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Scheduling delegate's final decisions: ACCS, December 2014

Scheduling medicines and poisons

16 December 2014

Book pagination

Final decisions on matters referred to an expert advisory committee: 1.1-1.4

1.1 1-propanaminium compounds

Scheduling decision
  • 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) (OR stearoxypropyltrimonium chloride) is covered by the existing Schedule 5 and 6 entries for QUATERNARY AMMONIUM COMPOUNDS.
  • The delegate has determined to set aside the interim decision for 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18 and C18-unsaturated acyl) derivatives, inner salts (OR babassuamidopropyl betaine) and to seek further advice from the ACCS.
Scheduling proposal

The ACCS considered the following proposal referred by the delegate for advice:

  • Whether 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) and/or 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N(C8-18 and C18-unsatd. Acyl derivs., inner salts) meet the criteria for inclusion in the generic Schedule 5 and Schedule 6 entries for quaternary ammonium compounds or whether to create a new Schedule 6 and Appendix F entries for 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) and/or 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N(C8-18 and C18-unsatd. Acyl derivs., inner salts).

The committee considered and discussed the resolutions with an implementation date of 1 February/1 June/1 October 2015.

On 13 September 2013, the National Industrial Notification and Assessment Scheme (NICNAS), under its New Chemicals programme, requested that the delegate consider creating new Schedule 6 and Appendix F entries for 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) and 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N(C8-18 and C18-unsatd. Acyl derivs., inner salts).

The delegate's reason for referring this scheduling proposal to the ACCS was that the primary use of both compounds will be in leave-on and rinse-off cosmetic products and hair conditioners. Both compounds have a typical toxicological profile of quaternary ammonium compounds, with acute toxicity, skin-eye irritancy and sensitisation potential as the key factors requiring controls via scheduling. The issue that requires ACCS advice is whether the two compounds need individual schedule entries, or whether they are adequately covered by the generic entries for quaternary ammonium compounds in Schedules 5 and 6.

The delegate asked the ACCS the following questions:

  • Are the toxicological profiles of 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) and 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N(C8-18 and C18-unsatd. Acyl derivs., inner salts) comparable with other quaternary ammonium compounds, and are scheduling matters adequately covered by the current Schedules 5 and 6 entries? Note that for the second of these compounds, the toxicological profile has been derived by read-across from an analogue which differs only in the oil source for the fatty acid.
  • Are the cut-offs in the current quaternary ammonium entries (Schedule 5 for 5-20% and exemption in less than 5%) appropriate for these two compounds?
  • NICNAS has noted that the upper concentration likely to be used in cosmetic and hair conditioner products in Australia is 6%, meaning that if the current quaternary ammonium compound cut-offs are applied, no products containing these two specific compounds are likely to be classified Schedule 6, and most would be either Schedule 5 or exempt from scheduling. Is this consistent with NICNAS advice that listing in Schedule 6 is the preferred option, with strong warning statements about skin/eye irritation and sensitisation potential?
  • If separate schedules are recommended for either compound, should they be listed with the above chemical names, or their INCI names (stearoxypropyltrimonium chloride and babassuamidopropyl betaine, respectively)?
Substance summary

Please refer to the NICNAS assessment reports for stearoxypropyltrimonium chloride and 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18 and C18-unsatd. acyl) derivs., inner salts (INCI name: Babassuamidopropyl Betaine. These reports are publicly available on the NICNAS website:

Scheduling status

Neither 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) nor 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N (C8-18 and C18-unsatd. acyl derivs., inner salts) is specifically scheduled. The substances are quaternary ammonium compounds which are listed in Schedules 5 and 6, and also included in Appendix E. Some quaternary ammonium compounds, such as benzalkonium chloride are specifically listed in Schedules 5 (more than 1% and 10% or less), 6 and appendix E.

SCHEDULE 5
  • QUATERNARY AMMONIUM COMPOUNDS in preparations containing 20 per cent or less of quaternary ammonium compounds except:
    1. when separately specified in these schedules;
    2. dialkyl or dialkoyl quaternary ammonium compounds where the alkyl or alkoyl groups are derived from tallow or hydrogenated tallow or similar chain length (C16/C18) sources; or
    3. in preparations containing 5 per cent or less of such quaternary ammonium compounds.
SCHEDULE 6
  • QUATERNARY AMMONIUM COMPOUNDS except:
    1. when separately specified in these Schedules;
    2. when included in Schedule 5;
    3. dialkyl or dialkoyl quaternary ammonium compounds where the alkyl or alkoyl groups are derived from tallow or hydrogenated tallow or similar chain length (C16/C18) sources; or
    4. in preparations containing 5 per cent or less of such quaternary ammonium compounds.
APPENDIX E
Poisons Standard statements

Quaternary ammonium compounds except when separately specified

  • above 20 per cent

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.

E2 - If in eyes, hold eyelids apart and flush the eyes continuously with running water. Continue flushing until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor, or for at least 15 minutes.

  • 20 per cent and below

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).

E2 - If in eyes, hold eyelids apart and flush the eyes continuously with running water. Continue flushing until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor, or for at least 15 minutes.

  • in pressurised spray paints

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).

E2 - If in eyes, hold eyelids apart and flush the eyes continuously with running water. Continue flushing until advised to stop by a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor, or for at least 15 minutes.

G6 - If sprayed in mouth, rinse mouth with water.

Scheduling history

Neither 1-Propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) nor 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N (C8-18 and C18-unsatd. acyl derivs., inner salts) has been previously considered for scheduling; therefore, scheduling history is not available.

The following is the scheduling history for quaternary ammonium compounds.

In August 1973, the Poisons Schedule Sub-Committee (PSSC) decided to create a new Schedule 5 entry for preparations containing more than 10% of quaternary ammonium compounds.

In November 1997, the NDPSC decided to amend the Schedule 5 entry to include preparations containing 5 to 20% of quaternary ammonium compounds in Schedule 5 and created a new Schedule 6 entry for all other preparations containing quaternary ammonium compounds.

In November 1998, the NDPSC decided to amend the Schedules 5 and 6 entries to exempt dialkyl quaternary ammonium compounds where the alkyl groups are derived from tallow or hydrogenated tallow or similar alkyl chain length sources from these listings.

In November 2000, the NDPSC decided to exempt from scheduling all dialkyl quaternary ammonium compounds.

Pre-meeting public submissions

One submission was received. The submission indicated that, technically, both compounds are quaternary ammonium compounds and would be captured under the current schedule entry for quaternary ammonium compounds. The submission noted that the toxicity of 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18 and C18-unsatd. acyl) derivs., inner salts is significantly different from other quaternary ammonium compounds and warrants separate consideration. The submission stated that the current scheduling requirements for quaternary ammonium compounds are too restrictive to apply to babassuamidopropyl betaine and other amidopropyl betaines derived from fatty acids (with carbon chain length of C6-C20) and these substances should be exempt from scheduling.

Summary of ACCS advice to the delegate

The ACCS advised that 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) and 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N(C8-18 and C18-unsatd. Acyl derivs., inner salts) meet the factors of the SPF for including them in the generic Schedule 5, Schedule 6 and Appendix E entries for quaternary ammonium compounds. A separate listing in the Schedules is, therefore, not required for these substances.

Delegate's interim decision

The delegate notes, and accepts, ACCS advice that the toxicological profiles of the three substances referred in the NICNAS report are sufficiently similar to other quaternary ammonium compounds covered by the generic listing in Schedules 5 and 6, and that separate listings are therefore not required. This interim decision includes a determination that the current cut-offs from Schedule 6 to Schedule 5 (20%) and to exempt (5%) remain appropriate for these three substances.

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.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors1;
  • Other relevant information.
Public submissions on the interim decision

One submission was received. The submission noted that:

  • the delegate's interim decision on 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) (OR stearoxypropyltrimonium chloride) may fit the typical description of a quaternary ammonium compound. However, this is not the case for 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18 and C18-unsaturated acyl) derivatives, inner salts (OR babassuamidopropyl betaine) and other amidopropyl betaines.
  • chemically, these two substances fit into different categories: stearoxypropyltrimonium chloride is a cationic surfactant (like most quaternary ammonium compounds); babassuamidopropyl betaine, like other amidopropyl betaines, is a zwitterionic surfactant (ie a neutral molecule). While amidopropyl betaines contain a quaternary ammonium segment within the molecule and may be described by some as a quaternary ammonium compound, it also contains an organic acid segment and may be described as an organic acid. Amidopropyl betaines are used in cosmetics as a milder substitute for sodium lauryl sulfates and sodium lauryl ether sulfates, and provide similar foaming properties as these substances.
  • it would be more appropriate to schedule amidopropyl betaine in a separate schedule entry, with controls that are aligned with lauryl sulfates; this approach would address the concerns regarding some existing products that may become scheduled (S5), noting that due to the differences in chemistry of amidopropyl betaines from typical quaternary ammonium compounds, these may not have been considered quaternary ammonium compounds by some in industry. Separate scheduling would align with the which concluded that household laundry and cleaning products containing cocamidopropyl betaines raise no safety concerns for the consumers. The Cosmetics Ingredient Review has noted that amidopropyl betaines are safe for use in cosmetics if they are formulated to be non-sensitising (noting that sensitisation potential was likely due to an impurity rather than the substance itself).

The submission requested consideration of the following separate schedule entry for amidopropyl betaines to align with lauryl sulfate. This schedule entry allows higher concentrations of the surfactant in wash-off preparations (than quaternary ammonium compounds), while decreasing the amount allowed in leave-on preparations.

Schedule 6
  • AMIDOPROPYL BETAINES except:
    1. in cosmetic wash-off preparations containing 30 per cent or less of amidopropyl betaine and, if containing more than 5 per cent of amidopropyl betaine, when labelled with a warning to the following effect:
      • IF IN EYES WASH OUT IMMEDIATELY WITH WATER;
    2. in cosmetic leave-on preparations containing 1.5 per cent or less of amidopropyl betaine.
    3. in other preparations containing 30 per cent or less of amidopropyl betaine and, if containing more than 5 per cent of amidopropyl betaine, when labelled with warnings to the following effect:
      • IF IN EYES WASH OUT IMMEDIATELY WITH WATER; and
      • IF SKIN OR HAIR CONTACT OCCURS, REMOVE CONTAMINATED CLOTHING AND FLUSH SKIN AND HAIR WITH RUNNING WATER.
Delegate's final decision

The delegate notes the submissions received in response to publication of the interim decision and has determined to confirm the decision that 1-propanaminium, N,N,N-trimethyl-3-(octadecyloxy)-, chloride (1:1) (OR stearoxypropyltrimonium chloride) is covered by the existing Schedule 5 and 6 entries for QUATERNARY AMMONIUM COMPOUNDS. The delegate has confirmed that the reasons for the final decision on this substance are in keeping with those for the interim decision.

However, in relation to the substance 1-propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-(C8-18 and C18-unsaturated acyl) derivatives, inner salts (OR babassuamidopropyl betaine) the delegate has determined to set aside the interim decision and to seek further advice from the ACCS on whether the proposed Schedule 5 entry for AMIDOPROPYL BETAINES is a better way to manage the scheduling of this group of zwitterionic detergents.

1.2 2,4,7-decatrienoic acid, ethyl ester

Scheduling decision
  • The delegate has decided not to include this substance in the Poisons Standard.
Scheduling proposal

The ACCS considered the following proposal referred by the delegate for advice:

  • To create new Schedule 6 and Appendix F entries for 2,4,7-decatrienoic acid, ethyl ester with appropriate cut-off to exempt from scheduling.

The committee considered and discussed the resolutions with an implementation date of 1 February/1 June /1 October 2015.

On 13 September 2013, an application was received requesting that the delegate consider a proposal to include 2,4,7-decatrienoic acid, ethyl ester in Schedule 6 and Appendix E entries. The reasons for this request are that the substance is a slight to moderate skin irritant, a skin sensitiser and a slight eye irritant.

The delegate's reason for referring this scheduling proposal to the ACCS is that ACCS advice was needed on whether inclusion in the SUSMP is the most appropriate control measure, given its proposed use in low concentrations in fragrances, cosmetics and household cleaners.

The delegate asked the ACCS the following questions:

  • Given the relatively moderate toxicity profile of this chemical, and the fact that public exposure is only likely to occur through its use as a fragrance in cosmetic and household cleaning products containing up to 1%, does the ACCS consider that listing in the SUSMP is appropriate? If so, in which schedule should it be listed, and can the ACCS recommend a low cut-off concentration to exempt 2,4,7-decatrienoic acid, ethyl ester from scheduling? Are different cut-offs required for different product categories?
  • Noting that the pure chemical is a skin/eye irritant and a potential sensitiser, but there is limited information on these toxicities at the low concentrations proposed for consumer products, is this toxicity potential sufficient to warrant inclusion of the substance in Schedule 6? Are Appendix E & F statements required?
Substance summary

The chemical is intended to be used as a component of fragrances for a variety of cosmetic and household cleaning products at concentrations up to 1%.

Acute toxicity

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

Toxicity species 2,4,7-decatrienoic acid, ethyl ester SPF Classification
Acute oral toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Acute dermal toxicity LD50 (mg/kg bw) Not provided Not provided Unable to assess
Acute inhalational toxicity LC50 (mg/m3/4h) Not provided Not provided Unable to assess
Skin irritation Rabbit Irritant
Eye irritation Rabbit Slight irritant
Skin sensitisation Guinea pig Non-sensitiser
Repeated dose toxicity

No information was provided.

Mutagenicity

The chemical was not mutagenic in a bacterial reverse mutation study.

Genotoxicity

No information was provided.

Neurotoxicity

No information was provided.

Carcinogenicity

No information was provided.

Reproduction and developmental toxicity

No information was provided.

Observation in humans

No information was provided.

Public exposure

Repeat dose toxicity data are not available for the chemical. However, based on studies conducted on an analogue of an expected major metabolite of the chemical, systemic toxicity is not expected. The main risk associated with use of the chemical in fine fragrances, other cosmetic products and household cleaning products at concentrations up to 1%, is its potential to cause sensitisation by skin contact.

International regulations

No information was provided.

Scheduling status

2,4,7-Decatrienoic acid, ethyl ester is not specifically scheduled.

Scheduling history

2,4,7-Decatrienoic acid, ethyl ester has not been previously considered for scheduling; therefore, scheduling history is not available.

Pre-meeting public submissions

Two submissions were received. The submissions indicated that the substance should remain unscheduled.

Summary of ACCS advice to the delegate

The ACCS recommended that 2,4,7-decatrienoic acid, ethyl ester does not require a schedule listing.

Delegate's interim decision

The delegate accepts ACCS advice that the fragrance ingredient 2,4,7-Decatrienoic acid, ethyl ester does not require scheduling. The delegate notes that sensitisation potential is the toxicological finding that could justify inclusion in the schedules, and that the ACCS has made recommendations at this and previous meetings that it is not necessary to use the scheduling process to regulate fragrance chemicals when there is no evidence of a significant public health hazard associated with the low concentrations likely to be found in consumer products in Australia. There were no other toxicological factors that would justify scheduling. Accordingly, the interim decision of the delegate is to NOT include this chemical in the SUSMP.

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.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors;
  • Other relevant information.
Public submissions on the interim decision

One submission was received which supported the delegate's interim decision not to schedule 2,4,7-decatrienoic acid, ethyl ester.

Delegate's final decision

The delegate notes the submissions received in response to publication of the interim decision and confirms the interim decision, as no evidence has been received to alter the interim decision. The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

1.3 2-butenedioic acid (2E)-, DI-C12-15 alkyl esters

Scheduling decision
  • The delegate has decided not to include this substance in the Poisons Standard.
Scheduling proposal

The ACCS considered the following proposal referred by the delegate for advice:

  • To create new Schedule 6 and Appendix F entries for preparations containing 10% or more of 2-butenedioic acid (2E)-, di-C12-15-alkyl esters.

The committee considered and discussed the resolutions with an implementation date of 1 February/1 June/1 October 2015.

On 13 September 2013, NICNAS, under its New Chemicals programme, requested that the delegate consider including preparations containing 10% or more of 2-butenedioic acid (2E)-, di-C12-15-alkyl esters in Schedule 6 and Appendix F. The reason for this recommendation was that the substance is a skin sensitiser that meets theSPF Schedule 6 criteria.

The delegate's reason for referring this scheduling proposal to the ACCS was that, while the NICNAS assessment report proposed listing this new chemical in Schedule 6, ACCS advice was needed on whether inclusion in the SUSMP is the most appropriate control measure, given its proposed use as a skin conditioning agent/emollient in cosmetic products (e.g. in leave-in and rinse-off cosmetics) at concentrations up to 10%.

The delegate asked the ACCS the following questions:

  • The main features of the toxicity profile of this chemical are low acute toxicity (LD50 >2000mg/kg; no evidence of skin/eye irritancy) but some evidence of sensitisation potential (positive at 100%, but negative at 75%). Does the ACCS consider that listing in the SUSMP is appropriate? If so, in which schedule should it be listed, and does the ACCS support the proposed low cut-off concentration to exempt at 10%? Are different cut-offs required for different product categories?
  • If scheduled, what name should be used in the listing - the INCI name of Di-C12-15 Alkyl fumarate, or the chemical name 2-Butenedioic acid (2E)-, di-C12-15-alkyl esters?
  • The basis for the NICNAS scheduling recommendation is the estimated risk of sensitisation associated with its use in cosmetics at up to 10%. Is this toxicity potential sufficient to warrant inclusion of the substance in Schedule 6? Are Appendix E & F statements required?
Substance summary

Please refer to the NICNAS assessment report for 2-butenedioic acid (2E)-, di-C12-15-alkyl esters (INCI Name: di-C12-15 alkyl fumarate). This report is publicly available on the NICNAS website:

Scheduling status

2-Butenedioic acid (2E)-, di-C12-15-alkyl esters is not specifically scheduled.

Scheduling history

2-Butenedioic acid (2E)-, di-C12-15-alkyl esters has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

One submission was received. The submission indicated that the substance should remain unscheduled.

Summary of ACCS advice to the delegate

The ACCS recommended that 2-butenedioic acid (2E)-, di-C12-15-alkyl esters does not require a schedule listing.

Delegate's interim decision

The delegate accepts ACCS advice that the fragrance ingredient 2-butenedioic acid (2E)-, di-C12-15-alkyl esters does not require scheduling. The delegate notes that sensitisation potential is the toxicological finding that could justify inclusion in the schedules, and that the ACCS has made recommendations at this and previous meetings that it is not necessary to use the scheduling process to regulate fragrance chemicals when there is no evidence of a significant public health hazard associated with the low concentrations likely to be found in consumer products in Australia. There were no other toxicological factors that would justify scheduling. Accordingly, the interim decision of the delegate is to NOT include this chemical in the SUSMP.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: 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.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors;
  • Other relevant information.
Public submissions on the interim decision

One submissions was received which supported the delegate's interim decision not to schedule 2-butenedioc acid (2E)-, di-C12-15-alkyl esters.

Delegate's final decision

The delegate notes the submissions received in response to publication of the interim decision and confirms the interim decision, as no evidence has been received to alter the interim decision. The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

1.4 2-hydroxypropyl methacrylate

Scheduling decision
  • To create a new Schedule 5 entry:

2-HYDROXYPROPYL METHACRYLATE in nail preparations except when labelled'avoid contact with skin'.

  • Implementation date, 1 January 2016
Scheduling proposal

The ACCS considered the following proposal referred by the delegate for advice:

  • To create a new Schedule 5 entry for 2-hydroxypropyl methacrylate with appropriate concentration cut-offs for preparations containing low concentrations of 2-hydroxypropyl methacrylate.

The committee considered and discussed the resolutions with an implementation date of 1 February/1 June/1 October 2015.

On 23 April 2014, the National Industrial Notification and Assessment Scheme (NICNAS), under its Inventory Multi-tiered Assessment Prioritisation (IMAP) programme, requested that the delegate consider a proposal to include 2-hydroxypropyl methacrylate in Schedule 5. The reasons for the recommendation are that the substance is a skin sensitiser and may also cause skin and eye irritation.

The delegate's reason for referring this scheduling proposal to the ACCS was that the NICNAS IMAP report noted 2-hydroxypropyl methacrylate's sensitisation potential and recommended inclusion in Schedule 5, with a low level cut-off to exempt from scheduling and appropriate warning statements to avoid skin contact. While this particular cosmetic ingredients is not currently listed in the schedules, there are entries for related esters, methyl and ethyl methacrylates. ACCS advice is needed to determine the most appropriate schedule and to advise on potential regulatory impacts.

The delegate asked the ACCS the following questions:

  • Does the ACCS support the NICNAS recommendation to list 2-hydroxypropyl methacrylate in Schedule 5, with Appendix F warning statements to avoid skin contact?
  • Are there sufficient similarities between the toxicological profiles of the methyl, ethyl and 2-hydroxypropyl esters of methacrylate to use current schedule entries as a template? Methyl methacrylate is currently listed in Schedule 6, with exemptions for preparations containing 1% or less, and for cosmetic use (but note that cosmetic uses of methyl methacrylate are proscribed via listing in Appendix C). Ethyl methacrylate is listed in Schedule 5, but only for cosmetic use and is exempt from scheduling in preparations containing 1% or less. To what extent are these entries consistent with the NICNAS recommendation?
  • Note that the Minutes of the February 2007 meeting of the NDPSC include a detailed discussion of the rationale for setting a 1% exemption for both methyl and ethyl methacrylates. Is such an exemption cut-off appropriate for 2-hydroxypropyl methacrylate?
  • Is listing under the name 2-hydroxypropyl methacrylate appropriate, given that it is usually a mixture of two isomers with different CAS numbers - 2-propenoic acid, 2-methyl-, monoester with 1,2-propanediol (CAS No. 27813-02-1) and 2-propenoic acid, 2-methyl, 2-hydroxypropyl ester (CAS No. 923-26-2)?
Substance summary

Please refer to the NICNAS IMAP human health Tier II assessment report for 2-hydroxypropyl methacrylate. This report is publicly available on the NICNAS website:

The NICNAS scheduling proposal is based on the assessment of two substances: 2-propenoic acid, 2-methyl-, monoester with 1,2-propanediol (CAS No. 27813-02-1) and 2-propenoic acid, 2-methyl, 2-hydroxypropyl ester (CAS No. 923-26-2). NICNAS indicated that 2-propenoic acid, 2-methyl-, monoester with 1,2-propanediol (CAS No. 27813-02-1) consists of two isomers. This occurs due to the method of industrial production, which is usually either the reaction between methacrylic acid and propylene oxide, or methacrylic acid esterification of 1,2-propanediol. The predominant isomer is the secondary alcohol 2-propenoic acid, 2-methyl, 2-hydroxypropyl ester, which is assigned the CAS No. 923-26-2. Therefore toxicity information for both CAS No. 923-26-2 and CAS No. 27813-02-1 is considered to be applicable to both chemicals. NICNAS indicated that their evaluation report is a human health Tier II assessment for 2-hydroxypropyl methacrylate and their scheduling recommendation is for structurally related methacrylates.

Scheduling status

2-Hydroxypropyl methacrylate is not specifically scheduled. Other methacrylates, namely methyl methacrylate (MMC) and ethyl methacrylate (EMC) are listed in the SUSMP. Methyl methacrylate is listed in Schedule 6, Appendices C and F. Ethyl methacrylate is listed in Schedule 5 and Appendix F.

SCHEDULE 6
  • † METHYL METHACRYLATE (excluding its derivatives) except:
    • for cosmetic use; or
    • in preparations containing 1 per cent or less of methyl methacrylate as residual monomer in a polymer.
APPENDIX C

METHYL METHACRYLATE for cosmetic use except in preparations containing 1 per cent or less of methyl methacrylate as residual monomer in a polymer.

APPENDIX F
Poison Warning Statement Standard Statement
Methyl methacrylate 28. (Over) (Repeated) exposure may cause sensitisation.

4. Avoid contact with skin.

9. Use only in well ventilated area.

23. Keep away from heat, sparks and naked flames.

SCHEDULE 5

ETHYL METHACRYLATE (excluding its derivatives) for cosmetic use except in preparations containing 1 per cent or less of ethyl methacrylate as residual monomer in a polymer.

APPENDIX F

9. Use only in well ventilated area.

23. Keep away from heat, sparks and naked flames.

Poison Warning Statement Standard Statement
Ethyl methacrylate 28. (Over) (Repeated) exposure may cause sensitisation. 4. Avoid contact with skin.
Scheduling history

In May 1974, the Drugs and Poisons Scheduling Sub-Committee (DPSSC) decided to include EMC along with several dozen other compounds in Appendix B without any clear rationale being recorded.

In August 1995, the NDPSC decided to delete the entire Appendix B entry. The NDPSC felt that Appendix B was being misinterpreted. It was also noted that jurisdictions did not in general adopt Appendix B.

In February 2003, the NDPSC agreed to reinstate Appendix B, including the EMC, listing.

In October 2006, the NDPSC considered MMC for the first time and also reconsidered EMC. The NDPSC decided to include cosmetic preparations containing EMC in Schedule 5 and Appendix F. The NDPSC also decided to delete the Appendix B entry for EMC. The NDPSC agreed that Schedule 6 (excluding derivatives) and Appendix F entries may be appropriate for MMC and decided to foreshadow this decision.

In February 2007, the NDPSC decided to include MMC in Schedule 6 and Appendices C and F.

Pre-meeting public submissions

One submission was received. The submission noted that the substance is not regulated in EU or the USA, therefore a schedule listing for the substance is not required. If, however, a warning statement "avoid contact with skin" is required, appropriate transition time should be allowed e.g. for amendments to labels, 12-24 months from the publication of the final decision would be required.

Summary of ACCS advice to the delegate

The ACCS recommended that nail preparations containing 2-hydroxypropyl methacrylate be listed in Schedule 5 except when labelled'avoid contact with skin'.

The ACCS recommended an implementation date of 1 July 2015.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the committee included: (b) the purposes for which a substance is to be used and the extent of use of a substance.

The reason for the recommendation was:

  • its current wide use in nail preparations where application may result in skin contact means management of the risk of skin sensitisation through labelling is required.
Delegate's interim decision

The delegate accepts ACCS advice that a new Schedule 5 entry be created for 2-hydroxypropyl methacrylate. Its toxicological profile is consistent with the SPF criteria for Schedule 5, including relatively low acute toxicity, skin/eye irritancy and sensitisation potential. The delegate notes, and accepts, ACCS advice that the entry be specific for its use in cosmetic products used on the cuticles (nails). The toxicity of 2-hydroxypropyl methacrylate appears to be less severe than the methyl- and ethyl-methacrylates currently listed in Schedule 5, 6 and Appendix C, although there is some potential for cross-sensitisation to occur between these methacrylate derivatives when used in nail preparations. The delegate accepts ACCS advice that a'reverse scheduling' exemption from Schedule 5 could apply for products labelled with a warning statement'avoid contact with skin'. Since the Schedule 5 listing is specific for products used on the nails, there is no need for a similar warning statement in Appendix F, because application of such a warning statement via Appendix F would actually exempt any Schedule 5 product.

The delegate 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 and (d) the dosage, formulation, labelling, packaging and presentation of a substance.

A long implementation time is necessary to allow for orderly relabelling of any affected products, therefore the implementation date for this decision is 1 July 2015.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989; and
  • Scheduling factors;
  • Other relevant information.
Public submissions on the interim decision

One submission was received, which supported the delegate's interim decision but would like to seek an extension of the implementation date for this decision to 1 January 2016. This would allow for orderly labelling of any affected products.

Delegate's final decision

The delegate notes the submissions received in response to publication of the interim decision and, except for changing the proposed implementation date, confirms the interim decision, as no evidence has been received to alter the interim decision. The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

The delegate notes that delayed publication of the interim decision justifies the requested extension of the implementation date. The implementation date is 1 January 2016.

Schedule entry
Schedule 5 - New Entry

2-HYDROXYPROPYL METHACRYLATE in nail preparations except when labelled 'avoid contact with skin'.

Footnotes

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