FAO/PL:1968/M/9/1
WHO/FOOD ADD./69.35
1968 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD
THE MONOGRAPHS
Issued jointly by FAO and WHO
The content of this document is the result of the deliberations of the
Joint Meeting of the FAO Working Party of Experts and the WHO Expert
Committee on Pesticide Residues, which met in Geneva, 9-16 December,
1968.
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
WORLD HEALTH ORGANIZATION
Geneva, 1969
ENDOSULFAN
Since the previous evaluation (FAO/WHO, 1968), additional data has
become available and is summarized and discussed in the following
monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Biochemical aspects
A full account of the metabolism of endosulfan in rats and mice has
been reported by Schuphan et al. (1968) which extends the previous
report of Ballschmitter et al. (1967).
After oral or intraperitoneal doses of endosulfan-A or endosulfan-B (4
or 8 mg/kg) were given to rats, the unchanged compounds, along with
endosulfate, alpha-hydroxy endoether, and endolactone were excreted in
the faeces in a ratio of 10 : 0.3 : 0.3 : 1 respectively. Endodiol and
endoether were not metabolites. In the urine after oral administration
of endosulfan-A, the ratio of endosulfan-A to endosulfate,
endolactone, and an unidentified metabolite, M1, was 3 : 1 : 1 : 2;
after endosulfan-B was administered the ratio of unchanged
endosulfan-B to endosulfate, endolactone, and M1 was 2 : 1 : 6 : 20.
In the bile following endosulfan-A administration by means of a
duodenal fistula there were large amounts of endoketone and traces of
M1 present, while after endosulfan-B administration there were large
amounts of M1 and traces of endolactone. Using C14-labelled
endosulfan in mice, it was found that the identified lipophilic
metabolites comprised 20 per cent of the total endosulfan metabolites
(Schuphan et al. 1968).
Undiluted endosulfan is slowly and incompletely absorbed in the
digestive tract of warm-blooded animals. Absorption is more rapid in
the presence of alcohols, oils and emulsifiers. These substances also
accelerate the absorption of endosulfan through the skin (Maier-Bode,
1968).
The danger of accumulation of endosulfan appears to be slight
(Hoescht, 1965).
Acute toxicity
No further information available.
Reproduction study
Groups of eight male and 16 female rats were fed diets containing
endosulfan at levels of 2 and 50 ppm through three generations. No
adverse effects wore noted among either the parental animals or their
progeny in all the generations. The growth, mortality, behavioural
reactions, organ weights, gross- and histo-pathology, reproduction
performances and survival indices of the progeny were comparable in
both the test and control groups of animals (Industrial Bio-Test
Laboratories, 1965).
Comments
From the available data, a no-effect level in two species of animals
can now be set.
TOXICOLOGICAL EVALUATION
Level causing no significant toxicological effect
Rat: 50 ppm in the diet, equivalent to 2.5 mg/kg per day
Dog: 0.75 mg/kg per day
Estimate of acceptable daily intake for man (endosulfan A,
endosulfan B and endosulfan sulfate)
0-0.0075 mg/kg body-weight
RESIDUES IN FOOD AND THEIR EVALUATION
Residues resulting from supervised trials
McCaskey and Liska (1967) have studied losses in subsequent processing
of endosulfan sulfate added, both by oral administration and by direct
dissolution, to milk. Endosulfan sulfate, but not endosulfan, residues
were found in the whole milk after feeding high doses (2 g per cow for
11 days).
The level of both endosulfan and endosulfan sulfate decreased on
processing, as shown below:
Endosulfan residues (ppm on fat basis) in milk and milk products
From dosed cows By direct addition
Milk Fat (per cent.) Residue Fat (per cent.) Residue
(ppm)* (ppm)
Raw 3.95 15.2 3.15 15.9
Forewarmed 3.94 12.7 3.14 12.7
Condensed 7.92 12.6 7.04 11.4
(continued)
Endosulfan residues (ppm on fat basis) in milk and milk products
From dosed cows By direct addition
Milk Fat (per cent.) Residue Fat (per cent.) Residue
(ppm)* (ppm)
Spray-dried 29.7 8.8 24.8 10.1
Evaporated 7.92 8.8 7.04 9.9
Drum-dried 28.8 4.5 18.85 8.0
* Endosulfan sulfate.
There is some indication for residues on apples and corn that, for an
initial ratio of alpha to beta isomers of about 3 : 2 the final ratio
is of the order of 1 : 2 (apples, 21 days) or 2 : 3 (corn, 35 days)
(Hoechst, 1968).
Evidence of residues in food in commerce or at consumption
Residue data summarized previously (FAO/WHO, 1968) has been
consolidated and presented in greater detail by Maier-Bode (1968).
Some total residue levels for endosulfan A, endosulfan B and
endosulfan sulfate are included but these residues are not separately
reported. There is some evidence to show that, as the residues
disappear, endosulfan sulfate becomes an important feature, and that
endosulfan B is somewhat more stable than endosulfan A. The total
residue at harvest can contain a significant proportion (about 30 per
cent) of endosulfan sulfate. In general, however, the amount of
endosulfan sulfate residue cannot be assessed from the extensive
residue data evaluated in 1967. There is still a need, therefore, for
further information on the total residues of endosulfans A and B and
endosulfan sulfate in treated produce.
Duggan (1968) has summarized the results from the United States
dietary residue monitoring programme for the period mid-1963 to
mid-1967. Endosulfan (thiodan) residues were found in 1.2 per cent of
raw agricultural produce (only 0.4 per cent of imported produce) the
average level not exceeding 0.005 ppm; and in only 1.4 per cent of
the ready-to-eat composite samples, the average level not exceeding
0.001 ppm. Results (in ppm) for individual market basket samples were
as follows:
Domestic (a) Imported (a) Composite (b)
Large fruit T T TT
Small fruit T T -
Leaf, stem vegetables 0.01 T -
Vine, ear vegetables T T -
(a) Raw; (b) ready-to-eat; T = less than 0.005 ppm;
TT = less than 0.001 ppm.
No information is given for grains and cereals, root vegetables,
beans, eggs, nuts, milk or milk products. No endosulfan isomers or
endosulfan sulfate were detected in total diet studies in 1966-67 in
England and Wales (Abbott et al. 1969) using methods of analysis
sensitive to 0.001 ppm. Some information is also available for total
diet samples collected in the Federal Republic of Germany. No
alpha- or beta-endosulfan or endosulfan sulfate was detected in any
sample, the limits of detectability in the different food groups being
0.001 ppm for cereals, vegetables, meat and fish, fruits, sugar,
preserves, beverages, and 0.005 ppm for milk products, fats and eggs.
All samples contained DDT; in addition, lindane was also found in
cereals, meat and fish.
RECOMMENDATIONS FOR TOLERANCES AND PRACTICAL RESIDUE LIMITS
Appraisal
Endosulfan is a broad spectrum insecticide, but nevertheless
relatively harmless to bees. Data from supervised trials in which
endosulfan is used in accordance with good agricultural practice
suggest that for fruit and vegetables there is a requirement for
residue levels of combined endosulfan A and B (and including also in
some cases endosulfan sulfate) of up to 2.0 ppm. Some evidence is
available on the pattern of terminal residues arising in treated
produce which tends to show that, as they disappear, endosulfan
sulfate becomes the predominant residue whilst endosulfan B is
somewhat more stable than endosulfan A. However, the total residue at
harvest can contain a significant proportion (about 30 per cent) of
endosulfan sulfate. In general, the amount of endosulfan sulfate
residue cannot be assessed from the extensive residue data evaluated
in 1967, although there is some additional data which give a total
figure for the combined residues of endosulfans A and B and endosulfan
sulfate. There is still a need, therefore, for further information on
the total residues of endosulfans A and B and endosulfan sulfate in
treated produce, either separately or together.
Recommendations
Temporary tolerances
Since an adi has now been established, and in the light of the residue
data discussed above, the following temporary tolerances to be in
effect until 1971 are recommended:
Fruit and vegetables 2.0 ppm
The individual residues of endosulfan A, endosulfan B and endosulfan
sulfate are to be determined individually but expressed as their sum.
The above temporary tolerances are to apply to raw agricultural
products moving in commerce unless otherwise indicated. In the case of
fruit and vegetables the tolerances should be applied as soon as
practicable after harvest and in any event prior to actual retail to
the public. In the case of commodities entering international trade,
the tolerances should be applied by the importing country at the point
of entry or as soon as practicable thereafter.
Further work or information
Required before 30 June 1971
1. Further information on the relative amounts of endosulfan A,
endosulfan B, and endosulfan sulfate on fruit and vegetables - in
particular on lettuce, celery and brassicas - arising from the use of
technical endosulfan in accordance with good agricultural practice.
2. Data on the disappearance of the residues during storage and
processing.
3. Comparative evaluation of multidetection systems of analysis
(including sample extraction techniques for agricultural produce) to
select a method suitable for consideration as a referee method for
residues of endosulfan A, endosulfan B, and endosulfan sulfate,
determined separately.
4. Data on residue levels of endosulfan A, endosulfan B, and
endosulfan sulfate in total diet studies.
Desirable
1. Clarification of the extent of use, if any, other than on fruit and
vegetables.
2. Metabolic studies in man, with particular reference to storage of
the original compound and metabolites.
REFERENCES
Abbott, D. C., Holmes, D. C. and Tatton, J. O'G. (1969) Organochlorine
pesticide residues in total diet in England and Wales (In press)
Ballschmitter, K., Schuphan, I. and Tölg, G. (1967) The metabolization
of endosulfan in insects and mammals. Paper presented to the VI
International Plant Protection Congress, Vienna
Duggan, R. E. (1968) Residue in food and feed. Pesticides Monitoring
J., 2 (1): 2-12
FAO/WHO. (1968) 1967 Evaluations of some pesticide residues in food
(FAO, PL: 1967/M/11/1; WHO/Food Add./68.30)
Hoechst. (1965) Farbwerke Hoechst, A. G. Data sheet for
endosulfan/Thiodan. Unpublished report
Hoechst. (196) Farbwerke Hoechst, A. G.
Hoechst. (1968) Farbwerke Hoechst, A. G. (Private communication to
FAO).
Industrial Bio-Test Laboratories, Inc. (1965) Three generation
reproduction study on Thiodan - Albino rats. Unpublished report.
Maier-Bode, H. (1968) Properties, effects, residues and analytics of
insecticide endosulfan. Residue Reviews, 22: 1.44
McCaskey, T. A. and Liska, B. J. (1967) Effect of milk processing
methods on endosulfan, endosulfan sulfate and chlordane residues in
milk. J. Dairy Sci., 50: 1991-1993
Schuphan, I., Ballschmitter, K. and Tölg, G. (1968) Zum Metabolismus
des Endosulfans in Ratten und Mäusen. Z. Naturforsch., 23: 701-706