see Table 13)
vary considerably from country to country for the same crop, as a
result of different meteorological conditions and differences in
agricultural practices - both factors which can influence the rate of
breakdown of a pesticide.
TABLE 13 Examples of withholding periods for methidathion
Crop last treatment Country
Pome fruits 42 Switzerland
35 Austria, Belgium
28 Argentina, Germany, Fed. Rep. of
21 South Africa, Netherlands
Stone fruits 23 South Africa
cherries 14 Belgium, Yugoslavia
peaches 30 Israel
Grapes 56 South Africa
30 Italy, Israel
Citrus fruit 60 Israel
56 South Africa
Hops 21 England
Vegetables 35 Austria, Belgium
TABLE 13 (Cont'd.)
Crop last treatment Country
Potatoes 35 Austria
21 Germany, Fed. Rep. of; Switzerland
6 South Africa
Cotton 30 Israel
plants 3 Australia
Cereals 42 Australia
Forage crops 21 Germany, Fed. Rep. of; Switzerland
Methidathion is a broad spectrum organo-phosphorus insecticide/
acaricide introduced in 1964. It is effective against a wide variety
of pests of pome and stone fruits, grapes, citrus fruit, cotton,
potatoes, beet, hops, cereals, vegetables, olives, sugarcane, oilseed
crops, pastures and forage crops. The main field of application are
pome and stone fruits, citrus fruit, cotton and forage. It has both
contact action and stomach poison effect. The technical product
contains a minimum of 95% methidathion.
Methidathion is registered for use in many countries. The rate of
application varies according to pest and ranges from 30-60 g a.i./100
l or 250-1 000 g a.i./ha. Its action is independent of prevailing
temperatures, though weather conditions influence the duration of
insecticidal effect. Depending upon crop species, rate of application
and weather, effective action ranges from one to three weeks.
No post-harvest applications have been developed.
Extensive residue data were available to the meeting from trials
conducted in 15 different countries on 28 major crops comprising seven
different crop classes. Many of the trials involved the examination of
different crop parts, different stages of growth and analysis for
metabolites as well as parent compound.
Much of the residue data were subjected to statistical analysis, and
it was possible to present the dissipation curves on various crops as
regression lines. These curves indicate that methidathion is rapidly
degraded, the residues decreasing exponentially with time.
The statistical analysis of residue data from trials on pome and stone
fruits, grapes, oranges and alfalfa showed that the rate of
dissipation is not significantly dependent on the rate of application
or the formulation used. In the case of cherries, the initial residue
level was comparatively high (2.5-5 ppm), but this was rapidly reduced
by fruit growth and enzymatic processes in the cherries. The half-life
was only two days, in contrast to six to seven days in most other
In the case of apples, the level of residues depends largely on
variety. Varieties such as Delicious retain more residues for a longer
time than other varieties possibly because of the higher wax content
in the peel. The methidathion residue penetrates the peel and is to be
found in the flesh and even the core when treated apples are stored
for long periods. Citrus fruit, on the other hand, retain all the
residue in the outer skin.
Numerous studies on the metabolism of methidathion in plants and
animals and on the fate of deposits applied to plants and soil were
available. There is very little tendency for translocation, but a high
proportion of the amount taken up by plants is quickly metabolized to
CO2. The only significant metabolite found in plants is the oxygen
analogue. The desmethyl derivative of methidathion is unstable and
water-soluble. It does not inhibit cholinesterase. The
methoxy-thiadiazolene moiety is only found in trace amounts in plant
The presence of methidathion could not be demonstrated in soil three
to five weeks after direct application. A considerable proportion is
converted to CO2 in that time, due apparently to the activity of
Studies available to the meeting demonstrated the fate of methidathion
fed to cattle and poultry at rates greatly in excess of those likely
to be encountered in practice. Feeding treated forage, pasture or
plant parts to ruminant animals or poultry is unlikely to give rise to
residues of methidathion or metabolites in animal tissues, milk or
eggs at levels above the limit of determination (0.01 ppm).
The use of treated hops containing 2.4 ppm of methidathion did not
give rise to residues in beer above the limit of determination of
0.0001 ppm. Likewise, treated tea does not give rise to residues in
A number of studies were available to show the effect of cooking on
residues in several fruits and vegetables. Residues at the level
resulting from approved uses are degraded by at least 90% after 15
minutes of cooking. After 30 minutes of cooking, the residue levels
fall below the limit of determination (0.04 ppm).
Specific analytical methods are available, utilizing sodium thermionic
and electrolytic conductivity detectors in gas-liquid chromatography.
These procedures are useful for routine analysis and the method of
Eberle and Hörmann (1971) appears satisfactory for regulatory
purposes. The limit of determination in most plant products is 0.01
ppm. The major metabolites have been determined by thin layer
chromatography with a detection limit of 0.01 ppm.
The following temporary tolerances are based on residues likely to be
found at harvest following currently approved use patterns. The
temporary tolerances are expressed as methidathion as it is known that
the oxygen analogue, if present, does not occur at concentrations
above 0.05 ppm.
The time interval between application and harvest which has been used
in determining the maximum residue limits is appropriate to the
agricultural practices in numerous countries. Residues are known to
degrade rapidly with a half-life of six to seven days on most crops.
Crop Temporary on which
(ppm) is based
Apples and pears 0.5 14
Apricots, cherries, nectarines,
peaches, plums, prunes 0.2 14
Grapes 0.2 28
Citrus fruit 2 21
Leafy vegetables 0.2 21
Cabbage, cauliflower 0.2 21
Beans, peas, tomatoes 0.1 7
Maize, sorghum (grain) 0.1 42
Cottonseed 0.2 10
Cottonseed oil (crude) 1 10
Hops (dried) 3 21
Tea (dry manufactured) 0.1 7
Potatoes 0.02 *
Milk and milk products (fat basis) 0.02 * ( from feeding
Meat, fat and edible offal of cattle, ( ontreated forage
sheep, goats, pigs and poultry 0.02 * ( and plant
Eggs (shell free) 0.02 * ( products
* at or about the limit of determination
FURTHER WORK OR INFORMATION
REQUIRED (by 30 June 1975)
A study to elucidate the formation of pigment and the nature of the
liver lesion which leads to increased serum transminase levels in
1. Metabolic studies in man to determine comparative degradation
between man and other species.
2. A study to determine dose levels causing no carboxylesterase
(aliesterase) activity depression.
3. Further information on the fate of residues in storage and
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Unveröffentlicht, Geigy, J.R. AG.
Aeppli, L. (1970a) Akute Toxizität, Ratte per os, A 3628 blaugefärbt.
Unveröffentlicht, Geigy, J.R. AG.
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