BA is produced by a manufacturing process that involves the utilization of raw materials such as toluene and manganese naphthenates [22]. This process may raise environmental issues due to the potential release of volatile organic compounds (VOCs) of toluene, VOCs are compounds that have a high vapor pressure and easily evaporate at room temperature [23]. Additionally, there exists a potential for contamination linked to BA production when utilizing toxic chemical compounds such as manganese or cobalt naphthenate catalysts [24, 25].

As shown in Figure 1, to produce BA, cobalt or manganese naphthenates catalyze the partial oxidation of toluene with air [26]. This technology, the toluene oxidation process, is popular since it is efficient and cheap. The process involves toluene, a solvent, and a catalyst that are heated and pressurized with oxygen existence [27]. While there are other ways to synthesize BA, the majority of them are impractical from both an economic and environmental perspective [28]. Crystallization or other separation methods to purify the BA are then applied to make it appropriate for food preservation, pharmaceutical products, and other industrial usages [29].

Today's ecologically conscious world requires medicinal eco-friendly technology. This reduces the industry's environmental impact and aids climate change mitigation and resource conservation. Green chemistry, renewable energy, and more efficient manufacturing can reduce waste, energy use, and toxic emissions in pharmaceutical companies. These merits can considerably reduce potential environmental risk during BA manufacturing processes.

BA originates naturally in a variety of plants and foods, including fruits and vegetables, with varying quantities depending on the plant's growing conditions [30]. Due to its use in food preservation, chemical synthesis, and pharmaceuticals, BA was produced at 538,770 tons worldwide in 2020, and it is expected to grow to 628,350 tons by 2026 [31]. In 2022, the pharmaceutical industry uses 12% of total BA annual production, as illustrated in Figure 2 [32]. BA is a versatile pharmaceutical product utilized for its antimicrobial, antifungal, and preservative properties [33-36]. It is often found in medications that are put on the skin to treat rashes, irritation, eczema, and fungal diseases [37]. Also, BA or its derivatives like salicylic acid are added to creams and ointments that are used to treat skin diseases like psoriasis and seborrheic dermatitis [38, 39] and may assist with the removal of dead skin cells when it is present in higher quantities [40]. Because of its antibacterial properties, it is utilized in numerous non-prescription medications for the treatment of small cuts and burns [41]. BA is also utilized as a preservative in pharmaceutical compositions to maintain the stability of medicines and prolong their shelf life [42-44]. BA and its salts, such as sodium benzoate, are commonly included in liquid medicines, lotions, and certain oral formulas to inhibit the growth of germs and yeast [45]. Some cough medicines to help patients cough up and get rid of mucus contain BA and its derivatives [46].

BA undergoes a quick metabolism and is excreted by urine during 24 hours [47], it is quickly taken up by the digestive system and combined with glycine in the liver, resulting in the formation of hippuric acid. Within 6 hours of being absorbed, practically all of the hippuric acid is eliminated in the urine [48]. The BA is efficiently absorbed in the gastrointestinal tract. BA is metabolized in the liver after absorption. Hepatocyte mitochondrial glycine N-acyltransferase conjugates glycine with hippuric acid (benzoylglycine) in the major metabolic pathway [49]. Hippuric acid is the main metabolite eliminated in urine for most of BA consumed [50]. A secondary mechanism forms benzoyl glucuronide, which is eliminated in urine, by conjugating with glucuronic acid. Cytochrome P450 enzymes, can hydroxylate tiny quantities of BA to 4-hydroxybenzoic acid. Metabolites, mostly hippuric acid, are excreted by the kidneys, mostly by urine. BA's efficient metabolism and elimination reduce systemic buildup, reducing its toxicity in humans [51]. BA can also be absorbed through inhalation or human skin with an overall mean flux equal to 16.54 + 11.87 µ g/cm2/h [52]. It should be noted that certain derivatives of BA, such as sodium benzoate and benzoyl peroxide, can be absorbed by the skin or consumed in medical formulations [53]. Once absorbed, they are transformed into BA and enter the bloodstream. Upon absorption and ingestion, these derivatives undergo metabolism, resulting in the presence of BA in the bloodstream. Subsequently, BA is then excreted through the urine system [54].

Most people are considered safe with BA-containing treatments as long as they follow the directions on approved medications. Most harmful effects occur when individuals consume high levels or experience prolonged exposure. According to the Food and Drug Administration (FDA) recommendations, BA is considered acceptable for use in food as an antibacterial or preservation agent and adjuvant, as long as it does not exceed a maximum level of 0.1%. The FDA has not determined whether significantly different conditions of use would be generally recognized as safe (GRAS) [55]. No specific level has been identified for BA toxicity in medications yet; nevertheless, in food, a threshold of an acceptable daily intake (ADI) value of 5 mg/kg/day was adopted in 2016, according to a joint committee of the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) [56].

The topical application of BA might cause specific side effects and allergic reactions such as skin irritation, redness, and itching, particularly at higher concentrations [57-59]. Individuals may develop allergic responses to BA or its salts, which might manifest as mild contact dermatitis [60] like urticaria [61]. Furthermore, experiencing gastrointestinal discomfort when consuming excessive quantities of BA orally (about 677.9 mg/kg bw-day), might result in symptoms such as vomiting [62]. Metabolic acidosis can occur in rare instances, especially in neonates or those with compromised liver function, when excessive dosages of BA or its salts are administered [63]. Since glycine is utilized by the liver and kidneys for BA detoxification [64, 65], excessive consumption of glycine results in a reduction of its levels in the body, which may lead to several consequences, like diarrhea, muscular weakness, seizures, reduced activity, and extreme weight loss, when a high quantity of BA is taken [66]. The most significant adverse effect of BA consumption in humans is its ability to displace bilirubin from albumin [67]. This condition might trigger serious diseases like encephalopathy, particularly in infants [68]. While BA is not carcinogenic, it can react with ascorbic acid (vitamin C) to produce benzene, a known carcinogen, through decarboxylation. This primarily concerns the use of non-alcoholic beverages or their consumption with medications [69]. BA may interact with other substances and significantly affect liver function or pH equilibrium in the body [70, 71].

The toxicity of BA might have mitodepressive and genotoxic effects at very low concentrations of 10 mg/L. This was identified using Allium cepa as a biomarker, affecting physiological, biochemical, cytological, and genetic characteristics [72]. Depending on the dosage, BA can induce significant genotoxic effects in human lymphocyte cells, such as sister chromatid exchange (SCE), chromosomal aberrations (CA), mitotic index (MI) reduction, and micronuclei (MN) increase [73]. Toxicity from BA typically occurs when high doses are consumed, overwhelming the body's metabolic capacity to detoxify and excrete it [74]. However, when intake exceeds the liver's ability to process it, unmetabolized BA can accumulate in the bloodstream, leading to adverse effects. Symptoms of toxicity may include metabolic acidosis, characterized by a drop in blood pH, which can cause various adverse effects. Toxicity is more likely in individuals with compromised liver or kidney function, as these organs are critical for the detoxification and elimination of BA and its metabolites [62].

In addition to their widespread use in pharmaceutical products, BA is extensively used as a raw material in industry, to produce chemicals such as benzoyl chloride, phenol, and benzoate plasticizers [75, 76]. BA is also classified as a food supplement (E210) and is extensively utilized as preservatives in the food industry [77]. Several food products, including soft beverages, canned vegetables and fruits, fruit juices, and fish products, commonly include BA as a dietary supplement [78, 79]. The average concentration levels of benzoic acid used in food products range from 0.05% to 0.1% [80].

The industrial manufacturing process of BA, mostly through the partial oxidation of toluene, generates a range of waste compounds, which might result in organic byproducts and unreacted materials, especially organic cyclic compounds that have considerable impacts on aquatic quality and are very harmful for individuals and the environment [81], these waste streams may contain traces of BA. There may also be wastewater and solid waste during the purification process. Besides amounts of BA, the wastewater includes different types of liquid wastes with dissolved salts and organic impurities, and the solid wastes include used catalysts, filter cakes, and separation residue [82, 83]. BA traces found also in industrial discharge originated from other industrial sources, as BA is commonly employed as an intermediate chemical, preservative, and antiseptic in various food, beverage, cosmetic, and petrochemical industries [84]. Various aromatic and cyclic hydrocarbons are released from petroleum refining and petrochemical industry; the effluents may contain considerable traces of BA [85]. As an example, the industrial wastewater produced during the manufacturing of purified terephthalic acid (TPA), which is a key ingredient in various textile and plastic products, contains a significant quantity of BA. This BA, along with four other organic compounds, makes up approximately 75% of the chemical oxygen demand (COD) present in the influent wastewater [86], while a wastewater containing both BA and TPA with other metals has a COD of 3320 mg/L and a biochemical oxygen demand (BOD) of 316.2 mg/L for BA [87]. The industrial wastewater effluents containing BA may exhibit a total organic carbon (TOC) concentration of 67.5 mg/L and a pH value of 3.5 [88].

It is difficult to distinguish between BA traces in municipal wastewater from drugs or food, so both sources are considered. The majority of BA is found in municipal wastewater because it is widely used as a preservative in food and pharmaceuticals, in their original form or as metabolized substances and is discharged into surface water through excrement [89]. BA is released into the wastewater as a result of its widespread use as a preservative. It originates from the excreta of individuals and wastewater from hospitals [90], resulting in elevated levels of BA in certain water bodies worldwide. Despite undergoing various treatments, BA concentrations in groundwater samples from Florida reached as high as 27.5-67 mg/L [91].

Effective waste management measures, such as recycling technologies and wastewater treatment, are critical to reducing BA production's environmental impact. Physical, chemical, and biological methods can treat cyclic organic industrial effluents. These include extraction, adsorption, coagulation, oxidation, biofilm, and membrane [92]. Examples of these processes are presented in Table 1. Factors such as convenience of design, cost, and efficiency should be considered while selecting an appropriate approach [93].

Many adsorption approaches have been proposed for treating BA in wastewater, as BA at specific concentrations may impair aquatic ecosystems, disrupt soil microbial balance, and induce toxicity in particular species. The extraction of BA through adsorption using carbon nanotubes plays a crucial role in enhancing the removal of pollutants from wastewater by means of functionalization and treatment [94]. Various carbon nanotube pretreatments for enhancing the adsorption capacity of BA are studied, such as oxidized, purified carbon nanotubes, and calcined carbon nanotubes [95]. The Fenton reaction is one of the more interesting advanced oxidation processes (AOPs) for treating water and wastewater containing BA because of its quick reaction rate, ease of usage, and eco-friendly [96]. The emulsion liquid membrane (ELM) process is also proposed for extracting organic acids from wastewater. ELM is created by combining two phases that do not mix and then spreading the resulting emulsion into a third phase, which is the continuous phase of the wastewater [97]. Photocatalysis, a type of AOP, is also commonly employed for the degradation of pharmaceuticals in wastewater due to its numerous benefits, such as the generation of free radicals, a high rate of removal, and minimal sludge production [98]. Air flotation is an efficient and expedient method compared to precipitation for segregating lightweight particles and oils from wastewater, resulting in a reduced amount of sludge. The efficacy of eliminating organic substances can exceed 98%, contingent upon variables such as duration and intensity of separation, dose of chemical additives, dimensions of gas bubbles, and duration of saturation [99]. Other approaches using chemical oxidation processes have been explored for BA treatment, for example, a heterogeneous system of UV-persulfate oxidation for the oxidative degradation of organic contaminants, including BA, by using UV-activated green rust [100]. Bio-film degradation in constructed wetlands (CWs) uses natural mechanisms to remove BA from wastewater. Aerobic and anaerobic biodegradation, photo-degradation, substrate adsorption, and plant uptake and degradation are the main CW processes for BA’s treatments [101].

Despite the extensive treatment of BA in wastewater plants, significant amounts of BA still make their way to the environment through water bodies, sediment, and finally soil. Figure 3 illustrates the main pathways of BA occurrence in the environment.

Since BA, at certain concentration, is moderately toxic to aquatic organisms, can alter microbial communities in soil, inhibit plant growth, and in the presence of other compounds, BA can potentially form derivatives. Some of which might be persistent organic pollutants (POPs) such as chlorinated BA [102], these pollutants are resistant to chemical or biological degradation, highly environmentally mobile, and bioaccumulate in the food chain [103]. BA can be introduced into the environment via the discharge of wastewater treatment plants (WWTPs). The issue arises when the compound is not completely eliminated during the treatment processes, hence enabling its release into the receiving water bodies [104]. Although WWTPs are intended to eliminate various pollutants, BA may persist through the treatment phases, particularly when present in large concentrations or if the treatment method is not specifically adapted to remove it [105]. Releasing this substance into water ecosystems raises worries about potential environmental consequences, as BA has the ability to alter the quality of water and the species that live in it [106], especially in places with a large concentration of people or industrial activity. During wastewater treatment, aromatic hydrocarbons, preservatives, and some pharmaceuticals partially biodegrade [107-109]. Many complex molecules are converted into simpler ones, including BA. For example, the breakdown of preservatives like benzyl alcohol, commonly used in food and pharmaceuticals, produces BA [110]. BA can also arise from complicated pharmaceuticals and personal care products (PCPs) that include aromatic rings during biodegradation. In WWTPs, while numerous organic contaminants undergo degradation, the process is not consistently thorough. Due to their resistance to biodegradation, substances like BA can remain intact during treatment and be released into surface water or soil [111]. Surface water typically contains BA as an intermediate result of the organic breakdown. Once in the environment, BA may degrade further, but at a slower rate, contributing to its detection in surface water bodies and soils. Due to the slow degradation of sewage sludge from treatment plants, substantial amounts of BA are still present in the sewage sludge upon disposal [112]. In fact, after using biodegradation strains, BA was found in discarded sludge in various ratios [113]. The use of biosolids from WWTPs may lead to the gradual accumulation of BA in the environment [114]. BA in soil will likely persist for a long time after release into the environment because of its high sorption and poor biodegradation rates [115 116]. Once disposed of in landfills or applied to soils, BA can also leach into the groundwater, causing groundwater contamination that has already been detected in many places [117 118]. The already complicated chemical mixture of the aquatic system's water cycle is further complicated when leachate enters from the soil, which in turn affects the food chain [119]. Contamination of the environment occurs as a result of inadequate treatment of BA from WWTPs and the subsequent discharge of effluents. BA can form as a disinfection by-product (DBP) during drinking water treatment and enter water bodies [120]. BA is released into air, water, and soil, with water being the primary medium, mainly through wastewater treatment plant discharges. During production, VOCs like toluene can release it into the air, contributing to pollution. In water, BA often persists through treatment, entering rivers and lakes, potentially harming aquatic ecosystems. In soil, it accumulates via biosolids application, leaching into groundwater due to its slow degradation, causing contamination. While released into all three media, water is the dominant pathway, emphasizing the need for improved treatment and waste management to reduce its environmental impact and protect ecosystems and water quality.

Because BA is a degradation intermediate, which means that it is further mineralized [125], it needs more sophisticated ways to fully be mineralized to have less of an effect on aquatic environments. BA occurs also naturally in soil; it comes from plant debris and fallen leaves [126]. Biodegradation breaks down BA into simpler products [127]. BA affects soil pH and microbial activity, improving soil health and fertility [128 129], when it exists at allowable levels [130]. It illustrates the complex natural mechanisms that support soil ecosystems and recycle nutrients. BA concentrations in the environment range widely, as shown in Table 2, indicating the importance of the BA contamination issue.

The presence of BA in surface water from WWTP effluents can have a variety of environmental consequences. One significant impact is on aquatic ecosystems; for instance, BA, although low in toxicity, can contribute to the overall chemical load, potentially disrupting microbial communities at high BA levels that are crucial for nutrient cycling and maintenance of water quality [131]. For example, the inhibition of nitrifying bacteria, essential for converting ammonia to nitrate, can lead to elevated ammonia levels, which are harmful to fish and other aquatic organisms [132].

Furthermore, the existence of BA can have a synergistic impact with other pollutants, intensifying their harmful effects. When combined with other organic acids, it has the potential to impact the growth and reproduction of algae, which are crucial species in aquatic food chains. This disturbance can propagate throughout the environment, impacting higher trophic levels, such as fish and invertebrates [133].

The presence of BA in surface water can serve as an indicator for the existence of other recalcitrant organic pollutants, implying inadequate treatment of wastewater and presenting long-term hazards to both the environment and human well-being. If they are not effectively eliminated, they can lead to the persistence of other detrimental compounds such as pharmaceuticals and endocrine disruptors [134]. This can pose a greater risk to aquatic life and potentially result in these substances entering the human food chain through bioaccumulation.

The widespread use of BA releases it into the environment, and high intake poses health risks to humans and animals. The prolonged presence of benzoic acid in the environment leads to the selection of biofilm and microorganisms (mold, yeast, bacteria) that are resistant to the inhibitory effect of this pollutant [135-137]. In anaerobic environments, such as sediments or waterlogged soils, the half-life of BA can range from weeks to months, depending on the availability of specific anaerobic degraders. In soil, BA degradation followed first-order kinetics, with half-lives ranging from 37.46 to 66.00 days [138]. In considering anaerobic conditions, especially in sediment, BA degradation can be slower. The half-life of benzoic acid in anaerobic environments can range from weeks to months, depending on the microbial community and conditions [139]. Efficient drinking water treatment is essential to prevent the risk of the pollutant returning through water resources [140 141]. Unqualified water purification systems often fail to remove all contaminants, allowing pollutants to cycle back to humans, while the application of energy-efficient technologies in treatment processes not only enhances purification effectiveness but also reduces the environmental impact and operational costs associated with water treatment [142].

Investigating the microbiome of areas contaminated with synthetic aromatic chemicals will enable the identification and analysis of novel aerobic bacterial strains that have the ability to break down aromatic contaminants, including BA. Table 3 shows recent studies about the toxicities of BA in the environment. Biotechnological approaches based on aerobic bacteria capabilities can be used as an effective and safe way for remediating chemically polluted environments [157], especially for BA. Consequently, investigating biodegradation potentials techniques is considered significant for BA removal.

The concentrations of BA observed in Table 2 vary significantly across different environmental media, and their potential toxicity can be assessed using the toxicity data in Table 3. In surface water, concentrations range from 0.8 µg/L in Germany to 230.45 µg/L in China, which are generally below the chronic NOEC (No-Observed Effect Concentration) of 10 mg/L for sensitive aquatic species like Daphnia magna. However, groundwater samples show much higher concentrations, such as 9488 µg/L in Germany and 9424 µg/L in the UK, which could approach or exceed toxic thresholds for some organisms. Soil and sediment concentrations, ranging from 12.2 µg/kg to 10,522.3 µg/kg, are also below the NOEC for earthworms (50 mg/kg). Overall, while most surface water and soil concentrations are unlikely to cause toxicity, certain groundwater samples may pose a risk, particularly in contaminated areas. The PNEC (Predicted No-Effect Concentration) for aquatic environments (0.1 mg/L) and soil (0.5 mg/kg) suggests that only the highest concentrations in groundwater and some sediments could be of concern.