Polihexanide
(endorsed 2011)
Guideline
Based on human health concerns, polihexanide in drinking water should not exceed 0.7 mg/L.
Related chemicals
Polihexanide (CAS 50641-36-6) is a polymer of chlorhexidine. There are no 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, polihexanide would not be a health concern unless the concentration exceeded 0.7 mg/L. Excursions above this level even for a short period are of concern, as the health-based guideline is based on short-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: Polihexanide is a disinfectant used to control microorganisms in veterinary hospitals and animal accommodations, and as a sanitiser for milk-handling equipment.
There is at least one registered product containing polihexanide in Australia. Polihexanide products are intended for professional use and are available as a concentrate. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main sources of public exposure to polihexanide are residues in food (dairy products), and exposure to treated surfaces.
Use of polihexanide as a disinfectant may potentially lead to contamination of source waters through processes such as run-off or entry into groundwater.
Typical values in Australian drinking water
No reports of polihexanide in Australian drinking waters have been identified.
Treatment of drinking water
There is insufficient information on the treatment of polihexanide in drinking water, but it is expected that advanced treatment methodologies such as ozonation and advanced oxidation would be effective.
Measurement
No suitable analytical techniques have been identified, but the use of high performance liquid chromatography–tandem mass spectrometry is expected to be suitable for residue levels of this pesticide in water.
History of the health values
The current acceptable daily intake (ADI) and acute reference dose (ARfD) for polihexanide is 0.2 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 20 mg/kg bw/day from a rabbit developmental study. The NOEL was based on maternotoxicity in pregnant rabbits. The ADI and ARfD incorporate a safety factor of 100, and were established in 2007.
A health value has not been previously established by NHMRC for polihexanide.
Health considerations
Metabolism: Polihexanide is poorly absorbed via the gastrointestinal tract and is rapidly excreted mainly in the faeces (94%), with the absorbed portion excreted in urine. The metabolic fate of polihexanide is unknown.
Acute effects: Polihexanide has a low acute oral and dermal toxicity. It is a skin sensitiser in guinea pigs.
Short-term effects: Repeat-dose dermal exposure in rats caused reddening and inflammation of the skin at 200 mg/kg bw/day. Ninety-day dietary studies were conducted in rats and dogs. In rats, there was reduced bodyweight gain and haemosiderin deposits in the liver at 68 mg/kg bw/day. In dogs, there were haemosiderin deposits in the spleen at 68 mg/kg bw/day.
Long-term effects: Long-term studies were conducted in mice (2-years), rats (2-years) and dogs (1-year). In mice, there were treatment-related effects in the liver (increase in haemangiosarcomas) and recto-anal junction (inflammation, hyperplasia and squamous cell carcinomas) at 180 mg/kg bw/day. In rats, there was some evidence of an increase in haemangioma/haemangiosarcomas in the liver at 100 mg/kg bw/day. In dogs, there was evidence of systemic toxicity at 45 mg/kg bw/day.
Carcinogenicity: Polihexanide induced an increased incidence in haemangiomas/haemangiosarcomas in the liver of mice at a high dose level that is well in excess of the normal level of human exposure. The increased incidence of squamous cell carcinomas in the recto-anal junction was considered to be a consequence of irritation/inflammation at the high dose level and not relevant to human exposure.
Genotoxicity: Polihexanide is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproduction and developmental effects: A reproduction study in rats and developmental studies in rats and rabbits did not show any evidence of effects on reproductive parameters or on foetal development. The NOEL for maternal toxicity in rabbits was 20 mg/kg bw/day, and this was the basis for the ADI.
Poisons Schedule: Polihexanide 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 value of 0.7 mg/L for polihexanide was determined as follows:
where:
20 mg/kg bw/day is the NOEL based on a developmental study in rabbits.
70 kg is taken as the average weight of an adult.
0.1 is a proportionality factor based on the conservative 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 a safety factor applied to the NOEL from a developmental study conducted in rabbits. The safety factor incorporates a factor of 10 for interspecies extrapolation and 10 for intraspecies variations.
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.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th Edition, British Crop Production Council, UK.
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