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Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, March 2016

Scheduling medicines and poisons

12 May 2016

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1.13 Streptomyces lidicus

Part A - Interim decisions on scheduling proposals referred to an advisory committee (March 2016)

1. Advisory Committee on Chemicals Scheduling (ACCS#16)

1.13 Streptomyces lidicus

Referred scheduling proposal
  • To create a new Schedule 6 entry for Streptomyces lydicus WYEC 108 for agricultural use, with an exemption for preparations containing 0.037% or less.
Scheduling application

In December 2015, the Office of Chemical Safety (OCS), based on an application made to the Australian Pesticides and Veterinary Medicines Authority (APVMA) for the approval of Streptomyces lydicus WYEC 108 as a new active constituent and the registration of a product, Actinovate BioFungicide, containing Streptomyces lydicus WYEC 108, recommends that the delegate consider creating a new entry for Streptomyces lydicus WYEC 108 in Schedule 6 of the SUSMP with cut-off exemptions (to unscheduled) when used in preparations containing 0.037 per cent or less of Streptomyces lydicus WYEC 108 for agricultural use.

The reasons for the request are:

  • The OCS assessment estimated Streptomyces lydicus WYEC 108 to be a potential skin and respiratory sensitiser, therefore meeting the Scheduling Policy Framework criteria for Schedule 6.
  • The OCS assessment concluded that the product Actinovate BioFungicide containing 0.037% (w/w) Streptomyces lydicus WYEC 108 did not meet the Scheduling Policy Framework criteria, and as such, an exemption cut-off was proposed at 0.037 per cent or less for agricultural use.

Specific issues/questions raised by the delegate

The delegate's reasons for referring this to the Committee for advice were: the overall low toxicity profile of this biological pesticide suggests that scheduling is not required, but seeks advice from the ACCS to determine whether there is sufficient evidence of skin/respiratory sensitisation potential to justify listing in Schedule 6, with an exemption for a product containing 0.037% or less of Streptomyces lydicus WYEC 108.

The Delegate has sought advice from the Committee on the following questions:

  • Does the ACCS agree with the OCS evaluation that, despite a lack of studies with the specific strain of Streptomyces lydicus, there is sufficient knowledge of the skin/respiratory sensitisation potential of this fungus, to assume that it meets SPF criteria for listing in Schedule 6?
  • Does the ACCS agree that any sensitisation potential is sufficiently ameliorated at low concentration to warrant an exemption clause for the product containing 0.037% in the Schedule 6 entry?
Substance summary
Acute toxicity

The acute toxicity end-points for Streptomyces lydicus WYEC 108 are listed below.

Toxicity Species Results SPF* Classification
Acute oral toxicity LD50 (mg/kg bw) Rat

>5050

(~ 2.5 x 109 CFU/kg bw)

No deaths

N/A
Acute dermal toxicity LD50 (mg/kg bw) Rat

>5050

(~ 9.95 x 109 CFU/kg bw)

No deaths

N/A
Acute inhalation toxicity Estimated Low N/A
Acute pulmonary toxicity/ pathogenicity Rat

LD50 > 9.1 x 108 CFU/rat

No deaths

Not a pulmonary toxicant/pathogen

N/A
Acute intravenous injection toxicity/pathogenicity Rat

LD50 > 9.33 x 108 CFU/rat

No deaths

Non-toxic/Non-pathogenic

N/A
Skin irritation Rabbit Non-irritant N/A
Eye irritation Rabbit Slight eye irritant N/A
Skin and respiratory sensitisation Estimated Potential sensitiser Schedule 6

*Scheduling Policy Framework for Medicines and Chemicals (SPF, 2015)

The acute toxicity end-points for Actinovate BioFungicide are listed in the below table.

Toxicity Species Results SPF* Classification
Acute oral toxicity LD50 (mg/kg bw) Rat (F only)

LD50 >5000

No deaths

N/A
Acute dermal toxicity LD50 (mg/kg bw) Rat

LD50 >5050

1 death

N/A
Acute inhalation toxicity Estimated Low N/A
Skin irritation Rabbit Non-irritant N/A
Eye irritation Rabbit Non-irritant N/A
Skin and respiratory sensitisation Estimated Non-sensitising N/A

*Scheduling Policy Framework for Medicines and Chemicals (SPF, 2015)

Other toxicity data

In a pulmonary toxicity/pathogenicity and infectivity study, no mortalities were observed in rats following intra-tracheal injection at dose of 9.1 x 108 CFU of Streptomyces lydicus strain WYEC 108 per animal. No treatment-related signs of toxicity were observed. The microbial pest control agent (MPCA) was detected in the kidney, liver, mesenteric lymph nodes and in the lungs of treatment test animals up to Day 21, but had cleared by Day 28 or earlier. Streptomyces lydicus WYEC 108 was not considered to be toxic/pathogenic when administered via intra-tracheal injection to rats at 9.1 x108 CFU/animal.

In an intravenous injection infectivity study, no mortalities or significant signs of toxicity were observed in rats following injection with Streptomyces lydicus WYEC 108 at 9.33 x 108 CFU per animal. Streptomyces lydicus WYEC 108 was detected in the blood, brain, kidney, mesenteric lymph nodes, lungs, liver and spleen up to Day 21, but cleared from all test animals by Day 28 or earlier. Streptomyces lydicus WYEC 108 was not considered to be toxic/pathogenic when administered via intravenous injection to rats at 9.33 x 108 CFU/animal.

Acute inhalation toxicity on Streptomyces lydicus WYEC 108 was not provided. Extrapolating from the pulmonary toxicity/pathogenicity and infectivity study, the OCS considered that Streptomyces lydicus WYEC 108 was a low acute inhalation toxicant in rats as no treatment-related effects were observed. However, the study was not suitable to establish an acute inhalational LC50.

Observation in humans

No information was provided.

Public exposure

At this time, the proposed agricultural use of Streptomyces lydicus WYEC 108 is not expected to result in general public exposure. Spray drift considerations have not been considered.

International regulations

Products similar to, and containing Streptomyces lydicus WYEC 108 at the same concentration as Actinovate BioFungicide, are available in the USA, Canada and New Zealand.

Current scheduling status

Streptomyces lydicus strain WYEC 108 is not specifically scheduled. Dihydrostreptomycin and streptomycin are both listed in Schedule 4 of the Poisons Standard.

Relevant scheduling history

Streptomyces lydicus strain WYEC 108 has not been previously considered for scheduling; therefore, scheduling history is not available.

Pre-meeting public submissions

No public submissions were received.

ACCS advice to the delegate

In response to the Delegate's request, the Committee have advised that there is insufficient evidence of skin and respiratory sensitisation potential to warrant inclusion of the substance in Schedule 6, and advocated for the substance to be included in Appendix B.

The committee recommended the following amendments to the Poisons Standard:

Appendix B, Part 3 - New entry

STREPTOMYCES LYDICUS WYEC 108

Part 1 - Reasons for Entry - a) low toxicity

Part 2 - Area of Use - 1.3 - Fungicide

The matters under subsection 52E(1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: a) low risk of adverse effects compatible with Appendix B; b) to be used in the agricultural setting, as a fungicide and soil supplement; c) Low toxicity and infectivity potential; d) Product to be used in agricultural and industrial setting.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors13;
  • Other relevant information.
Delegate's interim decision

The delegate notes, and accepts, ACCS advice that this biofungicidal preparation, containing the bacterium Streptomyces lydicus strain WYEC 108, does not satisfy any of the SPF criteria for listing in the schedules and should be listed in Appendix B. It is noted that the evidence for potential skin sensitisation and irritancy was considered by the ACCS to be insufficient to warrant scheduling, and that no other toxicity, infectivity or pathogenicity was apparent from the studies presented.

The proposed implementation date is 1 October 2016. Since listing in Appendix B is not equivalent to a decision to list a substance in a schedule, an implementation date is not strictly relevant. However, early advice to the APVMA of this decision will facilitate prompt registration of products under consideration by the APVMA. Accordingly, amendment of Appendix B at the earliest revision of the Poisons Standard is recommended.

The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (b) the purposes for which a substance is to be used and the extent of use of a substance; and (c) the toxicity of a substance.

Appendix B, Part 3 - New entry

STREPTOMYCES LYDICUS WYEC 108

Part 1 - Reasons for Entry - a) low toxicity

Part 2 - Area of Use - 1.3 - Fungicide


Footnotes

  1. Scheduling Policy Framework for Medicines and Chemicals (SPF, 2015)

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