It must be noted that the issue of a Data Sheet for a particular pesticide does not imply endorsement of the pesticide by WHO or FAO for any particular use, or exclude its use for other purposes not stated. While the information provided is believed to be accurate according to data available at the time when the sheet was compiled, neither WHO nor FAO are responsible for any errors or omissions, or any consequences therefrom.

The issue of this document does not constitute formal publication. It should not be reviewed, abstracted or quoted without the agreement of the Food and Agriculture Organization of the United Nations or of the World Health Organization.

Ce document ne constitue pas une publication. Il ne doit faire l'objet d'aucun compte rendu ou résumé ni d'aucune citation sans l'autorisation de l'Organisation des Nations Unies pour l'Alimentation et l'Agriculture ou de l'Organisation Mondiale de la Santé.

diflubenzuron (ISO, BSI and ANSI).

Difluron; Dimilin^R; DU 112307; ENT 29 054; Micromite;

OMS 1804; PDD6040-I; PH 60-40; TH 6040; Vigilante.

Diflubenzuron is a halogenated benzoylphenyl urea, an effective stomach and contact insecticide acting by inhibition of chitin synthesis and so interfering with the formation of the cuticle. It has no systemic activity in plants, and does not penetrate plant tissue, hence plant sucking insects are in general unaffected, forming the basis of its selectivity. All chitin-synthesizing organisms are sensitive to diflubenzuron.

Diflubenzuron is a white crystalline solid, the technical material is off-white to yellow crystals. The melting point of the technical material is 210-230 ºC, and of the pure form 230-232 ºC (both with decomposition).

The compound is sparingly soluble in water, 0.2 mg/litre at 20 ºC. In polar solvents the solubility is moderate to good depending on the degree of polarity.

No detectable decomposition after one week storage at 50 ºC; 0.1 mg/litre solution in water (pH 7) after three weeks has 8% decomposition.

Virtually non-volatile.

A wettable powder (25% AI); an oil-based dispersible concentrate (45% AI); suspension concentrate (48% AI) and a granular formulation locally used for specific situations.

Apple rust mite, codling moth, leaf miners, leaf rollers, pear suckers, winter moth, plum fruit moth, olive moth, citrus rust mite and weevil, cotton ball weevil and leaf worms, army worms, rice water weevil, rice leaf roller, mosquitos.

The recommended rate of application is 1.5-30 g AI/100 litre of water effective against: leaf-feeding larvae and leaf miners in forestry, top fruit, citrus, field crops including cotton and soyabeans, horticular crops. It is also effective against the larvae of sciaridae and phoridae in mushrooms (1 g/m² casing at case mixing, or as a drench in 2.5 litres of water to the finished casing); mosquito larvae (20-45 g/ha water surface); fly larvae as a surface application in animal housing (0.5-1.0 g/m² surface).

Diflubenzuron is non-toxic to plants. All chitin-synthesizing organisms show susceptibility to diflubenzuron.

Used against mosquito and fly larvae (see 1.4.3).

No recommended use.

In experimental animals, diflubenzuron is absorbed from the digestive tract and to a lesser extent through the skin. There is a saturable absorption mechanism in the rat gastrointestinal tract. Consequently, a large proportion of orally administered diflubenzuron is found in the faeces. Diflubenzuron has widespread distribution in the tissues, but it does not accumulate.

Not known, methaemoglobinemia has been demonstrated after oral, dermal and inhalatory exposure to diflubenzuron in various species.

The major route of elimination is via the faeces, ranging from 70 to 85% in cats, pigs and cattle. In sheep, elimination is roughly equally distributed between the urine and faeces. Urinary excretion in rats and mice decreases proportionally with increasing dosage level. Less than 1% of an oral dose is recovered in exhaled air. Only trace residues are found in milk.

The metabolic fate of diflubenzuron has been studied in various species. The major route of metabolism in mammals is via hydroxylation. Hydrolysis of diflubenzuron may occur at any of the three carbon-nitrogen bonds. In pigs and chickens the major route of hydrolysis is at the ureido bridge. In rats and cows the major metabolic pathway is hydroxylation. The major metabolites in sheep, swine and chickens are 2,6-difluorobenzoic acid and 4-chlorophenylurea; minor metabolites are 2,6-difluorobenzamide and 4-chloroaniline. In rats and cattle 80% of the metabolites are 2,6-difluoro-3-hydroxydiflubenzuron, 4-chloro-2-hydroxy-diflubenzuron and 4-chloro-3-hydroxydiflubenzuron. The metabolic studies indicate that little or no 4-chloroaniline is formed in rats or cattle.

Rat (M,F) >4640 mg/kg*

Mouse (M,F) >4640 mg/kg

Rat (M,F) >10,000 mg/kg

Rabbit (M,F) >4,000 mg/kg (50% paste)

Rat (M,F) >2,49 mg/L (actual)

Rabbit >3,75 mg/L (actual)

Mouse (M,F) >2150 mg/kg (actual)

* used in WHO classification

Diflubenzuron is not a skin irritant and not a skin sensitizer. It is marginally irritant to the eyes of rabbits.

Male rats received diflubenzuron (technical) by gavage in a daily dose level of 5000 mg/kg b.w. during 8 days. Met- and sufhaeomoglobin levels were significantly increased when compared with the control group. The increase of the methaemoglobin was about 6%.

After dermal application of technical diflubenzuron at a dose level of 70%, 1.5 ml/kg b.w. during 18 days to rabbits, the methaemoglobin level was increased. Rats were exposed daily for a one hour period to dust of diflubenzuron technical with an actual concentration of 0, 0.12, 0.87 and 1.85 mg/litre respectively. Exposures were repeated over a period of three weeks during 5 days per week. The methaemoglobin levels in male rats of the 2 lower concentrations and female rats of all test groups were significantly higher than those of controls.

Accumulation of compound: There is no accumulation.

Short-term: In mice administered diflubenzuron at levels of 16, 50, 400, 2000, 10000 and 50000 mg/kg feed for 13 weeks, met- and sulph-haemoglobin concentrations increased in all but the lowest dose group. Changes in other haematological parameters and alkaline phosphatase activity were apparent at higher dose levels. Compound related effects were noted on the weights of the liver and spleen. Liver lesions and haemosiderosis of the spleen and liver were observed.

Diflubenzuron was administered to rats at dietary levels of 10000 and 100000 mg/kg feed for 9 weeks followed by a 4-week withdrawal period. The formation of methaemoglobin occurred in both diet groups with approximately 5 to 8% of the available haemoglobin being transformed to methaemoglobin. After a withdrawal period of 4 weeks methaemoglobin concentration was less than 2%.

Levels of 0, 3.125, 12.5, 50 and 200 mg/kg diet were fed to rats for 13 weeks. At the highest dose level, haematocrit, haemoglobin concentration and the erythrocyte number were decreased while SGOT and SGPT were increased. Also an increase in the incidence of necrotic parenchymal cells and mononuclear inflammatory cell infiltration in the liver was observed. Similar histopathological changes were noted at 50 mg/kg feed in addition.

No treatment-related effects were noted in a 13 week dog dietary study at 0, 10, 20, 40 and 160 mg diflubenzuron/kg diet with the exception of elevated SAP and SGPT values at 40 and 160 mg/kg. After six weeks, met-haemoglobin and other abnormal pigments were observed in dogs fed 160 mg/kg with some recovery by 12 weeks of administration.

Long-term: Diflubenzuron was fed to groups of mice at dietary levels of 0, 16, 80, 400, 2000 and 10000 mg/kg feed during 91 weeks. There was no indication of a treatment related effect on survival, food consumption and body weight gain. Dosage related increases in methaemoglobin levels were found from week 26 onwards and in sulfhaemoglobin levels from week 52 onwards in the 80 mg/kg groups and higher. Increased liver and spleen weights, as well as an increased extramedullary haemopoesis were seen at 10000 mg/kg. There was no treatment-related effect on tumour incidence. NOEL was 16 mg/kg feed equivalent to 2.4 mg/kg b.w.

In rats, diflubenzuron was fed at concentrations of 0, 10, 20, 40 and 160 mg/kg feed for 104 weeks. Met-haemoglobin levels were increased in the high dose group of both sexes after 52 and 78 weeks. No increased incidence of tumours was observed. The no effect level was 40 mg/kg diet, equivalent to 2 mg/kg b.w./day.

Diflubenzuron was administered to dogs in gelatin capsules at dose levels of 2, 10, 50 or 250 mg/kg b.w. per day for 52 weeks. Dose related marginal increases in met- and sulfhaemoglobin were recorded from 10 mg/kg upwards. The NOEL based on the increase in met- and sulfhaemoglobin was 2 mg/kg b.w.

Carcinogenicity: In carcinogenicity studies in mice and rats at dietary levels up to 10000 mg/kg in the diet, there were no treatment-related effects on tumour incidence. Specifically, there were no mesenchymal neoplasms of the spleen or liver as observed in carcinogenicity studies with 4-chloroaniline, which is one of the minor metabolites.

Teratogenicity: No evidence of teratogenicity was observed in studies of pregnant rats and rabbits after gavage administration of diflubenzuron at doses of 0, 1, 2 and 4 mg/kg b.w. per day for days 6 to 15 or 6 to 18 of gestation, respectively.

Reproduction: In several reproductive toxicity studies on rats, mice, rabbits and three avian species, no effects were seen on reproduction and there was no embryotoxicity.

Mutagenicity: Diflubenzuron and its main metabolites have been examined in a variety of in vitro and in vivo mutagenicity tests. Neither diflubenzuron nor its major metabolites has a mutagenic effect.

Other: The minor metabolite, 4-chloroaniline, was shown to be positive in several in vitro mutagenicity assays using various end-points. It is carcinogenic in rats and mice. The neoplastic lesions related to administration of 4-chloroaniline were benign and malignant mesenchymal tumours in the spleens of male rats and haemangiomas and haemangiosarcomas, primarily in the spleen and liver of male mice.

No information for absorption, metabolism and elimination in humans is available.

Single: Not known.

Repeated: Not known.

No information available.

No information available.

No information available.

There are no reports of human poisoning with diflubenzuron.

The diflubenzuron metabolite, 4-chloroaniline, has been reported to cause methaemoglobinaemia in exposed workers and in neonates inadvertently exposed. Some individuals who are deficient in NADH-methaemoglobin reductase may be particularly sensitive to 4-chloroaniline and hence to diflubenzuron exposure.

In field experiments, fish kills have never been recorded.

A 5-day dietary study on the mallard duck and bobwhite quail with levels of up to 4640 mg/kg feed revealed no observable signs of toxicity. Small songbirds in the forest ecosystem were not affected after aerial application of diflubenzuron at 350 g/ha.

Aquatic invertebrates show variable responses to diflubenzuron. Molluscs are insensitive, the LC₅₀ being greater than 200 mg/litre. LC₅₀ for other invertebrates ranged from 1 to > 1000 μg/litre, reflecting the effects of the compound on juvenile, moulting stages. A MATC for Daphnia has been estimated at > 40 and < 93 mg/litre; as expected, larval mayflies and other aquatic insect juveniles are highly susceptible. Overspray of water bodies would be expected to kill some aquatic invertebrates. The oral and contact LD₅₀ for honey-bees is greater than 30 μg/bee. Honeybee colonies were not affected after aerial application of 350 g/ha diflubenzuron.

[For definition of categories see the "Introduction to data sheets".]

Formulations in Category 5: Should be transported and stored in clearly labelled, rigid leakproof containers, out of reach of children, away from food and drink.

Formulations in Category 5: No facilities other than those needed for the handling of any chemical are required.

All formulations: Containers may be decontaminated (for method see Section 4.3 of part 4). Decontaminated containers should not be used for food and drink. Containers that are not decontaminated should be burned or should be crushed and buried below topsoil. Care must be taken to avoid subsequent contamination of water sources.

Formulations in Category 5: Warning of workers to minimize contact is essential.

All formulations: Pilots and loaders should have special training in application methods. Flagman should wear overalls and a broad brimmed hat and be well away from the dropping zone.

Formulations in Category 5 - Minimum Cautionary Statement:

This formulation contains diflubenzuron, it may be poisonous if swallowed. Keep the material out of the reach of children and well away from foodstuffs, animal feed and food containers.

Maximum residue limits of 1 mg/kg for diflubenzuron have been recommended by the Joint FAO/WHO Meeting on Pesticide Residues. Acceptable Daily Intake was set at 0.02 mg/kg b.w.

Diflubenzuron is a halogenated benzoylphenyl urea of very low toxicity to mammals. It may be absorbed from the gastrointestinal tract and, to a lesser extent, through the intact skin and by inhalation of dust or spray mist.

No information. Closed systems and forced ventilation may be required to reduce, as much as possible, the exposure of workers to the chemical.

When opening the container and when mixing, care should be taken to avoid contact. Mixing, if not mechanical, should always be carried out with a paddle of appropriate length. The applicator should avoid working in spray mist and avoid contact with the mouth, skin and eyes. Splashes must be washed immediately from the skin or eyes, with large quantities of water. Before eating, drinking or smoking, hands and other exposed skin should be washed.

Persons exposed to diflubenzuron and associated with its application should wear protective clothing and observe the precautions described above in 4.1.3 under "Mixes and applicators".

With good application practice, subject to 4.2 below, other persons are not likely to be exposed to hazardous amounts of diflubenzuron.

Unprotected persons should be kept out of the treated area until the compound has dried.

Residues in containers should be emptied in diluted form into a shallow pit taking care to avoid groundwaters. The empty containers may be decontaminated by rinsing two or three times with water and scrubbing the sides. An additional rinse should be carried out with 5% sodium hydroxide solution which should remain in the container overnight. Impermeable gauntlets should be worn during the work and a soakage pit should be provided for the rinsings. Decontaminated containers should not be used for food or drink. Spillage of diflubenzuron and its formulations should be removed by washing with 5% sodium hydroxide solution and then rinsing with large quantities of water.

No clinical or laboratory signs of toxicity to man or other animals are known.

The person should stop work immediately, remove contaminated clothing and wash the affected skin with soap and water. If signs of illness appear, supportive therapy should be given. If a large quantity of the compound has been ingested and if the individual is conscious vomiting should be induced.

Diflubenzuron is a halogenated benzoylphenyl urea pesticide of low mammalian toxicity. The primary manifestation of its toxicity in a range oftest animal species is methaemoglobin indication.

Diflubenzuron is not sufficiently toxic to produce clearly recognizable clinical or laboratory signs of toxicity in man or other animals.

No information available.

If signs of poisoning appear after large amounts of diflubenzuron have been ingested, provide supportive therapy. Unless the patient is vomiting, rapid gastric lavage should be performed. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of water.

Not applicable since acute poisoning is not expected even with large ingested doses.

None.

None.

Product analysis may be performed by HPLC according to instruction given in CIPAC Proceedings 1981, 3, p.185. Residues of diflubenzuron in food may be determined also by HPLC or GLC after its conversion into a derivative (Rabenort B, et al. (1978), Anal Methods Pestic Plant Growth Regul 10: 57).

FAO/WHO (1986), Pesticide Residues in Food - 1985 Evaluations, Part II - Toxicology. FAO Plant Production and Protection Paper 72/2, Rome, Food and Agriculture Organization of the United Nations.

Registry of Toxic Effects of Chemical Substances. (NIOSH) Y 6200000 MEDLARS.

The Pesticide Manual, A World Compendium (10th edition 1994), Tomlin, C., ed., British Crop Protection Council, 20 Bridport Road, Thornton Heath, CR4 7QG, United Kingdom.

WHO (1996), Environmental Health Criteria No. ..., Diflubenzuron. UNEP/ILO/WHO, Geneva.

    See Also:
       Toxicological Abbreviations
       Diflubenzuron (EHC 184, 1996)
       Diflubenzuron (HSG 99, 1995)
       Diflubenzuron (Pesticide residues in food: 1981 evaluations)
       Diflubenzuron (Pesticide residues in food: 1983 evaluations)
       Diflubenzuron (Pesticide residues in food: 1984 evaluations)
       Diflubenzuron (Pesticide residues in food: 1985 evaluations Part II Toxicology)
       Diflubenzuron (JMPR Evaluations 2001 Part II Toxicological)