Sponsored jointly by FAO and WHO


    Food and Agriculture Organization of the United Nations


    pesticide residues in food:
    1981 evaluations

     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

    Geneva, 23 November-2 December 1981

    Rome 1982



         Edifenphos was evaluated by the 1976 and 1979 Joint Meetings.* A
    temporary ADI was allocated in 1976 and extended in 1979. Temporary
    MRLs recommended by the 1976 Meeting were increased in 1979.

         Further studies were required on hepatic involvement observed in
    several animal species and the results of a carcinogenicity study was
    also required. Information was also desired on humans relative to
    occupational exposure and on residues of edifenphos and its p-hydroxy
    metabolite in food animals arising from the use of rice straw and bran
    in animal feeds.

         Data were received on the carcinogenicity study in mice, as well
    as additional data on residue levels in rice and in animal products,
    and are evaluated in this monograph addendum.



    Rat and mouse - distribution and excretion

         Comparative studies on the metabolic fate of 35S-labelled
    edifenphos in rats and mice have been reported (Ueyama  et al. 1978).
    Dose levels were 10 mg/kg in female rats and 20 mg/kg in mice and male
    rats. Edifenphos was rapidly absorbed and metabolized by both species
    following oral administration. The major metabolic pathway was the
    cleavage of the P-S bond, accompanied by the release of benzene thiol
    (Fukami  et al. 1969; Ueyama and Takase 1976, Ueyama  et al 1978).
    Only 15 to 30% of the administered radioactivity was detected in
    digestive organs 6 h after administration. At 72 h, only a trace
    amount of radioactivity was found over the whole body of the animals.
    The major part of the radioactivity was excreted in urine (75-90%) and
    faeces (5-20%). The main metabolite in the rat was ethyl hydrogen-S-
    phenyl phosphorothiolate (54-59%) and that in mice was dihydrogen-S-
    phenyl. Diphenyl disulphide was found in faeces in both species, but
    metabolites such methyl phenyl sulphide and its derivatives were


    *  See Annex II for FAO and WHO documentation.

    Poultry - distribution and excretion

         Five groups of 4 chickens each were fed Hinosan at levels of 0,
    1.5, 4.5, 15 and 45 ppm in the diet for 28 days. Only slight weight
    losses were noted in the two highest feeding levels. Only two giblet
    samples from the highest feeding level (45.0 ppm) showed any
    measurable residues (0.08 mg/kg). All other tissue samples had gross
    residues <0.01 mg/kg; 26-and 28-day egg samples from all the feeding
    studies indicated less than 0.001 mg/kg residue levels. No adverse
    effects could be detected on egg production for any of the treated
    groups compared to the control birds (Morris 1976).

    In vitro hepatic subcellular metabolism

         The metabolism of 35S-edifenphos by hepatic subcellular
    fractions of five mammalian species was studied  in vitro in order to
    investigate the effect of inhibitors against drug metabolism enzymes
    and to observe metabolism and degradation in hepatic microsomes that
    were induced by administration with phenobarbital. Additionally,
    animal species-related differences of metabolic patterns, degradation
    and metabolism of edifenphos in five different species of mammalian
    hepatic sub cellular fractions, including humans was examined by the
    comparative method (Ueyama  et al 1976).

         The salient results were as follows: (a) enzymatic
    degradation of edifenphos occurred in both microsomal and soluble
    (105,000 g-supernatant) fractions; (b) degradation of edifenphos by
    microsomes was accelerated by addition of NADPH and inhibited by SKF
    525-A or piperonyl butoxide; (c) 35S-edifenphos was more rapidly
    metabolized by rat hepatic microsomes that were previously induced by
    administration with phenobarbital; (d) the above mentioned results
    suggested that a part of enzymatic degradation of edifenphos was
    accomplished by drug metabolizing enzymes; (e) the degradation of
    35S-edifenphos by the soluble fraction was not increased by addition
    of glutathione; (f) the difference of metabolic patterns of edifenphos
    by hepatic microsomes of five mammalian species implied that the
    metabolic activity for edifenphos was as follows: guinea pig > rabbit
    > mouse > human > rat; (g) in the water soluble fractions of these
    mammalian microsomes, ethyl hydrogen S-phenyl phosphorothiolate was
    found for human and mouse, and dihydrogen S-phenyl phosphorothiolate
    was also found for mouse and rabbit.

    Antiesterase activity in vitro and in vivo

         The  in vitro anticholinesterase action of Hinosan was measured
    by addition of the compound at several concentrations to homogenized
    rat brain in the cholinesterase system. Hinosan was a potent direct
    inhibitor of cholinesterase  in vitro producing 50% inhibition of
    cholinesterase at a concentration of 1.05 × 10-6M (Chen  et al 

         The effect of Hinosan on cholinesterase activity  in vivo was
    studied by giving 5/8 of the acute i.p. LD50 to male and female rats.
    Because of the sex difference in susceptibility, equitoxic doses
    amount to 16 mg/kg for females and 41 mg/kg for males. Hinosan is a
    very effective inhibitor  in vivo, which gains access to and inhibits
    the cholinesterase activity of both the central nervous system and
    peripheral tissues and hence produces a generalized cholinergic
    action. The rapid onset of action and the extremely slow reversal of
    its inhibitory action on cholinesterase are two distinguishing
    features of this compound (Chen  et al. 1972).

    Aliesterase inhibition

         Data obtained by feeding Holtzman rats various levels of Hinosan
    in the diet (0.75, 5, 12.5, 25, 50, 75 and 100 ppm) for 1 week
    demonstrated that Hinosan was a strong inhibitor of aliesterases. The
    inhibitory effect of Hinosan on the enzymes that were examined was in
    the order of tributyrinase (the most susceptible), diethylsuccinase
    (the next most sensitive) and cholinesterase (the most resistant)
    (Chen  et al 1972). (A similar order of susceptibility was obtained
    with several insecticidal organophosphorus compounds, Su  et al 1971)

         The dietary levels producing 50% inhibition of enzyme activity
    were obtained by plotting percent inhibition of the enzyme against the
    logarithm of the dietary levels. From this plot of data, 50%
    inhibition of hydrolysis of diethylsuccinate by liver and serum were
    found to occur at the levels of 11.5 and 7.4 ppm respectively for
    female rats, and 18.4 and 10.2 ppm respectively for male rats. The
    levels that produced 50% inhibition of tributyrin hydrolysis by liver
    and serum were found to be 5.4 and 9.5 ppm respectively for female
    rats, and 4.9 and 8.4 ppm respectively for male rats.

         In a few experiments, Hinosan was fed at a dietary level of 5 ppm
    to young rats (28 days old) for 1 week. There was 60% inhibition of
    diethylsuccinate hydrolysis and 70% inhibition of the liver
    tributyrinase in young rats as compared with 50% and 50% of the
    diethylsuccinase and tributyrinase, respectively, of adult rat liver
    at this same dietary level. However, the greater enzyme induction in
    the livers of young rats might be due to higher dietary intake,
    relative to body weight, than in adults (Chen  et al. 1972).

    Effects of pre-treatment with microsomal enzyme inducers

         Pre-treatment of animals with microsomal enzyme inducers has
    been shown to protect against the toxicity of various organophosphorus
    compounds. Pre-treatment of rats with phenobarbital, DDT,
    3-methylcholanthrene or testosterone markedly reduced the
    anticholinesterase action of Hinosan (Chen  et al 1972). The amount
    of inhibition of cholinesterase of brain and submaxillary gland of

    female rats was somewhat less than in male rats after treatment with
    the inducing agents. Phenobarbital and DDT were more effective in
    protecting against Hinosan toxicity than 3-methylcholanthrene and

    Pesticide potentiation

         To ascertain the degree of potentiation of malathion toxicity by
    Hinosan, groups each containing 4 Holtzman rats were given a sublethal
    dose of malathion (400 mg/kg)i.p. after they had been fed for 1 week
    with various dietary levels of Hinosan. After feeding dietary levels
    of 0, 5 and 25 ppm, the mortality resulting from 400 mg/kg of
    malathion was 0, 25 and 100% respectively. Thus, Hinosan was shown
    to increase markedly the susceptibility of rats to malathion (Chen
     et al 1972).


    Acute toxicity

         Edifenphos is intermediate in toxicity among the organophosphorus
    insecticides. A sex difference in the acute toxicity (oral and i.p.)
    to rats was observed, with male rats exhibiting greater resistance
    than females (see Table 1).

         In acute toxicity studies of orally administered edifenphos
    conducted on buffalo calves, it was shown that doses of 30, 45 and
    60 mg/kg resulted in maximal inhibition of blood cholinesterase to the
    extent of 59.3, 71.4 and 73.9% respectively after 12 to 24h of
    edifenphos administration (Malik  et al 1978a). The onset of severe
    toxic symptoms with higher doses (45 and 60 mg/kg) correlated well
    with the maximum inhibition of cholinesterase activity. The inhibited
    enzyme recovered slowly after 4 weeks, returning to 86.5 and 81.6% of
    the pre-treatment level with 30 and 45 mg/kg of edifenphos
    respectively. Doses of 45 and 60 mg/kg increased the serum glutamic-
    pyruvic transaminase levels (SGPT) while elevation in levels of serum
    glutamic-oxalacetic transaminase (SGOT) was found with all the doses,
    suggesting that edifenphos can induce internal tissue damage. Doses of
    30 and 45 mg/kg resulted in a gradual rise of the SGOT level, which
    approached its peak at the second week and began recovering
    afterwards, but remained elevated 4 weeks after administration of
    edifenphos. No change in serum alkaline phosphatase activity was
    observed (Malik  et al 1978a).

    TABLE 1.  Acute toxicity of edifenphos in four animal species

    Species        Sex    Route   LD50(mg/kg)    Reference

    Rat            M      oral    340            Martin 1972

                   M      oral    212            Bayer 1976

                   F      oral    150            Martin 1972

                   F      oral    100            Bayer 1976

                   M      i.p.    66.5 ± 7.7     Chen et al 1972

                   F      i.p.    25.5 ± 0.8     ibid.

                          i.p.    26             Melnikov 1971

    Mouse          M      oral    214            Bayer 1976

                   F      oral    218            Martin 1972

    Guinea pig            oral    3501           Bayer 1976;
                                                 Wisswesser 1976

    Rabbit                oral    3502           ibid; ibid.

    1  Technical product in ethanol/propylene glycol
    2  Technical product in Lutrol (polyethylene glycol 400).

    Short-term studies


         Edifenphos was administered orally in daily doses of 4 and
    8 mg/kg bw for 28 days to male buffalo calves  (Bubalus bubalis). The
    lower dose did not produce any apparent toxic manifestation. With the
    higher dose all the animals died within 13 to 17 days. A gradual and
    significant inhibition of blood cholinesterase was noted with both the
    doses (p <0.01). The extent of inhibition of blood cholinesterase was
    not related to the severity of toxicosis. No significant change in
    levels of blood glucose, blood lactic acid, serum total cholesterol
    and serum creatinine was observed after the administration of the drug
    (Malik  et al 1978a, b).

         Edifenphos given at 4 mg/kg/day did not produce toxic symptoms
    until 28 days had passed, while doses of 8 mg/kg brought on toxic
    symptoms between days 11 and 14. The toxic symptoms included anorexia,
    depression, increased salivation, lachrymation and diarrhoea.
    Diarrhoea was more pronounced in the later stages and was followed by
    weakness of the hind legs and paralysis. Animals receiving 8 mg/kg of
    edifenphos showed maximum increases in SGOT levels of 141.73 and
    167.77% on day 28 and 12 after the start of the study. The SGOT
    elevation was both dose and time dependent. SGPT levels were
    increased, but not significantly. No significant changes were noted in
    the serum alkaline phosphatase activity throughout the period (Malik
     et al 1978c).


         Groups of male and female rats were treated daily for 28 days
    with the following dosage regimens: (a) Hinosan, 20 mg/kg; (b)
    Hinosan/thiophenol (20:1), 5 and 20 mg/kg and (c) thiophenol, 1 and
    10 mg/kg.

         Hinosan 20 mg/kg bw as well as Hinosan/thiophenol (20:1), 5 and
    20 mg/kg caused a reduction in cholinesterase activity. Doses of 5 mg
    of Hinosan/thiophenol 20:1 should be considered a no-effect dosage for
    both plasma cholinesterease as well as erythrocyte cholinesterase.

         The liver metabolized all three of the above samples similarly,
    with no apparent differences. The effects found were: (a) increases in
    liver enzymes and liver weight (the effect was more pronounced in male
    than in female rats); (b) in the investigated dose levels no liver
    damage could be observed. All 3 samples induced definite kidney
    damage. In male rats, no minimal safe dose could be established for
    Hinosan or Hinosan/thiophenol (20:1 mixture) and thiophenol. A
    borderline dose for male rats with thiophenol is 1 mg/kg bw. Female
    rats tolerated 1 mg/kg bw thiophenol during the 28-day treatment
    without any damage. As a borderline dose for female rats, the
    following were considered: Hinosan/thiophenol (20:1 mixture)-5 mg/kg
    bw; thiophenol-10 mg/kg bw. The results indicate that the 3 test
    samples using the above mentioned dosages could induce kidney damage
    and somatic changes in the liver (Thyssen and Schilde 1978).

    Long-term studies

         Groups of 40 male and 40 female NMRI mice were maintained for 108
    weeks on a diet containing SRA 7847 (supplied as a 50% premix) at
    dietary concentrations of 2, 15 and 100 ppm, respectively. The control
    group also consisted of 40 males and 40 females. Subgroups consisting
    of 20 male and 20 female mice each were additionally formed for
    haematological and clinical chemical tests. Physical appearance,
    behavioural patterns and survival rate of both males and females were
    not affected by administration of SRA 7847 even at the highest dietary

    level. No differences were seen between treated mice and controls with
    respect to growth rate and food consumption. The haematological and
    urinalysis data recorded for the treated groups and the controls were
    within the physiological range.

         Glutamate-pyruvate transaminase (GPT) and alkaline phosphatase
    (AP) activities did not show any variations from normal in any of the
    groups. Blood plasma and erythrocyte cholinesterase activities in mice
    of the 15 and 100 ppm groups showed nonphysiological depression (more
    than 20%).

         Statistically significantly increased thyroid weights (100 ppm
    group) and statistically significantly increased brain weights (15 and
    100 ppm groups) were recorded, but only in male mice. A statistically
    significantly lower heart weight was additionally noted in the 100 ppm

         The number of tumours noted in all groups corresponded to the
    known spontaneous tumour rate for the animal strain used in the study.
    There was no indication of a dose/incidence relationship. Under the
    described experimental conditions SRA 7847 was not carcinogenic.
    Although benign pituitary tumours were observed in males of the 2 ppm
    group, the incidence was comparable to that in the control group.

         Taking account of the cholinesterase activities, the no-effect
    dose in the chosen experimental design was stated to be 2 ppm SRA 7847
    (Mohr 1980).

    Special studies on acute oral toxicity of Hinosan metabolites

         Four metabolites, e.g., S-36 [O-ethyl-S-phenyl-S-
    (4-hydroxyphenyl)-phosphorodithioate]; S-37 [S,S-diphenyl
    phosphorodithioate]; S-39 [O-ethyl-S-phenyl-phosphorothioate] and
    S-64 [O-ethyl-S-phenyl-S-(3-hydroxyphenyl)-phosphorodithioate] were
    administered in a diluent of Lutrol (polyethylene glycol 400) to
    Sprague-Dawley rats fasted for 18 to 20 h. Dose volumes were given at
    0.5% body weight. Lethargy, diarrhoea and ataxia were symptoms for
    S-39 treated animals. S-64 treated animals showed symptoms of
    lethargy, diarrhoea, muscular fasciculations, salivation and
    lachrymation. Occurrence and severity of symptoms were dose related.
    Although minor lung lesions occurred in a few animals on each
    compound, these lesions did not appear to be compound-induced. No
    other lesions were noted (Lamb and Matzkanin 1976). Table 2
    illustrates the acute toxicity of the 4 metabolites in terms of the
    structures of S-36, S-37, S-39 and S-64; doses administered to rats of
    both sexes; observations (deaths) symptoms/number of animals exposed;
    time of beginning and end of symptoms, time and death and LD50's.

        TABLE 2.  Acute oral toxicity of Hinosan metabolites to rats1

                                                                Observations    Symptoms               Time of
                                                      Dose      Deaths/         Begin       End        Death
    Sample                        Weight (g)   Sex              Symptoms/No.    within      within     within     LD50
                                                      (mg/kg)   Exposed         (h)         (h)        (h)        (mg Samples/kg)

    S36: O-ethyl-S-phenyl-S-      270-320      M        500     0/0/5           ---         ---        ---        >500


                                  178-240      F        500     0/0/5           ---         ---        ---
                                                       1000     0/0/5           ---         ---        ---        >1000

    S37: S,S-diphenyl.            222-377      M        500     0/0/5           ---         ---        ---
         phosphorodithioate                            1000     0/5/5           1.5         24         ---        >1000; <2000
                                                       2000     4/5/5           0.5         48         16


                                  180-253      F        500     0/0/5           ---         ---        ---
                                                       1000     1/5/5           1           24         1.5        >1000; <2000
                                                       2000     5/5/5           0.5         ---        2

    TABLE 2.  (con't)

                                                                Observations    Symptoms               Time of
                                                      Dose      Deaths/         Begin       End        Death
    Sample                        Weight (g)   Sex              Symptoms/No.    within      within     within     LD50
                                                      (mg/kg)   Exposed         (h)         (h)        (h)        (mg Samples/kg)

    S39: O-ethyl-S-phenyl-        230-364      M        500     0/5/5           1.5         24         ---
         phosphorothioate                              1000     1/5/5           1.5         24         2          >1000; <2000
                                                       2000     4/5/5           0.5         48         2.5


                                  180-242      F        250     0/0/5           ---         ---        ---
                                                        500     2/5/5           1.5         24         2.5        616 (397 to 954)2
                                                       1000     4/5/5           1           24         3
                                                       2000     5/5/5           0.5         ---        1

    S64: O-ethyl-S-phenyl-S-      156-266      M        500     0/5/5           2           24         ---
         (3-hydroxyphenyl)-                            1000     2/5/5           1           72         16         approx. 1000


                                  168-198      F        250     0/0/5           ---         ---        ---
                                                        500     2/5/5           2           48         3          approx. 500
                                                       1000     4/5/5           2           7 days     24

    1  From Lamb and Matzkanin 1976;  2  95% confidence limits.
        Special studies on mutagenicity

         Edifenphos, tested at a concentration of 1 mg/ml in DMSO with
    screening methods consisting of the rec-assay procedure (a sensitivity
    test utilizing H17Rec+ and M45Rec- strains of  Bacillus subtilis)
    as well as the reversion assays on plates utilizing auxotrophic
    strains of  Escherichia coli (WP 2) and  Salmonella typhimurium
    strains TA1535 (reversible by base change type mutagens) and TA 1536,
    1537 and 1538 (reversible by frameshift mutagens), was found to be
    nonmutagenic (Shirasu  et al 1976).

         In the dominant lethal test, no mutagenic effects were noted when
    edifenphos was administered to male mice in an acute oral dose of
    100 mg/kg bw (Herbold 1980a).

         A micronucleus test was performed with edifenphos according to
    the procedure of Schmid. The doses of edifenphos were 2 × 40 mg/kg and
    2 × 80 mg/kg bw and for the positive control (Endoxan) 2 × 660 mg/kg
    orally administered to mice. No mutagenic effects were noted for
    edifenphos at the doses tested (Herbold 1980b).




         Supervised trials were carried out at 3 locations in the USA in
    1976. Hinosan 4.5 EC was applied one to four times at rates of 0.63
    and 1.26 kg a.i./ha, which are in the recommended dose rate interval
    (0.3 to 0.8 kg a.i./ha) or somewhat higher (Mobay 1976). Hinosan DF
    and EC formulations were used at supervised trials in Japan. In 7
    experiments edifenphos was applied three to four times at rates of
    0.45 to 1 kg/ha (Nihon 1979).

         Samples were taken 21 to 30 days after the last treatment, with
    two exceptions when samples were taken 60 days after the last
    application. Rice in husk, hulled rice, polished rice, rice bran,
    straw and hulls were analysed separately in most of the experiments.
    The limits of determination of analytical methods applied were
    0.005 mg/kg in the Japanese experiments and 0.02 mg/kg in the USA

         The intact edifenphos was detected alone in all of the
    experiments. The results of these experiments, summarized in Table 3,
    showed no difference in the distribution of residues in samples taken
    21 to 31 days after the last treatment, independently of the number of
    applications or dose rates. Measurable residue (0.005 to 0.16 mg/kg)
    was detected in polished rice and the residues in rice in husk were
    significantly higher than those found in previous experiments
    evaluated by the 1976 Joint Meeting.

        TABLE 3.  Residues of edifenphos in rice

    Sample              Dosage                            Number of samples in residue ranges (mg/kg)
                        (a.i. kg/ha)   <0.02     <0.05     <0.1      <0.2      <0.5      <1        <2        <5        <10

    Rice in husk        0.45-0.63        1         1         1                   1        1         1
                        1-1.26           2                                                          2

    Rice (bulled)       0.45-0.63        2         1         3
                        1-1.26           7         1         1         1

    Rice (polished)     0.45-0.63        9
                        1-1.26          10

    Rice bran           0.45-0.63        4                   1                   4        1
                        1-1.26           3                   1         2         2        1

    Straw               0.45-0.63        2                                                                    3
                        1-1.26           1                   2                            2         1         1

    Hulls               0.45-0.63                            1         2         2                  2         1
                        1-1.26                               2         1         1                  2         2         1
             Soil samples, taken from depths of 0 to 15 and 15 to 30 cm
    in the rice field at the same time as the rice samples, contained no
    detectable residue (<0.01 mg/kg) in all cases.


    In animals

         Lactating dairy cows were fed, via bolus, with technical
    edifenphos twice daily in equal portions for 28 consecutive days.
    Dosages administered to animals were 0.9 mg/kg and 5.7 mg/kg on a dry
    feed basis, which were approximately equivalent to 0.03 and 0.17 mg/kg
    bw/day respectively.

         Residues in milk samples taken 26 to 28 days after the first
    treatment were below the limit of determination (<0.001 mg/kg) in all

         In another experiment, edifenphos was mixed in alfalfa meal and
    pressed into pellets to provide 5, 15 and 50 mg/kg concentrations in
    the feed. The pellets were fed to lactating cows for 28 days (Mobay
    1976b). The animals were sacrificed 28 days after first application
    and brain, heart, liver, kidney, muscle and fat samples were analysed
    for edifenphos. No residue (<0.01 mg/kg) was detectable in any
    of the samples with the exception of liver, in which 0.02, 0.07 and
    0.13 mg/kg edifenphos was found at the 50 mg/kg feeding level.

         Laying hens kept on a diet containing 1.5, 4.5, 15 and 45 mg/kg
    technical edifenphos were sacrificed 28 days after consecutive
    feeding. Eggs were collected on the 26th and 28th days. Giblet,
    muscle, fat, skin and eggs were sampled and analysed for edifenphos.  
    Two of the three giblet samples contained 0.08 mg/kg residue, but
    none was detected in any tissues or in eggs above the limit of
    determination, i.e. 0.01 mg/kg in tissues and 0.001 mg/kg in eggs.



         Satisfactory data were received detailing the results, required
    by the 1979 JMPR, of the carcinogenicity study in mice. These
    alleviated concern with respect to this aspect of toxicology.

         The concerns regarding effects on the liver in experimental
    animals previously reported were reconsidered. They were deemed to be
    of doubtful significance since they appeared to result from liver
    microsomal enzyme induction. Hence an ADI was allocated.

         Results of supervised trials, carried out in the USA and Japan,
    indicated no difference in the distribution or levels of residues in

    samples taken 21 to 31 days post-treatment, independently of the
    number of applications or dose rates. These results support the
    changes proposed by the 1979 JMPR for rice, in husk, rice, hulled and
    rice, polished.

         The residue of edifenphos was below the limit of determination in
    various tissues (<0.01 mg/kg), milk or eggs (<0.001 mg/kg) of
    lactating dairy cows and laying hens fed with feed containing
    edifenphos up to 15 mg/kg.

         The liver of cattle and poultry giblets were the only samples
    containing detectable residues up to 0.13 and 0.08 mg/kg at a diet of
    50 and 45 mg edifenphos per kg, respectively, for 28 days. The results
    of feeding studies indicate that no detectable residue can be expected
    in animal products deriving from animals fed with straw and bran of
    rice treated with edifenphos according to good agriculture practice.

    Level causing no toxicological effect

         Mouse : 10 ppm in the diet equivalent to 1.53 mg/kg bw/day

         Rat : 5 ppm in the diet equivalent to 0.25 mg/kg bw/day

         Dog : 20 ppm in the diet equivalent to 0.58 mg/kg bw/day

    Estimate of acceptable daily intake for man

         0 - 0.003 mg/kg bw


         On the basis of the new data the Meeting recommends the following
    additional temporary maximum residue limits. The levels refer to the
    parent compound only.

    Commodity                          MRL (mg/kg)

    Rice bran                          1
    Milk                               0.01 *
    Carcass meat of cattle             0.02 *
    Cattle meat by-product             0.02 *
    Meat of chicken                    0.02 *
    Chicken by-products                0.02 *
    Eggs                               0.01 *

    *  Limit of determination.


    Chen, T.S., Kinoshita, F.K. and DuBois, K.P. Acute toxicity and
    1972      antiesterase action of O-ethyl-S,S-diphenyl
              phosphorodithioate (Hinosan). Toxicology and Applied
              Pharmacology, 23:529-527

    Fukami, J., Shisido, T. and Fukunaga, F. Abstracts of papers. Annual
    1969      Meeting of Agricultural Chemical Society, Tokyo, Japan, p.

    Herbold, B. SRA 7847 - Edifenphos. Hinosan-Wirkstoff Dominant-Lethal
    1980a     Test an der Männ-lichen Maus zur Prüfung auf mutagene
              Wirkung, 26. November, Bericht Nr.9575, Bayer AG, Institut
              für Toxikologie. Report submitted by Bayer AG to WHO.

    1980b     SRA 7847 - Edifenphos - Hinosan-Wirkstoff Mikronucleus-Test
              an der Maus zur Prüfung auf mutagene Wirkung, 26. November,
              Bericht Nr. 9576, Bayer AG, Institut für Toxikologie. Report
              submitted by Bayer AG to WHO. (Unpublished)

    Lamb, D.W. and Matzkanin, C.W. The acute oral toxicity of Hinosan
    1976      metabolites to rats, Report No. 48840. Mobay Chemical Corp.,
              Agr. Div. Report submitted by Bayer AG to WHO. (Unpublished)

    Malik, J.K., Verma, S.P., Gars, B.D. and Ahmad, A. Studies on blood
    1978a     enzymes during acute toxicity of O-ethyl-S,S-diphenyl
              phosphorodithioate (Hinosan) in buffalo calves, Indian
              Journal of Pharmacology, 10: 7-14.

    Malik, J.K, Garg, B.D., and Ahmad, A. Experimental subacute toxicity
    1978b     and anticholinesterase action of O-ethyl-S,S-diphenyl
              phosphorodithioate in buffalo calves. Indian Journal of
              Animal Science, 48 (5): 358-361.

    Malik, J.C., Garg, B.D., Verma, S.P. and Ahmad A. Serum transaminases
    1978c     and alkaline phosphatase activities during subacute toxicity
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    See Also:
       Toxicological Abbreviations
       Edifenphos (Pesticide residues in food: 1976 evaluations)
       Edifenphos (Pesticide residues in food: 1979 evaluations)