Tag Archives: health effects

Fluoride Effects IQ of 12-14 Year-Old Children, India

Razdan P, Patthi B, Kumar JK, Agnihotri N, Chaudhari P, Prasad M. Effect of Fluoride Concentration in Drinking Water on Intelligence Quotient of 12-14-Year-Old Children in Mathura District: A Cross-Sectional Study. Journal of International Society of Preventive and Community Dentistry. 2017 Sep-Oct;7(5):252-258. doi: 10.4103/jispcd.JISPCD_201_17.

AIMS: The aim was to assess and correlate the influence of the concentration of fluoride in ingested water on the intelligence quotient (IQ) of 12-14-year-old youngsters in Mathura district.

MATERIALS AND METHODS: A total of 219 children were selected, 75 from low F area, 75 medium F area, and 69 from high F area. The concentration of fluoride in the routinely ingested water was estimated using “Ion Selective Electrode method”; then, Raven’s Test was utilized to estimate the IQ of the study participants. Independent t-test, Tukey’s post hoc, Chi-square an analysis of variance tests were used to associate the mean and proportion IQ scores in high-, medium-, and low-fluoride regions along with inter-group significant differences (P ≤ 0.05).

RESULTS: The comparison of IQ score showed that 35 (46.7%) participants from the high fluoride and 10 (13.3%) participants from the medium-fluoride areas had below average IQ. Further, it was noted that the lowest mean marks were obtained by the children in the high-fluoride region (13.9467) followed by those in medium (18.9467) and uppermost in least noted fluoride area (38.6087). However, gender-based intergroup comparison did not produce a significant relation with fluoride (P ≥ 0.05).

CONCLUSION: Concentration of Fluoride in the ingested water was significantly associated with the IQ of children. It has also coined the proportional variability in mental output in accordance to the ingested fluoride level. As two sides of a coin, fluoride cannot be utterly blamed for a lower intelligence in a population; it puts forward a fact that intelligence is a multifactorial variable with a strategic role played by genetics and nutrition to develop cognitive and psychosomatic activities in an individual.

Prenatal Fluoride Exposure Associated with Lower Cognitive Function, Mexico

Bashash M, Thomas D, Hu H, Angeles Martinez-Mier E, Sanchez BN, Basu N, Peterson KE, Ettinger AS, Wright R, Zhang Z, Liu Y, Schnaas L, Mercado-García A, María Téllez-Rojo M, Hernández-Avila M. Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6-12 Years of Age in Mexico. Environmental health perspectives. 2017 Sep 19;125(9):097017. doi: 10.1289/EHP655.

BACKGROUND: Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants.

OBJECTIVE: Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development.

METHODS: We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6-12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children’s Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6-12.

RESULTS: We had complete data on 299 mother-child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299) and children with available urine samples (n=211) were 0.90 (0.35) mg/L and 0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: -5.42, -0.87) and 2.50 (95% CI -4.12, -0.59) lower offspring GCI and IQ scores, respectively.

CONCLUSIONS: In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6-12 y. https://doi.org/10.1289/EHP655.

Fluoride and Human Lung Cell Toxicity

Ying J, Xu J, Shen L, Mao Z, Liang J, Lin S, Yu X, Pan R, Yan C, Li S, Bao Q, Li P. The Effect of Sodium Fluoride on Cell Apoptosis and the Mechanism of Human Lung BEAS-2B Cells In Vitro. Biological trace element research. 2017 Jan 22. doi: 10.1007/s12011-017-0937-y.

Sodium fluoride (NaF) is a source of fluoride ions used in many applications. Previous studies found that NaF suppressed the proliferation of osteoblast MC3T3 E1 cells and induced the apoptosis of chondrocytes. However, little is known about the effects of NaF on human lung BEAS-2B cells. Therefore, we investigated the mode of cell death induced by NaF and its underlying molecular mechanisms. BEAS-2B cells were treated with NaF at concentrations of 0, 0.25, 0.5, 1.0, 2.0, and 4.0 mmol/L. Cell viability decreased and apoptotic cells significantly increased as concentrations of NaF increased over specific periods of time. The IC50 of NaF was 1.9 and 0.9 mM after 24 and 48 h, respectively. The rates of apoptosis increased from 4.8 to 37.7% after NaF exposure. HE staining, electron microscopy, and single cell gel electrophoresis revealed that morphological changes of apoptosis increased with exposure concentrations. RT-PCR and Western blotting were used to detect the apoptotic pathways. The expressions of bax, caspase-3, caspase-9, p53, and the cytoplasmic CytC of the NaF groups increased, while bcl-2 and mitochondrial CytC decreased compared with that of the control group (P < 0.05). Further, the fluorescence intensities of ROS in the NaF groups were higher than those in the control group, and the membrane potential of mitochondria in the NaF group was significantly lower than that of the control group (P < 0.05). These findings suggested that NaF induced apoptosis in the BEAS-2B cells through mitochondria-mediated signal pathways. Our study provides the theoretical foundation and experimental basis for exploring the mechanisms of human lung epithelial cell damage and cytotoxicity induced by fluorine.

No Clear Association Between Manganese Exposure and Cognitive Development in Sample of School-Age Children

Bouchard MF, Surette C, Cormier P, Foucher D. Low level exposure to manganese from drinking water and cognition in school-age children. Neurotoxicology. 2017 Jul 15. pii: S0161-813X(17)30154-7. doi: 10.1016/j.neuro.2017.07.024.

BACKGROUND: Manganese (Mn) is an element found in the environment and certain geographic areas have elevated concentrations in soil and water du to natural conditions or anthropic activities. A growing body of data suggests that exposure to manganese in drinking water could be neurotoxic.

OBJECTIVE: Firstly, we aimed to examine the association between exposure to manganese from drinking water and cognition in children consuming well water. Secondly, we also aimed to examine the relation between cognition and manganese concentrations in children’s hair, nail, and saliva.

METHODS: A total 259 children from 189 households consuming well water were included in the present study (ages 5.9 to 13.7 years). We assessed children’s cognition with the WISC-IV, and we used five indicators of manganese exposure: concentration in tap water, intake from the consumption of water divided by child’s weight, manganese concentration in children’s hair, toe nail, and saliva. We used General Estimating Equation analysis to assess the relation between manganese exposure indicators and IQ scores, adjusting for potential confounders, and taking into account family clusters.

RESULTS: Drinking water manganese concentrations were generally low, with 48% of children consuming water <5>g/L, 25% >50>g/L, and 4% >400>g/L. Results differed by sex. In girls, higher manganese concentration in water, hair, and toe nail were associated with poorer Performance IQ scores but this was significant only for toe nail (for a 10-fold increase in manganese, β: -5.65, 95% CIs: -10.97, -0.32). Opposite associations were observed in boys, i.e., better Performance IQ scores with higher manganese concentration hair, toe nail, and water, the latter being significant (β: 2.66, 95% CIs: 0.44, 4.89). Verbal IQ scores did not seem to be associated with manganese exposure indicators.

CONCLUSIONS: Drinking water manganese levels were considerably lower than in previous studies reporting neurotoxic effects. There was no clear indication of an association between exposure to manganese and cognitive development in this sample of school-age children although the data suggest there might be sex-specific associations. Given the low levels of exposure and sex-specific associations, a larger sample size would have been required to increase the statistical power and better characterize the relations.

Pulmonary Fluorosis

Ameeramja J, Perumal E. Pulmonary fluorosis: a review. Environmental science and pollution research international. 2017 Aug 25. 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.

Taiwan Arsenic Study of Limited Value

The confidence intervals on the data analysis presented here are very wide. A lower confidence interval of 1 indicates no effect. Studies such as this showing no association or a weak association are of very limited usefulness.

Hsu LI, Hsieh FI, Wang YH, Lai TS, Wu MM, Chen CJ, Chiou HY, Hsu KH. Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study. Am J Kidney Dis. 2017 Aug 23. pii: S0272-6386(17)30800-4. doi: 10.1053/j.ajkd.2017.06.012.

BACKGROUND: Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified.

STUDY DESIGN: The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study.

SETTING & PARTICIPANTS: 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively.

PREDICTOR: Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration.

OUTCOMES: Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan’s National Health Insurance database 1998 to2011.

MEASUREMENTS: HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression.

RESULTS: We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 104 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria.

LIMITATIONS: Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured.

CONCLUSIONS: This study describes the temporal relationship between arsenic concentrations ≥ 10μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria.

Allowable Concentrations of Aluminum in Drinking Water

Willhite CC, Ball GL, McLellan CJ. Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water. Critical reviews in toxicology. 2012 May;42(5):358-442. doi: 10.3109/10408444.2012.674101.

Maximum contaminant levels are used to control potential health hazards posed by chemicals in drinking water, but no primary national or international limits for aluminum (Al) have been adopted. Given the differences in toxicological profiles, the present evaluation derives total allowable concentrations for certain water-soluble inorganic Al compounds (including chloride, hydroxide, oxide, phosphate and sulfate) and for the hydrated Al silicates (including attapulgite, bentonite/montmorillonite, illite, kaolinite) in drinking water. The chemistry, toxicology and clinical experience with Al materials are extensive and depend upon the particular physical and chemical form. In general, the water solubility of the monomeric Al materials depends on pH and their water solubility and gastrointestinal bioavailability are much greater than that of the hydrated Al silicates. Other than Al-containing antacids and buffered aspirin, food is the primary source of Al exposure for most healthy people. Systemic uptake of Al after ingestion of the monomeric salts is somewhat greater from drinking water (0.28%) than from food (0.1%). Once absorbed, Al accumulates in bone, brain, liver and kidney, with bone as the major site for Al deposition in humans. Oral Al hydroxide is used routinely to bind phosphate salts in the gut to control hyperphosphatemia in people with compromised renal function. Signs of chronic Al toxicity in the musculoskeletal system include a vitamin D-resistant osteomalacia (deranged membranous bone formation characterized by accumulation of the osteoid matrix and reduced mineralization, reduced numbers of osteoblasts and osteoclasts, decreased lamellar and osteoid bands with elevated Al concentrations) presenting as bone pain and proximal myopathy. Aluminum-induced bone disease can progress to stress fractures of the ribs, femur, vertebrae, humerus and metatarsals. Serum Al ≥100 µg/L has a 75-88% positive predictive value for Al bone disease. Chronic Al toxicity is also manifest in the hematopoietic system as an erythropoietin-resistant microcytic hypochromic anemia. Signs of Al toxicity in the central nervous system (speech difficulty to total mutism to facial grimacing to multifacial seizures and dyspraxia) are related to Al accumulation in the brain and these symptoms can progress to frank encephalopathy. There are four groups of people at elevated risk of systemic Al intoxication after repeated ingestion of monomeric Al salts: the preterm infant, the infant with congenital uremia and children and adults with kidney disease. There is a dose-dependent increase in serum and urinary Al in people with compromised renal function, and restoration of renal function permits normal handling of systemically absorbed Al and resolution of Al bone disease. Clinical experience with 960 mg/day of Al(OH)(3) (~5 mg Al/kg-day) given by mouth over 3 months to men and women with compromised renal function found subclinical reductions in hemoglobin, hematocrit and serum ferritin. Following adult males and females with reduced kidney function found that ingestion of Al(OH)(3) at 2.85 g/day (~40 mg/kg-day Al) over 7 years increased bone Al, but failed to elicit significant bone toxicity. There was one report of DNA damage in cultured lymphocytes after high AlCl(3) exposure, but there is no evidence that ingestion of common inorganic Al compounds presents an increased carcinogenic risk or increases the risk for adverse reproductive or developmental outcomes. A number of studies of Al exposure in relation to memory in rodents have been published, but the results are inconsistent. At present, there is no evidence to substantiate the hypothesis that the pathogenesis of Alzheimer’s Disease is caused by Al found in food and drinking water at the levels consumed by people living in North America and Western Europe. Attapulgite (palygorskite) has been used for decades at oral doses (recommended not to exceed two consecutive days) of 2,100 mg/day in children of 3-6 years, 4,200 mg/day in children of 6-12 years, and 9,000 mg/day in adults. Chronic ingestion of insoluble hydrated Al silicates (in kg) can result in disturbances in iron and potassium status, primarily as a result of clay binding to intestinal contents and enhanced fecal iron and zinc elimination. Sufficiently high doses of ingested Al silicates (≥50 g/day) over prolonged periods of time can elicit a deficiency anemia that can be corrected with oral Fe supplements. There is essentially no systemic Al uptake after ingestion of the hydrated Al silicates. Rats fed up to 20,000 ppm Ca montmorillonite (equivalent to 1,860 ppm total Al as the hydrated Al silicate) for 28 weeks failed to develop any adverse signs. The results of dietary Phase I and II clinical trials conducted in healthy adult volunteers over 14 days and 90 days with montmorillonite found no adverse effects after feeding up to 40 mg/kg-day as Al. Since the Al associated with ingestion of hydrated Al silicates is not absorbed into the systemic circulation, the hydrated Al silicates seldom cause medical problems unless the daily doses consumed are substantially greater than those used clinically or as dietary supplements. A no-observable-adverse-effect-level (NOAEL) of 13 mg/kg-day as total Al can be identified based on histologic osteomalacia seen in adult hemodialysis patients given Al hydroxide for up to 7 years as a phosphate binder. Following U.S. EPA methods for calculation of an oral reference dose (RfD), an intraspecies uncertainty factor of 10x was applied to that value results in a chronic oral reference dose (RfD) of 1.3 mg Al/kg-day; assuming a 70-kg adult consumes 2 L of drinking water per day and adjusting for a default 20% relative source contribution that value corresponds to a drinking water maximum concentration of 9 mg/L measured as total Al. A chronic NOAEL for montmorillonite as representative of the hydrated Al silicates was identified from the highest dietary concentration (20,000 ppm) fed in a 28-week bioassay with male and female Sprague-Dawley rats. Since young rats consume standard laboratory chow at ~23 g/day, this concentration corresponds to 56 mg Al/kg-day. Application of 3x interspecies uncertainty factor and a 3x factor to account for study duration results in a chronic oral RfD of 6 mg Al/kg-day. Of note, this RfD is 5-10 fold less than oral doses of Al silicates consumed by people who practice clay geophagy and it corresponds to a maximum drinking water concentration of 40 mg Al/L. To utilize the values derived here, the risk manager must recognize the particular product (e.g., alum) or source (e.g., groundwater, river water, clay or cement pipe) of the Al found in tap water, apply the appropriate analytical methods (atomic absorption, energy dispersive X-ray diffraction, infrared spectral analysis and/or scanning transmission electron microscopy) and compare the results to the most relevant standard. The drinking water concentrations derived here are greater than the U.S. EPA secondary maximum contaminant level (MCL) for total Al of 0.05-0.2 mg/L [40 CFR 143.3]. As such, domestic use of water with these concentrations is likely self-limiting given that its cloudy appearance will be greater than the maximum permitted (0.5-5.0 nephalometric turbidity units; 40 CFR Parts 141 and 142). Therefore, the organoleptic properties of Al materials in water determine public acceptance of potable water as contrast to any potential health hazard at the concentrations ordinarily present in municipal drinking water.