You are here

Scheduling delegate's final decisions, January 2017

Scheduling medicines and poisons

16 January 2017

Book pagination

1.3. 2-Chloro-6-(ethylamino)-4-nitrophenol

Final decisions on matters not referred to an expert advisory committee

1. Chemicals not referred to the November 2016 ACCS

1.3. 2-Chloro-6-(ethylamino)-4-nitrophenol

Referred scheduling proposal

An application was submitted to create a new entry for 2-chloro-6-(ethylamino)-4-nitrophenol in Schedule 6 to restrict its use in hair dyes and to determine whether an appropriate exemption concentration cut-off is required.

Current scheduling status and relevant scheduling history

2-Chloro-6-(ethylamino)-4-nitrophenol is not currently scheduled and has not been previously considered for scheduling; therefore, scheduling history is not available.

However, a homologue of 2-chloro-6-(ethylamino)-4-nitrophenol, 2-amino-6-chloro-4-nitrophenol is currently listed in Schedule 6 for use in hair dye and eyebrow/eyelash colouring preparations as follows:

Schedule 6

2-AMINO-6-CHLORO-4-NITROPHENOL in hair dye and eyebrow/eyelash colouring preparations, except:

  1. in preparations containing 2 per cent or less of 2-amino-6-chloro-4-nitrophenol when applied directly to the hair, or containing 2 per cent or less of 2-amino-6-chloro-4-nitrophenol after mixing and 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.

  2. b) in eyelash and eyebrow tinting products containing 1.5 per cent or less of 2-amino-6-chloro-4-nitrophenol after mixing for use when the immediate container and primary pack are labelled with the following statement:

    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 1.5mm in height.

Appendix E, Part 2 − 2-AMINO-6-CHLORO-4-NITROPHENOL

Standard statements: A, E1.

Appendix F, Part 3 − 2-AMINO-6-CHLORO-4-NITROPHENOL

Warning statement: 28.

International regulations

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:

  1. the Association of Southeast Asian Nations (ASEAN) Cosmetic Directive Annex III-Part 1, with the same use restrictions as described above for the EU; and
  2. the New Zealand Cosmetic Products Group Standard-Schedule 5-Table 1: Components cosmetic products must not contain except subject to restrictions and conditions laid down. While a maximum concentration (of 3.0%) only appears to apply to ready for use preparations of non-oxidising (semi-permanent) colouring agents for hair dyeing, the maximum concentration applied to hair must not exceed 1.5% for both permanent and semi-permanent application types.
Scheduling application

General application.

The applicant's proposed amendments to the SUSMP are as follows:

Schedule 6 – New Entry

2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL except when used in hair dye and eyebrow/eyelash colouring products at a concentration of 1.5 per cent or less of 2-chloro-6-(ethylamino)-4-nitrophenol after mixing for use and 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.

Written in letters not less than 1.5 mm in height.

Appendix E, Part 22-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL

Standard statements: E1 (if in eyes wash out immediately with water).

Appendix F, Part 32-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL

Warning statements: 28 ((over) (repeated) exposure may cause sensitisation).

The applicant's reasons for the request are:

  • Reported use of 2-chloro-6-(ethylamino)-4-nitrophenol as an ingredient in both permanent and semi-permanent hair dyes in Australia;
  • 2-Chloro-6-(ethylamino)-4-nitrophenol is a skin sensitiser;
  • 2-Chloro-6-(ethylamino)-4-nitrophenol is acutely toxic following oral exposure;
  • Overseas restrictions for use of 2-chloro-6-(ethylamino)-4-nitrophenol in hair dyes; and
  • When 2-chloro-6-(ethylamino)-4-nitrophenol is used as a hair dye, there is a potential risk of for skin sensitisation, which may be controlled through concentration restrictions and warning labels, as have previously been applied to other sensitising hair dyes considered for inclusion in the SUSMP.
Substance summary

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 1.3: Chemical structure of 2-chloro-6-(ethylamino)-4-nitrophenol
Figure 1.3: Chemical structure of 2-chloro-6-(ethylamino)-4-nitrophenol

Table 1.3A: Chemical properties and identifiers 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)
Table 1.3B: Acute toxicity end-points for 2-chloro-6-(ethylamino)-4-nitrophenol
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
Acute Toxicity

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.

Irritation

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.

Sensitisation

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%).

Repeat-dose toxicity

Based on the available information, 2-chloro-6-(ethylamino)-4-nitrophenol is not considered to cause serious damage to health through repeated oral exposure.

Mutagenicity/Genotoxicity

Based on the weight of evidence from the available, well-conducted, in vitro and Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal
  • NICNAS IMAP Tier II Report
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling Policy Framework (SPF 2015) criteria
  • Other relevant information.
Delegate's final decision

The delegate's final decision is to create a new Schedule 6 entry for 2 chloro 6 (ethylamino) 4 nitrophenol with a 1.5 per cent cut-off of 2 chloro 6 (ethylamino) 4 nitrophenol after mixing for use in hair dye preparations as follows:

Schedule 6 − New 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 – 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 – 2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL

Warning statements: 28 ((over) (repeated) exposure may cause sensitisation).

The delegate notes that the main route of exposure to 2-chloro-6-(ethylamino)-4-nitrophenol is through the skin. The acute oral toxicity and skin sensitisation are consistent with Schedule 6 criteria. Recent decisions for previously considered similar sensitising hair dyes have allowed for some products to be exempted where there are label statements warning of the potential for skin sensitisation, and recommending testing for individual susceptibility before use. This scheduling decision is in alignment with international regulations for 2-chloro-6-(ethylamino)-4-nitrophenol and is consistent with recent decisions agreed on previously considered similar sensitising hair dyes.

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 implementation date is 1 February 2017.

Book pagination