scholarly journals Hazard assessment of beta-lactams: Integrating in silico and QSTR approaches with in vivo zebrafish embryo toxicity testing

2022 ◽  
Vol 229 ◽  
pp. 113106
Author(s):  
Ying Han ◽  
Yuanyuan Ma ◽  
Bo Chen ◽  
Jingpu Zhang ◽  
Changqin Hu
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.


2019 ◽  
Vol 20 (6) ◽  
pp. 1434 ◽  
Author(s):  
Toshikatsu Kawada ◽  
Junya Kuroyanagi ◽  
Fumiyoshi Okazaki ◽  
Mizuki Taniguchi ◽  
Hiroko Nakayama ◽  
...  

Background: Down and feather materials have been commonly used and promoted as natural stuffing for warm clothing and bedding. These materials tend to become more allergenic as they become contaminated with microorganisms, in addition to being subjected to several kinds of chemical treatments. The biological or chemical contaminants in these materials pose a major risk to human health, to consumers and manufacturers alike. Here, we report the development of an integrative evaluation method for down and feather materials to assess bacterial contamination and in vivo toxicity. Methods: To assess bacterial contamination, we quantified 16S ribosomal RNA, performed culture tests, and established a conversion formula. To determine in vivo toxicity, we performed a zebrafish embryo toxicity testing (ZFET). Results: Washing the material appropriately decreases the actual number of bacteria in the down and feather samples; in addition, after washing, 16S rRNA sequencing revealed that the bacterial compositions were similar to those in rinse water. The ZFET results showed that even materials with low bacterial contamination showed high toxicity or high teratogenicity, probably because of the presence of unknown chemical additives. Conclusions: We established an integrative evaluation method for down and feather safety, based on bacterial contamination with in vivo toxicity testing.


2003 ◽  
Vol 37 (10) ◽  
pp. 2262-2266 ◽  
Author(s):  
Yiannis Kiparissis ◽  
Parveen Akhtar ◽  
Peter V. Hodson ◽  
R. Stephen Brown

2021 ◽  
Vol 136 ◽  
pp. 111218
Author(s):  
Zohreh Salari ◽  
Hadi Tavakkoli ◽  
Ahmad Khosravi ◽  
Elahe Karamad ◽  
Ehsan Salarkia ◽  
...  

2013 ◽  
Vol 26 (8) ◽  
pp. 1168-1181 ◽  
Author(s):  
Jingpu Zhang ◽  
Jianqin Qian ◽  
Junwei Tong ◽  
Dousheng Zhang ◽  
Changqin Hu

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siti Rokhiyah Ahmad Usuldin ◽  
Wan Abd Al Qadr Imad Wan-Mohtar ◽  
Zul Ilham ◽  
Adi Ainurzaman Jamaludin ◽  
Nur Raihan Abdullah ◽  
...  

AbstractNatural mycelial biomass (MB) and exopolysaccharides (EPS) of Malaysian tiger milk mushroom Lignosus rhinocerus are considered high-end components due to their high commercial potential value in drug discovery. This study aims to evaluate the toxicity of the mushroom extracts’ generated in a bioreactor using the zebrafish embryo toxicity (ZFET) model assay as a new therapy for treating asthma. Both MB and EPS extracts, at concentrations 0.16–10 mg/mL, were tested for ZFET and early development effects on Zebrafish Embryos (ZE) during 24–120 h post-fertilisation (HPF). Findings revealed that MB was deemed safe with an LC50 of 0.77 mg/mL; the EPS were non-toxic (LC50 of 0.41 mg/mL). Neither MB nor EPS delayed hatching nor teratogenic defects in the treated ZE at a 2.5 mg/mL dose. There were no significant changes in the ZE heart rate after treatments with MB (130 beats/min) and EPS (140 beats/min), compared to that of normal ZE (120–180 beats/min). Mixing both natural compounds MB and EPS did not affect toxicity using ZFET testing; thus, intimating their safe future use as therapeutic interventions. This represents the first study to have used the ZFET assay on MB and EPS extracts of L. rhinocerus for future health applications.


2014 ◽  
Vol 21 (6) ◽  
pp. 2508-2518 ◽  
Author(s):  
Àngels Ruyra ◽  
Amirali Yazdi ◽  
Jordi Espín ◽  
Arnau Carné-Sánchez ◽  
Nerea Roher ◽  
...  

Toxics ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 126
Author(s):  
John C. Achenbach ◽  
Cindy Leggiadro ◽  
Sandra A. Sperker ◽  
Cindy Woodland ◽  
Lee D. Ellis

The movement away from mammalian testing of potential toxicants and new chemical entities has primarily led to cell line testing and protein-based assays. However, these assays may not yet be sufficient to properly characterize the toxic potential of a chemical. The zebrafish embryo model is widely recognized as a potential new approach method for chemical testing that may provide a bridge between cell and protein-based assays and mammalian testing. The Zebrafish Embryo Toxicity (ZET) model is increasingly recognized as a valuable toxicity testing platform. The ZET assay focuses on the early stages of embryo development and is considered a more humane model compared to adult zebrafish testing. A complementary model has been developed that exposes larvae to toxicants at a later time point during development where body patterning has already been established. Here we compare the toxicity profiles of 20 compounds for this General and Behavioral Toxicity (GBT) assay to the ZET assay. The results show partially overlapping toxicity profiles along with unique information provided by each assay. It appears from this work that these two assays applied together can strengthen the use of zebrafish embryos/larvae as standard toxicity testing models.


Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
B Ovalle-Magallanes ◽  
A Madariaga-Mazón ◽  
A Navarrete ◽  
R Mata

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