Decreased intelligence in children and exposure to fluoride and arsenic in drinking water.

Abstract

Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L; As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3 microg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.

EXCERPTS:

Study population

All children attending the first through third grades in public schools in three rural areas in Mexico were screened for study eligibility through in-person interviews (n = 480). They included questions about age of the child, time of residence, and address. The locations of the communities are shown in Figure 1. Moctezuma and Salitral are located in the northwest region of San Luis Potosí State and 5 de Febrero is located in the central region of Durango State.

The three selected communities were similar in population and general demographic characteristics. Children who had lived in the area since birth and who were from 6 to 10 years old at the time of the study were eligible to participate (n = 308). Of those eligible, 155 children were randomly selected for study participation. The response rate was 85%. No significant differences in age, gender proportion, or time of residence were observed between study participants and non-participants.

Results

Sociodemographic characteristics for children from the three communities are presented in Table 1. When comparing the mean concentrations of F and As in water, statistically significant differences were observed between Moctezuma and both Salitral and 5 de Febrero (p < 0.001). Mean levels of F in water were almost 3.5 and 6 times higher than WHO limits in Salitral and 5 de Febrero, respectively. Mean levels of As in water were 17 and 19 times higher than WHO limits in Salitral and 5 de Febrero, respectively. No statistically significant differences were observed in participant’s age, mother’s education, gender proportion, or z-scores (weight-for-age and height-for-age) between the three communities. However, there were statistically significant differences (p < 0.01) in socioeconomic status and proportion of children with transferrin saturation below 20%.

Concentrations of F and As in urine and Pb in blood are shown in Table 2. Mean levels of F in urine were similar for 5 de Febrero and Salitral, but the differences between each of them and Moctezuma were statistically significant. Statistically significant differences in As in urine were observed between Moctezuma and both Salitral and 5 de Febrero. The proportions of children with As in urine levels above the CDC intervention limit were 80% and 52% for Salitral and 5 de Febrero, respectively, compared with 3.8% for Moctezuma. There was a statistically significant difference in mean Pb levels in blood between 5 de Febrero and Moctezuma. The proportion of children with values above 10µg/dL ranged from 4.5 to 10%.

To test the association between F in urine or F in water and IQ scores (Performance, Verbal, and Full), multiple regression models were calculated. Results are shown in Table 3. For F in urine, the coefficients (b values) for Performance, Verbal, and Full IQ scores, adjusted for Pb blood, socioeconomic status, mother’s education, height-for-age z-score, and transferrin saturation, were -13.0, -15.6, and -16.9, respectively (all p values < 0.001). For F in water, the coefficients (b values), also adjusted for the same confounders mentioned above, were -6.7, -11.2, and -10.2, respectively (all p values < 0.001).

As exposure data are shown in Table 4. After adjusting for confounders (Pb blood, socioeconomic status, mother’s education, height-for-age z-score, and transferrin saturation), As in urine was found to be inversely associated with Full IQ scores (b = -5.72, p = 0.003). We also observed inverse relationships for Performance and Verbal IQ scores, however they were not as significant (b = -4.19, p = 0.08; b = -5.50, p = 0.06, respectively). After adjusting for confounders, As in water showed inverse associations with Performance, Verbal, and Full IQ scores (b values = -4.30, -6.40, and -6.15, respectively; all p values < 0.001).

Discussion

We found that exposure to F in urine was associated with reduced Performance, Verbal, and Full IQ scores before and after adjusting for confounders (b values = -13.0, -15.6, and -16.9, respectively; all p-values < 0.001). The same pattern was observed for models with F in water as the exposure variable (b values = -6.7, -11.2, and -10.2, respectively; all p-values < 0.001).

The impact of F on IQ has been reported in several studies by Chinese researchers. In one study conducted in 1995, mean IQ scores were compared between children living in areas with different prevalence of dental fluorosis. The mean IQ score of residents in the severe fluorosis area (mean urinary F of 2.69mg/L and index of dental fluorosis of 3.2) was 80.3 points, whereas in the low fluorosis area (mean urinary F of 1.02mg/L and index of dental fluorosis < 0.4) it was 89.9 points. The difference between groups was statistically significant ⁹. Another study compared IQ scores between children living in two villages with different mean levels of F in water (4.12mg/L vs. 0.91mg/L). Although the authors did not control for confounding factors and did not measure F in urine, they report that the average IQ of children in the high fluoride area (97.69 points) was significantly lower than in the low fluoride area (105.21 points) ¹⁰. The two studies just mentioned used the Rui Wen Test to measure IQ. In 2000, another report compared IQ scores for children from two areas in China (F in drinking water 3.15mg/L vs. 0.37mg/L). They also measured the concentration of F in urine (mean urinary F of 4.99mg/L vs. 1.43mg/L). The mean IQ score for children in the more exposed area (92.2 points) was lower than for children living in the less exposed area (103.05 points) ¹¹. Finally, another Chinese study evaluated 118 children from two villages. The mean IQ score for the high-fluoride area (92.02 points; F in water 2.47mg/L) was significantly lower than for the low-fluoride area (100.41 points; F in water 0.36 mg/L). In this study, a mild inverse association between F in urine and IQ scores (r = -0.17, p = 0.003) was reported. No adjustment was made for confounders ¹². Despite having several shortcomings (lack of adjustment for confounders, no biological markers, no quantification of other potential neurotoxic pollutants, etc.), all of these studies suggest that F negatively impacts IQ scores, with observed reductions in IQ ranging from 8 to 11 points between exposed and non-exposed children.

The levels of children’s exposure to F in the present study were higher than in the Chinese studies. F in drinking water was 3.5 and 6 times higher than the WHO reference guideline for two of the communities. On average, the value of F in urine was 6.6mg/g crt. Additionally, more than 50% of the children in the two high exposure areas had As in urine above the CDC reference value of 50µg/g crt. 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. The proportion attributable to F in urine alone was 17% above the contribution of other measured factors. The variance in Full IQ explained in the adjusted model was 25%. Regarding As in urine, we observed an inverse association with Full IQ scores (b = -5.72, p = 0.003). We also observed an inverse relationship for Performance and Verbal IQ scores, although with less significance (b = -4.19, p = 0.08; b = -5.50, p = 0.06, respectively). We also found that As in water was inversely correlated with Performance, Verbal, and Full IQ scores (b values = -4.30, -6.40, and -6.15; all p values < 0.001). Compared to F, the effect attributable to As was smaller.

There are also data in the literature supporting the possible role of As in IQ reduction. In one study conducted by our group, a negative association was observed between urinary As (mean = 62.9µg/g crt) and Verbal (r = -0.43, p = 0.008) and Full IQ scores (r = -0.33, p = 0.04), after adjustment for confounders, in children living around a smelter complex ¹⁵. Another study conducted in Bangladesh reported an inverse association between water As and Performance and Full IQ scores (b values = -1.45 and -1.64, respectively; p < 0.001 in both cases) ¹³.

The adverse effects of F and As on the human central nervous system are supported by experimental data. When F crosses the blood brain barrier, the hematoencephalic barrier, it accumulates in the brain, inducing structural and cognitive alterations in the central nervous system ^17,25. Rats exposed to F in drinking water at weaning had elevated fluoride levels in 6 of 7 brain regions and plasma fluoride levels 7 to 42 times higher than those found in control animals. These elevated plasma and brain F levels were associated with behavior alterations, such as cognitive deficits ¹⁷. Learning deficits in a delayed alternation task and alterations in a spatial learning task have been reported for groups exposed to As as compared to control groups ^18,26,27.

The design of the present study precluded testing statistically the interaction between F and As. However, a previous study conducted by our research group in the city of San Luis Potosí, IQ scores were evaluated using WISC-RM in a population of children exposed to F in drinking water (values ranged from 1.5 to 3mg/L). The mean levels of F and As in urine were 4.3±1.5mg/g crt and 41±1.5µg/g crt, respectively. This study did not demonstrate any effect on IQ scores, but did show a positive relationship between F in urine and reaction time (r = 0.28, p = 0.04) and an inverse relationship between F in urine and visual-spatial organization scores (r = -0.27, p = 0.05) ¹⁶. These data may lend support to the hypothesis that exposure to both toxicants could worsen children’s performance on neuropsychological tests and thus indicates the need for further investigation.

Our results regarding Pb in blood indicate that the observed deficits in IQ scores cannot be attributed to Pb exposure. When Pb in blood was included in the adjusted model for F in urine, the correlation remained significant with only a small contribution to the variance, whereas, in the adjusted model for As in urine, it was not significant.

Although this was a cross-sectional study and F and As in urine are biomarkers of recent exposure, we have data about past exposures for two of the communities included in this study. In 5 de Febrero, levels of F in water reported from 1997 to 2004 ranged from 8.7mg/L to 10.2mg/L. As values for the same period ranged from 130µg/L to 215µg/L. Levels of both pollutants in water were above WHO standards. Data for Salitral from 2002 and 2003 show that F levels were on average 5.3mg/L and As ranged from 141µg/L to 150µg/L. Although we do not have historical data regarding levels of F in water in Moctezuma, we can assume that they were similar to our findings because none of the children had dental fluorosis, an indicator of chronic exposure to F. Based on this information and because F and As in water were highly correlated (r = 0.86, p < 0.001), we assume that the exposure scenario has not changed over time and the current exposure to F or As in drinking water can be used as a proxy for past exposure. Some of the effects on brain dysfunctions are observed years after exposure. The children in the study sample were exposed since birth and remained exposed until the study data were collected. Biological levels of F and As are clearly better indicators of actual exposure because they integrate all sources and changes in exposure. Fifty-three percent of people from 5 de Febrero reported using bottled water for drinking but not for cooking, whereas this figure was 27% for the Salitral community.

In conclusion, the data from this research support the conclusion that F and As in drinking water have a potential neurotoxic effect in children. It is urgent that public health measures to reduce exposure levels be implemented. Millions of people around the world are exposed to these pollutants and are therefore potentially at risk for negative impact on intelligence. This risk may be increased where other factors affecting central nervous system development, such as malnutrition and poverty, are also present. The risk is particularly acute for children, whose brains are particularly sensitive to environmental toxins. Furthermore, it would be advisable to reexamine the benefits of F given the documented health risks.