Particle Safety Assessment in Additive Manufacturing: From Exposure Risks to Advanced Toxicology Testing

Abstract

Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles’ physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle—spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.

NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity

“…An exception is crystalline silica particles, where studies have demonstrated both phagocytosis-dependent ( 41 ) and -independent ( 78 ) NLRP3 inflammasome activation. These contrasting results may be due to differences in the properties of the silica particles, including size, shape, surface properties, or formation of a protein corona coating the particles ( 79 ). Following the formation of the phagolysosome, particles may interact with the (phago)lysosomal membrane leading to lysosomal membrane permeabilization (LMP) or rupture with subsequent release of lysosomal content into the cytosol that in turn will activate the NLRP3 inflammasome.…”

Journey of micronanoplastics with blood components

“…This inflammasome may be used as a sensor for detecting the immunotoxicity of MNPs. 231 Polystyrene MNPs triggered ROS buildup and activation of the NLRP3 inflammasome in human primary macrophages, 232 human monocytic (THP-1) 233 and mouse lung (MLE-12) cell lines, 234 and in mouse hepatocytes (AML12 cell line). 36 Polystyrene MNPs have been proven to activate the NLRP3/caspase-1 signaling pathway in rat 235 and mouse 236 models in vivo , triggering inflammatory reactions and pyroptosis.…”

“…(5) MNPs have been discovered to be phagocytosed by immune cells, such as macrophages, as evidenced by an increase in the generation of proinflammatory cytokines (interferons, interleukins, tumor necrosis factors, NLRP3 inflammasome, 231 etc. ) and prostaglandins.…”

“…WBC count was drastically reduced in C57BL/6 mice treated with 0.5 mg of 5 mm PSMPs, which supports the abovementioned effects. 174 (5) MNPs have been discovered to be phagocytosed by immune cells, such as macrophages, as evidenced by an increase in the generation of proinammatory cytokines 231 etc.) and prostaglandins.…”

Comprehensive Analysis of Two H13-Type Starting Materials Used for Laser Cladding and Aerosol Particles Formed in This Process

“…The nanoparticle emission of laser-DED machines has been recognized, and some studies have already addressed the chemical and physical characterization of the emitted particles [ 10 ] and investigated occupational health-related issues [ 5 , 11 ]. The toxic properties of metal nanoparticles are now well known [ 5 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ] and their effects need to be taken into account in working environment design and laser-DED machine construction. Although exposure protection and regulatory measures in related industries (welding, etc.)…”