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Article history: There has been public concern about childrens intellectual performance at high levels of uoride expo-
Received 28 October 2010 sure, but few studies provide data directly to the question of whether low uoride exposure levels less
Received in revised form than 3.0 mg/L in drinking water adversely associated with childrens intelligence. In this survey, we inves-
18 December 2010
tigated the effects of low uoride exposure on childrens intelligence and dental uorosis. 331 children
Accepted 20 December 2010
aged from 7 to 14 were randomly recruited from four sites in Hulunbuir City, China. Intelligence was
Available online 25 December 2010
assessed using Combined Raven Test-The Rural in China while dental uorosis was diagnosed with Deans
index. Mean value of uoride in drinking water was 1.31 1.05 mg/L (range 0.242.84). Urine uoride
Keywords:
Urine uoride
was inversely associated with IQ in the multiple linear regression model when childrens age as a covari-
IQ ate variable was taken into account (P < 0.0001). Each increase in 1 mg/L of urine uoride associated with
Dental uorosis 0.59-point decrease in IQ (P = 0.0226). Meanwhile, there was a doseresponse relationship between urine
Children uoride and dental uorosis (P < 0.0001). In conclusion, our study suggested that low levels of uoride
exposure in drinking water had negative effects on childrens intelligence and dental health and con-
rmed the doseresponse relationships between urine uoride and IQ scores as well as dental uorosis.
0304-3894/$ see front matter 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jhazmat.2010.12.097
Y. Ding et al. / Journal of Hazardous Materials 186 (2011) 19421946 1943
2. Materials and methods mixed 5 ml urine samples with 5 ml total ionic strength adjustment
buffer (TISAB) at PH 5, then used F-ion selective electrode (Yingke
2.1. Sample selection Crystal Materials Company) to detect those samples. All the sam-
ples were analyzed in twice (independent aliquots), and the means
Hulunbuir is a region that is governed as a prefecture-level of two aliquots were calculated to derive the urine uoride concen-
city in northeastern Inner Mongolia, China. Until October 10, 2001, tration. Recovery rate of this method was in the range of 95105%.
Hulunbuir was administered as a League. Hulunbuir is divided into The quantitation limit of this method is 0.05 mg/L.
13 different country-level jurisdictions: one district, ve country- Water samples were collected from small-scale central water
level cities, four banners and three autonomous banners [19]. Many supply system and tube wells with handy pump respectively and
cross-sectional studies [2022] showed that uoride concentration kept in 4 C until used for analysis. The Institute for Endemic Fluoro-
in drinking water in this area had been higher than the upper limit sis Control, Center for Endemic Disease Control, China CDC, using a
of 1 mg/L prescribed in Chinese Standards for Drinking Water Qual- national standardized method in China (WS/T 106-1999) [26], car-
ity [12] for a long period. Meanwhile, studies related to uoride ried out all analytical measurements for uoride in drinking water.
exposure in drinking water have found large number of children In the analysis, we mixed 5 ml water samples with 5 ml TISAB at
accompanied by dental uorosis in this region. In accordance with PH 5, using the F-ion selective electrode (Yingke Crystal Materials
the principles of matching such social and natural factors like eco- Company) to detect those samples. All the samples were analyzed
nomic situation, educational standard and geological environments in twice (independent aliquots), and the means of two aliquots
as much as possible, we conducted our investigation by randomly were calculated to derive the uoride concentration in drinking
identifying 340 subjects who were aged from 7 to 14 from four ele- water. Quality assurance validation was obtained through periodic
mentary schools among four nearby sites-Mianduhe Town, Donghu analysis of National Institute for Environmental Reference Mate-
District, Nan District and Zhalainuoer Country in Manzhouli City in rials (IERM, Beijing) Standard Reference Material of water-based
Hulunbuir according to the Inner Mongolia Statistical Yearbook in uoride (3.47 0.21 mg/L). The quantitation limit of this method is
2009 [23] (Fig. 1). These four elementary schools chosen to carry out 0.2 mg/L.
our investigation appear to be very similar in teaching quality based
on the information provided by local educational bureau. None of
these four sites was exposed to potential neurotoxic that are recog- 2.3. Standards for detection of dental uorosis
nized as contaminates inuencing IQ value, like arsenic in drinking
water [13], nor delimitated into endemic areas of iodine deciency Our investigation adopted Deans index [27] recommended by
disorders. For the current study, we nally excluded ve children WHO to diagnose dental uorosis. An individuals uorosis condi-
who had lived in these areas for less than 1 year and four children tion is based on the most severe form of uorosis found on two or
who did not consent to take IQ test, resulting in 331 subjects eligi- more teeth. An individuals dental status can be classied into six
ble for our study. The institutional review board of Harbin Medical parts: normal, questionable, very mild, mild, moderate and severe.
University approved the study, and all the parents or guardians The same professional examiner who was unaware of childrens
provided written informed consent. uoride exposure status was specied to conduct all the testing
measurements to guarantee the accuracy and consistency for diag-
nostic criteria.
2.2. Collection and analysis of water and urine samples
Instant urine samples were collected using 15 ml tubes and kept 2.4. Assessments of intelligence
in 18 C until used for analysis. All collection tubes were carefully
washed with detergent before immersing in 10% aqueous nitric Children were administered to take the Combined Ravens Test-
acid solution for 8 h and then washed in distilled water for 3 times The Rural in China (CRT-RC3) [28] to evaluate their intellectual
in accordance with the national standard of China (GB/T 5750.2- ability. The seven categories of this test scores are as follows:
2006) [24]. The Institute for Endemic Fluorosis Control, Center for 69 retarded (low); 7079 borderline (below average); 8089 dull
Endemic Disease Control, China CDC, using a national standard- normal (low average); 90109 normal (average); 110119 high
ized method in China (WS/T 89-1996) [25], carried out all analytical normal (high average); 120129 superior (good); 130 very supe-
measurements for urine uoride. In the procedure of analysis, we rior (excellent).
1944 Y. Ding et al. / Journal of Hazardous Materials 186 (2011) 19421946
Table 2
Age, sex, IQ and urine uoride levels against dental uorosis condition among children in Hulunbuir, China.
Normal (N = 136) Questionable (N = 54) Very mild (N = 74) Mild (N = 39) Moderate (N = 28)
Table 3
The relationship between dental uorosis and urine uoride levels.a
Q1 Q2 Q3 Q4
0.389 0.12 0.676 0.07 1.035 0.15 2.058 0.62
Sample number
Dental uorosis 22 32 40 47
Normalb 61 50 43 36
OR value 1.77 2.58 3.62
95% CI 0.923.43 1.354.94 1.886.95
a
CochranArmitage test for trend was used to evaluate the association between dental uorosis and urine uoride levels (Z = 4.099, P < 0.0001).
b
Normal group included normal and questionable status of dental uorosis..
IQ Differences
from Mean Value
10
-5
-10
0 0.5 1 1.5 2 2.5 3
Urine Fluoride Concentration (mg/L)
Fig. 2. The relationship between IQ differences and urine uoride concentrations. Multiple linear regression model was carried out to conrm the association of urine uoride
exposure with IQ scores (F = 9.85, P < 0.0001).
urine uoride levels. Moreover, mean IQ scores of the last ve The results in our investigation were derived from full range of
groups were primarily below the mean value of total IQ scores. urine uoride concentrations based on individual exposure con-
Obviously, the data showed a negative doseresponse relationship ditions and the usage of multiple linear regression model was
between urine uoride levels and IQ scores. Multiple linear regres- very accurate to estimate the doseresponse relationship between
sion model that included age as covariate variable was carried childrens IQ and urine uoride exposure levels. In addition, the
out to further conrm the association of urine uoride exposure majority of children involved in this investigation were boarding
with IQ scores. Adjusted estimate (95% condence interval) of the students that balanced educational background and ordinary learn-
effect of urine uoride exposure on IQ test scores is a decrease ing behavior well between participants. Nevertheless, it should be
of 0.59 (1.09, 0.08) points in 1 mg/L increase of urine uoride recognized that the limitation of this study was its disability to
concentration (P < 0.0001). In other words, an increase in the urine describe the inuence of confoundings related to parents on chil-
uoride concentration of 1 mg/L associated with a decrease of 0.59 drens intelligence. The present investigation was initially carried
IQ scores. out to investigate intellectual ability of children exposed to low
Many literatures [5,13,32] have shown that exposure to high uoride levels in drinking water. We will study carefully the corre-
levels of uoride in drinking water associate with decits towards lation of childrens IQ with urine uoride exposure including other
childrens intelligence. These results were mainly illustrated by covariates, especially the ones related to parents, such as parents
comparing mean IQ scores in different exposure groups that were educational attainment, mothers age at delivery, mothers intelli-
selected based on uoride concentrations in drinking water. Com- gence and household income [3436] in future works.
pared to external exposure that is distinct in person due to The association of dental uorosis with childrens IQ scores is
individual difference in the absorption rate, urine uoride con- presented in Table 4. Number of children with IQ 89 did not have
sidered as internal exposure can truly reect the exposure levels signicant differences (2 = 2.362, df = 2, P = 0.307) among normal,
and preventing some negative inuences from external exposure. very mild and mild group of dental uorosis. Actually, the mean
Meanwhile, the association between levels of internal exposure IQ score in the mild group was higher and the number of chil-
and specic effect is more stable and consistent [33]. Our study dren with IQ 89 was less than the two of normal and very mild
demonstrated clearly that, across the full range of urine uoride groups. Despite the mean value of IQ in moderate dental uoro-
and using a measure to focus on individuals IQ scores, higher urine sis group had no signicant difference against the other groups
uoride levels were associated with decits of intellectual perfor- (F = 0.71, P = 0.548), percentage of childrens number with IQ 89
mance, even when the external exposure levels were not relatively was much higher.
high.
The characteristic of ecological investigation makes it unavoid- Table 4
able to select subjects in different regions for possession of the The association of dental uorosis condition with IQ scores.
different exposure levels of uoride in drinking water. From a Dental uorosis Number IQ scores
general standpoint, childrens intelligence is very susceptible to
many social and natural factors like economic situation, culture Mean SD IQ 89 (%)
and geological environments. Therefore, it seems difcult to deter- Normala 190 103.77 13.61 23 (12.11)
mine whether the difference of childrens IQ scores in two different Very mild 74 101.70 13.68 12 (16.22)
Mild 39 107.36 13.62 2 (5.13)
regions is caused by the uoride exposure or other factors. To
Moderate 28 103.27 13.68 6 (21.43)
reduce the possibility of interruption of intellectual confounding
a
factors, we limited this survey in only one region-Hulunbuir City. Normal group included normal and questionable status of dental uorosis.
1946 Y. Ding et al. / Journal of Hazardous Materials 186 (2011) 19421946
Fomons study [37] suggested that the occurrence of dental u- [9] S. Suthar, V.K. Garg, S. Jangir, et al., Fluoride contamination in drinking water
orosis was very sensitive to uoride toxicity, which made people in rural habitations of Northern Rajasthan, India, Environ. Monit. Assess. 145
(2008) 16.
exposed to lower dose of uoride got dental uorosis in their early [10] Q.Q. Tang, J. Du, H.H. Ma, et al., Fluoride and childrens intelligence: a meta-
childhood. On the other hand, the pace of development of childrens analysis, Biol. Trace Elem. Res. 126 (2008) 115120.
intelligence is comparatively slow and factors affecting intellectual [11] M. Liu, C. Qian, Effect of endemic uorosis on childrens intelligence develop-
ment: a meta analysis, Chin. J. Contemp. Pediatr. 10 (2008) 723725.
ability are much more than dental uorosis. Therefore, children [12] Ministry of Health of the Peoples Republic of China, Standards for Drinking
with very mild or mild dental uorosis probably have no difference Water Quality (GB 5749-2006), 2006.
on intellectual performance against normal children. Although we [13] S.X. Wang, Z.H. Wang, X.T. Cheng, et al., Arsenic and uoride exposure in drink-
ing water: childrens IQ and growth in shanyin county, shanxi province, China,
did not explore the biological mechanisms of this nding, there was Environ. Health Perspect. 115 (2007) 643647.
an animal experiment [3] suggesting that a relatively low level of [14] S.S. Liu, Y. Lu, Z.R. Sun, L.N. Wu, et al., The investigation of childrens intelligence
uoride exposure (100 mg/L in drinking water for 6 weeks) which in high uoride area, Chin. J. Control End. Dis. 15 (2000) 231232.
[15] J.P. Ruan, A. Brdsen, A.N. strm, et al., Dental uorosis in children in areas
could cause dental uorosis had little impact to weaning rats on
with uoride-polluted air, high-uoride water, and low-uoride water as well
their behavior disruption. However, the situation is quite different as low-uoride air: a study of deciduous and permanent teeth in the Shanxi
in children with moderate dental uorosis condition, because the province, China, Acta Odontol. Scand. 65 (2007) 6571.
severer condition of dental uorosis is, the higher exposure to u- [16] J. Narbutaite, M.M. Vehkalahti, S. Milciuviene, Dental uorosis and dental caries
among 12-yr-old children from high- and low-uoride areas in Lithuania, Eur.
oride in environment it means to children that can cause decits J. Oral Sci. 115 (2007) 137142.
in the development of intelligence. Hence, the explanation seems [17] G.S. Li (Ed.), Pathogenesis of Endemic Disease, Science Press, Beijing, 2004, pp.
logical and coherent that the proportion of children with severer 165173.
[18] H. Spencer, I. Lewin, E. Wistrowski, et al., Fluoride metabolism in man, Am. J.
dental uorosis condition in relatively low IQ scores is much more Med. 49 (1970) 807813.
likely to be larger than that of normal children. [19] Q.T. Hu (Ed.), Inner Mongolia Today: Hulun Buir, Inner Mongolia Peoples Pub-
lishing House, Hohhot, 1997, pp. 128129.
[20] Z.Y. Liu, S. Liu, S.Y. Guo, The analysis of the rusults of rural drinking water quality
4. Conclusions monitoring in zhalainuoer district, Manzhouli city, Chin. Prev. Med. 10 (2009)
427428.
Overall, our study suggested that low levels of uoride exposure [21] Q.B. Liu, Z.J. Wang, X.H. Liu, et al., The radiological difence of drinking brick-
tea type uorosis and drinking water type uorosis in Hulunber city, inner
in drinking water had negative effects on childrens intelligence and Mongolia, Chin, J. Control End. Dis. 22 (2007) 89.
dental health. The results also conrmed the doseresponse rela- [22] H.R. Li, Q.B. Liu, W.Y. Wang, et al., Fluoride in drinking water, brick tea infusion
tionships between urine uoride concentrations and IQ scores as and human urine in two counties in Inner Mongolia, China, J. Hazard. Mater.
167 (2009) 892895.
well as dental uorosis condition. Either a small decline in IQ scores [23] National Bureau of Statistical of China, Inner Mongolia Statistical Yearbook,
or the sickness of dental uorosis can lead a profound inuence for 2009.
individuals on their developments. Thus, these ndings may have [24] Ministry of Health of the Peoples Republic of China, Standard Examination
Methods for Drinking Water-Collection and Preservation of Water Samples
policy implications for a country like China to put more effort on
(GB/T 5750.2-2006), 2006.
the water improving and deuoridation projects to alleviate toxic- [25] Ministry of Health of the Peoples Republic of China, Determination of Fluoride
ity of long-term effects of uoride exposure to local residents and in Urine-ion Selective Electrode Method (WS/T 89-1996), 1996.
their offspring. [26] Ministry of Health of the Peoples Republic of China, Method for Determination
of Fluoride in Drinking Water of Endemic Fluorosis Areas (WS/T 106-1999),
1999.
Acknowledgements [27] H.T. Dean, The investigation of physiological effects by the epidemiological
method, in: F.R. Moulton (Ed.), Fluoride and Dental Health, American Asso-
ciation for the Advancement of Science, Washington, DC, 1942, pp. 2331.
This research was supported by National Natural Science Foun- [28] D. Wang, M. Di, M. Qian, A Report on the third revision of combined Ravens
dation of China (Project Nos. 3057161and 30800956). The authors Test (CRTC3) for Children in China, Chin. J. Clin. Psychol. 15 (2007) 559568.
declare they have no competing nancial interests. [29] D.L. Wu, Y.L. Li, The investigation of the total amount of fIuoride intake with cor-
relative dental uorosis polluted by burn coal in the epidemic fIuorosis districts,
Chin. J. Prev. Med. 24 (1990) 15.
References [30] Q.Y. Xiang, L.S. Chen, C.S. Wang, Study on the bench mark dose of urine uoride
in children and its relaonship to the prevalence of dental urosis, Chin. J.
[1] C.X. Wu, X.L. Gu, Y.M. Ge, J.H. Zhang, et al., Effect of high uoride and arsenic Control End. Dis. 20 (2005) 6871.
on brain biochemical indexes and learning-memory in rats, Fluoride 39 (2006) [31] S.D. Heintze, J.R.D.M. Bastos, R. Bastos, Urinary uoride levels and prevalence of
274279. dental uorosis in three Brazilian cities with different uoride concentrations
[2] Y.M. Shivarajashankara, A.R. Shivashankara, P.G. Bhat, et al., Histological in the drinking water, Commun. Dent. Oral Epidemiol. 26 (1998) 316323.
changes in the brain of young uoride-intoxicated rats, Fluoride 35 (2002) [32] L.B. Zhao, G.H. Liang, D.N. Zhang, et al., Effect of a high uoride water supply on
1221. childrens intelligence, Fluoride 29 (1996) 190192.
[3] P.J. Mullenix, P.K. Denbesten, Ann Schunior, et al., Neurotoxicity of sodium [33] L.M. Li, The Epidemiology, fth ed., Peoples Medical Publishing House, Beijing,
uoride in rats, Neurotoxicol. Teratol. 17 (1995) 169177. 2003.
[4] WHO, Fluorides, Environmental Health Criteria, vol. 227, WHO, Geneva, 2002. [34] M. Fulton, G. Thomson, R. Hunter, et al., Inuence of blood lead on the ability
[5] M.H. Trivedi, R.J. Verma, N.J. Chinoy, et al., Effect of high uoride water on and attainment of children in edinburge, Lancet 329 (1987) 12211226.
intelligence of school children in india, Fluoride 40 (2007) 178183. [35] R.L. Caneld, C.R. Hederson Jr., et al., Intellectual impairment in children with
[6] Y.X. Chen, F.L. Han, Z.L. Zhou, et al., Research on the intellectual development blood lead concentrations below 10 g per deciliter, New Engl. J. Med. 348
of children in high uoride areas, Fluoride 41 (2008) 120124. (2003) 15171526.
[7] D.J. Sun, Surveillance on endemic uorosis of drinking water type in China: [36] T.A. Jusko, C.R. Henderson Jr., B.P. Lanphear, et al., Blood lead concentra-
a two-year report of 2003 and 2004, Chin. J. Epidemiol. 26 (2007) 161 tions<10 g/dL and child intelligence at 6 years of age, Environ. Health Perspect.
164. 116 (2008) 243248.
[8] V. Shitumbanuma, F. Tembo, J.M. Tembo, et al., Dental uorosis associated [37] S.J. Fomon, J. Ekstrand, E.E. Ziegler, Fluoride intake and prevalence of dental
with drinking water from hot springs in Choma district in southern province, uorosis: trends in uoride intake with special attention to infants: review
Zambia, Environ. Geochem. Health. 29 (2007) 5158. and Commentory, J. Public Health Dent. 60 (2000) 131139.