Returning personal genetic information on susceptibility to arsenic toxicity to research participants in Bangladesh.

BACKGROUND: There is growing consensus that researchers should offer to return genetic results to participants, but returning results in lower-resource countries has received little attention. In this study, we return results on genetic susceptibility to arsenic toxicity to participants in a Bangladeshi cohort exposed to arsenic through naturally-contaminated drinking water. We examine the impact on behavioral changes related to exposure reduction. METHODS: We enrolled participants from the Health Effects of Arsenic Longitudinal Study who had (1) high arsenic (≥150 µg/g creatinine) in a recent urine sample and (2) existing data on genetic variants impacting arsenic metabolism efficiency (AS3MT and FTCD). We used genetic data to recruit three study groups, each with n = 103: (1) efficient metabolizers (low-risk), (2) inefficient metabolizers (high-risk), and (3) a randomly-selected control group (NCT05072132). At baseline, all participants received information on the effects of arsenic and how to reduce exposure by switching to a low arsenic well. The two intervention groups also received their arsenic metabolism efficiency status (based on their genetic results). Changes in behavior and arsenic exposure were assessed using questionnaires and urine arsenic measures after six months. RESULTS: Clear decreases in urine arsenic after six months were observed for all three groups. The inefficient group self-reported higher levels of attempted switching to lower arsenic wells than the other groups; however, there was no detectable difference in urine arsenic reduction among the three groups. Participants showed strong interest in receiving genetic results and found them useful. The inefficient group experienced higher levels of anxiety than the other groups. Among the efficient group, that receiving genetic results did not appear to hinder behavioral change. CONCLUSION: Returning genetic results increased self-reported exposure-reducing behaviors but did not have a detectable impact on reducing urine arsenic over and above a one-on-one educational intervention.

Assessing the health risks of coal-burning arsenic-induced skin damage: A 22-year follow-up study in Guizhou, China.

Risk assessment of arsenic-induced skin damage has always received significant global attention. Theories derived from arsenic exposure in drinking water may not be applicable to the coal-burning type to arsenic-exposed area. Furthermore, very few studies have successfully determined the reference value of cumulative arsenic (CA) exposure that leads to specific skin lesions. In this study, we conducted a 22-year follow-up investigation to assess the risk of skin lesions and cancer resulting from long-term, multi-channel arsenic exposure from hazard identification, dose-response assessment, exposure assessment, and risk characterization. The results show that the arsenic exposure can significantly increase the prevalence of skin lesions. For each interquartile range increase of hair arsenic (HA) and CA, the risk of skin damage increased by 1.91 and 3.90 times, respectively. The lower confidence limit of the benchmark dose of HA of arsenic-induced various skin lesions ranged from 0.07 to 0.12 µg·g-1, and 932.57 to 1368.92 mg for CA. The chronic daily intake, lifetime average daily dose in the arsenic-exposed area after the comprehensive prevention and control measures have decreased significantly, but remained higher than the daily baseline level of 3.0 µg·kg-1·d-1. Even as recently as 2020, the hazard quotients and hazard index still exceeded 1, measuring 155.33 and 55.20, and the lifetime excess risk of skin cancer (2.80 × 10-3) remains significantly higher than the acceptable level of 10-6. Our study underscores the effectiveness of comprehensive prevention and control measures in managing high arsenic exposure in coal-burning arsenic poisoning areas. However, it is crucial to acknowledge that the risk of both non-carcinogenic and carcinogenic effects on the skin remains substantially higher than the acceptable level. We recommend setting reference limits for monitoring skin damage among individuals exposed to arsenic, with a recommended upper limit of 0.07 µg·g-1 for HA and a maximum acceptable level of 935.57 mg for CA.

Arsenic causing gallbladder cancer disease in Bihar.

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.

Significance of the prime factors regulating arsenic toxicity and associated health risk: a hypothesis-based investigation in a critically exposed population of West Bengal, India.

The suffering from arsenic toxicity is a long-standing concern in Asian countries. The role of the key factors (arsenic intake, age and sex) regulating arsenic toxicity is aimed to evaluate for a severely exposed population from Murshidabad district, West Bengal. Mean arsenic concentrations in drinking water supplied through tube well, Sajaldhara treatment plant and pipeline were observed as 208, 27 and 54 µg/l, respectively. Urinary arsenic concentration had been observed as < 3-42.1, < 3-56.2 and < 3-80 µg/l in children, teenagers and adults, respectively. Mean concentrations of hair and nail arsenic were found to be 0.84 and 2.38 mg/kg; 3.07 and 6.18 mg/kg; and 4.41 and 9.07 mg/kg, respectively, for the studied age-groups. Water arsenic was found to be associated with hair and nail (r = 0.57 and 0.60), higher than urine (r = 0.37). Arsenic deposition in biomarkers appeared to be dependent on age; however, it is independent of sex. Principal component analysis showed a direct relationship between dietary intake of arsenic and chronic biomarkers. Nail was proved as the most fitted biomarker of arsenic toxicity by Dunn's post hoc test. Monte Carlo sensitivity analysis and cluster analysis showed that the most significant factor regulating health risk is 'concentration of arsenic' than 'exposure duration', 'body weight' and 'intake rate'. The contribution of arsenic concentration towards calculated health risk was highest in teenagers (45.5-61.2%), followed by adults (47.8-49%) and children (21-27.6%). Regular and sufficient access to arsenic-safe drinking water is an immediate need for the affected population.

Association and risk of circulating inflammatory markers with hyperglycemia in coal-burning arsenicosis.

BACKGROUND: Several lines of evidence support a significant relationship between exposure to arsenic and diabetes. However, the underlying pathophysiological mechanisms remain incompletely elucidated. OBJECTIVE: This study examined the association and risk of circulating inflammatory mediators with hyperglycemia in coal-induced arsenicosis. METHODS: A cross-sectional study was conducted in the typical coal-burning area in which arsenicosis is endemic in Xingren County, Guizhou, China. A total of 299 arsenicosis subjects and 137 non-arsenic exposed volunteers were recruited for the present study. Participant's hyperglycemia-related parameters, including fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment for both insulin resistance (HOMA-IR) and pancreatic ß-cell function (HOMA-ß), as well as circulating inflammatory biomarkers i.e., Interleukins-1ß (IL-1ß), IL- 2, IL - 6, IL-10, IL- 17, IL-18 and TNF-α), were determined and analyzed after completing questionnaire investigation and physical examination. RESULTS: The results clearly showed that coal-burning arsenic exposure was significantly associated with hyperglycemia-related outcomes. Specifically, arsenicosis subjects from the coal-burning endemic area showed a higher level of FBG (median 5.87 mmol/L vs. 4.65 mmol/L) and increased prevalence of hyperglycemia (26.76% vs.16.79%) than reference subjects from the non-arsenic endemic area. Increased HOMA-IR (median 1.93 vs.1.44) and declined HOMA-ß (median 96.23 vs. 84.91) were also noted in arsenicosis subjects. Moreover, arsenic exposure was significantly associated with the increased risk of hyperglycemia (adjusted OR = 2.32, 95% CI: 1.37,3.93). In addition, a positive association between arsenic exposure and inflammatory response was observed, and the alteration in circulating inflammatory markers were found to be significantly associated with hyperglycemia-related parameters. Meanwhile, there was a positive relationship between elevated circulating IL-1ß, IL-18, IL-6, as well as decreased IL-10 and the increasing risk of arsenic-induced hyperglycemia [adjusted OR = 2.19 (95% CI: 1.26, 3.13);1.13 (95%CI: 1.08, 1.37); 1.19 (95% CI: 1.13, 1.56); 1.15(95% CI: 1.05, 1.36); respectively]. Path analysis further revealed that the mediating effect of IL-1ß and IL-18 on the relationship between arsenic exposure and hyperglycemia was closely associated with pancreatic ß-cell dysfunction, while those of IL-6 and IL-10 on the association between arsenic exposure and hyperglycemia were partially through insulin resistance. CONCLUSIONS: This population-based study indicated that arsenic exposure has a clear disruptive effect on glucose homeostasis, and an elevated inflammatory response was implicated in the risk of arsenic-induced hyperglycemia.

Epigenetic modifications from arsenic exposure: A comprehensive review.

Arsenic is a notorious element with the potential to harm exposed individuals in ways that include cancerous and non-cancerous health complications. Millions of people across the globe (especially in South and Southeast Asian countries including China, Vietnam, India and Bangladesh) are currently being unknowingly exposed to precarious levels of arsenic. Among the diverse effects associated with such arsenic levels of exposure is the propensity to alter the epigenome. Although a large volume of literature exists on arsenic-induced genotoxicity, cytotoxicity, and inter-individual susceptibility due to active research on these subject areas from the last millennial, it is only recently that attention has turned on the ramifications and mechanisms of arsenic-induced epigenetic changes. The present review summarizes the possible mechanisms involved in arsenic induced epigenetic alterations. It focuses on the mechanisms underlying epigenome reprogramming from arsenic exposure that result in improper cell signaling and dysfunction of various epigenetic components. The mechanistic information articulated from the review is used to propose a number of novel therapeutic strategies with a potential for ameliorating the burden of worldwide arsenic poisoning.

Detailed Analysis of Neurological Symptoms and Sensory Disturbances Due to Chronic Arsenic Exposure in Toroku, Japan.

As a result of population growth and the development of tube wells, humans' exposure to arsenic has increased over the past few decades. The natural course of organ damage secondary to arsenic exposure is not yet well understood. In Toroku, Japan, an arsenic mine was intermittently operated from 1920 to 1962, and residents were exposed to high concentrations of arsenic. In this paper, we analyzed 190 consecutive residents for whom detailed records of neurological symptoms and findings were obtained from 1974 to 2005. All participants were interviewed regarding the presence of general, skin, hearing, respiratory, and neurological symptoms. Neurological symptoms were classified into extremity numbness or pain, constipation, dyshidrosis, sensory loss, and muscle atrophy. Superficial and vibratory sensation was also evaluated. More than 80% of participants experienced extremity numbness, and numbness was the most common neurological symptom. Numbness was associated with superficial sensory disturbance, and was correlated with the subsequent development of other neurological symptoms, including autonomic and motor symptoms. No previous studies have investigated the natural course of chronic arsenic intoxication; thus, these data serve as a guide for detecting early symptoms due to arsenic exposure.

Long-term Lung Cancer Risk Associated with Sputum Atypia: A 27-Year Follow-up Study of an Occupational Lung Screening Cohort in Yunnan, China.

BACKGROUND: Sputum cytologic atypia is associated with increased lung cancer risk. However, little is known about the long-term magnitude and temporal trend of this risk. METHODS: An extended follow-up was conducted in a prospective screening cohort among occupational tin miners in Yunnan, China. Sputum samples were collected prospectively at baseline and 7 annual screenings since enrollment. The associations between sputum cytologic results from baseline screening, the first 4 consecutive rounds of sputum screening, and lung cancer risk were analyzed by time-varying covariate Cox regression model. RESULTS: A moderate or worse cytologic result was associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared with negative screening results, the adjusted hazard ratios of baseline-moderate or worse atypia, at least one moderate or worse atypia in the first 4 consecutive screening rounds during the first 10 years of follow-up were 3.11 [95% confidence interval (CI): 2.37-4.07], 3.25 (95% CI: 2.33-4.54) respectively. This association was stronger for persistent atypia (adjusted hazard ratio = 17.55, 95% CI: 8.32-37.03); atypia identified in the recent screening rounds (adjusted HR = 4.14, 95% CI: 2.70-6.35), and those were old in age, had higher level of smoking, occupational radon, and arsenic exposure. In terms of histology, this increased risk was significant for squamous cell carcinoma and small cell lung cancer. CONCLUSIONS: Although decreasing over time, an increased lung cancer risk concerning moderate or worse sputum atypia can continue at least for 10 years. IMPACT: Sputum atypia might be helpful for identifying high-risk individuals for screening, surveillance, or chemoprevention of lung cancer.

High nuclear expression of HIF1α, synergizing with inactivation of LIMD1 and VHL, portray worst prognosis among the bladder cancer patients: association with arsenic prevalence.

PURPOSE: Our study was aimed to understand the importance of LIMD1-VHL-HIF1α pathway in development of bladder carcinoma (BlCa) in association with arsenic prevalence. METHODS: At first, the mRNA expression pattern of the genes of this pathway (LIMD1, VHL and HIF1α) was checked in GEO datasets and in our samples. Next, genetic and epigenetic profiling of LIMD1 and VHL was done in our sample pool, validated in T24 BlCa cell line. The results were next correlated with various clinico-pathological parameters. RESULTS: Differential under-expression of LIMD1 and VHL genes was found in muscle-invasive BlCa (MIBC) in comparison to non-muscle-invasive BlCa (NMIBC). However, HIF1α protein, but mRNA, was found to be overexpressed among the MIBC samples; depicting the probability of HIF1α protein stabilization. Analysis of genetic and epigenetic profiles of LIMD1 and VHL exposed a frequent promoter methylation of LIMD1 gene in MIBC samples. Further, in-depth look into the results unveiled that the high nuclear expression of HIF1α was significantly correlated with genetic alterations of LIMD1, alone or in combination with VHL. Moreover, treating the T24 cells with a de-methylating agent (5-aza-2'-deoxycytidine) re-expressed the methylated LIMD1 and VHL genes, which in turn, reduced the HIF1α protein level significantly. Additionally, patients with high arsenic content (> 112 ng/g, AsH) seemed to have recurrent promoter methylation in LIMD1, as well as co-methylation/alteration of LIMD1 and VHL gene. Lastly, high nuclear expression of HIF1α in association with co-alteration of VHL and LIMD1 showed the worst overall survival (OS) among the patients. CONCLUSION: To conclude, MIBC samples portrayed higher alterations in VHL and LIMD1, thereby, stabilizing HIF1α protein and lowering the OS of patients.

Assessing the risk of coal-burning arsenic-induced liver damage: a population-based study on hair arsenic and cumulative arsenic.

Exposure to arsenic-contaminated air and food caused by the burning of coal in unventilated indoor stoves is a major environmental public health concern in Guizhou Province, China. The liver is one of the main target organs for coal-fired arsenic exposure; however, there is little information about the risk assessment between cumulative arsenic exposure and the prevalence of liver damage. This study first evaluated the chronic daily intake (CDI) for two exposure pathways (inhalation and ingestion) and five environmental media (i.e., indoor and outdoor air, drinking water, rice, corn, and chili peppers) in 1998, 2006, 2014, and 2017. Then, the dose-effect and dose-response relationship between hair arsenic (HA) and cumulative arsenic (CA) levels and liver damage was analyzed. The results clearly show that the CDI in 1998 was 34.9 µg·kg-1·d-1, 22.9 µg·kg-1·d-1 in 2006, 11.7 µg·kg-1·d-1 in 2014, and 6.7 µg·kg-1·d-1 in 2017 in the arsenic exposure area. All of these values were higher than the daily baseline level of 3.0 µg·kg-1·d-1 as recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and the increased HA and CA can increase the risk of coal-fired arsenic-induced liver damage. In addition, we analyzed the possible maximum acceptable CA exposure level for coal-fired arsenic-induced liver damage using the Bayesian benchmark dose. The recommended maximum acceptable CA exposure level for liver damage caused by coal-burning arsenic is 7120 mg. This study provides scientific insight into understanding the dose-response relationship of liver damage caused by coal-burning arsenic exposure and the monitoring and prevention of arsenic poisoning.

Assessment of arsenic exposure in the population of Sabalpur village of Saran District of Bihar with mitigation approach.

Arsenic poisoning through groundwater is the world's greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 µg/L) with 244.20 µg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.

Association of arsenic-induced cardiovascular disease susceptibility with genetic polymorphisms.

Inorganic arsenic (iAs) exposure has been reported to have an impact on cardiovascular diseases (CVD). However, there is not much known about the cardiac tissue injury of CVD patients in relation to iAs exposure and potential role of single nucleotide polymorphisms (SNPs) of genes related to iAs metabolism, oxidative stress, endothelial dysfunction and inflammation which may play important roles in such CVD cases. In this dual center cross-sectional study, based on the exclusion and inclusion criteria, we have recruited 50 patients out of 270, who came from known arsenic-affected and- unaffected areas of mainly Chittagong, Dhaka and Rajshahi divisions of Bangladesh and underwent open-heart surgery at the selected centers during July 2017 to June 2018. We found that the patients from arsenic affected areas contained significantly higher average iAs concentrations in their urine (6.72 ± 0.54 ppb, P = 0.028), nail (529.29 ± 38.76 ppb, P < 0.05) and cardiac tissue (4.83 ± 0.50 ppb, P < 0.05) samples. Patients' age, sex, BMI, hypertension and diabetes status adjusted analysis showed that patients from arsenic-affected areas had significantly higher iAs concentration in cardiac tissue (2.854, 95%CI 1.017-8.012, P = 0.046) reflecting higher cardiac tissue injury among them (1.831, 95%CI 1.032-3.249, P = 0.039), which in turn allowed the analysis to assume that the iAs exposure have played a vital role in patients' disease condition. Adjusted analysis showed significant association between urinary iAs concentration with AA (P = 0.012) and AG (P = 0.034) genotypes and cardiac iAs concentration with AA (P = 0.017) genotype of AS3MT rs10748835. The AG genotype of AS3MT rs10748835 (13.333 95%CI 1.280-138.845, P = 0.013), AA genotype of NOS3 rs3918181 (25.333 95%CI 2.065-310.757, P = 0.002), GG genotype of ICAM1 rs281432 (12.000 95%CI 1.325-108.674, P = 0.010) and AA genotype of SOD2 rs2758331 (13.333 95%CI 1.280-138.845, P = 0.013) were found significantly associated with CVD patients from arsenic-affected areas. Again, adjusted analysis showed significant association of AA genotype of AS3MT rs10748835 with CVD patients from arsenic affected areas. In comparison to the reference genotypes of the selected SNPs, AA of AS3MT 10748835, AG of NOS3 rs3918181 and AC of rs3918188, GG of ICAM1 rs281432, TT of VCAM1 rs3176867, AA of SOD2 rs2758331 and GT of APOE rs405509 significantly increased odds of cardiac tissue injury of CVD patients from arsenic affected areas. The results showed that the selected SNPs played a susceptibility role towards cardiac tissue iAs concentration and injury among CVD patients from iAs affected areas.

Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk.

Reportedly, 300 million people worldwide are affected by the consumption of arsenic contaminated groundwater. India prominently figures amongst them and the state of Bihar has shown an upsurge in cases affected by arsenic poisoning. Escalated arsenic content in blood, leaves 1 in every 100 human being highly vulnerable to being affected by the disease. Uncontrolled intake may lead to skin, kidney, liver, bladder, or lung related cancer but even indirect forms of cancer are showing up on a regular basis with abnormal arsenic levels as the probable cause. But despite the apparent relation, the etiology has not been understood clearly. Blood samples of 2000 confirmed cancer patients were collected from pathology department of our institute. For cross-sectional design, 200 blood samples of subjects free from cancer from arsenic free pockets of Patna urban agglomeration, were collected. Blood arsenic levels in carcinoma patients as compared to sarcomas, lymphomas and leukemia were found to be higher. The geospatial map correlates the blood arsenic with cancer types and the demographic area of Gangetic plains. Most of the cancer patients with high blood arsenic concentration were from the districts near the river Ganges. The raised blood arsenic concentration in the 2000 cancer patients strongly correlates the relationship of arsenic with cancer especially the carcinoma type which is more vulnerable. The average arsenic concentration in blood of the cancer patients in the Gangetic plains denotes the significant role of arsenic which is present in endemic proportions. Thus, the study significantly correlates and advocates a strong relation of the deleterious element with the disease. It also underlines the need to address the problem by deciphering the root cause of the elevated cancer incidences in the Gangetic basin of Bihar and its association with arsenic poisoning.

Progress in the prevention and control of water-borne arsenicosis in China.

In this report, we provided an overview of the prevalence, control, and prevention of water-borne arsenicosis in China during 2001-2016. Random sampling was continuously performed during 2001-2010 to find villages having high levels of arsenic (>50 µg/L) in drinking water. The high-arsenic-exposure villages with more geographically dispersed water supplies were subsequently analyzed for characteristics of arsenic distribution, and villages with relatively large populations were investigated for arsenicosis. The results showed that among 32,673,677 inhabitants in 36,820 villages, 1,894,587 inhabitants in 2,476 villages were at risk of high arsenic exposure. Among the 33,318 drinking water sources surveyed in 625 high-arsenic-exposure villages, 9,807 drinking water sources that contained high levels of arsenic (>50 µg/L) were identified. The overall prevalence rate of arsenicosis was 1.93%. Further, some representative villages were chosen to monitor arsenicosis annually, showing that the prevalence rate of arsenicosis was lower in villages with arsenic-safe water supplies than in villages without arsenic-safe water supplies. To the best of our knowledge, this report provides the most comprehensive assessment of the distribution of high arsenic exposure and arsenicosis in China until now.

Association of arsenic exposure and cognitive impairment: A population-based cross-sectional study in China.

BACKGROUND: The influence of chronic arsenic exposure on cognitive impairment has been explored broadly by previous studies. However, most of them focused mainly on children rather than adults. In addition, in China, studies in this field are not sufficient. To illustrate how long-term arsenic exposure affects cognitive function, we designed a cross-sectional study involving 1556 adults. METHODS: All of them came from three locations around the Realgar Plant. The cognitive function of the participants was evaluated using a Chinese version of the Mini-mental state Examination (MMSE). The participants' internal arsenic exposure status (hair arsenic concentrations) and the external arsenic exposure status (the distance between the participants' location of residence and the Realgar Plant) were measured. RESULTS: Our research revealed that both of hair arsenic concentrations and the prevalence of arsenicosis, two important indexes, were significantly higher in the cognitive-impaired (CI) group than in the cognitive-normal (CN) group (P < 0.05). In addition, distance from the Realgar Plant was positively correlated with the MMSE scores and was negatively correlated with the prevalence of cognitive impairment. Moreover, our results demonstrated that there was a negative correlation between hair arsenic concentrations and MMSE scores. We conducted a two-level Logistic regression analysis and further confirmed that even after adjusting for potential confounding variables, arsenicosis retained a risk factor for cognitive impairment (odds ratio (OR) = 1.84, P < 0.05). CONCLUSIONS: Our results indicated that chronic arsenic exposure could impair adults' cognitive function in a dose-dependent manner. Additionally, arsenicosis could be an independent risk factor for cognitive impairment.

Arsenic metabolism differs between child and adult patients during acute arsenic poisoning.

Epidemiological studies on chronic arsenic poisoning have clarified the relationship between various adverse effects and methylation efficiency or methylation capacity. However, no study has similarly investigated such effects on patients with acute arsenic poisoning. In the present work, we studied 61 patients with acute oral arsenic poisoning occurring after consumption of an arsenic trioxide-laced meal (curry soup). The cohort included children (defined as under 15 year old [y/o], n = 22) and adults (over 16 y/o, n = 39) whose urinary arsenic profiles were analyzed. None of these patients had received treatment with chelating agents. The estimated median (IQR) arsenic intake was 64.5 mg (48.3-80.5 mg) in children and 76.0 mg (56.0-91.0 mg) in adults, and these values were not significantly different. Symptoms of poisoning in children improved approximately 1 week after hospitalization. However, the symptoms in most adults deteriorated with severe signs of arsenic poisoning. Urinary arsenic profiles of all the patients were analyzed to obtain the following information: % monomethylarsonic acid (MMA), % dimethylarsinic acid (DMA), second methylation ratio (DMA/MMA), and secondary methylation index (SMI, DMA/MMA + DMA). The levels of these parameters may help identify patients at risk for worsening symptoms. %MMA, an indicator of incomplete methylation, increased more in adults, who experienced more severe symptom progression, compared with children. In contrast, %DMA, which indicates more complete and efficient methylation, increased particularly in children with mild symptoms. Overall the present results indicate that children possess an excellent capacity for methylation (second methylation ratio) of arsenic to DMA and therefore, experience relatively less severe progression of symptomology during acute arsenic poisoning.

Association of arsenic with recurrence of urinary bladder cancer.

Arsenic is known to be an important aetiological factor for the development of urinary bladder cancer. It is known to be found excessively in ground water in certain geographical areas, including West Bengal. We have studied patients with recurrent bladder cancer from different areas of this Indian state and correlated arsenic as a causative aetiological factor for development and aggressiveness of the biological behaviour of urinary cancer. We included 31 patients from various parts of West Bengal state with recurrent bladder cancer who were operated in our institute. Their clinical and residential data and their arsenic content of tumour tissue were measured. Statistical analysis was performed to test the association of tissue arsenic with clinicopathological features of recurrent disease. We found very high levels of arsenic in tumour tissue in all residents of the districts with high prevalence of arsenic in the drinking water. We also observed more aggressive clinicopathological progression and early recurrence in patients with high arsenic content. We conclude that arsenic is a causal factor in the clinicopathological progression of recurrent urinary bladder cancer. Measures to decrease the level of arsenic in drinking water should be taken as this may both improve clinicopathological outcomes in the recurrence of urinary bladder carcinoma, as well as reducing its overall incidence.

Global impact of atmospheric arsenic on health risk: 2005 to 2015.

Arsenic is a toxic pollutant commonly found in the environment. Most of the previous studies on arsenic pollution have primarily focused on arsenic contamination in groundwater. In this study, we examine the impact on human health from atmospheric arsenic on the global scale. We first develop an improved global atmospheric arsenic emission inventory and connect it to a global model (Goddard Earth Observing System [GEOS]-Chem). Model evaluation using observational data from a variety of sources shows the model successfully reproduces the spatial distribution of atmospheric arsenic around the world. We found that for 2005, the highest airborne arsenic concentrations were found over Chile and eastern China, with mean values of 8.34 and 5.63 ng/m3, respectively. By 2015, the average atmospheric arsenic concentration in India (4.57 ng/m3) surpassed that in eastern China (4.38 ng/m3) due to the fast increase in coal burning in India. Our calculation shows that China has the largest population affected by cancer risk due to atmospheric arsenic inhalation in 2005, which is again surpassed by India in 2015. Based on potential exceedance of health-based limits, we find that the combined effect by including both atmospheric and groundwater arsenic may significantly enhance the risks, due to carcinogenic and noncarcinogenic effects. Therefore, this study clearly implies the necessity in accounting for both atmospheric and groundwater arsenic in future management.

Human arsenic exposure and lung function impairment in coal-burning areas in Guizhou, China.

To evaluate the effect of coal-burning arsenic (As) exposure on lung function and the potential underlying mechanisms, a total of 217 As-exposed subjects and 75 reference subjects were recruited into this study. Hair arsenic (H-As), pulmonary function tests, and serum inflammatory markers CC16, SP-A, MMP-9, and TIMP-1 were evaluated. Residents from As-exposed areas showed higher H-As concentrations (median 0.25 µg/g) than subjects from the reference area (median 0.14 µg/g). Large reductions in lung function parameters were noted in the As-exposed group. A significant negative correlation was observed between H-As concentrations and lung function. Specifically, monotonic negative dose-response relationships were observed between H-As and FEV1(%), FEV1/FVC (%) and FEF75 (%) (all P < 0.05), while the associations between H-As and FVC (%), FEF25 (%), and FEF50 (%) were nonlinear (P for nonlinearity = 0.03, 0.001, 0.01, respectively). In addition, there was a direct positive relationship between H-As and the inflammatory response. Alterations in inflammatory biomarkers (CC16, SP-A, MMP-9, and MMP-9/TIMP-1) were significantly associated with As-induced lung function impairment. Thus, this population-based study revealed that As exposure has significant toxic effects on lung function and increased inflammation may occur during this toxic process. We provide scientific evidence for an As-induced alteration in inflammatory biomarkers and pulmonary damage in an As-exposed population. The results of this study can inform risk assessment and risk control processes in relation to human As exposure in coal-burning arsenicosis areas.

Association between chronic arsenic exposure and the characteristic features of asthma.

Widespread contamination of arsenic (As) has become a global public health concern. Exposure to As causes respiratory complications. Asthma, a major respiratory complication, is increasing worldwide. However, the effect of chronic As exposure on the risk of asthma remains to be clarified. This study aims to examine the associations between As exposure (water, hair and nail As) and the risk of asthma among 842 individuals exposed to a wide range of As concentrations through drinking water in Bangladesh. Subjects' As exposure levels were measured with ICP-MS. Lung function was examined by a handheld spirometer. Characteristic features of asthma were evaluated by bronchodilator-mediated reversibility in airway obstruction and asthma-like symptoms through a structured questionnaire. Total serum immunoglobulin E (sIgE) levels were measured by immunoassay. As exposure metrics showed inverse associations with lung function measures (FEV1, FEV6, and FEV1/FEV6 ratio) and positive associations with the risks of airway obstruction (AO), reversible airway obstruction (RAO), and asthma-like symptoms. The majority of AO patients (70 of 97) were RAO with one or more characteristic symptoms of asthma. Intriguingly, subjects' As exposure levels showed positive associations with total sIgE levels. Total sIgE in RAO patients was significantly (p < 0.001) higher than that in the control group. Thus the results revealed that chronic As exposure was associated with the risk of the characteristic features of asthma. Additionally the association between As exposure and subjects' total sIgE levels and an elevated level of total sIgE in RAO group suggested that As exposure-related asthma might be allergic in nature.