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    PESTICIDE RESIDUES IN FOOD - 1983


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1983





    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, 5 - 14 December 1983

    Food and Agriculture Organization of the United Nations
    Rome 1985

    ETHOPROPHOS

    TOXICOLOGY

    IDENTITY

    Chemical Name

    O-ethyl S,S - dipropyl phosphorodithioate

    SYNONYMS

    Ethroprop; ProphosR; MocapR; VC9 - 104

    Structural Formula

                 O
                 "
           C2H50-P-(SC3H7)2

    Empirical Formula

           C8H19O2PS2

    Other Information on Identity and Properties

    Molecular weight              242

    Physical state                clear liquid with yellow tint

    Melting point                 not applicable

    Vapour pressure               4.6 × 10-4mm Hg (26°C)

    Boiling point                 86 - 91°C (0.2 mm Hg)

    Partition coefficient         140 (octanol water)

    Density                       1.094 g/ml (25°C)

    Solubility                    750 mg/l water (25°C); very soluble in
                                  organic solvents

    Stability                     Thermal stability is good for 12
                                  weeks at 50°C. Very stable in
                                  acid aqueous medium from 25°C to,
                                  100°C; hydrolysis moderately fast
                                  in basic medium at 25°C and rapid
                                  at 100°C.

    Flammability                  not inflammable

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, Distribution, Elimination and Biotransformation

    Male and female rats orally treated once with 14C-ethyl-ethoprophos
    (1.28 × 106 counts/min/rat) or 14C-propyl-ethoprophos (3 × 106
    counts/min/rat) excreted about 55 to 65 percent of the administered
    radioactivity in the urine. (Actual dosage of ethoprophos administered
    to the animals was not given). Less than 1 percent of the administered
    14C was recovered in the faeces. Most of the radioactivity found in
    the urine was eliminated during the first six hours post-treatment and
    was in the form of hydrolytic products. Among the latter was 
    O-ethyl-S-propyl phosphorothioic acid, which was the major urinary
    metabolite accounting for approximately 40 percent of the given
    radioactive dose. Other water-soluble metabolites identified in the
    urine included O-ethyl-phosphoric acid, S-propyl-phosphorothiolic acid
    and S, S-dipropyl-phosphorodithioic acid. In the urine of rats treated
    with the 14C-propyl-labelled compound, organo-extractable
    metabolites, viz. methyl propyl sulphide, methyl propyl sulphoxide and
    methyl propyl sulphone, were also detected. These latter metabolites
    together amounted to about 2 percent of the administered radioactivity
    (Iqbal & Menzer, 1972).

    In vitro, the NADPH - dependent microsreal enzymes from the liver of
    rats and rabbits were able to biotransform 14C-ethyl-ethoprophos or 
    14C-propyl-ethoprophos to O-ethyl-S-propyl-phosphorothioic acid, the
    major metabolite and, depending on the substrate to 0-ethyl-phosphoric
    acid (from the ethyl-14C-labelled compound) or 
    S-propyl-phosphorothiolic acid (from the propyl-14C-labelled
    compound). Incubation of liver supernatant preparations from rats and
    rabbits with ethoprophos, in the presence of reduced glutathione, led
    to the production of O-ethyl S-propyl phosphorothioic acid as the
    major metabolite. Additionally, S-ethyl glutathione and 
    (S-S-dipropyl-phosphorodithioic) acid were formed, respectively, when
    the ethyl-14C- or the propyl-14C-labelled compound was used as the
    substrate (Iqbal & Menzer 1972).

    TOXICOLOGICAL STUDIES

    Special Studies on Reproduction

    Rat

    Groups of 10 male and 20 female rats (Fischer 344, 44-days old) were
    fed diets containing technical ethoprophos (95.3 percent pure) at 0,
    60.5, 131 or 262 ppm for 56 days prior to mating to initiate a 
    three-generation (two litters/generation) reproduction study.
    Weanlings from the second litters were selected to become parents of
    the next generation. All parental animals and weanlings from each
    progeny generation were subjected to gross pathological examination.

    Additionally, all F1b and F2b parents plus 5 male and 5 female
    weanlings per group from F1a, F2a, F3a and F3b litters were
    evaluated histopathologically. Mortality was unaffected but growth was
    slightly depressed at 131 ppm and above in all parental generations.
    Data on food consumption were not available. A dose-related increase
    in incidence of dams cannibalizing their young was noted in all
    treated groups of the Fo generation, mainly in the second litters.
    Pregnancy rate (in percentage) was reduced in all treated groups (75,
    60, 55, 55, respectively, at 0, 60.5, 131, 262 ppm) of the F1a
    litters and at 262 ppm in F3a and F3b litters. At both 131 and 262
    ppm, incidence of litters with at least one dead pup at birth was
    elevated in F1b litters and weanling weight (not determined for F1a
    and F1b litters) was depressed in F2a and F2b litters. Other effects
    that were observed but were limited to the top dosage level included,
    e.g. a tendency for decreased litter size at birth through almost all
    progeny generations, reduced pup survival from day 4 to weaning in
    F1b, F2a and F2b litters, a prolongation of mean gestation period in
    F1b litters, occurrence of bilateral lenticular opacity and of
    anophthalmia, respectively, in 29 percent and 3 percent of F2a
    weanlings (information on litter distribution of these abnormalities
    was not available), but in none of the concurrent controls or
    weanlings of lower dosage groups, and an increased incidence of
    multifocal granuloma of mesenteric lymph nodes in F2b adults. Since
    the increase in incidence of Fo dams cannibalizing their young and
    the slight decrease in pregnancy rate in F1a litters even at 60.5 ppm
    were not recurrent over the generations and were probably related to
    maternal toxicity, this level might be considered as a virtual 
    no-effect level on reproduction (Fletcher et al. 1981).

    Special Studies on Teratogenicity

    Rat

    Groups of 25 to 35 mated female Sprague-Dawley rats (TAC: N(SD)FBR)
    were intubated with technical ethoprophos (94 percent pure) at 0,
    0.16, 1.6 or 16 mg/kg b.w./day on gestation days 6 through 15 (day 0 =
    day vaginal sperm plug observed). The dams were sacrificed on day 20
    and the foetuses were removed for gross, skeletal and visceral
    examination. Pregnancy rate was comparable in all groups. During, the
    gestation period, 1/24 and 18/30 pregnant dams, respectively, at 1.6
    mg/kg b.w. and 16 mg/kg b.w. died. Growth was depressed on gestation
    days 15 and 20 at 16 mg/kg b.w. There was no significant, difference
    between control and treated groups in the mean number of corpora
    lutea, implantation sites, live foetuses, dead foetuses or
    resorptions, mean foetal weight and sex ratio. According to data
    available as summary on skeletal findings and soft tissue
    abnormalities in foetuses, the notable observations were a significant
    increase in incidence of rudimentary and extra ribs at 1.6 mg/kg b.w.
    only and the occurrence of incomplete ossification of the vertebrae in
    all treated groups. This latter anomaly, not observed at all in any of
    the 169 concurrent control foetuses from a total of 22 litters, was
    found at 0.16, 1.6 and 16 mg/kg b.w., respectively with incidences

    (percentages) of 10, 7, 17 (the foetus as the sampling unit) or 43,
    39, 58 (the litter as the sampling unit). Background data on the
    incidence of this particular anomaly were not submitted. It may be
    noted that incomplete ossification of the vertebrae also occurred in
    82/84 (98 percent) foetuses from 15/15 (100 percent) litters of the
    positive control group. The latter, treated with acetylsalicylic acid
    at 250 mg/kg b.w., exhibited, a number of other skeletal abnormalities
    and soft tissue malformations in the foetuses in addition to maternal
    and foetal toxicity. (Knickerbocker & Re 1979). 

    Rabbit

    Groups of 17 female rabbits (New Zealand White), artificially
    inseminated were orally treated with technical ethoprophos (95.7
    percent pure) at 0, 0.125, 0.5 or 2 mg/kg b.w./day on days 6 through
    18 of gestation (day 0 = day of insemination). The surviving does were
    sacrificed on day 29 of gestation and foetuses were removed for
    external, visceral and skeletal examinations. No treatment-induced
    mortality occurred. Does of all treated groups showed an increased
    incidence of anorexia during and after the dosing period and a
    seemingly dose-related but not statistically significant decrease in
    mean body weight gain between days 6 and 18. There were no significant
    differences between control and treated groups with respect to
    pregnancy rate, mean number of corpora lutea, implantations,
    resorptions, dead foetuses or live foetuses, mean foetal weight, mean
    foetal crown-rump distance, sex ratio, uterine weight with or without
    foetuses, frequency of foetal gross and visceral abnormalities. An
    increase in total incidence of skeletal variants was observed in
    foetuses of all treated groups. However, the increase was not 
    dose-related and frequency of any particular type of skeletal variant,
    when considered alone, did not follow a dose-response relationship.
    The teratogenic no-effect level appeared to be 2 mg/kg b.w. (Wolfe
    et al 1981).

    Special Studies on Mutagenicity

    Ethoprophos, at the non-toxic concentrations ranging from 2.5 to 25 
    nl/ml, did not induce a detectable level of unscheduled DNA synthesis
    in primary rat hepatocytes in vitro (Myhr & Brusick 1981).

    Technical ethoprophos was tested for its mutagenic activity in a
    murine lymphoma L5178Y specific-locus mutation assay. Under the
    conditions of the experiment, the compound did not significantly
    increase mutation frequency in the absence of metabolic activation at
    concentrations ranging from 0.237 to 0.0316 )µl/ml (showing total
    growth for the cultures between 18 and 126 percent) or in the presence
    of S-9 mix (from liver of rats induced with Areclor 1254) at
    concentrations ranging from 0.0237 to 0.0032 µl/ml (showing total
    growth for the cultures between 10 and 106 percent) (Thomson et
    al. 1981).

    In an in vivo cytogenetic study, groups of male Sprague-Dawley rats
    were treated orally with technical ethoprophos (95.7 percent) at O, 2,
    9 or 20 mg/kg b.w./day for five consecutive days. The animals were
    given colchicine i.p. at 4 mg/kg b.w. four hours after the last dose
    and then sacrificed two hours later for metaphase analysis of bone
    marrow cells. There was no significant difference between control and
    treated groups in the incidence of bone marrow cells with chromosomal
    aberrations (Skinner et al. 1981).

    Special Studies on Carcinogenicity  (See under "Long Term Studies".)

    Special Studies on Neurotoxicity

    Two groups of ten deep-litter hens (1.4-2.1 kg in weight; age not
    specified) were intubated with a single dose of technical ethoprophos
    at 5.62 µl/kg b.w. (equivalent to 6.15 mg/kg b.w. and stated to
    represent the acute oral LD50 obtained from a previous study
    performed at the testing laboratory), or TOCP at 500 µg/kg b.w. Four
    untreated hens were used as negative controls. In the 
    ethoprophos-treated hens, there were no gross signs of ataxia or
    paralysis, although symptoms of transient inactivity and "depression"
    were noted between 1 and 48 hours. Four hens in this group died within
    48 hours of dosing. The positive control birds exhibited clinical
    signs characteristic of delayed neurotoxicity. Histopathological
    examination of sections of spinal cord and sciatic nerve, stained by
    the Weil-Weigert method (not referenced), from birds of negative
    control, positive control and ethoprophos-treated groups at the end of
    a 21-day observation period reportedly revealed no evidence of
    demyelination (Weir & Murphy 1967).

    Special Studies on Skin and Eye Irritation

    A single application of 0.1 ml of undiluted technical ethoprophos
    (equivalent to approximately 44 mg/kg b.w.) to one eye of each of
    three New Zealand white rabbits produced moderate erythema and
    vascularization of the sclera and nictating membrane in all of the
    treated eyes. All three animals died within one hour of treatment
    (Weir 1965).

    In a primary dermal irritation study, all six male New Zealand White
    rabbits with clipped skin exposed under an occlusive patch to 0.5 ml
    of undiluted technical ethoprophos (equivalent to approximately 243
    mg/kg b.w.) died within the first 8 hours of treatment (Becker & Parke
    1977).

    Acute Toxicity

    The acute toxicity of four animal species to ethoprophos is summarized
    in Table 1.


        Table 1.   Acute Toxicity of Ethoprophos in Animals

                                                                                                             

    Species              Sex         Route          Vehicle          LD50               Reference
                                                                     (mg/kg b.w.)
                                                                                                             
    Mouse                M&F         oral           water            31                 Pasquet & Mazuret
    (OF1(I.O.P.S.))                                                                     1982

    Mouse                M           dermal         acetone          18                 Ellison 1979
    (CD-1)                           (24-h
                                     exposure

    Rat                  M           oral           maize oil        62                 Hazleton
    (Sprague             F                                           33                 Laboratories 1965
    Dawley)

    Rat                  M&F         dermal         water            226                Pasquet & Mazuret
    (CD, C.O.B.S.)                   (24-h                                              1982
                                     exposure)

    Rat                  M&F         inhalation1    none             250 mg/l air2      Kopp et al 1980
    (Wistar)                         (4-h
                                     exposure)

    Rabbit               F           oral           ?                33                 Schwartz 1978
    N.2.W)

    Pig                  M           dermal         none             327                Rucci 1979
    (Yorkshire)                      (24-h
                                     exposure)
                                                                                                             

    1 Animals were exposed to the liquid technical material as an aerosol in a "nose-only" exposure chamber 
    with particle sizes < 10 µm

    2 Four-hour LC50 expressed as actual chamber concentration.
    
    Signs of oral poisoning

    Toxic symptoms noted in the treated species were characteristic of
    anticholinesterase poisoning and usually persisted for up to 48 hours
    in mice and 72 hours in rats surviving treatment. In general, deaths
    occurred within 4 hours (mice) or 1 hour to 3 days (rats) post-dosing.
    Information on duration of symptoms and time of death in rabbits was
    not available (Pasquet and Mazuret 1982; Hazleton Laboratories 1965;
    Schwartz 1978).

    Short-Term Studies

    Rat

    Groups of 25 male and 25 female rats (Charles River Cesarean - derived
    strain)were fed diets containing technical ethoprophos in acetone at
    0, 0.3, 1 or 100 ppm for three months. (Control group was given basal
    diet containing "a volume of acetone equivalent to the volume used for
    the test diets"). No mortality or treatment - induced toxic signs were
    observed. Growth was depressed (< 10 percent) in males at 1 ppm and
    above and in females at 100 ppm during the last six weeks of the
    study. Food consumption was unaffected. Haematology, clinical
    chemistry and urinalysis performed on 5M and 5F/group at one and three
    months indicated no significant compound-related findings. Measurement
    of cholinesterase activity in plasma, erythrocytes and brain at four
    intervals during the study and terminally showed marked inhibition
    (25-100 percent) of the enzyme at 100 ppm in the tissues tested at all
    sampling intervals, with the degree of depression being greatest with
    erythrocyte cholinesterase and least with brain cholinesterase.
    Maximum inhibition of the enzyme occurred on day 8 or 16, Male rats at
    both 0.3 and 1 ppm exhibited a reduction (24-28 percent) of
    erythrocyte and plasma cholinesterase activity on day 8 and of brain
    cholinesterase level at termination. In the females, brain
    cholinesterase was inhibited (20-25 percent) at both 0.3 and 1 ppm on
    day 8 and at 1 ppm on day 16 also. Additionally, inhibition (23-26
    percent) of plasma and erythrocyte cholinesterase occurred at 1 ppm on
    day 16. At the end of the study, absolute and relative weights of the
    adrenals were elevated in females of all treated groups.
    Histopathological evaluation of about 20 selected tissues, including
    the adrenal from five males and five females of the control and top
    dosage groups, failed to show any significant changes attributable to
    inclusion of ethoprophos in the diet. Based on the data 0.3 ppm
    appeared to be a minimum-effect level on cholinesterase. For other
    monitored parameters, the no-effect level was at least 0.3 ppm (Weir
    1967a).

    Dog

    Groups of three male and three female young adult pure-bred beagles
    were fed dietary levels of technical ethoprophos at 0, 1, 3 or 100 ppm
    for 13 weeks. There was no mortality. Emesis was noted once in each of
    the animals at both 3 and 100 ppm. Body weight, food consumption,
    haematological, biochemical and urinalysis values measured at one and
    three months were not significantly affected by treatment. Plasma
    cholinesterase was inhibited at and above 3 ppm (both sexes) by 27-88
    percent at practically all of the seven sampling intervals and at 1
    ppm in males by 20-27 percent at the two last sampling periods.
    Depression (> 20 percent) of erythrocyte cholinesterase occurred in
    both sexes of the top dosage group at all but the first two or three
    sampling intervals and in females at 3 ppm on one occasion only. At
    termination, no compound-related effects in organ weights or gross
    pathological changes were noted. Histopathological evaluation of about
    20 tissues from each animal of the control and top dosage groups only
    revealed no significant findings other than the observation of a focus
    or foci of perivascular myocardial swelling, with loss of striations
    in 1/3 female controls and 2/3 M and 1/3 F at 100 ppm. In all of the
    three affected dogs at 100 ppm, swelling and vacuolation of Purkinje
    fibres were also seen. Such changes were "thought(by the pathologist)
    to represent an artifact induced in the processing of the tissues". If
    the latter statement could be substantiated or microscopic examination
    of the heart(if and when undertaken) from animals of the lower dosage
    groups failed to show similar cardiac lesions, 1 ppm might be
    considered as a virtual no-effect level for the study (Weir 1967b).

    Long-Term Studies

    Rat

    Groups of 10 male and 10 female rats (Fischer 344) were fed diets
    containing technical ethoprophos (95.3 percent) at 0, 60.5, 131 or 262
    ppm for 8 weeks prior to mating (one male and two females). (According
    to information provided on "Materials and Methods" in the report, the
    Fo generation comprised 10 males and 20 females per group. However,
    under "Results and Evaluation", it was stated that approximately 16
    males and 32 females were mated per dose level. The complete absence
    of data on the reproduction phase precluded verification of the
    information from either source. It was indicated in the report that
    analytical raw data for dietary analysis were not available). Ten days
    after the detection of a positive vaginal smear, the females were
    separated from the males and were continually maintained on the test
    diets until weaning of their pups. This part of the study constituted
    the reproductive phase. Weanlings from the reproductive phase (60
    males and females per group) were randomly selected from control and
    treated groups and fed ethoprophos-treated diets at 0, 4.5, 9 or 18
    ppm during weeks 0 to 12 and at 0, 49, 98 or 196 ppm during weeks 13
    to 109 of a chronic feeding/oncogenicity study. In this 109-week
    study, all animals dying or sacrificed in moribund condition during
    the study, all terminal survivors and the ten males and ten females

    per group sacrificed after 52 weeks of dietary feeding were subjected
    to gross necropsy and histopathological examination of a wide range of
    tissues plus all gross lesions.

    Data for the reproductive phase were not available. For the 109-week
    study, mortality was increased in males of the top dosage group during
    the first seven months. The terminal survival rate was, however,
    comparable in all groups, including the control. Between 53 and 63
    percent of the animals in control and treated groups survived the
    entire duration of the study. Other than the appearance of emaciation
    in animals of the high-dosage group, there were no compound-related
    clinical signs. Growth was depressed in the top-dosage group
    throughout the study and in the mid-dosage group through most of the
    study. Food consumption was reduced frequently in both sexes of mid
    and high-dosage groups during the first 52 weeks. Weekly water
    consumption, monitored between weeks 102 and 109, was unaffected.
    Haematology, blood chemistry and urinalysis performed at the end of
    weeks 52 and 109 revealed a decrease of erythrocyte, haematocrit and
    haemoglobin values in males of two high-dosage groups and in females
    of the top-dosage group after 52 weeks. Assay of cholinesterase in
    erythrocytes, serum and brain, conducted at termination only,
    indicated dose-related depression of serum cholinesterase by 71-93
    percent and of brain cholinesterase by 30-65 percent in all treated
    groups (both sexes). Erythrocyte cholinesterase was not inhibited.
    Organ weights analysed at 52-week interim sacrifice and at terminal
    sacrifice showed deviations from controls for a number of tissues,
    such as spleen, liver, kidney and testis, but these were essentially
    limited to the top-dosage level and were not accompanied by
    microscopic lesions. Gross pathologic alterations were not
    significantly different from those in the controls.
    Histopathologically, male terminal survivors at the top-dosage level
    exhibited an increased incidence of "scleral mineralization" of the
    eye. Microscopic lesions that might be attributable to the compound
    were not evident in the other tissues examined.

    An evaluation of tumour data indicated the only notable finding as a
    statistically significant increase in incidence of thyroid C-cell
    adenoma in male terminal survivors at the top-dosage level. Thus,
    incidence of the tumour was 2/34 (5.9 percent), 3/31 (9.7 percent),
    1/29 (3.5 percent), 9/33 (27.3 percent), respectively, in control,
    low-, mid and high-dosage groups. (Calculated as No. of terminal
    survivors bearing the tumour/ No. of terminal survivors examined
    histopathologically). Only one additional case of C-cell adenoma of
    the thyroid occurred among male rats in the study. It was present in
    one male of the top-dosage group, which died or was sacrificed in
    moribund condition during the study. Data on background incidence of
    the tumour in question were not submitted. There was no significant
    difference between control and treated groups in the incidence of
    animals with tumours (benign and/or malignant), malignant tumours or
    multiple primary tumours. It may be noted that interstitial cell
    adenoma of the testis in males and pituitary adenoma in females were
    the most frequently observed spontaneous tumours in the study, with

    nearly 90 percent of males and over 50 percent of females,
    respectively, in the concurrent control group being affected by such
    tumours (Barnett et al. 1983).

    COMMENTS

    A limited excretion and elimination study in the rat identified 
    O-ethyl S-propyl phosphorothioate as a major metabolite in the urine.

    Ethoprophos is acutely toxic to rats, mice and rabbits with the oral
    LD50 ranging from 30 to 60 mg/kg b.w.

    A three generation reproduction study in rats demonstrated no adverse
    reproductive effects at a dietary level of 60.5 ppm. Teratology
    studies in rats and rabbits were negative for teratogenic effects at
    0.16 mg/kg b.w. and 2 mg/kg b.w. respectively. The mutagenicity
    studies available, including unscheduled DNA synthesis in primary rat
    hepatocytes, a mouse lymphoma assay and an in vivo cytogenetic study
    in rats, were negative. A 109-week oncogenicity study in rats showed
    an increased incidence of thyroid C-cell adenomas in surviving 
    high-dose males. Compound-related cholinesterase inhibition was
    evident in all dose groups for both plasma aud brain enzymes.
    Erythrocyte cholinesterase was not affected. A no-effect level (NOEL)
    was not demonstrated in this study.

    A delayed neurotoxicity study in hens was inadequate.

    A short-term study in rats did not demonstrate a NOEL since
    cholinesterase levels were depressed in all treatment groups. A 90-day
    dog study demonstrated no adverse effects on cholinesterase at 1 ppm.

    The Meeting could not estimate an acceptable daily intake because the
    data were inadequate.

    REFERENCES - TOXICOLOGY

    Barnett, J.W., Jr.,          Evaluation of the chronic toxicity and
    Jenkins, L.J. & Parent, R.A. oncogenic potential of ethoprop in
    1983                         Fischer 344 rats. Report from Gulf South
                                 Research Institute submitted to WHO by 
                                 Rhône-Poulenc Agrochimie. (Unpublished)

    Becker, J. & Parke,          A primary dermal irritation study of
    G. St. E. 1977               ethoprop 93% technical grade on abraded
                                 and nonabraded skin of New Zealand
                                 albino rabbits. Report from Cannon
                                 Laboratories, Inc. submitted to WHO by
                                 Rhône-Poulenc Agrochimie. (Unpublished)

    Ellison, T.                  A comparative dermal toxicity evaluation
    1979                         in mice (Ethoprop and nine chemical
                                 analogs). Report from Bio/dynamics
                                 Inc. submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Fletcher, M.J.,              Evaluation of effects of ethoprop on
    Springer, S.T.,              reproductive performance by a three-
    D'Addamio, G.H., Conzeln &   generation reproduction study in Fischer
    Pullin, T.G.                 344 rats. Report from Gulf South
    1981                         Research Institute submitted to WHO by
                                 Rhône-Poulenc Agrochimie. (Unpublished)

    Hazleton Laboratories        V-C 9-104 (Technical grade) Acute oral
    1965                         administration - Rats. Acute dermal
                                 application - rabbits. Report from
                                 Hazleton Laboratories, Inc. submitted to
                                 WHO by Rhône-Poulenc Agrochimie.
                                 (Unpublished)

    Iqbal, Z.M. & Menzer, R.E.   Metabolism of O-ethyl S, S-dipropyl
    1972                         phosphorodithioate in rats and liver
                                 microsomal systems. Biochem. Pharmacol.
                                 21: 1569-1584.

    Knickerbocker, M. & Re, T.A. Teratologic evaluation of ethoprop MCTR-
    1979                         603-78 in Sprague-Dowley rats. Report
                                 from Food & Drug Research Laboratories,
                                 Inc. submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Kopp, R., Gunzel, P.,        Acute inhalation toxicity to the rat
    Rosskamp, G., Schmidt, M. &  (M&F) of liquid ethoprophos following
    Schuppler, J.                single 4 hours continuous exposure
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                                 submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Myhr, B.C. & Brusick, D.J.   Evaluation of MOBIL No. 01238101 in the
    1981                         primary rat hepatocyte unscheduled DNA
                                 synthesis assay. Report from Litton
                                 Bionetics, Inc. submitted to WHO by
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    Pasquet, J. & Mazuret, A.    Ethoprop (46 095 R.P.). Toxicite aigue
    1982                         approchee chez la souris par voie orale
                                 et le rat par voie percutanee.
                                 Report from Rhône-Poulenc submitted to
                                 WHO by Rhône-Poulenc Agrochimie.
                                 (Unpublished)

    Rucci, G.                    EthopropR technical grade: MCTR-60-78,
    1979                         Approximate acute dermal toxicity (LD50)
                                 in young Yorkshire White pups. Report
                                 from Food and Drug Research
                                 Laboratories, Inc. submitted to WHO by
                                 Rhône-Poulenc Agrochimie. (Unpublished)

    Schwartz, C.S.               Acute oral LD50 determination of ethoprop
    1978                         in female New Zealand White rabbits.
                                 Letter report to Mobil Oil Company
                                 submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Skinner, M.J., Irwin, S.E.,  Metaphase analysis of rat bone marrow
    Schreiner, C.A.,             cells treated with ethoprop, technical.
    Mackerer, C.R. &             Report from Mobil Environmental & Health
    Mehlman, M.A.                Science Laboratory submitted to WHO
    1981                         by Rhône-Poulenc Agrochimie.
                                 (Unpublished)

    Thomson, M.A.,               A murine lymphoma mutagenesis assay,
    Blackburn, G.R. &            heterozygous at at the thymidine kinase
    Mackerer, C.R.               locus for the determination of the
    1981                         potential mutagenicity of ethoprop.
                                 Report from Mobil Environmental & Health
                                 Science Laboratory submitted to WHO by
                                 Rhône-Poulenc Agrochimie. (Unpublished)

    Weir, R.J. & Murphy, J.C.    Neurotoxity test - hens. Technical VC 
    1967                         9-104. Final report from Hazleton
                                 Laboratories Inc. U.S.A. submitted
                                 to WHO by Rhône-Poulenc Agrochimie.
                                 (Unpublished)

    Weir, R.J.                   Acute eye application - rabbits. V-C
    1965                         9-104 (technical grade). Final report
                                 from Hazleton Laboratories Inc.
                                 submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Weir, R.J.                   Three-month dietary administration -
    1967 a                       rats. Technical VC9-104. (Mocap). Report
                                 from Hazleton Laboratories Inc,
                                 submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Weir, R.J.                   13-week dietary administration - dogs.
    1967b                        Technical VC9-104. Unpublished report
                                 from Hazleton Laboratories, Inc.
                                 submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)

    Wolfe, G.W., Durloo, R.S. &  Rabbit teratology study. Ethoprop
    Phipps, R.B.                 Technical - 01238101. Final report
    1981                         from Hazleton Laboratories America, Inc.
                                 submitted to WHO by Rhône-Poulenc
                                 Agrochimie. (Unpublished)



    See Also:
       Toxicological Abbreviations
       Ethoprophos (ICSC)
       Ethoprophos (Pesticide residues in food: 1984 evaluations)
       Ethoprophos (Pesticide residues in food: 1987 evaluations Part II Toxicology)
       Ethoprophos (JMPR Evaluations 1999 Part II Toxicological)