Carboxin
(endorsed 2011)
Guideline
Based on human health concerns, carboxin in drinking water should not exceed 0.3 mg/L.
Related chemicals
Carboxin (CAS 5234-68-4) belongs to the carboxamide class of chemicals. Other pesticides in this class include oxycarboxin (a metabolite of carboxin) (Tomlin 2006).
Human risk statement
With good water quality management practices, the exposure of the general population to carboxin 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, carboxin would not be a health concern unless the concentration exceeded 0.3 mg/L. 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: Carboxin is a systemic fungicide for the control of smut and bunt in seeds (wheat, barley, oats and maize) prior to planting.
There are currently products registered in Australia that contain carboxin. These products are intended for professional use and are available as concentrated solutions to be applied directly or in diluted form as a seed dressing. A dust formulation is also available. The seed dressing is applied prior to sowing. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to carboxin and its metabolites is residues in food. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of carboxin may potentially lead to contamination of source waters through processes such as run-off or entry into groundwater.
Reported values in Australian waters
No data were found on carboxin in Australian waters. In the USA, modelling by the United States Environmental Protection Agency suggests maximum concentrations of 0.63 µg/L and 0.095 µg/L in surface water and groundwater, respectively (USEPA 2004).
Treatment of drinking water
No specific data on the treatment of carboxin in drinking water have been identified.
Measurement
Carboxin in water can be measured by gas chromatography–mass spectrometry, with a method detection limit of 1.4 µg/L (USEPA 1995).
History of the health values
The current acceptable daily intake (ADI) for carboxin is 0.08 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 8.5 mg/kg bw/day from a long-term (2-year) dietary study. The NOEL is based on liver effects in mice. The ADI incorporates a safety factor of 100 and was established in 1987.
The previous health value was 0.3 mg/L (NHMRC and NRMMC 2004).
Health considerations
Metabolism: Carboxin is readily absorbed via the gastrointestinal tract. It is extensively metabolised, and is excreted in the urine and faeces almost completely within 96 hours. A major metabolite is oxycarboxin, which also has fungicidal activity.
Acute effects: Carboxin has low to very low acute oral and dermal toxicity. Carboxin is not a skin sensitiser.
Short-term effects: A four-week dietary study in rats reported liver effects at dose levels above 90 mg/kg bw/day. These effects were still present (although not as severe) 3 weeks after cessation of treatment.
Two 90-day dietary studies in rats reported effects on both the liver and kidney at dose levels above 10 mg/kg bw/day.
Long-term effects: Long-term dietary studies in mice reported decreased survival in females and effects on the lung at 750 mg/kg bw/day, and effects on the liver at 375 mg/kg bw/day and above. The NOEL based on changes in the liver was 8.5 mg/kg bw/day.
Long-term dietary studies have also been performed on rats and dogs. Effects reported in rats include decreased bodyweight, decreased food consumption and decreased survival (males only) at 30 mg/kg bw/day. There was no evidence of toxicity in dogs at 15 mg/kg bw/day.
Genotoxicity: Carboxin is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproduction and developmental effects: A 3-generation reproduction study and a developmental study in rats did not produce any evidence of reproductive or teratogenic effects. A developmental study in rabbits reported effects only at dose levels well in excess of the likely level of human exposure.
Poisons Schedule: Carboxin 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 0.3 mg/L for carboxin was determined as follows:
where:
8.5 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 variation 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.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th Edition, British Crop Production Council, UK.
USEPA (United States Environmental Protection Agency) (1995). Method 525.2. Determination of organic compounds in drinking water by liquid-solid extraction and capillary column gas chromatography/mass spectrometry. Revision 2.0.
USEPA (United States Environmental Protection Agency) (2004) – Reregistration Eligibility Decision for Carboxin. Available online at https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=2000E85Q.txt
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