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Lung Cancer and Arsenic Concentrations in Drinking Water in Chile
Abstract
Cities in northern Chile had arsenic concentrations of 860 microg/liter in drinking water in the period 1958-1970. Concentrations have since been reduced to 40 microg/liter. We investigated the relation between lung cancer and arsenic in drinking water in northern Chile in a case-control study involving patients diagnosed with lung cancer between 1994 and 1996 and frequency-matched hospital controls. The study identified 152 lung cancer cases and 419 controls. Participants were interviewed regarding drinking water sources, cigarette smoking, and other variables. Logistic regression analysis revealed a clear trend in lung cancer odds ratios and 95% confidence intervals (CIs) with increasing concentration of arsenic in drinking water, as follows: 1, 1.6 (95% CI = 0.5-5.3), 3.9 (95% CI = 1.2-12.3), 5.2 (95% CI = 2.3-11.7), and 8.9 (95% CI = 4.0-19.6), for arsenic concentrations ranging from less than 10 microg/liter to a 65-year average concentration of 200-400 microg/liter. There was evidence of synergy between cigarette smoking and ingestion of arsenic in drinking water; the odds ratio for lung cancer was 32.0 (95% CI = 7.2-198.0) among smokers exposed to more than 200 microg/liter of arsenic in drinking water (lifetime average) compared with nonsmokers exposed to less than 50 microg/liter. This study provides strong evidence that ingestion of inorganic arsenic is associated with human lung cancer.
... The toxicity of arseniccontaining compounds is highly dependent on chemical speciation and oxidation state, with the inorganic species being classified as carcinogenic by the International Agency for Research on Cancer (IARC) [1]. The sum of the inorganic species, arsenite and arsenate, is often referred to as inorganic arsenic (iAs) and exposure has been linked to bladder, lung, and skin cancers, as well as diabetes, cardiovascular disease, and pulmonary disease [2][3][4][5][6][7][8][9]. Ingestion of food or drinking water is the major exposure route to iAs, with rice and cereals being significant contributors to dietary intake [10]. ...
... iAs Briefly, 100 mg of freeze-dried ground material was added to quartz digestion tubes with 10 mL of 1% (v/v) HNO 3 and 3% (v/v) H 2 O 2 solution. H 2 O 2 was included in the extraction solution to oxidise As(III) to As(V) so the sum of both inorganic arsenic species could be quantified as As(V), without conversion of organoarsenic species to iAs [17]. ...
... Total As Total arsenic measurements were performed using an Agilent SPS4 autosampler and Agilent 7900 ICP-MS with an octopole collision cell in He gas mode. An external calibration in the range 0-200 µg L −1 was used for quantification and standards were prepared by serial dilution in 2% HNO 3 . Tuning of the ICP-MS was performed daily, and a 1000 µg L −1 indium internal standard was introduced continuously during analysis through a T-piece. ...
Seaweed is becoming increasingly popular in the Western diet as consumers opt for more sustainable food sources. However, seaweed is known to accumulate high levels of arsenic—which may be in the form of carcinogenic inorganic arsenic (iAs). Here we propose a fast method for the routine measurement of iAs in seaweed using HPLC-ICP-MS without coelution of arsenosugars that may complicate quantification. The developed method was optimised using design of experiments (DOE) and tested on a range of reference materials including TORT-3 (0.36 ± 0.03 mg kg ⁻¹ ), DORM-5 (0.02 ± 0.003 mg kg ⁻¹ ), and DOLT-5 (0.07 ± 0.007 mg kg ⁻¹ ). The use of nitric acid in the extraction solution allowed for the successful removal of interferences from arsenosugars by causing degradation to an unretained arsenosugar species, and a recovery of 99 ± 9% was obtained for iAs in Hijiki 7405-b when compared with the certified value. The method was found to be suitable for high-throughput analysis of iAs in a range of food and feed matrices including Asparagopsis taxiformis seaweed, grass silage, and insect proteins, and offers a cost-effective, fast, and robust option for routine analysis that requires minimal sample preparation. The method may be limited with regards to the quantification of dimethylarsenate (DMA) in seaweed, as the acidic extraction may lead to overestimation of this analyte by causing degradation of lipid species that are typically more abundant in seaweed than other marine matrices (i.e. arsenophospholipids). However, the concentrations of DMA quantified using this method may provide a better estimation with regard to exposure after ingestion and subsequent digestion of seaweed.
... Fifteen studies met the inclusion criteria for the meta-analysis: six studies reporting incidence and nine studies reporting mortality from lung cancer. Study locales included -Taiwan (8 studies) (Chen et al., 2004;Chen et al., 1988a;Chiou et al., 1995;Yang et al., 2013;Chung et al., 2013;Morales et al., 2000;Su et al., 2011;Tsai et al., 1999), Chile (4 studies) (Ferreccio et al., 2000;Steinmaus et al., 2013;Steinmaus et al., 2014a;Roh et al., 2018), USA (1 study) (Ferdosi et al., 2016), Argentina (1 study) (Hopenhayn-Rich et al., 1998) and Japan (1 study) (Tsuda et al., 1995). ...
... Eighteen of the reviewed 51 studies did not include covariate adjustments in their analysis and eight studies failed to account for tobacco smoking. The remaining 25 studies controlled for smoking either by direct adjustment, stratification or by including socioeconomic status as a proxy variable for tobacco smoking (Chen et al., 2010;D'Ippoliti et al., 2015;Chen et al., 2004;Chiou et al., 1995;Yang et al., 2013;Chung et al., 2013;Ferreccio et al., 2000;Steinmaus et al., 2013;Steinmaus et al., 2014a;Mendez Jr. et al., 2017;Chen et al., 1986;Mostafa et al., 2008;Heck et al., 2009;Steinmaus et al., 2010;Dauphine et al., 2013;Ferreccio et al., 2013;Melak et al., 2014;Steinmaus et al., 2014b;Baastrup et al., 2008;Garcia-Esquinas et al., 2013;Hsu et al., 2013;Argos et al., 2014;Wu et al., 2016;Hsu et al., 2017;Nuvolone et al., 2023). Among the 15 studies included in the meta-analysis (Hopenhayn-Rich et al., 1998;Tsuda et al., 1995;Chen et al., 2004;Chen et al., 1988a;Chiou et al., 1995;Yang et al., 2013;Chung et al., 2013;Morales et al., 2000;Su et al., 2011;Tsai et al., 1999;Ferreccio et al., 2000;Steinmaus et al., 2013;Steinmaus et al., 2014a;Roh et al., 2018;Ferdosi et al., 2016), eight (six ecological and two cohort) studies did not account for tobacco smoking (Hopenhayn-Rich et al., 1998;Tsuda et al., 1995;Chen et al., 1988a;Morales et al., 2000;Su et al., 2011;Tsai et al., 1999;Roh et al., 2018;Ferdosi et al., 2016). ...
... The remaining 25 studies controlled for smoking either by direct adjustment, stratification or by including socioeconomic status as a proxy variable for tobacco smoking (Chen et al., 2010;D'Ippoliti et al., 2015;Chen et al., 2004;Chiou et al., 1995;Yang et al., 2013;Chung et al., 2013;Ferreccio et al., 2000;Steinmaus et al., 2013;Steinmaus et al., 2014a;Mendez Jr. et al., 2017;Chen et al., 1986;Mostafa et al., 2008;Heck et al., 2009;Steinmaus et al., 2010;Dauphine et al., 2013;Ferreccio et al., 2013;Melak et al., 2014;Steinmaus et al., 2014b;Baastrup et al., 2008;Garcia-Esquinas et al., 2013;Hsu et al., 2013;Argos et al., 2014;Wu et al., 2016;Hsu et al., 2017;Nuvolone et al., 2023). Among the 15 studies included in the meta-analysis (Hopenhayn-Rich et al., 1998;Tsuda et al., 1995;Chen et al., 2004;Chen et al., 1988a;Chiou et al., 1995;Yang et al., 2013;Chung et al., 2013;Morales et al., 2000;Su et al., 2011;Tsai et al., 1999;Ferreccio et al., 2000;Steinmaus et al., 2013;Steinmaus et al., 2014a;Roh et al., 2018;Ferdosi et al., 2016), eight (six ecological and two cohort) studies did not account for tobacco smoking (Hopenhayn-Rich et al., 1998;Tsuda et al., 1995;Chen et al., 1988a;Morales et al., 2000;Su et al., 2011;Tsai et al., 1999;Roh et al., 2018;Ferdosi et al., 2016). Although the remaining studies accounted for tobacco smoking, more than half of these did not control for other important covariates, including socioeconomic status or other diseaserelated characteristics (e.g., body mass index, family history of cancer, or comorbidities) (Chiou et al., 1995;Yang et al., 2013;Chung et al., 2013;Steinmaus et al., 2014a). ...
... Moreover, these indices tended to be elevated for agents already known or suspected to cause lung cancer (e.g., arsenic and asbestos), but not for agents not linked to lung cancer (e.g., solvents). Even though some data were already known, and a synergistic relationship between arsenic and smoking in lung cancer risk has been previously shown [20,52], the novelty of this study is the analysis of the combined effect of arsenic with second-hand tobacco smoke. ...
... In conclusion, the smoke-arsenic interaction was negligible at low arsenic concentrations (<100 μg/L), while there was a synergistic effect at high exposures on lung cancer risk, as reported in four of the included studies [30,32,36,37] and in agreement with previously published papers. Nevertheless, the previously published papers discussed the synergism between arsenic exposure and smoke without distinguishing between low and high exposure [20,52]. ...
Although a higher lung cancer risk has been already associated with arsenic exposure, the contribution of arsenic and its compounds to the carcinogenic effects of other agents, such as tobacco smoke, is not well characterized. This systematic review examined the relationship between occupational and non-occupational arsenic exposure and tobacco smoking on lung cancer risk using papers published from 2010 to 2022. Two databases, PUBMED and Scifinder, were used for the searches. Among the sixteen human studies included, four were about occupational exposure, and the others were about arsenic in drinking water. Furthermore, only three case-control studies and two cohort studies evaluated an additive or multiplicative interaction. The interaction between arsenic exposure and tobacco smoke seems to be negligible at low arsenic concentrations (<100 μg/L), while there is a synergistic effect at higher concentrations. Finally, it is not yet possible to assess whether a linear no-threshold (LNT) model for lung cancer risk can be applied to the co-exposure to arsenic and tobacco smoke. Although the methodological quality of the included studies is good, these findings suggest that rigorous and accurate prospective studies on this topic are highly needed.
... Reviews of carcinogenic and non-carcinogenic health effects of arsenic have been published earlier [20][21][22] . Arsenic ingestion has been associated with several types of cancers, including skin and several other organs, including bladder, kidney, liver, prostate and lung [23][24][25][26][27] . In addition to several types of cancers, arsenic-related diseases include several other diseases and neuropathies [28][29][30][31] . ...
Arsenic is widespread in groundwater in India. High levels of arsenic in the three districts of Amritsar, Gurdaspur and Tarn Taran (also called Majha belt) have caused a crisis in Punjab. According to the Indian Council of Agriculture Research report, 13 districts of Punjab have arsenic content beyond the safety limit. This study aims to estimate probable health hazards due to ingestion of water with high levels of arsenic in the groundwater of Majha belt. Analysis of groundwater samples done using inductively coupled plasma mass spectrometry were collected from the Department of Water Supply and Sanitation, Government of Punjab, Mohali. The highest arsenic contamination of 111 ppb was found in the groundwater of Amritsar district, followed by Gurdaspur and Tarn Taran districts. The average value of hazard quotient (HQ) for children and adults in Amritsar district is estimated to be 11.13 and 8.0 respectively. HQ values for all the 650 habitations surveyed in the Majha belt of Punjab are greater than 1, which is a matter of concern because of high-risk potential for developing adverse carcinogenic and non-carcinogenic health hazards. The predicted values for cancer induction in children and adults of Amritsar district are 500 and 360 per million respectively. Miti-gation of arsenic in groundwater is an urgent need in the Majha belt of Punjab.
... Cu, Pu, Zn, Cd, Pb, Hg, Cr, Ni), metalloids (As, S), chlorides (Cl), and radioactive isotopes (Cs, I, U, Ra) [15,16,17,18]. Additionally, common table salt (NaCl) can accumulate in water sources, leading to excessive salinity [19], while some heavy metals (As, Hg, Pb, Cd, Cr) can bioaccumulate up the food chain [20]. ...
Water pollution exerts a negative impact on the health of both women and men, inducing hormonal changes, accelerating aging, and consequently leading to the premature onset of age-related health problems. Water pollutants can in general be classified as chemical (both organic and inorganic), physical, and biological agents. Certain chemical pollutants have been found to disrupt hormonal balance by blocking, mimicking, or disrupting functions within the intricate homeostasis of the human body. Moreover, certain water pollutants, including specific pesticides and industrial chemicals, have been associated with neurological and psychiatric disorders, such as mood swings, depression, cognitive decline, and anxiety, impacting both women and men. Water pollution is also associated with physical ailments, such as diarrhea, skin diseases, malnutrition, and cancer. Exposure to specific pollutants may promote premature menopause and vasomotor symptoms, elevate the risk of cardiovascular disease, and reduce bone density. In men, exposure to water pollution has been shown to reduce LH, FSH, and testosterone serum levels. The oxidative stress induced by pollutants prompts apoptosis of Sertoli and germ cells, inhibiting spermatogenesis and altering the normal morphology and concentration of sperm. Environmental estrogens further contribute to reduced sperm counts, reproductive system disruptions, and the feminization of male traits. Studies affirm that men generally exhibit a lower susceptibility than women to hormonal changes and health issues attributed to water pollutants. This discrepancy may be attributed to the varied water-related activities which have traditionally been undertaken by women, as well as differences in immune responses between genders. The implementation of effective measures to control water pollution and interventions aimed at safeguarding and enhancing the well-being of the aging population is imperative. The improvement of drinking water quality has emerged as a potential public health effort with the capacity to curtail the onset of cognitive impairment and dementia in an aging population.
... 42 Arsenic is predominantly associated with squamous cell carcinoma histology, and in this Chilean region, it accounts for about two-thirds of lung cancers. 43,44 A study performed using comparative genomic hybridization showed differential copy number alterations to non-arsenic exposed tumors; however, the mutational profile of arsenic-associated lung cancers remains to be elucidated. 43 Other carcinogens, such as residential radon gas exposure, have been scantly studied in Latin America. ...
Lung cancer poses a global health challenge and stands as the leading cause of cancer-related deaths worldwide. However, its incidence, mortality, and characteristics are not uniform across all regions worldwide. Understanding the factors contributing to this diversity is crucial in a prevalent disease where most cases are diagnosed in advanced stages. Hence, prevention and early diagnosis emerge as the most efficient strategies to enhance outcomes. In Western societies, tobacco consumption constitutes the primary risk factor for lung cancer, accounting for up to 90% of cases. In other geographic locations, different significant factors play a fundamental role in disease development, such as individual genetic predisposition, or exposure to other carcinogens such as radon gas, environmental pollution, occupational exposures, or specific infectious diseases. Comprehensive clinical and molecular characterization of lung cancer in recent decades has enabled us to distinguish different subtypes of lung cancer with distinct phenotypes, genotypes, immunogenicity, treatment responses, and survival rates. The ultimate goal is to prevent and individualize lung cancer management in each community and improve patient outcomes.
... Several epidemiological studies have revealed that Bangladesh, India, China and USA are the most arsenitecontaminated countries in the world (Raju 2022;Kumar et al. 2023). In addition, several preclinical studies have revealed that arsenite induces the generation of reactive oxygen species (ROS) and consequently oxidative stress, inflammation and apoptosis which have been suggested to be the primary mechanisms involved in arsenite-induced organ toxicity (Ferreccio et al. 2000;Jomova et al. 2011;Duan et al. 2022;Rachamalla et al. 2023). ...
Inorganic arsenic is a well-known environmental toxicant, and exposure to this metalloid is strongly linked with severe and extensive toxic effects in various organs including the lungs. In the present study, we aimed to investigate the acute and chronic effects of arsenite exposure on pulmonary tissue in young and adult mice. In brief, young and adult female Balb/C mice were exposed to 3 and 30 ppm arsenite daily via drinking water for 30 and 90 days. Subsequently, the animals were sacrificed and various histological and immunohistochemistry (IHC) analyses were performed using lung tissues. Our findings showed arsenite was found to cause dose-dependent pathological changes such as thickening of the alveolar septum, inflammatory cell infiltrations and lung fibrosis in young and adult mice. In addition, arsenite exposure significantly increased the expression of inflammatory markers NF-κB and TNF-α, indicating that arsenite-exposed mice suffered from severe lung inflammation. Moreover, the IHC analysis of fibrotic proteins demonstrated an increased expression of TGF-β1, α-SMA, vimentin and collagen-I in the arsenite-exposed mice compared to the control mice. This was accompanied by apoptosis, which was indicated by the upregulated expression of caspase-3 in arsenite-exposed mice compared to the control. Adult mice were generally found to be more prone to arsenite toxicity during chronic exposure relative to their younger counterparts. Overall, our findings suggest that arsenite in drinking water may induce dose-dependent and age-dependent structural and functional impairment in the lungs through elevating inflammation and fibrotic proteins.
... However, arsenic in water sources is principally comprised of the more toxic inorganic arsenic forms, such as trivalent (III) or pentavalent (V) arsenic (Saxe et al., 2006;ATSDR, 2007ATSDR, , 2016Gault et al., 2008;Karagas et al., 2000). Ingestion of inorganic arsenic has been associated with various cancers, including bladder, skin, kidney, and liver (Celik et al., 2008;Chiang et al., 1993;Ferreccio et al., 2000;Liu & Waalkes, 2008;Speer et al., 2023;Tseng et al., 1968;Yuan et al., 2010), as well as skin lesions, cardiovascular disease, kidney disease, respiratory problems, diabetes, and neurodegeneration (Parvez et al., 2010;Tolins et al., 2014;Zheng et al., 2015;Abdul et al., 2015;Olabode Fatoki & Abiodun Badmus, 2022). Many population studies have been conducted in arsenicpolluted sites worldwide including Europe (Buekers et al., 2023), Africa (Nyanza et al., 2019), Taiwan (Lan et al., 2011), India (Maity et al., 2012;Mazumder & Dasgupta, 2011), and Bangladesh (Ali et al., 2010;Smith et al., 2000). ...
Toenails are a common monitoring tool for arsenic exposure, but the risk of external contamination of toenails has cast doubt on its usefulness. The main objective of this study is to investigate the micro-distribution of arsenic through the dorsoventral plane of nail clippings to understand endogenous vs exogenous sources. We used laser-ablation inductively coupled plasma mass spectrometry to measure arsenic through a dorsoventral cross-section of the nail plate collected from reference (N = 17) and exposed individuals (N = 35). Our main results showed (1) bulk toenail concentrations measured using ICP-MS in this study ranged from 0.54 to 4.35 µg/g; (2) there was a double-hump pattern in arsenic concentrations, i.e., dorsal and ventral layers had higher arsenic than the inner layer; (3) the double-hump was more pronounced in the exposed group (ventral: 6.25 μg/g; inner: 0.75 μg/g; dorsal: 0.95 μg/g) than the reference group (ventral: 0.58 μg/g; inner: 0.15 μg/g; dorsal: 0.29 μg/g) on average; (4) the distribution was, in part, associated with different binding affinity of nail layers (i.e., ventral > dorsal > inner); (5) most individuals in the higher exposure group showed > 25% contamination in ventral and dorsal nail layers; and (6) there were no statistically significant correlations between LA-ICP-MS arsenic with either bulk toenail arsenic or urine arsenic from the same individuals. Our results on micro-distribution and binding affinity provide insight into the impact of external contamination on arsenic concentrations and show how LA-ICP-MS can access the protected inner nail layer to provide a more accurate result.
... Consuming lower level arsenic polluted water have lower association with the lung cancer. Ferreccio et al [8] presented a study in chile relating to the arsenic carcinogen. The evaluation of the level of arsenic by reveals that arsenic concentration level is 860mg/l which is considered to be high. ...
Most survey reveals that 40% of cancer deaths are caused by Lung cancer. It is very unfortunate that even the drinking water contaminants may aggravate lung cancer when contaminated water is consumed regularly. Among various carcinogens polluting water arsenic is proved to more hazardous in triggering lung cancer by modifying DNA through genetic mutations. Measure of levels and percentages of carcinogens present in drinking water can direct the research to analyse how the domestic drinking water turns as a killer by causing life threatening problem of lung cancer. The research is carried out with patient data of non-smoking persons who aggravated lung cancer with prolonged usage of arsenic polluted water for drinking and few other factors like childhood pneumonia, genetical history, poor diet and carcinogens in working environment. Chi-square test is performed with non-smoking patient data record and results are evaluated with the discussion of preventive measures.
... As a consequence of widespread metal contamination, water-borne diseases have become very common in Pakistan, constituting about 80% of total diseases and about 30% of deaths [19]. Due to the continuous use of contaminated water, people are at a high risk of cancer, birth defects, post-neonatal mortality, and other chronic diseases [20,21]. Therefore, it is necessary to regularly monitor the water quality of all major water bodies to design the appropriate mitigation strategies. ...
Background
With rapid industrial development, heavy metal contamination has become a major public health and ecological concern worldwide. Although knowledge about metal pollution in European water resources is increasing, monitoring data and assessments in developing countries are rare. In order to protect human health and aquatic ecosystems, it is necessary to investigate heavy metal content and its consequences to human health and ecology. Accordingly, we collected 200 water samples from different water resources including groundwater, canals, river and drains, and investigated metal contamination and its implications for human and ecological health. This is the first comprehensive study in the region that considered all the water resources for metal contamination and associated human health and ecological risks together.
Results
Here we show that the water resources of Lahore (Pakistan) are highly contaminated with metals, posing human and ecological health risks. Approximately 26% of the groundwater samples are unsuitable for drinking and carry the risk of cancer. Regarding dermal health risks, groundwater, canal, river, and drain water respectively showed 40%, 74%, 80%, and 90% of samples exceeding the threshold limit of the health risk index (HRI > 1). Regarding ecological risks, almost all the water samples exceeded the chronic and acute threshold limits for algae, fish, and crustaceans. Only 42% of groundwater samples were below the acute threshold limits. In the case of pollution index, 72%, 56%, and 100% of samples collected from canals, river Ravi, and drains were highly contaminated.
Conclusions
In conclusion, this comprehensive study shows high metal pollution in water resources and elucidates that human health and aquatic ecosystems are at high risk. Therefore, urgent and comprehensive measures are imperative to mitigate the escalating risks to human health and ecosystems.
... The connection between lung cancer and ingested arsenic was discovered during this metalloid's therapeutic application in psoriasis patients (Martinez et al. 2011, Robson and Jelliffe 1963, Sommers and McManus 1953, Williamson 1960. Subsequently, an increased lung cancer risk following exposure to arsenic in drinking water was demonstrated by several studies (Ferreccio et al. 2000, Gibb et al. 2011, IARC 2004, Martinez et al. 2011, Tsai, Wang and Ko 1999. ...
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... The connection between lung cancer and ingested arsenic was discovered during this metalloid's therapeutic application in psoriasis patients (Martinez et al. 2011, Robson and Jelliffe 1963, Sommers and McManus 1953, Williamson 1960. Subsequently, an increased lung cancer risk following exposure to arsenic in drinking water was demonstrated by several studies (Ferreccio et al. 2000, Gibb et al. 2011, IARC 2004, Martinez et al. 2011, Tsai, Wang and Ko 1999. ...
Medicinal and aromatic plants have been used in the prevention and treatment of diseases since ancient times. Today, they have been used in the production diverse commodities such as food, perfumery, cosmetics, medicine, textile, spices, paints, and pesticides. Prostate cancer is the second most common type of cancer in men. Early treatment of prostate cancer becomes important, and it becomes important to develop different treatment methods.
This chapter envisaged to represent the work performed on caper (Capparis spinosa L.), carob (Ceratonia siliqua L.), hawthorn (Crataegus monogyna L.), quinoa (Chenopodium quinoa L.), rosehip (Rosa canina L.), golden grass (Helichrysum arenarium L.), mallow (Malva parviflora L.), stevia (Stevia rebaudiana L.), gojiberry (Lycium barbarum L.), and coriander (Coriandrum sativum L.). Extracts obtained from these plants will be characterized by mass spectrometry and their activities will then be screened on some of the important proteins cancer (Protein Data bank ID: 3RUK, 6XXP, 3A99, 3G1R, 2AMA and 3EQM) by molecular docking approach. Afterwards, ADME/T properties of the promising extract components will be characterized.
... However, when arsenic exposure levels were lower than 0.64 mg l −1 , this effect was minimal [50]. In addition, research has shown that the combined effects of smoking and ingesting arsenic from drinking water are far more likely to result in lung cancer [51]. ...
... Arsenic has been classified as a class I human carcinogen by International Agency of Research on Cancer (IARC), which denotes that arsenic possesses the property of not only changing the configuration of the cellular activity but also modifying the gene functions at the genome level in human beings. In the recent studies, skin and several types of internal cancers such as bladder, kidney, liver, prostate and lung have been associated with arsenic ingestion 51,[68][69][70][71] . Arsenic usually affects the cellular activities mainly by two pathways -arsenic induced oxidative stress and also through epigenetic changes. ...
In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient’s biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient’s blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients’ biological samples—gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis.
... Different elements were found in drinking water to increase the risk of cancer. Ferreccio et al. (2000) found that lung cancer and arsenic concentrations in drinking water in Chile were relevant to understand local cancer distribution. Page et al. (1976) found drinking water from the Mississippi River related to cancer mortality in Louisiana, which was attributed to the presence of organic chemicals or some unknown carcinogens in the water. ...
During decades of cancer research, different disciplines have made important contributions to the development of our knowledge about cancer. Identification of complex problems not being solved using a single discipline has directed scientists toward interdisciplinary approaches. Cancer is a complex problem that, regardless of great advances in different scientific fields, remains to be properly addressed. Early diagnosis, personalized treatment, minimum treatment side effects, optimal treatment outcomes, and effective preventive measures can be achievable by adopting interdisciplinary approaches in cancer research. This chapter is an interdisciplinary collaboration of scientists from different fields of science, in which the contribution of different disciplines to cancer research is reviewed. In addition, the framework of cancer research in 2050 is depicted as a guide for future research.
... The calculation was divided into a worst-and a bestcase scenario, and a typical ratio of fresh mass to dry mass of 10 was used (Kalač 2000). For the worst-case, the lowest BMDL 01 (0.3 µg iAs kg −1 bw) for lung cancer (Ferreccio et al. 2000) and for the best-case the BMDL 0.5 (3 µg iAs kg −1 bw) recommended by the EChA was taken into consideration. Furthermore, we compared our results to the only available European limit for iAs in food, namely the EU's iAs limit for rice, although it has to be pointed out that rice is usually more commonly and regularly eaten than mushrooms. ...
... Thus, dietary exposure to iAs has a food safety priority worldwide (EFSA et al., 2021) with rice as the primary dietary source of iAs exposure if populations are not exposed to iAs through contaminated drinking water (Meharg et al., 2008). A range of benchmark-dose lower confidence limits (BMDL) 01 of 0.3 to 8 μg kg −1 body weight (bw) per day has been derived as toxicological reference range related to the 95 % lower confidence limit of an 1 % extra risk for cancer (EFSA, 2009;Ferreccio et al., 2000). Currently, no health-based guidance value could be derived for iAs since it was not deemed appropriate to identify a dose without appreciable health risk due to uncertainties the dose-response relationship in the low concentration range in epidemiological studies (EFSA, 2009;JECFA, 2011). ...
For risk assessment purposes, the dietary exposure to total arsenic and inorganic arsenic was estimated within the first German total diet study (BfR MEAL Study) for the whole population in Germany. Therefore, occurrence data of 356 different foods from the BfR MEAL Study were combined with consumption data from German nutrition surveys. Due to the different toxicological potentials of other water-soluble organic arsenic species present in rice-based foods, fish and seafood, dietary exposure to dimethylarsinic acid, monomethylarsonic acid and arsenobetaine was assessed in consumers in Germany through such foods for the first time. Related to the bodyweight, dietary exposure to total arsenic and inorganic arsenic in infants and young children (0.5–<5 years) were higher than in adolescents/adults (≥14 years). The highest median exposure estimates to inorganic arsenic resulted for the age group of infants from 0.5 to <1 year under modifies lower bound conditions and for young children from 1 to <2 years under upper bound conditions (0.17 μg kg⁻¹ bodyweight day⁻¹–0.24 μg kg⁻¹ bodyweight day⁻¹ and 0.26 μg kg⁻¹ bodyweight day⁻¹–0.34 μg kg⁻¹ bodyweight day⁻¹, respectively). ‘Grains and grain-based products’ (especially rice) were identified as the main contributors for dietary exposure to total arsenic and inorganic arsenic for all age classes. Especially, for infants and young children, high consumption of rice-based foods and fish fingers is driving the dietary exposure to dimethylarsinic acid. The dietary exposure calculations indicate that a further reduction of dietary exposure to inorganic arsenic and further investigations to water-soluble organic arsenic species are necessary.
... Arsenic has been classified as a class I human carcinogen by International Agency of Research on Cancer (IARC), which denotes that arsenic possesses the property of not only changing the configuration of the cellular activity but also modifying the gene functions at the genome level in human beings. In the recent studies, skin and several types of internal cancers such as bladder, kidney, liver, prostate and lung have been associated with arsenic ingestion 51,[68][69][70][71] . Arsenic usually affects the cellular activities mainly by two pathways -arsenic induced oxidative stress and also through epigenetic changes. ...
In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient’s biologicalsamples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated forthe presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 μg/Lin GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of2166 μg/kg, in gallbladder stones 635 μg/kg, in bile samples 483 μg/L and in hair samples 6980 μg/kg respectively. Moreover, the n = 512 gallbladder cancer patient’s blood samples study revealed verysignificant arsenic concentration in the population of Bihar with maximum arsenic concentration as746 μg/L. The raised arsenic concentration in the gallbladder cancer patients’ biological samples—gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis.
... Further, historiographical studies determined that water scarcity was mainly related to a demographic increase in the Atacama Desert, omitting the correlation between the rise in mining exploitation and that in water consumption (Álvarez, 1999;Alvear, 1975;Castro and Martínez, 1997;Martínez, 1993;Niemeyer, 1980;Recabarren and Maino, 2008;Vergara, 1998). Additionally, most of the research that addressed the arsenic health issues neither related them to the changes in drinking water sources caused by mining expansion (but see, e.g., Santolaya Biondi et al., 1995) nor to the technological asymmetry of its treatment or the management of the State's public policies (Borgoño et al., 1977;Chen et al., 1988;Ferreccio et al., 2000;Ferreccio and Sancha, 2006;Galetovic and Fernicola, 2003;Hopenhayn-Rich et al., 2000;Jaafarzadeh et al., 2022;Montalva, 2016;Montoya-Aguilar, 2007;Puga et al., 1973;Rivara and Corey, 1995;Sancha, 1998;Solar et al., 2012;Yuan et al., 2007). Thus, insular analyses limited to their authors' respective scientific disciplines gave rise to fragmented and non-dialogical interpretations. ...
This article describes and analyzes an unfortunate consequence of implementing a sulfide treatment plant at Chuquicamata in northern Chile, the world's largest copper mine during the twentieth century. In 1952, the plant increased its water demand for mining processes, limiting the regional population's drinking water supply. In addition, a misleading public policy forced the region's population to consume water from the naturally poisoned arsenic Toconce River. The water's high concentrations of arsenic generated unforeseen consequences on the health of the inhabitants of the Atacama Desert, a derivation of the region's mining expansion and extractive policies that have not yet received sufficient attention.
... One of the study shows that UV-caused skin cancers have been directly linked with exposure to trivalent arsenite (Hong et al., 2014;Rossman et al., 2004). Furthermore, several researchers have examined the dose-dependent correlation between As ingestion and the prevalence of lung cancer (Ferreccio et al., 2000;Smith et al., 2006). In a research carried out in Taiwan, individuals who had drunk high-arsenic-polluted drinking water for the past 5 decades had an increased death rate; lower As levels of drinking water resulted in lower lung cancer death rates (Chiu et al., 2004;Hong et al., 2014). ...
Groundwater is consumed by a large number of people as their primary source of drinking water globally. Among all the countries worldwide, nations in South Asia, particularly India and Bangladesh, have severe problem of groundwater arsenic (As) contamination so are on our primary focus in this study. The objective of this review study is to provide a viewpoint about the source of As, the effect of As on human health and agriculture, and available treatment technologies for the removal of As from water. The source of As can be either natural or anthropogenic and exposure mediums can either be air, drinking water, or food. As-polluted groundwater may lead to a reduction in crop yield and quality as As enters the food chain and disrupts it. Chronic As exposure through drinking water is highly associated with the disruption of many internal systems and organs in the human body including cardiovascular, respiratory, nervous, and endocrine systems, soft organs, and skin. We have critically reviewed a complete spectrum of the available ex situ technologies for As removal including oxidation, coagulation–flocculation, adsorption, ion exchange, and membrane process. Along with that, pros and cons of different techniques have also been scrutinized on the basis of past literatures reported. Among all the conventional techniques, coagulation is the most efficient technique, and considering the advanced and emerging techniques, electrocoagulation is the most prominent option to be adopted. At last, we have proposed some mitigation strategies to be followed with few long and short-term ideas which can be adopted to overcome this epidemic.
Graphical abstract
... Arsenic (As) is a naturally occurring metalloid classified as a group 1 carcinogen to humans by the International Agency for Research on Cancer (IARC). Chronic environmental exposure to inorganic arsenic (In-As) has been frequently associated with different types of cancer, which include squamous cell carcinoma of the skin [1,2] and lung [3,4], as well as bladder cancers [5,6]. The bladder is one of the identified target tissues for arsenic toxicity as some of the toxic methylated metabolites of In-As (thioarsenicals) excreted through urine have been detected in organs, particularly in the bladder in in vitro and in vivo models ystems [7]. ...
Arsenic (sodium arsenite: NaAsO2) is a potent carcinogen and a known risk factor for the onset of bladder carcinogenesis. The molecular mechanisms that govern arsenic-induced bladder carcinogenesis remain unclear. We used a physiological concentration of NaAsO2 (250 nM: 33 µg/L) for the malignant transformation of normal bladder epithelial cells (TRT-HU1), exposed for over 12 months. The increased proliferation and colony-forming abilities of arsenic-exposed cells were seen after arsenic exposure from 4 months onwards. Differential gene expression (DEG) analysis revealed that a total of 1558 and 1943 (padj < 0.05) genes were deregulated in 6-month and 12-month arsenic-exposed TRT-HU1 cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that cell proliferation and survival pathways, such as the MAPK, PI3K/AKT, and Hippo signaling pathways, were significantly altered. Pathway analysis revealed that the enrichment of stem cell activators such as ALDH1A1, HNF1b, MAL, NR1H4, and CDH1 (p < 0.001) was significantly induced during the transformation compared to respective vehicle controls. Further, these results were validated by qPCR analysis, which corroborated the transcriptomic analysis. Overall, the results suggested that stem cell activators may play a significant role in facilitating the arsenic-exposed cells to gain a survival advantage, enabling the healthy epithelial cells to reprogram into a cancer stem cell phenotype, leading to malignant transformation.
... Between October 2007 and December 2010, a single first morning urine sample was collected from each of 283 cancer patients and 347 controls matched on age and gender. Drinking WAs concentrations reported from various sources, including government agencies, scientific research, and commercial water suppliers, were assigned to each subject based on municipality of residence (Steinmaus et al. 2013;Borgoño et al 1980;Rivara et al. 1997;Zaldívar 1974;Ferreccio et al. 2000;CONAMA 2000;Sancha & O'Ryan 2008). Weekly intakes of various types of foods, as well as typical volumes of water consumed per day, were ascertained for each subject based on a food frequency questionnaire (Hall et al. 2017). ...
Unless a toxicant builds up in a deep compartment, intake by the human body must on average balance the amount that is lost. We apply this idea to assess arsenic (As) exposure misclassification in three previously studied populations in rural Bangladesh (n=11,224), Navajo Nation in the Southwestern United States (n=619), and northern Chile (n=630), under varying assumptions about As sources. Relationships between As intake and excretion were simulated by taking into account additional sources, as well as variability in urine dilution inferred from urinary creatinine. The simulations bring As intake closer to As excretion but also indicate that some exposure misclassification remains. In rural Bangladesh, accounting for intake from more than one well and rice improved the alignment of intake and excretion, especially at low exposure. In Navajo Nation, comparing intake and excretion revealed home dust as an important source. Finally, in northern Chile, while food-frequency questionnaires and urinary As speciation indicate fish and shellfish sources, persistent imbalance of intake and excretion suggests imprecise measures of drinking water arsenic as a major cause of exposure misclassification. The mass-balance approach could prove to be useful for evaluating sources of exposure to toxicants in other settings.
In the face of flourishing industrialization and global trade, heavy metal and metalloid contamination of the environment is a growing concern throughout the world. The widespread presence of highly toxic compounds of arsenic, antimony, and cadmium in nature poses a particular threat to human health. Prolonged exposure to these toxins has been associated with severe human diseases, including cancer, diabetes, and neurodegenerative disorders. These toxins are known to induce analogous cellular stresses, such as DNA damage, disturbance of redox homeostasis, and proteotoxicity. To overcome these threats and improve or devise treatment methods, it is crucial to understand the mechanisms of cellular detoxification in metal and metalloid stress. Membrane proteins are key cellular components involved in the uptake, vacuolar/lysosomal sequestration, and efflux of these compounds; thus, deciphering the multilevel regulation of these proteins is of the utmost importance. In this review, we summarize data on the mechanisms of arsenic, antimony, and cadmium detoxification in the context of membrane proteome. We used yeast Saccharomyces cerevisiae as a eukaryotic model to elucidate the complex mechanisms of the production, regulation, and degradation of selected membrane transporters under metal(loid)-induced stress conditions. Additionally, we present data on orthologues membrane proteins involved in metal(loid)-associated diseases in humans.
The world is facing an escalating water crisis, posing significant challenges and urgent imperatives for global sustainability. This review delves into the multifaceted dimensions of this crisis, examining its origins, current status, and potential future trajectories. We analyze the complex interplay of factors driving water scarcity, including population growth, climate change, urbanization, pollution, and unsustainable resource management practices. Moreover, we explore the profound socioeconomic and environmental impacts of water scarcity on human health, agriculture, industry, and ecosystems, highlighting its disproportionate effects on vulnerable communities. By synthesizing insights from interdisciplinary research, policy documents, and expert perspectives, we identify key strategies and interventions aimed at addressing the water crisis. These include enhancing water governance frameworks, investing in water infrastructure and technology, promoting water conservation and efficiency measures, and fostering international cooperation and partnerships. Furthermore, we underscore the need for innovative approaches, such as nature-based solutions and integrated water resources management, to build resilience and adaptability in the face of uncertain climatic and demographic trends. Urgent action is required at local, national, and global levels to mitigate the impacts of the water crisis, safeguard water security, and ensure equitable access to this vital resource for current and future generations. This review provides a comprehensive synthesis of knowledge and insights to inform policy formulation, planning, and decision-making processes aimed at addressing the critical challenges posed by the escalating water crisis on a global scale.
Despite decades of declining mortality rates, lung cancer remains the leading cause of cancer death in the United States. This article examines lung cancer incidence, stage at diagnosis, survival, and mortality using population‐based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Over the past 5 years, declines in lung cancer mortality became considerably greater than declines in incidence among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually), reflecting absolute gains in 2‐year relative survival of 1.4% annually. Improved outcomes likely reflect advances in treatment, increased access to care through the Patient Protection and Affordable Care Act, and earlier stage diagnosis; for example, compared with a 4.6% annual decrease for distant‐stage disease incidence during 2013–2019, the rate for localized‐stage disease rose by 3.6% annually. Localized disease incidence increased more steeply in states with the highest lung cancer screening prevalence (by 3%–5% annually) than in those with the lowest (by 1%–2% annually). Despite progress, disparities remain. For example, Native Americans have the highest incidence and the slowest decline (less than 1% annually among men and stagnant rates among women) of any group. In addition, mortality rates in Mississippi and Kentucky are two to three times higher than in most western states, largely because of elevated historic smoking prevalence that remains. Racial and geographic inequalities highlight longstanding opportunities for more concerted tobacco‐control efforts targeted at high‐risk populations, including improved access to smoking‐cessation treatments and lung cancer screening, as well as state‐of‐the‐art treatment.
The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL05) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties.
Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in-utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to understand how environmental exposure contributes to adverse pregnancy-related cardiovascular events. This study seeks to understand the impact of trivalent inorganic arsenic exposure during gestation on maternal cardiac remodeling in late pregnancy, as well as offspring outcomes. C57BL/6J mice were exposed to 0 (control), 100 or 1000 microg/L sodium arsenite (NaAsO2) beginning at embryonic day (E) 2.5 and continuing through E17.5. Maternal heart function and size were assessed via transthoracic echocardiography, gravimetric measurement, and histology. Transcript levels of hypertrophic markers were probed via qRT-PCR and confirmed by western blot. Offspring outcomes were assessed through echocardiography and gravimetric measurement. We found that exposure to 1000 microg/L iAs abrogated normal physiologic growth of the maternal heart during late pregnancy and reduced transcript levels of estrogen receptor alpha (ERa;), progesterone receptor membrane component 1 (Pgrmc1) and progesterone receptor membrane component 2 (Pgrmc2). Both 100 and 1000 microg/L iAs also reduced transcription of protein kinase B (Akt) and atrial natriuretic peptide (ANP). Akt protein expression was also significantly reduced after 1000 microg/L iAs exposure in the maternal heart with no change in activating phosphorylation. This significant abrogation of maternal cardiac hypertrophy suggests that arsenic exposure during pregnancy can potentially contribute to cardiovascular disease. Taken together, our findings further underscore the importance of reducing arsenic exposure during pregnancy and indicate that more research is needed to assess the impact of arsenic and other environmental exposures on the maternal heart and adverse pregnancy events.
Heavy metals/metalloids are generally defined as having density more than 5 g cm−3. Many of them, like Cu, Co, Zn, Fe, Mn, Mo, etc., are biologically essential in trace amounts, however, toxic at high concentrations. On the other hand, several toxic heavy metals/metalloids, such as arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), are nonessential and deleterious to environment and human health. Although traces of these elements are naturally present in rocks and aquifers, however, their high concentrations have been found at several places, both through natural and anthropogenic sources. Mining, industrial production and uses, metal containing pesticides and fertilizers, etc. are major anthropogenic sources of most of the heavy metals in water and soil, while contamination of metalloid As in most parts of the world is from natural geogenic processes, e.g., through dissolution of As-rich sediments under reducing environment of groundwater aquifers and volcanic hot springs. High concentration of these toxicants in water adversely affects not only flora and fauna of aquatic system but also human health through bioaccumulation and biomagnification in fishes. Further, the use of heavy metal-/metalloid-contaminated water for irrigation leads to their high concentration in soil. Crops and vegetables grown in contaminated areas accumulate significant amount of heavy metals/metalloid from soil in different plant parts including in cereal grains. Thus, humans get exposed to these toxicants through drinking water and contaminated food resulting in many folds higher dietary intake of these elements than their respective maximum tolerable daily/weekly intake values (MTDI/MTWI), set by various regulatory bodies. For instance, it has been reported that consumption of contaminated vegetables alone may contribute to over 50% of provisional tolerable daily intake of individual element. Similarly, rice is the main source of dietary As and Cd for population on rice-based diet, and fish is the main source of Hg. Chronic exposure to these toxicants through water and food results in severe health hazards to humans which is discussed in the subsequent chapter in sequence. In the current chapter, the major sources of different metal/metalloid in environment, the accumulation in food chain and the global status of contamination in water, soil, and food have been discussed.
Heavy metals/metalloids are generally defined as having density more than
5 g cm-3. Many of them, like Cu, Co, Zn, Fe, Mn, Mo, etc., are biologically
essential in trace amounts, however, toxic at high concentrations. On the
other hand, several toxic heavy metals/metalloids, such as arsenic (As), lead
(Pb), mercury (Hg), and cadmium (Cd), are nonessential and deleterious to
environment and human health. Although traces of these elements arenaturally present in rocks and aquifers, however, their high concentrations
have been found at several places, both through natural and anthropogenic
sources. Mining, industrial production and uses, metal containing pesticides
and fertilizers, etc. are major anthropogenic sources of most of the heavy
metals in water and soil, while contamination of metalloid As in most parts
of the world is from natural geogenic processes, e.g., through dissolution of
As-rich sediments under reducing environment of groundwater aquifers and
volcanic hot springs. High concentration of these toxicants in water
adversely affects not only flora and fauna of aquatic system but also
human health through bioaccumulation and biomagnification in fishes.
Further, the use of heavy metal-/metalloid-contaminated water for
irrigation leads to their high concentration in soil. Crops and vegetables
grown in contaminated areas accumulate significant amount of heavy
metals/metalloid from soil in different plant parts including in cereal
grains. Thus, humans get exposed to these toxicants through drinking
water and contaminated food chain resulting in many folds high dietary
intake of these elements than their respective maximum tolerable daily/
weekly intake values (MTDI/MTWI), set by various regulatory bodies. For
instance, it has been reported that consumption of contaminated vegetables
alone may contribute to over 50% of provisional tolerable daily intake of
individual element. Similarly, rice is the main source of dietary As and Cd
for population on rice-based diet, and fish is the main source of Hg. Chronic
exposure to these toxicants through water and food results in severe health
hazards to humans which is discussed in the subsequent chapter in sequence.
In the current chapter, the major sources of different metal/metalloid in
environment, the accumulation in food chain and the global status of
contamination in water, soil, and food have been discussed
Arsenic is commonly found in Earth’s crust and ranks 20th in terms of abundance. It can enter the human body through drinking water, inhalation, and diet, but drinking water is the most common source. The toxic effects of arsenic are widespread in both developed and developing countries. Arsenic exposure over a prolonged period can lead to skin, lungs, CNS, and reproductive health disorders. Arsenic is a human carcinogen well known for affecting multiple organs. Recent evidence suggests that arsenic exposure causes reproductive toxicity, which leads to teratogenic and developmental effect. Arsenic exposure at high levels increases the chances of developing diabetes mellitus.KeywordsHealth effectsChronic arsenicMulti-organ damageReproductive toxicityTeratogenicity
Arsenic, Antimony, and Bismuth are members of Group V of the Periodic Table of Elements. These elements have been used for a variety of medicinal and pest control purposes over a number of centuries. They have also been used in metallic alloys and in the production of III–V semiconductors to increase electronic speeds of computer chips. Arsenicals are largely metabolized by methylation pathways and bismuth is known to induce the metal‐binding protein metallothionein and to form electron–dense cytoplasmic and intranuclear inclusion bodies.
Contamination in the environment is a major concern because of the harmful effects on ecosystems and human health, and dyes are increasingly common industry-contributed pollutants. This book offers a comprehensive analysis of the primary, secondary, and tertiary wastewater treatment systems that are in use across the globe. Covering the latest research in water purification techniques, the book contains analysis of photocatalysis and the mechanisms involved, findings of an in-depth investigation into different dyes, their preparation and the threats they pose, and concludes with discussion of the chemistry of green biopolymers and their doping impact with metal, metal oxides, and metal sulfide nanomaterials. The book will appeal to researchers and postgraduate students working in the fields of materials science, nanoscience and nanotechnology for environmental remediation.
Metalloids are released into the environment due to the erosion of the rocks or anthropogenic activities, causing problems for human health in different world regions. Meanwhile, microorganisms with different mechanisms to tolerate and detoxify metalloid contaminants have an essential role in reducing risks. In this review, we first define metalloids and bioremediation methods and examine the ecology and biodiversity of microorganisms in areas contaminated with these metalloids. Then we studied the genes and proteins involved in the tolerance, transport, uptake, and reduction of these metalloids. Most of these studies focused on a single metalloid and co-contamination of multiple pollutants were poorly discussed in the literature. Furthermore, microbial communication within consortia was rarely explored. Finally, we summarized the microbial relationships between microorganisms in consortia and biofilms to remove one or more contaminants. Therefore, this review article contains valuable information about microbial consortia and their mechanisms in the bioremediation of metalloids.
A recently discovered set of historical documents related to the cemetery in Chuquicamata's abandoned camp provides novel data regarding 2,353 cases of the local population's causes of death. We quantitatively and qualitatively analyze and characterize the mortality of the Chuquicamata copper mine and of the company town's population between 1915 and 1923, a period corresponding to the Guggenheim family administration. Furthermore, we show the correlation between the causes of death, their time frame, gender distinctions, and the working and environmental conditions within the mine and the camp. Under Guggenheim's administration, Chuquicamata's production increased, becoming the world's largest copper mine. This economic expansion was made possible by the implantation of new technological and technical systems that modified the environment and the local mining society's social relations. In addition, the camp workers and inhabitants subsidized the foreign mining project with their bodies.
During the expansion of Tawantinsuyo, the Inca Empire sustained its hegemony by using multiple strategies, including moving specialized groups called mitimaes to their conquered territories. This study examines bioarchaeological evidence from the Camarones 9 (CAM-9) Inca period cemetery at the mouth of the Camarones Valley in northern Chile. The waters in this valley contain concentrations of arsenic that are 100 times above the norm (10 μg/L) for human ingestion, causing serious health consequences. We study the environmental health effects on this population, using atomic absorption spectrometry and hydride generation to investigate arsenic concentration in the bone tissues of 16 individuals sampled from this burial site. Three of four individuals presented arsenic levels in their bones that were beyond the standard 1 μg/g, with a median of 3.6 μg/g; in some, the levels were nine times higher than those currently recommended by the World Health Organization. Considering previous and current bioarchaeological evidence, especially the high arsenic levels found in these individuals, we postulate that the CAM-9 site population corresponds to mitimaes who settled on the Camarones coast. This study is relevant to all regions of the world that present ecotoxic loads.
Arsenic a genotoxic metalloid has become a major threat to the living world in the present scenario. Its distribution in the environment and the many sources of exposure make it more hazardous to humanity. Various sources of arsenic exposure from contaminated groundwater have become a global public health concern, with over 300 million people affected worldwide. Bihar is the second most arsenic-affected state after West Bengal in India. Out of 38 districts of Bihar, 22 districts have been severely affected by arsenic. It is estimated that currently 10 million population are exposed to arsenic in the state. The exposed population is continuously consuming potable water contaminated with arsenic above the WHO recommended concentration of 10 μg/L. It is currently associated with several health problems, including skin, liver, lung, kidney, prostate, and gallbladder cancer. Moreover, the exposed population is also exhibiting severe health-related problems such as skin manifestations—hyperkeratosis, melanosis, raindrop pigmentation, loss of appetite, gastrointestinal problems, anemia, hormonal disorders, etc. The International Agency for Research on Cancer has also classified the disease as a Group I human carcinogen. The mechanism of the arsenic-induced tumor involves alteration of DNA repair, methylation, gene regulation, and gene expression ultimately leading to genomic instability. It induces reactive oxygen species which damage various signaling pathways resulting in abnormal cell division. Autophagy is a natural cell repair process by which damaged cells or cellular components are degraded in the lysosome to maintain homeostasis. Any defect in the autophagy mechanism causes chronic inflammation leading to carcinogenesis. In the arsenic exposed individuals, there is a complete cellular failure by which there is continuous inflammation in the system causing a breach in the defense mechanism. The uncontrolled disease impairment, in the long duration of arsenic exposure, causes failure in the autophagy mechanism causing the disease of cancer in the exposed population.
Arsenic is an environmental toxicant that significantly enhances the risk of developing disease, including several cancers. While the epidemiological evidence supporting increased cancer risk due to chronic arsenic exposure is strong, therapies tailored to treat exposed populations are lacking. This can be accredited in large part to the chronic nature and pleiotropic pathological effects associated with prolonged arsenic exposure. Despite this fact, several putative mediators of arsenic promotion of cancer have been identified. Among these, the critical transcription factor NRF2 has been shown to be a key mediator of arsenic's pro-carcinogenic effects. Importantly, the dependence of arsenic-transformed cancer cells on NRF2 upregulation exposes a targetable liability that could be utilized to treat arsenic-promoted cancers. In this chapter, we briefly introduce the “light” vs “dark” side of the NRF2 pathway. We then give a brief overview of arsenic metabolism, and discuss the epidemiological and experimental evidence that support arsenic promotion of different cancers, with a specific emphasis on mechanisms mediated by chronic, non-canonical activation of NRF2 (i.e., the “dark” side). Finally, we briefly highlight how the non-canonical NRF2 pathway plays a role in other arsenic-promoted diseases, as well as research directions that warrant further investigation.
Lung cancer is the second most common and the most lethal malignancy worldwide. It is estimated that lung cancer in never smokers (LCINS) accounts for 10-25% of cases, and its incidence is increasing according to recent data, although the reasons remain unclear. If considered alone, LCINS is the 7th most common cause of cancer death. These tumors occur more commonly in younger patients and females. LCINS tend to have a better prognosis, possibly due to a higher chance of bearing an actionable driver mutation, making them amenable to targeted therapy. Notwithstanding, these tumors respond poorly to immune checkpoint inhibitors (ICI). There are several putative explanations for the poor response to immunotherapy: low immunogenicity due to low tumor mutation burden and hence low MANA (mutation-associated neo-antigen) load, constitutive PD-L1 expression in response to driver mutated protein signaling, high expression of immunosuppressive factors by tumors cells (like CD39 and TGF-beta), non-permissive immune TME (tumor microenvironment), abnormal metabolism of amino acids and glucose, and impaired TLS (Tertiary Lymphoid Structures) organization. Finally, there is an increasing concern of offering ICI as first line therapy to these patients owing to several reports of severe toxicity when TKIs (tyrosine kinase inhibitors) are administered sequentially after ICI. Understanding the biology behind the immune response against these tumors is crucial to the development of better therapeutic strategies.
Background: More than 80% of sewage generated by human activities is discharged into rivers and oceans without any treatment, which results in environmental pollution and more than 50 diseases. 80% of diseases and 50% of child deaths worldwide are related to poor water quality.
Methods: This paper selected 85 relevant papers finally based on the keywords of water pollution, water quality, health, cancer, and so on.
Results: The impact of water pollution on human health is significant, although there may be regional, age, gender, and other differences in degree. The most common disease caused by water pollution is diarrhea, which is mainly transmitted by enteroviruses in the aquatic environment.
Discussion: Governments should strengthen water intervention management and carry out intervention measures to improve water quality and reduce water pollution’s impact on human health.
In some Chilean cities, levels of arsenic (As) in drinking water reached 800 µg/L between 1950 and 1970, while current levels are 40 µg/L. To evaluate the causal role of this exposure in lung and bladder cancers, we conducted a case-control study in Regions I, II, and III of the country. From 1994 to 1996, cases diagnosed as lung cancer and two hospital controls were entered in the study; one control was a patient with a cancer, while the other was a patient without cancer, both conditions unrelated to As. Controls were matched with cases by age and sex. A standard survey containing questions about residence, employment, health history, was administered to study subjects. Data on As concentrations in water were obtained from records of the municipal water companies. A total of 151 lung cancer cases and 419 controls (167 with cancer and 242 without cancer) were enrolled. Median level of lifetime As exposure was significantly higher among cases, with a clear dose-response relationship between mean As exposure levels, with an OR (95% CI) of: 1, 1.7 (0.5-5.1), 3.9 (1.2-13.4), 5.5 (2.2-13.5), and 9.0 (3.6-22) for strata one to five respectively. This study provides new evidence that As in drinking water can cause internal cancers and gives an estimate of the form of this relationship.
In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.
Inorganic arsenic is known to cause skin cancer by ingestion and lung cancer by inhalation. However, whether arsenic ingestion causes internal cancers is still a matter of debate. This paper has reviewed the epidemiologic literature that bears on this question. Published studies of populations who have ingested arsenic in medicines, wine substitutes, or water supplies, as well as workers exposed to arsenic by inhalation, were considered in terms of whether the observed associations might be explained by the presence of biases, the consistency of the evidence, and the biologic plausibility of the associations. Many studies were found to be uninformative because of low statistical power or potential biases. The most informative studies, which were from Taiwan and Japan, involved exposure to arsenic in drinking water. These studies strongly suggest that ingested inorganic arsenic does cause cancers of the bladder, kidney, lung, and liver, and possibly other sites. However, confirmatory studies are needed.
A total of 69 bladder cancer, 76 lung cancer and 59 liver cancer deceased cases and 368 alive community controls group-matched on age and sex were studied to evaluate the association between high-arsenic artesian well water and cancers in the endemic area of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous arsenic exposure. According to a standardized structured questionnaire, information on risk factors was obtained through proxy interview of the cases and personal interview of the controls. A positive dose-response relationship was observed between the exposure to artesian well water and cancers of bladder, lung and liver. The age-sex-adjusted odds ratios of developing bladder, lung and liver cancers for those who had used artesian well water for 40 or more years were 3.90, 3.39, and 2.67, respectively, as compared with those who never used artesian well water. Multiple binary logistic regression analyses showed that the dose-response relationships and odds ratios remained much the same while other risk factors were further adjusted.
In order to elucidate the dose-response relationship between ingested inorganic arsenic and internal cancers, a total of 263 patients with blackfoot disease and 2293 healthy residents in the endemic area of arseniasis were recruited and followed up for 7 years. The information on consumption of high-arsenic artesian well water, sociodemographic characteristics, life-style and dietary habits, and personal and family history of cancers was obtained through standardized interviews. The occurrence of internal cancers among study subjects was determined through annual health examinations, home visit personal interviews, household registration data checks, and national death certification and cancer registry profile linkages. A dose-response relationship was observed between the long-term arsenic exposure from drinking artesian well water and the incidence of lung cancer, bladder cancer, and cancers of all sites combined after adjustment for age, sex, and cigarette smoking through Cox's proportional hazards regression analysis. Blackfoot disease patients had a significantly increased cancer incidence after adjustment for cumulative arsenic exposure.
A historical cohort study was conducted to investigate the long-term effect of exposure to ingested arsenic. The 454 residents who had been identified in a list made in 1959 were followed until 1992. They lived in an arsenic-polluted area, called Namiki-cho, Nakajo-machi, in Niigata Prefecture, Japan, and used well water containing inorganic arsenic. The exposure period was estimated to be about 5 years (1955–1959). Death certificates for the people who died between 1959 and 1992 were examined, and a total of 113 of the 454 residents were estimated to have drunk well water containing a high dose of arsenic (≥1 ppm). The standardized mortality rate ratios of these 113 residents were 15.69 for lung cancer (observed/expected = 8/0.51; 95% confidence interval (CI) 7.38–31.02) and 31.18 for urinary tract cancer (observed/expected = 3/0.10; 95% CI 8.62–91.75). Cox's proportional hazard analyses demonstrated that the hazard ratios of the highest exposure level group (≥1 ppm) versus the background exposure level group (0.001 ppm) were 1.74 (95% CI 1.10–2.74) for all deaths and 4.82 (95% CI 2.09–11.14) for all cancers. The analysis according to the skin signs of chronic arsenicism in 1959 showed that they were useful risk indicators for subsequent cancer development. In the development of lung cancer, there was evidence of synergism between arsenic intake and smoking habit.
We assembled data from numerous studies to examine whether active smoking and occupational exposure to arsenic act synergistically (more than additively) to increase the risk of lung cancer. Although several smaller studies lacked the power to reject simple additive relations, the joint effect from both exposures consistently exceeded the sum of the separate effects by about 70 to 130%. The only study not showing a greater than additive effect appeared to have inadequate data to address this question. We calculated the excess fractions for the synergism; these showed that a minimum of between 30% and 54% of lung cancer cases among those with both exposures could not be attributed to either one or the other exposure alone. Previous authors addressing the synergism between arsenic exposure and smoking have evaluated deviations from a multiplicative model, which is inappropriate for this purpose. Reports of no interaction or "negative" interaction have therefore been misleading. Taken as a whole, the evidence is compelling that arsenic and smoking act in a synergistic manner to produce lung cancer. Substantial reductions in the lung cancer burden of smokers occupationally exposed to arsenic could be achieved by reductions in either exposure. The mechanism for the synergism is unclear.
Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964-1966 were available in 42 villages of the study area, while mortality and population data during 1973-1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age-adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study.
The objective of this study was to examine multiple risk factors and correlated malignant neoplasms of blackfoot disease (BFD), a unique peripheral vascular disease related to continuous exposure to high-arsenic artesian well water. A total of 241 BFD cases, including 169 with spontaneous or surgical amputations of affected extremities, and 759 age-sex-residence-matched healthy community controls were studied to explore the risk factors of BFD. Multiple logistic regression analysis showed that artesian well water consumption, arsenic poisoning, familial history of BFD, and undernourishment were significantly associated with the development of BFD. The life-table method used to analyze cancer mortality of 789 BFD patients followed for 15 years showed a significantly higher mortality from cardiovascular diseases, peripheral vascular diseases, and cancers of bladder, skin, lung, and liver among BFD patients as compared with the general population in Taiwan or residents in the BFD-endemic area. The results imply the atherogenicity and carcinogenicity of the artesian well water in the BFD-endemic area.
The objective of this study is to elucidate the association between high-arsenic artesian well water and cancers in endemic area of blackfoot disease, a unique peripheral vascular disease related to continuous arsenic exposure. As compared with the general population in Taiwan, both the standardized mortality ratio (SMR) and cumulative mortality rate were significantly high in blackfoot disease-endemic areas for cancers of bladder, kidney, skin, lung, liver, and colon. The SMRs for cancers of bladder, kidney, skin, lung, liver, and colon were 1100, 772, 534, 320, 170, and 160, respectively, for males, and 2009, 1119, 652, 413, 229, and 168, respectively, for females. A dose-response relationship was observed between SMRs of the cancers and blackfoot disease prevalence rate of the villages and townships in the endemic areas. SMRs of cancers were greater in villages where only artesian wells were used as the drinking water source than in villages using both artesian and shallow wells, and even greater than in villages using shallow wells only.
A historical cohort study was conducted to investigate the long-term effect of exposure to ingested arsenic. The 454 residents who had been identified in a list made in 1959 were followed until 1992. They lived in an arsenic-polluted area, called Namiki-cho, Nakajo-machi, in Niigata Prefecture, Japan, and used well water containing inorganic arsenic. The exposure period was estimated to be about 5 years (1955-1959). Death certificates for the people who died between 1959 and 1992 were examined, and a total of 113 of the 454 residents were estimated to have drunk well water containing a high dose of arsenic (> or = 1 ppm). The standardized mortality rate ratios of these 113 residents were 15.69 for lung cancer (observed/expected = 8/0.51; 95% confidence interval (CI) 7.38-31.02) and 31.18 for urinary tract cancer (observed/expected = 3/0.10; 95% CI 8.62-91.75). Cox's proportional hazard analyses demonstrated that the hazard ratios of the highest exposure level group (> or = 1 ppm) versus the background exposure level group (0.001 ppm) were 1.74 (95% CI 1.10-2.74) for all deaths and 4.82 (95% CI 2.09-11.14) for all cancers. The analysis according to the skin signs of chronic arsenicism in 1959 showed that they were useful risk indicators for subsequent cancer development. In the development of lung cancer, there was evidence of synergism between arsenic intake and smoking habit.
Occupational studies in three countries have related quantitative estimates of arsenic exposure to lung cancer risks. Mine exposures in China appear to incur a higher relative risk than arsenic exposures elsewhere. All of the studies with quantitative data are consistent with a supralinear dose-response relationship. Two studies are also consistent with a linear relationship over an elevated background risk of lung cancer among arsenic-exposed workers. Neither toxicokinetic mechanisms nor confounding from age, smoking, or other workplace carcinogens that differ by exposure level appear likely to explain this curvilinearity. Plausible explanations include (i) synergism (with smoking) which varies in magnitude according to the level of arsenic exposure, (ii) long-term survivorship in higher exposure jobs among the healthier, less susceptible individuals, (iii) exposure estimate errors that were more prominent at higher exposure levels as a result of past industrial hygiene sampling or worker protection practices.
Studies in Taiwan and Argentina suggest that ingestion of inorganic arsenic from drinking water results in increased risks of internal cancers, particularly bladder and lung cancer. The authors investigated cancer mortality in a population of around 400,000 people in a region of Northern Chile (Region II) exposed to high arsenic levels in drinking water in past years. Arsenic concentrations from 1950 to the present were obtained. Population-weighted average arsenic levels reached 570 microg/liter between 1955 to 1969, and decreased to less than 100 microg/liter by 1980. Standardized mortality ratios (SMRs) were calculated for the years 1989 to 1993. Increased mortality was found for bladder, lung, kidney, and skin cancer. Bladder cancer mortality was markedly elevated (men, SMR = 6.0 (95% confidence interval (CI) 4.8-7.4); women, SMR = 8.2 (95% CI 6.3-10.5)) as was lung cancer mortality (men, SMR = 3.8 (95% CI 3.5-4.1); women, SMR = 3.1 (95% CI 2.7-3.7)). Smoking survey data and mortality rates from chronic obstructive pulmonary disease provided evidence that smoking did not contribute to the increased mortality from these cancers. The findings provide additional evidence that ingestion of inorganic arsenic in drinking water is indeed a cause of bladder and lung cancer. It was estimated that arsenic might account for 7% of all deaths among those aged 30 years and over. If so, the impact of arsenic on the population mortality in Region II of Chile is greater than that reported anywhere to date from environmental exposure to a carcinogen in a major population.
Studies in Taiwan have found dose-response relations between arsenic ingestion from drinking water and cancers of the skin, bladder, lung, kidney and liver. To investigate these associations in another population, we conducted a study in Córdoba, Argentina, which has a well-documented history of arsenic exposure from drinking water.
Mortality from lung, kidney, liver and skin cancers during the period 1986-1991 in Córdoba's 26 counties was investigated, expanding the authors' previous analysis of bladder cancer in the province. Counties were grouped a priori into low, medium and high arsenic exposure categories based on available data. Standardized mortality ratios (SMR) were calculated using all of Argentina as the reference population.
We found increasing trends for kidney and lung cancer mortality with arsenic exposure, with the following SMR, for men and women respectively: kidney cancer, 0.87, 1.33, 1.57 and 1.00, 1.36, 1.81; lung cancer, 0.92, 1.54, 1.77 and 1.24, 1.34, 2.16 (in all cases, P < 0.001 in trend test), similar to the previously reported bladder cancer results (0.80, 1.28, 2.14 for men, 1.22, 1.39, 1.81 for women). There was a small positive trend for liver cancer but mortality was increased in all three exposure groups. Skin cancer mortality was elevated for women only in the high exposure group, while men showed a puzzling increase in mortality in the low exposure group.
The results add to the evidence that arsenic ingestion increases the risk of lung and kidney cancers. In this study, the association between arsenic and mortality from liver and skin cancers was not clear.
In some Chilean cities, levels of arsenic (As) in drinking water reached 800 (micrograms/L between 1950 and 1970, while current levels are 40 (micrograms/L. To evaluate the causal role of this exposure in lung and bladder cancers, we conducted a case-control study in Regions I, II, and III of the country. From 1994 to 1996, cases diagnosed as lung cancer and two hospital controls were entered in the study; one control was a patient with a cancer, while the other was a patient without cancer, both conditions unrelated to As. Controls were matched with cases by age and sex. A standard survey containing questions about residence, employment, health history, was administered to study subjects. Data on As concentrations in water were obtained from records of the municipal water companies. A total of 151 lung cancer cases and 419 controls (167 with cancer and 242 without cancer) were enrolled. Median level of lifetime As exposure was significantly higher among cases, with a clear dose-response relationship between mean As exposure levels, with an OR (95% CI) of: 1, 1.7 (0.5-5.1), 3.9 (1.2-13.4), 5.5 (2.2-13.5), and 9.0 (3.6-22) for strata one to five respectively. This study provides new evidence that As in drinking water can cause internal cancers and gives an estimate of the form of this relationship.
Impacto en Salud atribuible a exposición a Arsénico: un estudio Ecológico. Monograph FONDEF Proyecto 2-24
- C Ferreccio
- C González
- V Milosavjlevic
- G Marshall
- Am Sancha
Ferreccio C, González C, Milosavjlevic V, Marshall G, Sancha AM. Impacto
en Salud atribuible a exposición a Arsénico: un estudio Ecológico. Monograph FONDEF Proyecto 2-24. Santiago, Chile: Facultad Ciencias Físicas y
Matemáticas, Universidad de Chile, 1997.