subject 어린이들의 뇌 발달에 불소노출이 미치는 영향:하바드대 논문 2012년
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date 18-12-11 09:38
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2012 Oct;120(10):1362-8. doi: 10.1289/ehp.1104912. Epub 2012 Jul 20.

Developmental fluoride neurotoxicity: a systematic review and meta-analysis.

불소의 신경독성 발현

Abstract

BACKGROUND:

Although fluoride may cause neurotoxicity in animal models and acute fluoride poisoning causes neurotoxicity in adults, very little is known of its effects on children's neurodevelopment.

OBJECTIVE:

We performed a systematic review and meta-analysis of published studies to investigate the effects of increased fluoride exposure and delayed neurobehavioral development.

METHODS:

We searched the MEDLINE, EMBASE, Water Resources Abstracts, and TOXNET databases through 2011 for eligible studies. We also searched the China National Knowledge Infrastructure (CNKI) database, because many studies on fluoride neurotoxicity have been published in Chinese journals only. In total, we identified 27 eligible epidemiological studies with high and reference exposures, end points of IQ scores, or related cognitive function measures with means and variances for the two exposure groups. Using random-effects models, we estimated the standardized mean difference between exposed and reference groups across all studies. We conducted sensitivity analyses restricted to studies using the same outcome assessment and having drinking-water fluoride as the only exposure. We performed the Cochran test for heterogeneity between studies, Begg's funnel plot, and Egger test to assess publication bias, and conducted meta-regressions to explore sources of variation in mean differences among the studies.

RESULTS:

The standardized weighted mean difference in IQ score between exposed and reference populations was -0.45 (95% confidence interval: -0.56, -0.35) using a random-effects model. Thus, children in high-fluoride areas had significantly lower IQ scores than those who lived in low-fluoride areas. Subgroup and sensitivity analyses also indicated inverse associations, although the substantial heterogeneity did not appear to decrease.

CONCLUSIONS:

The results support the possibility of an adverse effect of high fluoride exposure on children's neurodevelopment. Future research should include detailed individual-level information on prenatal exposure, neurobehavioral performance, and covariates for adjustment.

연구결과는 어린이들의 불소노출이 뇌발달에 부작용을 초래할 수 있음을 뒷받침한다. 

 

 

Studies Finding Association Between Fluoride & Reduced IQ:

기타 불소와 IQ에 관련된 연구들

 

IQ Study #53: (Yu-2018)
Citation:Yu X, Chen J, Li Y, Liu H, et al. (2018). Threshold effects of moderately excessive fluoride exposure on children’s health: A potential association between dental fluorosis and loss of excellent intelligence. Environment International, Jun 2; 118:116-124.
Location of Study:In endemic and non-endemic fluorosis areas in Tianjin, China.
Size of Study:2,886 resident children
Age of Subjects:  7 to 13 years
Source of Fluoride:Drinking water
Water Fluoride Level:The water fluoride concentration ranged from 0.20 mg/L to 1.00 mg/L, with a mean value of 0.50 ± 0.27 mg/L in the normal fluoride exposure group, and from 1.10 mg/L to 3.90 mg/L, with a mean value of 2.00 ± 0.75 mg/L in the high-fluoride exposure group (Table 1).
Type of IQ Test:

We examined the dose-response effects of low-to-moderate fluoride exposure on dental fluorosis (DF) and intelligence quotient (IQ), and evaluated the potential relationships between DF grades and intelligence levels using piecewise linear regression and multiple logistic regression, respectively.IQ scores were measured using the second edition of Combined Raven’s Test–The Rural in China (CRT-RC2) (Liu et al., 2009) for children aged 7 to 13 years. The CRT-RC2 is a validated test for basic cognitive abilities, and has been widely adopted in China after modifications, as it is non-verbal and less affected by language, and cultural and ethnic differences (Sun et al., 2015).

Dean’s fluorosis index (WHO criteria) (Molina-Frechero et al., 2015) was used to estimate the prevalence and severity of DF. Each participant was examined by two qualified and independent experts, who had rich experience on examination of dental fluorosis… The final diagnosis was made only when judgments from the two experts were in agreement; if not, a third expert would join in and offer suggestion. For repeatability, 10% of participants were double checked and the Kappa value was 0.82.

Results:The adjusted odds ratios (ORs) of DF were 2.24 (95% confidence interval [CI]: 2.02 to 2.48) for every 0.1 mg/L increment in the water fluoride concentration in the range of 0.80 to 1.50 mg/L, and 2.61 (95% CI: 2.32 to 2.93) for every 0.5 mg/L increment in the urinary fluoride level up to 1.80 mg/L. Every 0.5 mg/L increment in the water fluoride level was associated with a reduction of 4.29 in the IQ score (95% CI: -8.09 to -0.48) in the range of 3.40 to 3.90 mg/L, and a decreased probability of developing excellent intelligence (IQ ?130, OR = 0.60, 95% CI: 0.47 to 0.77) in the range of 0.20-1.40 mg/L, respectively. Every 0.5 mg/L increment in the urinary fluoride level was related to a decrease of 2.67 in the IQ scores (95% CI: -4.67 to -0.68) between 1.60 mg/L to 2.50 mg/L. Excellent intelligence decreased by 51% in children with higher urinary fluoride, and by 30% with each degree increment of DF.
Conclusions:In conclusion, chronic exposure to excessive fluoride, even at a moderate level, was inversely associated with children’s dental health and intelligence scores, especially excellent intelligence performance, with threshold and saturation effects observed in the dose-response relationships. Additionally, DF severity is positively associated with the loss of high intelligence, and may be useful for the identification of individuals with the loss of excellent intelligence. Thus, it is important to monitor water quality, and supply fluoride-free drinking water to safeguard children’s health.
IQ Study #52: (Bashash 2017)
Citation:Bashash M, Thomas D, Hu H, Angeles Martinez-Mier E, et al. (2017). Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age in Mexico. Environmental Health Perspectives, Sept 19;125(9):097017.
Location of Study:Participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project.
Size of Study:299 mother–child pairs, of whom 287 and 211 had data for the General Cognitive Index and IQ analyses, respectively.
Age of Subjects:Tests of cognitive function in the offspring at age 4 and 6–12 years.
Source of Fluoride:Fluoridated salt (at 250?ppm) and to varying degrees of naturally occurring fluoride in drinking water.
Water Fluoride Level:Natural water fluoride levels in Mexico City may range from 0.15 to 1.38 mg/L
Type of IQ Test:“At age 4 y, neurocognitive outcomes were measured using a standardized version of McCarthy Scales of Children’s Abilities. For children 6–12 y old a Spanish-version of the Wechsler Abbreviated Scale of Intelligence.”
Results:“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.”
IQ Study #51: (Valdez Jiménez 2017)
Citation:Valdez Jiménez L, López Guzmán OD, Cervantes Flores M, Costilla-Salazar R, Calderón Hernández J, Alcaraz Contreras Y, Rocha-Amador DO. 2017. In utero exposure to fluoride and cognitive development delay in infants. Neurotoxicology Mar;59:65-70.
Location of Study:Durango City and Lagos de Moreno, Jalisco, Mexico. Both are endemic hydro-fluorosis areas.
Size of Study:“65 mother-infant pairs recruited from 2013 to 2014. Inclusion criteria were: 12 weeks of gestation, with no history of thyroid disease, without clinically diagnosed diabetes, and a minimum 5 years of residence in the study area.”
Age of Subjects:“The average age of children assessed was 8 months (3–15 months) and almost 70% were girls.” The average age of the mothers was 22.4 ±4.0.
Source of Fluoride:The study was performed in an endemic hydrofuorosis area. According to the authors: ‘in Mexico F in water remains as the main source of F exposure. In endemic hydrofuorosis areas of Mexico only non-fluorinated salt is distributed according to the NOM-040-SSA1-1993.”
Water Fluoride Level:

F levels in tap water mean concentrations for each trimester were: 2.6 ±1.1 mg/l, 3.1 ±1.1 mg/l and 3.7 ±1.0 mg/l respectively. It is worthy to note that over 81.5% of the samples of tap water were above 1.5 mg/l (NOM-127- SSA1-1994) with the highest value of 12.5 mg/.

33.8% of women reported drink tap water and 78.4% use it for cooking. The practice of use tap water for drink or cooking is crucial because exposure to F could be increased when the infant change to bottle feeding and starts solid foods. Regarding, bottled water it is important to mention that we have analyzed several brands of this water and 65% of the samples exceeded the 0.7 mg/l value (NOM-041-SSA1-1993) and 22.9% had values over 1.5 mg/l (NOM-127-SSA1-1994) data not shown.

Type of IQ Test:“Neurodevelopment was assessed with the Bayley Scales of Infant Development II (BSDI-II) (Bayley, 1993). This test has good reliability and validity; it is applied to evaluate developmental delay in children between 3 months to 5 years in Mexico by the SSA (CNPSS, 2013). The Mental Development Index scale (MDI) of the Bayley test evaluate aspects of functioning such as eye-hand coordination, manipulation, understanding of object relation, imitation and early language development whereas the Psycho-motor Development Index (PDI) scale assesses gross motor development… To standardize the raw scores for children who were born prematurely, the number of months of prematurity was subtracted from their chronological age. The scores below 85 points indicated a possible developmental delay.”
Results:

In this study near to 60% of the children consumed contaminated water and the prevalence of children with IQ below 90 points was 25% in the control group (F urine 1.5 mg/g creatinine) in comparison with the 58% of children in the exposed group (F urine >5 mg/g creatinine) (OR = 4.1, CI 95% 1.3–13.2) (data unpublished).

Only 66.2% of the babies were at term. “We found higher levels of F in urine across trimester in premature compared with full term 2.4 vs 1.6 mg/l (1st); 2.3 vs 1.8 mg/l (2nd); and 4.1 vs 2.8 mg/l (3rd) (data not shown)

 Conclusions:“After adjusting for potential confounding factors (gestational age, age of child, marginalization index and type of water for consumption), the MDI [Mental Development Index] showed an inverse association with F levels in maternal urine for the first (b = -19.05, p = 0.04) and second trimester (b = -19.34, p = 0.01). Our data suggests that cognitive alterations in children born from exposed mothers to F could start in early prenatal stages of life.
IQ Study #50: (Das 2016)
Citation:Das K, Mondal NK. (2016). Dental fluorosis and urinary fluoride concentration as a reflection of fluoride exposure and its impact on IQ level and BMI of children of Laxmisagar, Simlapal Block of Bankura District, W.B., India. Environmental Monitoring & Assessment 188(4):218.
Location of Study:West Bengal, India
Size of Study:149 schoolchildren
Age of Subjects:6 to 18
Source of Fluoride:Water
Water Fluoride Level:Average = 2.1 mg/L (S.D. = 1.64 mg/L)
Type of IQ Test:Combined Raven’s Test for RuralChina (CRT-RC)
Results:

“IQ has anegative significant correlation with dental fluorosis (r=0.253,P<0.01). Dental fluorosis acts as an indicator of decreasing level of IQ. As fluorosis is a consequence of fluoride exposure, so IQ has a negative significant correlation with exposure dose (r =0.343, P<0.01) which was considered as a fluoride input source.”

“IQ values were plotted against the urinary fluoride concentration and it was found that they have a significant negative correlation (r=0.751, P<0.01).”

Conclusion“[C]hildren residing in areas with higher than normal water fluoride level demonstrated more impaired development of intelligence and moderate [dental fluorosis]. Millions of children including adults around the world are affected by higher level of fluoride concentration through their drinking water and are therefore potentially at risk. It is concluded that for the benefit of the future generation, urgent attention should be paid on this substantial public health problem.”
IQ Study #49: Mondal (2016)
Citation:Mondal D, et al. (2016). Inferring the fluoride hydrogeochemistry and effect of consuming fluoride-contaminated drinking water on human health in some endemic areas of Birbhum district, West Bengal. Environmental Geochemistry & Health 38(2):557-76.
Location of Study:Birbhum district, India
Size of Study:40 children (20 from endemic fluorosis area; 20 from control area)
Age of Subjects:10 to 14 years old
Source of Fluoride:Water
Water Fluoride Levels:“Mean F concentration in the study area varies from 0.32 to 13.29 mg/L.”
Type of IQ Test:Raven Standard Theoretical Intelligence Test
Results:“This study indicates that students exposed to high F (children of Junidpur and Nowapara) show an average IQ of 21.17 ± 6.77 in comparison with low-F exposed students (children of Bilaspur, Mohula, Bhalian) having an average IQ of 26.41 ± 10.46. . . . Statistical analysis (Z test) demonstrates that there is a significant (Z = 2.59) difference in IQ among the high- and low-F area student.”
Conclusion“[S]tudents of the study area have less IQ than students of non-contaminated area, demonstrating that consumption of F also has a major role with the intellectual development of
children.”
IQ Study #48: Khan (2015)
Citation:Khan SA, et al. (2015). Relationship between dental fluorosis and intelligence quotient of school going children in and around Lucknow district: a cross-sectional study. Journal of Clinical & Diagnostic Research 9(11):ZC10-15.
Location of Study:Lucknow district, India.
Size of Study:429 schoolchildren
Age of Subjects:6-12 years old
Source of Fluoride:Water
Results:“In this study, on comparison of children at two locations according to IQ grades [Table/Fig-4], majority of the children (74.8%) living in low fluoride area had an IQ grade 2 (definitely above the average in intellectual capacity). None of the children from the low fluoride area had an IQ grade 4 and 5 (definitely below average and intellectually impaired). On the other hand, majority of children (58.1%) from high fluoride area fall under IQ grade 3 (intellectually average). None of the children from high fluoride area had an IQ grade 1 (intellectually superior). This difference in IQ grades of children amongst the two areas was found to be statistically significant (p<0.001).””[I]t is clearly evident that with increase in the grade of fluorosis, a trend of increase in the IQ grade (decrease in intellectual capacity) was observed indicating a strong correlation between fluorosis grade and IQ grade (Spearman’s p=0.766).”
Conclusion:“The data from this research may support the hypothesis that excess fluoride in drinking water has toxic effects on the nervous system.”
IQ Study #47: Sebastian (2015)
Citation:Sebastian ST, Sunitha S. 2015. A cross-sectional study to assess the intelligence quotient (IQ) of school going children aged 10-12 years in villages of Mysore district, India with different fluoride levels. Journal of the Indian Society of Pedodontics and Preventive Dentistry 33(4):307-11.
Location of Study:Mysore district, India
Size of Study:405 schoolchildren (135 children from high fluoride area; 135 children from “normal” fluoride area; 135 chidren from “low” fluoride area)
Age of Subjects:10-12 years old
Source of Fluoride:Water
Water Fluoride Levels:High-fluoride: 2.2 mg/L; “Normal” Fluoride: 1.2 mg/L; “Low” Fluoride: 0.4 mg/L
Type of IQ Test:Raven’s colored Progressive Matrices Test
Results:“In bivariate analysis, significant relationships were found between water fluoride levels and Intelligence Quotient of school children (P < 0.05). In the high fluoride village, the proportion of children with IQ below 90, i.e. below average IQ was larger compared to normal and low fluoride village. Age, gender, parent education level and family income had no significant association with IQ.”
Conclusion:“School children residing in area with higher than normal water fluoride level demonstrated more impaired development of intelligence when compared to school children residing in areas with normal and low water fluoride levels.”
IQ Study #46: Kundu (2015)
Citation:Kundu H, et al. (2015). Effect of fluoride in drinking water on children’s intelligence in high and low fluoride areas of Delhi. Journal of the Indian Association of Public Health Dentistry 13(2):116-121. April-June.
Location of Study:Delhi, India.
Size of Study:
200 school children: 100 from low F area and 100 from high F area.
Age of Subjects:8-12 years of age.

 

Equal numbers of male and female children were included in the study.
Source of Fluoride:Water
Type of Cognitive Tests:
Ravens Standardized Progressive Matrices Test
Results:“Comparison of mean IQ of children in both high (76.20 ± 19.10) and low F (85.80 ± 18.85) areas showed a significant difference (P = 0.013). Multiple regression analysis between child IQ and all other independent variables revealed that mother’s diet during pregnancy (P = 0.001) along with F in drinking water (P = 0.017) were the independent variables with the greatest explanatory power for child IQ variance (r2 = 0.417) without interaction with other variables.”
Conclusion:“Fluoride in the drinking water was significantly related with the IQ of children. Along with fluoride, mother’s diet during pregnancy was also found to be significantly related with IQ of children.”
IQ Study #45: Choi (2015)
Citation:Choi A, et al. (2015). Association of lifetime exposure to fluoride and cognitive functions in Chinese children: A pilot study. Neurotoxicology & Teratology 47:96-101.
Location of Study:Southern Sichuan Province, China.
Size of Study:51 children from elevated fluoride area
Age of Subjects:Avg = 7.1 years old
Source of Fluoride:Water
Urine Fluoride Levels:Mean = 1.64 mg/L; Range = 0.22 to 5.84 mg/L
Water Fluoride Levels:Mean = 2.2 mg/L; Range = 1.0 to 4.07 mg/L
Confounding Factors:

“In this rural community, social differences are limited. The parents or guardians completed a questionnaire on demographic and personal characteristics including the child’s sex, age at testing, parity, illnesses before age 3, past medical history of the child and caretakers, parental or guardian age, education and occupational histories, and residential history, and household income. It is known that iron deficiency can impair motor and mental developments in children, iron concentration was therefore considered as a covariate. These potential confounders were used for adjustment in the statistical analysis.”

“Among possible confounders, both arsenic and lead are known to be low in drinking water in the area.”

Type of Cognitive Tests:WRAML, WISC-R, WRAVMA
Results:“Results of our pilot study showed that moderate and severe dental fluorosis was significantly associated with deficits in WISC-R digit span. Children with moderate or severe dental fluorosis scored significantly lower in total and backward digit span tests than thosewith normal or questionable fluorosis. These results suggest a deficit in working memory. Scores on other tests did not show significant relationships with indices of fluoride exposure.”
Conclusion:“Results of our field study raise a concern about the safety of elevated systemic exposure to fluoride from high concentrations in the drinking water.While topical fluoride treatment confers benefits of reducing caries incidence, the systemic exposure should not be so high as to impair children’s neurodevelopment especially during the highly vulnerable windows of brain development in utero and during infancy and childhood and may result in permanent brain injury. We are planning a larger scale study to better understand the dose–effect relationships for fluoride’s developmental neurotoxicity in order to characterize the appropriate means of avoiding neurotoxic risks while securing oral health benefits.”
IQ Study #44: Zhang (2015)
Citation:Zhang S, et al. (2015). Modifying Effect of COMT Gene Polymorphism and a Predictive Role for Proteomics Analysis in Children’s Intelligence in Endemic Fluorosis Area in Tianjin, China. Toxicological Sciences 144(2):238-45. April.
Location of Study:Tianjin City, China
Size of Study:180 children (96 from control area; 84 from “high fluoride” area)
Age of Subjects:Avg = 11 years old
Source of Fluoride:Water
Water Fluoride Levels:High = 1.4 mg/L
Control = 0.63 mg/L
Urine Fluoride Levels:High = 2.4 + 1.01 mg/L
Control = 1.10 + 0.67 mg/L
Serum Fluoride Levels:High = 0.18 + 0.11 mg/L
Control = 0.06 + 0.03 mg/L
Type of IQ Test:Combined Raven’s Test for Rural China (CRT-RC)
Confounding Factors:“Covariates included the indicator variables for age, gender, educational levels of parents (primary and below, junior high school, senior high school, and above), and continuous variables for drinking water fluoride (mg/l) and levels of thyroid hormones (T3, T4, and TSH).”
Results:“[T]he present work demonstrated that the IQ scores of children exposed to high fluoride drinking water were significantly lower than those who lived in control area . . . . [O]ur findings further showed that, across the full range of serum and urinary fluoride, children’s IQ decreased gradually with the increase of fluoride contents in serum and urine, in a dose-dependent manner.”
Conclusion:“In summary, our data suggest that the intelligence of children is affected by the COMT gene polymorphism and, in particular, this SNP plays a role in modifying the effect of fluoride exposure on cognition. Children with COMT reference allele had a higher risk for cognitive impairments after fluoride exposure. Additionally, proteomics analysis represents early specific markers of developmental fluoride neurotoxicity. Hence, our findings provide certain basis for clarifying the mechanisms and identifying molecular targets of pharmacological interventions for potential delayed therapy.”
IQ Study #43: Bai (2014)
Citation:Bai Z, et al. (2014) Investigation and analysis of the development of intelligence levels and growth of children in areas suffering fluorine and arsenic toxicity from pollution from burning coal. Chinese Journal of Endemiology 33(2):160-163.
Location of Study:Shaanxi Province, China.
Size of Study:303 children (120 children from high-fluoride area; 95 from mid-fluoride area, 98 from low-fluoride area)
Age of Subjects:8 to 12 years old
Source of FluorideCoal burning
Urine Fluoride Levels:“The median urinary fluoride levels for children 8–12 years old in the areas of significant, minor and no morbidity were, respectively, 1.96, 0.81 and 0.54 mg/L.”
Results:“The children’s urinary fluoride and urinary arsenic levels versus intelligence [quotients] were both negatively correlated (r=-0.560, -0.353, all P<0.05).”
Conclusion“Exposures to fluorine and arsenic are deleterious to the development of intelligence and the development of growth in children”
 IQ Study #42: Wei (2014)
Citation:Wei N, et al. (2014). The effects of comprehensive control measures on intelligence of school-age children in coal-burning-borne endemic fluorosis areas. Chinese Journal of Endemiology 33(3):320-22.
Location of Study:Bijie City, Guizhou Provinc, China.
Size of Study:741 children (104 children from low-fluoride area; 298 children from an endemic fluorosis area with long-term defluoridation measures; 339 children from endemic fluorosis area with short-term defluoridation measures).
Age of Subjects:8-12 years old
Source of Fluoride:Coal
Urinary Fluoride Levels:Control: 1.34 ± 0.64 mg/L; Long-term defluoridation: 2.33 ± 0.18 mg/L; Short-term defluoridation: 3.03 ± 0.16) mgL.
Results:“Above average IQ of children in the control group was 97.1% (101/104),which was significantly higher than that of long and short treatment groups; after a lengthy treatment, mental retardation detection rate was significantly lower in the low-age group,8-10 year-old children(x2 =7.542,P < 0.01). Urinary fluoride content was negatively correlated with the level of IQ (r =-0.553,P < 0.01).
Conclusion:“The intelligence development of children in coal-burning-borne endemic fluorosis area is significantly delayed. After a certain period of comprehensive treatment,the decreased level of cognition is inhibited and the mental retardation in the low-age group is improved.”
 IQ Study #41: Nagarajappa (2013)
Citation:Nagarajappa R, et al. (2013). Comparative assessment of intelligence quotient among children living in high and low fluoride areas of Kutch, India: a pilot study. Iranian Journal of Public Health 2(8): 813–818.
Location of Study:Kutch District, Gujarat, India
Size of Study:100 children (50 children from high-fluoride area; 50 children from control area)
Age of Subjects:8-10 years old
Source of Fluoride:Water
Water Fluoride Levels:High Fluoride: 2.4 to 3.5 mg/L; Control: 0.5mg/L.
Type of IQ Test:Seguin Form Board Test
Results:“Mean scores for average, shortest and total timing category were found to be significantly higher (P<0.05) among children living in Mundra (30.45±4.97) than those living in Bhuj (23.20±6.21). Mean differences at 95% confidence interval for these timings were found to be 7.24, 7.28 and 21.78 respectively.”
Conclusion:“Chronic exposure to high levels of fluoride in water was observed to be associated with lower intelligence quotient.”
 IQ Study #40: Singh (2013)
Citation:Singh VP, et al. (2014). A correlation between serum vitamin, acetylcholinesterase activity and IQ in children with excessive endemic fluoride exposure in Rajasthan, India. European Academic Journal 2(4):5857-5869.
Location of Study:Jaipur, Rajasthan (India)
Size of Study:42 children (70 from high-fluoride area; 72 from control area)
Age of Subjects:9 to 14 year olds
Source of Fluoride:Water
Levels of Fluoride in Water:High Fluoride = 6.8 mg/L
Control area = <1.03 mg/L
Confounding Factors:“The subjects were similar in living conditions, parental literacy, socioeconomic status, and health history. Moreover, age and sex matched controls were selected from the [low-fluoride area].”
Type of IQ Test:Raven’s Test
Conclusion:“We observed reduced AChE activity in [the high fluoride area] which may be directly correlate[d] with the reduced intelligence score of the subjects.”
IQ Study #39: Karimzade (2014)
Citation:Karimzade S, et al. (2014). Investigation of intelligence quotient in 9-12-year-old children exposed to high- and low-drinking water fluoride in West Azerbaijan province, Iran. Fluoride 47(1):9-14.
Location of Study:Poldashi and Piranshahr, West Azerbaijan province, Iran.
Size of Study:39 male children (19 from high-fluoride area; 20 from control area)
Age of Subjects:9 to 12 year olds
Source of Fluoride:Water
Water Fluoride Levels:High Fluoride = 3.94 mg/L
Control = 0.25 mg/L
Confounding Factors:No significant differences were found in the potential confounding factors of educational, economic, social, cultural, and general demographic characteristics between the high- and low-F regions.
Type of IQ Test:Iranian version of the Raymond B Cattell test
Results:“The IQ of the 19 children in the high-F region was lower (mean±SD: 81.21±16.17), than that of the 20 children in the low-F region (mean±SD: 104.25±20.73, p=0.0004). In the high-F region, 57.8% had scores indicating mental retardation (IQ <70) or borderline intelligence (IQ 70–79), while this figure was only 10% in the low–F region.”
Conclusions:“The study found that children residing in a region with a high drinking water F level had lower IQs compared to children living in a low drinking water F region (p<0.001). The differences could not be attributed to confounding educational, economic, social, cultural, and general demographic factors.”
IQ Study #38: Trivedi (2012)
Citation:Trivedi MH, et al. (2012). Assessment of groundwater quality with special reference to fluoride and its impact on IQ of schoolchildren in six villages of the Mundra Region, Kachchh, Gujurat, India. Fluoride 45(4):377-83.
Location of Study:Gujurat, India
Size of Study:84 children (34 from high-fluoride villages, 50 children from control village)
Age of Subjects:6th and 7th grade students
Source of Fluoride:Water
Water Fluoride Levels:High Fluoride = 2.3 + 0.87 mg/L
Control = 0.83 + 0.38 mg/L
Urine Fluoride Levels:High Fluoride = 2.69 + 0.92 mg/L
Control = 0.42 + 0.23
Confounding Factors:Same socioeconomic status (E on an A-E scale); same attendance status at school (regular students attending more than 80% of classes)
Type of IQ Test:Questionnaire prepared by Prof. JH Shah; standardized on the Gujarati population with 97% reliability rate in relation to the Stanford-Binet Intelligence Scale
Results:“The average IQ score of the 34 students drinking the high F water was significantly lower (p?0.05) than among the 50 students drinking the low F water.”
Conclusions:“the present investigation concludes that the three villages of Chhasara, Gundala, and Mundra, are F-contaminated villages. Because of high F concentrations in the [groundwater], children in these villages have greater exposure to F that may lead in to low IQ as compared to the nearby villages of Baroi, Zarpara, and Pragpar, which have low F in their [groundwater].”
IQ Study #37: Seraj (2012)
Citation:Seraj B, et al. (2012). Effect of high water fluoride concentration on the intellectual development of children in Makoo/Iran. Journal of Dentistry, Tehran University of Medical Sciences 9(3): 221-29.
Location of Study:Makoo, Iran.
Size of Study:293 children (91 children in control village; 106 children in medium F village; 96 children in high F village)
Age of Subjects:6 to 11 years old
Source of Fluoride Exposure:Water
Water Fluoride Levels:Control = 0.8+0.3 ppm
Medium fluoride = 3.1+0.9 ppm
High fluoride = 5.2+1.1 ppm
Confounding Factors:Age, gender, child’s educational level, mother’s educational level, father’s educational level, fluorosis intensity, iodine level in water, lead level in water.
IQ Test:Raven’s Color Progressive Matrices (RCPM)
Results:“The mean IQ scores decreased from 97.77+18.91 for the normal fluoride group to 89.03+12.99 for the medium fluoride group and to 88.58+16.01 for the high fluoride group (P=0.001).”
Conclusion: “Since all potentially confounding factors were adjusted, the difference in IQ scores may reveal the potential effect of high fluoride exposure on the intellectual development of children.”
IQ Study #36: Saxena (2012)
Citation:Saxena S, et al. (2012). Effect of fluoride exposure on the intelligence of school children in Madhya Pradesh, India. Journal of Neurosciences in Rural Practice 3(2):144-49.
Location of Study:Madhya Pradesh, India.
Size of Study:173 children (120 children in three high-F areas and 53 children from a control group)
Age of Subjects:School children in the 5th & 6th grades
Source of Fluoride Exposure:Water
Water Fluoride Levels:Group 1 = >4.5 ppm
Group 2 = 3.1-4.5 ppm
Group 3 = 1.5-3.0 ppm
Control = <1.5 ppm
Urine Fluoride Levels:Group 1 = 7.01+1.02
Group 2 = 4.85+0.50
Group 3 = 3.28+0.48
Control = 2.25+0.28
Confounding Factors:(1) No significant differences in urinary lead, arsenic, or iodine levels between the four groups. (2) No significant differences in gender ratio, socio-economic status, SES, parental education, height/age ratio, and weight/height ratio. (3) Children were excluded if they were not lifelong resident of area, if they had changed their water source since birth, or if they had history of congenital or acquired neurological disease and/or head injury.
IQ Test:Raven’s Standard Progressive Matrices
Results: “Reduction in intelligence was observed with an increased water fluoride level (P 0.000). The urinary fluoride level was a significant predictor for intelligence (P 0.000).”
Conclusion: “This study indicates that exposure to fluoride is associated with reduced intelligence in children. We have found a significant inverse relationship between intelligence and the water fluoride level, and intelligence and the urinary fluoride level. After adjusting for confounders, urinary fluoride was the significant predictor for intelligence.”
IQ Study #35: Ding (2011)
Citation:Ding Y, et al. (2011). The relationships between low levels of urine fluoride on children’s intelligence, dental fluorosis in endemic fluorosis areas in Hulunbuir, Inner Mongolia, China. Journal of Hazardous Materials 186(2-3):1942-46.
Location of study:Hulunbuir, Inner Mongolia, China
Size of study:331 children from four sites
Age of Subjects:7-14 years old
Source of Fluoride:Water
Water Fluoride Levels:Mianduhe town=0.28+0.03 mg/L
Nan district=0.79+0.33 mg/L
Donghu district=1.78+0.60 mg/L
Zhalainuoer county=1.82+1.00 mg/
Urine Fluoride Levels:No dental fluorosis = 0.80+0.55 mg/L
Questionable fluorosis = 1.13+0.73 mg/L
Very mild fluorosis = 1.11+0.74 mg/L
Mild fluorosis = 1.31+0.78 mg/L
Moderate fluorosis =1.46+0.79 mg/L.
Confounding Factors:(1) Sites selected to match social and natural factors like economic situation, educational standard, and geological environments. (2) Schools had similar teaching quality. (3) Sites are not exposed to known neurotoxins (e.g. arsenic) in drinking water, nor are they endemic areas for iodine deficiency disorders. (4) Five children who had not lived in these areas at least 1 year were excluded.
IQ Test:CRT-RC3 (Combined Raven’s Test for Rural China)
Results:Children’s IQ was inversely related to urinary fluoride content, (p<0.0001). Each increase in 1 mg/L of urine F was associated with 0.59 point decrease in IQ (p=0.0226).
Conclusion: “In conclusion, our study suggested that low levels of fluoride exposure in drinking water had negative effects on children’s intelligence and dental health and confirmed the dose-response relationships between urine fluoride and IQ scores as well as dental fluorosis.”
IQ Study #34: Poureslami (2011)
Citation:Poureslami HR, et al. (2011). Intelligence quotient of 7 to 9 year-old children from an area with high fluoride in drinking water. Journal of Dentistry and Oral Hygiene 3(4):61-64.
Location of study:Kerman Province, Iran: Koohbanan (high-F) and Baft (low-F)
Size of study:120 children: 60 children per city
Age of Subjects:7-9 years old
Source of Fluoride:Water
Water Fluoride levels:High-F = 2.38 mg/L
Low-F = 0.41 mg/L
Confounding Factors:(1) Exclusion criteria: genetic, congenital, or acquired diseases related to the nervous system, past or present. (2) Inclusion criteria (high-F village): signs of grade III TSIDF (total surface index of Dental Fluorosis) or more. (3) Inclusion criteria (low-F village): similar physical and mental health criteria adopted, but children lacked any sign of Dental Fluorosis. (4) Both towns at high altitude.
Type of IQ TestRaven’s Progressive Matrices Intelligence Test (Persian version)
Results:Average IQ of High F group (91.37+16.63) is significantly lower than average IQ of Low-F group (97.80+15.95), p < 0.05.
Conclusion:“Based on the findings, chronic exposure to high levels of fluoride can be one of the factors that influence intellectual development.”
IQ Study #33: Eswar (2011)
Citation:Eswar P, et al. (2011). Intelligent quotients of 12-14 year old school children in a high and low fluoride village in India. Fluoride 44:168-72.
Location of study:Ajjihalli (low F) and Holesirigere (high F) villages, Davangere district, Karnataka, India.
Size of study:133 children total (low F village=65; high F village=68)
Age of Subjects:12-14 years old
Source of Fluoride:Water
Water Fluoride levels:High F village=2.45 mg/L
Low F village =0.29 mg/L
Confounding Factors:(1) Children included were continuous residents of study villages since birth; drinking water from same public water supply (1 per village); (2) attended same high school (1 per village). (3) Children with history of trauma or injury to head; affected by congenital or acquired neurological disorders, psychological disorders were excluded.
Type of IQ TestRaven’s Standard Progressive Matrices Test
Results:63.2% of children in high F area had IQ less than 90, versus 47.7% of children in low F village. (p=0.06).
Conclusion:“Though there was a trend in our study towards lower IQ in a greater number of children from high F village than in the low F village, probably the small sample size of the present study failed to establish a statistically significant difference.”
IQ Study #32: Shivaprakash (2011)
Citation:Shivaprakash PK, et al. (2011). Relation between dental fluorosis and intelligence quotient in school children of Bagalkot district. J Indian Soc Pedod Prev Dent. 29(2):117-20.
Location of study:Bagalkot district, Karnataka state, India
Size of study:160 children
Age of Subjects:7-11 years old
Source of Fluoride:Water
Water Fluoride Levels:high F village = 2.5-3.5 mg/L
low F village = < 0.5 mg/L
Confounding Factors:(1) Children included in study had normal birth history, were permanent residents in the region of study, had no history of trauma to the head, no history of chronic illness, not on medication. (2) Villages have similar culture, standard of living, and lifestyle habits.
Type of IQ TestRaven’s Colored Progressive Matrices Test
Results:(A) Children with dental fluorosis had lower IQ (66.63+18.09) than those without dental fluorosis (76.36+20.84), p < 0.05. (B) Children with mild dental fluorosis had lower IQ (66.73) than those without dental fluorosis (75.89), p < 0.05.
Conclusion:“Previous studies had indicated toward decreased Intelligence in children exposed to high levels of fluoride and our study also confirmed such an effect.”
IQ Study #31: Sudhir (2009)
 Citation:Sudhir KM, et al. (2009). Effect of fluoride exposure on intelligence quotient (IQ) among 13-15 year old school children of known endemic area of fluorosis, Nalgonda District, Andhra Pradesh. Journal of the Indian Association of Public Health Dentistry 13:88-94.
Location of Study:Nalgonda District, Andhra Pradesh, India
Size of Study:1000 children
Age of Subjects:13-15 years old
Source of Fluoride:Water
Water Fluoride Levels:Four areas were studied: <0.7 mg/L; 0.7-1.2 mg/L; 1.2-4.0 mg/L; >4 mg/L
Type of IQ Test:Raven’s standard progressive matrices
Results:“Number of intellectually impaired children were gradually increased with the increase in fluoride  concentration in the drinking water.”
Conclusion:“Findings of this study suggest that overall IQ levels in children’s exposed to high fluoride level were significantly lower than the low fluoride areas.”
IQ Study #30: Li (2009)
Citation:Li F, et al. (2009). The impact of endemic fluorosis caused by the burning of coal on the development of intelligence in children. Journal of Environmental Health 26(4):838-40.
Location of study:Xinhua County, Hunan Province, China
Size of study:80 children total: 20 children from “mild” fluorosis area, 20 from “medium” fluorosis area, 20 from “severe” fluorosis area, and 20 from non-fluorosis area.
Age of Subjects:8-12 years old
Source of Fluoride:Coal burning
Fluoride exposure levels:

Urine F (by region):

severe = 2.34+1.13 mg/L
medium = 1.67+0.66 mg/L
mild = 1.24+0.43 mg/L
control = 0.96+0.52 mg/L

Urine F (by dental fluorosis type):

severe = 2.66+1.09 mg/L
medium = 2.01+0.80 mg/L
mild = 1.64+0.68 mg/L
very mild = 1.17+0.48 mg/L
suspected = 1.09+0.36 mg/L
no fluorosis = 0.87+0.23 mg/L.

Confounding Factors:(1) All children were born and raised in the respective areas. (2) Children were excluded if they had been diagnosed with physical deformation, developmental disorders, delayed mental development, emotional/behavioral obstacles or challenges, or other forms of mental disorders.
Type of IQ TestCRT-RC (Combined Raven’s Test for Rural China)
Results:– IQ decreased with increasing F level in urine (p < 0.01) – IQ was significantly reduced among children with severe fluorosis as compared to children without fluorosis (p < 0.05) – A trend (albeit not statistically significant) for IQ to decrease with increasing severity of dental fluorosis (NS) and with increasing severity of the region’s fluoride poisoning
Conclusion:“High exposure to fluoride most definitely has an adverse effect on the development of intelligence in children, in particular on the capability of abstract inference.”
IQ Study #29: Rocha-Amador (2007)
Citation:Rocha-Amador D, et al. (2007). Decreased intelligence in children and exposure to fluoride and arsenic in drinking water. Cadernos de Saude Publica 23(Suppl 4):S579-87.
Location of study:Durango State, Mexico & San Luis Potosi State, Mexico
Size of study:132 children
Age of Subjects:6 to 10 years old
Source of Fluoride Exposure:Water
Water Fluoride LevelsLowest F village: 0.8+1.4 mg/L
Middle F village: 5.2+0.9 mg/L
Highest F village: 9.4+0.9 mg/L
Urine Fluoride LevelsLowest F village: 1.8+1.5 mg/L
Middle F village: 6.0+1.6 mg/L
Highest F village: 5.5+3.3 mg/L
Confounding Factors:(1) A multiple regression analysis was used that controlled for blood lead levels, socioeconomic status, mother’s education, height-for-age (an index of malnutrition), and transferrin saturation. (2) Each child’s water fluoride level, and urine fluoride level, levels were individually determined. (3) The test examiner was blinded as to the children’s fluoride exposure.
IQ Test: Wechsler Intelligence Scale for Children–Revised Mexican Version (WISC-RM)
Results:(1) Both fluoride in urine, and fluoride in water, were significantly correlated with IQ, and this correlation remained significant after controlling for lead exposure, socioeconomic status, mother’s education, malnutrition, and transferrin. (2) Fluoride’s effect on IQ was larger than the effect from arsenic.
Conclusion:“We found that exposure to F in urine was associated with reduced Performance, Verbal and Full IQ scores before and after adjusting for confounders. The same pattern was observed for models with F in water as the exposure variable. . . . The individual effect of F in urine indicated that for each mg increase of F in urine a decrease of 1.7 points in Full IQ might be expected.”
IQ Study #28: Wang (2007)
Citation:Wang SX, et al. (2007). Arsenic and fluoride exposure in drinking water: children’s IQ and growth in Shanyin county, Shanxi province, China. Environmental Health Perspectives 115(4):643-7.
Location of study:Shanyin County, Shanxi Province, China
Size of study:720 children: 21-196 per village (3 villages for each of the arsenic groups)
Age of Subjects:8-12 years old
Source of Fluoride:Water
Water Fluoride Levels:High-Arsenic group = 0.9+0.5 mg/L
Medium-Arsenic group = 1.7+1.1 mg/L
High-Fluoride group = 8.3+1.9 mg/L
Control group = 0.5+0.2 mg/L
Urine Fluoride levels:High-Arsenic group = 1.0+1.7 mg/L
Medium-Arsenic group = 2.8+1.9 mg/L
High-Fluoride group = 5.1+2.0 mg/L
Control group = 1.5+1.6 mg/L
Confounding Factors:(1) Arsenic used as variable. Similar manganese levels in water for all groups. (2) All groups lived in rural areas with similar geographic and cultural conditions and a comparable level of socioeconomic development (years of parental education, average income, years of exposure). (3) All children currently attending school.
Type of IQ TestCRT-RC (Combined Raven’s Test for Rural China)
Results:– Average IQ in high-arsenic area (95.1+16.6) is significantly lower than IQ in control area (104.8+14.7). p < 0.05 – The average IQ in high-fluoride area (100.5+15.8) is also significantly lower than average IQ in control area (104.8+14.7). p < 0.05 – Significantly more children with IQ lower than 70 (mental retardation) in high-F area (4%), medium-arsenic area (3.3%), and high-arsenic area (8.3%) as compared to control (0%).
Conclusion:“This study indicates that exposure to fluoride in drinking water is associated with neurotoxic effects in children.”
 IQ Study #27: Trivedi (2007)
Citation:Trivedi MH, et al. (2007). Effect of high fluoride water on intelligence of school children in India. Fluoride 40(3):178-183.
Location of study:– High F area: Sachana, Sanand district, Gujarat, India – Medium F area: Chandlodia, Ahmedabad, India
Size of study:190 children (89 in high F area; 101 in medium F area)
Age of Subjects:12-13 years old
Source of Fluoride:Water
Water Fluoride Levels:High F area=5.55+0.41 mg/L
Medium F area=2.01+0.009 mg/L
Urine Fluoride Levels:High F area = 6.13+0.67 mg/L
Medium F area = 2.30+0.28 mg/L
Confounding Factors:(1) The study included only those children who were life-long residents of the areas. respective location. (2) The areas have similar nutritional status and both have middle class socioeconomic status (although Sachana is slightly poorer). (3) Iodized salt is used in both areas.
Type of IQ TestQuestionnaire prepared by Prof. JH Shah; standardized on the Gujarati population with 97% reliability rate in relation to the Stanford-Binet Intelligence Scale
Results:(A) Average IQ is lower in High-F area (91.72+1.13) than in Low-F area (104.44+1.23), p<0.001. (B) High F area has 28.09% of children with IQ below normal (over twice the percentage found in lower F area).
Conclusion: “In agreement with other studies elsewhere, these findings indicate that children drinking high F water are at risk for impaired development of intelligence.”
IQ Study #26: Fan (2007)
Citation:Fan Z, et al. (2007). The effect of high fluoride exposure on the level of in
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