4 Final decision(s) (without interim decision) made pursuant to regulation 2ZCZU
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Final decision in relation to Acequinocyl
Pursuant to regulation 42ZCZU of the Regulations, a Delegate of the Secretary has made a final decision to amend the current Poisons Standard in relation to acequinocyl as follows:
Schedule 5 - New Entry
Index - New Entry
Reasons for the final decision (including findings on material questions of fact)
In making this final decision, I have considered the following:
- The Applicant's application to amend the current Poisons Standard with respect to acequinocyle;
- Subsection 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; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters considered necessary to protect public health;
- The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
- Scheduling Handbook (V 1.0, January 2018).
Findings on material questions of fact
An application was submitted by the Australian Pesticides and Veterinary Medicines Authority (APVMA) to amend the Poisons Standard with respect to acequinocyl. The application proposes to create a new Schedule 5 entry for acequinocyl in the Poisons Standard.
The Applicant's proposed amendments to the Poisons Standard are:
Schedule 5 - New Entry
Index - New Entry
The Applicant's reasons for the proposal are:
- The proposal is to consider a new substance, acequinocyl, which it is considered appropriate for inclusion in Schedule 5 of the Poisons Standard, based on sufficient toxicological data being available to recommend a scheduling decision.
- Acequinocyl belongs to the quinoline class of miticides and the mode of action is binding to the Qo centre of Complex III in the mitochondria of the mite cells and inhibiting electron transfer. Acequinocyl is a known Vitamin K antagonist and thereby is thought to disrupt blood coagulation.
- Acequinocyl has low acute toxicity by oral, dermal and inhalational routes, although it resulted in evidence of significant respiratory irritation. It is a slight skin and eye irritant and although it was a skin sensitiser in the guinea pig via the Guinea Pig Maximisation Test (GPMT), it was not under the Buehler method, a method considered more relevant for occupational exposure.
- The active is not a developmental or reproductive toxicant, is not genotoxic in a battery of in vivo and in vitro assays and was not carcinogenic in life time studies in mice and rats. In repeat-dose studies in laboratory animals, the primary target was the coagulation system, characterised by increased prothrombin time (PT), increased activated partial thromboplastin time (APTT) and internal haemorrhage.
- Such effects were seen across the database which was largely administered by the oral route, but also following repeat dermal application in rats. Mechanistic studies showed prolonged PT and APTT in rats following a single dose, and the reversibility of these effects.
- The product, XXXXXXXX XXXXXXXX containing 156 g/L of acequinocyl has low acute toxicity by the oral, dermal and inhalational routes, is not a skin irritant, is slightly irritating to the eyes and is not a skin sensitiser in guinea pigs (Buehler method).
- The management of acequinocyl toxicological risks would be adequately achieved through a listing in Schedule 5 of the Poisons Standard with no cut-off or exemptions.
Current scheduling status and scheduling history
Acequinocyl is not specifically scheduled in the current Poisons Standard and has not been previously considered for scheduling. Therefore, a scheduling history is not available.
- Acequinocyl is not available for use as an active ingredient in human therapeutic products as it is not listed in the TGA Ingredient Database.
- There are currently no medicines active on the Australian Register of Therapeutic Goods (ARTG) that contain acequinocyl as an active ingredient.
- Acequinocyl is not permitted to be included in listed medicines as it is not included in the Therapeutic Goods (Permissible Ingredients) Determination No.1 of 2020.
- Acequinocyl is not listed on the TGA prescribing medicines in pregnancy database.
- The Therapeutic Goods (Medicines Advisory Statements) Specification 2019 does not contain warning statements pertaining to acequinocyl.
- There are no adverse events reported for acequinocyl on the Database of Adverse Event Notifications (DAEN).
- There are no products containing acequinocyl as an active ingredient that are listed on the Public Chemical Registration Information System Search (PubCRIS).
- Acequinocyl is classified as Group 20B Miticide (Insecticide Resistance Action Committee, 2005).
- As of September 2003, acequinocyl is registered as an active ingredient for use in pesticides in the United States according to the United States (U.S) Environmental Protection Agency.
- Acequinocyl is currently registered to XXXXXX XXXXXXXXXXX XXXXX XXXXXXX XXXXXXXXXXXX as a 15% soluble-concentrate (SC) formulation.
- The European Chemicals Agency (ECHA) hazard classification and labelling for acequinocyl identifies it as 'Danger! According to the harmonised classification and labelling (ATP03) approved by the European Union, this substance causes damage to organs, is very toxic to aquatic life, is very toxic to aquatic life with long lasting effects and may cause an allergic skin reaction'.
- In New Zealand, there are no registered products containing acequinocyl according to the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the New Zealand Inventory of Chemicals (NZIoC).
- In Canada, acequinocyl is registered as an active ingredient in 3 registered products on Canada's Pest Management Regulation Agency. There are no registered medicines containing acequinocyl according to the Canadian (Health Canada) Drug Product Database.
Acequinocyl is a new active constituent which is not currently scheduled in the Poisons Standard. Acequinocyl is in the quinoline class of miticides and is for the control of certain mites in pome and stone fruits. Toxicity studies on acequinocyl and its product have been submitted to the APVMA in support of the active approval and product registration.
|Molecular weight||384.5 g/mol|
|IUPAC and/or common and/or other names|| |
IUPAC: 3-dodecyl-1,4-dihydro-1,4-dioxo-2-naphthyl acetate
Common name: Acequinocyl
Other names: 3-dodecyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate
|Toxicity||Species||Endpoint||SPF (2018) Classification for acequinocyl||XXXXXXXX XXXXXXXX||SPF (2018) Classification for XXXXXXXX XXXXXXXX|
|Acute oral toxicity||Mice||LD50 >5000 mg/kg bw1||-||LD50 >5000 mg/kg bw||-|
|Rat||LD50 >5000 mg/kg bw1||-||LD50 >5000 mg/kg bw||-|
|Acute dermal toxicity||Rat||LD50 >2000 mg/kg bw||Schedule 52||LD50 >2000 mg/kg bw||Schedule 52|
|Acute inhalational toxicity||Rat||LC50 >840 mg/m3 (whole body; 4-h)||Schedule 53||LC50 >4560 mg/m3(whole body; 4-h)||Schedule 54|
|Skin irritation||Rabbit||Slightly irritating||Schedule 5||Non-irritating||-|
|Eye irritation||Rabbit||Slightly irritating||Schedule 5||Slightly irritating||Schedule 5|
|Skin sensitisation (Buehler)||Guinea pig||Non-sensitiser5||-||Non-sensitiser||-|
- Note that this was the only dose tested, with no deaths and no clinical signs of toxicity (other than watery faeces up to 2 h after administration) for either acequinocyl or the product tested.
- Note that this was the only dose tested, with no deaths and no clinical signs of toxicity for either acequinocyl or the product tested.
- 1/10 deaths at 840 mg/m3 and 1/10 deaths at 690 mg/m3. This was reported to be the maximal attainable concentration achievable under the test conditions, and particle size was of adequate respirability. There was clinical signs and histopathology indicative of severe pulmonary inflammatory reactions.
- There were no deaths and clinical signs during exposure were considered consistent with exposure to a high concentration of aerosol and not specific toxicity.
- Skin sensitisation via GPMT was positive, but Buehler is considered more representative of occupational exposure.
Reasons for final decision
In determining that this matter will be a delegate-only decision I have taken into account the information provided in the application from the Applicant (APVMA), and the matters outlined under Section 52E of the Therapeutic Goods Act 1989 and the Scheduling Policy Framework (SPF, 2018). In particular, I note that:
- The proposed change to the Poisons Standard to include a new entry for acequinocyl, indicates that there are benefits to the agricultural industry from the introduction of this new pesticide (miticide), to control for the two-spotted mite (Tetranychus urticae) in pome and stone fruit. The product containing the new substance (acequinocyl) is intended for professional use in orchards, with limited potential for exposure to the general public. The risks associated with human exposure to the substance have been adequately addressed by the pesticide regulator (APVMA) in its application (52E(1)(a)).
- The purpose and extent for which the substance is to be used has been adequately outlined by the Applicant. I have also noted the current registration of similar products for use in a range of fruit and vegetable crops, and ornamental plants in the USA, Canada and Europe (52E(1)(b)).
- The data indicate that acequinocyl has a low acute toxicity by the oral, dermal and inhalational routes of administration, although the undiluted substance is expected to be a respiratory irritant. It is slightly irritating to the eyes and skin, but is not expected to be a skin sensitiser. Acequinocyl was not genotoxic in a battery of in vitro and in vivo assays and was not considered carcinogenic in chronic/lifetimes studies in mice and rats. Acequinocyl was not a reproductive toxicant in rats or a developmental toxicant in rats and rabbits. There was no evidence of teratogenicity in either species, and any embryotoxicity occurred at maternotoxic doses. The potential for inhalational toxicity/irritation due to acequinocyl was considered on the whole to be a limited driver to place the substance in Schedule 6, according to the criteria set out in the SPF (2018). Moreover, the inhalation toxicity of a product containing 15.6% acequinocyl was shown to be low (LC50 >4560 mg/m3(whole body; 4-h)), lending further support to the classification of the substance into Schedule 5 (52E(1)(c)).
- The Applicant has demonstrated that appropriate risk mitigation measures will be put in place for the proposed product containing the substance that may be registered for use in Australia, and that account for the dosage (application rate), formulation, labelling, packaging and presentation of the substance. As a result, no additional measures are required in the Poisons Standard. Further use of the substance in other pesticide products will be addressed by the pesticide regulator (APVMA) in any future applications to the regulator (52E(1)(d)).
- There is no information to indicate that products containing the substance could pose a risk to humans from abuse of the substance (52E(1)(e)).
- National and International Health Based Guidance Values have been or will be established for the substance that will protect consumers from residues of the substance in food (52E(1)(f)).
Therefore, I have decided to amend the current Poisons Standard in the manner set out in the application. The proposed amendment was not referred to an expert advisory committee.
Date of effect of the decision
1 June 2020