Hexazinone
(endorsed 2011)
Guideline
Based on human health concerns, hexazinone in drinking water should not exceed 0.4 mg/L.
Related chemicals
Hexazinone (CAS 51235-04-2) belongs to the triazinone class of chemicals. Another pesticide in this class is metribuzin. This class of chemicals is structurally similar to the triazine class (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, hexazinone would not be a health concern unless the concentration exceeded 0.4 mg/L. Minor excursions above this level would need to occur over a significant period to be a 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: Hexazinone is a herbicide used for the control of annual and perennial weeds in pine forest plantations, and annual and perennial grasses, broad-leaf weeds, and vines in industrial areas and sugar cane crops.
There are registered products that contain hexazinone in Australia. The products are intended for professional use and all are available as soluble concentrates intended to be diluted and applied by handspray when used in public areas, and by groundspray and aerial spray when used in other areas. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to hexazinone is residues in food. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of hexazinone may potentially lead to contamination of source waters through processes such as run-off, spray drift or entry into groundwater.
Typical values in Australian drinking water
No data on the occurrence of hexazinone in Australian waters could be found. Groundwater contamination has been reported in the USA up to 0.034 mg/L, and the concentration of hexazinone in surface waters can be as high as 0.14 mg/L up to 6 months after application (USEPA 1994).
Treatment of drinking water
No data on drinking water treatment removal efficiency could be found for hexazinone.
Measurement
Hexazinone can be measured by routine gas chromatography–mass spectrometry analysis, with a limit of reporting of 0.01 µg/L (Queensland Health 2007).
History of the health values
The current acceptable daily intake (ADI) for hexazinone is 0.1 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 10 mg/kg bw/day from a long-term (2-year) dietary rat study. The NOEL is based on decreased bodyweight gain at 125 mg/kg bw/day. The ADI incorporates a safety factor of 100 and was first established in 1978.
The previous health value was 0.3 mg/L (NHMRC and NRMMC 2004).
Health considerations
Metabolism: Hexazinone is readily absorbed from the gastrointestinal tract. It is extensively metabolised by hydroxylation of the cyclohexyl ring, and monodemethylation of the diethylamino group. Excretion is almost complete by 24 hours, mostly as metabolites in urine and to a lesser extent in faeces.
Acute effects: Hexazinone has low acute oral toxicity and low dermal toxicity. It is not a skin sensitiser.
Short-term effects: In 90-day oral studies in rats and dogs, there was decreased bodyweight gain at doses of 100 mg/kg bw/day in rats and at 300 mg/kg bw/day in dogs.
Long-term effects: In long-term (2-year) dietary studies in mice and rats, effects were confined to decreased bodyweight gain in rats at doses of 30 mg/kg bw/day, and hepatocellular hypertrophy and increased relative liver weight at doses of 125 mg/kg bw/day in mice. The lowest overall NOEL was 10 mg/kg bw/day in rats. This NOEL is the basis for the current ADI.
Carcinogenicity: Based on a 2-year studies in mice and rats, there is no evidence of carcinogenicity for hexazinone.
Genotoxicity: Hexazinone is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproductive and developmental effects: No reproduction studies have been conducted. Developmental toxicity studies in rats and rabbits did not produce any evidence of effects on foetal development.
Poisons Schedule: Hexazinone is in Schedules 5 and 6 of the Standard for the Uniform Scheduling of Medicines and Poisons No.1, 2010 (the Poisons Standard)(DoHA 2010), depending on its concentration and use. Current versions of the Poisons Standard should be consulted for further information.
Derivation of the health-based guideline
The health-based guideline of 0.4 mg/L for hexazinone was determined as follows:
where:
10 mg/kg bw/day is the NOEL based on a long-term (2-year) dietary study in rats.
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.
Queensland Health (2007). Organochlorine, organophosphorous and synthetic pyrethroid pesticide, urea and triazine herbicides and PCBs in water. QHFSS SOP 16315.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th edition, British Crop Production Council, UK.
USEPA (United States Environmental Protection Agency) (1994). Reregistration eligibility decision (RED) for hexazinone. USEPA.
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