European Report Provides Animal Alternative Test Adoption Timetable

Skin and eye irritation are the next areas where in vitro tests for cosmetics safety could replace animal tests, an ad-hoc group of European regulators and stakeholders predicted in a report outlining a timetable for the validation and adoption of alternative test methods.

"In both these areas, advanced methods are currently available for, or are undergoing, validation," the report points out.

Those areas of research would be followed by toxicokinetics and metabolism, "which is regarded as a bottleneck for the development of in vitro testing strategies for systemic toxicity," the document states.

The replacement of animal tests is expected to take the longest in the areas of repeated dose toxicity, skin sensitization, subacute and subchronic toxicity, carcinogenicity and reproductive and developmental toxicity," according to the document.

The report, developed by representatives from the European Commission, the Organization for Economic Development and Cooperation and industry, was compiled in light of the impending ban on cosmetics tested on animals in Europe in 2009.

Issued in July, the document also addresses the progress that has been made in terms of alternative test methods, current gaps in testing and hurdles to the development and adoption of in vitro tests, including funding and regulatory approval procedures (see ¹ (Also see "Animal Alternative Reg Improvements Should Be Considered – Report" - HBW Insight, 29 Aug, 2005.) ).

Some cosmetics safety issues can already be assessed using alternative methods. Those include skin corrosion, skin absorption and acute phototoxicity.

In the area of skin irritation, where alternative methods are well into development, the European Center for the Validation of Alternative Methods has reviewed three validated alternatives (EpiDerm human skin model, Episkin human skin model and the mouse skin integrity function test).

These tests could gain EU regulatory acceptance by 2007/2008 and would allow a reduction in animal experimentation, but reversibility and dose response would still need to be addressed before full animal replacement is achieved, the report notes.

"It is estimated that this will represent a challenge that will keep scientists occupied beyond 2009," the committee reports.

Progress also has been made in the area of eye irritation, although the Draize rabbit eye test is unlikely to be replaced by a single in vitro test. The committee estimated that six years would be needed for replacing animal experimentation with tests accepted by regulatory authorities in this area.

For testing skin sensitization, a test battery could lead to the replacement of animal methods, but guidance will be needed on the validation of the test batteries, the group says.

"The time foreseen for achieving the validation of an alternative test battery for skin sensitization is 10-12 years, 12-14 years being the time required for regulatory acceptance at the EU level in relation to the Seventh Amendment," the report states.

While "good progress" has been made in predicting basal cytotoxicity, a component of potential acute toxicity replacement tests, the committee says the timeline for achieving complete animal replacement in the area of acute toxicity will be at least 10 years.

Areas of subacute and subchronic toxicity are still in the research and development phase.

"The participating experts estimated that the validation of the existing models would need more than 10 years, and that the time necessary to achieve full animal replacement with regulatory accepted tests and strategies will depend on the progress at the research and development level, and on adequate prioritization, funding and coordination of the effort," the report says.

Although the group notes that several in vitro tests have been accepted assessing genotoxic and mutagenic potential of a chemical, current methods lack human-like metabolic capacity and toxicokinetics and are oversensitive.

"For these reasons, the group of experts suggested a completely new test strategy, specifically tailored for the cosmetic industry," the reports says.

As a result, the full replacement of animal tests for genotoxicity and mutagenicity is not feasible within the next 12 years and will depend upon the development of in vitro tests relevant to cosmetics and progress in the areas of toxicokinetics and metabolism, the group predicts.