Sodium fluoride’s effect on the male reproductive system

Posted on May 27th, 2010 qbit

From fluoridealert.org

Date
Effects
Study
ATSDR (2003) response to studies

2003

Human population study

3-27mg/day

objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day.
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 high fluoride group. A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r = 0.333, P = 0.028) in the low fluoride group. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r = 0.163) in the high fluoride group … The results obtained indicate that a fluoride exposue 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.
Environ Res 2003. Sep;93(1):20-30.

Fluoride-induced disruption of reproductive hormones in men.
Ortiz-Perez and Rodriguez-Martinez et al.

Laboratorio de Toxicologia Ambiental, Facultad de Medicina, Universidad Autonoma de San Luis Potosi, San Luis Potosi, Mexico

[As ATSDR’s report has a publish date of September 2003, this study is not counted as one that ATSDR did not cite.]

2002

RAT

NaF 20mg/kg/day for 29 days
oral gavage

exerts an adverse effect on the male reproductive system and this effect is associated with indicators of oxidative stress.

significant diminution in the relative wet weight of the testis, prostate, and seminal vesicle

Epididymal sperm count was decreased significantly

Reprod Toxicol 2002 Jul;16(4):385

Testicular toxicity in sodium fluoride treated rats: association with oxidative stress.

Ghosh D, Das(Sarkar) S, Maiti R, Jana D, Das

Department of Human Physiology with Community Health, Reproductive Endocrinology and Family Welfare Research Unit, Vidyasagar University, West Bengal, Midnapore, India

Not cited by ATSDR

2002

Ram semen

5 hr incubation at 381⁄4C

0.38; 1.9; 3.8 ppm F

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 381⁄4C. Both indices decreased significantly in the presence of NaF at concentrations ranging from 20 ugmol/L to 0.1 mol/L. The activities of androgen-dependent enzymes – acid phosphatase (ACP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (y-GT-10S) – decreased significantly when the ejaculate was treated with NaF at concentrations of 20, 100, 200 ugmol/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 asparate transaminase (AspAT) displayed a large increase with the increasing lower F- concentration. These changes undoubtedly affect the physiological functions of the sperm.
Fluoride 2002; 35(3):153-160

In vitro influence of sodium fluoride on ram semen quality and enzyme activities

Zakrzewska H, Udala J, Blaszczyk B

Dept. of Biochemistry, Agricultural University, 17 Slowackiego Street, 71-434 Szczecin, Poland

Not cited by ATSDR

2000

RAT

150 mg/L NaF in drinking water

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

GSH-Px activities in the tissues of testis and epididymis were observed in ascorbic acid and fluoride group

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, Ying CJ, Liu SH, Yang KD, Wang QZ.

Department of Clinic Nutrition, Tongji Hospital Tongji Medical University, Wuhan, China.

Article in Chinese. Suggest NRC translate

Not cited by ATSDR

2000

MOUSE

100, 200 and 300 ppm NaF
drinking water for 4 or 10 weeks

Fertility was significantly reduced at all three concentrations by exposure for 10 weeks

results indicate that long-term ingestion of NaF adversely affects fertility in male mice

Full report 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.

Department of Applied Biological Sciences,
Faculty of Science, Jordan University of Science and Technology, Irbid, Jordan.

Not cited by ATSDR

2000

MOUSE

NaF
10 mg NaF/kg BW

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.

It is concluded that fluoride has a definite effect on male reproduction and fertility.

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

Cited by ATSDR

Page 167: Administration of ascorbic acid and/or calcium and cessation of sodium fluoride exposure enhanced the
recovery of sperm function and morphology and testicular damage, as compared to no treatment, in rats
(Chinoy et al. 1993), mice (Chinoy and Sharma 2000),

1999

MOUSE

Fed a protein-deficient diet treated with NaF
5, 10, 20 mg/kg BW for 30 days

caused a significant decrease in protein levels in testes, cauda epididymis, and vas deferens.

levels of cholesterol in testis and glycogen in the vas deferens were significantly enhanced as compared to controls.

Fluoride 1999; 32(4):204-214

Effects of protein supplementation and deficiency on fluoride-induced toxicity in reproductive organs of male mice

NJ Chinoy and Dipti Mehta

Reproductive Endocrinology and Toxicology Unit, Department of Zoology, School of Sciences, Gujarat University, Ahmedabad, India

Not cited by ATSDR

1998

MOUSE

NaF
10 mg/kg BW

significant decrease epididymis weight

significant decline in cauda epididymal sperm motility and viability

significant reduction in fertility rate. The cauda epididymal sperm count was also significantly reduced

Full report 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

Reproductive Endocrinology and Toxicology Unit, UGC Department of Special Assistance and COSIST in Zoology, School of Sciences, Gujarat University, Ahmedabad 380009, India.

Cited by ATSDR

Page 167:Postexposure
administration of vitamins E and/or D was also effective in the recovery of sodium-fluoride induced testicular effects in mice (Chinoy and Sharma 1998).

1998

MOUSE

NaF
10 mg/kg/day for 28 days

RAT: NaF
1 mg/kg/day and
10 mg/kg/day for 28 days

In order to contribute to the clarification the effects of NaF in animal fertility we have assessed:
1) the effect of fluoride on spermatozoa (sperm.) motility, epididymis (Epidid.) and seminal vesicles (sem. ves.) weight and fructose (fruc.) levels in sem. ves., in mice after 28 days of treatment with 10 mg/kg/day of NaF;
2) Effect of 1 mg/kg/day and 10 mg/kg/day (Groups F1 an F2, respectively) of NaF represted treatment for 28 days in rat on sperm. count, epidid., sem. ves. and testis weight, fruc. levels in sem. ves. and testosterone (testost.) levels.

Conclusions: The modification of some parameters related to fertility by the repeated oral NaF intake, in rodents, suggest that NaF has potential to disturb male fertility.

Toxicology Letters, Volume 95, Supplement 1, July 1998, Page 214

NaF may disturb male fertility in rodents

R. Pinto, C. Vieira, H. Mota-Filipe and B. Silva-Lima

Lab. Pharmacology, Fac. Pharmacy, University of Lisbon, Portugal

Not cited by ATSDR

1997

RAT

10 mg NaF/kg BW
for 30 days

the protein profile was disturbed more in testis than in cauda epididymis, whereas phospholipids and gluthathione levels were affected more in cauda than in testis.
Fluoride 1997; 30(1):41-50
Fluoride toxicity on rat testis and cauda epididymal tissue components and its reversal

Chinoy NJ*, Shukla S, Walimbe AS, Bhattacharya S

* Professor and Head, Zoology Department, School of Sciences, Gujarat University, Ahmedabad, India.

Not cited by ATSDR

1997

GUINEA PIG

NaF 30 mg kg-1 body weight
30-days

ATSDR – Page 82
LOAEL 4.5 (mg/ kg/ day
(decr sperm motility and viability)

The cauda epididymal spermatozoa were highly sensitive to the effects of NaF as their structural and metabolic alterations led to marked decreases in their motility, live:dead ratio and sperm mitochondrial activity index but increases in sperm abnormalities and alterations in sperm membrane phospholipids, particularly phosphatidylinositol and phosphatidyl serine. The activities of ATPase and succinate dehydrogenase as well as glutathione levels were decreased in testis by NaF treatment, revealing disturbances in its metabolism.
Med Sci Res 1997 25(2):97-100.

Fluoride toxicity in the testis and cauda epididymis of
guinea pig and reversal by ascorbate.

Chinoy NJ, Patel BC, Patel DK, et al.

Zoology Department, School of Sciences, Gujarat University, Ahmedabad, India.

Cited by ATSDR

ATSDR states:

Page 179:alterations in sperm
morphology or spermatogenesis

See also: Pages 82 and 113

1997

RABBIT

ATSDR – Page 85
LOAEL 4.5 mg/ kg/day
Leydig cell damage

LOAEL 4.5 mg/ kg/ day
Leydig cell damage

As cited by ATSDR, page 85

Environ Sci 5(2):79-94.1997.

Ultrastructural studies on the leydig cells of rabbits exposed to chronic
fluoride toxicity.

Susheela AK, Kumar A.

Cited by ATSDR

1997

GERBIL

High fluoride (HF)pups = 2.3 ug F/g BW/day from birth to 24 days whereafter food contained 37 mg F/kg.

Low fluoride (LF)pups: from 24 days old food contained 7 mg F/kg.

At 16 weeks:
Mean testes weight of High fluoride group significantly less than Low fluoride group
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 pineal gland

Jennifer Anne Luke

Not cited by ATSDR

1996

Serum testosterone concentrations inpatients with skeletal fluorosis

Circulating serum testosterones in skeletal fluorosis patients were significantly lower than those of Control 1 at p < 0.01.
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.

Cited by ATSDR

Page 112:
study found significantly decreased serum testosterone
levels in 30 men diagnosed with skeletal fluorosis and in 16 men related to men with fluorosis and living in the same house as the patient (Susheela and Jethanandani 1996). The mean drinking water fluoride levels were 3.9 ppm (approximately 0.11 mg fluoride
/kg/day), 4.5 ppm (0.13 mg fluoride
/kg/day), and
0.5 ppm (0.014 mg fluoride/kg/ day) in the patients with skeletal fluorosis, related men, and a control group of 26 men living in areas with low endemic fluoride levels… One limitation of this study is that the control men were younger (28.7 years) than the men with skeletal fluorosis (39.6 years) and the related men (38.7 years). In addition, the groups are small and potentially
confounding factors are not well addressed.

Also, pages 177, 179

1996

BANK VOLE

200 micrograms F/ml drinking water for 4 months

histopathologic changes in the germinal epithelium.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1996 Jan;113(1):81-4

Photoperiodic elevation of testicular zinc protects seminiferous tubules against fluoride toxicity in the bank vole (Clethrionomys glareolus).

Krasowska A, Wlostowski T.

Institute of Biology, Bialystok Branch of Warsaw University, Poland.

Not cited by ATSDR

1995

RAT

NaF
10 mg/kg BW
for 30 and 50 days

ATSDR – Page 81
LOAEL 4.5 mg/ kg/ day
(decreased sperm motility and count)

A significant reduction in electrolyte levels of sperm also occurred which would also affect their viability. The protein levels in cauda epididymal sperm suspension, vas deferens, seminal vesicle and prostate were significantly decreased after NaF administration

The results, corroborated by earlier data from our laboratory, show that fluoride has a definite effect on male reproduction and fertility.

Fluoride 1995; 28(2):75-86

Amelioration of fluoride toxicity in some accessory reproductive glands and spermatozoa of rat

Chinoy NF, Narayana MV, Dalal V, Rawat M, Patel D

Reproductive Endocrinology and Toxicology Unit, School of Sciences, Gujarat University, Ahmedabad 380 009, India

Cited by ATSDR

1995

RAT

NaF in drinking water
100 mg/L, and 200 mg/L for 2, 4, and 6 weeks.

Results suggest that fluoride may have some harmful effects on the reproductive system in male rats.
Fluoride 1995; 28(3):128-130

The influence of fluoride on the content of testosterone and cholesterol in rat

Zhao ZL, Wu NP, Gao WH

Department of Preventive Medicine, Ningxia Medical College, 750004 China

Not cited

ATSDR cites in References only, not in text

1995

RABBIT

10 mg NaF/kg BW/day for 20 and 23 months

ATSDR – Page 84
LOAEL 4.5 M mg/ kg/ day
(structural damage of the spermatid and epididymal spermatozoa)

The structural changes observed in the caput and cauda ductus epididymis might adversely affect the maturation of spermatozoa
Int J Exp Pathol 1995 Feb;76(1):1-11

Effects of chronic fluoride toxicity on the morphology of ductus epididymis and the maturation of spermatozoa of rabbit.

Kumar A, Susheela AK.

Department of Anatomy, All India Institute of Medical Sciences, New Delhi.

Cited by ATSDR

1994

RAT

NaF
10 mg/kg BW for 50 days

The histomorphometric studies revealed significant change in the Leydig cell diameter in correlation with the androgen levels. These results indicate that fluoride does interfere with steroidogenesis in short-term low-dose exposures in rats.
Fluoride 1994; 27(1):7-12

Effect of fluoride on rat testicular steroidogenesis

MV Narayana and NJ Chinoy

Zoology Department, School of Sciences, Gujarat University, Ahmedabad 380 009, Gujarat, India

Cited by ATSDR:

Page 112: “In contrast [to Sprando 1997], significant decreases in serum testosterone levels were observed in rats receiving daily gavage doses of 4.5 mg fluoride /kg/day as sodium fluoride for 50 days (Narayana and Chinoy 1994) and in rats exposed for 60 days to 4.5 mg fluoride/kg /day as sodium fluoride in the diet (Araibi et al. 1989).”

1994

RAT
(21-24 days old)

NaF
10 mg/kg BW
for 30 days

changes resulted in a significant decrease in sperm motility and thereby fertility rate.
Fluoride 1994; 27(2):67-75

Beneficial effects of ascorbic acid and calcium on reproductive functions of sodium fluoride-treated prepubertal male rats

Chinoy NJ, Reddy VVPC, Michael M

Not cited by ATSDR

1994

RAT

NaF
10 mg/kg BW
50 days

sperm acrosomal hyaluronidase and acrosin were reduced

low sperm motility and count

International Journal of Fertility 39 (6) 337-346. 1994.

Reversible effects of sodium fluoride ingestion on spermatozoa of the rat.

Narayana MV, Chinoy NJ.

Reproductive Endocrinology & Toxicology Unit, School of Sciences, Gujarat University, Ahmedabad, India.

Not cited by ATSDR

1994

RABBIT

10 mg NaF/kg BW daily for 18 months

ATSDR – Page 84
LOAEL 4.5 M mg/ kg/day
(structural damage of the
spermatid and epididymal spermatozoa)

The abnormalities observed render the sperm nonfunctional and ineffective, and thus there is a possible role of fluoride in causing infertility
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.

Cited by ATSDR

1994

Human spermatozoa

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
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.

Not cited by ATSDR

1992

RAT

F
100- and 200 ppm in their drinking water for 6- and 16 weeks.

ATSDR – Page 112
after 16 weeks of exposure, seminiferous tubule atrophy was observed at
7.5 mg fluoride/kg/day and higher

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;

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.

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.

Comp Biochem Physiol C. 1992 Sep;103(1):31-4.
The effect of high fluoride intake on tissue trace elements and histology of testicular tubules in the rat.

Krasowska A, Wlostowski T.

Institute of Biology, Bialystok Branch of Warsaw University, Poland.

Cited by ATSDR.

1992

MOUSE

NaF
10 mg 20 mg/kg BW for 30 days.

ATSDR – Page 81
LOAEL: 4.5 mg/ kg/ day (decr sperm motility and count and infertility)

significant decrease in sperm count and motility

large numbers of deflagellated spermatozoa, with acrosomal, midpiece and tail abnormalities

The treatment caused loss of fertility rate when normal cycling female mice were mated with treated males.

Fluoride 1992; 25(2):71-76

Reversible fluoride induced fertility impairment in male mice

NJ Chinoy and E Sequeira

Dept. of Zool., Univ. Sch. of Sciences, Gujarat Univ., Ahmedabad-380 009, India.

Cited by ATSDR

Page 113:
The alterations in sperm and the infertility were reversible 30–60 days after termination of a 30-day exposure period (Chinoy and Sequeira 1992).Decreased sperm counts, sperm motility, and sperm viability (the ratio of live to dead sperm) have been observed in rats exposed to 2.3 mg fluoride/kg/ day and higher (Chinoy et al. 1992, 1995) and mice (Chinoy and Sequeira 1992)

1992

RAT

NaF
5 and 10 mg/kg BW/day) for 30 days

ATSDR – Page 81
LOAEL: 2.3 mg/ kg/ day (decreased fertility and sperm counts)

succinate dehydrogenase activity in testis was inhibited. Similarly, adenosine triphosphatase activity and sialic acid levels in epididymides were also suppressed with more pronounced effect on cauda epididymis. Consequently, sperm motility and count were decreased leading to a significant decline in fertility by fluoride treatment.
Journal of Environmental Biology 13 (1) 55-61. 1992.

Effects of fluoride ingestion on the physiology of reproductive organs of male rats

Chinoy NJ, Pradeep PK, Sequeira E.

Dept. of Zool., Univ. Sch. of Sciences, Gujarat Univ., Ahmedabad-380 009, India.

Cited by ATSDR

Page 113:
When exposed male rats were mated with unexposed females, decreased fertility was observed at 2.3 mg fluoride/kg/ day as sodium fluoride and higher (Chinoy and Sequeira 1992;Chinoy et al. 1992).
Decreased sperm counts, sperm motility, and sperm viability (the ratio of live to dead sperm) have been observed in rats exposed to 2.3 mg fluoride/kg/ day and higher (Chinoy et al. 1992, 1995)

1992

RABBIT

NaF
5, 10, 20, and 50 mg/kg BW/day

abnormal accumulation of lipids in testes.

The increase of concentration of all lipid classes except free fatty acids in testes was directly correlated with the increase in dosage of fluoride administered.

Fluoride 1992; 25(3):149-154

Biochemical effects of fluoride on lipid metabolism in the reproductive organs of male rabbits

A Shashi

Department of Zoology, Punjabi University, Patiala, India.

Not cited by ATSDR

1992

RABBIT

NaF 5, 10, 20 and 50 mg
via subcutaneous injections for a period of 3-1/2 months

The testicular structural, nuclear and total proteins were significantly depleted in all test groups of animals as compared to the control. There was a significant (p < 0.001) reduction in the testicular DNA after drug administration.
Indian J Pathol Microbiol. 1992 Oct;35(4):351-6.

Testicular proteins and DNA in experimental fluorosis.

Shashi, Kaur D.

Department of Zoology, Punjabi University, Patiala, India.

Not cited by ATSDR

1991

RAT

chronic fluorosiswas developed with drinking water containing high fluoride in male rat.

Ultrathin sections of testes and prostate gland were observed under transmission electron microscope. The results were as follows: in the interstitial cell, microvilli on the surface of the cell decreased. Decrease or impairment of mitochrondria to various extent and distention of the smooth endoplasmic reticulum in cytoplasma were observed. Increase of lysosome, the multiform changes of mitochondria, distention and vesiculization of smooth endoplasmic reticulum and deposition of large lipid droplets appeared in some of sertoli cells of seminiferous tubule. Significant change did not appear in spermotogonium but appeared in spermatid. Spermiogenesis was blocked.There were impairment in the epithelium and interstitial tissue to some extent. The results in this experiment suggest that: interstitial cell of testes could be damaged and spermiogenesis could be blocked.
J CHINA MED UNIV; 19 (5). 1991. 339-342.

Ultrastructural observations of testes and prostate gland in rat with chronic fluorosis.

Song K et al.

Dep. Histoembryol.

Article in Chinese. Suggest NRC translate

Not cited by ATSDR

1991

RABBIT

10 mg NaF/kg BW for 18 or 29 months.

ATSDR – Page 84
LOAEL 4.5 mg/ kg/day
(complete cessation of spermatogenesis)

In animals treated for 29 months, the spermatogenic cells in the seminiferous tubules were disrupted, degenerated and devoid of spermatozoa.

Spermatogenesis ceased only in animals treated for 29 months.

J Reprod Fertil 1991 Jul;92(2):353-60

A study of the effect of high concentrations of fluoride on the reproductive organs of male rabbits, using light and scanning electron microscopy.

Susheela AK, Kumar A.

Department of Anatomy, All India Institute of Medical Sciences, New Delhi.

Cited by ATSDR

Page 84, 112

1991

RABBIT

NaF
20 and 40 mg/kg BW for 30 days

Reduction in sperm motility, count, and changes in their morphology and metabolism led to the significant decline in fertility of the treated animals.
Fluoride 1991; 24(1):29-39
Effects of vitamin C and calcium on the reversibility of fluoride-induced alterations in spermatozoa of rabbits

Chinoy NJ , Sequeira E, Narayana MV

Department of Zoology, University School of Sciences, Gujarat University, Ahamadabad, India.

Cited by ATSDR

Page 167:
Chinoy and associates have examined the effectiveness of calcium, ascorbic acid, vitamin E, and vitamin D in reversing the reproductive effects associated with oral exposure to sodium fluoride.
Administration of ascorbic acid and/or calcium and cessation of sodium fluoride exposure enhanced the recovery of sperm function and morphology and testicular damage, as compared to no treatment, in rats
(Chinoy et al. 1993), mice (Chinoy and Sharma 2000), and rabbits (Chinoy et al. 1991).

1991

RAT

single microsose (50 ug/50 ul) NaF into vasa deferentia of Rattus norvegicus

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.

Reproductive Toxicology 1991;5(6):505-512

Microdose vasal injection of sodium fluoide in the rat

Chinoy NJ, Rao MV, Narayana MV, Neelakanta E

Department of Zoology, University School of Sciences, Gujarat University, Ahamadabad, India.

Not cited by ATSDR

1990

RABBIT

NaF
5, 10, 20 and 50
mg/kg/day
for 100 days

Deficient maturation and differentiation of the spermatocytes and an increase in the amount of interstitial tissue were found in the experimental animals. In the higher dosage groups, spermatogenesis stopped and the seminiferous tubules became necrotic.
Folia Morphol (Praha) 1990;38(1):63-5

Histopathological changes in rabbit testes during experimental fluorosis.

Shashi.

Department of Zoology, Punjabi University, Patiala, India.

Not cited by ATSDR

1989

RAT

100 or 200 ppm NaF
60 days

ATSDR (2003) – Page 80
LOAEL 4.5 mg/ kg/ day
(50% reduction in fertility, decr in percentage of seminiferous tubules containing spermatozoa and decr testosterone levels)

dose-related decrease in reproductive performance

decrease in serum testosterone at 200 ppm

ATSDR in its 1991 Toxicological profile for fluorides, hyrdogen fluoride, and fluorine, stated (page 63):
“Male CD rats fed 5 or 10 mg fluoride/kg/day as sodium fluorideexhibited a significant increase in the thickness of the peritubular membrane of the seminiferous tubules. Both treated group also exhibited a significant decrease in the percentage of seminiferous tubules containing spermatozoa and a significant decrease in serum testosterone. As a result, there were fewer pregnancies and fewer offspring among treated animals.”

J BIOL SCI RES; 20 (1). 1989. 19-30.
Effect of high fluoride on the reproductive performance of the male rat.

Araibi AA, Yousif WH, Al-Dewachi OS.

Cited by ATSDR

1989

MOUSE

NaF
10 mg 20 mg/kg BW
for 30 days.

NaF treatment caused severe disorganization and denudation of germinal epithelial cells of seminiferous tubules with absence of sperm in the lumina.

epithelial cell nuclear pyknosis and absence of luminal sperm were observed.

Reprod Toxicol 1989;3(4):261-7

Effects of fluoride on the histoarchitecture of reproductive organs of the male mouse.

Chinoy NJ, Sequeira E.

Not cited by ATSDR

1989

MOUSE

NaF
10 mg 20 mg/kg BW
for 30 days.

testis succinic dehydrogenase levels decreased, in the epididmides sialic acid and ATPase levels decreased; in the vas deferens glycogen levels increased, seminal vesicles fructose levels increased in the prostate glands, acid phosphatase and total protein levels increased.
Fluoride 1989; 22(1):78-85

Fluoride induced biochemical changes in reproductive organs of male mice

Chinoy NJ, Sequeira E.

Not cited by ATSDR

1987

MOUSE

NaF
10, 20, 40 mg/kg
Different assays were used

Incidence of micronucleus and sperm abnormality increased with dose.

… Of all the assay results in the present study, the sperm abnormality was highest …

Caryologia 1987, 40:1-2; 79-87

Genotoxic effect of an environmental pollutant, sodium flouride, in mammalian in vivo test system

Pati PC and Bhunya SP

Laboratory of Genetic Toxicology, Department of Zoology, Utkal University, Vani Vihar, Bhubaneswar, India

Not cited.

ATSDR only cited chromosome aberrations in mouse bone

1985

RAT

5 ppm F

A lowering in the production of testosterone was thought to be due to Perfluorochemicals exposure. A series of tests using sodium fluoride exposure to rats were performed. “The results provide unequivocal evidence that 250 uM fluoride inhibits testosterone secretion by rat testes perfused in vitro… The present observation of deleterious effects by 250 uM fluoride (5 ppm) emphasizes the sensitivity of steroidogenesis to fluoride.”
3rd International Congress of Andrology, Boston,
Massachusetts.
J Androl 6:59 (1985)

Reproductive toxicology of fluoride

Chubb C

University of Texas Health Science Center, Dallas, Texas 75235.

Not cited

ATSDR cites in References only, not in text

1984

RAT

NaF
5.0 mg/kg and 20.0mg/kg

NaF at 5.0 mg/kg
glutathione-S-transferase activity increased 4-fold in the testis


NaF at 20.0 mg/kg
decrease in lipid peroxidation in testes
Toxicol Lett 1984 May;21(2):167-72

Alterations in drug metabolising enzymes and lipid peroxidation in different rat tissues by fluoride.

Soni MG, Kachole MS, Pawar SS.

Biochem. Div., Dept. Chem., Marathwada Univ., Aurangabad 431004, India.

Not cited by ATSDR

1983

RAT

A marked fall (P < 0.01) in the testosterone production was recorded at a fluoride concentration of 100 ppm and testosterone synthesis was maximally inhibited (P < 0.01) at 200 ppm. There was a noticeable, though marginal, inhibition in testosterone synthesis even at 10 ppm fluoride concentration… The fluoride ions which diffuse into the cells inhibit steroidogenesis…
IRCS Med. Sci. 11, 813-814 (1983)

In vitro inhibition of testosterone synthesis in the presence of fluoride ions

Kanwar KC, Vig PS, Kalla NR

Department of Biophysics, Panjab University, Chandigarh, India.

Not cited by ATSDR

1983

Chicken

NaF
600 ppm

98 days old to 158 days of age

NaF (150, 300 or 600 ppm) were added to the basal ration of Hisex male and female chickens (98 days old)… (until 158 days of age)… initiation of spermatogenesis was delayed in the testes of the 600 ppm group and giant spermatid cells were observed. Breed variation in the response of chicken to the added level of F- was suggested.
FLUORIDE; 16 (1). 1983. 37-43.

Effect of high fluoride intake on chicken performance, ovulation, spermatogenesis and bone fluoride content.

MEHDI A WR, AL-SOUDI KA, AL-JIBOORI N AJ,
AL-HITI MK

Dep. Vet. Physiol. Anim. Sci., Baghdad Univ., Coll. Agric., Baghdad, Iraq.

Not cited by ATSDR

1982

MOUSE

Inbred mice, fed a low-F- diet, 0.263 | .028 ppm F-, were given drinking water containing 0, 1, 5, 10, 50, 100 or 200 ppm F- for 3-6 wk

Cytological studies on bone marrow cell chromosomes and spermatocytes showed that 1-200 ppm F- (as NaF) 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 abnormalities included translocations, dicentrics, ring chromosomes, and bridges plus fragments, or fragments by themselves. There was a significant correlation between the amount of F- in the body ash and the frequency of chromosomal abnormalities.
FLUORIDE; 15 (3). 1982. 110-118

Cytological effects of sodium fluoride on mice.
Mohamed AH
Chandler ME

Dept. of Biology and School of Medicine, University of Missouri, Kansas City

Not cited

ATSDR cites in References only, not in text

1981

MOUSE

cytochemical alterations in Leidig cells and in the basal parts of the Sertoli cells
Fluoride 1981; 14(4):182-191

Fluorosis: geographical pathology and some experimental findings

AA Zahvoronkov and LS Strochkova

Institute of Human Morphology, Moscow, USSR

Not cited by ATSDR

1981

RAT

The effects of fluoride (F-) administration were studied on 2 groups of weanling male Wistar rats, a control fed a basal diet containing 0.09 mg% F- and the other fed a diet containing 50 mg% F- for 30 days… The amount of F- accumulated in brain, heart, thymus, kidney, testes, adrenal and femur of the F–fed group was significantly higher than those of controls.
J TOKYO MED COLL; 39 (3). 1981. 441-460.

Hygienic study on fluoride: 4. Physiological effects of fluoride on rat.

TOMOMATSU T

Dep. Biochem., Tokyo Med. Coll.

Not cited by ATSDR

1980

MOUSE

NaF
500 and 1000 ppm
in drinking water for 3 months

lack of maturation and differtiation of spermatocytes

spermatogenesis had stopped and seminiferous tubules became necrotic.

Fluoride 1980; 13(4):160-162

Histological Finding of Mice Testes Following Fluoride Ingestion

Kour K, Singh J.

Department of Anatomy, Government Medical College, Srinagar, Kashmir, India

Not cited.

Cited by ATSDR in its References but not in the text

1978

Human spermatozoa

Adenylate cyclase from ejaculated human spermatozoa was inhibited by fluoride
J Reprod Fertil 1978 May;53(1):59-61

Inhibitors of adenylate cyclase from ejaculated human spermatozoa.

Haesungcharern A, Chulavatnatol M.

Not cited by ATSDR

1978

RAT (immature)

NaF

increased frequency of occurrence of various seminiferous tubules containing spermatids

The mechanism of action of NaF may be hypothetical, but it probably consists of direct action on the seminiferous epithelium level.

Andrologia 1978 May-Jun;10(3):223-33

The influence of human menopausal gonadotropin, natrium fluoride and cyproterone acetate on the spermatogenesis in immature rats.

Kula K.

Not cited by ATSDR

1978

MOUSE

Impaired spermatogenesis
Iraqi Journal of Veterinary Medicine 1978:2,103-135

Effect of high fluoride intake on reproductive system of the male mice

Ridha M, Al-Jiboori N, Mehdi AW

Not cited by ATSDR

1977

Human males suffering from fluorosis

Compared to healthy controls, testosterone content proved to be decreased and FSH content elevated in patients with fluorosis
Probl Endokrinol (Mosk) 1977 Jul-Aug;23(4):104-7

[Effect of inorganic fluorine compounds on the functional state of the pituitary-testis system]

Tokar’ VI, Savchenko ON.

Article in Russian. Suggest NRC translate

Not cited by ATSDR

1977

RAT

NaF

androgen-binding protein (ABP) synthesis is inhibited at 0 degrees C or in the presence of cycloheximide, puromycin or sodium fluoride.

Immature (17-25-day-old rat) testes showed a higher rate of ABP synthesis per 100 mg tissue than adult rat testes during ‘baseline’ conditions

Mol Cell Endocrinol 1977 Oct;8(4):335-46

In vitro synthesis of rat testicular androgen-binding protein (ABP).

Ritzen EM, Hagenas L, Ploen L, French FS, Hansson V.

Not cited by ATSDR

1976

RAT

The enzyme of the spermatozoa from the cauda epididymidis was more sensitive to inhibition by ouabain and fluoride
J Reprod Fertil 1976 Sep;48(1):91-7

Changes in surface ATPase of rat spermatozoa in transit from the caput to the cauda epididymidis.

Chulavatnatol M, Yindepit S.

Not cited by ATSDR

1972

Patient with endemic fluorosis

bilateral calcification of the vas deferens
Fluoride 1972; 5(2):86-88

Cacification of the vas deferens in a patient with endemic fluorosis
Case report

SPS Teotia and M Teotia

Not cited by ATSDR

Note:
Kanwar et al. (1983) stated, “degeneration of the seminiferous tubules at high doses of fluoride intake was reported in 1934″ by Phillips PH and Lamb AR, Arch. Pathol. 17, 169.

ATSDR cites a 1933 study by Phillips and Lamb in its References:
Phillips PH, Lamb AR, Hart EB, et al. 1933. Studies on fluorine in the nutrition of the rat: II. Its influence on reproduction. Am J Physiol 106:356-364.

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