PARAQUAT JMPR 1976 Explanation This compound was evaluated by the Joint FAO/WHO Meeting on Pesticide Residues in 1970 (FAO/WHO, 1971b) and in 1972 (FAO/WHO, 1973b). Although an acceptable daily intake for man was estimated (0-0.002 mg/kg body weight), the 1972 Meeting considered it desirable that the following studies should be undertaken: 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. Data on these subjects have now become available. Moreover, since in addition to its use as a contact herbicide, which does not usually result in residues in animal feedstuff, paraquat may also be applied as a harvest aid or desiccant for a number of animal fodder crops such as grass, maize and alfalfa, a large number of studies on paraquat in farm animals were reported. The available data on metabolism in cows, goats, sheep, pigs and poultry, and on residues in their various organs and milk and eggs, together with other relevant material, are summarized below. EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, distribution, and excretion Studies have been carried out to a) compare the metabolism of paraquat in different species in an attempt to understand their different susceptibilities to paraquat, and b) to compare the distribution of paraquat in the organs of the rat to explain the affinity exhibited by paraquat for the lung. After oral administration of 14C-paraquat to rats, dogs and guinea pigs, most of the radioactivity was excreted in 4 days, mainly in the faeces as unchanged paraquat. The remaining label was present in urine which contained 12% (rats), 45% (dogs) and 9% (guinea pigs) of the dose administered. Thus dogs and guinea pigs absorb very different amounts of paraquat yet the oral LD50 is the same in the two species. Paraquat (I) was the main radioactive component of rat and dog urine (see Figure 1), with monoquat (II) and the dipyridone (IV) of paraquat accounting for 0.4%, 0.3% and 0.1% of the administered dose in rat urine and 0.4%, 0.5% and 0% of the dose in dog urine. Thus, there is very little metabolism of the parent compound following oral dosing. After subcutaneous administration of 14C-paraquat into rats over 90% of the administered radioactivity was excreted in the urine in 4 days. Whilst this was mainly paraquat, chromatography indicated that monoquat (II) (1.9%), paraquat monopyridone (III) (3.2%) and dipyridone (IV) (1.1%) were present. Although traces of monoquat and paraquat monopyridone were also found in rat faeces, there was no evidence for extensive metabolism of paraquat by gut microflora. Intestinal bacteria from rat caecal contents did not degrade paraquat in vitro to any measurable extent. It is concluded, therefore, that the previous observations of Daniel and Gage (1966), indicating a large amount of degradation by gut microflora were incorrect, and due to incomplete extraction of paraquat from faeces. There was no correlation between the toxicity of paraquat to the 3 species studied and the degree of absorption, rate of excretion or extent of metabolism. There were no species differences observed with respect to the metabolic products detected. Rat lung slices have been shown to possess an ability to accumulate paraquat in vitro to concentrations nearly ten times that of the medium over a period of two hours, brain slices to concentrations double that of the medium. The accumulation by both tissues has been shown to be energy, dependent. After oral dosing of paraquat to rats the lung concentration increased with time to six times that of plasma after 30 hours. Other organs, with the exception of the kidney, did not concentrate paraquat to the same extent. Lung slices from dog, monkey and rabbit have also been shown to possess the ability to accumulate paraquat in vitro but to a much lesser extent when compared with those from rat and man. Thus from the point of view of paraquat accumulation in the lung the rat is a good experimental model. Indeed the kinetics (V max and Km) of the process are very similar in the lung tissues of both species. (Rose et al., 1976). The cells in the lung that are damaged by paraquat are primarily the type I and II alveolar epithelial cells (Vijeyaratnam and Corrin, 1971). Accumulation of paraquat appears to be associated with these cells (Sykes et al., 1976) which only constitute a small fraction of the total cell population of the lung. After the initial damage of the type I cell, swelling of the type II cell mitochondria occurs and is followed by more extensive changes, including loss of microvilli, multivesicular bodies and electron density with an increase in the number of lipid droplets and damage. Thus, the selectivity of paraquat for lung is explained by accumulation and it is the type I and II cells in lung which accumulate high concentrations of paraquat via an energy-dependent process. This leads to the destruction of these cells with consequent impairment of the air/blood interface and death from respiratory failure. Biotransformation Studies of biotransformation in farm animals and poultry are described in this section. Further details of residues found in tissues, milk and eggs are given in the section "Fate of residues". Cows When cows were given a single oral dose of 14C-methyl paraquat at 8 mg/kg, 96% of the radioactivity was recovered in the faeces during the following 9 days; 0.7% was recovered in urine. Unchanged paraquat (I) accounted for most of the radioactivity in faeces (96%) and urine (62-90%), but traces of metabolites II and III were also detected in the urine. Only 0.003 - 0.004% of the radioactivity was recovered in milk; the maximum radioactive residue (0.005 mg/kg, paraquat ion equivalent) occurred on the day after dosing. About 15% of this radioactivity was present as unchanged paraquat (I). Compounds II and III (3-25%) were also found in milk. The radioactivity not identified as I, II or III was accounted for by incorporation into natural constituents of milk, resulting from the anabolism of the radioactive methyl group cleaved from paraquat (Hemingway et al., 1974). Cows were fed for three months with diets containing 25, 80 and 170 ppm of paraquat ion (equivalent to 0.8, 2.6 and 5.5 mg/kg body weight). The paraquat was present as a residue in dried grass obtained from a pasture which had been sprayed with "Gramoxone" and subsequently weathered. The diet was accepted satisfactorily and no toxicological effects were observed during the trial. Pathological examination of tissues from animals slaughtered within 24 hours of the end of feeding trial showed no toxic effects attributable to paraquat. The tissue residues including muscle and liver determined in cows at the two higher dose rates varied between 0.01 and 0.09 mg/kg except in the kidney where 0.21 - 0.31 mg/kg was found. These fell to low (0.04 mg/kg in kidney) or non-detectable levels in an animal fed the high paraquat rate diet for 30 days and then maintained on an untreated diet for 12 days before slaughter.Only very low residues of paraquat were present in milk samples taken weekly during the trial (121 samples <0.0001 - 0.0006 mg/kg: 1 sample = 0.001 mg/kg (Edwards et al., 1974). Goat 14C ring labelled paraquat was administered to a goat in mid-lactation twice daily for seven days at a dose equivalent to 100 ppm in the diet. Total radioactive residues in the milk were less than 0.01 mg/kg paraquat ion equivalent - 76% as unchanged paraquat. Total radioactive residues were 0.74, 0.56, 0.1 mg/kg in kidney, liver and muscles respectively. In all samples there was no significant metabolism of paraquat with the exception of the liver where 50% of the radioactivity was accounted for as paraquat and about 5% as each of the metabolites II and III (Hendley et al., 1976a). Sheep A dose of 14C-methyl labelled paraquat administered to a sheep via a rumen fistula was recovered quantitatively within 10 days. Approximately 4% of the dose was excreted in the urine and the remainder in the faeces. More than 95% of the radioactivity in urine and faeces was present as unchanged paraquat. Small amounts of compound II (1%) and compound III (2.3%) were also detected. (Hemingway et al., 1972) When injected subcutaneously, paraquat is also excreted rapidly in the urine (over 80% of the dose), 69% within the first day after treatment. Again unchanged paraquat accounts for most (90%) of the radioactivity, the monopyridone (III) derivative is present as 2-3% of the dose and monoquat (II) is a trace metabolite. This pattern of metabolism is virtually identical to that seen in the urine following dosing via the rumen. (Hemingway et al., 1972) Pigs and hens Oral dosing and feeding studies with pigs and hens are described in the section "Fate of residues", p. TOXICOLOGICAL STUDIES Acute toxicity The acute oral toxicity of paraquat was studied comparatively in rat, guinea pig and monkey. The LD50 was in the order rat monkey guinea pig. All animal species showed primary lesions in the lung. Rats and monkeys, but not guinea pigs, developed progressive interstitial fibrosis of the lung after 7-10 days. Focal necrosis in liver and kidneys was found in rats and guinea pigs but not in monkeys (Murray and Gibson, 1972). TABLE 1. Acute toxicity of paraquat oral LD50 (mg/kg Species body weight) References Mouse 104 (90-120) Fletcher, 1974 Rat 130 (110-160) " Guinea pig 30 (22-41) " Rabbit 126 (69-183) " Cat 35 " Hare 35 " Monkey 75 " Dog 25-50 " Sheep 65 " Cow 35-60 " Man about 30 " OBSERVATIONS IN MAN The potential of lungs from five different species (rat, dog, rabbit, monkey and man) to accumulate paraquat has been assessed by measuring the kinetic constants Km and Vmax of the process in lung slices (Rose et al., 1976). Human lung slices have the highest Vmax and one of the lowest Km's for this process which indicates that human lung possesses a very efficient accumulation system for paraquat. This will tend to make man one of the more sensitive species to paraquat as the lung will be able to accumulate toxic amounts of paraquat from very low concentrations present in the plasma. In studies of exposure of spray operators to paraquat which were probably closest to the extremes of exposure likely to occur in any agricultural operation, measurable levels of paraquat in the urine of certain workers were found but no noticeable clinical adverse effects (Staiff et al., 1975). The ingestion of 10-15 ml of the concentrate supplied to professional users (containing 20% paraquat cation) can be fatal if left untreated. The oral LD of paraquat cation to man has been estimated to be approximately 30 mg/kg body weight (Fletcher, 1974) which is similar to that measured for dogs and guinea pigs. Rats are less sensitive, having an oral LD50 of approximately 100 mg cation/kg body weight. COMMENTS In recent feeding studies with paraquat in farm animals, over 90% was excreted within a few days. Thus, tissue accumulation giving rise to significant tissue residues is unlikely. Paraquat was only slightly absorbed and was metabolised mainly in the gastrointestinal tract of the animals. Milk and eggs were found to contain small residues of two identified metabolites. The Meeting found the recent data on comparative toxicity and the metabolic and toxicological studies in laboratory animals reassuring and reaffirmed the previously established acceptable daily intake. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat: 30 ppm in the diet, equivalent to 1.5 mg/kg bw Dog: 50 ppm in the diet, equivalent to 1.25 mg/kg bw ESTIMATION OF ACCEPTABLE DAILY INTAKE FOR MAN 0 - 0.002 mg/kg bw as paraquat dichloride (equivalent to 0 - 0.0014 mg/kg bw, expressed as paraquat ion). RESIDUES IN FOOD AND THEIR EVALUATION The use of paraquat as a contact herbicide does not usually result in residues of this compound animal feeding stuffs. However paraquat can also be used as a harvest aid or desiccant for a number of animal fodder crops. such as grass, maize and alfalfa. In this case paraquat residues of 5-1000 mg/kg may be found in the resulting feeding stuff; this has stimulated a large number of studies on the fate of paraquat in farm animals. This work is described in the section "Biotransformation," p. Some additional details of residues arising in tissues, organs, milk and eggs are given in the following section, "Fate of residues". FATE OF RESIDUES In animals Cows When cows were given a single oral dose of 14C-methyl paraquat (I) at 8 mg/kg, 96% of the radioactivity was recovered in the faeces during the following 9 days. 0.7% was recovered in the urine. Unchanged paraquat accounted for most of the radioactivity in faeces (96%) and urine (62-90%) but traces of two metabolites (compounds II and III - Figure 1) were also detected in the urine. (Hemingway et al., 1974; Leahey et al., 1972; Stevens and Walley, 1966). Only 0.003-0.004% of the radioactivity was recovered in milk. The maximum radioactive residue (0.005 Ú Úg/g paraquat ion equivalents) occurred on the day after dosing. Only about 15% of this radioactivity was present as unchanged paraquat. Compounds II and III (Figure 1) were also found in the milk in the proportions shown in Table 2. The radioactivity not identified as I, II or III was accounted for by incorporation into natural constituents of milk (Hemingway et al., 1974; Leahey et al., 1972). TABLE 2. Radioactive compounds detected in the milk of a cow dosed with 14C-paraquat Percentage of Radioactivity in milk present as Day Milk Collected Paraquat Compound II* Compound III* 1 15 15 3 2 18 18 18 3 9 25 10 * Identified in Figure 1 Cows given 14C-methyl-labelled paraquat orally at 8 mg/kg/day for three successive days showed a maximum residue in the milk of 0.01 mg/kg paraquat ion equivalents. No paraquat was detected by residue analysis (limit of detection 0.005 mg/kg) (Daniel et al., 1971). In other trials cows were allowed to graze treated grasses containing up to 1000 mg/kg at the start of the test. A maximum residue of 0.02 mg/kg paraquat was detected in milk on the first day after grazing freshly treated fodder; thereafter residues were less than the normal limit of detection for milk, i.e. below 0.005 mg/kg (Calderbank et al., 1968). In a trial in which cows were fed for three months with diets containing 25, 80 and 170 mg/kg of paraquat, only very low residues of paraquat were found in weekly milk samples (121 samples in the range, <0.0001 - 0.0006 mg/kg; 1 sample 0.001 mg/kg (Edwards et al., 1974). Residues found in the meat, fat and offal of cows fed at various levels of paraquat in the diet for various periods are summarized in Table 3. Similar residue levels were found in the milk and tissues of two cows maintained for 30 days on a diet containing 150 ug/g of paraquat (Edwards et al., 1976). TABLE 3. Residues of paraquat in tissues of cows fed on paraquat- containing fodder Paraquat Interval between ion levels Feeding last feeding on Paraquat residues in fodder period treated fodder (mg/kg) in (mg/kg) (days) and sacrifice Liver Kidney Meat Fat 3.6 21 9 days <0.05 <0.05 <0.05 <0.05 25 86-95 <1 day <0.01 <0.06- <0.01 <0.01 0.13 80 " <1 day <0.01 0.14- <0.01 <0.01 0.31 170 " <1 day <0.01- 0.20- <0.01 <0.01 0.09 0.24 -0.02 0.02 135-450 32 3 days <0.01 0.05 <0.01 <0.01 13 days <0.01 <0.01 <0.01 <0.01 220-450 3 1 hour 0.04 0.15 <0.01 <0.01 7 1 hour 0.04 0.16 0.02 <0.01 Calderbank et al., 1968 Edwards et al., 1974 Lazanas, 1969 Litchfield, 1969 Goats Transfer of residues to the meat and milk of a goat fed on paraquat was very small, as in the cow. 14C-ring-labelled paraquat was administered to a goat in mid-lactation, twice daily for seven days at a dose equivalent to 100 ppm in the diet. Total radioactive residues in the milk were less than 0.01 mg/kg paraquat ion equivalents - 76% as unchanged paraquat (Hendley et al., 1976a). Total radioactive residues in goat tissues were as shown in Table 4. Unchanged paraquat accounted for at least 50%, and usually almost all, of these residues. TABLE 4. Total radiolabelled residues in tissues of a goat Paraquat Feeding Total radiolabelled residue ion level Period (mg/kg paraquat ion equivalent) in diet (mg/kg) (days) Liver Kidney Muscle Heart Fat 100 7 0.56 0.74 0.08- 0.16 0.02- 0.12 0.03 (Animals sacrificed four hours after receiving last dose.) Sheep As with other ruminants, paraquat is rapidly excreted from sheep, principally in the faeces, and very little metabolism occurs. A dose of 14C-methyl-labelled paraquat, administered to a sheep via a rumen fistula, was recovered quantitatively within 10 days. Approximately 4% of the dose was excreted in the urine and the remainder in the faeces. More than 95% of the radioactivity in urine and faeces was present as unchanged paraquat. Small amounts of compound II (1%) and compound III (2.3%) were also detected (Hemingway et al., 1972). Pigs Pigs excrete an oral dose of paraquat, principally in the faeces as unchanged paraquat. Residues in meat are small. Two pigs were dosed with 14C-labelled paraquat for seven consecutive days at a rate equivalent to 50 ppm in the diet. One was dosed with 14C-methyl and the second with 14C-ring-labelled paraquat. The pigs were sacrificed two hours after receiving the final dose. At this point 69-73% of the administered residue had been recovered in the faeces and approximately 3% in the urine. More than 90% of the radioactivity in the faeces was present as unchanged paraquat. Total radioactive residues in the tissues were low (Table 5). More than 90% of these residues were due to unchanged paraquat except in liver where approximately 70% was due to unchanged paraquat and 4-7% was due to compound II. (Leahey et al., 1976; Spinks et al., 1976) Pigs were also maintained on diets containing 8, 47 and 147 ppm of non-radioactive paraquat for 30 days. The residues of paraquat in the tissues of animals sacrificed within 24 hours of the cessation of feeding were similar to those detected in the experiment with the radioactive compound. Residues declined to 0.03 mg/kg or below after a further six days feeding on a control diet (Table 6) (Hemingway et al., 1975). TABLE 5. Total radio-labelled residue in tissues of pigs dosed at 50 ppm in the diet for 7 days, using 14C-labelled paraquat Total radio-labelled residue (mg/kg paraquat ion equivalent) Radio-label Liver Kidney Muscle Heart Fat 14C-methyl 0.20 0.46 0.03-0.06 0.12 0.02-0.06 14C-ring 0.10 0.38 0.05 0.08 0.01 TABLE 6. Residues of paraquat in tissues of pigs fed on paraquat-containing diet Paraquat ion level Paraquat residues (mg/kg) in in diet (mg/kg) Feeding Regime Liver Kidney Muscle Heart Fat 8 30 days on treated diet <0.01 <0.01 <0.01 <0.01 <0.01 30 days on treated diet + 6 days on control diet <0.01 <0.01 <0.01 <0.01 <0.01 47 30 days on treated diet 0.03 0.04 0.02 0.03 <0.01 30 days on treated diet + 6 days on control diet <0.01 <0.01 <0.01 <0.01 <0.01 147 30 days on treated diet <0.01 0.33 0.04 0.12 0.02 30 days on treated diet + 6 days on control diet <0.01 0.01- 0.01- 0.02- <0.01 0.03 0.02 0.03 Hens As in other animals, there is little metabolism of paraquat in the hen. Residues in meat and eggs are small. When a single oral dose of 14C-methyl-labelled paraquat was administered to the hen, all of the dose was recovered quantitatively in the faeces within three days. At least 98% of the recovered radioactivity was as unchanged paraquat. Analysis of the tissues of hens after about 3 weeks dosing with 14C-paraquat (6 ppm in the total diet) indicated that it did not accumulate in the hens (Hemingway and Oliver, 1974). Continuous dosing of hens with radio-labelled paraquat for up to 22 days, at rates up to 30 ppm in the diet, resulted in total radioactive residues in the eggs up to approximately 0.05 mg/kg paraquat ion equivalent. At least 80% of the radioactivity was due to unchanged paraquat. The residue was present almost entirely in the yolk rather than in the albumen (Hemingway and Oliver, 1974; Hendley et al., 1976b). When hens were maintained for up to 30 days on diets containing up to 3.6 ppm of unlabelled paraquat, no residues were detected in the eggs (limit of detection 0.01 mg/kg). At 7.2 and 36 ppm dietary inclusion levels, paraquat residues were 0.05 mg/kg or below (Leary, 1974). Paraquat was also administered to hens as a 40 mg/kg solution in their drinking water for 14 days. Residues in eggs were 0.1 mg/kg or below and declined rapidly once dosing ceased (Fletcher, 1967). During the above-mentioned continuous dietary feeding studies with radio-labelled and with unlabelled material, paraquat residues in tissues were small (Table 7). In the radio-labelled studies, paraquat was found to constitute 80% or more of the residue in the tissues. TABLE 7. Levels of paraquat in tissues of hens Paraquat ion level Feeding Paraquat residue (mg/kg) in in diet Period (mg/kg) (days) liver Kidney Muscle Heart Fat 1.8 30 <0.01 * <0.01 <0.01 <0.01 3.6 30 <0.01 * <0.01 <0.01 <0.01 7.2 30 <0.01 * 0.01 <0.01 <0.01 36 30 0.01 * 0.01 <0.01 <0.01 30 10 0.06 0.10 <0.01- 0.03 <0.01 0.04 (Animals sacrificed on cessation of dosing) * Tissue not analysed. Hendley et al., 1976b NATIONAL TOLERANCES REPORTED TO THE MEETING The following tolerances have been reported to the Meeting. Tolerance Commodity mg/kg USA Alfalfa 5 Almond hulls 0.5 Apples 0.05(N) Apricots 0.05(N) Avocados 0.05(N) Bananas 0.05(N) Barley grain 0.05(N) Beans (Dry) Exp. 8/28/76 0.5(T) Birdsfoot Trefoil 5 Cattle (Meat, Fat, Meat By-products) 0.01(N) Cherries 0.05(N) Citrus fruit 0.05(N) Clover 5 Coffee Beans 0.05(N) Corn fodder 0.05(N) Corn forage 0.05(N) Corn fresh (kernels plus cobs) 0.05(N) Corn grain 0.05(N) Cottonseed 0.5 Eggs 0.01(N) Figs 0.05(N) Guar beans 0.5 Goats (meat, fat, meat by-products) 0.01(N) Guavas 0.05(N) Hogs (meat, fat, meat by-products) 0.01(N) Hops, dried 0.2FA Hops, vine 0.5 Hops, fresh 0.1 Horses (meat, fat, meat by-products) 0.01(N) Lettuce 0.05(N) Melons 0.05(N) Milk 0.01(N) Nectarines 0.05(N) Nuts 0.05(N) Oat grain 0.05(N) Olives 0.05(N) Papayas 0.05(N) Passion fruit 0.2 Pasture grass 5 Peaches 0.05(N) Pears 0.05(N) Peppers 0.05(N) Pineapples 0.05(N) Tolerance Commodity mg/kg USA Plums (fresh prunes) 0.05(N) Potatoes 0.5 Poultry (meat, fat, meat by-products) 0.01(N) Range grass 5 Rye grain 0.05(N) Safflower seed 0.05(N) Sheep (meat, fat, meat by-products) 0.01(N) Small fruit 0.05(N) Sorghum forage 0.05(N) Sorghum grain 0.05(N) Sorghum grain (animal feed) 2(T) Soybeans 0.05(N) Soybean forage 0.05 Sugar beets 0.5 Sugar beet tops 0.5 Sugarcane 0.5 Sunflower seed 2 Sunflower seed hulls 6FA Tomatoes 0.05(N) Wheat grain 0.05(N) Netherlands Fruit and vegetables 0.05 Cereals 0.05 Potatoes 0.1 FA = Food additive tolerance (N)= Negligible residue tolerance (T)= Temporary tolerance APPRAISAL Since paraquat was last evaluated by the Joint Meeting in 1972 (FAO/WHO, 1973b) additional studies have been completed on the fate of paraquat in cows, goats, sheep, pigs and poultry. Although the use of paraquat as a contact herbicide does not usually result in residues of this compound on animal feed when it is used as a harvest aid or desiccant for fodder crops such as grass, maize or alfalfa residues; of 5-1000 mg/kg may be found in the resulting feed. Oral doses of paraquat given to cows are excreted mainly unchanged in faeces. Residues in milk and meat are extremely small. When cows were allowed to graze grasses containing up to 1000 mg/kg at the start of the test, a maximum residue of 0.02 mg/kg paraquat was detected in milk on the first day after grazing freshly treated fodder. Thereafter residues were less than the normal limit of detection for milk, i.e. below 0.005 mg/kg; it was estimated that the cows consumed one-half of the acute oral LD50 daily. The maximum residue limit of 0.01 mg/kg for milk, recommended by the Joint Meeting in 1972, is therefore confirmed. Levels in the meat are often below 0.01 mg/kg and rarely above 0.05, but higher levels are possible especially in kidney. Levels in tissues of pigs fed on a paraquat-containing diet were again generally below 0.01 but sometimes up to 0.05 mg/kg, and in kidney levels approaching 0.5 mg/kg have been reached. As in other animals, there was little metabolism of paraquat in the hen: residues in meat and eggs were small and rarely exceeded 0.01 mg/kg. Paraquat is also used as a spray directed at the ground to control weeds, and as a pre-emergence and preplanting spray for cereal crops. Very small residues at or about the limit of determination can arise from these uses presumably from adventitious particles of soil and vegetation adhering to the crop. RECOMMENDATIONS The following additional maximum residue limits are recommended. They refer to paraquat ion. Commodity Limit, mg/kg Sunflower seed 2 Kidney of sheep, cattle and pigs 0.5 Dried hops, passion fruit 0.2 Food commodities of plant origin other than those for which specific recommendations have been made, meat and edible offals other than kidney of sheep, cattle and pigs 0.05* Eggs 0.01* REFERENCES Calderbank, A., McKenna, R.H., Stevens, M.A., and Walley, J.K. 1968 Grazing trials on paraquat treated pastures. J.Sci. Food Agr., 19: 246. Daniel, J.W., Edwards, M.J., Slade, P., and Walker, G.H. 1971 Milk residues arising from the ingestion of 14C-paraquat by the cow. ICI Plant Protection Ltd. Report No. AR2282A. (Unpublished) *at or about the limit of determination Daniel, J.S., and Gage, J.C. Absorption and excretion of diquat 1966 and paraquat in rats. Brit. J. Indus. Med., 23: 133-136. Edwards, M.J., Hemingway, R.J., Kinch, D.A., and Slape, P. 1974 Paraquat: residue and toxicology trial with cows fed a treated grass. ICI Plant Protection Ltd. Report No. AR2465A(R), (Unpublished) Edwards, M.J., Hayward, G.J., and Ward, R.J. Paraquat: residues 1976 in milk and tissues of cows fed on paraquat treated grass. Unpublished report from ICI Plant Protection Division. Fletcher, K. Production and viability of eggs from hens treated 1967 with paraquat. Nature, 215: 1407 (Unpublished) Fletcher, K. In Forensic Toxicology, p. 86, ed. B. Ballantyne, 1974 John Wright & Sons Ltd., Bristol. Hemingway, R.J., Edwards, M.J., Jagatheeswaran, T., Davis, J.A., 1975 and Hayward, G. Paraquat residue transfer and toxicology trial in young growing pigs. ICI Plant Protection Ltd. Report No. AR2572A (Unpublished). Hemingway, R.J., Leahey, J.P., Griggs, R.E., and Davis, J.A. 1972 Paraquat: metabolism in sheep. ICI Plant Protection Ltd. Report No. AR2359A (Unpublished). Hemingway, R.J., Leahey, J.P., Griggs, R.E., and Davis, J.A. 1974 Paraquat-metabolism in ruminants. 3rd International Congress of Pesticide Chemistry (I PAC) Helsinki. Hemingway, R.J., and Oliver, C. Paraquat: A study of the metabolism 1974 and residues in hens and their eggs. ICI Plant Protection Ltd. Report No. AR2511A (Unpublished). Hendley, P., Leahey, P.J., Spinks, C.A., Neale, D., and Carpenter, 1976a P.K. Paraquat-metabolism and residues in goats. ICI Plant Protection Division, Report No. AR2680A (Unpublished). Hendley, P., Leahey, J.P., and Spinks, C.A. Paraquat: Metabolism 1976b and residues in hens. ICI Plant Protection Division. Report No. AR2676A (Unpublished) Lazanas, J.C. A study of the effects of sub-acute administration 1967 of paraquat to dairy cattle. Industrial Biotest Report. Leahey, J.P., Hemingway, R.J., Davis, J.A., and Griggs, R.E. 1972 Paraquat-metabolism in a cow. ICI Plant Protection Ltd. Report No. AR2374A. (Unpublished) Leahey, J.P., Hendley, P., and Spinks, C.A. Paraquat: Metabolism 1976 and residues in pigs using 14C-methyl labelled paraquat. ICI Plant Protection Division Report No. AR2694A. (Unpublished) Leary, J.B. Paraquat: Chicken feeding study. Chevron Chemical 1974 Co., Ortho Division Report File No. 741. 11 PQ. (Unpublished) Litchfield, M.H. Grazing trial on paraquat-treated pasture. Central 1969 Toxicology Laboratory Report IHR/257. (Unpublished) Murray, R.E., and Gibson, J.E. A comparative study of paraquat 1972 intoxication in rats, guinea pigs and monkeys. Exp. Mol. Pathol., 17: 317-325. Rose, M.S., Lock, E.A., Smith, L.L., and Wyatt, I. Biochem. 1976 Pharmacol., 25: 419-423. Sarfaty, A.B. Diquat and paraquat. Observational trials on toxicity 1963 to sheep and cattle. Staiff, D.C., Comer, S.W., Armstrong, J.F., and Wolfe, H.R. 1975 Bull. Environ. Contam. & Toxicol., 14: 334-340. Stevens, M.A., and Walley, J.K. Tissues and milk residues 1966 arising from the ingestion of single doses of diquat and paraquat by cattle. J. Sci., Food Agr., 17: 472. Spinks, C.A., Hendley, P., Leahey, J.P., and Carpenter, P.K. 1976 Paraquat: Metabolism and residues in pigs using 14C-ring labelled paraquat. ICI Plant Protection Division Report No. 2692A. (Unpublished) (This contains newly produced data) Sykes, B.I., Purchase, I.F.H., and Smith, L.L. J. Path. 1976 (In press) Vijevaratnam, G.S., and Corrin, B. J. Path., 103:123-129. 1971
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 (WHO Pesticide Residues Series 2) 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)