scholarly journals Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’

2010 ◽  
Vol 29 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Robert F Phalen
Keyword(s):  
21St Century ◽  
Toxicity Testing ◽  
In Vitro Testing ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
In Vitro Techniques ◽  
Human Monitoring ◽  
Animal Tests ◽  
In Silico Methods

Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007) presents a bold plan for chemical toxicity testing that replaces whole-animal tests with cell-culture, genetic, other in-vitro techniques, computational methods, and human monitoring. Although the proposed vision is eloquently described, and recent advances in in-vitro and in-silico methods are impressive, it is difficult believe that replacing in-vitro testing is either practical or wise. It is not clear that the toxicity-related events that occur in whole animals can be adequately replicated using the proposed methods. Protecting public health is a serious endeavor that should not be limited by denying animal testing. Toxicologists and regulators are encouraged to read the report, carefully consider its implications, and share their thoughts. The vision is for too important to ignore.

Commentary on ‘‘Toxicity Testing in the 21st Century: A vision and a Strategy’’

2010 ◽  
Vol 29 (1) ◽  
pp. 31-32 ◽  
Author(s):  
William J Waddell
Keyword(s):  
21St Century ◽  
Dose Response ◽  
Toxicity Testing ◽  
Pbpk Modeling ◽  
In Vitro Testing ◽  
Additional Observation ◽  
National Academy Of Sciences ◽  
Big Picture ◽  
Academy Of Sciences

The report of the National Academy of Sciences entitled ‘Toxicity Testing in the 21st Century: A Vision and a Strategy,’ hereinafter referred to as ‘The Report,’ is more of a vision than of a strategy. The present article addresses three observations made on The Report; namely, dose response, PBPK modeling, and in vitro testing. An additional observation this author has of the document is that a role for a scientist who can analyze the big picture is missing from the document. Science today is necessarily composed of specialists in many areas because science today encompasses many diverse, specific fields. Each specialist is in a world of his or her own and unable to integrate all the facts. Must we wait for another Newton or Einstein?

Reproductive Toxicity Testing: Evaluating and Developing New Testing Systems

1985 ◽  
Vol 4 (2) ◽  
pp. 163-171 ◽  
Author(s):  
J. C. Lamb
Keyword(s):  
Environmental Protection Agency ◽  
Food Additives ◽  
Reproductive Toxicity ◽  
Toxicity Testing ◽  
Reproductive Function ◽  
Test System ◽  
Toxic Substances ◽  
Animal Testing ◽  
In Vitro Techniques

Reproductive toxicity testing systems are used by national and international regulatory agencies. Protocols have not been standardized between agencies or even within certain agencies. Although there have been efforts at standardization, a certain amount of the differences between testing protocols is a reflection of the needs of the particular agency. New developments in in vitro techniques might lead to new test systems, but reproductive function is dependent upon the interaction of various cells and organs that cannot presently be copied in the test tube; this makes whole-animal testing systems a necessity. The present whole-animal models used by the Food and Drug Administration include the 3 segment reproduction studies used for testing drug safety and the multigeneration studies used for food additives. The Environmental Protection Agency has adopted 2 similar versions of a 2-generation study for the Office of Pesticide Programs and the Office of Toxic Substances. The National Toxicology Program, although not a regulatory agency, has taken a prominent role in reproductive toxicity testing, test system development, and test system evaluation. A new testing system, Fertility Assessment by Continuous Breeding (FACB), is currently being studied as a cost-effective and reliable alternative test system. The FACB protocol houses male and female mice as breeding pairs and removes offspring as soon as they are born during the first 14 weeks to allow continuous mating. Each breeding pair normally has up to 5 litters, and the last litter is saved to evaluate the second generation. The efficiency, reliability, and expense of the protocol are being compared to the existing testing systems.

scholarly journals PeBiToSens™: A Platform for PBT Screening of Fragrance Ingredients Without Animal Testing

2020 ◽  
Vol 74 (3) ◽  
pp. 168-175
Author(s):  
Heike Laue ◽  
Lu Hostettler ◽  
Gordon Sanders ◽  
Georg Kreutzer ◽  
Andreas Natsch
Keyword(s):  
The Body ◽  
Trophic Levels ◽  
Chemical Toxicity ◽  
Animal Testing ◽  
Ecotoxicological Assessment ◽  
Microbial Biodegradation ◽  
Animal Tests ◽  
Safe By Design

The determination of persistence (P), bioaccumulation (B) and toxicity (T) plays a central role in the environmental assessment of chemicals. Persistence is typically evaluated via standard microbial biodegradation tests. Bioaccumulation refers to the accumulation of chemicals in organisms and is usually assessed in fish exposed to the test chemical. Toxicity is determined at three trophic levels, with fish toxicity as the highest trophic level assessed. Thus, animal tests are classically needed for both B and T assessment. In vitro systems based on fish liver cells or liver S9 fractions ('RT-S9 assay') have been recently adopted by OECD to measure the biotransformation rates for the chemicals for B assessment. Biotransformation drives clearance from the body and reduces bioaccumulation. For T assessment, an assay based on in vitro toxicity on fish gill cells has been established ('RTgill-W1 assay'). Here we summarize our findings indicating that these tests are highly predictive for fragrance ingredients, and show with two case studies of our latest new registered substances how we apply these tests in particular during development and also for chemical registration. This platform of tests (PeBiToSens™) could fully replace animal tests in ecotoxicological assessment and is key in the Givaudan Safe by Design™ approach to develop safer and environmentally compatible novel fragrance ingredients.

scholarly journals Toxicity testing: Non-animal approaches and safety science

2014 ◽  
Vol 36 (3) ◽  
pp. 19-25 ◽  
Author(s):  
Fiona Reynolds ◽  
Carl Westmoreland ◽  
Julia Fentem
Keyword(s):  
Safety Assessment ◽  
Toxicity Testing ◽  
Chemical Safety ◽  
Research Investment ◽  
Highly Sensitive ◽  
Safety Science ◽  
Modelling Techniques ◽  
Animal Tests ◽  
Made In

New informatics capabilities and computational and mathematical modelling techniques, used in combination with highly sensitive molecular biology and mechanistic chemistry approaches, are transforming the way in which we assess the safety of chemicals and products. In recent years, good progress has been made in replacing some of the animal tests required for regulatory purposes with methods using cells and tissues in vitro. Nevertheless, big scientific challenges remain in developing relevant non-animal models able to predict the effects of chemicals which are absorbed systemically. The greatest breakthroughs in non-animal approaches for chemical safety assessment will most likely result from continued multi-disciplinary research investment in predictive (integrative and systems) biology. Some of our current research in this area is described in the present article.

Integrated Decision-tree Testing Strategies for Environmental Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 29-42 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Aquatic Toxicity ◽  
Toxicity Testing ◽  
Threshold Concentration ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME recently conducted a research project sponsored by Defra on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for environmental (aquatic) toxicity testing. The manuscript reviews tests based on fish cells and cell lines, fish embryos, lower organisms, and the many expert systems and QSARs for aquatic toxicity testing. Ways in which reduction and refinement measures can be used are also discussed, including the Upper Threshold Concentration — Step Down (UTC) approach, which has recently been retrospectively validated by ECVAM and subsequently endorsed by the ECVAM Scientific Advisory Committee (ESAC). It is hoped that the application of this approach could reduce the number of fish used in acute toxicity studies by around 65–70%. Decision-tree style integrated testing strategies are also proposed for acute aquatic toxicity and chronic toxicity (including bioaccumulation), followed by a number of recommendations for the future facilitation of aquatic toxicity testing with respect to environmental risk assessment.

In Vitro Thrombogenicity Testing of Artificial Organs

1998 ◽  
Vol 21 (9) ◽  
pp. 548-552 ◽  
Author(s):  
R. Paul ◽  
O. Marseille ◽  
E. Hintze ◽  
L. Huber ◽  
H. Schima ◽  
...  
Keyword(s):  
Heart Valves ◽  
Early Stage ◽  
Thrombus Formation ◽  
Testing Procedure ◽  
Artificial Organs ◽  
Coagulation System ◽  
In Vitro Testing ◽  
Animal Testing ◽  
Thrombogenic Potential

Thromboembolic complications remain as one of the main problems for blood contacting artificial organs such as heart valves, bloodpumps and others. In vitro evaluation of thrombogenesis in prototypes has not previously been part of the standard evaluation of these devices. In comparison to hemolysis testing, evaluation of the thrombogenic potential is more difficult to perform because of the complexity of the blood coagulation system. We present an in vitro testing procedure that allows the accelerated examination of the thrombogenic potential of different types of blood pumps. Additionally, first results are presented that indicate the reliability of the accelerated clotting test for mechanical heart valves. Results for the centrifugal pump BioMedicus and two microaxial pumps have shown typical thrombus formation at locations such as bearings. The results indicate that the accelerated clotting test is an excellent addition to the much more expensive animal testing of artificial organs or assist devices. In vitro testing permits studies of thrombus formation to be performed at an early stage and at low costs and also facilitates a more precise investigation of device areas known to be potential hot spots for thrombus formation.

scholarly journals A Framework for Ecotoxicity Testing in the 21st Century: Ecotox21

2019 ◽  
Vol 9 (3) ◽  
pp. 428
Author(s):  
Zhen-guang Yan ◽  
Xin Zheng ◽  
Fu Gao ◽  
Jun-tao Fan ◽  
Shu-ping Wang ◽  
...  
Keyword(s):  
21St Century ◽  
High Efficiency ◽  
Environmental Fate ◽  
Toxicity Testing ◽  
Chemical Exposure ◽  
The United States ◽  
Predictive Toxicology ◽  
Testing Strategies ◽  
Ecotoxicity Testing

To reduce the considerable investments of toxicity testing and protecting animal welfare, a new toxicity testing strategy based on response pathways of human cell lines has been proposed in the United States to evaluate the chemical exposure risks to human health. However, the in vitro high-throughput assays have not yet been fully applied in ecotoxicity testing. This paper proposes a framework for high-efficiency ecotoxicity testing strategies to evaluate the ecological risk of chemicals. It consists of pathway-based toxicity testing, embryo-based toxicity testing, and predictive toxicology and data extrapolation, etc., according to different situations. The results of ecotoxicity testing or data mining are analyzed together with physicochemical properties, environmental fate, and exposure data of chemicals to conduct a comprehensive risk assessment of chemicals. The framework provides valuable points to establish high-efficiency ecotoxicity testing strategies in the 21st century.

Chemical toxicity testing in vitro using cytochrome P450–expressing cell lines, such as human CYP1B1

2011 ◽  
Vol 6 (5) ◽  
pp. 677-688 ◽  
Author(s):  
Robert Landsiedel ◽  
Eric Fabian ◽  
Tewes Tralau ◽  
Andreas Luch
Keyword(s):  
Cytochrome P450 ◽  
Cell Lines ◽  
Toxicity Testing ◽  
Chemical Toxicity

Framework for Validation and Implementation of In Vitro Toxicity Tests: Report of the Validation and Technology Transfer Committee of the Johns Hopkins Center for Alternatives to Animal Testing

1993 ◽  
Vol 12 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Michael S. Dickens ◽  
Oliver Flint ◽  
Stephen D. Gettings ◽  
Richard N. Hill ◽  
Robert L. Lipnick ◽  
...  
Keyword(s):  
Toxicity Testing ◽  
Data Bank ◽  
Laboratory Animals ◽  
Toxicity Tests ◽  
In Vitro Toxicity ◽  
Tissue Banks ◽  
Animal Testing ◽  
The Creation ◽  
Effective Transfer

In toxicology the development and application of in vitro alternatives to reduce or replace animal testing, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend. However, at present there is no formal administrative process to organize, coordinate, or evaluate these activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technology from the research laboratory to practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. We recommend the creation of a Scientific Advisory Board of experts in toxicity testing, representing the academic, industrial and regulatory communities. Test validation acceptance is contingent upon broad buy-in by disparate groups in the scientific community: academia, industry and government. We believe that this can be achieved by early and frequent communication among the parties and agreement upon common goals. The committee hopes that the creation of a validation infrastructure built with the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of reduction, refinement and replacement alternatives in toxicity testing.

scholarly journals Alternative methods in toxicity testing: the current approach

2014 ◽  
Vol 50 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Gabrielle Luck de Araújo ◽  
Maria Augusta Amaral Campos ◽  
Maria Anete Santana Valente ◽  
Sarah Cristina Teixeira Silva ◽  
Flávia Dayrell França ◽  
...  
Keyword(s):  
21St Century ◽  
Toxicity Testing ◽  
Current Approach ◽  
Alternative Methods ◽  
New Paradigm ◽  
Community Regulation ◽  
Complex Process ◽  
New Methodologies ◽  
New Vision

Alternative methods are being developed to reduce, refine, and replace (3Rs) animals used in experiments, aimed at protecting animal welfare. The present study reports alternative tests which are based on the principles of the 3Rs and the efforts made to validate these tests. In Europe, several methodologies have already been implemented, such as tests of irritability, cell viability, and phototoxicity as well as in vitro mathematical models together with the use of in silico tools. This is a complex process that spans from development to regulatory approval and subsequent adoption by various official entities. Within this regulatory framework is REACH, the European Community Regulation for chemicals and their safe use. In Brazil, the BraCVAM (Brazilian Center for the Validation of Alternative Methods) was recently established to validate alternative methods and stimulate incorporation of new methodologies. A new vision of toxicology is emerging for the 21st century (Tox-21), and the subsequent changes are shaping a new paradigm.

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