Propyzamide
(endorsed 2011)
Guideline
Based on human health concerns, propyzamide in drinking water should not exceed 0.07 mg/L.
Related chemicals
Propyzamide (CAS 23950-58-5) belongs to the benzamide class of chemicals. Another herbicide in this class is isoxaben (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, propyzamide 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 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: Propyzamide is a pre- and post-emergent herbicide for the control of certain grasses and broad-leaf weeds in sports turf and grazing pastures, home garden lawns, and agricultural legume and lettuce crops.
There are registered products that contain propyzamide in Australia. The products are intended for professional and home garden use, and are available as concentrated solutions to be applied in diluted form using ground, aerial or hand-held sprays to soil or established crops. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to propyzamide and its metabolites are residues in food. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of propyzamide 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 reports of propyzamide in Australian drinking waters have been identified.
Treatment of drinking water
No specific data on the treatment of propyzamide in drinking water have been identified.
Measurement
Analysis of propyzamide in drinking water may be undertaken by high performance liquid chromatography–mass spectrometry (HPLC-MS). The analytical detection limit for this method is 8 ng/L (Di Corcia et al. 2000).
History of the health values
The current acceptable daily intake (ADI) for propyzamide is 0.02 mg per kg bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 1.9 mg/kg bw/day from a long-term (2-year) dietary study in mice. The NOEL is based on evidence of significant liver damage and an increased incidence of hepatocellular tumours. The ADI incorporates a safety factor of 100, and was first established in 1994. The safety factor does not include the evidence that the compound is a carcinogen for several organs.
The previous health value was 0.3 mg/L (NHMRC NRMMC 2004).
Health considerations
Metabolism: Propyzamide is readily absorbed via the gastrointestinal tract and extensively metabolised. The major metabolite is chloromethylbutane. Excretion occurred evenly between faeces (as metabolites and unabsorbed compound) and urine (as metabolites) and is complete within 6 days.
Acute effects: Propyzamide has low acute oral and dermal toxicity. It is not a skin sensitiser.
Short-term effects: In 4-week dietary studies in rats and dogs, there was slight hepatocellular hypertrophy and increased absolute and relative liver weight at 37 mg/kg bw/day in rats and 62 mg/kg bw/day in dogs. Other changes observed in dogs were also indicative of liver damage.
In 3-month dietary studies in rats and dogs, increased absolute liver weights were seen at doses of 7.5 mg/kg bw/day and above in rats. Other effects, including reversible hormonal effects, indicative of thyroid toxicity, were observed 50 mg/kg bw/day in rats.
Long-term effects: Two-year dietary studies were conducted in mice, rats and dogs. In mice, there was increased liver weight, evidence of bile duct obstruction associated with necrosis, and an increased incidence of liver carcinomas at 10 mg/kg bw/day. In rats, there was an increased incidence of thyroid adenocarcinoma, testicular adenomas and ovarian hyperplasia at 50 mg/kg bw/day. In dogs, there was an increase in kidney and heart weights, and decreased spleen weights (all without histological changes) at 7.5 mg/kg bw/day, and liver hypertrophy at 35 mg/kg bw/day. The lowest NOEL was 1.9 mg/kg bw/day in mice, and this is the basis of the current ADI.
Carcinogenicity: Propyzamide is associated with an increased tumour incidence in rodents, however, the tumours are considered to be rodent-specific or resulting from regenerative hyperplasia or hormonal changes, and not relevant to humans at the likely levels of exposure to propyzamide.
Genotoxicity: Propyzamide is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproductive and developmental effects: Two- and 3-generation reproductive studies in rats and developmental studies in rats and rabbits did not produce any evidence of effects on reproductive parameters or foetal development.
Endocrine effects: Special studies on thyroid function and endocrine regulation in the testes found tumour production was secondary to increased thyroxine turnover and perturbation of the pituitary-testicular endocrine axis, respectively.
Poisons Schedule: Propyzamide 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 propyzamide was determined as follows:
where:
1.9 mg/kg bw/day is the NOEL based on a long-term (2-year) dietary study in mice.
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.
Di Corcia A, Nazzari M, Rao R, Samperi R, Sebastiani E (2000). Simultaneous determination of acidic and non-acidic pesticides in natural waters by liquid chromatography-mass spectrometry. Journal of Chromatography A, 878(1):87-98.
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.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th edition, British Crop Production Council, UK.
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