# An Overview of Tools and Challenges for Safety Evaluation and Exposure Assessment in Industry 4.0
## 2 Airborne Hazards in the Workplace  
Exposure to particulate matter is a major concern in both occupational and residential settings [16]. Particulate matter is commonly grouped as inhalable or coarse particles with a diameter smaller than 10 \(\upmu\)m (PM10), respirable particles with a diameter under 4 \(\upmu\)m (PM4), and fine particles with a diameter under 2.5 \(\upmu\)m (PM2.5). According to their size, particles are differentiated based on their aerodynamic equivalent diameter; the smaller the particle size, the larger the surface per unit mass, increasing the potency of the particles that can reach the soft tissue, leading to adverse health effects [17,18]. In recent years, interest in ultrafine particles or nanoparticles smaller than 100 nm has increased [19]. Nanoparticles include particles that are either (i) natural (independent from any specific process), (ii) incidental (produced unintentionally during a process), (iii) engineered (purposefully manufactured). During inhalation, particles present different deposition patterns depending on their size [3]. A large portion of particles smaller than 10 \(\upmu\)m can enter the respiratory system while a substantial portion of PM4 can pass through the head airways and reach the alveoli. Particles between 100 nm and 1 \(\upmu\)m enter the respiratory tract but are mostly removed through exhalation. Ultrafine particles (UFPs) pose the highest risk since they are mainly deposited in the alveolar region [3]. They can be absorbed by blood circulation and translocate to other organs of the body or cause adverse brain effects by depositing in the olfactory pathway. Previous studies have shown that UFPs have the ability to penetrate the cellular membrane causing the generation of reactive oxygen species (ROS), leading to oxidating stress and subsequently mitochondrial damage [20] and apoptosis [21] (Figure 1). A detailed framework for occupational assessments of exposure to nanoparticles was developed by the Organisation for Economic Co-operation and Development (OECD) and published in 2015 [22]. This framework includes three tiers of increasing detail aimed at providing a cost-effective evaluation by moving to higher tiers only when substantial exposure cannot be excluded through lower assessment tiers. Following this approach, assessment begins with a detailed gathering of information related to materials, process, and workplace characteristics that may significantly impact exposure. At higher tiers, on-site real-time measurements of airborne particles are performed followed by the off-site analysis of air samples. The principles of the framework have been expanded to apply to the exposure assessment for larger particles [23]. Bioaerosols constitute a complicated and serious hazard in the workplace, which can lead to mucous membrane irritation, hypersensitivity pneumonitis, and benign organic dust toxic syndrome [24]. Known as \"organic dust\", bioaerosols contain biological agents, such as bacteria, fungi, viruses, or other allergens and microorganisms, from indoor or outdoor sources. Indoor sources can be linked to the occupational environment, leading to particles of cotton and wood dust, flour, and skin scales, or associated with human activity (e.g., breathing, sneezing, coughing) [25]. Exposure to bioaerosols is similar to airborne particulate matter, since the penetration of bioaerosol particles in the respiratory tract depends on several physical and chemical properties, such as their shape, size, and chemical composition. An occupational exposure assessment includes the collection or air samples via cyclones and dust cassettes and subsequent chemical analysis or cultivation- and culture-based methods concerning airborne fungi and bacteria [24; 26]. The great variety of biological agents hinders the analysis and evaluation of risks associated with bioaerosol exposure. Exposure to fumes in the workplace constitutes a significant health hazard, occurring in various activities, such as metal welding, soldering, and spray painting [27; 28].