PARAQUAT                                   JMPR 1972


    This compound was evaluated by the Joint Meeting in 1970 (FAO/WHO,
    1971). A temporary acceptable daily intake for man was proposed and
    temporary tolerances recommended.

    It was noted that no information was available on metabolites formed
    by the gut flora and a study of the toxic effects of these was
    requested. An additional reproduction study was required on at least
    one species as was a detailed comparison of paraquat metabolism and
    toxicity in different species to elucidate the reason for the
    comparatively high sensitivity of man to the compound. Investigation
    of the prophylaxis and treatment of the toxic effects of paraquat was
    considered desirable. Since that meeting the results of some
    additional experimental work and new data on residues have been



    Absorption, distribution and excretion

    When paraquat (50 mg/kg body-weight of 14C-labelled dichloride salt)
    was given to rats, 25% of the radioactivity excreted in the faeces
    could be attributed to products of metabolism by gut microflora.
    Examination of extracts indicated the presence of only one metabolite
    in addition to paraquat. Thirty percent of paraquat was broken down
    when incubated anaerobically with rat caecal contents; the metabolites
    are not yet identified. Urine from rats injected intraperitoneally
    with 14C-methyl labelled paraquat contained 87% of administered
    radioactivity in 24 hours which was entirely unchanged paraquat.
    Experiments in progress on sheep and goats have so far failed to
    demonstrate the presence of metabolites in these species (Plant
    Protection Ltd., 1972a).

    Following intravenous administration of 14C-paraquat, the initial and
    secondary half-lives in plasma were 23 min and 56 h. The concentration
    in kidney, lung and muscle declined at the same rate as plasma
    initially, but the rapid phase in lung ended after 20 min (compared
    with 1-4 h in other organs), after which it declined with a 50 h
    half-life. The lung became the organ of highest concentration after 4
    h, and between this time and 10 days the lung paraquat concentration
    was 30 - 80 times that of plasma (Sharp et al., 1972).


    Special studies on reproduction

    Groups of 12 male and 24 female rats were fed on diets containing 0,
    30 and 100 ppm paraquat ion from 35 days of age. Three generations
    bred from these animals received the same diets during the whole
    period under test.

    Two litters were bred from each generation, and the effects on growth,
    food intake, fertility, fecundity, neonatal morbidity and mortality
    noted. No evidence was seen of damage to germ cell production or of
    structural and functional damage in these animals, and pregnant and
    young animals did not appear from this study to be more vulnerable to
    paraquat than adults. However, the incidence of renal hydropic
    degeneration in 3-4 week-old offspring was slightly increased in the
    100 ppm group (Fletcher et al., 1972a).

    Special studies on teratogenicity

    On the second day after mating, groups of 10, 10, 6 and 5 female
    rabbits received, respectively, control diet, diet providing 1
    mg/kg/day paraquat ion, 2.4 mg/kg/day paraquat ion for 8 days
    intravenously followed by 1.2 mg/kg/day to term, or 1.2 mg/kg/day
    paraquat ion intravenously for ten days followed by approximately 4
    mg/kg/day orally in drinking water to term. Offspring were examined
    for congenital abnormalities. Fertility and litter sizes were similar
    in the control and the orally dosed groups. Only one and three animals
    of the third and fourth groups respectively survived treatment but
    these produced litters of normal size. No congenital abnormalities
    were detected (McElligott, 1966).

    Short-term studies


    Four groups of eight A/He strain mice 9 to 15 weeks old were
    administered 50, 100, 200 or 300 ppm paraquat in drinking water for up
    to 16 weeks. Mice were killed at intervals during the study, and the
    kidneys were examined by light and electron microscopy. Induction of
    smooth endoplasmic reticulum and the presence of lipidic lamellate
    cytosomes in the proximal convoluted tubule cells were observed in the
    kidneys of all paraquat treated animals (Fowler and Brooks, 1971).

    Long-term studies


    In order to investigate the carcinogenic potential of paraquat ion in
    mice, 4 groups of 70 males and 50 females received diets containing 0,
    25, 50 and 75 ppm of paraquat ion for 80 weeks. All levels caused a
    slight to moderate reduction in body-weight increments, and these
    paralleled a reduced food intake. Twelve to 24 males and 12 to 23
    females survived treatments for 80 weeks, the majority of deaths
    before this time being associated, in all groups, with respiratory
    disease and, in males, with the results of fighting. Thirty to 38
    males and 31 to 38 females were subjected to histological examination.
    The incidence and types of tumours and other pathological changes in
    animals dying or killed at or before 80 weeks were similar in control
    and experimental groups. (Fletcher et al., 1972b).


    Paraquat is irritant particularly to mucous membranes. Splashes of
    concentrate left in contact with skin cause irritation, inflammation
    and even blistering, and prolonged contact with nails leads to
    shedding. Contact with wounds delays healing. Inhalation of spray mist
    or dust will cause nosebleed. Contact of solid with mucous membranes
    causes soreness, and splashes of liquid concentrate in the eye lead to
    severe inflammation which develops gradually, reaching its maximum
    after 12-24 hours. There may be extensive stripping of superficial
    areas of corneal and conjunctival epithelium and healing may be slow,
    but even in severe cases is complete, given proper medical care. The
    immediate effects of ingestion are due to the local irritant action:
    vomiting, abdominal discomfort and diarrhoea and soreness of mouth and
    throat. Signs of severe kidney damage may appear in 2-3 days if large
    doses are absorbed. Large doses also cause tremors and convulsions.
    Signs of pulmonary injury may develop gradually after a few days, and
    these may lead on to dyspnoea and pulmonary oedema and fibrosis with
    death from respiratory insufficiency (D.H.S.S., 1972).

    The exact dose which is fatal to man is uncertain. The smallest dose
    known to cause death is 1 g, taken in the form of "Weedol" by a woman
    of 23. One man has survived 3 g of paraquat, again as "Weedol" (Plant
    Protection, 1972), and one man recovered after swallowing 10 ml of 20%
    paraquat solution, despite being untreated for six days (Fisher
    et al., 1971). From such evidence the lethal dose in man would seem
    to be approximately 30 mg/kg; estimates lower than this are based on
    accounts of subjects allegedly spitting out all of a dose, a process
    difficult to quantify.

    Between 1963 and the present time, no deaths have occurred in persons
    occupationally exposed to paraquat in the U.K., and only a few trivial
    cases of dermal exposure are reported each year (M.A.F.F., 1965). The
    only deaths from paraquat poisoning that have occurred in the United
    Kingdom, where it is widely used, have been from suicide or accidental
    ingestion of concentrate from unlabelled or mislabelled bottles
    (Hansard, 1971 - 1972).

    Paraquat has been shown to be passively reabsorbed by the kidney
    (Ferguson, 1971), and thus an increased urine flow should increase the
    renal clearance of this substance. Forced diuresis is thus advocated
    in treatment as is oral administration of Fuller's Earth which
    strongly adsorbs paraquat (Clark, 1972; D.H.S.S., 1972).


    Additional data as requested by the 1970 Joint Meeting was presented.

    Paraquat is not readily absorbed from the gastrointestinal tract. It
    is excreted mainly in faeces when administered orally and in urine
    when administered by I.V. injection. Metabolic studies are incomplete,
    but paraquat appears to concentrate in lung tissue.

    The initial signs and symptoms of paraquat poisoning are due to local
    irritant effects, but rapid progressive fibrosis of the lung then
    occurs in many species. Renal failure may also occur. Significant
    variation occurs in species sensitivity to paraquat, man being amongst
    the most sensitive.

    Two-year studies in rats and dogs indicate no-effect levels at 250 and
    50 ppm, respectively, with lung damage at 75 ppm in the dogs. In the
    rat, a study indicates no evidence of effects on reproduction,
    although kidney hydropic degeneration was observed at 100 ppm, and 30
    ppm is considered to be the no-effect level in this species. A
    teratogenicity study in rabbits and a carcinogenicity study in mice
    were negative.


    Level causing no toxicological effect

         Rat:      30 ppm in the diet, equivalent to 1.5 mg/kg

         Dog:      50 ppm in the diet, equivalent to 1.25 mg/kg


         0 - 0.002 mg/kg body-weight (equivalent to 0 - 0.0014 mg/kg
         body-weight, expressed as paraquat ion).



    Paraquat has been registered as an effective soybean harvest aid
    (Kirby, 1971). The uses and chemical characteristics of paraquat,
    together with its mode of action and toxicity, have been reviewed by
    Wheeler (1971). Intensive work on the mechanism of the action of the
    bipyridyls has also been published (Baldwin, 1969).


    Table 1 presents additional data on residues of paraquat in a variety
    of crops (Plant Protection Ltd., 1972b).

        TABLE 1  Paraquat residues in various crops following desiccant usage


    Crop             Rate of           Interval         Samples       Paraquat found
                     application       to harvest       (no.)         range            mean
                     (g a.i./ha)       (days)                                  (ppm)

    Maize            600               4 - 10           24            ND1 - 0.08       0.05

    Olives           400 - 600         3 - 5            8             ND - 0.87        0.24

    Potatoes         600 - 1 000       4 - 10           43            ND - 0.27        0.08

    Rice (in         200 - 600         3 - 10           25            ND - 9.00        4.00

    Rice             200 - 600         3 - 10           21            ND - 0.40        0.16

    Sorghum          600 - 1 000       4 - 10           21            ND - 1.20        0.34

    Soybean          600               4 - 10           5             ND               ND

    1  ND = not detected (0.01 ppm potatoes and olives; 0.05 ppm others)

    Some information regarding the fate and extent of residues of paraquat
    occurring in animal tissues resulting from grazing on treated pastures
    or feeding with treated fodder was reviewed in 1970 (FAO/WHO, 1971).
    In one of the tests, the cows were allowed to graze on grasses
    containing up to 1 000 ppm at the start of the test. It was estimated
    that they ingested approximately one half of the LD50 daily for the
    first two weeks. In other tests cows were dosed at 8 mg/kg of

    body-weight with 14C-labelled paraquat (both ring and methyl); this
    level was approximately one fifth of the cow LD50. Even at these very
    high dosage levels residues of 14C observed in the milk were very
    low, ranging from 0.009 to 0.046 ppm (as paraquat) and disappeared
    very rapidly after dosing ceased. There were no detectable residues in

    Two additional experiments were reported which fully corroborated the
    results of this earlier work. In the first (Daniel et al., 1971),
    two cows were dosed for three consecutive weeks at 8 mg/kg. Again, in
    each case the total 14C detected in the milk (expressed as paraquat)
    was less than 0.01 ppm. This would have included paraquat and all its
    metabolites. The average percentage of the applied dose excreted in
    the milk was 0.004, regardless of whether methyl or ring-labelled
    paraquat was used or whether single or multiple doses were given.

    The second report (Leakey et al., 1972) described a successful
    attempt to identify the nature of the compounds responsible for the
    radioactivity observed in the milk in these trials (less than 0.01 ppm
    as paraquat). Eighty percent of the radioactivity was accounted for as
    paraquat, monoquat (i.e. paraquat minus one methyl group),
    monopyridone and general incorporation (as lactose). Both monoquat and
    monopyridone have been shown to be acutely less toxic than paraquat to
    rats by oral dosing.


    In plants

    Paraquat is a contact herbicide that kills or severely scorches all
    green herbage with which it comes into contact. It is translocated to
    a minor degree, mainly under conditions of low light intensity at the
    time of application. Furthermore, it is quickly rendered biologically
    inactive by adsorption onto clay minerals in the soil and is thus
    immobile and unavailable for root uptake. When paraquat is used for
    weed control after crop emergence, there are usually no detectable
    residues in the crop harvested one to four months later. Plants may
    receive an initial scorch, from which they soon recover. Small
    residues have very occasionally been found in certain crops following
    this use, e.g., 0.09 ppm in cabbage harvested 51 days after an
    application of 2.2 kg paraquat/ha and 0.2 ppm in maize 49 days after
    an application of 1.1 kg/ha. Such residues are exceptional. The only
    exception to the rule that residues are non-detectable in crops
    following the use of paraquat for pre-planting weed control occurs
    when new growth picks up traces of the chemical from dead plant debris
    that it pushes through. This can lead to low residues in the harvested
    crop. In kale, 0.02 - 0.05 ppm paraquat have been found. Small amounts
    of paraquat (less than 0.2 ppm) can often be detected in the foliage
    of certain crops, e.g., sugar beet and cereal, but there are
    invariably no detectable residues in the edible portions at harvest
    (Plant Protection Ltd., 1972b).

    In soil

    The degradation of paraquat in soil by Lipomyces starkeyi was
    investigated by Burns and Audus (1970). They found that degradation
    only occurred in cultures containing organic components of the soil.
    Over a period of time, transfer to the inorganic constituents renders
    it unavailable for microbiological degradation. The adsorption and
    mobility of paraquat on different soils and soil constituents has been
    studied (Damanakis et al., 1970). Adsorption decreased as the ratio
    of the soil to water increased, while temperature had little effect.

    Giardina et al. (1970) studied the effect on the proteolytic urease
    and cellulose activity of soil microflora together with the influence
    on total bacterial flora and oxygen consumption of the soil. Paraquat
    was degraded to an extent of approximately 50% after ten days in soil.
    Watkin and Sagar (1971a,b) when investigating persistence factors,
    suggested that paraquat phytotoxicity is a surface, rather than a
    solution, phenomenon. The direct relationship between the germination
    inhibitory capacity of a paraquat treated soil and the amount of
    paraquat extracted by a 50-fold volume of 0.2 N NH4Cl was found by
    Radaelli and Martelli (1971). No inhibition was observed with soils
    having an extractable value of less than 20 mg/100 g, partial
    inhibition was associated with values of 20-85 mg/100 g and complete
    suppression of germination was observed at levels greater than 85
    mg/100 g. The phytotoxicity of various soils after spraying with
    paraquat was determined by the inhibition Lolium perenne (ryegrass)
    germination (Watkin and Sagar 1971a,b). Applied amounts of 0.05 and
    0.38 kg/ha respectively inhibited germination on sphagnum and peat
    soils, but higher doses of 0.75 and 1.5 kg/ha were necessary on
    compost and loam soils to obtain the same effect. On all soils,
    residual activity increased rapidly with dose once the minimum
    phytotoxic dose was reached.

    In water

    Earnest (1971) treated a pond with paraquat to give an initial
    concentration of 1.14 ppm; Chara and Spirogyra were found to
    contain 2 300 and 1 300 ppm of paraquat, respectively. Residues in the
    water were not detected after 16 days, and the amounts present in the
    mud were 1.13 ppm after 3 hours and 3.25 ppm after 99 days.

    The use of paraquat as an aquatic herbicide has been reviewed by
    Calderbank (1970). The effective concentration was found to be 1 ppm
    which was accumulated by plants and adsorbed on to suspended soil
    particles causing a decline to 0.1 ppm in 4-7 days. Under these
    conditions it was neither toxic to fish nor did they accumulate it,
    but death could occur if the herbicidal action caused a greatly
    decreased oxygen concentration.

    Evidence of residues in food in commerce or at consumption

    The great majority of crops treated for weed control showed no
    detectable residues (<0.05 ppm) when subsequently harvested (Plant
    Protection Ltd., 1972b).


    Paraquat type herbicides were determined in aqueous solutions by the
    colorimetric measurement of the complex formed with a-dipicrylamine
    hexanitrodiphenylmethane (Zhemchuzin, 1970). An ion exchange and
    colorimetric method has been used by Berry and Grove (1971) for the
    determination of paraquat in urine; the method was rapid with a
    detection limit of 0.01 µg ion/ml in 250 ml aliquots. Mueller and
    Worseck (1970) used a semi-quantitative thin-layer chromatographic
    method for the determination of paraquat in bees. The polarographic
    response of paraquat in five supporting electrolytes has been reported
    (Hance, 1970). Modified versions of Calderbank and Yuen's method
    (1965) were applied in a poisoning case for the analysis of body
    fluids, urine, blood and gastric aspirates (Tompsett, 1970). The
    method of Calderbank and Yuen (1965) is suitable for regulatory


    Since the evaluation of paraquat in 1970 (FAO/WHO, 1971) further
    residue data have become available. These have indicated the need to
    revise some of the earlier recommendations and allowed the proposal of
    tolerances for some additional crops.



    The following tolerances are recommended to replace the temporary ones
    proposed in 1970:

                                                      paraquat ion

         Rice (in husk)                               10
         Olives                                       1
         Sorghum, rice (polished)                     0.5
         Cottonseed, potatoes                         0.2
         Maize, soybeans                              0.1
         Cottonseed oil (refined)                     0.05
         Other vegetables                             0.05*
         Milk                                         0.01*

         * at or about the limit of determination



    1.   Detailed comparative toxicity and metabolism studies in order to
         elucidate the reason for the comparatively high sensitivity of
         man to this compound.

    2.   Comparative studies on the relationship between lung
         concentration and toxicity.


    Baldwin, B.C. (1969) In Progress in photosynthesis research. (H.
    Metzner, Ed.), Tübingen III, 1737.

    Berry, D.J. and Grove, J. (1971) Determination of paraquat
    (1,1'-dimethyl-4,4'-bipyridylium cation) in urine. Clinica Chim.Acta.,
    34: 5-11.

    Burns, R.G. and Audus, L.J. (1970) Distribution and breakdown of
    paraquat in soil. Weed Res., 10: 49-58.

    Calderbank, A. (1970) Fate of paraquat in water. Outlook Agr., 6:

    Calderbank, A. and Yuen, S.H. (1965) An ion-exchange method for
    determining paraquat residues in food crops. Analyst, Lond., 90:

    Clark, D.G. (1972) Inhibition of the absorption of paraquat from the
    gastrointestinal tract by adsorbents. Br. J. Industr. Med., 28:

    D.H.S.S. (1972) Poisonous chemicals used on farms and gardens: Notes
    for the guidance of medical practitioners. Department of Health and
    Social Security, London.

    Damanakis, M., Drennan, D.S.H., Fryer, J.D. and Holly, K. (1970)
    Adsorption and mobility of paraquat on different soils and soil
    constituents. Weed Res., 10: 264-277.

    Daniel, J.W., Edwards, M.J., Glade, P. and Walker, G.H. (1971) Milk
    residues arising from the ingestion of 14C-paraquat by a cow. Report
    AR 2282A, Plant Protection Ltd. (unpublished)

    Earnest, R.D. (1971) Effect of paraquat on fish in a Colorado farm
    pond. Progr. Fish Cult., 33: 27-31.

    FAO/WHO. (1971) 1970 Evaluation of some pesticide residues in food.
    FAO/AGP/1970/M/12/1; WHO/Food Add./71.42.

    Ferguson, D.M. (1971) Renal handling of paraquat. Br. J. Pharmac., 42:

    Fisher, H.K., Humphries, M. and Bails, R. (1971) Paraquat poisoning
    - recovery from renal and pulmonary damage. Ann. intern. Med., 75:

    Fletcher, K., Herring, C.M. and Robinson, V.M. (1972a) Paraquat
    three-generation reproduction study in rats. Report ICI Industrial
    Hygiene Research Laboratories. (unpublished)

    Fletcher, K., Flegg, R. and Kinch, D.A. (1972b) Paraquat: carcinogenic
    study in the mouse. Report ICI Industrial Hygiene Research
    Laboratories. (unpublished)

    Fowler, B.A. and Brooks, R.E. (1971) Effects of the herbicide,
    paraquat on the ultrastructure of mouse kidney. Am. J. Pathol., 63:

    Giardina, M.C., Tomati, U. and Pietrosanti, W. (1970) Hydrolytic
    activities of soil treated with paraquat. Meded. Fac. Landbouwwetensch
    Rijksuniv. Gent, 35: 615-626.

    Hance, R.J. (1970) Polarography of herbicides. A preliminary survey.
    Pestic. Sci., 1: 112-113.

    Hansard (1971-1972) Parliamentary debates, House of Commons official
    report. 827, written answers to questions, 261. H.M.S.O., London.

    Kirby, B.W. (1971) Paraquat - soybean harvest aid. Proc. S. Weed Sci.
    Soc., 24: 80-84.

    Lehey, J.P., Hemingway, R.J., Davis, J.A. and Griggs, R.E. (1972)
    Paraquat: metabolism in a cow. Report AR 2374A, Plant Protection Ltd.

    M.A.F.F. Ministry of Agriculture, Fisheries and Food. (1965) Reports
    on safety, health, welfare and wages in agriculture, 1961-1965.
    H.M.S.O., London.

    McElligott, T.F. (1966) Reproduction in paraquat-treated rabbits.
    Report ICI Industrial Hygiene Research Laboratories. (unpublished)

    Mueller, B. and Worseck, M. (1970) Method for the semi-quantitative
    determination by thin-layer chromatography of diquat (Reglone) and
    paraquat (Gramoxone). Monatsh. Veterinaermed, 25: 560-561.

    Plant Protection Ltd. (1972a) Data to support a revised acceptable
    daily intake and tolerance levels for paraquat. Report Plant
    Protection Ltd. (unpublished)

    Plant Protection Ltd. (1972b) Additional data to support the
    establishment of permanent tolerances for paraquat in human food
    crops. Report. (unpublished)

    Radaelli, L. and Martelli, M. (1971) Residual toxicity of paraquat
    adsorbed on soil. Agrochimica, 15: 344-350.

    Sharp, C.W., Ottolenghi, A. and Posner, H.S. (1972) Correlation of
    paraquat toxicity with tissue concentrations and weight loss of the
    rat. J. Toxicol. and Appl. Pharmacol., 22: 241-251.

    Tompsett, S.L. (1970) Paraquat Poisoning. Acta Pharmacol. Toxicol.,
    28: 346-358.

    Watkin, E.M. and Sagar, G.R. (1971a) Residual activity of paraquat in
    soils. I. Factors affecting persistence. Weed Res., 11: 1-11

    Watkin, E.M. and Sagar, G.R. (1971b) Residual activity of paraquat in
    soils. II. Adsorption and description. Weed Res., 11: 247-256.

    Wheeler, J.H. (1971) Diquat and paraquat. Proc. Annu. Calif. Weed
    Conf., 23: 154-157.

    Zhemchuzin, S.G. (1970) Determination of herbicides of paraquat type.
    Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki., 47(31): 133-135.

    See Also:
       Toxicological Abbreviations
       Paraquat (HSG 51, 1991)
       Paraquat (PIM 399)
       Paraquat (JMPR Evaluations 2003 Part II Toxicological)
       Paraquat (AGP:1970/M/12/1)
       Paraquat (Pesticide residues in food: 1976 evaluations)
       Paraquat (Pesticide residues in food: 1978 evaluations)
       Paraquat (Pesticide residues in food: 1981 evaluations)
       Paraquat (Pesticide residues in food: 1982 evaluations)
       Paraquat (Pesticide residues in food: 1986 evaluations Part II Toxicology)