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    PESTICIDE RESIDUES IN FOOD - 1984


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1984




    The monographs



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

    Food and Agriculture Organization of the United Nations
    Rome 1985

    ACEPHATE

    Explanation

         Acephate was evaluated by the Joint Meeting of the FAO Panel of
    Experts (JMPR) in 1976 (FAO/WHO, 1977) at which time an ADI was
    established, based on no-effect levels taken exclusively from IBT
    studies. Additional data were evaluated by the 1982 JMPR (FAO/WHO,
    1983) that changed the ADI to a temporary status, as relevant studies
    from IBT were found to be invalid. Studies required were a
    multigeneration reproduction study, a delayed neurotoxicity study, and
    individual animal data from the 28-month toxicity/carcinogenicity rat
    study. Some of these data have been made available and are summarized
    in the following monograph addendum.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, Distribution and Excretion

         Two male Sprague-Dawley rats received dermally a single treatment
    with S-methyl-14C-Acephate at level of 10 mg/kg bw. Blood and urine
    were collected at regular intervals and assayed for total 14C. 
    Acephate and its major metabolite (methamidophos) were also determined
    in the urine. The 14C-dose was rapidly absorbed into the blood, with
    the maximum concentration occurring at one to three hours. The 14C
    content of the blood then decreased with time and a secondary peak was
    observed at 48 h.

         The excretion profile of acephate in the urine is similar to the
    14C absorption profile into the blood. The maximum concentration of
    acephate occurred at six and 24 h for the two rats. After three days,
    approximately 35 percent of the 14C dose was excreted in the urine.
    Approximately 30 percent of the dermal treatment was excreted as
    unchanged acephate and 1 percent as methamidophos. The amount of the
    dose left on the treated area of the rats was not determined (Tucker,
    1974).

    Effects on Enzymes and other Biochemical Parameters

         The in vitro inhibitory activity (I50) of acephate technical
    on brain and RBC acetylcholinesterase (AChE) and plasma cholinesterase
    (ChE) was determined for the rat, monkey and human. The I50 for
    acephate was between 1  10-3 M and 5  10-3 M for all enzyme
    sources. Acephate was approximately 100 000 times less effective than
    eserine (positive control) as an inhibitor of AChE and 10 000 times
    less effective as an inhibitor of ChE. The inhibitory effect of
    acephate was more effective against rat brain and RBC AChE than
    against monkey and human brain. For plasma ChE, the I50 value was
    lower for the monkey and human than for the rat. For humans, the
    inhibitory activity (I50) was in the order: plasma > RBC > brain
    (Bennett & Morimoto, 1982).

                                                                      

                                     I50 VALUES
                   Brain             RBC AChE          Plasma
                                                                      

    Rat            1.6 x 10-3 M      1.3 x 10-3 M      4.5 x 10-3 M

    Monkey         3.4 x 10-3 M      2.7 x 10-3 M      2.3 x 10-3 M

    Human          5.4 x 10-3 M      2.7 x 10-3 M      1.8 x 10-3 M
                                                                      

    TOXICOLOGICAL STUDIES

    Special Studies on Reproduction

    Rat

         Groups of six-week-old SPF-CD rats (12 males and 24 females per
    group) were fed diets containing Acephate (technical, 92.8 percent
    purity) at levels of 0, 50, 150, or 500 ppm until they were 21 weeks
    old. At that time they were mated (one male to two females) to start a
    two-generation (one litter per generation) reproduction study. Diets
    were maintained during mating, gestation, and lactation.

         F1 offspring were weaned at three weeks of age, at which time 12
    males and 24 females per group were selected to form the basis of F1
    generation. The remaining offspring and all F0 parents were
    sacrificed. The selected animals were reared on their respective diets
    and mated at 21 weeks of age to produce the F2 generation.

         For parent animals, observations included regular inspection and
    regular recording of body weight, food consumption, and food
    conversion. Sample checks on water consumption were made, and breeding
    performance was monitored. Litter values were recorded and at
    termination all animals were subjected to macroscopic post-mortem 
    examination. More detailed macroscopic and microscopic examinations
    were made on all F1 males; some F1 females failing to produce live
    young; the majority of F1 females bearing live young; and a small
    sample (five males and five females per group) of F1 and F2 weanlings.
    The F1 adults selected for microscopic examinations were also
    subjected to organ weight analysis.

         Significantly reduced water consumption was recorded at 500 ppm
    for both sexes of F0 and F1 generations and at 150 ppm for F0 females.
    Food consumption and food conversion were unaffected by treatment.
    Overall body weight changes were variably affected but no consistent
    dose-related effects. However, [illegible text] demonstrated decreased
    body [illegible text] during lactation. Pregnancy rate for all F0
    generation dose groups, including control, was low. Pregnancy rate for
    F1 generation was decreased at 50 and 500 ppm, and only slightly at
    150 ppm. Duration of gestation was unaffected by treatment.

         There were no effects on organ weights, macroscopic or
    microscopic changes related to treatment.

         For both generations viable litter size of all test groups was
    lower than that of controls, with initial differences at birth
    maintained or enhanced during lactation. The difference was
    statistically different only for the 150 and 500 ppm groups.

         There were slightly lower litter weights in test groups at birth,
    enhanced during lactation, such that by day 21 post partum a
    significant dosage-related trend for reduced litter weight was evident
    for both generations. Intergroup differences from controls was
    statistically significant at 150 and 500 ppm in both generations.
    Histopathological examination of weanlings was unremarkable.

         Dietary concentrations of 150 and 500 ppm acephate adversely
    affected reproductive performance and rearing of offspring during
    lactation. As many effects were also observed at 50 ppm. A clear
    no-effect level was not determined (Palmer, et al. 1983).

    Special Studies on Mutagenicity

         See Table 1.

    Mouse

         Groups of CD-1 mice (75 males and 75 females/group) were given
    diets containing acephate (purity not reported) at levels of 0, 50,
    250, or 1 000 ppm for 104 weeks. The mice were observed daily for
    signs of toxicity, moribundity and mortality. Detailed observations
    were recorded weekly. Individual body weights and food consumption
    values were recorded weekly for the first eight weeks of study and
    monthly thereafter. Haematology was conducted on ten mice/sex/group at
    study termination. An interim sacrifice of ten mice/sex/group was
    conducted at 12 months of study.

         No compound- or dose-related changes in appearance, behaviour, or
    mortality were noted. Group mean body weights and average food
    consumptions were decreased for the 250 and 1 000 ppm mice when
    compared to the controls. No changes were seen in the haematological
    parameters. No compound-related gross necropsy lesions were observed
    for mice that died during the first 12 months of study. However, lung
    foci were observed grossly and alveolar macrophages identified
    microscopically at the 12-month interim sacrifice in the high dose
    group. At 12 months there were also microscopically visible
    compound-related liver hypertrophy and pigmented macrophages present
    among the high-dose males and females.


        TABLE 1.  Special Studies on Mutagenicity

                                                                                                          

    Test Organism                 Test Substance          Result                             Reference
                                                                                                          

    GENE MUTATION STUDIES

    Bacteria

    S. thyphimurium               Acephate techn.         -TA100: 7 samples weakly           Bullock,
                                  (eight samples)         mutagenic without metabolic        Carver &
                                                          activation in the range            Wong
                                                          2-50 mg/plate, one sample          1982a
                                                          negative without metabolic
                                                          activation in the range
                                                          0.01-50 mg/plate;
                                                          -TA98 and TA1537:4 samples
                                                          tested were not mutagenic
                                                          without metabolic activation
                                                          in the range 10-50 mg/plate.

                                  Acephate techn.         -TA100:5 samples weakly            Bullock,
                                  (six samples)           mutagenic without metabolic        Carver &
                                                          activation in the range 2-50       Wong
                                                          mg/plate; 1 sample inconclusive.   1982b

                                  Acephate techn.         -Very weakly mutagenic to          Simmon
                                  (93.5% purity)          TA100 at doses above 2.5           1979
                                                          mg/plate, with and without
                                                          metabolic activation.

                                  Acephate                -Positive TA100 without            Moriya,
                                                          metabolic activation at            et al.
                                                          concentration of 5 mg/plate        1983
                                                          and higher; Negative TA1535,
                                                          TA1537, TA1538, TA98.
                                                                                                          

    TABLE 1.  (continued)

                                                                                                          

    Test Organism                 Test Substance          Result                             Reference
                                                                                                          

    E.coli WP2 her                Acephate                -Positive                          Moriya, et al.
                                                                                             1983

    E.coli WP2                    Acephate techn.         -No significant increase of        Simmon
                                  (93.5% purity)          revertants, with and without       1979
                                                          activation, at doses up to
                                                          10 mg/plate.

    Yeasts and Fungi

    S. cerevisiae D3              Acephate techn.         -Increased mitotic recombination   Simmon
                                  (93.5% purity)          with and without metabolic         1979
                                                          activation, at concentrations
                                                          of 1 to 5%.

    S. cerevisiae D7              Acephate techn.         -Induction of mitotic crossing     Mortelmans,
                                  (93.5% purity)          over and gene conversion in        Riccio &
                                                          the 3 to 5% range, with and        Shepherd
                                                          without metabolic activation.      1980

    CHROMOSOMAL EFFECTS

    Cytogenetics-In Vitro
    Mouse Lymphoma                Acephate                -Dose-related increase in          Kirby
    L5178Y Cells                  (98.7% purity)          mutation frequency both with       1982a
                                                          and without metabolic activation
                                                          at TK+/-locus, in the range
                                                          500-5000 ug/ml.

                                  Acephate                -Dose-related increase in          Kirby
                                                          mutation frequency both with       1982b
                                                          and without metabolic activation
                                                          at TK+/-locus, in the range
                                                          500-5000 ug/ml.
                                                                                                          

    TABLE 1.  (continued)

                                                                                                          

    Test Organism                 Test Substance          Result                             Reference
                                                                                                          

                                                          -Dose-related increase in          Jotz &
                                                          mutation frequency both with       Mitchell
                                                          and without metabolic activation   1980
                                                          at TK+/-locus, in the range
                                                          1000-5000 ug/ml.

    Chinese Hamster               Acephate                -Dose-related increase of          Evans &
    ovary cells                                           Sister Chromatid Exchange,         Mitchell
    in vitro                                              with and without metabolic         1980
                                                          activation at concentrations
                                                          of 125-2000 ug/ml.

    Cytogenetics-In Vivo
    Mouse Bone                    Acephate                -Negative for Chromosomal          Esber
    Marrow                        (98.7% purity)          aberrations at doses of            1982
                                                          11.2-112 mg/kg bw.

                                  Acephate                -Negative for Sister Chromatid     Cimino &
                                  (98.7% purity)          Exchange (some cell cycle          Brusick
                                                          delay) at doses of 29-96 mg/       1983
                                                          kg bw.

    Monkey                        Acephate                -Negative for Chromosomal          Cummins
    Lymphocytes                   (98.7% purity)          aberrations and Sister             1983
                                                          Chromatid Exchange at dose
                                                          of 2.5 mg/kg bw/day.

    Micronucleus Test
    Mouse                         Acephate                -No increase of incidence of       Kirkhart
                                                          micronucleated polychromatic       1980
                                                          erythrocytes at doses of 75-300
                                                          mg/kg bw.
                                                                                                          

    TABLE 1.  (continued)

                                                                                                          

    Test Organism                 Test Substance          Result                             Reference
                                                                                                          

    Dominant Lethal
    Mouse                         Acephate                -Negative at dose of 50-500        Eisenlord
                                  (99%)                   mg/kg in the diet.                 1982

    DNA damaqe and repair
    Unscheduled DNA               Acephate                -Increase without metabolic
    synthesis                     (93.5% purity)          activation at doses of 1 mg/kg
    WI - 38 cells                                         and higher. Doubtful result
                                                          with metabolic activation.

    Differential toxicity
    S. typhimurium                Acephate                -Negative                          Mortelmans
    SL4525(rec+)-                 (93.5% purity)                                             & Riccio
    SL4700(rec-)                                                                             1981

    S. typhimurium                Acephate                -Negative                          Mortelmans
    TA1978(UVrB+)-                (93.5% purity)                                             & Riccio
    TA1538(UVrB-)                                                                            1981
                                                                                                          


    Special Studies on Carcinogenicity
    (See also under long-term studies)
    

         At terminal autopsy a dose-related increase of lung foci was
    macroscopically observed in males at 250 and 1 000 ppm, and in females
    of all the treated groups (6, 24, 53 and 73 percent for control, 50,
    250 and 1 000 ppm groups, respectively). Liver masses or hyperplastic
    nodules were present in 64.7 percent of the high-dose females, but
    were not significantly different from controls in the other two
    groups. In males, the incidence of liver masses or nodules were
    comparable in all groups. At terminal sacrifice there was a
    statistically significant increase in the mean relative weight of
    liver, ovaries and brain of high-dose females, and testes and brain of
    high-dose males.

         At the terminal sacrifice, an increased incidence of hyperplastic
    nodules and hepatocellular carcinoma was microscopically observed only
    in the livers of the high-dose females when compared to controls.
    Hepatocyte hypertrophy, nuclear enlargement (karyomegaly) and
    intranuclear inclusion bodies were increased only in the two 
    highest-dose groups (both males and females) in a dose-related manner.
    Mononuclear inflammatory cell foci were increased in treated groups of
    males in a dose-related manner.

         Lung lesions included alveolar hyalinosis and dark-pigmented
    alveolar macrophages which were increased in all treated groups in a
    dose-related manner, while eosinophilic foreign bodies were increased
    only in the highest-dose groups (both males and females). Increased
    incidence of acute rhinitis was also observed in all treated groups in
    a dose-related manner.

         Dark pigment in the reticuloendothelial cells of mediastinal
    lymph nodes was observed to be increased and dose-related in all male
    treated groups and in the females at the two highest doses. Incidence
    of neoplastic lesions was comparable with respect to type and site
    among all groups, except for the increase of hepatocellular carcinomas
    in high-dose females (Geil & Richtter, 1981).

    Special Studies on Skin Sensitization

         Twenty male Hartley albino guinea-pigs received dermal
    applications of Acephate at the concentration of 35 percent w/w in
    saline solution which was previously determined to be the maximum
    non-irritant concentration. The positive control material,
    1-chloro-2,4-dinitrotoluene 0.1% w/w in saline solution, and the
    saline vehicle were similarly each tested in ten male guinea-pigs. The
    induction phase of the study consisted of ten repeated topical
    applications, 0.4 ml of the test solution, on alternate days over a
    22-day period. Fourteen days following the tenth induction
    application, the test animals were challenged by applying the
    respective test material.

         Very slight to well-defined irritation was observed after the
    last induction application. No sensitization responses were observed
    either for the animals challenged with Acephate or for the vehicle
    control animals (Silveira, 1982).

    Toxicity

         See Table 2.

    TABLE 2.  Acute Toxicity of Acephate

                                                                                                  

    Animal         Sex        Route       Compound       LD50             Reference
                                          Purity
                                                                                              

    Rat            M+F        oral        98.7%          1.3-0.93         Duke,1982
                                                         g/kg bw

    Mouse          M          oral        98.7%          403              Esber,
                   F          oral        98.7%          323              1982
                                                         g/kg bw
                                                                                              
    
    Special Studies on Antidotes

         The LD50 values for groups of male and female Sprague-Dawley rats
    treated with atropine sulphate (10 mg/kg bw) 15 minutes following oral
    dosing with technical Acephate, were 4.2 and 6.6 times higher,
    respectively, than the LD50 of groups receiving no antidote.
    Similarly, the LD50 of groups of male and female Sprague-Dawley rats
    treated with pralidoxime chloride (2-PAM) (50 mg/kg bw/i.m.) 15
    minutes following oral dosing with Acephate technical, were each 2.9
    times higher than the LD50 of groups receiving no antidote (Duke,
    1982).

    Short-Term Studies

    Monkey - oral

         Two male and two female cynomolgus monkeys (Macaca
    fascicularis) received technical Acephate (98.7 percent pure) by
    oral gavage at doses of 0 or 2.5 mg/kg bw/day for up to 34 consecutive
    days (33 days for males, 34 days for females).

         No noteworthy differences between groups were observed with
    respect to clinical signs, food and water consumption, body weight
    changes, physical examination, haematology, blood chemistry (except
    cholinesterase activity), urinalysis, organ weights or macroscopic
    pathology at terminal autopsy.

         Cholinesterase activities were assayed in red blood cells and
    plasma every two days and in brain at sacrifice. Erythrocyte acetyl-
    and plasma acetyl- and butyrylcholinesterase activities were depressed
    in all treated monkeys compared to control animals. Maximum inhibition
    was observed after approximately six days for plasma cholinesterases
    and 14 days for erythrocyte cholinesterase.

         Mean inhibition (relative to mean pre-treatment values) of 42
    percent (males) and 43 percent (females) was recorded for plasma
    acetylcholinesterase activity and 37 percent (males) and 40 percent
    (females) for plasma butyrylcholinesterase activity during days 6 to
    34. Mean inhibition of 53 percent (males) and 47 percent (females) for
    erythrocyte acetylcholinesterase activity was recorded during days 14
    to 34. No erythrocyte butyrylcholinesterase activity was detected in
    treated or control animals. There was no relevant difference in the
    pattern of inhibition between plasma acetyl and butyryl activity or
    between sexes for each cholinesterase parameter.

         Brain cholinesterase activity after four weeks of treatment was
    lower in all treated animals compared to controls. Compared to
    contemporaneous control values treated animals showed mean
    inhibition of 16 percent (males) and 32 percent (females) for
    butyrylcholinesterase activity and 50 percent (males) and 43 percent
    (females) for acetylcholinesterase activity. Thus, brain
    cholinesterase inhibition was similar to (acetylcholinesterase) or
    less marked than (butyrylcholinesterase) that recorded for blood.
    These levels of cholinesterase inhibition were without any visible
    cholinergic signs (Cummins, 1983).

    Long-Term Studies

    (see also under Special Studies on Carcinogenicity)

    Rat

         Groups of Sprague-Dawley CD rats (75 males and 75 females per
    group) received Acephate technical (92.4 percent purity) in the diet
    at dose levels of 0, 5, 50, and 700 ppm for 28 months. Interim
    sacrifices were performed on ten animals/sex/group at four and 12
    months and on four or five sex/group at 22 months. Physical
    observations for signs of toxic or pharmacological effects and
    palpations for tissue masses were performed weekly throughout the
    study. Body weights and food consumption were monitored and clinical
    laboratory evaluations (haematology, clinical chemistry,
    cholinesterase activity, and urinalysis) were performed periodically
    on ten animals/sex/group. Ophthalmoscopic examinations were performed
    periodically on all animals. Complete gross post-mortem examinations
    were conducted on all animals and microscopic examinations were
    performed on all tissues from control and high-dose animals and on
    gross lesions, tissue masses, eyes and adrenals from low- and mid-dose
    animals. Organ weights were recorded at interim and terminal
    necropsies, and organ/body weight ratios were calculated.

         Evaluation of mortality, physical observations, haematology,
    clinical chemistry (except cholinesterase activity), and urinalysis
    revealed no significant differences between control and treated
    animals, which were considered compound-related. A slight, transient
    increase in the incidence of aggressive behaviour and/or increased
    activity occurred in high-dose animals during the first six months.

         Body weights of high-dose males were significantly lower
    (4-18 percent) than those of control males throughout the study. Also,
    the feed efficiency in high-dose males was significantly lower than in
    control males.

         Although the ophthalmoscopic examinations revealed a variety of
    abnormalities more frequently in treated than in control animals, they
    were not considered compound-related, due to the infectious or
    traumatic origin and the unilateral nature of many of the
    observations.

         Plasma and erythrocyte cholinesterase activities were
    significantly lower than control activities at most intervals for
    high-dose males and females. Mean plasma and erythrocyte
    cholinesterase activity ranged from 28 to 90 percent and 31 to 79
    percent of control activity, respectively, for high-dose animals and
    62 to 106 percent and 58 to 111 percent of control activity for
    mid-dose animals. No statistically significant decreases in plasma and
    erythrocyte cholinesterase activity occurred in low-dose animals. Mean
    brain cholinesterase activity of mid- and high-dose (but not low-dose)
    animals was significantly lower than control activity at all intervals
    (17 to 34 percent of control in high-dose animals and 55 to 67 percent
    in mid-dose animals). Statistically significant differences in organ
    weights and organ/body weight ratios occurred sporadically in mid- and
    high-dose animals with no consistent dose-related pattern.

         Grossly observable abnormalities were most common in the lung,
    liver, kidneys, pituitary glands and subcutaneous tissue, but there
    was no significant difference in the incidence between control and
    treated groups. Microscopically various non-neoplastic lesions were
    observed in most of the organs, lungs and kidney being most frequently
    affected. The incidence of these lesions does not indicate a
    treatment-related effect. Various neoplasms were observed in different
    organs and tissues examined microscopically. Based on these
    examinations, the number of neoplasm-free animals, the number of
    animals with benign neoplasms only and the number of animals with
    malignant neoplasms were similar among groups. Neoplasms most commonly
    observed were those of the pituitary gland. They were more frequent in
    female rats of all groups compared to males. There was no significant
    difference in the number of pituitary neoplasms between treated and
    control groups. Mammary gland neoplasm represented the second largest
    group; the incidence was 33/75 in control females compared to 43/73 in
    the high-dose group. The incidence of neoplasm of adrenal medulla was
    increased in all males of the treated group; however, historical
    control data demonstrate the relatively low control value for the
    present study and the great variability in the incidence of this

    neoplasm. Statistical analysis of these data was inconclusive. The
    incidence of thyroid gland neoplasm, though slightly increased in the
    high-dose group of both male and female rats when compared to
    controls, was below the mean value of the laboratory's historical
    control groups.

         The 5 ppm dose-level (equal to 0.2-0.6 mg/kg bw/day) may be
    considered the no-effect level for the parameters investigated
    (Auletta & Hogan, 1981).

    COMMENTS

         Acephate was first evaluated by the JMPR in 1976 and most
    recently re-evaluated in 1982, when invalid IBT studies and
    consideration of additional data caused the ADI to be changed to a
    temporary ADI with requirements for a multigeneration reproduction
    study, a delayed neurotoxicity study and data for individual animals
    in the 28-month rat toxicity/carcinogenicity study.

         A two-generation, one-litter-per-generation study showed that
    Acephate adversely affected reproduction and neonatal weight gain
    during lactation, but it was considered to be an inadequate study
    (JMPR report, 1982). The 28-month rat toxicity study showed no
    consistent biologically significant increased incidences of neoplasia,
    and mutagenicity tests were mostly negative. The previously requested
    delayed neurotoxicity study was not presented. In view of the
    inadequate multigeneration study and the lack of a delayed
    neurotoxicity study, only a temporary ADI, with a high safety factor,
    was allocated.

    Level Causing no Toxicological Effect

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

         Dog: 30 ppm in the diet, equivalent to 0.75 mg/kg bw.

    Estimate of Temporary Acceptable Daily Intake for Humans

         0 - 0.0005 mg/kg bw

    FURTHER WORK OR INFORMATION

    Required (by 1987):

         1.   An adequate multigeneration study, with two litters per
              generation.

         2.   An appropriate delayed neurotoxicity study.

    Desirable:

         Observations in humans.

    REFERENCES

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    1981      study with technical RE-12420 in rats. Report Project No.
              782135 from Big Dynamics Inc., New Jersey, submitted by
              Chevron, USA to WHO. (Unpublished)

    Bennett, E.L. & Morimoto. H. The comparative in vitro activity of
    1982      Acephate technical on brain, erythrocyte and plasma
              cholinesterases from the human, monkey, and rat. Chevron
              study S-2150 from University of California, submitted by
              Chevron, USA to WHO. (Unpublished)

    Bullock, C.H., Carver, J.H. & Wong, Z.A. Salmonella mammalian
    1982a     microsome mutagenicity test (Ames test) with eight samples
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              by Chevron, USA to WHO (Unpublished).

    Bullock, C.H., Carver, J.H., & Wong, Z.A. Salmonella mammalian
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              submitted by Chevron, USA to WHO. (Unpublished)

    Cimino, M.C., & Brusick, D.J. Mutagenicity Evaluation of Chevron
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    Duke, C.E. The efficacy of atropine sulfate and pralidoxime chloride
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    Esber, H.I. In vitro Cytogenetics study in mice. Acephate technical
    1982      (SX-1102). Report MRI-162-CCC-82-45 from EG and G/Mason
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              to WHO. (Unpublished)

    Eisenlord, G.H. Dominant lethal study of Acephate technical SX-1102.
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    Evans, E.L. & Mitchell A.D. An evaluation of the effect of Acephate on
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    Jotz, M.M. & Mitchell, A.D. An evaluation of mutagenic potential of
    1980      Acephate employing the L5178Y TK+/- mouse lymphoma assay.
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              Chevron, USA to WHO. (Unpublished)

    Kirby, P.E. L5178Y TK+/- mouse lymphoma mutagenesis assay with Chevron
    1982a     Acephate technical (SX-1102). Study No. T 1754.702 from
              Micro-biological Associates, Maryland, submitted by Chevron,
              USA to WHO. (Unpublished)

    Kirby, P.E. Mouse lymphomas mutagenesis assay with Chevron Acephate
    1982b     technical (SX-762). Study No. T 1753.702 from
              Microbiological Associates, Maryland, submitted by Chevron,
              USA to WHO. (Unpublished)

    Kirkhart, B. Micronucleus test on Acephate. Report from SRI
    1980      International, California, Project No. LSU-7558-19, EPA
              contract No. 68-02-2947, submitted by Chevron, USA to WHO.
              (Unpublished)

    Moriya, M., Ohta, T., Watanabe, K., Miyazawa, T., Kato, K., & Shirasu,
    1983      Y. Further mutagenic studies on pesticides in bacterial
              reversion assay systems. Mutat. Res. 116: 185-216.

    Mortelmans, K.E., Riccio, E.S., & Shepherd, G.F. In vitro detection of
    1980      mitotic crossing-over, mitotic gene conversion, and reverse
              mutation with S. Cerevisiae D7 for seven pesticides. Report
              from SRI International, California, Project No. LSU-7558-20,
              EPA contract No. 68-02-2947, submitted by Chevron, USA to
              WHO. (Unpublished)

    Mortelmans, K.E., & Riccio, E.S. Differential toxicity assays of
    1981      nineteen pesticides using Salmonella tiphimurium strains.
              Report from SRI International, California, Project No.
              LSU-7558-26, EPA Contract No. 68-02-2947, submitted by
              Chevron, USA to WHO. (Unpublished)

    Palmer, K.A., Barton, S.J., Offer, J.M., Gregson, R.L., Gibson, W.A. &
    1983      Almond, R.H. Effect of technical RE-12420 on reproductive
              function of multiple generations in the rat. Report CHR
              11/81957 from Huntingdon Research Centre, England, submitted
              by Chevron, USA to WHO. (Unpublished)

    Silveira, R.F. Modified BUEHLER test for the skin sensitization
    1982      potential of Chevron Acephate technical (SX-1102). Report
              Socal 1840 from Chevron Environmental Center, California,
              submitted by Chevron, USA to WHO. (Unpublished)

    Simmon, V.F. In vitro microbiological mutagenicity and unscheduled DNA
    1979      synthesis studies of eighteen pesticides. Report from SRI
              International, California, EPA publication 600/1-79-041
              submitted by Chevron, USA to WHO.

    Tucker, B.V. S-methyl-14C-Orthene. Dermal treatment of rats. Report
    1974      No. 721.11 from Chevron R. & D. Department, California,
              submitted by Chevron, USA to WHO. (Unpublished)


    See Also:
       Toxicological Abbreviations
       Acephate (ICSC)
       Acephate (Pesticide residues in food: 1976 evaluations)
       Acephate (Pesticide residues in food: 1979 evaluations)
       Acephate (Pesticide residues in food: 1981 evaluations)
       Acephate (Pesticide residues in food: 1982 evaluations)
       Acephate (Pesticide residues in food: 1984 evaluations)
       Acephate (Pesticide residues in food: 1987 evaluations Part II Toxicology)
       Acephate (Pesticide residues in food: 1988 evaluations Part II Toxicology)
       Acephate (Pesticide residues in food: 1990 evaluations Toxicology)
       Acephate (JMPR Evaluations 2002 Part II Toxicological)
       Acephate (JMPR Evaluations 2005 Part II Toxicological)