Sponsored jointly by FAO and WHO


    The monographs

    Data and recommendations of the joint meeting
    of the FAO Panel of Experts on Pesticide Residues
    in Food and the Environment and the
    WHO Expert Group on Pesticide Residues
    Rome, 24 September - 3 October 1984

    Food and Agriculture Organization of the United Nations
    Rome 1985



         Maleic Hydrazide (MH) was evaluated by the Joint Meeting on
    Pesticide Residues in 1976 and 1977 (FAO/WHO, 1977, 1978) wherein it
    was determined that data submitted were inadequate for the estimation
    of an acceptable daily intake (ADI). At the Joint Meeting in 1980
    (FAO/WHO, 1981) further data on carcinogenicity and mutagenicity were
    evaluated and a temporary ADI of 0-1.0 mg/kg bw was allocated, noting
    the need for further studies on teratogenicity. This temporary ADI was
    for Maleic Hydrazide of 99 percent purity containing less than
    1.5 mg/kg free hydrazine. Additional toxicological data have been
    submitted on the potassium salt of Maleic Hydrazide and are reviewed
    in the following monograph addendum.



    Special Study on Teratogenicity


         Groups of artificially inseminated Dutch Belted rabbits (16 per
    group) were intubated with potassium Maleic Hydrazide at 0, 100, 300
    and 1 000 mg/kg bw on days 6 through 27 of gestation, at a constant
    volume of 5 mg/kg. The does were sacrificed on day 28 and pups
    delivered by caesarean section for external, visceral and skeletal
    examinations. No treatment-induced mortality occurred. One control and
    two low-dose females aborted. The high-dose females exhibited slight
    inhibition of maternal body weight gain, an increase in the incidence
    of alopecia and soft stools. These findings were not evident among
    females in other groups.

         The mean number of viable foetuses, early and later resorptions,
    post-implantation loss, total implantations, corpora lutea, foetal sex
    ratio and mean foetal body weight were comparable to the controls. The
    incidence of external, visceral and skeletal malformations and
    developmental variations were comparable between treated and control
    groups. Potassium Maleic Hydrazide, at 1 000 mg/kg bw did not induce a
    teratogenic response in Dutch Belted rabbits (Aldrige, Schardein &
    Blair, 1983).

    Special Studies on Carcinogenicity


         Maleic Hydrazide (purity 98.5 percent as free acid, containing
    0.6 ppm hydrazine) was administered orally or by subcutaneous (s.c.)
    injection to C57BL/B6 mice from the IARC colony.

         Oral administration: 40 male and 42 female mice were given oral
    doses of 510 mg/kg bw/week of Maleic Hydrazide in olive oil from
    weaning (at age four weeks) for life. A group of 13 male and 13 female
    mice received only olive oil, and 51 males and 49 females formed the
    untreated control group.

         Subcutaneous injection: Maleic Hydrazide suspended in tricaprylin
    was injected s.c. into 163 newborn mice on days 1, 7, 14 and 21 after
    birth at single doses of 5, 10, 20 and 30 mg Maleic Hydrazide per
    mouse. The equivalent amount of solvent was given to a control group
    of 61 newborn mice.

         At 120 weeks all surviving mice were autopsied. Major organs
    as well as those showing gross abnormalities were examined
    histologically. Oral treatment had no effect on growth or survival and
    there were no significant differences in the number of tumour-bearing
    animals. The number of tumours found in the s.c.-treated mice was not
    significantly different from that in the solvent control group.
    However, the corresponding comparison between treated and untreated
    control groups demonstrated a significant increase in liver cell
    tumours in the high dose group. The incidence of other types of
    tumours was similar in MH treated, vehicle control and untreated
    control groups. Considering the potential contribution from free
    hydrazine, the results provide insufficient evidence of
    carcinogenicity of MH to mice (Cabral & Ponomarkov, 1982).

         Groups of Charles River CD-1 mice (50/sex/group) were fed diets
    containing potassium Maleic Hydrazide (purity 97 percent Maleic
    Hydrazide and 1.63 ppm hydrazine), at concentrations yielding 0,
    1 000, 3 200, and 10 000 ppm Maleic Hydrazide for 98 weeks. The
    control group was offered the basal diet mixed with an appropriate
    amount of potassium buffer (to equal the concentration of potassium in
    the high-dose test diet).

         Observations were made routinely for signs of toxicity,
    moribundity, mortality, body weight change and food consumption. No
    compound-related changes in appearance or behaviour, mortality, body
    weight or food consumption were noted. There were no macroscopic or
    microscopic lesions which could be attributed to the compound (Jessup,


         The 1980 JMPR considered carcinogenicity and mutagenicity data
    and allocated a temporary ADI, since further studies on teratogenicity
    were required. An acute toxicity study of the free acid and of the
    sodium or potassium salt were similar. New data on the potassium salt
    have now been presented and reviewed.

         Potassium Maleic Hydrazide, administered orally, was not
    teratogenic in rabbits at 1 000 mg/kg/day. A 98-week study of the
    potassium salt (97 percent pure; 1.6 ppm hydrazine) in CD-1 mice at
    doses up to 10 000 ppm was not oncogenic. A 120-week study of free
    Maleic Hydrazide (98.5 percent pure; 0.6 ppm hydrazine) administered
    orally to C57BL/B6 mice at 510 mg/kg/week showed no increased
    tumorigenicity; a similar study in which the Maleic Hydrazide was
    administered subcutaneously was considered to be negative. The free
    hydrazide and the potassium salt were evaluated and the results were
    considered applicable to the sodium salt, 99.9 percent pure and with
    not more than 1 ppm of hydrazine.

    Level Causing no Toxicological Effect

         Rat: 20 000 ppm equivalent to 1 000 mg/kg bw.

         Dog: 20 000 ppm equivalent to 500 mg/kg/bw.

    Estimate of Acceptable Daily Intake for Humans

         0 - 5.0 mg/kg bw (sodium or potassium salt, 99.9 percent pure
         with less than 1 ppm hydrazine).



    Observations in humans.


    Aldrige, B.S., Schardein, J.L. and Blair, M. Teratology study in
    1983      rabbits with potassium salt of Maleic Hydrazide.
              International Research and Development Corporation,
              Mattawan, Michigan. Submitted by Uniroyal Inc., Bethany, USA
              to WHO. (Unpublished)

    Cabral, J.R.P. and Ponomarkov, V. Carcinogenicity study of the
    1982      pesticide Maleic Hydrazide. Toxicology, 24: 169-173.
              Submitted by Uniroyal Inc., Bethany, USA, to WHO.

    Jessup, C. Lifetime oncogenicity study of potassium Maleic Hydrazide
    1981      in mice. International Research and Development Corporation.
              Submitted by Uniroyal Inc., Bethany, USA, to WHO.

    See Also:
       Toxicological Abbreviations
       Maleic hydrazide (Pesticide residues in food: 1976 evaluations)
       Maleic hydrazide (Pesticide residues in food: 1977 evaluations)
       Maleic hydrazide (Pesticide residues in food: 1980 evaluations)
       Maleic hydrazide (Pesticide residues in food: 1984 evaluations)
       Maleic hydrazide (Pesticide residues in food: 1996 evaluations Part II Toxicological)
       Maleic Hydrazide (IARC Summary & Evaluation, Volume 4, 1974)