Schedule Part E - cosmetic ultraviolet filters
Last update 30 November 2016
Part E of the schedule provides details of additional data required for new industrial chemicals that are to be used as an ultraviolet filter in a cosmetic to be applied to the skin.
This data is in addition to the toxicological endpoints specified in Part C. The additional data requirements and the guidance below substantially align the requirements with those applying to new active ingredients for sunscreens under the Therapeutic Goods Administration (TGA).
Where the new UV filter has been previously assessed by TGA and the report of that assessment can be provided to us, our assessment may be carried out in the modular category, with partial rebate of fees (See Section C5.3).
Suggested guidance documents and test guidelines are included below for the individual endpoints. For some endpoints, OECD test guidelines are available. For others, reference is made to EU guidelines adopted by TGA. If a particular guideline is not applicable or if other data are available to adequately address the endpoint, alternative approaches based on adequate scientific justification will be considered by NICNAS.
As with other parts of the Schedule there is provision for application for variation of schedule data requirements, as appropriate and where supported by scientific justification. Where the UV filter is to be used to stabilise a cosmetic product applied to the skin, rather than being a sunscreening agent to protect the skin, justification for variation of schedule data requirements may be based on the following issues:
- the toxicological profile of the chemical, and
- low concentration of use.
General comments on photosafety
Photosafety testing is carried out for several endpoints (phototoxicity, photoallergy, photogenotoxicity and photocarcinogenicity) to detect the adverse effects of substances in the presence of light. Photosafety testing is generally warranted for those chemicals that absorb light in the wavelength of 290-700 nm and are topically applied. These criteria would apply to chemicals covered by Schedule E.
General guidance on photosafety testing from the Therapeutic Goods Administration, European Medicines Agency and the EU Scientific Committee on Consumer Safety can be accessed at the following web locations:
i) Concept Paper on the Need for Revision of the Note for Guidance on Photosafety Testing: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003358.pdf
ii) Questions and answers on the Note for guidance of photosafety testing: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2011/04/WC500105109.pdf
iii) Section3-4.10 of the SCCS's Notes of Guidance for the Testing of Cosmetic Ingredients and Their Safety Evaluation, 7th Revision at: http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_s_004.pdf
You must provide data to demonstrate stability of the chemical in light. This is especially relevant because of the intended use of the products containing the chemicals under Schedule E. See photostability testing guidelines. Comparison of UV absorption spectra before and after stability studies may indicate the degree of degradation.
You must provide data on phototoxicity or photoirritation testing, which provides information on acute light-induced skin responses to a photoreactive chemical. An appropriate test method is OECD TG 432: In Vitro 3T3 NRU Phototoxicity Test.
Also see photosafety guidance documents listed in the introduction to this section.
You must provide data on photosensitisation or photoallergy testing, which is carried out to detect immunologically mediated reactions to a chemical, that are initiated by the formation of photoproducts. In vitro test methods are currently not available, and at present photosensitisation is mainly tested via modified guinea pig protocols (for example modified version of OECD TG 406 Skin Sensitisation).
Also see photosafety guidance documents listed in the introduction to this section.
You must provide data on bioavailability via the oral and dermal routes, in order for NICNAS to determine what proportion of the dose of a chemical is available systemically, and to enable interpretation of the toxicity studies. NICNAS does not require ADME studies.
See guidance on The Assessment of Systemic Exposure.
Determination of systemic exposure after oral dosing is described in the OECD TG 417 Toxicokinetics.
OECD TG 427 can be used for determining in vivo skin absorption and TG 428 for determining in vitro skin absorption.
General guidance from the OECD Series Testing and Assessment No. 156 Guidance Notes on Dermal Absorption can be accessed at: http://www.oecd.org/dataoecd/63/12/48532204.pdf
Repeated dose toxicity
Repeated dose toxicity data provides information on possible health hazards likely to arise from repeated exposures over a limited period of time. Under Schedule C a repeated dose 28-day study is already required. For chemicals to which Schedule E also applies, you must provide testing data for a longer period of time (3 months or 6 months) by both the oral and dermal routes. When longer studies are submitted under Schedule E, these will replace the need for you to submit 28-day studies by the same route of exposure.
Suitable test methods are OECD TG 408 Repeated Dose 90-Day Oral Toxicity Study in Rodents and OECD TG 411 Subchronic Dermal Toxicity: 90-Day Study.
Further information from the European Medicines Agency on carrying out repeated dose studies is available:
Note for Guidance on Repeated Dose Toxicity is at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003102.pdf and
Guideline on Repeated Dose Toxicity is at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/03/WC500079536.pdf
OECD Test Guidelines for longer (chronic) studies are OECD TG 452 Chronic Toxicity Studies and OECD TG 453 Combined Chronic Toxicity / Carcinogenicity Studies.
Testing for photomutagenicity / photogenotoxicity is carried out to detect any genotoxic response after exposure to a chemical photoactivated by UV or visible light. The main purpose of testing is to make an assessment of the potential of a substance to turn into a photochemical carcinogen. The studies you wouldneed to submit are a photomutagenicity test in bacteria and photogenotoxicity in a chromosomal aberration test.
Also see photosafety guidance documents listed in the introduction to this section, which include test strategies. It is noted that there are recent concerns about the applicability of photomutagenicity / photogenotoxicity studies and the above recommendations on testing may change in future.
You must provide data on the potential of the chemical to cause developmental and fertility effects, including toxicity to male fertility. The potential for endocrine disruption should also be evaluated, which could be done as part of repeat dose and/or reproductive toxicity studies.
Several OECD Test Guidelines are applicable to reproductive toxicity. Preferred protocols cover at least two generations to adulthood, and measure both developmental and fertility effects.
Carcinogenicity and photocarcinogenicity
You must provide data from in vivo carcinogenicity and photocarcinogenicity bioassays or a justification for their omission.
For example, justification for not including in vivo carcinogenicity bioassays could be based around the following issues:
- the expected pattern of use (e.g. extent of contact with body)
- results of in vitro and in vivo mutagenicity assays
- lack of similarity to other molecules with known carcinogenic activity
- low persistence in the skin
- low in vivo absorption
- lack of photosensitisation or phototoxic potential
- proven photostability
- lack of possible adverse effects on the skin (e.g change to epidermis/dermis at the microscopic level or effects on skin seen in repeated dose studies)
- length of submitted in vivo repeat dose toxicity studies, and
- lack of adverse activity in skin irritation and skin sensitisation studies.
See guidance on The Need for Carcinogenicity Studies of Pharmaceuticals and Note for Guidance on Carcinogenicity: Testing for Carcinogenicity of Pharmaceuticals
Specific photosafety testing strategies are described in the Note for Guidance on Photosafety Testing, referred to in the introduction.
Formulations containing sunscreen may contain more than one active ingredient. You must provide data on the potential for interaction of the new chemical with any UV filter or filters that will be likely to be usedin conjunction with the new chemical, in formulations to be applied to the skin. Evaluation of the interaction potential may be made via studies or published information, and information on the chemical characteristics of the UV filters.