Cyprodinil
(endorsed 2011)
Guideline
Based on human health concerns, cyprodinil in drinking water should not exceed 0.09 mg/L.
Related chemicals
Cyprodinil (CAS 121552-61-2) belongs to the anilinopyrimidine class of chemicals. Another pesticide in this class is pyrimethanil (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, cyprodinil would not be a health concern unless the concentration exceeded 0.09 mg/L. 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: Cyprodinil is a fungicide for the control of black spot in apples and pears; the control of blossom blight and brown rot in apricots, peaches, plums and nectarines; and, in combination with fludioxonil, the control of grey mould in grapes.
There are registered products that contain cyprodinil in Australia. These are intended for professional use and are available as water-dispersible granules to be applied as concentrated or dilute solutions, commonly using air blast, misters or hand-held 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 cyprodinil is residues in food. Residue levels in food produced according to good agricultural practice are generally low.
Agricultural use of cyprodinil 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 occurrence data for cyprodinil in Australian waters were found.
Treatment of drinking water
No data on drinking water treatment removal efficiency were found for cyprodinil.
Measurement
Cyprodinil in water can be analysed by adapting a solid-phase microextraction gas chromatrography mass spectrometry method developed for white wine (Otero et al. 2002), with a limit of detection of 0.2 µg/L.
History of the health values
The current acceptable daily intake (ADI) for cyprodinil is 0.02 mg per kg body weight (mg/kg bw), based on a no-observed-effect level (NOEL) of 2.7 mg/kg bw/day from a long-term (2-year) dietary study in rats. The NOEL is based on an increased incidence of liver lesions in males at the next highest dose of 36 mg/kg bw/day. The ADI incorporates a safety factor of 100 and was established in 1994.
A health value has not been previously established by NHMRC.
Health considerations
Metabolism: Cyprodinil is rapidly absorbed via the gastrointestinal tract in rats. The parent compound is completely metabolised and excreted mainly as conjugated derivatives. These are excreted mainly in the urine within 48 hours.
Acute effects: Cyprodinil has low acute oral and dermal toxicity. It is a skin sensitiser in guinea pigs.
Short-term effects: In 1- to 3-month studies in mice, rats and dogs, the liver was the main target of toxicity, although most effects occurred only at very high dose levels. In mice, liver necrosis was observed at 257 mg/kg bw/day. In dogs, increased liver weights were observed at 46 mg/kg bw/day. Rats showed increased plasma cholesterol and phospholipid levels at 3 mg/kg bw/day, and effects on the thyroid and kidney at 19 mg/kg bw/day.
Long-term effects: Long-term dietary studies conducted in mice, rats and dogs showed the liver to be the main target organ of toxicity. Effects on the liver were noted at 600 mg/kg bw/day in mice (increased relative liver weight), at 36 mg/kg bw/day in male rats (spongiosis hepatitis) and at 446 mg/kg bw/day in dogs (pigmentation of hepatocytes). The lowest NOEL was 2.7 mg/kg bw/day in the rat study and this is the basis for the ADI.
Carcinogenicity: Based on long-term studies in mice, rats and dogs, there is no evidence of carcinogenicity for cyprodinil.
Genotoxicity: Cyprodinil is not considered to be genotoxic, based on in vitro and in vivo short-term studies.
Reproductive and developmental effects: A 2-generation reproduction study in rats did not produce any evidence of reproductive effects. Developmental studies in rats and rabbits showed effects on foetal development in rats only, at dose levels above the maternotoxic dose, which are well in excess of the likely level of human exposure.
Poisons Schedule: Cyprodinil 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 0.09 mg/L for cyprodinil was determined as follows:
where:
2.7 mg/kg bw/day is the NOEL based on a long-term (2-year) 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.
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.
Otero RR, Ruiz CY, Grande BC, Gandara JS (2002). Solid-phase microextraction-gas chromatographic-mass spectrometric method for the determination of the fungicides cyprodinil and fludioxonil in white wines. Journal of Chromatography A, 942(1-2):41-52.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th Edition, British Crop Production Council, UK.
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