We live in a toxic world, which gives us at risk for carrying a body burden of synthetic chemicals. Body burden is the term for the concentration (or amount) of toxic exogenous substance or its metabolites in the body at any given time (Thornton et al., 2002, p. 315; Hayes' Handbook of Pesticide Toxicology, 2010). These toxic chemicals can accumulate in our fat tissue, blood and organs and can be passed through the body in breast milk, urine, stool, semen, hair and nails (Houlihan et al., 2003). In this case we are talking about xenobiotics, a chemical found in an organism but which is not normally produced or expected to be present in it. It can also include substances which are present in much higher concentrations than are usual. Humans evolved as a species with an effective detoxification system: blood, colon, kidneys, liver, lungs, lymph and skin. The liver plays an important role in protecting the organism from toxic chemical by converting fat-soluble into more water‐soluble metabolites which can be efficiently eliminated from the body. This protective mechanism depends on the presence of a wide variety biotransforming enzymes in the liver. Those enzymes catalyse the reaction of oxidation, reduction and hydrolysis (Phase I) and/or conjugation of functional groups on chemical molecules (Phase II). Although our detoxification system is effective in eliminating by-products from natural metabolic processes, it is often not fully efficient in coping with the chemical pollution in people. Toxicity results when the body is unable to eliminate chemical contaminants, resulting in a loss of homeostasis/balance in the cells, tissues, organs and body’s systems.
The effects of many xenobiotics are not known in detail, but it is known that the number of effects caused by xenobiotics is increasing. Exposure to toxic chemical has been associated with adverse health effects including immune- and neurotoxicity, reproductive toxicity, endocrine disruption, cognitive and behavioural impairment in children, and chronic diseases including asthma and cancer (Diamanti-Kandarakis et al., 2009; Gore et al., 2015; Robinson et al., 2015). The public health risks depend not only on how toxic various compounds are, but also on how many people are exposed, what kinds of chemicals they are exposed to, and the extent, period and routes of exposure. Once a toxic substance has contacted the body it may have either acute (short term) or chronic (long term) effects. After an initial exposure to a substance an individual may become sensitized to that substance. Subsequent exposures to the same substance, often at a much lower concentration than before, produces an adverse health effects. Many symptoms are wide-ranging and unspecific, including fatigue, headache, dizziness, nausea, sinus congestion, itching, sneezing, sore throat, chest pain, changes in heart rhythm, breathing problems, muscle pain or stiffness, skin rash, diarrhea, bloating, gas, confusion, trouble concentrating, memory problems, mood changes, and sleep problems.
IMMUNOTOXIC EFFECTS OF CHEMICALS
An experimental and epidemiological research data from around the world shows the effects of widely used pesticides on the immune system and the accompanying health problems. The immune system comprises of various specialized cell types which are involved in the defence of an organism against potential pathogens, abnormal or excessively growing cells. The immune response consists of the antigen-non-specific response (innate) and the antigen-specific one (adaptive). Specialized immune cells secrete inflammatory mediators, such as cytokines, chemokines, or reactive oxygen species (ROS), that can regulate innate or adaptive immunity, inflammatory processes and many other cellular activities. The actions of those cells result from a delicate balance supporting homeostasis (Brundage and Barnett, 2010). Observations in humans and animal studies have clearly demonstrated that this balance is vulnerable to the actions of a number of environmental and industrial chemicals. Alteration in the immune system may result in either decreased cell-mediated immunity (immunosuppression) to increased sensitivity (allergy). The development of autoimmunity has been linked with chemical exposure as well (reviewed in Pollard et al., 2010). Furthermore, xenobiotics decrease number of plasma responder cells and phagocytic ability, increase degranulation of mast cells and leukopenia, induce changes in the spleen, thymus, and lymph glands, and disturb foetal and perinatal immune regulation. It is documented that environmental factors play a role in the aetiology and pathogenesis of immune-mediated liver diseases (Stanca et al., 2008). Many cleansers contain ethylene-based glycol ethers and terpenes are linked with allergies and asthma (Choi et al., 2010). Also exposure to phthalates contribute to allergy development (Hoppin et al., 2013). Children living in homes with phthalate-containing vinyl floors, an alternative to carpet, have worse asthma symptoms compare to children in homes without vinyl floors (Bornehag et al., 2005). Exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse (DeLuca et al., 2018). Synthetic air fresheners containing p-dichlorobenzene (PDCB), a chlorinated VOC, increase cancer risks (Chin et al., 2013).
REPRODUCTIVE AND DEVELOPMENTAL TOXINS
Reproductive toxins are chemicals that can produce adverse effects in parents and developing embryos. Heavy metals, aromatic solvents (benzene, toluene, xylenes, etc.), and some therapeutic drugs are capable of causing these effects. Besides known effect of those chemicals on human reproduction, knowledge in this field (especially related to the male) is not as broadly developed as other areas of toxicology. The developing embryo is most vulnerable during the time before the mother knows she is pregnant. Therefore, it is important for all persons with reproductive potential to minimize chemical exposure.
BPA has been found to produce several defects in the embryo, such as feminization of male foetuses or embryo thyroid development (Manfo et al., 2014). Moreover, it is liked to atrophy of the testes, increased prostate size, and alteration of adult sperm parameters (e.g., sperm count, motility, and density). Serum BPA levels were reported to be associated with recurrent miscarriages (Sugiura-Ogasawara et al., 2005). Furthermore, pesticides are also linked to the birth defect (Garry et al., 2002). Exposure to those chemicals is associated with anencephaly, the absence of a major portion of the brain, skull and scalp that forms during embryonic development (Rudolph et al., 2004). Agricultural workers exposed to herbicides experience more pregnancy problems (Richard et al., 2005).
ENDOCRINE-DISRUPTING TOXINS
Endocrine-disrupting chemicals are defined as exogenous compounds that interfere with any aspect of endogenous hormones, including their production, release, transport, metabolism, binding, action, or elimination (Diamanti-Kandarakis et al., 2009). BPA has been shown to have oestrogenic properties in studies published already in 1936 (Dodds and Lawson, 1936). It is believed to mimic oestrogen by binding to the receptor sites meant for the hormone (Rubin, 2011). Long-term exposure of females to BPA can lead to endocrine disorders, causing pathological changes in ovary, uterus, vagina, and oviducts (Yan et al., 2013). BPA also impacts metabolic processes and increasing the risk of obesity (Li et al., 2013) and diabetes (Sabanayagam et al., 2013). People with high BPA concentrations in serum show increased circulating total and free testosterone levels (Takeuchi and Tsutsumi 2002; Takeuchi et al., 2004). These investigators also reported that women with polycystic ovary syndrome (PCOS) had higher BPA serum levels compared with women without PCOS (Takeuchi and Tsutsumi 2002; Takeuchi et al., 2004). Several human studies have shown an association between exposure to phthalates and circulating hormone levels. In a study of workers producing PVC flooring, urinary concentrations of metabolites of these phthalates were inversely associated with free testosterone levels (Pan et al., 2006). The potential for phthalates to affect thyroid function has been also demonstrated (Huang et al., 2007; Meeker et al., 2007). Likewise, decline in thyroid function has been associated with BPA (Richter et al., 2007; Wetherill et al., 2007). Air-borne pollutants also cause disruption to the endocrine system. Studies using samples of indoor air demonstrate that air does contain compounds in a gaseous state with oestrogenic and androgenic activities (Oziol et al., 2017). Synthetic fragrance compounds present in personal care and household cleaning products possess steroid agonist (Mori et al., 2007) or antagonist responses (Van der Burg et al., 2007), and increase proliferation of oestrogen-responsive cell (Bitsch et al., 2002). Similarly, polycyclic aromatic hydrocarbons (PAHs) emitted from vehicles, cigarettes or solid fuels act as agonists and antagonists of oestrogen action (Zhang et al., 2016). Furthermore, exposure to endocrine toxins leads to endocrine-responsive cancers. Components of air pollution can increase the incidence of lung cancer (Hamra et al., 2014; Hamra et al., 2015) and exposure to traffic-related air is associated with postmenopausal breast cancer (Crouse et al., 2010).
NEUROTOXINS
Accumulating evidence suggests that outdoor air pollution may have a significant impact on central nervous system including chronic brain inflammation, or white matter abnormalities leading to increased risk for autism spectrum disorders, lower IQ in children, neurodegenerative diseases (Parkinson’s disease, PD; Alzheimer’s disease, AD), multiple sclerosis, and stroke (reviewed in Block et al., 2012). The clinical signs and symptoms of xenobiotic poisoning may be expressed in the central, the peripheral and the autonomic nervous systems, and in skeletal muscle. They are often associated with pain, changes in the senses of taste, smell, visual acuity and hearing. An epidemiological study suggested that glyphosate herbicide impacts neurological development as children of pesticide applicators exposed to glyphosate herbicides had an increased incidence of neurobehavioral disorders, including attention deficit hyperactivity disorder (ADHD) (Garry et al., 2002). A clinical case study described a link between glyphosate herbicide an the developed of Parkinson’s disease (Barbosa et al., 2001). A separate case study found the same result, though in this case it is not clear if the exposure was to glyphosate alone or a complete formulation, as the exposure took place in a factory that manufactured herbicides (Wang et al., 2011). Moreover, chemical-based household products are linked to learning problems (Power et al., 2013) and impaired attention in children (Hoffman et al., 2010). Chronic exposure to phthalates, BPA and pesticides are linked to vision, hearing and balance problems (Shiue, 2013), difficulties in thinking or remembering (Shiue, 2015).
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