Home Physical Sciences Effect of excess Fluoride consumption on Urine-Serum Fluorides, Dental state and Thyroid Hormones among children in “Talab Sarai” Punjab Pakistan
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Effect of excess Fluoride consumption on Urine-Serum Fluorides, Dental state and Thyroid Hormones among children in “Talab Sarai” Punjab Pakistan

  • Sadia Zulfiqar , Humayun Ajaz , Shafiq ur Rehman EMAIL logo , Shan Elahi , Amer Shakeel , Farhat Yasmeen and Shehnila Altaf
Published/Copyright: March 18, 2020
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Open Chemistry
From the journal Open Chemistry Volume 18 Issue 1

Abstract

190 children aged 7-18 years from an endemic fluorotic village “Talab Sarai (n = 130) and a non-fluorotic, control, village “Ottawa” (n = 60) were selected for comparison. Children were examined for fluoride (F-) concentration in drinking water, urine, and serum as well as Dental fluorosis (DF) and thyroid hormone levels. The mean concentration of water fluoride (WF) in the sample group was 6.23 mg/L, urine fluoride (UF) 3.38 mg/L, and serum fluoride (SF) 0.21 mg/L, while DF was 93.07%. Significant elevations (P = 0.000) in the concentration of all these four variables were observed in sample group children as compared to control. Mean Free Tetra-iodothyronine (FT4), Free Tri-iodothyronine (FT3) and Thyroid Stimulating Hormone (TSH) concentrations in the sample group were 16.64pmol/L, 5.57 pmol /L and 4.41 mlU/L, respectively. No marked difference in FT4 (P = 0.1) was noted, while significant elevations in FT3 and TSH (P = 0.000) were found in the sample relative to the control group. 80% of the children displayed clear thyroid hormonal derangements, with 36.92% having high TSH and 43.07% with FT3 and FT4 disorders. A moderate to strong correlation among WF, UF, SF and DF (r = 0.94, 0.60, 0.60, 0.72) and a very strong correlation between WF and TSH (r = 0.9) were observed. Our results suggest that excess F- level that is four times greater than the “safe limit” is not only increasing fluoride concentration in body fluids but is also affecting thyroid hormones in 4 out of 5 children which could lead to abnormal physical and mental growth in later developmental stages.

Keywords: Water fluoride; Urine and Serum fluorides; Dental fluorosis; FT4; FT3 TSH

1 Introduction

Fluoride (F-) is micronutrients that is widely disseminated in the biosphere. Once it is ingested through the gastro intestinal tract, calcified tissues quickly absorb it. A very serious health complication associated with high F-consumption is fluorosis, which involves mottled tooth enamel, also known as dental fluorosis (DF), in early stages and bone deformity (skeletal fluorosis) later on [1]. DF is most prevalent in regions of the world where F-concentrations in household drinking water are greater than 1 mg/L.

Ground water with elevated F- levels occur in various parts of the world. As reported by the World Health Organization (WHO) in 2006, there are more than 29 countries (both developed and developing) which are endemic for fluorosis across the world [2]. Fluorosis prevalence of approximately 32% has been documented in various regions of the world [3].

F- concentrations of less than 1 ppm are beneficial for decreasing dental caries, but greater than 2 ppm result in accumulation of fluoride in the body, affecting teeth, bones and, most importantly, thyroid hormone production [1].

Thyroid hormones regulate body temperature, appetite, energy levels, growth, skeletal development, muscle tone and agility, cardiac rate, fluid balance, blood sugar levels, central nervous system functions, bowel functions, blood fat, carbohydrate and protein metabolism, and many other factors. Research has shown that the thyroid gland is the body organ that is most sensitive to F- [4]. Desun elaborated the abundant effects of F- on the synthesis of thyroid hormones [5], and. Yaming reported that the long run consumption of F- is a risk factor for the development of thyroid problems [6]. Lin and Wu demonstrated an elevation of TSH in mice, rats and pigs due to excessive F- intake [7,8]. Most significantly, studies have shown that interference of F- with thyroid hormone metabolism is a potential source of decline in brain activities and abnormal development in children [9].

Approximately sixty types of industries are contaminating air and water with excess F-, for instance, chemical production units, waste puddles, bricks manufacturing, and aluminum fertilizers as well as , steel, glass, tile, enamel, pottery, cement, metal casting, welding and brazing and magnesium foundries [10,11]. However, the major source of F- consumption is drinking water: foods prepared with F- contaminated water can make a significant addition to F- ingestion, especially in teenagers [12].

Dietary intake has currently been established as a path which can produce DF [13], which is an extremely common disorder. It is, characterized by hypo mineralization of tooth enamel caused by ingestion of excess F- during enamel formation. In moderate to severe fluorosis, teeth are physically damaged.

In addition to food, even salt and other, common spices and food dressings can be sources of F- accumulation in body. The concentration of F- content in tea is quite high among drinks and showed a range from 122-260 ppm in various brands with a mean of 186 ppm [14]. F- containing toothpaste is another important source of excess F- intake. Usually up to 20% toothpaste is absorbed per brushing, and on an empty stomach 100% F- gets absorbed.

Ground water with elevated F- level (> 1.5 ppm) is commonly observed in India, China, Sri lanka, Spain, Italy, and the West Indies. One of the most well-known high F- belts extends along the East African Rift from Eritrea to Malawi. A second belt passes through Iraq, Iran, Afghanistan, Pakistan, India, Northern Thailand and China. Identical belts exist in the Americas and Japan, and represents a potential source of increased F- in drinking water [2].

“Non-ionic fluoride” is the main form in which F- exist in human serum. Many studies have depicted a positive correlation between water and serum fluorides and their influence on thyroid hormones [13].

Some, very limited, studies from ‘Punjab,’ particularly from the its rural areas, are available regarding excess F- in water and body fluids [16,17,18], but their effect on thyroid hormones has not yet been studied. In order to prevent F- toxicity, it is necessary to analyze the ground water of fluorosis- affected regions and to study its consequences on the natives, particularly children in different stages of puberty, as most of the growth and development takes place during this period.

One such village, “Talab Sarai,” is examined in present study. It is located 4.95 km southwest of “Manga Mandi,” a known endemically fluorotic territory. This village was chosen due to very high F- in ground water, excessive teeth browning, and common symptoms of skeletal fluorosis in children. In this area, up till now, no such work has been available to shed light on concentrations of F- in household drinking water including: its levels in human urine and serum, especially in children, and its relation to dental deformities and thyroid aberrations, if any. Therefore, the purpose of this study was to determine the concentration of F- in ground water, urine and serum of the studied subjects and the magnitude of DF and level of thyroid hormones along with their derangements, and then to compare and correlate these parameters with a control group of the same age and socioeconomic conditions from a non-fluorosis territory .

2 Experimental

2.1 Subject Selection

Two villages about 90.4 km apart, namely Talab Sarai (TbS) and Ottawa (OTW), were selected for examination. TbS is situated in an endemically fluorotic territory with prominence of excess F-, mottled enamel and joint stiffness in the affected population. Ottawa, approximately 65 km from Lahore, was selected for control because it is a non-fluorosis, non-endemic village. A total of 190 children aged 7-18 years were chosen randomly from both villages after initial water testing. Written and informed consent of participation was obtained from the guardians/parents of every child. Those who did not agree, who were suffering from any health problem, or were not residents by birth were excluded from the study. The clinical protocol for this work was approved by the ethical committee of Institute of Chemistry, University of the Punjab. Along with collection of water, urine and serum from children, teeth of every child were examined by a dentist for the estimation of mottled enamel.

2.1.1 Reagents and Instruments

The following chemicals and instruments were used during the course of study:

Fluoride Ion Selective (combination) Electrode (Hanna HI 4110), pH/ISE/mV Meter (Hanna HI 4222), Electrode Holder (Hanna HI 76404), Magnetic Stirrer (Hanna HI 180), Plastic Beakers (Hanna HI 740036 P), Gamma Counter (Cap-RIA 16 CAPINTEC; Inc. USA), Vortex type Mixer (Barnstead Internationals-M 63210-33), Shaker (Gallenkamp- OSM-747), 500 UL Semi Programmed Pipette (Eppendorf), Small Test Tubes (Specially designed 5cm long, ɸ 14 mm, Fluoride Standard Solution 1000 ppm (Hanna HI 4010-03),Total Ionic Strength Adjustment Buffer (TISAB II, Hanna HI 4010-00), Reference Fill Solution (Hanna HI 7075), Deionized Water (<18MΩ/cm) for dilutions, FT4, FT3, TSH kits by Immunotech Inc. (Beckman).

2.1.2 Method used for Fluoride Analysis

F- measurements in water and body fluids were carried out with an F- ion selective (combination) electrode. The use of an ion selective electrode (ISE) is not very common in Pakistan, but this methodology was preferred because of its lower expense relative to other analytical procedures, such as Atomic Absorption Spectroscopy or Ion Chromatography. This method is simple and robust, and provides frequent measurements. It has wide range of applications and can be used over a broad concentration range. It provides accurate measurements in the range of 0.01 – 127,000 ppm.

2.2 Sampling and Testing

2.2.1 Water Collection

Collection of water samples was done in three successive visits from May-August 2017. A sample of drinking water was collected from each child’, s house, typically from the hold tap, which involves a (hand pump or electric motor reaching tube wells of the Water and Sanitation Agency (WASA). Sampling was done in prewashed, pre-cleaned, pre-coded polyethylene bottles. At sampling sites, each bottle was rinsed thrice with sampling water, and the tap was kept open for three minutes to get a representative sample. Plastic gloves were used to prevent any hand contamination in the sample. After collection each sample’s color, odour, and taste was recorded by physical examination while pH was determined immediately with a pH meter (Hanna HI 4222). All samples were moved to the laboratory one the same day and frozen at -20°C. They were thawed and analyzed for F- content within a week.

2.2.2 Urine Collection

Clean and coded polyethylene containers containing 0.2 g EDTA were provided to each participant, and casual urine samples were obtained “on the spot.” Mothers of children aged less than 12 helped their children, while older children provide urine samples themselves. Each urine sample, after packing in a separate polyethylene zipper, was placed in an ice box and moved to the laboratory and analyzed for F- content on the collection day.

2.2.3 Blood Serum Collection

With the help of new sterilized syringes, 5-7 ml blood was drawn intravenously from each participant. For clotting purpose, blood was immediately transferred into open glass vials for about 30 minutes. Then they were centrifuged at 4000 rpm for 10 minutes, which resulted in the separation of serum from blood cells. Serum was transferred to another vial and capped. Serum vials were kept frozen at -20°C until analysis [19].

2.2.4 Dental Fluorosis Survey

Due to the very common occurrence of teeth browning at TbS, an experienced dentist examined the teeth of all participating children in both of the villages. Teeth analysis was carried out with the help of mouth mirror, forceps and probe under ordinary light. Dean’s fluorosis index (revised six-point scale (1942)) was used to evaluate the grade of DF [20] according to the following scale.

Dean’s fluorosis index
Levels012345
DescriptionNormalQuestionableVery mildMildModerateSevere

2.3 Statistical Analysis

In order to compare the means of water, urine, serum fluorides, DF, FT4, FT3 and TSH among sample and control groups, student t-test using unequal variances was applied. 95% confidence interval (CI) and P-value less than 0.05 was assumed to indicate statistical significance. The Kolmogorov -–Smirnov test was used in order to determine the normality distribution of the data wherever required. For finding correlations among WF, UF, SF, DF, FT4, FT3 and TSH, ‘Pearson correlations’ and “regression analyses” were used at same CI and P-value. For comparing different groups of D.F with FT4, FT3 and TSH, means, standard deviations, student t-tests and ANOVA (single factor) were used. In order to find the variation between male/female and low, normal and high concentrations of FT4, FT3 and TSH, Chi square tests were employed.

2.4 Sample Preparation for Fluoride Analysis

A F- (ISE) (combination type (HI-4110) was used for the determination of F- in water, urine and serum. Deionized water with resistance less than 18 Ω/cm was used for dilution. The F- ISE was first calibrated with different F- standards and then analysis of individual samples was performed. The electrode was recalibrated with at least three F- standards after 40 minutes of use to ensure accurate measurements. Between samples, the electrode was washed with deionized water and dried before the next use.

2.4.1 Water Samples

To one part of sample, one part of total ionic strength adjustment buffer (TISAB II) was added. F- standards for the analysis were kept in the range of 0.1- 10 mg/L [16]. WF outcomes were presented as less than 10% Coefficient of variation (C.V) of the impression profile. To evaluate accuracy and validity of applied methods, water samples were spiked with F- standard dilutions. Recoveries were measured in the 0.2-3.2g range, and they resulted in spreads of 96.7-99.8% (mean 99%).

2.4.2 Urine Samples

For UF estimation, the same ratio of urine sample and TISAB II was used. A 0.5-5.0 mg/L range of F- standards was maintained to cover the wide range of F- concentration in the samples. Outcomes of the determination were presented as 10% C.V of impression profile. To measure accuracy and validation of the method, urine samples were spiked with F- standards. Mean percentage recovery was 99.1% in a range of 98-101.3%.

2.4.3 Serum Samples

Blood serum and TISAB II were combined in 1:1 ratios for estimation of F- in serum. For calibration purpose, F-standards were prepared in the range of 0.01-1 mg/L. In inter and intra assay precision, the means and C.V were 0.23% and 0.22%, respectively. Mean percentage recovery was observed to be 98%, with a range of 96-101.4%, which supports the accuracy and validity of the applied method.

2.5 Free T4, T3 and TSH Determination

Competetive Radioimmunoassays (RIA) and sandwitch-type Immunoradiometric Assays (IRMA) were used to estimate Free T4, T3 and TSH levels by using commercial kits of Immunotech Inc. (Beckman, Czech Republic). A computerized Gamma counter (Cap- RIA 16,CAPINTEC; Inc.USA) was used for the computation of radioactivity, adjustment of standard curves and sample analysis. Commercially- obtained control sera of at least three different concentrations were incorporated in each run to estimate the assay reliability. A maximum 10% C.V of the impression profile was used to express the results of RIA and IRMA.

3 Results and Discussion

One hundred and ninety children aged 7-18 years with average age of 12.40 ± 3.3 years were examined during the study. The sample group included 130 children (80 male and 50 female) from an endemic fluorosis village, Talab Sarai (TbS), which is near Manga Mandi. The control group was selected from a non-fluorosis village: Ottawa (OTW), 65 km from Lahore. The control group consisted of 60 children (30 male and 30 female) with an average age of 12. 13 ± 3.2 years.

At TbS, 84.6% water samples had F- concentrations greater than 1.5 mg/L (WHO permissible limit). In the control group, WF ranged between 0.13 and 1.1 mg/L.

The results (Table 1) indicated that the concentration of F- in the drinking water of the sample population was significantly (P = 0.000) elevated relative to that of the control group. The mean concentration of UF in sample and control villages is also presented in Table 1. Levels of urinary fluoride in TbS was clearly higher than that of the control (P= 0.000). 90.5% of urine samples from the sample village had F- concentrations more than the normal upper limit of 1 mg/L as defined by Jaganmohan [21].

Table1

Level of Fluoride in Water, Urine and Serum.

Village sNumber (No.) of samplesWater Fluoride (mg/L)Urine Fluoride (mg/L)Serum Fluoride (mg/L)
TbS1306.23 ± 3.31[a]3.38 ± 1.470.21 ± 0.1
0.1-14.1[b]0.1 -7.50.01 – 1
CNTL600.54 ± 0.151.52 ± 0.430.05 ± 0.04
0.13 -1.10.52 - 2.30.017- 0.45

  1. Note: Water Fluoride P = 0.000 (student t-test using unequal variances)

    Urine Fluoride P = 0.000

    Serum Fluoride P = 0.000

A scatter plot of WF vs. UF from the sample village is shown in Figure 1. The Pearson correlation coefficient (r = 0.94) suggested a very strong correlation between the two; in other words, these data are consistent with the idea that an excess amount of F- in water is a major cause of F- elevation in urine of children.

Figure 1 Scatter chart between Water and Urine Fluoride of sample Group Pearson Correlation Coefficient r = 0.94.
Figure 1

Scatter chart between Water and Urine Fluoride of sample Group Pearson Correlation Coefficient r = 0.94.

The mean SF in the sampled subjects was 0.21± 0.12, and 72.3% (n = 94/130) of subjects were found to have SF levels higher than the standard Limit [22]. These results are further strengthened by the clear difference in the SF concentrations of sample and control groups (P = 0.000, Table 1). A scatter chart of WF vs. SF exhibited a positive correlation (r = 0.56). A similar outcome was observed in the relationship between UF and SF (r = 0.60) of the sample group. These results suggest that elevated F- in drinking water is a main cause of excess F- excretion by the human body.

Concentrations of FT4 in children of “TbS and OTW” are presented in Table 2. Student t-test (unequal variances) showed no statistically significant difference (P = 0.10) in the mean concentration of FT4 between the two groups. Mean FT3 and TSH levels of sample versus control group showed clear differences, (P = 0.000, Table 2).

Table 2

FT4, FT3 and TSH Concentration in Serum of Subjects of the two Villages.

VillagesNo. of samplesMean FT4 (pmol/L)Mean FT3 (pmol/L)Mean TSH (mIU/L)
TbS13016.64 ± 3.785.57 ± 1.014.41± 2.29
8.5-33.53.34 -9.70.98-13.2
CNTL6017.55 ± 3.435.09 ± 0.532.36 ± 1.06
11.02-23.082.81-6.00.54- 6.12

  1. a = Mean ± Standard Deviation

    b = Range

    Note: FT4: P = 0.100 (student t-test using unequal variances)

    FT3: P = 0.000

    TSH: P = 0.000

The relationships of FT4 and, FT3 in serum with drinking WF among sample and control subjects displayed no statistically significant positive correlations; however, a strong positive relationship is seen between TSH and WF (r = 0.90, Figure 2).

Figure 2 Scatter chart between WF and TSH of sample Group r = 0.90.
Figure 2

Scatter chart between WF and TSH of sample Group r = 0.90.

To evaluate the levels of DF, all 190 participants were examined. 93.07% from TbS and 7% from OTW presented with this issue. The changes observed in tooth surfaces include white flecks, coverage of one quarter to one half of tooth surfaces with opaque paper white areas, marked wear on bitting surfaces, brown stains, convergent pits, and complete tooth surface damage.

Comparison of various degrees of DF (0-5) with their respective mean FT4, FT3 and TSH is presented in Table 3. Levels of mean FT4 varied considerably in DF levels 1-4, and mean TSH levels differed throughout the range of the fluorosis index, excepting level 3. FT3, on the other hand, displayed no apparent relationship to D.F.

Table 3

Comparison of Different Grades of D.F with FT4, FT3 and TSH in Sample Group.

D.FFT4FT3TSH
Grades(P-value)(P -value)(P -value)
1- 20.400.720.00
1-30.040.230.04
1-40.740.210.01
1-50.380.340.00
2-30.040.380.04
2-40.050.340.22
2-50.000.570.00
3-40.05---------------0.01
3-50.010.560.00
4-50.340.450.00

Comparison of mild, moderate and severe DF with FT4, FT3 and TSH by an “ANOVA single factor” test suggests a detectable difference between FT4 and the degree of DF but that this difference did not reach a statistically- significant level (F = 2.44, P = 0.09). The identical result is observed in the case of FT3 (F = 0.85, P = 0.43); however, in case of TSH, the difference was statistically significant (P < 0.05) (Figure 3). In TbS, severe (score 5) DF was observed most frequently (Figure 4), indicating a prominent influence of endemically fluorotic territory on tooth development. WF also presented a positive dose relation (r = 0.72) with DF, confirming the powerful influence of F- intake on tooth development. High, normal and low concentrations of FT4, FT3 and TSH by gender and age groups in TbS and control were also analyzed. The normal laboratory ranges of FT4, FT3 and TSH are 11.5-23 pmol/L, 2.5-5.8 pmol/L and 0.3-5 m IU/L, respectively [23]. Our results showed that 5,1 males (5 from TbS and 1 from control) and 2,1 females had elevated FT4, 23,1 males and 16,1 females had elevated serum FT3 while 24,1 males and 19,1 females had high serum TSH in TbS and controls group, respectively.

Figure 3 Comparison of Thyroid Hormones in Mild, Moderate and Severe D.F at TbS.
Figure 3

Comparison of Thyroid Hormones in Mild, Moderate and Severe D.F at TbS.

Figure 4 Percentage Distribution of Dental Fluorosis among Sample Group.
Figure 4

Percentage Distribution of Dental Fluorosis among Sample Group.

Both groups showed significant differences with respect to the number of children having elevated thyroid hormones (P = 0.000). The use of a Chi-square test indicated no statistically significant difference between males/females and level of FT4, FT3 and TSH in sample and control villages.

Concentrations of F- greater than 1.5 mg/L in drinking water have been shown to result in various kinds of fluorosis, renal and neurological abnormalities and myopathy [24,25]. In the present study, geological causes, fertilizers used in agriculture, and industrialization, particularly brick kiln units (dozens are in use in the surrounding area), are the major likely contributors of Fin ground water [26]. TbS lies on a well known F- belt, which is: rich in F- bearing minerals like fluorspar, cryolite fluorapatite and hydroxyapatite [27,28]. The weathering of these rocks and infiltration of rain through them increases the concentration of F- in ground water. All these sources added up to increase the level of F- in ground water (mean 6.23 mg/L at TbS as compared to 0.54 mg/L at the control site (OTW). Farooqi et al. (2007) found WF in the range of 2.47-21.1 mg/L in a nearby village, “Kalalanwala,” while Ahmed (2001) observed 86% water samples with fluoride concentrations greater than WHO limits (1.5 mg/L) in the same village [29,30].

This territory has a semiarid and subtropical continental climate characterized by sultry summer and cool winters. The mean temperature in summer in Punjab is 41°C [29]; in such climatic conditions, F- level in drinking water should not be more than 0.7 mg/L [31] because, the average water intake per child from April-August is 2.5 L, and 86-97% of F- from water directly becomes the part of body [32,33].

Fluoride toxication is most accurately computed in the form of urine and serum fluorides [34]. Normal limits of F- in urine and serum is 1.0 and 0.15 mg/L, respectively [21]. Kidneys are the main excretory organs for removal of absorbed fluoride via urine [6]. Chronic kidney problems are often seen in early aging society, and these problems lead to gradual declines of kidney function that may lead to permanent kidney failure, or even end-stage renal disease [35]. 3.38 mg/L (mean UF) and 0.21 mg/L (mean SF) in teenagers at TbS in this scenario is alarming.

The fact that very high fluoride concentrations in human body are induced from drinking water is strengthen by the positive correlations between WF-UF (r = 0.94),

WF-SF (r = 0.60) and UF- SF (r = 0.60). Similar findings are also reported by Qayyum et al. in “Sham Ki Bhatiyan,” a nearby village in Punjab, Pakistan [16,17].

About 50% of the F- intake becomes part of the calcified tissues within 24 hours [36]. This absorption is very active in adolescence and decreases with increases in age [8]. The present investigation displayed an increment in DF with an increase in household WF (r = 0.72). Viswanathan in South India also reported similar outcomes [8] under identical conditions. 93.07% mottled enamel was found in sampled children from TbS. It is not only a visible decoloration of tooth enamel but also a developmental disorder which indicates aberrant thyroid hormone metabolism. While comparing the serum free T4,T3 and TSH levels of sample group to those of controls, no significant alteration in FT4 level (P = 0.10) was seen but serum FT3 (P = 0.000) and TSH (P = 0.000) revealed clear differences between the two groups,

supporting the influence of SF on thyroid hormones. In the present investigation, weak to moderate, but statistically significant, correlations were found between SF-FT4, SF-FT3 and SF-TSH (r = 0.1, P =0.000, r = 0.14, P = and r = 0.60, P =0.000, respectively). These correlations support the role of SF in altering the level of thyroid hormones in the human body. In 2008, Wu observed analogous serum- thyroid correlations in animals [36].

In the present study, the effect of drinking water in elevating the thyroid hormones is noticed in TSH (r = 0.9, P = 0.005) but not in FT4 or FT3 : WF- FT4 (r = 0.1, P = 0.000) and WF- FT3 (r = 0.03, P = 0.000). Similar increases in TSH levels were observed by AK Shusheela in children living in an endemic fluorosis area in India [37]. According to the National Research Council (NRC), TSH is considered a “precise and specific barometer’ of thyroid status”. Fluoride could take part the subclinical hypothyroidism, which is a condition of “mild thyroid failure” marked by increased TSH and normal T3/T4.

Further compilation of results from this endemically fluorosis village indicated 79.23% well defined thyroid hormonal derangements in children: 36.92%, 30.77%, 5.38% had elevated TSH, FT3 and FT4 whereas 6.15% depicted low FT4 which give rise to following thyroid disorders:

  1. 23.85% (n = 31) had high TSH with normal FT3-FT4, which is: the first sign of thyroid malfunctioning known as “subclinical hypothyroidism”. Mild subclinical hypothyroidism in mothers can give rise to lower IQ and hearing impairment in children. As hearing development is under control of thyroid hormones, thyroid malfunctioning in late fetal and initial postnatal life severely affect the acoustic organ, as indicated from the deafness linked with congenital hypothyroidism. [38]

  2. 9.23% (n= 12) presented with high TSH-FT3 but normal FT4 which are the initial symptoms of “T3 Toxicosis”. This problem is associated with the elevation of T3 levels due to the disruption in deiodination of T4 to T3. The problem manifests in several ways, including anxiety, fatigue and weight loss [39].

  3. 3.85% (n = 5) presented with elevated FT4 but, normal FT3-TSH. These are the first signs of “Hyperthyroidism,” which gives rise to an elevated metabolic rate, which is: characterized by rapid heart rate, high blood pressure, weight loss, nausea, vomiting, and other signs.

  4. 2.31% (n = 3) had low FT4, high TSH and normal FT3. These levels are key indicators of primary hypothyroidism and iodine deficiency disorder, result in lethargy, depression and weight gain later on.

Identical hormonal abnormalities are also noticed in children of Dehli, India and as reported by the NRC (review of literature 2006) [37]. Such a large group of children with abnormal FT4, FT3 and TSH levels relative to controls groups (P = 0.000) suggests an important effect of high F- intake on thyroid function. Similar results are also expressed by Xiang, Susheela, and Singh regarding other regions of the world [41,37,41].

When comparing different degrees of DF (from normal to severe) with their respective mean FT4,FT3,TSH values, we noticed a significant alteration in FT4 concentrations in questionable- mild, very mild-mild, very mild- moderate, very mild- severe, mild-moderate and mild-severe grades on the fluorosis index (Table 3). No statistically significant difference in DF grades and FT3 concentration were obtained. DF and TSH revealed considerable differences in all grades except very mild-moderate levels (Table 3). Identical outcomes can be seen in F- and thyroid functions in two villages of China [42].

Comparison of mild, moderate and severe DF with their respective thyroid hormones present significant difference in mean TSH level. Identical outcomes were also noted by MB Hosur [43] in teenagers. These facts are advocating the role of mottled enamel as “developmental disorder that” is related to disturbance of thyroid activities.

4 Conclusion

It is obvious from the outcomes that the concentration of F- in drinking water of “Talab Sarai” is dangerously high, which is elevating its level in urine and serum of the resident adolescents. Increased F- in body fluids affects the production mechanism of thyroid hormones as this endocrine gland is the most F- sensitive organ in the human body. Results suggest that 93.07% teeth fluorosis and 80% thyroid hormone abnormalities in the sample area confirm excessive deterioration due to F- intoxication. Positive dose relationships between Fin water with all studied parameters (urine, serum, DF, thyroid hormones) strengthens our understanding of the immense role of F- towards abnormal growth, especially bones and teeth in children. There is a serious need to take preventive measures such as water purification and, use of calcium and, vitamin C, D and E supplements along with additional mapping of this endemic fluorosis territory.

  1. Conflict of interest: Authors declare no conflict of interest.

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Received: 2018-12-12
Accepted: 2019-07-30
Published Online: 2020-03-18

© 2020 Sadia Zulfiqar et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/chem-2020-0012
Keywords for this article
Water fluoride; Urine and Serum fluorides; Dental fluorosis; FT4; FT3 TSH
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Electrochemical antioxidant screening and evaluation based on guanine and chitosan immobilized MoS2 nanosheet modified glassy carbon electrode (guanine/CS/MoS2/GCE)
  3. Kinetic models of the extraction of vanillic acid from pumpkin seeds
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  11. Design, Synthesis and Characterization of Novel Isoxazole Tagged Indole Hybrid Compounds
  12. Comparison of kinetic and enzymatic properties of intracellular phosphoserine aminotransferases from alkaliphilic and neutralophilic bacteria
  13. Green Organic Solvent-Free Oxidation of Alkylarenes with tert-Butyl Hydroperoxide Catalyzed by Water-Soluble Copper Complex
  14. Ducrosia ismaelis Asch. essential oil: chemical composition profile and anticancer, antimicrobial and antioxidant potential assessment
  15. DFT calculations as an efficient tool for prediction of Raman and infra-red spectra and activities of newly synthesized cathinones
  16. Influence of Chemical Osmosis on Solute Transport and Fluid Velocity in Clay Soils
  17. A New fatty acid and some triterpenoids from propolis of Nkambe (North-West Region, Cameroon) and evaluation of the antiradical scavenging activity of their extracts
  18. Antiplasmodial Activity of Stigmastane Steroids from Dryobalanops oblongifolia Stem Bark
  19. Rapid identification of direct-acting pancreatic protectants from Cyclocarya paliurus leaves tea by the method of serum pharmacochemistry combined with target cell extraction
  20. Immobilization of Pseudomonas aeruginosa static biomass on eggshell powder for on-line preconcentration and determination of Cr (VI)
  21. Assessment of methyl 2-({[(4,6-dimethoxypyrimidin-2-yl)carbamoyl] sulfamoyl}methyl)benzoate through biotic and abiotic degradation modes
  22. Stability of natural polyphenol fisetin in eye drops Stability of fisetin in eye drops
  23. Production of a bioflocculant by using activated sludge and its application in Pb(II) removal from aqueous solution
  24. Molecular Properties of Carbon Crystal Cubic Structures
  25. Synthesis and characterization of calcium carbonate whisker from yellow phosphorus slag
  26. Study on the interaction between catechin and cholesterol by the density functional theory
  27. Analysis of some pharmaceuticals in the presence of their synthetic impurities by applying hybrid micelle liquid chromatography
  28. Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: the protective effect on periodontitis via reducing the release of IL-1β and TNF-α
  29. Incorporation of silver stearate nanoparticles in methacrylate polymeric monoliths for hemeprotein isolation
  30. Development of ultrasound-assisted dispersive solid-phase microextraction based on mesoporous carbon coated with silica@iron oxide nanocomposite for preconcentration of Te and Tl in natural water systems
  31. N,N′-Bis[2-hydroxynaphthylidene]/[2-methoxybenzylidene]amino]oxamides and their divalent manganese complexes: Isolation, spectral characterization, morphology, antibacterial and cytotoxicity against leukemia cells
  32. Determination of the content of selected trace elements in Polish commercial fruit juices and health risk assessment
  33. Diorganotin(iv) benzyldithiocarbamate complexes: synthesis, characterization, and thermal and cytotoxicity study
  34. Keratin 17 is induced in prurigo nodularis lesions
  35. Anticancer, antioxidant, and acute toxicity studies of a Saudi polyherbal formulation, PHF5
  36. LaCoO3 perovskite-type catalysts in syngas conversion
  37. Comparative studies of two vegetal extracts from Stokesia laevis and Geranium pratense: polyphenol profile, cytotoxic effect and antiproliferative activity
  38. Fragmentation pattern of certain isatin–indole antiproliferative conjugates with application to identify their in vitro metabolic profiles in rat liver microsomes by liquid chromatography tandem mass spectrometry
  39. Investigation of polyphenol profile, antioxidant activity and hepatoprotective potential of Aconogonon alpinum (All.) Schur roots
  40. Lead discovery of a guanidinyl tryptophan derivative on amyloid cascade inhibition
  41. Physicochemical evaluation of the fruit pulp of Opuntia spp growing in the Mediterranean area under hard climate conditions
  42. Electronic structural properties of amino/hydroxyl functionalized imidazolium-based bromide ionic liquids
  43. New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties
  44. Treatment of adhesions after Achilles tendon injury using focused ultrasound with targeted bFGF plasmid-loaded cationic microbubbles
  45. Synthesis of orotic acid derivatives and their effects on stem cell proliferation
  46. Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis
  47. Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives
  48. Adsorption kinetic characteristics of molybdenum in yellow-brown soil in response to pH and phosphate
  49. Enhancement of thermal properties of bio-based microcapsules intended for textile applications
  50. Exploring the effect of khat (Catha edulis) chewing on the pharmacokinetics of the antiplatelet drug clopidogrel in rats using the newly developed LC-MS/MS technique
  51. A green strategy for obtaining anthraquinones from Rheum tanguticum by subcritical water
  52. Cadmium (Cd) chloride affects the nutrient uptake and Cd-resistant bacterium reduces the adsorption of Cd in muskmelon plants
  53. Removal of H2S by vermicompost biofilter and analysis on bacterial community
  54. Structural cytotoxicity relationship of 2-phenoxy(thiomethyl)pyridotriazolopyrimidines: Quantum chemical calculations and statistical analysis
  55. A self-breaking supramolecular plugging system as lost circulation material in oilfield
  56. Synthesis, characterization, and pharmacological evaluation of thiourea derivatives
  57. Application of drug–metal ion interaction principle in conductometric determination of imatinib, sorafenib, gefitinib and bosutinib
  58. Synthesis and characterization of a novel chitosan-grafted-polyorthoethylaniline biocomposite and utilization for dye removal from water
  59. Optimisation of urine sample preparation for shotgun proteomics
  60. DFT investigations on arylsulphonyl pyrazole derivatives as potential ligands of selected kinases
  61. Treatment of Parkinson’s disease using focused ultrasound with GDNF retrovirus-loaded microbubbles to open the blood–brain barrier
  62. New derivatives of a natural nordentatin
  63. Fluorescence biomarkers of malignant melanoma detectable in urine
  64. Study of the remediation effects of passivation materials on Pb-contaminated soil
  65. Saliva proteomic analysis reveals possible biomarkers of renal cell carcinoma
  66. Withania frutescens: Chemical characterization, analgesic, anti-inflammatory, and healing activities
  67. Design, synthesis and pharmacological profile of (−)-verbenone hydrazones
  68. Synthesis of magnesium carbonate hydrate from natural talc
  69. Stability-indicating HPLC-DAD assay for simultaneous quantification of hydrocortisone 21 acetate, dexamethasone, and fluocinolone acetonide in cosmetics
  70. A novel lactose biosensor based on electrochemically synthesized 3,4-ethylenedioxythiophene/thiophene (EDOT/Th) copolymer
  71. Citrullus colocynthis (L.) Schrad: Chemical characterization, scavenging and cytotoxic activities
  72. Development and validation of a high performance liquid chromatography/diode array detection method for estrogen determination: Application to residual analysis in meat products
  73. PCSK9 concentrations in different stages of subclinical atherosclerosis and their relationship with inflammation
  74. Development of trace analysis for alkyl methanesulfonates in the delgocitinib drug substance using GC-FID and liquid–liquid extraction with ionic liquid
  75. Electrochemical evaluation of the antioxidant capacity of natural compounds on glassy carbon electrode modified with guanine-, polythionine-, and nitrogen-doped graphene
  76. A Dy(iii)–organic framework as a fluorescent probe for highly selective detection of picric acid and treatment activity on human lung cancer cells
  77. A Zn(ii)–organic cage with semirigid ligand for solvent-free cyanosilylation and inhibitory effect on ovarian cancer cell migration and invasion ability via regulating mi-RNA16 expression
  78. Polyphenol content and antioxidant activities of Prunus padus L. and Prunus serotina L. leaves: Electrochemical and spectrophotometric approach and their antimicrobial properties
  79. The combined use of GC, PDSC and FT-IR techniques to characterize fat extracted from commercial complete dry pet food for adult cats
  80. MALDI-TOF MS profiling in the discovery and identification of salivary proteomic patterns of temporomandibular joint disorders
  81. Concentrations of dioxins, furans and dioxin-like PCBs in natural animal feed additives
  82. Structure and some physicochemical and functional properties of water treated under ammonia with low-temperature low-pressure glow plasma of low frequency
  83. Mesoscale nanoparticles encapsulated with emodin for targeting antifibrosis in animal models
  84. Amine-functionalized magnetic activated carbon as an adsorbent for preconcentration and determination of acidic drugs in environmental water samples using HPLC-DAD
  85. Antioxidant activity as a response to cadmium pollution in three durum wheat genotypes differing in salt-tolerance
  86. A promising naphthoquinone [8-hydroxy-2-(2-thienylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione] exerts anti-colorectal cancer activity through ferroptosis and inhibition of MAPK signaling pathway based on RNA sequencing
  87. Synthesis and efficacy of herbicidal ionic liquids with chlorsulfuron as the anion
  88. Effect of isovalent substitution on the crystal structure and properties of two-slab indates BaLa2−xSmxIn2O7
  89. Synthesis, spectral and thermo-kinetics explorations of Schiff-base derived metal complexes
  90. An improved reduction method for phase stability testing in the single-phase region
  91. Comparative analysis of chemical composition of some commercially important fishes with an emphasis on various Malaysian diets
  92. Development of a solventless stir bar sorptive extraction/thermal desorption large volume injection capillary gas chromatographic-mass spectrometric method for ultra-trace determination of pyrethroids pesticides in river and tap water samples
  93. A turbidity sensor development based on NL-PI observers: Experimental application to the control of a Sinaloa’s River Spirulina maxima cultivation
  94. Deep desulfurization of sintering flue gas in iron and steel works based on low-temperature oxidation
  95. Investigations of metallic elements and phenolics in Chinese medicinal plants
  96. Influence of site-classification approach on geochemical background values
  97. Effects of ageing on the surface characteristics and Cu(ii) adsorption behaviour of rice husk biochar in soil
  98. Adsorption and sugarcane-bagasse-derived activated carbon-based mitigation of 1-[2-(2-chloroethoxy)phenyl]sulfonyl-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl) urea-contaminated soils
  99. Antimicrobial and antifungal activities of bifunctional cooper(ii) complexes with non-steroidal anti-inflammatory drugs, flufenamic, mefenamic and tolfenamic acids and 1,10-phenanthroline
  100. Application of selenium and silicon to alleviate short-term drought stress in French marigold (Tagetes patula L.) as a model plant species
  101. Screening and analysis of xanthine oxidase inhibitors in jute leaves and their protective effects against hydrogen peroxide-induced oxidative stress in cells
  102. Synthesis and physicochemical studies of a series of mixed-ligand transition metal complexes and their molecular docking investigations against Coronavirus main protease
  103. A study of in vitro metabolism and cytotoxicity of mephedrone and methoxetamine in human and pig liver models using GC/MS and LC/MS analyses
  104. A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity
  105. Erratum
  106. Erratum to: A one-step incubation ELISA kit for rapid determination of dibutyl phthalate in water, beverage and liquor
  107. Review Articles
  108. Sinoporphyrin sodium, a novel sensitizer for photodynamic and sonodynamic therapy
  109. Natural products isolated from Casimiroa
  110. Plant description, phytochemical constituents and bioactivities of Syzygium genus: A review
  111. Evaluation of elastomeric heat shielding materials as insulators for solid propellant rocket motors: A short review
  112. Special Issue on Applied Biochemistry and Biotechnology 2019
  113. An overview of Monascus fermentation processes for monacolin K production
  114. Study on online soft sensor method of total sugar content in chlorotetracycline fermentation tank
  115. Studies on the Anti-Gouty Arthritis and Anti-hyperuricemia Properties of Astilbin in Animal Models
  116. Effects of organic fertilizer on water use, photosynthetic characteristics, and fruit quality of pear jujube in northern Shaanxi
  117. Characteristics of the root exudate release system of typical plants in plateau lakeside wetland under phosphorus stress conditions
  118. Characterization of soil water by the means of hydrogen and oxygen isotope ratio at dry-wet season under different soil layers in the dry-hot valley of Jinsha River
  119. Composition and diurnal variation of floral scent emission in Rosa rugosa Thunb. and Tulipa gesneriana L.
  120. Preparation of a novel ginkgolide B niosomal composite drug
  121. The degradation, biodegradability and toxicity evaluation of sulfamethazine antibiotics by gamma radiation
  122. Special issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  123. Insight into the cadmium and zinc binding potential of humic acids derived from composts by EEM spectra combined with PARAFAC analysis
  124. Source apportionment of soil contamination based on multivariate receptor and robust geostatistics in a typical rural–urban area, Wuhan city, middle China
  125. Special Issue on 13th JCC 2018
  126. The Role of H2C2O4 and Na2CO3 as Precipitating Agents on The Physichochemical Properties and Photocatalytic Activity of Bismuth Oxide
  127. Preparation of magnetite-silica–cetyltrimethylammonium for phenol removal based on adsolubilization
  128. Topical Issue on Agriculture
  129. Size-dependent growth kinetics of struvite crystals in wastewater with calcium ions
  130. The effect of silica-calcite sedimentary rock contained in the chicken broiler diet on the overall quality of chicken muscles
  131. Physicochemical properties of selected herbicidal products containing nicosulfuron as an active ingredient
  132. Lycopene in tomatoes and tomato products
  133. Fluorescence in the assessment of the share of a key component in the mixing of feed
  134. Sulfur application alleviates chromium stress in maize and wheat
  135. Effectiveness of removal of sulphur compounds from the air after 3 years of biofiltration with a mixture of compost soil, peat, coconut fibre and oak bark
  136. Special Issue on the 4th Green Chemistry 2018
  137. Study and fire test of banana fibre reinforced composites with flame retardance properties
  138. Special Issue on the International conference CosCI 2018
  139. Disintegration, In vitro Dissolution, and Drug Release Kinetics Profiles of k-Carrageenan-based Nutraceutical Hard-shell Capsules Containing Salicylamide
  140. Synthesis of amorphous aluminosilicate from impure Indonesian kaolin
  141. Special Issue on the International Conf on Science, Applied Science, Teaching and Education 2019
  142. Functionalization of Congo red dye as a light harvester on solar cell
  143. The effect of nitrite food preservatives added to se’i meat on the expression of wild-type p53 protein
  144. Biocompatibility and osteoconductivity of scaffold porous composite collagen–hydroxyapatite based coral for bone regeneration
  145. Special Issue on the Joint Science Congress of Materials and Polymers (ISCMP 2019)
  146. Effect of natural boron mineral use on the essential oil ratio and components of Musk Sage (Salvia sclarea L.)
  147. A theoretical and experimental study of the adsorptive removal of hexavalent chromium ions using graphene oxide as an adsorbent
  148. A study on the bacterial adhesion of Streptococcus mutans in various dental ceramics: In vitro study
  149. Corrosion study of copper in aqueous sulfuric acid solution in the presence of (2E,5E)-2,5-dibenzylidenecyclopentanone and (2E,5E)-bis[(4-dimethylamino)benzylidene]cyclopentanone: Experimental and theoretical study
  150. Special Issue on Chemistry Today for Tomorrow 2019
  151. Diabetes mellitus type 2: Exploratory data analysis based on clinical reading
  152. Multivariate analysis for the classification of copper–lead and copper–zinc glasses
  153. Special Issue on Advances in Chemistry and Polymers
  154. The spatial and temporal distribution of cationic and anionic radicals in early embryo implantation
  155. Special Issue on 3rd IC3PE 2020
  156. Magnetic iron oxide/clay nanocomposites for adsorption and catalytic oxidation in water treatment applications
  157. Special Issue on IC3PE 2018/2019 Conference
  158. Exergy analysis of conventional and hydrothermal liquefaction–esterification processes of microalgae for biodiesel production
  159. Advancing biodiesel production from microalgae Spirulina sp. by a simultaneous extraction–transesterification process using palm oil as a co-solvent of methanol
  160. Topical Issue on Applications of Mathematics in Chemistry
  161. Omega and the related counting polynomials of some chemical structures
  162. M-polynomial and topological indices of zigzag edge coronoid fused by starphene
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