Carbendazim/Thiophanate-methyl
(endorsed 2011)
Guideline
Based on human health concerns, carbendazim in drinking water should not exceed 0.09 mg/L.
Related chemicals
Carbendazim (CAS 10605-21-7/ CAS 23564-06-9) belongs to the benzimidazole class of chemicals. Thiophanate methyl belongs to the thiophanate class of chemicals, although it is often regarded as a benzimidazole. Thiophanate-methyl is converted to carbendazim in the environment (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 of thiophanate-methyl or carbendazim, it would not be a health concern unless the concentration exceeded 0.09 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: Carbendazim is a broad-spectrum systemic fungicide used for the control of a wide range of fungal diseases such as mould, spot, mildew, scorch, rot and blight in a variety of crops, including cereals, fruit (pome, stone, citrus, cucurbits, strawberries, bananas, mangoes, etc), vines, ornamentals, pasture, and turf.
Thiophanate-methyl is a fungicide used for the control of soil-borne diseases of ornamental plants.
There are registered products containing carbendazim and registered products containing thiophanate-methyl in Australia. Carbendazim-containing products are intended for professional use and are generally available as suspension concentrates, to be mixed with water for application as a spray or dip. Some products are also used as timber preservatives. Thiophanate-methyl containing products are intended for professional use and are available as concentrated powders or granules, to be mixed into soil/potting mix before sowing or applied as a diluted drench directly to plant beds. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: Carbendazim is the major environmental degradant of thiophanate-methyl and is therefore the relevant environmental contaminant for both chemicals. The main source of public exposure to carbendazim is residues in food. Residue levels in crops grown according to good agricultural practice are generally low.
Agricultural use of carbendazim and/or thiophanate-methyl 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 carbendazim in Australian drinking waters have been identified.
Treatment of drinking water
No specific data on the treatment of carbendazim in drinking water have been identified.
Measurement
Carbendazim may be measured in drinking water using high performance liquid chromatography coupled with a variety of spectrometric detection techniques (JunkerBuchheit and Witzenbacher 1995, Crescenzi et al. 1997, Di Corcia et al. 2000, Hogendoorn et al. 2000, Van Hoof et al. 2002, Deng et al. 2007). Limits of detection below 1 µg/L can be achieved by most of these techniques.
History of the health values
The current acceptable dietary intake (ADI) for carbendazim is 0.03 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 2.5 mg/kg bw/day from a 2-year dog study. The NOEL is based on evidence of adverse effects on the liver. The ADI incorporates a safety factor of 100, and was established in 1979.
The current ADI for thiophanate-methyl is 0.02 mg/kg bw, based on a NOEL of 2 mg/kg bw/day from a long-term rat study. The NOEL is based on degeneration and atrophy in the testes. The ADI incorporates a safety factor of 100 and was established in 1991.
The previous health value for carbendazim was 0.1 mg/L (NHMRC and NRMMC 2004).
Health considerations
Since thiophanate-methyl is converted to carbendazim in the environment, the toxicity of carbendazim is the major consideration in relation to the health impact of thiophanate-methyl in drinking water.
Metabolism: Carbendazim is readily absorbed via the gastrointestinal tract, extensively metabolized, and excreted in the urine (86%) and faeces. The main metabolite is 5-hydroxy carbendazim (5-HBC-S). Approximately 98% of carbendazim and its metabolites are excreted within three days.
Acute effects: Carbendazim has low acute oral and dermal toxicity in rats. It is not a skin sensitiser.
Short-term effects: In short-term studies in rats, there were decreased sperm counts and testicular degeneration at 200 mg/kg bw/day. Liver toxicity was also observed at dose levels above 7.5 mg/kg bw/day.
Long-term effects: Long-term studies were conducted in mice, rats and dogs. In rats, there was evidence of diffuse testicular atrophy at 250 mg/kg/bw/day. In dogs, there were histopathological changes in the liver, increases in cholesterol, and changes in liver enzyme levels at 15 mg/kg bw/day. In both rats and dogs, there were testicular effects at 250 and 125 mg/kg bw/day, respectively. The NOEL of 2.5 mg/kg bw/day in the dog study is the basis for the ADI.
Carcinogenicity: There was an increase in hepatocellular adenomas and carcinomas in some strains of mice, but these were considered species-specific and not relevant to humans.
Genotoxicity: Carbendazim can cause aneuploidy as a result of interference with the formation of the mitotic spindle. It is negative for genotoxicity in other in vitro and in vivo studies.
Reproductive and developmental effects: In a reproduction study in rats, carbendazim produced testicular degeneration and reduced fertility at 50 mg/kg bw/d. Developmental studies conducted via gavage in rats (but not dietary studies) demonstrated skeletal malformations at 30-90 mg/kg bw/day in the absence of any maternal toxicity. In rabbits, gavage studies produced embryotoxicity at doses at and above 20 mg/kg bw/day and teratogenicity at 125 mg/kg bw/day.
Neurotoxicity: There was no evidence of delayed neurotoxicity.
Poison Schedule: Carbendazim is included in Schedule 7 of the Standard for the Uniform Scheduling of Medicines and Poisons No.1, 2010 (the Poisons Standard)(DoHA 2010). Thiophanate-methyl is included in Schedule 5 or 6 depending on the concentration. Current versions of the Poisons Standard should be consulted for further information.
Derivation of the health-based guideline
The health-based guideline of 0.09 mg/L for carbendazim/thiophanate-methyl was determined as follows:
where:
2.5 mg/kg bw/day is a NOEL based on a long-term (2-year) dog study with carbendazim.
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.
Crescenzi C, Di Corcia A, Guerriero E, Samperi R (1997). Development of a multiresidue method for analyzing pesticide traces in water based on solid-phase extraction and electrospray liquid chromatography mass spectrometry. Environmental Science and Technology, 31(2):479-488.
Deng HS, Xiang BR, Xie SF, Zhou XH (2007). Trace determination of carbendazim and thiabendazole in drinking water by liquid chromatography and using linear modulated stochastic resonance algorithm. Arzneimittel-Forschung-Drug Research, 57(11):717-722.
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.
Hogendoorn EA, Westhuis K, Dijkman E, Heusinkveld EAG, Chamraskul P, Biadul P, Baumann RA, Cornelese AA, van der Linden MA (2000). Determination of carbendazim in water, soil and sediment samples by RPLC with and without column switching and various spectrometric detection modes. International Journal of Environmental Analytical Chemistry, 78(1):67-85.
JunkerBuchheit A, Witzenbacher M (1995). Pesticide monitoring of drinking water with the help of solid-phase extraction and high-performance liquid chromatography. In: 5th Workshop on Chemistry and Fate of Modern Pesticides Paris, France, pp 67-74.
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.
Van Hoof F, Van Wiele P, Acobas F, Guinamant JL, Bruchet A, Schmitz I, Bobeldijk I, Sacher F, Ventura F, Boleda R (2002). Multiresidue determination of pesticides in drinking and related waters by solid-phase extraction and liquid chromatography with ultraviolet detection: Interlaboratory study. Journal of AOAC International, 85(2):375-383.