**1. Introduction**

Particulates span bioengineered nanoparticles (NP) to geologic detri and fume agglomerates, and either soft nanoparticles or hard particulates with distinct dissolution barrier energetics [1, 2] and forms of toxicity [3]. These types of nanoparticles include colloidal such as carbon black and soot [4]. Beryllium and transition metal

oxide agglomerates or aggregates [5], or unionized gold or silver colloidal nanoparticles with the oxidized electrophilic surface [6], shell-coated, aminosilane ionic coat on shell surface modification [7], and PEGylated with covalently-bound etheroylated isophilic repeating unit chain to coat [8]. Size distribution is between nanometers [9] to microns; composition, size, aspect and surface properties [10] are associated with particulate matter exposure-related toxicity [8, 11], which includes the nuisance dusts [12]. The initial observations on exposure-related effects of incompletely combusted products begin in 1775 with those of Percivall Pott on the soot composition being carcinogenic in chimney sweeps [13] as the initial cross-sectional study. The remainder of the evidence on association and causality subsequent to is by the application of non-parametric statistical methods, and is from the epidemiologic studies, both case-control with comparative groups and retrospective or prospective cohort [14].

Particulate toxicity can be studied at the single cell level, in experimental small animal subjects and by time-weighted average (TWA) air sampling-coupled to functional assessments of exposed persons, which is by air sampling with filter-threshold devices or flow density separation elutriation [15, 16], and study of nanoparticulate matter particle size distributions adsorbed on grids or of the sub-cellular morphology with electron diffraction imaging (TEM) [17], or by detection of size differences in solution with dynamic-light scattering (DLS) [18], and enhanced dark field microscopy (EDFM) with hyperspectral imaging (HSI) for accurate detection of sampled less dense NPs on filters (i.e. MCE) [19]. Isolation can be also be by specimen digestion and particle fractionation with detection at 10<sup>12</sup> M concentration resolution [20], and nanoparticle properties characterization is coupled to toxicity assessments at single cell molecular scale resolution; and in this day combined to high-sensitivity study of gene expression by quantitative PCR (qPCR), RNA sequencing, and epigenetic changes by bisulfite genomics imaging [21].

The *d*-orbital block detritus minerals between Group 3 – Group 12 are the transition metals with polyhedral bonding configuration to Group 16 nonmetals, and the subtypes of dichotomous earth particulates include the inosilicates such as Silicon dioxide (SiO2) or partial oxidation state ideal ores such as Copper ore (Cu12As4S13) with polyhedral bond configuration crystal lattice structures determinable by X-ray diffraction [22], inaddition to the asbestos classes of ionic minerals-containing rock with silica-based ionic composition; and there are also the other non-crystalline structure oxides such as the synthetic amorphous and biogenic silicates. There are several compositions of ore lithificates, and regional contamination secondary to industrial processes.

Inaddition to the naturally-occurring detritus particulates, there are the combustion-generated particulate oxides that agglomerate over time [23] with increased particle size with lower degradability and increased toxicity risk, and the chemically-synthesized monodisperse Zinc (II)- or Cadmium (II)- based transition metal-nonmetal (Se<sup>2</sup>, S<sup>2</sup>) semi-conductor materials that are valence-conduction band gap size-tunable for variable wavelength emission properties with applicability to electronic systems [24]. The hard NPs, ferrous or ferric iron oxides (FeO, Fe2O3) have been utilized for supraparamagnetic MRI (T2W) [25] and cell tracking by transfection loading [26]; whereas the others, soft nanoparticles, with the classic fourelectron C-atom bonding arrangement and exterior biocompatibility are within liposomal phospholipid encapsulation and in dendritic forms with diaminobutane cores that are utilized for biomedical application small molecule chemoxenobiotic enhanced permeation and retention (EPR). Toxicities include immediate systemic inflammatory

response and hypersensitivity with earlier formulations, immunogenic sensitization with repeated administrations that also applies to nervous tissue treatments [27], while biodistribution to reticuloendothelial cell-containing tissues also limits efficacy [28].

Both hard and soft matter are in the inhalable size range (1–100 μm) [29], and result in risk of direct toxicity through air, water or food, and waste bioaccumulates to environment including plastics. In this chapter, the current day principles on bioengineered NP and environmental particulate matter exposure-related pathology causation, particulates molecular structure and cell biomolecular pathways activation, regulatory standards for exposure limits, industrial hygiene and cell responses to the potential for either immediate or delayed cellular toxicity are presented.

### **2. Particulates, aerosols and droplets and respiratory tree deposition**

Nano-sized particulates (NPs), agglomerated nano- or micro-nanoparticles, can be defined as nanometer (nm) to micron size agglomerates with nanoparticle size in one dimension (1-D) being ≤100 nm, while particulate or agglomerate structural irregularity necessitates characterization by aerodynamic size with adjustment for air flow effects inhomogeneity in real conditions. The inhalable size range of particles, agglomerates and large aerosols includes Zika virus (45 nm, single), smoke (400– 700 nm), bacterium (1–5 μm), dust particle (2.5 μm), cells (RBC, 8 μm), pollen (15 μm) and extends into droplets (> 100 μm), **Table 1**. Detritus minerals and particulates. Fine particles are the 2 nm to 2 μm size range of nanoparticulates including atmospheric aerosols with several different molecules that are found in association include sulfate (SO4 <sup>2</sup>), carbon (soot), lead, ammonium (NH4 + ), As, Se and protons (H+ ); and coarse particles constitute the 2 μm to 100 μm interval of nanoparticulates with iron, calcium, titanium, magnesium, potassium, phosphate (PO4 <sup>2</sup>), silicon, aluminum and organic (i.e. pollen and plant matter). The formation of droplets in trimodal distributions results from volatile gas to hot vapor and condensation upon cooling to primary particles and chain aggregates (5 nm – 100 nm) [51], or gas chemical conversion to low volatility vapor, nucleation and condensation growth of aggregated nuclei into the larger droplet forms with coagulation (50 nm – 8 μm), while the mechanically-generated aerosol range (1–90 μm) is for combination aerosol particulates with emissions, dust, volcano ash and plant matter; with formation, the weighted increase in size results in rainout or sedimentation depending on size range, and the 90 nm to 2 micron range is known as the accumulation range.

The human respiratory tree accommodates a certain size range of particulate agglomerates in the breathing zone [29], and the particle aerodynamic equivalent diameter (*D*ae) is the diameter of a sphere with same falling velocity (*D*a) corrected for particle density (*ρ*). Based on the initial studies on human exposure to Amosite (A), Crocidolite (CR) or Chrysotile (CH) asbestos or glass (G) fibers, sampled and measured by the aerosol spectrometer [52], i) the fiber length/fiber diameter (aspect ratio) becomes independent of the aerodynamic equivalent diameter (*D*ae, *D*e)/fiber diameter ratio at aspect ratios greater than around 10: 1 and suggests that the width becomes the primary determinant of deposition, where *D*e/*D*<sup>f</sup> follows a fractional base-variable power function as particle diameters do not increase much for lengthier fibers; and ii) the equivalent diameter to fiber diameter relationship for three of the four fiber types is non-linear and weighted towards the equivalent diameter (A, CR, G) over the actual diameter (3.5 μm, 3 μm, 2.5 μm) but less weighted to the same in



*Bioengineered Nanoparticle and Environmental Particulate Matter Toxicity: Mechanisms… DOI: http://dx.doi.org/10.5772/intechopen.112595*


**Table 1.** *Detritus minerals*

 *and particulates.*

*fine* 

*PM/respirable,*

 *< 3.5–2.5 μm).*

case of the Chrysotile fiber type. Thus, i) the falling velocity of aspected fiber particle agglomerates is predictable mostly by the particulate equivalent fiber diameter (*D*e) that is inclusive of internal voids present in fiber aggregates; ii) particulates that possess minimal diameters are not subject to sedimentation or inertial impaction in the upper airway, and due to width dimension-weighting result in deep deposition within the respiratory tree [52]; and iii) particulate interception occurs within the respiratory tree for compact particles of different equivalent diameters than aspected particles of different lengths with earlier stage penetration within the respiratory tree for compact large size particulates, i.e. > 10 microns.

Based on review of studies 1969–1974, an inhalable particulate (IP) is defined as being ≤15 microns, and at between 2 and 3.5 microns is considered the limit by the ACGIH based on aerodynamic equivalent diameter [51] with the diameter being at 2.5 to 3.5 microns in maximal alveolar tissue accretion, and at 50% human airway penetration efficiency (*P*TB, *P*ET), agglomerate particle size is at 15 microns at normal flow during light exercise [29]. In the same study, the deposition of larger particles by impaction at either the laryngeal or tracheobronchial region is best-fitted by a non-linear model with co-variables, aerodynamic diameter (*d*a), inspiratory flow rate (*Q*total), tidal volume (*V*T), and a gender- and age- category-specific scaling factor (*SF*t), which models the deposition efficiency for a range of particle sizes and shows a higher deposition efficiency in the tracheobronchial (TB) region for a particle of the same size consistent with the findings of, 70%, *P*TB (tracheobronchial) versus 50%, PET (laryngeal).
