*Article* **Chemical Recycling of WEEE Plastics—Production of High Purity Monocyclic Aromatic Chemicals**

**Tobias Rieger 1, Jessen C. Oey 1, Volodymyr Palchyk 1, Alexander Hofmann 1, Matthias Franke 1,\* and Andreas Hornung 1,2**

**Abstract:** More than 200 kg real waste electrical and electronic equipment (WEEE) shredder residues from a German dismantling plant were treated at 650 ◦C in a demonstration scale thermochemical conversion plant. The focus within this work was the generation, purification, and analysis of pyrolysis oil. Subsequent filtration and fractional distillation were combined to yield basic chemicals in high purity. By means of fractional distillation, pure monocyclic aromatic fractions containing benzene, toluene, ethylbenzene, and xylene (BTEX aromatics) as well as styrene and α-methyl styrene were isolated for chemical recycling. Mass balances were determined, and gas chromatography–mass spectrometry (GC-MS) as well as energy dispersive X-ray fluorescence (EDXRF) measurements provided data on the purity and halogen content of each fraction. This work shows that thermochemical conversion and the subsequent refining by fractional distillation is capable of recycling WEEE shredder residues, producing pure BTEX and other monocyclic aromatic fractions. A significant decrease of halogen content (up to 99%) was achieved with the applied methods.

**Keywords:** WEEE; chemical recycling; pyrolysis; recovery of aromatics; oil upgrading; dehalogenation

### **1. Introduction**

Waste electrical and electronic equipment (WEEE) represents a significant source of almost all precious and critical metals, but their recovery potential is far from being fully exploited as things stand today. At the end of state-of-the-art WEEE treatment processes, one or more output fractions are left behind, which are usually sent to landfills or to energetic utilization in waste incinerators ([1] pp. 131–133), [2,3]. With those fractions, remaining metals get lost, irretrievable for material recovery ([1] pp. 209–212), [4]. At the same time, WEEE and its output fractions contain high-quality plastics like HIPS, ABS, epoxy resins, PS, PE, PP, and PVC [5–7]. However, these plastics show high concentrations of flame retardants (FR) as TBBPA, DDO, HBCD, and DDE [3], resulting in bromine and chlorine concentrations of 0.6–4.0 wt.% [8].

As mechanical recycling recovers plastics in their given polymeric composition, stateof-the-art processes are not able to remove or to eject flame retardants from FR-containing WEEE plastics effectively. The recovery of unpolluted plastics by means of mechanical recycling is thus mostly limited to FR-free fractions ([1] pp. 209–212), [2,3,9]. Against this background, pyrolysis seems to offer a promising solution to complement established mechanical recycling processes, especially regarding highly chlorinated and brominated WEEE-plastics ([1] pp. 131–133), [3,5,8,10].

Due to the importance of effectively recycling and decontaminating WEEE plastics [1–3,9,11–13], numerous researchers have investigated chemical recycling of WEEE or

**Citation:** Rieger, T.; Oey, J.C.; Palchyk, V.; Hofmann, A.; Franke, M.; Hornung, A. Chemical Recycling of WEEE Plastics—Production of High Purity Monocyclic Aromatic Chemicals. *Processes* **2021**, *9*, 530. https://doi.org/10.3390/pr9030530

Academic Editor: Daniel Vollprecht

Received: 15 February 2021 Accepted: 9 March 2021 Published: 16 March 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

of the flame retarded plastics present in such [14–24]. Most studies on novel recycling approaches regarding WEEE focus on the recovery of metals [4,25–27], whereas investigations on recycling of nonmetal fractions of real WEEE are limited [12].

Different chemical recycling technologies for WEEE plastics like thermal pyrolysis [4,21,22,28–32], co-pyrolysis [33–36], two step pyrolysis [33,37], catalytic pyrolysis [23,28,38–45], microwave-assisted pyrolysis [28,46,47], and combinations thereof [24,44,47,48] have been studied.

A very recent review by Charitopoulou et al. [12] on recycling of WEEE plastics comes to the conclusion that pyrolysis is considered a favorable technology to recycle FRcontaining plastics from WEEE. The formation of PXDD/F is theoretically suppressed due to the absence of oxygen. However, the oxygen already present in the nonmetal fraction of WEEE in practice leads to PXDD/F [11,41,48].

Several pretreatment technologies were studied to remove BFR from WEEE plastics prior to pyrolysis [31,49–56]. Examples of common pretreatment technologies are solvent extraction with isopropanol, toluene, or methanol, as well as supercritical fluid technologies with acetone, methanol, or ethanol as media. Such techniques were found to have good dehalogenation effectiveness. However, their high operational cost and energy consumption limit industrial implementation [12].

Patent research revealed several patent publications in the field of pyrolysis reactors or processes to treat mixed plastic wastes [57–64] as well as WEEE in particular [65–69]. Most reactor and process concepts are designed to either decompose WEEE in order to prevent landfilling of large volumes of hazardous wastes, dehalogenation, and/or to produce valuable chemicals or fuels at temperatures between 200 and 800 ◦C. Patented reactor concepts include screw reactors [58,70], U-shaped reactors [68], and fluidized bed reactors [61]. Most patents address thermal or catalytic pyrolysis. However, methods including vacuum pyrolysis [67] or the addition of other material, e.g., heavy oil or hydrocracking steams to a pyrolysis process [60,63], were published. Furthermore, methods comprising multistep processes are present. Examples are upstream technologies prior to pyrolysis [63,65,66] or downstream purification technologies to enhance product quality [57,59,60,67].  A crucial point in the thermochemical processing of FR-containing plastics is, however, the copper catalyzed formation of hazardous polyhalogenated dibenzo-*p*-dioxins and furans (PXDD/F) as precursors for PXDD/F, namely chlorine and bromine, are present in WEEE [2,73]. In order to prevent or to minimize their formation during thermochemical treatment, the critical temperature for PXDD/F formation between 200 and 600 ◦C [74,75] should be skipped quickly by rapidly heating up the plastics to >450 ◦C [4].

Consequently, Fraunhofer UMSICHT developed an innovative thermochemical conversion process for treatment of composite materials, including WEEE [70]. This process is based on an innovative auger reactor equipped with a unique heat exchanger (Section 2.1). The so-called iCycle® process (intelligent Composite Recycling) enables the conversion of WEEE fractions at very constant and controlled process conditions (heating up and retention time of feedstock, stability of process temperature). The current contribution deals with the recovery of chemicals from the liquid oil fraction generated during thermochemical treatment of shredder residues from a state-of-the art WEEE dismantling process. By use of iCycle® and downstream processing of the oil, the objectives of the current contribution are as follows:

### **2. Materials and Methods**

### *2.1. Thermochemical Conversion*

The residual WEEE fraction consisted of IT-appliances (collection group 5) and was provided by a manufacturer as shredder residue with a maximum particle size of 20 mm. This shredder residue contained around 40% metals and inorganics and 60% organics. 231 kg of the feedstock was treated in the continuous thermochemical demonstration plant (load capacity ~70 kg/h) illustrated in Figure 1. Prior to treatment, the plant was flushed with nitrogen overnight and heated up to an operating temperature of 650 ◦C.

**Figure 1.** Process flow diagram of the iCycle® pilot plant (thermochemical conversion process).

As seen in Figure 1, throughout the treatment, the feedstock material is fed by a screw conveyor (3) batch-wise from a receiver tank (2) into a lock, where it is flushed with N2 (1) to ensure that no ambient air enters the reactor. Thermochemical treatment and decomposition of the plastic fraction takes place in the reactor (4) at 650 ◦C. The reactor is a patented system with an innovative heat exchanger design. By use of an Archimedean screw, internal heating by externally preheated cycled spheres can be achieved. Along their way through the auger reactor, the spheres do not get in contact with the feedstock itself as they are moved forward in the inner section of the Archimedean screw. Thus, clogging of feedstock to the hot spheres is prevented. The system in combination with a relatively high temperature of 650 ◦C ensures a high heating rate of reaction media to avoid the formation of polyhalogenated dioxins and furans due to the presence of flame retardants [4,70]. In addition to the internal heat supply by cycled spheres, external heating is provided by heating sleeves covering the surface of the auger reactor.

Inside the reactor, the auger unit moves the solid material from the feeding point to the discharge point, where remaining solid matter drops out of the reactor and is transferred by a conveyer screw (5) into a collection reservoir (6). The heated auger reactor has a length of 6000 mm and a diameter of 470 mm. Gaseous and vaporous decomposition products (at 650 ◦C) leave the reactor through a cyclone (7) and subsequently the cooling and condensation train (9, 10), consisting of two tube bundle heat-exchangers, connection pipes, and a pump that transfers the condensate into a collection reservoir (11). All material found in the cooling and condensation train after the experiment is referred to as "condensate". The remaining gas is cleaned in a NaOH-scrubber unit (12) and an electrostatic particle

filter (ESP) (13) and is subsequently burned on sight (14, 15) in accordance with German Federal Emission Control Act (BImSchG).

### *2.2. Pyrolysis Oil Pretreatment*

Prior to fractional distillation, the pretreatment of condensate was performed to remove solids and aqueous phase present. Two pretreatment methods were conducted in this research. The first method was a vacuum filtration process using a filter paper and a Buchner funnel to separate solids from the crude condensate produced throughout the iCycle® process. Filtration was performed within two steps with two different pore sizes of filter paper, i.e., 40 μm and 2 μm. The condensate was then poured through the funnel into a borosilicate flask, and the solids that were larger than the pore size of the filter paper were separated. A vacuum pump (KNF, model: N810FT.18; 100 kPa) was used to initiate the oil suction and enhance the filtration process. The filter paper was frequently replaced, as soon as the filter paper clogs in order to prevent performance decrease. The mass of the total solids that remained in filter papers was measured and prepared for analysis.

Subsequently, a separation of the observable aqueous phase from the filtrate of the second filtration was conducted using a separation funnel. In this way, the lower phase (aqueous) was released by gravitational force via the stopcock (tap) at the bottom of the funnel. The weight of the separated phase was measured and the water phase prepared for analysis.

### *2.3. Fractional Distillation*

For the fractional distillation of 5 kg of the pretreated condensate (oil), a batch distillation system (PILODIST-104) was operated. The plant's column features a stainless-steel wire mesh (20 theoretical stages), arranged with a head temperature sensor and a reflux divider. The column was insulated by a heating mantle, where the temperature was adjusted to maintain at 5 K below the column head temperature to provide an adiabatic condition during the distillation process. The main condenser with a subsequent distillate cooler at the top of the column ensures a sufficient condensation of ascending distillate vapors. The distillation flask at the bottom of the column, surrounded by an insulation mantle, has a volume of 20 L. The heating of the flask was controlled according to the temperature difference (ΔT) between the heating device and the oil temperature inside the heating flask. The reflux ratio was defined by adjusting the off-take time and the reflux time of the distillate fraction. A vacuum pump was connected to the top of the condenser and the fraction collector to maintain the desired pressure. The system was constantly flushed with nitrogen with a flow rate of 0.5 L/min in order to prevent oxidation reactions. A liquid nitrogen cold trap was used to protect the vacuum pump during the distillation with reduced pressure. The following parameters were operated in order to distill the oil generated:

Based on the boiling points of benzene, toluene, ethylbenzene, and xylene (BTEX aromatics) as well as phenolic compounds present in the operated oil, the temperature intervals and operating pressures depicted in Table 1 were selected to divide the oil into distillate fractions comprising high purities of BTEX-aromatics and monocyclic aromatic substances as styrene, α-methyl styrene, phenol and cresols.

**Table 1.** Fractional distillation operating parameters.

1 Atmospheric equivalent temperature.

### *2.4. Analysis of Pyrolysis Oil and Fraction Characterization*

### 2.4.1. Gas Chromatography–Mass Spectrometry (GC-MS) Analysis

The composition of oil was analyzed on a gas chromatograph coupled with a mass spectrometer Shimadzu GCMS-QP2020. The chromatograph was equipped with a 30 m nonpolar 0.25 mm inner diameter (i. d.), 0.25 μm film thickness DB-5ms, and 2.5 m middle polar 0.15 mm i. d., 0.15 μm film thickness VF-17ms column set from Agilent Technologies. Helium with 5.0 purity was used as carrier gas for all experiments. The injection volume was set to 1 μL. Dilution was conducted with 1 mg of sample in 1 mL of DCM. The measurements were performed at a constant linear velocity 40 cm/min of carrier gas. The temperature of the GC oven was programmed using the settings starting at 40 ◦C, 3 min hold to 320 ◦C, 3 min hold at 10 ◦C/min. The temperatures of the injector, the MS-interface, and MS were set to 250, 280 and 200 ◦C, respectively. The quadrupole MS detector was operated at scan speed of 5000 Hz using a mass range of 35–500 m/z. Solvent cut time was 3 min, with the MS start at 3.2 min. Total analysis time was 34 min. BTEX, styrene, α-methyl styrene, phenol, cresols and naphthalene were identified using standards solutions of pure chemicals. NIST-17 Mass Spectral Library was used for all other substance identification. Only the substances detected with the similarity index (SI) of more than 70 were identified. The proportion of each substance in the sample was given in percentage area. Only the proportions of the substances of particular interest in this research were shown in the graph, while other substances were not included and were referred to as "others".

### 2.4.2. Energy Dispersive X-ray Fluorescence (EDXRF) Analysis

A quantitative halogen analysis of all the samples was made with an energy dispersive X-ray fluorescence spectrometer (EDXRF) from Shimadzu (EDX 720). The concentrations for chlorine and bromine in oils were calculated based on the calibration curve and the Cl/Br peak intensities measured by EDXRF. Standard solutions were made with 1,3,5 trichlorobenzene, 98% from Alfa Aesar™ for chlorine and with 1,3,5-tribromobenzene, and 98% from Alfa Aesar™ for bromine. Toluene at 99.8% from Merck was used as a solvent. Each sample was measured three times in order to get statistical data.

### 2.4.3. Water Content Analysis

Water content in pyrolysis oil and distillate fractions was measured using a Karl-Fischer volumetric titration method. HYDRANAL™—Composite 5 from Honeywell Fluka™ was used as one component reagent titrant and methanol ACS Reagent, while ≥99.8% from Honeywell Riedel-de Haën™ was used as a titration medium. All measurement were performed on Metrohm 915 KF Ti-Touch and leaned on DIN 51777. Same as in case of EDXRF, measurements were performed three times.

### **3. Results**

Real WEEE shredder residues were thermally converted by means of pyrolysis at 650 ◦C with a residence time of 30 min. Solid, liquid, and gaseous products were yielded from this process; these products will be termed solid residue, condensate, and gas hereinafter, respectively. The obtained condensate underwent two pretreatment steps, namely solids filtration and aqueous phase separation. The obtained product, termed "oil", has thereafter been divided into eight fractions (including residue) by a fractional batch distillation process. The aim of the processing of the WEEE shredder residues was to produce highly enriched monocyclic aromatic mixtures with reduced content of solids, aqueous phase, and halogen concentrations to make them valuable for industrial reuse. The results of the individual process steps are presented in the following section.

### *3.1. Thermochemical Conversion*

The weights of the treated feedstock material, the collected solid product, and the condensate were determined at 231, 74, and 67 kg. The weight of the gaseous products was determined by a difference at 89 kg. Hence, the products yields were approximately 32, 29, and 39 wt.% for the solid product, the condensate, and the gaseous product, respectively. The results are illustrated in Table 2.

**Table 2.** Mass balance of the thermochemical conversion process.

The GC-MS analysis of the condensate showed a composition of 6.26 area% benzene, 22.05 area% toluene, 8.39 area% ethylbenzene, 0.73 area% xylenes, 26.63 area% styrene, 6.94 area% phenol, 3.90 area% α-methyl styrene, and 1.91 area% cresols. It follows that the condensate consisted of 72.16 area% of monocyclic aromatic substances to be recovered potentially. The composition is also illustrated in Figure 2 in Section 3.3.


*4.5. The Poorly Damped Process*

A final case study is considered in this section, with the process described by the following transfer function:

$$P(s) = \frac{22.24}{s^2 + 0.6934s + 5.244}e^{-0.8s} \tag{22}$$

The indirect autotuning methods based on an S-shaped response cannot be applied for (21). An FO-PI controller tuned according to [36] is compared with a FO-PID obtained using the method in [40] and a FO-PI controller determined using [49]. First, the relay method is used to estimate the critical gain as *Kcr* = 0.0709 and *Pcr* = 2.8. These critical gain and period of oscillations allow the design of a FO-PID controller according to the first set of tuning rules in [42]. However, the proportional gain obtained in this way is negative and destabilizes the closed-loop system. Thus, the design is not included in this comparison. To tune the FO-PI controller [49], a sine test is firstly applied to the process to determine its phase, magnitude and phase slope. Then, the parameters of the FO-PI controller are determined such that the open-loop system achieves a gain crossover frequency of 0.09 rad/s and a phase margin of 75◦, along with the iso-damping property. The parameters of the fractional-order controllers are given in Table 10. Figure 18 shows the closed-loop results, as well as the required input signals. The performance measures are indicated in Table 11. The simulation results in Figure 18 and Table 11 show that the fastest settling time is achieved by the FO-PID controller [40], with a zero overshoot. However, in this case, the required control effort is the largest. The two FO-PI controllers determined using [36,49] have a similar overshoot, as well as control effort. For the latter, the settling and the disturbance rejection times are larger.

**Table 10.** FO-PID parameters computed for the poorly damped process.

**Figure 18.** (**a**) Output signals for FO-PID control of the poorly damped process. (**b**) Input signals for FO-PID control of poorly damped process. Controllers tuned according to [36,40,49].

**Table 11.** Closed-loop results obtained with the FO-PID controller for the poorly damped process.

For second-order poorly damped processes, most fractional order autotuning methods cannot be applied, except for [47,49]. The direct autotuning method in [47] leads to a FO-PI in series with a FO-PD controller, of the form given in (20), whereas the method in [49] produces a simpler FO-PI controller. Similarly to the results in Table 7, a faster settling time and better disturbance rejection are achieved using the fractional-order controller in [47], due to the FO-PD component.


During the late spermatogenesis in the mammalian germinal epithelium, the differentiating spertamids are highly susceptible to DNA damage due to important changes in the cytoarchitecture and dramatic remodeling of the chromatin during which most of the histones are removed from the DNA and are first replaced by transition proteins TP1 and TP2, and then by protamines P1 and P2 which are approximately half the size of histones. P1 and P2 are normally expressed in a 1:1 ratio in human sperm, and provide a tight packaging of the sperm DNA. The chromatin remodeling is facilitated by the coordinated loosening of the chromatin by histone hyperacetylation and by the DNA topoisomerase II (topo II), which produce temporary stand breaks in the sperm DNA to relieve torsional stress that results from supercoiling [96, 97]. This forms the basic packaging unit of sperm chromatin, a toroid, which is further compacted by the intramolecular and intermolecular disulfide cross-links between cysteine residues present in protamines. The tight packaging of the sperm DNA enables the entire haploid genome to be condensed and packed in a sperm head measuring 5 × 2.5 μm. This level of protect and ensures that the paternal genome is delivered in a form that allows developing embryo to accurately express genetic information Normally, these temporary strand breaks are repaired by nuclear poly (ADP-ribose) polymersases (PARP) and topoisomerase II prior to completion of spermiogenesis and ejaculation [98]. However in pathological cases, the error in chromatin remodeling and repair mechanism leads to the generation of high level of nicked and poorly protaminated nuclear DNA with relatively high nucleohistone content or abnormally high and low P1/P2 ratios [99–101]. Thus, defect in the chromatin remodeling process causes DNA damage in spermatids during spermiogenesis, this creates a state of vulnerability whereby spermatozoa become increasingly susceptible to oxidative damage.

### **7. Causes of DNA damage in spermatozoa**

presence of enzymes such as glutathione peroxidase or catalase that can scavenge H2

zoa simply turns a short-lived, membrane-impermeant, relatively inert free radical O2

ROS production and is positively correlated with the sperm concentration [92].

long-lived, membrane-permeate reactive oxidant, H2

loss of sperm motility, oxidative DNA damage followed by DNA fragmentation.

**6.2. DNA damage in spermatozoa**

78 Novel Prospects in Oxidative and Nitrosative Stress

spermatozoa.

excess of SOD and limited supply of glutathione peroxidase or catalase in human spermato-

**Figure 3.** (A) ROS-induced initiation and propagation of lipid peroxidation (LPO) generates lipid hydroperoxides plus a new carbon-centered radical that continues the chain reaction. (B) Mitochondrial ROS generation. The electrophilic aldehydes generated as a by-product of LPO process bind to protein of electron transport chain and further promote mitochondrial ROS generation. This process results in loss of mitochondrial membrane potential, low ATP generation,

membrane lipids due to elevated levels of ROS in mitochondria might affect the process of oxidative phosphorylation causing depletion of intracellular ATP levels leading to axonemal damage, decreased sperm viability, and increased mid-piece sperm morphological defects with deleterious effects on sperm capacitation and acrosome reaction and decline of motility and fertility [91]. The mitochondrial function as a measure of inner mitochondrial membrane potential is found to be decreased in the spermatozoa of infertile men with elevated levels of

Mitochondrial DNA is particularly vulnerable to free radical attack because it is essentially unprotected and has a very limited capacity for DNA repair [93]. Sperm nuclear DNA, on the other hand, is much resistant to damage because it is tightly compacted by replacing histones with small, positively charged molecules known as protamine [94, 95]. Sperm DNA maturation and appropriate packaging are vital steps in the proper development of

During the late spermatogenesis in the mammalian germinal epithelium, the differentiating spertamids are highly susceptible to DNA damage due to important changes in the cytoarchitecture

O2

O2 . But

− into a

[89, 90]. The damage of protein and

When the protection of DNA in spermatozoa, which is dependent on its close association with cysteine rich protaminesis is lost, the cells become very susceptible to oxidative DNA damage induced by several extrinsic and intrinsic factors. Deoxygenated guanine (dG) is more susceptible to oxidation than other nucleosides in DNA due to its low oxidation potential [102]. The enzyme 8-oxoguanine glycosylase 1 (OGG1) immediately clips the 8OHdG residues out of the DNA generating an abasic site, But due to the absence of base excision repair enzyme, the spermatozoa are ejaculated carrying a abasic sites in their DNA [103]. Studies have reported that the spermatozoa of subfertile patients contain particularly high levels of 8-hydroxy-2′ deoxyguanosine (8OHdG), the major oxidized base adduct formed when DNA is subjected to attack by ROS [104].

DNA repair does occur during spermiogenesis but stops post-spermiogenesis because spermatozoa are transcriptionally and translationally silent. They cannot undergo programmed cell death called apoptosis, due to their inherent physical architecture, the endonucleases released from the mitochondria have no access to the DNA. Thus, abortive apoptosis initiated post-meiotically, when the ability to drive the spermiogenesis process to completion is declined and the stand breaks are not repaired due to impairment in the repair process results in high levels of DNA fragmented sperm in the ejaculate [105]. Sperm with DNA fragmentation still has thepotential to fertilize and some types of stand DNA breaks in sperm can be repaired by oocytes, before the initiation of the first cleavage division, and generate normal offspring, but that

### depends on the type and level of chromatin damage and the capacity of the oocyte to repair it [106]. DNA-strand breaks are extremely harmful lesions if not repaired and can lead to genomic instability and cell death. In natural conception, percentage of DNA damage has been negatively correlated to the rate of fertilization. If post fertilization oocyte make mistake in the repair process, deletions or sequence errors may be introduced, then it fabricates the possibility for *de novo* mutations, which could have a profound impact on the health and well-being of the offspring [107]. Sperm DNA damage in context to assisted reproductive technique (ART) has important clinical implications. Sperm selected for ART mostly originates from environment experiencing oxidative stress and high percentage of these sperms may have damaged DNA. If such sperms are used clinically in the form of therapy then can lead to substantial risk in pregnancy outcome. In case of intrauterine insemination (IUI) and in vitro fertilization (IVF), the use of these spermatozoa may not be cause of concern. But in case of intracellular sperm injection (ICSI), this natural selection barrier is bypassed and the spermatozoa with damaged DNA are directly injected into oocytes. Studies have reported that DNA damaged spermatozoa used in ICSI have some capacity for fertilization, but percentage of DNA damage has been negatively correlated to the rate of fertilization [108]. ROS-mediated DNA damage may be linked to an increase in early embryo death, infertility in the offspring, and high incidence of childhood cancer [109, 110]. We propose that extrinsic and intrinsic sources of ROS could make a significant contribution to the induction of OS and DNA damage in spermatozoa which can decrease pregnancy rate and affect the fertility outcome, further additional studies are clearly needed to validate this concept.

**8.2. Dietary antioxidants**

potential of these cells [119].

**9. Conclusion**

**9.1. Suggestion**

As many studies suggested that oxidative stress is a major cause of unexplained male infertility, antioxidant therapy would be expected to have a therapeutic effect in such cases. There are evidences which have suggested that oral antioxidants and herbal products can also boost male reproductive functions [116, 117]. But, despite of known effect of antioxidant on oxidative stress, very few studies conducted have any validity due to small sample size, difference in dosage and duration of therapy, and lack controls [118]. In order to make the study valid, patient's selection criteria for the trial should be based on the evidence indication oxidative stress as a key element in their pathology, a thorough diagnosis is required to determine patients that need to be supplemented. However, if this strategy is pursued, great care must be taken in selecting the most appropriate antioxidants for clinical use. Since ROS plays an important role in regulating the signal transduction cascades that drive sperm capacitation, we should ensure that any antioxidants employed in vitro do not compromise the fertilizing

Role of Reactive Oxygen Species in Male Reproduction http://dx.doi.org/10.5772/intechopen.74763 81

The study of *in vitro* antioxidants is highly relevant in the era of assisted reproduction because sperm preparation techniques in ART are potential generators of exogenous stresses that

Oxidative stress has been recognized as a major contributory factor to male infertility. Spermatozoa are professional generator of ROS as physiological level of ROS is necessary to regulate critical redox-sensitive processes such as capacitation, hyperactivation, acrosome reactions, and signaling processes to ensure appropriate fertilization. On the other hand, many endogenous and exogenous factors can elevate ROS production which can overwhelm their antioxidant mechanism. This results in male infertility via mechanisms involving the induction of peroxidative damage to the sperm plasma membrane, DNA damage, which significantly impairs sperm function. Lack of repair mechanism and abortive apoptosis in mature spermatozoa results in high levels of DNA fragmented sperm in the ejaculate. In natural conception, oocytes can repair some of stand DNA breaks, but that depends on the type and level of chromatin damage and the capacity of the oocyte to repair it. If post fertilization oocyte make mistake in the repair process it may lead to failure in fertilization. But if fertilization occurs, then it creates the possibility for *de novo* mutations, which could have a profound impact on the health and well-being of the offspring. When the natural balance between ROS and antioxidants is disturbed, the first restorative measure to be taken should be changes in lifestyle, maintaining a healthy and balanced diet, and antioxidant supplementation may then

The conventional seminological parameter in infertile cases reflects the functional competence of the spermatozoa and the fertilizing potential of the ejaculate, but the underlying mechanisms of male fertility is not known. Thus in order to enrich the diagnostic value of this

make human spermatozoa vulnerable to oxidative stress and DNA damage.

be taken together to improve the patient's health outcomes.

### **8. Management of infertility caused by oxidative stress**

Oxidative stress plays an important role in the pathophysiology of male infertility, which is caused due to pathological level of ROS and the loss of antioxidant protection for the spermatozoa. There are many factors which can induce oxidative stress and can alter seminal parameters and rate of fertilization. Thorough examination and management of some of these factors may protect the ROS-induced DNA damage and improve a couple's chances of conception either naturally or via assisted reproduction.

#### **8.1. Behavior and life style modification**

Various behaviors and lifestyles factors such as alcohol consumption, cigarette smoking, obesity, excess exposure to environmental toxicants, and psychological stress are negatively correlated with spermatogenesis and may cause oxidative stress and reduction in sperm quality [111]. The increased consumption of simple sugars and high-fat food and physical inactivity are leading causes of the growing obesity. It is suggested that abnormal hormonal regulation, dysregulation of adipocytokine, and ROS generation lead to suboptimal semen quality these patients [112]. Several systemic diseases, such as diabetes mellitus, infection, and cancer are known to cause oxidative stress-induced male infertility [113, 114]. There are studies which have shown positive correlation of exercise with improvements in semen parameters, sperm DNA integrity, and pregnancy rate [115]. Nevertheless, modification in behavior and unhealthy living, regular exercise, stress free jobs, and treatment of a patient's underlying pathology should be the first steps to reduce or eliminate stress-provoking conditions to reverse sperm dysfunction.

#### **8.2. Dietary antioxidants**

depends on the type and level of chromatin damage and the capacity of the oocyte to repair it [106]. DNA-strand breaks are extremely harmful lesions if not repaired and can lead to genomic instability and cell death. In natural conception, percentage of DNA damage has been negatively correlated to the rate of fertilization. If post fertilization oocyte make mistake in the repair process, deletions or sequence errors may be introduced, then it fabricates the possibility for *de novo* mutations, which could have a profound impact on the health and well-being of the offspring [107]. Sperm DNA damage in context to assisted reproductive technique (ART) has important clinical implications. Sperm selected for ART mostly originates from environment experiencing oxidative stress and high percentage of these sperms may have damaged DNA. If such sperms are used clinically in the form of therapy then can lead to substantial risk in pregnancy outcome. In case of intrauterine insemination (IUI) and in vitro fertilization (IVF), the use of these spermatozoa may not be cause of concern. But in case of intracellular sperm injection (ICSI), this natural selection barrier is bypassed and the spermatozoa with damaged DNA are directly injected into oocytes. Studies have reported that DNA damaged spermatozoa used in ICSI have some capacity for fertilization, but percentage of DNA damage has been negatively correlated to the rate of fertilization [108]. ROS-mediated DNA damage may be linked to an increase in early embryo death, infertility in the offspring, and high incidence of childhood cancer [109, 110]. We propose that extrinsic and intrinsic sources of ROS could make a significant contribution to the induction of OS and DNA damage in spermatozoa which can decrease pregnancy rate and affect the fertil-

ity outcome, further additional studies are clearly needed to validate this concept.

Oxidative stress plays an important role in the pathophysiology of male infertility, which is caused due to pathological level of ROS and the loss of antioxidant protection for the spermatozoa. There are many factors which can induce oxidative stress and can alter seminal parameters and rate of fertilization. Thorough examination and management of some of these factors may protect the ROS-induced DNA damage and improve a couple's chances of con-

Various behaviors and lifestyles factors such as alcohol consumption, cigarette smoking, obesity, excess exposure to environmental toxicants, and psychological stress are negatively correlated with spermatogenesis and may cause oxidative stress and reduction in sperm quality [111]. The increased consumption of simple sugars and high-fat food and physical inactivity are leading causes of the growing obesity. It is suggested that abnormal hormonal regulation, dysregulation of adipocytokine, and ROS generation lead to suboptimal semen quality these patients [112]. Several systemic diseases, such as diabetes mellitus, infection, and cancer are known to cause oxidative stress-induced male infertility [113, 114]. There are studies which have shown positive correlation of exercise with improvements in semen parameters, sperm DNA integrity, and pregnancy rate [115]. Nevertheless, modification in behavior and unhealthy living, regular exercise, stress free jobs, and treatment of a patient's underlying pathology should be the first

steps to reduce or eliminate stress-provoking conditions to reverse sperm dysfunction.

**8. Management of infertility caused by oxidative stress**

ception either naturally or via assisted reproduction.

**8.1. Behavior and life style modification**

80 Novel Prospects in Oxidative and Nitrosative Stress

As many studies suggested that oxidative stress is a major cause of unexplained male infertility, antioxidant therapy would be expected to have a therapeutic effect in such cases. There are evidences which have suggested that oral antioxidants and herbal products can also boost male reproductive functions [116, 117]. But, despite of known effect of antioxidant on oxidative stress, very few studies conducted have any validity due to small sample size, difference in dosage and duration of therapy, and lack controls [118]. In order to make the study valid, patient's selection criteria for the trial should be based on the evidence indication oxidative stress as a key element in their pathology, a thorough diagnosis is required to determine patients that need to be supplemented. However, if this strategy is pursued, great care must be taken in selecting the most appropriate antioxidants for clinical use. Since ROS plays an important role in regulating the signal transduction cascades that drive sperm capacitation, we should ensure that any antioxidants employed in vitro do not compromise the fertilizing potential of these cells [119].

The study of *in vitro* antioxidants is highly relevant in the era of assisted reproduction because sperm preparation techniques in ART are potential generators of exogenous stresses that make human spermatozoa vulnerable to oxidative stress and DNA damage.

### **9. Conclusion**

Oxidative stress has been recognized as a major contributory factor to male infertility. Spermatozoa are professional generator of ROS as physiological level of ROS is necessary to regulate critical redox-sensitive processes such as capacitation, hyperactivation, acrosome reactions, and signaling processes to ensure appropriate fertilization. On the other hand, many endogenous and exogenous factors can elevate ROS production which can overwhelm their antioxidant mechanism. This results in male infertility via mechanisms involving the induction of peroxidative damage to the sperm plasma membrane, DNA damage, which significantly impairs sperm function. Lack of repair mechanism and abortive apoptosis in mature spermatozoa results in high levels of DNA fragmented sperm in the ejaculate. In natural conception, oocytes can repair some of stand DNA breaks, but that depends on the type and level of chromatin damage and the capacity of the oocyte to repair it. If post fertilization oocyte make mistake in the repair process it may lead to failure in fertilization. But if fertilization occurs, then it creates the possibility for *de novo* mutations, which could have a profound impact on the health and well-being of the offspring. When the natural balance between ROS and antioxidants is disturbed, the first restorative measure to be taken should be changes in lifestyle, maintaining a healthy and balanced diet, and antioxidant supplementation may then be taken together to improve the patient's health outcomes.

#### **9.1. Suggestion**

The conventional seminological parameter in infertile cases reflects the functional competence of the spermatozoa and the fertilizing potential of the ejaculate, but the underlying mechanisms of male fertility is not known. Thus in order to enrich the diagnostic value of this fundamental form of investigation, the detailed examination of sperm DNA damage may be incorporated as a potentially valuable tool to investigate the functional integrity of the spermatozoa at the molecular level.

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### **Author details**

### Sabiha Fatima

Address all correspondence to<EMAIL_ADDRESS>
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia

### **References**

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fundamental form of investigation, the detailed examination of sperm DNA damage may be incorporated as a potentially valuable tool to investigate the functional integrity of the sper-

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud

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013-0416-y

**Chapter 5**

**Provisional chapter**

**Particularities of Oxidative Stress in Newborns**

**Particularities of Oxidative Stress in Newborns**

DOI: 10.5772/intechopen.73369

The oxidative stress at newborns is augmented by different conditions like preterm birth, asphyxia, respiratory distress, and intraventricular hemorrhage. Preterm neonates associate a more pronounced oxidative stress than healthy term newborns. Several neonatal conditions like respiratory distress (RDS), asphyxia, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy, and necrotizing enterocolitis will increase the oxidative stress. The harmful effects of free radicals are linked to their capacity to react with polyunsaturated fatty acids of cell membranes, proteins, and nucleic acids. Free radicals

Oxidative stress represents all injuries caused by reactive oxygen species (ROS) on biomolecules, inducing the destruction of membranes, enzymes, receptors, as well as alteration of cell function. The consequence of oxidative stress is a disruption of the physiological balance

Newborn possesses defense mechanisms such us molecules protection, limitation of ROS production, and mechanisms for repair and adaptation to endogenous and exogenous ROS

Reactive oxygen species are involved in physiological processes such as physical exercise, hyperbarism, regulation of vascular tone, stimulation of cell growth and proliferation, stimulation of erythropoietin secretion, the learning and memory process, as well as in pathological

will produce protein alteration with function loss and lipid peroxidation.

**Keywords:** oxidative stress, new born, prematurity

between pro-oxidants and antioxidants [1, 2].

processes: inflammation, aging, carcinogenesis [1–3].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

Melinda Mátyás and Gabriela Zaharie

Melinda Mátyás and Gabriela Zaharie

http://dx.doi.org/10.5772/intechopen.73369

**Abstract**

**1. Introduction**

overproduction.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

**Provisional chapter**