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

Scheduling medicines and poisons

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2 February 2017

2.5 Fennel Oil

Part A - Interim decisions on matters referred to an expert advisory committee (November 2016)

2. Joint meeting of the Advisory Committee on Chemicals and Medicines Scheduling (ACCS-ACMS #14)

2.5 Fennel Oil

Referred scheduling proposal

The TGA has proposed that a new Schedule 5 entry be created for fennel oil (active component of fennel oil - methyl chavicol), with consideration of the appropriateness of low volume containers with a restricted flow insert, Medicines Advisory Statements, such as 'keep out of reach of children'; or exemption cut-off of 5 per cent or less of methyl chavicol.

Current scheduling status and relevant scheduling history

Fennel oil is not specifically scheduled in the SUSMP; however Basil Oil [which also may contain methyl chavicol (estragole)] is included in Schedule 5, Appendix E and Part 2.4 Child-resistant closures as follows:

Schedule 5

BASIL OIL - except:

  1. in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and compliant with the requirements of the Medicines Advisory Statements Specification;
  2. in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

    KEEP OUT OF REACH OF CHILDREN; or

  3. in preparations containing 5 per cent or less of methyl chavicol

Appendix E, Part 2

BASIL OIL

Standard Statements: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once).], G3 (If swallowed, do NOT induce vomiting).

Part 2 Control on Medicines and Poisons, 2.4 Child-resistant closures

Column 1
Name of the poison
Column 2
Nominal capacity
Basil oil when included in Schedule 5. 200 millilitres or less
Scheduling application

This is a general application. The applicant’s proposed amendments to the Poisons Standard are as follows:

FENNEL OIL except:

  1. in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and compliant with the requirements of the Medicines Advisory Statements Specification;
  2. in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

    KEEP OUT OF REACH OF CHILDREN; or

  3. in preparations containing 5 per cent or less of methyl chavicol.

The applicant's reasons for the request are:

  • Fennel oil should be included in Schedule 5 with the same restrictions as basil oil.
  • Fennel oil, as with basil oil, may contain methyl chavicol (estragole) (see Substance summary).
  • The reasons are identical to those for basil oil, which was added to Schedule 5 in February 2000 on the basis of the potential for basil oil to contain methyl chavicol (estragole), which has acute oral toxicity in rats and which can be metabolised to a carcinogenic metabolite (1'-hydroxyestragole).
  • In March 2016, the CMES of the TGA undertook a safety evaluation of fennel oil to ensure that the ingredient is appropriate for the low-risk listed complementary medicines. The safety evaluation of fennel oil incorporated information from international regulatory agencies, including the National Toxicology Program and academic literature.
Australian and international regulatory information

The ARTG contains multiple entries for listed medicines containing fennel oil.

Fennel oil is listed in the Therapeutic Goods (Permissible Ingredients) Determination No. 2 of 2016 as an active, excipient and homoeopathic preparation ingredient. There are no specific requirements applying to the ingredient.

Brief searches for drug products or medicines containing fennel oil, methyl chavicol, chavicol, or estragole on the FDA or Medsafe databases returned no information.

Substance summary

Fennel oil is extracted from the seeds of Foeniculum vulgare Mill. (Apiaceae; International Plant Names Index: kew-2813604). The Australian Approved Name is Fennel oil (53603) with a CAS No. 8006-84-6.

There are two varieties of fennel in use - sweet fennel (Foeniculum vulgare Mill. subsp. vulgare var. dulce (Mill.) Batt.) and bitter fennel (Foeniculum vulgare Mill. subsp. vulgare var. vulgare). The oils extracted from the two varieties differ slightly in their chemical composition.

Fennel oil is available for use in listed medicines without restriction (included in the S26BB list). It is currently used as an excipient in 17 listed medicines and as an active in eleven listed medicines.

Sweet and bitter fennel oils contain several components of which trans-anethole (50-80%) and estragole (methyl chavicol, 5-20%) are of concern due to their toxic effects.

The safety report concluded that on the basis of the unequivocal evidence of carcinogenicity for estragole, in combination with the current Schedule 5 entry for basil oil (containing a similar content of estragole), suggests that fennel oil should also be scheduled with the similar restrictions.

From the Safety Review:

Composition of sweet and bitter fennel oils extracted by steam distillation

Structure of major volatile components of fennel oil

Figure 2.5: Structure of major volatile components of fennel oil

Pre-meeting public submissions

One public submission was received. The submission did not indicate whether or not it supported the proposal. The main points were:

  • Assumes that the intent of the scheduling proposal for fennel oil is to create a new schedule entry for fennel oil in line with the existing schedule entry for basil oil.
  • The Schedule 5 proposal has the potential to impact on the use of fennel oil in non-medicinal uses and notes that the consideration of this scheduling proposal by the ACMS and related public notice may not have alerted those that may be impacted by the non-medicinal uses of fennel oil.
Summary of Joint ACCS-ACMS advice to the delegates

The committee advised that a new Schedule 5 entry be created for fennel oil as follows:

Schedule 5 - New entry

FENNEL OIL except:

  1. in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and compliant with the requirements of the Medicines Advisory Statements Specification;
  2. in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

    KEEP OUT OF REACH OF CHILDREN; or

  3. in preparations containing 5 per cent or less of methyl chavicol.

The committee also advised that new Appendix E and 2.4 Child-resistant closures entries be created for fennel oil as follows:

Appendix E, Part 2

FENNEL OIL

Standard Statements: A [For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], G3 (If swallowed, do NOT induce vomiting).

Part 2 Control on Medicines and Poisons, 2.4 Child-resistant closures

Column 1
Name of the poison
Column 2
Nominal capacity
Fennel oil when included in Schedule 5. 200 millilitres or less.

The Joint ACCS-ACMS advised an implementation date of 1 June 2017.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: 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; f) any other matters that the Secretary considers necessary to protect the public health.

The reasons for the advice comprised the following:

  • The substance remains available. It has no therapeutic benefit and is used primarily as a flavouring. There may be valid uses in aroma and flavour areas.
  • Acute toxicity and potential carcinogenicity of the component methyl chavicol.
  • There is potential for fennel oil containing methyl chavicol to result in human toxicity, as indicated by the acute oral toxicity in the rat and its carcinogenic metabolite.
  • The proposed controls will make the chemical available but ensure that accidental overexposure will be significantly reduced.
  • Smaller volumes and preparations containing methyl chavicol in concentrations less than 5% pose reduced risk and would be in line with basil oil scheduling.
Delegates' considerations

The delegates considered the following in regards to this proposal:

  • Scheduling proposal
  • Joint ACCS-ACMS advice
  • Public submissions received
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling Policy Framework (SPF 2015)
  • Other relevant information.
Delegates' interim decision

The delegates' interim decision is that a new Schedule 5 entry be created for fennel oil.

The proposed Schedule, Appendix E and Part 2.4 entries are as follows:

Schedule 5 - New Entry

FENNEL OIL except:

  1. in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and compliant with the requirements of the Medicines Advisory Statements Specification;
  2. in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

    KEEP OUT OF REACH OF CHILDREN; or

  3. in preparations containing 5 per cent or less of methyl chavicol.

Appendix E, Part 2

FENNEL OIL

Standard Statements: A (For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once).), G3 (If swallowed, do NOT induce vomiting).

Part 2, Control on Medicines and Poisons, 2.4 Child-resistant closures

Column 1
Name of the poison
Column 2
Nominal capacity
Fennel oil when included in Schedule 5. 200 millilitres or less

The proposed implementation date is 1 June 2017.

The delegates considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: 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; f) any other matters that the Secretary considers necessary to protect the public health.

The reasons for the interim decision are the following:

  • The delegates acknowledge and agree with the committee's advice.
  • There is potential for fennel oil containing methyl chavicol to result in human toxicity, as indicated by the acute oral toxicity in the rat and its carcinogenic metabolite.
  • The proposed controls will make the chemical available but ensure that accidental overexposure will be significantly reduced. The substance remains available. It has no therapeutic benefit and is used primarily as flavouring.
  • Smaller volumes and preparations containing methyl chavicol in concentrations less than 5% pose reduced risk and would be in line with basil oil scheduling.
  • Earliest possible implementation date.

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