IPCS INCHEM Home


    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
    


    See Also:
       Toxicological Abbreviations
       Endosulfan (EHC 40, 1984)
       Endosulfan (HSG 17, 1988)
       Endosulfan (PIM 576)
       Endosulfan (FAO Meeting Report PL/1965/10/1)
       Endosulfan (FAO/PL:1967/M/11/1)
       Endosulfan (WHO Pesticide Residues Series 1)
       Endosulfan (WHO Pesticide Residues Series 4)
       Endosulfan (WHO Pesticide Residues Series 5)
       Endosulfan (Pesticide residues in food: 1982 evaluations)
       Endosulfan (Pesticide residues in food: 1989 evaluations Part II Toxicology)
       Endosulfan (JMPR Evaluations 1998 Part II Toxicological)