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Scheduling delegate's final decisions, January 2017

Scheduling medicines and poisons

31 January 2017

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3. 2-Chloro-6-(ethylamino)-4-nitrophenol

Amendment to delegate-only final decisions not referred to an expert advisory committee

3. 2-Chloro-6-(ethylamino)-4-nitrophenol

Scheduling proposal

The chemicals scheduling delegate initiated a scheduling proposal to delete the Schedule 6 entry for 2-chloro-6-(ethylamino)-4-nitrophenol.

Current scheduling status and relevant scheduling history

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.

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:

  • 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
  • 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

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:

  • Information has been received from industry to indicate that the wording of the Schedule 6 entry may require further amendment to account for the use of 2-chloro-6-(ethylamino)-4-nitrophenol in other industry sectors.
  • The delegate will review the previous January 2017 decision and seek advice from the scheduling committees (ACCS and ACMS).

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 3: Chemical structure of 2-chloro-6-(ethylamino)-4-nitrophenol
Figure 3: Chemical structure of 2-chloro-6-(ethylamino)-4-nitrophenol

Table 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 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 in vivo genotoxicity studies, the chemical is not considered to be genotoxic.

Carcinogenicity

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.

Reproduction and developmental toxicity

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.

Observation in humans

No information was available.

Public exposure

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.

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; and
  • Other relevant information.

Delegate's final decision

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:

  • Information has been received from industry to indicate that the wording of the previous Schedule 6 entry may require further amendment to account for the use of 2-chloro-6-(ethylamino)-4-nitrophenol in other industry sectors.
  • The delegate will review the previous January 2017 decision and seek advice from the scheduling committees (ACCS and ACMS).

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