Scheduling of medicines and poisons
The delegate of the Secretary to the Department of Health hereby give notice of delegate's final decisions for amending the Poisons Standard (commonly referred to as the Standard for the Uniform Scheduling of Medicines and Poisons - SUSMP) under subsection 42ZCZX the Therapeutic Goods Regulations 1990 (the Regulations). This notice also provides the reasons for each decision and the date of effect (implementation date) of the decision.
The delegates' final decisions and reasons relate to scheduling proposals considered as delegate-only matters, i.e. not referred to an expert advisory committee.
A delegate may decide not to refer a scheduling proposal to an expert advisory committee for advice and instead may make a delegate-only decision. When deciding not to refer a matter to a committee, the delegate considers the scheduling guidelines as set out in the Scheduling Policy Framework for Chemicals and Medicines (SPF, 2015), available at SPF, February 2015.
The amendments to the Schedules, Appendices or other parts of the Poisons Standard are published electronically on the Federal Register of Legislation (FRL) as amendments to the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) prior to the date of effect (implementation date) of the final decisions. Further information, including links to the Poisons Standard on the Federal Register of Legislation (FRL), is available at SUSMP.
On 16 January 2017, the delegate made four delegate-only decisions. Following the release of the final decisions, feedback from industry indicated that some of the chemicals are used more broadly than initially considered. Hence, these four delegate-only decisions will undergo review to enable further consideration of their broader use pattern. It is anticipated that scheduling advice will be sought from the Advisory Committees on Medicines and Chemicals Scheduling (ACMS/ACCS).
Scheduling medicines and poisons
| Abbreviation | Name |
|---|---|
| AAN | Australian Approved Name |
| AC | Active constituent |
| ACCC | Australian Competition and Consumer Commission |
| ACCM | Advisory Committee on Complementary Medicines (formerly Complementary Medicine Evaluation Committee [CMEC]) |
| ACNM | Advisory Committee on Non-prescription Medicines (formerly Medicines Evaluation Committee [MEC]) |
| ACPM | Advisory Committee on Prescription Medicines (formerly Australian Drug Evaluation Committee [ADEC]) |
| ACSOM | Advisory Committee on the Safety of Medicines (formerly Adverse Drug Reactions Advisory Committee [ADRAC]) |
| ADEC | Australian Drug Evaluation Committee (now Advisory Committee on Prescription Medicines [ACPM]) |
| ADI | Acceptable daily intake |
| ADRAC | Adverse Drug Reactions Advisory Committee (now Advisory Committee on the Safety of Medicines [ACSOM]) |
| AHMAC | Australian Health Ministers' Advisory Council |
| APVMA | Australian Pesticides and Veterinary Medicines Authority |
| AQIS | Australian Quarantine and Inspection Service (now Biosecurity) |
| ARfD | Acute reference dose |
| ASCC | Australian Safety and Compensation Council |
| ASMI | Australian Self-Medication Industry |
| ARTG | Australian Register of Therapeutic Goods |
| CAS | Chemical Abstract Service |
| CHC | Complementary Healthcare Council of Australia |
| CMEC | Complementary Medicine Evaluation Committee (now Advisory Committee on Complementary Medicines [ACCM]) |
| CMI | Consumer Medicine Information |
| COAG | Councils of Australian Governments |
| CRC | Child-resistant closure |
| CTFAA | Cosmetic, Toiletry & Fragrance Association of Australia |
| CWP | Codeine Working Party |
| DAP | Drafting Advisory Panel |
| ECRP | Existing Chemicals Review Program |
| EPA | Environmental Protection Authority |
| ERMA | Environmental Risk Management Authority (New Zealand) |
| EU | European Union |
| FAISD | First Aid Instructions and Safety Directions |
| FDA | Food and Drug Administration (United States) |
| FOI | Freedom of Information Act 1982 |
| FSANZ | Food Standards Australia New Zealand |
| GHS | Globally Harmonised System of Classification and Labelling of Chemicals |
| GIT | Gastro-intestinal tract |
| GP | General practitioner |
| HCN | Health Communication Network |
| IMAP | Inventory Multi-tiered Assessment Prioritisation |
| INN | International Non-proprietary Name |
| IUPAC | International Union of Pure and Applied Chemistry |
| ISO | International Standards Organization |
| LC50 | The concentration of a substance that produces death in 50 per cent of a population of experimental organisms. Usually expressed as mg per litre (mg/L) as a concentration in air. |
| LD50 | The concentration of a substance that produces death in 50 per cent of a population of experimental organisms. Usually expressed as milligrams per kilogram (mg/kg) of body weight. |
| LOAEL | Lowest observed adverse effect level |
| LOEL | Lowest observed effect level |
| MCC | Medicines Classification Committee (New Zealand) |
| MEC | Medicines Evaluation Committee (now Advisory Committee on Non-prescription Medicines [ACNM]) |
| MOH | Ministry of Health (New Zealand) |
| NCCTG | National Coordinating Committee on Therapeutic Goods |
| NDPSC | National Drugs and Poisons Schedule Committee |
| NHMRC | National Health and Medical Research Council |
| NICNAS | National Industrial Chemicals Notification & Assessment Scheme |
| NOAEL | No observed adverse effect level |
| NOEL | No observable effect level |
| NOHSC | NOHSC |
| OCM | Office of Complementary Medicines |
| OCS | Office of Chemical Safety (formerly Office of Chemical Safety and Environmental Health [OCSEH]) |
| OCSEH | Office of Chemical Safety and Environmental Health (now Office of Chemical Safety [OCS]) |
| ODA | Office of Devices Authorisation |
| OMA | Office of Medicines Authorisation (formerly Office of Prescription and Non-prescription Medicines) |
| OOS | Out of session |
| OTC | Over-the-counter |
| PACIA | Plastics and Chemicals Industries Association |
| PAR | Prescription animal remedy |
| PBAC | Pharmaceutical Benefits Advisory Committee |
| PEC | Priority existing chemical |
| PGA | Pharmaceutical Guild of Australia |
| PHARM | Pharmaceutical Health and Rational Use of Medicines |
| PI | Product Information |
| PIC | Poisons Information Centre |
| PSA | Pharmaceutical Society of Australia |
| QCPP | Quality Care Pharmacy Program |
| QUM | Quality Use of Medicines |
| RFI | Restricted flow insert |
| SCCNFP | Scientific Committee on Cosmetic and Non-Food Products |
| SCCP | Scientific Committee on Consumer Products |
| SPF | Scheduling Policy Framework |
| STANZHA | States and Territories and New Zealand Health Authorities |
| SUSDP | Standard for the Uniform Scheduling of Drugs and Poisons |
| SUSMP | Standard for the Uniform Scheduling of Medicines and Poisons |
| SVT | First aid for the solvent prevails |
| TCM | Traditional Chinese medicine |
| TGA | Therapeutic Goods Administration |
| TGC | Therapeutic Goods Committee |
| TGO | Therapeutic Goods Order |
| TTHWP | Trans-Tasman Harmonisation Working Party |
| TTMRA | Trans-Tasman Mutual Recognition Agreement |
| WHO | World Health Organization |
| WP | Working party |
| WS | Warning statement |
Scheduling of medicines and poisons
On 16 January 2017, the delegate made four delegate-only decisions. Following the release of the final decisions, feedback from industry indicated that some of the chemicals are used more broadly than initially considered. Hence, these four delegate-only decisions will undergo review to enable further consideration of their broader use pattern. It is anticipated that scheduling advice will be sought from the Advisory Committees on Medicines and Chemicals Scheduling (ACMS/ACCS).
| Substance | Substance Final decision |
|---|---|
| m-Aminophenol | Schedule 6 – Delete EntryImplementation date: 1 February 2017 |
| Resorcinol (1,3-benzenediol) | Schedule 6 – Delete EntryImplementation date: 1 February 2017 |
| 2-Chloro-6-(ethylamino)-4-nitrophenol | Schedule 6 – Delete EntryImplementation date: 1 February 2017 |
| 2,4-Diaminophenoxyethanol hydrochloride | Schedule 6 – Amended Entry2,4-DIAMINO-PHENOXYETHANOL in hair dye preparations except in preparations containing 4 per cent or less of 2,4-diaminophenoxyethanol when the immediate container and primary pack are labelled with the following: KEEP OUT OF REACH OF CHILDREN WARNING – this product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dying eyelashes and eyebrow; to do so may be injurious to the eye. Written in letters not less than 1.5 mm in height. Appendix E, Part 2 – Current Entry2,4-DIAMINO-PHENOXYETHANOL 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.). Appendix F, Part 3 – Amended Entry2,4-DIAMINO-PHENOXYETHANOL Warning statement: 21 (WARNING – This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye.). Index – Current Entry2,4-DIAMINO-PHENOXYETHANOL Schedule 6 Implementation date: 1 February 2017 |
Scheduling medicines and poisons
m-Aminophenol is currently in Schedule 6 of the Poisons Standard.
In August 2016, the chemicals scheduling delegate received an application to create a new Schedule 6 entry for m-aminophenol. The delegate made a delegate-only decision in January 2017 with a 1 February 2017 implementation date. Prior to this date, m-aminophenol was unscheduled and had not previously been considered for scheduling.
New Zealand, ASEAN countries and the EU have restricted the use of m-aminophenol in cosmetics (see International regulations below); however, there are currently no restrictions in Australia on the use of the chemical in cosmetics or domestic products.
Considering the use of this chemical in permanent hair dyes in Australia and other potential domestic uses (based on overseas information), the main routes of public exposure are expected to be through the skin and inhalation from products applied as aerosols.
In the absence of regulatory controls, the characterised critical health effects (acute toxicity and skin sensitisation) have the potential to pose an unreasonable risk under the identified uses. The risk could be mitigated by implementing restrictions for the use of the chemical in hair dyes and other cosmetic products.
Use of the chemical in cosmetics in the EU is subject to the restrictions described in EU Cosmetics Regulation 344/2013 (as an amendment to the listing under Annex III of Regulation 1223/2009). The use of the chemical in hair dyes is restricted to a maximum concentration of 1.2% applied to hair after mixing under oxidative conditions (1:1 ratio with hydrogen peroxide). If the chemical is present at lower concentrations, sensitisation labelling is required.
Use of the chemical in cosmetics and domestic products is also restricted in several other countries as follows:
Under the above regulations, the use of the chemical in hair dyes is restricted to a maximum concentration of 1.2% applied to hair after mixing under oxidative conditions.
Delegate-initiated application.
The delegate's proposed amendments to the Poisons Standard are as follows:
Schedule 6 – Delete Entry
m-AMINOPHENOL except when in hair dye preparations containing 1.2 per cent or less of m-aminophenol when the immediate container and primary pack are labelled with the following statements:
KEEP OUT OF REACH OF CHILDREN, and
WARNING – This product contains ingredients which may cause skin sensitisation to certain individuals, and when used for eyelash or eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.
written in letters not less than 1.5 mm in height.
Appendix E, Part 2 – Delete Entry
m-AMINOPHENOL
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).
Appendix F, Part 3 – Delete Entry
m-AMINOPHENOL
Warning statements: 28 ((over) (repeated) exposure may cause sensitisation).
Index – Delete Entry
m-AMINOPHENOL
Schedule 6
Appendix E, Part 2
Appendix F, Part 3
The delegate's reasons for the proposal include:
The following toxicology information was extracted from the NICNAS IMAP Human Health Tier II assessment report for 3-aminophenol. Further information can also be found in the SCCP report for m-aminophenol.
Figure 1: Chemical structure of m-aminophenol
| Property/identifier | m-Aminophenol |
|---|---|
| Molecular formula | C6H4 |
| Molecular weight | 109.13 g/mol |
| CAS name | Phenol, 3-amino- |
| CAS number | 591-27-5 |
| IUPAC and/or common and/or other names | 3-hydroxyaniline (IUPAC); m-aminophenol (INCI) |
| SUSMP name | Not listed in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). Based on previously considered isomers, p-aminophenol (March 2016 ACCS meeting cycle) and o-aminophenol (July 2014 ACCS meeting cycle), the recommended SUSMP name is m-aminophenol. |
| Toxicity | Species | m-Aminophenol | SPF (2015) Classification |
|---|---|---|---|
| Acute oral toxicity LD50 (mg/kg bodyweight (bw)) | Rat | 812-1000 | Schedule 6 |
| Acute dermal toxicity LD50 (mg/kg bw) | N/A | No data | N/A |
| Acute inhalational toxicity LC50 (mg/m3/4h) | Rat | 1162 | Schedule 6 |
| Skin irritation | Rabbit | No irritation (2% m-aminophenol in a suspension of 0.5% methylcellulose in purified water) | N/A |
| Eye irritation | Rabbit | Mild irritation (2% m-aminophenol in a suspension of 0.5% methylcellulose in purified water) | N/A |
| Skin sensitisation (LLNA) | Mouse | Moderate to strong skin sensitiser (EC3 0.24-3.2%) | Schedule 6 |
| Skin sensitisation (Guinea pig maximisation test (GPMT)) | Guinea pig | Sensitiser. Positive reactions in 100% of animals tested at 5%, following 1% intradermal induction and 1% topical induction. |
m-Aminophenol has moderate acute oral and inhalation toxicity, warranting hazard classification. No data were available for acute dermal toxicity.
The available data from animal and human studies indicate that the chemical is not irritating to the skin or eyes.
Based on the available animal and human data, the chemical is considered to be a moderate to strong skin sensitiser and is recommended for classification.
Based on the available information, m-aminophenol is not considered to cause serious damage to health through repeated oral exposure at low doses. Systemic toxicity has not been demonstrated via the dermal route. No information was available for repeated dose toxicity by inhalation.
Based on the weight of evidence from the available in vitro and in vivo genotoxicity studies, m-aminophenol is not considered to be genotoxic.
Based on the available data and the lack of genotoxicity, m-aminophenol is not expected to be carcinogenic.
Based on the available information, m-aminophenol is not expected to be a reproductive or developmental toxin.
Sensitisation in humans exposed to the chemical has been observed both in repeat insult patch tests and during diagnostic patch testing.
In two semi-occlusive repeat insult patch tests, 0.1 mL doses of m-aminophenol (3% solution in Schultz vehicle II or similar) were applied to the backs of 98 and 99 test subjects over a six week period. There were 10 consecutive induction patch applications at 48–72 hours, followed by one day of no application. Challenge patch applications on previously unexposed skin on backs of humans were conducted 48 hours following the rest period. In both studies, irritant effects (erythema) were observed in several subjects during the induction phase. In the first study (98 subjects), no reactions to the challenge patches were observed. In the second study (99 subjects), two subjects showed reactions following application of the challenge patches, as well as following application of additional rechallenge patches on different parts of the body.
In an Australian case study, 164 hairdressers and hairdressing apprentices who presented with allergic contact dermatitis at a dermatology clinic were patch-tested against 36 chemicals used in hair salons. Four subjects, previously exposed to m-aminophenol in the workplace, had positive reactions when patch tested with the chemical
The delegate considered the following in regards to this proposal:
The delegate's final decision is to delete the Schedule 6 entry for m-aminophenol.
The implementation date is 1 February 2017.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of the substance; (b) the purposes for which the substance is to be used and (c) the toxicity of the substance.
The reasons for the decision comprise the following:
Scheduling medicines and poisons
The chemicals scheduling delegate initiated a scheduling proposal to delete the Schedule 6 entry for resorcinol.
Resorcinol is currently in Schedule 6 of the Poisons Standard.
In August 2016, the chemicals scheduling delegate received an application to create a new Schedule 6 entry for resorcinol (1,3-benzenediol). The delegate made a delegate-only decision in January 2017 with a 1 February 2017 implementation date. Prior to this date, resorcinol was unscheduled and had not previously been considered for scheduling.
Resorcinol was reported to be used in permanent hair dye preparations in Australia (NICNAS, 2007) and in overseas hair lotions and shampoos.
Currently, there are no restrictions in Australia on using this chemical in hair dyes, hair lotions and shampoos. In the absence of any regulatory controls, the characterised critical health effects (skin and eye irritation, and skin sensitisation) have the potential to pose an unreasonable risk under the identified uses. The risk could be mitigated by implementing concentration limits and labelling requirements for use in hair dyes, hair lotions and shampoos.
The EU has restricted the use of this chemical in oxidative hair colouring products at a maximum concentration of 2.5%. It is mixed with hydrogen peroxide in a 1:1 ratio just prior to use, which corresponds to a concentration of 1.25% when applied to hair (SCCS, 2010). Restricted use in hair lotions and shampoos was also reported to be the maximum authorised concentration in the finished cosmetic product of 0.5%.
Resorcinol is listed on the EU Cosmetic Directive 76/768/EEC Annex III Part 1: List of substances which cosmetic products must not contain except subject to the restrictions and conditions laid down below (Galleria Chemica): (a) Hair dye substance in oxidative hair dye products for general and professional use-after mixing under oxidative conditions the maximum concentration applied to hair must not exceed 1.25% (w/w); and (b) Hair lotions and shampoos- maximum authorised concentration in the finished cosmetic product of 0.5% (w/w).
Resorcinol is also listed on the following:
Delegate-initiated application.
The delegate's proposed amendments to the Poisons Standard are as follows:
Schedule 6 − Delete Entry
RESORCINOL except:
KEEP OUT OF REACH OF CHILDREN, and
WARNING – This product contains ingredients which may cause skin sensitisation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye.
written in letters not less than 1.5 mm in height; or
WARNING – This product contains ingredients which may cause skin sensitisation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used on the eyelashes or eyebrows; to do so may be injurious to the eye.
written in letters not less than 1.5 mm in height.
Appendix E, Part 2 − Delete Entry
RESORCINOL
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).
Appendix F, Part 3 − Delete Entry
RESORCINOL
Warning statements: 28 ((over) (repeated) exposure may cause sensitisation).
Index – Delete Entry
RESORCINOL
cross reference: 1,3-benzenediol
Schedule 6
Appendix E, Part 2
Appendix F, Part 3
The delegate's reasons for the proposal include:
The following toxicology information was extracted from the NICNAS IMAP Human Health Tier II assessment. Further information can also be found in the European Commission Scientific Committee on Consumer Safety (SCCS) report.
Figure 2: Chemical structure of resorcinol
| Property/identifier | Resorcinol |
|---|---|
| Molecular formula | C6H6O2 |
| Molecular weight | 110.1 g/mol |
| CAS name | 1,3-Benzenediol |
| CAS number | 108-46-3 |
| IUPAC and/or common and/or other names | Resorcinol (INCI name); benzene-1,3-diol (IUPAC); 1,3-dihydroxybenzene; and 3-hydroxyphenol. |
| Toxicity | Species | Resorcinol | SPF (2015) Classification |
|---|---|---|---|
| Acute oral toxicity LD50 (mg/kg bw) | Rats (Sprague Dawley) | 200-980 mg/kg bw/day. | N/A |
| Acute dermal toxicity LD50 (mg/kg bw) | Rabbits | > 2000 mg/kg bw/day. | N/A |
| Acute inhalational toxicity LC50 (mg/m3/4h) | Rats (Harlan Wistar) | > 7800 mg/m 3/1–hour (equivalent to 7.8 mg/L or 1732 ppm); and
> 2800 mg/m 3/8–hours (equivalent to 2.8 mg/L or 622 ppm) |
N/A |
| Skin irritation | Rabbit (albino) | Slight to severe skin irritant in diluted and semi-solid state, respectively (flaked and industrial grade). | Schedule 6 |
| Rabbit (New Zealand White) | Not irritating to skin (2.5% solution in water; 98.8% purity) | ||
| Eye irritation | Rabbit (albino) | Severe eye irritant (see below) | Schedule 6 |
| Skin sensitisation (Guinea Pig Maximisation Test: GPMT) | Guinea pigs (Pirbright white) | Sensitiser (relative incidence of the positive reactions in animals was > 30%) (99.9% purity) | Schedule 6 |
| Skin sensitisation (mouse local lymph node assay: LLNA) | Mice (CBA/Ca) | Moderate sensitiser with EC = 1.4 and 6.3%
(unspecified purity) |
The acute toxicity end-points of resorcinol are summarised in Table 2B.
Based on the weight of evidence, the chemical is considered to be slightly to severely irritating to skin when administered diluted in an aqueous solution or in semi-solid state (flaked or industrial grade):
Data from one study using the chemical (flaked and industrial grade diluted in an aqueous solution and semi-solid state, respectively) indicated that the chemical should be considered a severe eye irritant:
Based on the available animal and human data, the chemical is considered to be a moderate to strong contact skin sensitiser and is recommended for classification:
Human patch-testing using the chemical elicited allergic skin reactions in 0.7–0.8% of 1694 dermatitis patients. In further case histories of 34 dermatitis patients, the chemical was reported to cause reactions after epicutaneous testing.
No dermatitis of the hands was reported for 42 workers from a tyre factory after an epicutaneous test with the chemical.
In human patch tests with the chemical (2% in petrolatum), four out of 302 hairdressers suffering from contact dermatitis reported a positive reaction. No further details were available. In another case, one patient who developed contact dermatitis after application of paint to the skin was patch tested with the chemical (5% in petrolatum) and showed a positive result after 48 hours. In a third case, three female patients suffering from acne and contact dermatitis gave a positive patch test for the chemical (2% in petrolatum) after 48 and 72 hours.
Based on the weight-of-evidence, the chemical is not considered to cause serious damage to health from repeated oral exposure.
No information was available for repeated dose toxicity by the dermal route.
There is insufficient evidence to evaluate repeated dose inhalation toxicity.
Based on the weight-of-evidence from the available in vitro and in vivo genotoxicity studies, the chemical is not considered to be genotoxic.
Based on the available data, the chemical is not considered to be carcinogenic.
Based on the available data, the chemical is not considered to be a reproductive or developmental toxin.
The delegate considered the following in regards to this proposal:
The delegate's final decision is to delete the Schedule 6 entry for resorcinol.
The implementation date is 1 February 2017.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of the substance; (b) the purposes for which the substance is to be used and (c) the toxicity of the substance.
The reasons for the decision comprise the following:
Scheduling medicines and poisons
The chemicals scheduling delegate initiated a scheduling proposal to delete the Schedule 6 entry for 2-chloro-6-(ethylamino)-4-nitrophenol.
2-Chloro-6-(ethylamino)-4-nitrophenol is currently in Schedule 6 of the Poisons Standard.
In August 2016, the chemicals scheduling delegate received an application to create a new Schedule 6 entry for 2-chloro-6-(ethylamino)-4-nitrophenol. The delegate made a delegate-only decision in January 2017 with a 1 February 2017 implementation date. Prior to this date, 2-chloro-6-(ethylamino)-4-nitrophenol was unscheduled and had not previously been considered for scheduling.
Use of the chemical in cosmetics in the European Union (EU) is subject to the restrictions described in EU Cosmetics Regulation 344/2013 (as an amendment to the listing under Annex III of Regulation 1223/2009). This chemical may be used at maximum concentrations of 3.0% in ready-for-use preparations of oxidising (permanent) and non-oxidising (semi-permanent) colouring agents for hair dyeing. Additionally, after mixing under oxidative conditions (i.e. with hydrogen peroxide) the maximum concentration applied to hair must not exceed 1.5% for both permanent and semi-permanent application types. The Cosmetics Regulation also mandates label warning statements relating to the sensitisation potential of the chemical.
Use of the chemical in hair dyes is also restricted in several other countries as according to inclusion in the following listings:
Delegate-initiated application.
The delegate's proposed amendments to the Poisons Standard are as follows:
Schedule 6 – Delete Entry
2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL except when in hair dye preparations containing 1.5 per cent or less of 2-chloro-6-(ethylamino)-4-nitrophenol when the immediate container and primary pack are labelled with the following statements:
KEEP OUT OF REACH OF CHILDREN, and
WARNING – This product contains ingredients which may cause skin sensitisation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye, and
written in letters not less than 1.5 mm in height.
Appendix E, Part 2 – Delete Entry
2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
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).
Appendix F, Part 3 – Delete Entry
2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
Warning statements: 28 ((over) (repeated) exposure may cause sensitisation).
Index – Delete Entry
2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
Schedule 6
Appendix E, Part 2
Appendix F, Part 3
The delegate's reasons for the proposal include:
The following toxicology information was extracted from the NICNAS IMAP Human Health Tier II assessment report for phenol, 2-chloro-6-(ethylamino)-4-nitro-.
Figure 3: Chemical structure of 2-chloro-6-(ethylamino)-4-nitrophenol
| Property/identifier | 2-Chloro-6-(ethylamino)-4-nitrophenol |
|---|---|
| Molecular formula | C8H9ClN2O3 |
| Molecular weight | 216.62 g/mol |
| CAS name | Phenol, 2-chloro-6-(ethylamino)-4-nitro- |
| CAS number | 131657-78-8 |
| IUPAC and/or common and/or other names | 2-Chloro-6-(ethylamino)-4-nitrophenol (INCI name) |
| Toxicity | Species | 2-Chloro-6-(ethylamino)-4-nitrophenol | SPF (2015) Classification |
|---|---|---|---|
| Acute oral toxicity LD50 (mg/kg bodyweight (bw)) | Rat | 1728 | Schedule 6 |
| Acute dermal toxicity LD50 (mg/kg bw) | Rat | >2000 | Schedule 5 |
| Acute inhalational toxicity LC50 (mg/m3/4h) | - | No data | N/A |
| Skin irritation | Rabbit | Not irritating to the skin | N/A |
| Eye irritation | Rabbit | Insufficient data. | N/A |
| Skin sensitisation (LLNA) | Mouse | Skin sensitiser | Schedule 6 |
2-Chloro-6-(ethylamino)-4-nitrophenol has moderate acute oral toxicity, but low acute dermal toxicity based on results from animal tests. Additionally, the chemical is classified as hazardous with the risk phrase 'Harmful if swallowed' (Xn; R22) in the HSIS. The available data support this classification.
The available data from animal studies indicate that 2-chloro-6-(ethylamino)-4-nitrophenol is not irritating to the skin, but is a potential eye irritant. However, insufficient details on the eye irritation study are available, which do not allow for hazard classification.
2-Chloro-6-(ethylamino)-4-nitrophenol is classified as hazardous with the risk phrase 'May cause sensitisation by skin contact' (R43) in the HSIS. The positive results, reported in a local lymph node assay (LLNA), support this classification.
In an LLNA conducted according to OECD TG 429, the skin sensitising potential of 2-chloro-6-(ethylamino)-4-nitrophenol was tested in mice (5 animals/dose group) at concentrations ranging from 0.5–10% using a DMSO vehicle, and at 0.5–2.5% using an acetone/water/olive oil vehicle (mix ratio of 2:2:1). The estimated concentration needed to produce a three-fold increase in lymphocyte proliferation (EC3) value of 2.79% was determined based on the concentrations used with the DMSO vehicle; a stimulation index greater than three was not observed at the lower concentrations used with the acetone/water/olive oil vehicle (up to 2.5%).
Based on the available information, 2-chloro-6-(ethylamino)-4-nitrophenol is not considered to cause serious damage to health through repeated oral exposure.
Based on the weight of evidence from the available, well-conducted, in vitro and in vivo genotoxicity studies, the chemical is not considered to be genotoxic.
No animal toxicity data are available on the carcinogenicity of the chemical. Based on the available genotoxicity data and mechanistic information, the chemical is not considered to be carcinogenic.
Based on the available information, the chemical is not expected to be a developmental toxin. No reliable data examining the effect of the chemical on fertility are available.
No information was available.
Considering that the chemical is reported to be used in hair dye products in Australia, the main route of public exposure is expected to be dermal.
The delegate considered the following in regards to this proposal:
The delegate's final decision is to delete the Schedule 6 entry for 2-chloro-6-(ethylamino)-4-nitrophenol.
The implementation date is 1 February 2017.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of the substance; (b) the purposes for which the substance is to be used and (c) the toxicity of the substance.
The reasons for the decision comprise the following:
Scheduling medicines and poisons
The chemicals scheduling delegate initiated a scheduling proposal to amend the Schedule 6 entry for 2,4-diaminophenoxyethanol.
2,4-Diaminophenoxyethanol is currently in Schedule 6 of the Poisons Standard.
In March 2014, the Advisory Committee on Chemicals Scheduling (ACCS) included 2,4-diaminophenoxyethanol in Schedule 6 and Appendices E and F of the Poisons Standard. Although the applicant's scheduling proposal specifically referenced the sulfate salt, it was noted at the meeting that the hydrochloride salt (2,4-diaminophenoxyethanol dihydrochloride) was used in the toxicity assessment and that the sulfate salt and free alcohol will likely have comparable physical/chemical and toxicological properties. The implementation date was 1 October 2014.
In August 2016, the chemicals scheduling delegate received an application to amend the Schedule 6 entry for 2,4-diaminophenoxyethanol. The delegate made a delegate-only decision in January 2017 with a 1 February 2017 implementation date.
2,4-Diaminophenoxyethanol hydrochloride is listed on the Australian Inventory of Chemical Substances (AICS) and is reported to be used in permanent hair dye preparations in Australia (NICNAS, 2007).
The Association of South East Asian Nations (ASEAN), Canada, New Zealand and the European Union (EU) have restricted the use of this chemical in cosmetics. Following a safety evaluation, the Scientific Committee on Consumer Products (SCCP) concluded that the use of the chemical 'as an oxidative hair dye at a maximum concentration of 2.0% in the finished cosmetic product (after mixing with hydrogen peroxide) does not pose a risk to the health of the consumer, apart from its sensitising potential' (SCCP, 2006).
The chemical is listed on the following:
Delegate-initiated application.
The delegate's proposed amendments to the Poisons Standard are as follows:
Schedule 6 – Amended Entry
2,4-DIAMINO-PHENOXYETHANOL in hair dye preparations except in preparations containing 4 per cent or less of 2,4-diaminophenoxyethanol when the immediate container and primary pack are labelled with the following:
KEEP OUT OF REACH OF CHILDREN
WARNING – this product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dying eyelashes and eyebrow; to do so may be injurious to the eye.
Written in letters not less than 1.5 mm in height.
Appendix E, Part 2 – Current Entry
2,4-DIAMINO-PHENOXYETHANOL
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.).
Appendix F, Part 3 – Amended Entry
2,4-DIAMINO-PHENOXYETHANOL
Warning statement: 21 (WARNING – This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye.).
Index – Current Entry
2,4-DIAMINO-PHENOXYETHANOL
Schedule 6
Appendix E, Part 2
Appendix F, Part 3
The delegate's reasons for the proposal include:
The following information was extracted from the NICNAS IMAP Human Health Tier II group assessment report for Ethanol, 2-(2,4-diaminophenoxy)-, hydrochloride.
Figure 4: Structure of 2-(2,4-diaminophenoxy)ethanol
| Property/identifier | 2,4-Diaminophenoxyethanol hydrochloride |
|---|---|
| Molecular formula | C8H12N2O22HCl |
| Molecular weight | 241.119 g/mol |
| CAS name | ethanol, 2-(2,4-diaminophenoxy)-, hydrochloride (1:2) |
| CAS number | 66422-95-5 |
| IUPAC and/or common and/or other names | 2,4-diaminophenoxyethanol HCL (INCI); 2,4-diaminophenoxyethanol hydrochloride. |
| Toxicity | Species | 2,4-diaminophenoxyethanol | SPF (2015) Classification/th> |
|---|---|---|---|
| Acute oral toxicity LD50 (mg/kg bw) | Rat | 1000 | Schedule 6 |
| Mouse | 1160 | ||
| Acute dermal toxicity LD50 (mg/kg bw) | N/A | No data | N/A |
| Acute inhalational toxicity LC50 (mg/m3/4h) | N/A | No data | N/A |
| Skin irritation | Rabbit | Non-irritant | N/A |
| Eye irritation | Rabbit | Irritant | Schedule 5/6 |
| Skin sensitisation (local lymph node assay, LLNA) | Guinea pig | Moderate sensitiser | Schedule 6 |
| Mouse |
The chemical is considered to have moderate acute toxicity based on results from animal tests following oral exposure. The median lethal dose (LD50) was approximately 1000 mg/kg bw in Sprague Dawley (SD) rats and 1160 mg/kg bw in Swiss albino mice. No data were available for acute dermal and inhalation toxicity.
Based on the limited available data, the chemical is not considered to be a skin irritant.
Based on the available data, the chemical is considered to be an eye irritant:
Based on the available data, the chemical is considered to be a moderate skin sensitiser:
Based on the available data, 2,4-diaminophenoxyethanol hydrochloride is not expected to cause serious damage to health from repeated oral exposure. No information was available for repeated dose toxicity by dermal and inhalation routes.
Based on the negative results observed in several in vitro and in vivo genotoxicity studies, the chemicals are not expected to be genotoxic.
Based on the available data, the chemical is not considered to be carcinogenic.
Based on the available data, the chemical is not expected to have reproductive and developmental toxicity.
The delegate considered the following in regards to this proposal:
The delegate's final decision is to amend the Schedule 6 and Appendix F, Part 3 entries for 2,4-diaminophenoxyethanol as follows:
Schedule 6 – Amended Entry
2,4-DIAMINO-PHENOXYETHANOL in hair dye preparations except in preparations containing 4 per cent or less of 2,4-diaminophenoxyethanol when the immediate container and primary pack are labelled with the following:
KEEP OUT OF REACH OF CHILDREN
WARNING – this product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dying eyelashes and eyebrow; to do so may be injurious to the eye.
Written in letters not less than 1.5 mm in height.
Appendix F, Part 3 – Amended Entry
2,4-DIAMINO-PHENOXYETHANOL
Warning statement: 21 (WARNING – This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye.).
The implementation date is 1 February 2017.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of the substance; (b) the purposes for which the substance is to be used and (c) the toxicity of the substance.
The reasons for the decision comprise the following: