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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.
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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