Dynamic Qualities of Validation and the Evolution of New In Vitro Toxicological Tests

1996 ◽  
Vol 24 (3) ◽  
pp. 333-338
Author(s):  
Erik Walum ◽  
Anna Forsby ◽  
Cecilia Clemedson ◽  
Björn Ekwall
Keyword(s):  
Cell Biology ◽  
Tissue Concentration ◽  
Toxicity Testing ◽  
Test Methods ◽  
In Vitro Cytotoxicity ◽  
Cytotoxicity Test ◽  
Toxic Exposure ◽  
Cellular Tests ◽  
Toxicokinetic Data

This review summarises some aspects of the dynamics of the evolution of toxicological test methods based on cell biology. Within the multicentre evaluation of in vitro cytotoxicity (MEIC) programme, some general principles for validation have been proposed: a) a human database should be used as the source of reference data in the validation of new methods aimed at predicting human toxicity; b) the relevance of a test should be determined before its reliability is assessed; c) a parallel validation of methods is preferable to a serial validation; and d) toxicokinetic data should be included in the validation process to improve the predictivity of cytotoxicity test results. These toxicokinetic data can be used to extrapolate the cytotoxic in vitro concentrations to provide human toxic exposure levels. As part of test development, the cytotoxic concentration can also be compared directly with the critical toxic human blood or tissue concentration. This approach is being explored in the ERGATT/CFN integrated toxicity testing scheme (ECITTS) prevalidation project. The critical toxic concentrations are determined by using a set of neurospecific cellular tests, chosen and combined on the basis of knowledge of common neurotoxicity mechanisms. Another approach to selecting tests for prevalidation is through the development of tests that are found to be necessary and complementary to existing tests. Such a programme has been initiated on the basis of the results of the MEIC study. The progress made so far in this “missing tests programme” is presented in this paper.

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.

Cytocompatibility Comparative Study of Hydroxyapatite Coating on Titanium Alloy Treated with Two Chemical Routes

2013 ◽  
Vol 658 ◽  
pp. 61-66
Author(s):  
Qing Zong Si ◽  
Xiao Li An ◽  
Yang Li ◽  
Bin Liu ◽  
Jin Qing Wang
Keyword(s):  
Titanium Alloy ◽  
In Vitro Cytotoxicity ◽  
Combination Method ◽  
Cytotoxicity Test ◽  
X Ray Diffraction ◽  
Chemical Methods ◽  
X Ray ◽  
Ha Coating ◽  
Cell Adhesion And Proliferation

In order to prepare bioactive hydroxyapatite (Ca10 (PO4)6(OH) 2, HA) coating with ideal biocompatibility, the surface of titanium alloy was treated with the two kinds of chemical methods, which are the acid-alkali-combination method and Self-polymerization-adhesion of dopamine. After pretreatment, the treated titanium alloy plates were immersed in simulated body fluid (SBF) to form HA coating on their surface. The chemical composition of the coating was analyzed by an X-ray diffraction (XRD) and the morphology was observed by a scanning electron microscope (SEM). After that, the plates were training in vitro cytotoxicity test with MC3T3-E1 osteoblasts. Compared with the results of cell culture, the method of Self- polymerization -adhesion of dopamine showed better cell adhesion and proliferation..

scholarly journals Study of Icaritin Films by Low-Energy Electron Beam Deposition

2021 ◽  
Vol 23 (2) ◽  
pp. 77
Author(s):  
Tongfei Cheng ◽  
Jinxing Cao ◽  
Xiaohong Jiang ◽  
M.A. Yarmolenko ◽  
A.A. Rogachev ◽  
...  
Keyword(s):  
Electron Beam ◽  
In Vitro Cytotoxicity ◽  
Low Energy ◽  
Cytotoxicity Test ◽  
Soaking Time ◽  
Energy Beam ◽  
Electron Beam Deposition ◽  
Relative Cell Viability ◽  
Beam Deposition

In this paper, icaritin film was prepared by low-energy beam electron beam deposition (EBD). The material test showed that the structure and composition of icaritin were not changed after electron beam deposition. Then, the film was sliced and immersed in simulated body fluids, it can be seen that the film was released quickly in the first 7 days. With the extension of soaking time, the release rate gradually slowed down, and the release amount exceeded 90% in about 20 days. In vitro cytotoxicity test showed that the relative cell viability rate of the film was still 92.32±1.30% (p<0.05), indicating that the film possessed excellent cytocompatibility.

Novel rapid in vitro cytotoxicity test on mammalian cells based on an electrochemical measuring method

2014 ◽  
Vol 44 (8) ◽  
pp. 935-943 ◽  
Author(s):  
Michael Pescheck ◽  
Constanze Dürr ◽  
Luděk Bláha ◽  
Dieter Sell
Keyword(s):  
Mammalian Cells ◽  
Measuring Method ◽  
In Vitro Cytotoxicity ◽  
Cytotoxicity Test

Research on the Preparation of HA/PEEK Gradient Composites by Impregnation Method and the Biosecurity

2017 ◽  
Vol 893 ◽  
pp. 35-42 ◽  
Author(s):  
Rui Ma ◽  
Ling Jun Dai ◽  
Lin Wang ◽  
Yu Dian Song
Keyword(s):  
Mechanical Properties ◽  
Bone Formation ◽  
Structural Design ◽  
Injection Moulding ◽  
In Vitro Cytotoxicity ◽  
Leach Liquor ◽  
Cytotoxicity Test ◽  
Impregnation Method ◽  
The Poor

This study prepares the HA/PEEK gradient composites with special structural design by impregnation method, which eases the contradiction of the HA/PEEK composites between the lack of bioactivity due to low HA contents and the poor mechanical properties due to high HA contents, and effectively improves the bioactivity and mechanical properties of the PEEK-based materials, and then evaluates the biosecurity of HA/PEEK gradient composites. The main functional cell of bone formation—osteoblast is adopted for the co-culture with PEEK, HA/PEEK gradient composites and the leach liquor, and the effects of PEEK and HA/PEEK gradient composites on the proliferative functions of osteoblast are studied by in vitro cytotoxicity test. The results show that no harmful admixtures are produced in the process of injection moulding, and the leach liquors of PEEK and HA/PEEK gradient composites have no effects on the proliferative functions of osteoblast, with good osteoblast compatibility.

scholarly journals Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance

2018 ◽  
Vol 11 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Earnest Oghenesuvwe Erhirhie ◽  
Chibueze Peter Ihekwereme ◽  
Emmanuel Emeka Ilodigwe
Keyword(s):  
Toxicity Testing ◽  
Neutral Red ◽  
Test Methods ◽  
Systemic Toxicity ◽  
Regulatory Approval ◽  
Fixed Dose ◽  
Regulatory Body ◽  
Cytotoxicity Test ◽  
Food Ingredients ◽  
Neutral Red Uptake

Abstract Safety assessment of chemicals, pharmaceuticals, food and food ingredients, cosmetics, industrial products is very crucial prior to their approval for human uses. Since the commencement of toxicity testing (about 500 years ago, since 1520), significant advances have been made with respect to the 3Rs (reduction, refinement and replacement) alternative approaches. This review is focused on the update in acute systemic toxicity testing of chemicals. Merits and demerits of these advances were also highlighted. Traditional LD50 test methods are being suspended while new methods are developed and endorsed by the regulatory body. Based on the refinement and reduction approaches, the regulatory body has approved fixed dose procedure (FDP), acute toxic class (ATC) method and up and down procedure (UDP) which involves few numbers of animals. In terms of replacement approach, the regulatory body approved 3T3 neutral red uptake (NRU), the normal human keratinocyte (NHK), and the 3T3 neutral red uptake (NRU) phototoxicity test for acute phototoxicity. However, other promising replacement alternatives such as organ on chip seeded with human cells for acute systemic toxicity and 3T3 neutral red uptake (NRU) cytotoxicity test for identifying substances not requiring classification, as well as the in silico approaches are yet to receive regulatory approval. With this backdrop, a collaborative effort is required from the academia, industries, regulatory agencies, government and scientific organizations to ensure speedily regulatory approval of the prospective alternatives highlighted.

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.

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