FAO, PL:CP/15
    WHO/Food Add./67.32


    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party and the WHO Expert Committee on
    Pesticide Residues, which met in Geneva, 14-21 November 1966.1

    1 Report of a Joint Meeting of the FAO Working Party and the WHO
    Expert Committee on Pesticide Residues, FAO Agricultural Studies, in
    press; Wld Hlth Org. techn. Rep. Ser., 1967, in press


    (Addendum to 1965 Monograph)

    This pesticide was evaluated by the Joint Meeting of the FAO committee
    on Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues in its 1965 report (FAO Meeting Report No. PL/1965/10/1;
    WHO/Food Add./27.65). Since its publication some new experimental work
    has been reported on the compound. This new work in presented and
    discussed in the following monograph addendum.


    Biochemical aspects

    The alpha- and beta-isomer of desethylphosphamidon was isolated from
    bean plants (Vicia faba) in the ratio 1:2 (CIBA, 1964a).

    Acute toxicity

    In acute oral toxicity studies in male albino rats, the toxicity of
    phosphamidon was not potentiated when administered in combination with
    azinphos-methyl, carbaryl, carbophenothion, demeton, diazinon,
    dioxathion, EPN, ethion, malathion, methyl parathion, parathion,
    mevinphos, naled and schradan (Kay & Calandra, 1961).

    The oral LD50 in rats of desethylphosphamidon is: for beta-isomer,
    8.5 mg/kg; for alpha-isomer, 250 mg/kg body-weight (CIBA, 1964a).

    The oral LD50 of desmethylphosphamidon in male rats is 2500 + 420
    mg/kg. The oral LD50 of gamma-chlorophosphamidon is 126 + 6.8
    mg/kg in rats and 117 + 25 mg/kg in mice (CIBA, 1964b; Cervenka et
    al., 1964).

    In man a fatal case of oral poisoning and a probable case of mild
    poisoning is described. In the fatal case, post-mortem examination
    revealed a fatty liver, congestion of internal organs and brain damage
    of the type seen in anoxia. The clinical picture in both cases
    resembled that seen in poisoning with other organophosphates (Gitelson
    at al., 1965).

    Short-term studies

    Rat. Groups of 5 male and 5 female rats were exposed to inhalation
    of phosphamidon at concentrations of 0.05 and 0.5 mg/m3 or 4 hours a
    day for 6 weeks. A temporary decrease of cholinesterase activity in
    erythrocytes and in plasma was compensated after 2 weeks (CIBA, 1965).

    Groups of 50 male and 50 female rats were fed diets containing 0, 1,
    2, 3, 5 and 7.5 ppm phosphamidon for 12 weeks. The cholinesterase
    activity was measured in plasma, erythrocytes and brain. No
    significant inhibition of cholinesterase was found at the 2.0 ppm
    dietary level. (Kay & Calandra, 1961).

    Groups of 15 male and 15 female rats were fed phosphamidon in the diet
    for 13 months. The doses were 0, 0.1, 0.5, 1.25 and 5.0 mg/kg
    body-weight/day and were periodically compensated for change in
    body-weight and food consumption. A significant decrease of growth and
    depressed food intake was recorded only in the males fed 1.25 and 5.0
    mg/kg/day. The other 2 groups (0.1 and 0.5 mg/kg/day) were comparable
    with the control group. No difference in mortality, tumour incidence,
    peripheral blood picture, urine, and gross and microscopic appearance
    of tissues was seen between the groups. (Kohn et al., 1964).

    A 3-generation reproduction study was performed in rats. Three groups
    of 8 male and 16 female rats were fed 1.0, 7.5 and 15 ppm of a
    phosphamidon mixture (75 per cent phosphamidon, 22 per cent
    desethylphosphamidon, 3 per cent N,N-diethyl-a-chloroacetoacetamide)
    in the diet. Two other groups served as controls. The rats were mated
    at 74 and 105 days. The second litter served to produce 2 F2
    generations. In all three generations, body weight and weight gain
    were similar to those of the controls. No abnormal reaction was noted,
    and none of the deaths in the course of the experiment was attributed
    to the substance tested. Mating indices, fertility indices, incidence
    of pregnancy, parturition and gestation times, body-weight and
    histology were essentially comparable with control animals. Lactation
    indices were slightly lower in the P and F2 groups fed the highest
    dose (15 ppm). Litter survival was reduced at 15 ppm (Kennedy et al.,

    Dog. Groups of 3 male and 3 female beagles were given phosphamidon 
    orally in capsules at dose levels of 0, 0.05, 0.1, 0.5, 1.0, 2.0, 3.0, 
    4.0 and 5.0 mg/kg body-weight/day. The doses of 0.05-1 mg/kg/day were
    administered for 90 days. Plasma and erythrocyte cholinesterase
    activity was determined by an electrometric method. At a dose of 1
    mg/kg/day and higher significant inhibition of cholinesterase was
    caused in 9-16 days. No depression of cholinesterase was observed at
    dose levels of 0.5 mg/kg/day or lower within 90 days. (Kay & Calandra,

    Four groups of dogs (2 males and 2 females in each group) were given
    phosphamidon orally in gelatin capsules at dose levels of 0, 0.1, 2.5
    and 5.0 mg/kg body-weight/day for 2 years. Body-weight and food
    consumption, behavioural reactions and mortality were followed up, and
    haematologic studies, blood urea nitrogen determination, urine
    analyses including examinations for albumin, glucose and microscopic
    elements and liver function tests were conducted. The test was
    concluded by the determination of organ-weights together with their

    histopathologic examination. The dogs in the highest dose group (5
    mg/kg/day) perished in the course of the test, as a consequence of
    phosphamidon ingestion. In the group receiving a dose of 2.5
    mg/kg/day, slight muscular tremors were observed in females in the
    first year of the test, and in the second year slight muscular tremors
    appeared also in males, together with a slight salivation. At the
    highest dose level, alterations in organ weights and ratios were
    found. However, histologic examination revealed no alterations which
    could have been caused by Phosphamidon. No degenerative changes were
    noted in the myelin sheath. There were no significant effects detected
    at a dose level of 0.1 mg/kg/day. (Cervenka et al., 1964).


    In a 12-week experiment using rats, 2 ppm in the diet did not cause
    any significant decrease of cholinesterase in the plasma, erythrocytes
    and brain; in a 90-day test using dogs, 0.5 mg/kg/day did not result
    in any inhibition in plasma and erythrocytes.

    A mixture of phosphamidon and 2 of its metabolites had no effect on
    the reproductive capacity of rats at a dietary level of 7.5 ppm,
    equivalent to 0.37 mg/kg/day.

    Biochemical and metabolic fate studies in man exposed to this compound
    by different routes, reproduction studies in at least one more species
    other than the rat, and short-term toxicity studies of metabolites and
    break-down products of phosphamidon are desirable.


    Level causing no toxicological effect

    Rat ppm, equ. 0.1 mg/kg/day

    Dog 0.5 mg/kg/day

    Estimate of acceptable daily intake for man

    0-0.001 mg/kg body-weight


    Cervenka, H., Kay, J. H. & Calandra, J. C. (1964) Unpublished report
    submitted by CIBA.

    CIBA (1964a) Unpublished report by R. Anliker & E. Kühl.

    CIBA (1964b) Unpublished report by J. Tripod & R. Anliker

    CIBA (1965) Unpublished report by Bericht von A. Hoffman & K. H.
    Bergert (Batelle-Institut E.V.-Frankfurt am Main).

    Gitelson, S., Davidson, J. T. & Werczberger, A. (1965) Brit. J.
    industr. Med., 22, 236

    Kay, J. H. & Calandra, J. C. (1964) Unpublished report submitted by

    Kennedy, G., Fancher, O. E. & Calandra, J. C. (1966) Unpublished
    report submitted by CIBA

    Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964) Unpublished report
    submitted by CIBA

    Palazzolo, R. J., Kay, J. H. & Calandra, J. C. (1964) Unpublished
    report submitted by CIBA

    See Also:
       Toxicological Abbreviations
       Phosphamidon (ICSC)
       Phosphamidon (PIM 454)
       Phosphamidon (FAO Meeting Report PL/1965/10/1)
       Phosphamidon (FAO/PL:1968/M/9/1)
       Phosphamidon (FAO/PL:1969/M/17/1)
       Phosphamidon (WHO Pesticide Residues Series 2)
       Phosphamidon (WHO Pesticide Residues Series 4)
       Phosphamidon (Pesticide residues in food: 1982 evaluations)
       Phosphamidon (Pesticide residues in food: 1986 evaluations Part II Toxicology)