4.2 Agrobacterium radiobacter (Rhizobium rhizogenes)

4 Final decision(s) (without interim decision) made pursuant to regulation 2ZCZU

4.2. Final decision in relation to Agrobacterium radiobacter (Rhizobium rhizogenes)

Final decision

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 Agrobacterium radiobacter (Rhizobium rhizogenes) as follows:

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

Materials considered

In making this final decision, I have considered the following:

• The Applicant's application to amend the current Poisons Standard with respect to Agrobacterium radiobacter (Rhizobium rhizogenes);
• 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; and (e) the potential for abuse of a substance;
• 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 the Appendix B entry for Agrobacterium radiobacter. The application proposes to amend the Appendix B entry for Agrobacterium radiobacter and rename it to Rhizobia rhizogenes to reflect the reclassification in the scientific nomenclature of this organism.

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

The Applicant's reasons for the proposal are:

• The proposed change is purely an amendment to the entry in Appendix B to reflect the correct phylogenetic identification of this species.
• No public health impact is anticipated from this change, as it will not result in any change of the quantity of the substance available in the market, and will not change the current use pattern.
• Agrobacterium was originally included in Appendix B in 1989 based on very low oral toxicity, no skin or eye irritation and no evidence of sensitisation.

Current scheduling status

Agrobacterium radiobacter is currently included in Appendix B, Part 3 of the Poisons Standard as follows:

Scheduling history

In November 1989, the Drugs and Poisons Schedule Committee considered a proposal to exempt Agrobacterium radiobacter (var. Radiobacter strain K1026) from scheduling. The bacterium was noted to be developed by genetic manipulation and had been cleared for use by the Genetic Manipulation Advisory Committee. The Committee noted that no toxicological studies were available for strain K1026 but accepted that the toxicological profile of the related K84 strain which had demonstrated low toxicology. The Committee recommended an exemption from scheduling through the inclusion of Agrobacterium radiobacter in Appendix B of the Poisons Standard.

Australian regulations

• There is one (1) registered fungicide product containing Agrobacterium radiobacter listed on the Public Chemical Registration Information System Search (PubCRIS).^[30] Agrobacterium radiobacter is also listed as an approved active constituent on PubCRIS. In both listings, Agrobacterium radiobacter var radiobacter strain K1026, is specifically named as the active.
• There have been no adverse experiences reported between 2009-2019 for Agrobacterium radiobacter in the APVMA Adverse Experience Reporting Program database (AERP).^[31]
• Agrobacterium radiobacter is not identified in the following databases:
  • TGA Ingredient Database^[32]
  • Australian Register of Therapeutic Goods (ARTG)^[33]
  • Therapeutic Goods (Permissible Ingredients) Determination^[34] No.1 of 2020
  • TGA prescribing medicines in pregnancy database^[35]
  • Therapeutic Goods (Medicines Advisory Statements) Specification 2019^[36]
  • Database of Adverse Event Notifications (DAEN)^[37]
  • NICNAS Australian Inventory of Chemical Substances (AICS).^[38]

International regulations

• In the USA, Agrobacterium radiobacter strain K1026 is registered^[39] as an active ingredient in pesticide products registered with the United States Environmental Protection Agency's (US EPA) Office of Pesticides Programs.^[40]
• It is not listed on the United States Food and Drug Administration Approved Drug Products Database (Drugs@FDA).^[41]
• Agrobacterium radiobacter was not identified in the European Chemicals Agency (ECHA)^[42] or the European Commission database for information on cosmetic substances and ingredients database.^[43]
• While Agrobacterium radiobacter strain K1026 is not specifically listed in the European Union Pesticides Database,^[44] the related strain K84, is identified in this database although it is currently not approved.
• In New Zealand, Agrobacterium radiobacter is not registered for use as a pesticide or as an active in medicines according the New Zealand Inventory of Chemicals (NZIoC)^[45] and New Zealand Medicines and Medical Devices Safety Authority (MedSafe),^[46] respectively.
• In Canada, Agrobacterium radiobacter is not registered for use as a pesticide or as an active medicines according to Canada's Pest Management Regulation Agency^[47] and the Canadian (Health Canada) Drug Product Database,^[48] respectively.

Substance summary

Agrobacterium radiobacter strain K1026 is a microbial pesticide that can be used to treat germinating seeds or roots and stems of certain stone fruit and nut trees and ornamentals to protect them from crown gall disease.^[49] Products are intended for use in the greenhouse or in nurseries.

Agrobacterium radiobacter strain K1026 is a derivative (deletion of specific genetic material) of Agrobacterium radiobacter strain K84. Removal of this genetic material prevents the transfer of resistance from strain K1026 to other strains. Except for the deletion of a small portion of DNA removed in K84, the two strains are essentially identical and have the same characteristics. The naturally occurring bacterium Agrobacterium radiobacter strain K84 is widespread in soil and found near plant roots. A toxic compound produced by both K1026 and K84 controls certain other Agrobacterium spp. that cause crown gall disease.

An EPA assessment^[50] found Agrobacterium radiobacter strain K1026 microbe is not likely to produce adverse effects in humans. The very similar organism, Agrobacterium radiobacter strain K84, has been used for decades without any reports of adverse effects or reactions. Agrobacterium radiobacter strains K1026 and K84 are not known to cause any infectious diseases in humans. This microbial pesticide is not intended for use on food crops. Consequently, it is not likely to pose a hazard to human adults, infants, children, or other sensitive subpopulations via the dietary route of exposure. The potential aggregate exposure, derived from non-dietary and non-occupational exposure, should be minimal or non-existent. Tier 1 ecotoxicology studies were waived based on the derivation of Agrobacterium radiobacter strain K1026 from strain K84, minimal exposure to non-target organisms, and no evidence of any unintended effects on non-target species by strain K84. Based upon this evaluation, the EPA determined that Agrobacterium radiobacter strain K1026 is likely to pose only a minimal risk to the environment or non-target organisms.

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 update the scientific name of the organism will not affect the risk or benefits from the use of products containing this substance (organism). Agrobacterium radiobacter var radiobacter has been used in Australia for more than 40 years for the control of crown gall in a range of crops. It has been included in Appendix B of the SUSMP since November 1989, based on its low toxicity via the oral route, and no evidence of skin or eye irritation or skin sensitisation. No additional risks are anticipated with the change in name to the substance (organism) to read Rhizobium rhizogenes (52E(1)(a)).
• The pattern and extent of use is not expected to change following the change in the name of the substance (organism) to reflect current scientific nomenclature (52E(1)(b)).
• There has been no substantive change in the information available regarding the toxicity of the substance (organism) since it was last considered for Scheduling, which would warrant a change to its current exemption (Appendix B) in the Poisons Standard based on the criteria set out in SPF (2018) (52E(1)(c).
• The dosage (application rate), formulation, labelling, packaging and presentation of the substance (organism) will not change as a result of the name change, other than to provide a correction to the name of the active constituent on products containing the substance (organism) (52E(1)(d)).
• There is no information to indicate that products containing the substance (organism) could pose a risk to humans from abuse of the substance (organism). Furthermore, the change in name of the substance (organism) will not affect the potential for abuse (52E(1)(e).
• There were no other matters that were considered necessary to protect human health (52E(1)(f)).

Therefore, I have decided to amend the current Poisons Standard in the manner set out in the application with the minor change to the name of the genus. The name of the substance (organism) will be changed to Rhizobium rhizogenes. The proposed amendment was not referred to an expert advisory committee.

Date of effect of the decision

1 June 2020

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