Adverse Effects
Sodium fluoride
CAS No. 7681-49-4

 
 

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Activity: Insecticide, Wood preservative, US EPA List 4B Inert

Inorganic:

Sodium fluoride is a crystalline mineral once widely used in the United States for control of larvae and crawling insects in homes, barns, warehouses, and other storage areas. It is highly toxic to all plant and animal life. The only remaining use permitted is for wood treatement.
Ref: Recognition and Management of Pesticide Poisonings, 5th Edition,
The Office of Pesticide Programs, US EPA. Chapter 8

http://www.epa.gov/oppfead1/safety/healthcare/handbook/Chap08.pdf

Note from FAN:
Unfortunately the above is not correct. Sodium fluoride is also allowed for use on food crops as an US EPA "List 4 Inert." In pesticide formulations only the "Active Ingredient" is identified. The rest of the formulation consists of substances called "inerts" and they can account for as much as 99% of the pesticide. The term "inerts" in pesticidal formulations is a misnomer as they are often biologically active and for the majority of "inerts" used in pesticides today, there is little to no information available on their toxicity or health effects.

"Inerts" are treated as confidential proprietary information by US EPA and the public is denied the right to know which pesticides contain them or on what food crops they are used.

All "List 4 Inerts" (which includes Sodium fluoride) were approved for use in the US National Organic Program administered by the US Department of Agriculture- (see last paragraph on page 248). USDA's new Organic Standards, finalized in 2000, does not identify the several hundred List 4 Inerts that are allowed for use. They are identified only with the term "List 4 Inerts."

For more information on the issue of "Inerts" see: Toxic Secrets: "Inert" Ingredients in Pesticides1987-1997, published by Northwest Coalition for Alternatives to Pesticides.
-EC


• Note: The following is a limited selection of abstracts mainly from 1994 to present.
• The review of data was performed in 2003.
This is not an exhaustive list.
• When time allows more information will be added.

Adverse Effects:

The following
are listed below
in this section:

Due to length,
the following are presented
as separate sections

Cancer

Chemical Weapon
Precursor

CNS

Diabetes

Endocrine: Breast

Endocrine: Hypothalamus

Endocrine: Ovary

Endocrine: Uterus

Heart

Mesenteric artery

Pancreas

Salivary glands

Spleen

Teratogen

Violation/Fine

Environmental

Apoptosis

Blood

Bone

Brain

Clastogenic • Cytotoxic • Fetotoxic • Genotoxic or Mutagenic

Endocrine: Pineal Gland

Endocrine: Testicular

G-Proteins

I.Q.

Kidney

Liver

Lung

Endocrine: Pineal Gland

Reproductive

 

 


Cancer (click on for all fluorinated pesticides)

A New Jersey Department of Health study found that the rate of osteosarcoma occurred at higher rates in young males from fluoridated versus unfluoridated areas. Between the years 1970 and 1989, the rate of osteosarcoma (among 10-19 year old males) was found to be 3.5 to 6.3 times greater in the fluoridated versus unfluoridated areas.
Ref: Cohn PD. (1992). A Brief Report On The Association Of Drinking Water Fluoridation And The Incidence of Osteosarcoma Among Young Males. New Jersey Department of Health Environ. Health Service: 1- 17.

Abstract: The US National Toxicology Program has shown equivocal evidence of carcinogenic activity of sodium fluoride (NaF) in male F344/N rats based on the occurrence of five osteosarcomas in treated animals. In the study the osteosarcomas developed mainly in the rat vertebrae. To provide a possible mechanistic basis for the observed tumors, the genotoxic effects of NaF on the possible target organ of NaF carcinogenesis were examined. Rat vertebral body-derived (RVBd) cells were established from trabecular bone of vertebral bodies of a male F344/N rat 6 weeks of age and treated with NaF. RVBd cells in secondary culture exhibited a high level of alkaline phosphatase (ALP) activity when the cells at confluence were assayed by ALP staining. When the histochemical examination was performed on RVBd cell colonies, most of the colonies were stained positively for ALP. Confluent RVBd cells were responsive to 10(-8) M 1 alpha.25-dihydroxyvitamin D3 with a 7.7-fold increase in osteocalcin production over base line values. The von Kossa staining demonstrated that in the presence of 2 mM beta-glycerophosphate, RVBd cells that were allowed to grow past confluence for approximately 2 months formed mineralized nodules. When RVBd cells in tertiary culture were treated with NaF at 0.5-2.0 mM for 24-72 h, the growth and/or survival of the treated cells was reduced in a dose-dependent manner. Significant increases in the frequencies of chromosome aberrations were induced in a dose- and treatment time-dependent fashion when NaF was administered to RVBd cells at 0.5 and 1.0 mM for 24 and 48 h. The results indicate that NaF is genotoxic to rat vertebrae, providing a possible mechanism for the vertebrae, as a target organ of NaF carcinogenesis.
Ref: Mutat Res. 1996 May;368(1):7-13. Clastogenic activity of sodium fluoride to rat vertebral body-derived cells in culture.
Mihashi M, Tsutsui T.

In a 1990 National Toxicology Program fluoride rat study, a statistically-significant, dose-dependent trend increase in osteosarcoma among the fluoride-treated, male rats was reported. According to a review of NTP's findings by the World Health Organization:

In male F344/N rats receiving 0.2, 0.8, 2.5 or 4.1 mg fluoride/kg body weight per day, the incidence of osteosarcomas (three tumours in the vertebra and one in the humerus) was 0/80, 0/51, 1/50 and 3/80, respectively (NTP, 1990). A pairwise comparison of the incidence in the high-dose group versus controls was not statistically significant (P = 0.099); if an extraskeletal osteosarcoma, located in the subcutis of the flank of one high-dose male rat, was included in the total tumour incidence in this group of animals, the pairwise comparison with the control group remained statistically insignificant (P = 0.057). However, the osteosarcomas occurred with a statistically significant (P = 0.027, by logistic regression) dose-response trend (NTP, 1990) ...In assessing the evidence for the carcinogenicity of fluoride derived from studies conducted with laboratory animals, some significance might be attributed to the observation of a dose–response trend in the occurrence of osteosarcomas in male F344/N rats administered sodium fluoride in drinking-water (NTP, 1990). Such a trend associated with the occurrence of a rare tumour in the tissue in which fluoride is known to accumulate cannot be casually dismissed.
Ref: FLUORIDES. Environmental Health Criteria 227. World Health Organization, Geneva. 224 page report released August 8, 2002.
http://www.inchem.org/documents/ehc/ehc/ehc227.htm

Excerpt: “We previously reported the cancer morbidity from 1943 through 1987 for 422 male cryolite workers employed for more than 6 months at the mill from 1924 through 1961. We observed excess incidences of primary cancer of the lungs and of urinary bladder tumors (including bladder papilloma)... We have now extended the follow-up of this cohort by 12 years, at the end of which the total percentage of cohort members who had died exceeded 90%. These findings amplify our previous observation of increased bladder cancer rates among cryolite workers... We therefore believe that fluoride should be considered a possible cause of bladder cancer and a contributory cause of primary lung cancer.”
Ref: Extended follow-up of cancer incidence in fluoride-exposed workers. Grandjean P, Olsen JH. J Natl Cancer Inst. 2004 May 19;96(10):802-3.
Note: See FAN Science Watch #11 for a discussion of these findings.

2001 Abstract. Age-specific and age-standardized rates (ASR) of registered cancers for nine communities in the U.S.A. (21.8 million inhabitants, mainly white) were obtained from IARC data (1978-82, 1983-87, 1988-92). The percentage of people supplied with "optimally" fluoridated drinking water (FD) obtained from the Fluoridation Census 1985, U.S.A. were used for regression analysis of incidence rates of cancers at thirty six sites (ICD-WHO, 1957). About two-thirds of sites of the body (ICD) were associated positively with FD, but negative associations were noted for lip cancer, melanoma of the skin, and cancers of the prostate and thyroid gland. In digestive organs the stomach showed only limited and small intestine no significant link. However, cancers of the oral cavity and pharynx, colon and rectum, hepato-biliary and urinary organs were positively associated with FD. This was also the case for bone cancers in male, in line with results of rat experiments. Brain tumors and T-cell system Hodgkin's disease, Non-Hodgkin lymphoma, multiple myeloma, melanoma of the skin and monocytic leukaemia were also correlated with FD. Of the 36 sites, 23 were positively significant (63.9%), 9 not significant (25.0%) and 4 negatively significant (11.1%). This may indicate a complexity of mechanisms of action of fluoride in the body, especially in view of the coexising positive and negative correlations with the fluoridation index. The likelihood of fluoride acting as a genetic cause of cancer requires consideration.
Ref: J Epidemiol 2001 Jul;11(4):170-9. Regression analysis of cancer incidence rates and water fluoride in the U.S.A. based on IACR/IARC (WHO) data (1978-1992). International Agency for Research on Cancer; by Takahashi K, Akiniwa K, Narita K.

Abstract: The Okinawa Islands located in the southern-most part of Japan were under U.S. administration from 1945 to 1972. During that time, fluoride was added to the drinking water supplies in most regions. The relationship between fluoride concentration in drinking water and uterine cancer mortality rate was studied in 20 municipalities of Okinawa and the data were analyzed using correlation and multivariate statistics. The main findings were as follows.
(1) A significant positive correlation was found between fluoride concentration in drinking water and uterine cancer mortality in 20 municipalities (r = 0.626, p < 0.005).
(2) Even after adjusting for the potential confounding variables, such as tap water diffusion rate, primary industry population ratio, income gap, stillbirth rate, divorce rate, this association was considerably significant.
(3) Furthermore, the time trends in the uterine cancer mortality rate appear to be related to changes in water fluoridation practices.
Ref: J Epidemiol. 1996 Dec;6(4):184-91. Relationship between fluoride concentration in drinking water and mortality rate from uterine cancer in Okinawa prefecture, Japan; by Tohyama E.
Erratum in: * J Epidemiol 1997 Sep;7(3):184.

Chemical Weapon Precursor (click on for all fluorinated pesticides)

1993 Paper: ... some of the precursor chemicals which are early in the production process and/or are widely produced in industry (and hence not considered suitable for effective monitoring under the CWC [Chemical Weapons Convention]) have been included on the AGL [Australia Group List], because they are either known or suspected to have been sought for CW purposes. Such precursors include: ...the fluoride chemicals ... for the production of sarin-family nerve agents...
14 [potassium fluoride]
24 [hydrogen fluoride]
41 [potassium bifluoride]
42 [ammonium bifluoride]
43 [sodium bifluoride]

44 [sodium fluoride]

Ref: A COMPARISON OF THE AUSTRALIA GROUP LIST OF CHEMICAL WEAPON PRECURSORS AND THE CWC SCHEDULES OF CHEMICALS by Robert J. Mathews. September 1993. Quarterly Journal of the Harvard Sussex Program on CBW Armament and Arms Limitation. Issue No. 21.
http://www.fluoridealert.org/pesticides/chemical.weapon.precursors.pdf

1995 UN Monitoring and Verification of Iraq's Compliance. The organofluorines on this list include (pesticides highlighted in red):
List A (Precursors):
Hydrogen fluoride
(7664-39-3)
Potassium fluoride
(7789-23-3)
Ammonium bifluoride (
1341-49-7)
Sodium bifluoride
(1333-83-1)
Sodium fluoride
(7681-49-4)
Potassium bifluoride
(7789-29-9)
Fluorine
(7782-41-4)

List B:
Sarin
(107-44-8)
Soman
(96-64-0)
DF
(676-99-3)
PFIB (382-21-8).
Also included are fluoropolymers (e.g. Aflex COP, Aflon COP 88, F 40, Ftorlon, Ftoroplast, Neoflon, ETFE, Teflon, PVDF, Tefzel, PTFE, PE TFE 500 LZ, Haller).
 
Ref: 1995 - Chemical & Biological Weapons. Fluorine chemicals.

• See also Violation/Fine below

CNS (click on for all fluorinated pesticides)

2003 Abstract: In an attempt to elucidate the mechanism by which excessive fluoride damages the central nervous system, the effects of exposure of PC12 cells to different concentrations of fluoride for 48 h on nicotinic acetylcholine receptors (nAChRs) were characterized here. Significant reductions in the number of binding sites for both [3H]epibatidine and [125I]alpha-bungarotoxin, as well as a significant decrease in the B(max) value for the high-affinity of epibatidine binding site were observed in PC12 cells subjected to high levels of fluoride. On the protein level, the alpha3 and alpha7 subunits of nAChRs were also significantly decreased in the cells exposed to high concentrations of fluoride. In contrast, such exposure had no significant effect on the level of the beta2 subunit. These findings suggest that selective decreases in the number of nAChRs may play an important role in the mechanism(s) by which fluoride causes dysfunction of the central nervous system.
Ref: Toxicology 2003 Feb 1;183(1-3):235-42. Selective decreases of nicotinic acetylcholine receptors in PC12 cells exposed to fluoride by Chen J, Shan KR, Long YG, Wang YN, Nordberg A, Guan ZZ.

Diabetes (click on for all fluorinated pesticides)

Summary: Wistar rats were given 20 ppm fluroide in drinking water, or single administration of 115 mg/kg alloxan i.m. to induce diabetes, or single administraiton of 115 mg/kg alloxan i.m. followed by 20 ppm fluoride for 31 days. Blood sugar level increased in rats given alloxan and alloxan + fluoride. Body weight gain in rats given alloxan + fluoride decreased significantly compared to other groups. Decrease in haemoglobin and glutamic oxaloacetate transaminase (GOT) was seen only in rats given alloxan + fluoride. In this group alkaline phosphatase, the target enzyme in fluoride toxicosis, increased considerably. The toxicity of fluoride in diabetic rats was further reflected in organ weight data. This investigation shows that fluoride toxicity is greater in diabetic rats.
Ref: Fluoride 1997; 30(1):43-50. Toxicity of fluoride to diabetic rats; by Priya CATB, Anitha K, Mohan EM, Pillai KS, Murthy PB

Endocrine: Breast (click on for all fluorinated pesticides)

• Note from EC: I include this simply because of the unexpected results presented.

1954 Paper. GROUPS OF 94 C3H & 46 DBA FEMALE MICE, 4-12 MO OF AGE, WERE GIVEN 0.4, 1.0 OR 4.0 MG/L SODIUM FLUORIDE IN DISTILLED DRINKING-WATER FOR 7-12 MONTHS. GROUPS OF 96 C3H & 45 DBA FEMALES ... AS MATCHED CONTROLS ... ALSO FED DIET CONTAINING 20-38 MG/KG FLUORINE. /OTHER GROUPS OF/ 65 & 36 C3H MICE AND 66 & 66 DBA MICE, 2-9 MONTHS OF AGE, RECEIVED 1.0 & 10.0 MG/L, RESPECTIVELY, SODIUM FLUORIDE IN DISTILLED WATER FOR 10-17 MONTHS. ALL ... FED MIXED GRAIN DIET CONTAINING NEGLIGIBLE AMT OF FLUORINE. ... AMONG MICE THAT RECEIVED 10.0 MG/L FLUORIDE, 63% DIED OF MAMMARY GLAND CARCINOMAS, COMPARED WITH 50% OF CONTROLS (TAYLOR, 1954). [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. V27 271
(1985)]
Ref: Hazardous Substances Data Bank for SODIUM FLUORIDE CASRN: 7681-49-4 (online October 2003). Available at Toxnet

Endocrine: Hypothalamus (click on for all fluorinated pesticides)

1993 Abstract: Summary: Animal models of subacute and chronic fluorosis in female rats were developed with injection of large doses of NaF(IP) and with drinking water containing 100 ppm F-, respectively. The serotonin or 5-hydroxytryptamine (5-HT) content and turnover rate in the hypothalamus were determined with spectrofluorometry combined with degradation blockade. The 5-HT turnover rate decreased during both subacute and chronic fluorosis. The 5-HT content increased during subacute fluorosis, but decreased during chronic fluorosis. These results suggest that the influences of 5-HT metabolism of the two kinds of fluorosis are not completely identical. The decrease of 5-HT turnover rate in hypothalamus may be one of possible mechanisms of deficiency of pituitary prolactin (PRL) and milk secretion during fluorosis.
Ref: Fluoride 1993; 26(1):57-60. Changes of serotonin content and turnover rate in hypothalamus of female rat during fluorosis; by Yuan SD, Xie QW, Lu FY

1991 Abstract: The effect of fluorosis on lactation, lactotroph function and ultrastructure were studied in lactating rats. The results were as follows:
1) Inhibition of lactation in lactating rats with chronic fluorosis was assessed by stunting growth of pups and decrease in the amount of milk suckled by pups in 30 min. Metoclopramide, a blocker of dopamine receptor, could improve lactation in these rats.
2) During chronic fluorosis serum PRL level was decreased, however, PRL content in pituitary was increased. Electronmicroscopic examination showed accumulation of large mature secretory granules and appearance of extremely large abnormal secretory granules in lactotroph cytoplasma.
These findings indicate that hormone release of pituitary lactotrophs is obstructed in lactating rats with fluorosis, and the toxic effect of fluoride is mediated by an enhanced function of dopaminergic system in hypothalamus.
Ref: Sheng Li Xue Bao 1991 Oct;43(5):512-7. [An experimental study of inhibition on lactation in fluorosis rats]; by Yuan SD, Song KQ, Xie QW, Lu FY. [Article in Chinese]

1990 Abstract: The phosphoinositide (PI) transduction system has proven to be of major importance in several regions of mammalian brain. In this report, we examined in rats whether a PI system is present in the hypothalamic suprachiasmatic nuclei (SCN), the site of a biological clock that generate circadian rhythms. Autoradiographic localization of phorbol ester binding revealed moderate levels of protein kinase C, a component of the PI system, in the SCN. Hypothalamic explants containing SCN showed substantial incorporation of [3H]myoinositol into lipids. AlF4-, a non-specific activator of G proteins, produced a dose-dependent increase in inositol monophosphate (IP1) levels in the explants in calcium-free medium, with a maximum increase of 216% of control at 50 mM NaF. Medium containing 1.8 mM calcium stimulated a similar increase in IP1 levels, but the stimulatory effects of AlF4- and calcium were not additive, so that the effect of Al4- was obscured in medium containing calcium. AlF4- stimulated accumulation of IP1, as well as inositol bis-, and trisphosphate, over a 40-min time course in the presence and absence of lithium (10 mM LiCl). Lithium, a known inhibitor of phosphatases in the inositol phosphate recycling pathway, raised levels of all 3 inositol phosphates in SCN explants both at baseline (without A1F4-) and after 30 min AlF4- stimulation. The results show the existence of a lithium-sensitive PI system within the suprachiasmatic region of the rat hypothalamus.
Brain Res 1990 Jan 22;507(2):181-8. Aluminum fluoride reveals a phosphoinositide system within the suprachiasmatic region of rat hypothalamus; by Nadakavukaren JJ, Welsh DK, Reppert SM.

1989 Abstract: The mechanism of sodium fluoride (NaF) induced hypothermia was investigated on relations between the monoamine synthesis and metabolism in the rabbit brain. Five male rabbits per a group, weighing about 2.5kg and having rectal temperatures of 38.4 to 39.3 degrees C, were used in this experiment. The rectal temperature measurements were made by means of an electric thermometer for 5 hours at intervals of 15 or 30 minutes. Through this experiment, animals were housed in a room kept at 22 to 23 degrees C. The following drugs were used in this experiment: NaF (40 mg/kg i.v.), barbital sodium (0.1 g/kg s.c.), hexamethonium bromide (C6, 10 mg/kg i.v.), ergotamine tartrate (30 mg/kg s.c.), phenoxybenzamine hydrochloride (15 mg/kg i.v.), propranolol hydrochloride (5 mg/kg s.c.), pindolol (0.3 mg/kg s.c.), atropine sulfate (30 mg/kg s.c.), 2, 4-dinitrophenol (DNP, 20 mg/kg i.v.), l-DOPA (20 mg/kg i.v.), 5-HTP (20 mg/kg i.v.) Results
1. Intravenous injection of 30 mg/kg of NaF induced a drop of 0.66 degrees C in rectal temperature.
2. Pretreatment with 0.1 mg/kg of barbital sodium or 10 mg/kg of C6 prominently inhibited the NaF-induced hypothermia.
3. The alpha-blockade caused by ergotamine tartrate and phenoxybenzamine or the beta blockade by propranolol hydrochloride and pindolol resulted in an approximate 50% inhibition of maximum drop in body temperature induced by NaF administration. Both alpha- and beta-blockades caused by ergotamine tartrate and propranolol or by phenoxybenzamine and pindolol, however, made a remarkable inhibition of the NaF effect. Cholinergic blockade brought on by atropine sulfate, on the other hand, had no effect against NaF-induced hypothermia.
4. Bilateral splanchnicotomy completely inhibited drops in rectal temperature.
5. Intravenous injection of NaF 40 mg/kg failed to counteract the rise of rectal temperature caused by DNP 20 mg/kg.
6. Pretreatment with l-DOPA made a prominent inhibition of NaF-induced hypothermia. The inhibiting effects of 5-HTP, however, were slight.
7. Administration of NaF made a significant decrease in norepinephrine levels in the rabbit hypothalamus, but had no effect on 5-HT levels.
Ref: Shikwa Gakuho 1989 Mar;89(3):607-26. [The rabbit thermo-regulatory system. Effects of high dose of sodium fluoride]; by Machida H.[Article in Japanese]

1986 Abstract. Hormone-sensitive adenylate cyclase is believed to exist as a complex consisting of a catalytic subunit, guanine nucleotide binding regulatory unit and a hormone or neurotransmitter receptor. The diterpene compound, forskolin, is a potent stimulator of adenylate cyclase activity presumably interacting with a site directly on the catalytic subunit. Guanine nucleotides and sodium fluoride stimulate adenylate cyclase through a stimulatory guanine nucleotide binding regulatory subunit. In order to examine the role of the forskolin binding site in the rat brain, the distribution of [3H]forskolin binding sites has been compared with those of a radiolabeled guanine nucleotide analog. [3H]Forskolin densely labeled a few discrete brain regions including the caudate-putamen, nucleus accumbens, olfactory tubercle, globus pallidus and substantia nigra. Specific [3H]guanylyl-5'-imidodiphosphate ([3H]Gpp(NH)p) binding sites were found in high densities in not only these areas but also in the cerebral cortex, thalamus, hypothalamus and midbrain regions. In the hippocampal formation, guanine nucleotide binding sites were seen in the stratum oriens, stratum radiatum, stratum lacunosum molecular and the molecular layer of the dentate gyrus. On the other hand, forskolin labeled the hilus and the pyramidal cell layer of CA3 and CA4 with high density, a region where guanine nucleotide binding was relatively low. Sodium fluoride and Gpp(NH)p were found to enhance forskolin binding in regions in which [3H]Gpp(NH)p binding sites were present. These results indicate that most, but not all forskolin binding sites in the brain, are allosterically coupled with the stimulatory guanine nucleotide binding protein. Conversely, it has also been demonstrated that some forskolin binding sites in the hippocampus are probably not guanine nucleotide regulated.
Ref: J Pharmacol Exp Ther 1986 Dec;239(3):952-8. Regional modulation of [3H]forskolin binding in the rat brain by guanylyl-5'-imidodiphosphate and sodium fluoride: comparison with the distribution of guanine nucleotide binding sites; by Gehlert DR.

Endocrine: Ovary (click on for all fluorinated pesticides)

1994 Abstract: Summary. Forty-eight albino rabbits were administered fluorde as sodium fluoride subcutaneously in daily doses of 5, 10, 20, and 50 mg/kg body weight for three and a half months. Twelve controls received 1 cc distilled water/kg body weight/day for the same period. Ovaries from the control and fluoridated animals were analysed for DNA and RNA content. The experimental animals showed significant depletion (P < 0.001) of ovarian DNA and RNA compared to the controls. The data indicate that fluoride inhibits nucleic acid synthesis in the ovary. The findings also suggest that fluoride acts directly on DNA to produce structural changes in ovarian tissue which were subsequently confirmed by histopathological examination of control and treated animals. Further studies are desirable to define the possible role of fluoride in causing deleterious effects on reproduction such as delayed oestrus, repeated failure to conceive, and lowered viability detected earlier in experimental animals.
Ref: Fluoride 1994; 27(2):76-80. Preliminary observations on alterations in rabbit ovary DNA and RNA content in experimental fluorosis; by A Shashi

2001 Abstract: Summary. A study was made of the effects on ovary and uterus of adminis-tering sodium fluoride (10 mg/kg body weight) or aluminium chloride (200 mg/kg body weight) alone and in combination to female albino mice (Mus musculus) for 30 days. The reversibility of the induced effects by withdrawal of NaF + AlCl3 treatment and by administering ascorbic acid (AA), calcium (Ca), or vitamin E alone and in combination were also investigated. All treat-ments (NaF, AlCl3, and NaF + AlCl3) resulted in a significant decline of ovarian protein and 3 - and 17 -hydroxysteroid dehydrogenase activities which could be related to increased cholesterol levels in the ovary suggesting altered steroidogenesis. The treatment also caused a hypercholesterolemic effect in serum. Accumulation of glycogen in uterus could be related to inhibition of phosphorylase activity affecting carbohydrate metabolism. The withdrawal of combined treatment for 30 days brought about an incomplete recovery. However, AA, Ca, or vitamin E supplementation alone and in combination produced an additive effect for recovery of most of the parameters almost to control levels. Hence the effects of NaF and/or AlCl3 are transient and reversible.
Ref: Fluoride 2001; 34(1):9-20. Effects of sodium fluoride and aluminum chloride on ovary and uterus of mice and their reversal by some antidotes; by NJ Chinoy and TN Patel. Full report available at
http://www.fluoride-journal.com/01-34-1/341-9.pdf

1998 Abstract: SUMMARY: Sodium fluoride (5 mg/kg body weight) was effective from the 45th day of treatment in causing a significant decline in DNA and RNA levels of mice ovary and uterus, indicating alterations in nucleic acid and protein metabolism in these organs. The oestrus cycle was irregular with prolonged duration of the diestrus stage which in turn severely affected the fertility rate in treated mice. The administration of amino acids glycine and glutamine, individually and in combination along with NaF, helped in maintaining the status quo of all parameters as compared to control, thus elucidating their ameliorative role.
Ref: Fluoride 1998; 31(3):143-148. Ameliorative role of amino acids on fluoride-induced alterations in mice (Part II): ovarian and uterine nucleic acid metabolism; by D Patel and NJ Chinoy. This study is Part II of the earlier experiment reported in Fluoride 1996; 29(4):217-226. Full report at
http://www.fluoride-journal.com/98-31-3/313-143.htm

Endocrine: Uterus (click on for all fluorinated pesticides)

1998 Abstract: SUMMARY: Sodium fluoride (5 mg/kg body weight) was effective from the 45th day of treatment in causing a significant decline in DNA and RNA levels of mice ovary and uterus, indicating alterations in nucleic acid and protein metabolism in these organs. The oestrus cycle was irregular with prolonged duration of the diestrus stage which in turn severely affected the fertility rate in treated mice. The administration of amino acids glycine and glutamine, individually and in combination along with NaF, helped in maintaining the status quo of all parameters as compared to control, thus elucidating their ameliorative role.
Ref: Fluoride 1998; 31(3):143-148. Ameliorative role of amino acids on fluoride-induced alterations in mice (Part II): ovarian and uterine nucleic acid metabolism; by D Patel and NJ Chinoy. This study is Part II of the earlier experiment reported in Fluoride 1996; 29(4):217-226. Full report at
http://www.fluoride-journal.com/98-31-3/313-143.htm

1996 Abstract: Summary: The effects on female mice of sodium fluoride (NaF) administration, at a dose of 5 mg/kg body weight for varied durations (7, 15, 30, 45 and 60 days), were investigated in order to evaluate time-related changes in uterine carbohydrate metabolism. The therapeutic effects of simultaneous glycine and/or glutamine administration along with NaF, for 45 and 60 days, were also investigated. The results revealed that the NaF was effective from the 45th day of treatment, and was much more effective after 60 days. A significant decline in body weight and uterine weight was observed. Accumulation of glycogen in the uterus with a concomitant decrease in blood glucose could be correlated with inhibition of phosphorylase activity affecting uterine carbohydrate metabolism. The serum catecholamine concentrations were significantly enhanced, possibly due to stress induced by administration of fluoride. The elevated catecholamine levels may be one of the causative factors affecting carbohydrate metabolism, and would influence the hypothalamus gonadal axis. Decreased levels of protein in serum and uterus indicated altered uterine metabolsm in the presence of fluoride. Administration of the amino acids glycine and gluthamine, individually and in combination, along with NaF, helped to maintain the status quo of all parameters compared with controls. The results demonstrate that the amino acids glycine and glutamine have an ameliorative effect on NaF-treated animals. Hence it is suggested that a protein rich diet could mitigate the fluoride-induced health hazards in endemic areas the world over.
Ref: Fluoride 1996; 29(4):217-226. Ameliorative role of amino acids on fluorde-induced alterations in uterine carbohydrate metabolism in mice; by NJ Chinoy and D Patel.

1996 Abstract: The Okinawa Islands located in the southern-most part of Japan were under U.S. administration from 1945 to 1972. During that time, fluoride was added to the drinking water supplies in most regions. The relationship between fluoride concentration in drinking water and uterine cancer mortality rate was studied in 20 municipalities of Okinawa and the data were analyzed using correlation and multivariate statistics. The main findings were as follows.
(1) A significant positive correlation was found between fluoride concentration in drinking water and uterine cancer mortality in 20 municipalities (r = 0.626, p < 0.005).
(2) Even after adjusting for the potential confounding variables, such as tap water diffusion rate, primary industry population ratio, income gap, stillbirth rate, divorce rate, this association was considerably significant.
(3) Furthermore, the time trends in the uterine cancer mortality rate appear to be related to changes in water fluoridation practices.
Ref: J Epidemiol. 1996 Dec;6(4):184-91. Relationship between fluoride concentration in drinking water and mortality rate from uterine cancer in Okinawa prefecture, Japan; by Tohyama E.
Erratum in: * J Epidemiol 1997 Sep;7(3):184.

Heart (click on for all fluorinated pesticides)

2001 Abstract: SUMMARY: Young albino rabbits were administered 5, 10, 20, and 50 mg of sodium fluoride/kg body weight/day subcutaneously for 3.5 months. The control animals were given 1 mL of double distilled water/kg body weight/day. In the fluoridated rabbits, the myocardium showed cloudy swellings, sarcoplasmic vacuolization, and small hemorrhages followed by fibrous necrosis. The degenerative changes were most pronounced in animals treated with 50 mg of sodium fluoride/kg body weight/day. The myocardium exhibited fibrous necrosis, dissolution of nuclei, fibrillolysis, extensive vacuole formation and interstitial cells in the connective tissue. The degree of myocardial damage seemed to be directly proportional to the dosage of fluoride administered. In the control animals, the myocardium showed normal structure without any of the changes mentioned above.
Ref: Fluoride 2001; 34(1):43-50. Histopathology of myocardial damage in experimental fluorosis in rabbits; by A Shashi and SP Thapar. Full report available at
http://www.fluoride-journal.com/01-34-1/341-43.pdf

Heart and Mesenteric artery (click on for all fluorinated pesticides)

• Mesenteric artery, arteria mesenterica -- one of two branches of the aorta that pass between the two layers of the mesentery to the intestines

2000 Abstract: The purpose of this study was to determine the mechanism responsible for alterations in NaF-induced contractions of blood vessels from streptozotocin-induced diabetic rats. In the presence of AlCl3, NaF (¥7.5 mM) produced significantly greater contractions in diabetic aorta and mesenteric artery compared with age-matched controls. Pretreatment with 1 microM nifedipine eliminated the enhanced contractile responses of diabetic vessels to NaF, resulting in no difference in the magnitude of NaF-induced contractions between control and diabetic vessels. In the presence of 100 microM deferoxamine, an Al 3+ chela-tor, NaF-induced contractions of diabetic vessels were markedly attenuated, whereas only the responses to lower concentrations of NaF were reduced in control vessels. No significant difference was found in the peak amplitude of transient contractions induced by 10 microM cyclopiazonic acid between control and diabetic vessels. The addition of 10 microM okadaic acid produced attenuated contractions in diabetic vessels. These findings indicate no involvement of the inhibitory effects of NaF on endoplasmic reticular Ca 2+ -pump ATPase and protein phosphatases in the genesis of the enhanced responsive-ness of diabetic vessels to NaF. Western blot analysis showed a 2.5-fold in-crease in the expression of G(qalpha) in diabetic aortic membranes. In contrast, the G(ialpha) level was modestly decreased and the G(salpha) and G(betagamma) levels were unchanged in diabetes. The present results suggest that enhanced vascular contractions to NaF in diabetes is attributed predominantly to a G protein-mediated Ca 2+ channel acti-vation that results from markedly increased G(qalpha) expression in vascular tissues under this pathological state.
Ref: Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: association with an increased level of G(qalpha) expression
Hattori Y, Matsuda N, Sato A, Watanuki S, Tomioka H, Kawasaki H, Kanno M. J Pharmacol Exp Ther 2000 Feb;292(2):761-8 - As cited and abstracted in Fluoride 2000; 33(2):97-98

1996 Abstract:
1. Previous studies from this laboratory have demonstrated that alpha 1-adrenoceptor-mediated increases in tension and phosphoinositide metabolism are enhanced in the aorta and mesenteric arteries from diabetic rats. The purpose of the present investigation was to determine whether contractile responses to sodium fluoride (NaF), which directly stimulates GTP-binding proteins (G-proteins), are also enhanced in diabetic arteries.
2. NaF (1-20 mM) in the presence of 10 microM aluminium chloride produced slowly developing, concentration-dependent contractions in mesenteric arteries from three month streptozotocin-diabetic (60 mg kg-1, i.v.) male Wistar rats and age-matched control rats. The maximum contractile response but not the sensitivity to NaF was significantly greater in mesenteric arteries from diabetic than from control rats, as was the response to noradrenaline (NA). Maximum contractile responses of aorta and caudal artery from diabetic rats to NaF were also significantly enhanced.
3. Removal of the endothelium and denervation with 6-hydroxydopamine did not significantly alter the maximum contractile response of mesenteric arteries from either control or diabetic rats to NaF. Similarly, NaF had no effect on cyclic AMP levels in aorta, and no difference in cyclic AMP levels, either basally or in the presence of NaF, was detected between control and diabetic rat aorta.
4. Contractile responses of mesenteric arteries from both control and diabetic rats to NaF were diminished in calcium-free Krebs solution, but the NaF response remained significantly elevated in mesenteric arteries from diabetic rats compared to control.
5. Ryanodine (30 microM) which depletes intracellular calcium stores, nifedipine (3 microM) which blocks dihydropyridine-sensitive calcium channels and calphostin C (0.5 microM) which selectively inhibits protein kinase C, all significantly inhibited maximum contractile responses of mesenteric arteries from control and diabetic rats to NaF. There were no significant differences between control and diabetic arteries in the relative magnitude of the inhibition produce by the three antagonist.
6. These data suggest that there may be increased activation of the same signalling processes that mediate NA-stimulated vasoconstriction, perhaps contraction-associated G-proteins or the effectors coupled to these G-proteins, in response to NaF in mesenteric arteries from diabetic rats. This may also be responsible for the enhanced contractile responses of these arteries to alpha 1-adrenoceptor stimulation.
Ref: Br J Pharmacol 1996 May;118(1):115-22. Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride. Weber LP, Chow WL, Abebe W, MacLeod KM.

Pancreas (click on for all fluorinated pesticides)

2003 Abstract: The aim of this work was to examine the effect of fluoride ions on antioxidative enzyme activity in the pancreas of rats exposed during 4 months to NaF in drinking water. The study was carried out in 30 four-week-old male Wistar FL rats, that were randomly assigned to three equal groups and given distilled water ad libitum for three weeks. Subsequently, two examined groups of animals were exposed to NaF in drinking water: group 1 (10 rats) at 50 mg F(-)/L (2.63 mmol/L), group 2 (10 rats) at 100 mg F(-)/L (5.26 mmol/L). The control group (10 rats) received distilled water. After 4 months the animals were anesthetized with ether prior to collection of pancreas and cardiac blood. Serum concentrations of glucose and fluoride, as well as activities of the cytoplasmic (CuZn-SOD) and the mitochondrial (Mn-SOD) superoxide dismutase, glutathione peroxidase (GSH-Px) and concentrations of malondialdehyde (MDA) in the homogenized pancreas were measured. The activity of CuZn-SOD was reduced by 50% and a tendency to lower activities of Mn-SOD was observed. No changes were noted in the activity of GSH-Px or concentrations of MDA. We conclude that:
1) the fluoride caused hyperglycemia in rats in this study is not accompanied by an activation of the free radical production in the pancreas;
2) the hyperglycemia in the exposed rats cannot be attributed to pancreatic damage caused by fluoride ions (the cause in this case appears to be extrapancreatic);
3) the inhibition of pancreatic CuZn-SOD is probably due to the direct action of fluoride on the enzyme.
Ref: J Trace Elem Med Biol 2003;17(1):57-60. Activity of pancreatic antioxidative enzymes and malondialdehyde concentrations in rats with hyperglycemia caused by fluoride intoxication.
by Chlubek D et al.

2000 Abstract: Influence of fluoride on exocrine pancreas cells was examined morphologically with traditional and prolonged osmium fixation techniques for electron microscopy in the enamel fluorosis model rats injected subcutaneously twice a day with 20 mg/kg body weight of sodium fluoride. Although the rough endoplasmic reticulum (rER) of exocrine pancreas cells in control rats was laminated and oriented parallel to the circumference of the nucleus, the rER of the cells in NaF-treated rats was dilated, disrupted the laminated arrangement, and changed to the globular-shape rER. Many intracisternal granules were formed in these globular-shape rER of the cells exposed to fluoride. Lots of autophagosomes were also seen in the exocrine cells with NaF treatment. The autophagosomes were limited with a double or multiple membranes, and contained cytoplasmic organelles and/or the intracisternal granules. The outer and inner leaflets of double membranes of the autophagosomes were usually separated by a distinct electron-lucent area. In prolonged osmium fixation, the area between the double membranes of the autophagosome was filled with osmiun reaction deposits. Many autophagosomes were encircled with the single or multiple osmiophilic layers. In some cases, the osmium positive saccules also surrounded the free surface of the globular-shape rER containing intracisternal granules. These findings indicate that fluoride disrupts the export of zymogens from the rER, resulting in formation of intracisternal granules and autophagosomes, and that the osmiophilic saccules participate in sequestration of cytoplasmic organelles in forming autophagosomes.
Ref: Arch Toxicol 2000 Feb;73(12):611-7. Fluoride-induced ultrastructural changes in exocrine pancreas cells of rats: fluoride disrupts the export of zymogens from the rough endoplasmic reticulum (rER). by Matsuo S et al.

Salivary gland (click on for all fluorinated pesticides)

1999 Material Safety Data Sheet:
TARGET ORGAN DATA...
GASTROINTESTINAL (CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDS)
Ref: Material Safety Data Sheet. Valid 08/1999 - 10/1999. Sigma Chemical Co. P.O. Box 14508 St. Louis, MO 63178 USA
http://www.fluorideaction.org/pesticides/sodium.fluoride.msds.1999.htm

1995 Abstract: Summary: The effect of various concentrations of NaF on human salivary amylase was studied. Sodium fluoride was found to inhibit the enzyme when the fluoride concentration was at and above 5 x 10-2 M.
Ref: Fluoride 1995; 28(2):71-74. Effect of fluoride on human salivary amylase activity, by K Hara and M-H Yu


1988 Abstract: The effect of NaF on cAMP accumulation, cAMP-dependent protein kinase activity (cAMP-dPK) ratios and [14C]-glucosamine-labelled mucin release from these isolated cells was investigated. NaF (0.01-5 mM) increased significantly the cellular cAMP concentration and cAMP-dPK activity ratios in a dose- and time-dependent manner. NaF (5.0 mM) increased [14C]-glucosamine-labelled mucin release in a time-dependent manner. Thus the stimulation of prelabelled mucin secretion by NaF is mediated by an increase in the cAMP concentration, which exerts its effect, at least partly, via the activation of cAMP-dPK activity.
Ref: Arch Oral Biol 1988;33(5):347-51. Stimulation of mucin release from rat submandibular salivary-gland cells by NaF.Shahed AR, Allmann DW.

1987 Paper: The effect of NaF on salivary gland function by Allmann DW, Shahed AR.
No abstract available. Dtsch Zahnarztl Z 1987 Oct;42(10 Suppl 1):S95-8

1984 Abstract: Summary: This study examined the effect of intakes of 25 or 50 ppm fluoride via drinking water for four weeks on the amylase activity of the parotid gland, isoproterenol-stimulated (1 mg/100 g b.w., i.p.) salivary flow and on the amylase activity in saliva fractions. A significant elevation of the tissue amylase activity was seen in the F25 and F50 groups compared to control. The volume of saliva collected for 30 min after isoproterenol injection was higher in the fluoride-treated groups; the amylase activity was also increased. In the glandular tissue cAMP level was augmented. It appears that fluoride may affect the parotid function; it may also influence the salivary amylase activity, presumably by acting on the adenyl cyclase activity.
Ref: Fluoride 1984; 17(4):217-223. Effect of F- on major salivary glands. The amylase activity, stimulated salivary flow response and cAMP levels in parotid gland of rats consuming F- via drinking water, by Boros I, Mozsik G, Keszler P

1982 Abstract: One to 10 ppm fluroide added to drinking water enchance the activity of carbonic anhydrase in the submandibular salivary gland of rats. With 25 ppm fluoride in drinking water, the fluoride content of the parotid gland increased considerably. It is concluded that fluoride affects the function of the salivary gland.
Ref: Acta Physiologica Academiae Scientiarum Hungaricae 1979; 53:155. Functional changes in the salivary glands of rats after sodium fluoride treatment, by Boros I, Keszler P, Zelles T. As cited in Fluoride 1982; 15(1):50

Spleen (click on for all fluorinated pesticides)

2000 Objective: To examine qualitatively and quantitatively the histological changes in spleen of rats given sodium fluoride.
Material and Methods: Seventy-five female Wistar rats, each weighing approx. 200 g, were divided into three equal groups. Animals in groups 1 and 2 received intraperitoneally daily doses of 0.5 and 5 mg NaF, respectively, whereas group 3 (control) received physiological saline. The experiments were run for a period of 3 months.1 Afterwards, the spleen was removed for histological and histochemical examination and fixed in 1 0% formaldehyde solution. Histological sections were stained with haematoxylin and eosin, picrosirius red F3BA,2,3 and silver reagent according to Gomori. The ultrastructural changes in collagen fibres were investigated by optical polarisation methods.
Results: The lymphoid tissue mass of the spleen decreased and the relative proportion of reticulin and collagen structures increased. These changes correlated with the dose of fluoride.
Conclusions and Interpretation: The absolute and relative proportion of lymphoid tissue in spleen of rats given NaF decreased in a dose-related manner. Loss of lymphoid tissue may play an important role in the diminished reactivity of the organism and may be regarded as a consequence of fluoride toxicity.

Ref: Lymphoid depletion of spleen due to experimental fluorosis in rats; by M Bely. Fluoride 2000; 33(1):S1-S2. [XXIIIrd ISFR Conference abstracts, Szczecin, Poland, June 11-14 2000]. Full report available at:
http://www.fluoride-journal.com/00-33-1/331-s1.pdf

Teratogen (click on for all fluorinated pesticides)

2003 Abstract: Fluoride was first associated with fetal malformation shortly after water fluoridation was initiated in the 1940s. Since many chemicals can interact directly with the embryo to cause malformation, the effects of fluoride on embryonic and fetal development were investigated. The effects of sodium fluoride on the development of frog embryos were studied under conditions described by the Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a screening assay for teratogens. The most prominent malformations caused by sodium fluoride are reduction in the head-tail lengths and dysfunction of the neuromuscular system of the tadpoles. The values for LC(50), EC(50), and minimal concentration to inhibit growth (MCIG) of sodium fluoride met the limits established for a teratogen in frog embryos, showing that sodium fluoride is a direct acting teratogen on developing embryos. Since FETAX has a high degree of success in identifying mammalian teratogens, the observed teratogenic action of sodium fluoride on frog embryos would indicate a strong possibility that sodium fluoride may also act directly on developing mammalian fetuses to cause malformation.
Ref: Goh EH and Neff AW (2003). Effects of fluoride on Xenopus embryo development. Food Chem Toxicol. 2003 Nov;41(11):1501-8.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12963002&dopt=Abstract


1998 Abstract: The effect of fluoride on differentiation and proliferation of rat and mouse embryo limb bud cell were studied with micromass cultures in vitro. Embryo limb bud cells of rat (13-day) and mouse (12-day) were subjected to culture for 5 days. The results showed that fluoride could inhibit differentiation of cells without affecting cells proliferation. The concentrations of 50% inhibition of cell differentiation (ID50) were 6.8 micrograms/ml(rat) and 7.3 micrograms/ml(mouse). The concentrations of 50% inhibitions of cell proliferation (IP50) were 44.1 micrograms/ml (rat) and 63.6 micrograms/ml (mouse). The IP/ID50 values 6.4(rat) and 8.7 (mouse) were both greater than 5. According to the assessment criteria of Flint and Cheng Wanrong, the fluoride may be an embryo limb bud cells specific inhibitor. It could have potent teratogenicity.
Ref: Hua Xi Yi Ke Da Xue Xue Bao 1998 Sep;29(3):256-8, 268.
[Effect of fluoride on proliferation and differentiation in rat and mouse embryo bud cell in vitro]; by Zhang B, Wu D. [Article in Chinese]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10684086&dopt=Abstract

1994 Abstract: In this paper, the hydra polyps regeneration assay was used to screen and predict the teratogenicity of sodium benzoate, sodium pyruvate, sodium fluoride, sodium penicillin, and sodium nitrite. The results showed that sodium nitrite, sodium fluoride and sodium benzoate are teratogens, while sodium penicillin and sodium pyruvate are not teratogens. These experimental results accord with the results of mammalian teratogenicity assay. The test is valuable to screen and predict teratogenicity of chemicals.
Ref: [Predication of teratogenicity of chemicals using hydra regeneration assay]; by Cheng QY et al. Huan Ching Ko Hsueh; Mar;18(2):49-51, 1994. [Language: Chinese] - as cited in Dart Special at Toxnet.

1994 Abstract Summary:
1) The teratogenic effects of sodium fluoride on the ankle joint and toe bones of white leghorn chick embryos are reported.
2) Due to endochondrial osteofluorosis, the excessive growth of trabeculae in the epiphyses of distal tibiotarsus and proximal tarsometatarsus obliterated the ankle synovial joint space.
3) An increase occurred in the volume of bones, such as tibiotarsus, tarsometatarsus and phalanx.
4) Toe bones, namely phalanx and their articular surfaces with fibrocartilage containing spherical chondrocytes, were observed in control embryos. In fluoride-treated embryos, the distal and proximal regions of the phalanx grew enormously and irregularly, leaving little space for articulation.
5) Blackening and falling of feathers occurred in the fluoride-treated chick embryos.
Ref: Teratogenic effects of fluoride on chick embryo; by
S Krupanidhi and TM Dhanarajan. Fluoride 1994; 27(1):25-33

1998 Abstract: Down syndrome (DS) birth rates (BR) as a function of maternal age exhibit a relatively flat linear regression line for younger mothers and a fairly steep one for older mothers with the second line intersecting the first line a little above maternal age 30. Consequently, overall DS-BR for all maternal ages are not a very reliable parameter for detecting environmental influences, since they may be strongly affected by the ratio of the number of younger to older mothers. For this reason, data for mothers under age 30 were selected to detect an association between water fluoridation and DS for which the lower maternal age regression would be a much smaller contributing factor. The early research of I Rapaport indicating a link between fluoride in drinking water and Down syndrome was followed by studies claiming there was no such association. Application of sound methodology to the data in those later investigations shows that none of the criticisms against Rapaport's work are valid. For example, in the data of J D Erickson on maternal age-specific DS births in Metropolitan Atlanta, Georgia, when the three youngest maternal age subgroups are reasonably combined into single groups for areas with and without water fluoridation, a highly significant association (P less than 0.005) is revealed between fluoridated water and DS births. It also appears that the dose-response line (DRL) or DS-BR for daily fluoride intake may have no allowable level that does not induce fluoride-linked DS births. Therefore fluoride may be one of the major causes of DS other than aging of mothers. The number of excess DS births due to water fluoridation is estimated to be several thousand cases annually throughout the world.
Ref: Takahashi K (1998). Fluoride-linked Down syndrome births and their estimated occurrence due to water fluoridation. Author Address: Department of Internal Medicine and Biostatistics, Tokyo University Medical School, Tokyo, Japan. Source: Fluoride 1998 May;31(2):61-73.
As cited on Toxnet DART.

• Note from FAN: Uncertain of classification for Down syndrome.
Until clarified, we will include it in this section. - EC.

Violation/Fine (click on for all fluorinated pesticides)

February 19,1999. ALCOA Fined $750,000 by Commerce Department For Illegal Chemical Shipments.
-- The Commerce Department's Under Secretary for Export Administration, William A. Reinsch, imposed a civil penalty of $750,000 on Aluminum Company of America (ALCOA) for 100 violations of U.S. export regulations involving shipments of potassium fluoride and sodium fluoride.
-- The penalty results from Reinsch's affirming an administrative law judge's (ALJ) recommended findings in the case. The ALJ found that ALCOA exported potassium fluoride and sodium fluoride from the United States to Jamaica and Suriname on 50 separate occasions without obtaining the required Commerce Department export licenses. The violations occurred between June 1991 and December 1995. The ALJ also found that the company made false statements on export control documents in each shipment.
-- Potassium fluoride and sodium fluoride are controlled because they can be used to make chemical weapons. These chemicals were added to the Department's control list in March 1991, but ALCOA's export compliance program failed to recognize and incorporate the change. There was no indication that in this case the chemicals were used for weapons purposes.
-- Reinsch observed, "This penalty should send the message that there are significant advantages to having an internal compliance program that catches and reports problems quickly."
-- Reinsch's action imposes the maximum civil penalty of $10,000 for each of the 50 shipping without a license violations. He also imposed a penalty of $5,000 for each false statement.
-- Commerce's Export Administration Regulations provide that an administrative law judge administrative enforcement proceedings be conducted by who recommends an appropriate resolution of the case to the Under Secretary for Export Administration. The Under Secretary may affirm, modify, or vacate the ALJ's recommendation. In this case, Reinsch agreed with the findings but modified the penalties recommended by the ALJ. Reinsch's order and the ALJ's recommendations will be printed in the Federal Register.

Ref: Press Release. February 19,1999. ALCOA Fined $750,000 by Commerce Department For Illegal Chemical Shipments. U. S. Department of Commerce Bureau of Export Administration.
http://www.fluorideaction.org/pesticides/sodium.f.alcoa.fine.feb1999.htm

Some excerpts from the ALJ's decision published in the Federal Register, August 5, 1999:

DEPARTMENT OF COMMERCE
Bureau of Export Administration
[Docket No.: 97–BXA–20]

Re: Aluminum Company of America

On Friday, February 26, 1999, the Federal Register published the Decision and Order issued by the Under Secretary for Export Administration, Bureau of Export Administration, United States Department of Commerce (BXA) on February 19, 1999 (64 FR 9471). However, the Recommended Decision and Order of the Administration Law Judge (ALJ) was inadvertently not included with the Order of the Under Secretary. This notice is to hereby publish the December 21, 1998, Recommended and Decision Order of the ALJ.
Dated: July 21, 1999.
William A. Reinsch,
Under Secretary for Export Administration.

... 9. During the review period, the water treatment facility in Suriname used sodium fluoride to treat drinking water. Sodium fluoride was used by the ALCOA facility in Suriname to treat drinking water for people living in the Suralco refinery area. All of the sodium fluoride exported from the United States to Suriname was used by this ALCOA subsidiary facility and was fully consumed in the water treatment process. ALCOA sold the water treatment facility to the government of Suriname in July 1994. Therefore, Suralco no longer uses any sodium fluoride (See Respondent’s Answer dated January 20,
1998, page 3).

5. All of the potassium fluoride and Sodium Fluoride exports at issue in this case were sent to ALCOA’s refinery operations in Jamaica (Jamalco) and Suriname (Suralco). These refineries are located near bauxite mines. Bauxite is the raw ore for aluminum. The refineries process the bauxite so as to extract aluminum oride (alumina), which becomes the basic feedstock for ALCOA’s metal and chemical businesses. Both refineries were directly controlled by ALCOA during the period June 14, 1991 through December 7, 1995

3. Potassium fluoride is the key reagent used during the refining of alumina from its bauxite ore. Bauxite is crushed and mixed with a caustic soda solution. This solution dissolves the alumina present in the bauxite. Potassium fluoride is used to determine the level of dissolved alumina in the caustic solution. Only a small amount of potassium fluoride is used per metric ton of bauxite processed (see Respondent’s Answer dated January 20, 1998, page 2).

23. On March 13, 1991, through a notice published in the Federal Register, entitled Expansion of Foreign policy Controls on Chemical Weapons Precursors (56 Fed. Reg 10756), the Department of Commerce amended the Commerce Control List of the Export Administration Regulations (currently codified at 15 C.F.R. Parts 730–774 (1997)),2 ‘‘by expanding the number of countries for
which a validated license is required for 39 precursor chemicals
. Under the rule, the 39 chemicals will require a validated license for export to all destinations except NATO member countries, Australia, Austria, Ireland, Japan, New Zealand, and Switzerland.’’ Potassium fluoride and
sodium fluoride were included on the list of 39 chemicals


... Of all the aggravating factors in this case, one is particularly damming—that the Respondent, over a period of four and one-half (4.5) years, made 50 separate exports of potassium fluoride and/or sodium fluoride in violation of the Export Administration Regulations (emphasis added).
Importantly, ALCOA is not a new or small company that doesn’t understand the foreign export regulatory process. Quite to the contrary, the Respondent is a large multinational corporation which had a separate division (Export Supply Division) specifically dedicated to receiving requisitions, locating suppliers, purchasing products, and shipping the requested items in accordance with applicable export licensing requirements. Thus, ALCOA’s conduct, under this backdrop, was flatly inexcusable and the fact that the violations were not intentional or willful is only relevant to the fact that a federal criminal indictment was not handed down. Respondent’s failure to comprehend the change in the Federal Register Notice,
given the existence of its Export Supply Division, is also particularly troubling.1 Moreover, the fact that the unlawful shipments consisted of precursors for chemical weapons, regardless of the lack of
any potential diversion in these instances, is not something that should be viewed as a technical oversight and is clearly an aggravating factor.

In mitigation, ALCOA argues that had it applied for the necessary validated licenses, they would have been presumptively granted. This argument misses the point. Over the past 20 years, a terrorist threat has developed to our Republic and our interests aboard. In order to protect our country and our interests, laws and regulations were passed/implemented to allow the government to monitor and regulate the export of precursor chemicals and if necessary, prevent any such exports that pose a clear and present danger. Given the huge number of exports from the United States, how is the government suppose to monitor the export of precursor chemicals if it doesn’t know that the shipments were being made over a four and one-half year period? ALCOA responds that it filed under general license G–DEST and implies that the government was aware of these 50 separate exports over a four and one-half year period (See Respondent’s Answer dated January 20, 1998, page 8). I disagree. The Respondent did not submit any evidence to support this position. The Respondent cannot shift its responsibility to the government to do that which it is legally required to do. Given the volume of such exports and the limited public resources to regulate these shipments, at the refineries of the Respondent’s subsidiary companies in Jamaica and Suriname. Once again, ALCOA misses the point. The crucial point here is that the government was deprived of possible vital information in its fight to control terrorism. In other words, if the world-wide export of chemicals/biological agents were a puzzle being put together by a U.S. Department of Commerce security team, this information constituted 50 pieces of that puzzle that the government did not have. While it turned out that there was no problem, the fact remains that the government did not have the whole picture. Without the whole picture, or in this case, all of the information about precursor chemical exports, catastrophic errors in preventative decision-making could have occurred.

... The Respondent states that anything more than a nominal fine in this case is unreasonable. In support of this position, ALCOA argues that recent BXA enforcement orders based on settlement agreements establish a range from $2,000 per violation to $5,000 per violation, large portions of which were suspended. The Respondent cites the following settlements in support of it’s argument that the government’s proposed $7,500 per violation is excessive and inconsistent with past BXA practice:

... 3. Sierra Rutil America, Inc. case—The Respondent was charged with eight unlicensed exports of sodium fluoride to Sierra Leone over a two year period in violation of § 787.6. The settlement resulted in a $30,000 fine or $3,750 per violation with half of the fine remitted on probation. This case did not involve exports to controlled or affiliated entities.

... The Respondent argues in mitigation that it has no prior record of violations. I find this argument is entitled to little or no weight given the fact that for four and one-half years, the Respondent committed one hundred violations of the EAR. Indeed, It is not the prior record that is important here, but the
aggravating factor of 100 violations and the Indeed, the government might well have opted to argue in a criminal forum that ALCOA’s conduct was so grossly negligent as to constitute a willful disregard of federal law. In this case, the amount of care demanded by the standard of reasonable
conduct on the part of the Respondent must be in proportion to the apparent risk. As the danger becomes greater, the Respondent is required to exercise caution commensurate
with that increased risk. Since the Respondent was dealing with precursors for chemical weapons, the March 13, 1991 Federal Register Notice constructively put it on notice that it must exercise a great amount of care because the risk is great. It failed to do so.

Importantly, the government voluntarily lowered the sanction bar all the way down to the level of an administrative civil penalty in this case. That having been done, the Respondent argues that the government is being harsh and should lower the bar further. In effect, the Respondent is attempting to have the government negotiate with itself. This is wrong. Based upon the detailed discussion set forth above, I find the appropriate sanction for each of these unlawful shipments is $10,000. The Respondent is a huge multi-national corporation. As such, a $10,000 penalty per violation is minuscule for ALCOA who describes itself as ‘‘one of the world’s leading producers of aluminum.* * *’’. At no time during this proceeding, did ALCOA’s counsel raise financial hardships for mitigating any civil penalty. At some point, ALCOA has to stand up and take responsibility for it’s gross and long-standing breach of legal duty. Conversely, the United States government must set its civil penalties at a high enough level to insure that large multi-national corporations don’t ignore the law and if they get caught, merely consider the fine as a cost of doing business...

Environmental (click on for all fluorinated pesticides)

Effects of Fluoride on Fish Passage. The upstream migration of adult spring chinook salmon in the Columbia River has been subject to unusually long delays at John Day Dam. During the spring migration period, average passage times for radio-tagged salmonids at John Day Dam were 158 and 156 hours in 1979 and 1980, respectively. In contrast, average passage time at Bonneville Dam was less than 48 hours and at The Dalles Dam it was less than 24 hours. In addition, passage times for salmonids in the fall of 1982 were twice as long at John Day Dam as they were at The Dalles and McNary Dams. The delay of nearly 1 week at John Day Dam appeared to contribute to increased mortality and may have affected the spawning success of migrating adult salmonids.

... In 1982, preliminary studies conducted by CZES Division personnel assessed the distributions of many pollutants near John Day Dam. The results of this investigation suggested that the fish-passage delays might be related to contaminants discharged at an aluminum smelter outfall located on the Washington shore 1.6 km upstream from John Day Dam. In particular, high concentrations of fluoride in the vicinity of John Day Dam (0.3-0.5 mg/L in 1982) prompted investigators to focus sampling and research efforts on this contaminant.

In 1983 and 1984, behavior tests were conducted in which over 600 returning salmonids (chinook, coho, and chum, O. keta, salmon) were captured and tested with different concentrations of fluoride in a two-choice flume located in the spawning channel of Big Beef Creek, Washington. The conclusion from these experiments was that the behavior of upstream-migrating adult salmon would be adversely affected by fluoride concentrations of about 0.5 mg/L and that concentrations of 0.2 mg F/L were at or below the threshold for fluoride sensitivity of chinook and coho salmon.

Beginning in 1983 and continuing through 1986, fluoride discharges from the aluminum plant were greatly reduced. This was initially due to modifications in the plant's pollution-discharge system. However, it was also during this period that the Washington Department of Ecology (WDOE) took an active interest in the results of the CZES Division's water quality and behavior tests. The WDOE lowered significantly the discharge limitations for a number of contaminants, including fluoride, in the aluminum plant's wastewater discharge permit. With the reduction in fluoride discharged from the aluminum plant, there was a corresponding drop in fluoride concentrations in the river near the outfall and John Day Dam. Concurrently, fish passage delays and interdam losses of adult salmon decreased to acceptable levels.
Ref: April 1993.
NOAA Technical Memorandum NMFS-NWFSC-7. Coastal Zone and Estuarine Studies Division. RESEARCH ACTIVITIES AND ACCOMPLISHMENTS. 1980-89. Edited by Douglas B. Dey. National Marine Fisheries Service, Northwest Fisheries Science Center, Coastal Zone and Estuarine Studies Division, 2725 Montlake Blvd. E., Seattle WA 98112

[Earthworms]. The impact of four fluorides (NaF, KF, FCH2COONa [Sodium fluoroacetate] and CaF2) in sublethal concentrations on the earthworm Eisenia fetida was investigated (model experiments) in relation to its growth, maturity (clitellum-development) and fertility (number of cocoons and number of hatchlings). Fluoride-accumulation was determined at the end of the 22 weeks' test period. In higher concentrations NaF, KF and FCH2COONa reduced growth of E. fetida significantly. CaF2 had no effect. The maturity was delayed through higher concentrations of NaF and KF in the substrate. In the case of CaF2, most worms had a fully developed clitellum. Most cocoons were found in the experiments with FCH2COONa. Small concentrations of NaF, KF an FCH2COONa obviously raised cocoon-numbers, whereas higher concentrations of NaF and KF reduced it. Only NaF reduced the number of hatchlings per cocoon significantly. At the end of the test, all worms from the variants with NaF, KF and CaF2 had a significantly higher fluoride [abstract truncated]
Ref: Influence of different fluorides in sublethal concentrations on growth, fertility and fluoride-accumulation of Eisenia foetida (Oligochaeta, Lumbricidae). [Earthworm]; by VOGEL J, OTTOW J CG. PEDOBIOLOGIA; 36 (2). 1992. 121-128. [From Toxline at Toxnet].

 

 
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