You are here
Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, July 2016
Scheduling medicines and poisons
Red strikethrough textindicates text that has been deleted.
- Green italicised text indicates text that has been added.
Referred scheduling proposal
An application was submitted to create a new Schedule 6 entry for quinoline in preparations for use in cosmetics and domestic uses with an appropriate cut-off to exempt from scheduling for preparations with low concentration levels.
Current scheduling status and relevant scheduling history
Quinoline is not specifically scheduled and has not been previously considered for scheduling; therefore, scheduling history is not available.
Other relevant regulations
Although use in cosmetic or domestic products in Australia is not known, quinoline is reported to be used in cosmetic/domestic products as fragrance compounds overseas. However, information on the maximum use concentrations in consumer products as fragrance ingredients is not available.
The EU has prohibited the use of quinoline in cosmetics. Currently, there are no restrictions on using this chemical in Australia. In the absence of any regulatory controls, the characterised critical health effects have the potential to pose an unreasonable risk under the identified uses
The application's proposed amendments to the SUSMP are as follows:
Schedule 6 - New Entry
QUINOLINE in preparations for domestic use.
The applicants reasons for the request are:
- Quinoline has reported cosmetic and domestic use as a fragrance compound overseas;
- Quinoline is a Category 2 carcinogen and Category 3 mutagen;
- Quinoline has moderate acute oral and dermal toxicity;
- Quinoline is an irritant to the skin and a severe eye irritant;
- There are no data on reproductive and developmental toxicity;
- There are overseas restrictions for the use of quinoline in cosmetics; and
- Scheduling is an effective way of controlling the use of quinoline in cosmetic and domestic products.
Figure 3.4: Structure of quinoline
The following has been extracted from the NICNAS IMAP Human Health Tier II group assessment report for quinoline.
The acute toxicity end-points for quinoline (Figure 3.4) are listed in Table 3.4. Briefly, quinoline has moderate acute oral and dermal toxicity. It is classified as harmful if swallowed or in contact with skin. This is supported by the median lethal dose (LD50) values for oral and dermal exposure. Data for acute inhalation toxicity are insufficient to derive a conclusion. Quinoline is classified as irritating to the skin and eyes. Only limited data are available for skin irritation, showing moderate effects in rabbits. In an eye irritation study in rabbits (n = 6), 0.1 mL of quinoline was applied to one eye of each animal for 24 hours and the animals were observed for seven days. The combined irritation scores 72 hours after application were 0.8/1 for corneal irritation, 0.5/1 for iris irritation, 2/3 for conjunctival redness and 2.2/3 for conjunctival chemosis. Effects were not reversible within the 7-day observation period. Quinoline was reported to be severely irritating to the eyes. Based on the available data, quinoline is considered a non-skin sensitiser. Quinoline is a Category 3 mutagenic substance and a Category 2 carcinogenic substance. No information was available on reproductive and developmental toxicity.
|Toxicity endpoint||Species||Results||SPF (2015) Classification|
|Acute oral toxicity LD50 (mg/kg bw)||Rat||262-460||Schedule 6|
|Acute dermal toxicity LD50 (mg/kg bw)||Rabbit||590||Schedule 6|
|Acute inhalational toxicity LC50 (mg/m3/4h)||N/A||Insufficient data||N/A|
|Skin irritation||Rabbits||Moderate (Classified as irritant; only limited data available)||Schedule 5|
|Eye irritation||Rabbits||Severe (not reversible within the observation period of seven days)||Schedule 6|
|Skin sensitisation (LLNA)||Mouse||Not sensitising||N/A|
|Genotoxicity||Hamster, Mice, Rats||Genotoxic||N/A|
* See the NICNAS IMAP Human Health Tier II group assessment report for quinoline for more information
Based on the available data, quinoline is not considered to cause serious health effects from repeated oral exposure. No information was available for repeated dose toxicity by dermal and inhalation exposure.
In a repeated dose oral toxicity study (similar to OECD TG 407), male rats (n = 5/dose) were administered quinoline at 0, 25, 50, 100 or 200 mg/kg bw/day for 28 days. One death was reported in the highest dose group on day 12, and body weight gain was significantly decreased by approximately 24 % and 53 % in the 100 and 200 mg/kg bw/day groups, respectively, compared with controls. Clinical signs of toxicity included diarrhoea, reduced activity, and staining around the eyes and nose in the 200 mg/kg bw/day group.
In a repeated dose oral toxicity study (similar to OECD TG 453), male SD rats (n = 6 for control and n = 20/dose) were exposed to quinoline at 0, 0.05, 0.10 or 0.25 % (estimated to be equivalent to 0, 25, 50 or 125 mg/kg bw/day) in the diet for 40 weeks. Final body weights were reduced by 17.9, 33.4 or 51.2 % in rats exposed to quinoline at 0.05, 0.10 or 0.25 %, respectively, compared with controls. Absolute liver weights were increased in all treated rats. The non-neoplastic changes observed in rats at all doses included infiltration of liver progenitor (oval) cells, bile duct proliferation and fatty liver.
Pre-meeting public submissions
One (1) public submission was received which did not object to the proposal to schedule quinoline for cosmetic and domestic preparations if derivatives (specifically, 2- and 4-methyl quinoline) of quinoline are excluded from scheduling.
The public submission is available on the TGA website.
Summary of ACCS advice to the delegate
The committee advised that the proposal to include quinoline and its salts in Schedule 6 was appropriate with a cross reference to 2,3-benzapyridine in the index.
The ACCS advised an implementation date of 1 February 2017.
Members agreed that the relevant matters under Section 52E (1) of the Therapeutic Goods Act 1989 included: (c) the toxicity of a substance.
The reasons for the advice comprised the following:
- Moderate to high acute oral and dermal toxicity; and
- Severe eye irritancy.
The delegate considered the following in regards to this proposal:
- Scheduling proposal;
- ACCS advice;
- Public submissions received;
- Section 52E of the Therapeutic Goods Act 1989;
- Scheduling Policy Framework (SPF 2015); and
- Other relevant information.
Delegate's interim decision
The delegate notes and accepts the advice and reasons of the ACCS that the moderate to high acute oral and dermal toxicity and severe eye irritancy of quinoline is consistent with Schedule 6 criteria in the SPF. Accordingly, a new Schedule 6 entry for quinoline will be created for quinoline with a cross reference to 2,3-benzapyridine in the index and appropriate Appendix E and F statements and warnings to reflect its toxicity profile.
An early implementation date of 1 February 2017 is proposed in order to bring the regulation of this ingredient in products sold in Australia into alignment with international regulations.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (c) the toxicity of a substance.
Schedule 6 - New Entry
QUINOLINE and its salts (excluding other derivatives).
Index - New Entry
cross reference: 2,3-BENZAPYRIDINE
Appendix E, Part 2
Appendix F, Part 3
Appendix E and F - New Entries
Appendix E - QUINOLINE
Standard statements: A [for advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)], E1 (if in eyes wash out immediately with water), S1 (if skin or hair contact occurs, remove contaminated clothing and flush skin and hair with running water)
Appendix F - QUINOLINE
Warning statement: 79 (will irritate eyes).
Safety directions: 1 (avoid contact with eyes), 4 (avoid contact with skin).