Scheduling delegate's interim decisions and invitation for further comment:ACCS/ACMS, February 2014

Book pagination

27 February 2014

Interim decisions on proposal referred to an advisory committee: ACCS November 2013: (1.15-1.21)

1.15 Mercaptoacetic acid

Scheduling proposal

On 13 September 2013, NICNAS under the Inventory Multi-tiered Assessment Prioritisation (IMAP) process, requested that the delegate consider a proposal to include the substance in Schedule 6. This recommendation was based on the main critical effects to human health namely, severe eye irritation, skin sensitisation and harmful effects through contact with skin during short term or acute exposure. Long-term exposure may cause carcinogenicity.

The delegate's reason for referring this scheduling proposal to the ACCS is that this was one of several NICNAS-referred chemicals where the primary public exposure is likely to be via use of cosmetic products. The delegate needed ACCS advice on how best to manage the scheduling aspects of such submissions.

The delegate sought the following specific advice from the ACCS:

  • Does the ACCS support a Schedule 5 or 6 listing for this chemical with an appropriate cut-off (at 11 per cent or less with an exception to unscheduled or to Schedule 5)?
  • Does the ACCS recommend any additional scheduling controls, or specific references to, various cosmetic products (e.g. hair care and/or depilatory products)?
  • Is there a need to specify different scheduling cut-off levels for different cosmetic products, as in the EU Directive?
  • Does the ACCS consider that the schedule entry for this compound be made under the name mercaptoacetic acid, or thioglycolic acid, and that such an entry would capture all the salts considered in the NICNAS IMAP report?
  • Can the ACCS recommend suitable entries in Appendices E & F for this class of chemicals?
Substance details

Please refer to the NICNAS Inventory Multi-tiered Assessment Prioritisation (IMAP) Human Health Tier II Assessment Report, which is available on from the NICNAS website: Human Health Tier II Assessment for Mercaptoacetate salts.

Scheduling status

Mercaptoacetate salts are not specifically scheduled.

Scheduling history

Not applicable.

Public pre-meeting submissions

Two public submissions were received.

One submission indicated that although mercaptoacetic acid (or thioglycolic acid) is not currently scheduled it is in Annex III (restricted use) of the EU Cosmetics Directive. The safety of mercaptoacetic acid has also been reviewed by the Cosmetic Ingredients Review (CIR) panel. The CIR conclusion was that mercaptoacetic acid is "safe for use in hair straighteners permanent waves, tonics, dressings, and so forth, wave sets, other non-colouring hair products, and hair dyes and colours, at concentrations up to 15.2 per cent; hairdressers should avoid skin contact and minimize consumer skin exposure; safe for use in depilatories when formulated to be non-irritating under conditions of recommended use". The submission tentatively supported scheduling of mercaptoacetic acid (with cross reference to thioglycolic acid in the index) as Schedule 6 with exemptions for cosmetic products containing 15.2 per cent or less of mercaptoacetic acid.

The other submission did not provide comments regarding the delegate's proposal and indicated that it will provide comments, if required, based on delegate's interim decision.

ACCS advice to the delegates

The ACCS recommended that mercaptoacetic acid in cosmetic products be included in Schedule 6 except when in Schedule 5 or in preparations containing 5 per cent or less of mercaptoacetic acid.

The committee, in addition to recommending when included in Schedule 6, also recommended that Appendix E and F statements were required.

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

The reasons for the recommendation comprised the following:

  • Chemicals properties used in cosmetics but has a low to moderate toxicity at higher concentration levels. Is a skin irritant.
  • Use in cosmetics can be unscheduled but higher concentrations needs to be regulated.
  • Cut-off levels based on international regulatory approaches.
Delegates' 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 factors20;
  • Other relevant information.
Delegates' interim decision

The delegate accepts ACCS advice that new entries be created for the strongly acidic substance mercaptoacetic acid (thioglycolic acid) in Schedules 6 (cosmetic preparations with concentrations above 20%) and Schedule 5 (cosmetic preparations between 5 and 20%), with an overall exemption from scheduling at 5%. The entries are specific for cosmetic products, based on the main expected sources of public exposure through use in hair care and depilatory products, with potential for skin/eye irritancy and sensitisation driving the scheduling and cut-offs for the chemical and its salts. The delegate also accepts ACCS advice relating to new entries in Appendices E & F, providing for appropriate First Aid Instruction, Safety Directions and Warning Statements.

The delegate agrees to the implementation date of 1 June 2014.

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.

Scheduling entry
Schedule 6 - New entry

MERCAPTOACETIC ACID in cosmetic preparations except:

  1. when included in Schedule 5; or
  2. in preparations containing 5 per cent or less of mercaptoacetic acid.
Schedule 5 - New entry

MERCAPTOACETIC ACID in cosmetic preparations containing 20 per cent or less of mercaptoacetic acid, except in preparations containing 5 per cent or less of mercaptoacetic acid.

When in Schedule 6 the following Appendix E and F statements.

Appendix E, Part 2
Poison Standard statements
Mercaptoacetic acid

(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).

(E1) If in eyes washout immediately with water.

Appendix F, Part 3
Poison Warning statements Safety directions
Mercaptoacetic acid

(5) Irritant

(28) (Over) (Repeated) exposure may cause sensitisation.

(1) Avoid contact with eyes.

(31) Do not use on broken skin.

Appendix E and F statements when in Schedule 5.

Appendix E, Part 2
Poison Standard statements
Mercaptoacetic acid

(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).

(E1) If in eyes washout immediately with water.

Appendix F, Part 3
Poison Warning statements Safety directions
Mercaptoacetic acid (5) Irritant (1) Avoid contact with eyes.

In addition to the above entries, the delegate proposes cross-referencing in the SUSMP index as follows:

MERCAPTOACETIC ACID

See also THIOGLYCOLIC ACID

THIOGLYCOLIC ACID

See MERCAPTOACETIC ACID

1.16 1,3-cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester

Scheduling proposal

On 17 September 2013, the delegate received an application proposing the inclusion of 1,3-cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester in a schedule with exemption for scheduling for cosmetic products and fragrances containing less than 1 per cent of the substance. The basis for this recommendation is the results of the skin irritation and skin sensitisation tests.

Data also suggested that products containing the chemical at concentrations of 1 per cent or above available to the public must carry safety directions and warning statements on the label consistent with the following statement: 'May cause allergy.'

The delegate considered the proposal for including 1,3-cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester in a schedule with exemption for cosmetic products and fragrances containing less than 1 per cent and referred the proposal to the ACCS. This proposal is one of several chemicals where the primary public exposure is likely to be via use of cosmetic products. This issue therefore required ACCS advice on how best to manage the scheduling aspects of such submissions.

The delegate sought the following specific advice from the ACCS:

  • Given the relatively low toxicity profile of this chemical, and the fact that public exposure is only likely to occur through the use of cosmetic products containing up to 0.025 per cent of this fragrance chemical (or in perfumes at up to 1 per cent), does the ACCS consider that listing in the SUSMP is appropriate? If so, in which schedule should it be listed?
  • If scheduled, what name should be used in the listing (1,3-Cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester or a trade name?
  • Is the potential for skin sensitization associated with its use in fragrances sufficient to warrant scheduling of such substances? If so, which schedule is suggested and what Appendix E & F statements should be applied?
Substance details

The chemical will be used as a fragrance ingredient in a variety of cosmetic, toiletry and household products. It will be present at a maximum concentration of 1 per cent in fine perfumes, and a maximum of 0.025 per cent in other products.

End-point of acute toxicity Species 1,3-cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester SPF*
Acute oral toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Acute dermal toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Acute inhalation toxicity LC50 (mg/L) No data No data
Skin irritation Rabbit Irritating
Eye irritation Rabbit Slightly irritating with reversible effects.
Skin sensitisation Mouse Evidence of sensitisation.

*Scheduling Policy Framework for Medicines and Chemicals (2010)

Repeat-dose toxicity

Repeated exposure to the notified chemical for 28 days was investigated in the rat at dose levels of 30, 300 and 1000 mg/kg bw/day. The effects in the liver and thyroid were observed at 1000 and 300 mg/kg bw/day. Centrilobular hepatocyte enlargement of the liver was evident in animals of either sex treated with 1000 and 300 mg/kg/day. Thyroid changes identified as follicular cell hypertrophy were evident in animals of either sex treated with 1000 mg/kg bw/day or males only treated with 300 mg/kg bw/day. These effects were considered as adaptive changes to the treatment. The NOAEL was established as 1000 mg/kg bw/day, based on no adverse effects at this dose level.

Mutagenicity

The chemical was not mutagenic in a bacterial reverse mutation test and in a mammalian chromosome aberration test.

Genotoxicity

The chemical was not clastogenic to human lymphocytes treated in vitro under the conditions of the test.

Carcinogenicity

No data provided.

Public exposure

Public exposure to the notified chemical is expected to be widespread and frequent particularly through daily use of personal care products and household products containing the notified chemical. Exposure to the notified chemical will vary depending on individual use patterns. The principal route of exposure will be dermal and accidental ocular exposure may also occur. Inhalation exposure is also possible if products are applied by spray. Accidental ingestion from the use of these types of products is also possible from facial use. Considering the low concentrations used in personal care and household products (up to 0.025%), significant exposure is not expected from using these product types.

Public exposure to the notified chemical in fine fragrances at 1% was estimated using the Scientific Committee on Consumer Products' (SCCP's) Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation using 100% dermal absorption for a 60 kg female (SCCP, 2006).

Scheduling status

1,3-Cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester is not specifically scheduled.

Scheduling history

Not applicable.

Public pre-meeting submissions

Three submissions were received.

The first submitter noted that the identity of many fragrance components are considered commercial-in-confidence by the suppliers, it is possible that the substance is being used in consumer products and cosmetics and disclosed on the label simply as "fragrance". The submission asserted that control of fragrances and flavour components through the scheduling system is unwieldy and inefficient. This is particularly true when an international scientific assessment and risk management body like IFRA publishes Codes of Practice and Standards that are specifically relevant for fragrance and flavours. The submission indicated that it would support a separate discussion on the controls of fragrance and flavours rather than through individual scheduling consideration of each fragrance and flavour.

The second submission indicated that it was unclear on what concentration cut-off had been proposed and requested that the committee to consider that while not all these ingredients appear on the TGA e-BS ingredient list, some of these substances may be included in proprietary ingredients that are used in therapeutic goods. The submission further requested that the committee consider existing usage within proprietary ingredients and to propose cut-off concentrations that will not impact existing use in proprietary ingredients and in therapeutic goods.

The third submission did not provide comments regarding the delegate’s proposal and indicated that it will provide comments, if required, based on delegate’s interim decision.

ACCS advice to the delegates

The committee recommends that 1,3-cyclohexadiene-1-carboxylic acid, 4,6,6-trimethyl-, ethyl ester does not require a schedule listing.

Delegates' 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 factors21;
  • Other relevant information.
Delegates' interim decision

The delegate accepts ACCS advice 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 very low concentrations likely to be found in consumer products in Australia. Industrial uses are adequately regulated under other legislation, and there is an international scientific assessment and risk management body that publishes Codes of Practice and Standards that are specifically relevant for fragrance and flavours. 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 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.

1.17 3,7-dimethyl-2,6-octadienal isomers (citral, geranial and neral)

Scheduling proposal

On 29 August 2013, NICNAS under the Inventory Multi-tiered Assessment Prioritisation (IMAP) process, recommended that the delegate consider creating a new Schedule 6 entry for citral and its related compounds.

The delegate considered the proposal for including 3,7-dimethy-2,6-Octadienal (citral, geranial and neral) in Schedule 5.

The delegate reason for referring this scheduling proposal to the Advisory Committee on Chemicals Scheduling (ACCS) was that this scheduling submission relating to three isomers of 3,7-dimethy-2,6-Octadienal (citral, geranial and neral) is one of several NICNAS-referred chemicals where the primary public exposure is likely to be via use of cosmetics, fragrances and other domestic products (polishes, paints, washing and cleaning products, finger paints and modelling clay). There are other possible uses as a component of pest control products, flavourings and disinfectants. The delegate needed the ACCS advice on how best to manage the scheduling aspects of such submissions.

The delegate sought the following specific advice from the ACCS:

  • The relatively low toxicity profile of these chemicals suggests consistency with the SPF factors for Schedule 5. However, public exposure is only likely to occur through the use of products with concentrations ranging up to 5 per cent, at which concentration adverse health effects are unlikely. Does the ACCS consider that listing in the SUSMP is appropriate? If so, should they be listed in Schedule 5, with an appropriate cut-off to exempt (5 per cent)?
  • If scheduled, what name should be used in the listing (3,7-dimethy-2,6-Octadienal, with indexing cross references to the three isomers citral, geranial and neral)?
  • Although it is not known whether any of these isomers is present in geranium oil, is there any potential ambiguity with the current listing of geranium oil in Appendix B?
  • There are quite low concentration limits (0.001 per cent and 0.01 per cent) in EU Cosmetic Directive 76/768/EEC Annex III Part 1 specifying the highest concentrations permitted in cosmetic and personal care products without labelling. Is it feasible to include these limits in any scheduling proposal?

Is it feasible to include concentration limits in other types of products in the schedules, based on the calculations in the dermal sensitisation Quantitative Risk Assessment (QRA) of the International Fragrance Association (IFRA), as reported in the NICNAS IMAP report?

Substance details

Please refer to the NICNAS Inventory Multi-tiered Assessment Prioritisation (IMAP) Human Health Tier II Assessment Report, which is available on from the NICNAS website: Human Health Tier II Assessment for Citral and related compounds.

Scheduling status

Citral, geranial and neral are not currently scheduled.

Scheduling history

As the isomers of 3,7-dimethy-2,6-Octadienal are not scheduled, scheduling history is not available.

Public pre-meeting submissions

Four public submissions were received.

The first indicated that there are other fragrance compounds that are closely related to citral that may also be used widely (e.g. citrol) and the submission focus on citral due to the short timeframe for comments and the large number of agenda items. The organisation requested that any scheduling decisions made should reflect the fact that industry may not have had sufficient time to consider the impact of scheduling decisions on all derivatives of citral and other substances on the agenda. They indicated that in the EU and the USA citral must be disclosed on the label of cosmetic products when used in rinse-off products at concentrations greater than 0.01 per cent and in leave on products at concentration greater than 0.001 per cent. The submitter suggests that these criteria recognise that citral can cause allergic reactions in some individuals. They also stated that there appeared to be no restrictions on neral or geranial, or citral when used in consumer products. It was highlighted that the IFRA Standard restricts the use of citral in some consumer products and cosmetics and therefore the use of the scheduling process for fragrances and flavours would be inefficient. The submission therefore requested a separate discussion on the controls of fragrance and flavours rather than commenting on each individual fragrance and flavour.

The second submission indicated that it was unclear on what concentration cut-off had been proposed and requested that the committee to consider that while not all these ingredients appear on the TGA e-BS ingredient list, some of these substances may be included in proprietary ingredients that are used in therapeutic goods. The submission further requested that the committee consider existing usage within proprietary ingredients and to propose cut-off concentrations that will not impact existing use in proprietary ingredients and in therapeutic goods.

The third submitter indicated that citral should remain unscheduled as the safety of the ingredient when used in fragrances has been established by IFRA. Citral has been used in fragrances contained in their cosmetic products for many years with no known safety issues. Additionally no other market restricts the use of citral in cosmetic products. If a Schedule 5 entry is adopted we strongly urge the committee and the Delegate to exempt the use of citral in fragrances and flavours contained in cosmetic products.

The final submission did not provide comments regarding the delegate's proposal and indicated that it will provide comments, if required, based on delegate's interim decision.

ACCS advice to the delegates

The ACCS recommends that a new Schedule 5 entry for 3,7-dimethyl-2,6-octadienal isomers be created. However, there was insufficient information available to finalise the recommendation. The committee recommends that the Delegate seeks further information on:

  • the extent of use and concentrations of this material in commercial products in Australia
  • the possible regulatory impacts of scheduling
  • the basis for any possible cut-off concentrations to be applied to the Schedule
  • an implementation date suitable for this Schedule.

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, and c) the toxicity of a substance.

The reasons for the recommendation comprised the following:

  • The ubiquity in products in the public domain containing these isomers resulting in extensive potential exposure.
  • The potential for perceived public health concerns associated with these fragrances in domestic products.
  • The extensive use of these isomers in products in Australia.
  • The toxicological profile of these isomers being consistent with SPF factors for S5.

Recommendations for other action by delegate:

  • Committee recommends that this substance should be listed in Schedule 5 but is unable to provide advice on whether a cut-off to exempt from scheduling is warranted and if so at what level due to lack of data provided to the committee.
Delegates' 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 factors22;
  • Other relevant information.
Delegates' interim decision

The delegate has noted that this is not a straightforward scheduling matter. Ostensibly, the toxicity profile of the three isomers of 3,7-dimethy-2,6-Octadienal (citral, geranial and neral) appear to satisfy SPF factors for inclusion in Schedule 5, based on relatively low acute systemic toxicity, and mild skin irritancy potential. Sensitisation potential appears to be a driving force behind the NICNAS recommendation to include these substances in Schedule 5, with appropriate warning statements for those likely to suffer allergic reactions. Factors complicating the interim scheduling decision are:

  • The lack of information on the extent of use of the three isomers in fragrances used in Australian products.
  • The fact that some of these isomers (especially citral) may be components of essential oils that are already included in Appendix B (e.g. lemongrass oil, geranium oil), and therefore exempt from scheduling.
  • If they were to be included in Schedule 5, what cut-off concentration(s) to exempt would be appropriate, and should this be driven by overseas (e.g. EU) regulations on permitted concentrations in cosmetics and/or fragrances.

The interim decision of the delegate is to defer this scheduling matter, pending the receipt of further information from industry on product types, concentrations used and the likely presence of these isomers in various essential oils. When available, this information will be referred back to the ACCS for further consideration.

1.18 Zinc lactate

Scheduling proposal

On 13 September 2013, NICNAS under the New Chemicals Assessment scheme has requested that the delegate consider a proposal to include the preparations containing more than 2.5 per cent zinc lactate in Schedule 6 with strong warnings listed in Appendix F of the SUSMP and use of distinctive packaging. The basis for this recommendation is that it has moderate to high acute oral toxicity and eye irritancy. The maximum permitted concentration of the chemical in any product intended for human use (or in toothpastes) should not exceed 2.5 per cent.

The delegate considered the proposal for inclusion of zinc lactate to Schedule 6.

The delegate's reason for referring this scheduling proposal to the ACCS was that zinc lactate is a chemical referred by NICNAS following evaluation as a new chemical. Its proposed use is as an ingredient in toothpastes. Other potential uses that could result in public exposure have not been identified. The NICNAS recommendation is that inclusion in Schedule 6 is warranted on the basis of its acute toxicity profile, particularly its irritancy potential, but notes that use in toothpastes at up to 2.5 per cent should not produce adverse health effects. The NICNAS notes that this conclusion also applies to chronic exposure to absorbed zinc from the use of toothpastes. ACCS advice is needed on how to use scheduling to limit the use and concentration of this chemical in toothpastes.

The delegate sought the following specific advice from the ACCS:

  • Does the ACCS support inclusion of zinc lactate in Schedule 6, based on its acute toxicity profile, including its irritancy potential, with a cut-off to exempt at 2.5 per cent when an ingredient of toothpastes?
  • Since this chemical is a complex of zinc with lactic acid, is zinc lactate the most appropriate name for listing in the schedule (there are precedents for specifically listing other inorganic and organic zinc compounds)?
  • Is there a need to include a specific entry in Appendix C to limit its use in toothpastes, or is the Schedule 6 entry sufficient to control this use?
  • What Appendix E & F statements should be applied to scheduled products containing zinc lactate (if any, given that a secondary notification and NICNAS assessment would be required if other uses are contemplated)?
  • Are there likely to be any uses of zinc lactate inadvertently captured by the Schedule 6 entry, and should the 2.5 per cent exemption for toothpastes be a general exemption (in all products) at and below this concentration? If the exemption applies only to toothpastes, should it also specify the age range (adults and children over 12) to which the risk assessment applies?
  • Is there any need for a consequential amendment to the current Schedule 4 entry for zinc compounds (it currently applies only to preparations for internal human use)?
Substance details

Zinc lactate is used as a component of toothpaste. It can also be used as a dietary supplement23 and can be found in mouthwash, facial cleansers, breath fresheners, body wash and liquid hand soaps.24 However, it cannot be established that such products are available in Australia or what the concentration of zinc lactate is in these products, though it is expected to be minimal25.

Figure 5. Structural formula of zinc lactate.

Structural formula of zinc lactate

End-point of acute toxicity Zinc lactate SPF*
Acute oral toxicity LD50 (mg/kg bw) 500 - 2000 Moderate to high
Acute dermal toxicity LD50 (mg/kg bw) No data
Acute inhalation toxicity LC50 (mg/L/4h) No data
Skin irritation Not irritant
Eye irritation Irritant
Skin sensitisation No data

*Scheduling Policy Framework for Medicines and Chemicals (2010)

Repeated dose toxicity

No repeated dose toxicity studies on the notified chemical were provided. Several studies on zinc compounds have been conducted via the oral route, in both humans and animals. In the EU report of zinc distearate (EC, 2004), a NOAEL of 50 mg Zn2+/day (0.83 mg/kg bw/day) from human studies was chosen for risk assessment purposes, based on noted effects at higher dosage levels, in particular disruption of copper homeostasis.

The Recommended Dietary Intake (RDI) for zinc is 12 mg (4.5 mg for children aged 1-3 years). Zinc lactate is a permitted form (FSANZ, 2000).

Mutagenicity

No data on the mutagenicity potential for the notified chemical was provided.

Carcinogenicity

Limited studies on the carcinogenicity potential of zinc compounds are available. It is noted in the EU report (EC, 2004) that zinc deficiency or supplementation may influence carcinogenesis, but that there is no evidence for a direct carcinogenic action of zinc.

Reproductive toxicity

In the EU report (EC, 2004), a NOAEL of >19.9 mg Zn2+/kg bw/day was adopted for developmental toxicity in animals. It is noted that a zinc deficiency results in an impairment of fertility and foetal development. Therefore, zinc was determined not to be of concern with respect to reproductive toxicity in humans.

This risk to the public associated with the use of zinc lactate at concentrations of 2.5 per cent or less when used by adults and children aged 12 years or older is not considered to be unreasonable.

Scheduling status

Zinc lactate is not currently scheduled. A Schedule 4 entry exists for Zinc compounds for human internal use, however as the use for this substance is not for human internal use this entry does not apply.

Scheduling history

There is no scheduling history for zinc lactate.

Public pre-meeting submissions

Three public submissions were received.

The first submission indicated that currently medicines containing zinc compounds for human internal use are excluded from scheduling requirements if the recommended daily dose in preparations is 25 mg or less of zinc. If the recommended daily dose is between 25 mg and 50 mg, the preparations are exempted when compliant with the requirements of the Required Advisory Statements for Medicine Labels (RASML). The product notified to the NICNAS contained 2.5 per cent of zinc lactate, or approximately 0.75 per cent of zinc. At this concentration level, even if dilution factors are not taken into account, i.e. the full average daily amount of toothpaste used (2.75 g) is ingested, the zinc intake would be below 25 mg (approximately 20 mg). Medicines containing zinc compounds that are intended to be ingested are unscheduled when the daily dose of zinc is 25 mg or less of zinc (based on the information above). The submission indicated that zinc lactate as an ingredient in cosmetics does not require scheduling.

The second submitter indicated that there are some inconsistencies with the Australian Register of Therapeutic Goods (ARTG) entry restrictions for this ingredient when used in toothpastes. The ARTG entry for the ingredient also proposes a usage limit of 2.0 per cent or less of zinc lactate for dermal use.

The third submission did not provide comments regarding the delegate's proposal and indicated that it will provide comments, if required, based on delegate's interim decision.

ACCS advice to the delegates

The committee recommends that zinc lactate be included in Schedule 6 with an exception cut-off to unscheduled for a) preparations containing 2.5 per cent or less of zinc lactate; and b) if in tooth paste labelled 'not recommended for children under 12 years of age', with an implementation date of 1 June 2014.

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 and c) toxicity of a substance.

The reasons for the recommendation comprised the following:

  • Maintaining stability in relevant products, e.g. preservatives. Risk of ingestion of excessive amount of zinc.
  • Toxicity risk related to children's use of adult toothpaste. Ocular toxicity of zinc lactate.
Delegates' 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 factors26;
  • Other relevant information.
Delegates' interim decision

The delegate partially accepts the advice of the ACCS. The delegate notes that the primary purpose behind the recommendation in the NICNAS report on zinc lactate was to restrict the concentration in toothpastes to 2.5% and, based on risk assessment calculations of daily zinc systemic intake, to limit the use of toothpastes exceeding 2.5% to adults and children aged >12 years. The Schedule 6 proposal is also partly based on the imprecise estimate of the acute lethal dose of zinc lacate, and an uncertain characterisation of its eye irritancy potential. The delegate disagrees with ACCS advice that the Schedule 6 entry be generic, with exemptions for toothpastes <2.5%. There is insufficient evidence of its potential uses and public health hazards other than in toothpastes, and unknown implications for restricting use in a broader range of products. Therefore, the delegate has decided to limit the Schedule 6 entry to toothpastes containing 2.5% or more of zinc lactate and to apply an age exemption to products labelled with the warning 'not recommended for children under 12 years of age'.

The delegate agrees with the implementation date of 1 June 2014.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate 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) toxicity of a substance and d) the dosage, formulation, labelling, packaging and presentation of a substance.

Scheduling entry
Schedule 6 - New entry

ZINC LACTATE in toothpastes except:

  1. in toothpaste preparations containing 2.5 per cent or less of zinc lactate; and
  2. when in toothpaste labelled 'not recommended for children under 12 years of age'

1.19 Triethanolamine

Scheduling proposal

On 13 September 2013, NICNAS under the Inventory Multi-tiered Assessment Prioritisation (IMAP) process, requested that the delegate consider a proposal to reschedule triethanolamine listed in Schedule 5 to provide a cut-off to except cosmetic leave-on preparations containing 2.5 per cent or less of triethanolamine.

NICNAS recommendation for public health

The NICNAS in their IMAP report recommended that an amendment to the current listing of the chemical in the SUSMP be considered. Matters to be taken into consideration include:

  • a concern for irritation with leave on cosmetic products where the product contains ≥2.5 per cent of triethanolamine;
  • a concern for nitrosamine formation with use of the chemical in cosmetic products under certain conditions such as when used with nitrosating systems, particularly for leave-on cosmetic products;
  • pH of the cosmetic product and concentration of triethanolamine salts affecting free triethanolamine levels; and the intradermal application of the chemical is more likely to result in skin irritation, such as when used in certain tattoo removal procedures requiring intradermal administration. Therefore, it is recommended that regulatory controls to prevent the use of intradermal application of the chemical in certain tattoo removal cosmetics be considered.

Please refer to the NICNAS Inventory Multi-tiered Assessment Prioritisation (IMAP) Human Health Tier II Assessment Report, which is available on from the NICNAS website: Human Health Tier II Assessment for Ethanol, 2,2',2''-nitrilotris-.

The delegate's reason for referring this scheduling proposal to the ACCS was that, in accordance with section 4.2 of the Scheduling Policy Framework for Medicines and Chemicals27 (SPF, 2010), advice is required to be obtained from an expert advisory committee for all rescheduling proposals. The NICNAS IMAP report is a public document and it contains sufficient information for ACCS to provide advice. Furthermore, its recommendations would be known to industry.

Triethanolamine is already included in Schedule 5 with a cut-off to exempt for preparations containing less than 5 per cent. The NICNAS IMAP report addresses the potential for skin irritation to occur at concentrations above 2.5 per cent and recommends amending the Schedule 5 entry to include such preparations in the Schedule 5 entry (i.e. add an additional sub-clause to the exemption specific for leave-on (and other?) cosmetic preparations.

The NICNAS IMAP report also requests consideration of scheduling action to restrict preparations used by intradermal injection for tattoo removal.

The delegate sought the following specific advice from the ACCS:

  • Does the ACCS support the proposed amendment to the Schedule 5 cut-off for cosmetic preparations containing more than 2.5 per cent of triethanolamine?
  • Should this amended cut-off apply only to leave–on cosmetic preparations, or all cosmetic preparations?
  • Is the 5 per cent cut-off for other triethanolamine preparations (e.g. cleaners) still appropriate?
  • Should the current Appendices E & F statements be applied to the new clause; in particular, is a new set of Appendix F Statements needed for cosmetic products, deleting reference to Safety Direction No. 4 'avoid contact with skin'.
  • What scheduling actions could best give effect to the NICNAS recommendation to restrict the use of triethanolamine applied intradermally for tattoo removal? Would this be a specific listing in Appendix C, or a new entry in Schedule 4 (similar to that for ethanolamine)?
  • Does the ACCS have concerns about the potential for triethanolamine to promote the formation of nitrosamines, and is there any control that could be placed on this via scheduling?
Substance details
Use of Triethanolamine

The chemical is listed on the 2006 High Volume Industrial Chemicals List (HVICL) with a total reported volume of 1 000 – 9 999 tonnes. The following Australian uses were reported under previous mandatory and/or voluntary calls for information:

  • Cosmetic use i.e. pH control and neutralising agent or in tattoo removal cream.
  • Domestic use i.e. neutralising and emulsifying agent in laundry detergents and household cleaning products.
  • Commercial use i.e. in solvents, construction material, corrosion inhibitor and in paint and printing inks.
  • Site-limited use i.e. manufacturing other chemicals, explosives manufacture and in waste oil treatment.

The identified international uses of triethanolamine include:

  • Domestic use i.e. detergents (laundry powders), cleaning and polishing products (bathroom cleaners, leather and car waxes) and disinfectants (in aerosol disinfectant air fresheners).
  • Commercial use i.e. lubricants, corrosion inhibitors and paints.
  • Site-limited use i.e. extracting hydrogen sulphide gas, producing other chemicals (piperazine) and as a chelating agent.
Toxicity end-points

The NICNAS IMAP report notes that the critical health effects for risk characterisation of triethanolamines include acute toxicity (oral, dermal, inhalation, eye, skin and respiratory irration) and harmful effects following repeated oral exposure.

End-point of acute toxicity Triethanolamine SPF*
Acute oral toxicity LD50 (mg/kg bw) 5200 - 11 300 Low
Acute dermal toxicity LD50 (mg/kg bw) >2000 Low
Acute inhalation toxicity LC50 (mg/L/4h) 1800 Moderate to high
Skin irritation Not irritant
Skin irritation (humans) Irritant
Eye irritation Irritant
Skin sensitisation (Maximisation test and Lymph node assay) Not a sensitiser

*Scheduling Policy Framework for Medicines and Chemicals (2010)

Respiratory irritation

Based on the available information a classification for respiratory irritation is warranted (refer to Repeat dose toxicity-inhalation).

Observation in humans

The CIR (2013) reported that, in clinical provocative tests using 5-10 'hyperreactors,' 100 per cent triethanolamine produced an irritant reaction on non-scarified skin, 10 per cent triethanolamine was a marked irritant on scarified skin and 5 per cent triethanolamine in ethanol was slightly irritating to scarified skin (CIR, 2013).

In studies testing formulations containing 0.45-2.4 per cent of the chemical, no irritation was observed (CIR, 2013). According to the CIR expert panel, formulations containing 0.83-20.04 per cent triethanolamine were irritating. However, given the absence of detailed information regarding the formulations, this opinion is difficult to interpret.

Repeat dose toxicity
Oral

In the only available well reported study, the no observed adverse effect level (NOAEL) was >1000 mg/kg bw/day. Based on the available data, the chemical does not meet the factors for classification for repeated dose toxicity through the oral route.

Dermal

The chemical is reported to cause local (acanthosis, inflammation and ulceration of the skin) and systemic (increased kidney weights and nephropathy in female rats) effects following repeated dermal exposure.

The NOAEL for systemic renal effects was 250 mg/kg bw/day in female rats only (NTP, 1999). The systemic effects were observed at concentrations that do not warrant a hazard classification.

Inhalation

Based on the available information, no hazard classification for repeated dose inhalation toxicity is recommended. However, a classification for respiratory irritation is warranted.

Genotoxicity

Based on the weight of evidence from the available in vitro and in vivo genotoxicity studies, the chemical is not considered to be genotoxic.

Carcinogenicity

Considering the animal studies conducted, there is no evidence of carcinogenicity through the oral route and equivocal evidence of carcinogenicity through the dermal route. The available data do not warrant hazard classification.

The International Agency for Research on Cancer (IARC) has classified the chemical as 'not classifiable as to its carcinogenicity to humans' (Group 3), based on inadequate evidence for carcinogenicity in humans and experimental animals (IARC, 2000).

The Cosmetic Ingredient Review (CIR) Expert Panel reported that while the chemical does not directly react with N-nitrosating agents to form nitrosamines, the chemical could undergo hydrolytic cleavage that results in diethanolamine. This in turn can be N-nitrosated to chemicals that may be carcinogenic. Therefore, the chemical should not be used in consumer products where N-nitroso compounds could be formed (CIR, 2013).

Reproductive and developmental toxicity

The chemical does not show specific reproductive or developmental toxicity through the dermal route and is equivocal through the oral route. The available data do not warrant a hazard classification.

International restrictions include

European Union (EU) cosmetic restriction III/6228: Authorised use in leave-on products at a maximum concentration of 2.5 per cent in the finished product. Furthermore, for both leave-on and rinse-off products the following restrictions apply:

  • do not use with nitrosating systems;
  • minimum purity: 99 per cent;
  • maximum secondary amine content: 0.5 per cent (applies to raw materials);
  • maximum nitrosamine content: 50 microgram/kg; and
  • keep in nitrite-free containers.
Scheduling status

This chemical (excluding its salts and derivatives, except in preparations containing 5 per cent or less of triethanolamine) is listed in Schedule 5 of the SUSMP.

Triethanolamine is included in Appendix E with standard statement of 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', E1 'If in eyes was out immediately with water' and S1 'If skin or hair contact occurs, remove contaminated clothing and flush skin and hair with running water' and in Appendix F with a warning statement 'Irritant' and safety directions of 'Avoid contact with eyes' and 'Avoid contact with skin'.

Scheduling history

The toxicological information relating to triethanolamine, and other ethanolamines (diethanolamine and monoamine) have been considered by the NDPSC over several meetings in 1995, 1996 and 2000.

Public pre-meeting submissions

Four submissions were received.

One submitter indicated that the main concern for triethanolamine is the irritation potential. Based on the information in the NICNAS IMAP report on triethanolamine, irritation is likely to be induced by chemical reaction between triethanolamine and the skin and eyes rather than through other mechanisms e.g. TRPV1 receptor agonist. The irritation potential should therefore relate to the un-neutralised triethanolamine and not the salts of the triethanolamine, which could also the rationale for the current schedule entry. The submission indicated that re-scheduling of triethanolamine is unwarranted. The submission further noted that it was unaware of any concerns raised with consumer or cosmetic products containing triethanolamine with the current scheduling controls. This may be partly due to triethanolamine being used at levels lower than allowed by current scheduling.

Another submission did not provide comments regarding the delegates' proposal and indicated that it will provide comments, if required, based on the delegates' interim decision.

A third submission supported that the scheduling of triethanolamine remains as per the current schedule, and that the current allowable concentration in unscheduled products of up to 5 per cent remains unchanged. This submission commented that the regulatory restriction on concentration of triethanolamine in cosmetics was not consistent across overseas jurisdictions with restrictions in the European Union but not in the US or Canada.

The fourth submitter noted that some therapeutic goods contain triethanolamine salicylate as an active ingredient and requested that any scheduling amendment should exclude salts and derivatives from scheduling. The current Schedule 5 entry for the substance excludes salts and derivatives therefore for consistency, the proposed amendment should also excludes salts and derivatives of the substance.

ACCS advice to the delegates

The committee recommends that the current scheduling of triethanolamine remains appropriate, except when used for tattoo removal.

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

  • the risks and benefits of the use of a substance.

The reasons for the recommendation comprised the following:

  • evidence of significant adverse health effects when use in tattoo removal. This use potentially requires medical supervision.
Delegates' 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 factors29;
  • Other relevant information.
Delegates' interim decision

The delegate accepts ACCS advice that the current listing of triethanolamine in Schedule 5 remains appropriate and that there is insufficient evidence of a public health concern to lower the exemption threshold from 5% to 2.5%. The delegate notes concerns raised about the potential for adverse effects associated with the use of chemical products containing triethanolamine in tattoo removal. While listing such preparations in Schedule 4 may be the most appropriate way to control this use, the delegate accepts ACCS advice such use be referred for advice from a joint meeting of the ACCS and ACMS before taking any scheduling action.

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

1.20 Trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]-

Scheduling proposal

On 17 September, NICNAS under the New Chemicals Assessment process has recommended that the delegate consider including trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]- in Schedule 6 except when in make-up, face care products and rinse-off products at or below 34 per cent and in lip products at or below 20 per cent in which case the chemical should be included in Schedule 5.

The basis for this recommendation is:

  • The chronic, carcinogenicity and reproductive toxicity data indicate the chemical has a moderate risk of producing irreversible toxicity which meets the scheduling factors for Schedule 6.
  • A quantitative risk assessment based on repeat dose toxicity potential of the analogue substances (D4 and D5), indicated that body lotion should be excluded from the possible product types and the concentration of the chemical in lip products should be no more than 20 per cent.

The delegate's reason for referring this scheduling proposal to the ACCS was that this is one of several NICNAS-referred chemicals where the primary public exposure is likely to be via use of cosmetic products. The delegate requested the Advisory Committee on Chemicals Scheduling (ACCS) advice on how to best manage the scheduling aspects of such submissions.

The delegate sought the following specific advice from the ACCS:

  • Given the relatively low toxicity profile of this chemical, and the fact that public exposure is only likely to occur through the use of cosmetic products containing up to 34 per cent of this organosilane chemical, does the ACCS consider that listing in the SUSMP is appropriate? If so, in which schedule should it be listed?
  • If scheduled, what name should be used in the listing (1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]-trisiloxane or methyl trimethicone)?
  • If scheduled, what is an appropriate cut-off to a lower schedule or to exempt? Should this be 34 per cent for all cosmetic uses, or different cut-offs for different product types?
  • Can the ACCS advise on whether it is possible to implement, through scheduling, the NICNAS recommendation that the chemical should not be used in body lotions or aerosols?
  • Is there a need for Appendices E and F statements, given that public exposure to the pure chemical is unlikely to occur, and cosmetic products containing 34 per cent or less would not appear to warrant warning statements?
  • While there is no indication cosmetic products containing this organosilane will be injected or implanted, is there any need to amend the current Appendix C entry that prohibits such use for silicones?
Substance details

Organosilicones, such as trisiloxane, has been used in various industrial applications due to their unique active surface properties. In aqueous systems, hydrophilically substituted trisiloxane derivatives function as excellent wetting agents. Trisiloxane surfactants have been used as adjuvants in agricultural applications for a long time30.

Trisiloxane is used in the manufacture of various products, including resin, synthetic rubber, artificial synthetic fibers and filaments, pharmaceuticals and medicines, paints, coatings, adhesives, soap, cleaning compounds, toilet preparations, and household appliances31.

Trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]- will be used at ≤34 per cent concentration in a range of cosmetics, including facial cleansers, shampoos, conditioners, shower gels, make-up removers and lip products32.

Figure 6. Structure of trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]-

Structure of trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]-

End-point of acute toxicity Species Trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]- SPF*
Acute oral toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Acute dermal toxicity** Not provided Not provided Not provided
Acute inhalation toxicity** Not provided Not provided Not provided
Skin irritation Rabbit Non-irritant
Eye irritation Rabbit Non-irritant
Skin sensitisation Guinea pig Non-sensitiser

*Scheduling Policy Framework for Medicines and Chemicals (2010)

**Based on studies conducted on analogue substances, namely octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5), low acute dermal and inhalation toxicity is expected for the notified chemical.

Repeat-dose toxicity

A 28-day repeat-dose oral toxicity study was conducted on the notified chemical in rats. No deaths or clinical effects were recorded for this study. While this study established a no observed effect level (NOEL) of 1 500 mg/kg bw/day, only one dose of the test substance was administered and no haematological or clinical chemistry measurements were made.

Mutagenicity

Trisiloxane was not mutagenic in a bacterial reverse mutation study and was not clastogenic in an in vitro mammalian chromosome aberration test.

Genotoxicity

Trisiloxane was not a genotoxic.

Reproductive toxicity

No reproductive toxicity studies were provided on trisiloxane. Studies on an analogue substance (D4) have been conducted and this chemical is classified under category 3 for reproductive toxicity (R62 Possible risk of impaired fertility; HSIS). Reproductive toxicity effects were noted in rats following inhalation. These included an increase in pre-implantation loss, increased post-implantation loss suppression of luteinising hormone surge, reductions in corpora lutea and in the number of pups born to exposed dams. While the relevance of these findings to humans and to the notified chemical is uncertain, the possibility of chronic effects following repeated, long term exposure to the notified chemical via inhalation cannot be ruled out.

Carcinogenicity

No carcinogenicity studies on trisiloxane were provided. In chronic/carcinogenicity studies conducted on analogue chemicals (D4 and D5) in rats via inhalation, endometrial adenomas were observed at the highest dose level and were concluded to be due to threshold effects on the rat endocrine system (which was also supported by the lack of genotoxic potential). However, the relevance of these effects to humans and to the notified chemical is uncertain.

Public health

At the proposed use concentration of ≤34 per cent notified chemical in cosmetic products, acute toxicity effects are not expected. The repeated dose toxicity effects of the notified chemical have not been determined. However, based on the observation of adverse effects in analogue chemicals, D4 and D5, particularly with respect to reproductive toxicity and carcinogenicity, similar effects in the notified chemical cannot be ruled out.

Repeat dose toxicity potential was estimated by calculation of the margin of exposure (MOE) of the notified chemical using the worst case exposure scenario of 0.52 mg/kg bw/day and the no observed adverse effect level (NOAEL) of 17.8 mg/kg bw/day, which was established in toxicity studies involving the analogues D4 and/or D5. A MOE value ≥100 is considered acceptable to account for intra- and inter-species differences. Using the abovementioned NOAEL, a MOE of 34 was estimated. Thus, the risk to the public from use of the notified chemical at 34 per cent concentration in cosmetic products, including facial cleansers, shampoos, conditioners, shower gels, make-up removers and lip products is considered to be unreasonable.

In the exposure estimate, the greatest contributors were body lotion (based on the large daily exposure amount and large skin surface area) and lipstick (based on ingestion of the notified chemical). Exclusion of body lotion from the possible product types and reduction of the concentration of the notified chemical in lipstick products from 34 per cent to 20 per cent, allows recalculation of the combined internal dose to 0.182 mg/kg bw/day. A MOE of 98 is then estimated.

In light of the conservative parameters used, the risk to the public associated with the use of the notified chemical at ≤34 per cent concentration in make-up, face care products and rinse off products and ≤20 per cent in lip products is not considered to be unreasonable.

Scheduling status

Trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]- is not specifically scheduled.

Scheduling history

Not applicable.

Public pre-meeting submissions

Two public submissions were received.

One submission raised concerns with a number of aspects of the NICNAS assessment of methyl trimethicone and the scheduling proposal from scientific assessment and risk management viewpoints. The human health assessment, particularly the setting of the MOE was based on the NOAEL of "analogues" D4 (octamethylcyclotetrasiloxane) and/or D5 (Decamethylcyclopentasiloxane). It was NICNAS' decision to assign D4 and D5 as "analogues" of methyl trimethicone. The submission indicated that it failed to see the structural similarity between methyl trimethicone and D4/D5. All of these substances are silicone based and are similar in molecular weight [mass], however this is where the similarities appear to end. Without providing scientific justification for assigning D4/D5 as analogues of methyl trimethicone (e.g. mode of action for D4/D5 is known and it is likely, based on scientific logic that can be explained, that methyl trimethicone will also trigger the same toxicological response as D4/D5), the use of D4/D5 data for risk assessment of methyl trimethicone is inappropriate. There is no scientific justification in the public reports of NICNAS assessments. The only justification NICNAS put forward for the use of D4/D5 as analogues is that the three substances have similar molecular weight [mass], water solubility, partition co-efficient and vapour pressure. The submission did not support scheduling of methyl trimethicone, D4 or D5 based on all available information on these substances.

The other did not provide comments regarding the delegate's proposal and indicated that it will provide comments, if required, based on delegate's interim decision.

ACCS advice to the delegates

The committee recommends that trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy]- does not require a schedule listing.

Delegates' 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 factors33;
  • Other relevant information.
Delegates' interim decision

The delegate accepts ACCS advice that trisiloxane, 1,1,1,3,5,5,5-heptamethyl-3-[(trimethylsilyl)oxy] does not require scheduling, either under this name, or its INCI name, methyl trimethicone. The toxicity profile of this chemical suggests sufficiently low acute toxicity to not warrant scheduling. However, the delegate notes and agrees with concerns raised by both the ACCS and in an industry submission, that inferring a reproductive toxicity potential for this chemical, based on ‘read-across’ from studies with cyclic siloxanes of similar molecular weight, provides insufficient evidence of relevant toxicity for this to be considered in the scheduling process.

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

1.21 C11-C15-secondary, ethoxylated, oxirane and oxirane, ethyl (oxirane)

Scheduling proposal

On 29 August 2013 the delegate received an application proposing the inclusion of C11-C15-secondary, ethoxylated, oxirane and oxirane, ethyl in Schedule 6. The basis for this recommendation is that the substance's high acute oral toxicity and the slight to moderate eye irritancy. The acute oral LD50 for the neat chemical was 550 - 2000 mg/kg in rats. Eye irritation was slight to moderate in rabbits based on the level of corneal opacity, iritis and conjunctival irritation observed.

The delegate's reason for referring this scheduling proposal to the ACCS was that although substance's proposed uses are mainly industrial and there is little likelihood that any products containing a high enough concentration to warrant scheduling would appear in the retail marketplace, it would be useful to have ACCS's advice.

The delegate sought the following specific advice from the ACCS:

  • While the toxicity profile of this polymer appears to be consistent with Schedule 6 factors in the Scheduling Policy Framework, is this sufficient reason to consider including it in the SUSMP, given that the proposed use pattern is mainly industrial and there appears to be limited likelihood that products entering the domestic retail market would have concentrations high enough to warrant scheduling?
  • If scheduling is warranted, is there sufficient information on acute toxicity and/or irritancy potential to determine a cut-off to a lower schedule or to exempt?
  • If inclusion in Schedule 6 is supported by the ACCS, please indicate wording that would identify this specific polymeric chemical in the schedules, and suggest appropriate Appendix E (First Aid) and Appendix F (warning statements and safety directions) statements?
Substance details

The polymer contains alcohols, C11-C15-secondary, ethoxylated, oxirane and oxirane, ethyl (the polymer). The polymer is a non-ionic surfactant that will be used at up to 1 per cent concentration in products for a range of applications, including coatings (40 per cent of total import volume), industrial hard surface cleaners (25 per cent), food and non-dairy beverage cleaning (25 per cent), inks (5 per cent), and adhesives (5 per cent).

End-point of acute toxicity Species C11-C15-secondary, ethoxylated, oxirane and oxirane, ethyl (oxirane) SPF*
Acute oral toxicity LD50 (mg/kg bw) Rat 550-2000 Moderate to high toxicity
Acute oral toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Acute dermal toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Skin irritation Rabbit Slightly irritating
Eye irritation Rabbit Irritating
Skin sensitisation* Human No evidence of sensitisation

*Scheduling Policy Framework for Medicines and Chemicals (2010)

**Study performed on an analogue polymer.

Acute oral toxicity study

In the main study 3/4 animals treated at 2000 mg/kg bw died within 1-day of dosing, with notable signs of toxicity in these animals including hypoactivity, hunched posture and/or ano-genital staining. Red discolouration of the intestines was noted at necropsy in the animals that died during the observation period. No abnormalities were noted at necropsy in animals treated at the lower doses (550 and 175 mg/kg bw).

In a second acute oral toxicity study, the notified polymer was determined by the study authors to have an LD50 >2000 mg/kg bw. However, it is noted that 2/5 animals tested at 2000 mg/kg bw died within 1-day of dosing, with hypoactivity and/or ano-genital staining noted in these animals prior to death. Red discolouration of the intestines or lungs was noted at necropsy in the animals that died during the observation period.

Repeated dose toxicity

No repeated dose toxicity data were submitted for the notified polymer. However, reports from three studies (90-day feeding studies) conducted on an analogue polymer in rats (treated at 62.5, 125, 250 and 500 mg/kg bw/day) and dogs (treated at 82, 154 and 354 mg/kg bw/day) were submitted.

While limited details were provided (and/or limited parameters were tested), the results indicated statistically significant mean body weight gain reductions in male and female rats dosed with the test substance at ≥125 mg/kg bw/day. The absolute liver and kidney weights were statistically significantly decreased in rats dosed with the test substance at 500 mg/kg bw/day; however, the relative weights were not significantly reduced. The no observed adverse effect level (NOAEL) in rats was established by the study authors as between 62.5 and 125 mg/kg bw/day.

In dogs, doses of 354 mg/kg bw/day resulted in severe mean body weight losses and the subsequent halting of treatment at week 6. These animals re-gained weight on the control diet by the study completion. Statistically significantly reduced haemoglobin was noted in one dog receiving the test substance at 354 mg/kg bw/day. Hydrocephalus was noted in 1 male and 2 female dogs treated with the test substance at 354 mg/kg bw/day, however, this was considered to be non-treatment related by the study authors, on the basis that it is a common lesion in dogs (although in this study, control group dogs did not have any evidence of hydrocephalus). The NOAEL in dogs, for the notified polymer has been estimated to between 150 and 350 mg/kg bw/day.

Genotoxicity

The notified chemical was not mutagenic in a bacterial reverse mutation study and was not clastogenic in an in vitro mammalian chromosome aberration test.

Toxicity for reproduction

No reproductive and developmental toxicity data were submitted for the notified polymer. A reproductive and developmental toxicity study that was conducted on an analogue polymer in rats (treated at 60, 168 and 470 mg/kg bw/day) was submitted. The results of the study indicated that there were no adverse effects in foetuses, but there was some systemic toxicity in male and female adults (reductions in mean body weight, food consumption and clinical signs were noted) at doses ≥168 mg/kg bw/day. Therefore, a no observed effect level (NOEL) for parental toxicity of 60 mg/kg bw/day was established and a NOAEL for reproductive/developmental toxicity was established as ≥470 mg/kg bw/day.

Public health

The public may be exposed to the notified polymer when applying the paint containing <1 per cent notified polymer by brush or roller. Spray application is not anticipated, as this requires the use of special tools. DIY use is expected to be infrequent and users may wear some PPE to minimise exposure. In addition, painting is expected to occur in ventilated environments.

The public may come into contact with products to which the coatings, adhesives and inks containing the notified polymer have been applied. However, the polymer will be bound in a matrix and will be unavailable for exposure.

Therefore, under the proposed use scenarios, the risk to public health is not considered to be unreasonable.

Scheduling status

The polymer is not specifically scheduled.

Scheduling history

Not applicable.

Public pre-meeting submissions

Two public submissions were received.

One submission indicated that the substance name [C11-C15- secondary, ethoxylated, oxirane and oxirane, ethyl (oxirane)] did not appear to represent a chemical structure. Firstly, "ethoxylated" means reacted with oxirane (synonym for oxirane is ethylene oxide). It was noted in the submission that oxirane may have been accidentally repeated but noticed that "oxirane, ethyl" which is assumed to refer to butylene oxide, is not referenced in the substance name (e.g. butoxylated). Further the word "secondary" should refer to an alkyl chemical structure such as alcohols e.g. secondary ethoxylated alcohol - this does not appear to be the case. The submitter will be interested in any scheduling proposals for ethoxylated alcohols or scheduling amendment proposals for ethylene oxide.

The second submission did not provide comments regarding the delegate's proposal and indicated that it will provide comments, if required, based on delegate's interim decision.

ACCS advice to the delegates

The committee recommends that a polymer which contains alcohols, C11-C15-secondary, ethoxylated, oxirane and oxirane, ethyl- does not require a schedule listing.

Delegates' 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 factors34;
  • Other relevant information.
Delegates' interim decision

The delegate accepts ACCS advice that this polymer does not need to be included in any schedules of the SUSMP. While the polymer itself may have toxicological properties that appear to satisfy SPF factors for inclusion in Schedule 6, the likelihood is low that the public could be exposed to concentrations high enough to constitute a health hazard when it is used as a component of paints and coatings.

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

Footnotes

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