2.4. Picramic acid (including its salts)

2 Interim decisions on proposed amendments referred to the Advisory Committee on Chemicals Scheduling (ACCS #7, March 2020)

2.4. Interim decision in relation to picramic acid (including its salts)

Interim decision

Pursuant to regulation 42ZCZN of the Regulations, a Delegate of the Secretary has, in relation to the proposed amendment, made an interim decision to amend the current Poisons Standard in relation to picramic acid (including its salts) as follows:

Proposed date of effect of the proposed amendment

1 June 2021

Reasons for the interim decision (including findings on material questions of fact)

In making this interim decision, the Delegate considered the following material:

• The application to amend the current Poisons Standard with respect to picramic acid and its salts;
• Advisory Committee on Chemicals Scheduling's advice;
• The public submissions received in response to the pre-meeting consultation;
• Section 52E of the Therapeutic Goods Act 1989, in particular (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; (d) the dosage, formulation, labelling, packaging and presentation of a substance;
• Scheduling handbook: Guidance for amending the Poisons Standard; and
• Scheduling Policy Framework (SPF 2018).

Summary of ACCS advice/recommendations to the Delegate

The Advisory Committee on Chemicals Scheduling recommended that new Schedule 6, Appendix E and Appendix F entries for picramic acid (including its salts) in the Poisons Standard as follows:

The Committee also recommended an implementation date of 1 June 2021.

The reasons for the advice included:

1. risks and benefits of the use of a substance
   • Benefits
     • Sodium picramate, a non-reactive dye used as a direct hair colouring agent in many hair dye products.
2. the purpose for which a substance is to be used and the extent of use
   • The chemicals are used in cosmetics, colourants and in hair dye products of up to a maximum concentration of 0.6%.
   • The chemicals are also reported to be used for dyeing fur and in pyrotechnics.
3. the toxicity of a substance
   • Picramic acid and its salt are reported to be sensitising to the skin and reported to be toxic to the male reproductive system.
4. the dosage, formulation, labelling, packaging and presentation of a substance
   • NIL.
5. the potential for abuse of a substance
   • NIL.
6. any other matters that the Secretary considers necessary to protect public health
   • NIL.

Reasons for interim decision

I agree with the Committee's finding that the relevant provisions of section 52E of the Therapeutic Goods Act 1989 are (a) the 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 of a substance; and (c) the toxicity of a substance.

In my view, the relevant parts of the SPF 2018 are the Scheduling Factors for Schedule 6.

I have made a decision to create new Schedule 6, Appendix E and Appendix F entries for picramic acid (including its salts). In making my decision, I have taken into account the potential harms including skin sensitisation, arising from use of these substances in hair dye products.

Picramic acid and its salt, sodium picramate are used in hair colouring formulations up to a maximum concentration of 0.6%. While both substances are used in hair dyes, as the acid dissociation constant (pKa) of picramic acid is around 4, it is always the sodium picramate which is available in typical hair dye formulations (pH 6.5 - pH 10).

The main toxicological concern with these substances is skin sensitisation. Based on mouse local lymph node assay (LLNA) data, picramic acid and its salts are moderate skin sensitisers with the estimated concentration needed to produce a threefold increase in lymphocyte proliferation (EC3) determined to be 6.7 %. As moderate skin sensitisers, picramic acid and sodium picramate meet the SPF 2018 Scheduling Factors for inclusion in Schedule 6. The substances are also acutely toxic via all routes of exposure; harmful following chronic oral exposure at low concentrations in animal studies; and are toxic to the reproductive system, particularly in males, based on testicular damage observed in rats. In an acute oral toxicity study, the calculated LD50 of picramic acid was 110 mg/kg bw which is consistent with Schedule 6 (between 50 mg/kg - 2000 mg). I note also that the margin of safety (MOS) of 155, derived from the dermal absorption (1.12 μg/cm²) and 90-day repeat dose study (5 mg/kg bw/day) in rats, is not far above the threshold generally considered safe (MOS of 100) for use in cosmetics.

Material to my decision to include a maximum concentration cut-off of 0.6 per cent to unscheduled are the recommendations made in the report on picramic acid and sodium picramate by the European Scientific Committee on Consumer Safety (pdf,333kb) - external site (SCCS 2012). The SCCS is of the opinion that the use of picramic acid/sodium picramate, with a maximum on-head (i.e. what is administered on the head) concentration of 0.6% in oxidative and non-oxidative hair dye formulations, does not pose a risk to the health of the consumer, apart from its sensitising potential. I have taken into account that in Canada, sodium picramate is listed on the Cosmetic Ingredient Hotlist- List of Ingredients that are Restricted for Use in Cosmetic Products, with the maximum concentration permitted of 0.1%. However, I am satisfied that on balance, a concentration cut-off of 0.6% is protective based on the use patterns of products containing picramic acid and its salts and the likely toxicity end point of concern being skin sensitisation. While not material to my decision, I note that a concentration cut-off of 0.6% is also consistent with the Association of Southeast Asian Nations (ASEAN) cosmetic directive that specifies a concentration of 0.6 % applied to the head under oxidative conditions with appropriate warning labels.

In assessing the safety profile, I agree with the Committee's advice that picramic acid and its salts clearly present a risk to consumers when used in hair dye products at concentrations greater than 0.6%. Based on the information provided, I am satisfied that the potential risks can be controlled by mandating concentration restrictions and warning labels using an appropriate Schedule 6 entry. This Schedule 6 entry is consistent with other sensitising hair dyes that have previously been considered for inclusion in the Poisons Standard. Restricting the concentration exemption for picramic acid at its salts in hair dye products will also serve to mitigate any potential risk arising from repeated exposure.

Implementation date

In deciding on an appropriate implementation date, I have taken into consideration concerns raised in the public submissions that a minimum 12-month adequate transition period is required by industry to allow for compliance with any labelling and/or reformulation changes. As no immediate health signals have been identified, in order to minimise regulatory burden, I have decided on an implementation date of 1 June 2021.