Table of Contents

    Topic review

    Environmental Pollution's Impact on cancer

    View times: 5

    Definition

    Nowadays, cancer is the leading cause of death in humans before they reach old age , and some specific, once rare, types connected to environmental and occupational contamination are increasing (e.g., testicular cancer , thyroid cancer , non-Hodgkin’s lymphoma , leukaemia , etc.). After about three decades of research from the first evidence of a link between environmental pollution and cancer in the 1980s, it is easy to feel that we are all, directly or indirectly, subject to an uncontrolled experiment. This makes human studies difficult because humanity may, at this point, lack unexposed controls, such as human beings who have never been in contact with environmental pollution.

    1. Introduction: Prevent Cancers Instead of Fighting Them

    In a time when we are all concerned about the risks posed to human health by an unprecedented pandemic [1], we risk forgetting and underestimating the death toll of an old and lasting (at least, since the Industrial age) pandemic that affects almost a third of the human population worldwide: cancer (or, better, cancers). Cancers are now considered the second leading cause of death after only cardiovascular diseases. There is a higher prevalence of cancers in higher-income countries, from approximately 6% (which is about 34,000 people) of the population in the US down to around 0.4% in the poorest countries [2]. Globally, breast cancer is the most prevalent form, followed by prostate, colon, rectum, cervical, pulmonary, uterine, stomach, bladder, and other forms [3].

    This is because humanity considers, with good reasons, the number of COVID-19 victims intolerable but seems to accept the premeditated murder committed by cancers because of the anonymity of its victims. However, in the case of cancers, we are well aware to often be the victim of ourselves, in a sort of mass suicide: lifestyle has much to be blamed for cancer mortality, with obesity, sedentary habits, alcoholism, and smoking contributing as supposed major factors [4][5]. For instance, lung cancer also heavily affects non-smokers and is the sixth most common cause of cancer-related death (18,000–27,000 deaths each year are caused by lung cancer in people who are not active cigarette smokers, and 16,000 occur among lifelong non-smokers [6][7].

    What is, rather, emerging with the recent research in environmental health is that exposure to a mixture of pollutants, favoured by wrong lifestyles, psychosocial stressors, and genetic susceptibility, significantly increases the risk of developing cancer [8][9]. Global patterns of cancer incidence confirm this evidence [10]. However, almost no place can be considered safe nowadays on this planet, with an even higher risk in industrialised countries. Occupational exposures to certain chemicals increase the incidence [11], but about 220 widely distributed breast cancer carcinogens have been identified so far [12][13], and we have increasing evidence that most children’s cancers are strongly related to parental exposures [14][15].

    Our medical weapons against cancers have not improved too much in the last century, at least not in terms of the number of arrows in our quiver: Quite the opposite, our knowledge of the links between environmental pollution and cancer has surged from the 1980s. Researchers started discovering the dangers of indoor pollution from domestic chemicals of common use, some in the past and most in the present, such as phthalates (contained in toys, personal care products, vinyl flooring and wall covering, detergents, lubricating oils, food packaging, pharmaceuticals, etc.) that impair male development and pose a risk to human reproduction [16], PCBs (polychlorinated biphenyls, widely used in electrical equipment like capacitors and transformers) that reduce testosterone [17][18], PFAS (perfluoroalkyl and polyfluoroalkyl substances, a group of ~5000 synthetic chemicals in commercial production since the 1940s to make surfaces resist stains, water, and grease, where the most widely studied are PFOA used for decades to make non-stick pans) that can cause testicular and kidney cancer [19], flame retardants (present in manufactured materials, such as plastics and textiles, and surface finishes), and bisphenol A (found even in polycarbonate baby bottles and the epoxy lining of food cans), leached in most food items [20][21][22] that, in laboratories, induced precancerous lesions to form in the mammary and prostate glands in early life [23][24][25][26].

    Nonetheless, outdoor exposure to chemicals, particularly those used in agriculture, soon emerged as a major threat to human health. DDT (dichlorodiphenyltrichloroethane), a now-banned organochlorine insecticide in most countries, for a long time has been one of the most common pesticides found in fishes [27] (which also contain PCBs [28], and heavy metals [29]), in the bodies of migrating songbirds [30], in forest soils [31], in paints [32], in breast milk [33][34], and as residues on kitchen floors [35], together with other pesticides such as chlordane, chlorpyrifos, diazinon, fipronil, and permethrin. Moreover, hormonal effects (which can stimulate mammary and ovary cancer) of atrazine exposure were shown by many early studies [36][37][38][39][40][41][42]. Instead, very early on—already in the 1980s—the scientific community launched an alarm on the evidence that women with breast cancer have higher levels of DDE (a common breakdown product of DDT found in vertebrate’s bodies) and PCBs in their tumours [43], which was clearly linked to the increase of breast cancer among women born between 1947 and 1958 [44].

    Unfortunately, all this preliminary scientific evidence has not always been followed by governments and institutions, which still fail to pursue research on cancer’s environmental connections [45]. Nature (see for instance whales with bladder cancer in [46] and even our companion animals were revealing a truth that we have long ignored. Continuous studies, from 1938 up to now, suggested the evidence that exposure to herbicides, insecticide, and waste pollutants poses a risk of cancer, particularly of the bladder, to dogs [47][48][49][50][51][52]. Yet, the coincident rise of synthetic dyes and bladder cancer among textile workers [53] and the growing evidence of higher bladder cancer risk for workers in rubber and metal industries [54][55][56] did not do much to address socio-economic and political actions.

    The following sections report the main findings of a literature review that was conducted, following the guidelines of the PRISMA [57] and the COSMOS-E [58] approaches, on studies publicly available as of 28 February 2021 and reporting on the links between exposure to environmental pollutants and cancer. The inclusion criteria were the following: studies involving human participants and laboratory/domestic animal species (with some selected wild animal species exposed to anthropogenic pollutants), original research paper evaluating the association among environmental pollutants and cancer, or original research paper that reported at least one environmental pollutant as a potential cause of cancer. The exclusion criteria were the following: studies involving non-human and non-animal species, and publications containing editorials, letters to editor, case reports, and case series. In addition, non-English papers were also excluded.

    2. Carcinogens into Water

    So far, we have found, in water, about 35 of the 202 identified mammary carcinogens, including the triazine herbicides atrazine and symazine, acrylamide, DBCP, 1,2 dibromoethane, 1,2-dichloropropane, 1,2-dichloroethane, benzene, carbon tetrachloride, 3,3-dimethyoxybenzidine, styrene, and vinyl chloride [12]. In fact, most of the evidence about the cancerogenic effects of solvents and pesticides were brought to attention by the studies on contaminated drinking water [27][59]. Aquifers, lakes, and streams from which drinking water is taken can contain contaminants from personal care products, pharmaceuticals, hormones, and organic wastewater, which alter the endocrine system and, in turn, favour tumours [60][61][62].

    Not only evidently problematic contaminants, such as pesticides [63][64]; see also “Carcinogens into Soil,” Section 4), metal degreasers, and dry-cleaning fluids [65] can be found in drinking waters, but even the abused nitrates in agriculture that leach in the aquifers can pose serious risks of developing cancer [66][67].

    Paradoxically, drinking is not the only way to take in indoor carcinogens that are in outdoor water: dermal and inhalation routes of exposure have been shown as relevant sources of contamination due to volatilisation of chemicals [68][69][70][71]. These additional ways to come in contact with carcinogens from waters represent a serious danger to women and their infants who, for instance, during bathing and showering may be exposed to substances such as chloroform and trihalomethane, which increase the risk of developing tumours [70][72].

    Heavy metal pollution in drinking water constitutes another serious risk for human health and is associated with many cancer forms [73][74][75]. Chromium and arsenic, which can naturally be part of some soils, but are in high levels in industrially contaminated groundwaters, are of serious concern for bladder, prostate, and kidney cancers’ induction, even at low–moderate concentrations [76][77][78]. High concentrations of arsenic in drinking water cause chronic intoxication that may sometimes also result in the development of skin and lung cancer [79][80]. At the same time, even though the small amount of chlorine used for tap-water disinfection is of no concern for human health [81], there still exists a link between water chlorination and bladder and other cancers [12][82][83], which seems to be due to the presence in source waters of other organic contaminants that can create by-products, such as the carcinogen MX [84].

    Radioactivity from natural sources (e.g., uranium and dissolved radon in some rocky soils) and human activities (contamination from nuclear power plants, nuclear wastes, etc.) can be relatively high in drinking water and increase the risk of different cancer types, particularly of the digestive system [85][86][87]. However, most of these carcinogens are not currently checked for in routine and periodic controls of drinking waters made by local and national sanitary authorities.

    3. Carcinogens into Air

    The presence of carcinogens in the air is one of the most well-documented, because there is wide experimental evidence for the carcinogenicity of air pollutants [88]. There is, for instance, ample documentation of airborne carcinogens from industrial sites, road traffic, intensive farms, military bases, etc. [89][90]. Among air pollutants that may act as carcinogens, ultrafine particles are of higher concern because of their ability to penetrate deeply into the respiratory system [91][92][93].

    An example is ozone [94][95][96], that can be formed by nitrogen oxides, emitted mainly from internal combustion engines, and separated into nitric oxide (NO) and free atoms of oxygen (O), by the visible or ultraviolet energy of sunlight. When the free atoms of oxygen produced by NOx combine with molecular oxygen (O2), they form ozone (O3). In the presence of hydrocarbons, volatile organic compounds, and sunlight, these chemical reactions can take place and form photochemical smog [97], with secondary pollutants such as peroxyacetyl nitrates (PANs). Several epidemiological studies have evidenced an increasing incidence of lung adenocarcinoma [98][99][100], a strong association between air pollution and cancer mortality [101][102], a correlation between industrial air pollution and cancer [103][104][105][106], and occupational cancer [11][107].

    However, carcinogens in the air do not only trigger lung cancers but are documented risk factors for breast and bladder cancers [108][109][110]. Residence near industries and high traffic areas increases the risk of breast cancer [111][112], also because aromatic hydrocarbons, like the benzo[a]pyrene, which are emitted by the combustion of coal and petroleum derivates, are involved in the DNA mutagenesis of the mammary gland cells [113][114]. Similarly, bladder cancer is linked to air pollution, with a strong association of mortality among people living in residential districts polluted by industrial petrochemical plants [115][116][117][118].

    Despite recent progress in incinerator technology to reduce air pollutants, including dioxin and particulate (e.g., with “flameless” chambers, oxy-combustors, and molecular dissociation processes), what is ideally removed from air contaminants is, inevitably, concentrated in the residual fly ashes [119][120][121][122], which can be even more dangerous when stocked or dispersed into soil and water, even if vitrified [123]. Moreover, although modern technologies could reduce dioxin emissions, it is difficult to completely block the formation of easily escaping ultrafine particles [124][125], which forms even more and smaller particles at the high temperature of new incinerators [126]. The apparent advantage of volume reduction compared to “cold processing and dumping” is outweighed by the air emission of greenhouse gasses (CO2, CH4, etc.) and the concentration of even more toxic contaminants in the residual ashes that, however, must be stocked in special dumps. Additionally, when hospital waste is incinerated, it is one of the largest known sources of dioxin because it contains PVC (polyvinyl chloride) plastic, the dominant component of organically bound chlorine in waste such as bags, gloves, bedpans, tubing, and packaging [127].

    Unfortunately, incineration is not the only source of dioxin: domestic fireplaces, firewood heating, kitchen chimneys, and agricultural controlled fires are also main sources [128][129]. Chlorinated dibenzo-p-dioxins (CDDs) have been found in cow’s milk near incinerators [130][131], in rivers, fish, soil, and crops [132]. In several human and laboratory studies, dioxin showed the ability to induce liver and lung cancers [133][134], affect hormone production and growth factors [135][136], and act as a developmental toxicant [137][138][139]. It is becoming clearer that dioxin targets P450 enzymes and aryl hydrocarbon receptors (AhRs) in the human body, particularly during pregnancy, and this alters mammary epithelial cell proliferation and differentiation [134][140][141][142][143].

    Of no less importance, and deserving at least a mention, are other sources of carcinogens in the air. Another, jet fuels, which—besides fine particles and other pollutants—contain a high level of octane boosters to improve the acceleration of aircraft, such as toluene, that produces, by nitration, a mixture of nitrotoluenes in exhaust fuels [144]. One of them, dinitrotoluene, which is also a military chemical propellant and explosive, is considered a probable carcinogen because it is linked with breast, liver, and bladder cancers, may pose a serious risk to people living near military bases [108][145][146][147][148]. Other nitrification products, such as the o-toluidine also deriving from the manufacture of dye-stuffs and the production of rubber, chemicals, and pesticides, have shown carcinogenic properties [149][150] and can pose another risk to exposed populations living close to airports and factories that emit toluidine.

    An additional source of carcinogenicity in the air may be electromagnetic fields and indoor radon. Some evidence is emerging about the risk posed by electricity, communication, and wireless devices [151][152][153], and there is strong evidence for an association between leukaemia, breast, and brain cancers and residential or occupational exposure to electromagnetic low frequencies, including cell phones [154][155][156][157][158], even if further research is needed to better clarify the effects on human health of the new technologies for smartphones and 5G [159][160][161]. Indoor radon—which accumulates in closed spaces from the natural radioactive decay of uranium of rocks in the building foundations and construction materials, producing radioactive particles that can be deposited on the cells lining the airways—may damage DNA and cause lung cancer [162][163].

    4. Carcinogens into Soil

    The research history of carcinogens into soil can be dated back to the discovery of the links between bladder cancer and aromatic amines in the 1970s–1980s. The proof of their carcinogenicity came after some aromatic amines were removed from the chemical industry and the incidence of bladder cancer among affected workers declined considerably [164]. Although aromatic amines are a wide group of chemicals that include ingredients in tobacco smoke, most of their dissemination has been through pesticides in agriculture. Bladder cancer is common among farmers [165] and several aromatic amines, some of which are already banned in many countries (such as atrazine in Europe, but not in the USA), have been proven responsible for this.

    This chemical component of some pesticides is a proven endocrine disruptor, which affects the hypothalamic control of pituitary-ovarian function [39][166] and triggers human ovarian cancers [167][168][169][170][171][172]. Moreover, atrazine impacts breast development and shows adverse effects of prenatal exposure during a critical period of mammary gland growth [38][138][173][174]. Despite that other human studies are needed to understand the effects of this contaminant on early-life exposure, there is not much doubt about its carcinogenicity for exposed people [170][175] and persistence in the environment [176].

    Three other classic examples of persistent and dangerous pesticides are endosulfan, lindane, and parathion. Endosulfan is an organochlorine insecticide and acaricide chemically similar to DDT, largely sprayed on vegetables, apples, melons, and cotton for decades, which is being banned around the world only in recent years (in the USA only in 2010), although the evidence of its extreme risk is much older [177][178]. Lindane was widely used in the commercial tree industry but is being banned globally under the Stockholm Convention on Persistent Organic Pollutants, an international treaty negotiated at the United Nations Environment Programme (UNEP). All of these three insecticides, particularly in occupational exposure, showed links with cancer [179][180].

    Aldrin and dieldrin were used extensively in agriculture for at least two decades until their use was suspended in the 1970s in most countries, though these insecticides were being manufactured in many European countries at least until 1978 and are still found in some parts of the world [181]. Levels of both of these pesticides have decreased over the years since they are no longer produced or used, but some traces of them can still be found in soil and water [182]. Today, these chemicals are still around us, since they can be found in soils and buildings long after treatment on various crops or insects was performed [183]. People were usually exposed to these chemicals by eating foods in which these substances accumulate, like those high in animal fat, such as meat, fish, and dairy products [184].

    Unfortunately, the vertical mother–foetus passage of carcinogens is not isolated to chlordane and heptachlor but is quite common to most pesticides and can explain childhood and early-life cancers, particularly brain cancer and leukaemia [185][186][187][188][189]. Not only is contaminated food involved in this passage, but also exposition to pesticides in the homes of farmworker children plays a role [190][191]. Pesticides have been found even in carpet fibres of children of parents using pesticides outside [192][193]. However, also for women themselves, a new concern is emerging on the link between pesticide use and breast cancer risk [194][195][196][197].

    From the 1980s, the EU started to implement some bans on other specific pesticides, mainly persistent organochlorine compounds, due to growing evidence of human or environmental harm. Similarly, 80–90% of DDT produced in China is used to synthesise Dicofol, an acaricide used to protect plants from pests. Most African countries do not use this chemical for agricultural purposes, but in countries such as Ethiopia, South Africa, Uganda, and Swaziland, DDT is still used to control malaria. Apart from people living in producing and employing countries [198], this may pose a risk to other populations around the world through exported food and goods in a global market [199].

    Other, still-in-use potential carcinogens from pesticides are accumulating into soil worldwide. One of them, glyphosate, has been shown to cause harm in large doses [200]. The World Health Organization’s International Agency for Research on Cancer declared that it “probably” causes cancer [201], although the EPA and Bayer, the company that now owns the producer Monsanto, maintain that glyphosate does not cause cancer in humans [202]. Nonetheless, recent studies found a compelling link between exposures to glyphosate-based herbicides and increased risk for non-Hodgkin’s lymphoma and breast cancer [203][204].

    Among other suspected carcinogens into soil, nitrates, which accumulate after over-fertilisation in agricultural products and leaches in aquifers, may increase the risk of bladder cancer [205][206][207][208]. Illegal disposal of garbage and even legal landfills are another source of carcinogens’ percolation and soil contamination [209]. The risk increases when populations are exposed to illegal dumping of toxic wastes and their burning [210].

    The entry is from 10.3390/ijerph18116107

    References

    1. Cazzolla Gatti, R.; Menéndez, L.P.; Laciny, A.; Bobadilla Rodríguez, H.; Bravo Morante, G.; Carmen, E.; Dorninger, C.; Fabris, F.; Grunstra, N.D.S.; Schnorr, S.L.; et al. Diversity lost: COVID-19 as a phenomenon of the total environment. Sci. Total Environ. 2021, 756, 144014.
    2. ACS 2020. Available online: (accessed on 10 November 2020).
    3. WCRF 2020. Available online: (accessed on 15 December 2020).
    4. Osório-Costa, F.; Rocha, G.Z.; Dias, M.M.; Carvalheira, J.B. Epidemiological and Molecular Mechanisms Aspects Linking Obesity and Cancer. Arq. Bras. Endocrinol. Metabol. 2009, 53, 219–226.
    5. Khan, N.; Afaq, F.; Mukhtar, H. Lifestyle as risk factor for cancer: Evidence from human studies. Cancer Lett. 2010, 293, 133–143.
    6. Thun, M.J.; Henley, S.J.; Burns, D.; Jemal, A.; Shanks, T.G.; Calle, E.E. Lung Cancer Deaths in Lifelong Non-smokers. JNCI 2006, 98, 691–699.
    7. Ihsan, R.; Chauhan, P.S.; Mishra, A.K.; Yadav, D.S.; Kaushal, M.; Sharma, J.D.; Zomawia, E.; Verma, Y.; Kapur, S.; Saxena, S. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer. PLoS ONE 2011, 6, e29431.
    8. Reaves, D.K.; Ginsburg, E.; Bang, J.J.; Fleming, J.M. Persistent organic pollutants and obesity: Are they potential mechanisms for breast cancer promotion? Endocr. Relat. Cancer 2015, 22, R69–R86.
    9. Kim, H.B.; Shim, J.Y.; Park, B.; Lee, Y.J. Long-term exposure to air pollutants and cancer mortality: A meta-analysis of cohort studies. Int. J. Environ. Res. Public Health 2018, 15, 2608.
    10. Wild, C.P.; Weiderpass, E.; Stewart, B.W. (Eds.) World Cancer Report; IARC: Lyon, France, 2020.
    11. Hashim, D.; Boffetta, P. Occupational and environmental exposures and cancers in developing countries. Ann. Glob. Health 2014, 80, 393–411.
    12. Rudel, R.A.; Attfield, K.R.; Schifano, J.N.; Brody, J.G. Chemicals Causing Mammary Gland Tumors in Animals Signal New Directions for Epidemiology, Chemicals Testing, and Risk Assessment for Breast Cancer Prevention. Cancer 2007, 109, 2635–2666.
    13. Rodgers, K.M.; Udesky, J.O.; Rudel, R.A.; Brody, J.G. Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms. Environ. Res. 2018, 160, 152–182.
    14. O′Leary, L.M.; Hicks, A.M.; Peters, J.M.; London, S. “Parental Exposures and Risk of Childhood Cancer: A Review”. Am. J. Ind. Med. 1991, 20, 17–35.
    15. Vinson, F.; Merhi, M.; Baldi, I.; Raynal, H.; Gamet-Payrastre, L. Exposure to pesticides and risk of childhood cancer: A meta-analysis of recent epidemiological studies. Occup. Environ. Med. 2011, 68, 694–702.
    16. Hannon, P.R.; Flaws, J.A. The effects of phthalates on the ovary. Front. Endocrinol. 2015, 6, 8.
    17. Goncharov, A.; Rej, R.; Negoita, S.; Schymura, M.; Santiago-Rivera, A.; Morse, G. Lower Serum Testosterone Associated with Elevated Polychlorinated Biphenyl Concentrations in Native American Men. EHP 2009, 117, 1454–1460.
    18. Desdoits-Lethimonier, C.; Albert, O.; Le Bizec, B.; Perdu, E.; Zalko, D.; Courant, F.; Lesné, L.; Guillé, F.; Dejucq-Rainsford, N.; Jégou, B. Human testis steroidogenesis is inhibited by phthalates. Hum. Reprod. 2012, 27, 1451–1459.
    19. Steenland, K.; Winquist, A. PFAS and cancer, a scoping review of the epidemiologic evidence. Environ. Res. 2020, 110690.
    20. Sjodin, A.; Wong, L.Y.; Jones, R.S.; Park, A.; Zhang, Y.; Hodge, C.; Dipietro, E.; McClure, C.; Turner, W.; Needham, L.L.; et al. Concentrations of Polybrominated Diphenyl Ethers (PBDEs) and Polybrominated Biphenyl (PBB) in the United States Population: 2003–2004. Environ. Sci. Technol. 2008, 42, 1377–1384.
    21. Calafat, A.M.; Ye, X.; Wong, L.Y.; Reidy, J.A.; Needham, L.L. Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004. EHP 2008, 116, 39–44.
    22. Seachrist, D.D.; Bonk, K.W.; Ho, S.M.; Prins, G.S.; Soto, A.M.; Keri, R.A. A review of the carcinogenic potential of bisphenol A. Reprod. Toxicol. 2016, 59, 167–182.
    23. Durando, M.; Kass, L.; Piva, J.; Sonnenschein, C.; Soto, A.M.; Luque, E.H.; Muñoz-de-Toro, M. Prenatal Bisphenol A Exposure Induces Preneoplastic Lesions in the Mammary Gland in Wistar Rats. EHP 2007, 115, 80–86.
    24. Ho, S.M.; Tang, W.Y.; De Frausto, J.B.; Prins, G.S. Developmental Exposure to Estradiol and Bisphenol A Increases Susceptibility to Prostate Carcinogenesis and Epigenetically Regulates Phosphodiesterase Type 4 Variant 4. Cancer Res. 2006, 66, 5624–5632.
    25. Snedeker, S. Environmental Estrogens: Effects on Puberty and Cancer Risk. Ribbon 2007, 12, 5–7.
    26. Wilson, N.K.; Chuang, J.C.; Morgan, M.K.; Lordo, R.A.; Sheldon, L.S. An Observational Study of the Potential Exposures of Preschool Children to Pentachlorophenol, Bisphenol A, and nonylphenol at Home and Day-care. Environ. Res. 2007, 103, 9–20.
    27. Gilliom, R.J.; Barbash, J.E.; Crawford, C.G.; Hamilton, P.A.; Martin, J.D.; Nakagaki, N.; Nowell, L.H.; Scott, J.C.; Stackelberg, P.E.; Thelin, G.P.; et al. The Quality of Our Nation′s Waters: Pesticides in the Nation′s Streams and Ground Water, 1992–2001; U.S. Geological Survey: Reston, VA, USA, 2006.
    28. Straub, C.L.; Maul, J.D.; Halbrook, R.S.; Spears, B.; Lydy, M.J. Trophic Transfer of Polychlorinated Biphenyls in Great Blue Heron (Ardea Herodias) at Crab Orchard National Wildlife Refuge, Illinois, United States. Arch. Environ. Contam. Toxicol. 2007, 52, 572–579.
    29. Authman, M.M.; Zaki, M.S.; Khallaf, E.A.; Abbas, H.H. Use of fish as bio-indicator of the effects of heavy metals pollution. J. Aquac. Res. Dev. 2015, 6, 1–13.
    30. Harper, R.G.; Frick, J.A.; Capparella, A.P.; Borup, B.; Nowak, M.; Biesinger, D.; Thompson, C.F. Organochlorine Pesticide Contamination in Neotropical Migrant Passerines. Arch. Environ. Contam. Toxicol. 1996, 31, 386–390.
    31. Smith, W.H.; Hale, R.C.; Greaves, J.; Huggett, R.J. Trace Organochlorine Contamination of the Forest Floor of the White Mountain National Forest, New Hampshire. Environ. Sci. Technol. 1993, 27, 2244–2246.
    32. Xin, J.; Liu, X.; Liu, W.; Jiang, L.; Wang, J.; Niu, J. Production and use of DDT containing antifouling paint resulted in high DDTs residue in three paint factory sites and two shipyard sites, China. Chemosphere 2011, 84, 342–347.
    33. Cohn, B.A.; Wolff, M.S.; Cirillo, P.M.; Sholtz, R.I. DDT and breast cancer in young women: New data on the significance of age at exposure. Environ. Health Perspect. 2007, 115, 1406–1414.
    34. Bouwman, H.; Kylin, H.; Sereda, B.; Bornman, R. High levels of DDT in breast milk: Intake, risk, lactation duration, and involvement of gender. Environ. Pollut. 2012, 170, 63–70.
    35. Stout, D.M.; Bradham, K.D.; Egeghy, P.P.; Jones, P.A.; Croghan, C.W.; Ashley, P.A.; Pinzer, E.; Friedman, W.; Brinkman, M.C.; Nishioka, M.G.; et al. American Healthy Homes Survey: A National Study of Residential Pesticides Measured from Floor Wipes. Environ. Sci. Technol. 2009, 43, 4294–4300.
    36. Hayes, T.B.; Collins, A.; Lee, M.; Mendoza, M.; Noriega, N.; Stuart, A.A.; Vonk, A. Hermaphroditic Demasculinized Frogs after Exposure to the Herbicide Atrazine at Low Ecologically Relevant Doses. Proc. Natl. Acad. Sci. USA 2002, 99, 5476–5480.
    37. Rodriguez, V.M.; Thiruchelvam, M.; Cory-Slechta, D.A. Sustained Exposure to the Widely Used Herbicide Atrazine: Altered Function and Loss of Neurons in Brain Monoamine Systems. EHP 2005, 113, 708–715.
    38. Enoch, R.R.; Stanko, J.P.; Greiner, S.N.; Youngblood, G.L.; Rayner, J.L.; Fenton, S.E. Mammary Gland Development as a Sensitive End Point After Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats. EHP 2007, 115, 541–547.
    39. Cooper, R.L.; Laws, S.C.; Das, P.C.; Narotsky, M.G.; Goldman, J.M.; Lee Tyrey, E.; Stoker, T.E. Atrazine and Reproductive Function: Mode and Mechanism of Action Studies. Birth Defects Res. Part B 2007, 80, 98–112.
    40. Suzawa, M.; Ingraham, H.A. The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells. PLoS ONE 2008, 3, e2117.
    41. Lenkowski, J.R.; Reed, J.M.; Deininger, L.; McLaughlin, K.A. Perturbation of Organogenesis by the Herbicide Atrazine in the Amphibian Xenopus laevis. EHP 2008, 116, 223–230.
    42. Shibayama, H.; Kotera, T.; Shinoda, Y.; Hanada, T.; Kajihara, T.; Ueda, M.; Tamura, H.; Ishibashi, S.; Yamashita, Y.; Ochi, S. Collaborative Work on Evaluation of Ovarian Toxicity. 14) Two-or Four-week Repeated-Dose Studies and Fertility Study of Atrazine in Female Rats. J. Toxicol. Sci. 2009, 34, SP147–SP155.
    43. Wasserman, M. Organochlorine Compounds in Neoplastic and Adjacent Apparently Normal Breast Tissue. Bull. Environ. Contam. Toxicol. 1976, 15, 478–484.
    44. Davis, D.L.; Dinse, G.E.; Hoel, D.G. Decreasing Cardiovascular Disease and Increasing Cancer among Whites in the United States from 1973 through 1987: Good News and Bad News. JAMA 1994, 271, 431–437.
    45. Davis, D.L. The Need to Develop Centers for Environmental Oncology. Biomed. Pharmacother. 2007, 61, 614–622.
    46. Martineau, D.; Lagacé, A.; Massé, R.; Morin, M.; Béland, P. Transitional Cell Carcinoma of the Urinary Bladder in a Beluga Whale (Delphinapterus leucas). J. Wildl. Dis. 1985, 22, 289–294.
    47. Hueper, W.C. Experimental Production of Bladder Tumors in Dogs by Administration of betaNaphthylamine. J. Ind. Hyg. Toxicol. 1938, 20, 46–84.
    48. Hayes, H.M. Bladder Cancer in Pet Dogs: A Sentinel for Environmental Cancer? AJE 1981, 114, 229–233.
    49. Glickman, L.T.; Schofer, F.S.; McKee, L.J.; Reif, J.S.; Goldschmidt, M.H. Epidemiologic Study of Insecticide Exposures, Obesity, and Risk of Bladder Cancer in Household Dogs. JTEH 1989, 28, 407–414.
    50. Glickman, L.T.; Raghavan, M.; Knapp, D.W.; Bonney, P.L.; Dawson, M.H. Herbicide Exposure and the Risk of Transitional Cell Carcinoma of the Urinary Bladder in Scottish Terriers. J. Am. Vet. Med Assoc. 2004, 224, 1290–1297.
    51. Marconato, L.; Leo, C.; Girelli, R.; Salvi, S.; Abramo, F.; Bettini, G.; Comazzi, S.; Nardi, P.; Albanese, F.; Zini, E. Association between Waste Management and Cancer in Companion Animals. J. Vet. Intern. Med. 2009, 23, 564–569.
    52. Knapp, D.W.; Peer, W.A.; Conteh, A.; Diggs, A.R.; Cooper, B.R.; Glickman, N.W.; Bonney, P.L.; Stewart, J.C.; Glickman, L.T.; Murphy, A.S. Detection of herbicides in the urine of pet dogs following home lawn chemical application. Sci. Total Environ. 2013, 456, 34–41.
    53. NIOSH. Special Occupational Hazard Review for Benzidene-Based Dyes, DHEW (NIOSH) Pub. 80–109; NIOSH: Cincinnati, OH, USA, 1980.
    54. Monson, R.R.; Nakano, K. Mortality among Rubber Workers: I. White Male Union Employees in Akron, Ohio. AJE 1976, 103, 284–296.
    55. Cole, P.; Hoover, R.; Friedell, G.H. Occupation and Cancer of the Lower Urinary Tract. Cancer 1972, 29, 1250–1260.
    56. Vineis, P.; Di Prima, S. Cutting Oils and Bladder Cancer. Scand. J. Work. Environ. Health 1983, 9, 449–450.
    57. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097.
    58. Dekkers, O.M.; Vandenbroucke, J.P.; Cevallos, M.; Renehan, A.G.; Altman, D.G.; Egger, M. COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology. PLoS Med. 2019, 16, e1002742.
    59. Hawthorne, M. Dry Cleaners Leave a Toxic Legacy—Despite Cleanup Effort, Chemicals Still Taint Hundreds of Illinois Sites; Chicago Tribune: Chicago, IL, USA, 2009.
    60. Kuch, H.M.; Ballschmiter, K. Determination of Endocrine-disrupting Phenolic Compounds and Estrogens in Surface and Drinking Water by HRGC-(NCI)-MS in the Picogram per Liter Range. Environ. Sci. Technol. 2001, 35, 3201–3206.
    61. Kolpin, D.W.; Furlong, E.T.; Meyer, M.T.; Thurman, E.M.; Zaugg, S.D.; Barber, L.B.; Buxton, H.T. Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999–2000: A National Reconnaissance. Environ. Sci. Technol. 2002, 36, 1202–1211.
    62. Stackelberg, P.E.; Furlong, E.T.; Meyer, M.T.; Zaugg, S.D.; Henderson, A.K.; Reissman, D.B. Persistence of Pharmaceutical Compounds and Other Organic Wastewater Contaminants in a Conventional Drinking-Water Treatment Plant. Sci. Total. Environ. 2004, 329, 99–113.
    63. Cohen, B.; Wiles, R.; Bondoc, E. Weed Killers by the Glass: A Citizens′ Tap Water Monitoring Project in 29 Cities; Environmental Working Group: Washington, DC, USA, 1995.
    64. Wu, M.; Quirindongo, M.; Sass, J.; Wetzler, A. Poisoning the Well: How the EPA Is Ignoring Atrazine Contamination in Surface and Drinking Water in the Central United States; NRDC: New York, NY, USA, 2009.
    65. Rivett, M.O.; Turner, R.J.; Glibbery, P.; Cuthbert, M.O. The legacy of chlorinated solvents in the Birmingham aquifer, UK: Observations spanning three decades and the challenge of future urban groundwater development. J. Contam. Hydrol. 2012, 140, 107–123.
    66. Ward, M.H.; DeKok, T.M.; Levallois, P.; Brender, J.; Gulis, G.; Nolan, B.T.; VanDerslice, J. Workgroup Report: Drinking-water Nitrate and Health—Recent Findings and Research Needs. EHP 2005, 113, 1607–1614.
    67. Cantor, K.P.; Ward, M.H.; Moore, L.E.; Lubin, J.H. Water Contaminants. In Cancer Prevention and Epidemiology, 3rd ed.; Schottenfeld, D., Fraumeni, J.F., Eds.; Oxford University Press: New York, NY, USA, 2006.
    68. Howard, C.; Corsi, R.L. Volatilization of Chemicals from Drinking Water to Indoor Air: The Role of Residential Washing Machines. J. Air Waste Manag. Assoc. 1998, 48, 907–914.
    69. Nuckols, J.R.; Ashley, D.L.; Lyu, C.; Gordon, S.M.; Hinckley, A.F.; Singer, P. Influence of Tap Water Quality and Household Water Use Activities on Indoor Air and Internal Dose Level of Trihalomethanes. EHP 2005, 113, 863–870.
    70. Gordon, S.M.; Brinkman, M.C.; Ashley, D.L.; Blount, B.C.; Lyu, C.; Masters, J.; Singer, P.C. Changes in Breath Trihalomethane Levels Resulting from Household Water-Use Activities. EHP 2006, 114, 514–521.
    71. Richardson, S.D. Water Analysis: Emerging Contaminants and Current Issues. Anal. Chem. 2007, 79, 4295–4323.
    72. Weisel, C.P.; Jo, W.K. Ingestion, Inhalation, and Dermal Exposures to Chloroform and Trichloroethene from Tap Water. EHP 1996, 104, 48–51.
    73. Fernandez-Luqueno, F.; López-Valdez, F.; Gamero-Melo, P.; Luna-Suárez, S.; Aguilera-González, E.N.; Martínez, A.I.; García-Guillermo, M.D.S.; Hernández-Martínez, G.; Herrera-Mendoza, R.; Álvarez-Garza, M.A.; et al. Heavy metal pollution in drinking water-a global risk for human health: A review. Afr. J. Environ. Sci. Technol. 2013, 7, 567–584.
    74. Chhabra, D.; Oda, K.; Jagannath, P.; Utsunomiya, H.; Takekoshi, S.; Nimura, Y. Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac. J. Cancer Prev. 2012, 13, 187–190.
    75. Nyambura, C.; Hashim, N.O.; Chege, M.W.; Tokonami, S.; Omonya, F.W. Cancer and non-cancer health risks from carcinogenic heavy metal exposures in underground water from Kilimambogo, Kenya. Groundw. Sustain. Dev. 2020, 10, 100315.
    76. Zhitkovich, A. Chromium in drinking water: Sources, metabolism, and cancer risks. Chem. Res. Toxicol. 2011, 24, 1617–1629.
    77. Bulka, C.M.; Jones, R.M.; Turyk, M.E.; Stayner, L.T.; Argos, M. Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study. Environ. Res. 2016, 148, 450–456.
    78. Roh, T.; Lynch, C.F.; Weyer, P.; Wang, K.; Kelly, K.M.; Ludewig, G. Low-level arsenic exposure from drinking water is associated with prostate cancer in Iowa. Environ. Res. 2017, 159, 338–343.
    79. Marshall, G.; Ferreccio, C.; Yuan, Y.; Bates, M.N.; Steinmaus, C.; Selvin, S.; Liaw, J.; Smith, A.H. Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J. Natl. Cancer Inst. 2007, 99, 920–928.
    80. Yu, R.C.; Hsu, K.H.; Chen, C.J.; Froines, J.R. Arsenic methylation capacity and skin cancer. Cancer Epidemiol. Prev. Biomark. 2000, 9, 1259–1262.
    81. Hrudey, S.E.; Backer, L.C.; Humpage, A.R.; Krasner, S.W.; Michaud, D.S.; Moore, L.E.; Singer, P.C.; Stanford, B.D. Evaluating evidence for association of human bladder cancer with drinking-water chlorination disinfection by-products. J. Toxicol. Environ. Health Part B 2015, 18, 213–241.
    82. Cantor, K.P. Water Chlorination, Mutagenicity, and Cancer Epidemiology. AJPH 1994, 84, 1211–1213.
    83. Rahman, M.B.; Driscoll, T.; Cowie, C.; Armstrong, B.K. Disinfection by-products in drinking water and colorectal cancer: A meta-analysis. Int. J. Epidemiol. 2010, 39, 733–745.
    84. McDonald, T.A.; Komulainen, H. Carcinogenicity of the Chlorination Disinfection By-Product MX. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 2005, 23, 163–214.
    85. Ononugbo, C.P.; Avwiri, G.O.; Egieya, J.M. Evaluation of natural radionuclide content in surface and ground water and excess lifetime cancer risk due to gamma radioactivity. Acad. Res. Int. 2013, 4, 636.
    86. Radespiel-Tröger, M.; Meyer, M. Association between drinking water uranium content and cancer risk in Bavaria, Germany. Int. Arch. Occup. Environ. Health 2013, 86, 767–776.
    87. Karahan, G.; Taskin, H.; Bingoldag, N.; Kapdan, E.; Yilmaz, Y.Z. Environmental impact assessment of natural radioactivity and heavy metals in drinking water around Akkuyu Nuclear Power Plant in Mersin Province. Turk. J. Chem. 2018, 42, 735–747.
    88. Tomatis, L. (Ed.) Air Pollution and Human Cancer; Springer Science Business Media: Berlin, Germany, 2012.
    89. Pinter, A.; Bejczi, K.; Csik, M.; Kelecsenyi, Z.; Kertesz, M.; Surjan, A.; Török, G. Mutagenicity of Emission and Immission Samples around Industrial Areas. In Complex Mixtures and Cancer Risk; IARC Scientific Publications: Lyon, France, 1990.
    90. Mudipalli, A. Airborne Carcinogens: Mechanisms of Cancer. In Air Pollution and Health Effects; Springer: London, UK, 2015; pp. 151–184.
    91. Raloff, J. Bad Breath: Studies are Homing In on Which Particles Polluting the Air Are Most Sickening—And Why. Sci. News 2009, 176, 26.
    92. Buonanno, G.; Giovinco, G.; Morawska, L.; Stabile, L. Lung cancer risk of airborne particles for Italian population. Environ. Res. 2015, 142, 443–451.
    93. Cazzolla Gatti, R.; Velichevskaya, A.; Tateo, A.; Amoroso, N.; Monaco, A. Machine learning reveals that prolonged exposure to air pollution is associated with SARS-CoV-2 mortality and infectivity in Italy. Environ. Pollut. 2020, 267, 115471.
    94. Breslin, K. The Impact of Ozone. EHP 1995, 103, 660–664.
    95. Jakab, G.J.; Spannhake, E.W.; Canning, B.J.; Kleeberger, S.R.; Gilmour, M.I. The Effects of Ozone on Immune Function. EHP 1995, 103, 77–89.
    96. Valavanidis, A.; Vlachogianni, T.; Fiotakis, K.; Loridas, S. Pulmonary oxidative stress, inflammation and cancer: Respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms. Int. J. Environ. Res. Public Health 2013, 10, 3886–3907.
    97. Richters, A. Effects of Nitrogen Oxide and Ozone on Blood-Borne Cancer Cell Colonization of the Lungs. JTEH 1988, 25, 383–390.
    98. Charloux, A.; Quoix, E.; Wolkove, N.; Small, D.; Pauli, G.; Kreisman, H. The Increasing Incidence of Lung Adenocarcinoma: Reality or Artefact? A Review of the Epidemiology of Lung Adenocarcinoma. Int. J. Epidemiol. 1997, 26, 14–23.
    99. Mayoralas-Alises, S.; Diaz-Lobato, S. Air pollution and lung cancer. Curr. Respir. Med. Rev. 2012, 8, 418–429.
    100. Tseng, C.H.; Tsuang, B.J.; Chiang, C.J.; Ku, K.C.; Tseng, J.S.; Yang, T.Y.; Hsu, K.H.; Chen, K.C.; Yu, S.L.; Lee, W.C.; et al. The relationship between air pollution and lung cancer in nonsmokers in Taiwan. J. Thorac. Oncol. 2019, 14, 784–792.
    101. Dockery, D.W. An Association between Air Pollution and Mortality in Six, U.S. Cities. NEJM 1993, 329, 1753–1759.
    102. Raaschou-Nielsen, O.; Andersen, Z.J.; Beelen, R.; Samoli, E.; Stafoggia, M.; Weinmayr, G.; Hoffmann, B.; Fischer, P.; Nieuwenhuijsen, M.J.; Brunekreef, B.; et al. Air pollution and lung cancer incidence in 17 European cohorts: Prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Lancet Oncol. 2013, 14, 813–822.
    103. Blot, W.J.; Fraumeni, J.F.J. Geographic Patterns of Lung Cancer: Industrial Correlations. AJE 1976, 103, 539–550.
    104. Fernández-Navarro, P.; García-Pérez, J.; Ramis, R.; Boldo, E.; López-Abente, G. Industrial pollution and cancer in Spain: An important public health issue. Environ. Res. 2017, 159, 555–563.
    105. Cong, X. Air pollution from industrial waste gas emissions is associated with cancer incidences in Shanghai, China. Environ. Sci. Pollut. Res. 2018, 25, 13067–13078.
    106. American Lung Association, State of the Air. 2019. Available online: (accessed on 15 January 2020).
    107. Gustavsson, P.; Gustavsson, A.; Hogstedt, C. Excess Mortality among Swedish Chimney Sweeps. Br. J. Ind. Med. 1987, 44, 738–743.
    108. Brody, J.G.; Moysich, K.B.; Humblet, O.; Attfield, K.R.; Beehler, G.P.; Rudel, R.A. Environmental pollutants and breast cancer: Epidemiologic studies. Cancer Interdiscip. Int. J. Am. Cancer Soc. 2007, 109, 2667–2711.
    109. Yeh, H.L.; Hsu, S.W.; Chang, Y.C.; Chan, T.C.; Tsou, H.C.; Chang, Y.C.; Chiang, P.H. Spatial analysis of ambient PM2. 5 exposure and bladder cancer mortality in Taiwan. Int. J. Environ. Res. Public Health 2017, 14, 508.
    110. Sakhvidi, M.J.Z.; Lequy, E.; Goldberg, M.; Jacquemin, B. Air pollution exposure and bladder, kidney and urinary tract cancer risk: A systematic review. Environ. Pollut. 2020, 115328.
    111. Hystad, P.; Villeneuve, P.J.; Goldberg, M.S.; Crouse, D.L.; Johnson, K. Canadian Cancer Registries Epidemiology Research Group. Exposure to traffic-related air pollution and the risk of developing breast cancer among women in eight Canadian provinces: A case–control study. Environ. Int. 2015, 74, 240–248.
    112. White, A.J.; Bradshaw, P.T.; Hamra, G.B. Air pollution and breast cancer: A review. Curr. Epidemiol. Rep. 2018, 5, 92–100.
    113. Morris, J.J.; Seifter, E. The Role of Aromatic Hydrocarbons in the Genesis of Breast Cancer. Med. Hypotheses 1992, 38, 177–184.
    114. Korsh, J.; Shen, A.; Aliano, K.; Davenport, T. Polycyclic aromatic hydrocarbons and breast cancer: A review of the literature. Breast Care 2015, 10, 316–318.
    115. Pan, B.J.; Hong, Y.J.; Chang, G.C.; Wang, M.T.; Cinkotai, F.F.; Ko, Y.C. Excess Cancer Mortality Among Children and Adolescents in Residential Districts Polluted by Petrochemical Manufacturing Plants in Taiwan. JTEH 1994, 43, 117–129.
    116. Trichopoulos, D.; Petridou, F. Epidemiologic Studies and Cancer Etiology in Humans. Med. Exerc. Nutr. Health 1994, 3, 206–225.
    117. Liu, C.C.; Tsai, S.S.; Chiu, H.F.; Wu, T.N.; Chen, C.C.; Yang, C.Y. Ambient Exposure to Criteria Air Pollutants and Risk of Death from Bladder Cancer in Taiwan. Inhal. Toxicol. 2009, 21, 48–54.
    118. Tsai, S.S.; Tiao, M.M.; Kuo, H.W.; Wu, T.N.; Yang, C.Y. Association of Bladder Cancer with Residential Exposure to Petrochemical Air Pollutant Emissions in Taiwan. J. Toxicol. Environ. Health. Part A 2009, 72, 53–59.
    119. Connett, P.; Connett, E. Municipal Waste Incineration: Wrong Question, Wrong Answer. Ecologist 1994, 24, 14–20.
    120. Schneider, K. In the Humble Ashes of a Lone Incinerator, the Makings of a Law. New York Times, 18 March 1994.
    121. Ouyang, Z.; Liu, W.; Zhu, J. Flameless combustion behaviour of preheated pulverized coal. Can. J. Chem. Eng. 2018, 96, 1062–1070.
    122. Liu, W.; Ouyang, Z.; Cao, X.; Na, Y. The influence of air-stage method on flameless combustion of coal gasification fly ash with coal self-preheating technology. Fuel 2019, 235, 1368–1376.
    123. Weidmann, M.; Honore, D.; Verbaere, V.; Boutin, G.; Grathwohl, S.; Godard, G.; Gobin, C.; Kneer, R.; Scheffknecht, G. Experimental characterization of pulverized coal MILD flameless combustion from detailed measurements in a pilot-scale facility. Combust. Flame 2016, 168, 365–377.
    124. Brna, T.G.; Kilgore, J.D. The Impact of Particulate Emissions Control on the Control of Other MWC Air Emissions. J. Air Waste Manag. Assoc. 1990, 40, 1324–1329.
    125. Schraufnagel, D.E. The health effects of ultrafine particles. Exp. Mol. Med. 2020, 52, 311–317.
    126. Zhan, Z.; Chiodo, A.; Zhou, M.; Davis, K.; Wang, D.; Beutler, J.; Cremer, M.; Wang, Y.; Wendt, J.O.L. Modeling of the submicron particles formation and initial layer ash deposition during high temperature oxy-coal combustion. Proc. Combust. Inst. 2020.
    127. Thornton, J. Pandora′s Poison: Chlorine, Health, and a New Environmental Strategy; MIT Press: Cambridge, MA, USA, 2000.
    128. EPA. The Inventory of Sources and Environmental Releases of Dioxin-Like Compounds in the United States: The Year 2000 Update; EPA, National Center for Environmental Assessment: Washington, DC, USA, 2005.
    129. Dopico, M.; Gómez, A. Review of the current state and main sources of dioxins around the world. J. Air Waste Manag. Assoc. 2015, 65, 1033–1049.
    130. Connett, P.; Webster, T. An Estimation of the Relative Human Exposure to 2, 3, 7, 8-TCDD Emissions via Inhalation and Ingestion of Cow′s Milk. Chemosphere 1987, 16, 2079–2084.
    131. Liem, A.K.D.; Hoogerbrugge, R.; Kootstra, P.R.; Van der Velde, E.G.; De Jong, A.P.J.M. Occurrence of Dioxin in Cow′s Milk in the Vicinity of Municipal Waste Incinerators and a Metal Reclamation Plant in the Netherlands. Chemosphere 1991, 23, 1675–1684.
    132. Schecter, A. (Ed.) Dioxins and Health; Springer Science Business Media: Berlin, Germany, 2013.
    133. Tritscher, A.M.; Goldstein, J.A.; Portier, C.J.; McCoy, Z.; Clark, G.C.; Lucier, G.W. Dose-response relationships for chronic exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in a rat tumor promotion model: Quantification and immunolocalization of CYP1A1 and CYP1A2 in the liver. Cancer Res. 1992, 52, 3436–3442.
    134. Lucier, G.W.; Portier, C.J.; Gallo, M.A. Receptor Mechanisms and Dose-Response Models for the Effects of Dioxin. EHP 1993, 101, 36–44.
    135. Schecter, A.; Birnbaum, L.; Ryan, J.J.; Constable, J.D. Dioxins: An Overview. Environ. Res. 2006, 101, 419–428.
    136. La Merill, M. Mouse Breast Cancer Model-Dependent Changes in Metabolic Syndrome-Associated Phenotypes Caused by Maternal Dioxin Exposure and Dietary Fat. Am. J. Physiol. Endocrinol. Metab. 2009, 296, E203–E210.
    137. Jenkins, S.; Rowell, C.; Wang, J.; Lamartiniere, C.A. Prenatal TCDD Exposure Predisposes for Mammary Cancer in Rats. Reprod. Toxicol. 2007, 23, 391–396.
    138. Birnbaum, L.S.; Fenton, S.E. Cancer and Developmental Exposure to Endocrine Disruptors. EHP 2003, 111, 389–394.
    139. Vorderstrasse, B.A.; Fenton, S.E.; Bohn, A.A.; Cundiff, J.A.; Lawrence, B.P. A Novel Effect of Dioxin: Exposure During Pregnancy Severely Impairs Mammary Gland Differentiation. Toxicol. Sci. 2004, 78, 248–257.
    140. Sutter, T.R.; Guzman, K.; Dold, K.M.; Greenlee, W.F. Targets for Dioxin: Genes for Plasminogen Activator Inhibitor-2 and Interleukein-1B. Science 1991, 254, 415–418.
    141. Steenland, K.; Bertazzi, P.; Baccarelli, A.; Kogevinas, M. Dioxin Revisited: Developments Since the 1997 IARC Classification of Dioxin as a Human Carcinogen. EHP 2004, 112, 1265–1268.
    142. Lew, B.J.; Collins, L.L.; O’Reilly, M.A.; Lawrence, B.P. Activiation of the Aryl Hydrocarbon Receptor (AhR) during Different Critical Windows in Pregnancy Alters Mammary Epithelial Cell Proliferation and Differentiation. Toxicol. Sci. 2009, 111, 151–162.
    143. Bak, S.M.; Iida, M.; Hirano, M.; Iwata, H.; Kim, E.Y. Potencies of red seabream AHR1-and AHR2-mediated transactivation by dioxins: Implication of both AHRs in dioxin toxicity. Environ. Sci. Technol. 2013, 47, 2877–2885.
    144. Kim, D.; Martz, J.; Violi, A. A surrogate for emulating the physical and chemical properties of conventional jet fuel. Combust. Flame 2014, 161, 1489–1498.
    145. Stayner, L.T.; Dannenberg, A.L.; Bloom, T.; Thun, M. Excess hepatobiliary cancer mortality among munitions workers exposed to dinitrotoluene. J. Occup. Med. Off. Publ. Ind. Med Assoc. 1993, 35, 291–296.
    146. Letzel, S.; Göen, T.; Bader, M.; Angerer, J.; Kraus, T. Exposure to nitroaromatic explosives and health effects during disposal of military waste. Occup. Environ. Med. 2003, 60, 483–488.
    147. Harth, V.; Bolt, H.M.; Brüning, T. Cancer of the urinary bladder in highly exposed workers in the production of dinitrotoluenes: A case report. Int. Arch. Occup. Environ. Health 2005, 78, 677–680.
    148. Rocheleau, S.; Kuperman, R.G.; Simini, M.; Hawari, J.; Checkai, R.T.; Thiboutot, S.; Ampleman, G.; Sunahara, G.I. Toxicity of 2, 4-dinitrotoluene to terrestrial plants in natural soils. Sci. Total Environ. 2010, 408, 3193–3199.
    149. Carreón, T.; Hein, M.J.; Viet, S.M.; Hanley, K.W.; Ruder, A.M.; Ward, E.M. Increased bladder cancer risk among workers exposed to o-toluidine and aniline: A reanalysis. Occup. Environ. Med. 2010, 67, 348–350.
    150. Carreón, T.; Hein, M.J.; Hanley, K.W.; Viet, S.M.; Ruder, A.M. Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant. Occup. Environ. Med. 2014, 71, 175–182.
    151. Carpenter, D.O. Electromagnetic fields and cancer: The cost of doing nothing. Rev. Environ. Health 2010, 25, 75.
    152. Sun, J.W.; Li, X.R.; Gao, H.Y.; Yin, J.Y.; Qin, Q.; Nie, S.F.; Wei, S. Electromagnetic field exposure and male breast cancer risk: A meta-analysis of 18 studies. Asian Pac. J. Cancer Prev. 2013, 14, 523–528.
    153. Hauri, D.D.; Spycher, B.; Huss, A.; Zimmermann, F.; Grotzer, M.; Von Der Weid, N.; Spoerri, A.; Kuehni, C.E.; Röösli, M. Exposure to radio-frequency electromagnetic fields from broadcast transmitters and risk of childhood cancer: A census-based cohort study. Am. J. Epidemiol. 2014, 179, 843–851.
    154. Chen, C.; Ma, X.; Zhong, M.; Yu, Z. Extremely low-frequency electromagnetic fields exposure and female breast cancer risk: A meta-analysis based on 24,338 cases and 60,628 controls. Breast Cancer Res. Treat. 2010, 123, 569–576.
    155. Inskip, P.D.; Hoover, R.N.; Devesa, S.S. Brain cancer incidence trends in relation to cellular telephone use in the United States. Neuro-Oncology 2010, 12, 1147–1151.
    156. Hardell, L.; Carlberg, M.; Mild, K.H. Use of mobile phones and cordless phones is associated with increased risk for glioma and acoustic neuroma. Pathophysiology 2013, 20, 85–110.
    157. Destefanis, M.; Viano, M.; Leo, C.; Gervino, G.; Ponzetto, A.; Silvagno, F. Extremely low frequency electromagnetic fields affect proliferation and mitochondrial activity of human cancer cell lines. Int. J. Radiat. Biol. 2015, 91, 964–972.
    158. Zhang, Y.; Lai, J.; Ruan, G.; Chen, C.; Wang, D.W. Meta-analysis of extremely low frequency electromagnetic fields and cancer risk: A pooled analysis of epidemiologic studies. Environ. Int. 2016, 88, 36–43.
    159. Di Ciaula, A. Towards 5G communication systems: Are there health implications? Int. J. Hyg. Environ. Health 2018, 221, 367–375.
    160. Repacholi, M.H.; Lerchl, A.; Röösli, M.; Sienkiewicz, Z.; Auvinen, A.; Breckenkamp, J.; d’Inzeo, G.; Elliott, P.; Frei, P.; Heinrich, S.; et al. Systematic review of wireless phone use and brain cancer and other head tumors. Bioelectromagnetics 2012, 33, 187–206.
    161. Mortazavi, S.M.J. 5G Technology: Why Should We Expect a shift from RF-Induced Brain Cancers to Skin Cancers? J. Biomed. Phys. Eng. 2019, 9, 505.
    162. Catelinois, O.; Rogel, A.; Laurier, D.; Billon, S.; Hemon, D.; Verger, P.; Tirmarche, M. Lung cancer attributable to indoor radon exposure in France: Impact of the risk models and uncertainty analysis. Environ. Health Perspect. 2006, 114, 1361–1366.
    163. Sheen, S.; Lee, K.S.; Chung, W.Y.; Nam, S.; Kang, D.R. An updated review of case–control studies of lung cancer and indoor radon-Is indoor radon the risk factor for lung cancer? Ann. Occup. Environ. Med. 2016, 28, 1–9.
    164. Lerner, S.P.; Schoenberg, M.; Sternberg, C. (Eds.) Textbook of Bladder Cancer; Taylor and Francis: London, UK, 2006.
    165. Koutros, S.; Lynch, C.F.; Ma, X.; Lee, W.J.; Hoppin, J.A.; Christensen, C.H.; Andreotti, G.; Freeman, L.B.; Rusiecki, J.A.; Hou, L.; et al. Heterocyclic Aromatic Amine Pesticide Use and Human Cancer Risk: Results from the U.S. Agricultural Health Study. Int. J. Cancer 2009, 124, 1206–1212.
    166. Cooper, R.L.; Stoker, T.E.; Tyrey, L.; Goldman, J.M.; McElroy, W.K. Atrazine Disrupts the Hypothalamic Control of Pituitary-Ovarian Function. Toxicol. Sci. 2000, 53, 297–307.
    167. Donna, A.; Crosignani, P.; Robutti, F.; Betta, P.G.; Bocca, R.; Mariani, N.; Ferrario, F.; Fissi, R.; Berrino, F. Triazine Herbicides and Ovarian Cancer Neoplasms. Scand. J. Work. Environ. Health 1989, 15, 47–53.
    168. Rusiecki, J.A.; De Roos, A.; Lee, W.J.; Dosemeci, M.; Lubin, J.H.; Hoppin, J.A.; Blair, A.; Alavanja, M.C. Cancer Incidence Among Pesticide Applicators Exposed to Atrazine in the Agricultural Health Study. JNCI 2004, 96, 1375–1382.
    169. Young, H.A.; Mills, P.K.; Riordan, D.G.; Cress, R.D. Triazine Herbicides and Epithelial Ovarian Cancer Risk in Central California. J. Occup. Environ. Med. 2005, 47, 1148–1156.
    170. Crain, D.A.; Janssen, S.J.; Edwards, T.M.; Heindel, J.; Ho, S.M.; Hunt, P.; Iguchi, T.; Juul, A.; McLachlan, J.A.; Schwartz, J.; et al. Female Reproductive Disorders: The Roles of Endocrine-Disrupting Compounds and Developmental Timing. Fertil. Steril. 2008, 90, 911–940.
    171. Freeman, L.E.B.; Rusiecki, J.A.; Hoppin, J.A.; Lubin, J.H.; Koutros, S.; Andreotti, G.; Hoar Zahm, S.; Hines, C.J.; Coble, J.B.; Barone-Adesi, F.; et al. Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994–2007). Environ. Health Perspect. 2011, 119, 1253–1259.
    172. Inoue-Choi, M.; Weyer, P.J.; Jones, R.R.; Booth, B.J.; Cantor, K.P.; Robien, K.; Ward, M.H. Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women′s Health Study. Occup. Environ. Med. 2016, 73, 582–587.
    173. Rayner, J.L.; Enoch, R.R.; Fenton, S.E. Adverse Effects of Prenatal Exposure to Atrazine during a Critical Period of Mammary Gland Growth. Toxicol. Sci. 2005, 87, 255–266.
    174. Simpkins, J.W.; Swenberg, J.A.; Weiss, N.; Brusick, D.; Eldridge, J.C.; Stevens, J.T.; Handa, R.J.; Hovey, R.C.; Plant, T.M.; Pastoor, T.P.; et al. Atrazine and breast cancer: A framework assessment of the toxicological and epidemiological evidence. Toxicol. Sci. 2011, 123, 441–459.
    175. Roy, J.R.; Chakraborty, S.; Chakraborty, T.R. Estrogen-like Endocrine-Disrupting Chemicals Affecting Puberty in Humans—A Review. Med Sci. Monit. 2009, 15, RA137–RA145.
    176. Hayes, T.B. Atrazine has been used safely for 50 years? In Wildlife Ecotoxicology; Springer: New York, NY, USA, 2011; pp. 301–324.
    177. Wilson, V.S.; LeBlanc, G.A. Endosulfan Elevates Testosterone Biotransformation and Clearance in CD-1 Mice. Toxicol. Appl. Pharmacol. 1998, 148, 158–168.
    178. ATSDR. Toxicological Profile for Endosulfan; USDHHS: Washington, DC, USA, 2000.
    179. Purdue, M.P.; Hoppin, J.A.; Blair, A.; Dosemeci, M.; Alavanja, M.C. Occupational Exposure to Organochlorine Insecticides and Cancer Incidence in the Agricultural Health Study. Int. J. Cancer 2007, 120, 642–649.
    180. Engel, L.S.; Zabor, E.C.; Satagopan, J.; Widell, A.; Rothman, N.; O′Brien, T.R.; Zhang, M.; Van Den Eeden, S.K.; Grimsrud, T.K. Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case–control study nested within two prospective cohorts. Int. J. Cancer 2019, 145, 2360–2371.
    181. Mustafa, M.D.; Pathak, R.; Tripathi, A.K.; Ahmed, R.S.; Guleria, K.; Banerjee, B.D. Maternal and cord blood levels of aldrin and dieldrin in Delhi population. Environ. Monit. Assess. 2010, 171, 633–638.
    182. Najam, L.; Alam, T. Levels and distribution of OCPs, (specially HCH Aldrin, Dieldrin, DDT, Endosulfan) in Karhera Drain surface water of hindon river and their adverse effects. Orient. J. Chem 2015, 31, 20.
    183. Cassidy, R.A. Cancer and chlordane-treated homes: A pinch of prevention is worth a pound of cure. Leuk. Lymphoma 2010, 51, 1368–1369.
    184. Jeong, Y.; Lee, S.; Kim, S.; Choi, S.D.; Park, J.; Kim, H.J.; Lee, J.J.; Choi, G.; Choi, S.; Kim, S.; et al. Occurrence and exposure assessment of polychlorinated biphenyls and organochlorine pesticides from homemade baby food in Korea. Sci. Total. Environ. 2014, 470, 1370–1375.
    185. Ma, X.; Buffler, P.A.; Gunier, R.B.; Dahl, G.; Smith, M.T.; Reinier, K.; Reynolds, P. Critical Windows of Exposure to Household Pesticides and Risk of Childhood Leukemia. EHP 2002, 110, 955–960.
    186. Infante-Rivard, C.; Weichenthal, S. Pesticides and childhood cancer: An update of Zahm and Ward’s 1998 review. J. Toxicol. Environ. Health Part B 2007, 10, 81–99.
    187. Rudant, J.; Menegaux, F.; Leverger, G.; Baruchel, A.; Nelken, B.; Bertrand, Y.; Patte, C.; Pacquement, H.; Vérité, C.; Robert, A.; et al. Household Exposure to Pesticides and Risk of Hematopoietic Malignancies: The ESCALE Study (SFCE). EHP 2007, 115, 1787–1793.
    188. Rosso, A.L.; Hovinga, M.E.; Rorke-Adams, L.B.; Spector, L.G.; Bunin, G.R. A Case-Control Study of Childhood Brain Tumors and Fathers′ Hobbies: A Children′s Oncology Group Study. Cancer Causes Control 2008, 19, 1201–1207.
    189. Soldin, O.P.; Nsouli-Maktabi, H.; Genkinger, J.M.; Loffredo, C.A.; Ortega-Garcia, J.A.; Colantino, D.; Barr, D.B.; Luban, N.L.; Shad, A.T.; Nelson, D. Pediatric Acute Lymphoblastic Leukemia and Exposure to Pesticides. Ther. Drug Monit. 2009, 32, 495–501.
    190. Bradman, A.; Whitaker, D.; Quirós, L.; Castorina, R.; Claus Henn, B.; Nishioka, M.; Morgan, J.; Barr, D.B.; Harnly, M.; Brisbin, J.A.; et al. Pesticides and their metabolites in the homes and urine of farmworker children living in the Salinas Valley, CA. J. Expo. Sci. Environ. Epidemiol. 2007, 17, 331–349.
    191. Alavanja, M.C.; Ross, M.K.; Bonner, M.R. Increased cancer burden among pesticide applicators and others due to pesticide exposure. CA A Cancer J. Clin. 2013, 63, 120–142.
    192. Moses, M.; Johnson, E.S.; Anger, W.K.; Burse, V.W.; Horstman, S.W.; Jackson, R.J.; Lewis, R.G.; Maddy, K.T.; McConnell, R.; Meggs, W.J.; et al. Environmental Equity and Pesticide Exposure. Toxicol. Ind. Health 1993, 9, 913–959.
    193. Lewis, R.G.; Fortmann, R.C.; Camann, D.E. Evaluation of Methods for Monitoring the Potential Exposure of Small Children to Pesticides in the Residential Environment. Arch. Environ. Contam. Toxicol. 1994, 26, 37–46.
    194. Lewis-Michl, E.L.; Melius, J.M.; Kallenbach, L.R.; Ju, C.L.; Talbot, T.O.; Orr, M.F. Breast Cancer Risk and Residence Near Industry or Traffic in Nassau and Suffolk Counties, Long Island, New York. AEH 1996, 51, 255–265.
    195. Teitelbaum, S.L.; Gammon, M.D.; Britton, J.A.; Neugut, A.I.; Levin, B.; Stellman, S.D. Reported Residential Pesticide Use and Breast Cancer Risk on Long Island, New York. AJE 2007, 165, 643–651.
    196. Niehoff, N.M.; Nichols, H.B.; White, A.J.; Parks, C.G.; D′Aloisio, A.A.; Sandler, D.P. Childhood and adolescent pesticide exposure and breast cancer risk. Epidemiology 2016, 27, 326.
    197. Ellsworth, R.E.; Kostyniak, P.J.; Chi, L.H.; Shriver, C.D.; Costantino, N.S.; Ellsworth, D.L. Organochlorine pesticide residues in human breast tissue and their relationships with clinical and pathological characteristics of breast cancer. Environ. Toxicol. 2018, 33, 876–884.
    198. Tang, M.; Zhao, M.; Shanshan, Z.; Chen, K.; Zhang, C.; Liu, W. Assessing the underlying breast cancer risk of Chinese females contributed by dietary intake of residual DDT from agricultural soils. Environ. Int. 2014, 73, 208–215.
    199. Aamir, M.; Khan, S.; Li, G. Dietary exposure to HCH and DDT congeners and their associated cancer risk based on Pakistani food consumption. Environ. Sci. Pollut. Res. 2018, 25, 8465–8474.
    200. Andreotti, G.; Koutros, S.; Hofmann, J.N.; Sandler, D.P.; Lubin, J.H.; Lynch, C.F.; Lerro, C.C.; De Roos, A.J.; Parks, C.G.; Alavanja, M.C.; et al. Glyphosate use and cancer incidence in the agricultural health study. J. Natl. Cancer Inst. 2018, 110, 509–516.
    201. Van Bruggen, A.H.C.; He, M.M.; Shin, K.; Mai, V.; Jeong, K.C.; Finckh, M.R.; Morris Jr, J.G. Environmental and health effects of the herbicide glyphosate. Sci. Total Environ. 2018, 616, 255–268.
    202. Richmond, M.E. Glyphosate: A review of its global use, environmental impact, and potential health effects on humans and other species. J. Environ. Stud. Sci. 2018, 8, 416–434.
    203. Thongprakaisang, S.; Thiantanawat, A.; Rangkadilok, N.; Suriyo, T.; Satayavivad, J. Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem. Toxicol. 2013, 59, 129–136.
    204. Zhang, L.; Rana, I.; Shaffer, R.M.; Taioli, E.; Sheppard, L. Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence. Mutat. Res. Rev. Mutat. Res. 2019, 781, 186–206.
    205. Mirvish, S.S.; Grandjean, A.C.; Moller, H.; Fike, S.; Maynard, T.; Jones, L.; Rosinsky, S.; Nie, G. N-nitrosoproline Excretion by Rural Nebraskans Drinking Water of Varied Nitrate Content. Cancer Epidemiol. Biomark. Prev. 1992, 1, 455–461.
    206. Ward, M.H.; Cantor, K.P.; Riley, D.; Merkle, S.; Lynch, C.F. Nitrate in Public Water Supplies and Risk of Bladder Cancer. Epidemiol. 2003, 14, 183–190.
    207. Grosse, Y.; Baan, R.; Straif, K.; Secretan, B.; Ghissassi, F.E.; Cogliano, V. Carcinogenicity of Nitrate, Nitrite, and Cyanobacterial Peptide Toxins. Lancet Oncol. 2006, 7, 628–629.
    208. Jones, R.R.; Weyer, P.J.; DellaValle, C.T.; Inoue-Choi, M.; Anderson, K.E.; Cantor, K.P.; Krasner, S.; Robien, K.; Freeman, L.E.; Silverman, D.T.; et al. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ. Health Perspect. 2016, 124, 1751–1758.
    209. Di Lorenzo, G.; Federico, P.; De Placido, S.; Buonerba, C. Increased risk of bladder cancer in critical areas at high pressure of pollution of the Campania region in Italy: A systematic review. Crit. Rev. Oncol. Hematol. 2015, 96, 534–541.
    210. Rocco, G. Survival after surgical treatment of lung cancer arising in the population exposed to illegal dumping of toxic waste in the land of fires (‘Terra dei Fuochi′) of Southern Italy. Anticancer Res. 2016, 36, 2119–2124.
    More
    1. Please check and comment entries here.