Alternative Testing or Testing Alternatives?

Posted: November 5, 2007

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Alternative tests have, therefore, been developed, and some have now been accepted as alternative test methods. Julia Fentem of Unilever’s Safety & Environmental Assurance Centre (SEAC) writes,² “in February 2000, the European Union (EU) Member States approved the first replacement alternative (in vitro) methods to be mandated for use in regulatory toxicity testing. In vitro tests for skin corrosion (the rat skin transcutaneous electrical resistance [TER] method and tests employing human skin models) and phototoxicity (the 3T3 neutral red uptake [NRU] phototoxicity test) have both been shown unequivocally to be reliable and relevant, in extensive pre-validation and formal validation studies conducted under the auspices of ECVAM [European Centre for the Validation of Alternative Methods].”

So, these tests for skin corrosion and phototoxicity have been on the market for a while. Rich Ulmer, President and CEO of InVitro International, Irvine, CA, USA, writes:³ “On May 2, 2007, the first of several likely in vitro test methods to replace animal testing for skin and eye irritation was approved by a European Government Regulatory Agency--The European Centre for the Validation of Alternative Methods (ECVAM).” This skin irritation test came a lot later, not because ECVAM did not care, but maybe because they cared too much.

Jon Heylings, PhD, from Syngenta worked or maybe still works with Fentem in the ECVAM Management Team. My information is from April 2002 when Heylings gave a magnificent presentation for the Dutch Society of Cosmetic Chemists about his experience with setting up alternative tests. He outlined the whole procedure and to be honest, it is not something to be very happy about if you are a rabbit and waiting to be shaved if a testing alternative is not found in time.

Heylings told us that ECVAM funded a pre-validation study that lasted from 1999 until 2001 with the objective to find a replacement for the Draize rabbit skin irritation test to distinguish irritants from nonirritants. The challenge to the industry was to provide tests that could do this using 10 chemicals. The Task Force initially reviewed a test protocol, prediction model and supporting data used with the EpiDerm human skin model, recommending to ECVAM that this test was put forward for pre-validation. In addition, since it was felt preferable to be able to include other in vitro tests in such a pre-validation study, the Task Force recommended that an open “challenge” was set, which involved laboratories submitting data on 10 specified chemicals, and on 20% sodium lauryl sulfate as a reference standard, for review by the Task Force.

Following review of test protocols, prediction models and data submitted by test developers, the Task Force recommended that ECVAM should support a pre-validation study on four tests: EpiDerm, EPISKIN, PREDISKIN (BIOPREDIC, Rennes, France) and the nonperfused pig ear method. Again, on the recommendation of the management team, following its review of the test protocol, prediction model and supporting data, an additional test--the mouse skin integrity function test (SIFT)--was incorporated into the study in November 1999, following the completion of phase II with the four methods selected initially.