2.3 Interim decision in relation to tetraniliprole

2. Interim decisions on proposed amendments referred to the Advisory Committee on Chemicals Scheduling (ACCS #26, November 2019)

2.3. Interim decision in relation to tetraniliprole

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 tetraniliprole as follows:

Proposed date of effect of the proposed amendment

1 June 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 | Scheduling history | Australian regulations | International regulations | 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 tetraniliprole was considered.

The application proposed to exclude tetraniliprole from scheduling.

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

• The proposal is to consider a new substance, tetraniliprole, which it is considered does not require control by scheduling, based on sufficient toxicological data being available to recommend a scheduling decision. The data supports that tetraniliprole has low toxicity across the toxicological database and does not appear to present any substantial toxicological hazard. Tetraniliprole has low acute toxicity by the oral, dermal, and inhalational routes. Tetraniliprole is not a skin irritant in rabbits, is a slight eye irritant in rabbits and is slightly positive for skin sensitisation in mice. There is no evidence of neurotoxicity, genotoxicity, carcinogenicity, effects on reproduction or teratogenicity. The toxicity profile of tetraniliprole supports consideration for exemption from scheduling.
• There are no other concerns in relation to the potential health hazard when used according to the proposed draft label. No specialised equipment is required for safe use.

Current scheduling status

Tetraniliprole is not currently scheduled and has not been previously considered for scheduling. Therefore, a scheduling history is not available. However, there are several diamide insecticides scheduled in the Poisons Standard as follows:

Scheduling history

Flubendiamide

In October 2007, the National Drugs and Poisons Schedule Committee (NDPSC) considered the scheduling of flubendiamide. The Committee agreed that the toxicity profile generally aligned with the Schedule 5 criteria (i.e. low acute toxicity, slight eye irritant). A member asserted that the possibility of bioaccumulation was another reason that a Schedule 5 listing would be appropriate. A member noted the extended half-life of flubendiamide in the field could lead to possible human exposure. A member also noted the inability to measure inhalation toxicity for flubendiamide, but asserted that this was expected to be low given the formulation of the product. The Committee generally agreed that no low level cut-off could be set. The Committee decided to include a new entry in Schedule 5 for flubendiamide.

Cyantraniliprole

In February 2013, the chemical scheduling delegate made a delegate only decision to include cyantraniliprole, a new insecticide, in Schedule 5 with no cut-off. The Delegate's reasons for the decision stated that the toxicological profile of cyantraniliprole was well characterised and consistent with either listing in Schedule 5 or exemption from scheduling. The primary reason for considering that a Schedule 5 entry would be more appropriate was the slight eye irritancy observed with technical cyantraniliprole, along with the skin and eye irritancy observed with the proposed products (possibly aggravated by other formulation constituents).

Chlorantraniliprole

In February 2008, the NDPSC considered the scheduling of chlorantraniliprole. A member noted that the only toxicology issue was the eye irritancy, which was at the very low end of 'slight'. The liver effects were not an issue as they were only evident following long exposure at high doses. Therefore, the Committee agreed to include chlorantraniliprole in Appendix B, based on low toxicity.

Australian regulations

• Tetraniliprole is not listed on the TGA Ingredient Database.^[177]
• There are no medicines currently active on the Australian Register of Therapeutic Goods (ARTG)^[178] that contain tetraniliprole as an active ingredient.
• Tetraniliprole is not permitted to be included in listed medicines as it is not included in the Therapeutic Goods (Permissible Ingredients) Determination No.4 of 2019.^[179]
• There are no adverse events recorded on the Database of Adverse Event Notifications (DAEN).
• There are no products containing tetraniliprole listed on the Public Chemical Registration Information System Search (PubCRIS).^[180]

International regulations

• Currently, tetraniliprole is registered in Korea, with registrations under consideration in Chile, Japan, India, Malaysia, Pakistan, Mexico, Canada, New Zealand and the United States of America (USA).
• The European Chemicals Agency (ECHA)^[181] has the following hazard and classification labelling statement: 'Warning! According to the classification provided by companies to ECHA in REACH registrations this substance is very toxic to aquatic life, is very toxic to aquatic life with long lasting effects and may cause an allergic skin reaction.' The properties of concern state: 'A majority of data submitters agree this substance is skin sensitising.'

Summary of pre-meeting public submissions

No submissions were received response to the notice published under regulation 42ZCZK advising of the proposed amendment.

Summary of ACCS advice/recommendations to the Delegate

The Committee recommended that tetraniliprole be included in Schedule 5 of the Poisons Standard as follows:

The Committee also recommended an implementation date of 1 June 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; and (d) the dosage, formulation, labelling, packaging and presentation of a substance.

The reasons for the advice included:

52E(1) Considerations	Reasons
a - the risks and benefits of the use of a substance	Tetraniliprole is a new anthranilamide group of insecticides with low mammalian toxicity. It has the potential to replace older pesticide actives with higher mammalian toxicity.
b - the purposes for which a substance is to be used and the extent of use of a substance	Current use proposal is for professional use only but it could be used domestically in the future. A low application rate of 300 mL of product (or 60 g of tetraniliprole) per hectare is effective. The intended products contain 200 g/L tetraniliprole.
c - the toxicity of a substance	Skin sensitisation of tetraniliprole is consistent with a Schedule 5 classification. Tetraniliprole has low acute toxicity by the oral, dermal and inhalation routes. There is no evidence of neurotoxicity or genotoxicity. Tetraniliprole is not a skin irritant (rabbits). However, it is a slight eye irritant (rabbits). The product under consideration for registration contains tetraniliprole at 20% (w/v). At this concentration it is not considered a skin sensitiser.
d - the dosage, formulation, labelling, packaging and presentation of a substance	The product under consideration for registration contains a suspension concentrate formulation. The product under consideration for registration is intended for professional application only. It is not a general consumer product. A low application rate of 300 mL of product (or 60 g of tetraniliprole) per hectare is effective.
e - the potential for abuse of a substance	Nil.
f - 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 tetraniliprole;
• Advisory Committee on Chemicals Scheduling's advice;
• Section 52E 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; (c) the toxicity of a substance; and (d) the dosage, formulation, labelling, packaging and presentation of a substance.
• The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
• Scheduling Handbook (V 1.1, July 2019).

Reasons for the interim decision

I agree with the Committee's finding that the relevant provisions 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; and (d) the dosage, formulation, labelling, packaging and presentation of a substance.

In my view, the relevant parts of the SPF 2018 are Schedule 5 and Appendix B.

I have made a decision to include tetraniliprole at concentrations of 20 per cent or greater in Schedule 5 of the poisons Standard. In making my decision I have considered the requirements for inclusion of a substance in Appendix B and the Scheduling Factors for Schedule 5.

I have taken into account the toxicological data and hazard profile on tetraniliprole that was provided by the Applicant requesting an exemption from scheduling. However, I am satisfied that the information provided on tetraniliprole does not meet the requirements for inclusion in Appendix B to warrant it being considered exempt from scheduling. The criterion for a substance to be included in Appendix B requires that the substance must not meet the Scheduling Factors for any of the Schedules in the Poisons Standard. Tetraniliprole meets several acute toxicity endpoints under the SPF Schedule 5 Scheduling Factors. Therefore, it unsuitable for an exemption from the scheduling requirements under an Appendix B listing.

I find tetraniliprole to be consistent with the Scheduling Factors for Schedule 5 as it meets the acute oral (LD₅₀ >2000 mg/kg bw), dermal (LD₅₀ >2000 mg/kg bw) and inhalation (LC₅₀ >5010 mg/m³, 4-hour exposure) toxicological endpoints and is also a slight eye irritant and is slightly positive for skin sensitisation (GHS skin sensitisation category 1B). The data provided in the application also supports that tetraniliprole presents a low health hazard from repeated use as there is no evidence of neurotoxicity, genotoxicity effects on reproduction or teratogenicity. While there was evidence of neoplastic and non-neoplastic tumours in the reproductive tract in female rats, I agree with the Committee's advice that the carcinogenicity data may not be applicable to humans. Tumours were only seen in those animals that received the highest dose tested XXXXXXXXXXXXXXXXXXXXXXX, of tumours in this group was only slightly greater than in the control group (i.e. an increase of 1). Further, the females that received the highest dose showed the lower mortality. Furthermore, no carcinogenic effects were seen in mice at the highest dose tested XXXXXXXXXXXXX. While the impact of aging on tumourgenesis cannot not be fully excluded, carcinogenicity is more likely after a life time of exposure and considering the use pattern for tetraniliprole, lifetime exposure is considered to be unlikely.

I have taken into account that tetraniliprole is a new derivative of the anthranilide group of insecticides with low mammalian toxicity which has the potential to replace older pesticide actives with higher mammalian toxicity. A product containing 20 per cent (w/v) intended for professional use has been assessed by the APVMA and, in contrast to the technical grade active, is neither a skin sensitiser (negative for skin sensitisation in mouse LLNA test) nor an eye irritant. I have this taken into consideration together with its low toxicity and hazard profiles; the intended use pattern; the proposed APVMA labelling (which includes First Aid Instructions and Safety Direction to mitigate any potential health risks associated with the use of the formulated product); and the lack of pre-meeting submissions opposing the proposed exclusion from Scheduling, I am satisfied that on balance, the data supports a Schedule 5 entry with a cut-off to unscheduled of 20 per cent.

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