Green Toxicology Research Articles

Application of Green Toxicology in Personal Care Products

This research paper discusses green toxicology. Toxic substances are everywhere in our daily lives. Toxicology is usually applied in public health because all the drugs used for humans’ health are made of chemicals. With the application of toxicology, people can acknowledge the adverse effects of the drugs on people’s health. Then, people could develop safer drugs for people’s health—a little different from toxicology, green toxicology concerns both health and environmental impact. Green toxicology is a type of toxicology that applies toxicology to sustainable development and production in society. It uses toxicity testing in earlier stages of the production cycle to be time and cost-efficient. When green toxicology is applied to drug production, the production process would think about how to produce safer products with fewer adverse effects on people and the environment. As green toxicology relates to the impacts of toxins on the environment and people, the effects of contaminants on people’s health should be explored. Every material that people use is made up of harmful or beneficial chemical substances. Because much of the information about the chemicals has not been revealed until now, many products that people use, such as personal care products, might consist of toxic substances. Personal care products should be composed of safe products because many of those contact people's bodies and skin. Utilizing green toxicological methods in the production of personal care products is crucial. By examining the chemicals used and the production cycles, the possible solution by application of green toxicology will be stated.

In-silico green toxicology approach toward discovering safer ligands for development of safe-by-design metal–organic frameworks

A vast variety of chemical compounds have been fabricated and commercialized, they not only result in industrial exposure during manufacturing and usage, but also have environmental impacts throughout their whole life cycle. Consequently, attempts to assess the risk of chemicals in terms of toxicology have never ceased. In-silico toxicology, also known as predictive toxicology, has advanced significantly over the last decade as a result of the drawbacks of experimental investigations. In this study, ProTox-III was applied to predict the toxicity of the ligands used for metal–organic framework (MOF) design and synthesis. Initially, 35 ligands, that have been frequently utilized for MOF synthesis and fabrication, were selected. Subsequently, canonical simplified molecular-input line-entry system (SMILES) of ligands were extracted from the PUBCHEM database and inserted into the ProTox-III online server. Ultimately, webserver outputs including LD50 and the probability of toxicological endpoints (cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, and ecotoxicity) were obtained and organized. According to retrieved LD50 data, the safest ligand was 5-hydroxyisophthalic. In contrast, the most hazardous ligand was 5-chlorobenzimidazole, with an LD50 of 8 mg/kg. Among evaluated endpoints, ecotoxicity was the most active and was detected in several imidazolate ligands. This data can open new horizons in design and development of green MOFs.

Gold Nanoparticles (AuNPs)-Toxicity, Safety and Green Synthesis: A Critical Review.

In recent years, the extensive exploration of Gold Nanoparticles (AuNPs) has captivated the scientific community due to their versatile applications across various industries. With sizes typically ranging from 1 to 100 nm, AuNPs have emerged as promising entities for innovative technologies. This article comprehensively reviews recent advancements in AuNPs research, encompassing synthesis methodologies, diverse applications, and crucial insights into their toxicological profiles. Synthesis techniques for AuNPs span physical, chemical, and biological routes, focusing on eco-friendly "green synthesis" approaches. A critical examination of physical and chemical methods reveals their limitations, including high costs and the potential toxicity associated with using chemicals. Moreover, this article investigates the biosafety implications of AuNPs, shedding light on their potential toxic effects on cellular, tissue, and organ levels. By synthesizing key findings, this review underscores the pressing need for a thorough understanding of AuNPs toxicities, providing essential insights for safety assessment and advancing green toxicology principles.

Bio-QSARs 2.0: Unlocking a new level of predictive power for machine learning-based ecotoxicity predictions by exploiting chemical and biological information

Practical, legal, and ethical reasons necessitate the development of methods to replace animal experiments. Computational techniques to acquire information that traditionally relied on animal testing are considered a crucial pillar among these so-called new approach methodologies. In this light, we recently introduced the Bio-QSAR concept for multispecies aquatic toxicity regression tasks. These machine learning models, trained on both chemical and biological information, are capable of both cross-chemical and cross-species predictions. Here, we significantly extend these models’ applicability. This was realized by increasing the quantity of training data by a factor of approximately 20, accomplished by considering both additional chemicals and aquatic organisms. Additionally, variable test durations and associated random effects were accommodated by employing a machine learning algorithm that combines tree-boosting with mixed-effects modeling (i.e., Gaussian Process Boosting). We also explored various biological descriptors including Dynamic Energy Budget model parameters, taxonomic distances, as well as genus-specific traits and investigated the inclusion of mode-of-action information. Through these efforts, we developed Bio-QSARs for fish and aquatic invertebrates with exceptional predictive power (R squared of up to 0.92 on independent test sets). Moreover, we made considerable strides to make models applicable for a range of use cases in environmental risk assessment as well as research and development of chemicals. Models were made fully explainable by implementing an algorithmic multicollinearity correction combined with SHapley Additive exPlanations. Furthermore, we devised novel approaches for applicability domain construction that take feature importance into account. We are hence confident these models, which are available via open access, will make a significant contribution towards the implementation of new approach methodologies and ultimately have the potential to support “Green Chemistry” and “Green Toxicology”.

Alternative methods go green! Green toxicology as a sustainable approach for assessing chemical safety and designing safer chemicals

Green toxicology is marching chemistry into the 21st century. This emerging framework will transform how chemical safety is evaluated by incorporating evaluation of the hazards, exposures, and risks associated with chemicals into early product development in a way that minimizes adverse impacts on human and environmental health. The goal is to minimize toxic threats across entire supply chains through smarter designs and policies. Traditional animal testing methods are replaced by faster, cutting-edge innovations like organs-on-chips and artificial intelligence predictive models that are also more cost-effective. Core principles of green toxicology include utilizing alternative test methods, applying the precautionary principle, considering lifetime impacts, and emphasizing risk prevention over reaction. This paper provides an overview of these foundational concepts and describes current initiatives and future opportunities to advance the adoption of green toxicology approaches. Chal-lenges and limitations are also discussed. Green shoots are emerging with governments offering carrots like the European Green Deal to nudge industry. Noteworthy, animal rights and environ-mental groups have different ideas about the needs for testing and their consequences for animal use. Green toxicology represents the way forward to support both these societal needs with sufficient throughput and human relevance for hazard information and minimal animal suffering. Green toxi-cology thus sets the stage to synergize human health and ecological values. Overall, the integration of green chemistry and toxicology has potential to profoundly shift how chemical risks are evaluated and managed to achieve safety goals in a more ethical, ecologically-conscious manner.

Toxicological Aspects, Safety Assessment, and Green Toxicology of Silver Nanoparticles (AgNPs)-Critical Review: State of the Art.

In recent years, research on silver nanoparticles (AgNPs) has attracted considerable interest among scientists because of, among other things, their alternative application to well-known medical agents with antibacterial properties. The size of the silver nanoparticles ranges from 1 to 100 nm. In this paper, we review the progress of research on AgNPs with respect to the synthesis, applications, and toxicological safety of AgNPs, and the issue of in vivo and in vitro research on silver nanoparticles. AgNPs' synthesis methods include physical, chemical, and biological routes, as well as "green synthesis". The content of this article covers issues related to the disadvantages of physical and chemical methods, which are expensive and can also have toxicity. This review pays special attention to AgNP biosafety concerns, such as potential toxicity to cells, tissues, and organs.

A plea for the integration of Green Toxicology in sustainable bioeconomy strategies – Biosurfactants and microgel-based pesticide release systems as examples

A key aspect of the transformation of the economic sector towards a sustainable bioeconomy is the development of environmentally friendly alternatives for hitherto used chemicals, which have negative impacts on environmental health. However, the implementation of an ecotoxicological hazard assessment at early steps of product development to elaborate the most promising candidates of lowest harm is scarce in industry practice. The present article introduces the interdisciplinary proof-of-concept project GreenToxiConomy, which shows the successful application of a Green Toxicology strategy for biosurfactants and a novel microgel-based pesticide release system. Both groups are promising candidates for industrial and agricultural applications and the ecotoxicological characterization is yet missing important information. An iterative substance- and application-oriented bioassay battery for acute and mechanism-specific toxicity within aquatic and terrestrial model species is introduced for both potentially hazardous materials getting into contact with humans and ending up in the environment. By applying in silico QSAR-based models on genotoxicity, endocrine disruption, skin sensitization and acute toxicity to algae, daphnids and fish, individual biosurfactants resulted in deviating toxicity, suggesting a pre-ranking of the compounds. Experimental toxicity assessment will further complement the predicted toxicity to elaborate the most promising candidates in an efficient pre-screening of new substances.

Avoiding Regrettable Substitutions: Green Toxicology for Sustainable Chemistry.

Green chemistry seeks to design less hazardous chemicals, but many of the efforts to replace chemicals have resulted in so-called "Regrettable Substitutions", when a chemical with an unknown or unforeseen hazard is used to replace a chemical identified as problematic. Here, we discuss the literature on regrettable substitution and focus on an oft-mentioned case, Bisphenol A, which was replaced with Bisphenol S-and the lessons that can be learned from this history. In particular, we focus on how Green Toxicology can offer a way to make better substitutions.

The Green toxicology approach: Insight towards the eco-toxicologically safe development of benign catalysts

Green toxicology is a novel approach increasingly applied for the development of materials and chemicals that are more benign to the environment and human health than their conventional counterparts. It includes predictive eco-toxicological assessments of chemicals during the early developmental process to exclude adverse effects. In the present study, two guanidine zinc catalysts for the ring-opening polymerization of lactide were investigated using eco-toxicological tools. Namely, the fish embryo toxicity assay for teratogenic effects, the ER (α) CALUX assay for endocrine activity and the Ames fluctuation assay for mutagenic potential were applied. Both complexes showed no endocrine activity, mutagenicity or acute aquatic toxicity, however a delayed hatch could be observed, therefore suggesting potential effects on a molecular level. This proof-of-concept study aims to assess the toxicity of guanidine zinc catalysts and is a first step towards the incorporation of toxicological assessments into chemical developmental processes to achieve a sustainable and safe production of catalysts.

Green toxicology approach involving polylactic acid biomicroplastics and neotropical tadpoles: (Eco)toxicological safety or environmental hazard?

Different and alternative renewable-source materials, commonly called bioplastics, have been proposed due to the high production and consumption of petroleum-derived plastics and to their high toxicity in the biota. However, their toxicological safety has not yet been assessed in a comprehensive way; therefore, their effects on several animal groups remain completely unknown. Thus, we aimed at testing the following hypothesis: the exposure of Physalaemus cuvieri tadpoles to polylaic acid biomicroplastic (PLA BioMP) at environmentally relevant concentrations (760 and 15,020 μg/L) induces physiological changes in them. Based on the collected data, biopolymer uptake changed tadpoles' growth and development features, reduced their lipid reserves (it was inferred by decreased triglyceride levels), as well as increased reactive oxygen and nitric oxide species production after 14-day exposure. The proportional increase in total glutathione levels, and in superoxide dismutase and catalase activity, was not enough to counterbalance the production of reactive species. In addition, the two tested concentrations caused cholinesterase effect, which was marked by increased acetylcholinesterase and butyrylcholinesterase. This finding is indicative of the neurotoxic action of PLA BioMP. To the best of our knowledge, this is the first report on the harmful consequences of exposing amphibian representatives to the herein tested biopolymers. Therefore, this finding encourages further studies and contributes to demystify the idea that bioplastics are “harmless” to the aquatic biota in freshwater environments.

Green Toxicology: Connecting Green Chemistry and Modern Toxicology.

A major thrust in the concept of green chemistry is to eliminate the production of hazardous materials. Thus, sustainable toxicity testing is required for its successful implementation. Here, we present the principles of green toxicology, a concept less well known than green chemistry, but indispensable for the sustainable development of chemical products. Green toxicology entails early testing through non-animal methods, such as novel in vitro and in silico technologies in toxicity prediction, to obtain benign products in benign processes with reduced exposure. The future of non-testing toxicity prediction entails both an improved creation, management, and use of big data to optimize chemical space coverage and an increased mechanistic and biological pathway understanding which can be integrated in prediction tools. This perspective provides an introduction to chemists and toxicologists to the combined idea of green toxicology, rather than providing a comprehensive overview. Specifically, we (1) provide a brief overview of recently emerging technologies, (2) highlight the importance of collaboration between researchers to implement and integrate green toxicology in the chemical industry, and (3) present challenges that come along with the emerging technologies and propose possibilities for their better application and wider use in the future.

Green toxicological investigation for biofuel candidates

To avoid potential risks of biofuels on the environment and human, ecotoxicity investigation should be integrated into the early design stage for promising biofuel candidates. In the present study, a green toxicology testing strategy combining experimental bioassays with in silico tools was established to investigate the potential ecotoxicity of biofuel candidates. Experimental results obtained from the acute immobilisation test, the fish embryo acute toxicity test and the in vitro micronucleus assay (Chinese hamster lung fibroblast cell line V79) were compared with model prediction results by ECOSAR and OECD QSAR Toolbox. Both our experimental and model prediction results showed that 1-Octanol (1-Oct) and Di-n-butyl ether (DNBE) were the most toxic to Daphnia magna and zebrafish among all the biofuel candidates we investigated, while Methyl ethyl ketone (MEK), Dimethoxymethane (DMM) and Diethoxymethane (DEM) were the least toxic. Moreover, both in vitro micronucleus assay and OECD QSAR Toolbox evaluation suggested that the metabolites present higher genotoxicity than biofuel candidates themselves. Overall, our results proved that this green toxicology testing strategy is a useful tool for assessing ecotoxicity of biofuel candidates.

Aquatic toxicity of biofuel candidates on Daphnia magna

The increasing need for carbon-neutral, low-emission transportation sector has led to the development of advanced biofuels with tailor-made production and combustion processes. Even though the large-scale deployment of these advanced biofuels also increases the risk for their release into the environment, their toxic potency remains largely unknown. To identify hazardous biofuel candidates as early as possible, the fuel development process can be expanded by “Green Toxicology”. To demonstrate such early Green Toxicology testing, this study investigates the aquatic toxicity for the two biofuel candidates 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) on Daphnia magna. We performed the prolonged acute immobilisation assay (96 h) and the D. magna reproduction test. 2-MF induced acute effects on D. magna that were two orders of magnitude stronger than those of 2-MTHF. Furthermore, both substances affected the growth and reproductive output of D. magna in a 21 d reproduction test, with 2-MF already inducing effects with concentrations one to two orders of magnitude lower than those of 2-MTHF. Thus, our assessment of the aquatic toxicity suggests that further biofuel development should focus on 2-MTHF. Furthermore, the acute immobilisation test with D. magna was identified as a promising tool for a rapid and sensitive “Green Toxicology” screening of further biofuel candidates.

Correction to “Better Metrics for “Sustainable by Design”: Toward an in Silico Green Toxicology for Green(er) Chemistry”

Correction to “Better Metrics for “Sustainable by Design”: Toward an <i>in Silico</i> Green Toxicology for Green(er) Chemistry”

Green Toxicology-Know Early About and Avoid Toxic Product Liabilities.

Toxicology uniquely among the life sciences relies largely on methods which are more than 40-years old. Over the last 3 decades with more or less success some additions to and few replacements in this toolbox took place, mainly as alternatives to animal testing. The acceptance of such new approaches faces the needs of formal validation and the conservative attitude toward change in safety assessments. Only recently, there is growing awareness that the same alternative methods, especially in silico and in vitro tools can also much earlier and before validation inform decision-taking in the product life cycle. As similar thoughts developed in the context of Green Chemistry, the term of Green Toxicology was coined to describe this change in approach. Here, the current developments in the alternative field, especially computational and more organo-typic cell cultures are reviewed, as they lend themselves to front-loaded chemical safety assessments. The initiatives of the Center for Alternatives to Animal Testing Green Toxicology Collaboration are presented. They aim first of all for forming a community to promote this concept and then for a cultural change in companies with the necessary training of chemists, product stewards and later regulators.

Green toxicology – The future in sustainability in chemical and material development

Green toxicology – The future in sustainability in chemical and material development

Green toxicology and chemistry: Hand in glove

Green toxicology and chemistry: Hand in glove

Mechanism-specific and whole-organism ecotoxicity of mono-rhamnolipids

Biosurfactants like rhamnolipids are promising alternatives to chemical surfactants in a range of applications. A wider use requires an analysis of their environmental fate and their ecotoxicological potential. In the present study mono-rhamnolipids produced by a recombinant Pseudomonas putida strain were analyzed using the Green Toxicology concept for acute and mechanism-specific toxicity in an ecotoxicological test battery. Acute toxicity tests with the invertebrate Daphnia magna and with zebrafish embryos (Danio rerio) were performed. In addition, microbial and fungicidal effectiveness was investigated. Mutagenicity of the sample was tested by means of the Ames fluctuation assay. A selected mono-rhamnolipid was used for model simulations regarding mutagenicity and estrogenic activity. Our results indicate that mono-rhamnolipids cause acute toxicity to daphnids and zebrafish embryos comparable to or even lower than chemical surfactants. Rhamnolipids showed very low toxicity to the germination of Aspergillus niger spores and the growth of Candida albicans. No frameshift mutation or base substitutions were observed using the Ames fluctuation assay with the two tester strains TA98 and TA100. This result was confirmed by model simulations. Likewise it was computed that rhamnolipids have no estrogenic potential. In conclusion, mono-rhamnolipids are an environmental friendly alternative to chemical surfactants as the ecotoxicological potential is low.

Green toxicology.

Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.