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Scheduling delegate's final decisions: ACCS, December 2014

Scheduling medicines and poisons

16 December 2014

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Final decisions on matters referred to an expert advisory committee: 1.5-1.8

1.5 2-pentyl cyclopentanol

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 the delegate for advice:

  • To create new Schedule 5 and Appendix F entries for 2-pentyl cyclopentanol with appropriate concentration cut-off to exempt preparations with low concentrations.

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

On 13 September 2013, an application was received requesting that the delegate consider a proposal to include 2-pentyl cyclopentanol in Schedule 5 and Appendix F. The reasons for this request are that the substance has a slight to moderate skin and eye irritation potential.

The delegate's reason for referring this scheduling proposal to the ACCS was that ACCS advice was needed on whether inclusion in the SUSMP is the most appropriate control measure, given its 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 5%, 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? Are different cut-offs required for different product categories?
  • Noting that the pure chemical is a slight-moderate skin/eye irritant, but not a sensitiser, and 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 5? Are Appendix E & F statements required?
Substance summary

2-Pentyl cyclopentanol is intended to be used as a component of fragrances in a variety of cosmetic and household cleaning products at concentrations up to 5%.

Acute toxicity

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

Toxicity Species 2-Pentyl cyclopentanol SPF Classification
Acute oral toxicity LD50 (mg/kg bw) Rat >2000 Low toxicity
Acute dermal toxicity LD50 (mg/kg bw) Rabbit >2000 Low toxicity
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

2-Pentyl cyclopentanol was found to be non-mutagenic in a bacterial reverse mutation assay and was not clastogenic in an in vitro mammalian chromosome aberration test.

Genotoxicity

2-Pentyl cyclopentanol was found to be non-genotoxic in in vitro mammalian chromosome aberration.

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

There will be widespread and repeated exposure of the public to the chemical (at ≤5% concentration) through the use of the household cleaning products and rinse-off and leave-on cosmetic and personal care products. The principal route of exposure will be dermal, while ocular and inhalation exposure is also possible, particularly if products are applied by spray.

International regulations

No information was provided.

Scheduling status

2-Pentyl cyclopentanol is not specifically scheduled.

Scheduling history

2-Pentyl cyclopentanol has not been previously considered for scheduling; therefore, scheduling history is not available.

Pre-meeting public submissions

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

Summary of ACCS advice to the delegate

The ACCS recommended that 2-pentyl cyclopentanol does not require a schedule listing.

Delegate's interim decision

The delegate accepts ACCS advice that the fragrance ingredient 2-pentyl cyclopentanol does not require scheduling. The delegate noted evidence of mild skin/eye irritancy potential at high concentrations, but that, based on studies with limited numbers of treated subjects, there appeared to be no evidence of sensitisation potential. 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.

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-pentyl cyclopentanol.

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.

1.6 2-propyl heptanenitrile

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 a new Schedule 6 and Appendix F entries for preparations containing 2-propyl heptanenitrile with appropriate low concentration cut-off for low concentration preparations.

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-propyl heptanenitrile in Schedule 6 and Appendix F. The reasons for this request are that the substance has moderate to high acute oral toxicity and a slight to moderate skin irritant potential.

The delegate's reason for referring this scheduling proposal to the ACCS was that ACCS advice was needed on whether inclusion in the SUSMP is the most appropriate control measure, given its 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 0.5%, 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-propylheptanenitrile from scheduling? Are different cut-offs required for different product categories?
  • Noting that the pure chemical is a slight-moderate skin/eye irritant, but not a sensitiser and 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, or is it more consistent with SPF criteria for listing in Schedule 5? Are Appendix E & F statements required?
Substance summary

2-Propyl heptanenitrile is intended to be used as a component of fragrances for a variety of cosmetic and domestic products at concentrations up to 0.5%.

Acute toxicity

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

Toxicity species 2-Propyl heptanenitrile SPF Classification
Acute oral toxicity LD50 (mg/kg bw) Rat 2000 Moderate to high 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

2-Propyl heptanenitrile was found to be non-mutagenic in a bacterial reverse mutation assay and was not clastogenic in an in vivo mouse micronucleus test.

Genotoxicity

2-Propyl heptanenitrile was found to be non-genotoxic in an in vivo mouse micronucleus assay.

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

At the proposed usage concentration, acute toxicity effects are not expected. The repeated dose toxicity effects of the chemical have not been determined. However, exposure is expected to be limited by the low concentration of the notified chemical in end-use products.

International regulations

No information was provided.

Scheduling status

2-Propyl heptanenitrile is not specifically scheduled.

Scheduling history

2-Propyl heptanenitrile has not been previously considered for scheduling; therefore, scheduling history is not available.

Pre-meeting public submissions

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

Summary of ACCS advice to the delegate

The ACCS recommended that 2-propyl heptanenitrile does not require a schedule listing.

Delegate's interim decision

The delegate accepts ACCS advice that the fragrance ingredient 2-propyl heptanenitrile does not require scheduling. The delegate noted evidence of mild skin/eye irritancy potential at high concentrations, but that there appeared to be no evidence of sensitisation potential. 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‑propyl heptanenitrile.

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.

1.7 3-hexanone, 2-methyl-, oxime

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 3-hexanone, 2-methyl-, oxime.

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 considers a proposal to include 3-hexanone, 2-methyl-, oxime in Schedule 6 and Appendix F. The reasons for this request are that the substance has moderate to high acute oral toxicity, skin sensitisation potential, slight eye irritation and slight to moderate skin irritation potential.

The delegate's reason for referring this scheduling proposal to the ACCS was 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 0.5%, 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? Are different cut-offs required for different product categories?
  • Noting that the pure chemical has moderate acute toxicity (LD50 200 - 2000 mg/kg), is a slight-moderate 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, or is it more consistent with the factors in the Scheduling Policy Framework for listing in Schedule 5? Are Appendix E & F statements required?
  • Does the fact that estimates of repeated dose toxicity are based on studies with an unidentified structural analogue impact on the scheduling recommendation?
Substance summary

3-Hexanone, 2-methyl-, oxime is intended to be used as a component of fragrances for a variety of cosmetic and domestic products at concentrations up to 0.5%.

Acute toxicity

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

Toxicity species 3-Hexanone, 2-methyl-, oxime SPF Classification
Acute oral toxicity LD50 (mg/kg bw) Rat 200 - 2000 Moderate to high 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 Sensitiser
Repeated dose toxicity

No repeated dose toxicity data were provided for the chemical. However, a NOAEL of 25 mg/kg bw/day was established in a 13-week oral toxicity study (administration via drinking water) of a structurally similar analogue chemical in rats, based on effects on the haematopoietic system at higher concentrations.

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

A significant risk associated with use of the chemical in fine fragrances, other cosmetic products and household products at concentrations up to 0.5%, is its potential to cause sensitisation by skin contact.

International regulations

No information was provided.

Scheduling status

3-Hexanone, 2-methyl-, oxime is not specifically scheduled.

Scheduling history

3-Hexanone, 2-methyl-, oxime has not been previously considered for scheduling; therefore, scheduling history is not available.

Pre-meeting public submissions

Two submissions were received. Both submissions indicated that the substance should remain unscheduled. If the substance, however, requires a schedule listing, therapeutic preparations containing the substance should be exempted from scheduling.

Summary of ACCS advice to the delegate

The ACCS recommended that 3-hexanone, 2-methyl-,oxime does not require a schedule listing.

Delegate's interim decision

The delegate accepts ACCS advice that the fragrance ingredient 3-hexanone, 2-methyl-, oxime 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 was in support of the delegate's interim decision not to schedule 3-hexanone, 2-methyl-, oxime.

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.

1.8 3-isothiazolone, 2-methyl- or methylisothiazolone

Scheduling decision
  • The delegate has decided to refer this substance to a joint meeting of the ACCS-ACMS.
Scheduling proposal

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

  • To list 3-isothiazolone, 2-methyl- in an appropriate schedule with concentration cut-offs for low concentration preparations.

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

On 23 April 2014, NICNAS, under its IMAP programme, requested that the delegate consider a proposal to include cosmetic/personal care preparations containing 3-isothiazolone, 2-methyl- (described here as methylisothiazolone) in an appropriate schedule with low concentration exemption cut-off to exempt from scheduling. The reasons for this request are that the substance is a skin sensitiser and may also cause systemic acute toxicity (by all routes of exposure) and local effects (skin corrosion and the possibility of causing serious damage to eyes).

The delegate's reason for referring this scheduling proposal to the ACCS was that the IMAP report highlights the sensitisation potential of methylisothiazolone in cosmetic and other products and noted that international controls over its use in cosmetics limits the concentration to 0.01%. NICNAS proposed inclusion in a schedule of the SUSMP, with a low-concentration cut-off to exempt from scheduling. The sensitisation potential was also highlighted in a recent report in the Medical Journal of Australia by Cahill et al, 2014, particularly in association with its use in 'wet wipes'.

The delegate asked the ACCS the following questions:

  • Does the ACCS agree that the toxicity profile for methylisothiazolone (acute lethality, skin/eye irritancy and sensitisation potential) is consistent with listing in Schedule 6?
  • Which name should be used for any schedule entry – methylisothiazolone, 2-methylisothiazol-3(2H)-one or 3-isothiazolone, 2-methyl-?
  • Can the ACCS recommend a cut-off to a lower schedule, or exempt from scheduling for products containing a low concentration level of methylisothiazolone? Should this cut-off be 0.01%, as specified in several international regulations cited in the NICNAS IMAP report?
  • What weight should be given to reports of allergic reactions in humans at concentrations in currently used 'wet wipes' and other products, as reported by Cahill et al, 2014? Despite evidence from animal and in vitro studies that suggest a higher concentration threshold for sensitisation reactions, are these clinical reports consistent with others in the NICNAS IMAP report (including an assessment by the European SCCS) that contact allergies can occur at concentrations much lower than 0.01%?
  • What are the likely regulatory impacts on existing consumer products if the ACCS recommends listing in a schedule with no cut-off?
Substance summary

Please refer to the NICNAS IMAP human health Tier II assessment report for 3-isothiazolone, 2-methyl-. This report is publicly available on the NICNAS website:

Scheduling status

Methylisothiazolone is not specifically scheduled.

Scheduling history

Methylisothiazolone has not been previously considered for scheduling; therefore, scheduling history is not available.

Pre-meeting public submissions

Seven submissions were received.

The first submission requested that industrial and other preparations containing methylisothiazolone be excluded from scheduling. The submission also indicated that the consideration should be referred to the joint ACCS/ACMS meeting once the Cosmetic Ingredient Review (CIR) report is finalised.

The second submission requested the consideration be deferred until final recommendations of the CIR report are available or, if a decision is made which affects products currently on the market, the implementation date should be extended to 24 months.

The third submission indicated that aqueous dispersion preparations containing low concentrations of methylisothiazolone are considered not to be skin sensitisers. If a low concentration exemption cut-off of below 0.1% is chosen, this should be supported by toxicity and user data.

The fourth submission indicated that scheduling of methylisothiazolone may have impact on therapeutic preparations containing methylisothiazolone and suggested the substance should be consideration by the joint ACCS/ACMS. The submission did not object to harmonising cut offs.

The fifth submission supported regulatory alignment with overseas and harmonisation of appropriate risk management measures.

The sixth submission indicated that it did not believe in a "one size fits all applicability", due to the variability in end products and uses. A subsequent submission requested that products that do not have direct skin applications be exempted from scheduling due to lower risk profile. If cut-offs are applied to domestic preparations containing methylisothiazolone, they should be in line with those within Australia's hazardous substances classification scheme.

The seventh submission requested any cut-off assigned to methylisothiazolone be for cosmetics only.

Summary of ACCS advice to the delegate

The ACCS recommended that the delegate foreshadow that a new Schedule 6 entry be created for methylisothiazolone and seek further information on non-cosmetic uses and possible exemptions. This matter should be referred to a joint meeting.

Delegate's interim decision

The delegate notes that the ACCS was unable to make a scheduling recommendation relating to methylisothiazolone. The sensitising potential is the key driver for any scheduling action and the SPF criteria suggest this would warrant inclusion in Schedule 6, with an appropriate exemption for cosmetic and other products containing a low concentration. There is a significant disparity between the outcomes of the 2014 EU CSSR review of methylisothiazolone (no safe level of exposure in cosmetics) and the draft US CIR 2014 review (suggesting a cut-off at 100 ppm). The ACCS decided it would be prudent to await the final US CIR panel review before proceeding to set a cut-off for a foreshadowed Schedule 6 listing. The ACCS also noted that the matter should go to a joint meeting of the ACCS/ACMS, given the importance of this preservative in therapeutic goods as well as cosmetics.

The delegate's interim decision was, therefore, to defer further consideration of the scheduling of methylisothiazolone, pending the publication of the final US CIR decision. Further consideration of the scheduling of methylisothiazolone should involve referral to a joint meeting of the ACCS and ACMS, in order to consider potential impacts associated with its use in therapeutic goods, as well as scheduling consideration of the closely related preservative 5-chloro-2-methylisothiazolone. This is a position supported in most of the public submissions received.

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

Two submissions were received. Both submissions supported the delegate's interim decision to defer any decisions on this chemical until the final US Cosmetic Ingredients Review (CIR) report is made available.

The first submission referred to the EU regulatory decision on the mixture of 5-chloro-2-methylisothiazolin-3(2H)-one and 2-methylisothiazolin-3(2H)-one (CIT:MIT mixture) on 18 September 2014, available at: Amending Annex V to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products. This decision takes into account the 2009 Opinion of the Scientific Committee on Consumer Safety (SCCS) on CIT:MIT mixture.

In the EU, MIT continues to be allowed in cosmetic products in concentrations up to 100 ppm (0.01%). The submitter noted that if urgent action were required based on the SCCS opinion on MIT, the EU Commission would have taken this opportunity to amend the regulation of MIT.

The second submission requests the joint committee of ACCS-ACMS to consider appropriate implementation timeframes for any changes made to scheduling of MIT and to further clarify the types of products this concerns.

Delegate's final decision

The delegate notes the submissions received in response to publication of the interim decision and confirms the interim decision to defer further consideration until the next joint meeting of the ACCS /ACMS. The delegate will refer to the ACCS/ACMS, the information provided in the submission relating to recent consideration by the European Union. The delegate has confirmed that the reasons for the current deferral decision are in keeping with those for the interim decision.

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