3.2. Dicyclanil
3. Delegate-only decisions on agricultural and veterinary chemicals
Delegate's final decision
The delegate's final decision under regulation 42ZCZU of the Therapeutic Goods Regulations 1990 (the Regulations) is to amend the Poisons Standard Schedule 6 entry for dicyclanil as follows:
Note
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Deleted text is shown as red, smaller font, with a strikethrough.
Schedule 6 – Amended Entry
DICYCLANIL except in preparations containing 5 6.5 percent or less of dicyclanil.
Index
DICYCLANIL
Schedule 6
Implementation date: 1 February 2019
Materials considered
The delegate considered the following in regards to this proposal:
- The application to amend the current Poisons Standard with respect to dicyclanil
- The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
- Section 52E (1) of the Therapeutic Goods Act 1989 in particular: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; and (c) the toxicity of a substance
Reasons:
The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:
- the risks and benefits of the use of a substance:
Dicyclanil is an insecticide used for the prevention in blowfly strike in sheep. The risk profile of products containing 6.5 percent dicyclanil is considered to be very similar to that of products containing the same substance at a concentration of 5 percent.
- the purposes for which a substance is to be used and the extent of use of a substance:
Dicyclanil is an insect development inhibitor very specific for the prevention of blowfly strike in sheep. It does not control any other external parasites of sheep. It is used mainly as a spray-on. It is not used in other livestock, horses or pets.
- the toxicity of a substance:
Dicyclanil 6.5 percent has low acute oral, dermal and inhalational toxicity, and is a slight skin and eye irritant. It is not considered to be a skin sensitiser. It is concluded based on the weight-of-evidence from in vitro and in vivo studies conducted since the original approval of dicyclanil that it is non-genotoxic.
- the dosage, formulation, labelling, packaging and presentation of a substance:
Nil
- the potential for abuse of a substance:
Nil
- any other matters that the Secretary considers necessary to protect public health:
Nil
Applicant's scheduling proposal and reasons for proposal
An application was submitted by the Australian Pesticides and Veterinary Medicines Authority (APVMA) to amend the Schedule 6 entry for 'dicyclanil' in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) – the Poisons Standard.
The applicant's reasons for the proposal were:
- Submitted toxicity data for the product XXXXXXXXXXXXXXXXXXXXXXXXXXXX containing 6.5% dicyclanil, showed a similar hazard profile to an APVMA registered product, XXXXXXXXXXXXXXXXXXXX, containing 5% dicyclanil.
- XXXXXXXXXXXXXXXXXXXXXXXXXXXX was considered by the NDPSC in 1997 for the purpose of establishing a 5% cut-off for dicyclanil from Schedule 6.
- The formulation details for XXXXXXXXXXXXXXXXXXXXXXXXXXXX indicate that the product contains scheduled excipients but they are present at concentrations below their relevant cut-off levels.
Current scheduling status
Dicyclanil is currently in Schedule 6 of the Poisons Standard as follows:
Schedule 6
DICYCLANIL except in preparations containing 5 per cent or less of dicyclanil.
Scheduling history
In November 1997, the National Drugs and Poisons Schedule Committee (NDPSC) considered a proposal to create a new entry for the new active consistent dicyclanil in the Poisons Standard. The committee agreed that the toxicological profile of dicyclanil was unremarkable and agreed that Schedule 6 was appropriate for dicyclanil. Whether products containing 5% or less of dicyclanil should be Schedule 5 or exempt from scheduling was equivocal but on balance the Committee agreed to exemption for these low concentrations.
Australian regulations
- Dicyclanil is an APVMA approved active constituent XXXXXXX XXXXXXXXXXXX XXXXXXXXX XXXXXXX XXXXXXXXXXXXXXX
- XXXXX (50g/L) and XXXXXXXXXXXXXXXXXXXXXXXXX are APVMA approved products XXXXXXXXXXXXXXXXXXXXXXXXXXXXX.
- Dicyclanil is not listed on the Therapeutic Goods (Permissible Ingredients) Determination No. 3 of 2018.
- Dicyclanil is neither an excipient nor active in any medicines on the ARTG.
International regulations
XXXXXXXX (12.5 g/L) and XXXXX (50 g/L) and are registered in Europe (MRP registration in France, United Kingdom/Ireland, Netherlands, and Spain) and South Africa and XXXXXXXXXXX (65 g/L) is registered in the United Kingdom/Ireland.
XXXXXXXXX (12.5 g/L) and XXXXX(65 g/L) are registered in New Zealand. ERMA Approval number: XXXXXXXXXX.
Dicyclanil is in the ECHA Annex III Inventory (EC / List no. 601-192-4)[7] as follows:
# Suspected carcinogen: The Toolbox profiler Carcinogenicity (genotox and nongenotox) alerts by ISS gives an alert for carcinogenicity; ISS Carcinogenicity model in VEGA (Q)SAR platform predicts that the chemical is Carcinogen (moderate reliability) # Suspected hazardous to the aquatic environment: The Danish QSAR database contains information indicating that the substance has a 48h EC50 to Daphnia of 1.44 mg/L; The Danish QSAR database contains information indicating that the substance has a 96h EC50 to green algae of 4.66 mg/L # Suspected mutagen: The Toolbox profiler in vitro mutagenicity (Ames test) alerts by ISS gives an alert for mutagenicity # Suspected persistent in the environment: The Danish QSAR database contains information indicating that the substance is predicted as non-readily biodegradable
The maximum residue limited of dicyclanil in foodstuff according to EU regulation No. 37/2010[8] are as follows:
| Pharmacologically active Substance | Marker residue | Animal Species | MRL | Target Tissues |
Other Provisions (according to Article 14(7) of Regulation (EC) No 470/2009) |
Therapeutic Classification |
|---|---|---|---|---|---|---|
|
Dicyclanil |
Sum of dicyclanil and 2, 4, 6-triamino-pyrimidine-5-carbonitrile |
Ovine |
200 μg/kg 150 μg/kg 400 μg/kg 400 μg/kg |
Muscle Fat Liver Kidney |
Not for use in animals from which milk is produced for human consumption. |
Antiparasitic agents/Agents against ectoparasites |
The sum total limit value to dicyclanil in wool is 2 ppm in the EU.[9]
Substance summary
Dicyclanil is a pyrimidin derivative. Dicyclanil is an insect development inhibitor very specific for the prevention of blowfly strike in sheep. It does not control any other external parasites of sheep. It is used mainly as a spray-on. It is not used in other livestock, horses or pets.[10]
| Property | dicyclanil |
|---|---|
|
Chemical structure |
 |
|
Molecular formula |
C8H10N6 |
|
CAS numbers |
112636-83-6 |
|
IUPAC and/or common and/or other names |
IUPAC: 4,6-diamino-2-cyclopropylaminopyrimidine-5-carbonitrile CAS: 4,6-diamino-2-(cyclopropylamino)-5-pyrimidinecarbonitrile |
| Toxicity | Species | End-point (6.5% product)* | End-point (5% product)** | SPF (2018) Classification |
|---|---|---|---|---|
|
Acute oral toxicity LD50 (mg/kg bw) |
Rat |
>2000 (no deaths) |
>5000 (no deaths) |
S6 (for 6.5% product)* Nil (for 5% product)** |
|
Acute dermal toxicity LD50 (mg/kg bw) |
Rat |
>2000 (no deaths) |
>5000 (no deaths) |
Nil |
|
Acute inhalational toxicity LC50 (mg/m3/4h) |
No data |
>3000 (estimate) |
>3000 (estimate) |
Nil |
|
Skin irritation |
Rabbit |
Slight irritant |
Slight irritant |
Nil |
|
Eye irritation |
Rabbit |
Slight irritant |
Slight irritant |
Nil |
|
BCOP test |
Negative |
- |
||
|
Skin sensitisation |
Mouse (LLNA) |
Negative |
- |
Nil |
|
GPMT |
Negative |
Nil |
Studies on the product, XXXXXXXXXXXXXXXXXXXXXXXXXX (6.5% dicyclanil), were provided to APVMA for assessment. The outcome is summarised below.
Acute toxicity
OECD guideline-compliant studies in rats XXXXXXXXXXXXXXXXXXXXXXXXXXXX (6.5% dicyclanil), show that it has low acute oral toxicity, low acute dermal toxicity, and low inhalation toxicity.
Skin and eye irritation
OECD guideline-compliant studies in rabbits and in vitro in the BCOP test with XXXXXXXXXXXXXXXXXXXXXXXXXXXX (6.5% dicyclanil) show it to be a slight skin and eye irritant.
Sensitisation
An OECD guideline-compliant murine LLNA test with XXXXXXXXXXXXXXXXXXXXXXXXXXXX (6.5% dicyclanil) shows that it was not considered to be a skin sensitiser.
Genotoxicity
The APVMA has evaluated additional genotoxicity studies with the active constituent, dicyclanil (a new comet assay and a new micronucleus assay) together other genotoxicity studies that have been published since the original approval of dicyclanil in 1997. These studies do not alter the APVMA's previous conclusion that the weight-of-evidence indicates dicyclanil to be non-genotoxic and therefore do not impact on Scheduling considerations.