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Biomedical subjects

M Balls

Publications and source records attributed to M Balls.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

The FRAME multicentre project on in vitro cytotoxicology.

An in vitro method for assessing the relative acute toxicities of chemicals was developed through the collaboration of four tissue culture laboratories. Cytotoxicity was measured by using a dye-binding method to determine inhibition of the proliferation of BCL-D1 cells 72 hr after addition of the test chemical. A blind trial with 50 chemicals showed that the test procedure gave results with a high degree of interlaboratory reproducibility.

Biotransformation↗
PubMedDate not supplied

An evaluation of three in vitro cytotoxicity assays.

A number of methods for determining the general toxic effects of test chemicals on cells in culture are now at the validation stage. Three such methods based on measurement of total cell protein or neutral red uptake and on the detection of morphological effects have been compared. The cell line used was 3T3-L1 (a continuous fibroblast cell line derived from mouse embryos). The results obtained in a blind trial with 30 coded chemicals indicated a close correlation between the relative cytotoxicities of chemicals tested by all three methods.

Cell Survival↗
PubMedDate not supplied

Methods of in vitro toxicology.

In vitro methods are common and widely used for screening and ranking chemicals, and have also been taken into account sporadically for risk assessment purposes in the case of food additives. However, the range of food-associated compounds amenable to in vitro toxicology is considered much broader, comprising not only natural ingredients, including those from food preparation, but also compounds formed endogenously after exposure, permissible/authorised chemicals including additives, residues, supplements, chemicals from processing and packaging and contaminants. A major promise of in vitro systems is to obtain mechanism-derived information that is considered pivotal for adequate risk assessment. This paper critically reviews the entire process of risk assessment by in vitro toxicology, encompassing ongoing and future developments, with major emphasis on cytotoxicity, cellular responses, toxicokinetics, modelling, metabolism, cancer-related endpoints, developmental toxicity, prediction of allergenicity, and finally, development and application of biomarkers. It describes in depth the use of in vitro methods in strategies for characterising and predicting hazards to the human. Major weaknesses and strengths of these assay systems are addressed, together with some key issues concerning major research priorities to improve hazard identification and characterisation of food-associated chemicals.

Animal Testing Alternatives↗
PubMedDate not supplied

Ethical investment--what is it, and what are the implications for industry funding of research into alternatives?

This paper is intended to be a critical appraisal of ethical investment with respect to animal experimentation. It is aimed at a wide readership, ranging from scientists in the field and laypersons interested in laboratory animal welfare, potential investors, to senior management in industries directly or indirectly involved in animal testing.

Animal Testing Alternatives↗
PubMedDate not supplied

The importance of the prediction model in the validation of alternative tests.

An overview is presented of the validation process adopted by the European Centre for the Validation of Alternative Methods, with particular emphasis on the central role of the prediction model (PM). The development of an adequate PM is considered to be just as important as the development of an adequate test system, since the validity of an alternative test can only be established when both components (the test system and the PM) have successfully undergone validation. It is argued, however, that alternative tests and their associated PMs do not necessarily need to undergo validation at the same time, and that retrospective validation may be appropriate when a test system is found to be reliable, but the case for its relevance remains to be demonstrated. For an alternative test to be considered "scientifically valid", it is necessary for three conditions to be fulfilled, referred to here as the criteria for scientific relevance, predictive relevance, and reliability. A minimal set of criteria for the acceptance of any PM is defined, but it should be noted that required levels of predictive ability need to be established on a case-by-case basis, taking into account the inherent variability of the alternative and in vivo test data. Finally, in view of the growing shift in emphasis from the use of stand-alone alternative tests to alternative testing strategies, the importance of making the PM an integral part of the testing strategy is discussed.

Animal Testing Alternatives↗
PubMedDate not supplied

The role of ECVAM in promoting the regulatory acceptance of alternative methods in the European Union. European Centre for the Validation of Alternative Methods.

The roles played by the European Centre for the Validation of Alternative Methods (ECVAM) and its advisory committee, the ECVAM Scientific Advisory Committee (ESAC), in the evolution of alternative methods are described. Particular emphasis is given to the process by which ECVAM and the ESAC assess the scientific validities of alternative methods, and, in appropriate cases, initiate the progression of scientifically validated methods toward regulatory acceptance.

Animal Testing Alternatives↗
PubMedDate not supplied

A comparison of two cytotoxicity assays for the detection of metabolism-mediated toxicity in vitro: a study with cyclophosphamide.

The cytotoxicity to V79 Chinese hamster fibroblasts of cyclophosphamide (CPA) metabolites, generated by rat-liver S9 fractions, has been compared in two assay systems with different endpoints of toxicity, namely, reduction of cloning efficiency and inhibition of cell growth. The two assay systems were found to be equally sensitive in detecting the metabolism-mediated cytotoxicity of CPA and gave similar ID50 values. Further studies confirmed the cytochrome P-450 enzyme requirement for the bioactivation of CPA to cytotoxic metabolites. CPA activation was mediated by phenobarbitone-inducible forms of cytochrome P-450, but not by beta-naphthoflavone-inducible forms.

7-Alkoxycoumarin O-Dealkylase↗
PubMedDate not supplied

The effect of glucose, insulin and dexamethasone upon 7-ethoxycoumarin O-deethylase activity of adult rat hepatocytes in primary culture.

The influence of glucose, insulin and/or dexamethasone on the 7-ethoxycoumarin O-deethylase activity of rat hepatocytes in primary culture was investigated. The addition of extra glucose to the medium attenuated the fall in enzyme activity observed during the first 24 h in culture, this effect being dose-dependent. The inclusion of insulin further enhanced this effect, but glucose + insulin did not prevent the decrease in enzyme activity in the subsequent 48 h. The inclusion of dexamethasone, alone or in combination with glucose + insulin, also attentuated the initial decline in enzyme activity. After 24 h in culture, the enzyme activity increased such that after 72 h in culture, the activity was greater than that measured in the freshly isolated cells.

7-Alkoxycoumarin O-Dealkylase↗