ENDOCRINE-DISRUPTING CHEMICALS (EDCS), THEIR SOURCES, HEALTH CONCERNS AND BIODEGRADATION OF EDCS USING LACCASE

exposed individuals. Laccase is a copper-containing enzyme that has shown its potential to degrade Endocrine-disrupting chemicals. The microbial production of laccase requires a rich source of lignin along with cellulose, hemicelluloses, and other proteins. Thus, lignocelluloses rich wastes may be considered as good substrates for the production of laccase using microorganisms. In this article, we have discusses the fate of endocrine disruptors, and role of laccase in the biodegradation of endocrine disruptors.

Generally agriculture is assumed to be environmentally friendly activitiy but many agricultural practices negatively effect the nature of the environment.Agricultural activities like cultivation, weed removal, and pest management are ivolved with usage of chemicals to increase the productivity.There is increasing usage of chemical fertilizers, herbicides, and pesticides to increase the agricultural productivity.The nonscientific use of these chemicals are causing imbalance of nutrients in the soil, and environment pollution.Even the use of new herbicides are not providing sustainable results [22].Even, inappropriate use of pesticides and herbicides is contributing to the development of resistance in pests, and weeds against these agents.Including this, these chemicals enter into soil, and water sources, and also becoming potent source of environmental pollution.Moreover, some of them persist in environment, enters in the tisues of invertibfates, and vertebrates, bioaccumulate and entres in food chains.The humans are being exposed to pesticides through environmental and dietary exposure.Moreover, pesticides such as 2,4-D, acetochlor, aldrin, carbofuran, DDT etc are also recognoized as endocrine disruptors [25].
The technology always aims to provide the solution of any problem in a sustainable way and integrated strategy may be used to manage the harmful environmental pollutant by biodegradation using enzymes.These approaches using enzymes are considered as ecofriendly and cost effective.In

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Figure 1 -EDCs are present in a wide variety of daily used items such as water bottles, cosmetics, pharmaceuticals, pesticides, and toothpaste etc this article, the authors have discussed the properties of EDCs, their health impact, and the role of laccase to degrade the EDCs.
Endocrine-disrupting chemicals.Endocrine-disrupting chemicals or endocrine disruptors (EDCs) are substances found in the environment that interfere with the synthesis of the hormones, secretion, transport, and metabolism, or mimic the structure of hormone that causes an alteration in hormone-associated homeostasis that affects the growth and development of individuals [11].
Both types of compounds i.e. manmade and natural compounds have been identified as endocrine disruptors.Any compound is characterized as an endocrine disruptor on the basis of certain properties such as compound should possess endocrine property, and it should demonstrate hormone receptor association to exhibit endocrine action in the individuals [26,31].
EDCs are found in many household products including cosmetic, human, and animal food items, consumer goods, and pharmaceuticals.EDCs can be categorized on the basis of origin into different groups such as industrial (alkylphenols, polychlorinated biphenyls (PCBs), and dioxins), agricultural (fungicides, herbicides, insecticide, pesticides, and phytoestrogens, etc), residential (bisphenol A, polybrominated biphenyls, and phthalates, etc.), and pharmaceutical (parabens) (Fig. 1).Including this, many types of heavy metals like mercury, lead, cadmium, and arsenic are also categorized as EDCs (Lauretta et al. 2019).A large number of EDCs have been identified their systematic role (table 1).
The widespread usage of EDCs, universal consumption, improper disposal of compounds having EDCs, and accidental discharge are causing the release of EDCs into the environment.A large number of EDCs have been identified in soil and water sources (surface water, groundwater, and sewage water) and are also associated with adverse effects on marine life, make prone to exposure to EDCs.It is found that EDCs can exhibit their role even at very low concentrations (fig.2) [32,35].Thus removal of EDCs from the environment is necessary for human health and urgent Impact of EDCs on Health.Studies on human, animal models, cell lines and epidemiological analysis have revealed that EDCs pose a major worry to public health (table 1).It is found that EDCs follow different mechanisms of action to exhibit their effects.Initially, it was assumed that EDCs performed impairment in the hormonal activity by interacting with nuclear hormone receptors but scientific studies have revealed that EDCs interact with many receptors including nuclear receptors, non-steroid receptors, membrane-bound receptors, orphan receptors, and many pathways such as steroid hormone synthesis or metabolism-related enzymatic pathways, and other mechanisms affecting endocrine and reproductive systems (fig.2).It is suggested that common disorders caused by EDCs are; problems associated with the female and male reproductive system, cancer, thyroid, metabolic disorders, diabetes, obesity, and cardiovascular diseases [11].
EDCs as the target for degradation are classified based on the functional groups, chemical structures, and pharmacological properties into five different groups such as organic pollutants (dioxins, phenols, and polycyclic aromatic hydrocarbons), hormones having hydroxyl and phenolic carbonyl groups, pesticides containing heterocyclic rings and aromatic rings, plasticizers (phthalates and bisphenols), and additives of personal care (phenones and parabens) [37].
Degradation of EDCs.Different techniques ranging from physical, chemical, and biological have been explored for the treatment of EDCs into complete degradation or conversion into less harmful products form but the wide applicability of EDCs, continuous population rise, and limited waste management approaches have made the removal of EDCs as a challenge.A variety of molecules originating from home and industry are released into water bodies without regulation; including emerging pollutants suspected to have effects on the environment and health [12].
The common methods to remove EDCs from water sources are adsorption, membrane treatment, flocculation, precipitation, and conventional wastewater treatment processes but these con-

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ventional approaches are not efficient and have associated technical limitations [7,19].It is found that flocculation and precipitation are not effective in the removal of nonylphenol and Bisphenol A. The removal efficiency for bisphenol A was found less than 10 % [15].Similarly, the membrane treatment method was not good and failed to remove hormones especially Bisphenol F [15].Photocatalytic degradation is the process that uses solar radiation to degrade EDCs.Though photocatalytic degradation of EDCs seems to be a considerable approach however the efficiency of the processes is dependent on photocatalyst [26,37].
Bioremediation or biodegradation is considered an environment-friendly technique to eliminate EDCs.Generally, three types of bioremediation processes are being used for the elimination of EDCs and these are bio-stimulation, bio-augmentation, bio-stimulation, and natural attenuation.There are varieties of microorganisms (Bacillus subtilis, Enterobacter sp., Klebsiella pneumonia, Paenibacillus sp., Phanerochaete chrysosporium, Pseudomonas putida, Serratia marcescens, and Trametes versicolor, etc.) that have been identified for the biodegradation of EDCs [5,6,13 ].
Since aerobic biodegradation of EDCs is very slow and many EDCs may remain present for up to more than 40 years [24].Thus, there is a requirement for an alternative method that is efficient and fast.Enzyme-based biodegradation of EDCS is an attractive and promising approach for the degradation of EDCs [33].Among these, oxidative enzymes are the choice of molecules for degradation of EDCs due to their versatility, the possibility of large-scale production, and properties modification [21].Many types of enzymes used in the biodegradation of EDCs are laccases, lipases, and Peroxidases.Out of these enzymes, laccase is considered one of the promising candidates for the sustainable removal of EDCs.It has been observed that laccase caused enhanced biotransformation of EDCs, such as nonylphenol, bisphenol A, and triclosan.A biodegradation efficiency of 89-100 % has been observed of EDCs removal [16].
Degradation of EDCs using laccase.Laccases are explored in many industrial applications such as textile, food, pharmaceutical, and, pulp

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and paper industry, etc (fig.3).These enzymes may also be used in the designing of biofuel cells, biosensors, and bioremediation agents.Laccases have attained attention due to their potential to perform oxidation of both nonphenolic and phenolic lignin-related compounds as well as recalcitrant environmental contaminants [9,27,29].
Laccase-mediated degradation of emerging contaminants and xenobiotic chemicals is one of the recent and important advantages to treat waste material and drinking water.These are involved in the catalysis of the oxidation of a wide category of xenobiotics compounds with the reduction of molecular oxygen to water.It is suggested that this property (oxidative degradation) has enabled the use of laccase to treat endocrine disruptors attractively than other enzymes because these enzymes do not require additional co-substrate or cofactor for activity.Though, researchers have demonstrated the role of mediators (acetosyringone) to enhance the efficacy of the reaction.Including this, the use of immobilized enzyme techniques is gaining attention as it is considered cost-effective and may be used at the industrial level.It has increased reusability, easier product separation, catalytic stability, and reduction of product inhibition [3,8].
Natural sources of laccase.Laccases are broadly present in nature and present in a variety of organisms.These enzymes may be isolated from bacteria, fungi, lichen, plants, and insects, etc.Including this, laccases isolated from different sources demonstrate specific sequences and catalytic characteristics.In each category, different organisms produce laccases [9].
Bacteria.Laccases have been isolated from many types of bacteria such as Azospirillum lipoferum, Bacillus, Haloferax volcanii, Klebsiella, Marinomonas, Nitrosomonas, Proteobacterium, Pseudomonas, Streptomyces, and Yersinia [29].Bacterial laccases have many properties such as stability in the range of pH, temperature, salt concentrations, and organic solvents [18,29].It is also found that bacterial laccases show activity in neutral to alkaline pH and these are more stable enzymes as compared to laccases isolated from fungal sources.Bacterial laccases are used in many processes such as metal oxidation, pigmentation, sporulation, UV protection, and xenobiotic degradation, etc.These enzymes are also a very good choice for wastewater treatment at a high salt concentration [34].Due to the versatility of source microorganisms, bacterial laccases possess optimum alkaline pH, greater thermostability, salt tolerance, and low redox potentials, bacterial laccases are considered valuable func-tional complements as compared to fungal laccases in various biotechnological and industrial applications [1].
Fungi.Laccase enzymes are produced by Ascomycetes, Basidiomycetes, and Deuteromycetes, and out of these common sources of the fungal laccases are basidiomycetes (white-rot fungi such as Phlebia radiata, Pleurotus ostreatus, and Trametes versicolor).Further, many species of Trichoderma (such as; T. atroviride, T. longibrachiatum, and T. harzianum, etc.) have been studied as a source of laccases [17,30].Other fungal sources of laccases are Agaricus bisporus, Coprinus cinereus, Pleurotus ostreatus, Pycnoporus sanguineus and Phanerochaete chrysosporium [4,36].Fungal laccases have been found optimally active at acidic pH and they are not active at high temperature.Fungal laccases are generally glycosylated and the sugar portion provides conformational stability to the enzyme and also provides protection against inactivation from radicals and proteolysis [23].Including this, the recombinant fungal laccases also have been used for the bioremediation process.It is found that most of the naturally occurring species are poor producers of laccases.
Plants.The laccases isolated from plants share their structure and reaction mechanisms with the fungal laccases but plant-based laccases are not extensively used in bioremediation and other industrial applications.Laccases have been isolated from many plants such as; Toxicodendron vernicifluum, Gossypium hirsutum, A. thaliana, Oryza sativa, Nicotiana tabacum, and Asparagus densiflorus, etc [1].CONCLUSION Endocrine disruptor chemicals are used in the manufacture of the large number of daily use items and these compounds are released into environment during usage and disposal.These chemicals are found to interfere with the normal activity of hormones.Including this, human exposure to these chemicals may cause growth and development-related health disorders.Thus presence of EDCs in the environment is major health concern and their removal from the environment is required.Different methods are being used for the degradation of ECCs from the environment such as chemical, physical and biological.Out of these biological methods are considered environment frieldly approaches for EDCs removal.Laccase enzyme has many industrial applications including degradation of endocrine disruptors.Laccase enzymes are reported to catalyze the oxidation of various phenolic and non-phenolic compounds.Thus, these enzymes have a wide

Figure 2 -
Figure 2 -Different properties of endocrine-disrupting chemicals reflect their health risks

Figure 3 -
Figure 3 -Applications of laccase in various industrial activities

Медицина и экология, 2023, 4 Обзоры литературы Endocrine Disrupter compounds Sources Effect on Humans
Skin rashes, Mental disorders like swings of mood and loss of memory, loss or reduction of hearing and peripheral vision, destruction movement coordination like writing or walking, body & hands feels like 'pins & needles' feeling every time, Muscle weakness Dioxin Meat, Fish, Milk, Eggs and Butter Diabetes, Heart problems, Reduced fertility, reduced sperm activity and low counts, interfered Embryo development and miscarriage, many type of Cancers Atrazine Corn crops, Drinking water Breast cancer, belated puberty and prostate inflammation in animals, Prostate tumours Phthalate Plastics, drinking water bottles, Pesticides, Ventilator tubes, Blood collecting bags and infusion tubing, nutrition feeding bags, soft toys, plastic, food packing Hormone misbalancing, Lower sperm count and reduced mobility, defects in the male reproductive system by birth, Diabetes, Obesity and

Table 1 -
Source and effect of different endocrine disrupter chemicals on human health

Обзоры литературы EDCs Affect growth and development Affect hormanal Homeostasis Effective at very low concentration Exhibit Bioaccu mulation Mimic the structure of hormones Persistent in nature problem
. EDCs are also considered difficult to eliminate from the environment.