Chlorfenvinphos
(endorsed 2011)
Guideline
Based on human health concerns, chlorfenvinphos in drinking water should not exceed 0.002 mg/L.
Related chemicals
Chlorfenvinphos (CAS 470-90-2) belongs to the organophosphate class of chemicals. There are many other pesticides in this class including fenthion, parathion, profenofos and ethoprophos (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, chlorfenvinphos would not be a health concern unless the concentration exceeded 0.002 mg/L. Excursions above this level even for a short period are of concern, as the health-based guideline is based on both short-term and 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: Chlorfenvinphos is an insecticide that is used primarily as a parasiticide treatment for cattle, sheep, horses and to a lesser extent, deer, goats and working dogs. Agricultural use of chlorfenvinphos was cancelled and veterinary use restricted following a review in 2000 (AVPMA 2000).
There are registered products containing chlorfenvinphos in Australia. These products are intended for veterinarian or farm worker use and are applied as a topical suspension or spray, or as a dip for cattle. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to chlorfenvinphos is residues in food. Residue levels in food produced according to good agricultural practice are generally low.
The veterinary use of chlorfenvinphos provides some potential for contamination of drinking water through the washing of equipment near dams, streams or watercourses.
Typical values in Australian drinking water
No data are available on the concentrations of chlorfenvinphos in Australian drinking water.
Treatment of drinking water
Relatively high removal rates of chlorfenvinphos have been achieved using conventional flocculation, adsorption onto activated carbon and ozonation (Ormad et al. 2008).
Measurement
Several methods have been reported for the analysis of chlorfenvinphos in water including solid phase extraction with gas chromatography–tandem mass spectrometry, with a limit of detection (LOD) of 4 ng/L (Ruiz-Gill et al. 2008), solid phase extraction with liquid chromatography–tandem mass spectrometry (LOD 10 ng/L, Greulich et al. 2008) and stir-bar sorptive extraction with gas chromatography–mass spectrometry (LOD 4.3 ng/L, Ochiai et al. 2008).
History of the health values
The current acceptable daily intake (ADI) for chlorfenvinphos is 0.0005 mg per kg of bodyweight (mg/kg bw), based on a no-observed-effect level (NOEL) of 0.05 mg/kg bw/day from a 4-week dietary study in rats, a 2-year dietary study in rats and a 2-generation reproduction study in rats. This NOEL is based on plasma and/or brain cholinesterase inhibition. The ADI incorporates a safety factor of 100 and was established in 1998.
The previous Australian ADI for chlorfenvinphos was 0.002 mg/kg bw, based on a NOEL of 0.15 mg/kg bw/day for plasma cholinesterase inhibition seen in a 2-year rat dietary study and using a 100-fold safety factor.
The acute reference dose (ARfD) of 0.02 mg/kg bw/day for chlorfenvinphos was established in 2000, based on a NOEL of 1.9 mg/kg bw/day from a 14-day mouse study for inhibition of red blood cell cholinesterase activity. The ARfD incorporates a safety factor of 100.
The previous health value was 0.005 mg/L (NHMRC and NRMMC 2004).
Health considerations
Metabolism: Chlorfenvinphos is absorbed readily and extensively via the gastrointestinal tract. The rate of metabolism of chlorfenvinphos is species-specific, with dogs much higher than rats. In a human volunteer study, there was rapid excretion in the urine (94% in 26 hours). The main metabolite was desethyl chlorfenvinphos.
Acute effects: Chlorfenvinphos has low to high acute toxicity depending on the species. In rats, the acute oral and dermal toxicity was high. It was not a skin sensitiser. Clinical signs of acute poisoning were typical of cholinesterase inhibition and included hyperexcitability, salivation, bronchoconstriction, headache, vomiting and other behavioural changes. These have been observed in humans as well as animals.
Short-term and long-term effects: Short-term and long-term dietary studies with chlorfenvinphos reported symptoms indicative of nervous system toxicity caused by depression of cholinesterase activity. Short-term studies in mice reported brain cholinesterase inhibition at 0.2 mg/kg bw/day and plasma cholinesterase inhibition at 1.9 mg/kg bw/day. In a 2-year mouse study, plasma cholinesterase levels were depressed at 3.9 mg/kg bw/day. Both plasma and brain cholinesterase had similar level of sensitivity in the rat. Four-week and 2-year studies in rats reported plasma cholinesterase inhibition at dose levels of 0.15 mg/kg bw/day and above. The NOEL of 0.05 mg/kg bw/day from the rat studies is the basis for the current ADI.
Carcinogenicity: Based on long-term studies in mice and rats, there is no evidence of carcinogenicity for chlorfenvinphos.
Genotoxicity: Chlorfenvinphos is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproductive and developmental effects: Multigeneration reproduction studies in rats reported decreased fertility and decreased pup survival, but only at dose levels causing cholinesterase inhibition. In developmental toxicity studies in rats and rabbits, foetal development was impaired only at dose levels caused significant cholinesterase inhibition.
Poisons Schedule: Chlorfenvinphos is included in Schedule 7 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 0.002 mg/L for chlorfenvinphos was determined as follows:
where:
0.05 mg/kg bw/day is the NOEL based on a short-term (4-week) dietary study in rats, a long-term (2-year) dietary study in rats, and a 2-generation reproduction 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.
APVMA (Australian Pesticides and Veterinary Medicines Association) (2000) The NRA Review of Chlorfenvinphos – Interim Report Volume 1. Available at https://apvma.gov.au/sites/default/files/publication/14696-chlorfenvinphos-irr-vol1.pdf
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.
Greulich K, Alder L (2008). Fast multiresidue screening of 300 pesticides in water for human consumption by LC-MS/MS. Analytical and Bioanalytical Chemistry, 391:183-197.
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.
Ochiai N, Sasmoto K, Kanda H, Pfannkoch E (2008). Sequential stir bar sorptive extraction for uniform enrichment of trace amounts of organic pollutants in water samples. Journal of Chromatography A, 1200:72-79.
Ormad MP, Miguel N, Claver A, Matesanz JM, Ovelleiro JL (2008). Pesticides removal in the process of drinking water production. Chemosphere, 71, 97–106.
Ruiz-Gill L, Romero-Gonzalez R, Frenich AG, Vidal JLM (2008). Determination of pesticides in water samples by solid phase extraction and gas chromatography tandem mass spectrometry. Journal of Separation Science, 31:151-161.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th Edition, British Crop Production Council, UK.
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