Hazard identification screening tests

Chemical reactivity risk. See Risk assessment Chemical reactivity tests, 84-90 decision point, 90 deflagration screening tests, 85,87 reaction calorimetry, 88-90 screening data interpretation, 85, 86 small-scale screening tests, 87-88 Chemical structure and bonds, hazards identification, 80, 82 CHETAH program (ASTM), 79,82 Clean Air Act Amendments (CAAA) of 1990, 174... 

Hazard Identification. The first step is to determine whether a substance is mutagenic. For this purpose, inexpensive and sensitive short-term tests have been developed and are extensively used, nils report discusses the general features of these tests and proposes a specific mutagenicity screening program to detect potential mammalian mutagens. 

From the standpoint of screening and hazard identification, a notable point relating to the interpretation of data from FOB and motor activity studies is whether the effects observed in response to toxicant exposure represent a direct effect of the toxicant on the nervous system or are secondary to changes in other systems since such apical tests rely on the functional integrity of multiple systems. In some circumstances, the fact that the toxic effect is ultimately expressed in behavior may minimize the importance... 

HPRT L5178Y mouse lymphoma CHO, V79, CHL, AS52. Tested in AHH-1, MCL-5, and TK6 human lymphoblastoids Gene mutations Any mutation inferred on the X-linked HPRT gene Screening, hazard identification... 

MNvit Rodent CHO, V79, CHL/ IU, L5178Y, and human peripheral blood lymphocytes. Tested in human TK6 and HepG2, and SHE Structural and numerical chromosome aberrations Aneugenic and clastogenic chromosomal events Screening, hazard identification... 

Additional parameters that are readily incorporated into a stand-alone immune function test such as the KLH-TDAR model include ex vivo lymphocyte proliferation, cytokine protein expression, and immunophenotype analysis any or all of which can enhance hazard identification and characterization of a potential immunotoxicant. While the KLH-TDAR is an example of a combined immune function screen and mechanistic study, the ex vivo methodologies described herein are generally applicable to toxicology studies that do not include an immunization protocol. Moreover, the methodologies are not species-specific however, responsiveness to various stimulants to induce ex vivo lymphocyte proliferation and cytokine production may differ across species and strain, requiring procedural optimization for a given species and ex vivo test. 

The in vitro human whole blood assay and the outbred mouse are considered binary (yes/no) hazard identification tools in lead optimization screening for compound selection. In our experience to date, chemically modified conjugate siRNAs do not provoke acute pro-inflammatory effects in subsequent rodent or nonrodent studies or in clinical trials if they test negative in these two assays. Lacking positive controls, it is not yet feasible to assess whether the immuno-stimulation screening during lead optimization is predictive or relevant for human outcomes. 

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