Collaboration between ZEBET, FRAME, and ECVAM: FRAME's contribution to establishing the Three Rs in Europe.

FRAME has more than any other institution contributed to the implementation of the Three Rs concept in Europe. The first step was achieved by establishing the European Research Group on Alternatives to Toxicity Testing (ERGATT), in which individual scientists in several European countries began to collaborate to promote the development and validation of in vitro toxicity tests in order to refine, reduce and replace the use of animals in toxicity testing. The first successful project was the start of the INVITOX in vitro toxicology database, which is today managed by ECVAM.

The ECVAM international validation study on in vitro tests for acute skin irritation: report on the validity of the EPISKIN and EpiDerm assays and on the Skin Integrity Function Test.

ECVAM sponsored a formal validation study on three in vitro tests for skin irritation, of which two employ reconstituted human epidermis models (EPISKIN, EpiDerm), and one, the skin integrity function test (SIFT), employs ex vivo mouse skin. The goal of the study was to assess whether the in vitro tests would correctly predict in vivo classifications according to the EU classification scheme, "R38" and "no label" (i.e.