ALTERNATIVE TESTING METHODOLOGIES FOR ORGAN TOXICITY

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 fo r the major target organs of toxic agents. This includes liver, kidney , neural tissue, the hematopoietic system, the immune system, reproduc tive 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 indust ry for safety assessment and in government for regulatory purposes. Me mbers of the working group (WG) felt that access to high-quality human material is essential for better use of in vitro organ and tissue cul tures in the risk assessment process. Therefore, research should focus on improving culture techniques that will allow better preservation o f human material. The WG felt that it is also important to develop and make available relevant reference compounds for toxicity assessment i n each organ system, to organize and make available via the internet c omplete 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 s trategies.