Chemical health hazards and toxicity of environmental pollutants on humans, animals and others: An overview

: Toxicology, rooted in ancient civilizations and evolving through pivotal historical figures like Paracelsus and Alice Hamilton, has become a multidisciplinary field encompassing various branches such as pharmacology, medical, forensic, and environmental toxicology. This exploration embarks on a journey through time and science, unravelling the intricate interplay between chemicals, pollutants, and their profound impacts on human, animal, and environmental well-being. Spanning from ancient practices like the use of hemlock in Greek capital punishment to modern-day concerns surrounding industrial chemicals and pesticides, the review delves into the mechanisms by which toxins disrupt biochemical pathways and induce organ dysfunctions. From heavy metals and pesticides persistent effects on the nervous and reproductive systems to the carcinogenic properties of polychlorinated biphenyls (PCBs), hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). The review highlights the diverse range of toxicants and their widespread impact on human health. Additionally, the review underscores the importance of proactive measures to mitigate exposure to harmful substances, advocating for the development of antidotes, bioremediation techniques, and stricter environmental regulations. By addressing the urgent need for comprehensive strategies to combat toxicological hazards, this review aims to contribute to ongoing efforts to safeguard public health and environmental sustainability in the face of evolving chemical threats.


Introduction
Ancient toxicology provides a fascinating perspective covered by Elsevier in ancient Egypt, the death of Cleopatra, hemlock (Greek capital punishment), the case against Socrates, poisoning in ancient Rome, the snake as a biological symbol, poisonous medicine in ancient China-aconite (Chinese poison arrow) [1].The uses of poison vary widely, such as the use of arsenic to achieve the "milk and roses" complexion many women envied and the treatment of syphilis with mercury [2].Toxicology or Agada Tantra is one of the eight clinical specialties of Ayurveda and has been exclusively associated with healing cases of envenomation [3].In the medieval and Renaissance periods, medicine and toxicology were mostly filled with beliefs in folklore, superstitions, and religion.Subsequently, a new era started with Paracelsus, a Swiss physician alchemist (1493-1541), who is considered the father of toxicology.Paracelsus demonstrated the specific toxicity of chemicals in plants and animals.He also stated that there is nothing that is not poison.The judicious use of the right dose differentiates poison from remedy and also moots the concept of a dose-response relationship [4].Georgius Agricola published the book "De Re Metallica" on mining and metallurgy in 1556 [5].Thereafter, during the mid-19th century, Alice Hamilton carried out pioneering work in the field of industrial toxicology, particularly dealing with industrial chemicals and metals in the USA.Her work largely helped in understanding the occupational diseases associated with mining operation [6].Henri Becquerel, a French physicist, and Nobel laureate, while studying phosphorescence in uranium salt, discovered radioactivity in 1896 [7].From 1900 to 1930, there was an emergence of chemical elixirs, many chemicals of therapeutic importance, warfare chemicals, and insecticides.During this time, the U.S. Food and Drug Administration, and Drug and Cosmetics Act were developed.Thereafter, many toxicological regulatory bodies were established, including the International Union of Toxicology, the International Society for the Study of Xenobiotics, the Academy of Toxicological Sciences, and the American Board of Toxicology, and many important toxicological books were published [8].Also, many accidents and disasters of toxicological significance occurred, such as the Bhopal disaster (the release of methyl isocyanate from a Union Carbide production plant), the eruption of a carbon dioxide bubble in Lake Nyos, chemical spillage and fire at the Sandoz Laboratory which led to tons of chemical spillage into the Rhine river in Basel, and the Chornobyl accident (nuclear power plant meltdown and harmful radioactive waste release) which resulted in atmospheric poisoning to millions of people and many more events have occurred causing numerous toxicological and harmful effects on humans and the environment at large [9].Furthermore, our modern scientific knowledge, advanced analytical methods, and technology helped us to understand how poisons/toxins/toxicants and therapeutic agents act differently on the human body and organ functions, and their underlying mechanism(s) of action [10].Some of the observations on toxicology research helped us to use toxic compounds as a tool for the development of animal models for pharmacological screening (e.g., MPTP, toxins of plant and microbial origin).Modern toxicology helped us in developing research methodologies including invitro techniques and move away from the traditional approaches of animal testing to harm-free roots of experimentation [11].
The word toxicology is derived from the Greek word "toxion", and the scientific study "logos" was coined in the 17th century [2].Today, toxicology encompasses diverse scientific disciplines such as biology, chemistry, pharmacology, medicine, etc., and deals with the study of adverse effects on humans, animals, and other living organisms [12].Furthermore, it even includes the practice of diagnosis and remedial measures for the treatment of toxin/toxicant effects (in short management of toxicity).Alternatively, some scientists have defined broadly toxicology as a science of study to characterize the effects of chemicals, gases, pollutants, biologicals, xenobiotics, drugs, and toxins on humans and other living organisms.Thus, definitions of toxicology have undergone many transformations over the years.The term toxicity is the inherent capacity of chemicals or foreign substances to cause injury, harmful effects, and health hazards [13].
The multidisciplinary toxicology has been classified into different branches-all with some similarities but many differences.They are medical toxicology, analytical toxicology, applied toxicology, foreign toxicology, industrial toxicology, immune toxicology, genetic toxicology, environmental toxicology, reproductive toxicology, and investigative and regulatory toxicology (refer Figure 1).Each branch of toxicology has been briefly defined and explained in the figure itself.Hence, they will not be discussed or elaborated.The aim of this review is to elucidate the toxic and adverse effects of various chemicals on the human body and organ functions.Additionally, it seeks to present the state-of-the-art knowledge in the field of toxicology, with special emphasis on toxic manifestations, associated mechanisms, and their outcomes on human health.Furthermore, this review aims to provide an overarching environmental perspective within which humans, animals, and other organisms coexist.

Environmental pollutants and their effect on human health, animals, and others
Many chemicals exposure/ingestion leads to biological effects by interfering with functions associated with specific biochemicals or metabolic pathways and/or macromolecules within the tissue (e.g.warfarin inhibits vitamin K-dependent posttranslational modifications of clotting factors in hepatic tissue) [14].In addition, vapor, chemicals, solvents, pure hydrocarbons, containing hydrogen and carbon (chief components of different types of fuels, also exist in the form of gas, liquid, solid, or polymers) to partially oxidized hydrocarbons to organic compounds containing chlorine, sulphur and nitrogen, polyunsaturated biphenyls (mainly polychlorinated biphenyls and its congeners) used in plastics, fluorescent lighting ballast, transformers, capacitors, organochlorine pesticides, other new generation pesticides, herbicides; asbestos, silica, cigarette smoke all these substances known to induce ill effects/toxic adverse effects on the human body as well as various organ functions and ultimately manifest various disorders or diseases [15] (Figure 2). Figure 2. The exposure of environmental chemicals, gases, particles, ingestion including drug treatment, and various aspects on physiological events and general effects on the human body.

Effects of gases, aerosol, solvents, and chemicals
Environmental pollutants such as gases, dust, aerosol, and volatile organic compounds in the presence of sunlight react with nitrogen oxide emitted from industrial facilities, electric utilities, and motor vehicle exhaust to form ozone, which in turn helps the formation of fine particles.Furthermore, chemicals from the environment include inorganic metals (mercury, arsenic, antimony, lead, cadmium, silicon, zinc, chromium, manganese, etc.), salts of metals (oxide, sulphates of metals, and others), ammonia, nitrates, etc. Organic chemicals like pesticides, herbicides, preservatives, antibiotics, biotoxins, artificial colours, hydrocarbons, organic heavy metals, and carcinogenic compounds also persist in the atmosphere, water, and foods [16,17].
When such pollutants enter the human body via inhalation, skin contact (at workplace) and reach alveoli absorbed rapidly and then distributed to various organs via blood stream.The particles retained in the alveoli exert toxic effects locally (refer Figure 2).Furthermore, chemicals or toxins from exogenous sources when ingested, inhaled, or absorbed in the body either from water, air, foods, drugs etc. also produce toxicity either by the parent molecules present or its metabolic products formed by its metabolism in different organs.High blood flow organs (brain, kidney) are also vulnerable to toxic effects of chemicals.Cardiac tissue is more sensitive to toxininduced alterations of ionic gradients.
Effects of air pollutants such as metal particles (originated from industries, fertilizers usage, burning of fossil fuels etc.) and water pollutants largely dissolved chemicals, metal salts and persistence in water and food, when enter the body causes cellular damages in vital organs (viz.liver, lungs, kidneys) (Figures 2-5).
Similarly, exposure to corrosive chemicals leads to local irritations/caustic effects at the site of location due to the denaturation of macromolecules (proteins, and cleavage of chemical bonds required for the function of biomolecules) which are often termed as non-selective.Heavy metals, which cannot be metabolized persist in the body and induce toxic effects by combining with one or more reactive groups (ligands) that are essential for physiological functions (particularly -O, S-and Ncontaining ligands which are known to form -OH, -COO-, -OPO3H, C=O, -SH, -S-S, -NH2 and -NH) leading to oxidative stress and culminating into impairment of endogenous antioxidant enzyme defensive system viz, superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), catalase [18].

Asbestos
A fibrous silicate minerals used widely in building materials, range of manufactured goods (automobile clutch, brake, and transmission parts) and heat resistance fabrics, packaging materials gaskets and coatings.The chronic exposure of asbestos especially at workplace or inhalation of asbestos fibres can lead to serious lung disorders.Many of them are described below.
Asbestosis is a chronic interstitial lung disease largely caused by the inhalation of asbestos fibers (composed of mineral silicates formed due to damaged and degraded asbestos material in the environment) affecting people working in the shipyard, mining, painting, aerospace, building construction, installation of the asbestos board, sprayer, and asbestos stripping, insulation workers.In addition, general community exposure to road surfaces, playground material, and chemical paints.
The three diseases that are most commonly associated with asbestos exposure are asbestosis, mesothelioma (it is a rare type of cancer that occurs in the region of the chest wall), and lung cancer.Asbestosis is caused due to the inhalation of asbestos fibres over an extended period.Once these fibres enter the lungs, they can cause inflammation and scarring of the lung tissue.Over time, this scarring is known as fibrosis.Further, the fibre in the lungs leads to the accumulation of macrophages turned into fibroblasts, the other participating biological events are: 1) reactive oxygen species originating from immune cells and phagocytes in response to asbestos fibres causes oxidative injury (type 1 alveolar cells, development of fibroblast growth factor-beta) that results in fibrosis.2) Macrophages produce tissue necrosis factor, interleukins, and stimulation of phospholipase C pathway such mediators are generated due to above mentioned pharmacological events play a key role in stimulating lymphocytes, myofibroblasts leading to the proliferation of fibroblasts and increased (2-fold) in the number of cells in the matrix.Macrophagesderived fibroblast growth factor, platelet, and insulin-like growth factor also participate in the development of fibrosis such as biological alterations in the lungs which leads to a significant combination of fibrosis, pleural thickening, and inflammation resulting in progressive impairment of lung function [19,20].The reported major clinical symptoms are shortness of breath, persistent cough with mucus, clubbing of fingers, and inability to perform day-to-day physical activities.It is estimated that more than 55,000 deaths per year in the world due to asbestosis [21,22] (Figure 4).
Increased levels of ROS, cytokines, and growth factors due to chronic exposure of asbestos may produce harmful effects on lungs.The pathogenesis of asbestos induced pulmonary diseases derived long term interplay between constant or persistent free radical production and expression of cytokines, growth factors and other inflammatory cell products.

Pesticides and herbicides
Pesticides are synthetic chemical compounds used for plant protection and kill pests/insects.Pesticides are used to eliminate or control a large spectrum of agricultural pests including vectors of human and animal disease.Herbicides are chemicals used in agriculture and known as weed killer.

Organophosphates
Organophosphates are comprised of diverse groups of chemical compounds (diazinon, phosmet, malathion, parathion, chlorpyrifos, and many more) and are largely used as pesticides and herbicides, also nerve agents in chemical warfare.Organophosphate exerts toxicity in mammals through the inhibition of acetylcholinesterase which results in the accumulation of excess acetylcholine.The accumulated acetylcholine manifests with cholinergic toxidrome, which includes effects on both nicotinic and muscarinic receptors and CNS.The mortality rates caused by organophosphate insecticides range globally from 2% to 25%.The serious effect is respiratory collapse (bronchorrhea and bronchospasms) which may be the major cause of death.Respiratory distress is also accompanied by bradycardia.The onset of clinical symptoms varies based on the type of compound and manifests immediately and reversal can take many weeks.Most organophosphate compounds are readily absorbed in the body after inhalation or ingestion.However, systemic absorption via dermal exposure is comparatively slow.Overstimulation of nicotinic receptors causes myoclonic jerking, which finally results in flaccid paralysis due to depolarization blockade.The clinical symptoms are hypertension, sweating, tachycardia, miosis-induced blurred vision, diaphoresis, and leucocytosis with the left shift [23][24][25].
OPs exposure to human (males) induces adverse effects on semen normal quality and morphology.This effect is mainly due DNA of spermatozoa and alterations in testicular somatic cell functions [26] (refer Figures 4 and 7).Most of the pesticides including OPs and their metabolites affects any of reproductive or developmental end points in multiple mammalian species including humans (Table 1).Chronic sub-lethal dose to birds reduced fertility, suppression of egg formation and chick rearing behaviour [27].OPs on chronic exposure also reported to induce lung, kidney, liver, and breast cancer (Table 1).

Carbamates
Exposure to carbamates and its derivatives causes inhibition of kisspeptin neurons, which lead to low levels of Gonadotropin-releasing hormone (GnRH) in the hypothalamus, which consequently inhibit the synthesis of Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the anterior pituitary.Such hormonal changes ultimately compromise steroid synthesis in the testis.This effect causes reduction of epididymal, and testicular sperm counts as well as testosterone concentration.Thus, chronic carbamates exposure led to male fertility problems (Figure 5).
Carbamates are derived from N-methyl carbamic acid and have been classified as Class II by the Environmental Protection Agency and World Health Organization, indicating they are moderately toxic.Some carbamate derivatives are considered endocrine-disrupting chemicals (EDC) based on their specific adverse effects.(refer to Figures 6 and 7) which depicts the profile of action of EDS (endocrine disrupting substances).
Carbamates inhibit acetylcholinesterase and melatonin receptors.The clinical symptoms following ingestion inhalation or exposure are tachycardia, hypertension and mydriasis, and flaccid paralysis at a toxic level.Both organophosphates and carbamates induce similar types of toxicity (derived from muscarinic and nicotinic receptors).However, the toxicity symptoms subsided after 24 to 48 h in carbamateinduced intoxication as compared to organophosphates.This is because during the phosphorylation of organophosphates to acetylcholinesterase carbamatecholinesterase bond hydrolyse rapidly within hours [28][29][30].
Extensive usage of carbamates for increased food production and other purposes, their residual contents are alarming high in soil, wastewater effluents, and many food products all over the world [28].

Pyrethroids
Pyrethroids are synthetic insecticides composed of an acid and alcohol derived from pyrethrins and used in controlling insect pests in agricultural production, and public and animal health.Pyrethroids exert both mammalian and insect toxicity by modifying voltage-gated sodium channels in neuronal membranes and thereby disrupting the electrical signalling throughout the central and peripheral nervous systems.The major toxicity symptoms include impaired motor coordination, tremors, convulsions, burning, and itching sensations.Pyrethroids act as potential dermal and respiratory allergens, and chronic exposure can result in contact dermatitis or asthma-like clinical conditions.Death occurs in humans largely due to respiratory failure.Pyrethroids are more toxic to insects due to their limited ability to eliminate these compounds.At high concentrations, pyrethroids act on GABA-gated chloride channels, nicotinic Ach receptors, and intracellular gap junctions and induce seizures.They are also reported to be toxic to aquatic organisms including fish at an extremely low level (4 parts per million).Beneficial insects such as bees, dragonflies, mayflies, and bottleflies are extremely sensitive and can be eradicated [31].
The recent research reports demonstrated influence of oxidative stress generated by pyrethroids on the modification of DNA, RNA, proteins, lipids both in cells and extracellularly [32].The molecular basis of patho-mechanisms of the pyrethroids effects are of detrimental in nature.

Rotenone, a phytoinsecticide
Rotenone, a plant product (isoflavone) used as a broad-spectrum insecticide in a large number of crops.It mainly acts by inhibiting the oxidation of the reduced form of nicotinamide adenine dinucleotide (interfering with the electron transport chain within the complex system in mitochondria).Thus, creating reactive oxygen species (ROS) which can damage DNA and other components of mitochondria.Rotenone is toxic not only to insects and fish but also to humans and animals.
The rotenone study in animals demonstrated that low doses induce oxidative damage and death of dopaminergic neurons and exhibit symptoms of Parkinson's disease.The dust preparation is highly irritating to the eyes (causing conjunctivitis), skin (causing contact dermatitis), rhinitis, and pharyngitis [33].
Acute poisoning is characterized, respiratory stimulation followed by respiratory depression, ataxia, convulsions, and death due to respiratory arrest.And it is not a human carcinogen.

Herbicides
Herbicides are routinely used to control noxious plants or for falling or inhibiting growth of unwanted plants such as agricultural weed.Bioherbicides are phytotoxins, pathogens and other microbes used as biologic weed control.Chemical herbicides, mainly chlorophenoxy, glyphosate, and bipyridyl herbicides are the most widely used for the destruction of weeds or undesirable vegetation.Biosynthetic pathways of amino acids are the major site of action of herbicides.Bipyridyliums and heteropentalenes induce generations of superoxide radicals by energy divergence from photosystem I of photosynthesis [34].Also reported that lipid synthesis is the site of action of a broad array of herbicides that are used for controlling monocot weeds.The chemical grouping of dioxins is highly toxic and can cause problems with reproduction development and the immune system.They are also known for disrupting endocrine hormones and leading to cancer.In humans, 2,4-dioxane in large doses can cause coma and muscle hypotonia.In animal experiments, herbicides have demonstrated a fair degree of nephrotoxic and hepatotoxic.Occupational hazards particularly with the chlorophenoxy herbicides have been implicated in cancer risk.A greater degree of exposure to chlorophenoxy herbicides has been associated with soft tissue sarcoma and non-Hodgkin lymphoma.Glyphosate is reported to be an irritant to the eyes and skin.Female mice treated with tridiphane, a dinitro aniline herbicide, exerted embryo toxicity during early pregnancy [35].
Paraquat and diquat belong to the bipyridyl group and are the most important herbicides reported to cause liver damage in animals and humans.The cytotoxicity of paraquat established by an increase in lipid peroxidation and complete oxidation of both NADPH and NADH occurs at a lower concentration than LC50 level.Furthermore, also stimulates glucose oxidation at subtoxic doses [36].The study of paraquat and diquat demonstrated inhibition of microsomal mixed function oxidase (MFO) and NADPH oxidation in lung and kidney microsomal preparations in concentration concentration-dependent manner.It is documented that the degree of NADPH oxidation is an important biological event and is considered to be an important index in the inhibition of xenobiotic metabolism [37].Its toxicity rating is 4, which places the probable human lethal dosage at 50-500 mg/kg.Paraquat accumulates slowly in the lungs by a special active process which leads to inflammation, edema, and alveolitis and then develops progressive fibrosis.Paraquat may induce the pathogenesis of dopaminergic neurons via oxidative stress [38].Symptoms observed after the oral injections are mainly hematemesis and bloody stools.A few days later delayed toxicity manifests such as respiratory distress, and progressive development of congestive haemorrhagic pulmonary edema associated with the widespread cellular proliferation.Death may occur after several weeks of ingestion.No successful method of treatment is available for such toxicity manifestations till today.Organic herbicides (amide compounds) are more toxic to animals.Haemolysis, methemoglobinemia and immunotoxicity have occurred on experimental exposure [39].

Volatile organic compounds (VOCs)
All halogenated hydrocarbons and aromatic hydrocarbons are volatile solids and liquids and are also known to emit gases.The concentration of many VOCs is consistently higher indoors (ten times) than outdoors.Household products such as paints, varnishes, wax, disinfectants, air fresheners, cosmetics, degreasing and hobby products, pesticides, preservatives, fuels, aerosol sprays, cleansers, and dry clean clothing all have ingredients of organic chemicals and release organic compounds while using them.They can expose themselves and even stored materials also release very high organic compounds.The elevated concentration can persist in the air longer time.Similarly, office equipment (copiers, printers, correction fluids, photographic solutions, graphics) also contain organic compounds.The most common toxic symptoms reported on short/long exposure to these diverse volatile organic chemicals are eye, skin, and throat irritation, headache, allergic skin reactions, emesis, nausea, etc. Excessive exposure may cause liver, kidney, CNS, and visual disorders [40].
Exposure to solvents and organic chemicals of a liquid nature is having major health risk in the workplace.Vapours of solvents accumulate in confined places and persist for a long time.Solvents enter the body by inhalation, swallowing, and skin contact.Solvents and their vapours and mist induce a variety of effects on human health such as narcotic effects, fatigue, dizziness, and toxic manifestations.Higher levels of these solvents may cause unconsciousness.In addition, they are known to induce skin disorders and dermatitis.Some solvents even enter the blood circulation via the skin [41].Furthermore, solvents also induce liver, kidney, heart and blood vessels, bone marrow, and CNS and manifest toxic effects.Benzene, carbon disulfide (CS2), carbon tetrachloride (CCl4), and toluene solvents are excreted mainly via the kidney (urine), skin (sweat), and lungs by exhalation.Ventilation is the most important while handling and using solvents.Personal protective equipment (aprons, gloves, masks, and filters) should be considered and available [42][43][44].
Major national exposures to benzene occur through tobacco smoking.Low levels of exposure to benzene cause headaches, loss of appetite and gastrointestinal disturbances, irritation of the nose, throat.Long-term benzene exposure in humans induces hematopoietic toxicities of which the most alarming effects are agranulocytosis and leukemia (acute myelogenous leukemia).The other path of exposure is non-occupational type to benzene which occurs due to combustion of fossil fuels, automobile gasoline (petrol pump workers and other oil refinery unit operations, regular vehicular traffic, and consumption of contaminated water) [45].

Table 2.
Gaseous and Solvent based pollutants, their toxicity, and clinical symptoms.

Environmental gaseous pollutants Nature of toxicity and clinical symptoms
Carbon monoxide Restrict oxygen supply to tissue/organs via binding to haemoglobin, headache, vomiting, dizziness, seizures, and coma.
Chlorine, ammonia, sulphur dioxide, nitrogen oxide Local irritant gas-corrosive action leading to cough, wheezing, pneumonia Cyanide Restricting cellular oxygen used via binding to cytochrome a3, producing headache, nausea, vomiting, convulsions, and coma Hydrogen sulphide, ozone Same as above.Formation of highly reactive free radicals, intermediate produces bronchitis, emphysema and pulmonary fibrosis.

Benzene
Targeting pluripotential bone marrow, stem cells as well as other stem cells, excessive bleeding.Produce bone marrow injury, aplastic anaemia, leucopenia, thrombocytopenia, leukemia, changes in blood vessels of antibodies, myeloma, lymphoma.
Toluene CNS depression skin and eye irritation.It is fetotoxic.
Other effects of long-term exposure to organic solvents associated with aromatic organic chemicals cause aplastic anaemia which results in erythropoiesis.Also causes respiratory effects (pulmonary inflammation, forced vital capacity, and forced expiratory volume) and thyroid functions (changes in TSH levels, T3, T4) by the toxic substances present solvents and air pollutants via influencing hormones of the hypothalamic-hypophyseal-axis [46][47][48][49].Shoe factory workers who are exposed to organic solvents suffer from chronic airway impairment and non-bronchial hyperresponsiveness [50].The carbon monoxide emitted by internal combustion of engines from motor vehicles readily enters the blood through the respiratory and binds over 200 times more firmly to Hb than oxygen to form carboxy haemoglobin which interferes with blood oxygen transport capability finally results in hypoxia, consequently stimulating erythropoiesis.Such biochemical events induce the production of a greater number of RBCs and haemoglobin in circulating blood [51] (Figure 5 and Table 2).

Polycyclic aromatic hydrocarbons (PAH)
Ubiquitous environmental pollutants are generated during incomplete combustion of organic materials e.g.coal, oil, petrol, and wood.Some of are originate from open burning, petroleum spillage or coal deposits, and volcanic activities.Other sources of PAHs are the surface of lakes, streams, and oceans, coal gasification and liquefying plants, carbon black, coal tar pitch, coke, and aluminium production petroleum refineries as well as motor vehicle exhaust.They are used as intermediates in pharmaceuticals, agricultural products, thermosetting plastics, lubricating materials, and other chemical industries [52].They are lipophilic and hence readily absorbed from the GI tract of mammals and distributed to various tissues, but largely localized in body fat [52,53].Workplace exposure to high levels of pollutants and mixtures containing PAHs causes irritation, inflammation, nausea, vomiting, and diarrhoea.Anthracene and benzopyrene elicit allergic reactions both in animals and humans.Chronic exposure to PAHs may cause decreased immunity, cataracts, nephrotic and hepatic damage, asthma-like symptoms, and pulmonary function abnormalities [54].The basic biochemical underlying mechanisms involved the binding of reactive epoxides and dihydrodiols of PAH metabolites to cellular proteins and DNA.Such molecular events result in disruptions and cell damage which lead to mutations, developmental malformations, tumors, and cancer.PAHs induce moderate to high acute toxicity in fish and birds [52].
Carbon tetrachloride is an important chemical used for multiple purposes.Generally, people are exposed to carbon tetrachloride (CCl4) through consumption of contaminated drinking water.Low-level inhalation produces irritation of the eyes, at higher levels, it produces nausea, vomiting, depression, incoordination, paresthesia, seizures, coma, and death [55].
Non-lethal acute exposure can occur in 7 hours to several days and induces liver and kidney damage.The liver damage is from enhanced lipid peroxidation largely due to free radical intermediates which causes intracellular and intramembranous lipid destruction.Also due to the formation of metabolite phosgene which is also responsible for hepato-toxicity [56,57] (refer Table 1 and Figure 5).

Polychlorinated biphenyls (PCBs)
Figure 8.The schematic representation of effects of EDCs (endocrine-disrupting chemicals) on Human Health.Polychlorinated biphenyls, polychlorinated dibenzo-p-dioxin (PCDDs), or die oxides of which the most important is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).In addition, there is a larger group of dioxin-like compounds including certain polychlorinated dibenzofurans (PCDFs) and co-planer biphenyls [58].PCBs are oily liquids and solids and stable mixtures that are persistent to extreme temperatures and pressure.Industrial production of PCBs began in 1929, it is estimated that 1.2 to 1.5 million metric tons have been produced.They are used in many products, from lubricants to pesticides, paper adhesives, plastic paint, and flame retardants.Animal studies demonstrated that PCBs could affect the immune, endocrine, and reproductive systems, but such effects are not established in humans [59].When PCBs are fed to animals in large doses over a shorter period (4 to 6 weeks) can induce cancer.However, humans exposed to high levels for prolonged periods did not cause cancer.Therefore, they are classified as cancer-causing chemicals [60].Numerous documented studies indicated environmental and occupational exposure to such chemicals especially from building constructions (refer to an earlier statement on chemicals and pollutants) and waste cycling sites (highest PCB contamination).PCB contaminated working place, workers often suffer from different health problems such as psychological, and neurobehavioral deficits, dementia, impaired immune system, cardiovascular disorders, and cancer.Furthermore, accumulation can induce adverse effects on the reproductive system which is manifested in offspring.Despite of ban on their use in the 1970s their resistance to chemical and thermal degradation results in bioaccumulation in marine animals/organisms and humans.Hence PCBs continue to be a serious problem to the environment and humans at large and the same has been included in EDS.They have been reported to induce in humans predominantly developmental toxicity, immunotoxicity, metabolic diseases such as type-2 diabetes, thyroid disorders, and impairment of female and male reproductive health [61].
BPA affect liver-spleen axis increase androgen activity cause low grade inflammation in the development of polycystic ovarian syndrome (PCOS) (refer Figure 8).

Antidotes for chemical and metal poisoning
Some selective chemicals dote for insecticide acute intoxications are available only in a small number.Some of the chemical antidotes are outlined below: Atropine is a muscarinic receptor antagonist; hence, it has been used to block the access of increased acetylcholine to muscarinic receptors.It is an important antidote for insecticide intoxication in organophosphates and carbamates.However, the dose of atropine use depends upon the state of intoxication.The second dote is pralidoxime, which is less effective, and its doses used vary very much [62,63].

Penicillamine (D-b, b-dimethyl cysteine)
Penicillamine is an effective chelator of copper, mercury, zinc, lead and thereby accelerate the excretion of these metals in urine.N-acetylpenicillamine is more effective than penicillamine in protecting especially the toxic effects of mercury.Animal studies have demonstrated polycarboxylic acid chelators (CaNa2 EDTA) and calcium trisodium diethylenetriaminepentaacetate EDTA.(Pentate calcium trisodium; Ca-DTPA), can be effective when administered immediately after exposure to cadmium.Dimercaprol and penicillamine are used to treat chronic exposure to arsenic.In methyl mercury poisoning L-cysteine can be infused into the arterial blood entering the dialyser to convert methylmercury into diffusible form.This method has been found to be effective in humans [64].In acute cyanide poisoning antidotes such as sodium nitrate, sodium thiosulphate are reported to very effective by intramuscular route in various clinically relevant animal models [65].
Enhancement of detoxification of toxic agents: Some toxic substances which hepatotoxic and metabolised by the liver via cytochrome P450.In such cases, treatment with N-acetylcysteine shall serve as a substitute for glutathione.This will bind and inactivate the reactive metabolite and minimize the hepatic toxicity by the toxicant [66].Chelators are known to form covalent bonds specifically with cationic metals.The chelators form a metal complex and are then excreted in urine, which may enhance excretion of the heavy metals.However, chelators are not specific to heavy and essential metals and some of the chelators induce serious adverse effects.
Hence, physicians need to outweigh the risks associated with chelation therapy.Dimercaprol is used to chelate mercury and arsenic along with calcium disodium edetate to treat lead intoxication.It is to be administered intramuscularly as it is not effective by oral route.Since dimercaprol is known to elevate blood pressure and heart rate, physicians should be careful when it is used especially in hypertensive people [67].
Succimer, a derivative of dimercaprol is effective by oral route and its lack of effects on blood pressure and heart rate.Today, succimer is approved for the treatment of lead toxicity.Further, it is also found effective in chelation of other heavy metals.Calcium disodium edetate is used for lead and other heavy metals intoxication intravenous or intramuscular route only.However, it is known to cause kidney damage, but the damage is reversible after the stoppage of treatment [22,68].

Summary and conclusion
In the present review, we try to present the impact of chemicals and pollutants on humans, animals, and environmental health.We explained and discussed various pollutants such as industrial chemicals, pesticides, heavy metals, and air pollutants.Also referred to the sources, pathways of exposure, and toxic events on physiological and organ functions of the body.These pollutants elicit a large spectrum of toxic effects on CNS, CVS, respiratory system, liver, kidney, etc. by interfering with or impairing biochemical and metabolic pathways viz.oxidative, mitochondrial electron transfer system, enzyme inhibition, voltage-gated channel(s).Local skin, eye, and mucus membrane irritation are produced by denaturation of macromolecules and/or cleavage of chemical bonds.Clinical symptoms are diverse and related to the specific organ system, and the type and nature of chemicals or toxicants.The genetic effects via mutational or larger damage of genetic apparatus led to different types of cancer and also reproduction and developmental-related effects on offspring.
Overall, our review underscores the urgent need for proactive approaches to address the impact of chemicals and pollutants on human, animal, and environmental health.A concerted research work needs to be pursued to develop new generations of antidots and antagonists, and bio-remedial measures for minimizing air and water pollution.Exploring isolation of new microbes whose metabolites and enzymes may be helpful in removing chemicals and other harmful pollutants from environment ecofriendly ways.
Furthermore, a better understanding of the cellular and molecular mechanism(s) responsible for the developmental effects of air pollution on human body and organ systems are also essential because it may lead to develop specific therapeutic intervention.It is needless to say that any efforts/approaches towards diminishing emissions and thereby improve air quality would be warranted.

Figure 3 .
Figure 3. Metals affecting different intricate structural part of kidney.

Figure 4 .
Figure 4. Underlying molecular mechanisms of asbestos induced lung disease.

Figure 5 .
Figure 5. Potential effects of pesticides on developmental and reproduction processes in humans.

Figure 6 .
Figure 6.Exposure of chemicals, vapours, and other environment pollutants at workplace.

Figure 7 .
Figure 7.The Pathway Associated Toxicity with BPA and Other EDC (endocrinedisrupting chemicals).

Table 1 .
Biochemical and cellular effects of pollutants (of environmental origin) that lead to carcinogenesis*.