2.3. Interim decision in relation to broflanilide

Interim decisions on proposed amendments referred to the Advisory Committee on Chemicals Scheduling (ACCS #25, June 2019)

Interim decision in relation to broflanilide

Interim decision

Pursuant to regulation 42ZCZN of the Regulations, a Delegate of the Secretary has, in relation to the proposed amendment, made an interim decision to amend the current Poisons Standard in relation to broflanilide as follows:

Proposed date of effect of the proposed amendment

1 February 2020

Reasons for the interim decision (including findings on material questions of fact)

In this section: Applicant's scheduling proposal and reasons for the proposal | Current scheduling status | Australian regulations | International regulations | Substance summary | Summary of pre-meeting public submissions | Summary of ACCS advice/recommendations to the Delegate | Delegate's considerations | Reasons for the interim decision

Applicant's scheduling proposal and reasons for the proposal

An application to amend the current Poisons Standard with respect to broflanilide was considered. The application proposed to create a new Schedule 6 entry for broflanilide, with a concentration cut-off of 3 per cent for Schedule 5.

The Applicant's proposed amendments to the Poisons Standard were:

The Applicant's main points provided in support of the proposed amendment were as follows:

• Broflanilide and its products are of low acute toxicity. While broflanilide is not genotoxic, ovarian and uterine tumours were seen in rats, with a clear dose threshold. This is consistent with a Schedule 6 entry for broflanilide, with a risk of producing irreversible harm. The proposal for a cut off at 3 per cent to Schedule 5 is a reflection of the clear thresholds resulting in products at this level, which are unlikely to produce irreversible toxicity. No specialised equipment is required for safe use, and the likelihood of injury can be mitigated through appropriate packaging and simple label warnings. Broflanide will only be made publically available in formulated products which will be labelled appropriately.
• Broflanilide is a new meta-diamide pro-pesticide, classified as a benzamide, acting through a novel mechanism. Its active invertebrate metabolite acts as a gamma-aminobutyric acid receptor antagonist. It is effective against pests with resistance to cyclodienes and fipronil.
• The Australian Pesticides and Veterinary Medicines Authority (APVMA) has received an application for the new active constituent broflanilide and a set of products including aerosol, granular bait and bait products containing between 0.045 g/kg and 2.5 g/kg broflanilide.
• Broflanilide is of very low acute toxicity from the oral, dermal and inhalational route. It is slightly irritating to the eyes, not irritating to the skin, and is not a skin sensitiser.
• In repeat dose studies in laboratory animals, broflanilide primarily affects the adrenal glands and, in females, the ovaries.
• Broflanilide is not considered to be genotoxic. In rats, an increase in benign ovarian tumours was seen, along with an increase in uterine adenocarcinomas at high doses, which correlated with an increase of endometrial hyperplasia at lower doses. The mode of action of these tumours is likely considered to be non-genotoxic with a clear dose threshold.
• Broflanilide did not demonstrate developmental toxicity and there were no adverse effects on fertility or reproduction in multi-generation studies.
• A range of other insecticides for use as baits and for crack and crevice treatments exist, including products containing abamectin, fipronil, hydramthylnon, imidacloprid and pyriproxyfen.

Current scheduling status

Broflanilide is not specifically scheduled in the current Poisons Standard. Therefore a scheduling history is not available.

Australian regulations

• Broflanilide is not listed on the TGA Ingredient Database.
• As of 7 May 2019, broflanilide is neither an excipient nor active ingredient in any medicines on the Australian Register of Therapeutic Goods (ARTG)^[34].
• Broflanilide is not permitted to be included in listed medicines as it is not included in the Therapeutic Goods (Permissible Ingredients) Determination No. 2 of 2019^[35].
• As of 7 May 2019, the Database of Adverse Event Notifications (DAEN)^[36] contains no reports of adverse events for products containing broflanilide as an active ingredient.
• As of 7 May 2019, there are no products containing broflanilide listed on the Public Chemical Registration Information System Search (PUBCRIS)^[37].

International regulations

• Broflanilide is not listed on the European Chemicals Agency (ECHA) website.
• There are no products containing broflanilide currently approved/registered in America, Canada, the European Union or New Zealand. Applications are currently under consideration in America, Canada, Mexico and India.

Substance summary

Table 1: Chemical information for broflanilide

Property	Broflanilide
Chemical structure
Molecular formula	C25H14BrF11N2O2
Molecular weight	663.28 g/mol
CAS name	3-(benzomethylamino)-N-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl)-6-(trifluoromethyl)phenyl]-2-fluorobenzamide
CAS number	1207727-04-5
IUPAC and/or common and/or other names	N-[2-bromo-4-(perfluropropan-2-yl)-6-(trifluormethyl)phenyl]-2-fluoro-3-(N-methylbenzamido)benzamide (IUPAC)

Summary of pre-meeting public submissions

No public submissions were received in response to the proposed amendment.

Summary of ACCS advice/recommendations to the Delegate

The Committee recommended that new Schedule 5 and 6 entries for broflanilide be created as follows:

The Committee also recommended an implementation date of 1 February 2020.

Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance.

The reasons for the advice included:

1. risks and benefits of the use of a substance:
   • Risks:
     • The irreversible toxicity data is consistent with a Schedule 6 listing but there is a clear threshold for these effects (ovarian and uterine tumours in rats).
   • Benefits:
     • A very low concentration of broflanilidie is required, resulting in low level exposure for users.
     • New pesticide active for control of insects with novel action.
2. the purpose for which a substance is to be used and the extent of use:
   • Pesticide for control of insects.
   • Currently proposed products include domestic uses.
   • Broflanilide is proposed for use in a range of products as a bait product to control insect pests, including flies, ants, termites and cockroaches in a range of indoor and outdoor situations, including domestic, commercial, industrial and agricultural patterns of use containing between 0.045 g/kg and 2.5 g/kg broflanilide.
3. the toxicity of a substance:
   • Although of low acute toxicity, the repeat dose toxicity is consistent with Schedule 6.
   • Consistent with Schedule 5 at 0.3% or less - low toxicity, non-corrosive, has a low health hazard and low potential of causing harm reduced by packaging and simple warning and safety directions on the label.
4. the dosage, formulation, labelling, packaging and presentation of a substance:
   • Products proposed for non-food producing uses contain low levels of broflanilide and low daily use rates.
   • Appropriate labelling and packaging controls for these products will be assigned by the APVMA.
   • A number of products are currently under consideration containing broflanilide for non-food producing use between 0.045 g/kg and 2.5 g/kg broflanilide.
   • Appropriate labels, including directions for use and appropriate First Aid and Safety Directions will be approved by the APVMA.
5. the potential for abuse of a substance:
   • There are currently no reports of misuse or overdose with broflanilide.
   • There is not expected to be any potential for broflanilide to be converted into a controlled substance.
6. any other matters that the Secretary considers necessary to protect public health:
   • Nil.

Delegate's considerations

In making this interim decision, I have considered the following material:

• The application to amend the current Poisons Standard with respect to broflanilide;
• Advisory Committee on Chemicals Scheduling's advice;
• Section 52E of the Therapeutic Goods Act 1989, in particular: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance;
• The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
• The Australian Health Ministers' Advisory Council's Scheduling Handbook (V 1.0, January 2018).

Reasons for interim decision

I agree with the Committee's finding that the relevant matters of section 52E of the Therapeutic Goods Act 1989 are: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance.

In my view, the relevant parts of the Scheduling Policy Framework (SPF) 2018 are the scheduling factors for Schedule 5 and Schedule 6.

I have made the decision to amend the current Poisons Standard by creating new Schedule 5 and Schedule entries for broflanilide and I have set out my reasons below.

Having considered the SPF 2018, it is my view that a parent schedule entry for broflanilide in Schedule 6 is appropriate. While broflanilide is not genotoxic, ovarian and uterine tumours were seen in rats but not mice with a clear dose threshold. This is consistent with the Schedule 6 scheduling factors that broflanilide has a moderate risk of producing irreversible harm. Further, taking the results of the carcinogenicity study in rats into account, and the fact that broflanilide is a new pesticide active acting through a novel mechanism, I am persuaded that broflanilide presents as a moderate health hazard and in accordance with the Scheduling Factors for Schedule 6.

I am satisfied that broflanilide exhibits low acute toxicity and clear thresholds which are unlikely to produce irreversible toxicity at concentrations below 0.3%. At below 0.3%, broflanilide has a low health hazard that is consistent with the Schedule 5 scheduling factors.

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