A Strategy Towards the Generation of Testable Adverse Outcome Pathways for Nanomaterials

被引:12
作者
Murugadoss, Sivakumar [1 ]
Vrcek, Ivana Vinkovic [2 ]
Pem, Barbara [2 ]
Jagiello, Karolina [3 ,4 ]
Judzinska, Beata [3 ]
Sosnowska, Anita [3 ]
Martens, Marvin [5 ]
Willighagen, Egon L. [5 ]
Puzyn, Tomasz [3 ,4 ]
Dusinska, Maria [6 ]
Cimpan, Mihaela Roxana [7 ]
Fessard, Valerie [8 ]
Hoet, Peter H. [1 ]
机构
[1] Katholieke Univ Leuven, Unit Environm & Hlth, Lab Toxicol, Dept Publ Hlth & Primary Care, B-3000 Leuven, Belgium
[2] Inst Med Res & Occupat Hlth, Zagreb, Croatia
[3] QSAR Lab Ltd, Gdansk, Poland
[4] Univ Gdansk, Fac Chem, Gdansk, Poland
[5] Maastricht Univ, Dept Bioinformat BiGCaT, NUTRIM, Maastricht, Netherlands
[6] Norwegian Inst Air Res NILU, Hlth Effects Lab, Dept Environm Chem, Kjeller, Norway
[7] Univ Bergen, Fac Med, Dept Clin Dent, Bergen, Norway
[8] Anses French Agcy Food Environm & Occupat Hlth &, Fougeres Lab, Toxicol Contaminants Unit, Fougeres, France
基金
欧盟地平线“2020”;
关键词
CARBON NANOTUBES; IN-VITRO; ENGINEERED NANOMATERIALS; SILICA NANOPARTICLES; DECISION-MAKING; RISK-ASSESSMENT; ZINC-OXIDE; NANO-QSAR; TOXICITY; EXPOSURE;
D O I
10.14573/altex.2102191
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Manufactured nanomaterials (NMs) are increasingly used in a wide range of industrial applications leading to a constant increase in the market size of nano-enabled products. The increased production and use of NMs are raising concerns among different stakeholder groups with regard to their effects on human and environmental health. Currently, nanosafety hazard assessment is still widely performed using in vivo (animal) models, however the development of robust and regulatory relevant strategies is required to prioritize and/or reduce animal testing. An adverse outcome pathway (AOP) is a structured representation of biological events that start from a molecular initiating event (MIE) leading to an adverse outcome (AO) through a series of key events (KEs). The AOP framework offers great advancement to risk assessment and regulatory safety assessments. While AOPs for chemicals have been more frequently reported, the AOP collection for NMs is limited. By using existing AOPs, we aimed to generate simple and testable strategies to predict if a given NM has the potential to induce a MIE leading to an AO through a series of KEs. Firstly, we identified potential MIEs or initial KEs reported for NMs in the literature. Then, we searched the identified MIE or initial KEs as keywords in the AOP-Wiki to find associated AOPs. Finally, using two case studies, we demonstrate how in vitro strategies can be used to test the identified MIE/KEs.
引用
收藏
页码:580 / 594
页数:15
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