Diflubenzuron
(endorsed 2011)
Guideline
Based on human health concerns, diflubenzuron in drinking water should not exceed 0.07 mg/L.
Related chemicals
Diflubenzuron (CAS 35367-38-5) belongs to the benzoylurea class of chemicals. Other pesticides in this class include chlorfluazuron (Tomlin 2006).
Human risk statement
With good water quality management practices, the exposure of the general population is expected to be well below levels that may cause health concerns.
If present in drinking water as a result of a spillage or through misuse, diflubenzuron would not be a health concern unless the concentration exceeded 0.07 mg/L. Minor excursions above this level would need to occur over a significant period to be of health concern, as the health-based guideline is based on long-term effects.
With good water quality management practices, pesticides should not be detected in source waters used for drinking water supplies. Persistent detection of pesticides may indicate inappropriate use or accidental spillage and investigation is required in line with established procedures in the risk management plan for the particular water source.
General description
Uses: Diflubenzuron is an insecticide and a parasiticide for the control of blowfly and lice in cattle and sheep.
There are registered products that contain diflubenzuron in Australia. These products are intended for professional use and are available as topical solution/suspension formulations to be diluted and applied by dipping or hand jetting, or directly by pour-on along the midline of the back of sheep and cattle. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to diflubenzuron is residues in food. Residue levels in food produced according to good agricultural practice are generally low.
The veterinary use of diflubenzuron provides some potential for contamination of drinking water through the washing of equipment near dams, streams or watercourses.
Typical values in Australian drinking water
No published reports on diflubenzuron occurrence in Australian drinking water supplies were found. Exposure to diflubenzuron through drinking-water is expected to be negligible.
Treatment of drinking water
No specific data on treatment for diflubenzuron have been found. However, the low aqueous solubility (0.08 mg/L) and relatively high log Kow of 3.7 suggest that it may be amenable to adsorption by activated carbon (WHO 2006). Reverse osmosis is also expected to be effective in removing diflurobenzuron, given its high molecular weight (310 g/mol).
Measurement
Diflubenzuron can be determined by high-performance liquid chromatography with ultraviolet detector. The method can achieve a limit of quantitation (LOQ) of 0.05 mg/L (Miliadis et al. 1999). A high-performance liquid chromatography with atmospheric pressure chemical ionisation and mass spectrometry method can achieve a LOQ of 0.025 mg/L (Barnes et al. 1995). Diflubenzuron in drinking water can also be determined by liquid chromatography with electrospray ionization and mass spectrometry, achieving a LOQ of 0.01 μg/L (Li et al. 2006). Automated solid-phase extraction and high-performance liquid chromatography with diode-array detection method can achieve a LOQ of 0.1 μg/L for diflubenzuron (Nouri et al. 1995). On-line pre-concentration method for the analysis of diflubenzuron in ground water samples using two C18 columns, and fluorescence detection after photochemical induced fluorescence post-column derivatization can achieve a LOQ of 0.01 μg/L (García et al. 2006).
History of the health values
The current acceptable daily intake (ADI) for diflubenzuron is 0.02 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 2.0 mg/kg bw/day from long-term dietary studies in rats and dogs. The NOEL is based on haematotoxicity and liver damage. The ADI incorporates a safety factor of 100 and was established in 1985.
A health value has not been previously established by NHMRC.
Health considerations
Metabolism: Diflubenzuron is relatively well absorbed from the gastrointestinal tract in rats (up to 50%). The two major metabolic routes are via hydroxylation of the aromatic rings (80%) and via scission of the ureido bridge (20%). Diflubenzuron is rapidly excreted in the urine and faeces, almost completely within 72 hours. There is no accumulation in body tissues.
Acute effects: Diflubenzuron has low acute oral and dermal toxicity. Its skin sensitisation potential has not been tested.
Short-term effects: Medium-term dietary studies were conducted in rats and dogs. In rats, there was an increase in relative adrenal weights and an increase in the incidence of necrotic foci in the liver at 2.5 mg/kg bw/day and above. Haematological changes indicative of anaemia were observed in males at 10 mg/kg bw/day. In dogs, methaemoglobin, sulfaemoglobin and spleen weights were elevated and there was evidence of liver toxicity at 6.6 mg/kg bw/day.
Long-term effects: Long-term dietary studies were conducted in rats and dogs. The 2-year rat study reported elevated methaemoglobin levels at 8 mg/kg bw/day. The 1-year dog study reported increased methaemoglobin and sulfaemoglobin levels, and increased pigmentation in macrophages and Kupffer cells of the liver at 10 mg/kg bw/day. Liver and spleen weights were significantly elevated at 50 and 250 mg/kg bw/day, respectively. The NOEL was 2 mg/kg bw/day in both the rat and dog studies, and is the basis for the current ADI.
Carcinogenicity: Based on long-term studies in mice and rats, there is no evidence of carcinogenicity for diflubenzuron.
Genotoxicity: Diflubenzuron was positive in some in vitro short-term assays, but negative in all in vivo studies. Overall, it is not considered to be genotoxic.
Reproductive and developmental effects: 1-, 2- and 3-generation reproduction studies in rats and developmental studies in rats and rabbits did not produce any evidence of effects on reproductive parameters or foetal development. Maternotoxicity occurred only at dose levels well in excess of the likely human exposure level.
Poisons Schedule: Diflubenzuron is included in Schedule 5 of the Standard for the Uniform Scheduling of Medicines and Poisons No.1, 2010 (the Poisons Standard)(DoHA 2010). Current versions of the Poisons Standard should be consulted for further information.
Derivation of the health-based guideline
The health-based guideline of 0.07 mg/L for diflubenzuron was determined as follows:
where:
2.0 mg/kg bw/day is the NOEL based on long-term dietary studies in rats (2-years) and dogs (1-year).
70 kg is taken as the average weight of an adult.
0.1 is a proportionality factor based on the assumption that 10% of the ADI will arise from the consumption of drinking water.
2 L/day is the estimated maximum amount of water consumed by an adult.
100 is the safety factor applied to the NOEL derived from animal studies. This safety factor incorporates a factor of 10 for interspecies extrapolation and 10 for intraspecies variation.
References
NOTE: The toxicological information used in developing this fact sheet is from reports and data held by the Department of Health, Office of Chemical Safety.
Barnes KA, Startin JR, Thorpe SA, Reynolds SL, Fussell RJ (1995). Determination of the pesticide diflubenzuron in mushrooms by high-performance liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry. Journal of Chromatography A, 712(1):85-93.
DoHA (2010) The Poisons Standard; Schedule 1-Standard for the Uniform Scheduling of Medicines and Poisons, Department of Health and Ageing, Commonwealth of Australia, Canberra.
García MDG, Galera MM, Martínez DB, Gallego JG (2006). Determination of benzoylureas in ground water samples by fully automated on-line pre-concentration and liquid chromatography-fluorescence detection. Journal of Chromatography A, 1103(2):271-277.
Li Y, George JE, McCarty CL, Wendelken SC (2006). Compliance analysis of phenylurea and related compounds in drinking water by liquid chromatography/electrospray ionization/mass spectrometry coupled with solid-phase extraction. Journal of Chromatography A, 1134(1-2):170-6.
Miliadis GE, Tsiropoulos NG, Aplada-Sarlis PG (1999). High-performance liquid chromatographic determination of benzoylurea insecticides residues in grapes and wine using liquid and solid-phase extraction.. Journal of Chromatgraphy A, 835:113-120
Nouri B, Fouillet B, Toussaint G, Chambon P, Chambon R (1995). High-performance liquid chromatography with diode-array detection for the determination of pesticides in water using automated solid-phase extraction. Analyst, 120:1133-1136.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th edition, British Crop Production Council, UK.
WHO (World Health Organization) (2006). Diflubenzuron in Drinking Water Use for Vector Control in Drinking Water Sources and Containers. Background document for development of WHO Guidelines for Drinking-Water Quality, WHO.
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