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    AGP:1970/M/12/1

    WHO/FOOD ADD/71.42

    1970 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD

    THE MONOGRAPHS

    Issued jointly by FAO and WHO

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Working Party of Experts and the WHO Expert
    Group on Pesticide Residues, which met in Rome, 9-16 November, 1970.

    FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

    WORLD HEALTH ORGANIZATION

    Rome, 1971

    2,4,5-T

    IDENTITY

    Chemical name

    2,4,5-trichlorophenoxyacetic acid

    Synonyms

    2,4,5-T Acid
    Weedone 2,4,5-T

    Structural formula

    CHEMICAL STRUCTURE 

    Other relevant chemical properties

    The pure acid is a white crystalline solid with a melting point of
    158C and a water solubility of 278 mg/l. It is soluble in acetone,
    ethanol and ether (Martin, 1968). The salts with alkali metals and
    amines are water soluble but insoluble in petroleum oils; esters are
    water insoluble but soluble in oils. The technical acid is stable and
    non-corrosive.

    Purity

    The technical acid has a melting point at approximately 150-151c. A
    typical production lot assayed 95+ percent
    2,4,5-trichlorophenoxyacetic acid, 2.9 percent
    dichloromethoxyphenoxyacetic acids, 0.6 percent related
    trichlorophenoxyacetic acid, 0.5 percent dichlorophenoxyacetic acids,
    0.4 percent bis-(2,4,5-trichlorophenoxy)-acetic acid and less than
    0.5 ppm 2,3,7,8-tetrachlorodibenzo-p-dioxin (Dow, 1970a). This last
    impurity, hereinafter referred to as the "dioxin", is a highly toxic
    potent chloracnegen and has been reported to be present in one sample
    of commercially produced 2,4,5-T at a level of approximately 27 ppm
    (Courtney et al., 1970a; Emerson et al., 1970).

    2,4,5-T is formulated for use as a herbicide in water soluble
    formulations of various amine salts (e.g. triethylamine) or as
    formulations of esters (e.g. iso-octyl) dispersible in oil and/or
    water.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

    The plasma half-life of an amine salt of 2,4,5-T has been reported to
    be approximately three hours in the rat, following the administration
    of a single dose of 100 mg/kg body-weight (Erne, 1966a). See also
    "Fate of residues, in animals".

    Mice were injected with a single dose of 100 mg/kg body-weight of
    2,4,5-T in dimethylsulfoxide solution. The animals were sacrificed at
    various intervals after injection and analyzed in toto for 2,4,5-T.
    The amounts recovered as percentage of the amount injected indicated
    decreasing levels at the following time intervals after dosing: at 0
    hours, 77.1 percent; at 16 hours, 56.9 percent and at 24 hours, 23.7
    percent (Zielinski and Fishbein, 1967).

    Effect on enzymes and other biochemical parameters

    As is the case with 2,4-D and other auxin herbicides, it appears that
    treatment of plants with 2,4,5-T may result in an increased nitrate
    formation and produce toxic effects in grazing animals (Way, 1969).
    See also the monograph on 2,4-D.

    TOXICOLOGICAL STUDIES

    Special studies on carcinogenicity

    Mouse

    Groups of 18 mice of each sex, from two hybrid strains, were given
    2,4,5-T acid from seven days of age for 18 months. The compound was
    given by gavage at 0 or 21.5 mg/kg body-weight until weaning, after
    which time 2,4,5-T was incorporated into the diet at 0 or 60 ppm.
    There was no significant increase in tumour incidence between the
    control and treated groups (Innes et al., 1969).

    Special studies on teratogenicity

    Mouse

    Two strains of pregnant mice received one or more of the following
    daily dose levels of 2,4,5-T: 0, 21.5, 46.4 or 113 mg/kg body-weight.
    The compound was administered subcutaneously in dimethyl sulfoxide
    solution or orally in honey on gestation days 6 to 14 or days 9 to 17
    or days 6 to 15 inclusive. A significant increase in cleft palate and
    cystic kidney was observed in the foetuses from the animals which were
    given 46.4 or 113 mg/kg on days 6 to 14 or 9 to 17 of gestation. In
    the group given 113 mg/kg orally, there was increased foetal
    mortality. The level of "dioxin" impurity in the sample of 2,4,5-T
    used was approximately 30 ppm; thus the animals received at 0, 0.6,

    1.4 or 3.4 g/kg of the "dioxin". The authors concluded that the
    sample of 2,4,5-T used was teratogenic and foetocidal in the two
    strains of mice when administered orally or subcutaneously throughout
    the period of organogenesis (Courtney et al., 1970a).

    Additional studies have been conducted with three strains of mice
    using (a) purified 2,4,5-T estimated to contain less than 0.1 ppm of
    the "dioxin", (b) commercially produced 2,4,5-T containing
    approximately 0.5 ppm of the "dioxin", (c) 2,4,5-T from a chemical
    supply house, (d) the sample of 2,4,5-T used in the previously
    described study and (e) pure "dioxin". The compounds were administered
    to pregnant mice by subcutaneous injection in dimethylsulfoxide on
    gestation days 6 to 15 inclusive (ten doses) unless otherwise noted.
    The doses of 2,4,5-T used were 50, 100, 113 or 150 mg/kg body-weight/
    day. The purified sample (a) was tested in one strain of mice at a
    level of 100 mg/kg/day only, when a significant increase over the
    controls of cleft palate and "kidney involvement" (not otherwise
    described) was observed. In the same strain of mice, the sample of
    commercial 2,4,5-T (b) gave no adverse effects at doses of 50 or 100
    mg/kg/day. At 150 mg/kg/day this sample, (b), resulted in a
    significant number of cleft palates and increased foetal mortality,
    but resulted in no "kidney involvement". In another strain of mice,
    the commercial samples of 2,4,5-T (b) and (c) were judged to have
    caused an increase in cleft palate at doses of 100 mg and 113
    mg/kg/day, respectively. There was no increased "kidney involvement"
    or foetal mortality from either sample. In the third strain of mice,
    100 mg/kg/day of commercial 2,4,5-T, (b), caused no significant
    increase in cleft palate or "kidney involvement", but there was an
    increase in foetal mortality. Pure "dioxin" at doses of 1 or 3 ug/kg
    body-weight caused "kidney involvement" in all tests, but resulted in
    significant increases in cleft palates and foetal mortality only in
    some tests, not in others (Courtney at al., 1970b).

    Rat

    2,4,5-T containing approximately 30 ppm of the "dioxin" impurity was
    administered orally to one strain of rats at daily dose levels of 0,
    4.6, 10 or 46.4 mg/kg body-weight on gestation days 10 to 15
    inclusive. The lowest dose level of 4.6 mg/kg produced a significant
    increase in the percentage of abnormal litters or incidence of foetal
    mortality, The high dose levels produced a dose related incidence of
    increased foetal mortality and abnormal foetuses. Cystic kidney
    appeared to be the major manifestation of abnormality (Courtney et
    al., 1970a).

    Rats were administered various samples of the 2,4,5-T orally as
    follows: (a) "pure" at 150 mg/body-weight/day (days 13 to 14 only),
    (b) commercial production at 10, 21.5, 46.4 and 80 mg/kg/day, (d) the
    sample containing 30 ppm of the "dioxin" at 10 and 21.5 mg/kg/day. No
    terata were reported in any test. Increased foetal mortality resulted
    from the "pure" (a) sample at the 150 mg/kg/day dose given on days 13
    and 14 of gestation, and with the commercial production sample (b) at

    a dose of 80 mg/kg/day (LD40 dose for the dams). The sample (d) at
    the dose of 10 mg/kg/day gave an increase in "kidney involvement" that
    was statistically significant; however, there was no increase noted at
    the 21.5 mg/kg/day dose. Pure "dioxin" administered at 0.5 and 2 g/kg
    body-weight resulted in no terata or increase in foetal mortality, but
    both doses were judged to have resulted in significant increases in
    "kidney involvement" (Courtney at al., 1970b).

    Five treatment groups, each consisting of 25 female rats were
    administered 1, 3, 6, 12 or 24 mg/kg/body-weight/day of 2,4,5-T
    containing <1 ppm of the "dioxin" by gavage on gestation days 6
    through 15 inclusive. A single group of 50 females served as controls.
    The following studies were made: clinical observations, maternal
    body-weights (pre-breeding and day 20), number and position of
    foetuses and resorptions, number of corpora lutea, pup weight and
    sex, gross external examination of pups and microscopic examination
    for intestinal haemorrhage in pups. Representative stained histologic
    sections through the head, thorax and abdomen of ten control and ten
    foetuses from dams administered the high dose levels were studied for
    histopathologic changes. No clinical or gross pathologic signs of
    adverse chemical effect were observed in the treated dams. The other
    observations did not reveal any teratogenic or embryotoxic effects
    (Emerson at al., 1970).

    Pure "dioxin" was administered by gavage to rats at dose levels of 0,
    0.03, 0.125, 0.5, 2.0 and 8.0 g/kg body-weight/day to groups of 24
    (controls) and 12 (treatment) animals on gestation days 6 to 15
    inclusive. The foetuses were taken by caesarean section on day 20 of
    gestation.

    No differences were observed in the foetuses taken from dams treated
    at the dosage of 0.03 g/kg/day and the controls. At the 0.125
    g/kg/day dosage there was a slight decrease in average weight of
    foetuses, three dead foetuses, incidence of intestinal haemorrhage
    (18/127) and of subcutaneous oedema (22/80). One foetus at this level
    had a rudimentary tail. At the 0.5 ug/kg/day level, the number of
    foetuses was reduced and the number of resorptions and foetal deaths
    was increased to six. The average weight of the viable foetuses was
    slightly decreased. The incidence of intestinal haemorrhage (36/99)
    and subcutaneous oedema (31/65) was markedly increased over that seen
    in the 0.125 g/kg/day treatment. At the 2.0 g/kg/day level, only
    seven viable foetuses were obtained. These were from four of the 11
    litters examined. Resorptions were numerous, intestinal haemorrhage
    was frequent (4/7) and subcutaneous oedema was present in all of the
    four foetuses examined. One foetus from this treatment level was found
    to have a kinked tail and two of its feet were somewhat misshapen, but
    skeletal examination revealed no evidence of bone abnormalities. The
    8.0 g/kg/day dosage level proved to be toxic to the dams. There were
    no viable foetuses in the dams examined on day 20 of gestation. All
    resorptions occurred early, and no evidence of foetal tissue was
    found. Skeletal examinations of foetuses from all dams used in this

    experiment revealed delayed ossification of some sternebrae and skull
    bones. This manifestation occurred generally throughout the various
    groups, including controls (Sparschu et al., 1970).

    Rabbit

    Groups of 20 pregnant female rabbits each were given oral doses of
    2,4,5-T containing <1 ppm of the "dioxin" by capsule from gestation
    day 6 to 18 inclusive. The daily doses of 2,4,5-T administered were 0,
    10, 20 and 40 mg/kg body-weight. The rabbits ware artificially
    inseminated, and caesarean sections were performed on day 29. The
    following studies were made: clinical signs, maternal body-weight,
    conception rate, gross visceral examination, number of corpora lutea
    and implantations, number of kits, resorptions and still-births; kit
    weight and sex; gross external examinations; viability following
    24-hour incubation; detailed visceral and skeletal examination of kits
    from the control and 40 mg/kg groups. There were no dose-related
    trends evident from the results of these studies. A high incidence of
    neonatal mortality, which was not compound-related, was observed in
    the control and treated groups. a 40 mg/kg level dam aborted on day
    24; the litter was apparently completely resorbed, and bacterial focal
    hepatic necrosis was observed in the dam. This animal had started to
    lose weight prior to treatment with 2,4,5-T. It was concluded that
    under the conditions of the study, 2,4,5-T was not embryotoxic or
    teratogenic in rabbits when administered orally during the period of
    organogenesis (Emerson et al., 1970).

    Acute toxicity

                                                                  
                            LD50 mg/kg
    Animal         Route    body-weight    References
                                                                  

    Mouse          oral        389         Rowe and Hymas, 1954

    Rat            oral        500         Rowe and Hymas, 1954

    Guinea pig     oral        381         Rowe and Hymas, 1954

    Dog            oral       >100         Drill and Hiratzka, 1953
                                                                  

    In a study in pigs, to compare the acute toxicity of 2,4,5-T as
    compared to 2,4-D, it is reported that single doses of 100 mg/kg
    body-weight caused anorexia, vomiting, diarrhoea and ataxia only in
    the two pigs given 2,4,5-T. At autopsy, gastrointestinal irritation
    and congestion of the liver and kidney were observed (Bjrklund and
    Erne, 1966).

    Short-term studies

    Turkey

    Groups of male turkeys received 0.25 percent of an ester of 2,4,5-T in
    their diet for 11 days. Based upon the amount of food consumed, the
    birds received the equivalent of 62 mg/kg body-weight of the free
    2,4,5-T acid. There was no appreciable change in the rate of
    body-weight gain or in food consumption (Roberts and Rogers, 1957).

    Rat

    Groups of ten male and ten female rats per group were maintained for
    90 days on diets containing 2,4,5-T which had < 1 ppm of the "dioxin"
    impurity. The levels in the diet were adjusted so that the animals
    received 0, 3, 10, 30 or 100 mg/kg body-weight of 2,4,5-T daily.
    Visual observation revealed no changes in appearance or behaviour in
    any of the rats, nor were there any deaths. Evidence of
    compound-related effects was minimal and was limited to the animals
    given 30 and 100 mg/kg. Changes found in both sexes fed 100 mg/kg/day
    included depression in body-weight gain, slight decrease in food
    intake and elevated serum alkaline phosphatase levels. Gross necropsy
    examination revealed an inconsistent slight paleness and accentuated
    lobular pattern of the livers of some rats of both sexes at this dose
    level with inconsistent minimal amounts of hepatocellular swelling
    observed upon histopathologic examination. Male rats at this dose also
    had slightly increased serum glutamic-pyruvic transaminase levels and
    slight decreases in red cell counts and in haemoglobin. There were
    some detectable similar changes at 30 mg/kg/day, but these changes
    were considered to be of questionable toxicological significance. At
    doses of 3 or 10 mg/kg/day, there were no compound-related changes
    observed (Dow, 1970b).

    Groups of male and female rats (ten of each sex per group) were
    maintained for 90 days on diets containing 0, 100, 300, 1000 and 3000
    ppm of a standardized mixture of mono- di-, and tripropylene glycol
    butyl ether esters of 2,4,5-T (equivalent to 0, 6.2, 18.6, 62 and 186
    mg/kg body-weight of free acid). No evidence of adverse effects was
    noted at the 100 or 300 ppm levels, based on gross appearance and
    behaviour, mortality, food consumption, haematological indices and
    gross and microscopic examination of the tissues. Increase in
    spleen-weight in the males fed 100 and 300 ppm and increased
    body-weight of the females fed 100 ppm was considered to be unrelated
    to the administration of 2,4,5-T ester, and no pathological changes
    were observed. At the 1000 ppm level, histopathology revealed slight
    cloudy swelling of the parenchymal cells with central lobular necrosis
    in the liver in two of ten animals of both sexes examined, as well as
    some hypercellularity of the glomerular tuft, with cloudy swelling of
    the renal tubular epithelium in the females. There was significant
    increase in the average weight of the kidney in male rats at this
    level, but there were no differences compared to the control group

    with respect to all other above-mentioned parameters. At the 3000 ppm
    level, growth retardation was evident and kidney to body-weight ratios
    were increased in the males only. The livers of both sexes were large
    and light in colour and histopathology revealed a generalized cloudy
    swelling of the parenchymal cells and a slight central lobular
    necrosis. The kidneys displayed some cloudy swelling of the tubular
    epithelium, which was more marked in the females than the males. Some
    kidney necrosis was also evident in the females. Serum alkaline
    phosphatase was elevated in the males at this level (Dow, 1961).

    Dog

    2,4,5-T was administered orally in capsules to groups of from two to
    four adult mongrel dogs, of mixed sex, for five days a week over a
    13-week period. The levels administered were 0, 2, 5, 10 and 20 mg/kg
    body-weight/day. All dogs receiving 10 mg/kg or less survived the 90
    day test period. The dogs on 20 mg/kg/day died between days 11 and 75.
    There was no effect on haemoglobin; red cell, white cell or
    differential count of dogs that survived or died during the study, nor
    were there any changes in the organ weights among the dogs that
    survived the study. Histopathology revealed no significant changes in
    the heart, lungs, thyroid, ovaries, testes, adrenals, or liver.
    Duodenal hyperaemia in one dog at 10 mg/kg and one at 20 mg/kg was
    evident as well as early infiltration of the mucosal cells. An
    occasional slight increase in the number of casts in kidney sections
    was not dose-related and was considered to be of doubtful
    significance. (Drill and Hiratzka, 1953).

    Long-term studies

    No comprehensive long-term studies appear to have been conducted.

    OBSERVATIONS IN MAN

    The effect of work exposure to 2,4,5-T on the health of employees
    engaged in the manufacture of the herbicide has been studied. A total
    of 130 employees having a work experience from two months to over
    three years and range of exposure of 2 to 8 mg of 2,4,5-T per day were
    studied. The workers were given extensive physical examinations,
    including a battery of at least 20 laboratory tests. No differences
    were found between the groups of men exposed to 2,4,5-T and a control
    group of 4600 men. In addition, karyotyping was carried out on 52
    exposed men. There was no indication that 2,4,5-T exposure had
    affected the structural integrity or rearranged the genetic material
    of the lymphocyte chromosomes (Dow, 1970c).

    In workers employed in factories manufacturing chlorinated phenols, a
    moderately high incidence of urinary porphyria, chloracne and
    hirsutism has been reported. The authors suggest that a highly
    chlorinated phenolic ether may be the compound responsible (Bleiberg
    et al., 1964).

    Sporadic outbreaks of severe acne have been encountered in workers in
    chemical plants where 2,4,5-trichlorophenol is manufactured or used.
    It is stated that one of the agents responsible is
    2,3,7,8-tetrachlorodibenzo-p-dioxin (Anon, 1970).

    COMMENT

    Considerable information on the potential teratogenic effect of
    2,4,5-T of varying degrees of purity is available in mice, rats and
    rabbits. The evidence so far presented is inconclusive to determine
    whether the teratogenic effects shown in mice and to a lesser extent
    in rats are due solely to the presence of the impurity
    2,3,7,8-tetrachlorodibenzo-p-dioxin (called the "dioxin").
    Information from two independent laboratories appear to indicate some
    conflicting results with respect to teratogenicity.

    Thus, in one study with mice using a "pure" sample of 2,4,5-T (i.e.
    one alleged to contain <0.1 ppm of the "dioxin") foetal abnormalities
    were produced at the only level tested, which was 100 mg/kg
    body-weight. This level would be equivalent to receiving less than
    0.01 g/kg body-weight of the "dioxin". On the other hand, when 0.03
    g/kg of the "dioxin" alone was administered to pregnant rats, there
    were no terata produced, although abnormalities were evident at 0.125
    g/kg and higher levels of the "dioxin". In rabbit reproduction
    studies, using 2,4,5-T containing <1 ppm of the "dioxin", no terata
    were produced at any dose level, although foetal mortality was evident
    at 40 mg/kg body-weight.

    The need for further studies with respect to teratogenicity in several
    species, including, if possible, non-human primates was stressed. It
    was pointed out that there is no scientifically verifiable evidence
    that 2,4,5-T has caused teratogenic effects in man.

    Attention was drawn to the reported occurrence of chloracne and other
    unpleasant toxic effects encountered among some workers involved in
    the manufacture of 2,4,5-T and/or related compounds.

    The toxic effects reported to be due to increased nitrate formation in
    plants treated with 2,4,5-T were not considered to present a hazard to
    man under conditions of normal use of the compound.

    Because of the reported teratogenic effects, which may or may not be
    related to impurities in the samples of 2,4,5-T used, and because
    there are no comprehensive long-term feeding studies in any species
    (or a two-year feeding study in a non-rodent mammalian species), an
    acceptable daily intake for man could not be established. It was
    recognized that measurable levels of 2,4,5-T or its breakdown products
    could appear in food commodities (see following). In such cases, the
    establishment of an acceptable daily intake for 2,4,5-T will be
    necessary in assessing the problem of pesticide residues in food. It
    was stressed that in order to establish such a figure, a level causing

    no toxicological effect would have to be determined. It was further
    emphasized that indiscriminate use of 2,4,5-T should be discouraged.

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Control of certain weeds in cereal crops and lawns, spot control of
    nettles in pasture and used selectively in forestry for control of
    woody weeds. Used mainly on non-edible crops.

    FATE OF RESIDUES

    In animals

    Erne (1966 a and b) studied the distribution and elimination of
    2,4,5-T in farm animals; amine and alkali salts were readily absorbed
    and distributed in the body. The highest tissue levels were found in
    liver, kidney, spleen and lungs; the levels found in these organs
    exceeded levels found in plasma.

    St. John et al., (1964) studied the fate of 2,4,5-T in cattle; it was
    eliminated an soluble salts in the urine, and no residue was found in
    the milk. Urine and milk samples were analysed from cows fed 2,4,5-T
    over a period of four days; over 90 percent was recovered from the
    urine excreted over a period of six days.

    In plant

    After foliar application, 2,4,5-T, being a lipoid-soluble compound,
    seem to be limited to the phloem in its movement out of leaves, being
    accumulated in the more active metabolic region. Residual 2,4,5-T has
    been shown to persist on the leaf surface of apricots or at least one
    month following foliar application of 14C labelled 2,4,5-T (Maxie et
    al., 1956). No evidence was obtained for metabolism of 2,4,5-T in
    either leaves or fruits of apricots.

    Evidence of residues in food in commerce or at consumption

    Some unpublished data were presented (Boehringer Sohn, 1970) regarding
    residues of 2,4,5-T in cereals (grain and straw) found to occur
    following applications of the herbicide, either alone or in admixture
    with other phenoseyacid herbicides (recoprop, MCPA, 2,4-DP). A summary
    of the data relating to 2,4,5-T is given in Table I.

    TABLE I

    Residues of 2,4,5-T in cereals
                                                                   

                                Interval
                Rate of         (days)       Residues found, ppm
    Crop        Application     Applic.
                g/ha            Harvest      Grain       Straw
                                                                   

    Barley      120               64         0.04        0.80
                                  77         n.d.1       0.13
                                  89          -          0.06
                                 100          -          n.d.
                380               64         n.d.        0.30
                                  77         n.d.        0.12
                                  89          -          0.04
                                 100          -          n.d.
                520               64         0.04        0.40
                                  77         n.d.        0.10
                                  89          -          0.04
                                 100          -          n.d.

    Wheat       120               76         0.03        0.17
                                  89         0.025       0.09
                380               76         0.03        0.15
                                  89         0.02        0.11
                520               76         0.03        0.21
                                  89         0.02        0.11

    Oats        120               76         n.d.        0.20
                                  89         n.d.        n.d.
                380               76         n.d.        n.d.
                                  89         n.d.        n.d.
                520               76         n.d.        0.23
                                  89         n.d.        n.d.

    Rye         120               76         0.02        0.15
                                  89         n.d.        0.10
                380               76         0.02        0.15
                                  89         n.d.        0.08
                520               76         0.02        1.0
                                  89         n.d.        0.22
                                                                   

    1 n.d. = not detected

    METHODS OF RESIDUE ANALYSIS

    Residues of 2,4,5-T may be determined by suitable combinations of
    extraction, separation and end determination by ultraviolet
    spectrophotemetry, gas chromatography, paper and thin-layer
    chromatography and radiometric methods. Bradley and Thompson (1964)
    used GLC of the methyl esters after methylation with diazomethane.
    Gordon and Beroza (1952), after extraction and separation by partition
    chromatography, determined 2,4,5-T by spectrophotometry at 289 nm;
    this method may be used for alfalfa hay extracts. By use of paper and
    thin-layer chromatography for detection, separation and
    identification, Abbott et al. (1964) determined 2,4,5-T in soil and
    water. Hindin et al. (1964) analysed surface and ground water by paper
    chromatography and GLC. Edgerton and Lisk (1963) determined 2,4,5-T in
    applies by radio-isotopic and GLC methods. Clark (1969) determined
    2,4,5-T and its propylene glycol butyl ether esters in animal tissue,
    blood and urine. He converted to methyl esters and analysed by
    microcoulometric GLC; recoveries at 0.05 - 20 ppm levels of 2,4,5-T
    were 89.3 - 93.6% and of the ester 70.5 - 92.5%. Gas chromatography of
    the methyl ester of 2,4,5-T should be suitable as a procedure for
    regulatory purposes.

    NATIONAL TOLERANCES
                                                                       

    Country                  Crop                               Tolerance
                                                                (ppm)
                                                                       

    Netherlands              Vegetables (except                 0.1
                             potatoes), fruits of
                             vegetables, fruit crops.

    Fed. Repub. Germany      Leafy, other sprouting             0.01
                             vegetables, fruiting
                             vegetables, root
                             vegetables
                                                                       

    APPRAISAL

    2,4,5-T in a selective herbicide, mostly used for the control of woody
    weeds in non-edible crops, forestry, etc. There is a limited need in
    parts of Europe for its use in cereals, in admixtures with other
    phenoxyacid herbicides, for the control of certain weed species.
    Evidence regarding the residues that can accrue in grain and straw
    following such uses was provided. No evidence regarding the need to
    establish practical residue limits was apparent. Gas chromatographic
    methods are available which should be adaptable for regulatory
    purposes where required.

    When used an recommended for the limited use on some cereals, the
    following residues of 2,4,5-T can occur:

    Wheat, barley, oats, rye grain     0.05 ppm
    Wheat, barley, oats, rye straw     1  ppm

    FURTHER WORK OR INFORMATION

    REQUIRED (before an acceptable daily intake for man can be
             established)

    1. An adequate long-term oral study in order to establish a no-effect
       level using (i) a commercially available material, (ii) the purest
       available 2,4,5-T and (iii) 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    2. Studies on reproduction and teratogenicity with 2,4,5-T using (i) a
       commercially available material, (ii) the purest available 2,4,5-T 
       and (iii) 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    DESIRABLE

    Information on the availability of acceptable methods for the
    detection and determination of chlorinated dibenzodioxin impurities in
    technical 2,4,5-T and its formulations at the 0.01 - 0.05 ppm level.
    Current attempts to standardize the specifications of 2,4,5-T products
    in regard to their content of chlorinated dibenzodioxin compounds
    should be continued and encouraged.

    REFERENCES

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    Anon. (1970) Another herbicide on the blacklist. Nature, 226:
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    Bjorklund, N-E and Erne, K. (1966) Toxicological studies of 
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    Bleiberg, J., Wallen, M., Brodkin, R, and Applebaum, I.L, (1964)
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    Boehringer Sohn. (1970) Residues of 2,4,5-T in cereals and straw.
    Unpublished report

    Bradley, J.K. and Thompson, W.K. Determination of 2,4-D and 2,4,5-T in
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    Clark, D.E. (1969) Determination of 2,4,5-trichlorophenoxyacetic acid
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    and urine. J.Agr.Fd. Chem., 17: 1168-1170

    Courtney, K.D., Gaylor, D.W., Hogan, M.D., Falk, H.L., Baton, R.R. and
    Mitchell, I. (1970a) Teratogenic evaluation of 2,4,5-T. Science,
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    Courtney, K.D., Moore, J.A., Gaylor, D.W., Hogen, M.D. and Falk, H.L.
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    Dow (1961) Results of 90-day dietary feeding studies on Dowanol 97B
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    Dow (1970a) Assay of a commercial production lot of 2,4,5-T.
    Unpublished data, The Dow Chemical Company

    Dow (1970b) A 90-day dietary feeding study on 2,4,5-T
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    Dow (1970c) A study of the effects of work exposure to 2,4,5-T on
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    Drill, V.A. and Hiratzka, T. (1953) Toxicity of
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    Emerson, J.L., Thompson, D.J., Strebing, R.J., Gerbig, C.G. and
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    Submitted to Fd. Cosmet. Toxicol. for publication

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    Gordon, N. and Beroza, M. (1952) Spectrophotometric determination of
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    Hindin, E., May, D.S. and Dunstan, G.E. (1964) Collection and analysis
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    Innes, J.R.M., Ulland, B.M., Valerio, M.G., Petrucelli, L., Fishbein,
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    Martin, H. (1968) Pesticide manual, British Crop Protection Council,
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    Roberts, R.E. and Rogers, B.J. (1957) The effect of 2,4,5-T brush
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    Zielinski, W.L. Jr. and Fishbein, L. (1967) Gas chromatographic
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    See Also:
       Toxicological Abbreviations
       T, 2,4,5- (Pesticide residues in food: 1979 evaluations)
       T, 2,4,5- (Pesticide residues in food: 1981 evaluations)