Endothal
(endorsed 2011)
Guideline
Based on human health concerns, endothal in drinking water should not exceed 0.1 mg/L.
Related chemicals
Endothal (CAS 145-73-3) belongs to the dicarboxylic-acid class of chemicals. There are currently no other pesticides in this chemical class registered for use (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, endothal would not be a health concern unless the concentration exceeded 0.1 mg/L. While the health-based guideline is based on long-term effects, there is potential for effects on the gastrointestinal tract after short-term exposure at levels 2-3 times higher than the health-based guideline. Therefore, excursions above this level even for a short period are of concern.
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: Endothal is a selective contact herbicide used for the control of winter grass in turf crops and lawns.
There are currently products registered in Australia that contain endothal, with both containing endothal as its di-potassium salt. Endothal products are intended for professional use on lawns. Products are liquid concentrates that are applied in diluted form using hand spray or boom spray equipment. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to endothal and its metabolites residues in foods such as potato and cotton seed oil. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of endothal 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
There are no published reports on endothal occurrence in Australian drinking water supplies.
Treatment of drinking water
Endothal can be removed from drinking water using granular activated carbon.
Measurement
Endothal can be detected in drinking water using liquid-solid extraction followed by gas chromatography and electron capture detection, with a limit of detection (LOD) of 11.5 µg/L (EPA Method 548). Endothal has been analysed using derivatisation ion exchange extraction, acidic methanol methylation, and gas chromatography with mass spectrometry (GC/MS), with a LOD of 1.8 µg/L (EPA Method 548.1). Determination can be done using a flame ionisation detector instead of GC/MS, with a reported LOD of 0.7 µg/L (Hodgeson et al. 1992).
History of the health values
The current acceptable daily intake (ADI) for endothal is 0.03 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 3.75 mg/kg bw/day from a long-term (1-year) study in dogs. This NOEL is based on liver necrosis and stomach hyperplasia and hyperkeratosis. The ADI incorporates a safety factor of 100 and was established in 1990.
The previous ADI for endothal was 0.1 mg/kg bw/day, established in 1977 and based on a NOEL of 10 mg/kg bw/day in a 2-year study in dogs and a 100-fold safety factor. This study was later found to be inadequate for regulatory purposes, and the ADI was amended in 1990.
The previous health value was 0.1 mg/L (NHMRC and NRMMC 2004).
Health considerations
Metabolism: Endothal is well absorbed via the gastrointestinal tract and widely distributed. Peak levels in blood are reached at 1 hour after dosing. Metabolism is limited and endothal is excreted unchanged in the urine within 48 hours (99% of total dose). A small amount of unidentified metabolites is excreted in the faeces.
Acute effects: The di-potassium salt of endothal has a moderate acute oral toxicity in rats and endothal itself has a high acute dermal toxicity in rabbits. No studies are available on the skin sensitisation potential of endothal.
Short-term effects: The main toxic effect of endothal in oral short-term toxicity studies was gastrointestinal toxicity. In dogs treated for 6 weeks there was significant gastrointestinal tract erosion at the lowest dose tested, 10 mg/kg bw/day. A NOEL was not obtained for this study. A NOEL of 50 mg/kg bw/day was obtained from a short-term (28-day) dietary study in rat. In this study, high mortality rates associated with gastrointestinal necrosis and overt signs of toxicity were seen at doses of 500 mg/kg bw/day.
Following repeated dermal application of endothal to rabbits, mortality with associated histological changes in skin, liver, and kidney resulted at the lowest dose of 50 mg/kg bw/day.
Long-term effects: In long-term toxicity studies, the main toxic effects are on the stomach and liver. Stomach hyperplasia and hyperkeratosis was seen at 7.5 mg/kg bw/day in rats and 25 mg/kg bw/day in dogs. Liver necrosis was observed at 11 mg/kg bw/day in dogs, and liver hyperplasia/adenoma and ovarian cysts at 15 mg/kg bw/day in rats. The lowest NOEL was 3.75 mg/kg bw/day in a 1-year study in dogs, and this is the basis for the current ADI.
Carcinogenicity: Based on long-term toxicity studies in rats, there is no evidence of carcinogenicity for endothal.
Genotoxicity: Endothal 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 mice did not produce any evidence of reproductive effects, delayed development or teratogenicity.
Poisons Schedule: Endothal is in Schedules 6 and 7 of the Standard for the Uniform Scheduling of Medicines and Poisons No.1, 2010 (the Poisons Standard)(DoHA 2010), depending on the concentration and use pattern. Current versions of the Poisons Standard should be consulted for further information.
Derivation of the health-based guideline
The health-based guideline of 0.1 mg/L for endothal was determined as follows:
where:
3.75 mg/kg bw/day is the NOEL based on a long-term (1-year) dietary study in dog.
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.
Hodgeson JW, Collins J, Bashe WJ (1992). Method 548.1 Determination of Endothall in Drinking Water by Ion-Exchange Extraction, Acidic methanol Methylation and Gas Chromatography/Mass Spectometry. Revision 1.0. Environmental Monitoring Systems Laboratory Office of Research and Development, USEPA, Cincinnati, Ohio.
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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