13th Meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): alternative testing methodologies for organ toxicity.

Abstract

In the past decade in vitro tests have been developed that represent a range of anatomic structure from perfused whole organs to subcellular fractions. To assess the use of in vitro tests for toxicity testing, we describe and evaluate the current status of organotypic cultures for the major target organs of toxic agents. This includes liver, kidney, neural tissue, the hematopoietic system, the immune system, reproductive organs, and the endocrine system. The second part of this report reviews the application of in vitro culture systems to organ specific toxicity and evaluates the application of these systems both in industry for safety assessment and in government for regulatory purposes. Members of the working group (VWG) felt that access to high-quality human material is essential for better use of in vitro organ and tissue cultures in the risk assessment process. Therefore, research should focus on improving culture techniques that will allow better preservation of human material. The WG felt that it is also important to develop and make available relevant reference compounds for toxicity assessment in each organ system, to organize and make available via the Internet complete in vivo toxicity data, including human data, containing dose, end points, and toxicokinetics. The WG also recommended that research should be supported to identify and to validate biological end points for target organ toxicity to be used in alternative toxicity testing strategies.

Subchronic and Chronic Toxicities of African Medicinal Plants

“…Therefore, current efforts are geared toward replacing animal chronic toxicity models with technologically driven human cell-based models. These nonanimal alternative models for chronic toxicity testing include human and animal perfused organs; organ tissue slices; isolated, suspended cells; primary cultured cells; cultured cell lines; genetically engineered cell lines; reaggregating cell cultures; three-dimensional cell cultures and co-cultures; and (quantitative) structure activity relationship [(Q)SAR] computational systems [84,85].…”

Use of Human Embryonic Stem Cell-based Models for Male Reproductive Toxicity Screening

“…Hence, it is crucial to explore the molecular mechanisms of germ cell specification and gamete development, and the factors that might disrupt these processes in vitro. To avoid the use of animals for toxicity screening, alternative in vitro cellular models using primary cultures or permanent cell lines have been developed [Scholz et al 1999;Spielmann et al 1998]. Cell lines established from specialized somatic cells are not identical with germ stem cells and do not recapitulate their differentiation processes.…”

Toxicological assessment of industrial solvents using human cell bioassays: assessment of short-term cytotoxicity and long-term genotoxicity potential

“…The types of organ and cell systems Á including the liver, kidney, neural tissue, the hematopoietic system, the immune system, the reproductive organs and the endocrine system Á currently available to perform in vitro tests for toxicity testing have been extensively reviewed (Tahti et al, 2003;O'Brien et al, 2004;Farkas and Tannenbaum, 2005). Perfused organs, such as the liver and kidney, brain, lung etc., are examples of one model used for in vitro testing (Speilman et al, 1998). The prime advantage of using entire organs is that the general morphology and cellÁcell interactions are preserved.…”

“…Their use permits longer-term studies encompassing a few days and/or a few passages. Some differentiated functions may be retained, and co-culture is possible with other cellular types (Speilman et al, 1998;Pfaller and Gstraunthaler, 1998;Costa, 1998). On the contrary, primary cell cultures have unstable phenotypes, and may quickly lose many differentiated functions.…”

“…On the contrary, primary cell cultures have unstable phenotypes, and may quickly lose many differentiated functions. The use of immortalized and continuous cell lines offers ease of propagation, and the ability to generate unlimited numbers of cells for testing (Speilman et al, 1998;Pfaller and Gstraunthaler, 1998;Costa, 1998). Many different cell types have been used in toxicity studies, including continuous renal epithelial cell lines to assess nephrotoxicity (Pfaller and Gstraunthaler, 1998;Prieto, 2002), neuroblastoma or glioma cell lines to assess neurotoxicity (Costa, 1998;Lindahl et al, 1999;Tahti et al, 2003;Madia et al, 2004), embryonic stem cells and ovarian and testicular cell types to assess reproductive and developmental toxicity (Spielmann, 1998;Riecke and Stahlmann, 2000;Bishop, 2003;Bremer et al, 2005).…”