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Testing the potential of sodium fluoride to affect spermatogenesis in the rat
Abstract
The potential of sodium fluoride (NaF) to affect spermatogenesis and endocrine function was assessed in P and F1 generation male rats. Male and female experimental rats received sodium fluoride in their drinking water at one of four concentrations (25, 100, 175, 250 ppm). P generation male and female rats were exposed to sodium fluoride in their drinking water for 10 wk and then males were mated to females within the same treatment groups. Reproductive tissues were collected from P generation male rats after approximately 14 wk of treatment. Pregnant females (P) were exposed to sodium fluoride via their drinking water through gestation and lactation. F1 generation weanling male rats remained within the same treatment groups as their parents. F1 generation male rats were exposed to sodium fluoride in their drinking water for 14 wk, at which time reproductive tissues were collected. Dose-related effects were not observed within the P and F1 treatment groups in testis weights, prostate/seminal vesicle weights, non-reproductive organ weights, testicular spermatid counts, sperm production per gram of testis per day, sperm production per gram of testis, LH, FSH or serum testosterone concentrations. Histological changes were not observed in testicular tissues from either the P or F1 generation. We conclude that prolonged exposure to sodium fluoride in drinking water at the doses administered in this study does not adversely affect spermatogenesis or endocrine function in the P and F1 generation male rats.
... In the group that was exposed for 29 months, spermatogenesis stopped (80,145). Sprando et al. (143) reported that no effects on spermatogenesis -changes in sperm count, testes volume, histopathologyand no endocrine effects -serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) -could be seen in rats given drinking water containing 25, 100, 175, or 200 mg NaF/l for 14 weeks. A similar study with the same exposure levels gives the equivalent fluoride intakes: about 1.5, 5.6, 8.5 and 12.7 mg F/kg/day (21,22). ...
... A similar study with the same exposure levels gives the equivalent fluoride intakes: about 1.5, 5.6, 8.5 and 12.7 mg F/kg/day (21,22). Nor were any effects on these parameters seen in the first generation of young (F 1 generation), exposed to these fluoride concentrations both in utero and after birth (143). In a follow-up study, no significant histological changes were seen in testes of F 1 rats exposed to these levels of sodium fluoride in utero and after birth (144). ...
... Reduced ossification of the hyoid bone was observed in the third generation (F 2 ) of rats given drinking water containing 250 mg NaF/l; no effects were reported in groups with lower intake (21,22). At this exposure there were no effects on spermatogenesis, no endocrine effects in F 0 or F 1 rats, and no testicular changes in F 1 rats (143,144). Rats were given drinking water with 150 mg NaF/l for 10 weeks before and during 3 gestations and subsequent lactation periods, and morphological changes were found in femur shafts. There were no skeletal effects in their pups (123,124). ...
... 4 Lower birth rates have also been found in areas with elevated F levels in the drinking water. 5 Various laboratory studies have investigated the effects of NaF on fetal development, 6,7 spermatogenesis, [8][9][10][11] and fertility. [12][13][14][15] Reproductive toxicity of F in cows and silver foxes has also been reported. ...
... Lower doses of NaF apparently do not impair spermatogenesis and endocrine function of male rats. [9][10][11] One of the main findings of the present work is that ingestion of NaF greatly diminished or abolished aggressive behavior postures. The other main finding is that the ingestion of NaF by adult male rats resulted in marked suppression of sexual performance as evidenced by prolongation of the intromission latency, decrease in the number of intromissions, and a marked increase in post-ejaculatory interval. ...
... 31 On the other hand, several workers reported that oral administration of 75 ppm and 250 ppm NaF had no effect on spermatogenesis in mice and rats, respectively. [8][9][10][11]32 The adverse effect of NaF on male rat fertility observed in this work may suggest a disturbance of reproductive endocrine functions along the hypothalamicpituitary-gonadal axis. Fluoride toxicity is also due to the inhibition of enzymes particularly those in which divalent metal cations act as cofactors. ...
Ingestion of sodium fluoride at 100 and 300 ppm in drinking water for 12 weeks by adult male Sprague-Dawley rats was investigated for effects on territorial aggression, sexual behavior, and fertility. Body weight and absolute and relative testes weights were not affected, but the average weights of epididymis, ventral prostate, seminal vesicles, and preputial glands decreased significantly. A significant decline of spermatogenesis in testes due to a decrease in the number of spermatocytes (primary and secondary) and spermatids in the treatment group is attributed to a significant decrease in testosterone. Sperm motility and density were also significantly decreased in the cauda epididymis and in testes in both NaF- treated groups. In addition, the treatment markedly diminished aggressive and sexual behavioral parameters such as lateralization, boxing bouts, and ventral presenting postures. It also prolonged the time to the first mount, increased the intromission latency, decreased the number of intromissions, prolonged the post- ejaculatory interval, and increased the number of fetal resorptions in female rats impregnated by these males, thereby reducing their fertility.
... Males and females within a treatment group were mated. Pregnant females (P) continued to be given NaF throughout gestation and lactation [60]. The weanlings (F 1 ) remained in the same treatment groups as their parents and were given NaF for 14 weeks. ...
... The weanlings (F 1 ) remained in the same treatment groups as their parents and were given NaF for 14 weeks. Even at 250 ppm (24 mg/kg bw/day), no adverse effects were observed in weights of organs including the reproductive organs, sperm parameters, serum LH, FSH and testosterone levels or the histopathology of the testes in P or F 1 males [60] or in the quantitative morphometry of the testes in F 1 males [61]. NaF was given to CD rats with the same regimen and procedure as above [60], and some pregnant P and F 1 females were sacrificed to examine the development of F 1 and F 2 fetuses, respectively, on GD 20 [62,63]. ...
... Even at 250 ppm (24 mg/kg bw/day), no adverse effects were observed in weights of organs including the reproductive organs, sperm parameters, serum LH, FSH and testosterone levels or the histopathology of the testes in P or F 1 males [60] or in the quantitative morphometry of the testes in F 1 males [61]. NaF was given to CD rats with the same regimen and procedure as above [60], and some pregnant P and F 1 females were sacrificed to examine the development of F 1 and F 2 fetuses, respectively, on GD 20 [62,63]. Although no adverse effects on reproduction or development were noted even at the highest dose of 250 ppm (24-28 mg/kg bw/day) [62], decreased ossification of the hyoid bone of F 2 fetuses was found at 250 ppm (28 mg/kg bw/day) [63]. ...
The present paper summarizes the results of animal studies on the reproductive and developmental toxicity of the degradation products of refrigerants, including trifluoroacetic acid (TFA), carbon dioxide (CO(2)), carbon monoxide (CO), carbonyl fluoride (CF), hydrogen fluoride (HF) and formic acid (FA). Excessive CO(2) in the atmosphere is testicular and reproductive toxic, embryolethal, developmentally neurotoxic and teratogenic in experimental animals. As for CO, maternal exposure causes prenatal and postnatal lethality and growth retardation, skeletal variations, cardiomegaly, blood biochemical, immunological and postnatal behavioral changes, and neurological impairment in offspring of several species. Very early studies of CO in rats and guinea pigs reported fetal malformations in exposed dams. The results of toxicological studies on sodium fluoride (NaF) were used to obtain insight into the toxicity of CF and HF, because CF is rapidly hydrolyzed in contact with water yielding CO(2) and HF, and NaF is similar in kinetics and dynamics to HF. Increased fetal skeletal variation, but not malformation, was noted after the maternal administration of NaF. Rat multiple-generation studies revealed that NaF caused retarded ossification and degenerative changes in the lung and kidney in offspring. There is a lack of information about the toxicity of TFA and FA.
... Eight studies published since 2017 investigated the effect of fluoride on learning and memory following exposure during development (Bartos et al. 2018;Chen et al. 2018a;Ge et al. 2018;McPherson et al. 2018;Mesram et al. 2017;Sun et al. 2018;Wang et al. 2018;Zhao et al. 2019); and five additional studies examined exposure during young Sprando et al. (1997Sprando et al. ( , 1998 adulthood (Dong et al. 2017;Li et al. 2019;Pulungan et al. 2018;Sharma et al. 2018a;Yang et al. 2018). Only one study among them was conducted according to the generally accepted guidelines considering all of the aforementioned key requirements (McPherson et al. 2018). ...
Recently, epidemiological studies have suggested that fluoride is a human developmental neurotoxicant that reduces measures of intelligence in children, placing it into the same category as toxic metals (lead, methylmercury, arsenic) and polychlorinated biphenyls. If true, this assessment would be highly relevant considering the widespread fluoridation of drinking water and the worldwide use of fluoride in oral hygiene products such as toothpaste. To gain a deeper understanding of these assertions, we reviewed the levels of human exposure, as well as results from animal experiments, particularly focusing on developmental toxicity, and the molecular mechanisms by which fluoride can cause adverse effects. Moreover, in vitro studies investigating fluoride in neuronal cells and precursor/stem cells were analyzed, and 23 epidemiological studies published since 2012 were considered. The results show that the margin of exposure (MoE) between no observed adverse effect levels (NOAELs) in animal studies and the current adequate intake (AI) of fluoride (50 µg/kg b.w./day) in humans ranges between 50 and 210, depending on the specific animal experiment used as reference. Even for unusually high fluoride exposure levels, an MoE of at least ten was obtained. Furthermore, concentrations of fluoride in human plasma are much lower than fluoride concentrations, causing effects in cell cultures. In contrast, 21 of 23 recent epidemiological studies report an association between high fluoride exposure and reduced intelligence. The discrepancy between experimental and epidemiological evidence may be reconciled with deficiencies inherent in most of these epidemiological studies on a putative association between fluoride and intelligence, especially with respect to adequate consideration of potential confounding factors, e.g., socioeconomic status, residence, breast feeding, low birth weight, maternal intelligence, and exposure to other neurotoxic chemicals. In conclusion, based on the totality of currently available scientific evidence, the present review does not support the presumption that fluoride should be assessed as a human developmental neurotoxicant at the current exposure levels in Europe.
... However, experimental results differ. Some reports indicate that sodium fluoride does not affect sperm quality in rats (Sprando et al., 1997;Collins et al., 2001) whereas other experimental studies suggest that fluoride can cause low sperm quality and diminished fertility (Ghosh et al., 2002;Wan et al., 2006). There are many conflicts regarding importance of fluoride for health and its toxic effects on vital physiological functions of man and animals. ...
... Furthermore, it has been reported that Zeranol could damage the cell membrane, lead to overflow of intracellular potassium and interfere electrolyte balance. These may also correlate with reduced sperm motility observed in this study [32,33]. Compared with the control group, the sperm malformation rates increased in Zeranol treated groups. ...
Aims:
To investigate the mechanisms of α-zearalanol (Zeranol)-induced male reproductive toxicity, the effects of Zeranol on spermatogenesis and sex hormone levels of male mice were studied.
Methods:
Forty healthy sexually mature male Kunming mice were randomly divided into four groups. The mice were mock-treated or treated with Zeranol 25, 50 or 100 mg/kg via oral gavage for 35 days. The epididymal sperms were counted and their morphology and motility were analyzed. The testicles were examined by light and electron microscopy. The levels of serum/testicular testosterone (T), serum follicle stimulating hormone (FSH) and serum luteinizing hormone (LH) were determined by radioimmunoassay.
Results:
Zeranol decreased the epididymal sperm count and sperm motility in a dose depend manner. While there were not significant differences in the sperm malformation rates between the Zeranol treated groups and the control group. Furthermore, Zeranol could decrease the weight and the organ coefficient of the seminal vesicles and the testicles and lead to significant pathological changes of the testicles. Zeranol could also decrease the levels of serum T, FSH, LH as well as the levels of testicular T of male mice.
Conclusions:
Zeranol induced reproductive toxicity in adult male mice. It could damage spermatogenesis via its direct effects on the testicles and interfere with sex hormone levels of male mice through its effects on the hypothalamic-pituitary-testicular axis.
... Species sensitivity also plays a major role in the differing effects observed on male reproductive function in sodium fluoride treated animals. 22 Considering studies done by Chinoy et al, [23][24][25][26] who found that toxic effects of fluoride disappeared after removal of the intoxication source, it is reasonable to conclude that the toxic effect of fluoride on reproduction is due to inhibition of enzyme activity, particularly of enzymes whose cofactor is the cation of a bivalent metal. 27 Fluoride is a well-known inhibitor of many enzymes. ...
The percentage of spermatozoa in ram semen with intact acrosomes and the level of spermatozoa motility decreased significantly after dilution and after 5 hr incubation at 38°C. Both indices decreased significantly in the presence of NaF at concentrations ranging from 20 μmol/L to 0.1 mol/L. The activities of androgen-dependent enzymes-acid phosphatase (ACP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (γ-GT-10S)-decreased significantly when the ejaculate was treated with NaF at concentrations of 20, 100, 200 μmol/L (0.38; 1.9; 3.8 ppm F-), but they returned to the initial value of the control at 0.1 mol/L (1900 ppm F-). The activity of aspartate transaminase (AspAT) displayed a large increase with the increasing lower F-concentrations and then showed a substantial decrease in activity at the high F- concentration. These changes undoubtedly affect the physiological functions of the sperm.
... These findings were in accordance with Ravi Sekhar et al. [26]. In contrary, Sprando et al. [27] reported NaF treatment did not adversely affect spermatogenic activity in NaF treated animals. This toxic effect of fluoride on reproduction is due to inhibition of enzyme activity, particularly of enzymes whose cofactor is the cation of a bivalent metal like Mg, Ca, Zn, and Se. ...
The present study was designed to evaluate the ameliorative effect of Aloe vera extract on fluoride induced toxic changes in soft tissues of rats. The present study was carried out by procuring 72 male Wistar albino rats that were randomly divided into four groups consisting of 18 rats in each group. Sodium Fluoride was gavaged per orally using water as vehicle @ 18 mg NaF/kg body weight to groups II and Aloe Vera @ 200 mg/kg body wt. in distilled water was given along with Sodium Fluoride to group IV for 6 weeks to study ameliorative effects. Group I and III were treated with distilled water and Aloe vera respectively. Six rats from each group were sacrificed at fortnight interval. Gross changes were noticed in liver, testis, lung and spleen. Histopathologically, the liver revealed perivascular and periportal infiltration of MNCs, vesicular fatty change, periportal fibroblast proliferation, extensive bile ductular proliferation. In kidneys, atrophied and cystic glomeruli, extensive degenerative changes in tubular epithelial cells were noticed. Cerebrum revealed gliosis and demyelinating changes and in cerebellum. In testes, interstitial edema, desquamation of germinal epithelium and eosiniphillic granular debris in the lumen of the seminiferous tubules and necrotic changes were noticed. In Aloe vera ameliorated rats, these changes in different organs were less intense and by the end of experiment liver came to near normal appearance.
... Experimental animal model studies reported that the serum testosterone, maternal F exposure significantly changed FSH and LH levels in the neonatal male rats (Reddy et al., 2007). In contrast, Sprando et al. did not find significant changes of serum FSH, LH and testosterone concentrations after sodium fluoride (NaF) exposure in parental (P) and first filial (F1) generation male rats (Sprando et al., 1997). However, few reports paid attention to the structure and gene expression levels from different tissues of HPTA at the same time. ...
... However, experimental results differ. Some reports indicate that sodium fluoride does not affect sperm quality in rats (Sprando et al., 1997;Collins et al., 2001) whereas other experimental studies suggest that fluoride can cause low sperm quality and diminished fertility (Ghosh et al., 2002;Wan et al., 2006). There are many conflicts regarding importance of fluoride for health and its toxic effects on vital physiological functions of man and animals. ...
... Although a single, small study on rats exposed to 2, 4, and 6 mg/L sodium fluoride for 6 months reported adverse affects on fertility and reproduction (reduced sperm motility), [177] other larger studies have shown no reproductive effects over multiple generations of rats exposed to fluoride in drinking water at doses up to 175 mg/L [178][179][180] and no effects on spermatogenesis in doses up to 100 mg/L. [181,182] A study of Mexican men found that fluoride intakes up to 27 mg/day did not affect sperm motility or other sperm parameters. Some of the men had occupational exposure to fluoride in addition to exposure from drinking water at a concentration of ≥3 mg/L. ...
The World Health Organization (WHO), along with many other international health
authorities, recommends fluoridation of water supplies, where possible, as the most
effective public health measure for the prevention of dental decay.
A large number of studies and systematic reviews have concluded that water fluoridation is
an effective preventive measure against tooth decay that reaches all segments of the
population, and is particularly beneficial to those most in need of improved oral health.
Extensive analyses of potential adverse effects have not found evidence that the levels of
fluoride used for community water fluoridation schemes contribute any increased risk to
public health, though there is a narrow range between optimal dental health effectiveness
and a risk of mild dental fluorosis. The prevalence of fluorosis of aesthetic concern is
minimal in New Zealand, and is not different between fluoridated and non-fluoridated
communities, confirming that a substantial proportion of the risk is attributable to the intake
of fluoride from sources other than water (most notably, the swallowing of high-fluoride
toothpaste by young children). The current fluoridation levels therefore appear to be
appropriate.
This analysis concludes that from a medical and public health perspective, water
fluoridation at the levels used in New Zealand poses no significant health risks and is
effective at reducing the prevalence and severity of tooth decay in communities where it is
used. Communities currently without CWF can be confident that this is a safe option that is
cost saving and of significant public health benefit – particularly in those communities with
high prevalence of dental caries.
... Entretanto, os resultados experimentais são divergentes. Algumas descrições indicam que o F não afeta a qualidade espermática de ratos (SPRANDO et al., 1997;COLLINS et al., 2001) e camundongos (DUNIPACE et al., 1989). Em outros experimentos, sugere-se que o F pode reduzir a qualidade espermática e a fertilidade (GHOSH et al., 2002;BATAINEH & NUSIER, 2006;WAN et al., 2006;HUANG et al., 2007). ...
The objective of the present study was to evaluate different reproductive parameters of ram lambs treated with sodium fluoride. Spermogram, indicators of seminal oxidative profile, seminiferous tubules diameter and cell height of the testicular epithelium, epididimus and vas deferens were analyzed. Twelve 5-month-old ram lambs were used. They were allocated into one of two experimental groups: The control, which received daily iodized salt (5g NaCl animal-1 + 0.2mg I kg-1 DM); and the treated, which received (5g NaCl animal-1 + 0.2mg I kg-1 DM + 4.7mg F kg-1 BW). After 150 days of treatment, animals went through a complete andrological exam, and were euthanized on the next day. No differences were observed in sperm motility, dead: alive ratio and morphology between the control and treated group. Also, seminal concentration of reduced glutathione and zinc, as well as, testicular weight, histology and morphometry of testicles, caudal portion of epididimus and vas deferens did not differ between groups. The seminal concentration of thiobarbituric acid reactive substances (TBARs) and seminal copper levels were lower (P<0.05) in the treated group. We conclude that chronic fluoride administration to lambs does not affect reproductive capacity as a whole. However, the data suggest that fluoride can induce a reduction in seminal lipoperoxidation and copper levels with are essential for sperm capacitation and fertilization.
... Ghosh et al. (2002) Rat 0, 1, 10, and 100 ppm in drinking water for 3 months Dvořáková-Hortováa et al. (2008) Rat 4.5 ppm and 9.0 ppm in drinking water for 75 days Pushpalatha et al. (2005) Mice 150 mg/l in drinking water for 49 days. Sun et al. (2009Sun et al. ( , 2010) Rabbit 20 mg/kg by orally for 30 days Kumar et al. (2012) Rat 30 mg/l in drinking water for 4 months Oncu et al. (2007) Rat 5 mg/kg by gavage for 8 weeks Vega et al. (2008) Rat 1.0, 2.0, and 3.0 mg/kg by intragastric gavage for 90 days Wang et al. (2009) Rat 150 mg/l in drinking water 50 days Wan et al. (2006) Rat 25, 100, 175, 250 ppm in drinking water for 14 weeks Sprando et al. (1997) Teratogenesis Reduction in head and tail length, decreased in the size of eggs and weight of hatchlings, malformation in developing brain, decline in learning and memory ability ...
Fluoride (F) is a naturally-occurring contaminant in the water. F is essential for normal maintenance of teeth and bones. However, prolonged exposure to high concentration of F is found to be deleterious to teeth, bones and other organs. Besides drinking water, F can enter the body through food, dental products, drugs and industrial emission. People living in areas where F contamination is much higher than the expected level, are found to suffer from not only teeth and bone problem but also other systems, including brain and its functions. Since animals respond to the toxic effects of F like human beings, the deleterious effects of F have been produced experimentally in animals in order to determine the mechanism involved in the action of F. The reports indicating the chronic harmful effects of F in teeth, bones, heart, liver, kidneys, gastrointestinal tract, lungs, brain, blood, hormones and biochemical parameters of experimental animals and in invitro studies have been reviewed in this article. The neurotoxic action of F that produces chiefly learning and memory impairment has also been included. The review also points out the harmful effects of F on reproduction, its teratogenic action and in inducing premature ageing. Finally, the reports indicating a reversal of certain toxicities of F in experimental animals after withdrawal of its exposure has been included.
... 1,2 Although research has been carried out on the effects of fluoride on the reproductive organs as well as fertility impairment in animal models, the results are controversial. [3][4][5][6][7][8][9] Moreover, the effects of arsenic and/or fluoride ingestion on the reproductive organs are not fully understood. Hence, an investigation was made of the toxic effects on the testis of mice ingesting fluoride and/or arsenic by mice for 30 days, followed by monitoring recovery after a 30-day withdrawal period with and without antidotes. ...
Administration of sodium fluoride (NaF, 5 mg/kg body weight) and/or arsenic trioxide (As2O3, 0.5 mg/kg body weight) for 30 days caused structural alterations (including the formation of giant cells) in mice testis, affected spermatogenesis, reduced protein levels, and lowered activities of 3β- and 17β- hydroxysteroid dehydrogenases (HSDs). In turn, the latter effect resulted in accumulation of cholesterol and a decline in testosterone levels, indicating a decrease in testicular steroidogenesis. Withdrawal of NaF + As2O3 for 30 days led to partial recovery, but supplementation with ascorbic acid, calcium, and vitamin E, individually or in combination, during the withdrawal period, caused significant recovery in testis.
... Tokar and Savchenko (1977) found that blood LH levels were increased only in those patients with fluorosis who had long contact with Fl compounds (over 15 years). Sprando et al. (1997) also reported that in rats administered drinking-water containing 0, 25, 100, 175, or 200 mg NaF L À1 for 14 weeks no changes in LH were noted. This study showed that serum FSH levels in the NaF-treated group (IIa) were significantly increased compared with control group (Ia). ...
Chronic fluoride (Fl) toxicity is a serious public health problem globally where drinking water contains more than 1 ppm of Fl. Sodium fluoride (NaF) produced male reproductive system toxicity. The aim of the present study was to evaluate the amelioration of Fl toxicity-induced fertility impairment by vitamin E and calcium during the withdrawal period. The study was carried out on 70 adult male albino rats divided into five main groups: group I control; subdivided into group Ia (maintained on standard diet and water ad libitum for 60 days) and group Ib (maintained on standard diet and water ad libitum for 120 days), group II was administered NaF and subdivided into group IIa (administered NaF for 60 day and sacrificed) and group IIb (administered NaF for 60 day then maintained on standard diet and water ad libitum for a further 60 days), and treated groups III, IV, and V were administered NaF. Rats were maintained during withdrawal from NaF, on vitamin E (10 mg kg−1 day−1 for 60 days), calcium (50 mg kg−1 day−1 orally for 60 days), and both vitamin E and calcium, respectively. The duration of NaF administration was 60 days at a dose 20 mg kg−1 day−1 for all treated groups. The following parameters were determined: body and organ weights, sperm motility, sperm morphology, sperm viability, fertility test, and hormone assays: testosterone, in vitro testosterone production, luteinizing hormone, and follicular stimulating hormone. The combined administration of vitamin E and calcium during withdrawal from NaF showed significant improvement from chronic FL-induced toxicity on male reproductive organs.
... December 18, 2008. Submission to South Central Strategic Health Authority -learning and behavior (Paul 1998;Zhang , 2001Ekambaram 2001;Bhatnagar 2002;Cagiano, 2007 andChioca, 2007) j) While studies conducted by FDA scientists in the US have failed to find reproductive effects in rats (Sprando 1996(Sprando , 1997(Sprando , 1998, studies from other countries have found a multitude of effects on reproduction in a whole range of animal species. At high doses fluoride wreaks havoc on the male reproductive system -it damages sperm and increases the rate of infertility in a number of different species (Kour 1980;Chinoy 1989;Chinoy 1991;Susheela 1991;Kumar 1994;Narayana 1994a, b;Zhao 1995;Elbetieha 2000;Ghosh 2002 andZakrzewska 2002). ...
... 1995). Administration of various concentration of sodium fluoride showed that it did not have effect on the testosterone and spermatogenesis and it can cause diminishing of capsule of testis with 100 ppm dosage (Sprando, 1997). Also, Sprando et al. (2000 indicated that linen seed decreased the volume of the seminiferous tubules. ...
The aim of the study was to determine the histological and histomorphometrical change of seminiferous tubule in mature and immature wistar rats after using Tribulus terresteris (TT). Twenty male wistar rats were selected and randomly divided into four groups: 1) Mature control group (MCG). 2) Mature experimental group (MEG) (orally received 75 mg/kg TT daily for 14 days). 3) Immature control group (ICG). 4) Immature experimental group (IEG) (orally received 75 mg/kg TT daily for 14 days). The number of leydig cells had increment in experimental group when compared with ICG. Result showed that the thickness of the wall of seminiferous tubule in experimental group significantly increased (P < 0.05). Also, TT treatment groups resulted the accumulation of spermatogenic cells were increased in the seminiferous tubule when compared with control group. In addition, sperm was not observed in ICG but sperm were also observed to increase in the treatment groups. It is concluded that TT may improves the sexual activity, increased testestrone by intensification of leydig cells and may caused early puberty in immature rat.
... Also, no structural defects were found in testes of F-1 generation Sprague-Dawley male rats exposed to 25-250 mg/L fluoride in utero and until 14 weeks post weaning (Sprando et al., 1998). When compared to a control group of rats, testosterone, luteinizing hormone (LH), and folliclestimulating hormone (FSH) serum concentrations from these fluoride-treated F-1 rats were not found to be significantly different (Sprando et al., 1997). More recently, the effects of sodium fluoride ingestion at concentrations between 25 and 250 ppm in drinking water measured in rats throughout three generations have been reported (Collins et al., 2001). ...
Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.
The halogens are those elements in group XVII of the periodic table, and include fluorine, chlorine, bromine, iodine, and astatine, the latter of which is a radioactive element of no industrial importance. The physical properties of the halogens are described. They indicate an almost perfect doubling of atomic weights progressing from fluorine to bromine, paralleled by increases in specific gravity and melting and boiling points, and by decreases in water solubility.
Chlorine and fluorine exist in the earth's crust in almost equal proportions (770 ppm for fluorine, 550 ppm for chlorine). The relative abundance of bromine and iodine are only about 2 and 0.04%, respectively, of that for chlorine. Seawater contains almost 19,000 ppm chlorine, compared to 65 ppm for bromine and less than 2 ppm for fluorine. Iodine exists only in trace quantities in seawater (about 0.05 ppm).
Elements become progressively less electronegative and have less oxidizing potential as atomic weight increases. Each halogen forms an acid in water and combines with metals to form salts; the reactivity of these compounds shows the same relationship as the elemental halogens.
Chemically, fluorine is the most powerful oxidizing agent known. It is the most reactive of all the elements. Free fluorine is rarely, if ever, found in nature. Elemental fluorine is produced on a commercial scale by electrolysis.
Common operations where fluorine exposure occurs include the manufacture of fluorochemicals and plastics, rocket propellants, and fluorinated intermediates, metal production such as aluminum potroom work, the fluorination of pharmaceuticals and consumer products such as dentifrices, and the fluoridation of public drinking‐water supplies. Environmental contamination and air pollution with fluorine and fluorides may occur as a result of emissions from facilities for aluminum production, glass and ceramic manufacture, fertilizer manufacture, and the processing of fluorspar.
Because of the reactivity of fluorine, exposures of humans and animals, and environmental contamination problems are almost always the result of fluorides, rather than fluorine gas. Most studies of fluorine itself are artificial and of academic rather than practical interest. Functionally, acute exposures to fluorine gas must be regarded as severe and potentially lethal corrosive exposures, with the added nuances of disturbances in calcium metabolism because of the reaction between the calcium ion and the fluoride ion.
Chlorine is associated with the largest array of industrially useful compounds of all the halogens; it is the ninth highest volume chemical produced in the United States. Chemically, chlorine is more reactive than either bromine or iodine; it displaces bromine and iodine from their salts and enters into substitution and addition reactions with both inorganic and organic substances. When moist, but not when dry, chlorine unites directly with most elements. The physical properties of chlorine are given. Recognition of widespread environmental contamination problems associated with persistent chlorinated organic compounds has led to pressure to reduce the use of chlorinated compounds in industrial chemicals. The outcome of this concern is unclear at this time, but it is likely to lead to substitution of other compounds for those containing environmentally persistent and toxic chlorinated materials. Although most of the identified compounds that present environmental contamination problems are higher molecular weight organic compounds, the use of chlorinated solvents in cleaning and degreasing operations has already been reduced and will be further reduced because of their impact on the ozone layer. Higher molecular weight organic compounds containing chlorine have been identified as possible xenoestrogens. The concern of the scientific community is high, and much research is under way to clarify the role of halogenated xenoestrogens in biological systems. It is likely that if the halogenated organic compounds are confirmed to be biologically detrimental, there will be a further reduction in the production and use of these compounds. The introduction of chemically reactive inorganic halogens, principally chlorinated compounds, into the environment in groundwater and air may lead to active halogenation of natural products to xenoestrogens. If this pathway is confirmed, this, too, will lead to a reduction in the use of chlorinated compounds.
Chlorine is noncombustible in air but will support the combustion of other materials. It reacts explosively or forms explosive mixtures with many common materials, including acetylene, turpentine, ammonia gas, fuel gas, hydrocarbons, hydrogen, and finely divided metals. Chlorine may also combine with water or steam to produce hydrogen chloride (HCl) fume.
The reactivity of bromine lies between that of chlorine and iodine. Bromine will cause ignition of organic materials, including wood, cotton, and straw. It reacts violently on contact with natural rubber and reacts explosively with a number of common substances, including aldehydes, ketones, carboxylic acids, acetylene, acrylonitrile, ammonia, ethyl phosphine, hydrogen, nickel carbonyl, ozone, oxygen difluoride, phosphorus, potassium, sodium, and sodium carbide. Because of its explosive potential, facilities where bromine is manufactured or used should be designed to dispose rapidly of liquid bromine spills.
Although it is estimated that 1015–1016 tons of bromine are contained in the earth's crust, it is widely distributed and found only in low concentrations in the form of bromide salts. The most readily recoverable form of bromine occurs as soluble salts in salt lakes, inland seas, brine wells such as those in Michigan and Arkansas, and seawater. Today, little bromine is extracted from seawater, which contains bromide salts in a concentration of only 65 ppm. The largest single current use of bromine is for the production of fire retardants.
Agricultural chemical production consumed about 10% of bromine production, primarily as methyl bromide. However, recent restrictions on the use of brominated pesticides, such as ethylene dibromide and DBCP and proposed limitations on such fumigants as methyl bromide are expected to further reduce the use of these brominated chemicals in the future.
Skin or eye contact with vapor or liquid bromine pentafluoride causes painful, deep‐seated, long‐lasting burns. The acute effect of this substance on the lung is similar to that of phosgene.
Iodine is the 47th most abundant element in the earth's crust. The name iodine derives from the Greek word for violet‐colored, ioeides , which was used to describe the purple vapor generated by heating iodine. It is the heaviest of the halogens that are of industrial interest. Under ordinary conditions, iodine takes the form of gray‐black plates or granules that have a metallic, crystalline luster. It volatilizes at room temperature to yield a sublimed, violet vapor. Iodine's physical properties are shown.
Although iodine resembles other members of the halogen group, it is the least electronegative; it is thus the least chemically reactive of the halogens and forms the weakest bonds with more electropositive elements.
Iodine is used both in animal and human medicine, where its disinfectant and antiseptic properties are valued. The lack of iodine causes goiter (compensatory hypertrophy of the thyroid gland), and iodine is used both to treat iodine deficiency and hyperthyroidism. Principal iodine compounds and their industrial uses are shown.
The inorganic iodine compounds of commercial interest, and their physical properties, are discussed. The iodides, an important class of inorganic iodine compounds, have less tendency to form complexes than the other halides. Chlorine and bromine freely displace iodine from the iodides. Iodine forms industrially useful and important compounds with hydrogen, metals, the other halogens, and oxygen. Those presented here are typical.
The halogens are those elements in group XVII of the periodic table, and include fluorine, chlorine, bromine, iodine, and astatine, the latter of which is a radioactive element of no industrial importance. The physical properties of the halogens are described. They indicate an almost perfect doubling of atomic weights progressing from fluorine to bromine, paralleled by increases in specific gravity and melting and boiling points, and by decreases in water solubility.
Chlorine and fluorine exist in the earth's crust in almost equal proportions (770 ppm for fluorine, 550 ppm for chlorine). The relative abundance of bromine and iodine are only about 2 and 0.04%, respectively, of that for chlorine. Seawater contains almost 19,000 ppm chlorine, compared to 65 ppm for bromine and less than 2 ppm for fluorine. Iodine exists only in trace quantities in seawater (about 0.05 ppm).
Elements become progressively less electronegative and have less oxidizing potential as atomic weight increases. Each halogen forms an acid in water and combines with metals to form salts; the reactivity of these compounds shows the same relationship as the elemental halogens.
Chemically, fluorine is the most powerful oxidizing agent known. It is the most reactive of all the elements. Free fluorine is rarely, if ever, found in nature. Elemental fluorine is produced on a commercial scale by electrolysis.
Common operations where fluorine exposure occurs include the manufacture of fluorochemicals and plastics, rocket propellants, and fluorinated intermediates, metal production such as aluminum potroom work, the fluorination of pharmaceuticals and consumer products such as dentifrices, and the fluoridation of public drinking‐water supplies. Environmental contamination and air pollution with fluorine and fluorides may occur as a result of emissions from facilities for aluminum production, glass and ceramic manufacture, fertilizer manufacture, and the processing of fluorspar.
Because of the reactivity of fluorine, exposures of humans and animals, and environmental contamination problems are almost always the result of fluorides, rather than fluorine gas. Most studies of fluorine itself are artificial and of academic rather than practical interest. Functionally, acute exposures to fluorine gas must be regarded as severe and potentially lethal corrosive exposures, with the added nuances of disturbances in calcium metabolism because of the reaction between the calcium ion and the fluoride ion.
Chlorine is associated with the largest array of industrially useful compounds of all the halogens; it is the ninth highest volume chemical produced in the United States. Chemically, chlorine is more reactive than either bromine or iodine; it displaces bromine and iodine from their salts and enters into substitution and addition reactions with both inorganic and organic substances. When moist, but not when dry, chlorine unites directly with most elements. The physical properties of chlorine are given. Recognition of widespread environmental contamination problems associated with persistent chlorinated organic compounds has led to pressure to reduce the use of chlorinated compounds in industrial chemicals. The outcome of this concern is unclear at this time, but it is likely to lead to substitution of other compounds for those containing environmentally persistent and toxic chlorinated materials. Although most of the identified compounds that present environmental contamination problems are higher molecular weight organic compounds, the use of chlorinated solvents in cleaning and degreasing operations has already been reduced and will be further reduced because of their impact on the ozone layer. Higher molecular weight organic compounds containing chlorine have been identified as possible xenoestrogens. The concern of the scientific community is high, and much research is under way to clarify the role of halogenated xenoestrogens in biological systems. It is likely that if the halogenated organic compounds are confirmed to be biologically detrimental, there will be a further reduction in the production and use of these compounds. The introduction of chemically reactive inorganic halogens, principally chlorinated compounds, into the environment in groundwater and air may lead to active halogenation of natural products to xenoestrogens. If this pathway is confirmed, this, too, will lead to a reduction in the use of chlorinated compounds.
Chlorine is noncombustible in air but will support the combustion of other materials. It reacts explosively or forms explosive mixtures with many common materials, including acetylene, turpentine, ammonia gas, fuel gas, hydrocarbons, hydrogen, and finely divided metals. Chlorine may also combine with water or steam to produce hydrogen chloride (HCl) fume.
The reactivity of bromine lies between that of chlorine and iodine. Bromine will cause ignition of organic materials, including wood, cotton, and straw. It reacts violently on contact with natural rubber and reacts explosively with a number of common substances, including aldehydes, ketones, carboxylic acids, acetylene, acrylonitrile, ammonia, ethyl phosphine, hydrogen, nickel carbonyl, ozone, oxygen difluoride, phosphorus, potassium, sodium, and sodium carbide. Because of its explosive potential, facilities where bromine is manufactured or used should be designed to dispose rapidly of liquid bromine spills.
Although it is estimated that 1015–1016 tons of bromine are contained in the earth's crust, it is widely distributed and found only in low concentrations in the form of bromide salts. The most readily recoverable form of bromine occurs as soluble salts in salt lakes, inland seas, brine wells such as those in Michigan and Arkansas, and seawater. Today, little bromine is extracted from seawater, which contains bromide salts in a concentration of only 65 ppm. The largest single current use of bromine is for the production of fire retardants.
Agricultural chemical production consumed about 10% of bromine production, primarily as methyl bromide. However, recent restrictions on the use of brominated pesticides, such as ethylene dibromide and DBCP and proposed limitations on such fumigants as methyl bromide are expected to further reduce the use of these brominated chemicals in the future.
Skin or eye contact with vapor or liquid bromine pentafluoride causes painful, deep‐seated, long‐lasting burns. The acute effect of this substance on the lung is similar to that of phosgene.
Iodine is the 47th most abundant element in the earth's crust. The name iodine derives from the Greek word for violet‐colored, ioeides , which was used to describe the purple vapor generated by heating iodine. It is the heaviest of the halogens that are of industrial interest. Under ordinary conditions, iodine takes the form of gray‐black plates or granules that have a metallic, crystalline luster. It volatilizes at room temperature to yield a sublimed, violet vapor. Iodine's physical properties are shown.
Although iodine resembles other members of the halogen group, it is the least electronegative; it is thus the least chemically reactive of the halogens and forms the weakest bonds with more electropositive elements.
Iodine is used both in animal and human medicine, where its disinfectant and antiseptic properties are valued. The lack of iodine causes goiter (compensatory hypertrophy of the thyroid gland), and iodine is used both to treat iodine deficiency and hyperthyroidism. Principal iodine compounds and their industrial uses are shown.
The inorganic iodine compounds of commercial interest, and their physical properties, are discussed. The iodides, an important class of inorganic iodine compounds, have less tendency to form complexes than the other halides. Chlorine and bromine freely displace iodine from the iodides. Iodine forms industrially useful and important compounds with hydrogen, metals, the other halogens, and oxygen. Those presented here are typical.
Allgemeine Substanzbeschreibung Vorkommen Verbreitung in Lebensmitteln Kinetik und innere Exposition Wirkungen Gesundheitliche Bewertung Grenzwerte, Richtwerte, Empfehlungen, gesetzliche Regelungen Vorsorgemaßnahmen Zusammenfassung Literatur
Mulberry leaves soaked in gradient NaF solutions and fed to fourth instar larvae of the silkworm Bombyx mori for 48 hr had no significant adverse effects on fecundity. However, significant adverse effects occurred if NaF was administered in the fifth instar at a concentrations above 618 mg F/kg dried mulberry leaves to the fluoride-tolerant silkworm variety Zhenong 1 or in excess of 110.5 mg F/kg to the fluoride-sensitive variety Hang 8. Interestingly, a stimulatory effect on fecundity was found around 60 mg F/kg for highly fluoride-tolerant silkworms.
Two new studies have demonstrated that fluoride can impair male fertility. The first, in mice, found fluoride decreases sperm hyperactivation and Catsper1 gene expression. The second, in rats, reports that fluoride decreases sperm motility, enhances oxidative stress in testis, and increases testis apoptosis. These findings are consistent with many earlier reports of adverse fluoride effects, including some of reduced fertility in animals drinking water containing 1 ppm of fluoride. The current recommendation by some authorities for adding fluoride to community water supplies is likely to impair male fertility.
Sixty-four forty-day old male Wistar rats were divided randomly into two groups of thirty-two each. With one group untreated as controls, the other group was administered 150 mg NaF/L (68 ppm F-) in their drinking water to assess the effects of high fluoride on sperm quality and testicular histology at different developmental stages. In contrast to the control group, the F-treated rats exhibited a decline in sperm viability and a significant increase of sperm abnormalities 50, 80, 100, and 120 days after administration of sodium fluoride. Sperm density declined markedly at day 80 and day 120. The number of seminiferous epithelium cell layers (NSECL), the thickness of the seminiferous tubule (TST), and the diameter of the seminiferous tubule (DST) in the testis all decreased at day 50, 100, and 120. In short, the semen quality was impaired by fluoride in the drinking water, and the histological changes in the seminiferous epithelium of testicular tissues may be responsible for the diminished sperm quality in male rats.
Chronic fluorosis is a slow and progressive process causing symptoms related to several systems particularly musculo-skeletal and dental systems. This study is aimed at investigating the biochemical and histological effects of chronic fluorosis on first generation (F1) rat lung tissues.
Adult Wistar albino rats were used in order to obtain F1 male rats. Female rats were mated with males at a 2:1 ratio. The pregnant rats were given drinking water containing 100 mg/L sodium fluoride during gestation period. The rats had labour at 21±2 days. During the lactation period the mother rats were given the similar fluoridated water (100 mg/L fluoride). After weaning period, the young animals (1st generation; F1) were given the similar fluoridated water for 4 months time. Then, 9 male rats (F1) were chosen randomly and were sacrificed, and the lungs were removed for biochemical and histological examination. Control group rats were given commercial water containing of 0.07 mg/L fluoride.
In F1 rats, plasma fluoride levels and the levels of thiobarbituric acid reactive substance (TBARS) in the homogenates of lung tissues were found to be increased significantly when compared with the control group. There were markedly histological changes in lung tissues of F1 rats. Alveolar congestion, descuamation of alveolar epithelium, thickened interalveolar septae were observed. Mononuclear cell infiltrations and hyperemic vessels were evident in the parenchymal areas. Moreover, some emphysematous areas were observed. Our biochemical and histopathological results clearly show that chronic fluorosis causes a marked destruction in lung tissues of F1 rats.
Although cadmium (Cd) and fluoride may both have adverse effects on bone, most studies focus on a single agent. In this study, we investigated the effects of cadmium and fluoride on bone at a relative low level. Sprague-Dawley male rats were assigned randomly into four groups which were given sodium chloride, cadmium (50mg/L), and fluoride (20mg/L) alone, or in combination via drinking water. At the 12th week, urine, blood, and bone tissues were collected for biomarker assay, biomechanical assay, and histological assay. Cadmium had significantly adverse effects on bone mineral density, bone biomechanical property, and bone microstructure. Fluoride slightly increased vertebral bone mineral density but negatively affected bone biomechanical property and bone microstructure. Fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium but could not improve the damage of bone biomechanical property and microstructure caused by cadmium. Tartrate-resistant acid phosphatase 5b levels in rats treated with cadmium and fluoride or in combination were 1-2.5 folds higher than the control. Our data suggest that low level of fluoride could reverse the decrease of vertebral bone mineral density caused by cadmium exposure but has no influence on appendicular skeleton damage caused by cadmium.
Fluoride occurs naturally in soil, water, plants and animals in trace quantities. When fluoride is ingested, some is taken up by body tissues, with long-term deposition in teeth and bones. Following the demonstration of a significant reduction in dental caries in childhood within populations exposed to higher levels of fluoride in drinking water, between 1964 and 1975 several Local Authority water fluoridation schemes were introduced in England and Wales, whereby the fluoride content was artificially increased to a level of 1ppm (1mgL−1). Although evidence continues to support the premise that fluoride in water helps protect children's teeth against caries, there are a number of potential adverse impacts, notably dental fluorosis (mottling of teeth). The situation is complicated by the fact that many individuals receive additional exposure to fluoride through the use of fluoride toothpaste, for example. Nonetheless, fluoridation of water continues to be generally regarded as a safe, simple and cost-effective public health measure to reach children most at risk and reduce the incidence of dental caries.Available evidence on risk of hip and other bone fractures suggests no effect of fluoride in water, although a small percentage change (in either direction) cannot be ruled out. There appears to be no link between water fluoridation and either cancer in general or any specific cancer type, but an updated analysis of UK data on fluoridation and cancer rates has nonetheless been recommended. Evidence for additional health outcomes suggested by some to be associated with fluoride ingestion, and on other concerns related to the chemicals that are added during the fluoridation process and indirect effects such as increased leaching of lead from pipes and aluminium from cooking utensils, is weak but the area deserves to be kept under review.
Although millions of Americans take psychoactive medicines (e.g. Prozac and Ritalin), few social scientists believe biological theories and findings should be integrated with research on human behavior. Four topics illustrate current studies linking politics and the life sciences: (a) Developments in genetics and medicine indicate that governmental policies have greatly underrated the dangers posed by radiation and the social transformations that will result from DNA sequencing, (b) Research on brain structures and neurochemistry shows how toxic chemicals undermine normal emotions and behavior. Heavy metal burdens are higher in violent criminals, and exposure to these toxins is significantly correlated with rates of violence (controlling for socioeconomic, ethnic, and demographic factors), (c) An untested chemical used to treat water supplied to 140 million Americans significantly increases both odds of dangerous lead uptake and behavioral dysfunctions in children and adults, (d) The complexity of gene-environment interactions challenges accepted theories of gender, sociopolitical inequalities, ethnocentrism, and history. Such research in biopolitics can illuminate policy controversies in education, substance abuse, and crime.
: Sexually mature male Swiss mice were exposed at 60 days of age to 100, 200 and 300 ppm sodium fluoride (NaF) in their drinking water for 4 weeks or 10 weeks. The effect of NaF exposure on fertility was assessed by breeding these males with untreated female mice after the exposure periods. Fertility was significantly reduced at all three concentrations by exposure for 10 weeks but not for 4 weeks. The number of implantation sites and viable fetuses was significantly reduced in females mated with males that had in-gested NaF at a concentration of 200 ppm for 10 weeks. Relative weights of seminal vesicles and preputial glands were significantly increased in mice exposed to 200 and 300 ppm NaF for 4 weeks but not in mice exposed for 10 weeks. These results indicate that long-term ingestion of NaF adversely af-fects fertility in male mice.
In the absence of toxicological data on a chemical, the threshold of toxicological concern (TTC) approach provides a system to estimate a conservative exposure below which there is a low probability of risk for adverse health effects. The original toxicology dataset underlying the TTC was based on NOELs from repeat dose studies. Subsequently there have been several efforts to assess whether or not these limits are also protective for reproductive/developmental effects. This work expands the database of chemicals with reproductive and developmental data, presents these data in a comprehensive and transparent format and groups the chemicals according to the TTC "Cramer Class" rules. Distributions of NOAELs from each of these classes were used to assess whether the previously proposed TTC values based on repeat dose data are protective for reproductive/developmental toxicity endpoints as well. The present analysis indicates that, for each Cramer Class, the reproductive and developmental endpoints would be protected at the corresponding general TTC tiers derived by Munro et al. (1996).
O presente estudo objetivou avaliar as características espermáticas, os indicadores do metabolismo oxidativo do sêmen, o diâmetro dos túbulos seminíferos e a altura do epitélio testicular, do epididimário e do canal deferente de ovinos tratados com fluoreto de sódio. Foram utilizados 12 ovinos, com idade aproximada de cinco meses. Os animais foram divididos em grupo controle, o qual recebeu diariamente sal iodado (5g de NaCl animal-1 + 0,2mg I kg-1 matéria seca), e tratado, que recebeu sal iodado adicionado de fluoreto de sódio (4,7mg F kg-1 de peso corporal). Aos 150 dias de tratamento, foram realizadas coletas de sêmen e, em seguida, os animais foram eutanasiados. Na comparação entre o grupo controle e o tratado, não foram observadas diferenças no percentual de motilidade, vivos : mortos e morfologia espermática, na concentração da glutationa reduzida seminal, no teor de zinco seminal, no peso testicular, na morfometria e na histologia do testículo, na cauda do epidídimo e no canal deferente. A concentração de substâncias reativas ao ácido tiobarbitúrico (TBARs) e o teor de cobre no sêmen foram menores (P<0,05) no grupo tratado. Conclui-se que a administração crônica de flúor para ovinos jovens não afeta a capacidade reprodutiva de uma forma geral. Entretanto, os dados sugerem que o flúor pode reduzir a lipoperoxidação e os teores de cobre que são essenciais para a capacitação espermática e a fertilização
This study provides quantitative information on the effect of sodium fluoride (NaF) on the testes of F1 generation male rats exposed in utero and during lactation to NaF at one of four concentrations (25, 100, 175, 250 ppm). At weaning, the F1 generation males were exposed to NaF in their drinking water for 14 weeks, after which time testicular tissues were perfusion-fixed with glutaraldehyde and observed after being embedded in plastic. The seminiferous tubules comprised 89%, 87%, 88%, 88% and 88% of the total testis volume while the interstitial space occupied 9.3%, 11.2%, 10.2%, 9.8% and 9.9% of the total testis volume for the 0, 25, 100, 175 and 250 ppm NaF treatment groups, respectively. Statistically significant differences between control and NaF-treated rats were not observed with respect to absolute volume of the seminiferous tubules, interstitial space, Leydig cells, blood vessels boundary layer, lymphatic space, macrophages, tubular lumen or absolute tubular length and absolute tubular surface area, mean Sertoli cell nucleoli number per tubular cross-section, mean seminiferous tubule diameter and the mean height of the seminiferous epithelium. A statistically significant decrease in the absolute volume and volume percent of the lymphatic endothelium was observed in the 175 and 250 ppm NaF-treated groups and in the testicular capsule in the 100 ppm NaF-treated groups. The significance of this finding is unknown at the present time. Overall, the quantitative information obtained suggests that exposure to NaF at the doses used in the present study does not adversely affect testis structure or spermatogenesis in the rat.
The anatomy of the reproductive tract of the male sand rat, Psammomys obesus, was examined by light microscopy. Histologically, the reproductive tract is similar to other rodent species. Seminiferous tubules in the 1-month-old sand rat do not contain a tubular lumen but Sertoli cells, spermatogonia and spermatocytes are present. A full complement of germ cells is present in the seminiferous tubules by 2.5 months and spermatogenesis is well established. The interstitial space is not well defined until 2.5 months when cell types typical of most rodent species are observed. The epididymis is not noticeably segmented into lobules. An epididymal lumen is not observed until 2.5 months. Cauda epididymal sperm are not observed in the 1 or 2.5-month-old animals and cauda epididymal sperm counts from the 7.5 and 12.5-month-old animals are highly variable. The epididymis, proximal and middle regions of the vas deferens, seminal vesicles and prostate display morphological and histological characteristics similar to other rodent species. The distal end of the vas deferens is not expanded to form an ampulla.
Unlabelled:
Previous epidemiological studies have associated silicofluoride-treated community water with enhanced child blood lead parameters. Chronic, low-level dosage of silicofluoride (SiF) has never been adequately tested for health effects in humans. We report here on a statistical study of 151,225 venous blood lead (VBL) tests taken from children ages 0-6 inclusive, living in 105 communities of populations from 15,000 to 75,000. The tests are part of a sample collected by the New York State Department of Children's Health, mostly from 1994-1998. Community fluoridation status was determined from the CDC 1992 Fluoridation Census. Covariates were assigned to each community using the 1990 U.S. Census. Blood lead measures were divided into groups based on race and age. Logistic regressions were carried out for each race/age group, as well as above and below the median of 7 covariates to test the relationship between known risk factors for lead uptake, exposure to SiF-treated water, and VBL >10 microg/dL.
Results:
For every age/race group, there was a consistently significant association of SiF treated community water and elevated blood lead. Logistic regressions above and below the median value of seven covariates show an effect of silicofluoride on blood lead independent of those covariates. The highest likelihood of children having VBL> 10 microg/dL occurs when they are both exposed to SiF treated water and likely to be subject to another risk factor known to be associated with high blood lead (e.g., old housing). Results are consistent with prior analyses of surveys of children's blood lead in Massachusetts and NHANES III. These data contradict the null hypothesis that there is no difference between the toxic effects of SiF and sodium fluoride, pointing to the need for chemical studies and comprehensive animal testing of water treated with commercial grade silicofluorides.
Since the mid 1940s, fluoride has been added to tap water in American communities in an effort to reduce the incidence of dental caries in the population. When the levels of fluoride in drinking water were tested and set, water was the only measurable source of fluoride for most communities. Now, adults and children ingest fluoride with foods and beverages prepared with fluoridated water, and they are exposed to fluoride-containing dental products. As a result, exposure to fluoride is greater than had been anticipated. In the early 1990s, the existing reproductive studies were reviewed in several reports and were considered to be inadequate to determine potential reproductive or developmental hazards. The effects of sodium fluoride ingestion at 0, 25, 100, 175 or 250 ppm in drinking water measured in rats throughout three generations are reported here. Feed and fluid consumption, body weights and clinical signs were recorded at regular intervals. Decreased fluid consumption observed at 175 and 250 ppm was attributed to decreased palatability and did not affect reproduction. No cumulative effects were observed in the three generations. Mating, fertility and survival indices were not affected. Organ-to-body-weight ratios and organ-to-brain weight ratios were not affected. Sodium fluoride up to 250 ppm did not affect reproduction in rats.
Sodium fluoride (NaF) has been used to fluoridate drinking water in the United States since the mid 1940s. Because of the lack of reliable studies on the multigeneration effects of the compound, NaF (0, 25, 100, 175 or 250 ppm in drinking water) was given to rats continuously during three generations. Parental (F0) generation rats were treated for 10 weeks and mated within groups. At gestation day 20, caesarean sections were performed and eight F0 females per group and their litters (F1) were observed for implant status, fetal weight and length, sex and morphological development. The remaining F0 females (29-32 per group) were allowed to litter. F1 offspring (36 of each sex per group) were mated within groups, and caesarean sections were performed at gestation day 20. The F1 females and their litters (F2) were observed for implant status, fetal weight and length, sex and morphological development. In addition, F2 fetuses were evaluated for internal (soft-tissue) and skeletal development. Decreased fluid consumption for F0 and F1 dams at 175 and 250 ppm was attributed to decreased palatability of the solution. No dose-related effects in feed consumption or mean body weight gain were observed in either F0 or F1 females. Numbers of corpora lutea, implants, viable fetuses and fetal morphological development were similar in all groups. No dose-related anomalies in internal organs were observed in F2 fetuses. Ossification of the hyoid bone of F2 fetuses was significantly decreased at 250 ppm. Because of the decreased ossification of the hyoid bone, 250 ppm is considered the effect level.
Sodium fluoride (NaF), a widespread natural pollutant was given to sperm-positive female rats throughout gestation and lactation at a dose of 4.5 and 9.0 ppm via drinking water. The neonates were allowed to grow up to 90 days on tap water, and then sperm parameters, testicular steroidogenic marker enzyme activity levels, and circulatory hormone levels were studied. The sperm count, sperm motility, sperm coiling (hypoosmotic swelling test), and sperm viability were decreased in experimental rats when compared with controls. The activity levels of testicular steroidogenic marker enzymes (3beta hydroxysteroid dehydrogenase and 17beta hydroxysteroid dehydrogenase) were significantly decreased in experimental animals indicating decreased steroidogenesis. The serum testosterone, follicle stimulating hormone and luteinizing hormone levels were also significantly altered in experimental animals. Our data indicate that exposure to NaF during gestation and lactation affects male reproduction in adult rats by decreasing spermatogenesis and steroidogenesis.
ABSTRACT: OBJECTIVE: To address the role of fluoride in causing defects to spermatids and epididymal spermatozoa. METHODS: Male rabbits were treated with 10 mg NaF/kg body weight daily for 18 months and maintained under identical laboratory conditions along with the control rabbits not given NaF. Testis and epididymis (caput) were investigated for ultrastructural details of spermatids and spermatozoa. RESULTS: A wide variety of structural defects were observed in the flagellum, the acrosome, and the nucleus of the spermatids and epididymal spermatozoa of fluoride-treated rabbits. Abnormalities included absence of outer microtubules, complete absence of axonemes, structural and numeric aberrations of outer dense fibers, breakdown of the fibrous sheath, and structural defects in the mitochondria of the middle piece of the flagellum. Detachment and peeling off of the acrosome from the flat surfaces of the nucleus were also observed. CONCLUSION: The abnormalities observed render the sperm nonfunctional and ineffective, and thus there is a possible role of fluoride in causing infertility.International journal of fertility and menopausal studies 1994; 39(3):164-71.
Fluoride was orally administered to rabbits at 10 mg NaF/kg body weight for 18 or 29 months. The animals were then killed and the structure of the testis, epididymis and vas deferens studied under light and scanning electron microscopes. In animals treated for 29 months, the spermatogenic cells in the seminiferous tubules were disrupted, degenerated and devoid of spermatozoa. In animals treated for 18 or 29 months, loss of cilia on the epithelial cells lining the lumen of the ductuli efferentes of the caput epididymidis and of stereocilia on the epithelial cells lining the lumen of the vas deferens was observed. In some regions of the epithelial lining of the lumen of the ductuli efferentes and vas deferens, the boundaries of the cells were not clear and appeared to be peeled off. Mucus droplets were abundant in the vas deferens of control animals, but absent in both the treated groups. Spermatogenesis ceased only in animals treated for 29 months. The difference in the structural changes observed in the testes of the 2 treated groups may have been due to the blood-testis barrier. It is concluded that ingestion of high concentrations of fluoride has harmful effects on the male reproductive system.
Treatment of washed, ejaculated bovine sperm with 30 mM sodium fluoride immobilized the cells in a characteristically rigid form. In cells metabolizing endogenous substrates, fluoride decreased respiration by about 60%, but did not inhibit the cells' ability to produce adenosine-5'-triphosphate (ATP) via oxidative phosphorylation and did not block access to endogenous substrates. Fluoride-immobilized sperm maintained maximal ATP titers for at least 60 min, but oligomycin treatment rapidly depleted ATP, indicating that ATP synthesis and metabolism was occurring in immobilized sperm. The putative phosphodiesterase inhibitor caffeine (2.5 mM) restored motility and increased respiration in fluoride-treated sperm, but 8-bromo-adenosine-3',5'-monophosphate (8-bromo-cAMP) did not, even though 8-bromo-cAMP stimulated respiration in control (untreated) sperm. Carboxyfluorescein analysis of the intracellular pH of untreated sperm indicated a normal pH of 6.3. Fluoride addition decreased the apparent intracellular pH slightly, but this effect was attributable to dilution. Caffeine did not change internal pH in untreated or fluoride-immobilized sperm. Fluoride did not appear to affect cAMP metabolism, but caffeine increased intracellular cAMP titers by about 35% in both untreated and fluoride-inhibited sperm. However, caffeine treatment did not mimic 8-bromo-cAMP, as analyzed by electrophoresis and autoradiography of sperm proteins labeled with 32P from endogenously generated [32P]ATP. Clearly, caffeine is not stimulating motility in fluoride-treated sperm by affecting the cyclic AMP system. Fluoride also inhibited motility in digitonin-permeabilized sperm by a mechanism that may have involved magnesium depletion, but caffeine had no stimulatory effect on either untreated or fluoride-immobilized, permeabilized sperm.
Some of the fascination which Bonnet so marvellously expressed in his letter to Spallanzani, we surely share to this day; to a great extent it arises from the fact that spermatozoa, unlike other body cells, are endowed with two clearly discernible biological properties (of which at last we begin to know rather more than our illustrious predecessors), namely the capacity to move fast and to fertilize, a remarkable combination of attributes, each inherent in a different constituent structure of the sperm cell.
Free ionic fluoride concentrations were measured in the maternal blood plasma, cord blood plasma and the urine of pregnant and age matched nonpregnant women in two groups of subjects. Group 1 included females who had been living in endemic fluorosis areas with the mean intake of 21 mg/day of fluoride from drinking water and Group 2 consisted of women from non-endemic areas with the mean daily intake of 1.5 mg of fluoride from drinking water. The ionized fluoride concentrations in the maternal plasma and the urine decreased during the course of pregnancy; they were at their lowest at 36 weeks of gestation. In the nonpregnant controls these values remained largely unchanged. In the maternal and cord blood plasm obtained at the time of cesarean section the fluoride concentrations were similar and did not support the concept of a placental fluoride barrier. The higher fluoride content in the plasma and urine of the women in the endemic group (10 ppm F - in drinking water) indicated a direct relationship of these values to the amount of fluoride ingested. The fall in the maternal plasma and urine fluoride concentration during pregnancy is believed to be due to increasing accumulation of fluoride in the rapidly mineralizing fetal skeleton.
Inbred mice, fed a low-fluoride diet, 0.263 ± 0.28 ppm F-, were given drinking water containing 0, 1, 5, 10, 50, 100, or 200 ppm F- for 3 to 6 weeks. Cytological studies on bone marrow cell chromosomes and spermatocytes showed that 1 - 200 ppm F- (as sodium fluoride) was able to induce chromosomal changes in a dose-dependent manner. The frequency of the induced chromosomal damage was significantly higher in each treatment than in the controls. The observed abnormalities included translocations, dicentrics, ring chromosomes, and bridges plus fragments, or fragments by themselves. There was a significant correlation between the amount of fluoride in the body ash and the frequency of the chromosomal abnormalities.
The study was designed in order to assess the relationship between infertility and histological structure of testes following administration of varying doses of sodium fluoride. One hundred adult male albino mice were fed 10 ppm (Group A), 500 ppm (Group B) and 1000 ppm (Group C) of sodium fluoride in drinking water. The Group A animals were sacrificed at the end of one month, Group B after two and Group C after three months. The testes were removed and, after being processed in the usual manner, they were stained with hematoxylin and eosin. In Groups B and C, the higher dosage groups, there was a lack of maturation and differentiation of spermatocytes. In animals sacrificed at the end of three months, spermatogenesis had stopped and the seminiferous tubules had become necrotic. A definite relationship between fluorosis and damage to the testes has, therefore, been established by this study.
The endemic hypoplasia of the permanent teeth known as chronic endemic dental fluorosis, or mottled enamel, is a water borne disease associated with the ingestion of toxic amounts of fluorides in the water used for cooking and drinking during the period of calcification of the affected teeth. The permanent teeth in particular are affected, although in areas of medium to marked severity the signs of mottled enamel are at times observable on certain of the deciduous teeth.The causative factor of mottled enamel is operative during the period of tooth development. Hence the affected teeth erupt, showing the characteristic markings of the hypoplasia. Normally calcified teeth erupt showing a smooth, glossy, translucent structure, usually of a pale creamy white color. Teeth affected with mottled enamel, on the contrary, erupt showing a dull, chalky white appearance which in many instances later take on a characteristic brown stain, the frequency of brown
Leydig cells prepared routinely (glutaraldehyde--osmium) for ultrastructural studies are generally found to be lacking in subcellular detail as a result of poor membrane preservation and a dense cytoplasmic matrix. A method modified after that of Karnovsky (1971), utilizing a ferrocyanide--osmium mixture for post-treating glutaraldehyde fixed tissued, was found to yield routinely excellent preservation of Leydig cells. The primary advantages of this method were the enhancement of contrast within the Leydig cell and greatly improved membrane preservation. In addition, the smooth endoplasmic reticulum always appeared as an extensive network of interconnected tubules of uniform diameter; mitochondria, lysosomes, peroxisomes, multivesicular bodies, and Golgi were especially prominent. Glycogen and microfilaments, not readily seen in routine preparations, were found to be abundant in these cells. New observations on the numbers and distributions of subcellular organelles are described and are discussed in relation to their possible role in the steroidogenic process. In view of the greatly improved tissue preservation observed in this study, it is suggested that this treatment be used routinely for preservation of rat Leydig cells.
The variations off supply to infants and small children have been mapped as far as possible; the greatest increase of F supply, occurs with water-diluted powder formulas, notably when water containing >1 ppm ofF is used. Earlier recommended F supplement schemes may in some cases cause tempo;,ary overdosage, particularly if combined with a powder formula feeding. In addition, considerable evidence points to a special influence on enamel formation from the plasma F peaks caused by single, rapidly absorbed F doses. Conservative principles for caries-preventive F supply to small children are suggested. Important areas for further research are pointed out.
Adenylate cyclase from ejaculated human spermatozoa was inhibited by fluoride, Cu2+, Zn2+, Ni2+ and several carboxylic acids.
A recent report suggests that fluoride has mutagenic activity in mice. To examine the potential clastogenic effect of ingested fluoride, we examined the frequencies of baseline SCE and mitomycin C induced SCE as well as baseline chromsomal aberrations and cell-cycle kinetics in mice raised on high and low fluoride diets. The lack of significant differences in any of these parameters between the two groups of animals indicates that dietary fluoride is not clastogenic and supports the continued use of water fluoridation.
Rats were considered to be pubertal at 50 days of age when spermatozoa were first found in the tail of the epididymis. Sperm production/g testis increased up to 75 days of age and testicular weight increased until 100 days of age. Sperm reserves in the tail of the epididymis were not maximal until 100 days of age. Therefore, Wistar rats are not sexually mature until 100 days. Sexually mature rats had testes weighing 3.7 g, produced 86 x 10(6) spermatozoa or 24 x 10(6) spermatozoa/g testicular parenchyma daily, and their paired epididymides contained 295 x 10(6) spermatozoa in the head + body and 440 x 10(6) spermatozoa in the tail.
1. Male Wistar rats were exposed to fluoride (F) at concentrations of 100- and 200 ppm in their drinking water for 6- and 16 weeks. 2. The high F intake caused several-fold increase in the F concentrations in the testes and bone as compared with control rats, both after the 6- and 16 wk exposure; the bone F, but not testicular F, appeared to increase with dose and time. 3. F exposure (100- and 200 ppm) decreased significantly the concentrations of zinc (Zn) in the testes, plasma, liver and kidneys particularly in the 16 wk groups; in the bone Zn tended to increase, however. 4. The iron concentrations of the testes and plasma were not affected by F, whereas those of the liver, kidneys and bone appeared to increase under the influence of F. 5. The concentrations of copper and manganese in the testes, liver and kidneys were not changed by F exposure. 6. Fifty percent of the 100- and 200 ppm F rats after 16 weeks exhibited histopathologic changes in the germinal epithelium of the testes, which resembled those in Zn-deficient rats. 7. The data suggest that a deprivation of testicular Zn due to a high F intake may be directly responsible for the injury of testicular tubules.
Placental transfer of fluoride was studied in 40 Holstein cows and related to a previous 7 1/2 y study for comparative purposes. Animals were randomly assigned to fluoride dosage groups of control, 0.51, 1.31 or 2.66 sodium fluoride/d (10, 25, 50 or 100 ug/g feed). Each animal received the dose daily via gelatin bolus for 4-14 d prior to parturition. Maternal heparinized blood samples were collected before dosing and after parturition. Placental cotyledon and calf blood samples were collected from each animal immediately after parturition. Maternal and calf plasma and placental cotyledon fluorine concentrations were determined. Increased levels of fluoride given to pregnant cows resulted in significantly increased (p less than 0.05) maternal plasma and placental cotyledon fluorine concentrations. Calf plasma fluorine concentrations at birth did not significantly increase in relation to the fluoride treatment level of dams. The data support the concept that under normal circumstances in cattle there is a partial placental barrier to fluoride that operates to limit fluoride concentrations in the fetal circulation and tissues.
A single microdose (50 micrograms/50 microL) injection of sodium fluoride (NaF) into the vasa deferentia of adult male albino rats (Rattus norvegicus) caused arrest of spermatogenesis and absence of spermatozoa in the lumina of the seminiferous tubules of the testes, which consequently led to a decline in the sperm count in the caudae epididymides. Scanning electron microscopy of cauda and vas deferens sperm revealed deflagellation and tail abnormalities. This is probably related to the alterations in the internal milieu of these organs which rendered the spermatozoa immotile and consequently caused fertility impairment in the experimental animals. Thus microdoses of sodium fluoride were found to affect reproductive function and fertility rate.
Placental transfer of fluoride was investigated by fluoride determination in the bones and teeth of newborn rabbits whose mothers had been treated with fluoride during pregnancy. The mothers were given doses of 0, 0.10, 0.52 and 1.05 mmol fluoride per kg body weight as sodium fluoride, from the 16th day after conception to the end of pregnancy. All the doses produced a significant increase of fluoride level in the bones and teeth of newborn rabbits, indicating that the placenta was no barrier for the passage of fluoride.
Until now, transplacental passage of fluoride could only be checked during delivery. Recent developments in fetal blood sampling techniques in utero have made it possible to study its passage in pregnancy. Two tablets of 2.212 mg of sodium fluoride (Zymafluor) were given to 11 women with an average age of 27 1/2 years whose pregnancies on an average had lasted 22 weeks. They were having prenatal diagnosis by ultrasound guided fetal blood sampling in any case. The levels of fluoride were measured by the use of a specific electrode before the mother took fluoride and 40 minutes after she had taken it in both maternal and fetal blood samples. The results were compared with a controlled group of 11 pregnant women with similar characteristics: maternal age, duration of pregnancy and basal maternal fluoride levels. Fetal blood levels of fluorides in mothers who had taken sodium fluoride was statistically higher than in the controlled group (2.6 mumol/l and less than 1 mumol/l); this demonstrates in a statistically significant way that fluoride passes across the placenta in the fifth and sixth months of pregnancy which is the time when the milk teeth start to develop in the uterus.
The effects of sodium fluoride (NaF) ingestion in two doses (10 and 20 mg/kg body weight) for 30 days on histology and histocytometry of reproductive organs of the adult male mouse were investigated. In order to study reversibility, treatment was withdrawn for one and two months. The testes, epididymides, vas deferens, prostate, and seminal vesicle were utilized for the study by standard hematoxylin-eosin staining and an ocular eye piece and micrometer scale. NaF treatment caused severe disorganization and denudation of germinal epithelial cells of seminiferous tubules with absence of sperm in the lumina. The Leydig cell and nucleus diameters were not affected. The caput epididymis showed fewer changes than the cauda. However, epithelial cell nuclear pyknosis and absence of luminal sperm were observed. A reduction in epithelial cell height, nuclear pyknosis, denudation of cells, and absence of sperm occurred in the cauda epididymis. The vas deferens epithelium showed nuclear pyknosis, clumped stereocilia, and cell debris but no sperm in the lumen and an increase in the lamina propria. The prostate and seminal vesicles were not affected by treatment. Withdrawal of treatment caused marked recovery in the histoarchitecture of these organs. The effects of NaF treatment are therefore transient and reversible.
We conducted this study to measure maternal plasma, fetal plasma, and fetal enamel fluoride concentrations for four hours following an oral F dose to near-term pregnant guinea pigs.
We placed female guinea pigs on de-ionized (Group I) or 3-ppm-F (Group II) drinking water prior to breeding and during gestation. On the 57th day of gestation, we administered a maternal dose of NaF solution (0.6 mg Flkg) by stomach tube. We collected samples of maternal plasma, fetal plasma, and fetal enamel at baseline, at 15 and 30 min, and at one, two, and four h after administration of the dose. We assayed samples for F using a modification of the micro-diffusion and ion-specific electrode method.
Group I mean baseline F values were: maternal plasma, 0.016; fetal plasma, 0.002 ; and fetal enamel, 7. 0 ppm. Group II mean values were: 0.055, 0.004, and 19.0 ppm. After the maternal fluoride dose, the mean maternal plasma [F] rose sharply for 30 to 60 min and declined to about 50% of peak values by four h. Fetal plasma [F] changed less in absolute values, but similarly to maternal changes relative to baseline. Fetal enamel mean [F] rose more in Group II than in Group I.
Baseline F status had an important effect on F uptake in fetal enamel following an actue maternal fluoride dose.
To better understand, to optimize, and to validate the technique of intratesticular (i.t.) injection, several parameters related to i.t. injection were examined. Volumes exceeding 50 microliters could be injected i.t.; however, testes frequently became excessively turgid and backflow of injected fluids occurred. Thus, a volume of 50 microliters or less was deemed optimal for injection. To determine the rate of distribution of substances throughout the testis, trypan blue was injected i.t. near the caudal pole of the testis, and the movement of dye was monitored. Within 2 min, the dye had spread approximately 1 cm from the site of injection, and in 5 min it had spread twice that distance. In 2 h, the dye had become distributed throughout the testis except at its extreme cranial pole. Seminiferous tubules did not take up dye, indicating that the spread of dye was via peritubular lymphatics. Seminiferous tubule histology appeared virtually unaffected by i.t. injection, even at regions adjacent to the site of injection, when a sterile 26-gauge or smaller bore needle was utilized. To determine disappearance from the testis, radiolabeled inulin was injected i.t. Half time for absorption was achieved at 1.75 h. Potential vehicles were explored in which compounds with a variety of physical properties could be injected. Gum tragacanth, normal saline, ethylene glycol, dimethyl sulfoxide (DMSO) mixed 1:1 with normal saline, sesame oil, and propylene glycol were found to be suitable injection vehicles, whereas ethanol, dissolved in normal saline in concentrations as low as 0.5% was found unsuitable. To assess vehicle efficiency, various vehicles were utilized with a known testicular toxin (taxol) and injected into one testis, and the histology was compared with the contralateral testis injected with vehicle alone. All vehicles, found suitable above, allowed dispersion of taxol to influence areas distant from the site of injection. Intratesticular injection assesses the potential of agents to directly affect the testis, and systemic metabolism is avoided. Their rapid spread throughout the lymphatics of the testes allows seminiferous tubules to be exposed to agents in innocuous vehicles more rapidly and in higher concentration than is often possible when using systemic injections.
Previous studies have shown that fluoride is present in beverages prepared with fluoridated water. The purpose of this study was to determine the availability of fluoride from beverages consumed in adjacent fluoridated and non-fluoridated communities taking into account fluoride supplementation regimens. Children in grade six were invited to participate in recording of beverage intake in two cities in Alberta, Canada: Wetaskiwin, with water supplies fluoridated at 1.08 ppm F, and Camrose, non-fluoridated with water supplies at 0.23 ppm F. Three-day beverage intake records--"Drink Diaries"--were collected from 179 children in Wetaskiwin and 230 children in Camrose. Fluoride values, based on the analyses of Hargreaves, were assigned to the reported consumption of the children with the three highest and three lowest total beverage intakes in each community. A wide range of available fluoride was found. A substantial source of fluoride was shown to be available in the non-fluoridated community from beverages other than water, primarily from carbonated beverages commercially prepared with fluoridated water. Available beverages and actual consumption should be considered in the prescription of fluoride supplementation for children with minimal fluoride in their drinking water.
There has been little information and much confusion regarding the genotoxic effects of fluoride. The purpose of this study was to examine the spermatogenic influence of sodium fluoride (NaF) on the germ cells by means of the mouse sperm morphology test. Male mice of genotype B6C3F1 were obtained at about eight weeks of age and maintained on a low-fluoride diet (less than 0.2 ppm F) and distilled water ad libitum throughout the experiment. At approximately 13 weeks of age, the animals were randomly assigned to eight groups. Group I was intubated with the Maximum Tolerable Dosage (MTD) of NaF (70 mg/kg). Groups II through VI received NaF by stomach intubation at doses of 35, 20, 10, 1, and 0.1 mg/kg, respectively. Group VII served as a negative control and was intubated with distilled water. The positive control, Group VIII, was exposed to a known mutagen, cyclophosphamide (20 mg/kg, i.p.). The animals were treated daily for five days, and killed by cervical dislocation 35 days after the first exposure to chemicals. Slides of sperm from the cauda epididymides were prepared and blindly scored for morphological abnormalities. Weight of the testes was recorded, and the femurs were saved for fluoride (F) analysis. Analysis of bone F demonstrated the effective absorption of fluoride following intubation. The counts of abnormal sperm and the weights of the testes for mice exposed to NaF doses up to the MTD were not significantly different from those of the negative control. The results of this study showed that NaF did not have adverse effects on mouse sperm morphology.
Fluoride concentrations were determined in plasma of 50 pregnant women, 44 samples of amniotic fluid and fetal cord blood of 29 fetuses at various stages of normal pregnancies, from an area with a relatively low water fluoride (less than 0.5 ppm) content. The mean concentrations of fluoride from maternal plasma, cord plasma and amniotic fluid (+/- S.D.) were 0.033 +/- 0.003, 0.028 +/- 0.005 and 0.017 +/- 0.003 ppm, respectively. Maternal and fetal plasma fluoride concentrations did not differ significantly. In the older age group fetal cord plasma fluoride concentration was significantly lower than maternal plasma levels (0.012 +/- 0.08 ppm vs. 0.023 +/- 0.001, respectively; p less than 0.05). Amniotic fluid fluoride levels were significantly higher at term than in midtrimester pregnancy, 0.017 +/- 0.0018 vs. 0.010 +/- 0.009 ppm (P less than 0.05), respectively. This higher concentration may imply higher fetal urinary excretion of fluoride at term due to the lower sequestration of fluoride as the process of bone calcification is more complete.
Oral administration of up to 84 mg/kg of NaF to adult male rats did not induce DNA-strand breaks in testicular cells when measured by alkaline elution. Although plasma fluoride levels were as high as 12 ppm is rats given 84 mg/kg of NaF, testicular fluoride levels in most cases were only 10-20% of plasma levels. Fluoride did not accumulate in the testes after 5 daily treatments. Therefore, it is unlikely that NaF, even at high doses, poses a hazard with respect to heritable genetic effects.
A new approach to rapid male sterilization has been developed in rats. This involves chemical induction of obstruction of the vas deferens by injection of 50 microliters of sclerosing agents directly into the vas. A wide variety of sclerosing agents have been tested and 95% ethanol appears to produce complete blockage of the vas in a large series of animals. Long term sterility has been determined through mating. In addition, ejaculates have been confirmed to be completely free of sperm following treatment. The pathological changes produced in the vas by these sclerosing agents are described. This procedure can be accomplished in human cadavers without surgery by direct injection through the scrotum into the vas. This new technique is rapid and effective, and may be applicable to massive voluntary sterilization programs in underdeveloped countries.
Female mice were fed a low fluoride diet (0.1 to 0.3 ppm fluoride) plus drinking water containing 0, 50, 100 or 200 ppm fluoride as sodium fluoride. Toxic effects of fluoride were evidenced by retarded growth and impaired reproduction in mice with intakes of 100 and 200 ppm fluoride, and the higher level resulted in a high mortality rate (50% deaths in 5 wk). Mice with a low fluoride intake developed signs of fluorine deficiency, with a progressive development of infertility in 2 successive generations. Growth rate and litter size were not affected by the low fluoride intake, but the percentage of mice producing litters was lower, and the age at delivery of the first litter was greater than in mice receiving 50 ppm fluoride.
PIP
This study was undertaken to develop a simple non-surgical technic for achieving male sterility. The method induces obstruction in the vas deferens by injecting sclerosing chemical agents through the skin of the scrotum directly into the vas. Previous success in rats using 95% ethanol have been reported. This sutdy used 95% ethanol, 10% silver nitrate, 36% acetic acid, 3.6% formaldehyde, 3% sodium tetradecyl sulfate, 5% sodium morrhuate, 5% potassium permanganate, 3.6% formaldehyde in 90% ethanol, and for controls .9% sodium chloride. 25 or 50 mcl of the agent being tested was injected into each vas deferens of mature Sprague-Dawley rats. 2 weeks after treatment the rats were exposed to continuous mating. All of the rats treated with ethanol, silver nitrate, acetic acid, formaldehyde, and sodium tetradecyl sulfate have remained sterile for 8 months. 33% of those treated with potassium permanganate and 67% of those treated with sodium morrhuate have remained fertile. When the experiment was repeated in dogs using 95% ethanol, 10% silver nitrate, or 3.6% formaldehyde in 90% ethanol (100 or 500 mcl injected through the skin of the scrotum) the same obstructing sclerosis was found and a reduction in size of the vas was visible for approximately 2 cm. No sperm granulomas were found either grossly or microscopically. The method has not be used in humans but injections of methylene blue dye in alcohol have been made in several human autopsy specimens. The dye was contained within the sheath of the vas and penetrated the full thickness of the wall of the vas. The method is believed to be suitable for humans, would avoid post-surgical hemorrhage and infection, would require less equipment, and more rapid accomplishment and lower cost would follow if paramedical personnel could be taught the procudre in less developed countries for mass voluntary sterilizations. The results appear to be permanent. Surgical reversibility has not be determined.
Fluoride concentrations in maternal and cord blood were measured for the first time with a method specific for inorganic fluoride. The concentrations averaged 0.88 μM in blood from 16 mothers and 0.68 μM in the cord blood, with a correlation of 0.86. These results are consistent with the hypothesis that fluoride diffuses passively across the placenta. The term placenta, as previously reported, can have much higher concentrations (average 50 μM), but the acid-stable organic fluoride averaged only 4 μM, which is similar to the valves found in human sera.
Maternal (uterine) artery, maternal (uterine) vein, umbilical artery, and umbilical vein blood were obtained simultaneously at the time of 16 cesarean sections. Calcium determinations of these blood plasma samples and those from women in their ninth month of pregnancy suggest either that a calcium "pump" operates in the placenta supplying a higher concentration of calcium to the fetal blood supply than is found in the maternal circulation or that the calcium homeostatic mechanisms operate at different levels in the maternal and fetal organisms. The fluoride concentrations found in the blood plasmas suggest that the placental barrier to the transport of fluoride ion does not operate so as to maintain a difference in concentration of fluoride between the maternal and fetal body fluids.
Fluoride passes the placenta in limited amounts and may bestow caries resistance upon developing teeth. In a recent report, offspring of rats fed a diet containing sodium pentafluorostannite during gestation were found to have reduced caries incidence compared to offspring of rats fed sodium fluoride. In order to determine whether this observation was related to increased placental transfer of fluoride, pregnant rats were fed diets containing 50, 100, and 200 ppm fluoride or equivalent, from the following salts: sodium pentafluorostannite, so dium pentachlorostannite, sodium fluoride, stannous fluoride, or a mixture of sodium and stannous fluorides. On day 20 of gestation, fetuses and placentas were obtained for analyses. The average fluoride levels of the fetuses from rats fed 50, 100, and 200 ppm fluoride diets ranged from 0.6 to 0.9 ppm, 1.1 to 2.0 ppm, and 3.0 to 4.0 ppm fluoride, respectively. None of the salts appeared to have a significantly different efficiency of placental transfer of fluoride. Fetal tin values were elevated when the maternal diet contained tin salts, but without apparent relation to dietary tin level. J. Nutr. 101: 525-532, 1971.
The basal ATPase activity of 30S dynein, whether obtained by extraction of ciliary axonemes with a high (0.5 M NaCl) or low (1 mM Tris-0.1 mM EDTA) ionic strength buffer is increased by NaCl, NaNO3, and Na acetate, with NaNO3 causing the largest increase. The calmodulin-activated ATPase activity of 30S dynein is also increased by addition of NaCl, NaNO3, or Na acetate, but the effects are less pronounced than on basal activity, so that the calmodulin activation ratio (CAR) decreases to 1.0 as salt concentration increases to 0.2 M. These salts also reduce the CAR of 14S dynein ATPase to 1.0 but by strongly inhibiting the calmodulin-activated ATPase activity and only slightly inhibiting the basal activity. Sodium fluoride differs both quantitatively and qualitatively from the other three salts studied. It inhibits the ATPase activity of both 14S and 30S dyneins at concentrations below 5 mM and, by a stronger inhibition of the calmodulin-activated ATPase activities, reduces the CAR to 1.0. Na acetate does not inhibit axonemal ATPase, nor does it interfere with the drop in turbidity caused by ATP and extracts very little protein from the axonemes. NaCl and, especially, NaNO3, cause a slow decrease in A350 of an axonemal suspension and an inhibition of the turbidity response to ATP. NaF, at concentrations comparable to those that inhibit the ATPase activities of the solubilized dyneins, also inhibits axonemal ATPase activity and the turbidity response. Pretreatment of demembranated axonemes with a buffer containing 0.25 M sodium acetate for 5 min followed by extraction for 5 min with a buffer containing 0.5 M NaCl and resolution of the extracted dynein on a sucrose density gradient generally yields a 30S dynein that is activated by calmodulin in a heterogeneous manner, ie, the "light" 30S dynein ATPase fractions are more activated than the "heavy" 30S dynein fractions. These results demonstrate specific anion effects on the basal and calmodulin-activated dynein ATPase activities, on the extractability of proteins from the axoneme, and on the turbidity response of demembranated axonemes to ATP. They also provide a method that frequently yields 30S dynein fractions with ATPase activities that are activated over twofold by added calmodulin.
Despite the chronic exposure of the US population to fluoridated drinking water since the 1940s, existing studies have been judged inadequate to determine any potential reproductive or developmental hazard. This study was conducted to determine the effects of sodium fluoride (NaF) on foetal development. Sperm-positive female rats were given 0, 10, 25, 100, 175 or 250 ppm NaF daily throughout gestation. They were dosed by drinking water to mimic human exposure to fluoridated water. No dose-related behavioural changes or maternal clinical signs were noted. Fluid consumption by females in the 175- and 250-ppm groups was significantly less than that of the control females. Because of this decreased fluid consumption, the daily amount of NaF ingested (0, 1.4, 3.9, 15.6, 24.7 and 25.1 mg/kg body weight) was less than expected at the two high levels. Feed consumption decreased significantly at 250 ppm, and body weights of pregnant females reflected feed consumption trends. The mean number of viable foetuses per female in all treated groups was similar to that of the control group. The significant decrease in the mean number of implants per litter in the 250-ppm group is probably linked to the lower mean number of corpora lutea in this group. The occurrence of in utero deaths was similar in the control and treated groups. Foetal growth (in terms of foetal body weight and crown-rump length) was not affected by NaF, despite the fact that the dams in the 250-ppm group ate significantly less feed and drank significantly less fluid. There was no dose-related increase in the number of external anomalies in foetuses due to NaF ingestion. At the doses given, NaF had no effect on the development of specific bones, including sternebrae. A significant increase was seen in the average number of foetuses with three or more skeletal variations in the 250-ppm group; the number of litters with foetuses with three or more skeletal variations was increased in the 250-ppm group also, but the increase was not significant. There was no dose-related effect of NaF on the incidence of soft tissue variations.
The effects of ingestion of sodium fluoride (NaF), 10 mg/kg body weight for 50 days, on the structure and metabolism of sperm of albino rats (Rattus norvegicus), were investigated. In different groups of rats, the reversible effects upon withdrawal of NaF treatment and by administering some therapeutic agents, viz., ascorbic acid and calcium alone and in combination with NaF (50 and 70 days), on sperm structure and metabolism were also studied. The results revealed that the sperm acrosomal hyaluronidase and acrosin were reduced after 50 days of NaF treatment. Sperm stained with acidic alcoholic silver nitrate revealed acrosomal damage and deflagellation, which might be causative factors for the reduced activity of the enzymes. These alterations also resulted in a decline in sperm motility. The cauda epididymal sperm count was decreased, perhaps because of spermatogenic arrest. Thus, the low sperm motility and count ultimately contributed toward reduction in fertility by NaF treatment. However, withdrawal of NaF treatment for 70 days produced incomplete recovery, while administration of ascorbic acid and calcium, individually and in combination, brought about significant recovery of fluoride-induced effects. Thus, the effects of fluoride on sperm structure and metabolism of rats are transient and reversible.
Effects of sodium fluoride (NaF) on washed, ejaculated human spermatozoa at doses of 25, 50, and 250 mM were investigated in vitro at intervals of 5, 10, and 20 min. Sodium fluoride (NaF) did not affect the extracellular pH of sperm, except that a slight acidification was caused by the 250 mM dose only. The treatment caused a significant enhancement in acid phosphatase (ACPase) and hyaluronidase activities after 5 and 10 min. However, the decrease in the lysosomal enzyme activity after 20 min treatment could have been due to the gradual increase in fluoride accumulation by spermatozoa leading to membrane damage. Silver nitrate staining of sperm revealed elongated heads, deflagellation, and loss of the acrosome together with coiling of the tail. Sperm glutathione levels also showed a time-dependent decrease with complete depletion after 20 min indicating rapid glutathione oxidation in detoxification of the NaF. The altered lysosomal enzyme activity and glutathione levels together with morphologic anomalies resulted in a significant decline in sperm motility with an effective dose of 250 mM.
Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, stillbirths, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake decreases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.
A review of fluoride toxicity showed decreased fertility in most animal species studied. The current study was to see whether fluoride would also affect human birth rates. A U.S. database of drinking water systems was used to identify index counties with water systems reporting fluoride levels of at least 3 ppm. These and adjacent counties were grouped in 30 regions spread over 9 states. For each county, two conceptionally different exposure measures were defined, and the annual total fertility rate (TFR) for women in the age range 10-49 yr was calculated for the period 1970-1988. For each region separately, the annual TFR was regressed on the fluoride measure and sociodemographic covariables. Most regions showed an association of decreasing TFR with increasing fluoride levels. Meta-analysis of the region-specific results confirmed that the combined result was a negative TFR/fluoride association with a consensus combined p value of .0002-.0004, depending on the analytical scenario. There is no evidence that this outcome resulted from selection bias, inaccurate data, or improper analytical methods. However, the study is one that used population means rather than data on individual women. Whether or not the fluoride effect on the fertility rate found at the county level also applies to individual women remains to be investigated.
The potential of sodium fluoride to affect spermatogenesis in the rat was assessed by intratesticular injection. Experimental rats' left testis was injected with sodium fluoride (50, 175 and 250 ppm) in vehicle (0.9% physiological saline); control testes were injected with vehicle. The right testis served as a non-injected control. Testicular tissues collected 'at' and 'distal to' the injection site and from the non-injected control testes were evaluated microscopically 24 hr and 1, 2 and 3 wk post-injection. Testicular tissues obtained at and distal to the injection site in all fluoride-injected groups resembled tissues collected from corresponding areas in the controls. Seminiferous tubule damage observed in both the vehicle-injected control testes and the fluoride-injected testes but not in the non-injected testes was attributed to injection trauma. Polymorphonuclear leucocyte infiltration was observed 24 hr post injection only at the injection site in the vehicle- and fluoride-injected groups. Leydig cells were unaffected. Leucocyte infiltration with seminiferous tubule damage was not considered to be a fluoride treatment-related effect because it was observed in both vehicle- and fluoride-injected testes. The results demonstrate that the rat is not adversely affected by direct exposure to fluoride at levels 200 times greater than those under normal conditions.