Alternatives to Laboratory Animals
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Published By SAGE Publications

0261-1929, 2632-3559

2021 ◽  
pp. 026119292110618
Author(s):  
Vivek Patel ◽  
Khalid Amin ◽  
David Allen ◽  
Lindsey Ukishima ◽  
Adam Wahab ◽  
...  

As non-animal alternatives gain acceptance, a need for harmonised testing strategies has emerged. Arguably the most physiologically-relevant model for assessing potential respiratory toxicants, that based on human precision-cut lung slices (hPCLS) has been utilised in many laboratories, but a variety of culture methodologies are employed. In this pilot study, combinations of three different hPCLS culture methods (dynamic organ roller culture (DOC), air–liquid interface (ALI) and submersion) and various media (based on E-199, DMEM/F12 and RPMI-1640) were compared. The hPCLS were assessed in terms of their viability and responsiveness to challenge. The endpoints selected to compare the medium–method (M–M) combinations, which included histological features and viability, were evaluated at day 14 (D14) and day 28 (D28); protein and adenylate kinase (AK) content, and cytokine response to immunostimulants (lipopolysaccharide (LPS) at 5 μg/ml; polyinosinic:polycytidylic acid (Poly I:C) at 15 μg/ml) were evaluated at D28 only. Based on the set of endpoints assessed at D28, it was clear that certain culture conditions significantly affected the hPCLS, with the tissue retaining more of its native features and functionality (in terms of cytokine response) in some of the M–M combinations tested more than others. This pilot study indicates that the use of appropriate M–M combinations can help maintain the health and functional responses of hPCLS, and highlights the need for the standardisation of culture conditions in order to facilitate effective inter-laboratory comparisons and encourage greater acceptance by the regulatory community.


2021 ◽  
pp. 026119292110602
Author(s):  
Courtney V. Thompson ◽  
James W. Firman ◽  
Michael R. Goldsmith ◽  
Christopher M. Grulke ◽  
Yu-Mei Tan ◽  
...  

Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration–time profile at the target site. Physiologically based kinetic (PBK) models can predict organ-level concentration–time profiles — however, the models are time and resource intensive to generate de novo. Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel® spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.


2021 ◽  
pp. 026119292110622
Author(s):  
Michael Balls

The Three Rs ( reduction, refinement, replacement) concept put forward by Russell and Burch now appears to be widely accepted. However, their warnings concerning reliance on animals as models for humans, the insurmountable problem of species differences and the impact of human variation, have been downplayed or even ignored. Schemes for harm–benefit analysis have been introduced, but the focus has largely been on harm to the animals, rather than on the direct and indirect benefit to humans, which is much more difficult to evaluate. Greater recognition should be given to the direct or indirect harm to humans resulting from the current over-reliance of biomedical research and testing on data obtained from animal experiments. That will be hard to achieve in the current climate, given the vigorous defence of animal experimentation by those with vested interests, confusion over responsibilities for regulating animal experimentation, hierarchies of regulatory authorities which require or limit experiments on animals, and exaggerated claims about the current availability of new approach methodologies (NAMs) and relevant and reliable strategies for their use. Those who defend animal experimentation at almost any cost must bear part of the responsibility for the human harms which result. Meanwhile, much greater effort should be put into the development, validation and application of new approaches not involving animals.


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