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.

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.

The EYTEX™ System and the Neutral Red Uptake Inhibition Assay in Cultured Hep G2 Cells as Alternative Methods for In Vivo Eye Irritation Following the EEC Protocol

1990 ◽  
Vol 17 (4) ◽  
pp. 325-333
Author(s):  
Paul J. Dierickx ◽  
Virginia C. Gordon
Keyword(s):  
Neutral Red ◽  
Alternative Methods ◽  
Inhibition Assay ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Eye Irritation ◽  
Uptake Inhibition ◽  
In Vitro Methods ◽  
Neutral Red Uptake

The neutral red uptake inhibition assay and the EYTEX™ system were investigated as alternative methods for the assessment of eye irritation, determined according to the EEC protocol. The 17 test chemicals used were mainly organic solvents. The xenobiotics were applied to Hep G2 cells for 24 hours at different concentrations. Neutral red uptake inhibition was then measured. The results are expressed as the NI50 value, which is the concentration of test compound required to induce a 50% reduction in neutral red uptake. The same chemicals were also tested as coded samples by the EYTEX™ test according to the manufacturer's directions. A nearly identical quantitative correlation was found for both in vitro methods with corneal opacity scores: r = 0.84 for EYTEX™ scores and r = 0.83 for log NI50, expressed in μg/ml. Whilst these correlations are certainly not perfect, it is clear that both in vitro methods can be used as valuable prescreening methods.

scholarly journals The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing

2013 ◽  
Vol 32 (1) ◽  
pp. 47-63 ◽  
Author(s):  
Pekka Kohonen ◽  
Emilio Benfenati ◽  
David Bower ◽  
Rebecca Ceder ◽  
Michael Crump ◽  
...  
Keyword(s):  
Data Warehouse ◽  
Toxicity Testing ◽  
Systemic Toxicity ◽  
Repeated Dose

scholarly journals Biological Innocuousness of a Device developed to select the Optimum Spermatozoa to be used in the Treatment of Infertility

2021 ◽  
Author(s):  
Marisa A Cubilla ◽  
Hector A Guidobaldi ◽  
Laura C Giojalas
Keyword(s):  
Colony Formation ◽  
Physiological State ◽  
Neutral Red ◽  
Sperm Selection ◽  
Neutral Red Uptake

The sperm selection assay (SSA) is a method based on chemotaxis to obtain spermatozoa at the optimum physiological state to successfully fertilize the egg. It consists of a device made of acrylic and an attractant solution which includes progesterone. We evaluate potential cytotoxicity interactions by means of Neutral Red uptake, the MTT and colony formation assays, according to ISO normative. Here we showed that even stressing the conditions of the assays, the SSA device alone or together with the progesterone solutions employed, showed to be innocuous for the cells. Suggesting that SSA could be incorporated into the ART procedures.

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