Mechanisms of Toxicity of Chemical Compounds and Natural Compounds

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: 24 April 2026 | Viewed by 545

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Guest Editor
Faculty of Veterinary, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: in vitro and in vivo studies; agrochemicals; medicinal plant extracts; cytotoxicity; toxicology
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Special Issue Information

Dear Colleagues,

Knowledge, understanding, and analysis of the toxicity mechanisms of chemical compounds, such as xenobiotics or natural compounds, are essential for assessing risks to human health, animal health, and the environment.

This Special Issue is dedicated to acute or chronic toxicity studies based on standardized protocols such as those of the OECD, which address the toxic effects of both chemical and natural substances using in vivo and in vitro models, mainly through experimental testing.

It includes research focused on the characterization of acute or chronic cytotoxic, genotoxic, hepatotoxic, and neurotoxic effects, among others, as well as mechanistic studies exploring molecular pathways, oxidative stress, mitochondrial dysfunction, inflammation, and programmed cell death. Contributions related to new toxicological assessment methodologies, biomarkers of exposure and toxicity, and alternative strategies to animal experimentation are also valued. This Special Issue aims to provide a platform for the exchange of knowledge between scientists, regulatory and legislative agencies, and health professionals, promoting a better understanding of the toxicological and safety impact of the different compounds to which all species of toxicological interest are constantly exposed.

Dr. José Luis Rodríguez Gutiérrez
Guest Editor

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Keywords

  • chemical compounds
  • natural compounds
  • toxicity mechanisms
  • in vivo
  • in vitro
  • assessing risks
  • toxicological assessment
  • exposure
  • health

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Published Papers (2 papers)

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Research

19 pages, 3437 KB  
Article
Enterohepatic Recirculation-Mediated Reabsorption of Aristolochic Acid I: Revealed by Toxicokinetics and Metabolite Identification in Rats
by Lieyan Huang, Lixing Nie, Xiao Ye, Zhi Lin, Ying Liu and Feng Wei
Toxics 2025, 13(11), 919; https://doi.org/10.3390/toxics13110919 (registering DOI) - 27 Oct 2025
Abstract
Aristolochic acid I (AAI) is widely recognized as a genotoxic and cytotoxic compound. To rationally propose detoxification strategies, it is essential to fully elucidate the in vivo disposition of AAI. Nevertheless, the toxicokinetic characteristics of AAI, particularly the possible involvement of the recirculation [...] Read more.
Aristolochic acid I (AAI) is widely recognized as a genotoxic and cytotoxic compound. To rationally propose detoxification strategies, it is essential to fully elucidate the in vivo disposition of AAI. Nevertheless, the toxicokinetic characteristics of AAI, particularly the possible involvement of the recirculation process, remain incompletely understood. In this research, toxicokinetics of AAI was studied following a single oral administration of AAI in Fisher rats (10, 30 and 100 mg/kg, n = 6). A method of ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was developed to achieve the quantitation of AAI in rat plasma. Plasma concentration–time profiles and kinetic parameters were analyzed to characterize the toxicokinetic behavior of AAI. A secondary elevation was observed in the plasma concentration–time profiles of AAI, suggesting the existence of AAI reabsorption. The non-linear elimination kinetics of AAI might be attributed to capacity-limited excretion via bile. Additionally, the biliary excretion of AAI and several key metabolites was also explored through qualitative analysis of bile samples. For the first time, AAI-O-glucuronide was identified in bile, providing further support for enterohepatic recirculation (EHR)-mediated reabsorption of AAI. In conclusion, these findings provided solid evidence for EHR-mediated reabsorption of AAI in rats. The recirculation process might be a key mechanism responsible for the prolonged retention of AAI. In the future, detoxification strategies targeting the EHR process could be effective approaches to minimize the systemic exposure of AAI. Full article
(This article belongs to the Special Issue Mechanisms of Toxicity of Chemical Compounds and Natural Compounds)
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16 pages, 2155 KB  
Article
Toxicological Evaluation and Antimicrobial Activity of a Natural Thymol–Eucalyptol-Based Mixture
by Boris Lira-Mejía, Luis Barrios-Arpi, Carlos Villaorduña, Tatiana Ancajima, José-Luis Rodríguez, Alejandro Romero, Víctor Puicón and Hugo Patiño
Toxics 2025, 13(10), 875; https://doi.org/10.3390/toxics13100875 - 14 Oct 2025
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Abstract
Currently, safe alternatives with very low toxicity and good antimicrobial activity are being sought to replace chemical compounds that can be harmful to animal and human health. For this reason, this study evaluated the safety and biofunctional microbiocidal potential of an extract composed [...] Read more.
Currently, safe alternatives with very low toxicity and good antimicrobial activity are being sought to replace chemical compounds that can be harmful to animal and human health. For this reason, this study evaluated the safety and biofunctional microbiocidal potential of an extract composed of thymol and eucalyptol. Toxicity tests showed low toxicity in both chickens (2000 mg/kg bw) and Artemia salina (EC50 = 2003 mg/L) and Daphnia magna (EC50 = 87 mg/L), indicating a safe usage profile. Oxidative stress biomarkers (nitrite and MDA) and antioxidant enzymes (SOD and catalase) improved in treated chickens at 20 days of age. The hematological and biochemical parameters of the treated birds showed normal values similar to those of the control group chickens, with better protein levels and lower AST levels. Histology of the kidney, intestine, and liver showed no changes in any group, confirming the absence of systemic adverse effects. At the molecular level, an improvement in the expression of tight junction proteins (claudin and occludin) was observed, suggesting a strengthening of the intestinal barrier integrity. Finally, the extract demonstrated an antimicrobial effect (E. coli, C. perfringens, Salmonella sp. and Pseudomonas sp.) comparable to that of organic acids commonly used as food preservatives, positioning it as a promising alternative in applications. Full article
(This article belongs to the Special Issue Mechanisms of Toxicity of Chemical Compounds and Natural Compounds)
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