WHO/FOOD ADD./70.38



    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
    Group on Pesticide Residues, which met in Rome, 8 - 15 December 1969.



    Rome, 1970



    Chemical name

    Dinocap is a mixture of dinocap-4 and dinocap-6 (British Standard 1831
    : 1969).

    Dinocap-4 is a mixture of the following isomers:

    I 2,6-dinitro-4-(1-methylheptyl) phenyl crotonate

    II 2,6-dinitro-4-(1-ethylhexyl) phenyl crotonate

    III 2,6-dinitro-4-(1-propylpentyl) phenyl crotonate

    Dinocap-6 is a mixture of the following isomers:

    IV 2,4-dinitro-6-(1-methylheptyl) phenyl crotonate

    V 2,4-dinitro-6-(1-ethylhexyl) phenyl crotonate

    VI 2,4-dinitro-6-(1-propylpentyl) phenyl crotonate

    The ratio of dinocap-4 to dinocap-6 in technical dinocap is likely to
    be of the order of 1 : 2.

    G.L.C. analyses of the mixture of methyl ethers prepared from the
    unesterified precursor of dinocap gave the following ratio of isomers
    present (Clifford et al., 1965):

    I 12 per cent

    II 15 per cent

    III 11 per cent

    IV 12 per cent

    V 26 per cent

    VI 24 per cent


    Karathane(R), Crotothane(R)

    Structural formula


    Other relevant chemical properties

    Technical dinocap is a dark red, viscous liquid with very slight
    solubility in water but good solubility in the usual organic solvents.
    Information on vapour pressure is not available, but persistence on
    surfaces is shorter than that of binapacryl.

    Incomplete esterification in the manufacturing process leads to the
    presence of the free phenols corresponding to the six esters mentioned
    above; these are reported (Rohm and Haas, 1969) to form 5 to 6 per
    cent of the technical product. A smaller proportion, less than 1 per
    cent, consists of mono-nitrophenols. These three classes together form
    about 80 per cent of the technical product. Of the remainder, about 4
    per cent consists of a mixture of octenes, formed by dehydration of
    the starting material, capryl alcohol, and another 2 per cent is
    crotonic acid. There are also four unknowns that produce peaks on the
    G.L.C. chart, totalling 2 to 3 per cent, and 10 to 12 per cent of the
    technical product in 'not volatile'.

    Formulations include wettable powders usually claimed to contain 25
    per cent active ingredients; Karathane(R) W.P. is now claimed to
    contain 19.5 per cent active ingredients; no further information is
    available concerning Crotothane(R) W.P. Another commercial formulation
    is a liquid concentrate; Karathane LC was formerly claimed to contain
    48 per cent active ingredients, but is now claimed to contain 39 per
    cent ; Liquid Crotothane is sold an containing 50 per cent active
    ingredients. There are also dusts containing less than 10 per cent



    Absorption, distribution and excretion

    No residues of dinocap were detected in the subcutaneous and
    intraperitoneal fat obtained from an unspecified number of rats fed
    500 ppm of dinocap in their diet for one month. The method of analysis
    was sensitive to 1 ppm (Larson et al., 1959).

    Effect on enzymes and other biochemical parameters

    Dinocap was compared with 2,4-dinitrophenol in oxygen consumption
    studies in rats. Six rats (four males and two females) were given a
    single oral dose of 600 mg/kg body-weight of dinocap. Measurements
    made at various intervals showed that a steady increase in oxygen
    consumption occurred in the females, which reached a maximum of 63 per
    cent of the zero-time level after 24 hours. Measurements made on two
    of these animals after 48 hours showed that the level had fallen to 29
    per cent. No increase in oxygen consumption occurred during 24 hours
    in the males fed dinocap. A comparable study with six other rats (two
    males and four females) given a single oral dose of 40 mg/kg
    body-weight of 2,4-dinitrophenol resulted in a maximum increase in
    oxygen consumption of 116 per cent for the females and 90 per cent for
    the males after three hours, followed by a gradual decrease after that
    time. Thus, dinocap produced an increase in oxygen consumption in
    female rats only, this effect being of longer duration although lower
    in magnitude than the effect which occurred in both sexes with
    2,4-dinitrophenol (Larson et al., 1959).

    The compound 4-isooctyl-2,6-dinitrophenol (a constituent of technical
    dinocap) was found to be 7 to 25 times more potent than
    2,4-dinitrophenol in stimulation of respiration of rat-liver
    mitochondria. The author concluded that the pKa and the lipid
    solubility of the compounds as well as the pH of the media were the
    factors influencing this activity, and that there was no intrinsic
    structure-activity relationship relative to the size of the octyl
    group (Hemker, 1962).


    Special studies on cataract formation


    Chicks were fed dietary levels of dinocap or binapacryl which were
    equivalent on a molar basis to levels of 500 or 1000 ppm of
    2,4-dinitrophenol. No lens opacities resulted from 17 to 28 days
    administration of either of these compounds at these levels. Feeding
    2,4-dinitrophenol at 2000 ppm under the same conditions also did not
    result in the formation of lens opacities. However, when the dietary
    level of dinocap or binapacryl was increased to 2000 ppm molar
    equivalent to dinitrophenol a distinct incidence of cataracts
    occurred. When fed at 4000 ppm absolute dietary level no difference
    could be observed between dinocap and binapacryl with regard to
    incidence of cataract formation (Cervenka and Kay, 1963).


    Dinocap was compared with 2,4-dinitrophenol in studies to determine if
    cataracts were formed in ducks. Three series of studies were conducted
    using the technical grade dinocap throughout.

    In the first experiment groups comprising 10 ducklings, each of about
    10 days of age, were fed dietary levels of 0, 50, 250, or 2500 ppm of
    dinocap or 0, 25, 125, 250 or 1250 ppm of 2,4-dinitrophenol for 12
    weeks. Survival was adversely affected at the 500 and 2500 ppm levels
    of dinocap and the 1250 ppm level of 2,4-dinitrophenol. Growth was
    depressed at 250 ppm and higher concentrations of dinocap and at all
    concentrations of 2,4-dinitrophenol. The 1250 ppm level of
    2,4-dinitrophenol produced cataracts within 24 hours, and all other
    levels both of dinocap and 2,4-dinitrophenol produced cataracts within
    seven weeks. No cataracts occurred in the controls. After the
    cataracts had developed, withdrawal of the substances from the diet
    for a five-week period did not result in regression of the cataracts
    (Larson et al., 1959).

    In the second experiment, groups each containing 10 ducklings, 
    received diets containing 0, 2, 5, 10 or 25 ppm of dinocap or 0, 25,
    125, 250 or 1250 ppm of 2,4-dinitrophenol. Most of the ducks including
    all of the controls developed cataracts by the end of seven weeks and
    the test series was discarded. A conclusion was drawn that cataracts
    had developed from some unknown cause (Larson et al., 1959).

    The third experiment was conducted using the same conditions as have
    been described for the second. Ophthalmologic examinations made after
    5, 9 and 13 weeks on the test diet showed no cataracts in any treated
    group (Larson et al., 1959).

    In a more recent study, ducklings were fed 250 ppm of
    dinitrooctylphenol (the isomer or mixtures thereof not specified) for
    13 weeks and none developed cataracts. When 2,4-dinitrophenol was also
    fed as a positive control to ducklings, cataracts developed in all
    cases. The explanation of the erratic results from the earlier
    cataract studies with dinocap has been suggested to be at least partly
    related to the variation in composition of the technical product
    relative to the presence of significant impurities. There may,
    however, be other explanations (Swisher, 1969).

    Acute toxicity

                             (technical grade*)
    Animal        Route       mg/kg body-weight      Reference

    Rat (M)       oral              980           Larson et al., 1959

    Rat (M)       iv.                23           Larson et al., 1959

    Rat (F)       oral             1190           Larson et al., 1959

    Rabbit (M)    oral             2000           Larson et al., 1959

                             (technical grade*)
    Animal        Route      mg/kg body-weight        Reference

    Dog           oral              100           Larson et al., 1959

    * Technical grade is here defined as:
        2,4-dinitro-6-(2-octyl)-phenyl crotonate
        2,4-dinitro-6-(3-octyl)-phenyl crotonate
        2,4-dinitro-6-(4-octyl)-phenyl crotonate .......  73 per cent
        2,6-dinitro-4-(2-octyl)-phenyl crotonate
        2,6-dinitro-4-(3-octyl)-phenyl crotonate
        2,6-dinitro-4-(4-octyl)-phenyl crotonate

        nitrocctylphenols (principally dinitro-) .......   5 per cent

        inert ingredients (octenes, crotonic
        acid and related compounds) ...................   22 per cent

    Short-term studies


    Groups, each containing three dogs of unspecified sex and age, were
    fed diets containing 10, 50, 100, 250 and 1000 ppm of technical
    dinocap for one year. One dog in the 250 ppm group died within six
    weeks, another was sacrificed after marked weight loss and the third
    was transferred to a control diet. Two dogs in the 1000 ppm group died
    within six weeks and the third was transferred to the control diet.
    (No other control group was reported to have been used). Decreased
    appetite and drastic weight loss preceded death. Moderate weight loss
    was evident at the 100 ppm level but not at 50 ppm. Hepatic necrosis
    occurred in the dogs fed 250 and 1000 ppm. Haematologic values were
    normal at all dose-levels (Larson et al., 1959).


    Groups containing 10 weanling rats of each sex were fed diets
    containing 0, 10, 50, 250, 1000 and 2500 ppm of technical dinocap for
    six months. Growth and survival were reduced at the 2500 ppm level and
    growth was reduced at 1000 ppm. Enlarged spleens occurred in the males
    receiving 2500 ppm. Haematological and microscopic examinations
    revealed no changes attributable to treatment (Larson et al., 1959).

    Long-term studies


    Groups containing 10 weanling rats of each sex were fed diets
    containing 0, 10, 50, 250, 500 and 1000 ppm of technical dinocap for
    two years. There was decreased weight gain during the first year only
    in the male rats fed 1000 ppm, but the effect on bodyweight during the
    second year was not reported. No other effect of treatment, either
    gross or histopathological was noted at any of the dose-levels studied
    (Larson et al., 1959).


    Patch tests were performed on the forearms of 50 human subjects using
    dinocap formulated either as an emulsion or as a wettable powder.
    Exposure was for 48 hours. Moderate irritation resulted from the
    emulsion in 11 subjects and from the powder in three. Similar results
    occurred when the opposite forearms were patched 12 days later, 25
    subjects reacting to the emulsion and nine to the powder. Intensified
    reactions resulted during succeeding days in three subjects (Larson et
    al., 1959).


    On the basis of animal data a no-effect level for rats has been
    established. Since the chemical structure of 2,4-dinitrophenol is
    similar to dinocap and because 2,4-dinitrophenol produces cataracts in
    man, the possibility of cataract formation in man from dinocap is of
    concern. For this reason dinocap should be used with great caution.
    Inconclusive experiments in ducks gave a possible indication of
    cataract formation. Additional studies with other species of animals
    are needed to establish the exact dosage of dinocap which does not
    produce cataracts. In addition, the data on the toxicology of dinocap
    were obtained between 1954 and 1958, and are incomplete especially in
    relation to metabolism. Skin sensitization is reported in human
    subjects but no other data on man are available. The technical product
    appears to be of variable composition.



    Pre-harvest treatments

    Dinocap in a non-systematic fungicide; only its activity against
    powdery mildews is of commercial importance. It also restricts the
    development of populations of several tetranychid phytophagous mites,
    and in view of the widespread resistance of such species to specific
    acaricides, this role is very valuable.

    Powdery mildews are important on apple, apricot and peach, and less so
    on pear and cherry among deciduous fruits; dinocap has become the
    leading fungicide for control on apple, apricot and pear, and second
    only to sulphur on peach (Kirby, 1969). In the U.K., over 15,000
    hectares of apples were sprayed with dinocap in 1967; a smaller area
    of pears was also sprayed. For 10-14 day interval spraying, the usual
    rate of use on apple in the U.K. is 2.24 kg of the wettable powder per
    ha; according to the recent claim for Karathane WP, this is 0.44 kg
    a.i, per ha. According to the U.S.A. manufacturers, U.S.A. regulations
    allow up to 1.75 kg a.i. per ha to be applied on each occasion. In the
    U.K., at least one week must elapse between the final application and
    harvest on all edible crops; in the U.S.A. this period applies to
    cucurbits, but 21 days must elapse on all fruits, except apricots and
    peaches which need 45 days and almonds where use is allowed up to the
    'jacket stage'.

    Post-harvest use

    Use of dinocap post harvest does not arise on perennial crops.

    Other uses

    The widespread occurrence of powdery mildews on almost all
    ornamentals, annual and perrenial, leads to widespread use of dinocap
    by nurserymen as well as public and private gardeners throughout the
    summer and early autumn. No use on animals is known.


    On apples, trials on two cultivars in two States of the U.S.A. showed
    that, in the absence of heavy rain, the half-life of dinocap was 1.9
    days over a range of initial deposits from at least 50 to 200 ppm.
    Heavy rainfall was found to reduce deposits very considerably (Rohm
    and Haas, 1958, unpublished).

    Trials conducted by or for Rohm and Haas Company provide the following
    results for deposits and residues on various crops:

                                                     Pre-harvest          Deposit or residue
                        No. of          Rate          interval        Range                Average
    Crop              applications    g/a.i./ha         days          ppm                  ppm

    Apple               3               380              28           Nil                   Nil

                        5               570               0           0.26-0.57             0.41

                                                         21           <0.05

                        1               380               0           0.29-0.40             0.33

                                                     Pre-harvest          Deposit or residue
                        No. of          Rate          interval        Range                Average
    Crop              applications    g/a.i./ha         days          ppm                  ppm

                                                         14           Nil-0.07              0.04

                                                         21           Nil-0.01              0.01

                      ( 2               190 )
                      (                                  27           No detectable residue
                      (12               130 )

                        6               850               0           0.20-0.43             0.33

                                                          7           0.06-0.12             0.09

                                                         14           No detectable residue

    Pear                4               510               5           0.04-0.20             0.11

                                                         21           No detectable residue

    Apricot             2               380               0           0.35-0.70             0.55

                                                         21           No detectable residue

    Apricot             2                                 0           Nil-0.15              0.08
                                                         14           No detectable residue

    Peach               1               255               0           0.17-0.85             0.54

                                                         21           No detectable residue

                        3               255              18           No detectable residue

    Blackberry          3               760              44           0.05-0.07             0.06

    Boysenberry         1               380               0           0.36-0.51             0.41

                                                          7           No detectable residue

    Raspberry           3                95              10           No detectable residue

    Grape               1                95               0           Nil-1.15              0.54

                                                          7           0.17-0.95             0.33

                                                     Pre-harvest          Deposit or residue
                        No. of          Rate          interval        Range                Average
    Crop              applications    g/a.i./ha         days          ppm                  ppm
                                                         14           Nil-0.37              0.13

                                                         21           Nil-0.50              0.12

                                                         28           No detectable residue

                      ( 1               180 )             0           0.02-0.10             0.04
                      (                     )
                      ( 2                86 )            20           Nil-0.03              0.01

    Grape (juice)     ( 1               180 )
                      (                     )            29           Nil-0.01              0.01
                      ( 2                86 )

    Strawberry          3               380               0           0.81-1.43             1.02

                                                         10           0.08-0.15             0.11

                                                         21           No detectable residue

    Cantaloup          18               130               3           (Pulp)Nil-0.08        0.027

    Honeydew melon     18               130               3           (Pulp)No detectable residue

    Cucumber          ( 2                95 )
                      (                     )             0           No detectable residue
                      ( 1               130 )

    Pumpkin             5               130               4 hours     (Pulp)0.20-0.34       0.24

                                                                      (whole)Nil-0.60       0.24

    Squash              4                95               0           Nil-0.15              0.08

                                                          3           No detectable residue

    Muskmelon         ( 9               130 )                         (Pulp)0.00-0.10       0.02
                      (                     )             0           (Rind)0.00-0.10       0.04
                      ( 5               195 )

    The short half-life on foliage, approximately two days, already
    mentioned means that dinocap readily disappears from leaves. A longer
    half-life, about four days, on strawberries was found by Kilgore and
    Cheng (1963) who made a single application 21 days before harvest.

    Nothing has been found in the literature concerning breakdown


    Several colorimetric methods sensitive to about 0.1 ppm have been
    proposed for the determination of residues of dinocap in apples,
    strawberries, grapes, tomatoes and animal tissue (Rosenthal et al.,
    1957; Skerrett and Baker, 1962; Kilgore and Cheng, 1963). However,
    with the fuller recognition of the relative importance of the various
    components of commercial formulations of dinocap (Clifford et al.,
    1965; Kirby and Elvidge, 1965; Kirby and Hunter, 1965) a gas
    chromatographic procedure to likely to prove more generally useful.
    Clifford and Watkins (1968) have described suitable gas
    chromatographic conditions for the examination of a range of
    dinitroalkyl phenols. Boggs (1966) and Yip and Howard (1968) preferred
    to convert the phenols to methyl others before gas chromatography with
    electron capture detection. No complete extraction, clean-up and gas
    chromatographic determination procedure can be recommended for
    residues of the active ingredients of dinocap at the present time but
    the development and establishment of such a procedure is recommended.


    Dinocap is defined B.S. 1831:1969 as "a mixture of dinocap-4 and
    dinocap-6"; it is a mixture of six isomeric dinitro-s-octylphenyl
    crotonates, not merely one of them as previously defined (B.S.
    1831:1965), The commercial "active material" also contains a small
    percentage of unesterified dinitro-s-octylphenols, together with
    mononitrophenols and some 20% of "inactive" ingredients.

    Commercial preparations, both wettable powders and liquid
    formulations, are used throughout the world for the control of powdery
    mildews of apple, pear, peach, apricot, grape, soft fruits, cucurbits,
    rose and other ornamentals. It is also a non-ovicidal acaricide and
    its use for control of powdery mildews also provides control of
    certain mites, notably the fruit tree red spider mite (European red
    mite) as long as spraying is continued. Curative (not eradicant)
    action against powdery mildews is nearly as good as protective action,
    but there is no evidence of systemic activity even within the leaf.

    Solubility in water is low, but persistence on plant surfaces
    (half-life) is very short. Deposits from recommended spray rates
    rarely reach 1 ppm on the day of application, and residues of the
    order of 0.05 ppm are to be expected within 7 days.

    Several colorimetric procedures have been used for dinocap residues,
    but in view of the complex nature of the product, gas chromatographic
    procedures are likely to give much more valuable information.


    The data were insufficient to enable recommendations to be made.


    REQUIRED (before an acceptable daily intake or tolerances can
              be established)

    1. Additional studies with more animals to establish the exact dosage
       of dinocap which does not produce cataracts.

    2. Extension of the chronic toxicity experiment in dogs or other
       non-rodent mammalian species.

    3. Metabolic studies including determination of phenols in the blood.

    4. Information on the compounds included in dinocap and assurance of a
       standardized technical product.

    5. Investigation aimed at clarifying physiological lesions with regard
       to cellular respiratory control.

    6. Reproduction studies in animals.

    7. Information is required on the nature of terminal residues,
       including the identity of the substances giving peaks by the GLC
       method of examination.

    8. Residue data are required from countries other than the U.S.A.


    The development and establishment of a GLC method for the
    determination of residues of the active ingredients.


    Boggs, H. (1966) Gas chromatography of dinitro herbicides. J. Assoc. 
    Offic. Anal. Chem. 49:772-3

    Cervenka, H. and Kay, J.H. (1963) Cataractogenic studies. Unpublished 
    report from Industrial Bio-test Laboratories Inc., to Niagara Chemical
    Division, FMC Corporation. Submitted by Farbwerke Hoechst AG.

    Clifford, D.R., Watkins, D.A.M. and Woodcock, D. (1965) Composition 
    of commercial dinocap preparations. Chemy Ind., pp.1654-5

    Clifford, D.R. and Watkins, D.A.M. (1968) The gas chromatography of
    dinitroalkyl phenols. J. Gas Chromatog., 6:191-2

    Hemker, H.C. (1962) Lipid solubility as a factor influencing the 
    activity of uncoupling phenols. Biochim. Biophys. Acta, 63:46-54

    Kilgore, W.W. and Cheng, K.W. (1963) Extraction and determination of
    Karathane residues in fruits. J. agric. Fd Chem., 11:477-79

    Kirby, A.H.M. and Elvidge, J.A. (1965) Composition of commercial 
    dinocap preparations. Chemy Ind., 2103

    Kirby, A.H.M. and Hunter, L.D. (1965) Identification of 
    dinitro-octylphenols in certain commercial fungicides. Nature,

    Kirby, A.H.M. (1969) Fungicides for deciduous top fruit: a survey in 
    1968. Wd. Rev. Pest Central. 8:45-58

    Larson, P.S., Finnegan, J.K., Smith, R.B. Jr., Haag. H.B., Hennigar,
    G.R. and Patterson, W.M. (1959) Acute and chronic toxicity studies on
    2,4-dinitro-6-(l-methylheptyl) phenyl crotonate (Karathane).
    Arch. int. Pharmacodyn., 119:31-42

    Rohm and Haas. (1969) Karathane: chemical description, registered uses
    (labels), residue studies. Rohm and Haas Company, Philadelphia,
    Penn., U.S.A.

    Rosenthal, I., Gordon, C.F., Stanley, E.L. and Perlman, M.H. 
    (1957) Microdetermination of the fungicide 
    dinitrocapryl-phenylcrotonate in food crops and animal tissues.
    J. Agr. Fd Chem., 5:914-18

    Skerrett, E.J. and Baker, E.A. (1962) The determination of spray
    residues of 'Karathane' 87:228-9

    Swisher, E.M. (1969) Report of a study on cataract formation in ducks
    conducted in 1966 at the Medical College of Virginia. Unpublished 
    information submitted by Rohm and Haas Co.

    Yip, G. and Howard, S.F. (1968) Extraction and clean-up procedure
    for the gas chromatographic determination of four dinitrophenolic
    pesticides. J. Assoc. Offic. Anal, Chem., 51:24-28

    See Also:
       Toxicological Abbreviations
       Dinocap (WHO Pesticide Residues Series 4)
       Dinocap (Pesticide residues in food: 1989 evaluations Part II Toxicology)
       Dinocap (JMPR Evaluations 1998 Part II Toxicological)