Validation of In Vitro Cytotoxicity Tests — Past and Present Strategies

1991 ◽  
Vol 19 (2) ◽  
pp. 226-233
Author(s):  
Björn Ekwall ◽  
Inger Bondesson ◽  
Sven Hellberg ◽  
Johan Högberg ◽  
Lennart Romert ◽  
...  
Keyword(s):  
Large Scale ◽  
Toxicity Testing ◽  
Short Review ◽  
Animal Experimentation ◽  
In Vitro Cytotoxicity ◽  
In Vitro Methods ◽  
General Acceptance

In recent years, conventional toxicity testing in animals has been reinforced by in vitro methods. As a result, toxicity testing in some sectors has become more effective and at the same time more ethical. This trend is probably only at its beginning, as many of the newly-developed methods have not yet won general acceptance as a basis for the large-scale replacement and reduction of animal experimentation. What limits the wider use of these methods is validation, i.e. the evaluation of their reliability and relevance. The present paper is a short review of the validation efforts made hitherto, including projects being planned and under discussion. Our own MEIC approach is compared with other strategies. Finally, our opinion on the effectiveness of one large consensus project relative to several different smaller validation programmes is expressed — we advocate the latter strategy, because it will save time and reduce costs.

Analogy Models for Prediction of Human Toxicity

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 103-116
Author(s):  
Sven Hellberg ◽  
Lennart Eriksson ◽  
Jörgen Jonsson ◽  
Fredrik Lindgren ◽  
Michael Sjöström ◽  
...  
Keyword(s):  
Human Subjects ◽  
Toxicity Testing ◽  
In Vitro Cytotoxicity ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
In Vitro Tests ◽  
Human Toxicity ◽  
Efficient Data ◽  
Basal Cytotoxicity

Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.

Miniaturized In Vitro Methods in Toxicity Testing

1998 ◽  
pp. 423-433 ◽  
Author(s):  
Robert O’Connor ◽  
Mary Heenan ◽  
Conor Duffy ◽  
Martin Clynes
Keyword(s):  
Toxicity Testing ◽  
In Vitro Methods

Diverse polyketides and alkaloids from Penicillium sp. KHMM: structural elucidation, biological and molecular docking studies

2019 ◽  
Vol 74 (5-6) ◽  
pp. 131-137 ◽  
Author(s):  
Abdelaaty Hamed ◽  
Mohamed Ismail ◽  
Mohammad M. El-Metwally ◽  
Marcel Frese ◽  
Tarek M.A. Ibrahim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Large Scale ◽  
Carcinoma Cell ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Cervix Carcinoma ◽  
Pathogenic Microorganisms ◽  
Mass Measurements ◽  
Human Cervix

Abstract As a continuation of our earlier research concerning the investigation of microbial bioactive secondary metabolites from the terrestrial Penicillium sp.KH Link 1809 isolate KHMM, the fungus was re-cultivated on a large scale to explore its bioactive compounds intensively. Fifteen compounds, including seven alkaloids (1–7), one sesquiterpene (8), an acetylenic system (9), two sterols, and sphengolipid, were identified. Their structures were established on the bases of extensive one- and two-dimensional nuclear magnetic resonance and mass measurements, and by comparison with literature data. The antimicrobial activity of the fungal extract and the corresponding compounds were studied using a panel of pathogenic microorganisms, and their in vitro cytotoxicity against the human cervix carcinoma cell line (KB-3-1) was reported as well. The molecular docking of the isolated compounds showed promising affinities for the alkaloidal compounds 4–6 towards α, β tubulins.

scholarly journals RUBBER TREE CLONAL PLANTATIONS: GRAFTED VS SELF-ROOTED PLANT MATERIAL

2017 ◽  
Vol 332 ◽  
pp. 57-68
Author(s):  
Aurélien Masson ◽  
Olivier Monteuuis
Keyword(s):  
Large Scale ◽  
Rubber Tree ◽  
Forest Tree ◽  
Field Trials ◽  
Tree Plantations ◽  
Rooted Cuttings ◽  
In Vitro Methods ◽  
Cloning Method ◽  
Increasing Demand

The forest tree species Hevea brasiliensis is extensively planted in the humid tropics to meet the increasing demand for natural rubber. Huge quantities of planting stock are therefore needed. The seed option remains the easiest and cheapest way to establish plantations of rubber trees but those show a great variability for vigor and also for latex yield. The rationale of produ- cing clones for overcoming this variability was already obvious in the early 1910’s but due to the difficulties encountered at that time for rooting shoots, grafting was used as an alternative cloning method. The striking increase in yield noticed from the graft-derived clonal plantations warranted their large scale development. Eventually, the budded clones by virtue of their much higher and uniform produc- tivity supplanted the seedlings in most industrial plantations. However, grafting is also associated with drawbacks and for decades efforts aiming at mass producing selected rubber tree clones on their own roots by rooted cuttings have been pur- sued. However, this approach was pro- gressively abandoned due to disappoin- ting rooting results and, from the 70’s onwards, priority has been given to in vitro methods which were booming during this period. But despite 40 years of heavy investments, industrial H. brasiliensis clones could still not be mass micropro- pagated in vitro efficiently enough to meet the requirements of large scale produc- tion. The situation may change radically soon, however, due to the development of new nursery techniques adapted to the mass clonal production by rooted cuttings of any H. brasiliensis selected genotype. Efforts to improve the techniques as well as the establishment of new field trials are underway in order to determine if self-rooted rubber tree clones are more productive than grafted ones. This old issue is becoming of overriding impor- tance considering the increasing pres- sure on land availability reducing thereby the prospects for expanding rubber tree plantations. 

scholarly journals Cigarette Mainstream Smoke: The Evolution of Methods and Devices for Generation, Exposure and Collection

2016 ◽  
Vol 27 (4) ◽  
pp. 137-274 ◽  
Author(s):  
Hubert Klus ◽  
Barbara Boenke-Nimphius ◽  
Lutz Müller
Keyword(s):  
Large Scale ◽  
Toxicity Testing ◽  
Scale Production ◽  
Mainstream Smoke ◽  
Technical Problems ◽  
Test Pieces ◽  
Artifact Formation ◽  
Cigarette Mainstream Smoke

SUMMARYThe objective of this review is to support tobacco scientists when evaluating information published on smoking machines, and on cigarette mainstream smoke (in vivoandin vitro) exposure systems and collection devices.The intriguing development of smoking machines (mainly for cigarettes) is followed for more than 170 years - from the first simple set-ups in the 1840s to the sophisticated and fully automated analytical smoking machines available today. Systems for the large-scale production of smoke (condensate) for preparative work are equally considered. The standardization of machine smoking methods and test pieces has solved several technical problems and produced sensible rules but, at the same time, given rise to new controversies like the compatibility of artificial and human smoking, and the implementation of more intense machine smoking regimes.Adequate space is allotted for the discussion of configurations forin vivosmoke exposure of rodent and non-rodent species and the machines generating the required smoke (condensate). Covered as well is the field ofin vitrotoxicity testing, including the increasingly informative new techniques of air-liquid interface exposure, which are becoming more and more refined with the use of organotypic cultures and genetic analyses.The review is completed by the examination of the considerable variety of mainstream smoke collection devices (filters and traps) developed over time - some for very specific purposes - and refers to the perpetual problem of artifact formation by aging.

A Reproducibility Study of the Model Cavity Method for the In Vitro Toxicity Testing of Dental Restorative Materials

1984 ◽  
Vol 12 (4) ◽  
pp. 215-223
Author(s):  
Sylvia D. Meryon ◽  
Pat F. Uphill ◽  
Ann D. Cordery ◽  
Roger M. Browne
Keyword(s):  
Toxicity Testing ◽  
In Vitro Cytotoxicity ◽  
Research Centre ◽  
In Vitro Toxicity ◽  
Cavity Method ◽  
Dental Restorative Materials ◽  
Reproducibility Study ◽  
Restorative Materials ◽  
Dental Restorative

A reproducibility study of the model cavity system for evaluating the in vitro cytotoxicity of dental restorative materials was undertaken at Birmingham Dental School and Huntingdon Research Centre. Using a precise experimental protocol drawn up following liaison between the two centres, a number of materials were tested independently. Toxicity was assessed by measurement of reduction in fibroblast and macrophage numbers relative to controls. Overall reproducibility was good, and the ranking of the toxicity of the test materials by both centres was almost identical.

Richard Clothier: An Appreciation

2007 ◽  
Vol 35 (5) ◽  
pp. 531-537
Author(s):  
Michael Balls
Keyword(s):  
Toxicity Testing ◽  
Research Programme ◽  
In Vitro Cytotoxicity ◽  
Alternative Methods ◽  
Comparative Immunology ◽  
East Anglia ◽  
Cell Functions ◽  
Reed College ◽  
The University

The career of Richard Clothier is reviewed in the light of his long-standing collaboration with Michael Balls and Laurens Ruben at the University of East Anglia (UEA), the University of Nottingham, and Reed College, Portland, Oregon, USA. It began with work at UEA on the aetiology of the lymphosarcoma of Xenopus laevis, followed by studies on the effects of exposure to N-nitroso- N-methylurea on T-cell functions, which led to many contributions to comparative immunology. This was followed by the establishment of the FRAME Research Programme, which led to participation in extensive studies on the development of in vitro cytotoxicity tests and their application in acute and topical toxicity testing. A FRAME Trustee since 1983, Richard Clothier was a co-founder, and subsequently Director, of the FRAME Alternatives Laboratory in the University of Nottingham Medical School, where he led successful collaborations with a number of industrial partners and, in particular, with the European Centre for the Validation of Alternative Methods (ECVAM).

Sign in / Sign up

Export Citation Format

Share Document