Current Nanoscience 1875-6786/20 $65.00+.00 © 2020 Bentham Science Publishers Nelson Durán 1,2,3,4, * , Wagner J. Fávaro 1,2,3 and Amedea B. Seabra 2,3,4, * 1 Institute of Biology, Urogenital, Carcinogenesis and Immunotherapy Laboratory, Department Genetics, Evolution and Bioagents, University of Campinas, (UNICAMP), Campinas, SP, Brazil; 2 Laboratory on Nanostructures, Synthesis and Biological Interactions (NanoBioss), Institute of Chemistry, University of Campinas, SP, Brazil; 3 Nanomedicine Research Unit (Nanomed), Federal University of ABC (UFABC), Santo André, Brazil; 4 Center for Natural and Human Sciences, Federal University of ABC (UFABC), Santo André, SP, Brazil A R T I C L E H I S T O R Y Received: May 28, 2018 Revised: July 3, 2018 Accepted: July 28, 2018 DOI: 10.2174/1573413714666180809121322 Abstract: Actually, many discussions on the potential risks of silver nanoparticles (AgNPs) have been reported; however, unfortunately, very few considered the great differences between the nature of silver and sources of their syntheses. All data suggested that the effects on toxicity of AgNPs are related to the combination of the specific properties of AgNPs. In this context, this review presents and discusses the recent progress in the nanotoxicity of AgNPs, obtained by different biogenic syn- thetic protocols, in comparison with chemical synthetic methods, driving to the formation of nanoparticles with diverse structures, and size distributions. Biogenic syntheses of AgNPs using several biological sources and other chemical agents are presented and discussed. Toxicity in differ- ent animals is also presented and discussed. By considering the actual state of the art, it can be as- sumed that oral, intravenous and inhalation doses of AgNPs from 0.1 to 2 mg/Kg in mice and rats are considered a safe administration. In terms of ecotoxicity, it is more concerning since many of the in vivo assays showed a very low lethal dose, i.e., 50% (LD50). Therefore, we have to be very careful with the AgNPs residues in the environment. Keywords: Silver nanoparticles, biogenic nanoparticles, toxicology, nanotoxicity, in vivo, in vitro. 1. INTRODUCTION Many discussions on the potential risks with silver nanoparticles (AgNPs) have been published. However, very few considered the great differences between the nature of silver and sources of their syntheses. Wijnhoven et al. [1] reported an inventory in order to recognize evident gaps that were known previously as risks for both man and the envi- ronment which can be estimated for non-nanosized chemi- cals. There are several suggestions that the toxicity of AgNPs is due to the association of the special properties of AgNPs and the generation of Ag + (silver ions) from the nanomaterials. Another topic, which they pointed out, was to determine to what extent AgNPs will enter the body. A similar view was presented by Durán et al. [2], related to the estimation of the potential uses of AgNPs to control patho- gens with an emphasis on their action against bacteria, toxic- ity and action´s mechanisms. *Address correspondence to these authors at the Institute of Biology, Uro- genital, Carcinogenesis and Immunotherapy Laboratory, Department Genet- ics, Evolution and Bioagents, University of Campinas, (UNICAMP), Campinas, SP, Brazil; Tel: +55-11-3356-7665; E-mails: duran@iqm.unicamp.br; nelsonduran1942@gmail.com Center for Natural and Human Sciences, Universidade Federal do ABC (UFABC), Santo André, SP, Brazil; Tel: +55-11-4996-8374; E-mail: amedea.seabra@ufabc.edu.br Several in vitro studies indicated that AgNPs are toxic to the mammalian cells derived from lung, skin, liver, brain, vascular system, and reproductive organs. In vivo biodistribution and toxicity researches on mice and rats have shown that AgNPs applied by inhalation, oral or intraperitoneal injection were found in blood, causing toxic- ity in many organs. All these facts were summarized and specifically demonstrate the actual studied highlights on unfavorable effects of AgNPs on human health [3]. An im- portant aspect is the necessity of exhaustive characterization of AgNPs before they are used in medical care in environ- mental studies. It is important to emphasize that genotoxicity not only depends on particle size, surface modification, and exhibi- tion route, but also on the time duration. Six years ago, available data on animal suggested different mechanisms by living organisms interacting upon their contact with nanopar- ticles. Despite considerable inconsistencies in the data report and the scarcity of validated tests and/or methods, safety hazard assessment of engineered nanomaterials was yet lim- ited in that time [4]. It has been demonstrated that biogenic AgNPs were less cyto/genotoxic in vivo as compared with using the chemical synthesized method of AgNPs. Then, human cells demonstrated to have a higher resistance to the toxicity of AgNPs as compared with other organisms [5, 6]. Send Orders for Reprints to reprints@benthamscience.net 292 Current Nanoscience, 2020, 16, 292-320 REVIEW ARTICLE What do we Really Know about Nanotoxicology of Silver Nanoparticles In vivo? New Aspects, Possible Mechanisms, and Perspectives