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    PESTICIDE RESIDUES IN FOOD - 1982


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1982





    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, 23 November - 2 December 1982

    Food and Agriculture Organization of the United Nations
    Rome 1983

    TRIAZOPHOS

    IDENTITY

    Chemical names

    O,O-diethyl O-1-phenyl-1,2,4-triazol-3-yl phosphorothioate; O,O-
    diethyl O-(1-phenyl-1H-1,2,4-triazol-3-yl) phosphorothioate; 1-phenyl-
    1,2,4-triazolyl-3-(O,O diethyl-thionophosphate)

    Synonyms

    Hoe 02960

    Trade name

    RHostathion

    Structural formula

    CHEMICAL STRUCTURE 1

    Empirical formula

    C12H16N303PS

    Molecular weight

    313.3

    Other information on identity and properties

    Pure active ingredient

    Density                  1.247 g/cm3 at 20C

    Melting point            2 - 5C

    Vapour pressure          1  10-5 Torr at 38C
                             1  10-3 Torr at 74C

    Flash point

         Open                192  5C (Cleveland)

         Closed              135  2C (Pensky-Martens)

    Solubility               at 20C

                             water          35 ppm  5 ppm
                             n-hexane       0.9%
                             toluene        >33%
                             ethyl acetate  100%
                             acetone        100%
                             ethanol        >33%

    Technical active ingredient

    Physical form            light yellow to dark brown liquid.

    Odour                    characteristic of phosphoric ester

    Density                  1.24 g/cm3  0.05 g/cm3 at 20C

    Melting point            0C to 5C

    Solubility               soluble in aromatic hydrocarbons, alcohols,
                             esters and ketones

    Stability

         Chemical stability  decomposed by acids and alkalies
         Thermal stability   not stable in undiluted form

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, Distribution, Elimination and Biotransformation

    Rat

         In male and female rats (Wistar SPF) treated with a single oral
    dose of 14C-triazophos (labelling at the 3-position of the triazole
    ring) at 2.76 mg/rat or approximately 15-21 mg/kg bw, about 76% of the
    administered radioactive dose was excreted in the urine and 21% in the
    faeces within 48 hours of dosing. No significant sex difference in
    rate and route of elimination was evident. Analyses of tissues from
    these animals sacrificed four days after treatment indicated 14C
    residues detected (as % of administered dose) to be invariably less
    than 0.04% in kidney, gonads, brain, muscle and skin, 0.089% in liver
    and 0.31% in the gastrointestinal tract. The rapid elimination of
    14C-triazophos was similarly observed when male and female rats were
    intubated with the radioactive compound at 0.56 mg/rat or
    approximately 3.1-4.3 mg/kg bw/day for 12 consecutive days. Thus, 69.5
    - 83.4% of the daily administered dose was recovered in the urine and
    18.1 - 30.9% in the faeces during the dosing period. At sacrifice four
    days after termination of the 12-day treatment period, none of the
    tissues analyses (subcutaneous fat, kidney, gonads, liver, brain,
    muscle and skin) had 14C residues greater than 0.0008% of the
    administered dose. An exception was the gastrointestinal tract, which
    still contained 0.5% of the given dose.

         The major urinary metabolite was urea-14C, amounting to
    approximately 85% of the radioactivity excreted via this route. Other
    metabolites detected in the urine were 1-phenyl-1,2,4-triazol-3-ol-3-
    14C, 1-phenylsemicarbazide-3-14C and semicarbazide-14C, all as
    conjugates with glucuronic acid. Each of these three metabolites
    accounted for 3-5% of the 14C eliminated in the urine. In the faeces,
    unchanged 14C-triazophos (40% of the total activity in this route)
    and 1-phenyl-l,21-4-triazol-3-ol-3-14C (60% of the activity) were
    identified (Bock and Thier 1976).

    Effects on Enzymes and Other Biochemical Parameters

         See under Observations in Humans.

    TOXICOLOGICAL STUDIES

    Special Study on Reproduction

         In a standard 3-generation (2 litters/generation) reproduction
    study, 10 male and 20 female newly weaned rats (Wistar derived) were
    fed dietary levels of triazophos at 0, 0.3, 1.0 or 10 ppm and mated at

    weeks 12 and 20 to produce two successive litters. Weanlings of the
    second litters (i.e. F1b and F2b) were selected to become parents of
    the next generations. F3b weanlings, 10 males and 10 females/group,
    were maintained on dietary feedings for 4 weeks for a toxicity study.
    Based on summary data available (no data on individual litters
    provided in the report), mortality, behaviour and body weight and
    pregnancy rate were unaffected in any of the parental generations.
    Except for a decrease in pup weight at 10 ppm on day 20 in the F2a
    litters, there were no dose- or treatment-related effects as judged by
    litter size at birth, sex ratio, mortality and body weight of young
    during lactation, resorption quotient (number of implantation sites/
    number of young born) and gross malformations of pups at birth. The
    reduced pup weight on day 20 at 10 ppm appeared to be of doubtful
    significance in the light of its occurrence in only a single progeny
    generation (F2a litters). In F3b weanling pups maintained on dietary
    feeding for four weeks, there was no mortality or adverse effect on
    body weight. Significant inhibition (21%) of plasma cholinesterase
    occurred at 10 ppm in the females after 23 days. Erythrocyte
    cholinesterase assayed at the same period was not significantly
    depressed in the treated groups. At terminal sacrifice, there were no
    significant variations from controls in brain cholinesterase activity,
    organ weights and gross pathological changes. Histopathological
    evaluation of selected tissues from animals of control and top dosage
    groups revealed no treatment-related alterations (Til  et al 1975).

    Special Studies on Mutagenicity

         Triazophos was tested for its mutagenic potential in a reverse
    mutation assay in the presence or absence of a metabolic activation
    system (S-9 homogenate of liver from rats induced with Arochlor 1254).
    The tester strains used were  Salmonella typhimurium TA 98,
    TA 100, TA 1535 and TA 1537. At the concentrations used, 0.2 to
    5 000 g/plate, triazophos was not mutagenic to any of the tester
    strains with or without the presence of the metabolic activation
    preparation (Gericke 1977).

    Special Studies on Carcinogenicity

         See under Long-Term Studies.

    Special Studies on Neurotoxicity

    Hen

         Two groups of 6 white Leghorn hens (mean weight 1.75 kg) were
    intubated with a single dose of 25 mg/kg bw of triazophos. Survivors
    were similarly treated again with another dose of the same magnitude
    21 days later and observed for a further period of 21 days. (The acute
    oral LD50 of triazophos in hens was determined to be approximately

    24 mg/kg bw prior to initiation of the neurotoxicity study.) Hens in
    one of these groups were treated with atropine (10 mg/kg bw) and
    Toxagonin (4 mg/kg bw) by an unspecified route once before and four or
    five times after the first and second dose of triazophos. The
    untreated control group comprised 6 hens. One hen in each of the
    treated groups died after the first dose. Following the second dose,
    mortality occurred in 2 hens protected with antidotes and in 3
    unprotected hens. No neurotoxic signs were noted in any of the treated
    birds at any time during the study, although toxic symptoms indicative
    of anticholinesterase poisoning, such as disturbed equilibrium,
    salivation, lethargy and extensor spasms, were present during the
    first two days after each dose of triazophos. Histopathological
    examination of the spinal medulla (cervical medulla, cervical
    enlargement, thoracic medulla and lumbar enlargement) and sciatic
    nerve from 5 surviving hens (3 of these with antidote treatment) at
    25 mg/kg bw and 1 untreated control hen surviving terminally revealed
    no morphologically demonstrable changes characteristic of delayed
    neurotoxic effects. One of the 5 hens at 25 mg/kg bw, however, showed
    macroscopic and microscopic lesions in medulla oblongata and spinal
    medulla classified with chicken gliomata, which was considered to be
    independent of treatment. Positive control hens, treated with TOCP,
    displayed clinical symptoms and histopathological changes typical of
    delayed neurotoxicity (Kramer and Weigand 1974).

    Special Studies on Skin and Eye Irritation

         Results of a patch test with rabbits (SPF-albino Himalayan
    strain) indicated triazophos, as a 1% or 10% dilution in sesame oil,
    to be practically non-irritating to the skin. However 5 of the 6
    treated rabbits died 24-48 hours after 0.5 ml of undiluted triazophos
    was applied to each of the two sites (one abraded) on their clipped
    skin (Hollander and Weigand 1977a).

         An eye irritation study in rabbits (SPF - albino Himalayan
    strain) suggested undiluted triazophos, 1% or 10% dilutions of
    triazophos in sesame oil, to be of a low irritant potential to eyes. A
    single dose of 0.1 ml of the undiluted material applied to one eye
    was, however, fatal to 1/6 treated rabbits in 48 hours (Hollander and
    Weigand 1977a).

    Acute Toxicity

         Toxic signs of oral poisoning similar in mice and rats, were
    characterized by tremors, abdominal position and squatting. Mortality
    usually occurred 10 minutes to 5 days after lethal doses. No specific
    information was given on the time of onset and duration of symptoms
    (Hollander and Weigand, 1977b, 1977c, 1977d; Scholz and Weigand 1969,
    Hollander and Weigand 1977e). The LD50 in these two species is
    reported in Table 1 for different treatment routes and vehicles.

        Table 1.  Acute Toxicity to Triazophos in the Mouse and Rat
                                                                                                                       

    Species                  Sex       Route          Vehicle             LD50                Reference
                                                                          (mg/kg bw)
                                                                                                                       

    Mouse                    M         oral 1         sesame oil          31                  Hollander and Weigand
    (SPF-NMRI)                                                                                1977b
                             F         29                                                     Hollander and
                                                                                              Weigand 1977c

    Rat                      M         oral           starch              68                  Hollander and
    (SPF-Wistar)                                      suspension                              Weigand 1977d

                             F         oral           starch slurry       66                  Scholz and Weigand 1969

                             F         oral           starch mucilage     64                  Hollander and Weigand
                                                                                              1977e

    Rat                      F         i.p.           oil of benne        107                 Scholz and Weigand 1968
    (SPF-Wistar)

    Rat                      F         dermal 2       sesame oil          1100                Weigand 1972
                                       (24-hour
                                       exposure)
                                                                                                                       

    1  In the oral studies, animals were fasted 15 to 18 hours prior to dosing.

    2  Treated site was occluded during the exposure period.
        Dog

         In groups of generally 2 beagle dogs (mixed sex; 20-hours fasted)
    treated with single doses of triazophos (93% pure) in sesame oil by
    gavage, no mortality occurred at 320 mg/kg bw and below. Both dogs at
    800 mg/kg bw and 1/2 dogs at 500 mg/kg bw died within 3 days of
    dosing. Vomiting was observed in 2/2 dogs at both 80 and 800 mg/kg bw,
    1/2 dogs at 125 mg/kg bw and 1/1 dog at 160 mg/kg bw usually 3 to 6
    hours after treatment, but in none of the 2 dogs each at 50, 320 and
    500 mg/kg bw. Other toxic symptoms included hypersalivation, tremors,
    miosis and staggering gait. The median lethal dose appeared to be in
    the vicinity of 500 mg/kg bw (Scholz and Brunk 1969).

    Short-Term Studies

    Rat

         Groups of 10 male and 10 female weanling rats (Wistar derived)
    were fed diets containing triazophos (90% pure) at 0, 1, 3, 10 or
    200 ppm for 13 weeks. The highest level was raised to 400 ppm in the
    6th week. Survival was 100%. Body weight, food consumption and
    behaviour as well as haematology, clinical chemistry and urinalysis
    parameters were not adversely affected. Activity of plasma
    cholinesterase was depressed (920%) in males of top dosage group and
    in females at 3 ppm and above at all sampling intervals (weeks 3, 6
    and 12). The enzyme was also inhibited in females at 1 ppm by 19% and
    in males at 10 ppm by 23% at week 12 only. Terminal brain
    cholinesterase and erythrocyte cholinesterase assayed at the three
    intervals were inhibited (>20%) only in the top dosage group (both
    sexes). The magnitude of depression of plasma, erythrocyte or brain
    cholinesterase was greater in females than in males at the same dosage
    levels. At terminal sacrifice, there were no gross pathological
    changes or organ weight variation associated with the compound. No
    treatment-induced histopathological changes were observed in a variety
    of tissues evaluated. The study suggested 1 ppm as a virtual no-effect
    level (Til  et al 1971).

    Dog

         Male and female purebred beagles (3 males and 3 females per
    group) were fed dietary levels of triazophos at 0, 0.03, 0.1, 0.3,
    1.0, 5.0 or 100 ppm for 13 weeks. There was no mortality or treatment-
    induced abnormal behaviour. Body weight, food consumption and
    haematological, biochemical (including kidney and liver function
    tests) and urinalysis values were not affected in any dose-response
    pattern. Inhibition (>20%, dose related) of plasma cholinesterase
    occurred at and above 1 ppm at weeks 3 and 7 and at both 5 and 100 ppm
    at week 12 also. Whole blood cholinesterase was reduced (>20%) in the
    top dosage group only at weeks 3, 7 and 12. Activity of terminal brain
    cholinesterase was not inhibited (>20%). At the conclusion of the

    study, organ weights and gross pathological changes were comparable in
    all groups. Histopathological examination of a set of over 30 tissues
    from each dog of the control and the treated groups at 1 ppm and above
    revealed no abnormalities related to ingestion of triazole. The no-
    effect level was 0.3 ppm (Til  et al 1971).

         Groups of 4 male and 4 female purebred beagles were fed
    triazophos (purity not specified) in their diet at 0, 0.3, 1.0 or
    3.0 ppm for 2 years. The highest dietary level was increased to 6 ppm
    after 5 weeks and to 200 ppm after 16 weeks. There were no treatment-
    related findings with respect to mortality, appearance and behaviour
    and food consumption. Growth was decreased in the top dosage group
    (both sexes) at week 36 and thereafter. Periodic haematological and
    biochemical studies and urinalysis during the study indicated
    significant changes, confined to the top dosage group, in values of
    SAP, serum albumin, SGOT and specific gravity of the urine.
    Measurements of plasma and erythrocyte cholinesterase nine times over
    the course of the experiment revealed dose-related inhibition (>20%)
    of plasma cholinesterase at and above 1 ppm at all intervals and at
    0.3 ppm at weeks 13 and 26. Erythrocyte cholinesterase was depressed
    (>20%) only at the top dosage group at week 17 and thereafter. Brain
    cholinesterase assayed terminally was not inhibited (>20%). Animals
    sacrificed at the end of the study exhibited an increase in absolute
    weight of the liver and organ/body weight ratio of the liver and the
    thyroid at the top dosage level. No compound-induced histopathological
    lesions were observed in a variety of tissues evaluated, including
    liver and thyroid. The dietary level of 0.3 ppm was a marginal no-
    effect level (Til  et al 1976).

    Long-Term Studies

    Rat

         Groups of 30 male and 30 female rats (Wistar derived) were fed
    dietary levels of triazophos (of unspecified purity) at 0, 0.3, 1.0,
    3.0, 10 or 200 ppm for 2 years. (The 0.3 ppm and 10 ppm groups
    were discarded at week 28 "because the plasma and erythrocyte
    cholinesterase was not inhibited in the 0.3 and 1 ppm groups and
    decreased in the 3 and 10 ppm groups".) Mortality, appearance and
    general behaviour and body weight were not affected by treatment.
    Between 23-70% males and 43-87% females of all groups, including the
    control, survived the duration of the study. (Over 50% males and at
    least 70% females per control and treated group were still alive at 96
    weeks.) Food consumption was slightly reduced at 200 ppm in males
    during the first year and in females after 47 weeks. Plasma
    cholinesterase was inhibited (>20%), in a dose-dependent pattern, at
    10 ppm at weeks 4 (females only), 13 and 26 (both sexes) and at 3 ppm
    in females at weeks 52 and 102. Animals at 200 ppm exhibited marked
    depression (>20%) of plasma and erythrocyte cholinesterase (both

    sexes) at all intervals and of terminal brain cholinesterase (females
    only). No compound-related effects were observed on haematological,
    biochemical and urine parameters measured periodically up to five
    times over the course of the study. At the conclusion of the
    experiment, there were some variations in organ/body weight ratio of
    several selected organs but they did not follow a dose-response trend.
    Histopathological evaluation of over 20 organs plus all grossly
    abnormal tissues from each animal, initially limited to 20 males and
    20 females of the control and 200 ppm groups (comprising terminal
    survivors supplemented with animals sacrificed in extremis or dying
    toward the end of the study) and later extended to all animals of the
    intermediate dosage groups, showed no alterations attributable to
    inclusion of triazophos in the diet. There were no dose- or compound-
    related increases in incidence of any particular type of tumour. Based
    on the data, 1 ppm was the no-effect level (Til and Leegwater 1975;
    Birkvens and Beems 1979).

    Observations in Humans

         In a preliminary study, a male volunteer (80 kg) was given
    triazophos orally for 4 consecutive mornings. The dose was 1 mg or
    0.0125 mg/kg body weight/day on day 1 and 5 mg (0.0625 mg/kg body
    weight/day) from days 2 through 4. Depression (=20%) of plasma
    cholinesterase, initially observed after the third dose and more
    pronounced after the fourth dose, was still evident 3 days after
    treatment withdrawal. No inhibition (<20%) of erythrocyte
    cholinesterase was noted at any time during the study. Headache was
    the only complaint reported, which began to occur after the second
    dose and persisted through the day following the last dose (Leegwater
    1971).

         Two male and two female volunteers were orally doses with
    0.0125 mg/kg bw/day of triazophos for 5 days. Compared to pre-
    treatment levels there was no depression (<20%) of cholinesterase in
    plasma or erythrocyte measured 5 hours after the second and fourth
    doses. Two days later, the same 2 male volunteers were given 2
    additional courses of triazophos with a rest period of 2 days between
    the courses. The first course comprised 5 daily doses at 0.03 mg/kg
    bw/day and the second course 5 daily doses at 0.05 mg/kg bw/day.
    Activity of plasma cholinesterase, slightly reduced (17-18%) in both
    subjects after 4 doses in the first course and after 3 doses in the
    second course, was significantly inhibited (>30%) after 4 days in
    the second course. Complete recovery of the enzyme was not apparent
    until 16 days following completion of the second course. Erythrocyte
    cholinesterase was not adversely affected at any time during the
    experiment (Leegwater 1972).

         Healthy adult volunteers (2 males and 3 females, aged 18-23
    years) were given 0.0125 mg triazophos/kg bw/day orally, 5 days/week
    for 3 consecutive weeks in a pilot study. All 5 subjects completed the

    study but one female missed one dose during the first dosing week.
    There was no significant change in the activity of plasma or
    erythrocyte cholinesterase at any time during the dosing period, as
    compared to that in the one-week, pre-exposure 'run-in' period. The
    only symptom reported was headache experienced by one female subject
    each morning about 1 1/2 hours after dosing on the first 3 days of the
    first treatment week. Medical examination and routine haematology,
    biochemistry and urinalysis conducted before and 13 days after the
    dosing period revealed no significant changes attributable to
    triazophos, although one female volunteer (the same one complaining of
    headache) showed a tendency toward anaemia (Cooper  et al 1973a). In
    a second pilot study, 3 male and 2 female healthy adult subjects were
    given 0.025 mg triazophos/kg bw/day, 5 times weekly for 3 weeks.
    Reduction of plasma cholinesterase (11-17%), which appeared to be
    related to duration of treatment, was stated to attain statistical
    significance in weeks 2 and 3 of treatment and during the first week
    of withdrawal, Erythrocyte cholinesterase was not adversely affected
    at any time during the study (Cooper  et al 1973b).

         Twenty-five healthy adult subjects (13 males and 12 females) were
    administered 0.0125 mg triazophos/kg bw/day, 5 days/week for 3
    consecutive weeks. Medical examination and routine haematology,
    biochemistry and urinalysis were conducted prior to the study and at
    the end of a 4-week post-dosing follow-up period. Plasma and
    erythrocyte cholinesterase was assayed prior to the study and at least
    three times weekly throughout the dosing and follow-up periods. All 25
    subjects completed the study. Two males and 1 female were withdrawn
    from treatment during the second dosing week owing to progressive
    inhibition of plasma cholinesterase to less than 80% of the pre-dose
    levels, but dosing resumed for these 3 during treatment week 3. Two
    other subjects missed 1 or 2 doses, respectively, due to diarrhoea and
    sickness. (Based on the statement that "other subjects who had to
    unavoidably miss blood sampling (taken prior to the daily dose, i.e.
    approximately 24 hours after the previous dose) on occasions during
    the three dosing weeks were given their daily doses to take at the
    appropriate time on the following day", it would appear that
    additional subjects also might have missed an unspecified number of
    doses during the treatment period.) During the first dosing week, 50%
    of the female subjects reported urinary frequency with some degree of
    urinary urgency. Other complaints, isolated in incidence, included
    tiredness and lethargy, nausea and diarrhoea. There were some
    significant differences between pre- and post-treatment values in
    blood pressure, pulse rate and some laboratory parameters but the
    post-treatment values were within the limits normally considered
    acceptable to the testing laboratory. A comparison of the mean plasma
    cholinesterase activity (of all 25 subjects) obtained before the test
    with that at each dosing and follow-up week indicated no statistically
    significant difference. However, a total of 6 individuals (including
    the 3 withdrawn from treatment during the second week) exhibited a

    depression (> 20%) of plasma cholinesterase, mainly during the second
    and third week of dosing when their own pre-treatment levels were used
    as the basis of comparison. Recovery of the enzyme to pre-exposure
    levels were more or less complete in the majority of subjects by the
    end of the fourth follow-up week. No significant compound-inducted
    inhibition of erythrocyte cholinesterase was noted during the study.
    The data suggested 0.0125 mg/kg body weight as the minimum effect
    level with respect to plasma cholinesterase (Cracknell  et al 1973).

    COMMENTS

         Triazophos was evaluated for the first time by the present
    Meeting.

         In rats, triazophos, an organophosphorous insecticide, is rapidly
    eliminated predominantly in the urine and also in the faeces. It is
    readily degraded, with urea being the major urinary metabolite.
    Neither triazophos nor its metabolites appear to accumulate to any
    significant extent in the tissues. Metabolism data in mammalian
    species other than the rat are not available.

         Oral LD50 values of triazophos ranged from approximately
    30 mg/kg bw in mice, 65 mg/kg bw in rats to about 500 mg/kg bw in
    dogs, suggesting a significant species variation in sensitivity to
    acute toxicity of the compound. A significant sex difference was not
    evident.

         Summary data provided for a 3-generation reproduction study in
    rats suggested 10 ppm as a no-effect level on reproduction. There were
    no teratogenicity studies. An  in vitro microbial assay and a delayed
    neurotoxicity study in hens were negative. Nevertheless, the
    possibility exists that the dosage level used (equivalent to an oral
    LD50) in the hen study might be too low to permit an adequate testing
    of the compound for its delayed neurotoxic potential. Studies designed
    specifically to evaluate the carcinogenic activity of triazophos are
    not available, although a 2-year feeding study in rats indicated no
    increase in incidence of any particular type of tumour.

         No-effect levels had been defined in 13-week and 2-year feeding
    studies in rats and dogs, with plasma cholinesterase being
    demonstrated to be the most sensitive indicator of biological
    activity. Observations in humans suggested a significant individual
    variation to the effect of triazophos on plasma cholinesterase.

         Despite establishment of no-effect levels in two mammalian
    species, the Meeting could only allocate a temporary ADI since
    additional data, as listed below, are required to complete the
    toxicological data base.

    TOXICOLOGICAL EVALUATION

    Level Causing no Toxicological Effect

         Rat : 1 ppm in the diet, equivalent to 0.05 mg/kg bw

         Dog : 0.3 ppm in the diet, equivalent to 0.008 mg/kg bw

    Estimate of Temporary Acceptable Daily Intake for Man

         0 - 0.0002 mg/kg bw

    FURTHER WORK OR INFORMATION

    Required (by 1986)

    1.   A carcinogenicity study.

    2.   Teratogenicity study in at least one mammalian species.

    3.   Metabolism studies in additional mammalian species to explain
         species differences in acute toxicity.

    4.   Additional mutagenicity studies.

    Desirable

    1.   An appropriate delayed neurotoxicity study in hens.

    2.   Data on individual litters for the currently available three-
         generation reproduction study in rats.

    3.   Acute oral toxicity data on any metabolite of triazophos that is
         found in food crops.

    REFERENCES

    Bock, R. and Thier, W. Metabolism and fate of triazophos in rats.
    1976      Pesticide Science 7: 307-314.

    Berkvens, J.M. and Beems, R.B. Chronic (two-year) toxicity study with
    1979      Hoe 2960 in rats. Part 3. Microscopic pathological
              examination of intermediate dose animals. Report from
              Central Institute for Nutrition and Food Research, Zeist,
              submitted to the World Health Organization by Hoechst.
              (Unpublished)

    Cooper, A.J., Haynes, G., Street, A.E. and Rudd, C.J. A pilot study to
    1973a     observe the in-vivo effects of Hoe-2960 on the
              cholinesterase activity in man administered 0.0125 mg/kg day
              p.o. Report from Huntingdon Research Centre, England.
              Submitted to the World Health Organization by Hoechst.
              (Unpublished)

    1973b     A pilot study to observe the in vivo effects of Hoe-2960 on
              the cholinesterase activity in man administered 0.025
              mg/kg/day p.o. Report from Huntingdon Research Centre,
              England, Submitted to the World Health Organization by
              Hoechst. (Unpublished)

    Cracknell, D.D., Hawkes, G., Street, A.E. and Rudd, C.J. The in-vivo
    1973      effects of Hoe-2960 on the cholinesterase activity in man
              administered 0.0125 mg/kg/day. Report from Huntingdon
              Research Centre, England. Submitted to the World Health
              Organization by Hoechst. (Unpublished)

    Gericke, D. Test for mutagenicity in bacterial strains in the absence
    1977      and presence of a liver preparation. Hoe-02960 01 AS 101.
              Report from Hoechst. Submitted to the World Health
              Organization by Hoechst. (Unpublished)

    Hollander and Weigand. Hoe-02960 01 AS 101 Irritance to the rabbit
    1977a     skin and eye mucosa. Report from Hoechst, Submitted to the
              World Health Organization by Hoechst. (Unpublished)

    1977b     Hoe-02960 01 AS 101 Acute oral toxicity to the male SPF-NMRI
              mouse (vehicle: sesame oil). Report from Hoechst submitted
              to the World Health Organization by Hoechst. (Unpublished)

    1977c     Hoe-02960 01 AS 101 Acute oral toxicity to the female
              SPF-NMRI mouse (vehicle: sesame oil). Report from Hoechst
              submitted to the World Health Organization by Hoechst.
              (Unpublished)

    1977d     Hoe-02960 01 AS 101 Acute oral toxicity to the male SPF-
              Wistar rat (vehicle: starch suspension). Report from Hoechst
              submitted to the World Health Organization by Hoechst.
              (Unpublished)

    1977e     Akute orale toxizitat von Hoe 02960 01 AS 101 and weiblichen
              SPF-Wistar ratten (vehikel: starkeschleim). Report from
              Hoechst submitted to the World Health Organization by
              Hoechst. (Unpublished)

    Kramer and Weigand, Test of triazophos (Hoe-02960) for neurotoxicity
    1974      in hens. Report from Farbeverke Hoechst AG submitted to the
              World Health Organization by Hoechst. (Unpublished)

    Leegwater, D.C. Preliminary study on the in-vivo effect of Hoe-2960 in
    1971      man. Report from Central Institute for Nutrition and Food
              Research, Zeist. Submitted to the World Health Organization
              by Hoechst. (Unpublished)

    1972      In-vivo study on the effect of Hoe-2960/Op 22 on the blood
              cholinesterase of man. Report from Central Institute for
              Nutrition and Food Research, Zeist. Submitted to the World
              Health Organization by Hoechst. (Unpublished)

    Scholz and Weigand. Triazophos-determination of the acute
    1968      intraperitoneal toxicity. Report from Hoechst submitted to
              the World Health Organization by Hoechst. (Unpublished)

    1969      W12712 = Hoe-02960. 1-phenyl-1,2,4-triazolyl-3-(O,O-diethyl
              thionophosphate) (Op. Techn. No. 3, Content 93%). Report
              from Hoechst submitted to the World Health Organization by
              Hoechst. (Unpublished)

    Scholz and Brunk. W12712 = Hoe 2960. Acute oral toxicity in dogs.
    1969      Report from Hoechst submitted to the World Health
              Organization by Hoechst. (Unpublished)

    Til, H.P., Leegwater, D.C. and Seinen, W. Subchronic (90-day) toxicity
    1971a     study with Hoe-2960 Op. 22 in albino rats. Report from
              Central Institute for Nutrition and Food Research, Zeist,
              submitted to the World Health Organization by Hoechst.
              (Unpublished)

    Til, H.P., Seinen, W., Leegwater, D.C. and van der Meulen, H.C.
    1971b     Subchronic toxicity study with Hoe 2960, Op.22 in beagle
              dogs. Report from Central Institute for Nutrition and Food
              Research, Zeist, submitted to the World Health Organization
              by Hoechst. (Unpublished)

    Til, H.P., Hendriksen, C.F.M. and Leegwater D.C. Multigeneration study
    1975      with Hoe-2960 in rats. Report from Central Institute for
              Nutrition and Food Research, Zeist, submitted to the World
              Health Organization by Farbeverke Hoechst. (Unpublished)

    Til, H.P., Leegwater, D.C. and Kollen, C.H. Long-term (two year)
    1976      toxicity study with Hoe 2960 in dogs. Report from Central
              Institute for Nutrition and Food Research Zeist, submitted
              to the World Health Organization by Hoechst. (Unpublished)

    Til, H.P. and Leegwater, D.C. Chronic (two year) toxicity study with
    1975      Hoe-2960 in rats. Part I. Results of clinical haematological
              biochemical and organ weight measurements. Report from
              Central Institute for Nutrition and Food Research, Zeist,
              submitted to the World Health Organization by Hoechst.
              (Unpublished)

    Weigand. Testing of dermal toxicity in female SPF-Wistar rats of our
    1972      own breed, after a single treatment. Report (No. A 00092)
              from Hoechst, submitted to the World Health Organization by
              Hoechst. (Unpublished)


    See Also:
       Toxicological Abbreviations
       Triazophos (JMPR Evaluations 2002 Part II Toxicological)
       Triazophos (Pesticide residues in food: 1983 evaluations)
       Triazophos (Pesticide residues in food: 1986 evaluations Part II Toxicology)
       Triazophos (Pesticide residues in food: 1991 evaluations Part II Toxicology)
       Triazophos (Pesticide residues in food: 1993 evaluations Part II Toxicology)