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Scheduling delegate's final decisions: ACCS, November 2015

Scheduling medicines and poisons

19 November 2015

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2.8 Quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl)

Part A - Final decisions on matters referred to an expert advisory committee

2. Scheduling proposals referred to the August 2015 ACCS meeting

2.8 Quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl)

Scheduling proposal

The chemicals scheduling delegate has referred the following scheduling proposal for consideration by the Advisory Committee on Chemicals Scheduling (ACCS):

  • In April 2015 the delegate received a request to consider creating a new entry for quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl)- in Schedule 6, with appropriate cut-off exemptions when used in low concentrations.
Scheduling application

The reasons for the request were:

  • The chemical is a skin irritant and slight eye irritant, consistent with Schedule 5 factors.
  • The chemical is a skin sensitiser, consistent with Schedule 6 factors.

The NICNAS recommended usage concentrations of 0.03% in fine fragrances, 0.006% in other cosmetic products and 0.00075% in household products correspond to the maximum proposed usage concentrations by the notifier. The NICNAS assessment determined that there was no unreasonable risk to the public when used at these concentrations.

A margin of exposure (MoE) value of ≥ 100 was considered acceptable to account for intra- and inter-species differences. Using an NOAEL of 150 mg/kg bw/day, which was derived from a 28-day oral repeat dose toxicity study in rats, and an estimated exposure value of 0.018 mg/kg bw/day from use of the chemical in cosmetic and household products, a MoE of 8,343 was estimated. A quantitative risk assessment for skin sensitisation also indicated that use of the chemical at the proposed concentrations was not considered to be unreasonable.

The chemical has been early listed on to the Australian Inventory of Chemical Substances (AICS) at the request of the notifier and is therefore currently available for use by introducers other than the original notifier.

Delegate's reasons for referring this to the committee

The previous ACCS has considered a number of fragrance chemicals referred from NICNAS. For chemicals with a low toxicity profile and likely to be present at quite low concentrations in products in the retail market, the ACCS has advised that there is insufficient public health risk to warrant inclusion in a schedule of the SUSMP. At the November 2014 ACCS, there were five fragrance chemicals that generated such advice. At the November 2013 and July 2014 ACCS meetings, similar advice was offered in relation to two other fragrance ingredients. However, at the July 2014 meeting, ACCS advice in relation and one other fragrance chemical (4,4-dimethyl-1-cyclohexene-1 propanal) was to list it is Schedule 6, with exempt cut-offs at 0.1% to 1% for various cosmetic and other product types. The different ACCS advice appears to be related to the severity of the toxicity potential of the pure compound, with 4,4-dimethyl-1-cyclohexene-1 propanal recommended a Schedule 6 listing because of the severity of the skin/eye irritancy potential and sensitization potential.

The delegate asked the committee the following questions:

  • Does the ACCS consider that the toxicological profile of quinolone, 5,6,7,8-tetrahydro-8-(1-methylpropyl)- is sufficiently similar to the seven fragrance chemicals where no scheduling action was recommended, or is it more like 4,4-dimethyl-1-cyclohexene-1 propanal, where listing in Schedule 6 was recommended, along with different product-related exemption cut-offs?
  • If scheduling is recommended, is the chemical name quinolone, 5,6,7,8-tetrahydro-8-(1-methylpropyl)- the preferred name for listing (or some other name)?
  • Does the ACCS support different exempt cut-offs for a Schedule 6 entry for different product types, as proposed in the NICNAS report?
Substance summary

Please refer to the New Chemical assessment report for Quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl). This report is publicly available on the NICNAS website:

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Acute toxicity

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

Toxicity Species Quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl) SPF Classification
Acute oral toxicity LD50 (mg/kg bw) Rat > 2000 None
Acute dermal toxicity LD50 (mg/kg bw) Not provided Not provided
Acute inhalational toxicity LC50 (mg/m3/4h) Not provided Not provided
Skin irritation Rabbit Irritating Consistent with S5
Eye irritation Rabbit Slightly irritating Consistent with S5
Skin sensitisation (Local lymph node assay) Mouse Evidence of sensitisation (EC3 = 6.1%) Consistent with S6
Repeat dose toxicity

A 28-day repeat dose study by oral gavage was conducted in rats with the chemical at dose levels of 15, 50 and 150 mg/kg bw/day. Based on the results of this study, the No Observed Adverse Effect level was established at 150 mg/kg bw/day as the observed changes noted in the mid- and high-dose groups were either completely reversible or showed definitive trends towards reversibility. Furthermore, the changes were considered to be largely stress related rather than changes of systemic toxicity.

Mutagenicity

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

Genotoxicity

The chemical was not clastogenic in an in vitro mammalian chromosome aberration test.

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 ≤ 0.03% concentration) through the use of a wide range of cosmetic and household products. The principal route of exposure will be dermal, while ocular and inhalation exposures (e.g. through the use of spray products) are also possible.

International regulations

No information was provided.

Scheduling status

Quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl)- is not specifically scheduled. There is only one fragrance chemical currently listed in the Poisons Standard (see notes below). Where other quinolone derivatives have been listed in the Schedules (usually in Schedules 2, 3, 4 or 10), it relates to therapeutic uses of 8-hydroxyquinolines or quinolone antibiotics.

Scheduling history

Quinoline, 5,6,7,8-tetrahydro-8-(1-methylpropyl)- has not been previously considered for scheduling hence a scheduling history is not available.

Pre-meeting public submissions

No public submissions were received.

Summary of ACCS advice to the delegate

The committee recommended the substance does not require scheduling.

Delegate's interim decision

The reasons for the interim decision comprised the following:

This is one of three fragrance ingredients considered by the ACCS at the August 2015 meeting, and the only one where the recommendation was not to schedule. Only the skin/eye irritancy and sensitising potential are consistent with listing in Schedules 5 and 6, but the very low concentrations likely to be present in cosmetics and consumer products indicate there would be large margins of safety. The delegate has therefore decided to maintain consistency with previous decisions on fragrance ingredients and to accept ACCS advice that this fragrance ingredient does not need to be controlled via scheduling.

Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors10;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed 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.


Footnotes

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

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