The Use ofIn VitroSystems for Evaluating Immunotoxicity: The Report and Recommendations of an ECVAM Workshop

Abstract

This is the report of a workshop organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods that are of importance to the biosciences and which replace, reduce or refine the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organization of ECVAM workshops on specific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (Anonymous, 1994). The workshop on "The use of in vitro systems for evaluating Immunotoxicity" was held at ECVAM (Ispra), Italy, on 24th-26th November 2003. The participants represented academia, national organizations, international regulatory bodies and industry. The aim of the workshop was to review the state-of-the-art in the field of in vitro immunotoxicology, and to develop strategies towards the replacement of in vivo testing. At the end of this report are listed the recommendations that should be considered for prevalidation and validation of relevant and reliable procedures, that could replace the use of animals in chemical and cosmetics toxicity testing.

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

“…The same holds true especially for immunosuppression (Carfi et al, 2007;Galbiati et al, 2010;Gennari et al, 2005;Langezaal et al, 2001;Lankveld et al, 2010) but also for chronic cell injury, increased secretion of trophic hormones, oxidative stress, and reactive oxygen and nitrogen species (ROS and RNS). An assay for CYP450 induction in cryopreserved human hepatocytes also is currently under prevalidation (Abadie-Viollon et al, 2010;Richert et al, 2010).…”

Immunotoxicology: challenges in the 21st century and in vitro opportunities

“…Furthermore, it was established that the in vitro test should be validated against information gained from humans rather than the results from laboratory animal species. We followed this workshop with a more extensive one in 2003 (Gennari et al, 2005). the recommendations made then still stand and those not addressing sensitization are reproduced in table 2.…”

“…the major limitations of in vitro immunotoxicology and future research needs initially identified (Gennari et al, 2005) still stand as, ten year later, progress has been rather limited. limitations and needs are listed in table 3. the test systems under consideration for assessing chemicalinduced immunosuppression have not really changed (tab.…”

“…the authors have contributed to many that have already been published (Gennari et al, 2005;Corsini, 2006;Carfì et al, 2007;Corsini and Roggen, 2009;Galbiati et al, 2010;lankveld et al, 2010;Pfaller et al, 2010). Immunotoxicology in general is also well covered in reviews and book chapters (Descotes, 2004(Descotes, , 2006Kadow et al, 2009;Dietert, 2010;House, 2010;Rooney et al, 2012), and is even the subject of entire textbooks (Dean et al, 1994;House et al, 2006), though arguably the latter may no longer be entirely up to date.…”

Profiling Adverse Immune Effects

“…In 2003 a workshop hosted by ECVAM was held in order to review the state-of-the-art in the field of in vitro immunotoxicology [109]. Based on its recommendations, an ECVAM-sponsored project was undertaken in which several assays to measure immunosuppression in vitro were compared [110].…”