PESTICIDE RESIDUES IN FOOD - 1983 Sponsored jointly by FAO and WHO EVALUATIONS 1983 Data and recommendations of the joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues Geneva, 5 - 14 December 1983 Food and Agriculture Organization of the United Nations Rome 1985 PROCHLORAZ TOXICOLOGY IDENTITY Chemical Name(s) 1-(N-propyl-N-(2-(2,4,6-trichlorophenoxy)ethyl)) carbamoylimidazole (IUPAC) N-propyl-N-[2-(2,4, 6-trichlorophenoxy)ethyl]-1H-imidazole-l- carboxamide (American Chemical Society) Synonyms SPORTAKR, FCB Code No. BTS 40542. Structural formulaMolecular formula C15 H16 Cl3 N3 O2 Other information on Identity and Properties Molecular weight: 376.5 State The pure material is a colourless, odourless crystalline solid; the technical material is a white to brown solid. Melting point 38.5 - 41.0°C Vapour pressure 0.57 × 10-9 Torr at 20°C Solubility At 25°C 0.055 g/l in water; ca. 16 g/l in kerosene; ca. 2 500 g/l in chloroform, xylene, diethyl ether and toluene; ca. 3 500 g/l in acetone. Stability The stability in aqueous solution is pH-dependent, prochloraz being more stable under slightly acidic conditions than under slightly alkaline conditions. Hydrolysis under alkaline conditions leads to the formation of N-propyl-N-2-(2,4,6-trichlorophenoxy) ethylamine, the degradation following first order kinetics. At pH 4.95 and pH 6.98 and 22°C, no degradation of prochloraz was observed after 30 days. At pH 9.18 and 22°C, the half-life was 78.9 days. Prochloraz tends to decompose on prolonged heating at high temperatures (ca. 200°C). Further information on the stability of prochloraz in soil, water, during processing and storage and on photodecomposition can be found under "Fate of Residues". Technical Material and Impurities The Meeting was provided with information on impurities in the technical material, all of which were said to range from < 0.2 percent to < 1.2 percent. No evidence has been found for the presence of trichlorodibenzo-p-dioxins or tetrachlorobenzofurans and all analytical procedures employed have failed to detect (i.e. less than 1 ppb) any of the notably toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin. Identity of Prochloraz-Manganese Complex Chemical Name tetrakis-{1-[N-propyl-N-[2-(2, 4, 6-trichlorophenoxy)ethyl]] carbamoylimidazole} manganese (II) chloride complex. Synonyms Prochloraz-manganese complex is the trivial name given to the 4:1 manganese coordination complex of prochloraz. FBC Code No. BTS 46828 or FBC 31114. Structural formula
Molecular formula C15 H16 Cl3 N3 O2)4 MnCl2 Other information on Identity and Properties Molecular weight 1 632 Melting point 141-142.5°C Solubility At 25°C 4 g/l in water, 7 g/l in acetone. Stability The manganese complex is quickly dissociated in water to give prochloraz. A suspension of the 50 percent wettable powder of the manganese complex in distilled water has been shown to dissociate to free prochloraz and manganese chloride to the extent of approximately 55 percent in four hours at 25°C. This process is unlikely to be affected greatly at pH 6 to 9 Whiting & Dickson 1979. EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, Distribution and Excretion Mouse After a single oral dose of 14C-phenyl labelled prochloraz at 100 mg/kg b.w. was administered to a group of male and female mice, the over-all recovery of the given radioactivity was virtually complete within 72h. Total recovery was complete (104 percent) with urinary excretion (63 percent) being the major route. There were no significant sex differences in the rate or route of excretion. Tissue residues were highest in liver (5-7 mg/kg) and lowest in muscle, genitals, eyes, spleen and fat (0.5-1.0 mg/kg). In all other tissues the average value was below 2.5 mg/kg (Needham 1982a). Rat The excretion rate of prochloraz was monitored for 96 h in three male and three female rats administered a single oral dose of 14C-phenyl-labelled prochloraz (91 mg/kg b.w.). The over-all recovery of the administered radioactivity was 92.7 percent in male and 93.7 percent in female rate, urinary excretion being the predominant route. The mean radioactivity was 61.7 percent in the urine and 30.8 percent in the faeces of male rats. It was 54.8 percent in urine and 38.5 percent in the faeces of female rats. Highest residues, 96 h after dosing, were found in the liver (3.7-6.2 mg/kg) and kidney (1.5-2.5 mg/kg), the tissues of female rats having higher residues (Needham & Campbell 1980). The chemokinetics were studied over a 96 h period, using an oral dose of 100 mg/kg b.w. 14C-imidazole-radiolabelled prochloraz. Male rats excreted the administered radioactivity almost quantitatively, with approximately 83 percent in the urine, 9 percent in faeces and 2.4 percent in the expired air. Female rats excreted 56 percent in urine, 21 percent in faeces and 1.3 percent in expired air. Plasma radioactivity levels reached a peak in male rate approximately 4 h after dosing, whereas the levels in female rats remained relatively uniform but much lower. Liver radioactivity levels were significantly raised within 15 min. and, in the kidney, 30 min. after dosing. They generally remained constant for at least 8 h. Significant accumulation occurred in brain and adipose tissues, which persisted over 1-8 h and then declined markedly between 8 and 24 h. The levels of radioactivity in the gastrointestinal tract, 24 h after dosing were significantly higher in females compared to males. In general, plasma and tissues showed a decline in radioactivity levels over the 96 h period, after which time they reached small, though still significant, levels (Turner & Gilbert 1977). 14C-imidazole ring-prochloraz was administered orally in another study at 25 mg/kg b.w./day for 24 days. Residues of prochloraz appeared to reach a plateau at about 15 days in the adrenals, ovaries, female thyroid and male plasma, while other tissue levels continued to increase over the entire 24-day period. The highest residues after administration were found in the liver (20.88 ppm males and 25.03 ppm females), and the lowest in the fat (2.82 ppm males and 3.72 ppm females). The radioactivity was eliminated slowly from tissues, significant residues being found after 96 h. Liver and plasma residues had a half-life of less than three days and that of muscle was approximately 17 days in males and 30 days in females (Hamilton 1978a) 3H-phenyl-labelled prochloraz was administered daily in another study as repeated oral doses of 25 mg/kg for a 20-day period. Plasma and tissue radioactivity were measured at specified intervals throughout the period of treatment and at 96 h after the last daily dose. Plasma levels were higher in males than in females. Tissue levels for both sexes rose significantly for the first seven days of dosing and thereafter rose only slightly for the remainder of the dosing period. Highest levels of radioactivity were found in liver and kidney and lowest in muscle and fat. Within 96h after treatment, the radiolabelled phenoxy moiety of prochloraz was rapidly eliminated from the body without leaving significant tissue residues (Boardman 1979). Dog A group of two male and two female dogs was given a single oral dose of 14C-imidazole-labelled prochloraz at 20 mg/kg b.w., while a second group received the same amount of 3H-phenyl-labelled prochloraz. There was a marked difference between the plasma concentrations of 14C and 3H-labelled prochloraz, suggesting that the pesticide was metabolized by fission at the chain linking the imidazole and trichlorophenol moieties. The dogs were killed 24 h after the administration of the radioactive prochloraz and tissues subsequently assayed for radioactivity. Both 14C- and 3H-radio- labelled compounds showed high levels in bile and liver (Hamilton 1978b). The distribution and excretion were studied in other groups of male and female dogs following a single oral dose of 18 mg/kg b.w. of 14C-phenyl ring-labelled prochloraz. Peak plasma radioactivity occurred 8-24 h after dosing and plasma half life was approximately 72 h. Excretion was rapid, 60 percent of the dose being eliminated in the first 24 h; the over-all recovery after 96 hours was 96 percent with faecal excretion as the major route (64 percent of the total dose). No sex differences were noted in the rate of excretion or in the magnitude of the tissue residues. Highest residues were found in the liver and kidney (7.6 and 5.6 mg/kg, respectively) and lowest in bone, cerebellum and CSF (less and 1 mg/kg). High residues were present in the bile, indicating that biliary excretion represents a significant route of elimination in dogs. This finding agrees with the high percentage of radioactivity found in the faeces (Needham & Campbell 1982). Goat One lactating goat was treated with two oral doses of 14C-phenyl prochloraz at 60 mg/kg b.w. given at a 13-day interval. Milk residues after the first dose were highest 8 h after dosing (0.04 ppm) and declined to 0.01 ppm within 48 h. Plasma residues were highest at 24 h (0.33 mg/l), declining to 0.03 mg/l at 13 days. Twenty-four h after the second dose, the highest tissue residues were found in the liver (1.67 mg/kg), while residues in muscle were minimal (0.03 mg/kg) (Campbell 1980). Biotransformation The biotransformation was studied in a group of male and female rats given an oral dose of 100 mg/kg b.w. 14C-imidazole ring-or 14C-phenyl ring-labelled prochloraz as a suspension in gum acacia or dissolved in maize oil. A similar regimen was followed in separate experiments with mice and dogs, except that only 18 mg/kg b.w. of the labelled prochloraz was administered to dogs. Prochloraz was extensively metabolized in the rat, with no unchanged compound being excreted in the urine. The qualitative and quantitative profiles depicted in Figure 1 suggest that metabolism proceeds via cleavage of the imidazole ring into 2-carbon fragments, followed by hydroxylation of the phenyl ring and/or side chain hydrolysis to form more polar compounds. Two main metabolites: 2-(2,4, 6, trichlorophenoxy) ethanol (BTS 3037); 2,4,6, trichlorophenoxyacetic acid (BTS 9608) and five other minor metabolites were identified. The two main metabolites accounted for about 80 percent of the urinary metabolites. A similar metabolic pattern was found in the urine of mice, dogs and the female goat (Needham 1982b).
Effects on Enzymes and Other Biochemical Parameters In a series of investigations in male rats and mice prochloraz was found to be an inducer of hepatic mixed function oxidases (MFO). Rats were dosed orally with prochloraz at 10 and 100 mg/kg b.w. twice daily for four days and killed 18 h after the last dose. Potent induction of MFO occurred at the higher dose, but only a marginal effect was seen at the low dose. Relative liver weight and microsomal protein concentrations were increased at the high dose. The induction spectrum of MFO was similar to that of phenobarbitone, with the levels of cytochrome P-450, being increased by both dosages (Needham 1983a). A similar MFO induction was noted when male rats were fed prochloraz in their diet at 2 500 ppm for seven days. Rats fed a lower dose (100 ppm) showed only a small increase in cytochrome P-450 (Riviere 1983). The same pattern of hepatic MFO induction was observed in mice after oral administration of doses of 10 and 100 mg/kg b.w. twice daily for four days (Challis & Campbell 1983). Prochloraz was an inducer of MFO following dietary administration at 325 and 1 300 mg/kg in the diet for two weeks. When the compound was administered at 80 mg/kg for periods in excess of two weeks, the effect was marginal, indicating that this concentration is close to the threshold level for induction (Needham 1983b). Effect of Dog Gastric Juice or Plasma on Prochloraz In vitro studies showed prochloraz to be completely stable after incubation with dog gastric juice or plasma for 30 min. at 37°C or for 4 h at 37°C. Less than 2 percent underwent hydrolysis. The initial step in the metabolism of prochloraz is therefore likely to occur in the liver (Needham 1980). TOXICOLOGICAL STUDIES Special Study on Reproduction Rat Groups of rats (30 rats of each sex for the Fo generation and 25 of each sex for the F1 generation) were fed a diet containing 0, 37.5, 150 or 625 ppm prochloraz (nine weeks for Fo and eight weeks for F1) prior to mating and throughout mating, gestation and lactation. Two litters per generation were produced for two generations. Observations included growth, food consumption, mortality and the usual reproduction indices: mating, fecundity, male and female fertility, gestation, lactation, pup mortality, litter and mean pup weights, viability and terminal studies. In the males (Fo), receiving 625 ppm in the diet, a prolonged aggression was observed when rehoused after both matings; this was not apparent among F1 males. Among Fo females, the following overt clinical signs were noted in late gestation and/or in the perinatal period: hunched posture, walking on toes, piloerection and pallor. Sporadic mortality was recorded at the different dose levels and was generally related to dystocia. Food intake during the premating period showed no consistent dosage relationship for all animals of both generations. However, consumption was generally lower than that of the controls. Mean body weight gains were depressed only in the premating period in the Fo animals of both sexes, given 625 ppm, the same trend being noted during gestation. There were no significant effects associated with mating performance and pregnancy rate in the treated animals. Some adverse effects on gestation periods were noted only at 625 ppm in both generations, with a small number of females dying or being killed after exhibiting signs of dystocia. There was also an increase in the proportion of females with gestation periods in excess of 22 days. A small number of females dosed at 625 ppm showed a total loss of litters, a lowered mean litter size at birth, increased pup mortality at birth and evidence of reduced pup body weight gain in the immediate perinatal period at both matings of the Fo animals and at the first mating of the F1a animals. A slight lowering of mean litter size at both matings was recorded also for the Fo generation fed 150 ppm but not for the F1 generation. However, none of the findings were significantly different from the controls. At 37.5 ppm, a reduction in the mean litter size at birth to day 12 postpartum was noted in the first mating of the Fo generation. However, the results were again within the range for controls at the testing laboratory. No indication of any adverse incidence of structural anomalies associated with treatment were recorded at terminal macroscopic examination of the remaining F1a and F2a pups and all F1b and F2b offspring. Increased mean liver weight was recorded in weanling and adult F1a males and F2a weanling females given 625 ppm in the diet. In the same treated group, mean thymus weight in F1a weanlings of both sexes and mean brain weight in the F1a female weanlings was lower than in the controls. Microscopic examination of tissues of both sexes from weanling F1a and F2a generations and F1a adults selected from control and treated groups showed no changes that could be considered attributable to exposure to the test compound; 37.5 ppm represented the dietary no-effect level (Cozens et al 1982). Special Studies on Teratogenicity Rat Groups of 20 mated Charles River CD rats were given oral doses of 6, 25 or 100 mg/kg daily from day 1 to 20 post coitum (day 1 was the day when sperm was detected in the vaginal smear). A group of 31 rats given the vehicle of 10 percent aqueous acacia solution served as controls. Body weight, food consumption and overt signs of toxicity were recorded throughout the study. The dams were killed on day 21 of pregnancy. The 25 and 100 mg/kg daily dosage elicited maternal toxicity as evidenced by reduced food consumption, lower body weight and liver enlargement; in addition, the dams showed increased salivation and rubbed their noses in the sawdust litter. The only effect noted in the rats given 6 mg/kg was a marginally lower body weight gain. There were no macroscopic or microscopic findings attributable to treatment. The number of corpora lutea was similar for all groups. The highest dosage level appeared to be embryotoxic, as litter size, implantation index and viability index were all slightly lower, while the incidence of dead foetuses was marginally elevated. In addition, mean foetal weight was lower, one litter containing unusually small foetuses that appeared to have a gestational age of approximately 19 days. The mean placental weight for both the male and female foetuses was higher for the 25 or 100 mg/kg treated groups than for the control. A small number of foetal abnormalities was noted among the treated groups but no consistent pattern and no correlation between incidence and dosage level was noted. The degree of calcification of the sternebrae and vertebral arches was retarded in foetuses at the 100 mg/kg dose level. This dosage elicited toxicity in both dams and embryos but produced no teratogenic effects. The 25 mg/kg dosage was toxic in the dams. The only findings in the 6 mg/kg group were marginally reduced body weight gain and a very slight (non-significant) elevation of placental weight (Beswick 1980). Rabbit Groups of 15 rabbits (New Zealand white strain) were administered daily dosages of 0, 3, 12 and 48 mg/kg b.w. of prochloraz by intragastric intubation on days 1 to 28 of pregnancy inclusive (day 1 = day of mating). The control group of 15 rabbits was dosed with the vehicle, i.e. 10 percent acacia solution. All surviving dams were killed on day 29 of pregnancy for macroscopic examination and the foetuses removed for external visceral and skeletal examinations. No treatment-related clinical signs and mortality were noted. Food intake of the test group remained within 5 percent of the control value, with a slightly reduced weight gain in all test groups during the first week of dosing. The pregnancy rate was comparable for all groups. A significant increase was noted in liver weight, with liver discolouration in dams given 48 mg/kg day. A single dam from each of the low-and high-dosage groups aborted completely, while one of the control dams aborted partially. Litter size, post-implantation loss, litter weight and mean foetal weight were considered unaffected by treatment. Embryonic and foetal development, as assessed by incidence of major malformations, minor anomalies and skeletal variations, were similarly unaffected by treatment. No evidence of embryonic teratogenic activity was therefore noted in New Zealand white rabbits (Palmer et al 1980). Special Studies on Mutagenicity Ames test Purified and technical prochloraz were tested in the Ames test against Salmonella typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100. All tests were performed in the presence and absence of a liver microsome activation system (S-9) derived from phenobarbitone-induced rats and tested at levels of 62.5, 125, 250, 500 and 1 000 mcg/plate. Positive control mutagens were included in all tests to demonstrate the mutability of the bacterial strains and the metabolizing capacity of the S-9 preparation; these comprised cyclophosphamide, 6-aminochrysene and 2-animofluorene. Dimethyl sulphoxide served as the negative control throughout. There was no evidence of mutagenic activity against any of the strains employed but the antibacterial effects of prochloraz precluded evaluation of mutagenicity at concentration of 1 000, 500 and, in some cases, 250 mcg/plate (Wilcox 1977). Micronucleus assay Groups of five male and five female Charles River CD rats were given two intraperitoneal injections of 6.25, 25.0 or 100 mg/kg b.w. of prochloraz 24 h apart. Similar groups were given intraperitoneal injections of cyclophosphamide 200 mg/kg b.w. to serve as positive controls and intraperitoneal injections of the vehicle (maize oil) as the negative controls. Six hours after the second injection all animals were killed, smears from the bone marrow of the femur were prepared and examined microscopically to determine the incidence of micronuclei in the polychromatic erythrocytes. No significant increase in the incidence of micronuclei was observed in any of the groups of rats. Prochloraz was without clastogenic activity in rats of both sexes when tested up to 100 mg/kg b.w. (Everest & Cliffe 1980). Dominant lethal test Groups of 20 male CD1 strain pathogen-free male mice (age 5-6 weeks) were given 0, 6, 25 or 100 mg/kg/day prochloraz in the diet for eight weeks. After this treatment period, they were paired with untreated females on a 1:1 basis for one week and then with a second batch of untreated females for a further week. Approximately two weeks after the discovery of a vaginal plug or 14 days after the midweek of their pairing, the females were killed and their uterine contents examined. There were no signs of reaction to treatment and mean weight gains of all test groups compared favourably with that of the control group. Intergroup variations in mean food consumption throughout the entire treatment period were minimal and showed no consistent dosage-related trend. Mating performance of treated males and subsequent pregnancy rates among untreated females were unaffected by treatment at any dosage, except for one male at 25 mg/kg/day, which failed to induce pregnancy at either mating. No obvious treatment-related macroscopic changes were observed at terminal necropsy of the males. Mean weights of the testes of treated males were slightly higher than the control value but were not statistically significant. There was no evidence of a dose-related effect on the pregnancy rate, mean number of implantations, viable young, embryonic death and post-implantation losses. Prochloraz showed no evidence of a dominant lethal effect in male mice (Cozens et al 1980). Mouse lymphoma mutation assay Technical prochloraz was tested for mutagenic activity in mouse lymphoma cells L5178 Y rendered heterozygous at the thymidine kinase (TK) locus. The tests were carried out in the presence and absence of a post-mitochondrial supernatant fraction from Arochlor 1254-treated male rat livers and the co-factors required for mixed-function oxidase activity. In an initial test carried out over a dose range of 0.16 mcg/ml to 1.6 mg/ml indicated, that prochloraz was toxic to the cells, causing extensive cytotoxicity at a concentration of 158 mcg/ml. In two further independent experiments at 50.0 mcg/ml and the second at 70.0 mcg/ml no significant increases in mutation frequency in the prochloraz-treated cells over the vehicle control values were observed. The concurrent positive control substances were ethyl-methanesulphonate, which does not require the presence of S-9 mix, and 2-acetylaminofluorene, which requires the presence of S-9 mix for metabolism. In both cases, high mutation frequencies were obtained. Technical prochloraz was not mutagenic to mouse lymphoma L 5178 Y cells when tested over a series of dose levels, which extended into the toxic range, in the presence or absence of S-9 mix (McGregor et al 1983). Special Studies on Carcinogenicity Mouse Groups of 52 male and 52 female mice CD-1 strain mice were fed technical prochloraz in the diet at 78, 325 and 1 300 ppm. For each sex, treatment continued until survival reached 20 percent, which was 106 weeks for males and 121 weeks for females. An additional group of 104 males and 104 females received the normal diet only. Observations included clinical signs, mortality, body weight, food consumption and, at 52 weeks and terminally, haematology and weight of selected organs. Comprehensive histopathological examinations were made of tissues from all surviving animals. Clinical signs were not evident, except in mice given 1 300 ppm and in males treated at 325 ppm which were killed because of distended abdomens. These animals were subsequently found to have multiple liver tumours. No other overt signs of toxicity related to treatment were observed. There was no mortality in the course of the study attributable to prochloraz. Mice given 1 300 ppm showed slightly reduced body weight gain. No differences were noted, that were considered to be of toxicological significance, in the haematological parameters between treated and control mice. Slightly lower haemoglobin concentrations and lower total white blood cell counts, due to a lower lymphocyte count, were noted at week 104 in female mice treated with 1 300 ppm in diet. At necropsy, an increase of liver weights was recorded in both sexes given 1 300 ppm prochloraz. There was a dose-related increase in the incidence of adenomas and adenocarcinomas of the liver in both males and females. At 1 300 and 325 ppm, the increased incidence was statistically significant and liver tumours (of hepatocyte origin) were observed in both sexes, which were associated in a number of mice with more than one tumour. Some cases at 1 300 ppm showed multiple tumours as contributory factor to death. At 78 ppm, a slightly higher incidence of liver tumours in female mice (6 out of 52) compared to controls (5 out of 104) was noted, though the difference was not statistically significant. In the males, the incidence of liver tumours was similar in controls (37 out of 104) and treated mice (21 out of 52). There was no evidence of any other effects of treatment in terms of either neoplastic or non-neoplastic pathology. Treatment of mice was associated with a dose-related increase, evident in both sexes, of liver tumours of all types. The incidence of liver tumours was statistically significant at 1 300 ppm and 325 ppm but not at 78 ppm prochloraz. The dietary dosage of 78 ppm was equivalent to 7.5 mg/kg/day in males and 8.8 mg/kg/day in females (Colley et al 1983). Special Studies on Skin and Eye Irritation A moderate to severe skin irritation produced in the rabbit suggests that prochloraz is a skin irritant (Kynoch & Liggett 1979a). Instillation of dilute solution of prochloraz into the everted lower eyelid of one eye of New Zealand white stream rabbits produced a mild conjunctival irritation in some animals which persisted up to three days (Kynoch & Liggett 1979b). Acute Toxicity Prochloraz is of low toxicity to rodents when administered orally. In rats, the LD50 ranged from 1 600 to 2 400 mg/kg b.w. and in mice it was approximately 2 400 mg/kg b.w. Symptoms of intoxication became apparent within 30-60 minutes of dosing and included CNS depression, respiratory disturbance, ataxia, increased salivation, piloerection, increased lacrimation and distended abdomen with signs of gastrointestinal irritation. The acute toxicity of prochloraz in rodents is summarized in Table 1. Table 1. Acute Toxicity of Prochloraz in Rodents Species Route LD50 (mg/kg) References Rat Oral 1 600-2 400 Carter et al. 1978 Mouse Oral 2 400 Shaw & Carter 1976 Rat Dermal 5 000 Carter 1975 Rabbit Dermal 3 000 Kynoch & Liggett 1979a Rat Inhalation (6h LC50) >420 mg/cu.m. Alexander & Clark 1978 Rat Intraperitoneal 400-800 Smithson & Lancaster 1980 In dogs given a single oral dose of 10, 100 or 250 mg/kg b.w. of prochloraz, there were no deaths and the only toxic signs were emesis and diarrhoea at 100 and 250 mg/kg b.w. (Stobart et al. 1978). One female baboon given prochloraz at 50 mg/kg b.w. showed no toxic effect while 250 mg/kg b.w. produced only emesis (Morgan et al. 1977). Following dermal application to rabbits of 3 000 mg/kg for 24 h there were no toxic effects except moderate to severe erythema and oedema on the treated skin (Kynoch & Liggett 1979a). Short-Term Studies Mouse Groups of 9 male and 9 female and 15 male and 15 female CD-1 strain mice were fed prochloraz in the diet at 6, 25, 100 and 400 mg/kg/day for 6 weeks and 13 weeks, respectively. Groups of 9 or 24 mice of each sex, given a diet without prochloraz, acted as controls. Two additional groups of 15 mice of each sex were given a control diet for 17 weeks and a diet containing prochloraz at a nominal dose level of 400 mg/kg/day for 13 weeks, followed by a 4-week recovery period. Overt signs of toxicity were recorded daily and body weight and food consumption three times weekly; haematological and blood biochemistry analyses were done at 6 weeks, 13 weeks and 4 weeks off-dose. All mice were killed at the end of the dosing or recovery period, examined macroscopically, the main organs were weighed and microscopic examination of tissues performed. No deaths occurred that were attributable to treatment with prochloraz. An increased incidence of piloerection occurred in mice of both sexes given 400 mg/kg daily. Food consumption of both sexes given 400 mg/kg daily was higher than that of the controls throughout the dosing period and during the first week of the recovery period, but was similar to the controls thereafter. A slight weight loss was observed in the males given 100 mg/kg daily and in the females given 400 mg/kg daily. At week 6, haemoglobin concentration, PCV and red blood cell counts were increased in both sexes given 400 mg/kg daily; MCH was also marginally increased in the females and leucocyte counts were increased in females due to lymphocytosis. At week 13 or after four weeks recovery, these parameters were no longer affected by treatment. Plasma GPT activity was increased at week 6 in some mice of both sexes given 400 mg/kg daily and some males at 100 mg/kg daily. At week 13, it was increased in the majority of females given 400 mg/kg daily and in some mice of both sexes given 100 mg/kg daily. After four weeks recovery, some of the males given 400 mg/kg daily were still affected. Albumin content and consequently the albumin:globulin ratio, were slightly reduced in both sexes given 400 mg/kg daily and in the males given 100 mg/kg daily. At week 13, in both sexes at 400 mg/kg daily, urea-nitrogen was slightly decreased and glucose levels were increased. Liver weight was increased at week 13 in both sexes given 25, 100 or 400 mg/kg daily. The ovaries in the females and the prostate and seminal vesicles in males were small in the group at 400 mg/kg daily. After 4 weeks recovery, liver weights were still higher in both sexes given 400 mg/kg daily, but to a lesser extent than at weeks 6 and 13. Histopathological examination showed minor liver changes with loss of glycogen and periportal fat droplets in both male and female mice receiving 400 mg/kg and in females receiving 100 mg/kg for 13 weeks. Some male mice receiving 100 or 400 mg/kg also showed centrilobular hepatocyte enlargement. In both male and female mice killed after four weeks recovery, none of these changes were present. The no-effect level in mice was 6 mg/kg/day (Gale 1980; Lancaster 1982). Rat Groups of 20 male and 20 female Boots-Wistar rats were given a daily dose of prochloraz by oral gavage in 10 percent aqueous acacia suspension at 0, 6, 25 or 100 mg/kg b.w. for 13 weeks. Further groups of 20 male and 20 female controls given 100 mg/kg daily of prochloraz remained untreated for four weeks after the end of the dosing period and, in addition, groups of 10 males and females were given 0, 6, 25 or 100 mg/kg daily of prochloraz for six weeks. Overt signs of toxicity observed in rats of both sexes were increased salivation at 25 or 100 mg/kg daily and in a few given 6 mg/kg daily. The incidence of diarrhoea was increased during the first four weeks of dosing in the males given 100 mg/kg daily and possibly in the first week in the males given 25 mg/kg daily. In females, a few instances of diarrhoea were recorded at each dose level. Food consumption was not affected by treatment. However, test females gained somewhat more weight than the controls at 25 or 100 mg/kg daily. At week 6, the only consistent haematological change was a decreased haemoglobin concentration in males at each dose level and in females given 100 mg/kg daily. A leucocyte count increase was noted at each dose level in males due to lymphocytosis. At week 13, MCV was slightly decreased at each dose level in the males and haemoglobin concentration was slightly decreased in females treated at 25 or 100 mg/kg daily and in males given 100 mg/kg daily after the four weeks recovery period. Serum bilirubin was slightly decreased in both sexes at each dose level at week 6, in the male at each dose level and in the females given 6 or 100 mg/kg daily at week 13. Serum potassium was slightly increased at week 6 in the males at 25 or 100 mg/kg and females at 100 mg/kg daily. UGOT excretion was slightly elevated in a few rats of both sexes at each dose level. Urinary protein content was reduced in the females at each dose level and in males given 100 mg/kg daily. Liver weight at week 6 was increased in both sexes given 100 mg/kg daily and in the females given 6 or 25 mg/kg daily; kidney weight was increased in both sexes given 100 mg/kg daily; spleen weight was reduced in the males in each dose group; ovary weight was increased in each dose group and thyroid weight was also increased in females given 6 or 100 mg/kg daily. After the four-week recovery period, the weights of the liver, ovaries and thyroids of the females were slightly higher than the control values. The changes in liver cell size correlated closely with the increase in liver weight. The only instance where such correlation was not apparent was at week 13 in the females given 6 mg/kg daily, where the centrilobular cells were slightly larger but liver weight was unchanged. No other findings, that could be related to treatment, were observed at microscopic examination of tissues from the rats given 100 mg/kg daily and killed at week 13. Various treatment-related effects were noted in the rats of both sexes given 6 mg/kg daily of prochloraz and a no-effect level was therefore not established. However, all these effects were marginal (Lancaster & Shaw 1979a). Dog Groups of four male and four female beagles were given daily doses of 1, 2, 5, or 7 mg/kg of prochloraz by gastric intubation for 13 weeks. Groups of eight males and eight females received 20 mg/kg daily or the vehicle (10 percent aqueous acacia solution) concurrently. At the end of the dosing period, four males and four females from each of the 20 mg/kg and control groups were kept for another four weeks without treatment. Overt signs of toxicity observed during the dosing period included isolated bouts of emesis and increased salivation in some dogs from all groups, including controls, although these were more prevalent at the high dosage. All dogs at 20 mg/kg daily and one given 7 mg/kg daily occasionally produced yellow mucoid and/or liquid faeces. No effects of treatment were detected on faecal occult blood content. During the recovery period, no overt signs of toxicity were observed. Reduced food consumption was recorded during the dosing period in two dogs given 20 mg/kg daily. Body weight changes during the study were comparable in control and treated groups, although greater fluctuations were recorded in dogs given 20 mg/kg daily. There was no treatment-related effect detected by ophthalmoscopy or electrocardiography. Transient slight decreases in erythrocyte count and/or haemoglobin concentra- were recorded in a few females given 7 or 20 mg/kg daily. No other treatment-related changes in haematological parameters were noted. Changes in the activity of serum enzymes were recorded. The serum alkaline phosphatase was high during the dosing period in the majority of dogs given 20 mg/kg daily and in some given 7 mg/kg daily. Serum leucine aminopeptidase was slightly elevated at week 6 in some dogs given 20 and in one given 7 mg/kg and serum GPT was increased in a dog given 7 mg/kg daily. No change was observed in urinary parameters. At necropsy, all dogs given 20 mg/kg daily and three given 7 mg/kg daily had large and heavy livers. Low prostate weights were recorded at week 14 in three dogs and in another two dogs in the same group at 17 weeks. One of these dogs, killed at week 10, also had decreased testes weight. In addition, one dog, given 7 mg/kg daily, had a low prostate weight relative to body weight. In two females at the high dose killed at week 14, and one killed at week 18, clear brown exudate from freshly sectioned mammary glands was observed. There were no histopathological findings in dogs on the high prochloraz dosage. Counts of liver nuclei revealed no statistically significant difference in the cell liver size or in the micronuclei count between control and treated dogs. In dogs retained for the recovery period, liver size and weight returned generally to within normal limits, suggesting that any effect of treatment on these parameters was reversible. The changes of AP and LAP also returned to normal during the recovery period. The dose producing no adverse-effect was 2.27 mg/kg daily (Lancaster et al. 1979b; Lancaster 1980). Long-Term Studies Rat Groups of 150 male and 150 female rats constituted the controls. Two groups each of 80 males and 80 females were treated with 37.5 and 150 ppm and a further two groups of 90 males and 90 females were given 625 ppm prochloraz in their diet. When the survival approached 20 percent in any group, all animals of that sex group were killed (111 weeks of treatment for females and 115 weeks of treatment in the males). There were no overt signs of toxicity recorded during the study that could be considered related to the treatment. During weeks 20 and 21, the majority of rats from all groups showed signs indicative of sialodacryo-adenitis infection, with a further relapse of mild infection in a few rats from each group during the weeks 66 and 67. Male survival was similar to controls, while treated females survived longer than controls. A lower food consumption with a reduced body weight gain was recorded for both sexes given 625 ppm. At 150 ppm, food consumption was marginally lower throughout in males and until week 52 in the females. Ophthalmoscopic examination revealed no abnormalities related to treatment. In a few rats, minor changes were seen at week 26, which were considered sequelae of sialodacryo-adenitis infection. Periodic laboratory measurements of haematological, biochemical and urinalysis parameters in a few treated rats at 625 ppm showed changes, but these were minimal and considered of doubtful toxicological significance. The changes in urinalysis were minor, i.e. lower total protein and changes in the pH. A minimal higher activity of serum glutamic oxalacetic transaminase was noted. No macroscopic findings related to treatment were seen at interim kill in week 13. However, at the 52-week kill, enlarged or swollen livers were observed in one male and three females given 150 ppm and in four males and one female given 625 ppm in the diet. Heavier livers were noted in males and females given 625 ppm diet at week 52 and lower pituitary weights were also recorded in a few rats. Histopathological examination showed hepatic centrilobular enlargement in females given 625 ppm; periportal glycogen loss and centrilobular fat deposits were also present in some treated rats of both sexes. There were no other microscopic findings related to treatment. Enlarged and swollen livers were observed in a higher proportion of male rats given 625 ppm than in the controls, and slightly heavier liver weights were recorded for females given 625 ppm. The incidence of hyperplastic lesions in the liver was slightly higher than in the controls in both sexes given 625 ppm, but the differences were not statistically significant. The incidence of all other non-neoplastic findings was similar in all groups. There was no evidence of carcinogenicity from the chronic administration of prochloraz. The no-effect level for toxicological changes was 37.5 ppm, equivalent to a mean intake of 1.3 mg/kg/day in males and 1.6 mg/kg/day in females (Colley et al. 1982). Dog Technical prochloraz was fed to groups of five males and five females at levels of 0, 30, 135 and 600 ppm (increased to 1 000 ppm from week 57) for 104 weeks. Observations included clinical signs, mortality, food and water consumption and, at weeks 0, 13, 26, 51, 78 and 104, ophthalmoscopy, electrocardiography and clinical laboratory studies. These comprised haematology, biochemistry, urinalysis and faecal occult blood. At necropsy, organs were weighed and comprehensive macroscopic and microscopic examinations were carried out. There were four deaths during the study but none was attributable to treatment. There were no overt signs of toxicity or effects of treatment upon body weight, food or water consumption, ophthalmoscopic or electrocardiographic findings that could be related to treatment. There were a few changes in the biochemical parameters, including a higher level of SAP for males receiving 600 ppm in the diet during week 13 and, during weeks 16 and 50, the elevation was also apparent in the females. After the dietary level was increased to 1 000 ppm for this group, there was a marked increase in the SAP levels during week 60, which persisted throughout the rest of the dosing period. The mean level for males receiving 135 ppm was also higher than the control mean from week 13 onwards, but the difference was not so marked as at 600 ppm. There was a slight but inconsistent increase in the platelet count, glucose and cholesterol values in the group receiving 600 to 1 000 ppm, but these could not be related definitely to treatment. There was no effect of treatment on the urinary parameters or faecal occult blood content. Liver weights in five animals that received 600 to 1 000 ppm, one that received 135 ppm and one control, when expressed as a percentage of body weight, exceeded the normal upper limit. The mean prostate weight for animals in the same treatment group was significantly lower than the control mean weight. Histopathological examination showed minimal prostatic atrophy, low grade hepatitis and minimal swelling and rarefaction of centrilobular hepatocytis at 600 to 1 000 ppm. One male dog given 135 ppm also showed some liver changes. There were no other histopathological changes related to prochloraz. The no-effect level was 30 ppm in the diet, equivalent to approximately 0.92 mg/kg/day (Chesterman et al. 1981). Observations in Humans Prochloraz has been produced on a commercial scale since 1980. No adverse human effects have been detected since then from synthesis formulation or use of prochloraz or its formulation. No clinical or laboratory data were included (Bonsall 1982). COMMENTS Prochloraz has low oral toxicity. Following oral administration in the rat, 95 percent of the dose is rapidly absorbed. In rats, the major excretion is via the urine; in dogs it is via the faeces. Prochloraz is a demonstrated liver mixed function oxidase inducer. In rats and rabbits, no evidence of teratogenic effects was noted at maternally toxic dose levels. A multigeneration reproduction study in rats did not show any adverse effects at doses up to 37.5 ppm. Mutagenicity studies, including the Ames test, micronucleus test, mouse lymphoma assay and a dominant lethal study, were all negative. In 90-day studies in mice, rats and dogs, liver weight was increased in all species. No-effect levels of 6 mg/kg/day and of 2.27 mg/kg/day were established for mice and dogs, respectively. However, in rats 6 mg/kg/day induced increased liver weight and occasional signs of intoxication (increased salivation, diarrhoea). A two-year dog study established a no-effect level of 30 ppm. A long-term rat study did not result in any evidence of oncogenic potential. A no-effect level of 37.5 ppm in the diet was established. A mouse carcinogenicity study of 106 weeks duration indicated an increased incidence of liver adenomas and adenocarcinomas in both sexes at dose levels of 325 ppm and above. Prochloraz has been shown to be a hepatocarcinogen in mice. TOXICOLOGICAL EVALUATION Level Causing no Toxicological Effect Rat (male); 37.5 ppm in the diet, equal to 1.3 mg/kg b.w. Dog: 30 ppm in he diet, equal to 0.9 mg/kg b.w. Estimate of Acceptable Daily Intake for Man 0 - 0.01 mg/kg b.w. FURTHER WORK OR INFORMATION Desirable Observations in humans. REFERENCES-TOXICOLOGY Alexander, D.J. & Clark, G.C. Preliminary acute inhalation toxicity 1978 study in male and female rats with pure prochloraz (single exposure). Report TX78053 from Huntingdon Research Centre and Boots, submitted to WHO by FBC Ltd. (Unpublished) Boardman, L.E. Plasma and tissue distribution studies in the rat 1979 following single and repeated oral doses of 3H-prochloraz. Report AX79004 from Hazleton and Boots submitted to WHO by FBC Ltd. (Unpublished) Beswick, A.M. The teratogenicity study of technical prochloraz in male 1980 and female rats. Report TX80024 from Boots submitted to WHO by FBC Ltd. (Unpublished) Bonsall, J.L. The human exposure to prochloraz since synthesis in 1974 1982 and commercial production in 1980. Report submitted to WHO by FBC Ltd. (Unpublished) Campbell, J.K. Residues in milk and tissues of a goat dosed orally 1980 with 14C-prochloraz. Report AX80026 from Boots submitted to WHO by FBC Ltd. (Unpublished) Carter, O.A. Acute dermal toxicity of prochloraz to the male Boots 1975 Wistar rat. Report TXM75079 from Boots submitted to WHO by FBC Ltd. (Unpublished) Carter, O.A., Smithson, A. & Burnett, R. Acute oral toxicity of 1978 prochloraz, prochloraz pure material, stage 3 and stage 4 technical material and mother liquor concentrate impurities to male Boots Wistar rats. Report TX78118 from Boots submitted to WHO by FBC Ltd. (Unpublished) Challis, I.R. & Campbell, J.K. The effect of prochloraz on the hepatic 1983 mixed function oxidase system of the male mouse after oral administration. Report METAB/83/6 from FBC submitted to WHO by FBC Ltd. (Unpublished) Chesterman, H. et al. Two-year toxicity study in beagle dogs of 1981 technical prochloraz - final report - repeated dietary administration for 104 weeks. Report TOX/81/173-2 from Huntingdon Research Centre and FBC submitted to WHO by FBC Ltd. (Unpublished) Colley, J. et al. Prochloraz chronic toxicity and carcinogenicity 1982 study in rats by dietary administration - 104 weeks (final report). Report TOX/82/173-8 from Huntingdon Research Centre, and FBC submitted to WHO by FBC Ltd. (Unpublished) Colley, J. et al. Prochloraz tumorigenicity study in mice by dietary 1983 administration (final report). Report TOX/83/173/23 from Huntingdon Research Centre and FBC submitted to WHO by FBC Ltd. (Unpublished) Cozens, D.D., Reid, Y.J., Woodhouse, R.N., Almond, R.H. Anderson, J. 1980 & Ball, S.I. Dominant lethal gene assay of technical prochloraz in the male mouse. Report TX80077 from the Huntingdon Research Centre and Boots submitted to WHO by FBC Ltd. (Unpublished) Cozens, D.D. et al. The effect of prochloraz on reproductive function 1982 of multiple generations in the rat. Report TOX/82/173-5 from Huntingdon Research Centre and FBC submitted to WHO by FBC Ltd. (Unpublished) Everest, R.P. & Cliffe, S. Technical prochloraz micronucleus assay in 1980 male and female CD rats of prochloraz. Report TX80003 from Boots submitted to WHO by FBC Ltd. (Unpublished) Gale, E.P. 90-day oral toxicity study with prochloraz technical to 1980 male and female CD1 mice. Report TX80040 from Hazleton and Boots submitted to WHO by FBC Ltd. (Unpublished) Hamilton, D.Y. The distribution and level of 14C-labelled residues in 1978a rats following repeated oral dosing with 14C-prochloraz at 25 mg/kg/day. Report AX78008 from Boots submitted to WHO by FBC Ltd. (Unpublished) Hamilton, D.Y. The distribution and level of radiolabelled residues in 1978b the tissues of the dog following a single oral dose of prochloraz. Report AX78016 from Boots submitted to WHO by FBC Ltd. (Unpublished) Kynoch, S.R. & Liggett, M.P. Primary eye irritancy of prochloraz 40 1979a percent E.C. formulation (bfn 8099). Report TX79050 from Huntingdon Research Centre and Boots submitted to WHO by FBC Ltd. (Unpublished.) Kynoch, S.R. & Liggett, M.P. Primary skin irritancy of prochloraz 40 1979b percent E.C. formulation (bfn 8099). Report TX79074 from Huntingdon Research Centre and Boots submitted to WHO by FBC Ltd. (Unpublished) Lancaster, M.C. & Shaw, J.W. 90-day oral toxicity study with 1979a prochloraz technical in male and female Boots Wistar rats (4-week off-dose period). Report TX79028 from Boots submitted to WHO by FBC Ltd. (Unpublished) Lancaster, M.C., Morgan, H.E. & Stobart, J.E. 90-day oral toxicity 1979b study with prochloraz technical in male and female beagle dogs (4-week off-dose period). Report TX79010 from Boots submitted to WHO by FBC Ltd. (Unpublished) Lancaster, M.C. 13-week oral toxicity study with prochloraz technical 1980 (BX 9/DM 2723) in male and female dogs with a four-week off-dose period. Histopathological examination of the remaining tissues. Report TX80034 from Boots submitted to WHO by FBC Ltd. (Unpublished) Lancaster, M.C. PRochloraz: 13-week oral toxicity in the mouse - 1982 histopathological examination. Report TOX/82/173/-9 from FBC Ltd. submitted to WHO by FBC Ltd. (Unpublished) McGregor, D.B., Riach, C.G. & Brown, A.G. Technical prochloraz 1983 assessment of mutagenic potential in the mouse lymphoma mutation assay. Report TOX/83/173-22 from Inveresk and FBC submitted to WHO by FBC Ltd. (Unpublished) Morgan, G.E., Patton, D.S.G., Shepherd, G.M. & Stobart, J.E. The acute oral toxicity of bts 40542 (technical batch) to the female baboon. Report from Boots Laboratories submitted to WHO by FBC Ltd. (Unpublished) Needham, D. The effect of dog gastric juice or plasma on prochloraz. 1980 Report AX80011 from Boots submitted to WHO by FBC Ltd. (Unpublished) Needham, D. & Campbell, J.K. The excretion of 14C-phenyl-labelled 1980 prochloraz in male and female rats after a single oral dose. Report AX80037 by Boots submitted to WHO by FBC Ltd. (Unpublished) Needham, D. The excretion and tissue residues of 14C-prochloraz in 1982a male and female mice following a single oral dose of 100 mg/kg. Report METAB/82/32 from FBC submitted to WHO by FBC Ltd. (Unpublished) Needham, D. & Campbell, J.K. The excretion and tissue residues of 14C 1982 prochloraz in male and female dogs following a single oral dose of 18 mg/kg. Report METAB/82/30 by FBC submitted to WHO by FBC Ltd. (Unpublished) Needham, D. The metabolism of prochloraz in the rat after oral 1982b administration. Report METAB/82/31 from FBC submitted to WHO by FBC Ltd. (Unpublished) Needham, D. The effect of prochloraz on the hepatic mixed-function 1983a oxidase system of the male rat after oral administration. Report METAB/83/5 from FBC submitted to WHO by FBC Ltd. (Unpublished) Needham, D. The effect of prochloraz on the hepatic mixed function 1983b oxidase system of the mouse when administered at 80, 325 and 1 300 mg/kg diet for up to 14 weeks. Report METAB/83/7 from FBC submitted to WHO by FBC Ltd. (Unpublished) Palmer, A.K., Bottemley, A.M. & Billington, R. The effect of technical 1980 prochloraz on pregnancy of the New Zealand white rabbit. Report TX80083 from Huntingdon Research Centre and Boots submitted to WHO by FBC Ltd. (Unpublished) Rivière, J.L. Prochloraz, a potent inducer of the microsomal 1983 cytochrome P-450 system. Pestic. Biochem. Physiol., 19: 44-52. Shaw, J.W. & Carter, O.A. Acute oral toxicity to male CD 1 mice of 1976 prochloraz. Report TX76093 from Boots submitted to WHO by FBC Ltd. (Unpublished) Smithson, A. & Lancaster, M.C. Acute intraperitoneal toxicity of 1980 prochloraz to male CD rats. Report TX80004 from Boots submitted to WHO by FBC Ltd. (Unpublished) Stobart, J.E., Morgan, H.E., Patton, D.S.G. & Shepherd, G.M. Acute 1978 oral toxicity of prochloraz to male and female beagle dogs. Report TX78049 from Boots submitted to WHO by FBC Ltd. (Unpublished) Turner, D.M. & Gilbert, C.M. Pharmacokinetic studies on 14C-labelled 1977 prochloraz in the rat. Report AX77001 from Hazleton and Boots submitted to WHO by FBC Ltd. (Unpublished) Wilcox, P. Prochloraz in vitro bacterial mutagenicity testing of pure 1977 and technical prochloraz. Report TX78002 from Boots submitted to WHO by FBC Ltd. (Unpublished) RESIDUES RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Prochloraz is available as 40 percent and 45 percent emulsifiable concentrate (E.C.) formulations for foliar and postharvest treatments and is sold under the trademark Sportak. A 50 percent wettable powder formulation containing a 4:1 prochloraz-manganese coordination complex active ingredient (a.i.) (3.4 percent manganese) is available and recommended for foliar application to some broad leaf crops, ornamentals and mushrooms, which may be susceptible to phytotoxicity from E.C. formulations. Prochloraz is available in co-formulation with carbendazim, under the trademarks Sportak PF and Sportak ALPHA, for foliar application to cereal and oilseed rape. A 200 g/l liquid formulation is available for cereal seed treatment and a 25 percent E.C. disinfectant for rice seed. Prochloraz is used for the control of a variety of fungal diseases on a variety of crops and is said to be especially active against Ascomycetes and Fungi Imperfecti. It is currently registered or approved for use in eight countries and similar measures are pending or planned in many others. Nationally registered and/or approved uses are summarized in Table 1. RESIDUES RESULTING FROM SUPERVISED TRIALS Residue trials have been conducted in many countries, representing a wide range of food crops, climatic conditions, formulations and foliar, seed and postharvest treatments. Trials data are summarized in Tables 2-13. Trials data from countries with approved uses are available only for apples, watermelons, grapes (Taiwan, province of China), cereal (Belgium, Denmark, France, German Federal Republic, The Netherlands, United Kingdom) and mushrooms (The Netherlands). Sugarbeets No information was available on good agricultural practices for prochloraz on sugarbeets. The "recommended" application rate of active ingredient is said to be 0.5-1 kg/ha for foliar treatment. No preharvest interval (PHI) is given. Total residues of both free and conjugated residues of prochloraz (BTS 40 542), N-formyl-N'-propyl-N'-2(2,4,6-trichlorophenoxy) ethylurea (BTS 44596), N-propyl-N-2 (2,4,6-trichlorophenoxy) ethylurea (BTS 44595) and 2,4,6-trichlorophenol (BTS 45186), hereafter referred to as total residues of prochloraz and metabolites, are listed in Table 2. The values (corrected for 90 percent recoveries) are expressed as prochloraz equivalents but were determined as 2,4,6-trichlorophenol after hydrolysis. All residues and the 0.036 mg/kg control are below the limit of determination, said to be 0.1 mg/kg. Data are insufficient to support a maximum residue level, even if good agricultural practices were known. The "recommended" application rate of active ingredient to sugarbeet leaves is said to be 0.5-1 kg/ha for foliar treatment. No PHI was provided. Total residues of prochloraz and metabolites, expressed as prochloraz equivalents, on sugarbeet leaves were 0.97, 1.3 and 1.2 mg/kg at 5, 21 and 42 days, respectively, after the last treatment in three trials (Table 2). The control was 0.15 mg/kg. Lettuce No information was available on good agricultural practices on lettuce. Residues of prochloraz only, uncorrected for approximately 72 percent recoveries, ranged from 7.4 mg/kg 18 days after treatment to 0.41 mg/kg after 39 days and <0.07 mg/kg after 71 days with a limit of sensitivity said to be 0.01 mg/kg, although one of the three controls has apparent residues of 0.02 mg/kg. Recoveries were 65-76 percent at 0.1-0.5 mg/kg fortification levels. Watermelons Residue data reflecting good agricultural practices in Taiwan Province of China are presented in Table 2. Residues of prochloraz per se were 0.01 mg/kg in peel and flesh after the approved six-day interval from last application to harvest. Information was not provided on the analytical procedure used; a 0.003 mg/kg limit of detection was claimed. Citrus Fruits No information was provided on good agricultural practices on citrus fruits. Residues from postharvest trials, proposed for uses (25-70 g/hl for dip treatments or 100-300 g/hl for spray treatments) where the peels are discarded, are summarized in Table 3. A variety of treatment and storage conditions are given, representing 23 trials in five countries. In some cases prochloraz alone is determined, in others prochloraz and its metabolites and in one case BTS 45 186. Total residues are generally expressed as prochloraz equivalents, although they are usually measured as BTS 45 186. Total residues after storage at ambient of 4°C for up to 70 days and from a variety of treatments and locations ranged up to 18 mg/kg in peel, 0.44 mg/kg in flesh and 6 mg/kg on a whole fruit basis. Residue levels of free prochloraz were not substantially different than those for total residues, where a comparison was made. More details are reported under "Fate of Residues, Storage and Processing". Pome Fruits Information on good agricultural practice and residue data (prochloraz only) reflecting such practice on apples are available for Taiwan Province of China, as well as data for apples and pears from supervised trials in three additional countries for which good agricultural practices for prochloraz on pome fruit are not known. Apples The most pertinent data were those from Taiwan Province of China, for which information was available on good agricultural practices on apples. Data represent recommended and 2X the recommended application rate. No data were available for the recommended 9-day last treatment to harvest interval, but they were given for 6 and 12 days. Residues of prochloraz, per se, from nine applications were 0.07 and 0.01 mg/kg, respectively, at these intervals from the recommended application rate. No information is available on the analytical method used other than a claimed 0.003 mg/kg limit of detection. Other apple residue data (parent compound only) are from application rates three to eight times that for good agricultural practice known to the Meeting. Over-all recoveries among studies submitted range from 64-92 percent with claimed sensitivities ranging from 0.001-<0.01 mg/kg. Apparent residues in untreated controls, where given, are <0.01-0.02 mg/kg. A reasonable limit of determination would appear to be about 0.1 mg/kg. One study (Hayto 1977c) indicates a half-life in apples of 6-7 days. Pears No information on good agricultural practice was available for pears. The application rates are substantially greater than known good agricultural practice for apples and residues are higher, as would be expected. Stone Fruits No information on good agricultural practice for prochloraz on stone fruit were available to the Meeting. The "recommended" application rate for foliar treatment with the prochloraz-50 percent W.P. manganese complex formulation was reported as 15-30 g a.i./hl. No preharvest interval was given. Residue data were available on apricots, nectarines, peaches, cherries and plums from four countries (Table 2). Total residues of prochloraz and the metabolites were determined as 2,4,6-trichlorophenol and expressed as prochloraz. Residues in mature fruit ranged from a maximum of 0.19 mg/kg im plums at 3 days, 1 mg/kg at 14 days, 0.82 mg/kg at 24 days to <0.05 mg/kg over 75 days after multiple foliar treatments with either E.C. or W.P. (manganese complex) formulations. Residues were generally lower for other stone fruit at comparable intervals after treatment with the W.P. formulations. At fortification levels of 0.05-1 mg/kg recoveries are 70-113 percent over-all. Apparent residues in eight untreated stone fruit controls were 0.009-0.022 mg/kg except one value of 0.06 mg/kg in four controls (plums). The limit of determination for stone fruit was reported as 0.05 mg/kg. Grapes Information on good agricultural practice for the E.C. formulation and residue data reflecting 1, 1.5, 2 and 4X recommended application rates were available from one country. Residues from two applications at recommended rates ranged from 0.39 mg/kg on the day of application to <0.01 mg/kg after 21 days and 0.1 mg/kg at the recommended 9-day preharvest interval. Higher application rates and numbers of applications, with one or two exceptions, did not make an appreciable difference in the residue level at comparable intervals after application. No information was provided on apparent residues in un-treated controls or on the analytical procedure; a 0.003 mg/kg limit of detection was reported. TABLE 1. REGISTRATIONS AND APPROVED USES FOR PROCHLORAZ Country Product1 Commodity Approved Application Rate Number and timing of Pre-harvest Product a.i. Applications Interval (prochloraz) Belgium SPORTAK 45EC Winter 1 l/ha 0.45 kg/ha One application at earstage in mixture na wheat with either 0.125 kg/ha carbendazim, 1.2 kg/ha captafol or 1.6 kg/ha maneb. Winter barley 1 l/ha 0.45kg/ha One application at stage L or M2 Denmark SPORTAK Barley 100 ml/100 kg 0.2 g/kg na na BEJOSE (seed dressing) SPORTAK 45EC Spring 1 l/ha 0.45 kg/ha One application at stage 4-10.5 or a barley split dose at half rate with the first application at stage 4-6 and the second at stage 8-10.53. Winter 1 l/ha 0.45 kg/ha One (stage 4-10.5) or two (stage 4-6 cereals barley and 7-10.5) applications3. 1 month Winter 1 l/ha 0.45 kg/ha Two applications (stages 5-6 and 9- wheat 10.53). Winter 1 l/ha 0.45 kg/ha One application (stages 5-7)3 rye Eire SPORTAK 40EC Cereals 1 l/ha 0.4 kg/ha Up to three applications between leaf sheaf erection and complete ear emergence. na Table 1 (continued) Country Product1 Commodity Approved Application Rate Number and timing of Pre-harvest Product a.i. Applications Interval (prochloraz) France SPORTAK 40EC Wheat 1.125-1.875 0.45-0.75 Up to two applications (stages 6-7 l/ha kg/ha and 10.3-10.5)3 Barley 1.125 l/ha 0.45 kg/ha Up to two applications (stages 6-7 and 10.1)3 na SPORTAK 45EC Wheat 1-1.66 l/ha 0.45-0.75 Up to two applications (stages 6-7 kg/ha and 10.3-10.5)3. Barley 1 l/ha 0.45 kg/ha Up to two applications (stages 6-7 10.1)3 SPORTAK PF Wheat 1.5 l/ha 0.45 kg/ha Up to two applications (stages 6-7 and 10.3-10.5)3. Barley 1.5 l/ha 0.45 kg/ha Up to two applications (stages 6-7 10.1)3. Oil seed 1.5 l/ha 0.45 kg/ha Up to two applications, at beginning rape and end of flowering. na SPORTAK M Wheat 1.125 l/ha 0.45 kg/ha Up to two applications (stages 6-7 and 10.3-10.5)3. Barley 1.125 l/ha 0.45 kg/ha Up to two applications (stages 6-7 10.1)3. Table 1 (continued) Country Product1 Commodity Approved Application Rate Number and timing of Pre-harvest Product a.i. Applications Interval (prochloraz) German SPORTAK 40EC Wheat 1.2 l/ha 0.48 kg/ha One (stage 29-32) or two Federal (stages 29-59) applications5. Republic Cereals - Barley 1.2 l/ha 0.48 kg/ha One (stage 29-32) or two 35 days6 (stages 29-49) applications5. Winter 1.2 l/ha 0.48 kg/ha One application at stage 29-325. rye Restricted to a maximum of three applications in Winter cereal. Netherlands SPORTAK 45EC Wheat 1 l/ha 0.45 kg/ha 1-2 treatments after infection. Barley 1 l/ha 0.45 kg/ha 1-2 treatments after infection. Cereals - 8 weeks7 Winter 1 l/ha 0.45 kg/ha One or two applications. barley Ornamentals 0.4% 180 g/hl Flower bulb dip na SPORGON Mushrooms 3/g/l/m2 1.5g/l/m2 One application of casing soil Mushrooms - nine days after casing. 10 days Taiwan SPORTAK 25EC Rice 2000 x 12.5 g/hl 24 hour rice seed soak. na dilution Grape 6000 x 4.17 g/hl Two to three applications, Grape - dilution every 10 days. 9 days Apple 3000 x 8.33 g/hl Application every 10 days. Apple - dilution 9 days Table 1 (continued) Country Product1 Commodity Approved Application Rate Number and timing of Pre-harvest Product a.i. Applications Interval (prochloraz) Watermelon 4000 x 6.25 g/hl 10 days. 6 days dilution United SPORTAK 40EC Cereals 1 /ha 0.4 kg/ha Up to three applications between na Kingdom leaf sheath erection and complete ear emergence. Oil seed 1.25 l/ha 0.5 kg/ha Up to three applications between stem extension and 90% petal fall. Ornamentals - 2000 ppm Propagation cutting dip, drench, na foliar spray or compost incorporation. SPORTAK 45EC Cereals 1 /ha 0.45 kg/ha Up to three applications between na leaf sheath erection and complete ear emergence. Oil seed 1-1.33 /ha 0.45-0.6 Up to three applications between rape kg/ha stem extension and 90% petal fall. Ornamentals - 2000 ppm Propagation cutting dip, drench, na foliar spray or compost incorporation. SPORTAK Cereals 1.5 /ha 0.4 kg/ha Up to three applications between ALPHA leaf sheath erection and complete ear emergence. na Oil seed 1.5 /ha 0.4 kg/ha Up to three applications between rape stem extension and 90% petal fall. Table 1 (continued) Country Product1 Commodity Approved Application Rate Number and timing of Pre-harvest Product a.i. Applications Interval (prochloraz) Ornamentals - 2000 ppm Propagation cutting dip, drench, na foliar spray or compost incorporation. SPORTAK FE Cereals 4 kg/ha 0.66 kg/ha Up to three applications between leaf sheath erection and complete ear emergence. na Oil seed 3 kg/ha 0.5 kg/ha Up to three applications between rape stem extension and 90% petal fall. Ornamentals - 2000 ppm Propagation cutting dip, drench, na foliar spray or compost incorporation. SPORGON Mushrooms 3 g/l/m2 1.5 g/l/m2 One application, 1-10 days after Mushrooms - casing. 10 days 0.6 g/l/m2 0.3 g/l/m2 Three applications, one 1-10 days Mushrooms - after casing and then after the 2 days first and second flush 1.2 g/l/m2 0.6 g/l/m2 Two applications, one 1-10 days Mushrooms - after casing and then between 2 days second and third flush. Ornamentals - 2000 ppm Propagation cutting dip, drench, na foliar spray or compost incorporation. Table 1 (continued) Notes: na - not applicable nd - not defined ns - not specified 1. The following formulations have been registered: SPORTAK 40 EC - an emulsifiable concentrate containing 400 g/l prochloraz SPORTAK 45 EC - an emulsifiable concentrate containing 450 g/l prochloraz SPORTAK BEJDSE - a liquid seed dressing containing 200 g/l prochloraz SPORTAK PF - an emulsifiable concentrate containing 300 g/l prochloraz and 80 g/l carbendazim SPORTAK M - a twin-pack emulsifiable concentrate containing 400 g/l prochloraz and 450 g/l mancozeb SPORTAK ALPHA - an emulsifiable concentrate containing 266 g/l prochloraz and 100 g/l carbendazim SPORTAK FE - a wettable powder containing 165 g/kg prochloraz-manganese complex and 533.4 g/kg mancozeb SPORGON - a wettable powder containing 500 g/kg prochloraz-manganese complex 2. Baggiolini cereal growth stages. 3. Feekes-Large cereal growth stages. 4. Residues of prochloraz alone. 5. Zadoks Decimal cereal growth stages. 6. A proposed MRL of 0.5 mg/kg for prochloraz and metabolites in cereal grain has been submitted. 7. Under review, pending further residue analysis. 8. Residues of prochloraz and metabolites measured as 2,4,6-trichlorophenol and expressed as prochloraz. Table 2 Prochloraz Residues in Various Crops Following Supervised Trials Country/ No. of Formulation Application Interval after Residues, Reference Crop Year trials rate (a.i.) final application (mg/kg)1 (days) Sugarbeet Italy root 1981 1 40% E.C. 2 x 1 kg/ha 42-46 0.02 Longland 1983b leaves 1.17 root 1 40% E.C. 3 x 1 kg/ha 21-25 0.04 leaves 1.32 root 1 40% E.C. 4 x 1 kg/ha 5-6 0.06 leaves 0.97 Lettuce The Netherlands 1 8% dust 8 kg/ha 70-73 0.013 Hayto 1979d 1978 80 0.013 2 8% dust2 8 kg/ha 18-19 7.383 39 0.043 42-46 0.123 70-73 <0.013 80 <0.013 1 8% dust2 6.4 kg/ha 70-73 0.043 Maclaine Pont et al. 1980 1 8% dust2 8 kg/ha 70-73 0.033 8% dust2 9.6 kg/ha4 78 <0.013 Watermelon Taiwan Province peel of China 1982 1 25% E.C. 3 x 4.17 g/hl 0-1 0.013 Wang 1982 3 <0.013 5-6 <0.013 9 <0.013 12 <0.013 0-1 <0.013 3 <0.013 5-6 <0.013 9 <0.013 12 <0.013 Table 2 (continued) Country/ No. of Formulation Application Interval after Residues, Reference Crop Year trials rate (a.i.) final application (mg/kg)1 (days) Watermelon Taiwan Province 3 x 6.25 0-1 0.023 peel of China 3 <0.013 5-6 <0.013 9 <0.013 flesh 12 <0.013 0-1 <0.013 3 <0.013 5-6 <0.013 9 <0.013 12 <0.013 Apple The Netherlands 2 50% W.P.5 2 x 25 g/hl 63 <0.013 Maclaine Pont et al. 1980 1978 84 <0.013 United Kingdom 2 25% W.P. 7 x 60 g/hl 0-1 0.473 Hayto 1976 1977 14-16 0.083 30-31 0.023 25% E.C. 8 x 51.48 g/hl 0-1 4.183 Hayto 1977c 8 1.763 18-19 0.683 30-31 0.173 50 0.023 Taiwan Province 1 25% E.C. 9 x 8.33 g/hl 0-1 0.243 Wang 1982 of China 3 0.123 1982 5-6 0.073 12 0.013 14-16 0.053 18-19 0.023 Table 2 (continued) Country/ No. of Formulation Application Interval after Residues, Reference Crop Year trials rate (a.i.) final application (mg/kg)1 (days) Apple Taiwan Province 9 x 16.67 g/hl 0-1 0.813 of China 3 0.373 5-6 0.203 12 <0.013 14-16 0.083 18-19 0.073 Pear The Netherlands 1 50% W.P.5 1 x 0.1 kg/hl 21-25 0.033 Maclaine Pont et al. 1980 1978 1 x 0.2 kg/hl 21-25 0.063 2 x 0.1 kg/hl 14-16 0.263 2 x 0.2 kg/hl 14-16 0.243 Apricots Israel 1 50% W.P.5 1 x 60 g/hl 89 <0.05 Snowden 1983 1982 Cherries France 1 50% W.P.5 1 x 10 g/hl 70-73 <0.05 1982 1 x 20 g/hl 70-73 <0.05 4 x 20 g/hl 21-25 0.45 Nectarines France 1 50% W.P.5 5 x 20 g/hl 14-16 0.56 1982 Peaches South Africa 1 50% W.P.5 3 x 10 g/hl 132 <0.05 1982 1 3 x 20 g/hl 132 <0.05 1 8 x 10 g/hl 30-31 0.21 Plums Italy 1 40% E.C. 1 x 30 g/hl 102 <0.05 1982 1 2 x 30 g/hl 77 <0.05 1 3 x 30 g/hl 50 0.82 Table 2 (continued) Country/ No. of Formulation Application Interval after Residues, Reference Crop Year trials rate (a.i.) final application (mg/kg)1 (days) Plums South Africa 1 50% W.P.5 1 x 30 g/hl 50 0.21 1981 1 1 x 40 g/hl 50 0.28 1 2 x 30 g/hl 14-16 0.97 1 2 x 40 g/hl 14-16 0.60 1982 1 50% W.P.5 3 x 10 g/hl 104 <0.05 3 x 20 g/hl 104 <0.05 6 x 10 g/hl 5-6 0.12 4 x 10 g/hl 103 <0.05 4 x 20 g/hl 103 <0.05 7 x 10 g/hl 5-6 0.19 Grapes Taiwan Province 1 25% E.C. 2 x 4.17 g/hl 3 0.393 Wang 1982 of China 5-6 0.193 1982 8 0.203 9 0.103 12 0.073 21-25 0.103 39 0.053 42-46 <0.013 1 25% E.C. 2 x 6.25 g/hl 3 0.493 5-6 0.263 8 0.203 9 0.253 12 0.133 21-25 0.133 39 0.053 42-46 <0.013 Table 2 (continued) Country/ No. of Formulation Application Interval after Residues, Reference Crop Year trials rate (a.i.) final application (mg/kg)1 (days) Grapes Taiwan Province 1 25% E.C. 7 x 10 g/hl 3 0.203 of China 5-6 0.133 8 0.293 9 0.273 12 0.143 21-25 0.223 39 0.083 42-46 0.083 1 25% E.C. 7 x 16.67 g/hl 3 0.423 5-6 0.203 8 0.163 9 0.603 12 0.673 21-25 0.343 39 0.183 42-46 0.103 Strawberries The Netherlands 1 50% W.P.5 2 x 0.1 kg/hl 30-31 0.173 Maclaine Pont et al. 1980 1978 1 2 x 0.15 kg/hl 30-31 0.173 Almonds Israel shell 1982 1 50% W.P.5 2 x 0.1 kg/hl 0.616 Churchill & Longland 1983d kernel 0.106 whole nut 0.296 Table 2 (continued) 1 Total residues of prochloraz and major metabolites unless otherwise stated. Total residue measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residues by correcting for the molecular weight factor (1.906). 2 Co-formulation with dicloran. 3 Prochloraz residues only. 4 Preplanting application. 5 Prochloraz-manganese complex 50% wettable powder formulation. 6 Applications made at blossom and 20 days later. Preharvest interval estimated at about 2.5 to 3 months. Table 3. Supervised Residue Trials With Prochloraz on Citrus Fruits - Post-Harvest Applications Residues (mg/kg)1 Application Country/ Crop No. of Formulation rate (a.i.) Peel Flesh Whole Fruit3 Reference Year Trials and method Australia Oranges 1 40% E.C. 25g/hl dip3 1.40-3.4 <0.05 n.d. Browne 1981a 1981 (1.45-3.954) (0.3-0.104) 1 40% E.C. 50g/hl dip3 1.58-3.36 <0.05 n.d. (2.25-3.354) (<0.02-0.054) Italy Oranges 1 25% W.P. 50g/hl dip5 1.59-1.72 0.04-0.05 0.71-0.80 Browne & Manley 1981 1 25% E.C. 50g/hl dip5 4.57-6.40 0.09-0.16 1.80-2.35 1982b Lemons 1 25% W.P. 50g/hl dip5 3.61-4.04 0.08-0.14 1.58-1.83 1 25% E.C. 50g/hl dip 5.67-6.95 0.08-0.19 2.36-2.97 South Oranges 1 40% E.C. 100g/hl wax 1.38-2.79 0.03-0.08 0.38-0.72 Manley & Snowden Africa brush6 (0.34-0.478) 1982b 1982 1 40% E.C. 200g/hl wax 2.45-3.74 0.02-0.07 0.65-0.94 brush6 (0.91-1.198) 1 40% E.C. 200g/hl wax n.d. n.d. 1.36-1.698) brush7 Oranges 1 45% E.C. 50g/hl brush9 0.34 <0.05 0.08 Snowden & Manley (0.108) 1983 1 45% E.C. 100g/hl brush9 0.47 <0.05 0.13 (0.16-0.178) 1 45% E.C. 200g/hl brush9 1.84 <0.05 0.39 (0.39-0.438) 1 45% E.C. 400g/hl brush9 3.07 0.07 0.63 (0.70-0.758) Table 3 (continued) Residues (mg/kg)1 Application Country/ Crop No. of Formulation rate (a.i.) Peel Flesh Whole Fruit3 Reference Year Trials and method Spain Oranges 1 25% E.C. 50g/hl dip10 1.48-3.224 0.04-0.10 0.67-1.4511 Kelly 1982d 1979 1 25% E.C. 100g/hl dip10 1.40-4.084 0.04-0.11 0.67-1.8011 1980 Oranges 1 40% E.C. 300g/hl wax 3.3-4.74 0.32-0.38 n.d. Richards 1980b spray12 1 40% E.C. 300g/hl wax n.d. 0.005-0.00813 n.d. Richards 1980e spray12 1 40% E.C. 200g/hl wax 1.2-6.7 0.04-0.44 n.d. Richards 1980f spray12 1 40% E.C. 250g/hl wax 3.7-7.9 0.04-0.30 n.d. spray12 1 40% E.C. 300g/hl wax 5.4-6.4 0.06-0.13 n.d. spray12 1981 Oranges 1 40% E.C. 300g/hl shower14 4.7-8.4 0.11-0.39 1.50-2.47 Browne 1981b (1.7-7.34) (0.12-0.394) (0.64-2.434) 1981 Lemons 1 40% E.C. 300g/hl 11.0-17.9 0.17-0.33 3.66-6.13 Browne 1982c shower15 (9.1-15.64) (0.27-0.304) (3.14-5.554) United Oranges 1 40% E.C. 70g/hl dip16 5.78-7.81 0.07-0.15 1.37-2.07 Browne 1982i Kingdom (3.55-5.104) (0.05-0.124) (0.96-1.354) 1981 Table 3 (continued) n.d. - not determined. 1 Total residues of prochloraz and major metabolites unless otherwise stated (see notes 4 and 13). Total residue measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x 1.906). 2 Residue levels in whole fruit calculated from separate peel and flesh residues unless otherwise stated (see note 8). 3 Residue levels obtained from five sampling intervals at 1,2,4,8 and 16 days storage at ambient temperature after treatment. 4 Determination of free prochloraz levels only. 5 Fruit was stored for 57 days at 7°C after treatment. 6 Residue levels obtained from four sampling intervals under two storage conditions. Treated fruit was sent to the United Kingdom under normal commercial refrigerated shipment and then stored at either 20° or 4°C, 44 days later. Samples of fruit from each storage condition were then taken at 0,7,14 and 21-day intervals. 7 Prochloraz applied in mixture with 2,4,-0 and thiabendazole. Storage conditions as in Note 6 except sampled after 44 days refrigerated shipment and 21 days storage under ambient or cool conditions. 8 Residue analysis of whole fruit. 9 Fruit was treated in July 1982, sent to the United Kingdom under normal refrigerated shipment and stored at ambient temperature until September 1982. 10 Residue levels following storage of fruit for either 10 days at 20-22°C or 60 days at 3-4°C after treatment. 11 Residue level calculated from determination of free prochloraz residue in peel and total prochloraz plus major metabolites in flesh. 12 Residue levels following storage of fruit for either 7 or 14 days at ambient temperature after treatment. 13 Determination of free 2,4,6-trichlorophenol (BTS 45186) only, expressed as 2,4,6-trichlorophenol. 14 Residue levels following storage of fruit for either 14, 20 or 27 days at ambient temperature after treatment. 15 Residue levels following storage of fruit for either 12 or 16 days at ambient temperature after treatment. 16 Residue levels following storage of fruit for either 1,7, 21, 35 or 70 days in cold storage after treatment. Strawberries No information was provided on good agricultural practices for prochloraz on strawberries. Limited residue data from the use of the manganese complex W.P. formulation were provided (Table 2) with residues of 0.2 mg/kg prochloraz found 16 days after treatment. Recoveries were reported as >80 percent and sensitivity as 0.001-0.005 mg/kg. Fruit with Inedible Peel No information on good agricultural practice was available for the use of prochloraz on fruit with inedible peel. Residue data resulting from either foliar (Table 4) and/or postharvest applications (Table 5) were available for several of these crops. The "recommended" application rates were provided for most of them but no preharvest intervals were specified. Avocados No information on good agricultural practice was provided for avocados. Residue data at normal harvest and "recommended" application rates were available for both foliar and postharvest treatments. At 2X the 10-25 g a.i./hl "recommended" foliar W.P. (manganese complex) application rate, maximum total residues on whole fruit basis were 2.5 mg/kg seven days after treatment, with approximately 10 percent of the residue in the flesh (Table 4). No preharvest interval was given. However, these data are questionable because of conflicting peel residue levels in the data submission. Data were also available from multiple applications of an E.C. formulation at 25-50 g a.i./hl, although not even "recommended" uses were available for this formulation. In these trials residues continually declined from 14 to 63 days after treatment, with estimated half-lives ranging from 40-98 days (mean 75.4 days). At these longer intervals residues in flesh account for 20-30 percent of the whole fruit residue. The limit of determination was said to be 0.15 mg/kg, although control values were as high as 0.12, 0.16 and 0.39 mg/kg in flesh, peel and whole fruit, respectively. For postharvest treatments of avocados 25-50 g a.i./hl (formulation unspecified) is "recommended", although no good agricultural practice information was available. Ten trials reflecting the "recommended" application rates were conducted in one country with dip or spray E.C. applications (Table 5). Total residues ranged from 0.3 to 3.5 mg/kg on a whole fruit basis, with little difference in values between stored at 23° for eight days or fruit frozen immediately. Little difference was reported between 1X and 2X recommended application rates. These residues levels are generally comparable to those found from multiple foliar treatments. The limited data indicate residues in the flesh at levels up to 30 percent of those in whole fruit, even at relatively short intervals after treatment. Table 4 Prochloraz Residues in Fruit Following Supervised Trials - Foliar Application Country/ Crop No. of Year trials Formulation Application Interval after Mean residue level (mg/kg)1 Reference rate (a.i.) final application (days) Peel Flesh Whole fruit2 Australia Avocado 1 50% W.P. 7x15g/tree3 7 8.1-13.6 0.09-0.28 1.70-2.51 Cron & Longland 1983a 1981/2 (49.5 g/hl) (11)7 (0.16) (2.1) South Avocado 1 45% E.C. 2x25g/hl4 14 1.52 <0.10 0.44 Churchill & Africa 48 1.19 <0.10 0.36 Longland 1983b 1982 63 1.01 <0.10 0.30 1 45% E.C. 2x37.5g/hl4 14 1.85 0.12 0.61 48 1.45 <0.10 0.25 63 0.84 <0.10 0.25 1 45% E.C. 2x50g/hl4 14 2.63 0.17 0.83 48 1.94 0.18 0.59 63 2.16 0.14 0.60 Australia Mango 1 50% W.P. 6x100g/hl5 77 0.15-0.30 0.01-0.02 0.05-0.096 Browne & Manley 1982c 1981 (0.22)8 (0.01)8 (0.07)8 Israel Mango 2 50% W.P. 3x50g/hl 15 3.39-4.87 0.03-0.07 0.77-0.956 Longland & 1982 (4.2)8 Churchill 1983 Table 4 (continued) 1 Total residues of prochloraz and major metabolites, measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x1.906). 2 Residue in whole fruit (without stone) calculated from separate peel and flesh residues. 3 Applications made at approximately monthly intervals from fruit set to fruit full size. 4 Applications made with a seven-week interval between treatments. 5 Applications made from beginning of flowering to Pethenoccupic fruit drop. 6 Residue level in whole fruit including stone (calculated from peel/flesh residues). 7 Mean in parentheses. 8 Four samples. Table 5 Prochloraz Residues in Fruit Following Supervised Trials - Postharvest Application Mean residue level (mg/kg)1 Country/ Crop No. of Formulation Application rate Year trials (a.i.) Peel Flesh Whole fruit2 Reference Australia Avocado 1 40% E.C. 25 g/hl dip4 n.d. n.d. 0.88-1.313 Browne 1982a 1981 1 40% E.C. 50 g/hl dip4 n.d. n.d. 1.14-1.353 1982 2 45% E.C. 25 g/hl dip4 3.28-5.35 <0.10-0.12 0:30-0.557 Churchill & 2 45% E.C. 25 g/hi dip6 n.d. n.d. 0.16-1.019 Longland 1983e 1 45% E.C. 50 g/hl spray4 2.33-3.90 <0.10-0.11 0.28-0.367 1 45% E.C. 50 g/hl spray6 n.d. n.d. 0.34-0.429 1983 1 45% E.C. 25 g/hl dip6 n.d. n.d. 2.369 1 45% E.C. 50 g/hl dip6 n.d. n.d. 3.499 1981 Banana 1 40% E.C. 25 g/hl dip5 6.06-7.88 0.02-0.04 n.d. Browne 1982b 1 40% E.C. 50 g/hl dip5 5.18-9.97 0.03-0.05 n.d. South Banana 2 45% E.C. 25 g/hl dip8 6.5-9.1 0.10-0.20 2.78-3.94 Churchill & Africa 2 45% E.C. 50 g/hl dip8 9.8-16.6 0.14-0.23 4.02-6.75 Longland 1983a 1982 Israel Mango 1 40% E.C. 40 g/hl dip 6.10-8.32 0.02 1.277 Longland & 1982 Churchill 1983 Australia Papaya 1 45% E.C. 25 g/hl dip6 2.13-3.42 0.01-0.18 0.50 Cron & Longland 1983b 1982 1 45% E.C. 50 g/hl dip6 3.86-4.12 0.09-0.15 0.80 Table 5 (continued) n.d. - not determined. 1 Total residues of prochloraz and major metabolites, measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x 1.906). 2 Residue in whole fruit calculated from separate peel and flesh residues unless otherwise stated (see notes 3 and 9). 3 Residue analysis of whole fruit (excluding stone). 4 Fruit stored for 7-8 days at 23°C after treatment. 5 Mean residue levels following storage of fruit for either 9,10,12 or 16 days at ambient temperature after treatment. 6 Fruit frozen within one to four hours after treatment. 7 Calculated whole fruit residue including weight of stone. 8 Fruit stored for 7 days at 8°C after treatment. 9 Residue analysis of whole fruit (including stone). Bananas No information was provided on goad agricultural practices for the use of prochloraz on bananas. "Recommended" application rates for foliar application are 10-25 g a.i./hl WP (manganese complex) for foliar high volume applications (100-200 g a.i./ha low volume) and 25-50 g a.i./hl for postharvest treatment (formulation not specified). No trials data were available for foliar applications, but trials were reported from two countries for postharvest dips that reflected "recommended" application rates (Table 5). Total prochloraz and metabolite residues on a whole product basis ranged from 2.8-6.8 mg/kg when fruit was stored for seven days at 8°C, with less than 2 percent of the total fruit residue found in the flesh. No significant change in residues were observed over the storage intervals of 7 to 16 days or between 8°C and ambient temperatures. No significant difference between residues resulted from the two application rates. Analytical recoveries were generally 85 ± 15 percent. The limit of determination was estimated at 0.05-0.1 mg/kg, although apparent residues in untreated controls were as much as 0.32 mg/kg in the skin and <0.2 mg/kg in whole fruit. Mangoes No information on good agricultural practice was available for the use of prochloraz on mangoes. A 50 percent W.P. manganese complex is "recommended" for foliar treatments at 10-25 g a.i./hl and at 25-50 g a.i./hl for postharvest treatment, although no formulation is specified for the latter. One trial for foliar application was conducted in each of two countries with multiple applications at 2X to 4X the "recommended" foliar rate (Table 4). Maximum total residues on a whole fruit basis were 0.09 mg/kg from the higher application rate 77 days after treatment and up to 1 mg/kg 15 days after application at the lower rate. In both cases, most of the residue was in the peel, although flesh residues appeared to increase with time, being approximately 3 percent of total fruit residue after 15 days to over 10 percent after 77 days (based on peel: flesh:seed ratios from the 77-day study). One trial was conducted in one country for postharvest treatment which reflected the "recommended" application rate. At 1.27 mg/kg on a whole fruit basis, residues were similar to those of the 15-day preharvest trial, although residues in flesh were only approximately 1 percent of the total for the postharvest treatment. Over-all analytical recoveries for mangoes were generally 80 percent or better and apparent residues in untreated controls were <0.02 mg/kg on a whole fruit basis and up to 0.1 mg/kg on peel. The limit of determination was estimated at 0.1 mg/kg. Papaya No information was available on good agricultural practices for prochloraz on papaya. A 50 percent W.P. manganese complex is "recommended" for foliar treatment at 10-25 g a.i./hl and 25-50 g a.i./hl (formulation not specified) is "recommended" for postharvest treatments. No preharvest intervals were given. No residue information was available from foliar treatments, but two postharvest dip trials with an E.C. formulation were conducted in one country and reflected the "recommended" application rates (Table 5). Samples were frozen one hour after the dip treatment for analysis 45 days later. On a whole fruit basis, residues of prochloraz and metabolites (corrected for approximately 80 percent recoveries) were 0.5 and 0.8 mg/kg for the two application rates. Approximately 15 percent of the whole fruit residue was in flesh. Apparent residue in the untreated control was 0.023 mg/kg on a whole fruit basis. The limit of determination was estimated as 0.1 mg/kg in flesh and peel. Cereal Grains Over 270 residue trials were conducted in 10 European and one Asian country, which included foliar or seed treatments with six different E.C. formulations alone or in combination with other chemicals. Results are reported mostly as total residues of prochloraz and metabolites, determined as the trichlorophenol but expressed as prochloraz (Tables 6-9). Some are for residues of prochloraz only. Good agricultural practice information was available for eight countries. Wheat Over 100 field trials were conducted in nine countries, representing 270 samples from a variety of formulations and treatment conditions. Some trials reflected known good agricultural practices and good agricultural practices could not be determined for others. Over-all residues of prochloraz and major metabolites in mature grain from foliar treatment ranged from 0.01-0.3 mg/kg and in straw at harvest 0.08-16 mg/kg, although most grain residues were <0.1 mg/kg (Table 6). The high grain value is from a 38-day preharvest interval in a country whose good agricultural practices are not known, although the application rate and preharvest interval were compatible with good agricultural practices in other countries. Apparent residues in untreated controls were generally <0.02 mg/kg in grain and <0.3 mg/kg in straw, but were occasionally higher in the latter. Residues of prochloraz alone were lower and ranged from <0.01 to 0.03 mg/kg in mature grain and <0.01 to 0.19 mg/kg in straw. Table 6. Supervised Residue Trials with Prochloraz on Wheat at Harvest Country/ Formulation No. of Application rate2 No. of Interval after Residue (mg/kg)1 Reference Year trials (kg a.i./ha) samples final application (days) grain straw Austria 25% E.C. 2 0.5 2 70-78 <0.013 0.013 Kelly 1979a 1977 2 1.0 2 70-78 <0.01-0.013 <0.013 1978 22.5% E.C. 1 0.45 4 94 <0.02-0.02 3.66-8.39 Kelly 1979f 1 0.9 4 94 0.02-0.04 11.63-12.20 Belgium 45% E.C. 1 0.45 2 (0)5 0.02 n.d. Housden 1982a 1981 1 0.454 2 (0)5 0.01 n.d. Denmark 25% E.C. 3 0.625 6 95-98 <0.02-0.02 n.d. Kelly 1979g 1979 40% E.C. 1 0.6 2 77 <0.02 2.1-2.5 Richards 1980d 1982 45% E.C. 1 0.45 1 56 0.106 2.01 Housden 1982c 2 2 x 0.23(19)7 2 75-85 <0.02 1.47-1.94 2 0.23 x 0.45(19)7 2 75-85 <0.02 1.87-2.36 2 2 x 0.45(19) 2 75-85 <0.02-0.02 1.56-2.07 2 2 x 0.45(19)7 2 75-85 <0.02 1.72-2.79 Finland 45% E.C. 2 0.45 2 28-50 <0.02 n.d. Heinanen 1983 1982 France 25% E.C. 2 0.5 6 105 <0.01-0.023 <0.01-0.023 Hayto 1978b 1977 2 1.0 6 105 <0.01-0.013 <0.01-0.183 2 2 x 0.5(38-46) 6 67-69 <0.01-0.033 0.01-0.123 2 2 x 1.0(38-46) 6 67-69 <0.01-0.013 0.01-0.0733 1 0.5 3 105 <0.0058 n.d. Kelly 1980b 1 1.0 3 105 <0.0058 n.d. 1 2 x 0.5(38) 3 67 <0.0058 n.d. 1 2 x 1.0(38) 3 67 0.008-0.0158 n.d. Table 6 (continued) Country/ Formulation No. of Application rate2 No. of Interval after Residue (mg/kg)1 Reference Year trials (kg a.i./ha) samples final application (days) grain straw 1978 25% E.C. 3 0.45 18 55-113 <0.02-0.06 0.50-9.66 Kelly 1979h 3 0.75 18 55-113 <0.02-0.11 0.88-9.91 1979 40% E.C. 1 0.45 3 80 <0.02 2.42-3.22 Richards 1980a 3 2 x 0.45(23-28) 9 72-77 0.04-0.10 2.40-16.3 1 2 x 0.45(8)9 3 77 0.04-0.08 3.93-4.80 30% E.C.10 1 0.45 3 80 <0.02 2.23-2.55 3 2 x 0.45(22) 9 61-81 <0.02-0.08 2.29-6.16 Federal 25% E.C. 3 0.5 4 81-107 <0.01-0.013 0.01-0.023 Hayto 1979c Republic of 2 0.75 3 81 <0.013 0.01-0.023 Germany 1 1.0 1 107 <0.013 <0.013 1977 1978 25% E.C. 2 0.5 4 56-61 0.06-0.08 3.6-12.0 Kelly 1979c 1979 40% E.C. 3 2 x 0.48(21-30) 3 54-63 <0.02-0.06 1.0-5.9 Richards 1980g 1980 40% E.C. 3 2 x 0.48(17-23) 3 59-66 0.01-0.04 0.7-2.0 Reary 1981b 3 3 x 0.48(11-23/7-13) 3 59-66 0.03-0.06 1.1-3.6 1981 40% E.C. 5 3 x 0.48(11-29/8-19) 10 57-64 0.02-0.13 1.07-6.40 Browne 1982e 2 2 x 0.48(28-30) 3 43-60 0.06 1.88-3.59 Browne 1982f 3 3 x 0.48(9-22/8-19) 7 43-66 0.05-0.08 4.05-4.55 1 3 x 0.48(17/6) 1 55 0.05 0.4811 1982 30% E.C.10 1 0.45 3 85 <0.05 0.08-0.27 Housden & Longland 1983 Table 6 (continued) Country/ Formulation No. of Application rate2 No. of Interval after Residue (mg/kg)1 Reference Year trials (kg a.i./ha) samples final application (days) grain straw Italy 25% E.C. 2 0.07 6 55 <0.01-0.013 0.02-0.093 Hayto 1977b 1977 3 1.0 9 39-55 <0.01-0.013 0.02-0.193,12 1978 25% E.C. 1 0.5 2 38 0.08-0.17 4.82-15.76 Kelly 1979d 1 0.7 38 0.13-0.29 6.29-14.73 The 25% W.P. 1 0.375 3 71 <0.013 <0.013 Hayto 1978a Netherlands 25% E.C. 1 0.375 3 73 0.01-0.023 <0.01-0.013 1977 1 0.5 3 73 0.01-0.023 0.01-0.023 1978 25% E.C. 1 0.375 3 68 0.04 1.14-1.51 Kelly 1979e 1 0.75 3 68 0.04-0.06 5.66-8.14 1979 40% E.C. 1 0.5 4 71 <0.02 0.88-2.23 Kelly 1980c 1980 45% E.C. 2 0.45 6 69 0.01-0.02 0.41-0.77 Reary 1981c 1 0.675 2 106 0.01 0.21-0.51 1 2 x 0.45 (15) 3 69 0.01-0.02 2.21-3.29 Sweden 45% E.C. 8 0.45 8 67-91 <0.02 0.08-4.08 Longland 1983a 1982 2 2 x 0.45(15-29) 2 58-69 0.03-0.07 1.29-6.34 United 25% E.C. 2 0.4 6 90-115 <0.013 <0.013 Hayto 1977a Kingdom 2 1.0 6 90-115 <0.013 <0.013 1976 1977 25% E.C. 4 0.5 12 124-126 <0.013 <0.013 Hayto 1979a 1979 40% E.C 2 2 x 0.4(36-37) 6 69-79 <0.02-0.06 4.2-11.2 Richards 1980c 10% S.D.13 1 0.214 2 31015 <0.02 <0.02 Table 6 (continued) n.d.- not determined. 1/ Total residues of prochloraz and major metabolites, unless otherwise stated (see Notes 3 and 8). Total residue as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x 1.906). 2/ Figures in parentheses indicate interval in days between applications. 3/ Determination of free prochloraz residues only. 4/ Prochloraz applied in mixture with carbendazim. 5/ Growth stage at application : 0 - heading. 6/ Residue analysis of whole ears. 7/ Prochloraz applied in mixture with fenpropimorph. 8/ Determination of free 2,4,6-trichlorophenol (BTS 45186) residues only, expressed as BTS 45186. 9/ Prochloraz applied in mixture with mancozeb. 10/ Co-formulation of prochloraz with carbendazim. 11/ Mean residue level in whole ears. A mean residue level of 2.31 mg/kg was found in the whole plant. 12/ Results from two trials. 13/ Seed dressing co-formulation with carboxin. 14/ Rate of application in g a.i./kg seed. 15/ Days after sowing treated seed. Barley Information on good agricultural practice for barley was available from five countries and residue trials reflecting such uses were reported from those countries and others (Table 7). At-harvest residues of prochloraz and its major metabolites, from foliar applications, ranged from <0.01-0.68 mg/kg in mature grain and <0.01-15 mg/kg in straw (Table 7). Again, the higher values are generally from the shorter preharvest intervals, which reflect good agricultural practice, and from trials in which prochloraz was co-applied with either carbendazim or mancozeb. The rates reflect usage in the country where the trials were conducted. Most residues in grain were <0.2 mg/kg. Although grain residues from these shorter intervals were significantly higher than those from longer intervals, residues in straw were not. Analytical recoveries were variable, with means ranging from 70-100 percent. Apparent residues in untreated controls were <0.02 mg/kg in grain and up to 0.2 mg/kg in straw. Residues of prochloraz alone were substantially lower, ranging from <0.01-0.02 mg/kg in mature grain and <0.01-0.15 mg/kg in straw, which are comparable to the values reported in wheat. Rye Total prochloraz and its metabolites, from foliar treatments in mature rye grain or whole ears ranged from <0.02-0.1 mg/kg and in straw from 0.4-2.5 mg/kg. Application rates reflected good agricultural practice, although the preharvest interval of 72 to 109 days was significantly greater than the one month permitted (Table 8). Analytical recoveries were typically >80 percent in grain and somewhat lower in straw. Apparent residues in untreated controls were <0.01 mg/kg in grain but as high as 0.04 mg/kg in straw. Oats Information on good agricultural practice for oats was not available for the country in which residue trials were conducted or from other countries. Residues of prochloraz and its metabolites were <0.03 mg/kg and <1.6 mg/kg for whole ears and straw, respectively, 62 days after treatment at application rates considered good agricultural practice for other cereals (Table 8). Rice No information on good agricultural practice was available for rice, except for seed treatments in one country (for which there are no data). Residues of prochloraz alone in unpolished brown rice 7-21 days after treatment at application rates comparable to good agricultural practice on other cereals were <0.05 mg/kg (Table 8). Residues of prochloraz and its metabolites would be expected to be higher. Residues from seed treatments were lower, but the interval after treatment was 151-168 days. Analytical recoveries were 86 percent in grain and apparent residues in untreated controls were <0.005 mg/kg, the limit of detection. Summary data for residues in cereal grain at harvest (Table 9) represents foliar applications of all formulations. The data in Table 9 confirm those reported in Tables 6-8, since it is statistically shown that maximum residues of prochloraz and its metabolites would normally be less than 0.2 mg/kg at the longer preharvest intervals but residues up to 0.4 mg/kg can occur. Other trials at shorter intervals also resulted in higher grain residues than at longer intervals. Similarly, Table 11 confirms the findings reported in Tables 6-8 for residues in straw (up to 15 mg/kg). Tables 9 and 11 do not include more recent studies (Housden 1982c; Longland 1983a; Housden & Longland 1983; Heinanen 1983) reported in Tables 6-8, but these would not increase expected residues. Tables 9 and 11 also indicate that higher residues can be expected from multiple or higher doses. Residues of prochloraz alone were <0.03 mg/kg in cereal grains at harvest, except for rice where residues were as much as 0.05 mg/kg 7 to 21 days after treatment. From seed treatment alone, residues of prochloraz and its metabolites in mature grain were <0.02 mg/kg. Generally, there was no conclusive evidence of increased residues as a result of co-application of prochloraz and other agricultural chemicals. Residue decline studies are summarized in Table 10. Half-lives of approximately 6 to 17 days could be estimated for ears or whole plants of wheat or barley on the basis of sampling for at least three successive intervals. Residues of prochloraz and its metabolites ranged from 0.15 to 21 mg/kg on green plants or ears on the day of last treatment to 0.07-3.6 mg/kg at 21 to 48 days, which approximates typical preharvest intervals. Almonds No information was available on good agricultural practice for prochloraz on almonds. Foliar treatments with the 50 percent W.P. manganese complex are "recommended" at 15-30 g a.i./hl. No preharvest interval has been reported. One trial was conducted with foliar treatments at seven times the maximum recommended application rate (Table 2) with total residues corrected for recoveries of >86 percent of 0.61, 0.1 and 0.29 mg/kg in shell, kernel and whole nut (calculated from shell and kernel residues), respectively, about three months after the last treatment. Apparent residues were 0.06 mg/kg in un-treated controls on a whole nut basis and up to 0.09 mg/kg in the shell. The limit of determination was estimated at 0.1 mg/kg. Table 7 Supervised Residue Trials with Prochloraz on Barley at Harvest Country/ Formulation No. of Application rate2 No. of Interval after Residue (mg/kg)1 Reference Year trials (kg a.i./ha) samples final application (days) grain straw Austria 25% E.C. 2 0.5 2 61-73 <0.013 <0.01-0.02 1977 1 0.75 1 73 <0.013 0.023 1 1.0 1 61 <0.013 0.033 1 2x0.5(19) 2 54 <0.013 <0.013 1978 22.5% E.C. 2 0.45 69-75 <0.02-0.04 0.65-1.30 Kelly 1979f 1 0.9 75 0.02-0.04 1.0-2.1 Belgium 45% E.C. 3 0.45 6 (M)10 0.01-0.03 n.d. Housden 1982a 1981 7 0.4511 14 (M)10 0.01-0.11 n.d. 2 2x0.4511 (I+M)10 0.02-0.03 n.d. Denmark 25% E.C. 1 0.75 96 <0.02 n.d. Kelly 1979g 1979 40% E.C. 2 0.6 76-86 <0.02-0.10 1.9-4.6 Richards 1980d 20% E.C. 1 0.6 86 <0.02-0.04 2.5-3.4 20% S.D. 2 0.28 132-1399 <0.02 <0.02 1982 45% E.C. 2 0.234 3 75-87 <0.02-0.03 0.84-1.10 Housden 1982c 4 0.45 4 61-80 <0.02-0.02 1.45-3.24 1 0.45 1 60 0.0514 3.02 2 2x0.45(14) 61-73 <0.02-0.02 1.61-2.59 France 25% E.C. 2 0.5 62-74 <0.01-0.013 <0.01-0.053 Hayto 1978b 1977 2 1.0 62-74 <0.01-0.023 0.01-0.153 1978 25% E.C. 1 0.45 64 0.02-0.06 1.77-8.86 Kelly 1979h 1 0.9 64 0.02-0.08 2.67-10.48 1 2x0.45(19) 62 0.04-0.09 4.23-7.00 1 2x0.9 (19) 62 0.04-0.17 11.19-11.95 Table 7 (continued) Country/ Formulation No. of Application rate2 No. of Interval after Residue (mg/kg)1 Reference Year trials (kg a.i./ha) samples final application (days) grain straw 1979 40% E.C. 2 0.45 4 54-62 <0.02-0.17 5.76-10.81 Richards 1980a 2 2x0.45(21)5 6 38 0.36-0.68 7.20-12.12 30% E.C.6 2 2x0.45(13-21) 38-48 0.10-0.57 6.96-9.47 Fed. Rep. 25% E.C. 1 0.5 1 70 <0.013 <0.013 Hayto 1979c of Germany 1 0.7 1 70 <0.013 <0.013 1977 1980 40% E.C. 2 0.48 77-79 0.02-0.06 0.06-1.0 Richards 1981b 2 2x0.48(19)12 77-79 0.02-0.06 1.1 -1.3 1981 40% E.C. 2 2x0.48(11-12) 61-62 0.02-0.06 0.95-1.27 Browne 1982f 1982 30% E.C.6 3 0.45 62-76 <0.05 0.23-0.83 Housden & Longland 1983 Netherlands 45% E.C. 1 0.45 3 70 0.04-0.06 0.78-1.21 Reary 1981c 1980 Sweden 45% E.C. 4 0.45 61-72 <0.0213 0.19-1.27 Longland 1983a 1982 2 2x0.225(8-15) 53-55 <0.02 0.24-1.21 2 2x0.45(8-15) 53-55 <0.02 0.34-2.86 United 25% E.C. 3 0.4 54-74 <0.013 <0.01-0.023,7 Hayto 1977a Kingdom 4 0.5 19-64 <0.013 0.01-0.023,13 1976 2 1.0 64-74 <0.013 <0.013,20 1977 25% E.C. 4 0.5 76-78 <0.013 0.01-0.043 Hayto 1979c 2 1.0 76-78 <0.01-0.01 <0.01-0.02 1979 40% E.C. 3 2x0.4(18-29) 36-63 0.06-0.32 3.0 -14.5 Richards 1980c Table 7 (continued) n.d. not determined. 1/ Total residues of prochloraz and major metabolites, unless otherwise stated. Total residue measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x 1.906). 2/ Figures in parenthesis indicate interval in days between applications. 3/ Determination of free prochloraz residues only. 4/ Prochloraz applies in mixture with fenpropimorph. 5/ Prochloraz applied in mixture with mancozeb. 6/ Co-formulation of prochloraz with carbendazim. 7/ Results from two trials. 8/ Rate of application in g a.i./kg seed. 9/ Days after sowing treated seed. 10/ Growth stages at application: M-heading, I-first joint. 11/ Prochloraz applied in mixture with chlorothalonil. 12/ Interval between treatments not given in one trial. 13/ Results from three trials. 14/ Residue analysis of whole ears. Table 8 Supervised Residue Trials with Prochloraz on Cereals at Harvest Crop Country/ Formulation Number of Application rate No. of Interval after Residue (mg/kg)1 Reference Year trials (kg a.i./ha) samples application (days) grain straw Rye Austria 25% E.C. 1 0.5 1 91 0.013 <0.013 Kelly 1979a 1977 1 1.0 1 91 <0.013 <0.013 Denmark 45% E.C. 2 0.45 2 72-77 <0.02-0.10 1.44-2.48 Housden 1982c 1982 Fed. Rep. 40% E.C. 2 0.48 4 89-109 0.03-0.05 0.39-0.53 Browne 1982d of Germany 1981 Oats Denmark 45% E.C. 2 0.45 2 62 0.02-0.034 1.19-1.64 Housden 1982c 1982 Rice Japan 25% E.C. 2 0.75 12 7-21 <0.01-0.043 n.d. Gato 1980 (brown, 1980 25% E.C. 2 3x0.75 12 7-21 <0.01-0.043 n.d. unpolished) 25% E.C. 2 25 g/hl2 + 12 7-21 <0.01-0.043 n.d. 3x0.75 25% E.C. 2 25 g/hl2 4 151-168 <0.013 n.d. n.d. = not determined. 1/ Total residues of prochloraz and major metabolites, unless otherwise stated. Total residues measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x1.906). 2/ 48-hour seed soak. 3/ Determination of free prochloraz residues only. 4/ Residue analysis of whole ears. Table 9 Summary of Residues in Mature Grain Crop Application No. of Total residue (mg/kg) (kg a.i./ha) results Mean Std. Dev. Wheat 1 × 0.375-0.5 36 0.03 0.03 Wheat 2 × 0.375-0.5 36 0.04 0.03 Wheat 3 × 0.375-0.5 12 0.06 0.03 Wheat 1 × 0.6-0.9 31 0.07 0.18 Barley 1 × 0.4-0.5 42 0.03 0.03 Barley 2 × 0.4-0.5 20 0.091 0.091 Barley 1 × 0.6-0.9 14 0.03 0.03 Barley 2 × 0.9 3 0.09 0.05 Rye 1 × 0.48 2 0.04 1/ Excluding a set of 11 results from four replicated applications of prochloraz alone and with mancozeb, which were exceptionally high (mean 0.42, std. dev. 0.18 mg/kg), residues in straw were not exceptionally high. The high grain results may reflect poor separation of grain and chaff in these samples (Richards 1980a). Table 10 Supervised Trials on Residue Decline with Prochloraz Crop Country/ No of Formulation Application rate2 Residues (mg/kg)1 after References Year trials (kg/a.i./ha) final application (days) 35-36 56 75-85 Wheat Denmark 1 45% E.C. 0.45 whole plant 1.62 Housden 1982c 1982 whole ears 0.10 straw 2.01 2 45% E.C. 2x0.23(19)3 whole plant 0.33-0.94 grain <0.02 straw 1.47-1.94 2 45% E.C. 0.23+0.45(19)3 whole plant 1.11-1.76 grain <0.02 straw 1.87-2.36 2 45% E.C. 2x0.45(19) whole plant 0.70-2.02 grain <0.02-0.02 straw 1.56-2.07 2 45% E.C. 2x0.45(19)3 whole plant 1.38-1.44 grain <0.02 straw 1.72-2.79 Table 10 (Contd.) Crop Country/ No. of Formulation Application2 After After final application (days) References Year trials rate penultimate (kg a.i./ha) application (days) 20-29 0 15-22 37-42 54-63 Wheat Fed. Rep. 3 40% E.C. 2x0.48 green plant 0.80-1.644 1.62-2.554 of (21-30) ears 0.15-1.114 0.27-1.494 0.23-0.844 0.06-0.084 Richards Germany grain <0.02-0.06 1980g 1979 straw 1.0-5.9 17-23 0 8-19 39-44 59-66 1980 3 40% E.C. 2x0.48 green plant 0.15-2.7 (17-23) green ears 4.7 -13.6 0.84-2.2 0.28-0.61 Reary grain 0.01-0.04 1981b straw 0.7 -2.0 7-13 0 8-19 39-44 59-66 3 40% E.C. 3x0.48 green plant 0.2 -4.7 (11-23/ green ears 5.5 -16.8 0.61-3.3 0.35-0.58 7-13) grain 0.03-0.06 straw 1.1 -3.6 8-19 0 7-14 31-46 58-64 1981 5 40% E.C. 3x0.48 green ears 0.16-0.96 3.87-12.50 2.42-5.85 0.31-1.16 Browne (11-29/ whole plant 0.51-3.789 1982e 8-19) grain 0.04-0.31 0.02-0.13 straw 1.07-6.40 Table 10 (Contd.) Crop Country/ No. of Formulation Application2 After After final application (days) References Year trials rate penultimate (kg a.i./ha) application (days) 28-30 0 12-14 21-48 43-60 1981 2 40% E.C. 2x0.48 green ears 0.11-0.84 10.64-13.2 1.14-4.21 0.71-1.18 Browne (28-30) whole plant 2.078 1982f grain 0.038 0.06 straw 1.88-3.59 6-19 0 7-14 21-48 43-60 4 40% E.C. 3x0.48 green ears 2.96-8.27 13.90-21.40 3.61-7.25 0.49-2.32 (9-22/ whole plant 1.74-3.614 2.317 6-19) green ears+ 2.318 straw grain 0.03-0.217 0.05-0.08 straw 4.05-4.55 ears 0.487 0 17 42 57 85 Wheat Fed. 3 30% E.C.5 0.45 whole plant 7.99-13.64 0.74-1.95 0.21-0.94 0.45.0.62 Housden & Rep. of grain <0.05 Longland Germany straw 0.08-0.27 1983 1982 34-36 60-87 Barley Denmark 2 45% E.C. 0.233 whole plant 0.64-0.74 1982 grain <0.02-0.03 straw 0.84-1.10 Table 10 (Contd.) Crop Country/ No. of Formulation Application2 After After final application (days) References Year trials rate penultimate (kg a.i./ha) application (days) 34-36 60-87 5 45% E.C. 0.45 whole plant 0.77-2.32 grain <0.02-0.02 straw 1.45-3.24 whole ears 0.058 2 45% E.C. 2x0.45 whole plant 1.03-3.18 (14) grain <0.02-0.02 straw 1.61-2.59 19 0 13 33-34 77-79 Fed. 2 40% E.C. 0.48 green plant 5.1-10.1 0.4-1.5 0.6-1.7 Richards 1981b Rep. of grain 0.02-0.06 Germany straw 0.6-1.0 1980 2 40% E.C. 2x0.48 green plant 1.1-3.4 3.2-5.0 1.5-2.5 1.3-2.1 (19)6 grain 0.02-0.06 straw 1.1-1.3 11-12 0 10-18 27-48 61-62 1981 2 40% E.C. 2x0.48 green plant 0.91-7.99 10.40-18.60 Browne 1982f (11-12) green ears 0.52-3.62 0.07-0.50 ears + straw 0.218 grain 0.088 0.02-0.06 straw 0.95-1.27 Table 10 (Contd.) Crop Country/ No. of Formulation Application2 After final application (days) References Year trials rate (kg a.i./ha) 0 19 38-40 56 62-76 1982 3 30% E.C.10 0.45 whole plant 5.25-10.38 0.21-1.78 0.13-0.80 <0.05-0.78 Housden & grain <0.05 Longland 1983 straw 0.23-0.83 35 72-77 Rye Denmark 2 45% E.C. 0.45 whole plant 0.85-1.62 1982 whole ears <0.02-0.10 straw 1.44-2.48 0 11 21 34 55-56 69 83 89 93 109 Fed. Rep. 1 40% E.C. 0.48 whole plant 9.6 1.16 0.20 Browne of green ears 0.03 0.02 1982d Germany ears 0.03 1981 grain 0.03 0.05 straw 0.39 1 40% E.C. 0.48 whole plant 13.8 1.33 0.05 green ears 0.14 0.05 ears 0.02 grain 0.10 0.03 straw 0.53 36-37 62 Oats Denmark 2 45% E.C. 0.45 whole plant 0.37-0.88 Housden 1982 whole ears 0.02-0.03 1982c straw 1.19-1.64 Table 10 (Contd.) 1 Total residues of prochloraz and major metabolites, unless otherwise stated. Total residue measured as 2,4,6-trichlorophenol BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x 1.906). 2 Figures in parentheses indicate interval in days between applications. 3 Prochloraz applied in mixture with fenpropimorph. 4 Results from two trials. 5 Co-formulation of prochloraz with carbendazim. 6 Interval between treatments not given in one trial. 7 Results from three trials. 8 Result from one trial. 9 Results from four trials. Table 11 Summary of Residues in Mature Straw Crop Application No. of Total residue (mg/kg) (kg a.i./ha) results Mean Std. Dev. Wheat 1 × 0.375-0.5 35 2.83 3.07 Wheat 2 × 0.375-0.5 36 4.85 3.23 Wheat 3 × 0.375-0.5 11 3.20 1.60 Wheat 1 × 0.6-0.9 22 5.03 4.42 Barley 1 × 0.4-0.5 20 3.30 3.05 Barley 2 × 0.4-0.5 26 6.95 3.64 Barley 1 × 0.6-0.9 13 3.36 1.92 Barley 2 × 0.6-0.9 3 11.6 0.4 Barley 1 × 0.48 2 0.46 No information on good agricultural practice was available for the use of prochloraz on almonds. A 50 percent prochloraz-manganese complex is "recommended" as a foliar treatment at a 15-30 g a.i./hl application rate. Two applications at 3X this rate in one trial resulted in maximum residues up to 0.7 mg/kg (Table 2). The limit of determination has been estimated at 0.1 mg/kg although the apparent residues in an untreated control were 0.07 mg/kg. Recoveries from hulls amended with prochloraz at 1 mg/kg were 96±7 mg/kg. Oilseed Rape Information on good agricultural practice was available for prochloraz on oilseed rape from two countries, from which data on residue trials were also available. Residue data from 48 trials were also reported from two countries for which good agricultural practice was not known to the Meeting (Table 12). At preharvest intervals from 25 to 266 days, residues of prochloraz and its metabolites, reflecting good agricultural practice, ranged from 0.01 to 0.33 mg/kg. Preharvest intervals, if applicable, were not provided. The limit of sensitivity was estimated at 0.05 mg/kg. However, since apparent residues in untreated controls ranged from <0.01-0.15 mg/kg (but were usually less than 0.05 mg/kg), a 0.2 mg/kg over-all limit of determination may be more realistic. Analytical recoveries were > 85 ± 15 percent of amended levels of 0.2-1 mg/kg. Mushrooms Information on good agricultural practice and corresponding residue trials were available from two countries, as well as data from residue trials from another country (total of 31 trials, Table 13). The most common treatment was a single application of the prochloraz-manganese complex formulation 1-10 days after casing at 1.5 g a.i./l sq m with a 10-day preharvest interval, or three applications at 0.3 g a.i./l/m2, the first 1-10 days after casing and then after the first and second flush, with a two-day pre-harvest interval. A variation of the latter was also used at 2x 0.6 g a.i./l/sq m (Table 1), also with a two-day preharvest interval. Data extracted from Table 13 that reflect good agricultural practice are: Country/ Applications Residue (mg/kg) Interval after Approved preharvest and rate last application harvest (g a.i./sq m) (days) interval (days) The Netherlands 1 x 1.6 0.11-0.27 total residue 10 10 United Kingdom 2 x 0.6 1.4-1.6 total residue 4 2 0.6-0.8 free prochloraz 1 x 1.25 0.36 total residue 13 10 0.47 free prochloraz 28 10 3 x 0.3 0.24-0.43 total residue 2 2 0.07-0.1 free prochloraz 6 2 0.4-1.4 free prochloraz 3 2 Table 12 Supervised Residue Trials with Prochloraz on Rapeseed Country/ Formulation No. of Application rate2 No. of Interval after Residues1 References Year trials (kg a.i./ha) samples final application (mg/kg) (days) France 40% E.C. 2 0.45 8 73 0.02-0.04 Cron 1982 1980/1 2 0.453 8 73-76 0.01-0.03 1 0.60 4 73 0.02-0.03 30% E.C.4 2 0.45 8 73-76 0.02-0.03 1982 40% E.C. 4 0.45 12 37-51 0.03-0.15 Peatman & Snowden 1982 4 0.453 12 37-51 0.03-0.13 4 2x0.45 (12-15) 12 25-38 0.04-0.32 30% E.C.4 4 2x0.45 (12-15) 12 25-38 0.06-0.33 Denmark 45% E.C. 3 0.45 6 70-76 <0.05 Peatman & Snowden 1983 1982 3 2x0.45 (18-23) 7 53 0.07-0.19 Sweden 45% E.C. 3 0.45 6 47-72 0.12-0.28 Peatman & Snowden 1983 1982 United 40% E.C. 3 0.45 238-266 <0.05-0.07 Manley & Snowden 1982c Kingdom 3 0.45 3 119-133 <0.05-0.19 1981/2 3 2x0.4(91-109)5 3 119-133 <0.05 3 3x0.4(91-109/ 3 64-75 <0.05-0.09 51-58)5 2 3x0.4(92-103/ 2 72-73 <0.05-0.06 51-57) 2 3x0.5(92-103/ 1 72-73 0.06 51-57) Table 12 (continued) 1 Total residues of prochloraz and major metabolites, measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x 1.906). 2 Figures in parentheses indicate interval in days between applications. 3 Prochloraz applied in mixture with mancozeb. 4 Co-formulation of prochloraz with carbendazim. 5 Prochloraz applied in mixture with tolclofos methyl. Table 13 Supervised Residue Trials with Prochloraz on Mushrooms Country/ No. of No. of Application rate (a.i.) Residues (mg/kg)1 days after final application References Year trials samples and timing2 3 5 10 14 20 21 27 45 Australia 1 1.25g/sq m at casing 0.1 0.1 <0.1 Housden 1981 1 2.50g/sq m at casing 0.23 0.13 0.14 1982 1 1.25g/sq m at casing + 0.63g/sq m after first flush 0.41-0.63 0.22 (24-day interval) 1 2.50g/sq m at casing + 1.25g/sq m after first flush 1.16-1.63 (24-day interval) 1 2.50g/sq m at casing + 2.50g/sq m after first flush <0.1 (24-day interval) 1 0.63g/sq m after first flush 1.06-2.98 1 1.25g/sq m after first flush 4.48-4.61 1 1.25g/sq m after first flush+ 0.63g/sq m after second flush 0.29 (7-day interval) 1 2.50g/sq m after first flush+ 1.25g/sq m after second flush 0.37 (7-day interval) The 1 4 1.6g/sq m before inoculation 0.11-0.27 Browne Netherlands 1 4 0.75g/sq m before inoculation+ 0.15-0.24 1982 1980 0.75g/sq m 14 days later 4 0.75g/sq m before inoculation+ 0.75g/sq m after first flush 0.15-1.14 (23-days interval) Table 13 (Continued) Country/ No. of Application rate (a.i.) Residues (mg/kg)1 days after References Year trials and timing2 1st application 2nd application 3rd application 19 7 4 United 1 0.61g/sq m after casing + 0.04 0.10 0.08 Richards 1981c Kingdom 0.61g/sq m after first flush + 1980 0.61g/sq m after second flush (19- and 10-day intervals) 1st application 2nd application 21 28 4 12 18 1 0.61g/sq m after casing + 0.04 0.04-0.11 1.37-1.58 <0.02 0.61g/sq m after second flush (31-day interval) 14 0.61g/sq m after casing + 0.013 0.01-0.33 0.56-0.803 0.08-0.333 0.05-0.183 Whiteoak 1981 0.61g/sq m after second flush (31-day interval) Days after application 28 35 43 49 1 1.25g/sq m 7 days after inoculation 0.473 0.043 0.27-0.323 0.203 1 0.625g/sq m 7 days after inoculation 0.133 0.103 0.093 0.07-0.083 2nd application 3rd application 13 6 14 20 1 0.625g/sq m 7 days after inoculation 0.193 0.22-0.243 0.033 0.27-0.323 1 + 2x0.313g/sq m at 14-day intervals thereafter 1 0.313g/sq m 7 days after inoculation + 2x0.313g/sq m at 14-day intervals 0.133 0.07-0.103 0-323 0.053 thereafter Table 13 (Continued) Country/ No. of Application rate (a.i.) Residues (mg/kg)1 Year trials and timing2 Days after application 2nd application 3rd application 5 12 3 14 21 1981 1 0.15g/sq m five days after inoculation 0.323 0.123 0.62-0.653 0.193 0.093 Whiteoak 1981 + 2x0.15g/sq m at 18- and 14-day intervals thereafter 45 0.3g/sq m + 2x0.3g/sq m. Timing as 0.20-0.373 0.11-0.643 0.39-1.443 0.10-0.313 0.06-0.073 given above 1 0.9g/sq m + 2x0.3g/sq m. Timing as 0.423 0.213 1.293 0.543 0.21-0.243 given above 1 1.5g/sq m + 2x0.3g/sq m. Timing as 0.273 0.523 0.993 n.d. 0.063 given above 1 3.0g/sq m + 2x0.3g/sq m. Timing as 0.623 0.543 0.743 0.343 0.953 given above Table 13 (Continued) Country/ No. of Application rate Residues (mg/kg)1 days after References Year trials (a.i.) and timing2 1st application 2nd application 3rd application 13-14 15-16 18 3 5 7 10 12-13 14-16 2 3-4 7 9-10 12 14 17 United 1 0.3g/sq m 7 days after 0.24 0.20 0.79 0.426 0.30 0.30 0.377 0.23 0.51 0.43 0.33 1.03 0.32 0.23 0.28 0.22 Housden Kingdom casing + 2x0.3g/sq m & 1981 at 18- and 14-day Whiteoak intervals thereafter 1982 1982 1 0.3g/sq m 7 days after 0.26 0.14 0.85 0.24 0.24 0.26 0.58 0.24 0.61 0.45 0.61 casing + 2x0.3g/sq m (0.57)8 (1.11)8 at 15- and 17-day intervals thereafter Residues (mg/kg)1 days after application 13 15 18 22 25 28 31 34 36 39 42 1982 1 1.25g/sq m 7 days after casing 0.36 0.25 0.33 0.30 0.20 0.38 0.42 0.28 0.54 0.22 0.33 Table 13 (Continued) n.d. = not determined. 1 Total residues of prochloraz and major metabolites, unless otherwise stated (see note 3). Total residue measured as 2,4,6-trichlorophenol (BTS 45186) and converted to prochloraz-derived residue by correcting for the molecular weight factor (x1.906). 2 All treatments used the prochloraz-manganese complex 50% W.P. formulation. 3 Determination of residues of free prochloraz only. 4 Samples of mushroom also analysed for total residues of prochloraz and metabolites (see Richards 1981c) 5 Mean residue levels from four trials using spray volumes of 100, 200 or 400 l/sq.m. 6 Mean residue level in small and larger mushrooms (0.43 and 0.40 mg/kg respectively). 7 Mean residue level in small and larger mushrooms (0.52 and 0.21 mg/kg respectively). 8 Mushroom emerged before treatment (direct application). Therefore, residues of prochloraz and its metabolites or of prochloraz alone may be at least as much as 2 mg/kg from approved practices. Differences between residues of prochloraz and its metabolites, compared to free prochloraz, do not appear to be as high as in cereals. Analytical recoveries of total residues were generally > 70 percent, with apparent residues of 0.03 ± 0.02 mg/kg in untreated controls and > 77 percent and 0.01 mg/kg for free prochloraz. FATE OF RESIDUES The fate of prochloraz has been studied in plants and animals. In plants, it is metabolized to N-formyl-N'-1-propyl-N-(2-(2,4,6-trichlorophenoxy)ethyl) urea, also known as BTS 44596 or the "formyl urea"; to N-propyl-N-(2-(2,4,6-trichlorphenoxy)ethyl) urea, also known as BTS 44595 or "the urea"; to 2,4,6-trichlorophenoxyacetic acid (BTS 9608), and finally to 2,4,6-trichlorphenol (BTS 45186), all of which form stable conjugates (Figure 1). Animal metabolism has resulted in characterization of urinary metabolites (see Figure 1 under "Toxicology"), information of radioactivity distribution in tissues from oral or dermal administration and rate and route of excretion. Qualitatively, urinary metabolites are similar among several test animals, although the major plant metabolites have not been identified in the urine. Residues in animal tissues have not been identified. Metabolism studies have also been conducted on the major plant metabolite BTS 44596. In Animals Metabolism of prochloraz in rats, dogs, rabbits, mice and pigs is discussed under "Biochemical Aspects". Goat A study was conducted to indicate the level of residues that might occur in tissues and milk of lactating ruminant animals after ingestion of prochloraz. A lactating goat was given two 60 mg oral doses of 14C-phenyl labelled prochloraz by gelatin capsules, with 13 days between doses. The dosage was designed to reflect possible residues resulting from consumption of 3 kg of straw with residues of 20 mg/kg of prochloraz at each dosing (versus maximum straw residues of 12 mg/kg). Milk and plasma samples were taken at appropriate intervals after each dose and tissue samples 24 h after the second dose. After the first dose, residues of prochloraz equivalent in milk decreased from 0.04 mg/kg after 8 h to 0.01 mg/kg (limit of determination) after 48 h. Milk residues were 0.01 mg/kg and 0.03 mg/kg at 2.5 and 18.5 h, respectively, after the second dose. In tissues, residues of prochloraz equivalent were 1.7 mg/kg in liver, 0.2 mg/kg in kidney, 0.36 mg/kg in adrenal, <0.05 mg/kg in fat, 0.03 mg/kg in muscle and <0.2 mg/kg in other tissues. Rumen contents contained prochloraz equivalent of 0.65 mg/kg and bile 5.4 mg/kg. Residues were not characterized or identified (Campbell 1980). A second and similar experiment was conducted using the photodegradant and plant metabolite BTS 44596, with an interval of 8 h between doses. Results were similar to those for prochloraz, although the higher maximum milk residues of 0.07 mg/kg BTS-44596 equivalent 7 h after dosing decreased somewhat more rapidly (< 0.01 mg/kg after 31 h). Residues of BTS-44596 equivalent in tissues were somewhat less than for prochloraz (liver 0.59 mg/kg, kidney 0.12 mg/kg, fat <0.01 mg/kg, muscle <0.01 mg/kg and less in other tissues as well), Residues were not identified or characterized (Campbell & Needham 1980). In another study a lactating goat was fed ad libitum for four days with wheat straw containing 19 mg/kg field-incurred 14C-prochloraz equivalent residues. The straw was harvested at maturity 11 weeks after treatment at an equivalent rate of 0.94 kg a.i./ha (twice the recommended rate), Actual straw consumption was approximately 300 g/day (or approximately 6 mg of prochloraz equivalent/day), in addition to 1 700 g additional feed made available daily. After four days, maximum tissue residues of prochloraz equivalent, as determined by liquid scintillation counting was liver 0.05 mg/kg, kidney fat 0.04 mg/kg and 0.03 mg/kg in other tissues, with a reported limit of determination of 0.02 mg/kg. Bile and rumen residues were 0.12 and 0.13 mg/kg, respectively. Maximum residues in milk were 0.006 mg/l and in plasma 0.079 mg/l. The limit of determination for milk was 0.001 mg/kg in this experiment. Residues in milk were relatively consistent over the four-day feeding period. Milk residues were 0.002 mg/kg prior to the feeding of treated straw (Campbell 1983). In Plants The fate of prochloraz has been studied in wheat (various stages), citrus and apples. Soil uptake by sugar beet, which represents a likely rotational crop, was also studied. The metabolic fate in plants is illustrated in Figure 1. Wheat Wheat plants grown under glass were syringe treated at the sixth leaf stage with a 25 percent a.i. formulation of 3H-labelled prochloraz (labelled in the 3 and 5 positions of the benzene ring) at a rate equivalent to 1 kg/ha. After 19 days, the green wheat tissue was harvested and residues characterized and quantified by a variety of analytical techniques. Neutral, acid and basic fractions were analysed, with and without acid hydrolysis. After 19 days, 82.6 percent of the applied radioactivity remained and 96.7 percent of this was extractable by the analytical procedures used (acetone-water extraction). The principal residue was free BTS 44596, closely followed by free and conjugated residues of BTS 44595, with lower levels of free prochloraz and free and conjugated trichlorphenol, conjugated trichlorophenoxyacetic acid and seven unknowns. Terminal prochloraz equivalent was 7 mg/kg. Individual residues were: % of applied % of terminal radioactivity residue* BTS 44596: N-formyl-N'-l-propyl-N-(2-(2,4,6- trichlorophenoxy) ethyl) urea free 31.6 41 BTS 44595: N-propyl-N-(2-(2,4,6-trichlorophenoxy) free 11 13 ethyl) urea conj. 19.5 23.1 BTS 45186: 2,4,6-trichlorophenol free 1.4 1 conj. 6.8 4.9 BTS 9608 2,4,6-trichlorophenoxy- acetic acid conj. 0.21 0.2 BTS 40542: Prochloraz (unchanged) free 1.1 1.5 Unknown (seven) 5.5 7.7 Radioactivity undetected 0.93 1.3 Radioactivity unaccounted for 4.56 6.3 82.6 100.0 * Expressed as prochloraz equivalents None of the seven unknowns exceeded 4.3 percent of the terminal residue. Analysis of barley plants treated in a similar manner suggests that over 86 percent of the radioactivity applied to foliage was absorbed by the leaf within 24 h (McDougall 1979). In another study, separate plots of wheat at the flag leaf sheath opening stage were treated with a 25 percent a.i. formulation of either 3H-prochloraz labelled in the 3 and 5 positions of the phenyl ring or 14C-prochloraz labelled in the 2 position of the imidazole ring, at an equivalent rate of 1 kg a.i./ha. Mature wheat was harvested 13 weeks after treatment and the grain, straw and chaff were analysed. Total residues, expressed as prochloraz equivalents, from the phenyl-labelled prochloraz were grain 0.26 mg/kg, chaff 13.2 mg/kg and straw 26.5 mg/kg. An almost identical distribution resulted from the 14C-prochloraz treated wheat. From the 3H-prochloraz treated wheat 76-80 percent of the recovered radioactivity was extractable from both straw and grain. Attempts to hydrolyse polar fractions with HC1 were unsuccessful, but better results were achieved with pyridine hydrochloride, which hydrolyses conjugated residues containing the 2,4,6-trichlorophenyl moiety. The procedure liberates 2,4,6-trichlorophenol from both prochloraz and any metabolites containing the 2,4,6-trichlorophenyl moiety. Results of the analysis of the 3H-prochloraz treated wheat, expressed as a percentage of recovered radioactivity in mature tissue, are summarized below:
Straw Grain Free 2,4,6-trichlorophenol (BTPS 45186) 5.2 4.1 3.4 8.4 Residues containing the BTS-45186 moiety 58 37.9 53.9 39.5 Tritiated water 4.8 - 4.2 - Unidentified extractable residues 9.1 34 15.5 32.1 Unidentified residues in solids 22 24 24.7 20 99.1 100 101.7 100 Of the unidentified extractable residues no one of the grain or straw acidic, basic, volatile or aqueous fractions analysed contained more than 6.2 percent of the total residue. Formation and analysis of the glucosazone after hydrolysing starch extracted from the 14C-prochloraz treated grain demonstrated that 32.4 percent of the grain radioactivity was incorporated into the starch molecules. This is thought to result from the incorporation of 14C-carbon dioxide, resulting from decarboxylation of the metabolite BTS 44596. The remaining residues were separated into various fractions but were not identified (Kelly 1980d; Kelly & Krepski 1980). When wheat seeds were treated at an equivalent rate of 0.4 a.i./kg seed (approximating recommended usage) with a 20 percent a.i. liquid seed dressing and grown to maturity, residues at maturity (29 weeks) were: % of total Prochloraz applied Equivalents (mg/kg) Treated Controls Soil 58œ3 0.06 - Roots 15.1 1.5 - Chaff 0.1 0.04* 0.004* Grain 0.04 0.004* 0.002* Total aerial 6.6 0.16 - * mean of four determinations. Translocation into the aerial portion of the plant was complete after six weeks (Krepski 1982). Potted wheat seeds were allowed to germinate under glass after soil surface drench application of a diluted 3H-prochloraz formulation. Approximately 82 percent of the radioactivity (0.8 percent of applied) was retained in the root system at harvest after 21 days. Residues decreased with increased distance of plant parts from the root system; they decreased from 8.7 percent of residues recovered in leaves 1 and 2, 0.62 percent in leaf 3, to 0.08 percent in leaf 7. Soil contamination was suspected of contributing some of the residues for leaves 1 and 2 and lower plant parts. In this same report a 3H-prochloraz formulation was applied with a syringe at the fifth leaf stage to the third leaf of similarly grown wheat without the soil drench. Plant parts were harvested and analysed after 24 days; 99 percent of applied radioactivity was retained in leaves 3 and 4 (difficulty was encountered in discerning leaves during applications). Radioactivity decreased from 0.03 percent of that applied in leaf 5 to 0.01 percent in leaf 9 and increased from 0.23 percent in leaves 1 and 2 to 0.33 percent in the roots (McDougall 1980a). After spring wheat harvest from soil plots treated at a rate equivalent to 1 kg/ha with either imidazole ring-labelled 14C-prochloraz or phenyl-labelled 3H-prochloraz, the plots were re-sown with winter wheat and reharvested 10 months later. Soil samples at harvest of the winter wheat were 0.11 and 0.43 mg/kg for 14C and 3H treatments, respectively. Residues of 14C or 3H-prochloraz equivalent were < 0.01 mg/kg in grain, chaff and straw. Grain control values were about half that for grain, but not statistically different. Low uptake is suggested for 3H-prochloraz treated chaff and straw where experimental levels are 50 to 100 times that of the respective controls (Krepski 1981a). A 1.5 sq m plot was treated with 14C-phenyl labelled prochloraz formulation by garden sprayer at an application rate equivalent to 395 g a.i./ha, which approximates recommended usage for cereals. After 41 days the soil was turned by hand and sown with sugarbeets as a representative rotational crop. A control plot was also planted. Seedlings were sampled 23 days after planting and mature plants (roots and foliage) at 157 days after planting. Residues at planting in soil averaged 0.26 mg/kg prochloraz equivalents. At 23 days after planting, residues of 0.07 mg/kg in seedlings were significantly greater than the 0.006 mg/kg controls. At harvest, residues of 0.005 mg/kg in the soils were not significantly different than in controls, whereas the 0.0052 mg/kg prochloraz equivalent in foliage was slightly greater than the 0.003 mg/kg control. This difference is statistically significant, although residues in the foliage are less than the background level (McGibbon 1982). Citrus 3H-prochloraz, a 2.5 percent E.C. formulation, was applied by pipette wash, to simulate a 0.1 percent a.i. postharvest commercial treatment, to Washington Navel oranges in Spain. Storage was at 4°C in the dark from 10 to 60 days and at 20-22°C in diffuse light. From 1 to 10 days, surface residues were removed with a 0.1 percent ethylan BCP solution and those in peel and flesh by extraction with 90 percent acetone. Surface residues at room temperature decreased from 5.8 percent of applied radioactivity at 1 day to 0.8 percent at 10 days, and at 4°C from 3.8 mg/kg at 10 days to 1.1 mg/kg at 60 days. Corresponding residues in the flesh increased from 1.8 percent to 5 percent of the applied dose over the storage period for room temperature storage, but remained relatively constant at approximately 1.6 percent over the entire 60 day storage period at 4°C. Radioactivity in the peel remained relatively constant at 92.3-96 percent of the applied dose over the room temperature storage period and, similarly, 94.7 to 97.2 percent over the storage period at 4°C (Kelly 1980a). Similar unlabelled studies on citrus residues during storage are reported under "In Storage and Processing". Apples Formulations of phenyl-labelled 14C-prochloraz or its manganese complex BTS 46828 were applied to individual apples under glass at rates approximating commercial usage. In samples analysed after 20 days, residue distribution was similar in the surface, peel and flesh from either chemical. Residues in extracts from the prochloraz-treated apples (86 percent of the applied dose was recovered) were - wash 7.4 percent, peel 50 percent and flesh 16.9 percent (20 percent of recovered). BTS 46828 gave almost identical results (Krepski 1981b). In similar experiments (not carried out under glass) the metabolism of prochloraz and its manganese complex were compared at intervals between 0 and 54 days after application by syringe to individual apples. Radioactivity distribution was again shown to be similar from use of either chemical, although prochloraz from the E.C. formulation was initially absorbed into the peel at a faster rate than the Mn-complex W.P. and was somewhat more persistent. The manganese complex was also more susceptible to losses from precipitation shortly after application. As a percent of radioactivity recovered at 0 and 54 days, residues were: Prochloraz Mn - complex *day 0 day 54 *day 0 day 54 surface 32.3 1.9 67.6 1.2 flesh 0.0 0.8 0.0 1.2 peel 67.2 81.2 32.4 56.2 Total 100 83.9 100 58.6 * 5 hours (McDougall 1980b). In another similar study distribution and characterization of residues were investigated in two apple varieties at intervals ranging from 16 to 63 days after application by syringe of the Mn-complex to individual growing apples. As a percent of the applied dose, representative residues were: Days after Whole Peel treatment fruit Flesh Total Extractables 16 72 (83) 15.81 67 (78) 51.3 (61.4) 33 54.8 (76) 3.6 (5.2) 51 (71) 37.2 (55.2) 63 63.5 5.4 60 38 Numbers in parentheses correspond to the Worcester variety and others to the Cox variety. Extractable residues in peel were quantified and characterized in both varieties at 33 and 63 days after treatment. As a percent of extractable peel residues the metabolic profile at 63 days for the Cox variety was: Metabolite Percent Prochloraz or Unchanged BTS 46 828 5 ) BTS 45186 (free 2,4,6-trichlorophenol) 11.5 ) BTS 44595 15.2 ) BTS 44596 33.1 ) >77.8 Conjugated residues containing ) the BTS 45186 moiety 13 ) Unidentified polar metabolites 6 "Unknowns" 1.6,0.7 Unresolved background 13.9 Total unidentified (excluding conjugates with BTS 45186) 22.2 100.0 Results were similar at 33 days for both varieties, except that conjugated residues containing the BTS 45186 moiety were only 3 percent for the Worcester variety, only the first "unknown" was observed in Cox and the first and a different second "unknown" was found in Worcester. None of the residues exceeded 2 percent (Kelly 1982a). In Soil Prochloraz 25 percent E.C. formulations, labelled with 14C in the imidazole ring and separately in the phenyl ring with 3H, were separately applied to acidic sandy loam and silty clay loam soils in enclosed jars purged with CO2-free air under laboratory conditions for up to 52 weeks. Application was at 6 mg/g soil, equivalent to 0.7 kg a.i./ha (a recommended crop application rate). Silty clay loam was similarly treated with prochloraz labelled with 14C in the phenyl ring and studied over 9 months. Radioactivity losses as volatiles were about 50 percent of the applied dose to silty clay for both 14C-imidazole and 3H-phenyl labelled prochloraz after one year, as was the case for the 14C-phenyl labelled formulation at 9 months. Losses were more rapid from silty clay loam than from sandy loam, for which losses were half or less that in silty clay. Experimental evidence indicated, but did not prove, that volatiles from 14C-phenyl and 14C-imidazole labelled prochloraz were predominantly CO2. In the case of 3H-phenyl labelled prochloraz, evidence suggests volatile radioactivity in the form of tritiated water. The major extracted residue in all cases was prochloraz per se at 50-68 percent of the applied dose (80-90 percent of extracted) after 8 weeks to 12-30 percent (45-67 percent of extracted) after 52 weeks. Lower residues of BTS-44596 and BTS 45186 combined were <18 percent of the applied dose (<26 percent of extracted) after 52 weeks for 3H-labelled treatments. Binding was more pronounced in sandy loam. The half-life was reported as 3 and 5 months, respectively, in silty clay and sandy loams. In both cases the acidic pH would increase stability (Kesterton 1981a). In German standard soils the half-life of unlabelled prochloraz ranged from 115-135 days, with stability directly related to organic matter content. For both soils the pH was acidic, which is conducive to prolonged stability (McGibbon 1982). 14C-imidazole and 3H-phenyl labelled prochloraz, formulated as a 25 percent E.C., were incubated under anaerobic conditions at a rate equivalent to 0.7 kg a.i./ha and sampled at 14, 27 and 60 days. Residues of prochloraz remained relatively constant over the test period in silty clay loam (ca 68 percent of the applied dose) and decreased slightly (to ca 54 percent) in silty clay loam. The decrease in silty clay loam was accompanied by an increase in bound residues. Anaerobic conditions halted the continuous degradation and formation of volatiles observed under aerobic conditions. Other components indicated by TLC from 3H treatments were BTS 44596 and BTS 45186 at approximately 6 and 3 percent of the applied dose, respectively, whereas from 14C treatments prochloraz, imidazole and BTS 44596 were approximately 68, 2 and 1 percent, respectively (Kesterton 1981b). The absence of significant degradation of a 14C-phenyl labelled 2.5 percent E.C. prochloraz formulation in sandy loam and silty clay loam under sterile soil conditions for 30 days suggests that degradation is facilitated primarily by soil microorganisms as opposed to chemical degradation, at least under the experimental conditions (acidic pH and 50 percent soil moisture capacity) (Newby 1982). Sandy loam and silty clay loam soil were treated with a 14C-benzene labelled 25 percent E.C. prochloraz formulation at a rate equivalent to 0.44 kg a.i./ha, aged 13 days, added to the top of 30 cm × 7 cm diameter columns containing untreated soil and eluted with an equivalent of 1.5 cm rain for 18 days. Essentially all radioactivity was retained in the top 5 cm of soil, with less than 0.3 percent of the applied amount being detected in leachate (Kesterton & Newby 1980a). In a similar soil column study, except that the equivalent application rate was 0.8 kg/ha, the labelled prochloraz was applied to the same silty clay loam and aged for 30 days, after which it was eluted for 45 days with a daily equivalent of 0.5 cm rainfall. Results were similar to the first study in that <0.05 percent of the applied dose was detected in the eluant. However, even though 88-94 percent was in either the treated portion or the first 5 cm below it, 0.3-0.6 percent was detected in the bottom 25 cm, indicating some downward mobility other than that detected in the leachate (Kesterton & Newby 1981). When an unlabelled prochloraz formulation was applied to West German standard soil columns at a rate equivalent to 1 kg/ha, <0.05 percent was detected in the leachate (Maier-Bode 1980). In a similar experiment leachate contained <1.7 percent of the applied dose (Stockbauer 1983). Details of the preceding two experiments were not available. In soil thin-layer mobility tests, the mobility of prochloraz and soil metabolites BTS 44 596 and BTS 45186 were compared to that of atrazine and 2,4-D in four soil types. According to the Helling mobility index, over-all mobility in the four soils were, in order of increasing mobility, prochloraz, BTS 44596 (low mobility), BTS 45186 (low mobility), atrazine (intermediate mobility) and 2,4-D (mobile). Mobility of all tested materials was greatest in sand (even BTS 44596 and BTS 45186 would have intermediate mobility). Prochloraz and BTS 44596 were immobile in silt loam, whereas BTS 45186 was of intermediate mobility. The thin-layer studies confirmed the low, but positive, mobility detected in soil column experiments (Leake & Lines 1981). Adsorption/desorption of prochloraz, uniformly labelled in the phenyl ring and applied as an E.C. formulation to a sandy loam and silty clay loam, was investigated. The Kd of the sandy and silty soils were 152 and 256, respectively, indicating slightly more adsorption by the latter. The K values were 86.8 and 101.7, respectively, for these soils. Strong adsorption and minimal desorption is consistent with leaching studies (Kesterton & Newby 1980b). A trichlorophenol tritiated ring prochloraz E.C. formulation was applied to one sq m plots of barley and wheat in sandy loam at an equivalent rate of 1 kg/ha. Core samples from 32.5 cm deep were analysed after approximately 15 and 30 weeks; > 95 percent of prochloraz residues were found in the upper 10 cm and in some cases the top 2.5 cm. Somewhat similar distribution after 15 and 30 weeks suggests only slight leaching of bound residues as a result of additional (over 150 mm) rainfall in the latter period (Kesterton 1978). In Water No degradation of prochloraz was observed after 30 days in 22°C buffer solutions at a pH of 4.95 or 6.98. At pH 9.18 degradation does occur, with 77 percent of the added prochloraz remaining after 30 days. A first order degradation was indicated and a half-life estimated of approximately 79 days. The only degradant N-propyl-N-2-(2,4,6-trichlorophenyl) ethylamine (BTS 40348) was reported to account for more than 2 percent of the total radioactivity, although the quantitative analyses were not provided (Kelly 1982b). The 4:1 manganese complex of prochloraz (BTS 46 828), either as active compound or as a 50 percent W.P. formulation, disassociated to prochloraz and manganous chloride in the presence of water (pH 6.1). Approximately 50 percent of the complex was dissociated within four hours at 25°C (Whiting & Dickinson 1979). Biodegradability of prochloraz in water was studied using the closed bottle test according to OECD Guideline 301D. Tests indicate little biodegradation at 20°C up to 15 days after inoculation, but 13 percent degradation by 28 days, suggesting some initial bacterial adaptation (Douglas & Pell 1982). When bacteria preadapted to prochloraz were used as the inoculum, degradation commenced immediately and reached 47 percent biodegradation by 28 days (Douglas & Pell 1983). In Storage and Processing Processing Citrus - Oranges were postharvest brush-treated at 1 000 mg/kg with a 40 percent E.C. formulation and processed into "42% comminuted orange" and "special whole orange compound". These "whole oranges juices" (chopped oranges) are used for production of various orange drinks and utilizes most of the whole orange, except for removal of some coarse peel. It includes a pasteurization process up to 86°C, depending on which of two processes were used. Total residues (converted to 2,4,6-trichlorophenol for analysis) were 0.19 and 0.14 mg/kg expressed as prochloraz for the 42 percent comminuted orange and special whole orange compound, respectively, approximately 30 percent of the residues found in whole oranges (Manley & Snowden 1982b). Cereals - Winter wheat was treated post-emergence at two sites in the Federal Republic of Germany at growth stage 59 (mid-May to mid-June) with three applications of a 40 percent E.C. prochloraz formulation at the 0.48 kg/ha rate recommended in that country. Mature grain was sampled at 57-58 days after last application and portions milled and baked into bread. Total residues were determined by hydrolysis of the trichlorophenol containing moieties followed by EC analysis and use of a 1.906 factorial conversion to a prochloraz equivalent basis. Residues in grain and bread were <0.1 mg/kg, the limit of determination. Under similar conditions prochloraz was applied twice to barley. Total residues in barley malt, expressed as prochloraz, were 0.13 and 0.15 mg/kg compared with 0.07 mg/kg in a control. Limit of determination was 0.1 mg/kg. Rapeseed Oil - Mean residues of total prochloraz and metabolites hydrolysable to the trichlorophenol, and expressed as prochloraz, in mature rapeseed treated in each of four sites in France ranged from 0.06 to 0.2 mg/kg (over-all mean of 0.11 mg/kg). Treatment was with two applications of an E.C. formulation at a rate of 0.45 kg a.i./ha and harvest was 25-38 days after the last treatment. Mean residues of total prochloraz and its metabolites in hexane-extracted oil from these trials (omitting one individual 0.49 mg/kg outlier from six replicate results, otherwise ranging from 0.07-0.13 mg/kg) ranged from 0.11 to 0.29 mg/kg (over-all mean 0.10 mg/kg), indicating a residue concentration factor of approximately 3 times. Residues in the treated seed and oil only ranged from approximately 1-3 times that in controls from any given site and were therefore not far removed from the limit of determination in any one site, with a variation of from 0.05 to 0.2 mg/kg among the sites. In similar studies at three sites each in Denmark and Sweden, the concentration factor for prochloraz in the oil ranged from only 1.2 to 2 times that in the seed. Treatment-to-harvest intervals range from 47 to 76 days. In these studies, residues in treated seed and oil derived therefrom, although comparable to those in France, were significantly greater than in controls. The limit of determination was estimated at 0.05 and 0.1 mg/kg, respectively, for seed and oil. Mushrooms - Mushrooms were harvested in France 17 days after pre-emergence treatment with a 40 percent E.C. prochloraz formulation, administered at a rate of 40 g a.i./100 sq m. No information on good agricultural practice is available from France. The mushrooms were immediately processed by canning and dehydration, after which samples of canned mushrooms, the liquor and dehydrated mushrooms were analysed as total residues of prochloraz and its metabolites that were hydrolysable in the presence of pyridine hydrochloride to the trichlorophenol moiety. Total residues (apparently uncorrected for recoveries) and expressed as prochloraz were less than the 0.1 mg/kg limit of determination for canned mushrooms and the liquor, with control values of 0.03 and 0.05 mg/kg, respectively, reported. An apparent residue of 0.14 mg/kg in dehydrated mushrooms was less than the 0.23 mg/kg control value. Analytical recoveries were 64, 63 and 46 percent, respectively, for dehydrated mushrooms, canned mushrooms and the liquor (Browne 1982h). In experiments conducted in The Netherlands, total residues of prochloraz and its metabolites, expressed as prochloraz, were determined in canned mushrooms and the liquor after three treatment schedules with a 50 percent W.P. formulation of the prochloraz manganese complex, (1) 0.75 a.i./sq m post-casing and 0.94 g a.i./sq m 14 days after casing (2) 1.5 g a.i./sq m 9 days post casing (good agricultural practice in The Netherlands) and (3) 1.5 g a.i./sq m both at post-casing and after 14 days. Total residues expressed as prochloraz were equal to or less than the 0.1 mg/kg limit of determination in the six liquor samples and five of the six canned mushroom samples. For treatment (3) above, however, the residue was 0.23 mg/kg in the sixth mushroom sample and 0.1 mg/kg in the control. No information was available on the interval from last treatment to harvest. Recoveries were 81 and 94 percent, respectively, for canned mushrooms and the liquor. No analyses were available for the unprocessed mushrooms (Churchill & Longland 1983c). Storage Citrus - Data are available from a variety of treatment and storage conditions and are summarized in Table 3. Navel oranges were commercially treated postharvest in South Africa with a 40 percent E.C. prochloraz formulation at 1 000 and 2 000 mg/kg a.i. rates then waxed and shipped by refrigerated vessel to the United Kingdom. Samples were stored either in the dark at approximately 20°C or at 4°C. Sampling for analysis occurred at 0 (44 days after treatment), 7, 14 and 21 days after storage commenced. Mean (range in parentheses) residues, corrected for recovery, of total prochloraz and metabolites expressed as prochloraz at the lower treatment rate were 0.05 mg/kg (0.030.08 mg/kg) in flesh, 2.1 mg/kg (1.4-2.8 mg/kg) in peel and 0.49 mg/kg (0.3-0.7 mg/kg) on the whole fruit (calculated from peel to flesh weight ratios) for ambient and 4°C fruit combined over the entire storage period. Corresponding values for the higher treatment rate were 0.05 mg/kg (0.02-0.07 mg/kg), 3.3 mg/kg (2.5-3.7 mg/kg) and 0.84 mg/kg (0.7-1.7 mg/kg) respectively. The list of determination was reported as 0.05 mg/kg, which is consistent with uncontaminated control values of 0.01-0.02 mg/kg total residue. No observable trend in lower residues occurred during the 21-day storage period at either temperature and there were no noteworthy differences in residues between the storage temperatures. The trials also demonstrated that approximately 94 percent of the total residue was in the peel (Manley & Snowden 1982b). In similar postharvest treatments to oranges in Spain, with 0.05-0.1 percent solutions or 3-4 g a.i./tonne of fruit (usually in wax) with an E.C. formulation as a spray or dip, residues were determined after storage intervals typically ranging from 1-10 to 10-60 days at 4°C-22°C. Maximum peel residues were as much am 7.3 mg/kg for prochloraz alone and 8.4 mg/kg for total residues of prochloraz and its metabolites, both expressed as prochloraz. Total residues in flesh, expressed as prochloraz, were 0.04-0.44 mg/kg and on a calculated whole fruit basis up to 2.5 mg/kg. As in the South African study, a definite trend towards decreased residues could not be determined over the varied storage intervals and temperatures and little difference was observed in residues where application rates varied by a factor of two. Peel was repeatedly shown to contain most of the total whole fruit residue with typically <5 percent being present in the flesh (Richards 1980b,f; Kelly 1980a; Browne 1981b). Similar studies were conducted in the United Kingdom where oranges were dip-treated with a 0.07 percent a.i., 40 percent E.C. formulation and analysed after 1, 7, 21, 25 and 70 days cold storage (temperature not provided). Total residues were expressed as prochloraz. Residues of the parent compound in peel ranged from 3.6 to 5.1 mg/kg compared to 5.8 to 7.8 total residue. In flesh, the residues were 0.05 to 0.12 mg/kg and 0.07 to 0.15 mg/kg, respectively. No declining residue trend was observed over the 70-day maximum storage period, although total residues in flesh increased from about 4 percent of the whole fruit residue at 1-7 days to 11 percent after 70 days (Browne 1982i). No decline in residues on oranges was observed during storage at intervals from 1 to 16 days at ambient temperature in Australia after dip treatment with a 40 percent E.C. prochloraz formulation as a 250 to 500 mg/kg a.i. solution. Total residues determined as the trichlorophenol expressed as prochloraz were similar from the two application rates, as were residues of prochloraz alone. Residues of prochloraz when determined alone ranged from 1.5 to 3.9 mg/kg (2.9 mg/kg) in peel and from <0.02 to 0.1 mg/kg (0.04 mg/kg) in flesh over the 16-day storage interval for both concentrations. Total residues were similar 1.4-3.4 kg (2.5 mg/kg) and <0.05 mg/kg, respectively. Again, most of the residue was in the peel (Browne 1981a). Residues in Spanish lemons were investigated after a shower postharvest treatment with a 3 000 a.i. E.C. formulation in wax. Samples were analysed after 12 and 16 days of storage. The limit of determination was 0.02 mg/kg and 0.05 mg/kg for prochloraz alone and total residues expressed as prochloraz, respectively. Residues expressed as prochloraz were similar after both storage periods, with approximately 5 percent of the residue in the flesh. Residues of prochloraz alone and total residues were: Prochloraz alone (mg/kg) Total residues (mg/kg) Peel Flesh Whole Peel Flesh Whole* 9.1-15.6 0.27-0.3 3.1-5.0 10.6 0.17-0.33 3.7-6 (12.3 mean) (0.29) (4.6) (14) (0.23) (5.1) * Calculated from peel/flesh. Recoveries were 75 percent in peel and 77-100 percent in flesh (Browne 1982c). In 1980, postharvest trials on oranges in Spain, using a 40 percent E.C. prochloraz formulation, were made with 200 1 of wax formulation (3 g a.i./1 wax) to 150 tonnes of fruit (Richards 1980b). Samples of orange flesh from these trials were analysed for free 2,4,6-trichlorophenol (BTS 45186), since no metabolism study was available on orange and BTS 45186 has been found in low levels in wheat (Kelly 1980d). Samples were analysed after 7 and 14 days at 20-22°C. Residues were 0.005-0.01 mg/kg (0.008 mg/kg mean) after 7 days and 0.005 mg/kg after 14 days, as compared to <0.005 mg/kg for controls. Contrary to the findings in most other citrus postharvest trials, a slight trend of decreasing residues with time was indicated (Richards 1980e). In postharvest dip trials using a 25 percent E.C. or 25 percent W.P. prochloraz formulation on oranges and lemons in Italy residues were determined after 57 days storage at 7°C. Significantly higher residues resulted from E.C. applications in both fruits and lemon residues were higher than those in oranges (Browne & Manley 1982b). Oranges treated in South Africa with a postharvest fungicidal brush at 500-4 000 mg/kg a.i. 45 percent E.C. were analysed after two months storage at ambient temperature. Again, most of the residue was in the peel, with total residues, expressed as prochloraz, ranging from 0.08 mg/kg at the lower application rate to 0.73 mg/kg at the higher one. There was a good correlation of residue level with application rate (Snowden & Manley 1983). Bananas - Bananas were treated by postharvest dipping in Australia with 250 and 500 mg/kg a.i. solutions of 40 percent E.C. prochloraz and analysed after ambient storage for 9, 10, 12 and 16 days. Free and conjugated residues of prochloraz and its metabolites were determined as the trichlorophenol, expressed as prochloraz, with a 0.05 mg/kg limit of determination. Residues resulting from both treatment rates and over the entire storage period ranged from 5.2-10 mg/kg in skin and 0.02-0.05 mg/kg in flesh. No evidence of decline in residues was observed in skin or flesh over the storage period and there was no significant difference in residues between the two application rates (Browne 1982b). Photodecomposition Thin-layer chromatography and nuclear magnetic resonance (NMR) analysis of a photodecomposition product of an aqueous solution of prochloraz confirmed the presence of N-formyl-N-propyl-N',-2-(2,4,6-trichlorophenoxy) ethylurea (BTS 44596) (Haran 1978). Prochloraz aqueous solutions of 26.1 and 43.3 mg/kg concentrations in glass-stoppered flasks were exposed to artificial light (420-760 nm wavelength) at 32°C for 36 and 16 days, respectively, with periodic analyses by high pressure liquid chromatography. At the lower concentration residues decreased from 6.93 × 107 moles (26.1 mg/kg) initially to 1.94 × 107 moles after 36 days while BTS 44596 increased from 0.0 to 3.58 × 107 moles. At the higher concentration, residues decreased from 11.5 × 107 moles (43.3 mg/kg) at zero day to 5.8 × 107 moles after 16 days, while BTS 44596 increased from 0.0 to 35.8 × 107 moles. The first order decay half-lives were 20.5 and 18.1 days, respectively, for the two concentrations. Retention times indicated that a minor unquantified degradation product was N-propyl-N-2-(2,4,6-trichlorophenoxy) ethylurea (BTS 44595). This appeared only towards the end of the exposure period (Haran 1980). METHODS OF RESIDUE ANALYSIS Analytical methods are available for the analysis of free prochloraz or total free and conjugated residues of prochloraz and its major metabolites. Methodology for free prochloraz was first developed for the analysis of cereal grains and straw (Somerville 1980). Finely milled straw or ground grain are vigorously extracted with acetone, filtered, a small portion acidified with HCl and concentrated by rotary evaporation. The aqueous fraction is partitioned with petroleum ether, which is discarded, adjusted to pH 6-7 and again partitioned with petroleum ether, which is concentrated to dryness. The sample is taken up in ethyl acetate and analysed by electron capture gas chromatography utilizing a 7 percent OV-101 packed column. Analytical recoveries of wheat and barley grain, amended with prochloraz at 0.05-0.5 mg/kg, were 78 ± 10.6 percent and 91 ± 10.9 percent, respectively. For straw, the respective recoveries were 82 ± 12 percent and 80.6 ± 17 percent. The level of "sensitivity" has been estimated at 0.01 mg/kg for grain and straw, although in the field trials apparent untreated controls in cereal grain and straw were occasionally up to 0.02 mg/kg. With minor modifications, this method has been used for determining free prochloraz residues in apples, pears, citrus, mushrooms, strawberries and lettuce (FBC, (Hayto 1979b; Whiteoak 1981; Kelly 1980a; Browne 1981b, Maclaine Pont et al. 1980) with analytical recoveries of > 65 percent and usually > 80 percent. Apparent residues in untreated controls generally ranged from <0.01 to approximately 0.05 mg/kg depending on the commodity. A method is also available for measuring total free and conjugated residues of prochloraz and its major plant metabolites, N-formyl-N'-1-propyl-N'-[2-(2,4,6-trichlorophenoxy) ethyl] urea (BTS 44596), N-propyl-N-[2-(2,4,6-trichlorophenoxy) ethyl] urea (BTS 44595) and conjugated 2,4,6-trichlorophenol (BTS-45186), after converting all of them to the common moiety 2,4,6-trichlorophenol (Manley & Snowden 1982a). Any other metabolite containing the 2,4,6-trichlorophenol moiety would probably be measured as well. Although total residues are actually measured as BTS-45186, residues are usually expressed as prochloraz, after use of a molecular weight factor of 1.906. Thoroughly ground, milled, chopped or minced and mixed samples are Soxhlet extracted with acetone, filtered, dried by passing through anhydrous sodium sulphate and evaporated to near dryness by a rotary evaporator. The sample is refluxed with pyridine hydrochloride at 205°c for one hour to hydrolyse to the BTS-45186 moiety, after which HCl is added to the sample. The sample is liquid-liquid extracted after addition of petroleum ether. Potassium hydroxide is added, the sample partitioned and the aqueous phase collected and acidified with HCl. The sample is partitioned into toluene for analysis by electron-capture gas chromatography, utilizing a 20 percent carobowax 20M + 1.7 percent phosphoric acid packed column. The method was validated on fruits and cereal grains with mean over-all recoveries of 92 ± 15.9 percent when samples were amended at 0.2-10 mg/kg prochloraz. A 0.05 mg/kg limit of determination is considered attainable for most samples, although apparent residues of 0.2-0.3 mg/kg may be encountered occasionally, especially in cereal straw. With minor variations, this method has been successfully used for the analysis of cereal grain and straw, cereal grain green plant tissues, apples, citrus fruit (peel, flesh, whole fruit), orange juice, rapeseed, rapeseed oil, mushrooms, stone fruit and assorted fruit with inedible peel (Kelly 1979b; Richards 1981a; Reary 1981a; Browne & Manley 1982a; Manley & Snowden 1982a). Specifics on individual crops under actual use conditions are considered earlier in this evaluation under "Residues Resulting From Supervised Trials" or under "Fate of Residues." An analytical method is also available for the determination of free BTS-45186, which may be a minor component of the residue (Kelly 1980b; Richards 1980e). No analytical method suitable for enforcement purposes for products of animal origin was made available. NATIONAL MAXIMUM RESIDUE LIMITS REPORTED TO THE MEETING Country Commodity MRL (mg/kg) France cereal grains 0.05 1 rape seed 0.05 2 The Netherlands 3 Mushrooms 0.05 cereal grains 0.1 Milk 0.01 Meat 0.01 Other products 0 (0.01) German Federal Republic Cereals 0.5 4 1 Residues of prochloraz alone. 2 Residues included not specified. 3 For MRLs of The Netherlands, the residue is prochloraz and its metabolites, measured as 2,4,6-trichlorophenol and expressed as prochloraz. Residue on mushrooms and for most cereal grain trials conducted in The Netherlands were for total residues of prochloraz and its major metabolites. 4 A proposed 0.5 mg/kg NRL for prochloraz and metabolites has been submitted. APPRAISAL Prochloraz is a fungicide in use and/or under development for control of fungal diseases on a variety of commodities in number of countries. It is used as a foliar spray, for post-harvest or seed treatments and is available in a variety of formulations for these uses, including a prochloraz-manganese complex wettable powder formulation for sensitive plant species. Residue data are available from field trials on a number of commodities in several countries, mostly from foliar applications to fruit and cereal grains, use in mushroom culture and postharvest applications to citrus and certain other fruit. Some residue data are also available for vegetables. Residues were determined either as 2,4,6-trichlorophenol, prochloraz alone or prochloraz and its major metabolites, mostly the latter over-all. In select cases, data are available for both prochloraz alone and for prochloraz and its major metabolites. Apparently the earlier studies were for prochloraz alone, whereas in later studies total residues were emphasized. Data are insufficient and too variable to draw a general conclusion on the ratio of parent compound to parent plus metabolites. For example, there is little difference in residue measured for citrus or possibly for mushrooms, but for cereals residues appear to be substantially higher when total residues are determined. Residue trials on commodities for which there are known nationally approved or registered uses were available for watermelon, apple, grape, cereals, mushrooms and oil-seed rape. Therefore, only for these is consideration given for MRL estimates. However "recommended" were available for a number of other commodities and temporary limits are estimated for those with adequate data. Data were insufficient for estimation of maximum residue levels for sugarbeets, sugarbeet leaves, strawberries, almonds, almond hulls, lettuce, watermelon, apples, pears, rice and grapes. Information was available on the fate of residues in animals, plants, the environment and during storage and processing. In animals, prochloraz is rapidly metabolized from dermal or oral exposure. Most of the residue is rapidly excreted, with urinary excretion being the predominant route in most animals tested, although faeces is the predominant route in dogs. The principal metabolic products in the urine were 2,4,6-trichlorophenoxyacetic acid and 2,4,6-trichlorophenoxy-ethanol (mostly conjugated). The major plant metabolites have not been identified in the urine. Although residues were qualitatively similar in urine or in tissue distribution among animals studied, tissue residues have not been identified. The potential for residues in products of animal origin was investigated in two studies by feeding a lactating goat with 14C-phenyl-labelled prochloraz either by capsule or ad libitum with 14C-prochloraz field-treated wheat straw. The first study represents the worst case maximum expected theoretical exposure from wheat straw and the straw feeding is probably more reflective of maximum exposure under normal feeding conditions. These goat metabolism/feeding studies give insight into the maximum potential for residues, although residues in animal tissues are not identified. It is not known whether urinary metabolites are the same as those in milk or tissues. Although straw was used as a worst-case for potential residues, foraging would appear to be potentially equally important, if not more so, if not label-restricted, since it can be fed at higher levels in the diet, as can citrus pulp. However, citrus uses presumably are intended where peel is discarded. Although wheat or barley grain residues were relatively low, grain may comprise up to 50 and 80 percent of the diet of poultry and swine, respectively. No analytical method suitable for enforcement purposes for animal products is available, or at least known to be validated for that purpose. Additional information is needed to support a conclusion that the fate of residues in animals is adequately understood or to estimate maximum residue levels for products of animal origin. The fate of Prochloraz in plants was investigated in wheat (foliar, pre-emergence and seed treatments), citrus (postharvest), apples (foliar) and sugarbeet (soil uptake). In wheat plants, major residues at the vegetative stage from foliar treatment were free BTS-44596, free and conjugated BTS-44595 and 2,4,6-trichlorophenol in decreasing order, which together accounted for 83 percent of the terminal residue after 19 days. Less than 2 percent was unchanged prochloraz and only 0.2 percent was 2,4,6-trichlorophenoxy acetic acid. No single unidentified residue accounted for more than 6.3 percent of the remainder. Residues appear to be absorbed primarily within the first 24 hours. At the harvest stage, only the free trichlorophenol has been identified in straw or grain, and it occurs as 3-8 percent of the terminal residue. This, plus tritiated water and other presumably conjugated but unidentified residues containing the trichlorophenol moiety, account for 40-70 percent of the terminal residue. No single remaining unidentified residue fraction accounts for more than 6 percent of the terminal residue. When applied to wheat seeds or as a pre-emergence drench, most residue was in or near the root system, with little upward mobility, and there is little evidence of upward mobility when prochloraz is applied to foliage although low levels translocate towards the roots. Only very low levels of residue were found in chaff and straw when wheat was grown in soil treated with radioactive 3H-prochloraz ten months earlier. However, sugarbeet seedlings showed low residues when planted as a rotational crop, but only trace levels were found in the foliage at maturity and no significant residue in the roots. In apples, residues migrated into the peel and by 33-63 days approximately 60-80 percent of the terminal or applied residue was in the peel, <2 percent on the surface and generally <7 percent of the applied dose in the flesh, although it can be twice as much. Qualitatively extractable peel residues were similar to residues found in wheat at the vegetative stage with approximately 80 percent of the residues hydrolysable to 2,4,6-trichlorophenol. This, therefore, accounts for approximately 50-60 percent of the total fruit residue. Other residues (primarily peel fiber-bound) were not identified, and although unresolved background accounted for approximately 10 percent of the whole fruit residue (14 percent of peel extractable), no one peel extractable metabolite or fraction exceeded approximately 5 percent of the total fruit residues. The fate of residues in plants is reasonably well understood for the limited number and type of crops for which there are approved uses. If uses are expanded significantly to other food groups, additional metabolism studies would be prudent. Numerous experiments have been conducted on the fate of prochloraz residues in soil and water. Prochloraz is degraded under both aerobic and anaerobic conditions with formation of volatile compounds, probably CO2 and tritiated water. Residues remaining are predominantly prochloraz, BTS-44596 and BTS-45186, with binding to upper soil particles increasing with time. The half-life can range from 90-155 days, depending on conditions. Formation of volatiles is decreased under anaerobic conditions. Mobility is low in soils, although low mobility does occur under some conditions, especially for the metabolites in sand. Prochloraz is stable in water under acidic conditions, but does degrade under alkaline conditions. The fate of residues during processing was investigated for wheat made into bread, postharvest citrus, rapeseed oil and mushrooms after processing. Residues in bread made from wheat grain with <0.1 mg/kg prochloraz also showed <0.1 mg/kg residues. Since the limit of determination is 0.1 mg/kg, no conclusion could be made on the extent of residue concentration, if any. No information was available for residues in flour or other milling fractions. Similarly, low residues were found in malt from prochloraz-treated barley, but no information was available on the residue level in grain from which it was made. Residue levels concentrate from 1 to 3 times in oil processed from mature oilseed rape that has been field-treated with prochloraz. Residues in canned or dehydrated mushrooms or canning liquor after pre-emergence treatment with prochloraz were less than in untreated controls, except for one sample of canned mushrooms with a residue of 0.23 mg/kg. No information was available on residue levels before canning or dehydration. No conclusion can be drawn on the extent of residue concentration, if any. When oranges treated postharvest were processed into "42 percent comminuted orange" or "whole orange juices", which are used to manufacture various orange drinks, approximately 70 percent of the residue in the oranges from which it was processed was lost. The fate of residues during storage after various postharvest prochloraz treatments was investigated for citrus, bananas and avocadoes. Except for one study where free 2,4,6-trichlorophenol was determined and where treated citrus was stored under a variety of conditions (dark or light, cold or room temperature and at intervals ranging from one to 70 days) total residues were very persistent, with little evidence of a decreasing trend over the varied treatment or storage conditions. Modest increases (2X) in application concentrations had little effect on residue levels, approximately 90-95 percent of which were in the peel. There was evidence of continued gradual translocation into the flesh as the interval from treatment increases, especially at room temperature. This was also found in studies on foliar treatments of mango. Residue levels during storage of prochloraz alone were similar to those for prochloraz and its major metabolites, suggesting little degradation or conjugation. Emulsifiable concentrate formulations gave significantly higher residues than wettable powder formulations and residues in lemons were higher than those in oranges. In bananas treated postharvest with prochloraz, no trend of decreasing residues was observed over a 16-day storage period at ambient temperature. Residue levels were similar with modest increases (2X) in treatment rate and, as in the case of citrus, most of the residue was in the peel. In avocadoes treated postharvest with prochloraz, residues were comparable to those from multiple foliar treatments. Approximately 10-30 percent of the residue could occur in the flesh after relatively short preharvest intervals. The translocation was therefore somewhat greater than in citrus, bananas and apples. Photodecomposition of an aqueous prochloraz solution resulted in the formation of plant metabolite BTS-44596 and towards the end of a 36-day exposure to artificial light, a trace of plant metabolite BTS-44595. A half-life of approximately 20 days was observed. Analytical methods are available for enforcement purposes for a wide variety of plant commodities. Residues of prochloraz alone or total residues of prochloraz and its major plant metabolites may be determined, although more of the field trials data were determined by the latter. Analytical recoveries were generally better than 70 percent. No analytical methods have been validated for residues in animal products. The analytical methodology for the parent compound should be suitable and more appropriate for enforcement purposes and for estimating maximum residue levels (see Report of this Meeting, Section 2.3). RECOMMENDATIONS The Meeting examined residue data from supervised trials reflecting established or proposed good agricultural practice. From the data, the Meeting was able to estimate the maximum residue levels that are likely to occur when prochloraz is used in practice and when the reported intervals between last application and harvest or other restrictions are observed. Maximum residue limits are recommended where registered or approved uses are known and residues are determined as free prochloraz. Temporary maximum residue limits are recommended where only recommended uses are available or where total residues of prochloraz and its metabolites containing the 2,4,6-trichlorophenol moiety are determined. Regardless of the status of the ADI, these remain temporary pending receipt of information on approved or registered uses or data on supervised trials with residues determined as prochloraz. All estimates apply to foliar applications unless otherwise indicated. Estimated Interval from last Commodity maximum residue treatment to harvest (days) limits (mg/kg) on which recommendation Determined and expressed is based and other as prochloraz restrictions Barley 0.05** 40 Oats 0.05** 40 Rye 0.05** 40 Wheat 0.05** 40 Barley straw 0.2 40 Oat straw 0.2 40 Rye straw 0.2 40 Wheat straw 0.2 40 Mushrooms 2 2 3 Citrus 5 (TMRL)1, 4 postharvest Sum of prochloraz and metabolites expressed as prochloraz 4 Bananas 5 (TMRL) 1 postharvest Stone fruits 1 (TMRL) 1 14 Avocado 5 (TMRL) 1, 2 7 (preharvest) Mango 2 (TMRL) 1, 2 15 (preharvest) Papaya 1 (TMRL) 1 postharvest Rapeseed 0.5 (TMRL) 25 ** At or about the limit of determination. 1 No information on approved or registered uses. 2 Limit allows for cumulative residues from both preharvest and postharvest treatments, both of which are good agricultural practice. 3 Limit accommodates applications after casing or after flushes, but not direct treatment of mushrooms. 4 Temporary regardless of the status of the ADI. FURTHER WORK OR INFORMATION Required (by 1985) 1. In order to establish MRLs for products of animal origin, several requirements remain: (a) Metabolism studies in animals, including ruminants and poultry, at sufficiently high dosing levels to permit identification and quantification of tissue residues. (b) If metabolism studies in (a) above indicate any possibility of residues in animal tissues, feeding trials should be conducted in animals, including ruminants and poultry, in which tissues are analysed for residues of concern identified in metabolism studies. Feeding in an appropriate number of animals should as nearly as possible reflect maximum levels of weathered residues likely to occur in practice and, ideally, at an exaggerated level. (c) A validated analytical method suitable for enforcement purposes for products of animal origin. 2. Good agricultural practice information for those commodities for which temporary maximum residue limits are recommended, preferably for countries in which the residue trials were conducted or those in close proximity. 3. Additional data on residue trials reflecting good agricultural practice for commodities for which temporary maximum residue limits are recommended (except citrus). The additional data should be concurrently determined as both prochloraz and total residues of prochloraz and its metabolites containing the trichlorophenol moiety on the same samples. Sufficient data should be provided to permit further utilization of residue data already provided, therefore permitting recommendation of maximum residue limits expressed as prochloraz. Desirable 1. Additional national maximum residue limits. 2. Additional processing studies in cereals to permit a conclusion on the extent, if any, of residue concentration in milling fractions. Grain used should have residues sufficiently above the limit of determination for drawing conclusions. 3. Additional processing studies for mushrooms to permit a conclusion on the extent, if any, of residue concentration. Mushrooms should be analysed before and after processing. 4. Information on possible interference in prochloraz analysis in the presence of other pesticides, especially those containing the trichlorophenol moiety. If interferences are encountered, confirmatory analytical procedures for prochloraz and metabolites may be necessary. REFERENCES - RESIDUES Browne, P.M. Residues of prochloraz and major metabolites in oranges 1981a following postharvest dip treatment in Australia, 1981. FBC report RESID/81/72 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in oranges 1981b following postharvest shower treatment in Spain, 1981. FBC report RESID/81/72 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in avocados 1982a following postharvest dip treatment in Australia, 1981. FBC report RESID/82/2 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in bananas 1982b following post-harvest dip treatment in Australia, 1981. FBC report RESID/82/7 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in lemons 1982c following post-harvest shower treatment in Spain. FBC report RESID/82/8 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in winter 1982d rye treated post-emergence with a 40% E.C. formulation in West Germany, 1981. FBC report RESID/82/25 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in winter 1982e wheat treated postemergence with three applications of 40% E.C. formulation in Fed. Rep. Germany, 1981. FBC report RESID/82/29 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in spring 1982f wheat and barley postemergence with a 40% E.C. formulation (two or three applications) in West Germany, 1981. FBC report RESID/82/31 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in mushrooms 1982g following application of a 50 W formulation in Holland, 1980. FBC report RESID/82/39 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in processed 1982h mushrooms following application of a 40 E.C. formulation in France, 1981. FBC report RESID/82/68 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. Residues of prochloraz and major metabolites in 1982i oranges following post-harvest dip treatment in the U.K., 1981. FBC report RESID/82/83 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. & Manley, J.D. Analytical method for residues of 1982a prochloraz and major metabolites in orange juice. FBC report RESID/82/18 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. & Manley, J.D. Residues of prochloraz and major 1982b metabolites in oranges and lemons following postharvest dip treatment in Italy, 1979. FBC report RESID/82/32 submitted to FAO by FBC Ltd. (Unpublished) Browne, P.M. & Manley, J.D. Residues of prochloraz and major 1982c metabolites in mangoes treated with a 50% W.P. formulation in Australia, 1981. FBC report RESID/82/34 submitted to FAO by FBC Ltd. (Unpublished) Campbell, J.K. Residues in milk and tissues of a goat dosed orally 1980 with 14C-prochloraz. Boots report AX-80026 submitted to FAO by FBC Ltd. (Unpublished) Campbell, J.K. Residues of prochloraz in milk and tissues of a 1983 lactating goat fed straw containing residues of radioactive prochloraz. FBC report METAB/83/8 submitted to FAO by FBC Ltd. (Unpublished) Campbell, J.K. & Needham, D. Residues in milk and tissues of a goat 1980 dosed orally with 14C-BTS 44596 (major plant metabolite of prochloraz). Boots report AX-800333 submitted to FAO by FBC Ltd. (Unpublished) Churchill, J.H.M. & Longland, R.C. Residues of prochloraz and major 1983a metabolites in bananas following a single postharvest application with a 45% E.C. prochloraz formulation in South Africa, 1982. FBC report RESID/83/5 submitted to FAO by FBC Ltd. (Unpublished) Churchill, J.H.M. & Longland, R.C. Residues of prochloraz and major 1983b metabolites in avocadoes following application with a 45% E.C. formulation in South Africa. FBC report RESID/83/10 submitted to FAO by FBC Ltd. (Unpublished) Churchill, J.H. & Longland, R.C. Residues of prochloraz and major 1983c metabolites in processed mushrooms following application with a 50% W.P. formulation of prochloraz-Mn complex in Holland, 1981. FBC report RESID/83/23 submitted to FAO by FBC Ltd. (Unpublished) Churchill, J.H.M. & Longland R.C. Residues of prochloraz and major 1983d metabolites in almonds following foliar application with a 50% W.P. formulation in Israel, 1982. FBC report RESID/83/38 submitted to FAO by FBC Ltd. (Unpublished) Churchill, J.H.M. & Longland, R.C. Residues of prochloraz and major 1983e metabolites in avocadoes following postharvest treatment with a 45% E.C. formulation in Australia, 1982/83. FBC report RESID/83/55 submitted to FAO by FBC Ltd. (Unpublished) Cron, J. Residues of prochloraz and major metabolites in rapeseed 1982 following a single postemergence application with a 40 E.C. prochloraz and a prochloraz/carbendazim E.C. formulation in France 1980/81. FBC report RESID/82/74 submitted to FAO by FBC Ltd. (Unpublished) Cron, J.H. & Longland, R.C. Residues of prochloraz and major 1983a metabolites in avocadoes following multiple foliar application with a 50% W.P. formulation of prochloraz-Mn complex in Australia, 1981/82. FBC report RESID/82/120 submitted to FAO by FBC Ltd. (Unpublished) Cron, J.H. & Longland, R.C. Residues of prochloraz and major 1983b metabolites in papayas treated postharvest with a 45% E.C. formulation in Australia, 1982. FBC report RESID/83/1 submitted to FAO by FBC Ltd. (Unpublished) Douglas, M.T. & Pell, I.B. Assessment of the ready degradability of 1982 prochloraz. HRC and FBC report METAB/82/44 submitted to FAO by FBC Ltd. (Unpublished) Douglas, M.T. & Pell, I.B. Assessment of biodegradability of 1983 prochloraz by pre-adapted sewage organisms. HRC and FBC report METAB/83/10 submitted to FAO by FBC Ltd. (Unpublished) Goto, H. Residues of prochloraz in rice following seed soak or foliar 1980 application with a 25% E.C. formulation in Japan, 1980. Inst. Environ. Toxicol., Japan, Nissan and FBC report submitted to FAO by FBC Ltd. (Unpublished) Haran, G. Identification of a photodecomposition product of BTS-40 1978 542 (prochloraz). Boots report F-78014 submitted to FAO by FBC Ltd. (Unpublished) Haran, G. The effect of simulate& sunlight on aqueous solutions of 1980 prochloraz. Boots report F-80010 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 residues in wheat and barley. Boots report AX- 1977a 77002 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40 542 residues in wheat from Italy, 1977. Boots 1977b report AX-79003 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40 542 residues in apples from Thurgarton, U.K. Boots 1977c report AX-77011 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 residues in wheat from Holland, 1977. Boots 1978a report Ax-78006 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 residues in wheat and barley from France, 1977. 1978b Boots report AX-78020 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 residues in wheat and barley from the United 1979a Kingdom, 1977. Boots report AX-79001 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 residues in apples from Thurgarton, U.K., 1977. 1979b Boots report AX-79005 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 residues in cereals from Fed. Rep. Germany, 1979c 1977. Boots report AX-79008 submitted to FAO by FBC Ltd. (Unpublished) Hayto, E.M. BTS-40542 and dicloran residues in lettuces from Holland, 1979d 1978. Boots report AX-79010 submitted to FAO by FBC Ltd. (Unpublished) Heinanen, E. Investigation certification for residues of prochloraz in 1983 spring wheat from Finland, 1982. VML report 2940, 2942/82 submitted to FAO by FBC Ltd. (Unpublished) Housden, M.C. Residues of prochloraz and major metabolites in grain 1982a treated post-emergence with a 45% E.C. formulation in Belgium, 1981. FBC report RESID/82/1 submitted to FAO by FBC Ltd. (Unpublished) Housden, M.C. Residues of prochloraz and major metabolites in 1982b mushrooms following application of a 50W formulation in Australia, 1981/82. FBC report RESID/82/48 submitted to FAO by FBC Ltd. (Unpublished) Housden, M.C. Residues of prochloraz and major metabolites in cereals 1982c treated post-emergence with a 45% E.C. formulation (single or double application) in Denmark, 1982. FBC report RESID/82/111 submitted to FAO by FBC Ltd. (Unpublished) Housden, M.C. & Longland, R.C. Decline study of residues of prochloraz 1983 and major metabolites in winter barley and wheat treated once with a prochloraz/carbendazim suspension concentrate formulation in Fed. Rep. Germany, 1982. FBC report RESID/83/19 submitted to FAO by FBC Ltd. (Unpublished) Housden, M.C. & Whiteoak, R.J. Residues of prochloraz and metabolites 1982 in mushrooms following single and multiple applications (50w formulation) in the U.K. 1981 and 1982. FBC report RESID/82/63 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. BTS 40 542 residues in cereals from Austria, 1977. Boots 1979a report AX 79006 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of BTS 40 1979b 542, BTS 44 596 and BTS 45 186 in grain. Boots report AX 79007 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1979c (BTS 40 542), BTS 44 595, BTS 44 596 and BTS 45 186 in wheat grain and straw from Fed. Rep. Germany, 1978. Boots report AX 79015 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1979d (BTS 40 542), BTS 44 595, BTS 44 596 and BTS 45 186 in wheat grain and straw from Italy, 1978. Boots report AX 79017 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1979e (BTS 40 542), BTS 44 595, BTS 44596 and BTS 45 186 in wheat grain and straw from The Netherlands, 1978. Boots report AX 79 017 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1979f (BTS 40 542), BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in cereal grain and straw from Austria, 1978. Boots report AX 79 020 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1979g (BTS 40 542), BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in wheat and barley grain from Denmark, 1978. Boots report AX 79021 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1979h (BTS 40 542), BTS 44 595, BTS 44 596 and BTS 45 186 in wheat and barley grain and straw from France, 1978. Boots report AX 79023 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. Persistence and uptake of prochloraz in Spanish oranges 1980a following a post-harvest dip. Boots report AX 80003 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. BTS 45 186 residues in prochloraz-treated wheat grain from 1980b France, 1977. Boots report AX 80010 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The analysis of free and conjugated residues of prochloraz 1980c (BTS 40 542) and metabolites containing the 2,4,6-trichlorophenyl moiety in wheat grain and straw from The Netherlands, 1979. Boots report AX 80025 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The metabolism of 3H-prochloraz in mature wheat grain and 1980d straw. Boots report AX 80028 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The metabolism and distribution of BTS 46828 applied to 1982a the fruit of field-growing apples. FBC report METAB/82/18 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. The hydrolysis of prochloraz in aqueous solution under 1982b acid, neutral and basic conditions. FBC report METAB/82/28 submitted to FAO by FBC Ltd. (Unpublished) Kelly, I.D. & Krepski, W.J. The metabolism of prochloraz by wheat 1980 grain and straw. Boots report AX 80009 submitted to FAO by FBC Ltd. (Unpublished) Kesterton, M.S. Distribution of radio-labelled residues in field soil 1978 after application of 3H-BTS 40542. Boots report AX 78010 submitted to FAO by FBC Ltd. (Unpublished) Kesterton, M.S. Report on the aerobic metabolism of prochloraz in 1981a soil over a period of 12 months. Boots report AX 81002 submitted to FAO by FBC Ltd. (Unpublished) Kesterton, M.S. Report on the anaerobic metabolism of prochloraz in 1981b soil. Boots report AX 81004 submitted to FAO by FBC Ltd. (Unpublished) Kesterton, M.S. & Newby, S.E. A study of the leaching of prochloraz in 1980a soil. Boots report AX 80008 submitted to FAO by FBC Ltd. (Unpublished) Kesterton, M.S. & Newby, S.E. Adsorption and desorption studies of 1980b prochloraz in soil. Boots report AX 80012 submitted to FAO by FBC Ltd. (Unpublished) Kesterton, M.S. & Newby, S.E. Leaching study of prochloraz aged in a 1981 silty clay loam soil. Boots report AX 81003 submitted to FAO by FBC Ltd. (Unpublished) Krepski, W.J. The uptake of 14C-prochloraz and 3H-prochloraz soil 1981a residues into wheat. Boots report AX 81001 submitted to FAO by FBC Ltd. (Unpublished) Krepski, W.J. The metabolism of 14C-prochloraz and 14C-BTS 46828 by 1981b apples grown under glass. Boots and FBC report submitted to FAO by FBC Ltd. (Unpublished) Krepski, W.J. Translocation of 14C-prochloraz applied as a liquid seed 1982 dressing in wheat grown to maturity. FBC report METAB/81/30 submitted to FAO by FBC Ltd. (Unpublished) Leake, C.R. & Lines, D. The leaching of prochloraz and its major 1981 metabolites in four soil types using TLC. FBC report METAB/81/35 submitted to FAO by FBC Ltd. (Unpublished) Longland, R.C. Analysis of residues of prochloraz and major 1983a metabolites in grain and straw from Sweden following application of 45% E.C., 1982. FBC report RESID/82/114 submitted to FAO by FBC Ltd. (Unpublished) Longland, R.C. Residues of prochloraz and major metabolites in 1983b sugarbeet following application of a 40% E.C. formulation in Italy, 1981. FBC report RESID/83/58 submitted to FAO by FBC Ltd. (Unpublished) Longland, R.C. & Churchill, J.H. Residues of prochloraz and major 1983 metabolites in mangoes following foliar treatment with 50% W.P. and postharvest treatment with 40% E.C. formulations in Israel, 1982. FBC report RESID/83/7 submitted to FAO by FBC Ltd. (Unpublished) Maclaine Pont, M.A., Vogelzang, H.P. & Siegmann-Knoester, K.C. The 1980 residue analysis of prochloraz in combination with dicloran. Asepta-fabrik and Boots report AX 80020/2 submitted to FAO by FBC Ltd. (Unpublished) Maier-Bode, H. The leaching of prochloraz in three standard soils from 1980 Fed. Rep. Germany. HMB and FBC report submitted to FAO by FBC Ltd. (Unpublished) Manley, J.D. & Snowden, P.J. Analytical method for residues of 1982a prochloraz and major metabolites in miscellaneous fruit, cereal and vegetable crops (improved method). FBC report RESID/82/88 submitted to FAO by FBC Ltd. (Unpublished) Manley, J.D. & Snowden, P.J. Residues of prochloraz and major 1982b metabolites in oranges and processed oranges following commercial scale postharvest brush treatment with prochloraz (40 E.C.) in South Africa, 1982. FBC report RESID/82/89 submitted to FAO by FBC Ltd. (Unpublished) Manley, J.D. & Snowden, P.J. Residues of prochloraz and major 1982c metabolites in rapeseed following treatment with a 40% E.C. formulation in the U.K., 1981/1982. FBC report RESID/82/90 submitted to FAO by FBC Ltd. (Unpublished) McDougall, J. The metabolism of 3H-BTS 40 542 in wheat at a vegetative 1979 growth stage. Boots report AX 79009 submitted to FAO by FBC Ltd. (Unpublished) McDougall, J. The uptake and translocation of 3H-prochloraz in wheat. 1980a Boots report AX 80007 submitted to FAO by FBC Ltd. (Unpublished) McDougall, J. The relative uptake and persistence of prochloraz and 1980b BTS 46 828 in apples following treatment with 14C- prochloraz and 14C-BTS 46 828. Boots report AX 80015 submitted to FAO by FBC Ltd. (Unpublished) McGibbon, A.S. Uptake of prochloraz residues by sugarbeet from 1982 prochloraz-treated soil under field conditions. FBC report METAB/82/27 submitted to FAO by FBC Ltd. (Unpublished) Newby, S.E. The laboratory decline of prochloraz in two soils, a sandy 1982 loam and a silty clay loam, under sterile conditions. FBC report METAB/82/41 submitted to FAO by FBC Ltd. (Unpublished) Peatman, M.H. & Snowden, P.J. Residues of prochloraz and major 1982 metabolites in rapeseed treated with the 40% E.C. formulation in France, 1982. FBC report RESID/82/116 submitted to FAO by FBC Ltd. (Unpublished) Peatman, M.H. & Snowden, P.J. Residues of prochloraz and major 1983 metabolites in rapeseed treated with a 45% E.C. formulation in Denmark and Sweden, 1982. FBC report RESID/83/29 submitted to FAO by FBC Ltd. (Unpublished) Reary, J.B. Analytical method for free and conjugated residues of 1981a prochloraz, BTS 44595, BTS 44 596 and BTS 45 186 in cereals at different growth stages. FBC report RESID/81/13 submitted to FAO by FBC Ltd. (Unpublished) Reary, J.B. Residues of prochloraz and major metabolites in summer 1981b wheat treated post-emergence with a 40% E.C. formulation (two or three applications) in Fed. Rep. Germany, 1980. FBC report RESID/81/14 submitted to FAO by FBC Ltd. (Unpublished) Reary, J.B. Residues of prochloraz and major metabolites in cereals 1981c treated post-emergence with a 45% E.C. formulation in Holland, 1980. FBC report RESID/81/46 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1980a prochloraz (BTS 40 542) BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in wheat and barley, France, 1979. Boots report AX 80005 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1980b prochloraz (BTS 40 542), BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in Spanish oranges following a postharvest application, 1980. Boots report AX 80021 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1980c prochloraz (BTS 40 542), BTS 44 595, BTS 44 596 and conjugated residues of BTS 45 186 in wheat and barley, U.K., 1979. Boots report AX 80022 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1980d prochloraz (BTS 40 542), BTS 44 595, BTS 44 596 and conjugated residues of BTS 45 186 in wheat and barley, Denmark, 1979. Boots report AX 80023 submitted to FAO by FBC Ltd (Unpublished) Richards, M.E. BTS 45 186 residues in oranges treated with prochloraz, 1980e Spain, 1980. Boots report AX 80027 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1980f prochloraz, BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in Spanish oranges following a postharvest application, 1980. Report No. 2. Boots report AX 80030 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1980g prochloraz, BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in winter wheat, Fed. Rep. Germany, 1979. Boots report AX 80032 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1981a prochloraz, BTS 44 595 and BTS 44596 and conjugated residues of BTS 45 186 in grain and straw. Boots and FBC report AX 800 35 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1981b prochloraz, BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in winter barley, Fed. Rep. Germany, 1980. Boots and FBC report AX 81005 submitted to FAO by FBC Ltd. (Unpublished) Richards, M.E. The analysis of free and conjugated residues of 1981c prochloraz, BTS 44 595 and BTS 44 596 and conjugated residues of BTS 45 186 in mushrooms, U.K., 1980. FBC report METAB/81/17 submitted to FAO by FBC Ltd. (Unpublished) Snowden, P.J. Residues of prochloraz and major metabolites in stone 1983 fruit following foliar applications of prochloraz (50 E. and 40 E.C.) in Europe (1982) and South Africa (1981/2 and 1982/3). FBC report RESID/83/57 submitted to FAO by FBC Ltd. (Unpublished) Snowden, P.J. & Manley, J.D. Residues of prochloraz and major 1983 metabolites in Tambors oranges following commercial scale postharvest brush treatment with prochloraz (45% E.C.) in South Africa, 1982. FBC report RESID/83/9 submitted to FAO by FBC Ltd. (Unpublished) Somerville, L. The analysis of prochloraz residues in cereals. Boots 1980 report AX 80020/1 submitted to FAO by FBC Ltd. (Unpublished) Stockbauer, I. Leaching of Sportak PF (prochloraz and carbendazim) in 1983 German soils. ASU and FBC report submitted to FAO by FBC Ltd. (Unpublished) Wang, S.S. Residues of prochloraz in grapes, apples and watermelon 1982 following foliar application with a 25% E.C. formulation in Taiwan, Taiwan Plant Protection Centre report submitted to FAO by FBC Ltd. (Unpublished) Whiteoak, R.J. Residues of prochloraz in mushrooms following multiple 1981 applications of a 50% W.P. formulation in the U.K., 1980/81 (ADAS trial results), FBC report RESID/81/41 submitted to FAO by FBC Ltd. (Unpublished) Whiting, K.C. & Dickinson, W. The stability of the manganese complex 1979 of prochloraz in water. Boots report F 79005 submitted to FAO by FBC Ltd. (Unpublished)
See Also: Toxicological Abbreviations Prochloraz (JMPR Evaluations 2001 Part II Toxicological)