377. Thiometon (Pesticide residues in food: 1976 evaluations)

THIOMETON JMPR 1976

Explanation

In 1969 the Joint Meeting (FAO/WHO, 1970b) evaluated thiometon
in the light of information then available. No ADI could be
established and no maximum residue limits were recommended.
Thiometon was reviewed by the Joint Meeting in 1973 (FAO/WHO,
1974b) and a temporary ADI and some temporary maximum residue
limits were recommended. The 1973 Meeting listed three items on
which further work or information was required in order that the
temporary limits could be confirmed and additional maximum residue
limits recommended. Information has become available on the fate of
thiometon in plants, animals and soil. Further data on residues
from supervised trials and a GLC method of residue analysis have
also been reported. The new information is evaluated in this
monograph addendum.

The present Meeting was informed of a long-term study in rats
and a 2-year study in dogs which are in progress. The temporary ADI
has therefore been extended until 1979, when the compound will be
re-evaluated.

RESIDUES IN FOOD AND THEIR EVALUATION

RESIDUES RESULTING FROM SUPERVISED TRIALS

Additional data on residues resulting from supervised trials
which have become available since the 1973 Meeting are summarized
in Table 1.

FATE OF RESIDUES

In plants

Thiometon in plants (apples, Brussels sprouts, lettuce,
strawberries and sugar beets) persists for only a few hours after
application, being rapidly converted to the sulphoxide which occurs
as the main metabolite within the first 3 days after application.
The sulphoxide is further oxidised to the sulphone. Oxidation of
the P=S group with the formation of the phosphorothiolates
demeton-S-methyl, oxydemetonmethyl and demeton-S-methyl sulphone
was also observed, but the amounts detected in various plants were
small. These compounds, especially demeton-S-methyl, are usually
rapidly degraded and do not accumulate in plants.

The further degradation of thiometon and its metabolites takes
place by hydrolytic processes which are catalyzed by enzymic
systems. The predominant pathway can be O-dealkylation of the
CH₃-O-P group producing methanol and the corresponding diesters or
disruption of the acid-anhydride bond with the formation of
OO-dimethyl phosphorothionate or phosphate and the corresponding
side chain thiols (2-(ethylthio)-ethanethiol and its oxidation

TABLE 1. Thiometon residues resulting from supervised trials

Application (as spray) Residues, mg/kg
Rate, Time after last References
Commodity kg ai./ha No application Thiometon Total as
or concentration days sulphoxide Thiometon Thiometon No. of
Thiometon sulphone trials

apples 0.15-0.25 3 28 0.10-0.16 3 a

beans 0.15-0.25 3 21 <0.02-0.06 3 a

500ml 25%E.C. - 1-7 0.55-0.13(2) b
14 <0.1

cabbage 500ml 25%E.C. - 7-14 0.15-0.05(2) b

cottonseed 11 25% E.C. - 160 <0.1 b
oil

grain crops

barley 0.24-0.5 3 0 1.8-2.6 3 a
(whole plant) 28 <0.02-0.09 3

barley (grain) 42-59 <0.02 11 a,c
barley (straw) 42-73 <0.02 7

maize (leaves) 500ml 25%E.C. - 28 <0.1 b
stalks, cobs)

wheat (Spring 0.25 1 0 0.02 0.1 0.1 0.2 c
wheat, seed) 7-28 0.02 <0.02 <0.02 0.02

wheat (whole 0.15-0.5 3 0 0.7-3.4 3 a
plant) 28 0.02 6

TABLE 1. (Cont'd.)

wheat 0 0.3-5.8 6 a
(seed) 14 <0.02-0.25 4
28-56 0.02 4 a

wheat (seed) 0.25 1 33 0.06 <0.02 <0.02 approx. 0.06 c

wheat (seed) 375ml 25%E.C. - 7 4 b
14 0.2
21 0.05

wheat (straw) 0.15-0.5 3 0 0.9-6.3 5 a
14 0.02-0.3 6
28 0.02-0.04 3
42-56 0.02 3

groundnuts 375-500ml 25% E.C. - 7 0.14-0.19 b
(leaves)
(roots) <0.1-0.14

hops (green, fresh) 0.15-0.25 3 28 0.3-0.9 3 a

lettuce 0.15-0.25 3 21 <0.02-0.4 3 a

peaches 0.15-0.25 3 28 0.03-0.14 3 a

500ml 25%E.C. - 7 0.15 c
14 <0.1

peas (green 0.15-0.25 3 21 <0.02 a
in pods)

TABLE 1. (Cont'd.)

potatoes 11 25% E.C. - 27 <0.1 b

potatoes (fineke, 0.25 30-34 <0.01 14 d
Biutige)

sugar beets 0.15-0.25 3 0 <0.02-0.07 3 a
7 <0.02-0.11 2
14-118 <0.02 7

sugar beet leaves 0.15-0.25 3 0 1.4-4.8 9 a
7 0.1-0.3 6
14-118 <0.02 7

tomatoes 0.15-0.25 3 7 0.12-0.22 3 a

500ml 25%E.C. - 1 0.05 b
7 <0.05

a = Sandoz, 1976c; trials carried out in the Netherlands and/or Switzerland
b = Anon., 1976a; trials in South Africa
c = Anon., 1976b; trials in the Netherlands
d = TNO, 1973; trials in the Netherlands

products). These side chains are either conjugated within the plant or
cleaved by desalkylation with the formation of acetic acid, mercaptoacetic
acid and ethanethiol and its derivatives. Intermediate metabolites
containing a free hydroxyl function conjugate to form glycosides.

Results of many field trials on sugar beets (roots and leaves),
wheat plants, apples, lettuce and potato tubers show that residues
consist mainly of thiometon sulphoxide and sulphone. Residues of the
P=0 analogues, demeton-S-methyl and its sulphoxide and sulphone,
amount to less than 25% of the total residue recovered just after
treatment.

The other metabolites mentioned above decrease very rapidly; no
residues above 0.05 mg/kg can be detected 28 days after application.
The half-life period for the degradation of the total residue is
calculated to be 4 days or less (Sandoz, 1976a, where references to
the original authors are given).

In animals

It has been shown in many investigations of disulfoton, phorate
and demeton that the metabolism of these compounds in animals is
similar to that in plants. Several studies including in vitro and
in vivo experiments with boll weevil, bollworm, rat liver and the
mouse confirmed the finding. It is therefore reasonable to conclude
that thiometon is metabolised in animals in the same way as in the
plant.

Metabolites containing a free hydroxyl or a thiol group (e.g.
desmethylated thiometon or 2-(ethylthioethanethiol) are able to
conjugate, forming mainly glucoronides, sulphates and glutathione
conjugates which are readily excreted (Sandoz, 1976a).

In soil

The fate of thiometon in soil has been reviewed (Sandoz 1976b).
It is degraded rapidly. The half-life periods for degradation in the
soils tested (containing 1.7 and 4.5% organic matter) were found to be
less than 2 days. Thiometon sulphoxide was the main metabolite,
recovered in about 70% yield 3 days after incorporation. This compound
was further oxidised to thiometon sulphone yielding up to 65% of the
applied thiometon 14 days after treatment. Oxidation to
demeton-S-methyl and its sulphoxide and sulphone occurred to a limited
extent. The final yield calculated as the sum of these compounds
amounted to less than 18%.

Oxidation in soil may be catalysed by heavy metal ions bound to
the soil and/or by soil micro-organisms (Getzin and Chapman, 1960).
Micro-organisms and acidic and basic sites in clay minerals are able
to accelerate hydrolysis of thiometon and its primary metabolites.

In water

The fate of thiometon in water (50 mg/kg aqueous buffer solutions
of pH 3, 6 and 9) was investigated. Half-lives during hydrolysis at
5°C were 90, 83 and 43 days at pH3, 6 and 9. The corresponding periods
at 25°C were 25, 27 and 17 days. No oxidation products of thiometon
(Sulphoxide, sulphone and P=O analygues) were detected. It is assumed
that thiometon is hydrolyzed in the same way as similar
phosphorodithioates and thioates (Eto, 1974), yielding 2-(ethylthio)
ethanethiol in acidic solution, ethylthioethylene as an additional
product under alkaline conditions. Comparison with related compounds
(Muhlmann and Schrader, 1957) shows the following order of decreasing
stability: disulfoton demeton-S thiometon phorate (Sandoz, 1976d).

METHODS OF RESIDUE ANALYSIS

The method for determining thiometon residues in plant materials
and soil is based an extraction with acetonitrile containing acetic
anhydride, followed by oxidation with potassium permanganate in
aqueous buffer solution at pH 7.0 (Titrisol/phosphate). By this
treatment, thiometon and its sulphoxide are converted to thiometon
sulphone, and the P=O metabolite (demeton-S-methyl) and its sulphoxide
are oxidised to the P=O sulphone. Many tests have shown that oxidation
of the P=S group is less than 10%. The extract is cleaned up by
partition between water and methylene chloride/petroleum ether (9:1).
Quantitative and separate determination of the two sulphones dissolved
in toluene is achieved by GLC using the phosphorus-sensitive
thermionic detector with a column of 10% Dexsil 300 on Gas chrom Q.
The calibration curve is linear from 0.2 to 3.0 ng. the lower limit of
determination is about 0.02 to 0.1 mg/kg. In spiked samples at 0.1 to
1 mg/kg levels the overall recoveries in general ranged between 70 and
90% (Sandoz, 1975).

This method of analysis has been applied successfully to apples,
potatoes, wheat and soil. It should be mentioned that the sulphones
are more stable to the GLC conditions than the corresponding
sulphoxides which are determined by other GLC methods. The method
cannot at present be recommended for regulatory analysis because the
extent of interference by other organophosphorus compounds is not
known.

A similar GLC method was reported for the determination of
thiometon, its sulphoxide and sulphone and similar compounds as
sulphones in potatoes, where the lower limit of determination was
0.01 mg/kg (TNO, 1973).

Thin layer chromatography has also been used for the estimation
of thiometon, its sulphoxide and sulphone in samples of spring wheat
and wheat grain. A lower limit of detection of 0.02 mg/kg has been
reported. However as the final result is obtained by visual assessment
of a coloured spot of each of the compounds, the method can only be
described as semi-quantitative (Huntingdon Research Centre, 1971).

APPRAISAL

Since the 1973 Joint Meeting information has become available on
the metabolism of thiometon in plants, animals and soil. Further data
on residues from supervised trials and a sensitive GLC method of
residue analysis have also been reported.

In plants thiometon persists for only a few hours after
application, being rapidly converted to the sulphoxide which occurs as
the main metabolite during the first three days.The sulphone is also
formed. Oxidation of the P=S group leads to the formation of
demeton-S-methyl, its sulphoxide and its sulphone, but in only very
small quantities. Further degradation is by 0-dealkylation to methanol
and the corresponding demethylated compounds, and cleavage to 00-
dimethyl phosphorothioate or phosphate and 2-ethylthio-ethanethiol and
its oxidation products. Intermediate metabolites containing a free
hydroxyl group conjugate to form glycosides.

Metabolism in insects, mice and rats is similar to that in
plants. Metabolites containing a free hydroxyl or thiol group form
glucuronides, sulphates and gluthathione conjugates which are readily
excreted.

The fate of thiometon residues in soil is also similar to that in
plants. The half-life periods for degradation in the soils tested were
found to be less than two days.

A method for determining residues in plant materials and soil is
based on extraction with acetonitrile containing acetic anhydride,
followed by oxidation with potassium permanganate. Thiometon and its
sulphoxide as well as the P=O metabolite and its sulphoxide are
oxidised to the corresponding sulphones. Separate quantitative
determination of the two sulphones is achieved by GLC using a
thermionic or flame photometric detector. The lower limit of
determination is approximately 0.05 mg/kg (0.01-0.1 mg/kg).

RECOMMENDATIONS

The following recommendations for temporary maximum residue
limits are for the sum of thiometon, its sulphoxide and its sulphone,
expressed as thiometon. They are additional to those made in 1973,
except the limit for hops which replaces the 1973 limit of 0.5 mg/kg.

Commodity Temporary maximum
residue limit (mg/kg)

Hops (dried) 2

Apricots, cabbage, celery, chicory,
endives, parsley, peanuts (whole), quinces 0.5

Commodity Temporary maximum
residue limit (mg/kg)

Cottonseed oil, maize (leaves, stalks,
cobs), straw of grain crops 0.1

Fodder beets and tops, sugar beet tops 0.05*

* At or about the limit of determination

FURTHER WORK OR INFORMATION

Required (by 1979)

1. Submission of the long-term study in rats presently in progress.

Desirable

1. Information on the level and fate of residues in live stock
consuming feed containing thiometon residues.

REFERENCES

Anon. Letter from South Africa, 28 July 1976, to FAO (repeat of
1976a information originally sent from S. Africa in
1973).

Anon. Information from the Netherlands on pesticides to be considered
1976b by the JMPR 1976; Thiometon. Cl 1976/10; 30 August
1976.

Eto, M. Organophosphorus pesticides: organic and biological
1974 chemistry. pp. 57 (1974) CRC Press Inc.,
Cleveland.

FAO/WHO 1969 evaluations of some pesticide residues in food.
1970 FAO/PL: 1969/M/17/1; WHO/Food Add./70.38.

FAO/WHO 1973 evaluations of some pesticide residues in food.
1974 FAO/AGP/1973/M/9/1; WHO Pesticide Residues Series,
No. 3

Getzin, L. W. and Chapman, R. K. J. econ. Entomol., 53:47
1960

Huntingdon Research Centre; Determination of residues of Thiometon and
1971 its metabolites in Spring wheat and wheat seed.,
4350/71/506. Huntingdon, England

Mülhmann, R. and Schrader, G. Hydrolyse der Insektiziden
Phosphorsaureester., Z. Naturforschg., 126: 196

Sandoz; Ekatin. Thiometon residues in plant materials and soil;
1975 GLC determination method. AGRO DOK CBK 2194/76;
Basle, Switzerland

Sandoz; Thiometon. Metabolism in plants and animals. A review. ACGO
1976a DOK 2201/76. Basle, Switzerland.

Sandoz; Thiometon. Fate in Soil. AGRO DOK UK 2194/76; Basle,
1976b Switzerland

Sandoz; Thiometon. Summary Report on Residue Data from supervised
1976c trials in 1974/1975, AGRO DOK CBK 1976

Sandoz; Thiometon. Hydrolysis in aqueous buffer solution of pH3, 6
1976d and 9 at 5° and 25°C. AGRO DOK CBK 2202/76; Basle,
Switzerland

TNO; Residuen van oxydemeton methyl, thiometon en disulfoton en
1973 hun metaboliten in aardappelen. Centraal Instituut
voor Voedings=onderzoek, Utrechtsweg 48, Zeist,
Netherlands. Rapport Nr. R 3957, 1973.

    See Also:
       Toxicological Abbreviations
       Thiometon (ICSC)
       Thiometon (FAO/PL:1969/M/17/1)
       Thiometon (WHO Pesticide Residues Series 3)
       Thiometon (Pesticide residues in food: 1979 evaluations)