Category Archives: Health Effects

Susceptibility differs to the toxic effects of arsenic

Brenda C. Minatel1, Adam P. Sage1, Christine Anderson, Roland Hubaux, Erin A. Marshall, Wan L. Lam, Victor D. Martinez. Environmental arsenic exposure: From genetic susceptibility to pathogenesis. Environment International Volume 112, March 2018, Pages 183–197

More than 200 million people in 70 countries are exposed to arsenic through drinking water. Chronic exposure to this metalloid has been associated with the onset of many diseases, including cancer. Epidemiological evidence supports its carcinogenic potential, however, detailed molecular mechanisms remain to be elucidated. Despite the global magnitude of this problem, not all individuals face the same risk. Susceptibility to the toxic effects of arsenic is influenced by alterations in genes involved in arsenic metabolism, as well as biological factors, such as age, gender and nutrition. Moreover, chronic arsenic exposure results in several genotoxic and epigenetic alterations tightly associated with the arsenic biotransformation process, resulting in an increased cancer risk. In this review, we: 1) review the roles of inter-individual DNA-level variations influencing the susceptibility to arsenic-induced carcinogenesis; 2) discuss the contribution of arsenic biotransformation to cancer initiation; 3) provide insights into emerging research areas and the challenges in the field; and 4) compile a resource of publicly available arsenic-related DNA-level variations, transcriptome and methylation data. Understanding the molecular mechanisms of arsenic exposure and its subsequent health effects will support efforts to reduce the worldwide health burden and encourage the development of strategies for managing arsenic-related diseases in the era of personalized medicine.

Total THM long-term exposure not related to female breast cancer, Spain

Font-Ribera L, Gràcia-Lavedan E, Aragonés N, Pérez-Gómez B, Pollán M, Amiano P, Jiménez-Zabala A, Castaño-Vinyals G, Roca-Barceló A, Ardanaz E, Burgui R, Molina AJ, Fernández-Villa T, Gómez-Acebo I, Dierssen-Sotos T, Moreno V, Fernandez-Tardon G, Peiró R, Kogevinas M, Villanueva CM. Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN). Environment international. 2017 Dec 28;112:227-234. doi: 10.1016/j.envint.2017.12.031.

BACKGROUND: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited.

OBJECTIVES: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk.

METHODS: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85 years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated.

RESULTS: Mean adult-lifetime residential levels ranged from 0.8 to 145.7μg/L for TTHM (median=30.8), from 0.2 to 62.4μg/L for chloroform (median=19.7) and from 0.3 to 126.0μg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24μg/L) vs. lowest (<8μg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31μg/L vs. <6μg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48μg/L vs. <22μg/L).

CONCLUSIONS: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

Fluoride Exposure and Cognitive Functions, Chinese Children

Choi AL, Zhang Y, Sun G, Bellinger DC, Wang K, Yang XJ, Li JS, Zheng Q, Fu Y, Grandjean P. Association of lifetime exposure to fluoride and cognitive functions in Chinese children: a pilot study. Neurotoxicol Teratol. 2015 Jan-Feb;47:96-101. doi: 10.1016/ Erratum in Neurotoxicol Teratol. 2015 Sep-Oct;51():89.

BACKGROUND: A systematic review and meta-analysis of published studies on developmental fluoride neurotoxicity support the hypothesis that exposure to elevated concentrations of fluoride in water is neurotoxic during development.

METHODS: We carried out a pilot study of 51 first-grade children in southern Sichuan, China, using the fluoride concentration in morning urine after an exposure-free night; fluoride in well-water source; and dental fluorosis status as indices of past fluoride exposure. We administered a battery of age-appropriate, relatively culture-independent tests that reflect different functional domains: the Wide Range Assessment of Memory and Learning (WRAML), Wechsler Intelligence Scale for Children-Revised (WISC-IV) digit span and block design; finger tapping and grooved pegboard. Confounder-adjusted associations between exposure indicators and test scores were assessed using multiple regression models.

RESULTS: Dental fluorosis score was the exposure indicator that had the strongest association with the outcome deficits, and the WISC-IV digit span subtest appeared to be the most sensitive outcome, where moderate and severe fluorosis was associated with a digit span total score difference of -4.28 (95% CI -8.22, -0.33) and backward score with -2.13 (95% CI -4.24, -0.02).

CONCLUSIONS: This pilot study in a community with stable lifetime fluoride exposures supports the notion that fluoride in drinking water may produce developmental neurotoxicity, and that the dose-dependence underlying this relationship needs to be characterized in detail.

High Drinking Water Fluoride Associated with Reduced Children Intelligence Levels

Duan Q, Jiao J, Chen X, Wang X. Association between water fluoride and the level of children’s intelligence: a dose-response meta-analysis. Public Health. 2017 Dec 4;154:87-97. doi: 10.1016/j.puhe.2017.08.013.

OBJECTIVES: Higher fluoride concentrations in water have inconsistently been associated with the levels of intelligence in children. The following study summarizes the available evidence regarding the strength of association between fluoridated water and children’s intelligence.

STUDY DESIGN: Meta-analysis.

METHODS: PubMed, Embase, and Cochrane Library databases were systematically analyzed from November 2016. Observational studies that have reported on intelligence levels in relation to high and low water fluoride contents, with 95% confidence intervals (CIs) were included. Further, the results were pooled using inverse variance methods. The correlation between water fluoride concentration and intelligence level was assessed by a dose-response meta-analysis.

RESULTS: Twenty-six studies reporting data on 7258 children were included. The summary results indicated that high water fluoride exposure was associated with lower intelligence levels (standardized mean difference : -0.52; 95% CI: -0.62 to -0.42; P < 0.001). The findings from subgroup analyses were consistent with those from overall analysis. The dose-response meta-analysis suggested a significant association between water fluoride dosage and intelligence (P < 0.001), while increased water fluoride exposure was associated with reduced intelligence levels.

CONCLUSIONS: Greater exposure to high levels of fluoride in water was significantly associated with reduced levels of intelligence in children. Therefore, water quality and exposure to fluoride in water should be controlled in areas with high fluoride levels in water.

Pulmonary Fluorsis

Ameeramja J, Perumal E. Pulmonary fluorosis: a review. Environmental science and pollution research international. 2017 Oct;24(28):22119-22132. doi: 10.1007/s11356-017-9951-z.

The increased industrialization and improvised human lifestyle lead to a surge in environmental pollution nowadays. Even the chemicals which are known as prophylactic agents were currently liable to be toxic. One among them is inorganic fluoride whose wider application in numerous processes makes it as an inevitable environmental contaminant and industrial pollutant. Although the systemic toxicity of fluoride has been extensively studied, still there is lacuna in the field of pulmonary fluoride toxicity. Hence, we have focused on the molecular mechanism of action of fluoride compounds on pulmonary system. A study of literatures that focused on the potential physiological and toxicological consequences of fluoride on pulmonary system was carried out. The goal of this review is to present an overview of the research carried out till date on the molecular aspects of fluoride exposure with emphasis on pulmonary system and their possible mechanisms.

Evidence lacking for low-exposure adverse effects of arsenic

Hong YS, Ye BJ, Kim YM, Kim BG, Kang GH, Kim JJ, Song KH, Kim YH, Seo JW. Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water. International journal of environmental research and public health. 2017 Nov 27;14(12). pii: E1461. doi: 10.3390/ijerph14121461.

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents.

Another Ecologic Study on Arsenic and Bladder Cancer of Limited Utility

Ecologic studies such as this are not very informative because of limited exposure assessments. But they can certainly generate alarm. Even so, small associations such as this are questionable regardless of precise mathematical computations. Note the absence of confidence intervals on the estimates which sends a strong message to ignore the study altogether.

Saint-Jacques N, Brown P, Nauta L, Boxall J, Parker L, Dummer TJB. Estimating the risk of bladder and kidney cancer from exposure to low-levels of arsenic in drinking water, Nova Scotia, Canada. Environment international. 2017 Oct 28. pii: S0160-4120(17)31385-5. doi: 10.1016/j.envint.2017.10.014.

Arsenic in drinking water impacts health. Highest levels of arsenic have been historically observed in Taiwan and Bangladesh but the contaminant has been affecting the health of people globally. Strong associations have been confirmed between exposure to high-levels of arsenic in drinking water and a wide range of diseases, including cancer. However, at lower levels of exposure, especially near the current World Health Organization regulatory limit (10μg/L), this association is inconsistent as the effects are mostly extrapolated from high exposure studies. This ecological study used Bayesian inference to model the relative risk of bladder and kidney cancer at these lower concentrations-0-2μg/L; 2-5μg/L and; ≥5μg/L of arsenic-in 864 bladder and 525 kidney cancers diagnosed in the study area, Nova Scotia, Canada between 1998 and 2010. The model included proxy measures of lifestyle (e.g. smoking) and accounted for spatial dependencies. Overall, bladder cancer risk was 16% (2-5μg/L) and 18% (≥5μg/L) greater than that of the referent group (<2μg/L), with posterior probabilities of 88% and 93% for these risks being above 1. Effect sizes for kidney cancer were 5% (2-5μg/L) and 14% (≥5μg/L) above that of the referent group (<2μg/L), with probabilities of 61% and 84%. High-risk areas were common in southwestern areas, where higher arsenic-levels are associated with the local geology. The study suggests an increased bladder cancer, and potentially kidney cancer, risk from exposure to drinking water arsenic-levels within the current the World Health Organization maximum acceptable concentration.