Nicarbazin
(endorsed 2011)
Guideline
Based on human health concerns, nicarbazin in drinking water should not exceed 1 mg/L.
Related chemicals
Nicarbazin (CAS 330-95-0) does not belong to a recognised chemical class. It is a synthetic complex composed of an equimolar amount of 4,4’-dinitrocarbanilide (DNC) and 2-hydroxy-4,6-dimethylpyrimidine (HDP). There are no related pesticides (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, nicarbazin would not be a health concern unless the concentration exceeded 1 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
Users: Nicarbazin is a non-ionophoric parasiticide that is used as a coccidiostat feed additive for the prevention of faecal and intestinal coccidiosis in broiler chickens.
There are registered products containing nicarbazin in Australia. The products are intended for professional use and are available as concentrated granular and powder formulations for addition to feed. Data on currently registered products are available from the Australian Pesticides and Veterinary Medicines Authority.
Exposure sources: The main source of public exposure to nicarbazin and its metabolites is residues in food. Residue levels in chicken products produced according to good veterinary practice are generally low.
The veterinary use of nicarbazin 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 reports of nicarbazin in Australian drinking waters have been identified.
Treatment of drinking water
There is insufficient information on the treatment of nicarbazin in drinking water, but it is expected that advanced treatment methodologies such as ozonation and advanced oxidation would be effective.
Measurement
No suitable analytical techniques have been identified, but the use of high performance liquid chromatography–tandem mass spectrometry is expected to be suitable for residue levels of this pesticide in water. This technique has previously been used for the analysis of nicarbazin in poultry products.
History of the health values
The current acceptable daily intake (ADI) for nicarbazin is 0.4 mg per kg of bodyweight (mg/kg bw) based a no-observed-effect level (NOEL) of 200 mg/kg bw/day in a rat developmental study, with a safety factor of 500.
The previous ADI of 2 mg/kg bw established in 1982 was based on a NOEL of 200 mg/kg bw/day from a 2-year rat dietary study. The ADI incorporated a safety factor of 100.
The current acute reference dose (ARfD) is 0.4 mg/kg bw, based on a NOEL of 200 mg/kg bw/day in a rat developmental study with a safety factor of 500.
A health value has not been previously established by NHMRC.
Health considerations
Metabolism: Nicarbazin consists of equimolar amounts of 4,4’-dinitrocarbanilide (DNC) and 2-hydroxy-4,6-dimethylpyrimidine (HDP). HDP is readily absorbed via the gastrointestinal tract while DNC is not. There is no evidence of bioaccumulation. Elimination is mainly via the urine for HDP and via the faeces for DNC.
Acute effects: Nicarbazin has a low acute oral and dermal toxicity. It is not a skin sensitiser.
Short-term effects: Information on short-term effects is very limited. The available data indicate that in rats there are effects on the kidney at 500 mg/kg bw/day, while in dogs there is bile duct proliferation at 1600 mg/kg bw/day.
Long-term effects: A 2-year dietary study in rats reported no treatment-related effects up to 300 mg/kg bw/day of DNC plus 100 mg/kg bw/day of HDP. A 2-year dietary study in dogs reported transitory liver enzyme changes and slight effects on bile duct at highest dose only, namely, 600 mg/kg bw/day of DNC plus 200 mg/kg bw/day of HDP. The NOEL was 180 mg/kg bw/day DNC plus 60 mg/kg bw/day HDP.
Carcinogenicity: Based on long-term studies in rats, there is no evidence of carcinogenicity for nicarbazin.
Genotoxicity: Nicarbazin was weakly positive in in vitro bacterial studies, but in vivo studies were negative. There is insufficient information to determine its genotoxic potential.
Reproductive and developmental effects: There are no studies available to examine the potential effects of nicarbazin on reproductive parameters. A developmental study in rats reported effects on the dams and foetuses at 600 mg/kg bw/day, but the study was of poor quality. The NOEL was 200 mg/kg bw/day and is the basis of the current ADI.
Poisons Schedule: Nicarbazin 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 value of 1 mg/L for nicarbazin was determined as follows:
where:
200 mg/kg bw/day is the NOEL based on a developmental study in rats.
70 kg is taken as the average weight of an adult.
0.1 is a proportionality factor based on the conservative 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.
500 is a safety factor applied to the NOEL from a developmental study conducted in rats. The safety factor incorporates a factor of 10 for interspecies extrapolation, 10 for intraspecies variations, and an additional safety factor of 5 for limitations in the current database.
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.
Tomlin CD (ed) (2006). The Pesticide Manual: a world compendium, 14th Edition, British Crop Production Council, UK.
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