Piperonyl butoxide
(endorsed 2011)
Guideline
Based on human health concerns, piperonyl butoxide in drinking water should not exceed 0.6 mg/L.
Related chemicals
Piperonyl butoxide (CAS 51-03-6) is a derivative of safrole and does not belong to a recognised chemical class. There are no chemically-related pesticides (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, piperonyl butoxide would not be a health concern unless the concentration exceeded 0.6 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: Piperonyl butoxide is a synergist for pyrethrin and pyrethroid insecticides and parasiticides for the control of parasites and insects.
There are many registered products that contain piperonyl butoxide in Australia. It is only ever used in combination with insecticides and parasiticides to increase their efficacy. The products are intended for professional and domestic use. Products containing piperonyl butoxide are available as skin ointments, throat/ear drops, aerosol sprays, powders, shampoos and soluble concentrates. Products are applied topically when used as a parasiticide on pets or livestock, and are sprayed as aerosols or diluted solutions when used as an insecticide on fruit, cereal, and vegetable crops. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main sources of public exposure to piperonyl butoxide and its metabolites are dermal and inhalation exposure from the use of domestic insecticide products, and residues in foods. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of piperonyl butoxide may potentially lead to contamination of source waters through processes such as run-off, spray drift or entry into groundwater. The veterinary use of piperonyl butoxide 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 reports of piperonyl butoxide in Australian drinking waters have been identified.
Treatment of drinking water
No specific data on the treatment of piperonyl butoxide in drinking water have been identified.
Measurement
Piperonyl butoxide may be measured in drinking water by gas chromatography–mass spectrometry. The limit of reporting for this method is typically 0.1 μg/L (QFSS 2009 pers comm).
History of the health values
The current acceptable daily intake (ADI) for piperonyl butoxide is 0.1 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 16 mg/kg bw/day from a long-term study (1-year dietary study) in dogs. The NOEL is based on increased liver weight and associated hepatocellular hypertrophy, increased serum ALP activity, and increased thyroid weight. The ADI incorporates a safety factor of 100, and was established in 1997.
The previous ADI for piperonyl butoxide was 0.03 mg/kg bw, based on a NOEL of 3 mg/kg bw/day from the same long-term study in dogs. The ADI was amended in 1997 after a re-evaluation of this study.
The previous health value was 0.1 mg/L (NHMRC and NRMMC 2004).
Health considerations
Metabolism: Piperonyl butoxide is poorly but rapidly absorbed from the gastrointestinal tract. The absorbed fraction is mostly distributed to the liver and fat, and undergoes extensive metabolism. Excretion occurs relatively rapidly, through the urine (30%) and faeces and is essentially complete within 7 days.
The metabolites of piperonyl butoxide inhibit detoxification enzymes in the liver and are responsible for the synergising effects.
Acute effects: Piperonyl butoxide has low acute oral and dermal toxicity, and is not a skin sensitiser. In humans, no adverse effects were seen after a single oral dose of 0.7 mg/kg bw.
Short-term effects: A 4-week dietary study in rats reported histopathological changes in the liver at the lowest dose, 62.5 mg/kg bw/day. An 8-week dietary study in dogs reported decreased bodyweight, increased liver weight and hypertrophy, and decreased testis weights at 62 mg/kg bw/day. Medium-term studies mice reported decreased bodyweight gain, increased liver weight and hypertrophy, and clinical chemistry changes 100 mg/kg bw/day.
Long-term effects: In long-term dietary studies in dogs (1 year), mice (18 months), and rats (up to 22 months), changes included decreased bodyweight gain, increased liver and thyroid weight, and changes indicative of mild liver toxicity at doses of 62 mg/kg bw/day and above. Liver hyperplasia and increased kidney weight were also observed in rats and mice at higher doses. The lowest overall NOEL was 16 mg/kg bw/day in the 1-year study in dogs, and this is the basis for the ADI.
Carcinogenicity: Based on 18- to 22-month studies in mice and rats, there is no evidence of carcinogenicity for piperonyl butoxide.
Genotoxicity: Piperonyl butoxide is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproductive and developmental effects: A 3-generation reproduction study in rats and developmental studies in rats and rabbits did not produce any evidence of effects on reproductive parameters or on foetal development.
Poisons Schedule: Piperonyl butoxide is considered not to require control by scheduling due to its low toxicity and is therefore included in Appendix B 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 0.6 mg/L for piperonyl butoxide was determined as follows:
where:
16 mg/kg bw/day is the NOEL based on a long-term (1-year) dietary study in dogs.
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.
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.
NHMRC (National Health and Medical Research Council), NRMMC (Natural Resources Management Ministerial Council) (2004). Australian Drinking Water Guidelines. National Water Quality Management Strategy, Paper 6. NHMRC and NRMMC.
QFSS (Queensland Forensic and Scientific Services ) (2009). QFSS, Personal communication.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th edition, British Crop Production Council, UK.
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