Alternatives To Animal Testing In Toxicology

1. Alternative Approaches To Vertebrate Ecotoxicity Tests In The 21st Century: A Review Of Developments Over The Last 2 Decades And Current Status

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Alternative Approaches To Vertebrate Ecotoxicity Tests In The 21st Century: A Review Of Developments Over The Last 2 Decades And Current Status

By Hung-Jin Huang Hung-Jin Huang Scilit Preprints.org Google Scholar View Publications 1 , Yu-Hsuan Lee Yu-Hsuan Lee Scilit Preprints.org Google Scholar View Publications 2 , Yung-Ho Hsu Yung-Ho Hsu Scilit Preprints.org Google Scholar View Publications 3, 4, 5 , Chia-Te Liao Chia-Te Liao Scilit Preprints.org Google Scholar View Publications 4, 5, 6 , Yuh-Feng Lin Yuh-Feng Lin Scilit Preprints.org Google Scholar View Publications 1, 5, 6, * and Hui-Wen Chiu Hui-Wen Chiu Scilit Preprints.org Google Scholar View Publications 1, 5, 6, 7, *

Millions of experimental animals are widely used in the assessment of toxicological or biological effects of manufactured nanomaterials in medical technology. However, the animal consciousness has increased and become an issue for debate in recent years. Currently, the principle of the 3Rs (i.e., reduction, refinement, and replacement) is applied to ensure the more ethical application of humane animal research. In order to avoid unethical procedures, the strategy of alternatives to animal testing has been employed to overcome the drawbacks of animal experiments. This article provides current alternative strategies to replace or reduce the use of experimental animals in the assessment of nanotoxicity. The currently available alternative methods include in vitro and in silico approaches, which can be used as cost-effective approaches to meet the principle of the 3Rs. These methods are regarded as non-animal approaches and have been implemented in many countries for scientific purposes. The in vitro experiments related to nanotoxicity assays involve cell culture testing and tissue engineering, while the in silico methods refer to prediction using molecular docking, molecular dynamics simulations, and quantitative structure–activity relationship (QSAR) modeling. The commonly used novel cell-based methods and computational approaches have the potential to help minimize the use of experimental animals for nanomaterial toxicity assessments.

Experimental animals are widely used as a tool to evaluate the toxicological or biological effects of potential drug candidates for the development of new treatments. To date, animal ethics and animal consciousness have been growing, resulting in these topics becoming important issues over the last decade. Unfortunately, millions of animals continue to be used in medical research for scientific purposes each year. Alternative methods of animal research have been suggested as a good strategy to avoid unethical animal procedures and make scientific experiments more humane. Therefore, the concept of the replacement of animal testing was proposed by Charles Hume and William Russell in 1957 [1]. In 1959, the 3Rs (i.e., reduction, refinement, and replacement) strategy was first discussed in the book “The Principles of Humane Experimental Technique”, which was published by two English researchers, W. M. S. Russell (1925–2006) and R. L. Burch (1926–1996) [2, 3]. The principle of Russell and Burch’s 3Rs, including reduction, refinement, and replacement, aimed to reduce the number of animals used and minimize the stress to such experimental animals in medical and biological research. At present, the principle of the 3Rs is applied in laboratories where animals are used to perform more humane animal research. Implementation of the 3Rs principle has the potential to overcome the drawbacks of traditional animal tests, such as the time-consuming nature, expensive feeding requirements, and associated ethical problems [4, 5]. Nowadays, alternative methods are available to replace animal tests in the majority of commonly studied biomedical fields [6, 7], including cell-based cytotoxic testing, genotoxicity, and biochemical assay. Non-animal approaches, which can replace animal tests, can provide quicker, more effective, and cheaper chemical safety assessments that function as substitutes for traditional animal experiments. Alternative methods to animal tests include chemical-based tests, in vitro cell culture systems, in silico computational biomodeling, and ex vivo tests using tissue from dead animals [8]. Compared to ex vivo tests, tissue engineering is a more ethical approach to the potential replacement of animal models. Tissue is taken from dead humans or animals to perform ex vivo tests, while artificial tissue utilizes cell and material methods in tissue engineering without any possible ethical problems. In this review article, we discuss the recent applications of alternative non-animal systems, including cell-based tests, computer-based modeling, and tissue engineering, for nanotoxicity assessments in scientific experiments.

Biologia Futura: Animal Testing In Drug Development—the Past, The Present And The Future

The rapid growth of nanotechnology has contributed to the urgent requirement of safety assessments for manufactured nanomaterials. Therefore, analytical methods of nanotoxicity have received a great deal of attention due to the application of nanomaterials in diverse research areas, such as agriculture [9], food industries [10], medicine [11], and biotechnology [12]. Upon the development of a novel nanomaterial, an assessment of its toxic and biological impacts must be performed to understand the potential risk factors before the material can finally be applied for medical use. Nevertheless, the number of experimental animals used in nanoparticle (NP) toxicity tests has increased each year [13]. In order to reduce the use of animal testing, humane experimental techniques have been employed to investigate biological and pathological effects as alternative forms of nanomaterial toxicity assessments. In this review, we introduce that in vitro cell-based models and in silico computational models are the most commonly used alternative testing tools to evaluate the safety and toxicity of chemical substances in the field of nanotechnology (Figure 1) [14, 15, 16].

For in vitro experiments, cell-based tests and tissue models are widely used alternative models to determine chemical hazards. In general, in vitro studies can be applied to investigate the minimum toxic effects in a specific cellular environment via cell viability protocols [17], while in vitro methods do not represent a complete replacement for in vivo assessments. Hence, in silico methods, in the replacement of animal testing, are a useful strategy to explore the relationship between chemical and biological systems in medical product development and safety assessments. Via the pharmacokinetic information database [18], numerous in silico program tools can predict absorption, distribution, metabolism, and excretion/toxicity (ADME/T) properties, derived entirely from the structures of the chemicals of interest [19, 20, 21].

Cell-based tests, known as in vitro techniques, are commonly used to assess the safety and toxicity of drugs and chemicals in the replacement of animal testing [22]. In vitro studies are capable of providing faster, inexpensive, and valuable information that helps researchers to assess the potential risks or possible toxicity of newly developed nanomaterials before their final application [17]. Herein, we describe the commonly used novel in vitro methods that comply with the 3Rs principle and avoid the use of animal experimentation.

Alternatives To Animal Testing Drive Market

Currently, cell-based assessments are utilized for the treatment of various prominent disorders—including cardiovascular, neurological, ophthalmologic, skeletal, and autoimmune disorders—and for evaluating the toxicity associated with such treatments [23]. To date, various stem cell sources exist that can be used for toxicity testing, such as fibromatosis-derived stem cells (FSCs) [24], mesenchymal stem cells (MSCs) [25], cardiac stem cells (CDCs) [26], and embryonic stem cells (ESCs) [27, 28]. Human ESC research was first reported in 1998 [29], in which cells obtained from pre-implantation embryos were shown to be pluripotent in nature, with the ability to differentiate into various cell types. Thus, human ESCs may be suitable as a source of cells to be used in the development of tissue engineering [30]. Currently, several ethical and religious concerns remain within the context of using human ESCs for toxicological studies or experimentation purposes [31, 32]. Human ESC research is considered an ethical problem due to the destruction of human embryos [33]. In this context, alternative stem cell sources have received a great deal of attention in order to avoid ethical quandaries for investigators [34].

Induced pluripotent stem cells (iPSCs) are multipotent stem cells that are directly obtained from skin or blood cells, which can overcome the ethical considerations related to research and publication [35]. According to the seminal report from Shinya Yamanaka’s lab in 2006 [36], the first iPSC technique used four encoding transcription factors (named Oct4, Sox2, Klf4, and C-myc) to convert reprogrammed adult mouse fibroblasts into pluripotent stem cells. The above four factors, also called the “Yamanaka factors”, have the ability to reprogram mouse or human somatic cells and differentiate them into iPSCs. The iPSCs have self-renewing properties and can differentiate into all cell

Currently, cell-based assessments are utilized for the treatment of various prominent disorders—including cardiovascular, neurological, ophthalmologic, skeletal, and autoimmune disorders—and for evaluating the toxicity associated with such treatments [23]. To date, various stem cell sources exist that can be used for toxicity testing, such as fibromatosis-derived stem cells (FSCs) [24], mesenchymal stem cells (MSCs) [25], cardiac stem cells (CDCs) [26], and embryonic stem cells (ESCs) [27, 28]. Human ESC research was first reported in 1998 [29], in which cells obtained from pre-implantation embryos were shown to be pluripotent in nature, with the ability to differentiate into various cell types. Thus, human ESCs may be suitable as a source of cells to be used in the development of tissue engineering [30]. Currently, several ethical and religious concerns remain within the context of using human ESCs for toxicological studies or experimentation purposes [31, 32]. Human ESC research is considered an ethical problem due to the destruction of human embryos [33]. In this context, alternative stem cell sources have received a great deal of attention in order to avoid ethical quandaries for investigators [34].

Induced pluripotent stem cells (iPSCs) are multipotent stem cells that are directly obtained from skin or blood cells, which can overcome the ethical considerations related to research and publication [35]. According to the seminal report from Shinya Yamanaka’s lab in 2006 [36], the first iPSC technique used four encoding transcription factors (named Oct4, Sox2, Klf4, and C-myc) to convert reprogrammed adult mouse fibroblasts into pluripotent stem cells. The above four factors, also called the “Yamanaka factors”, have the ability to reprogram mouse or human somatic cells and differentiate them into iPSCs. The iPSCs have self-renewing properties and can differentiate into all cell