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•
Note: The following is a limited selection of abstracts from 1994
to present.
•
Due to length, we present this as a separate section
• Click here to return to the Reproductive
section for fluorine & organofluorine pesticides.
•
When time allows more information will be added.
1997. A dissertation
submitted to the School of Biological Sciences, University of Surrey,
in fulfilment of the requirements for the Degree of Doctor of Philosophy.
Guildford 1997.
The effect of fluoride on
the physiology of the pinal gland
Jennifer Anne Luke
Abstract:
The purpose was to discover whether fluoride (F) accumulates in
the pineal gland and thereby affects pineal physiology during
early development. The [F] of 11 aged human pineals and corresponding
muscle were determined using the F-electrode following HMDS/acid
diffusion. The mean [F] of pineal was significantly higher (p<0.001)
than muscle: 296 ± 257 vs. 0.5 ± 0.4 mg/kg
respectively. Secondly, a controlled longitudinal experimental
study was carried out to discover whether F affects the biosynthesis
of melatonin, (MT), during pubertal development using the excretion
rate of urinary 6-sulphatoxymelatonin, (aMT6s), as the index of
pineal MT synthesis. Urine was collected at 3-hourly intervals
over 48 hours from two groups of gerbils (Meriones unguiculatus),
low-F (LF) and high-F (HF) (12 f, 12 m/group): under LD: 12 12,
from prepubescence to reproductive maturity (at 9-12 weeks) to
adulthood, i.e., at 7, 9, 11 1/2 and 16 weeks. The HF pups received
2.3 ug F/g BW/day from birth until 24 days whereafter HF and LF
groups received food containing 37 and 7 mg F/kg respectively
and distilled water. Urinary aMT6s levels were measured by radioimmunoassay.
The HF group excreted significantly less aMT6s than the F group
until the age of sexual maturation. At 11 1/2 weeks, the circadian
profile of aMT6s by the HF males was significantly dimished but,
by 16 weeks, was equivalent to the LF males. In conclusion, F
inhibits pineal MT synthesis in gerbils up until the time of sexual
maturation. Finally, F was associated with
a significant acceleration of pubertal development in female gerbils
using body weights, age of vaginal opening and accelerated development
of the ventral gland. At 16 weeks, the mean testes weight of HF
males was significantly less (p<0.002) than that of the LF
males. The results suggest that F is associated with low circulating
levels of MT and this leads to an accelerated sexual maturation
in female gerbils. The results strengthen the hypothesis
that the pineal has a role in pubertal development.
Excerpt on the Newburgh-Kingston
NY study:
To the best of my knowledge, the Newburgh-Kingston
study is the only reference on the efffect of F on the timing
of puberty in humans. It is the largest, most ambitious
paediatric survey carried out to demonstrate the safety of water
fluoridation. The New York State Department of Health initiated
the study in 1944 because they realized that there would ultimately
be a need for a long-term evaluation of any possible systemic
effects as well as the dental changes from drinking fluoridated
water over a long period of time.
Similar groups of chidren were selected for long-term observation
from Newburgh (fluoridated to 1.0 to 1.2 mg/L in 1945) and Kingston
(essentially F-free for the duration of the study). Newburgh and
Kingston were chosen because they were well-matched: both situated
on the Hudson River about 35 miles apart with similar upland reservoir
water supplies; both had populations of about 30,000 with similar
demographic characteristics, social and economic conditions, levels
of dental care, etc. In Newburgh, out of 817 children (aged from
birth to nine years) who were selected in 1945, 500 were examined
in 1954-1955; in Kingston, out of 711 children who were selected
in 945, 405 were examined in 1954-55.
The medical and dental examinations began in 1944, and were repeated
periodically until 1955. An assessment of any possible systemic
effects arising from the consumption of fluoridated water was
made by comparing the growth, development and the prevalence of
specific conditions in the two groups of children as disclosed
by their medical histories, physical examinations, and laboratory
and radiological evidence. The age of onset
of menstruation in girls was used as an index of the rate of sexual
maturation.
At the end of ten years, the investigators repored no adverse
systemic effects from drinking fluoridated water because no
significant differences were found between the results from
the two groups. The average age of first
menarche was earlier among girls in Newburgh than those in Kingston:
12 years vs. 12 years and 5 months respectively
(Schlesinger et al, 1956). Although this difference
was not considered important, it does
suggest an association between the use of fluoridated drinking
water and an ealier onset of sexual maturation in girls. The
Newburgh girls had not had a lifelong use of fluoridated water.
For the first two years or so, they received unfluoridated water.
Furthermore, their only source of F was from the drinking water.
(pages 6-7)."
• Note from EC: Excerpts
are from the hard copy of Luke's thesis. Any spelling errors
are mine.
Artificial
water fluoridation causes fluoride poisoning in horses.
Lennart Krook
Professor of Pathology, Emeritus. Cornell Veterinary Medicine.
A community in Colorado fluoridated the water some 20 years ago
in a concentration of 1.3 parts per million (ranging from 0.35 to
1.35). For a local Quarter Horse operation, from 6 to 10 horses,
this was the only source of water. There were no phosphate fertilizer
used or any phosphate supplements for the horses. Signs of fluoride
poisoning started to appear after five years and included
interference with reproduction, crooked leg bones. Blood
analyses showed decreased levels of thyroid gland hormone. Post-mortem
examination of cannon-bones revealed pile-up of bone tissue on the
inner surface (endostosis) and chemical analysis of dried bone confirmed
the diagnosis of chronic dental fluorosis which grew worse with
time and finally showed severe destruction of tooth-supporting bone.
Over the years, 5 horses were killed because of progressive signs
of chronic fluoride poisoning.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8618252&dopt=Abstract
Ref: J Toxicol Clin Toxicol 1996;34(2):183-9.
Circulating
testosterone levels in skeletal fluorosis patients.
Susheela AK, Jethanandani P.
Fluoride and Fluorosis Research Laboratories, All India Institute
of Medical Sciences, New Delhi, India.
Abstract:
OBJECTIVE: The present study focuses on serum testosterone concentrations
in patients with skeletal fluorosis, in order to assess the hormonal
status in fluoride toxicity.
METHODS: Serum testosterones were compared for patients afflicted
with skeletal fluorosis (n = 30) and healthy males consuming water
containing less than 1 ppm fluoride (Control 1, n = 26) and a second
category of controls (Control 2, n = 16): individuals living in
the same house as the patients and consuming same water as patients
but not exhibiting clinical manifestations of skeletal fluorosis.
RESULTS: Circulating serum testosterones in skeletal fluorosis patients
were significantly lower than those of Control 1 at p < 0.01. Testosterone
concentrations of Control 2 were also lower than those of Control
1 at p < 0.05 but were higher than those of the patient group.
CONCLUSIONS: Decreased testosterone concentrations in skeletal fluorosis
patients and in males drinking the same water as the patients but
with no clinical manifestations of the disease compared with those
of normal, healthy males living in areas nonendemic for fluorosis
suggest that fluoride toxicity may cause adverse
effects in the reproductive system of males living in fluorosis
endemic areas.
PMID: 8618252 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7920753&dopt=Abstract
Int J Fertil Menopausal
Stud 1994 May-Jun;39(3):164-71
Ultrastructural
studies of spermiogenesis in rabbit exposed to chronic fluoride
toxicity.
Kumar A, Susheela AK
Department of Anatomy, All India Institute of Medical Sciences,
New Delhi, India.
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.
PMID: 7920753 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8032126&dopt=Abstract
Reprod Toxicol 1994
Mar-Apr;8(2):155-9.
In
vitro fluoride toxicity in human spermatozoa.
Chinoy NJ, Narayana MV
Department of Zoology, School of Sciences, Gujarat University,
Ahmedabad, India.
Abstract: 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.
PMID: 8032126 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1839778&dopt=Abstract
Reprod Toxicol 1991;5(6):505-12
Microdose vasal injection
of sodium fluoride in the rat.
Chinoy NJ, Rao MV, Narayana MV, Neelakanta
E
Department of Zoology, University School of Sciences, Gujarat University,
Ahamadabad, India.
Abstract: 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.
PMID: 1839778 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12865044&dopt=Abstract
Environ
Res. 2003 Sep;93(1):20-30.
Fluoride-induced
disruption of reproductive hormones in men.
Ortiz-Perez
D, Rodriguez-Martinez M, Martinez F, Borja-Aburto VH, Castelo J,
Grimaldo JI, de la Cruz E, Carrizales L, Diaz-Barriga F.
Laboratorio de Toxicologia Ambiental, Facultad de Medicina, Universidad
Autonoma de San Luis Potosi, Av. Venustiano Carranza 2405, Col.
Lomas Filtros, CP 78210, San Luis Potosi, Mexico.
Abstract: 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 3-27mg/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: 2-13mg/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 3-27mg/day
induces a subclinical reproductive effect that can be explained
by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.
PMID: 12865044 [PubMed - indexed for MEDLINE]
Full report available at:
http://www.fluoride-journal.com/00-33-3/333-128.pdf
Fluoride 2000;
33(3):128-134.
Fertility effects of sodium
fluoride in male mice
Ahmed Elbetieha, Homa Darmani, Ahmad S Al-Hiyasat.
Abstract: SUMMARY. 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 ingested 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 affects
fertility in male mice.
Dart Special at Toxnet
Chung-Kuo Kung Kung Wei Sheng (China Public
Health) 2000 Aug;16(8):697-8
[The primary study of antagonism
of selenium on fluoride-induced reproductive toxicity of male rat]
Zhu XZ et al.
Abstract: The protective effect of ascorbic acid at dose level
of 1.0 mg/L in drinking water against the fluoride-induced damage
on reproductive system of rat was studied. 150 mg/L sodium fluoride
(NaF) in drinking water of male rat can cause the significant
decrease of sperm count and mobility, the increase of serum and
testicular lipid peroxides (LPO) contents, and the adenosine triphosphatase
(ATPase) activity depression of epididymis. All of those
effects are reversible by adding adequate ascorbic acid in drinking
water simultaneously. The effects of ascorbic acid against fluoride-induced
damages are similar to those produced by 2.0 mg/L Na2SeO3 in the
drinking water of rats. However, no significant
recovery of fluoride-induced effects on GSH-Px activities in the
tissues of testis and epididymis were observed in ascorbic acid
and fluoride group. The mechanism of ascorbic acid on fluoride-induced
damage of male reproductive system need to be further studied.
Dart Special at Toxnet
Environmental Sciences: an International
Journal of Environmental Physiology and Toxicology. 2000;
7(1):29-38
Reversal of fluoride-induced
alteration in cauda epididymal spermatozoa and fertility impairment
in male mice.
Chinoy NJ and Sharma A
Abstract: The effects of sodium fluoride (NaF) ingestion (10 mg
NaF/kg body weight) and the possible therapeutic effects of ascorbic
acid (AA, 15 mg/animal/day) and/or calcium phosphate (Ca, 25 mg/animal/day)
on the reproductive functions and fertility of male mice were investigated.
NaF-ingestion brought about a significant
decline in sperm acrosomal acrosin and hyaluronidase. Cauda
epididymal sperm stained with alcoholic acidic silver nitrate reagent
revealed acrosomal damage and deflagellation. However, sperm
nuclear integrity was not affected by the treatment.
The reduced activity of the enzymes as well as the structural and
metabolic alterations in the sperm led to a significant decrease
in sperm count, and motility and live:dead ratios but an increase
in abnormal sperm which ultimately lead to a poor fertility rate.
The cessation of NaF-treatment was not conducive to bringing about
a complete recovery. However, the administration of AA or Ca to
NaF-treated mice revealed significant recovery from fluoride toxicity
in all the above parameters. The recovery was more pronounced in
the animal group treated with both AA and calcium in combination,
thus indicating a synergistic or additive action. It is concluded
that fluoride has a definite effect on male reproduction and fertility.
However, the effects are transient and reversible with the administration
of AA and Ca. Therefore, AA and Ca are proposed as therapeutic agents
for populations in endemic areas for the amelioration of fluoride
effects on reproductive functions.
Full report
available at
http://www.fluoride-journal.com/98-31-4/314-203.htm
Fluoride
1998; 31(4):203-216.
Amelioration
of fluoride toxicity by Vitamins E and D in reproductive functions
of male mice
NJ Chinoy
and A Sharma.
Abstract: SUMMARY. Studies
on the beneficial effects of vitamins E and D supplementation on
functions of caput and cauda epididymides, their spermatozoa, vas
deferens and seminal vesicle of sodium fluoride (NaF) treated (10
mg/kg body weight) male mice (Mus musculus) were carried out. The
NaF treatment resulted in significant decrease in the body and epididymis
weight but those of vas deferens and seminal vesicle were not affected.
NaF treatment brought about alterations in epididymal milieu as
elucidated by the significant decrease in levels of sialic acid
and protein as well as activity of ATPase in epididymides.
As a result, the sperm maturation process
was affected leading to a significant decline in cauda epididymal
sperm motility and viability. This
caused a significant reduction in fertility rate. The
cauda epididymal sperm count was also significantly reduced. The
data obtained suggest that fluoride treatment induced significant
metabolic alterations in the epididymides, vas deferens and seminal
vesicles of mice. The withdrawal
of NaF treatment (30 days) produced incomplete recovery.
On the other hand, supplementation of vitamins E or D during the
withdrawal period of NaF treated mice was found to be very beneficial
in recovery of all NaF induced effects, thus elucidating their ameliorative
role in recovery from toxic effects of NaF on the reproductive functions
and fertility. On the whole, a combination of vitamins E and D treatment
was comparatively more effective than that with vitamin E or D alone.
Therefore, vitamin therapy could be beneficial for the amelioration
of fluoride induced changes in reproductive functions.
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