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Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, March and July 2017

Scheduling medicines and poisons

15 September 2017

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3.7 Basic Red 76

Referred scheduling proposal

An application was submitted to amend the Schedule 7 entry of the Poisons Standard for the azo dyes that are derivatives by diazotisation and to create a new Schedule 6 entry for azo dyes to allow the use Basic Red 76 in cosmetic non oxidative hair, eyelash and eyebrow dye products containing no more than 0.001% free o-anisidine.

Scheduling application

This was a general application. The applicant's proposed amendments to the Poisons Standard are:

Schedule 7 – Amend Entry

AZO DYES that are derivatives by diazotisation of any of the following substances:

  • p-aminoazobenzene (CAS No. 60-09-3)
    o-aminoazotoluene (CAS No. 97-56-3)
    o-anisidine (CAS No. 90-04-0)
    p-chloroaniline (CAS No. 106-47-8)
    4-chloro-o-toluidine (CAS No. 95-69-2)
    6-methoxy-m-toluidine (p-cresidine) (CAS No. 120-71-8)
    2-naphthylamine (CAS No. 91-59-8)
    5-nitro-o-toluidine (CAS No. 99-55-8)
    2,4-toluenediamine (CAS No. 95-80-7)
    o-toluidine (CAS No. 95-53-4)
    2,4,5-trimethylaniline (CAS No. 137-17-7)

except when included in Schedule 6

Schedule 6 – New Entry

AZO DYES that are derivatives by diazotisation when used in non-oxidative hair, eyelash and eyebrow dye products where the percentage of free o-anisidine as listed in Schedule 7 is no more than 0.001%.

OR

AZO DYES that are derivatives by diazotisation when used in cosmetic hair, eyelash and eyebrow dye products where the percentage of free carcinogen as listed in Schedule 7 is no more than 0.001%.

The applicant's reasons for the request are:

  • A proposal to further the cascade of scheduling controls for o-anisidine based on risk from Schedules 10 and 7 to include a lower risk Schedule 6 entry to cover the presence of free
    o-anisidine in products at levels below 0.001% which is the cut-off included in Schedule 10.
  • The non-oxidative dye Basic Red 76, (formulated in rinse-off semi-permanent or non-oxidative colourants with short skin contact times and no strong reducing agents) does not decouple to release the carcinogen of concern, o-anisidine, as demonstrated by lack of colour change on application.
  • Although under percutaneous conditions as demonstrated by in vitro mutagenic studies, decoupling does occurs, these same studies demonstrated without rat liver S9 activation resulted in no decoupling.
  • Percutaneous adsorption of Basic Red 76 is very low at 0.47%, and absorption has to occur before decoupling can occur through metabolic processes. The contact time is short for
    non-oxidative hair dyes, typically 5 to 20 minutes, and the delivery base is normally a shampoo or conditioner that functionally removes dirt and debris from the hair and scalp including any excess hair dye and carcinogen.
  • The Scientific Committee on Consumer Safety (SCCS) in an Opinion, SCCS/1385/10, has classified Basic Red 76, when used as a non-oxidative hair dye up to 2%, as not posing a risk for consumers. Australia is currently out of alignment with the SCCS Opinion and the rest of the world on Basic Red 76.
  • Many products for New Zealand come into Australian warehouses as a combined shipment for Australia and New Zealand. If the current Poisons Standard restrictive entry continues to apply to hair dyes containing Basic Red 76 shipments for New Zealand (where Basic Red 76 is approved for use), this would be seen in Australia as being 'supplied' and therefore in contravention of the Poisons Standard.
  • When the scheduling of azo dyes (that are derivatives by diazotisation) was first proposed at the August 2015 meeting of the ACCS, the then delegate received a public submission concerned about the sheer number of dyes being entered as part of the group entry without due consideration for each individual dye. One dye of concern listed in the submission was Basic Red 76 (CAS 6831-30-0). In their final decision, the then delegate suggested 'that if this dye is of importance to the Australian industry, a submission should be made to exempt this specific substance from the proposed Schedule 7 generic entry, with proposals on how it should be regulated.'

Current scheduling status and relevant scheduling history

Basic Red 76 is not specifically scheduled in the Poisons Standard but is captured by the Schedule 7 entry for azo dyes.

Schedule 7

AZO DYES that are derivatives by diazotisation of any of the following substances:

p-aminoazobenzene (CAS No. 60-09-3)

o-aminoazotoluene (CAS No. 97-56-3)

o-anisidine (CAS No. 90-04-0)

p-chloroaniline (CAS No. 106-47-8)

4-chloro-o-toluidine (CAS No. 95-69-2)

6-methoxy-m-toluidine (p-cresidine) (CAS No. 120-71-8)

2-naphthylamine (CAS No. 91-59-8)

5-nitro-o-toluidine (CAS No. 99-55-8)

2,4-toluenediamine (CAS No. 95-80-7)

o-toluidine (CAS No. 95-53-4)

2,4,5-trimethylaniline (CAS No. 137-17-7).

o-Anisidine is also captured by the above Schedule 7 entry for azo dyes and on 1 February 2018 will have a specific entry in Schedule 10 as follows:

Schedule 10

o-ANISIDINE (excluding derivatives) in preparations for skin colouration (including tattoos) and dyeing of hair, eyelashes or eyebrows except in preparations containing 0.001% or less of o‑anisidine.

In November 2013, the Advisory Committee on Chemicals Scheduling (ACCS) considered scheduling a number of benzidine-based azo dyes due to their potential to be metabolised by azo reductases (diazotisation) in vivo to benzidine (CAS No. 92‐87‐5), a known human carcinogen. The committee noted that although these are useful chemicals (CAS No. 94249-03-3, 3567-65-5, 12217-14-0, 54579-28-1, 1937-37-7, 2429-73-4, 2602-46-2, 2429-82-5, 16071-86-6, 3626-28-6, 4335-09-5, 573-58-0 and 3530-19-6), their access for domestic use needed to be restricted due to concerns of carcinogenicity. The committee recommended that benzidine-based azo dyes be included in Schedule 7 and the delegate concurred. A delayed implantation date of 12 months to 1 June 2014 was implemented to allow industry to recall products and to enable consumers to make informed choices about using products that contain benzidine-based azo dyes.

In November 2014, the ACCS considered scheduling benzidine-congener-based dyes and benzidine-based azo dye C.I. Acid Black 29 (CAS No. 12217-14-0) in Schedule 7 due to the potential of these substances to be metabolised to carcinogenic benzidine-congeners, similar to that for benzidine-based azo dyes. The toxicological profile of the 66 benzidine-congener-based dyes presented to the committee was based on ‘read-across' (based on quantitative structure-activity relationships (QSAR)) from 6 of the benzidine-congener-based dyes; C.I. Direct Blue 14, C.I. Direct Blue 53, C.I. Direct Blue 1, C.I. Acid Red 114, C.I. Direct Blue 15 and C.I. Direct Blue 218. Given that benzidine-congener-based dyes are metabolised in vivo to carcinogenic dichlorobenzidine (3,3'-DCB), 3,3'-dihydroxybenzidine (3,3'-DHB), 3,3'-dimethoxybenzidine (3,3'-DMOB) or 3,3'-dimethylbenzidine (3,3'-DMB), the committee recommended that benzidine-congeners should not be accessible for domestic use and to list them in Schedule 7. The delegate agreed and a new Schedule 7 entry for BENZIDINE-CONGENER (3,3'-disubstituted) azo dyes was implemented on 1 June 2015.

In August 2015, the ACCS considered scheduling various azo dyes that could release selected carcinogenic and/or genotoxic amines and/or aromatic amine precursors through reductive cleavage of the azo linkages. A Schedule 7 entry was proposed in favour of a Schedule 10 entry to allow legitimate use of these dyes in industrial settings while preventing use in the domestic market. The delegate agreed to a new Schedule 7 listing for azo dyes, which are derivatives by diazotisation (i.e., that can be reduced by azoreductases to yield 8 specific carcinogenic aromatic amines) including: o‑anisidine (CAS No. 90-04-0), o-toluidine (CAS No. 95-53-4), p-aminoazobenzene (CAS No. 60-09-3), o‑aminoazotoluene (CAS No. 97-56-3), 2,4-toluenediamine (CAS No. 95-80-7), 5-nitro-o-toluidine (CAS No. 99-55-8), p-chloroaniline (CAS No. 106-47-8), and 4-chloro-o-toluidine (CAS No. 95-69-2). This decision was implemented on 1 February 2016.

  • The delegate received a public submission concerned about the sheer number of dyes being entered as part of the group entry without due consideration for each individual dye. One dye of concern listed in the submission was Basic Red 76 (CAS 6831-30-0). In their final decision, the then delegate suggested 'that if this dye is of importance to the Australian industry, a submission should be made to exempt this specific substance from the proposed Schedule 7 generic entry, with proposals on how it should be regulated.'
  • o-Anisidine was first included in Schedule 7 in February 2016 as part of the above azo dyes entry due to their carcinogenicity and genotoxicity. The toxicological data for o-anisidine provided to the committee in August 2015 were the same as those provided with this current application.

In November 2015, the ACCS considered azo dyes that could release selected carcinogenic amines (not listed on AICS). The ACCS recommended and the delegate agreed that the Schedule 7 listing for azo dyes be amended to extend the list of carcinogenic amines in order to include three extra azo dyes. An implementation date of 1 June 2016 was recommended to remove any such products from the Australian market on safety grounds. The delegate's final decision on azo dyes (not listed on AICS) was to add these to the generic Schedule 7 listing for azo dyes. The Delegate noted a public submission raised a point that some of the listed aromatic amines may be present as manufacturing impurities in the relevant azo dyes. However, the ACCS did not consider this to be a problem, since the objective is to control the parent dyes, and the resultant aromatic amines are not specifically listed as individual substances in Schedule7. At the meeting, the delegate noted that the point of the generic listing was for purposes of not creating an entire list of individual azo dyes and to capture substances that 'could be diazotised'.

In March 2016 the ACCS considered the scheduling of Disperse Yellow 3, and recommended to the delegate that the sensitisation and carcinogenic potential warrants control in cosmetic and consumer products and should not be used in hair dyes. The committee agreed it was appropriate to have both a Schedule 6 entry for general use and a Schedule 10 entry to specifically prohibit use in hair dyes and cosmetics. Members agreed that warning statements for general use to advise of the skin sensitization potential was warranted and that the name Disperse Yellow 3 be used in any

Schedule entry with a cross-reference to the chemical name

4-(2-hydroxy-5-methylphenylazo)acetanilide in the index. Members agreed that the substance was not captured by the existing benzidine azo dye entries or azo dyes derived by diazotisation and therefore should be listed separately. The delegate accepted the ACCS advice to create new listings for Disperse Yellow 3 in Schedules 6 and 10, and in Appendices E and F and noted that this substance would not be captured under any existing Schedule entries for phenylenediamines or azo dyes. The decision was implemented on 1 October 2016.

In March 2016 the ACCS also considered the scheduling of chrysoidine and its salts and recommended a Schedule 6 entry, based on toxicity, rather than capturing it in the other scheduled dyes entries. Further, it was noted that there is evidence of use in the hobby industry, and this should be considered when scheduling chrysoidine. The committee noted that the Schedule 6 will preclude use of chrysoidine and its salts in cosmetics (due to the requirement for POISON labelling), but this would not prevent use of these substances in hair dye products. Given this, a Schedule 10 entry was also recommended. The Delegate accepted the ACCS recommendations to create new listings for Chrysoidine in Schedules 6 and 10, and in Appendix E. This decision was implemented on 1 October 2016.

Australian regulatory information

Basic Red 76 (CAS No. 68391-30-0) is on the 'List of chemicals used as dyes in permanent and semi-permanent hair dyes in Australia' (NICNAS, 2007).

Basic Red 76 is not approved for therapeutic use in the TGA permissible ingredients repository.

Basic Red 76 is not listed in the Therapeutic Goods (Permissible Ingredients) Determination No. 3 of 2017.
Solvent Red 23 (CAS No 85-86-9) which is also an AZO DYE covered by the Schedule 7 entry as a derivative of p-aminoazobenzene is a TGA approved dye under the name of Sudan III and is 'Available for use as an Active Ingredient in: Biologicals, Prescription Medicines Available for use as an Excipient Ingredient in: Biologicals, Devices, Export Only, Listed Medicines, Over the Counter, Prescription Medicines (TGA Ingredient Summary 2017).' Its use is restricted to therapeutic products for topical use and has been approved and in use for at least the last 15 years.

International regulations

Basic Red 76

Table 3.7.1: Basic Red 76 – conditions of use in countries/jurisdictions

Example table with header cells in the top row only
Country/Jurisdiction Conditions
European Union Basic Red 76 is listed in the EU Cosmetics Regulation 1223/2009 Annex III—List of substances which cosmetic products must not contain except subject to the restrictions laid down. Basic Red 76 is allowed in non-oxidative hair dye products at a maximum concentration of 2 %.
ASEAN Annex III – allowed up to 2% in non-oxidative hair dyes
New Zealand Schedule 4 – allowed up to 2% in non-oxidative hair dyes
USA Approved
Canada Approved
Japan >Approved

o-Anisidine

o-Anisidine was first included in Schedule 7 in February 2016 as part of the azo dyes entry due to their carcinogenicity and genotoxicity. In February 2018, the scheduling of o-anisidine will change to Schedule 10 in preparations for skin colouration (including tattoos) and dyeing of hair, eyelashes or eyebrows except in preparations containing 0.001% or less of o-anisidine on 1 February 2018.
o-Anisidine is classified as a carcinogen in most countries around the world. However, different jurisdictions have set different thresholds for safe use:

EU
  • REACH Regulations: Annex XVII, o-Anisidine cannot be used in substances and preparations placed on the market for sale to the general public in individual concentrations >0.1 % (European Parliament and Council 1999; European Parliament and Council 2006; European Parliament and Council 2008). o-Anisidine is also included as part of 22 aromatic amines listed in Appendix 8 which places restrictions on their presence in leather or textile articles.
  • o-Anisidine is on the candidate list of substances of very high concern (SVHC) for eventual inclusion in Annex XIV (ECHA, 2013). In the EU, companies could have legal obligations if the chemical that they produce, supply or use is included on the candidate list whether on its own, in mixtures, or present in articles.
  • Cosmetics Regulation 1223/2009 Annex II – List of substances prohibited in cosmetic products (does not cover derivatives).
  • SCCS: 10 ppm in non-oxidation hair dye products (0.001%).
ASEAN
  • Annex II, not permitted for use in cosmetic products (does not cover derivatives).
NZ
  • HSNO Approval No. HSR004606. Hazardous Substances (Classes 6, 8, and 9 Controls) Regulations 2001 Regs 11-27 Limiting exposure to toxic substances through the setting of TELs. No ADE, PDE, TELs set at this time for this substance. Regs 46-48 Restrictions on use of substances in application areas.
  • Cosmetics Group Standard (As amended 2012): Schedule 4: Components cosmetic products must not contain (does not cover derivatives).
USA California Environmental Protection Agency
  • Cancer Potency: 0.14 mg/kg/day; 10-5 Risk Specific Intake: 5 μg/day.
IARC
  • Non threshold carcinogen 2.

Other cosmetic Azo Dyes

The chemicals Solvent Red 24; Solvent Red 23; Solvent Red 1; CAS No. 4482-25-1; CAS No. 5413-75-2; CAS No. 5421-66-9; CAS No. 8005-78-5; CAS No. 85136-74-9; CAS No. 68425-18-3; CAS No. 118658-98-3; CAS No. 118658-99-4 are listed in the:

  • Association of South East Asian Nations (ASEAN) Cosmetic Directive Annex II Part 1: List of substances which must not form part of the composition of cosmetic products;
  • EU Cosmetics Regulation 1223/2009 Annex II – List of substances prohibited in cosmetic products; and
  • New Zealand Cosmetic Products Group Standard – Schedule 4: Components cosmetic products must not contain.
  • Canada: Based on the information obtained from Galleria Chemica, the chemicals Solvent Red 24 (CAS Nos. 85-83-6) and Solvent Red 23 are listed in the Health Canada List of prohibited and restricted cosmetic ingredients (the cosmetic ingredient "Hotlist").
  • Philippines: The chemicals Solvent Red 24; Solvent Red 23; and CAS No. 131-79-3 are listed in the Philippines Restricted Ingredients For Use In Cosmetics – List of substances which must not form part of the composition of cosmetic products.
Solvent Red 24

The chemicals Solvent Red 24; CAS No. 85136-74-9; CAS No. 108225-03-2; and CAS No. 118658-99-4 are prohibited for all uses, whereas the other chemicals are prohibited when used as a substance in hair dye products.

Solvent Red 23

The chemical Solvent Red 23 (identified as CI 26100) is listed in the:

  • ASEAN Cosmetic Directive Annex IV Part 1 – List of colouring agents allowed for use in cosmetic products;
  • EU Cosmetics Regulation 1223/2009 Annex II – List of colourants allowed in cosmetic products; and
  • New Zealand Cosmetic Products Group Standard – Schedule 6: Colouring agents cosmetic products may contain with restriction.

In the above directives, Solvent Red 23 is specified as 'not to be used in products applied to mucous membranes'; purity criteria also apply.

Azo dyes

Azo dyes are restricted by Annex XVII to REACH Regulation as follows:

  • Azo dyes which, by reductive cleavage of one or more azo groups, may release one or more of the aromatic amines listed in Appendix 8, in detectable concentrations, i.e. above 30 ppm in the finished articles or in the dyed parts thereof, according to the testing methods listed in Appendix 10, shall not be used in textile and leather articles which may come into direct and prolonged contact with the human skin or oral cavity, such as:
    • clothing, bedding, towels, hairpieces, wigs, hats, nappies and other sanitary items, sleeping bags;
    • footwear, gloves, wristwatch straps, handbags, purses/wallets, briefcases, chair covers, purses worn round the neck;
    • textile or leather toys and toys which include textile or leather garments; and
    • yarn and fabrics intended for use by the final consumer.

Other azo dyes

The chemicals o-anisidine; o-toluidine; p-aminoazobenzene; 2,4-toluenediamine; o-aminoazotoluene; 5-nitro-o-toluidine; p-chloroaniline; and 4-chloro-o-toluidine are listed in Appendix 8 of EU REACH Annex XVII.

Substance summary

Basic Red 76 is used as a dyeing aid, a photographic developer and as an intermediate in drugs and perfumes.

Table 3.7.2: Chemical information for Basic Red 76
Property Basic Red 76
Chemical structure chemical structure of Basic Red 76
Molecular formula C20H22N3O2.Cl
Molecular weight 371.8 g/mol
CAS name 2-Naphthalenaminium,7-hydroxy-8-[(2-methoxyphenyl)azo]-N,N,N-trimethyl-,chloride
CAS number 68391-30-0
IUPAC and/or common and/or other names 8-(2-methoxyphenylazo)-7-hydroxy-2-naphthyltrimethylammonium chloride; C.I. Basic Red 76; 7-hydroxy-8-((2-methoxyphenyl)azo)-N,N,N-trimethyl-2-naphthalenam-inium chloride; Arianor Madder Red; C.I. 12245

Toxicity

Table 3.7.3: Acute toxicity end-points for Basic Red 76
Toxicity Species Basic Red 76 SPF (2015) Classification
Acute oral toxicity LD50 (mg/kg bw) Rat >2000 Schedule 5
Acute dermal toxicity LD50 (mg/kg bw) No data available No data available N/A
Acute inhalational toxicity LC50 (mg/m3/4h) No data available No data available N/A
Skin irritation Rabbit Non-irritating N/A
Eye irritation Rabbit Slight Schedule 5
Skin sensitisation (LLNA) Mice Negative N/A

Genotoxicity

The genotoxicity of Basic Red 76 is sufficiently investigated for the three endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Basic Red 76 did not induce gene mutations neither in bacteria (Ames Test) nor in mammalian cells. While an in vitro micronucleus test did result in an increase in V79 cells with micronuclei, this positive finding was not confirmed in an in vivo micronucleus test in mice (SCCS Opinion 2011).

Table 3.7.4: Acute toxicity end-points for o-anisidine
Toxicity Species Outcome SPF (2015) classification
Acute oral toxicity LD50 (mg/kg bw) Rats 1505–1890 Schedule 6
Acute dermal toxicity LD50 (mg/kg bw) Rats >2000 Schedule 5
Acute inhalational toxicity LC50 (mg/m3/4h) Rats >3870 Schedule 5
Skin irritation Rabbits Slight irritant Schedule 5
Eye irritation Rabbits Slight irritant Schedule 5
Skin sensitisation local lymph node assay (LLNA) and guinea pig maximisation test (GPMT) Equivocal N/A

Detailed claims against the requirements of section 52E(1) of the Therapeutic Goods Act 1989

(A) The risks and benefits of the use of a substance

Basic Red 76 does not cleave and form o-anisidine under the conditions of use for products containing Basic Red 76. Basic Red 76 is a non-oxidative hair dye used in semi-permanent hair colourants. These are sold worldwide. These colourants are applied to the hair, not the scalp, usually in a shampoo or conditioner base. They are left on the hair for 5 to 20 minutes and then thoroughly washed off. Poor removal will result in later colour residues being left on clothes and bedding. The application is pH 6.5. There is no hydrogen peroxide, ammonia or monoethanolamine that may be used with oxidation or permanent hair colourants that are high pH and much more reactive. These agents are not used for semi-permanent hair dyes. The azo chemical bond under normal conditions of use semi-permanent hair dye products is very stable. This is also demonstrated in in vitro testing where there is no o-anisidine present from cleavage when there is no metabolic activity. Metabolic cleavage does not occur with use of these products. In addition, the percutaneous absorption of Basic Red 76 into and through the skin is only 0.47% across 24 hours. A margin of exposure/safety calculation will show the level of risk from this absorption is very low.

Formation of aromatic amines such as o-anisidine by azo-cleavage is not expected in semi-permanent hair colourants and have not been found in finished products testing during storage or during application where time frames of these rinse off products are short and no loss of colour has been seen in the many applications to hair that have been applied over decades to human hair from these products.

(B) The purposes for which a substance is to be used and the extent of use of that substance

Basic Red 76 is to be used in rinse off non-oxidative hair colourants also called semi-permanent hair dyes at levels up to 2%. This use is aligned with the approved maximum expressed in the European Scientific Committee for Consumer Safety SCCS/1385/10 Opinion for Basic Red 76 and adopted into the European Regulation for Cosmetics, Annex III/267 for use in non-oxidative hair dye products with a maximum concentration of 2%.

(C) Toxicity and safety of the substance

How to access a pdf document

For full summary of toxicity assessment please refer to the SCCS Opinion on Basic Red 76 (pdf,315kb).

(D) Dosage, formulation, labelling, packaging and presentation of a substance

Information on formulations, labelling and packaging were included in the application.

(E) Potential for misuse/abuse of the substance

All products supplied come with detailed directions for use. The application method is simple – apply to the hair in the same way as someone would shampoo or condition their hair. There is no mixing with other packs as products containing Basic Red 76 are not permanent colourant products. These product dosage form may be liquids or mousses and be supplied in bottles or tubes. Child resistant closures are not generally required for these products.

(F) Any other matter that may be relevant to the scheduling of a substance

Nil.

Pre-meeting submissions

Six (6) public submissions were received, five (5) in support and one (1) opposed.

Main points in support:

  • Basic Red 76 is approved in the EU, USA, New Zealand and in all ASEAN counties.
  • In the European Union, Basic Red 76 is used in non-oxidative hair dyes up to 2% and is a common colourant.
  • Two submissions noted that they are unaware of any other countries besides Australia where Basic Red 76 is banned.
  • Basic Red 76 is essential to providing a full range of colours for use by professional hairdressers. This substance is also used to colour shampoos and other cosmetic products.
  • Australian regulations should align with the EU levels, and warning statements in line with other scheduled hair dye substances.
  • The carcinogen, o-anisidine, is not formed during the use of this hair dye in hair colourant products as this would destroy the colour provided by Basic Red 76 and result in the unsatisfactory consistency and appearance of the colour.
  • The proposal to exclude Basic Red 76 is supported along with proposed wording for the new Schedule 6 entry of Basic Red 76. The proposed entry suggests a maximum 2% in non-oxidative hair dye preparations and eyelash and eyebrow products when the packets are labelled with safety and warning statements.
  • Three submissions also supported the reinstated use of colour CI 26100 (CAS No 85-86-9; synonyms Solvent Red 23, Sudan III) for general use in cosmetic products as a colourant, as this colourant has also been caught by the current Schedule 7 entry for azo dyes.

Main points opposed:

  • There needs to be a comprehensive review of the impact of the Schedules 5, 6 and 7 entries for azo dyes on therapeutic goods, with the preferred outcome being that therapeutic goods should be excluded from any schedule entry for azo dyes.
  • There remains confusion as to which substances are specifically captured by the Schedule 7 entry of azo dyes as the list of captured substances is not comprehensive. The impact on therapeutic goods was not included in the original scheduling decision in November 2015 and it is unclear how many products are registered and listed on the ARTG that have the potential to be affected by scheduling decisions relating to azo dyes.

The public submissions will be made available on the TGA website.

Summary of ACCS advice to the delegate

The committee recommended that the Schedule 7 entry for azo dyes be amended as follows:

Schedule 7 – Amend Entry

AZO DYES that are derivatives by diazotisation of any of the following substances:

p-aminoazobenzene (CAS No. 60-09-3)

o-aminoazotoluene (CAS No. 97-56-3)

o-anisidine (CAS No. 90-04-0)

p-chloroaniline (CAS No. 106-47-8)

4-chloro-o-toluidine (CAS No. 95-69-2)

6-methoxy-m-toluidine (p-cresidine) (CAS No. 120-71-8)

2-naphthylamine (CAS No. 91-59-8)

5-nitro-o-toluidine (CAS No. 99-55-8)

2,4-toluenediamine (CAS No. 95-80-7)

o-toluidine (CAS No. 95-53-4)

2,4,5-trimethylaniline (CAS No. 137-17-7)

except for BASIC RED 76 (CAS No. 68391-30-0) when included in Schedule 6.

The committee recommended that a new Schedule 6 entry for Basic Red 76 be created as follows:

Schedule 6 – New Entry

BASIC RED 76 (CAS No. 68391-30-0) in non-oxidative hair dye preparations and eyebrow/eyelash colouring products containing 2 per cent or less of BASIC RED 76 and 0.001 per cent or less of free o-anisidine.

The committee recommended the following Appendix E and F entries for Basic Red 76 be created as follows:

Appendix E, Part 2 – New Entry

BASIC RED 76

Standard Statement: A (Poisons Advice hotline)

Appendix F, Part 3 – New Entry

BASIC RED 76

Warning Statement: 5 (Wear protective gloves when mixing or using).

The committee recommended a new index entry for Basic Red 76 be created as follows:

Index – New Entry

BASIC RED 76 (CAS No. 68391-30-0)

cross reference: [7-HYDROXY-8-[(2- METHOXYPHENYL)AZO]-2-NAPHTHYL]TRIMETHYLAMMONIUM CHLORIDE (CAS No. 68391-30-0)

Schedule 7
Schedule 6

The committee also recommended an implementation date of 1 February 2018.

Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use; and (c) the toxicity of a substance.
The reasons for the advice were:

  • While Basic Red 76 is used by industry in hair dyes, there is a potential risk of dermal absorption of the genotoxic carcinogen, o-anisidine.
  • Basic Red 76 has comparatively widespread use in non-oxidative hair dyes.
  • Basic Red 76 has low toxicity. There is a small risk of decoupling to o-anisidine in non-oxidative hair/eyebrow/eyelash dyes.
  • There is a potential for skin bacteria to convert Basic Red 76 to the genotoxic carcinogen, o‑anisidine.

Delegate's considerations

The delegate considered the following regarding this proposal:

  • Scheduling proposal
  • ACCS advice
  • Public Submissions received
  • Section 52E of the Therapeutic Goods Act 1989
  • Scheduling Policy Framework (SPF 2015)
  • Other relevant information

Delegate's interim decision

The delegate's interim decision is to amend the Schedule 7 entry for azo dyes, create new entries for Basic Red 76 in Schedule 6 and Appendix E and F and to create a new index entry for Basic Red 76. The proposed Schedule entry is as follows:

Schedule 7 – Amend Entry

AZO DYES that are derivatives by diazotisation of any of the following substances:

p-aminoazobenzene (CAS No. 60-09-3)

o-aminoazotoluene (CAS No. 97-56-3)

o-anisidine (CAS No. 90-04-0)

p-chloroaniline (CAS No. 106-47-8)

4-chloro-o-toluidine (CAS No. 95-69-2)

6-methoxy-m-toluidine (p-cresidine) (CAS No. 120-71-8)

2-naphthylamine (CAS No. 91-59-8)

5-nitro-o-toluidine (CAS No. 99-55-8)

2,4-toluenediamine (CAS No. 95-80-7)

o-toluidine (CAS No. 95-53-4)

2,4,5-trimethylaniline (CAS No. 137-17-7)

except for BASIC RED 76 (CAS No. 68391-30-0) when included in Schedule 6.

Schedule 6 – New Entry

BASIC RED 76 (CAS No. 68391-30-0) in non-oxidative hair dye preparations and eyebrow/eyelash colouring products containing 2 per cent or less of BASIC RED 76 and 0.001 per cent or less of free o-anisidine.

Appendix E, Part 2 – New Entry

BASIC RED 76

Standard Statement: A (Poisons Advice hotline)

Appendix F, Part 3 – New Entry

BASIC RED 76

Warning Statement: 5 (Wear protective gloves when mixing or using).

Index – New Entry

BASIC RED 76 (CAS No. 68391-30-0)
cross reference: [7-HYDROXY-8-[(2- METHOXYPHENYL)AZO]-2-NAPHTHYL]TRIMETHYLAMMONIUM CHLORIDE (CAS No. 68391-30-0)

Schedule 7
Schedule 6

The proposed implementation date is 1 February 2018, as this is the earliest possible implementation date.

The matters under subsection 52E(1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; and (c) the toxicity of a substance.

The reasons for the interim decision are:

  • While Basic Red 76 is used by industry in hair dyes, there is a potential risk of dermal absorption of the genotoxic carcinogen, o-anisidine.
  • Basic Red 76 has comparatively widespread use in non-oxidative hair dyes.
  • Basic Red 76 has low toxicity. There is a small risk of decoupling to o-anisidine in non-oxidative hair/eyebrow/eyelash dyes.
  • There is a potential for skin bacteria to convert Basic Red 76 to the genotoxic carcinogen, o‑anisidine.

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