PESTICIDE RESIDUES IN FOOD - 1982 Sponsored jointly by FAO and WHO EVALUATIONS 1982 Data and recommendations of the joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues Rome, 23 November - 2 December 1982 Food and Agriculture Organization of the United Nations Rome 1983 BENDIOCARB IDENTITY Chemical Name 2,3-isopropylidene-dioxyphenyl methyl carbamate 2,2-dimethyl-1,3-benzodioxol-4-yl N-methyl carbamate 2,2-dimethyl-1,3-benzodioxol-4-ol methyl carbamate Synonyms FicamR: GarvoR: SeedoxR: TurcamR: MultamatR: NiomilR: TattooR: Ent-27695: OMS 1394: NC 6897. Structural formulaMolecular formula C11 H13 NO4 Other Information on Identity and Properties Molecular weight 223.25 State white crystalline solid Melting point 132°C Vapour pressure 5.0 × 10-6mm Hg at 25°C Solubility At 25°C 0.04 g/l in water: 0.35 g/l in hexane: 0.3 g/l in kerosene: 10 g/l in trichloroethylene and o-xylene: 40 g/l in benzene and ethanol: 200 g/l in acetone, chloroform, dichloromethane and dioxane: 300 g/l in glycerol and dimethyl sulphoxide: 640 g/l in dimethyl formamide. Stability In aqueous solution at 25°C the half-life of bendiocarb is 48 days at pH5, 81 hours at pH7 and 45 minutes at pH9. At pH9 hydrolysis of bendiocarb results in the formulation of the phenol, NC 7312 whereas below pH5 bendiocarb slowly degrades to pyrogallol and acetone. Bendiocarb is stable at temperatures of up to 100°C and on non-absorptive surfaces and at low humidity it resists oxidation. In aqueous solutions above pH6 hydrolysis rather than photolysis is the principal method of degradation but below pH5 hydrolysis has little effect and the photolysis half life is 51 hours. Specification of technical material Current technical material has a typical purity of about 98%, the main impurities being 2,2- dimethyl-1,3-benzoxdiol-4-ol(NC 7312), and to a lesser extent, pyrogallol tris (methyl carbamate). Physical and Chemical Data on NC 7312, a metabolite of Bendiocarb Chemical Names 2,2-dimethyl-1,3-benzoxodiol-4-ol Synonyms 2,2-dimethyl-4-hydroxy-1,3-benzodioxole 2,3-isopropylidene dioxyphenol Structural formula
Molecular formula C9H10O3 Other information on identity and properties Molecular weight 166 State White crystalline solid Melting point 91-93°C Solubility At 25°C 20 g/l in water and 50 g/l in dichloromethane; very soluble in methanol, ethanol and acetone. Vapour pressure 2.34 × 10-3mm Hg at 25°C. EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, Distribution, Excretion and Biotransformation Mouse In groups of male mice (CFLP strain) acutely intubated with 14C-bendiocarb (14C-bendiocarb with label at the heteroclyclic ring was used in this and all of the other available metabolism studies on bendiocarb) at 1, 5 or 10 mg/kg body weight, over 80% of the administered dose was excreted in 24 hours, primarily in the urine. Less than 10% of the administered 14C was recovered in the faeces. The proportion of metabolites formed in the urine, but not the rate and route of elimination, was dose-dependent. Thus, the level of NC 7312 (2,2-dimethyl-1,3-benzoxodiol-4-ol) (as conjugates) recovered in the urine was 36, 32, 17 (as % of administered radioactivity), respectively, at 1, 5, 10 mg/kg. Only one urinary metabolite other than conjugated NC 7312 was detected, which was believed by the authors of the report to be probably a conjugate of 6-hydroxybendiocarb (Challis and Adcock 1977a). Another similar mouse study with groups of males of the CD-1 strain treated orally with single doses of 14C-bendiocarb at 1, 5 or 10 mg/kg body weight indicated recovery of about 80% of the administered radioactive dose in 24 hours, predominantly in the urine. A significant dose-dependent relationship was not evident with respect to rate and route of elimination or metabolic profile of bendiocarb. About 33-56% of the administered 14C-doses was recovered in the urine as conjugates of NC 7312. Conjugated 6-hydroxy bendiocarb was believed by the authors of the study to be the only other major urinary metabolite (Pearce et al 1977). Rat Male and female rats treated with a single oral dose of 14C-bendiocarb at approximately 10 mg/kg body weight eliminated over 95% of the administered radioactivity in urine (89%), expired air (6%) and faeces (2%) within 2 days of dosing. There was no significant sex different in rate and route of elimination. Following an acute oral dose of 14C-bendiocarb at 1 mg/kg body weight, plasma levels in male and female rats peaked at 10 minutes post treatment with plasma half- life being calculated at 4.4 hours for both sexes. The major urinary metabolite was the phenol (NC 7312) which, excreted as ß-glucuronide and sulphate conjugates, accounted for more than 85% of the administered dose recovered in the urine during the first 24 hours after treatment. The remaining 15% eliminated over this time period comprised a mixture of sulphate and ß-glucuronide conjugates of at least seven minor metabolites. One of the latter appeared to be N-hydroxy methyl bendiocarb. No unchanged parent compound was found in the urine. In the faeces free NC 7312 was the primary metabolite with a small amount of 14C-bendiocarb being detectable (Adcock and Challis 1976a). Conjugated NC 7312 was found to be the primary metabolite in urine collected during 0-24 hours after treatment withdrawal in male and female rats (CFY strain) fed 20 ppm of 14C-bendiocarb in the diet for 10 days. At sacrifice 6 days after termination of dietary feeding, detectable 14C residues were found in the tissues analysed (fat, liver, kidney, muscle and brain) with the fat tissue having the highest residue level. According to the partition characteristics of the 14C residue in fat into organic solvents, radioactive residue in fat was probably not mainly due to bendiocarb or NC 7312 (Pearce and Adcock 1978). Hamster Groups of 6 or 10 male hamsters were intubated with 14C-bendiocarb in glycerol formal at 1, 5 or 10 mg/kg. Four female hamsters were similarly treated at 10 mg/kg body weight. Over 90% of the administered 14C-dose was recovered in 24 hours in the faeces and the urine, with the latter being the primary route of elimination. The rate and route of excretion was not modified by sex or dosage level. The proportion of total radioactivity recovered in the urine as conjugates of NC 7312 was about 37% at 1 mg/kg, 16% at 5 mg/kg and 19% at 10 mg/kg. Besides conjugated NC 7312, urine of male hamsters contained two metabolites in approximately equal amounts, while that of female hamsters had only one radioactive component. A conjugate of 6-hydroxy bendiocarb was believed by the authors to be the major urinary metabolite in both males and females. The other urinary metabolite in male hamsters had not been identified. The seeming sex difference in metabolic fate of bendiocarb remains to be ascertained, since the male and female hamsters used in the study were housed and dosed at different laboratories (Challis and Adcock 1977b). Rabbit Groups of pregnant rabbits were intubated on day 20 of gestation with one dose of 2.5 or 10 mg/kg body weight of 14C bendiocarb. Within 24 hours of dosing, nearly 90% of the administered dose had been eliminated, primarily in the urine, with only a small amount (<2.5%) being detected in the faeces. The rate and route of elimination and metabolic profile of bendiocarb appeared to be independent of dosage. The major urinary metabolite was identified as NC 7312, which accounted for 90% of the radioactivity extracted from urine samples following enzyme (sulphatase and ß-glucuronidase) hydrolysis (Challis 1980). Dog Groups of one male and one female beagles (fasted overnight and for 8 hours following dosing) were treated once with 14C-bendiocarb in gelatin capsules at 0.1, 1.0 or 10 mg/kg body weight. Regardless of dosage level, the radioactive dose was almost completely excreted during the first 24 hours post-dosing, primarily in the urine. The amount of radioactivity found in the urine of both sexes over the 48-hour period seemingly decreased with dosage (about 90% at 0.1 mg/kg body weight, 80% at 1.0 mg/kg body weight and 70% at 10 mg/kg body weight). This appeared to be accompanied by a corresponding increase in faecal recovery (about 19%, 21% and 24%, respectively, at 0.1, 1.0 and 10 mg/kg body weight). In the urine, approximately 84%, 67% and 43% of the administered radioactivity, respectively, at 0.1, 1.0 and 10 mg/kg body weight occurred as sulphate and ß-glucuronide conjugates of NC 7312 with no recovery of any 14C-bendiocarb. Analysis of urine samples from male dogs at 10 mg/kg body weight indicated the probable presence of ring hydroxylated derivatives of bendiocarb as minor metabolites. Unchanged 14C-bendiocarb was the only component identified in the faeces and amounted to about 80% of the radioactivity recovered via this route (Warner et al 1977). Effects on Enzymes and Other Biochemical Parameters Mouse In male and female mice (Charles River CD-1 strain) fed technical bendiocarb containing 0.09% w/w of dimethoate) in their diets at 0 or 1 250 ppm for 19 days, whole blood cholinesterase in blood sampled between 06:00 hour and 08:00 hour, but not between 09:00 hour and 11 hours (peak feeding period stated to occur between 22:00 hour and 09:00 hour) was depressed (>20%) only in treated males in weeks 2 and 3 (Hounsell and Rush 1980). Male CFLP mice and male CD 1 mice were fed dietary levels of technical bendiocarb at 0, 500 or 1 000 ppm for up to 7 days. In the CFLP strain, whole blood cholinesterase activity was reduced (>20%) at 1 000 ppm in animals fed the diet ad libitum and in those following a 1-hour feeding period on the 7th day after an overnight fast. In the CD-1 mice, whole blood cholinesterase was depressed (>20%) in the 500 and 1 000 ppm groups following an overnight fast and exposure to the diet for 1 hour on day 7. Ad libitum feeding resulted in decreased whole blood cholinesterase in the 500 but not in the 1 000 ppm groups (Hounsell 1981a). Rat Groups of rats (sex unspecified) were treated orally with 4 mg/kg/day of technical bendiocarb in glycerol formal for three consecutive days. Inhibition (65-85%) of cholinesterase in whole blood and plasma peaked at 10 minutes after each dose on days 1 and 3. Recovery of whole blood and plasma cholinesterase began to occur 30 minutes following each dose, and was practically complete three days after treatment withdrawal. Whole blood cholinesterase appeared to be more sensitive than plasma cholinesterase to the inhibitory effect of bendiocarb (study cited by Kemp and Hounsell 1974). Male rats (CFY Sprague-Dawley) were fed dietary levels of technical bendiocarb up to 10 ppm for 14 days, followed by an overnight fast. Whole blood cholinesterase, assayed in the morning of the 15th day after a 1-hour feeding period, was not significantly inhibited (<20%) (Hounsell 1981b). Another similar study with the same strain and sex of rats fed diets containing technical bendiocarb for up to 23 days indicated that, following overnight fasting and a one-hour feeding period, animals exhibited a depression (20%) of whole blood cholinesterase at 50 ppm on days 15 or 16 and 22 or 23 (Hounsell 1981c). Dog In 4 male beagles (fasted the day before the test) fed a diet containing 1 000 ppm of technical bendiocarb for up to one hour (actual intake of the test material estimated at 6 - 8.6 mg/kg body weight), inhibition (>50%) of brain and whole blood cholinesterase was apparent 15 minutes after the feeding period. Whereas depression of whole blood cholinesterase peaked at 2 hours and was completely reversible at 3 hours following the feeding period, the extent of inhibition of brain cholinesterase remained fairly constant between 15 minutes and 3 hours (the last sampling interval) after the dosing period (Hounsell 1974). Another experiment with 2 female beagles (24-hour fasted) fed a dietary level of 10 ppm of technical bendiocarb for about 10 minutes (actual intake of the test material estimated at approximately 32.4 mg/kg) showed reduction of whole blood cholinesterase activity of about 27% and 52% of the pretreatment level at 1 hour and 6 hours, respectively, post dosing. Cholinegesic symptoms were noted within 24 minutes of the initiation of feeding. Complete recovery of whole blood cholinesterase activity and from toxic signs occurred 24 to 25 hours after treatment (Kemp and Hounsell 1974). Cow A lactating dairy cow was fed technical bendiocarb in the daily diet at 3.6 ppm for two consecutive days (ration was offered twice daily). No reduction (<20%) in whole blood cholinesterase was observed at any of the 8-hourly intervals following the morning feeding on both days (Roberts 1979). TOXICOLOGICAL STUDIES Special Studies on Reproduction Rat Groups of 17 to 21 mated rats (Sprague-Dawley CFY strain) were fed diets containing technical bendiocarb at 0, 200, 400 or 800 ppm from 14 days post-coitum until weaning of their pups. A decrease in maternal body weight gain was noted at 800 ppm on days 17 and 20 post- coitum and practically throughout the 21-day lactation period. At this dietary level, survival and weight gain of pups were depressed throughout lactation. No treatment-related effects were observed on other parameters monitored, i.e. mortality and clinical signs of pregnant dams, sex ratio and gross abnormalities of offspring (Jackson 1978). Groups of 10 males and 20 female rats (SPF, CFY strains) were fed dietary concentrations of bendiocarb (presumably technical grade) at 0, 200, 400 or 800 ppm for one week prior to mating. The females were maintained on test diets through day 18 of gestation and the males until termination. There were no mortalities or toxic symptoms. Growth was slightly depressed in males at 800 ppm and in females at 400 ppm and above. Pregnancy rate, duration of gestation period and terminal gross pathology were not adversely affected. Medium precoital time (as an indication of mating performance) of dams was lengthened at both 400 and 800 ppm. In the progeny generation, except for a slight decrease at 400 ppm and above in mean pup weight at birth, no apparent dose- or treatment-related effects were evident on litter size at birth, survival and weight of pups through lactation period to weaning, sex ratio and incidence of gross abnormalities of weanlings (Palmer and Allen 1978). Groups of 30 males and 30 females (Charles River CD strain) were fed dietary levels of technical bendiocarb at 0, 10, 50 or 250 ppm for 90 days prior to mating to initiate a reproduction study covering three generations with two litters per generation. Weanlings from the second litters were selected to become parents of the next generation. After the second mating trial in each generation, the dams in each group were divided into two approximately equal sub-groups. One sub-group was allowed to deliver and rear their young until 25 days post-partum. Another sub-group was sacrificed on day 21 of gestation for examination of uterine contents. Foetuses were examined for external, skeletal and soft tissue malformations. In the parental generations, no mortality or clinical signs attributable to the compound were evident. Dams displayed slight growth depression during the gestation period of F1a litters at 50 ppm and above and of F2b litters at 250 ppm. Food consumption was normal, but water intake was slightly decreased at 250 ppm in F1 females. Males of the F2 generation seemed to exhibit an increase in incidence and severity of "geriatric nephropathy" at and above 50 ppm. Ophthalmoscopic examination conducted on F2 adults between 31 and 35 weeks of age revealed no treatment-related findings. At terminal sacrifice of parental animals after weaning of the second litters, some variations from controls in absolute weights and/or organ/body weight ratios of certain tissues such as adrenal, pituitary, thyroid, seminal vesicles and uterus were noted at both 50 and 250 ppm, but these observations were not consistently present through the generations and were not accompanied by histopathological lesions of the organs. Mating and fertility indices as well as length of gestation period were not modified by bendiocarb. There was an increase in frequency of F0 females being acyclic or pseudopregnant at 250 ppm and of F2 females with irregular oestrous cycles at 50 ppm and above, prior to the first mating trial in both cases. Pre-coital interval was lengthened at 250 ppm in the F0 generation (first mating). Over the three progeny generations, the viability index was slightly depressed in F1a litters at 250 ppm from days 10 through 25 and in F2b litters at 50 ppm and above on day 25. Pup weight was reduced at 250 ppm in F1a and F1b litters on day 25 and in F2b litters at birth through day 25. In F2a litters, pup weight on day 25 was decreased in all treated groups, but the difference was indicated by the authors of the report to be statistically significant only at 10 ppm, but not above. There were no significant differences between control and treated groups in litter size (at birth and on day 1), sex ratio, ophthalmoscopic observations of F3b pups between 19 and 31 days of age, organ weight and histopathological findings of 25-day old F3b pups. Examination of 25-day old pups from the second litters of each generation for rate of physical development and sensory functions revealed "the onset of pinna unfolding, hair growth, tooth eruption and eye opening was marginally delayed in all treated (F1b) litters, but the overall pattern of physical development was essentially similar in all groups, and "the onset of pinna unfolding and hair growth was marginally delayed (in F2b litters at both 50 and 250 ppm) but eye opening and tooth eruption was unaffected". Teratological investigation of F1b, F2b and F3b litters showed no significant differences between control and treated groups with respect to number of implantations, number of viable young, early or late resorptions, post-implantation loss and foetal weight. A rise in pre-implantation loss in F1b litters was noted at 250 ppm. Also at the top dosage level, there were higher incidences of generalized subcutaneous oedema, incomplete ossification of cranial bone, uni/bilateral hydronephrosis and bilateral ureter in F1b litters and of subcutaneous scapular haemorrhage in F3b litters, as compared to concurrent controls. Based on the data, a dietary level of 10 ppm was without significant adverse effect on the reproductive parameters evaluated. The teratogenic "no effect" level was demonstrated to be 50 ppm (Tesh et al 1981). Special Studies on Teratogenicity (also see under "Special Studies on Reproduction") Rat Groups of 24 mated rats (Sprague-Dawley derived, CD strain) were intubated with technical bendiocarb as a suspension in gum tragacanth at 0, 0.25, 1 or 4 mg/kg body weight/day between gestation day 6 and day 15 (day 0 = day of positive vaginal smear). The dams were sacrificed on gestation day 21 and foetuses were removed by caesarean section for external, visceral and skeletal examination. There was no mortality. Dams at 4 mg/kg body weight/day exhibited toxic symptoms characteristic of cholinesterase inhibition and slight growth inhibition on gestation day 21. Two dams (out of 21) at 4 mg/kg body weight/day and 1/22 dams at 1 mg/kg body weight/day displayed a large number of late uterine deaths. Mean litter size was depressed at 4 mg/kg body weight/day. There were no significant differences between control and treated groups in pregnancy rate, number of corpora lutea or implantation sites, number of early resorptions, foetal weight and frequency of foetal abnormalities. The study demonstrated bendiocarb to be non-teratogenic under the conditions of the experiment (Tucker 1974). Rabbit Groups of 27-29 female rabbits (New Zealand White) that had been artificially inseminated were intubated with technical bendiocarb as a suspension in aqueous gum tragacanth at 0, 1, 2.5 or 5 mg/kg body weight/day from day 6 to day 28 inclusive of gestation. (Day 0 = day of insemination.) The does were sacrificed on day 29 of gestation and uterine contents were examined. Foetuses were subjected to evaluation for external, skeletal and internal malformations. Six to eight females per control or treated group died 6 to 29 days after insemination mainly due to "tracheal intubation". Clinical signs such as increased respiratory rate and prostration were noted at and above 2.5 mg/kg body weight/day. Growth was slightly depressed at 5 mg/kg body weight/day between gestation days 16 and 28. Whole blood cholinesterase assayed 30 minutes post-dosing on day 28 was depressed (31-70%), in a dose-dependent manner, in all treated groups. One doe each at 2.5 and 5 mg/kg body weight/day aborted on day 22 and 20, respectively. Premature parturition occurred in one doe each of 2.5 and 5 mg/kg body weight/day groups on day 28. An increase was observed in the mean number of late resorptions per litter and the incidence of pregnant does with late resorptions at both 2.5 and 5 mg/kg body weight/day. Post-implantation loss (number of implantations - number of viable foetuses/number of implantations × 100) was elevated at 2.5 mg/kg body weight/day and above. Other parameters monitored, including number of corpora lutea, implantations, viable young, or early resorptions, pre-implantation loss, foetal weight and placental weight, were not adversely affected by treatment. There was a dose-related increase in incidence of foetuses with eye anomalies (mainly "cloudy areas in eyes") and with absence of pubic bones at both 2.5 and 5 mg/kg body weight/day. Incidence of litters containing foetuses showing such abnormalities was also elevated at and above 2.5 mg/kg body weight/day. In the absence of background data on frequency of the abnormalities in question, 1 mg/kg body weight/day may be considered as a clearcut "no effect" level with respect to teratogenicity (Tesh et al 1980). Special Studies on Mutagenicity Two separate experiments were conducted with technical bendiocarb and NC 7312 to evaluate their genetic activity in vitro microbial systems (plate assays), with or without the addition of a mammalian metabolic activation preparation (S-9 mix from the liver of male rats pre-treated with Aroclor 1254 i.p. at 500 mg/kg/day for five days). Indicator organisms used were Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98. Results suggest non-mutagenicity of the test compounds to any of the tested strains at the (non-toxic) concentrations used (3.3-1 000 µg/plate of bendiocarb and 10-3 300 µg/plate of NC 7312) in the presence or absence of metabolic activation and under the conditions of the assays (McConville and McGregor 1979; McConville and Harris 1979). Negative results were also obtained in another reversion mutation test using Escherichia coli WP2 and five strains of the Salmonella typhimurium TA series as indicator organisms in the presence of absence of a liver metabolic activation system at concentrations of technical bendiocarb ranging from 5 to 1 000 µg/plate (Moriya et al 1981). A rec-assay conducted with Bacillus subtilis H17 (rec+) and M45 (rec-) in the absence of a metabolic activation preparation indicated that technical bendiocarb, at concentrations of 20 to 5 000 µg/disc, did not induce any inhibitory zone in either tested strain (Moriya et al 1981). Technical bendiocarb was evaluated for its mutagenic activity in a mouse lymphoma L5178Y specific locus mutation assay. Under the conditions of the test, there appeared to be no consistent indications of mutagenicity of the compound in the absence or presence of a metabolic activation system (S-9 homogenate of liver from male adult Fischer rats induced with Aroclor 1254) at concentrations ranging from 5 to 20 µg/ml (McGregor and Ross 1981). In a micronucleus test, groups of male mice were treated with technical bendiocarb i.p. at 0, 0.625, 1.25 or 2.5 mg/kg body weight/day for two consecutive days (the two doses were given 24 hours apart). The animals were sacrificed 6 hours after the second dose and the femurs were removed for the preparation of bone marrow smears. There was no significant increase in the frequency of polychromatic erythrocytes containing micronuclei or change in polychromatic/ normochromatic ratio in any treated group (Hounsell and Walker 1982). Groups of 20 sexually mature virgin male rats (Sprague-Dawley CD strain) were fed diets containing technical bendiocarb at 0, 10, 50 or 250 ppm for 13 consecutive weeks and then mated with sexually mature virgin female rats for seven days in a dominant lethal assay. (Each group was sub-divided into sub-groups A and B with commencement of dietary feeding of the groups being staggered by one week.) The females were sacrificed 14 ± 1 days after mating and autopsied for the examination of uterine contents. The treated males exhibited no clinical signs and their body weight and food consumption were not adversely affected by treatment. The incidence of non-fertile males were 1/20 at 50 ppm and 2/20 each at 10 ppm and 250 ppm. With the exception of one infertile male at 250 ppm, abnormally small testes and epididymis were found in the other four infertile males. An increase (not dose-related) in incidence of litters with at least one early death was observed (in sub-group B only) at 10 ppm and 250 ppm, but this was not accompanied by a rise in the number of early deaths per litter. There were no significant differences between control and treated groups with respect to pregnancy rate, number of corpora lutea, number of total implants, number of viable implants and pre- implantation loss. Bendiocarb did not appear to induce dominant lethal mutation under the experimental conditions used (Kemp and Jackson 1977). Special Studies for Carcinogenicity Mouse Groups of 50 males and 50 females (HaM/ICR Swiss mice CD-1; about 35 days old) were fed diets containing technical bendiocarb, found to contain up to 0.5% dimethoate or dimethoate decomposition products, at 50, 250 or 1 250 ppm. The control group consisted of 100 males and 100 females. The experiment was originally scheduled to be terminated at a predetermined survival level or 104 weeks at the latest. The predetermined level was reached after 89 weeks in males and 94 weeks in females. Mortality rate was increased in females at 1 250 ppm after 85 weeks. Less than 40% of animals in control and treated groups were still alive at termination, but over 50% of animals of all groups, including the control, survived at least 82 weeks. All animals that died or were sacrificed in moribund condition during the study and those sacrificed terminally were necropsied. A wide range of tissues and any unusual lesions from animals of all groups, including the control, found dead or sacrificed moribund and from all terminal survivors of control and top dosage groups were examined microscopically. Any unusual lesions from terminal survivors at both 50 and 250 ppm were also subject to histopathological evaluation. Clinical signs, body weight, food and water consumption were not significantly different from those in the controls. Ophthalmoscopic examination conducted at four intervals during the study seemed to suggest a probable increase at week 89 in incidence of cataract ("posterior cortical or more advanced") in males at 1 250 ppm. At terminal sacrifice, males at 1 250 ppm showed an increase in absolute testes weight and testes/body weight ratio and females of all treated groups displayed a dose-related increase in absolute weight and organ/body weight ratio of kidney. There were no treatment-related microscopic changes in the tissues evaluated, including testes and kidney. Analysis of tumour data appeared to indicate no significant difference between control and top dosage groups in the incidence of any particular type of tumour. Under the conditions of the study, bendiocarb was not carcinogenic to the mouse (Serota et al 1981). Rat See under Long-Term Studies. Special Studies on Neurotoxicity Hen Seven adult hens (15 months old) were given a single subcutaneous dose of bendiocarb ("laboratory grade") at 60 mg/kg body weight (the subcutaneous LD50 of bendiocarb in hens was indicated to be about 80 mg/kg body weight). A second dose was given 3 weeks later. The control group consisted of seven untreated hens. The birds were observed for a total of 6 weeks from the initial dose before sacrifice for gross pathology and histopathological examination of the spinal cord and sciatic nerve. There were no clinical signs or histopathological evidence suggestive of delayed neurotoxicity of the compound in any of the treated hens (Sanderson and Hounsell 1969). Groups of domestic hens, approximately 14-months old (20 birds in the top dosage group and 10 birds in each other group) were acutely intubated with technical bendiocarb in maize oil at 0, 189, 378 or 757 mg/kg body weight and observed for 21 days prior to sacrifice for histopathological examination of the brain, spinal cord and distal sciatic nerve. The hens were given 10 mg/kg body weight of atropine intramuscularly immediately before the dose of bendiocarb. (Before initiation of the neurotoxicity study, the oral LD50 of bendiocarb was found to be 137.3 mg/kg body weight in hens not pretreated intramuscularly with 10 mg/kg body weight of atropine and 757 mg/kg body weight in atropine-protected hens.) One hen at 378 mg/kg body weight and a total of 8 hens at 757 mg/kg body weight died. Except for "doubtful signs" of ataxia noted in 1/10 hens at 189 mg/kg body weight on days 9 and 10 only, there were no delayed neurotoxic signs in any other treated birds during the 21-day exposure observation period. None of the bendiocarb-treated survivors or negative controls exhibited microscopic evidence of neurological lesions. Positive controls, dosed orally with TOCP at 500 mg/kg body weight, displayed typical neurotoxic signs and significant morphological changes of the nervous tissues (Ross et al 1978). Special Studies on Skin and Eye Irritation Technical bendiocarb was shown to be a mild irritant when applied to the skin of New Zealand White rabbits (Cuthbert 1978). An eye irritant study in New Zealand White rabbits indicated technical bendiocarb to be minimally irritating to the eye (Cuthbert 1980). Special Studies on the Acute and Subacute Oral Toxicity of NC 7312 Rat The oral LD50 of NC 7312 (2,2-dimethyl-1,3-benzoxodiol-4-01) a metabolite of bendiocarb) in male and female rats (CFY strain) was greater than 4 640 mg/kg body weight. Cholinergic symptoms were observed at dosages above 464 mg/kg body weight (Mallyon and Sanderson 1977). Groups of rats (CFY strain, 10 male and 10 female controls, 5 males and 5 females per treated group) were intubated with NC 7312 as a suspension in aqueous gum tragacanth at 0, 5, 20, 80, 320 or 1 280 mg/kg body weight/day for 16 days. There were neither mortality nor compound-related effects on clinical signs, haematological, blood chemistry and urinalysis parameters. Growth, food conversion factor and water intake were slightly decreased in females at 1 280 mg/kg body weight on week 2. Terminal survivors sacrificed showed no gross or histopathological changes associated with treatment. Absolute weight and organ/body weight ratio of ovary were reduced at 80 mg/kg body weight and above, but concomitant microscopic changes of the tissue were not evident (Kemp and Brooks 1978). Acute Toxicity The acute toxicity of several animal species to bendiocarb is summarized in Table 1. Toxic signs were characteristic of anticholinesterase poisoning and seen within a few minutes after oral, intraperitoneal or inhalation exposure in all species of mammals tested. Deaths usually occurred after 5 minutes to 2 hours and survivors began to recover after 1/2 to 2 hours. Within 24 hours of dosing, survivors recovered completely from clinical signs. After dermal exposure, toxic signs began to appear after 2 to 21 hours with recovery being much slower than that following acute oral doses (Sanderson 1921). Short-Term Studies Rat - dietary In a 28-day study with groups of five female rats (Sprague-Dawley CFY strain) fed diets containing 0, 400, 600 or 800 ppm of technical bendiocarb, mortality, body weight, food consumption, oestrous cycle (as evidenced by vaginal cytology taken from the fourth day to termination) and terminal gross pathology were not affected by treatment. Whole blood cholinesterase was inhibited (52-62%) at all test levels and toxic symptoms were observed at both 600 and 800 ppm on day 28 after the animals (fasted overnight) were given access to an appropriate test diet for a restricted one-hour feeding period (Jackson 1977). Table 1. Acute Toxicity of Bendiocarb in Animals LD50 Species Sex Route Vehicle (mg/kg body Reference weight) Mouse F oral glycerol 45 (CFW) formal Sanderson 1971 Rat M oral glycerol 40-64 Sanderson 1970; (Wistar) formal Sanderson 1971, F 34-40 Sanderson 1971 Rat M oral aqueous 108-156 Crome and Sanderson (Charles River gum 1980 COBS CD tragacanth Sprague-Dawley) Rat M&F i.p. glycerol 8 Sanderson 1971 (Wistar) formal Rat F dermal glycerol 566-800 " (Wistar) (24-hour formal Ben-Dyke 1932 M exposure) 566 Rat (Carworth M inhalation1/ None 250 mg Sanderson and Sprague-Dawley) (6-hour a.i./l air2/ Mallyon 1979 exposure) Hamster F oral water 141 " (Syrian) Guinea pig F oral glycerol 35 Sanderson 1971 formal Rabbit M oral glycerol 40 " F formal 35 1/ Animals were exposed to an 80% wettable powder as a dust in a "nose only" exposure chamber with 58% particles of size 10 microns and 18% particles 5 microns. 2/ 6-hour LD50 in terms of actual chamber concentration of the active ingredient. Groups of 10 male and 10 female rats (Sprague-Dawley CFY strain) were fed dietary levels of technical bendiocarb at 0, 2, 10, 50 or 250 ppm for 13 weeks. Mortality, clinical signs, body weight, food and water consumption, ophthalmoscopic findings, clinical chemistry, haematological and urinalysis parameters were not influenced by the presence of the compound in the diet. Whole blood cholinesterase, determined in animals (fasted 16 hours) shortly after a 1-hour feeding period, was depressed (20%) at 250 ppm in both sexes during weeks 4 and 9, at both 50 and 250 ppm in males and at 250 ppm in females during week 13. Terminal gross pathological changes and organ weights were not significantly different from those in the controls. Histopathological evaluation of a variety of tissues from animals of the control and top dosage groups suggested the only notable finding to be an increase in incidence of males at 250 ppm showing vacuolated centrilobular hepatocytes. This liver lesion, not noted even at 200 ppm in the long-term rat study (see under Long-Term Studies), was considered unlikely to occur in the lower dosage groups of the study, although there were no data to confirm this supposition. It would appear that the no-effect level was 10 ppm on the basis of cholinesterase levels and was 50 ppm on the basis of the other tested parameters (Hunter et al 1978). Hamster Groups of hamsters (20 male and 20 female controls, 10 males and 10 females per treated group) were fed technical bendiocarb in their diet at 0, 4, 20, 100 or 500 ppm for 30 days. There were no indications of any treatment-related effect at levels up to 500 ppm as judged by mortality, clinical signs, body weight, food and water intake, terminal haematology, organ weight and histopathology of selected tissues from control and 500 ppm groups (Hounsell and Brooks 1981). Dog Groups of four male and four female beagles were fed dietary levels of technical bendiocarb at 0, 20, 100 or 500 ppm for 16 weeks with the top dosage level being raised to 1 000 ppm on day 89 (test diets were offered to the dogs for a 1-hour period morning and evening). Inclusion of the compound in the diet did not adversely affect survival, clinical signs, food consumption, terminal haematology, blood chemistry and urinalyses values. Males of the highest dosage group exhibited actual weight loss at termination. Assays1/ at weeks 5, 9, 14, 15 and 16 of cholinesterase in whole 1/ Whole blood was diluted 1:1 200 in the assay. No data were available on the amount of diet actually consumed by individual animals during the 1-hour feeding period prior to sampling for assay of cholinesterase in blood and brain. blood and plasma of animals (fasted overnight) following a 1-hour feeding period indicated depression (>20%) at the top dosage level of cholinesterase in plasma and whole blood at most sampling periods. Whole blood cholinesterase was decreased (>20%) even at 100 ppm in males at week 9 and in females at weeks 9 and 15. Terminal brain cholinesterase of the top dosage group (males and females) was also inhibited (>20%). At the conclusion of the study, organ weights and gross pathological changes were unaffected by the compound. Microscopic examination of about 20 tissues from each animal suggested no treatment-related changes other than the occurrence of thyroid lesions (focal C-cell hyperplasia and focal atrophy) in 1/4 males and 1/4 females of the top dosage group but in none of the concurrent controls or of animals in the lower dosage groups. The study suggested the no-effect level with respect to cholinesterase and other criteria evaluated to be 20 ppm and 100 ppm, respectively (Litton 1974). Groups of 8 male and 8 female purebred beagles were fed a diet containing technical bendiocarb at 0, 20, 100 or 500 ppm for 2 years (control or treated diet was given to each animal every morning). Survival, clinical symptoms and growth during the study as well as haematology, urinalysis and ophthalmoscopic parameters evaluated at five more intervals over the course of the experiment were not significantly affected by the presence of the test material in the diet. Less food was consumed by animals (both sexes) of all treated groups throughout the study. Nevertheless, the authors of the report stated that "statistical analysis of food residue for weeks 1-3, 1-26, 1-52, 53-104 and 1-104 did not reveal any statistically significant difference between control and test group means". Based on weekly mean food consumption and mean body weight data at the end of each week, the dietary levels of 20, 100 and 500 ppm were equivalent to 0.7, 3.1 and 16.3 mg/kg body weight/day (males and females combined). Water consumption was slightly but consistently increased in both sexes at 100 ppm and above during weeks 36-39 and at 500 ppm not infrequently thereafter. Serum cholesterol was elevated at 500 ppm (both sexes) at several sampling intervals. A dose-related decrease in serum calcium level was noted at both 100 and 500 ppm in weeks 14 and 25. Measurement of whole blood cholinesterase in animals (fasted overnight) shortly after a 60-minute feeding period at eight sampling intervals during the study showed a tendency to frequent depression (>20%) of the enzyme at 500 ppm. Brain cholinesterase in animals (fasted overnight) sacrificed following a 1-hour feeding period was depressed (>20%) at 500 ppm after 52 and 104 weeks and probably also at 100 ppm after 104 weeks. Organ weight analysis, gross pathological examination and histopathological evaluation of over 30 tissues from each animal sacrificed at the end of 52 weeks (3 males and 3 females/group) or terminally (all survivors per group) showed no significant alterations related to treatment. The dietary level of 20 ppm appeared to be a no-effect level on the tested criteria. It was noteworthy that the actual amount of bendiocarb ingested by animals during the 1-hour feeding period prior to the assay of tissue cholinesterase varied markedly, even among animals in the same dosage group, owing to substantial individual variation in the quantity of diet (ranging from 0 to 400 g per animal) consumed. Also, there were incidences where individual animals of a high dosage group, e.g. 500 ppm, actually had a lower intake of bendiocarb than those of a lower dosage group (100 ppm) (Chesterman et al 1980). Rat - dermal Groups of 6 rats (Wistar strain) were exposed dermally to an 80% wettable powder of bendiocarb as a 40% w/v aqueous suspension at 50, 100, 200, 400 or 800 mg a.i./kg body weight under an occlusive patch for a period of 6 hours/day, 5 days/week for a total of 15 applications in 21 days. The treated site was washed at the end of each exposure period. There was no mortality. Toxic signs, characteristic of anticholinesterase poisoning and dose-related in severity, were noted at 200 mg/kg body weight and above. Whole blood cholinesterase, determined at the end of the 6-hour exposure period, was inhibited by more than 30% at 200 mg/kg body weight and above after only one dose and at 50 mg/kg body weight and above after 15 exposures. No gross pathological changes or microscopic evidence of dermal irritation attributable to treatment were apparent at terminal sacrifice (Sanderson 1972). Long-Term Studies Rat Groups of male and female rats (CFY strain, 60 male and 120 female controls, 30 male and 60 female per treated group) were fed dietary levels of technical bendiocarb at 0, 2, 20 or 200 ppm for 7 days and then caged together (1 male and 2 females). At the end of a 20-day mating period, the females were individually housed and allowed to litter and rear their pups to weaning. This part of the study was known as the reproductive phase. A sufficient number of weanlings from the control and treated groups were randomly selected to initiate another segment of the study referred to as the main phase. The latter comprised the main group and the satellite group. In the main group, weanlings (50 males and 50 females per treated group, 100 male and 100 female controls) were given bendiocarb-treated diets at 0, 2, 20 or 200 ppm for 104 weeks. For the satellite group, used primarily for laboratory investigations, animals (30 males and 30 females per control or treated group) were fed bendiocarb at the same dietary levels, but only for 60 weeks. The 2 ppm level was raised to 10 ppm after 2 weeks in the main phase, and this group will be known as the 2-->10 ppm group hereafter for the purpose of identification. Dietary administration was continued throughout both the reproduction and main phase. All animals died or sacrificed in extremis during the 104-week study and those sacrificed terminally were necropsied. Animals of all groups, including the control, dying or sacrificed in extremis during the study and terminal survivors of the control and top dosage groups were subjected to microscopic examination of a set of about 30 selected tissues plus grossly observed nodules and tissue masses. Additionally, all suspected tumours from terminal survivors of lower dosage groups were evaluated histopathologically. For the reproductive phase, mortality and behaviour of parental animals, pregnancy rate, duration of gestation period, litter size and pup weight at birth, sex ratio and incidence of external abnormalities of pups were not affected by bendiocarb. There were some indications of adverse effects related to treatment at 200 ppm on maternal body weight gain during gestation, litter size on lactation day 4 and pup weight from lactation day 4 through weaning. A dietary level of 20 ppm was a no-effect level on this phase of the study. In the 104-week study (main group) of the main phase, mortality rate, although unaffected by the compound, was high in all groups, including the control, Only about 16-26% of males and 24-42% of females survived 104 weeks. Nevertheless, over 55% of males and females lived at least 82 weeks. A number of findings associated with treatment were noted at 200 ppm. These included an increased incidence of males exhibiting hyperactivity in response to external stimuli, growth depression during the first 52 or 56 weeks, depressed water consumption during week 6-12 but not in week 25. Periodic measurements of haematological, biochemical and urinalysis values at several intervals over the course of the study revealed significant changes in several parameters (e.g. total WBC, neutrophil and lymphocyte counts, levels of serum cholesterol and total protein) to be also confined only to the top dosage group. There was a dose-related decrease in body weight gain associated with a depression in food consumption in males of all treated groups during the first two weeks of the study but not thereafter. Ophthalmoscopic examination of the surviving animals in the main group only for a total of seven intervals between 13 and 102 weeks indicated a statistically significant increase in incidence of lenticular opacities in males at 200 ppm at all intervals from 52 weeks onward. A statistically significant trend (p <0.01) for dose-dependent incidence of this eye lesion was indicated to be apparent for males at both 20 and 200 ppm from 66 weeks onward and for males of all treated groups at 80 weeks and thereafter. It was pointed out that the difference in frequency of lenticular opacities was not statistically significant between males of control and low dosage (2-->10 ppm) groups or among female groups at any time interval. The lenticular opacities observed reportedly were "essentially atypical of chemically induced lenticular lesions in the rat". Overall, 2-->10 ppm might probably be considered a borderline no-effect level with respect to the particular eye lesion. Activity of whole blood cholinesterase determined in animals (fasted overnight) following a one-hour feeding period at several intervals during the study (animals of the satellite group) and at termination (animals of the main group) was frequently depressed (>20%) at 200 ppm in both sexes. Whole blood cholinesterase activity in animals fasted overnight without access to food immediately prior to sampling of blood was not reduced. The brain cholinesterase level was inhibited (>20%) at 200 ppm in animals (both sexes) sacrificed at 52 weeks but not terminally. Organ weight determination at 52- and 60-week interim sacrifice and at terminal sacrifice showed deviations from controls of several tissues such as liver, thymus, prostate and adrenals, but these were essentially restricted to the top dosage level only and were not accompanied by histopathological lesions. Gross pathological changes were not significantly different from those in the controls. Histopathologically, an increase in incidence of stomach lesions, characterized by "hyperplasia/hyperkeratosis/ acanthosis with or without inflammation of the non-glandular portion", occurred in the male terminal survivors at 200 ppm. There were no microscopic lesions observed in any of the other tissues examined that were attributable to the compound. An evaluation of tumour data suggested a dose-related increase of incidence of total lymphoreticular tumours in males of all treated groups (incidence 3, 8, 10, 12%) respectively at 0, 2-->10, 20 and 200 ppm), with the difference from concurrent controls being statistically significant only at 200 ppm. Frequency of each type of lymphoreticular tumour (lymphosarcoma, thymic lymphosarcoma, reticulum cell sarcoma, lymphatic leukaemia and myeloid leukaemia), when considered alone, was not significantly increased in any treated group. Latency period (or time of detection of the tumour when the animal died or was sacrificed) was also not modified by treatment. Other than the particular malignancy just mentioned, incidence, type and location of tumours were not significantly higher at 200 ppm than in the controls. It may be noted that 56% of males and 92% of females of the concurrent control groups were bearers of tumours with pituitary adenoma (both sexes), mammary tumour (females) and pheochromocytoma (both sexes) being the most frequently observed tumours. Based on the available data, 20 ppm was without any significant effect on cholinesterase. The lowest tested level, 2-->10 ppm (indicated to be equivalent to an average achieved intake, throughout the study of 0.38 mg/kg body weight/day) may be acknowledged as a marginal no-effect level on the other tested parameters (Hunter et al 1981). Observations in Humans In a male volunteer given a single oral dose of 9.8 mg or approximately 0.12 mg/kg of 14C-bendiocarb, over 99% of the administered dose was excreted in the urine in 22 hours. The plasma half-life and the half-life for renal elimination for total radioactivity was estimated at 3.5 and 3.3 hours, respectively. The major urinary metabolites were sulphate and ß-glucuronide conjugates of NC 7312, which together amounted to 95% of the radioactivity dose excreted. Small amounts of conjugated bendiocarb and N-hydroxy methyl bendiocarb were the only compounds detected in the urine (Adcock and Challis 1976b). An area on the forearm of each of two male volunteers was exposed for 3 hours to 14C-bendiocarb (as an aqueous solution in a wetting agent) at an average dosage of approximately 0.0013 mg/kg body weight under occluded conditions in one experiment and non-occluded conditions in another. (No information was available on the time interval between the two experiments.) Over the 48-hour period following exposure, an average of 58% of the applied dose under occluded conditions vs. an average of 12.5% under non-occluded conditions was recovered in the urine, suggesting better absorption of bendiocarb through occluded skin. The only urinary metabolite found was NC 7312 as conjugates of sulphate and ß-glucuronide (Warner and Adcock 1980). In a 60-year old male volunteer given bendiocarb (as an 80% wettable powder) orally in H2O serially at 0.004, 0.012, 0.037, 0.125, 0.187 and 0.25 mg/kg body weight (dosage in terms of w.p.) with at least a 48-hour interval between doses, 0.125 mg/kg was found to be a clear-cut no-effect level on symptoms and whole blood cholinesterase. Toxic sumptoms such as mild vertigo, nausea and vomiting together with significant inhibition (30-40%) of whole blood cholinesterase were induced after the single dose at 0.25 mg/kg body weight. The symptoms subsided in 30 minutes and whole blood cholinesterase recovered completely in 4 hours post-treatment. In the same subject, doses of the 80% w.p. at 0.125 mg/kg given orally at an interval of 4 hours, but not less, produced no toxic signs or inhibition of whole blood cholinesterase. A double-blind cross over experiment involving three other male volunteers indicated a single dose of 0.004 mg/kg body weight, the only dose administered, of the 80% w.p. resulting in no adverse effects on any of the parameters assessed (heart rate, clinical signs, mean diastolic/systolic pressure and whole blood cholinesterase). Following a single dose of 0.12 mg/kg body weight of the 80% w.p. given orally to the same three volunteers 72 hours later in another similar experiment, a transient depression (21% of whole blood cholinesterase was observed in one of the three subjects at 30 minutes post-treatment (Drummond and Kemp 1976). The safety of bendiocarb (80% wettable powder), when used as an insecticide against adult mosquitoes, to operators and inhabitants was evaluated in Iran and Indonesia. The studies were organized along the line of the WHO expanded Stage V evaluation programme. Each trial involved the treatment of 13 villages with a total population of over 4 000 by 15 or 16 spray operators. Results indicated that very few operators reported any toxic signs or symptoms and the latter, when noted, were usually mild and transient. Inhibition of whole blood cholinesterase, slight to mild, was only infrequently observed and was readily reversible. Analysis of urine collected from the operators suggested absorption of only low levels of bendiocarb during spraying. No complaints were received from the villagers (Motabar et al 1981; Bonsall et al 1981). COMMENTS Bendiocarb, a carbamate insecticide, evaluated for the first time by the Meeting, was rapidly absorbed and readily eliminated primarily in the urine in all of the mammalian species studied, including humans. The major metabolic pathway in these species involved cleavage of the carbamate ester group to yield the corresponding phenol (NC 7312). There was no evidence of tissue accumulation in mammals. Mammalian acute oral toxicity varied between strains and species, but not between sexes. A 3-generation reproduction study, including teratological evaluation, in rats demonstrated 10 ppm and 50 ppm to be the no-effect level, respectively, on reproductive parameters and teratogenicity. A teratogenic study in the same species failed to give any indication of teratogenicity even at the top dosage level (4 mg/kg body weight) tested. In a rabbit teratology study, 1 mg/kg body weight was shown to be a clear-cut teratogenic no-effect level. The available mutagenic studies including reversion mutation and rec assays, mouse micronucleus test, mouse lymphoma assay and dominant lethal assay in rats were all negative. A carcinogenicity study in mice revealed no carcinogenic activity of the compound, under the conditions of the experiment. In a long-term feeding study with rats, a significant increase in incidence of total lymphoreticular tumours, but not individual type of lymphoreticular tumours, was noted in males of the highest dosage group (200 ppm). Latency period of these tumours was not reduced. Although the possibility of the finding in question regarding lymphoreticular tumours being related to bendiocarb does not appear likely, it cannot be entirely excluded. Background data on incidence of total lymphoreticular tumours in CFY strain of rats maintained in the testing laboratory would be helpful to resolve the uncertainty. It should be noted that concurrent controls in the study had a high incidence of spontaneous tumours. Additionally, less than 25% males and 45% females survived the duration of the 104-week study, although over 50% of animals in all groups including the control were still alive at the end of 82 weeks. Together these factors might compromise sensitivity of the study to detect carcinogenic activity of the compound. This study also demonstrated an increased incidence of lenticular opacities in male rats at the two top dietary levels. Neurotoxicity studies in hens gave no indications suggestive of delayed neurotoxic potential of the insecticide. No-effect levels were determined in short-term studies in rats (13-week) and dogs (16-week and 2-year) and a long-term study in rats. In the dog, however, the Meeting noted the possible adverse effects of dilution during the determination of tissue cholinesterase, and also the practice of tissue sampling from overnight-fasted dogs following a 1-hour feeding period. Furthermore, there was some concern on the absence of data on the levels of food ingestion during the 1-hour feeding period in one study, and food intake was extremely variable in the second study. Observations in humans indicated rapid reversal of cholinesterase inhibition and of clinical symptoms following both acute and subacute exposures. Because of the concerns regarding the increased incidence of lymphoreticular tumours in male rats of the top dose group in the long-term study, and the probability that the no-effect level established for dogs is nominal rather than actual, only a temporary ADI was allocated. TOXICOLOGICAL EVALUATION Level Causing no Toxicological Effect Rat: 0-0.38 mg/kg bw/day Dog: 0-0.07 mg/kg bw/day Estimate of Temporary Acceptable Daily Intake for Man 0-0.002 mg/kg bw FURTHER WORK OR INFORMATION Required (by 1984) 1. Historical data on the incidence of total lymphoreticular tumours in the CFY strains of rats used in the long-term study. 2. Short-term (28-day) study in dogs to clarify the relationship between dietary intake of bendiocarb and terminal erythrocyte and brain cholinesterase activity, using an appropriate method for cholinesterase determination. Desirable Further investigation on the cataractogenic activity of bendiocarb at low dosage levels in rats. REFERENCES Adcock, J.W. and Challis, I.R. The metabolism of 14C-bendiocarb in 1976a the rat. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) 1976b The pharmacokinetics and metabolism of bendiocarb in man. Report from Fisons Ltd. submitted to the World Health Organization by FBC Limited. (Unpublished) Ben-Dyke, R. The toxicology of NC 6897. Acute dermal toxicity of 1972 technical bendiocarb, Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Bonsall, J.L., Foulkes, D.M., Goose, J., Leake, C.R. and Reary, 1981 J.B. Safety studies with bendiocarb in a village-scale field trial against mosquitoes in Indonesia, 1981. Document (WHO/VBC/81.831), World Health Organization, Geneva. Challis, I.R. The metabolism of bendiocarb in the pregnant rabbit, 1980 Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Challis, I.R. and Adcock, J.W. The metabolism of bendiocarb in the 1977a mouse. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) 1977b The metabolism of bendiocarb in the hamster. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Chesterman, H., Heywood, R., Allen, T.R., Street, A.E., Gopinath, 1980 C., Harling, S., Majeed, S. and Prentice, D.E. NC 6897 Toxicity study in beagle dogs (final report dietary intake for 104 weeks). Report from Huntingdon Research Centre, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Crome, S.J. and Sanderson, D.M. A comparison of the acute oral 1980 toxicities of three batches of bendiocarb CR 4971/2, CR 4799/9 and CR 4500/20 to the male rat. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Cuthbert, J.A. Technical bendiocarb EX Muskegon primary eye irritancy 1980 in rabbits. Report from Inveresk Research International, Scotland, submitted to the World Health Organization by FBC Limited. (Unpublished) 1978 Technical bendiocarb. Primary skin irritancy study on rabbits. Report from Inveresk Research International, Scotland, submitted to the World Health Organization by FBC Limited. (Unpublished) Drummond, P. and Kemp, A. The effects of the acute oral administration 1976 of NC 6897 80 WP to male volunteers. Report TOX/76/133-58 from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Hounsell, I.A. Brain cholinesterase inhibition in dogs fed NC 6897. 1974 Report from Fisons Limited Agrochemical Division submitted to the World Health Organization by FBC Limited. (Unpublished) Hounsell, I.A. and Rush, K.C. The effect of dietary administration 1980 of NC 6897 at 1 250 ppm on whole blood cholinesterase activity in mice. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Hounsell, I.A. and Brooks, P.N. The 30-day subchronic oral toxicity 1981 of NC 6897, technical CR 4799/1 in the diet to the hamster. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Hounsell, I.A.G. The effect of dietary administration of NC 6897 at 1981a 500 and 1 000 ppm on whole blood cholinesterase activity in male mice of the CFLP and CD1 strains. Report from FBC Limited submitted to the World Health Organization by FBC Ltd. (Unpublished) 1981b The effect of dietary administration of NC 6897 at 0.4, 2 and 10 ppm on whole blood cholinesterase activity in male rats. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) 1981c The effect of dietary administration of NC 6897 at 0.4, 2, 10 and 50 ppm on whole blood cholinesterase activity in male rats. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Hounsell, I.A. and Walker, A.K. A micronucleus study in mice using 1982 technical NC 6897, CR 4971/2. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Hunter, B., Watson, M., Heywood, R., Street, A.E., Offer, J.M. and 1978 Gregson, R.L. NC 6897 Toxicity to rats when administered in the diet for 13 weeks. Final Report from Huntingdon Research Centre, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Hunter, B., Watson, M., Heywood, R., Street, A.E., Prentice, D.E., 1981 Gopinath, C. and Gibson, W.A. NC 6897 Toxicity and tumorigenicity to rats in long-term dietary administration. Report from Huntingdon Research Centre, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Jackson, C.M. Effects on adult female rats of one month exposure to 1977 high dietary concentration of NC 6897 (technical). Report from Fisons Limited Agrochemical Division submitted to the World Health Organization by FBC Limited. (Unpublished) Jackson, C.M. A peri- and post-natal study in rats with technical NC 1978 6897, Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Kemp, A. and Hounsell, I. Evidence for the reversal of cholinesterase 1974 inhibition by NC 6897 in laboratory animals. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Kemp, A. and Jackson, C.M. A test for the induction of dominant lethal 1977 mutations in male rats by NC 6897. Report from Fisons Limited Agrochemical Division submitted to the World Health Organization by FBC Limited. (Unpublished) Kemp, A. and Brooks, P.N. The effects of the daily oral administration 1978 of NC 7312 to male and female rats for 16 days. Report from Fisons Limited Agrochemical Division submitted by FBC Limited. (Unpublished) Litton. 16-week subacute toxicity study in dogs. NC 6897 technical. 1974 Report from Litton Bionetics Inc., U.S., submitted to the World Health Organization by FBC Ltd. (Unpublished) Mallyon, B.A. and Sanderson, D.M. The acute oral toxicity of NC 7312 1977 to male and female rats. Report from Fisons Limited Agrochemical Division submitted by FBC Limited. (Unpublished) McConville, M. and McGregor, D.B. Testing the mutagenic activity of 1979 technical NC 6897, Report from Inveresk Research International, Edinburgh, Scotland, submitted to the World Health Organization by FBC Limited. (Unpublished) McConville, M. and Harris, W.J. NC 7312: Ames test for mutagenic 1979 activity. Report from Inveresk Research International, Scotland, submitted to the World Health Organization by FBC Limited. (Unpublished) McGregor, D.B. and Ross, C.A. NC 6897: The assessment of mutagenic 1981 potential in the mouse lymphoma mutation assay. Report from Inveresk Research International, Scotland, submitted to the World Health Organization by FBC Limited. (Unpublished) Moriya, M., Ohta, T. and Shirasu, Y. KNT (bendiocarb): microbial 1981 mutagenicity study. Report from the Institute of Environmental Toxicology, Japan, submitted to the World Health Organization by FBC Limited. (Unpublished) Motabar, M., Mallyon, B.A., Goose, J. and Adcock, J.W. Document 1981 (WHO/VBC/81.821) World Health Organization, Geneva. Palmer, A.K. and Allen, P.A. Effect of NC 6897 on neonatal pup 1978 mortality, Report from Huntingdon Research Centre, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Pearce, J.C., Warner, P.A. and Adcock, J.W. The metabolism of 1977 bendiocarb in the mouse (strain CD 1). Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Pearce, J.C. and Adcock, J.W. Investigation of residue accumulation 1978 in the rat following repeated administration of 14C-bendiocarb. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Roberts, N.L. Blood cholinesterase levels in the cow following dietary 1979 inclusion of bendiocarb. Report from Huntingdon Research Centre, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Ross, D.B., Roberts, N.L., Cameron, D.M., Prentice, D.E. and Majeed, 1978 S.K. Examination of NC 6897 for neurotoxicity in the domestic hen. Report from Huntingdon Research Centre, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Sanderson, D.M. The toxicity of NC 6897: Acute toxicity to the rat of 1970 technical grade NC 6897. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) 1971 The toxicology of NC 6897: Acute toxicity of pure NC 6897. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) 1972 Toxicology of NC 6897: 15-dose cumulative dermal study with Ficam in male rats. Report from Fisons Limited submitted to the World Health Organization by FBC Limited (Unpublished) Sanderson, D.M. and Hounsell, I.A. The toxicology of NC 6897. Test for neurotoxicity of NC 6897 to the chicken. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Sanderson, D.M. and Mallyon, B. The acute oral toxicity to the 1977 hamster of technical bendiocarb. Report from Fisons Limited Agrochemical Division submitted to the World Health Organization by FBC Limited. (Unpublished) 1979 The acute inhalational toxicity to rats of Ficam 80W, an 80% wettable powder formulation of bendiocarb, CR 13374/27H. Report from Fisons Agrochemical Division submitted to the World Health Organization by FBC Limited. (Unpublished) Serota, D.G., Voelker, R.W. and Fezio, W.L. A chronic toxicity and 1981 carcinogenicity study in mice, NC 6897. Final report from Hazleton Laboratories America, Inc. submitted to the World Health Organization by FBC Limited. (Unpublished) Tesh, J.M., Bartlett, A., Tesh, S.A., Whitney, J.C. and Finn, J.P. Technical NC 6897 (CR 4799/1): Effects of dietary administration upon reproductive performance and teratogenic response in rats treated continuously through three successive generations. Report from Life Science Research, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Tesh, J.M., Ross, F.W. and Tesh, S.A. Technical NC 6897: Effects of 1980 oral administration upon pregnancy in the rabbit. Report from Life Science Research, England, submitted to the World Health Organization by FBC Limited. (Unpublished) Tucker, M.L. NC 6897: Teratogenicity study in the rat. Report from 1974 Consultox Laboratories Ltd., England, submitted to the World Health Organization by FBC Limited. (Unpublished) Warner, P.A., Adcock, J.W. and Pearce, J.C. The metabolism of 1977 14C-bendiocarb in the dog. Report from Fisons Limited submitted to the World Health Organization by FBC Limited. (Unpublished) Warner, P.A. and Adcock, P.A. The dermal absorption of 14C-bendiocarb 1980 in man. Report from FBC Limited submitted to the World Health Organization by FBC Limited. (Unpublished) BENDIOCARB RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Bendiocarb is available as a wide range of formulations, including wettable powders (200, 500 and 800 g a.i./kg); granules (30, 50 and 100 g a.i./kg); dust (10 g a.i./kg); oil suspension for ULV application (250 g a.i./kg); residual sprays, paint-on and granular baits and aerosols. Bendiocarb is used for the controls of soil and foliar insect pests on a wide range of crops, ectoparasites on domestic animals and mosquitos and nuisance pests. The Meeting was informed that it is sold for these uses in approximately 100 countries. Information was provided to the Meeting on official nationally approves uses (good agricultural practices, GAP) by the Netherlands. Good agricultural practices of The Netherlands are summarized in Table 1 (Netherlands 1982). Table 1. Bendiocarb Good Agricultural Practices, Netherlands 1982 Application Used Crop Pests rate (kg/ha) Formulation Treatment Since Sugarbeet Fritfly, wireworm, 0.3-0.4 3% G seed furrow 1979 spring tails, 0.4 80% WP seed furrow 1981 pygmy beetle 500 g/l liquid 6.4 g/kg " seed dressing 1981 seed Maize Fritfly, 0.3-0.4 3% G seed furrow 1979 wireworm 4 g/kg 80% WP seed dressing 1981 seed 500 g/l liquid The Meeting was provided with a tabulation of recommended application rates, which are summarized in Table 2 (Netherlands 1982). No information was provided on preharvest intervals. The recommended application rates are consistent with GAP of The Netherlands for maize and sugarbeets. Information was not provided on whether the recommended uses other than on sugarbeet and maize are also nationally approved and, if so, where. Table 2. Recommended Application Rates of Bendiocarb, Netherlands 1982 Crop Major pests Formulation Rate (a.i.) Maize Wireworm, symphlids, fritfly Granule 0.3-0.35 kg/ha Wireworm, symphlids, fritfly Seed dressing 4 g/kg seed Corn rootworm Granule 0.84-1.12 kg/ha Soil pests (in furrow) Spray 0.4 kg/ha Sugarbeet Wireworm, pygmy beetle, springtails Granule 0.3-0.35 kg/ha Wireworm, pygmy beetle, springtails Seed dressing 6 g/kg seed Soil pests (in-furrow) Spray 0.4 kg/ha Rice Rice water weevil, stem borer Granule 2 kg/ha Leafhoppers, planthoppers Spray 0.5 kg/ha Leafhoppers, planthoppers Dust 0.5-0.75 kg/ha Oilseed Flea beetle Granule 0.14-0.28 kg/ha rape Spray 0.1-0.2 kg/ha Ryegrass Fritfly, wireworm, leatherjackets Granule 0.75 kg/ha Spray 0.5-0.75 kg/ha Seed dressing 10 g/kg seed Cereals Fritfly, wireworm, leatherjackets Spray 0.75 kg/ha Seed dressing 2-4 g/kg seed Potatoes Colorado beetle Spray 0-125-0.25 kg/ha tuber moth Spray 0.5 kg/ha Brassicas Diamond-back moth Spray 0.1-0.8 g/l Peas Pea moth, pea weevil Spray 0.2-0.5 kg/ha Apple/Pear Codling moth, tortrix moth, aphids Spray 0.25-0.6 kg/ha (LV) Mushrooms Mushroom fly Wall spray 30-50 g/100 m2 Preharvest Uses Residue trials utilizing preharvest treatments have been conducted on a variety of plant and animal products. Results are detailed under "Residues Resulting From Supervised Trials". Postharvest Uses The Meeting was informed of residue investigations in wheat grain stored in small bins for six months after treatment of interior surfaces, but no details were provided. Likewise, no details were provided on studies said to have been conducted on foodstuffs treated in food-handling premises. Other Uses The Meeting was informed that 80 W or ULV formulations may be used for control of mosquitos and the ULV formulation against warehouse pests. Studies have been conducted to determine the extent of potential exposure. Although contamination levels were said to be within safe limits, details of these studies were not provided. Bendiocarb is said to be widely used for control of cockroaches and other nuisance pests in and around the home, hotels, food-handling establishments, aircraft etc. and as a paint for fly control in animal houses. No details on these uses were provided. RESIDUES RESULTING FROM SUPERVISED TRIALS Residue trials have been conducted in many countries on a wide range of commodities, representing a variety of treatments and climatic conditions. Root and Tuber Vegetables Potatoes Twenty five trials were conducted in three European countries either by spray, broadcast or in-furrow treatments with either 3G or 20W formulations. Results are summarized in Table 3 (FBC 1982a; Reary 1979d; Browne and Reary 1981; Browne 1981e). Although most of the data were from application of the 3G formulation, no information was provided on recommended or approved uses for that formulation on potatoes. The wettable powder spray applications were at one and two times the recommended rate. Recoveries were generally 75% or better for bendiocarb and 60% or better for NC 7312. The limit of determination is said to be approximately 0.01 and 0.02 mg/kg for bendiocarb and NC 7312, respectively. Table 3. Bendiocarb Residues in Potatoes, from Supervised Trials No. Application Interval Residues (mg/kg)1/ 2/ Country No. Trials Replicates Formulation Rate (a.i.) Method (days) Bendiocarb NC 7312 U.K. 2 4-5 3G 1 kg/ha In-furrow 119-155 0.01-0.03 <0.02,0.26 1978 2 4-5 3G 2 kg/ha In-furrow 119-155 0.01-0.04 0.02,0.58 2 4-5 3G 3 kg/ha In-furrow 119-155 0.01,0.03 0.04,0.69 1 7 3G 1 kg/ha Broadcast 112 0.01 0.02 1 7 3G 1.5 kg/ha Broadcast 112 0.04 0.05 2 4-7 3G 2 kg/ha Broadcast 112-155 <0.01-0.03 <0.02,0.07 2 4-7 3G 3 kg/ha Broadcast 112-155 <0.01-0.04 <0.02,0.11 2 4-7 3G 4 kg/ha Broadcast 112-155 0.01-0.03 0.03,0.08 3 Untreated controls 0.003-0.008 0.003-0.0.7 German Federal 3 3 20W 0.12 kg/ha Spray 03/ <0.01 0.014-0.12 Republic 3 3 (<0.005-0.017) (<0.01-0.14 1980 2 3 7 <0.01 <0.01-0.14 (<0.005-0.009) (<0.01-0.15) 14 <0.01 0.01-0.15 (<0.005-0.015) (<0.01-0.18) 1 3 15 <0.005) 0.014 3 2 - - Untreated controls - 0.001-0.044/ (<0.01-0.024) 0.001-0.007 Table 3 (con't) No. Application Interval Residues (mg/kg)1/ 2/ Country No. Trials Replicates Formulation Rate (a.i.) Method (days) Bendiocarb NC 7312 U.K. 1 (3 plots) 20W 0.53 kg/ha Spray 145/ <0.01 0.03-0.05 1981 1 (3 plots) 20W 1.06 kg/ha 145/ 0.005 0.06-0.07 1 Untreated controls <0.005 0.01 1/ Limit of determination 0.01 mg/kg for bendiocarb and 0.02 mg/kg for NC 7312. 2/ Means of replicates; range of individual replicates in parentheses. 3/ Day 0 represents final spray of a weekly 3-spray programme, each application at 0.12 kg/ha. 4/ <0.01 except the 0.04 mg/kg value. 5/ Days after final spray of 2- or 3-spray programme, commencing 7 or 14 days before the final application. Maximum bendiocarb residues at harvest resulting from at or before harvest treatments were 0.04 mg/kg (mean of replicates) and 0.7 mg/kg for NC 7312. From multiple spray applications, maximum bendiocarb residues at harvest were < 0.01 mg/kg (mean of replications) or 0.017 mg/kg for individual replicates. Maximum residues of NC 7312 were 0.15 mg/kg (mean of replicates) or 0.18 mg/kg for individual replicates. For both the means of the replicates and individual replicates residues of bendiocarb and NC 7312 were each generally comparable from 0 to 15 days after last application. Apparent residues in untreated controls were generally < 0.01 mg/kg for bendiocarb and < 0.02 mg/kg for NC 7312. Residues of NC 7312 at harvest were 1-20 times that of bendiocarb per se, and averaged six times higher. Since residues from in-furrow or broadcast applications can be 0.04 mg/kg and untreated controls can, on occasion, reach this level, a 0.05 mg/kg for bendiocarb per se can be supported. If NC 7312 were also included, a limit of 0.5 mg/kg would be in order for combined residues. Sugarbeet Thirty one supervised residue trials were conducted in five European countries and residue decline studies in three (Table 4) (Browne 1982c; FBC 1982b; Reary 1974, 1975e, 1979h,i,n,q, 1980f,j). The seed treatment applications of 80W were at 0.8-2.7 times the recommended 6 g/kg rate, which is also consistent with GAP of The Netherlands. In-furrow applications of a granular formulation were representative of the 0.3-0.4 kg a.i./ha GAP of The Netherlands and recommended application rates. In the supervised trials, bendiocarb residues at harvest were below 0.01 mg/kg. Some samples were also analysed for the metabolite NC 7312 and all were below the 0.01 mg/kg limit of determination. Similarly, in the decline studies, residues in sugarbeet roots were less than the 0.02 mg/kg limit of determination. Residues in untreated controls were generally < 0.01 mg/kg, except for one set of trials where residues ranged up to 0.11 mg/kg (average 0.005 mg/kg). The same basic analytical procedure was used in all of the trials, but modified in some to permit analysis of NC 7312. The limit of determination for sugarbeet generally ranged from 0.005-0.02 mg/kg for bendiocarb and 0.01-0.02 mg/kg for NC 7312. Recoveries were generally > 75% for parent compound and > 60% for NC 7312. In general, recoveries were less in tops than in roots and less for NC 7312 than for bendiocarb. Table 4. Bendiocarb Residues in Sugarbeets From Supervised Trials and Residue Decline Studies No. No. Application Interval Residue 1/2/3/4/ Country/Year Trials Samples Formulation Rate (a.i.) Method (days) (mg/kg) Denmark 1 1 80W 15 g/kg seed Pelleted seed 204 roots <0.005 1974 1 untreated controls roots <0.005 France 2 8 80W 12 g/kg seed Pelleted seed 163 roots <0.005 1974 2 untreated controls roots <0.005 German 1 1 6 g/kg seed Seed dressing 196 roots <0.005 Federal 1 1 196 tops <0.005 Republic 1 1 80W 12 g/kg seed Seed dressing 196 roots <0.005 1974 1 1 196 tops <0.005 untreated controls roots or tops <0.005 U.K. 2 4 80W 8 g/kg seed Pelleted seed 213 roots <0.005 1974 untreated 213 tops <0.0055/ 2 control roots <0.005 tops <0.0055/ France 3 3 3G 0.36 kg/ha In furrow 160-168 roots <0.005 1976 3 3 160-168 tops <0.01 3 6 3G 0.45 kg/ha In furrow 171-190 roots <0.005 3 6 171-190 tops <0.01 3 6 untreated controls tops and roots <0.006 Table 4. (con't) No. No. Application Interval Residue 1/2/3/4/ Country/Year Trials Samples Formulation Rate (a.i.) Method (days) (mg/kg) France 2 2 3G 0.46 kg/ha In furrow 180-185 roots <0.005 1977 2 2 180-185 tops <0.01 2 2 untreated controls tops and <0.006 roots France6/ 2 3G 0.3 kg/ha In furrow 152-170 roots <0.01 1978 2 152-170 tops <0.01 2 3G 0.6 kg/ha In furrow 152-170 roots <0.01 2 2 untreated controls tops and roots <0.005 Italy6/ 1 1 3G 0.3 kg/ha In furrow 110 roots <0.01 1978 1 1 110 tops <0.01 1 1 3G 0.6 kg/ha In furrow 110 roots <0.01 1 untreated controls tops and roots <0.005 U.K.6/ 3 3 3G 0.3 kg/ha In furrow 154-188 roots <0.01 1978 3 3 154-188 tops <0.01 1 1 3G 0.33 kg/ha In furrow 202 roots <0.01 1 1 202 tops <0.01 1 1 3G 0.4 kg/ha In furrow 188 roots <0.01 188 tops 1 1 untreated controls tops and roots <0.007 Table 4. (con't) No. No. Application Interval Residue 1/2/3/4/ Country/Year Trials Samples Formulation Rate (a.i.) Method (days) (mg/kg) U.K.6/ 6 1 3G 0.3 kg/ha In furrow 144-167 roots <0.01 1979 6 1 144-167 tops <0.01 6 6 untreated controls tops and roots <0.01 Italy6/ 1 3G 0.30 kg/ha In furrow 154 roots <0.01 1981 1 154 tops <0.01 1 3G 0.32 kg/ha In furrow 183 roots <0.01 1 183 tops <0.01 2 2 Untreated roots <0.001 controls tops 0.003 German 4 12 80W 5 g/kg seed Seed dressing 71-166 roots <0.02 Federal tops <0.02 Republic 4 12 Untreated roots 0.002-0.11 1978 4 12 controls (0.005 av.) tops 0.005-0.015 (0.008 av.) 3 8 3G 0.33 kg/ha In furrow 56-70 roots <0.01 3 9 tops <0.01 71-166 tops <0.015 5 Untreated 71-166 roots <0.01 controls tops <0.01 Table 4. (con't) No. No. Application Interval Residue 1/2/3/4/ Country/Year Trials Samples Formulation Rate (a.i.) Method (days) (mg/kg) U.K. 1 5 3G 0.3 kg/ha In furrow 25-40 roots 1.367/ 1979 41-55 roots 0.127/ 56-70 roots <0.01 71-166 roots <0.01 7 56-70 tops <0.01 71-166 tops <0.01 1 5 Untreated 56-70 roots <0.01 controls tops <0.01 1/ Bendiocarb only (see also 6/); 2/ Corrected for recoveries of >75% except for 59% recovery in tops. Fortification levels ranged from 0.02-0.01 mg/kg; 3/ Limit of determination in individual trials generally ranged from 0.005-0.02 mg/kg; 4/ Duplicate analyses of 0.006 and 0.003 mg/kg; 5/ Individual values up to 0.07 mg/kg but <0.005 mg/kg when repeated; 6/ Sample also analysed for primary metabolite NC 7312. Residues after 56 days were generally below the 0.01 mg/kg limit of detection except one 0.03 mg/kg value in tops (limit of determination in that trial or a 0.02 limit of determination. Residues in seedlings were 0.42 and 0.07 mg/kg at 28 and 41 days respectively after in-furrow application at planting; 7/ Seedlings analysed whole. Since residues are below the claimed limits of determination, a limit of 0.02 mg/kg bendiocarb per se would probably not be unrealistic. However, because of high apparent residues in one untreated control, a 0.05 mg/kg limit at or about the limit of determination may be more suitable. Based on a 0.02 mg/kg limit of determination for NC 7312, a limit on the order of 0.1 mg/kg would be appropriate if both bendiocarb and free NC 7312 were included. Actual residues were too low to determine whether residues of NC 7312 exceed those of bendiocarb, but judging from those found in potatoes, it is likely. Leafy Vegetables, Except Brassicas Sugarbeet leaves From the residue trials and decline studies discussed previously (Table 4), residues in sugarbeet tops at harvest from recommended application rates were generally less than the 0.01-0.03 mg/kg limits of determination. Only one trial had a limit of determination of 0.03 mg/kg for tops. The limit of determination was considered to be < 0.02 mg/kg for the remaining 30 trials. Bendiocarb residues were 1.4 and 0.12 mg/kg in seedlings at 28 and 41 days, respectively, after in furrow treatments at planting. The data support a 0.05 mg/kg at or about limit of determination at harvest as the maximum residue level. Brassica Leafy Vegetables Cabbage No information was available on specific nationally approved uses. Supervised trials with a wettable powder formulation were conducted in one country (Table 5) (Browne 1981a,c, 1982a,b; Browne and Manley 1982), at application rates up to 0.25 times the maximum recommended application rate (Table 2). No specific preharvest interval was recommended. Maximum residues ranged from 0.18 mg/kg one day after the last of seven applications to <0.01 mg/kg after 14 days. Untreated controls were < 0.02 mg/kg and analytical recoveries averaged 82% from fortification levels at 0.08-0.2 mg/kg. The limit of determination was said to be 0.01 mg/kg, but considering untreated control analyses, a 0.05 mg/kg limit of determination may be more practical. Because the trials do not reflect maximum recommended application rates, recommended usage does not specify the number of applications or a preharvest interval and the data are minimal, a maximum residue level for bendiocarb in cabbage cannot be estimated with confidence. Table 5. Bendiocarb and NC 7312 in Crops from Supervised Trials Application Country/ Rate Preharvest Crop Year No. (kg a.i./ha Formulation interval Residues (mg/kg) No. samples No. replicates or % a.i.) (days) Bendiocarb NC 7312 Cabbage1/ Philippines 7 0.06 50W 1 0.1 3 1981 0.1 a.i./l 3 0.04 3 7 0.01 3 14 <0.01 3 0.12 50W 1 0.18 3 0.2 g a.i./l 3 0.05 3 7 0.02 3 14 <0.01 3 Untreated 1 <0.01 3 control 3 0.02 3 7 0.01 3 14 <0.01 3 Peas2/ U.K. 1 0.2 50SC3/ 27 <0.01 <0.01 5 flowering 1981 1 0.3 <0.01 <0.01 5 stage (MarQ) 1 0.4 <0.01 <0.01 5 1 0.05 <0.01 <0.01 5 Untreated control <0.01 <0.01 5 4-leaf 1 0.2 27 <0.01 <0.01 5 stage 1 0.3 <0.01 <0.01 5 1 0.4 <0.01 <0.01 5 1 0.5 <0.01 <0.01 5 Untreated control <0.01 0.01 5 Table 5. (con't) Application Country/ Rate Preharvest Crop Year No. (kg a.i./ha Formulation interval Residues (mg/kg) No. samples No. replicates or % a.i.) (days) Bendiocarb NC 7312 Pea pods 1 0.2 50SC3/ 83 <0.01 <0.02 5 flowering 1 0.3 <0.01 <0.06 5 stage 1 0.4 <0.01 0.07 5 1 0.5 <0.01 0.03 5 Untreated control <0.01 0.03 5 4-leaf stage 1 0.2 83 <0.01 0.05 5 1 0.3 <0.01 0.05 5 1 0.4 <0.01 0.08 5 1 0.5 <0.01 0.06 5 Untreated <0.01 0.05 5 control Apple (Cox's U.K. 24/ 0.04 and 20W 57 <0.01-0.01 <0.01 6 Orange 1981 0.08% 50W, Pippin) 50 SC Untreated 0.006 0.005 1 14/ 0.04 and 20W, 106 <0.01-0.01 <0.01-0.01 6 0.08% 50W, 50SC 0.009 0.003 1 4/ Untreated 2 0.02, 20W, 98 <0.01-0.01 <0.01-0.01 9 0.04 and 50W, 0.08% 50SC untreated 0.003 0.008 1 Table 5. (con't) Application Country/ Rate Preharvest Crop Year No. (kg a.i./ha Formulation interval Residues (mg/kg) No. samples No. replicates or % a.i.) (days) Bendiocarb NC 7312 Pear 14/ 0.02% 50SC 158 0.01 <0.01 1 (Conference) 14/ 0.04% 0.02 0.01 1 14/ 0.08% untreated 0.01 0.005 1 Mushrooms The Netherlands 1980 2 5 50SC 21 0.04-0.06 0.01-0.03 4 (50 g a.i./ <0.05 av.) (<0.02 av.) 100 m2) 2 7.5 50SC 21 0.08-0.12 0.01-0.04 4 (75 g a.i./ (0.1 av.) (0.02 av.) 100 m2) 2 10 50SC 21 0.11-0.14 0.02-0.06 4 (100 g a.i./ (0.13 av.) (0.04 av.) 100 m2) Untreated <0.01-0.02 <0.01-0.1 4 (0.01 av.) (0.01 av.) U.K. g a.i./100 m2 1981 wall spray5/ 1 52.2 50SC 69 N.D.6/ <0.02 1 untreated 69 N.D. N.D. 1 1 20 80W 33 N.D. N.D. 1 untreated 33 0.001 N.D. 1 1 48 80W 41 <0.02 0.02 1 untreated 41 0.04 0.02 1 (g a.i./100 m2 wall spray 5/) Table 5. (con't) Application Country/ Rate Preharvest Crop Year No. (kg a.i./ha Formulation interval Residues (mg/kg) No. samples No. replicates or % a.i.) (days) Bendiocarb NC 7312 Mushrooms U.K. 1 20 80W 26 <0.02 <0.02 1 1981 untreated 26 N.D. N.D. 1 1 20 80W 33 <0.02 <0.02 1 untreated 33 N.D. 0.003 1 1 20 80W 52 N.D. <0.02 1 20 80W 60 0.04 0.02 1 untreated 52 N.D. N.D. 48 80W 42 0.06 0.1 1 48 80W 42 0.09 0.13 1 48 80W 42 0.08 0.10 1 1/ Residue results corrected for mean analytical recovery of 82% with fortification at 0.08-0.2 mg/kg. 2/ Results corrected for recoveries. Harvest (127 days after planting) said to be 2-3 weeks after normal harvest. 3/ SC = Suspendable concentrate. 4/ 1.5 1 spray solution per tree. 5/ Mushroom plots established the day after wall treatment. 6/ N.D. = no detectable chromatographic peaks. Legume Vegetables Peas Supervised residue trials were conducted in the U.K. with single applications at rates consistent with recommended ones. No information was available on specific nationally approved good agricultural practices, nor was information available on recommended numbers of applications or preharvest intervals. Peas were sampled at 2-3 weeks after normal harvest (127 days after planting). At all application rates tested, residues of either bendiocarb or NC 7312 (corrected for recovery) were <0.01 mg/kg in peas, including untreated controls (Table 5). The same is true for bendiocarb in pea pods, but residues of NC 7312 ranged from 0.03-0.08 mg/kg (0.05 mg/kg av.), and untreated controls were 0.02 and 0.05 mg/kg. Although bendiocarb residues were at or about the limit of determination, the data suggest that terminal residues of NC 7312 may be 2-10 times that of bendiocarb. Analytical recoveries averaged 86 and 72% for bendiocarb and NC 7312, respectively, in peas from fortification levels of 0.04 and 0.2 mg/kg. Recoveries in pods averaged only 58 and 63%, respectively. The limit of determination was said to be 0.01 mg/kg for bendiocarb and NC 7312 in both peas and pods. However, based on untreated controls, 0.05 mg/kg may be a more appropriate limit of determination for NC 7312 in pea pods. Because GAP information is unavailable and samples were not harvested at normal harvest, a maximum residue level cannot be estimated with confidence. Pome Fruit Apples and Pears Residue data were available from supervised trials in the U.K. at application rates of 0.02-0.08% active ingredient (1.5 1/tree), representing several formulations. Applications were at pre- or post-blossom and/or at codling stage, and fruit was sampled at normal harvest of 57-158 days after last treatment. No information was available on specific nationally approved agricultural practices. Recommended applications rates of 0.25-0.5 kg/ha are not directly comparable to the 0.02%-0.08% used in the field trials. No information was provided on recommended preharvest intervals or numbers of applications. Of the 24 apple and pear samples treated in three locations and in untreated controls, residues of bendiocarb and NC 7312 were < 0.01 mg/kg, except for one 0.02 mg/kg value for pears treated once with a 0.08% 50 SC formulation (Table 5). Mean recoveries of bendiocarb and NC 7312 on apples and pears were 94 and 73%, respectively, when fortified from 0.1 to 0.4 mg/kg. The limit of determination is said to be 0.01 mg/kg for both bendiocarb and NC 7312. If the formulations, application rates, number of applications and preharvest intervals of the field trials represent GAP, the data could support a maximum residue level of 0.02 mg/kg for bendiocarb per se or 0.05 mg/kg for combined residues of bendiocarb and NC 7312. Cereal Grains Barley Fourteen supervised trials were conducted in the U.K. with in-furrow granular, 50W spray or 80W seed dressing applications. No nationally approved agricultural practice information was provided, although recommended uses for cereals were reported (Table 2). No recommended uses for the granular formulation (2 trials) were provided. Only two of the trials were from spray treatments and the remainder were from seed treatments. The spray applications at 0.5 and 1.0 kg a.i./ha reasonably reflect the recommended 0.75 kg a.i./ha although the data are limited (Table 6) (Browne and Reary 1980c,d,e; Housden and Reary 1981; Reary 1978 h,i,j,n; Reary 1979e,f,g,j,k,l,m,o, 1980a,e; Reary and Browne 1978). The seed treatments at 2-5 g a.i./kg seed reflect the recommended rate of 2-5 g a.i./kg. Residues of bendiocarb at normal harvest in barley grain were <0.02 mg/kg and <0.03 mg/kg in straw. Untreated controls in barley grain and straw were at the same level. Some samples were also analysed for combined conjugated metabolites, NC 7312 and N-hydroxymethylbendiocarb. In all three trials, metabolite residues were <0.02 mg/kg. Mean analytical recoveries for bendiocarb in barley during the supervised trials were 94 and 84%, respectively, for grain and straw when fortified at 0.02-0.2 mg/kg. In a separate study, bendiocarb recoveries in barley grain were 61-125% (av. 94%) after fortifications at 0.02-0.2 mg/kg (Reary 1979b). Table 6. Bendiocarb Residues in Cereals from Supervised Trials No. No. Application Interval after Residues Country Trials Samples Formulation Rate (a.i.) Method application Sample (mg/kg) (days) Barley, wheat and oats U.K. 1 1 80W 4 g/kg seed Seed dressing 148 barley grain <0.02 1977 1 1 148 barley straw <0.02 1 2 80W Seed dressing 148 wheat grain <0.02 1 2 148 wheat straw <0.02 1 2 50SC 4 g/kg seed Seed dressing 148 barley grain <0.02 1 2 148 barley straw <0.02 1 2 50SC Seed dressing 148 wheat grain <0.02 1 2 148 wheat straw <0.02 U.K. 3 3 80W 4 g/kg seed Seed dressing 113-145 barley grain <0.02 1978 2 2 113-145 barley straw <0.03 2 2 124-137 wheat grain <0.02 1 1 124-137 wheat straw <0.06 3 3 (10 rep) 134-141 oat grain <0.02 2 2 (10 rep) 134-141 oat grain <0.02 2 2 80W 8 g/kg seed Seed dressing 136-147 oat grain 0.47 3 2 136-147 oat straw 0.02-0.05 U.K.1/ 1 1 3G2/ 0.5 kg/ha In furrow 148 barley grain <0.01 1979 1 1 148 barley straw <0.01 1 1 3G2/ 1.0 kg/ha In furrow 148 barley grain <0.01 1 1 148 barley straw <0.01 1 1 50W2/ 0.5 kg/ha Spray 148 barley grain <0.01 148 barley straw <0.01 Table 6. (con't) No. No. Application Interval after Residues Country Trials Samples Formulation Rate (a.i.) Method application Sample (mg/kg) (days) 1 1 50W2/ 1.0 kg/ha Spray 148 barley grain <0.01 1 1 148 barley straw <0.01 1 1 80W 2 g/kg seed Seed dressing 336 wheat grain <0.01 1 1 336 wheat straw <0.01 3 3 80W 4 g/kg seed Seed dressing 119-148 barley grain <0.01 119-148 barley straw <0.01-0.02 3 3 127-336 wheat grain <0.01 2 2 127-336 wheat straw <0.01 2 2 105-125 oat grain <0.012 2 2 105-125 oat straw <0.01,<0.03 2 2 80W 5 g/kg seed Seed dressing 119-127 barley grain <0.01 2 2 119-127 barley straw <0.01,<0.02 1 1 127 wheat grain <0.01 1 1 127 wheat straw <0.01 2 2 105-125 oat grain <0.01 2 2 105-125 oat straw <0.01 Maize harvest samples Canada 22 37 10G 0.84-2.24 band 153-189 grain <0.02 U.S. 8 8 kg/ha at 132-165 cob <0.02 1977-78 21 38 plant 132-189 stover3/ <0.03 10 28 110-134 silage <0.023 Table 6. (con't) No. No. Application Interval after Residues Country Trials Samples Formulation Rate (a.i.) Method application Sample (mg/kg) (days) German 25 30 3G 0.2-0.8 in furrow 133-184 grain <0.024/ Fed. Rep. 26 36 kg/ha at plant 128-184 cobs <0.024/ 5 12 128-184 plants <0.01 U.K. 10 10 146-184 foliage <0.01 France 5 5 135-164 silage <0.02 Italy 133-154 stover <0.02 1976-79 France 30 36 76 or 2-16 g/kg seed 125-189 grain <0.035/ U.K., U.S. 30 24 80W seed treatment 160-161 cob <0.026/ 1975-1979 18 23 125-167 silage <0.02 11 10 160-189 stover <0.02 14 8 141-164 plants <0.056/ Rice (rough) harvest samples Philippines7/ 1 1 5G 1.5 + 0.5 Incorporation + 53 grain <0.01 1978 surface applied straw <0.02 1 1 5G 2.0 + 0.6 Incorporation + 53 grain <0.01 surface applied straw <0.02 1 1 50W 0.5 kg/ha Spray 90 grain 0.01 straw <0.02 1 1 50W 0.6 kg/ha Spray 90 grain <0.01 straw <0.02 Table 6. (con't) No. No. Application Interval after Residues Country Trials Samples Formulation Rate (a.i.) Method application Sample (mg/kg) (days) 2 2 80W 0.5 kg/ha Spray 60-90 grain <0.01 straw <0.02 2 2 80W 0.6 kg/ha Spray 60-90 grain <0.01 straw <0.02 Philippines7/ 1 1 50W 0.5 kg/ha Spray 248/ grain <0.01 1979 straw <0.01 1 1 50W 0.7 kg/ha Spray 248/ grain <0.01 straw 0.01 1 1 50W 1.0 kg/ha Spray 248/ grain 0.01 straw <0.01 1 1 50W 0.5 kg/ha Spray 459/ grain 0.01 straw - 1 1 50W 0.75 kg/ha Spray 459/ grain <0.01 straw - 1 1 50W 0.5 kg/ha Spray 4910/ grain <0.01 straw <0.01 1 1 50W 0.75 kg/ha Spray 4910/ grain 0.01 straw 0.02 South Korea7/ 1 1 50W 0.75 kg/ha Spray 10 grain 0.6, 1.111/ 1979 straw <0.6 1 1 2D 0.8 kg/ha Dust 10 grain 1.5, 1.411/ straw <0.65 1 1 3GW 0.9 kg/ha Seed box 119 grain 0.06, 0.03 incorporation straw 0.02 (100 g/box) straw <0.02 Table 6. (con't) No. No. Application Interval after Residues Country Trials Samples Formulation Rate (a.i.) Method application Sample (mg/kg) (days) 1 1 5G 1.5 kg/ha Soil 100 grain <0.6 incorporation straw 0.04 Philippines 1980 1 1 50W 0.25 kg/ha Spray 6212/ grain <0.02 straw <0.01 1 1 50W 0.50 kg/ha Spray 6212/ grain <0.02 straw <0.01 1 1 50W 0.75 kg/ha Spray 6212/ grain <0.02 straw <0.01 1/ Also analysed for combined residues of conjugated NC 7312 and N-hydroxymethylbendiocarb. All metabolite residues were < 0.02 mg/kg except for residues of 0.07 and 0.05 mg/kg from one trial in oat grain from seed dressing of spring oats with an 80 WP formulation at 4 and 5 g a.i./kg seed. The two residues resulted from oat grain samples with bendiocarb residues 0.012 and 0.007 mg/kg respectively. Untreated controls were 0.011 mg/kg. 2/ Seed previously treated with an 80% WP formulation 3/ Stover = leaves and stems after removal of cobs. 4/ Analysis of oil from kernels with <0.02 mg/kg residue from one site showed no residue greater than the 0.02 mg/kg limit of determination. 5/ The 0.03 mg/kg on grain resulted from treatments at 8 and 12 g a.i/kg seed. At <4 g a.i./kg seed residues were <0.02 mg/kg in grain. 6/ Maize (sweet corn) comprised 14 of the trials at 2-8 g a.i./kg. All plants in this group were sweet corn. The 0.05 mg/kg residue on sweet corn plants resulted from 2-4 g a.i./kg seed. Table 6 (con't) 7/ Also analysed for metabolite NC 7312. No residues above the limits of detection (0.01 mg/kg in grain and 0.02 mg/kg in straw) were found, except for 0.11 and 0.17 mg/kg in grain from dust and spray treated samples at the 10-day interval and one 5G formulation at 100 days, in which it was 0.03 mg/kg. In the latter, the control was also 0.03 mg/kg. 8/ Period between final application and harvest in multi-spray programme. Sprays, at same rates, were made 17, 27, 39, 52, 66 and 80 days after transplanting. 9/ Period between final application and harvest in multi-spray programme. Sprays, at same rates, were made 10, 25 40 and 55 days after transplanting. 10/ Period between final application and harvest in multi-spray programme. Sprays, at same rates, were made 7, 20 and 45 days after transplanting. 11/ Values reflect residue determination by electron capture and fluorescence, respectively. 12/ Period between final application and harvest in multi-spray programme. Sprays, at same rates, were made 22, 35, 51 and 68 days after transplanting. The limit of determination was said to be 0.01 mg/kg for both cereal grain straws and grains, although apparent residues in controls (<0.02 and <0.03 mg/kg in barley grain and straw, respectively) suggest 0.02 or even 0.05 mg/kg may be a more realistic estimate for both. When considered with data from other cereal grains and straws, a 0.05 mg/kg limit for bendiocarb per se at or about the limit of determination could be supported if recommended uses represent GAP. A 0.1 mg/kg limit would be appropriate if both bendiocarb and metabolites are included. Maize Over 100 supervised trials were conducted in six countries, two in North America and four in Europe (Table 6). Applications were made with granular formulations at planting, either by band or in-furrow treatment and seed was treated with wettable powder formulations. In-furrow applications of a 3G formulation at 0.2-0.8 kg a.i./ha corresponds to the 0.3-0.4 kg a.i./ha Netherlands GAP, although no data were available from The Netherlands. The recommended uses on maize provided to the Meeting did not include the method of application for granular formulations. Granular band treatments at planting of 0.84-2.24 kg a.i./ha did not correspond with certainty to either The Netherlands GAP or recommended usage for maize. The 2-16 g a.i./kg wettable powder seed treatments more than accommodate the 2-4 g a.i. GAP of The Netherlands or recommended application rates. Additional information on official national GAP is needed. Maximum residues of bendiocarb per se from all treatments were <0.03, <0.02, <0.023, 0.05 and <0.01 mg/kg in grain, cobs, stover, silage, plants and foliage, respectively. Analysis of oil from one grain sample with field-incurred residues of <0.02 mg/kg also showed residues of less than the 0.02 mg/kg limit of determination. The 0.03 mg/kg level in grain resulted from applications at 2-3 times the recommended rate. At recommended rates all grain residues were <0.02 mg/kg. The 0.05 mg/kg residue on plants was on maize (sweet corn) treated according to recommended rates. The limit of determination was said to be 0.01-0.02 mg/kg for the various maize fractions. Apparent residues in untreated controls were also in this range. Analytical recoveries during the trials averaged approximately 81, 78, 72, 80 and 78% for grain, cob, silage, stover and plants, respectively. A 0.05 mg/kg limit at or about the limit of determination could be supported for bendiocarb per se in maize (field corn) grain, fodder and/or forage. Additional data would be required for inclusion of metabolites. In addition to the trials at harvest, 12 residue decline trials were conducted in four countries (FBC 1982a; Browne and Reary 1979d; Reary 1978l,m, 1979p, 1980h,i), mostly from granular in-band or in-furrow treatments at planting ranging from 0.3-2.24 kg a.i./ha. Residues in grain from granular treatments were <0.01 mg/kg. In plants, residues ranged from <0.05-0.9 mg/kg at 25-40 days after treatment (0.9 at 29 days), declining to <0.07 mg/kg after 49 days and <0.02 after 56-70 days. Residues in stover and cobs were <0.02 and <0.02 mg/kg, respectively, after 71 days. From the single 4 g a.i./kg seed treatment with a wettable powder formulation, residues on plants were 12.4 mg/kg 29 days after treatment but rapidly declined to _0.023 mg/kg after 42 days. Oats Residue data were available for seven supervised trials in the U.K. from 4-8 g a.i./kg seed 80W seed dressings (Table 6). No information was provided on specific nationally approved practices. At application rates approximating the 4 g a.i./kg seed recommended application rate, residues in oat grain at normal harvest were 0.02 mg/kg and in straw were _0.02 mg/kg. One of the two grain samples treated at 8 g a.i./kg seed had a residue of 0.47 mg/kg. Contamination of this sample and its 0.12 mg/kg untreated control was suspected by the manufacturer to have occurred during sampling. Maximum residues in straw from the 8 g a.i/kg seed application rate were 0.05 mg/kg. While this could be aberrant, as the untreated control was 0.12 mg/kg, it is not necessarily so, since residues are as high as 0.03 mg/kg in straw of oats and barley from recommended application rates. Residues in untreated controls were <0.02 and <0.04 mg/kg in grain and straw, respectively, except for 0.12 mg/kg from a grain and straw sample with suspected contamination. A limited amount of residue data were also available for combined conjugated metabolites (NC 7312 and N-hydroxymethylbendiocarb) in some oat samples, with residues being <0.012 mg/kg and <0.01 mg/kg in grain and straw, respectively. Mean recoveries of bendiocarb were 89 and 94% for oat grain and straw, respectively. The limit of determination was said to be 0.02 mg/kg for both, but based on the 0.035 mg/kg apparent residue in untreated controls, 0.05 mg/kg may be more appropriate, especially when barley and wheat are also considered. A 0.05 mg/kg limit at or about the limit of determination could be supported for bendiocarb per se if recommended uses represent GAP. A 0.1 mg/kg limit would be required if both bendiocarb and metabolites were included. Rice Residue data (corrected for mean recoveries) were available from 22 supervised trials on rough rice at normal harvest in The Philippines and South Korea (Table 6). Applications were by granular, spray and dust formulations. No information was available on nationally approved agricultural practices on rice. Recommended application rates for rice are 2 and 0.5 kg a.i./ha for granular and spray formulations, respectively, and 0.5-0.75 kg a.i./ha for dust, as summarized in Table 2. No information was provided on approved intervals from last application or maximum number of applications. Only one trial utilized a dust formulation, and the application rate reflects the recommended use. Bendiocarb residues were 1.5 mg/kg and 0.65 mg/kg, respectively, for grain and straw 10 days after application as compared to 0.6-1.1 mg/kg for a spray application after the same interval. Residues for NC 7312 were 0.17 mg/kg at the same 10-day interval. Untreated controls were <0.3 mg/kg and 0.04 mg/kg, respectively, for grain and straw. Spray applications of 0.25-0.75 kg a.i./ha covers the 0.5 kg/ha recommended rate. As in the case of dust treatments, the spray applications at 10 days before normal harvest resulted in higher residues than at longer intervals, measuring <1.1 and <0.5 mg/kg, respectively, for grain and straw. Similarly, residues were higher for NC 7312 in grain, being 0.11 mg/kg. The same control as for the 10-day interval dust treatment applies. At longer intervals from last treatment with 50W or 80W formulations (24-90 days) and up to 1.5 times the recommended rate, residues were <0.02 mg/kg for both grain and straw. Untreated controls for spray treatments, except for the 10-day interval treatment, were <0.021 and <0.02 mg/kg, respectively, for bendiocarb in grain and straw, except for one untreated straw sample at 0.04 mg/kg. Residues of NC 7312 were <0.03 mg/kg and 0.02 mg/kg for grain and straw, respectively, from spray treatments. Four trials were conducted with either 3G or 5G formulations at rates reflecting the recommended application rate and different application methods. Maximum residues of bendiocarb were <0.6 mg/kg and 0.04 mg/kg, respectively, in grain and straw. Untreated controls were <0.07 and <0.04 mg/kg bendiocarb in grain and straw, respectively. Residues of NC 7312 were <0.03 and <0.02 mg/kg in grain and straw, respectively. Analytical recoveries of bendiocarb during the trials averaged 77 and 68%, respectively, in rice grain and straw from fortifications at 0.02-0.25 mg/kg. Average recoveries were less (64 and 56%) for NC 7312. In a separate study on recoveries (Browne and Reary 1979b) at similar fortification levels, mean recoveries were better, being 86 and 74% for bendiocarb in grain and straw, and 70 and 56%, respectively, for NC 7312. In the absence of GAP information, 2 mg/kg and 1 mg/kg limits would be required for bendiocarb per se in rice grain and straw, respectively, to accommodate the uses of the supervised trials. Wheat Residue data, corrected for recoveries, were available from eight supervised trials in the U.K. from seed treatments with 80W or 50SC at 2-5 g a.i./kg seed (Table 6). No information was available on specific nationally approved agricultural practices, although the application rates used reflect the 2-4 g a.i./kg seed recommended rate for cereals. Residues for bendiocarb at harvest were <0.02 mg/kg for both grain and straw, except for one 0.06 mg/kg value for straw. This 0.02 mg/kg level is approximately the claimed limit of determination. Untreated controls were <0.04 mg/kg and <0.12 mg/kg, respectively, for grain and straw. The 0.12 mg/kg for straw is from the same study in which the high treated sample residue was found. Contamination was suspected. Other values were <0.02 mg/kg. Analytical recoveries from the individual studies were relatively low, averaging only 63-65% for grain and straw at fortification levels of 0.02-0.2 mg/kg. In a separate determination (Reary 1979b) recoveries of bendiocarb in grains were better, averaging 84%. The limit of determination for barley, oats and wheat is said to be <0.02 mg/kg for grain and straw. Overall data support a 0.05 mg/kg limit for bendiocarb per se. Limited data were also available for combined conjugated residues of NC 7312 and N-hydroxymethylbendiocarb. Residues were <0.01 and <0.12 mg/kg for wheat grain and straw, respectively, although analytical recoveries were only 62 and 67% in cereal grains and straw, respectively. Fodders and Straws Fodders and straws of cereal grains have been discussed previously. The other member of this group for which data were provided is grass fodder, or more specifically turf and grass. Data were available from 72 supervised trials in the U.K., U.S. and Australia from 1975-1980, representing a variety of formulations, single or multiple applications at several rates, intervals, and methods of application as well as irrigated and unirrigated conditions (Table 7) (Browne 1981d; FBC 1982c; Reary 1975d, 1978f,g, 1980b,d,e,k, 1981m; Reary and Whiteoak 1977a,b,c,d). No information was available on specific national agricultural practices, although recommended rates for rye grass is given in Table 1. Granular treatments, both single and multiple broadcasts, were mostly at application rates 6-12 times the recommended rate (for rye grass). Three granular broadcast trials (single applications) at 1.6 times the recommended rate resulted in maximum residues ranging from 0.24 mg/kg at 43 days after treatment to 0.09 mg/kg after 55 days. Residues were <0.1 mg/kg from three granular seed mix trials (single application) at 0.6-1.4 times the recommended granular application rate when analysed 196 days after treatment. As in the case of granular treatments, single or multiple spray treatments were mostly at rates 6-12 times the maximum recommended application rate for rye grass. After single applications at rates approximating recommended rates (1-1.6x), maximum residues from spray treatments ranged from 103 mg/kg (193 mg/kg dry basis) at day of application to 0.03 mg/kg after 141 days. No recommended rates were available specifically for ULV aerial applications. Residues from a single application at 0.28 kg/ha ranged from 50 mg/kg (111 mg/kg dry basis) on day of application to 5.5 mg/kg (12 mg/kg dry basis) after 29 days. Seed dressing trials were conducted at treatments rates of 1-4 times the recommended rate of 10 g a.i./kg seed. Residues were <0.2 mg/kg at all rates after 43 days. Although many of the treatments with the various formulations were at exaggerated application rates, these trials did permit estimations of decline rates, the potential of residue accumulation and effect of irrigation on residues. Residue half-lives were greater for granular broadcast applications, for which 37-42 days was estimated. For spray application half-lives ranged from 2-15 days, depending on the trial. The half-lives were 5.3 and 2.4 days for seed treatments and aerial ULV treatments, respectively. In general, irrigation did not significantly affect decline rates from granular broadcast or wettable powder spray treatments as compared to rates measured under non-irrigated conditions. Residues did not accumulate from multiple applications at 28-day intervals. Table 7. Bendiocarb Residues in Grass and Turf from Supervised Trials Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis U.K. 1 - 80W 1 kg/ha Spray Rye grass <1 130 1 1975 1-5 <109 3 6-10 <40 2 11-20 <15 2 21-50 <7 3 U.S. 1* 4.3 76W 2.24 kg/ha Spray Turf grass <1 <236 6 1976 1-5 <225 6 6-10 <115 4 11-20 <19 2 1* Thatch <1 <25 6 1-5 <26 6 6-10 <9 4 11-20 <1 2 1* 76W 4.48 kg/ha Spray Turf grass <1 <326 6 1-5 <386 6 6-10 <190 4 11-20 <46 2 1* Thatch <1 <36 6 1-5 <97 6 6-10 <79 4 11-20 <1.6 2 1* 2-4 76W 2.24 kg/ha Spray Turf grass <1 <293 5 1-5 <201 4 6-10 <4 4 11-20 <2.8 2 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 1* Thatch <1 <19 5 1-5 <13 4 6-10 <16 4 11-20 <21 2 1* 76W 4.48 kg/ha Spray Turf grass <1 <607 5 1-5 <710 4 6-10 <30 4 11-20 <7.5 2 Thatch <1 <56 5 1-5 <18 4 6-10 <32 4 11-20 <26 2 1* 5G 2.24 kg/ha Broadcast Turf grass <1 <1.4 5 1-5 <2.7 4 6-10 <0.6 4 11-20 <0.3 2 1* Thatch <1 <13 5 1-5 <11 4 6-10 <18 4 11-20 <17 2 1* 5G 4.48 kg/ha Broadcast Turf grass <1 <3 5 1-5 <6 4 6-10 <8 4 11-20 <0.7 2 1* Thatch <1 <34 5 1-5 <42 4 6-10 <47 4 11-20 <27 2 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 1977 2* 5-15* 76W 4.48 kg/ha Spray Turf grass 1-5 <30 4 6-10 <34 2 11-20 <10 2 21-50 <7 4 51-80 <3 2 81-110 <1.2 2 111-140 <0.3 3 >141 0.2 1 2* 76W 8.96 kg/ha Spray Grass 1-5 <125 5 6-10 <109 2 11-20 <19 2 21-50 <23 2 51-80 <2.5 2 81-110 <0.8 2 111-140 <0.4 3 >141 0.3 1 2* 5.6-14 76W Multi-spray1/ Turf grass 1-5 6-10 21-50 51-80 81-110 111-140 >141 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 2* 5-15 76W 4.48 kg/ha Spray Turf grass 1-5 <30 4 6-10 <34 2 11-20 <10 2 21-50 <7 4 51-80 <3 2 81-110 <1.2 2 111-140 <0.3 3 >141 0.2 1 2* 76W 8.96 kg/ha Spray Grass 1-5 <125 5 6-10 <109 2 11-20 <19 2 21-50 <23 2 51-80 <2.5 2 81-110 <0.8 2 111-140 <0.4 3 >141 0.3 1 2* 5.6-14 76W Multi-spray1/ Turf grass 1-5 6-10 11-20 21-50 51-80 81-110 110-140 >141 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 2* 76W Multi-spray2/ Turf grass 1-5 <16 3 6-10 <16 2 11-20 <9 2 21-50 <2 2 51-80 <0.9 2 81-110 <0.3 2 111-140 <0.1 2 >141 0.1 1 2* 76W Multi-spray3/ Turf grass 1-5 <24 2 6-10 <2 2 11-20 <3 2 21-50 <1.7 2 51-80 <1.1 2 81-110 <0.3 2 111-140 0.1 1 2* 76W Multi-spray4/ Turf grass 1-5 <37 4 6-10 <2.5 2 11-20 <3.4 2 21-50 <1 2 51-80 <0.4 2 81-110 0.1 1 2* 76W Multi-spray5/ Turf grass 1-5 <80 4 6-10 <80 4 11-20 <20 2 21-50 <3.7 2 51-80 0.5 1 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 2 37-42 5G Broadcast6/ Turf grass 1-5 <8 5 6-10 <3.3 2 11-20 <1.9 2 21-50 <3.7 2 51-80 <8.1 2 81-110 <2.6 2 111-140 <1.6 2 >141 <0.5 2 2 5G Broadcast1/ Turf grass 1-5 <7 5 6-10 <7 2 11-20 <1.4 2 21-50 <2.8 2 51-80 <0.16 2 81-110 <0.7 2 111-140 <0.55 2 >141 0.16 1 2 5G Broadcast2/ Turf grass 1-5 <9.5 4 6-10 <4.7 2 11-20 <4.4 2 21-50 <3.5 2 51-80 <0.7 2 81-110 <0.7 2 111-140 <0.7 2 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 2 5G Broadcast3/ Turf grass 1-5 <1.0 2 6-10 <9.0 2 11-20 <8.0 2 21-50 <4.0 2 51-80 <2.0 2 81-110 <0.8 2 111-140 0.8 1 2 5G Broadcast4/ Turf grass 1-5 <9.1 4 6-10 <8.2 2 11-20 <7.4 2 21-50 <7.6 2 51-80 <3.9 2 2 5G Broadcast5/ Turf grass 1-5 <7.3 4 6-10 <6.1 2 11-20 <5.7 2 21-50 <2.8 2 Australia 1 80W 1.6 g/kg seed Seed dressing Grass (pasture) 81-110 <0.02 2 1979 111-140 <0.02 2 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis U.K. 3 80W 10 g/kg seed Seed dressing Grass (grazing) 21-50 0.09 1 1979 51-80 <0.06 2 3 80W 40 g/kg seed Seed dressing Grass " 21-50 0.17 1 51-80 <0.11 2 3 3G 1.2 kg/ha Broadcast Grass (grazing) 21-50 0.24 1 51-80 <0.09 2 3 50SC 1.2 kg/ha Spray Grass (grazing) 21-50 <0.2 3 2 50SC 10 g/kg seed Seed dressing Grass (grazing) >141 <0.01 3 1 50SC 15 g/kg seed Seed dressing " " >141 0.01 1 2 50SC 20 g/kg seed " " " " >141 <0.01 3 2 50SC 0.5 kg/ha Spray Grass (grazing) >141 <0.01 3 1 50SC 0.75 kg/ha Spray " " >141 0.03 1 2 50SC 1.0 kg/ha Spray " " >141 <0.015 3 U.S. 1 6 50SC 0.84 kg/ha Spray Wheat grass <1 103 1 193 1979 1-5 <97 2 <139 6-10 26 1 34 11-20 16 1 18 21-50 <9.3 2 <16 U.K. 2 5.3 80W 10 g/kg seed Seed Dressing Grass (grazing) 51-80 <0.02 2 1980 2 80W 15 g/kg seed Seed dressing " " 51-80 <0.03 2 2 80W 20 g/kg seed Seed dressing " " 51-80 <0.1 3 1 50SC 5×0.5 kg/ha Spray Grass (grazing) 51-80 <0.03 6 81-110 0.01 1 Table 7. (con't) Country/ No. Half- Application Application Sample Interval after Residues No. of Dry Year Trials life Formulation Rate (a.i.) Method application (mg/kg) Samples weight (days) (days) basis 2 50SC 0.75 kg/ha Spray Grass (grazing) 51-80 <0.02 2 2 50SC 1.0 kg/ha Spray Grass " 51-80 <0.03 2 1 5G 0.75 kg/ha Seed mix Grass (grazing) 51-80 <0.08 2 1 3G 0.45 kg/ha Seed mix Rye Grass >141 <0.1 2 1 5G 0.75 kg/ha Seed mix Rye grass >141 <0.1 2 1 7G 1.05 kg/ha Seed mix Rye grass >141 <0.1 1 U.S. 1 2.4 25ULV 0.28 kg/ha Aerial Spray Rangeland grass <1 50 1 111 1980 1-5 5.36 2 <73 6-10 1.7 1 4 11-20 0.7 1 2 21-50 5.5 1 12 * Trials irrigated and non-irrigated. Residue levels maximum found. 1/ Rate of 4.48 kg/ha. 2/ Multi-application programme of 4.48 + 2.24 kg/ha, 28 days apart. 3/ Multi-application programme of 4.48 + 2.24 + 2.24 kg/ha each 28 days apart. 4/ Multi-application programme of 4.48 + 2.24 + 2.24 kg/ha, each 28 days apart. 5/ Multi-application programme of 4.48 + 2.24 + 2.24 + 4.48 kg/ha, each 28 days apart. 6/ Rate of 8.96 kg/ha. Apparent bendiocarb in untreated grass controls were generally <0.2 mg/kg, although they occasionally approached 1 mg/kg and were 1.8 mg/kg in one sample. The limit of determination was said to be 0.01-0.1 mg/kg, depending on the trial. Based on untreated controls, 1 mg/kg may be a more realistic limit of determination for grass. Analytical recoveries during the trials ranged from 43 to 119% and the mean for all the trials was approximately 80%. Legume Animal Fodders See discussion on pea pods under legume vegetables. Oilseeds Bendiocarb residue data on oilseed rape resulting from supervised trials were available from one country where applications of a 5G formulation was applied at sowing with the seed at application rates of 0.140 and 0.28 kg a.i./ha which is the recommended rate for granular formulations (Table 2) (Browne and Reary 1980f). No information was available on specific nationally approved agricultural practices. Nine replicates were analysed for bendiocarb per se on mature seed (114 days after application) at each rate with residues <0.006 mg/kg. Samples were not analysed for conjugates of NC 7312 and N-hydroxymethylbendiocarb, although a metabolism study has shown these to be the major metabolites in rape seed (see section on "Fate of Residues in Plants"). Residues in untreated controls were also <0.006 mg/kg with mean analytical recoveries of 84% for fortifications at 0.05-0.5 mg/kg. These data are inadequate for estimating a maximum residue level. Additional data from granular applications as well as data from spray treatments reflecting GAP are needed, as well as information on nationally approved uses, including preharvest intervals and number of applications. Meat Cattle Residue data available from two feeding studies and two dermal treatment studies are given in Table 8 (Browne and Reary 1978a,b; Reary 1978a, 1979a, 1980c). Table 8. Bendiocarb Residues in Milk and Cattle Tissues after Feeding Trials or Dermal Treatments1/ 28-Day Feeding Studies at Given 1% Dust Dermal Treatments at Given Treatment Dietary Levels (mg/kg) Levels (g product/treatment/cow) Single Self Manual treatment Manual Treatment5/ treatment6/ (7 successive days) Tissue 0.25 0.75 2.5 7.5 25 5 15 25 5 5 25 Milk (non-conjugated2/ residues) <0.01 <0.01 <0.01 <0.01 <0.01 0.014 0.005 0.015 0.06 <0.02 <0.04 Milk (conjugated3/ <0.02 <0.02 <0.02 <0.02 <0.02 0.027 0.027 0.039 0.057 <0.02 <0.02 residues) Muscle4/ <0.02 <0.02 <0.02 <0.02 <0.02 - - - - <0.01 <0.01 Omental fat4/ <0.02 <0.02 <0.02 <0.02 <0.02 <0.02 <0.03 Perirenal fat4/ <0.05 <0.05 <0.05 <0.05 <0.02 <0.05 <0.04 Subcutaneous- muscle4/ <0.01 <0.01 fat4/ <0.15 <0.12 Table 8. (con't) 28-Day Feeding Studies at Given 1% Dust Dermal Treatments at Given Treatment Dietary Levels (mg/kg) Levels (g product/treatment/cow) Single Self Manual treatment Manual Treatment5/ treatment6/ (7 successive days) Tissue 0.25 0.75 2.5 7.5 25 5 15 25 5 5 25 liver4/ <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 kidney4/ <0.1 <0.1 <0.1 <0.1 <0.1 <0.05 <0.11 1/ Corrected for mean recoveries; 2/ Bendiocarb and non-conjugated NC 7312 and N-hydroxymethyl bendiocarb (fat fraction); 3/ Total conjugated NC 7312 and N-hydroxymethyl bendiocarb (aqueous or lactose fraction); 4/ Total residues of bendiocarb and non-conjugated metabolites plus conjugated NC 7312 and N-hydroxymethylbendiocarb; 5/ Analysed 6 hours post-treatment; 6/ 7-21 day self-treatment. Treatment rate estimated to be approximately 5 g product/cow/day. In a feeding study (Browne and Reary 1978a), lactating dairy cows were fed for a minimum of 28 days with a diet containing 0, 0.25, 0.75 and 2.5 mg/kg bendiocarb. A maize premix was the vehicle for adding bendiocarb to the diet twice daily. Premises were stored at -4°C prior to use. Each treatment group consisted of two cows. Milk samples were pooled for both cows in each treatment group over 24 hours. Samples were taken before treatment and after 1, 2, 4, 8, 12, 16, 22 and 28 days on the bendiocarb fortified diet. Milk extracts were separated into a fat fraction (hexane/ether soluble) and a lactose fraction (water soluble), the first of which was analysed for total non-conjugated residues of bendiocarb, NC 7312 and N-hydroxymethylbendiocarb. The lactose fraction was analysed for total conjugated residues. Residues (bendiocarb equivalent in milk) in all fat samples were less than the estimated 0.01 mg/kg limit of determination, corrected for mean recoveries of 64%. Residues in the lactose fraction were also <0.01 mg/kg, but the limit of determination was considered 0.02 mg/kg because of chromatographic interferences. Based on the chromatograms, 0.05-0.1 mg/kg may be a more realistic limit of determination for the aqueous fraction when interfering co-extractives are taken into consideration. In each case, untreated controls gave no apparent residue above the estimated limits of determination. Samples of omental fat, perirenal fat, muscle, liver and kidney were taken from each animal at sacrifice (within 18 hours of final bendiocarb intake). Each was analysed for total residues of bendiocarb and metabolites, conjugated and non-conjugated. No residue (corrected for recovery) was found above the estimated limits of determination of 0.02 mg/kg for muscle and omental fat, 0.05 mg/kg for liver and perirenal fat and 0.1 mg/kg for kidney. Muscle samples at the 0.25 and 0.75 mg/kg dietary feeding level did show apparent residues at the 0.02 mg/kg limit of determination as did one untreated control. Based on representative chromatograms, the above estimated limits of determination appear to be reasonable, except that a 0.2 mg/kg may be more realistic for kidney. Mean recoveries determined separately on unconjugated bendiocarb, NC 7312 and N-hydroxymethylbendiocarb from cattle meat and fat tissues were approximately 70%, with a standard deviation ranging from 10 to 22. The large standard deviations reflect rather poor recoveries, especially of bendiocarb per se, (< approximately 50%) in a number of muscle, kidney and liver samples. For example, recoveries of bendiocarb averaged only 60% in muscle and kidney. Another feeding study (Reary 1978a) was conducted in a similar fashion but at higher dietary levels (7.5 and 25 mg/kg in the diet). Maximum residues in milk were <0.01 mg/kg (limit of determination for the fat soluble fractions) and <0.02 mg/kg for the aqueous portion. As in the lower level feeding study, apparent residues of total bendiocarb and conjugated and non-conjugated metabolites were <0.02 mg/kg in muscle, <0.02 in omental fat and <0.05 mg/kg in perirenal fat and liver. Residues were at the estimated 0.1 mg/kg limit of determination for kidney (one control sample was also at this level). This supports the view that 0.2 mg/kg is a more realistic limit of determination for cattle kidney. Analytical recoveries averaged approximately 70% with standard deviations from 11-21%, reflecting rather poor recoveries. Average recoveries were only 56% for bendiocarb in muscle and 52% for the N-hydroxy metabolite in liver. No information was provided on national GAP or recommended uses for dermal applications to dairy or beef cattle. Results of investigations for proposes uses for fly control by dermal applications with a 1% bendiocarb dust formulation were provided. A 5g dust treatment (50 mg a.i.) was described as a "normal" daily dose. In one set of experiments (Reary 1979a) lactating dairy cattle were manually treated at measured rates for safety evaluations or by hessian bag self-treatment for efficacy evaluations. In the safety evaluations, groups of three shorthorn cows were manually brushed on the head, neck and shoulders with 0, 5, 15 and 25 g of the 1% dust formulation; milk was analysed pre-treatment and six hours post- treatment for each animal. As in the feeding studies, milk was separated into fat and lactose fractions. Non-conjugated residues in milk ranged from 0.003-0.015 mg/kg (0.009 mg/kg mean) for all application rates, with no discernible difference between application rates. Total conjugated residues ranged from 0.019 to 0.039 mg/kg (0.028 mg/kg mean). Control means for the safety evaluation trials were 0.006 and 0.032 mg/kg for non-conjugated and conjugated residues, respectively. Limits of determination were considered to be 0.02 and 0.05 mg/kg for the fat and aqueous fractions, respectively. In the efficacy trials, four herds were self-treated at an estimated rate of 5 g of dust formulation/day/cow. Milk was pooled for each herd at 7, 14 and 21 days after the beginning of treatment. For the fat soluble non-conjugated fractions, residues were <0.017 mg/kg at 7-21 days, except for one pooled milk sample from one herd at 7 days, for which a residue of 0.06 mg/kg was detected. Therefore, non- conjugated residues did occur at and above the limit of determination. Conjugated residues were <0.057 mg/kg, or just over the estimated limit of determination. Samples used as untreated controls had mean residues of 0.005 mg/kg and <0.028 mg/kg for fat soluble and aqueous fractions, respectively. In another dermal treatment investigation (Reary 1980c) groups of three lactating dairy cows were manually treated on the head, neck and back daily for seven successive days with a 1% dust formulation at 0, 5 or 25 g product/cow/treatment. Daily milk production from each of two daily milkings for each cow was kept separate. Samples of muscle, omental fat, perirenal fat, liver, kidney and subcutaneous fat were taken within 18 hours after the final treatment. Non-conjugated residues in milk (fat fraction) after correction for analytical recoveries ranged from <0.01-0.04 mg/kg for 78 samples. All but six were <0.01 mg/kg. All residues >0.02 mg/kg were from the higher treatment rate, except for one sample at 0.02 mg/kg. Comparable residues in 24 untreated controls were <0.01 mg/kg, except for one sample at 0.02 mg/kg. All conjugated residues (aqueous fraction) were <0.02 mg/kg and untreated controls were <0.02 mg/kg. Mean analytical recoveries were 82% and 72% for the milk fat and lactose fractions, respectively. The limit of determination was considered to be 0.01 and 0.02 mg/kg for the fat and lactose fractions, respectively. In tissues, residues at both treatment levels were <0.01 mg/kg in muscle, <0.03 mg/ kg in omental fat, <0.05 mg/kg in perirenal fat, <0.01 mg/kg in subcutaneous muscle and <0.15 mg/kg (mean 0.08 mg/kg) in subcutaneous fat. Except for subcutaneous muscle, for which there were no untreated controls, apparent residues in controls for these tissues were _0.03 mg/kg, except for one 0.04 mg/kg sample of subcutaneous fat. Residues from both levels were <0.05 mg/kg in liver and <0.11 mg/kg in kidney. All residues >0.05 mg/kg in kidney were from the higher treatment level. Apparent residues in untreated controls were <0.03 mg/kg in liver and kidney. An estimate of potential residues in meat, milk and meat by- products must take into consideration all potential routes to animal exposure, which include the dietary and dermal routes. Of the feed crops for which residue data and good agricultural practice information were provided, the greatest potential for residues in cattle meat, fat and meat by-products and milk would be expected from uses on maize (field corn). Assuming maximum residues are <0.05 mg/kg in maize grain, forage and/or fodder, total conjugated and non-conjugated residues of bendiocarb and metabolites would be expected to be <0.05 mg/kg in cattle carcase meat, cattle fat and cattle meat by-products (except kidney) and <0.01 mg/kg (claimed limit of determination) in kidney, although a 0.2 mg/kg limit of determination may be more realistic for kidney. Residues in milk would not be expected to exceed the approximate limits of determination of 0.01 mg/kg and 0.02 mg/kg for non-conjugated and conjugated residues, respectively, or a total of 0.03 mg/kg. These estimates should also be adequate from feeding of rice. Data from the use of bendiocarb on grasses or as a dermal treatment on cattle suggests a possible need for higher limits than would be required for maize grain, forage and fodder if such uses are, or should become, good agricultural practice. Additional information on good agricultural practices are necessary before maximum residue estimates can be made for these uses. Any additional information should provide the formulation, application rate, number of applications, type of application and preharvest intervals or other restrictions. Depending on these uses, feeding studies at higher levels may be necessary before maximum residue levels can be estimated. Poultry meat, meat by-products and eggs Laying hens in groups of ten were fed (free access) a diet containing 0, 0.05, 0.15 and 0.5 mg/kg bendiocarb for 21 days to permit estimation of potential residues resulting from the feeding of maize grain, for which maximum residues of 0.05 mg/kg are assumed (Reary 1978b). Owing to analytical difficulties, information on the stability of residues over the feeding period was not provided. Information was not provided on storage conditions of the fortified pre-mix. Eggs were individually collected and labelled; 98 were analysed at higher feeding levels and later sampling intervals. Apparent total residues (corrected for recovery) of bendiocarb and metabolites (conjugated and non-conjugated) at all treatment levels were <0.02 mg/kg 1-21 days after treatment. The limit of determination was reported as approximately 0.02 mg/kg, supported by sample chromatograms, although pre-treatment controls were <0.013 mg/kg. Analytical recoveries of bendiocarb and unconjugated metabolites ranged from 44-85% (67% av.). Samples of breast muscle, leg muscle, liver, kidney, subcutaneous fat and heart were taken after sacrifice on day 21 of feeding the fortified diet, with completion of dissection the following day. The sum of bendiocarb and its major metabolites conjugated and non- conjugated, was determined. No hen tissue residues were found in excess of the claimed limits of determination of 0.02 mg/kg for legs, breast, liver and subcutaneous fat and 0.05 mg/kg for kidney and heart. Sample chromatograms tend to confine these limits of determination, although apparent residues near the claimed limits of determination in untreated controls of breasts (<0.016 mg/kg), liver (<0.014 mg/kg) and fat (<0.016 mg/kg) suggest that 0.05 mg/kg may be a more practical limit of determination for each of the tissues. As in cattle tissues and eggs, analytical recoveries were only marginally acceptable, ranging from 40-98% for bendiocarb or its major non-conjugated metabolites. Mean residues of bendiocarb and its non- conjugated metabolites (NC 7312 and N-hydroxymethylbendiocarb) ranged from only 56% in chicken legs to 79% in fat. Improved analytical methodologies are needed for commodities of animal origin. Mushrooms Supervised trials were conducted in The Netherlands and the U.K. In The Netherlands mushroom plots were presumably sprayed directly with a bendiocarb 50SC formulation and in the U.K. the plots were established the day following wall treatments with either a 50SC or 80W spray. No information was provided on approved agricultural practices for these uses, including preharvest intervals, although recommended wall spray application rates of 30-50 g/100 m2 (Table 2) were provided. In the first trials (Browne 1981a) a 50SC bendiocarb formulation was sprayed twice at rates of 50, 75 and 100 g a.i./100 m2 (5, 7.5 and 10 kg a.i./ha), first after spawning and the second after casing. Harvest was 21 days after the last treatment. Residues of bendiocarb and non-conjugated NC 7312, corrected for mean recoveries, are summarized in Table 5. Maximum residues were 0.013 mg/kg and 0.04 mg/kg, respectively, for bendiocarb and NC 7312 at the highest application rate. Residues increase with increased application rate and residues of NC 7312 tend to be less than those of bendiocarb under the test conditions. In the series of trials in the U.K., (Browne, 1982a) mushroom plots were established the day following hut wall treatments with either 50SC or 80W bendiocarb formulations at application rates of 20-53 g a.i./100 m2. Harvest was 26-69 days after the treatments, which reflected the recommended application rates. Bendiocarb residues ranged from <0.02 to 0.09 mg/kg and NC 7312 from <0.02 to 0.13 mg/kg, both corrected for recoveries (see Table 5). In contrast to the trials discussed above, residues of NC 7312 in these trials were of the same order of magnitude as for bendiocarb. The limit of determination for bendiocarb in mushrooms was reported to be 0.01-0.02 mg/kg for bendiocarb or NC 7312, depending on the trials. Based on apparent residues of 0.04 mg/kg of bendiocarb and 0.02 mg/kg of NC 7312 in more than one untreated control, limits of determination of 0.05 mg/kg may be more practical. Analytical recoveries averaged approximately 82% for bendiocarb and 73% for non- conjugated NC 7312 from fortifications of both at 0.04-0.2 mg/kg, although standard deviations were 14-19. As no information was available even on recommended uses for bendiocarb other than for wall treatments, data from wall treatments are more pertinent to the estimation of maximum residue levels. Based on recommended application rates, the available residue data are consistent with a maximum residue level of 0.1 mg/kg for bendiocarb per se and 0.2 mg/kg if NC 7312 is also included. This is based on the assumption of minimum application to harvest intervals. Information on nationally approved agricultural practices for bendiocarb use on mushrooms is needed. Additional data from supervised trials are desirable. FATE OF RESIDUES Metabolism studies have been carried out in a range of plants and animals and in soil. In most plant species examined, the major metabolites formed are glycoside conjugates of the phenol NC 7312 and N-hydroxymethyl bendiocarb. Metabolism in animals generally involves cleavage of the carbamate ester group to yield NC 7312, which is excreted as sulphate and beta-glucuronide conjugates. In soil under aerobic conditions, the only extractable radioactivity is unchanged bendiocarb, degradation occurring to CO2, and an unidentified bound residue. Under anaerobic conditions, bendiocarb is hydrolysed to NC 7312. In animals For discussions on the metabolic fate of bendiocarb in the rat, dog, hamster, rabbit, mouse and humans, see "Biochemical Aspects". Residue feeding and/or dermal studies on cattle and/or poultry have been discussed under "Residues from Supervised Trials". In addition to the aforementioned studies, the metabolic fate of bendiocarb has been investigated in the pig, cow and hen. Pig Pigs were orally dosed once by gelatin capsule at 0.2 mg/kg/bw with 14C-bendiocarb (Adcock et al 1976b). Urine samples were collected over a period of four days, after which the animals were sacrificed and samples of liver, kidney, muscle, perirenal fat and subcutaneous fat were taken. Seventy-eight percent of the administered dose was excreted in the urine as equal levels of sulphate and ß-glucuronide conjugates of NC 7312 within one day and 84% within four days. No residues of unchanged bendiocarb were detected. Corresponding residues in faeces were 2.4 and 7.2% for a total recovery of 91.5% of administered radioactivity recovered in urine and faeces after four days. The residues in faeces were not identified. No residues were found in tissues at the 0.01 mg/kg limit of sensitivity for bendiocarb equivalents. The finding of relatively large levels of NC 7312 sulphate was of considerable interest, since phenolic sulphates are generally minor in pigs. The metabolism is similar to that in humans and the rat, involving cleavage of the carbamate ester to yield NC 7312, which becomes conjugated as sulphates and glucuronides. Cow A lactating dairy cow was given 14C-bendiocarb by a single gelatin capsule at a dose of 0.2 mg/kg/bw (Adcock et al 1976a). Urine was collected at intervals of 4-96 hours after dosing and faeces every 24 hours. Milk was collected morning and evening until sacrifice on the fourth day, at which time samples of liver, kidney, muscle, heart, perirenal fat, omental fat and subcutaneous fat were taken for analysis. Milk was separated into lactose, fat and casein fractions. No residues of unchanged bendiocarb were found in the urine. Seventy-nine percent of the administered radioactivity was excreted in the urine within eight hours and 92% after two days, after which little was excreted in urine. Corresponding residues in faeces were 5.3% at one day and 12.3% after two days. The urinary metabolites were determined to be sulphate and glucuronide conjugates of NC 7312 at 90% and 10% each, respectively. Residues in faeces were not identified. Bendiocarb equivalents were found in milk the first day up to a level of 0.002 mg/kg, but none were detectable thereafter. Over 80% was in the lactose fraction, 2% in the hexane fraction and most of the remainder in the casein fraction. Tissue residue levels were below the 0.01 mg/kg limit of sensitivity as bendiocarb equivalents. Metabolism in the cow appears to be similar to that in the rat, human and pigs. Poultry Three laying hens were each dosed once with 14C-bendiocarb by oral gavage at 0.25 mg/kg/bw (equivalent to 5 mg/kg in the diet) and excrement and eggs collected at intervals from 24-96 hours after dosing. Liver, kidney, muscle and fat samples were taken at sacrifice four days after treatment (Lewis and Challis 1978). Sixty-one to 90% of administered radioactivity was excreted within 24 hours, and 73-91% within 4 days. Recovery was inexplicably low (73%) in two of the hens. Losses were presumed to be due to expiration and/or losses during dosing or excrement collection, since residues in tissues were low. However, as a percent of radioactivity excreted in the first 24 hours, residues were 10-57% free NC 7312, 26-63% NC 7312 conjugates, 12-19% unidentified unhydrolysed water soluble residues, 2-5% other non-polar metabolites and 1-3% other unidentified conjugates. Conjugation of NC 7312 occurred more rapidly in the hen in which radioactivity excretion was more rapid and complete. Radioactivity in egg white and yolk represented only 0.01% of the administered dose. The maximum bendiocarb equivalent was highest in egg white on the first day (max. 0.009 mg/kg) and on day four in yolk (0.003 mg/kg), both above the limits of sensitivity. The maximum bendiocarb equivalent was 0.004 mg/kg in liver and fat, 0.002 mg/kg in kidney and below the 0.001 mg/kg limit of sensitivity in leg and breast muscle. In Plants Metabolism studies have been carried out in sugarbeet, maize, rice, barley and oilseed rape, both in the laboratory and under field conditions. A variety of separative, determinative and conjugative hydrolysis steps were utilized. In all these crops, the major identified metabolite was the phenol NC 7312, with lower levels of N-hydroxymethylbendiocarb, both primarily as glycoside conjugates. In some of the crops studied, sampling at harvest showed small quantities of unconjugated N-hydroxymethylbendiocarb. Three metabolism studies were conducted in sugarbeets. In one study, radioactive bendiocarb was applied under greenhouse conditions to the potted soil or to the leaves by direct syringe applications (Challis 1975). Residues were characterized in the plant tops only. Metabolic products were qualitatively similar in both cases, resulting in residues of free bendiocarb, bendiocarb glycoside, free NC 7312 (foliar application only), NC 7312 glycosides, N-hydroxymethylbendiocarb, N-hydroxymethylbendiocarb glycosides, unidentified glycosides, unidentified water soluble residues and unextractable unidentified fibre-bound residues. The major metabolites from soil application were glycoside conjugates of NC 7312 and N-hydroxymethylbendiocarb. Trace amounts of free N-hydroxymethylbendiocarb were also found. Unidentified residues accounted for 36 and 67% of radioactivity 8 and 34 days after treatment, respectively, with a ratio of about 1:3 water soluble to fibre-bound residues. From foliar applications, over 93% of leaf-applied bendiocarb was present on the leaf surface after 34 days. A bendiocarb glycoside was the major metabolite. Unidentified residues accounted for 48% of the total residue after eight days, but this was reduced to 25% after 34 days. Low levels of free NC 7312 were also present. The proposed metabolic pathway for bendiocarb in sugarbeet tops is illustrated in Figure 1. Except for the omission of substantial at-harvest
unidentified water soluble and fibre-bound residues, other metabolism studies discussed below suggest that the pathway is similar in other plants. In a second sugarbeet metabolism study (Adcock 1976), 14C-bendiocarb was applied as a seed dressing for plants grown in outdoor drums in sandy loam soils at 6.7 and 7.5 pH values at a rate equivalent to 16 g a.i./kg seed. Leaves and/or roots were analysed for radioactivity at intervals from 13-114 days after sowing, although the residues were not identified. In accordance with decreased bendiocarb stability in more alkaline soils, extractable and fibre-bound residues were less than the 0.02 mg/kg limit of detection (bendiocarb equivalents) in foliage and roots of the more alkaline soil after 114 days. Residues were greater at earlier intervals. For example, at 36 days residues were on the order of 0.1 mg/kg bendiocarb equivalent in leaves or roots from either extractable or fibre-bound sources. Consistent with pH stability, residues were higher in the more acidic soil, being up to 0.06 mg/kg and 0.02 mg/kg extractable residues in leaves and roots, respectively, after 114 days; they were appreciably higher at shorter intervals. A maximum of 18% of applied radioactivity was found in immature sugarbeet (36-72 days after sowing). In the third sugarbeet metabolism study (Challis and Adcock 1978), the crop was grown under field conditions and treated at sowing with 14C-bendiocarb granules at the recommended rate of 0.36 kg a.i./ha. Plants were harvested at intervals ranging from 46-190 days after treatment. Results were similar to those of Challis (1975). After 90 days, radioactivity was too low to permit determination of individual metabolite levels. In harvested beets, mean residues of only 0.009 mg/kg bendiocarb equivalent were found after 190 days. Extractable residues were below the limits of sensitivity. As would be expected, residues were greater at earlier intervals and identification was possible. For example, at 46 days residues (bendiocarb equivalent) were 1.0, 0.22, 0.14, 0.76 and 0.45 mg/kg for bendiocarb, NC 7312 conjugates, N-hydroxymethylbendiocarb conjugates, unidentified water soluble residues and fibre-bound residues, respectively. There were lesser amounts of free metabolites and other conjugates. Bendiocarb metabolism was investigated in maize under glasshouse conditions by applying a solution of 14C-bendiocarb to pH 5.4 soil in drums with newly germinated maize plants at a rate equivalent to 1.1 kg a.i./ha (Challis and Adcock 1977). Plants were analysed at intervals from 10-125 days. Mean residues of bendiocarb per se in plants ranged from 1.4 mg/kg after 10 days to 0.01 mg/kg after 125 days and unidentified soluble residue (bendiocarb equivalent) in kernels and cobs were 0.005 and 0.001 mg/kg, respectively, after 125 days. As a percentage of total radioactivity, the major residues after 10, 60 or 125 days were: Foliage Kernels Cob 10 days 60 days 125 days 125 days 125 days Bendiocarb 38.1 24.2 N-hydroxymethylbendiocarb 8.2 5.3 8 NC 7312 conjugates 163.3 2.7 20 Water soluble 13.6 11 9.1 (non-hydrolysable) Fibre-bound 13.6 27 61 89 97 Free NC 7312, other non-polar metabolites and other conjugates were also present at lower levels. Seventy percent of the residues in plants at harvest were either water non-hydrolysable of fibre-bound unidentified residues. Although they occurred at very low levels, fibre-bound unidentified residues constituted 89 and 97 percent of total radioactive residues in kernels and cobs, respectively, at harvest. Investigations were conducted on paddy rice metabolism of 14C-bendiocarb applied as a solution with a syringe under glass to either the foliage or flood water surrounding rice transplants (Lewis and Challis 1979). Application rates were equivalent to 0.6 kg a.i./ha and plant samples were taken at intervals ranging from 15-174 days after treatments. Foliage and grain were analysed separately at 174 days. Qualitatively, residues were similar to those in sugarbeet and maize, although N-hydromethylbendiocarb or its conjugates were not specifically identified in rice. They could have been present under residues described either as other non-polar metabolites or other conjugates. Mean free bendiocarb in rice plants ranged from 1.7 mg/kg after 15 days to 0.0022 mg/kg (total radioactivity as bendiocarb equivalents) after 174 days from the foliar treatments. The most abundant metabolite by far was NC 7312, mostly as a conjugate (0.006 mg/kg bendiocarb equivalent). Residues were 0.009 mg/kg in rice husks and flour after 174 days. In plants growing in treated water, residues of free bendiocarb at 15 days were approximately one tenth of that from foliar treatments, the major residue being NC 7312 conjugates at 0.54 mg/kg. Individual residues could not be determined after 60 days. At harvest, total radioactivity levels are similar regardless of the type of treatment. Quantitatively, major residues in plants as a percent of total radioactivity at 15 or 174 days are: 15 days 174 days Foliar Water Foliar Water Bendiocarb 37 12 NC 7312 13 37 39 31 conjugates Water soluble 7 10 (unhydrolysable) Fibre-bound 33 33 61 69 All of the radioactive residue at harvest in rice husks or flour was NC 7312 conjugates, regardless of whether application was by foliar or water treatment. As in the case of maize foliage, residues in rice plants were mostly unidentified fibre-bound ones at harvest. The difference was in the grain, which contained mostly unidentified fibre-bound residues in maize and mostly NC 7312 conjugates in rice. Greenhouse-grown barley plants were treated with 14C-bendiocarb at rates equivalent to 1 kg/ha. A solution was applied by pipette to soil surrounding the plants which were analysed at intervals ranging from 4-94 days after treatment. Samples at 94 days were separated into foliage, husks and grain, which were analysed separately (Challis and Swalwell 1980). Results of this investigation were similar to that of rice. However, in the case of barley, conjugates of N-hydroxymethylbendiocarb were identified, but total radioactive residues in husks and grain at 94 days (1.46 and 0.09 mg/kg bendiocarb equivalent, respectively) were not characterized. Free bendiocarb residues in foliage ranged from 0.09 mg/kg at 4 days, declined through 60 days and increased to <0.07 mg/kg at 94 days. Similar patterns were observed for conjugates of NC 7312 and N-hydroxymethylbendiocarb, the major components of the residue throughout the period. Again, unidentified water soluble or fibre-bound residues constituted a major part of the residue, which increased until harvest (12 and 42% of total radioactivity, respectively). The metabolism of 14C-bendiocarb was studied in greenhouse grown oilseed rape treated at the seedling stage at application rates equivalent to 140 and 500 g a.i./ha. Application was by pipette to soil surrounding the plant (Warner 1980). Plant samples were taken at intervals ranging from 5 to 140 days after treatment. At 140 days, samples were separated into foliage, pods, and seed, which were analysed separately. As in the case of barley, the major residues in the plants were highest at earlier intervals and, except for free bendiocarb, declined and then increased by harvest. In both cases this was probably due to plant growth patterns and dessication near harvest. Free bendiocarb was the major residue at day 5 (66-69%), but declined rapidly thereafter (2.5 mg/kg at day 5 to 0.01 mg/kg at 140 days from the high treatment rate). Again, conjugates of NC 7312 and N-hydroxymethylbendiocarb were the major identified metabolites and, by harvest, unidentified water soluble materials and fibre-bound residues formed the major portion of total radioactivity which was 26 and 43%, respectively, from the higher treatment rate. Although residue levels were dependent on the application rate, on the basis of percentage of total residue, results were similar at both application rates. Extractable residues in pods, seeds and foliage at harvest were 0.09, 0.001 and 0.16 mg/kg, respectively, at the low application rate and 0.74, 0.011 and 0.84 mg/kg, respectively, at the high rate. In Soil Laboratory studies on residue decline in a pH 7.7 sandy loam soil treated in flasks or jars with 5 mg/kg 14C-bendiocarb showed degradation to CO2 and unidentified bound residues under aerobic conditions, with a half-life of 5 days for the parent compound. No NC 7312 was detected. With flooding or nitrogen flushing and under sterile anaerobic conditions, bendiocarb was hydrolysed to NC 7312, with little or no further degradation (Adcock et al 1975a). In a laboratory soil leaching study with the same soil type, 60% of the radioactivity applied to a 30 cm column as 14C-bendiocarb was eluted with 50 cm of water over 11 days, mostly as NC 7312 (Adcock et al 1975b). Presumably, conditions were effectively anaerobic and the rapid degradation of bendiocarb did not permit estimation of its leachability. In another leaching study, 14C-bendiocarb, leachability was investigated for an agricultural sand (pH 5.3), a clay loam (pH 7.3), a sandy loam (pH 7.8) and a silt loam (pH 7.2) using soil column and thin-layer techniques (Adcock 1978). The 30 cm columns were percolated over a 2-9 day period with a 20 cm column of water. The percentage of radioactivity recovered in leachate was 75, 11.9, 7.9 and 0.8% for the respective soils, decreasing with increased organic content. Recovery in leachate was slightly less than for 2,4-D in agricultural sand and clay loam, and substantially less in the other two soils under similar conditions. Thin-layer results confirm these observations and show that NC 7312 is somewhat less leachable than the parent compound in all four soil types. It also shows that bendiocarb is more leachable than trietazene, which places it in the moderately mobile class. When bendiocarb 80%WP, 3%G and 1% dust formulations were leached from sand (pH 7-7.6) loamy sand (pH 6-6.5) and sand loam (pH 5.6-7.8) in 30 cm × 5 cm columns with 20 cm water over 48 hours, leachability was again inversely proportional to organic matter content of the soil (Reary 1975a; Browne and Reary 1979a, 1980a). As a percent of the amount applied, bendiocarb recovery in leachate ranged from 0 to 93% WP, 0.6 to 84% dust and 0 to 22% granular. From the same formulations leachate contained 0 to 25% bendiocarb and 0 to 68% NC 7312; 0 to 45% bendiocarb, 0 to 62% NC 7312 and 0 to 4% bendiocarb, 0 to 19% NC 7312, respectively. Therefore, leachability decreased in the order of WP, dust and granular formulations. Bendiocarb stability in standard soils has been shown to be dependent on soil pH, being much slower at low pHs (Reary 1975b). The half-life was 10 days in one soil at pH 2.2 and 58 days in another at pH 5.2. Soil residue decline studies have also been carried out in trials determining bendiocarb residues in turf and maize. Results again show that the rate of degradation of bendiocarb is pH-dependent. Repeated applications showed no evidence of a build-up of bendiocarb residues in soil. Dissipation rates (in days) for various formulations in various soil types and pHs are given in Table 9 (Browne and Reary 1978c; Reary 1975b, 1978f, g, k, 1980g; Reary and Whiteoak 1977a, b, d). In Storage and Processing It was noted under the section on "Residues from Supervised Trials" and in Table 6 that oil processed from maize with field- incurred residues of <0.02 mg/kg bendiocarb also contained residues of <0.02 mg/kg. In another investigation, 10G was applied as a band along the maize row at sowing at 1.1-2.2 kg a.i./ha and the maize sampled at normal harvest. Oil was solvent-extracted from the grain, which had residues of <0.01 mg/kg, the limit of determination. Analysis of the oil showed no residues in excess of the 0.05 mg/kg limit of determination (Reary 1978c). Investigation with radio-labelled bendiocarb in granular application trials in France, the U.K. and the U.S. showed residues in solvent-extracted oil to be 0.008, 0.011 and 0.021 mg/kg, respectively, from kernels with residues of 0.011, 0.013 and 0.022 mg/kg, respectively. In most kernel or oil samples residues were <2X the reported limit of sensitivity (Lewis and Adcock 1978a, b, c). RESIDUES ON FOOD IN COMMERCE OR AT CONSUMPTION No information was provided on residues in commerce or at consumption. The Meeting considered such information desirable. Table 9. Summary of Bendiocarb Dissipation Rates in Soil Soil Dissipation time (days) Type pH Formulation 50% 75% 90% Sandy loam 5.2 Technical1/ 58 ? ? Sandy 6.5 76W 25 50 75 loam 76W2/ 12-34 24-69 37-104 Sandy loam 6.5 5G2/ 26-70 52-140 78-210 Silty clay 6.5 10G 19 38 57 Silty clay loam 6.7 76W 30 60 ? Sand 6.8 Technical1/ 10 24 50 Loam 7.2 10G 7.5-10 15-20 22.5-30 Loam 7.7 76W 12 24 36 Sandy 7.7 76W 2.4 4.8 7.2 loam 76W2/ 2-5 3-10 5-15 Sandy loam 7.7 5G2/ 12-26 30-52 45-78 Sandy loam 7.8 3G 12 24 36 1/ Laboratory studies. 2/ Multiple applications at up to 5-monthly intervals; dissipation times determined after each application. METHODS OF RESIDUE ANALYSIS Residue analysis methods for various plant substrates have been developed for bendiocarb alone or for bendiocarb plus the non- conjugated metabolite NC 7312, either separately or as a total residue. In animal substrates, enzymic liberation of NC 7312 from conjugates is more successful than in plants. Consequently, residue methods for animal tissues, milk and eggs include determinations of the conjugated residues. As the carbamate functional group does not possess strong electron capturing properties, derivatization of the bendiocarb molecule is necessary to facilitate the measurement of low residue concentrations. Formation of the 2,4-dinitrophenyl ether was found to be most suitable. This results in a product with strong electron capturing properties and a long gas chromatographic (GLC) retention, thus ensuring excellent sensitivity and minimal co-extractive interference. In the standard procedure (Reary 1975c) the carbamate is hydrolysed in an alkaline buffer containing 1-fluoro-2, 4-dinitrobenzene so that the dinitrophenyl ether is formed immediately after hydrolysis. This method has the added advantage the phenolic degradation product, NC 7312, forms the same product in the reaction. Thus, the combined residue can be measured unless bendiocarb and NC 7312 are separated prior to derivatization. This separation is readily effected by high pressure liquid chromatography (HPLC) or with commercially available liquid chromatographic cartridges. Collection of the appropriate fraction allows individual analysis for bendiocarb and NC 7312 from the same extract (Brown and Reary 1979b). Bendiocarb is extracted from soil (Reary 1978d), grass (Reary 1978e) sugarbeet (Reary 1975c), maize (Browne and Reary 1979c), cereal grain (Reary 1979b), rice (Browne and Reary 1979b), rape seed (Browne and Reary 1980b), potatoes (Reary 1979c), cabbage (Browne 1981b), mushrooms (Browne 1982a), apples/pears (Browne 1982b) and peas (Browne and Manley 1982), under reflux with dichloromethane or by shaking with diethyl ether. Oily extracts are improved by partition between hexane and acetonitrile. Further clean up, when required, is by silica gel chromatography. This is easily done using commercially available disposable cartridges, which can eliminate or separate any NC 7312 present in the extract. A method has been developed for the residue analysis of bendiocarb and major metabolites in milk, eggs, meat, fat and offal (Browne and Reary 1978b). Residues are extracted under reflux with acetonitrile. Conjugated metabolites are hydrolysed with snail digestive juice before formation of the dinitrophenyl derivative. All major bendiocarb related metabolites form the same derivative, which is then analysed by the standard method as a total residue. In general, mean analytical recoveries in most commodities were >75% for bendiocarb and >60% for NC 7312. Analytical sensitivities, recoveries, recoveries of fortified commodities and apparent residue in untreated controls for individual commodities are discussed under "Residues Resulting from Supervised Trials." Information represents field-type conditions and is somewhat less assuring than mean recoveries presented with the reports on each individual analytical method. Although mean analytical recoveries appeared acceptable, at least for bendiocarb per se, the range of residues was generally large, resulting in standard deviations ranging from 6 to 33. In animal tissues in particular, and to some extent in cereal grains and fodder/forage, analytical recoveries were frequently low. For example, in animal products analytical recoveries were frequently only 50-60% for bendiocarb per se or the N-hydroxy metabolite, and sometimes less. NATIONAL MAXIMUM RESIDUE LIMITS Information on national maximum residue limits were available from only one country. Limits have been proposed in four other countries (Table 10). Table 10. National Maximum Residue Limits Country Commodity MRL (mg/kg) Netherlands1/ "All commodities"3/ 0 (0.05)4/ Australia2/ Poultry meat, eggs 0.05 Milk, milk by-products, meat and other edible offal 0.1 Cereal grain 10.0 Belgium2/ Maize and sugarbeet 0.02 Switzerland2/ General foodstuffs (excl. milk) 0.2 Milk 0.005 U.S.2/ Maize (grain fodder, forage) 0.05 Maize oil 0.1 Milk, eggs, meat fat, meat by-products (except kidneys) of cattle, goats, pigs horses, poultry, sheep 0.05 Kidneys of cattle, goats, pigs, horses, poultry, sheep 0.1 1/ Established; 2/ Proposed; 3/ It is unclear whether "all commodities" include commodities other than maize and sugarbeet, for which good agricultural practice information was provided; 4/ 0 (0.05) mg/kg presumed to mean no residues allowed with a 0.05 mg/kg limit of determination. Large-scale use. APPRAISAL The Meeting reviewed substantial information on residue levels from supervised trials in a variety of commodities, fate of residues and analytical methodology for bendiocarb, a carbamate pesticide used for control of a wide range of agricultural and public health pests. Information on official nationally approved agricultural practices and national maximum residue limits were available for only two commodities (maize and sugarbeet) in one country, although recommended application rates were provided for a number of commodities. Since information on good agricultural practices for all commodities except maize and sugarbeet is lacking, only TMRLs are estimated for other than these two commodities. National tolerances have been proposed in at least four countries, mostly on maize and other cereals and animal products. Residue data were available from supervised trials on a variety of commodities in several countries and using a variety of formulations and agricultural practices. In most cases, free bendiocarb per se was the only residue measured. In a few cases, the major metabolite 2,2-dimethyl-1,3-benzoxodiol-4-ol (NC 7312) was measured in its free form and in some cereals, combined residues of conjugated NC 7312 and N-hydroxymethylbendiocarb were measured as well. Data were inadequate for estimating a limit for oilseed rape, cabbage and peas, although the Meeting was informed that additional data are being compiled for the latter. For root or tuber vegetables, data were available for potatoes and sugarbeet. Data on potatoes show residues of free NC 7312 at harvest to be up to 20 times that of the parent compound (average 6X). This rate could not be determined for sugarbeet with available data. Limited data were available in pome fruit from one country and residues of NC 7312 were equal to or less than those of the parent compound. The Meeting was informed that additional data are being gathered. Bendiocarb residue data on cereals were available for barley, oats, wheat, maize and rice. For the latter, limited data were also available for free NC 7312, and the first three, for combined residues of conjugates of NC 7312 and N-hydroxymethylbendicarb. Data were mostly from seed treatments in barley, oats and wheat. No data were available for metabolites in maize, although metabolism studies have shown >50% of residues in foliage to be metabolites and/or unidentified water-soluble or bound residues; in kernels at harvest, approximately 90% of radioactivity was unidentified fibre-bound residues. Analytical recoveries were only marginally acceptable in some cereal trials, especially those in wheat. Considerable data were available for grass and turf, mostly at higher than recommended rates. Half-lives were greater from granular broadcast applications than from spray applications and irrigation did not significantly affect decline rates for either. As in maize, data for oilseed rape were for the parent compound only, and metabolism studies showed >50% of residues at harvest to be conjugated metabolites and (mostly) unidentified water-soluble or fibre-bound residues. Data were available for mushrooms from spray treatments (plot presumed) and wall treatments (before plot establishment). Residues increased with application rates and residues of free NC 7312 from wall treatments were on the same order of magnitude as those of the parent compound, but were less following direct spray treatment. No information was provided on good agricultural practices for direct spray treatment. Animal feeding trials were conducted in which lactating dairy cattle were fed diets for 28 days containing up to 25 mg/kg bendiocarb. In contrast to field trials, in which the parent compound was determined separately from metabolites, animal tissues were analysed for total residues of free bendiocarb and non-conjugated metabolites plus conjugated NC 7312 and N-hydroxymethylbendiocarb. Milk was separated into a fat fraction and lactose (aqueous) fraction. The fat fraction was analysed for bendiocarb and non-conjugated NC 7312 and N-hydroxymethylbendiocarb and the lactose fraction for the conjugated residues of the two metabolites. Studies using topical treatments were also conducted, but no information was provided on approved or recommended uses for such treatments. Dermal treatments generally resulted in higher residues in tissues and milk than feeding trials. In the absence of good agricultural practice information for dermal treatments (or grass uses) residue estimates in cattle are based on potential residues from the feeding of maize, for which national good agricultural practice information was available. From this potential source of exposure, no residues are expected in products of animal origin above the limit of determination at or about 0.05 mg/kg (0.2 mg/kg in kidney). In animal products in general, analytical recoveries were disappointingly low, frequently only 50-60% or less for some residues in some tissues, and thus can be considered marginally acceptable for enforcement purposes only, since residues are expected to be relatively low as a result of uses considered in residue level estimates. Animal metabolism studies were conducted in the rat, dog, hamster, rabbit, mouse, pig, cow and poultry and in humans. In the pig, cow and poultry single dosing was with 14C-bendiocarb, by gelatin capsule in pig and cow and by gavage in poultry. Approximately 80% of applied radioactivity was eliminated in the urine within one day or less in pigs and cows and 61-90% in poultry. It consisted mostly of the sulphate or glucuronide conjugates of NC 7312 in all three, although in poultry significant levels of unidentified water-soluble residues were also present, as well as low levels of free NC 7312 and other unidentified moieties. Low levels of NC 7312 sulphate and glucuronide were also present in faeces of cows and pigs. In pigs the NC 7312 sulphate to glucuronide ratio was unexpectedly high. In animal tissues and milk, residue levels were generally not far from the limit of determination and only 0.01% of the administered dose was found in eggs. Owing to the low levels, they were not identified. Bendiocarb metabolism in cows, pigs and poultry appears to be similar to that in smaller animals. Carbamate is hydrolysed to NC 7312, which forms glucuronide and sulphate conjugates. The apparent major difference is the lack of conjugates of N-hydroxymethylbendiocarb also found in plants, and 5,6, or 7-hydroxybendiocarb found or tentatively identified in the smaller animals. However, dosing rates of 0.2-0.25 mg/kg bw in cows, pigs and hens were substantially less than the maximum dosage rates of 10 mg/kg bw used for the smaller animals. More importantly, cows, pigs and poultry were sacrificed four days after dose administration, which precludes measurement or characterization of additional radioactivity closer to administration. This could also account for residue levels in animal products (cows, pigs and poultry) being too low for identification. A metabolism study conducted in both ruminants and poultry at high levels and a much shorter sacrifice interval would have been preferred and are desirable. Such a metabolism study should be considered essential if higher than the current ones for animal products are required from the feeding of grain, fodders or straw of cereals. Metabolism studies in sugarbeet, maize, barley, rice and oilseed rape under laboratory or field conditions showed similar quantitative results, although ratios of the various metabolites and degradation products varied considerably, depending on the plant, type of application, interval from application to harvest, part of plant and other factors. A major metabolic pathway for bendiocarb in some plants is hydrolysis to NC 7312, which becomes conjugated as a glycoside. In another pathway, bendiocarb can first be oxidized to N-hydroxymethylbendiocarb, which may hydrolyse to NC 7312 before glycosidic conjugation or become conjugated as N-hydroxymethylbendiocarb glycoside. Another route can be direct glycosidic conjugation of bendiocarb per se. This was a major residue in beet leaves following a surface application, but NC 7312 conjugates were found following surface treatments to rice. Undoubtedly other pathways exist, since low levels of unidentified conjugates are known to occur. In one beet study, limited leaf penetration was detected from surface application. As the interval from application to harvest increased, residues of bendiocarb per se decreased with an increase in NC 7312 and N-hydroxymethylbendiocarb conjugates, which were frequently the major identified metabolites. Unidentified water-soluble, non-hydrolysable residues and unidentified fibre-bound residues have also been shown to increase in the foliage of several plants; at harvest they constitute 26 and 60%, respectively, of the total remaining radioactivity. In maize kernels and cobs at harvest the fibre-bound unknown was shown to consist of >90% of the remaining low residue. Low levels of free NC 7312 and other unidentified unconjugated residues were found in some plants. Free NC 7312 exceeded that of the parent compound in potatoes and probably in pea pods. In other plants, free NC 7312 residues were either less than or equal to that of the parent compound. Differences in method of application (for example, foliar versus ground application) affected the ratios of the various metabolites in some, but not all, plants tested, although residues were qualitatively similar. In soils, bendiocarb was degraded to CO2 and unidentified bound residues under aerobic conditions whereas degradation was mostly to NC 7312 under anaerobic conditions. Bendiocarb stability was dependent on soil pH, being much more stable under acidic conditions. Half-lives ranged from 2-70 days, depending on conditions. Leaching studies carried out on a variety of soils, under different conditions and with several formulations showed leaching to be largely dependent on the organic content of the soil, decreasing with higher levels of organic matter. Although generally considered to be in only a moderately leachable category, significant leaching of bendiocarb can occur in sandy soils with low organic matter content. Leachability appears to increase somewhat from granular to dust to wettable powder formulations. One study indicated that NC 7312 leached slightly less than bendiocarb per se. Although build-up of soil residues of bendiocarb per se do not appear to be indicated, any potential residues of bendiocarb or its metabolites in ground water would be greatest from sandy soils of low organic matter content. Most investigations on possible residues of bendiocarb in processed products were conducted on oil, husks or flour from cereal grain. Although no concentration of residues was demonstrated in these studies, residues in the grain from which the products were processed had residues below or near the limits of determination. Therefore, firm conclusions cannot be drawn. Analytical methods are available for the determination of free bendiocarb in all plant commodities examined and free NC 7312 in some. In the basic procedure, bendiocarb is hydrolysed to its phenol under alkaline conditions in the present of 1-fluoro-2,4-dinitrobenzene to form the dinitrophenyl ether, which is preferably determined by electron capture gas chromatography using an internal standard. Bendiocarb and NC 7312 can be determined together or separately, if they are separated by HPLC or silica gel chromatography prior to derivitization. In most commodities of plant origin, field trials were for the free parent compound only and free NC 7312 was also determined separately in a few. Analytical recoveries were highly variable on some commodities, especially cereals. For animals, the same basic analytical approach is used, except that a hydrolysis step is included to hydrolyse conjugated residue. Hydrolysis has been accomplished by a variety of enzymatic and/or acidic conditions. Enzymatic approaches are preferred and snail gastric juice is frequently used. In contrast to plants, residues determined for animal tissues and milk include the sum of residues of bendiocarb and non-conjugated metabolites plus conjugated NC 7312 and N-hydroxymethylbendiocarb. Aqueous (lactose) and non-aqueous (fat) fractions of milk are analysed separately. Analytical recoveries for products of animal origin are only marginally acceptable for enforcement purposes. Improved analytical methods are needed for any uses requiring maximum residues levels in products of animal origin that are higher than the current limits of determination. RECOMMENDATIONS The Meeting considered information on residues resulting from good agricultural practices or recommended application rates on a number of commodities and possible residues in animals resulting from the feeding of grain, fodders or straw of cereals treated according to good agricultural practice and concluded that the maximum residue levels or temporary maximum residue levels below are suitable for establishing maximum residue limits. Regardless of the status of the ADI, temporary status was designated for all commodities except maize, maize fodder and forage, sugarbeet and sugarbeet tops, pending availability of good agricultural practice information. Except for potatoes, some fruit, rice and rice straw, estimated residue levels apply to treatment before planting and/or seed application only. In the absence of good agricultural practice information, the temporary limits are based on supervised trials data only. Residues for products of plant origin refer to residues of unconjugated bendiocarb. Residues in products of animal origin refer to the sum of free and conjugated bendiocarb, NC 7312, and N-hydroxymethylbendiocarb, expressed as bendiocarb. Limitations or Interval TMRL last application to Commodity (mg/kg) harvest (days) Potatoes 0.051/ 100 (granular) 0 (spray) Sugarbeet 0.051/ 150 Sugarbeet tops 0.051/ 150 Pome fruit 0.021/ 50 Cereal Grains Barley 0.051/ 100 Oats 0.051/ 100 Wheat 0.051/ 125 Maize (field) 0.051/ 125 Rice (in husk) 2 10 Fodders and Straws Barley 0.051/ 125 Oats 0.051/ 100 Wheat 0.051/ 125 Maize 0.051/ 125 Rice 1 10 Mushrooms 0.12/ 50 (con't) Limitations or Interval TMRL last application to Commodity (mg/kg) harvest (days) Animal Products3/ Carcase meat of cattle 0.051/ Fat of cattle 0.051/ Meat by-products of cattle (except kidney) 0.051/ Kidney of cattle 0.21/ Milk 0.051/ Poultry 0.051/ Fat of poultry 0.051/ Poultry meat by-products 0.051/ Eggs 0.051/ 1/ At or about the limit of determination. 2/ Limit reflects maximum residues expected from wall treatments prior to establishment of plots. 3/ Limits reflect maximum residues expected from the feeding of cereal grains, fodders or straws harvested at given intervals from application to harvest. FURTHER WORK OR INFORMATION Required (by 1984) Information on nationally approved agricultural practices for the use of bendiocarb on all commodities for which limits are estimated, except for maize and sugarbeet. Desirable 1. Additional metabolism studies in ruminants and poultry at sufficiently high dosing levels and with sacrifice at a short interval after dosing, instead of several days thereafter, to permit a more complete characterization of residues in tissues, milk and eggs. The analyses should include all residues identified, or tentatively identified, in smaller animals and in plants. These studies should be considered required before new limits or future upward revisions of established ones on feed items are established significantly higher than at current limits of determination. The same is true should substantially higher limits on tissues, eggs or milk be required for approved dermal treatments. 2. Additional residue data, reflecting nationally approved uses especially on, but not limited to, mushrooms and pome fruit. 3. Information on the possible occurrence of residues in food in commerce or at consumption. REFERENCES Adcock, J.W. Investigation of residues in sugarbeet following the 1976 use of 14C-bendiocarb as a seed dressing. Fisons Report METAB/76/1. (Unpublished) 1978 The leaching of 14C-bendiocarb in four soil types. Fisons Report METAB/78/11. (Unpublished) Adcock, J.W., Bentley, A.P., Challis, I.R. and Pearce, J.C. The 1975a decline of NC 6897 in a sandy loam soil. Fisons Report METAB/75.2.(Unpublished) Adcock, J.W., Challis, I.R. and Pearce, J.C. Soil leaching of NC 1975b 6897 and degradation products. Fisons Report METAB/75/3. (Unpublished) Adcock, J.W., Challis, I.R., and Warner, P.A. The metabolism of 1976a 14C-bendiocarb in the dairy cow. Fisons Report METAB/76/23. (Unpublished) Adcock, J.W., Warner, P.A. and Challis, I.R. The metabolism of 1976b 14C-bendiocarb in the pig. Fisons Report METAB/76/19. (Unpublished) Browne, P.M. Residues of Bendiocarb and NC 7312 in mushrooms 1981a treated with a 50SC formulation in Holland, 1980. FBC Report RESID/8140. (Unpublished) Browne, P.M. Analytical method for residues of bendiocarb in 1981b cabbage. FBC Report RES/81/65. (Unpublished) 1981c Residues of bendiocarb in cabbage following repeat applications of a 50WP formulation in the Philippines, 1980-81. FBC Report RESID/81/53. (Unpublished) 1981d Residues of bendiocarb in rye grass after autumn applications of granular and seed treatment formulations in the U.K., 1980. FBC Report RESID/81/69. (Unpublished) 1981e Residues of bendiocarb and NC 7312 in potatoes sprayed with a wettable powder formulation (20W) in the U.K., 1981. FBC Report RESID/81/74. (Unpublished) 1982a Residues of bendiocarb and NC 7312 in mushrooms following wall spray treatment with 80WP or 50SC. FBC Report RESID/82/20. (Unpublished) 1982b Residues of bendiocarb and NC 7312 in apples and pears following treatment with 20W, 50W or 50SC formulations in the U.K., 1981. FBC Report RESID/82/41. (Unpublished) 1982c Residues of bendiocarb and NC 7312 in sugarbeet following application of a granular (3G) formulation in Italy, 1981. FBC Report RESID/82/13. (Unpublished) Browne, P.M. and Manley, J.D. Residues of bendiocarb and NC 7312 in 1982 peas and pea pods following treatment with a 50SC formulation in the UK, 1981. FBC Report RESID/82/61. (Unpublished) Browne, P.M. and Reary, J.B. Residues in milk and tissues following 1978a a 28-day feeding study with bendiocarb in dairy cows. Fisons Report RESID/78/58. (Unpublished) Browne, P.M. and Reary, J.B. Analytical method for residues of 1978b bendiocarb metabolites in milk and tissues of dairy cows. Fisons Report RESID/78/54. (Unpublished) 1978c Bendiocarb residue decline in soil after treatment of maize plots with a 10G formulation in Illinois, 1977. Fisons Report RESID/78/93. (Unpublished) 1979a Laboratory leaching study with a granular (3G) formulation of bendiocarb in three standard soils from West Germany. Fisons Report RESID/79/78. (Unpublished) 1979b Analytical method for residues of bendiocarb 7312 in rice grain and straw. Fisons Report RESID/79/22. (Unpublished) 1979c Improved method for the analysis of bendiocarb residues in maize grain, stover and whole silage plants. Fisons Report RESID/79/24. (Unpublished) 1979d Residues of bendiocarb in maize at different growth stages, after application of a 3G formulation in France, 1978. Fisons Report RESID/79/2. (Unpublished) 1980a Laboratory leaching study with a 1% dust formulation of bendiocarb in three standard soils from West Germany. Fisons Report RESID/800/111. (Unpublished) 1980b Analytical method for residues of bendiocarb in rape seed. Fisons Report RESID/80/59. (Unpublished) 1980c Residues in silage maize grown in the U.K. from seed dressed with bendiocarb, 1979. Fisons Report RESID/80/12. (Unpublished) 1980d Residues of bendiocarb in maize treated with a granular (3G) formulation in Italy, 1979. Fisons Report RESID/80/13. (Unpublished) 1980e Residues of bendiocarb in maize following the use of a granular (3G) formulation in West Germany, 1979 (2nd Report). Fisons Report RESID/80/20. (Unpublished) 1980f Residues of bendiocarb in rape seed after application of a granular (5G) formulation in Canada, 1979. Fisons Report RESID/80/60. (Unpublished) 1981 Residues of bendiocarb and NC 7312 in potatoes sprayed with a wettable powder formulation (20W) in West Germany, 1980. FBC Report RESID/81/9. (Unpublished) Challis, I.R. The metabolism of 14C-bendiocarb in sugarbeet. Fisons 1975 Report METAB/75/15. (Unpublished) Challis, I.R. and Adcock, J.W. The metabolism of bendiocarb in maize 1977 plants. Fisons Report METAB/77/32. (Unpublished) 1978 The metabolism of bendiocarb in sugarbeet grown under field conditions. Fisons Report METAB/78/19. (Unpublished) Challis, I.R. and Swalwell, L.M. The metabolism of bendiocarb by 1980 barley plants. Fisons Report METAB/80/9. (Unpublished) FBC Bendiocarb, submission to the Joint Meeting of the FAO 1982a Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues, FBC Limited, Registration Department, Saffron Walden, Essex, England 1982. 1982b Harvest residues of bendiocarb (NC 6897) in sugarbeet after application of a granular (3G) formulations. (Unpublished) 1982c Residues in grass following the use of bendiocarb (50SC) (CR 15 340) as a seed dressing or spray dressing or spray treatment in the U.K., autumn 1979. (Unpublished) Housden, M.C. and Reary, J.B. Bendiocarb residues in rice treated 1981 with a 50WP formulation in the Philippines during the 1980 dry season. FBC Report RESID/81/16. (Unpublished) Lewis, J.A. and Adcock, J.W. Investigation of residue levels in 1978a maize plants treated with 14C-bendiocarb in France. Fisons Report RESID/78/50. (Unpublished) 1978b Investigation of residue levels in maize treated with 14C-bendiocarb granules in the U.K. Fisons Report METAB/78/19. (Unpublished) 1978c Investigation of residue levels in maize plants treated with 14C-bendiocarb granules. Fisons Report METAB/78/7. (Unpublished) Lewis, J.A. and Challis, I.R. The metabolism of 14C-bendiocarb in 1978 the hen. Fisons Report METAB/78/28. (Unpublished) 1979 The metabolism of 14C-bendiocarb in paddy rice. Fisons Report METAB/79/1. (Unpublished) Netherlands. Information on pesticides included in the JMPR priority 1982 list provided by The Netherlands Government. Reary, J.B. Harvest residues of bendiocarb in sugarbeet following 1974 its use as a seed dressing. Fisons Report RESID/74/36, December 1974. (Unpublished) 1975a Soil percolation experiments with bendiocarb. Fisons Report RESID/75/12. (Unpublished) 1975b Laboratory study of bendiocarb degradation in two standard soils from West Germany. (Unpublished) 1975c Analytical method for residues of bendiocarb in sugarbeet. FBC Report RESID/75/26. (Unpublished) 1975d Bendiocarb (NC 6897) residue decline on laboratory grown rye grass sprayed with Ficam W. Fisons Report RESID/75/5. (Unpublished) 1975e Harvest residues of bendiocarb (NC6897) in sugarbeet following its use as a seed dressing in West Germany (1974). Fisons Report RESID/75/12. (Unpublished) 1978a Residues in milk and tissues following a 28-day feeding study with up to 25 ppm bendiocarb in the diet of dairy cows. Fisons Report RESID/78/101.(Unpublished) 1978b Residues in eggs and tissues following a 21-day feeding study with bendiocarb in laying hens. Fisons Report, RESID/78/59. (Unpublished) 1978c Residues of bendiocarb in laboratory-extracted oil from maize harvested after band application of a granular (10G) formulation in the U.S., 1977. Fisons Report RESID/78/95. (Unpublished) 1978d Analytical method for bendiocarb residues in soil. Fisons Report RESID/78/37. (Unpublished) 1978e Analytical method for bendiocarb residues in grass. Fisons Report RESID/78/61. (Unpublished) 1978f Bendiocarb residue decline on grass and soil after treatment of turf with repeated applications of a 76 WP formulation at 28-day intervals, in California and Massachusetts, 1977. Fisons Report RESID/78/9. (Unpublished) 1978g Bendiocarb residue decline on grass and soil after treatment of turf with repeated applications of a 5G formulation at 28-day intervals in California and Massachusetts, 1977. Fisons Report RESID/78/32. (Unpublished) 1978h Residues in maize grown in the U.K. from seed dressed with bendiocarb 80W, 1977. Fisons Report RESID/78/86. (Unpublished) 1978i Residues of bendiocarb in maize treated with a granular (3G) formulation in the U.K., 1977. Fisons Report RESID/78/97. (Unpublished) 1978j Residues in maize grown in France during 1975, 1976 and 1978 from seed dressed with bendiocarb 80W. Fisons Report RESID/78/106. (Unpublished) 1978k Bendiocarb residue decline in soil after band treatment of maize plots with a 10G formulation in Missouri, 1977. Fisons Report RESID/78/50. (Unpublished) 1978l Residues of bendiocarb in maize (corn) at different growth stages, after band application of a 10G granular formulation in Missouri, 1977. Fisons Report RESID/78/51. (Unpublished) 1978m Residues of bendiocarb in maize (corn) at different growth stages, after band application of a granular (10G) formulation in Illinois, 1977. Fisons Report RESID/78/60. (Unpublished) 1978n Residues of bendiocarb in the mature maize crop (grain, cobs and stover) after band application of a granular (10G) formulation in regions of the U.S., 1977. First Revision, Fisons Report RESID/78/61/1. (Unpublished) 1979a Residues in milk from cows treated dermally with FICAM D in Australia, 1979. Fisons Report RESID/79/49. (Unpublished) 1979b Analytical method for bendiocarb residues in barley, wheat, oats and maize (corn) grain. Fisons Report RESID/79/17. (Unpublished) 1979c Residues of bendiocarb and NC 7312 in potatoes treated with a granular (3G) formulation in the U.K., 1978. (Extract of analytical method from the above report). Fisons Report RESID/79/9. (Unpublished) 1979d Residues of bendiocarb and NC 7312 in potatoes treated with a granular (3G) formulation in the U.K., 1978. Fisons Report RESID/79/9. (Unpublished) 1979e Residues of bendiocarb in barley, wheat and oats grown from treated seed in the U.K., 1977 and 1978. Fisons Report RESID/79/3. (Unpublished) 1979f Residues of bendiocarb in silage maize treated with a granular (3G) formulation in the U.K., 1978. Fisons Report RESID/79/12. (Unpublished) 1979g Residues in silage maize grown in the U.K. from seed dressed with an 80W formulation of bendiocarb, 1978. Fisons Report RESID/79/13. (Unpublished) 1979h Harvest residues of bendiocarb and NC 7312 in sugarbeet after application of a granular formulation (3G) in the U.K., 1978. Fisons Report RESID/79/14. (Unpublished) 1979i Residues of bendiocarb and NC 7312 in sugarbeet after application of a granular (3G) formulation in France and Italy, 1978. Fisons Report RESID/79/15. (Unpublished) 1979j Residues of bendiocarb in maize treated with a granular (3G) formulation in Italy, 1978. Fisons Report RESID/79/16. (Unpublished) 1979k Residues of bendiocarb and NC 7312 in rice treated with a granular (3G) or spray (50W or 80W) application in the Philippines, 1978. Fisons Report RESID/79/23. (Unpublished) 1979l Residues of bendiocarb in maize (corn) grown in the U.S., from seed dressed with a 76WP formulation, 1977 and 1978. Fisons Report RESID/79/25. (Unpublished) 1979m Residues of bendiocarb in maize (corn) after band application of a granular (10G) formulation in Canada, 1978. Fisons Report RESID/79/26. (Unpublished) 1979n Residue analysis of fodder beet following the use of bendiocarb as a seed dressing in West Germany, 1978. Fisons Report RESID/79/45. (Unpublished) 1979o Residues of bendiocarb in silage and mature (grain and stover) maize after band application of a granular (10G) formulation in the U.S., 1978. Fisons Report RESID/79/57. (Unpublished) 1979p Residues of bendiocarb in maize following the use of a granular (3G) formulation in West Germany, 1979. Fisons Report RESID/79/76. (Unpublished) 1970q Residues of bendiocarb in sugarbeet following the use of a granular (3G) formulation in West Germany, 1979. Fisons Report RESID/79/75. (Unpublished) 1980a Residue in barley, wheat and oats following seed treatment with bendiocarb in the U.K., 1979 (80WP) batch 8A8, 50W spray or 15 181 and 3G or 15 094. Fisons Report RESID/80/80. (Unpublished) 1980b Bendiocarb residue decline on rangeland grass after ULV treatment (by air) with a 25% formulation (15 15 458) in Montana, U.S., 1980. Fisons Report RESID/80/95. (Unpublished) 1980c Preliminary report on residues in milk and tissues from dairy cows treated dermally with bendiocarb dust for 7 days. Fisons Report RESID/79/55. (Unpublished) 1980d Residues of bendiocarb in grass grown from treated seed in Australia, 1979. Fisons Report RESID/80/9. (Unpublished) 1980e Residues in grass following the use of bendiocarb as a granular (3G), seed dressing (80W) or spray (50W) treatment in the U.K., Spring 1979. Fisons Report RESID/80/11. (Unpublished) Reary, J.B. Residue decline in sugarbeet treated with bendiocarb 3G 1980f in the U.K., 1979. Fisons Report RESID/80/4. (Unpublished) 1980g Residue decline in soil after furrow application of bendiocarb 3G granules at Shelford, U.K., 1979. Fisons Report RESID/80/14. (Unpublished) 1980h Residue decline in maize treated with bendiocarb 3G in the U.K., 1979. Fisons Report RESID/80/17. (Unpublished) 1980i Residue decline in maize grown from seed dressed with bendiocarb in the U.K., 1979. Fisons Report RESID/80/18. (Unpublished) 1980j Residues in sugarbeet from grower trials with a granular (3G) formulation of bendiocarb in the U.K., 1979. Fisons Report RESID/80/29. (Unpublished) 1980k Bendiocarb residue decline on rangeland grass after low volume treatment with a 50SC formulation (CR 15 340) in Montana, U.S., 1979. Fisons Report RESID/80/37. (Unpublished) 1980l Residues in rice treated with bendiocarb formulations in the Philippines and Korea 1979. Fisons Report RESID/80/46. (Unpublished) 1981m Residues in grass following the use of bendiocarb as a seed dressing, granular or spray treatment in the U.K., 1980. FBC Report RESID/81/10. (Unpublished) Reary, J.B. and Browne, P.M. Residues of bendiocarb (NC 6897) in 1978 mature maize, after application of a granular formulation in France, 1976 and 1977. Fisons Report RESID/78/23. (Unpublished) Reary, J.B. and Whiteoak, R.J. Bendiocarb residue decline on soil, 1977a grass and thatch after treatment of turf with a 76WP formulation in Mississippi, 1976. Fisons Report RESID/77/43. (Unpublished) 1977b Bendiocarb residue decline in soil, grass and thatch after treatment of turf with a 76WP formulation in Ohio, 1976. Fisons Report RESID/77/52. (Unpublished) 1977c Bendiocarb residue decline on soil, grass and thatch after treatment of turf with a granular formulation in Ohio, 1976. Fisons Report RESID/77/61. (Unpublished) 1977d Bendiocarb residue decline on grass and soil after treatment of turf with a 76WP formulation in California and Massachusetts, 1977. Fisons Report, RESID/77/62. (Unpublished) Warner, P.A. The metabolism of 14C-bendiocarb in oilseed rape. Fisons 1980 Report METAB/80/20. (Unpublished)
See Also: Toxicological Abbreviations Bendiocarb (Pesticide residues in food: 1984 evaluations) Bendiocarb (Pesticide residues in food: 1984 evaluations)