Measurement and characterization of the three-dimensional coherence function in neutron interferometry.
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Biomedical subjects
Publications and source records attributed to R Clothier.
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Non-animal toxicity tests and testing strategies for use in identifying the potential toxic hazard of chemicals and products, and in providing information for use in risk and safety assessment, are in the course of development, validation and evaluation. Possible replacement alternatives to the rabbit Draize eye irritancy test are discussed, and results obtained for two in-vitro tests developed by FRAME (the kenacid blue test and the neutral red release test), applied to 19 surfactants and 32 formulations, are discussed. It is concluded that there are now legal and moral requirements that relevant and reliable non-animal tests should be developed and accepted for use whenever possible.
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The ability of EL-4 thymoma cells to produce interleukin-2 (IL-2) following exposure to phorbol-12-myristate 13-acetate (PMA) and Concanavalin A (Con A) has been studied in vitro using medium containing either 10% or 1% fetal calf serum (FCS). The potent stimulatory effect of PMA on IL-2 production by EL-4 cells has been confirmed by measuring 3H-thymidine incorporation by the IL-2-dependent T cell line, CTLL-2, in the presence of conditioned medium (CM) from stimulated cultures. EL-4 cells produced several times more IL-2 when cultured in medium containing 10% FCS than when only 1% FCS was present. Added together, PMA and Con A acted synergistically in some EL-4 cell cultures. The ability of E:-4 cells to produce IL-2 was maintained after further incubation without stimulants. CM with IL-2 activity from stimulated EL-4 cells could prove useful in immunotoxicity testing.
The safety evaluation of new chemicals involves a range of investigations, including acute and sub-acute toxicity testing, long-term toxicity testing, studies on mutagenicity, carcinogenicity, and reproductive toxicity, and special investigations involving the interaction of the chemical under test with particular parts of the body, such as the skin or the nervous system. We shall consider the potential role of differentiated cell and organ culture in toxicity testing, and the criteria available for assessing cell viability, damage, and death, with a view to establishing whether such methods could be used for determining the relative acute toxicities of chemicals. We shall also consider methods for studying the effects of chemicals on general and specific aspects of cell structure and function, including liver cell and organ cultures both as primary targets themselves susceptible to damage and as providers of metabolically activated compounds able to affect other cells and tissues.
Young adult Xenopus laevis were treated with N-methyl-N-nitrosourea at doses which temporarily or permanently remove the thymic cortex and suppress allograft immune competence. Their ability to mount a carrier-primed, helper T cell-mediated, hapten-specific response was tested in terms of numbers of antigen binding cells in the spleen. Animals which had retained skin allografts for more than 300 days lacked helper activity, while those which had eventually rejected their allografts were able to mount an anti-hapten response. All groups of Xenopus exposed to the carcinogen rejected skin xenografts after the same time as untreated control animals.
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Validation in the context of in vitro toxicity tests is defined, and various aspects of the validation process are discussed, including the design and conduct of interlaboratory validation schemes; the selection of tests, participating laboratories, and test chemicals; the selection and use of in vivo data; in vivo/in vitro data comparison; the question of "false" results; in vitro cytotoxicity as a predictor of actual lethal toxicity; and the validation of alternatives to the Draize eye irritancy tests. It is concluded that a thorough reevaluation of current practice is essential if the promise and potential of nonanimal toxicity tests are to be fully realized and if valid alternative tests acceptable to regulatory agencies are to be developed.