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Final decisions amending, or not amending, the current Poisons Standard, November 2018

Part B - Amendments to the Poisons Standard not referred to expert advisory committee

29 November 2018

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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

New text is shown as green, larger font, with a horizontal line above it.

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:

Reasons:

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  1. 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.

  2. 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.

  3. 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.

  4. the dosage, formulation, labelling, packaging and presentation of a substance:

    Nil

  5. the potential for abuse of a substance:

    Nil

  6. 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]

Table 2.1: Chemical information for dicyclanil
Property dicyclanil

Chemical structure

chemical structure of dicyclanil

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

Table 2.2: Acute toxicity end-points for XXXXXXXXXXXXXXX and XXXXXXXXXXXXXXXX XXXXXXXXXXXXX
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.


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