1978 Fluoride Abstracts. Fluoride Action Network Pesticide Project.

The effects of fluoride on the growth and L-ascorbic acid levels of tissues from the domestic chicken (Gallus domesticus)

MH Yu and CJ Driver

Huxley College of Environmental Studies, Western Washington University, Bellingham

Summary: The growth or organs and the content and distribution of ascorbic acid in tissues have been studied in growing chicks fed a died supplemented with 150 ppm of fluoride (as NaF). No differences in the body weight were observed between the control and the fluoride-treated birds at the end of 4 weeks, but the experimental birds showed a sharp increase in the weight of tibia and pectoralis and a decrease in the size of the comb. A slight weight gain was also shown in the gizzard, heart, kidney, and liver in these birds. The fluoride treatment caused a marked decrease in the ascorbic acid concentration in the heart, spleen, brain, gizzard, pancreas, and pectoralis, while the level was elevated in the lung and kidney. The experimental data suggest that supplementary fluoride intake by growing chicks even at the 150 ppm safe level can cause marked physiological and biochemical changes including changes in tissue ascorbic acid metabolism.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=210869&dopt=Abstract

Blood Vessels 1978;15(5):286-98

Presence of hormonally-sensitive adenylate cyclase receptors in capillary-enriched fractions from rat cerebral cortex.

Baca GM, Palmer GC.

The 10 000 g particulate fraction from capillary-enriched fractions isolated from rat cerebral cortex was shown to possess an adenylate cyclase highly sensitive to activation by sodium fluoride, norepinephrine, epinephrine, isoproterenol and dopamine. To a lesser extent histamine and three dopamine agonists, namely M-7 (5,6-dihydroxy-2-dimethylamino tetralin), ET-495 (methane sulfonate of pyribedil), and S-584 (metabolite of pyribedil) stimulated the enzyme preparation. The action of norepinephrine was blocked by propanolol while phenotolamine and haloperidol were relatively ineffective except at highest concentrations. Phentolamine and propanolol at only highest concentrations (10(-4) M) antagonized the action of dopamine. Haloperidol was seen to be a potent inhibitor of either dopamine- or dopamine agonist-sensitive adenylate cyclase. No effects on the enzyme were observed with methoxamine, octopamine or serotonin. These preliminary data suggest the presence of a mixed population of receptors for adenylate cyclase in rat brain capillaries.

PMID: 210869 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=96669&dopt=Abstract

Adv Cyclic Nucleotide Res 1978;9:85-99

Calcium-dependent regulation of brain adenylate cyclase.

Brostrom MA, Brostrom CO, Breckenridge BM, Wolff DJ.

The adenylate cyclase activity of a particulate preparation of rat cerebral cortex is comprised of two contributing components, only one of which requires a CDR for activity. The CDR-dependent component was inhibited by high ratios of Mg2+ to Ca2+, responded in a biphasic manner (activation then inhibition) to increasing free Ca2+ concentrations, was inhibited by 0.1 to 0.4 mM chlorpromazine, and was activated by 1 to 100 micrometer cocaine. This enzyme form, which represented approximately 80% of tge basal activity of a cortex homogenate, was stable during pretreatment of homogenates at 45 degrees C but was completely deactivated by the removal of CDR during the preparation of the particulate fraction. Adenylate cyclase activity that did not depend on CDR was unaffected by the removal of CDR during the preparation of the particulate fraction, had elevated activity at high ratios of Mg2+ to Ca2+, was inhibited by Ca2+, was unaffected by 0.1 to 0.4 mM chlorpromazine and was slightly inhibited by 1 to 100 micrometer cocaine, and was not stable during pretreatment of homogenates at 45 degrees. The CDR-dependent component of adenylate cyclase activity was activated by 5 mM NaF to varying degrees depending on the concentration of CDR present in the assay. NaF decreased the concentration of CDR required to produce half-maximal velocity obtained at optimal concentrations of CDR. Activation by NaF required the presence of Ca2+ and was immediately and completely reversed by EGTA. In contrast, the component that did not respond to CDR was activated four- to fivefold by NaF. This activation was not influenced by Ca2+ or CDR and was not reversed by EGTA. The observed effects of effects of divalent cations on the CDR-dependent enzyme are discussed in relation to the cation-binding properties of CDR. The relationship of the CDR-dependent form of adenylate cyclase to other forms of this enzyme remains to be determined.

PMID: 96669 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=647495&dopt=Abstract

Can J Neurol Sci 1978 Feb;5(1):33-40

Cytochemical localization of adenylate cyclase in broken cell preparations of the cerebral cortex.

French SW, Palmer DS, Caldwell M.

Broken cell preparations derived from rat cerebral cortical grey matter were studied cytochemically to localize adenylate cyclase (AC) activity in subcellular organelle membranes. AC activity was localized by visualizing reaction product in brain particulate fractions by electron microscopy. Activity was found in the endoplasmic reticulum, on the inside of the inner mitochondrial membrane and on both leaflets of the nuclear membrane. Reaction product was found in the postsynaptic density area of most synapses. The reaction product tended to be more prominent in the presence of fluoride. A synaptosome-rich fraction was shown to have NE stimulated AC activity which was blocked in vitro by both a alpha- and an beta-blocker and in vivo by propranolol.

PMID: 647495 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=686403&dopt=Abstract

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

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

Kula K.

Human menopausal gonadotropin (HMG), natrium fluoride (NaF) and cyproterone acetate (CYA) were applied to immature male rats between the 26th and 32nd day of life and histological examination was performed in testes of 33rd-day-old rats. HMG treatment alone slightly influenced the spermatid completion process, while NaF evidently increased frequency of occurrence of various seminiferous tubules containing spermatids. CYA alone damaged the spermatid completion process (especially the cap-phase of spermiogenesis), produced a degeneration of meiotic spermatocytes, and decreased the tubular diameter. Those changes were prevented by addition of HMG to the CYA treated animals. The results suggest a possible regulatory role of FSH at the end of the first meiosis, and, also, in the progression of spermiogenesis. The mechanism of action of NaF may be hypothetical, but it probably consists of direct action on the seminiferous epithelium level.

PMID: 686403 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=718951&dopt=Abstract

Biochim Biophys Acta 1978 Oct 12;526(2):613-25

Properties of particulate and detergent-solubilized adenylate cyclase of rat testis. Effects of follitropin stimulation.

Abou-Issa H, Reichert LE Jr.

Basal, fluoride and follitropin stimulated activities of adenylate cyclase have been studied in the testes of immature rats. The enzyme was maximally activated (about twice the basal activity) by low concentrations of follitropin, with an apparent Km of about 9 . 10(-10) M. Both Mg2+ and Mn2+ activate the enzyme but the apparent Ka for Mg2+ is about 10 times that for Mn2+. However, the apparent Km values for MgATP2- and MnATP2- are nearly the same (1.4 . 10(-4) M) and the cation activation of the enzyme is mainly through an increase in V. Ca2+ inhibited all expressions of testicular adenylate cyclase activity. Follitropin and fluoride stimulated adenylate cyclase activity at all Mg2+ concentrations but did not significantly affect the apparent Ka for Mg2+ or the Km for the substrate (MgATP2-). The stimulatory effect of the hormone or fluoride is mainly through an increase in V. Testicular adenylate cyclase could be solubilized with Triton X-100 or Lubrol-PX. The detergent-solubilized enzyme exhibited Km for substrate and Ka values for divalent cations similar to those of the membrane-bound enzyme and remained responsive to stimulation by fluoride. The stimulatory effect of follitropin, however, was lost. Responsiveness to follitropin was also lost by membrane-bound adenylate cyclase after treatment with phospholipase, although the fluoride effect was unchanged. These results reflect the essential role of lipids in the regulation of the follitropin-specific response.

PMID: 718951 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=641898&dopt=Abstract

J Reprod Fertil 1978 May;53(1):59-61

Inhibitors of adenylate cyclase from ejaculated human spermatozoa.

Haesungcharern A, Chulavatnatol M.

Adenylate cyclase from ejaculated human spermatozoa was inhibited by fluoride, Cu2+, Zn2+, Ni2+ and several carboxylic acids.

PMID: 641898 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=294626&dopt=Abstract

Rev Bras Odontol 1978 Nov-Dec;35(5):28-31

[Fluoride transplancental passage and its clinical significance]

[Article in Portuguese]

Cruz Rde A, Farias ER.

PMID: 294626 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=278984&dopt=Abstract

Proc Natl Acad Sci U S A 1978 Aug;75(8):3693-7

Properties of the interaction of fluoride- and guanylyl-5'-imidodiphosphate-regulatory proteins with adenylate cyclase.

Hebdon M, Le Vine H 3rd, Sahyoun N, Schmitges CJ, Cuatrecasas P.

The mechanism of activation of adenylate cyclase by guanylyl-5'-imidodiphosphate [Gpp(NH)p] and NaF has been investigated by studying the reconstitution of Gpp(NH)p and NaF sensitivity of an enzyme rendered insensitive to these agents by differential detergent extraction of a particulate brain enzyme. Such reconstitution can be achieved by the addition of macromolecular regulatory factors from membranes of various tissues. Trypsin digestion and thermal inactivation provide evidence for the existence of two distinct regulatory functions, one capable of restoring the Gpp(NH)p response and another the NaF response. The regulatory protein(s) seem to interact with their respective activators in an easily reversible, divalent cation-independent reaction. This appears to be followed by a high-affinity interaction between the catalytic and regulatory components of adenylate cyclase in a slow, temperature-dependent, divalent cation-dependent process tha produces the persistently activated state of the enzyme. The enzyme activation can be reversed by methods that separate catalytic from regulatory components and the resulting enzyme activity can be restimulated by the reconstitution technique.

PMID: 278984 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=641898&dopt=Abstract

J Reprod Fertil 1978 May;53(1):59-61

Inhibitors of adenylate cyclase from ejaculated human spermatozoa.

Haesungcharern A, Chulavatnatol M.

Adenylate cyclase from ejaculated human spermatozoa was inhibited by fluoride, Cu2+, Zn2+, Ni2+ and several carboxylic acids.

PMID: 641898 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=752679&dopt=Abstract

J Assoc Physicians India 1978 Nov;26(11):995-1000

No Abstract available

Endocrine aspects of endemic skeletal fluorosis.

Teotia SP, Teotia M, Singh RK, Taves DR, Heels S.

PMID: 752679 [PubMed - indexed for MEDLINE]

Cell Biol Intl Reports 1978; 2:551-559

As cited (and abstracted) in Fluoride 1979; 12(3):167-168

Cellular resistance to fluoride

RI Holland and JK Hongslo

Excerpt from abstract:
The authors studied the development of resistance of cultured cells to the toxic action of fluoride. They noted that the minimum concentration of fluoride toxic to cells ranges between 0.4 to 1.3 mM NaF (7.6 - 24.7 ppm). At this concentration fluoride inhibits in vitro, protein and DNA synthesis and disturbs the polyamine metabolism; at higher concentrations, complete growth arrest and eventual cell lysis occurs. Immediate growth arrest and massive cell death occurs at 2.5 to 3.5 mM and at higher concentrations the entire culture can be extinguished. Cells the growth of which has been inhibited, however, can recover and reach a growth rate similar to that of non-exposed cells. Fluoride resistance can be established by gradually increasing the concentration of the culture medium...

Ann Intern Med 1978; 89 (Part 1): 607-611

Hillman D, Bolenbaugh D, Convey EM

Excerpts: During 1975 and 1976 more than 75 Michigan dairymen reported in their cows subnormal milk production, loss of weight after calving, failure to exhibit estrus or to re-breed as expected as well as a high incidence uterine infections and lameness. Death from undetermined causes ranged between 10 and 15 percent among adult cows and among calves up to 1 year or more in age many failed to grow normally or died from undetermined causes. Analysis of milk and tissue fat for PBB (polybrominated biphenyls) which had been responsible for a similar epidemic in Michigan reealed no detectable traces. Severe dental fluorosis and exostoses of etatarsal bones led to the discovery that mineral suppements containing up to 6300 ppm of fluoride and protein supplements containing up to 1088 ppm fluoride consumed by the cows were responsible for this epidemic.

... The thyroids of calves were enlarged 2 to 5 times their normal weight and the cows afficted with fluorosis showed evidence of hypo-thryoidism. The depression of the serum thyroxine (T4) and triiodothyronine (T3) correlated with the increase in urinary fluoride, with the number of red blood cells, with the hemoglobin, serum cholesterol, calcium, glucose and albumin. Fluoride also decreased the serum cholesterol at a lower level of significance (P <.06).

With respect to the hematological findings eosinophilia increased in correlation with urinary fluoride (P <.004) and should be considered an early manifestation of fluoride toxicity. Moreover fluorotic animals manifested anemia...

The authors suggested that the National Research Council recommendation of a level of 30 ppm maximum dietary fluoride "may be too high for high producing dairy cattle fed phosphate sources of fluoride."

Retention of fluoride from diets containing materials produced during aluminum smelting

Effects of a case of airborne fluoride pollution on the health of the surrounding population

Excerpt: The book written in Dutch with an English summary, is a compilation of extensive environmental and health data concerning airborne fluoride pollution near the Belgium town of Bruges. The study was prompted by illness and sudden death in 1974 of cattle grazing near the Bayer-Rickman enamel factory situated in the northern part of the city in close proximity to three residential areas and concerns, primarily, the health of the surrounding population...

The fluoride conent of mechanically deboned meat was measured by a new rapid analytical procedure by means of the specific ion electrode. Deboned comminuted meat is defatted with petroleum ether. Disodium EDTA is added in order to complex calcium and a total ionic strength adjustor to complex interfering ions such as aluminum and iron and to provide a constant background ionic strength to decomplex fluoride and to adjust the pH of the solution. The fluoride is then determined by comparison to a standard curve on semilogarithmic graph paper of fluoride ions vs millivolt readings.

The method is applicable to pork, beef and poultry which has been deboned either by hand or mechanically. Levels above 25.0 ppm are measured by analyzing additional standards and extending the curve into a third cycle. Samples less than 0.7 ppm can be estimated by extrapolation. The average recoveries amounted to 92+-4.2%. The standard deviation of duplicates within the laboratory was 0.5 ppm in the above-stated range.

The analysis of deboned meat (beef, pork and poultry) by the conventional diffusion method and the one reported here gave very satisfactory comparable results in the range from 0.7 ppm to 35 ppm. Mechanically deboned meat contained much more fluoride than that deboned by hand. The highest concentrations recorded were 33.8 and 35.0 ppm.

Excerpts: The fluoride content of soil is of considerable importance in the assessment of the biological role of the halogen. To a large extent soil fluoride determines its levels in water, vegetation, domestic and wild animals, and indirectly in humans, whose food is derived from the above sources. It is, therefore, not surprising that biologiss have devoted considerable attention to the determination of fluoride in soil.

Data on the fluoride content of soil have shown variations ranging as widely as from near 0 up to 184,000 ppm. The latter value was recorded near a fluorspar mine in Great Britain (1). In an endemic fluorosis area of India Jolly et al. reported an average of 241.1 ppm (2). The overflow of a pond collecting the waste water from a phosphate fertilizer factory resulted in the accumulation of 93 to 384 ppm fluoride in the surrounding acreage (3). Hani observed fluoride levels of the order of 0.096 in acid soil and 0.33 in limed soil in Liebefeld near Bern, Switzerland (this issue page 20).

Treatment by fluoride-bearing phosphate fertilizers and pollution from industrial sources account to a large extent for such wide fluctations. Another major source which is not man-made is volcanic eruptions (4). Fertilization adds from 8 to 20 kg/ha/year to soil (5). Macuch et al. observed fluoride depositions of an average of 10.7 kg/ha/year near a Czechoslovakian aluminum factory (6).

... Robinson and Edginton noted greater fluoride accumulation in soil with increasing depth (7). At the surface they found 200 ppm and at a depth of 9 to 14 cm 1300 ppm. This trend is reversed in a polluted area. For instance, near a Scottish aluminum smelter 1010 ppm was recorded at the surface (up to a depth of 1 inch) in contrast to 161 ppm at a depth of 11 to 15 inches (8).

... data on the total composition of the soil are significant since the uptake of fluoride in plants is determined markedly by the amount and kind of other minerals present. The acidity of the soil and, particularly, its content of calcium and aluminum to which fluoride has a strong affinity affects its biological action on plants as demonstrated by Hani. High levels of boron in the soil account for greater fluoride uptake (13).

In relating fluoride in soil to its uptake inplants, Johnson pointed out that the amount of fluoride in soil does not parallel that taken up by plants, although he observed a direct correlation of the water-soluble fluoride in the soil to fluoride in plants (1).

Aconitate hydratase activity and citrate content of heart and kidney in fluoride affected cows

Summary: Heart and kidney tissues from Holstein, Hereford and cross bred beef cows suffering from chronic fluoride toxicosis were analyzed for citric acid content and aconitate hydratase (citrate (isocitrate) hydro-lyase, E.C. 4.2.1.3) activity and the results were compared with those obtained with tissues from healthy cattle. Citric acid concentration was decreased 54-60% in kidney and heart of fluoride affected cattle. Aconitate hydratase activity in heart tissue showed an increase of about 25% in the heart tissue and a decrease of about 52% in the kidneys. The possible mode of action of these findings is discussed.

Interactions by fluoride with a mineral soil containing illite and alterations of maize plants gown in this soil

Swiss Federal Research Station for Agricultural Chemistry and Hygiene of Environment, Liebefeld-Bern

Summary: The changes in soil following addition of sodium fluoride and their effect on plants were investigated. Fluoride dissolves aluminum-organic matter out of the Liebefeld soil. More of these compouns go into solution from acid soil than from limed soil. Titration of the soil extracts showed that the dissolved organic matter belongs to the low molecular weight fraction (<1000).

The fluoride and the aluminum compounds are taken up by maize plants. Plants grown in extracts of acid soil with higher concentrations of aluminum and fluoride undergo more damage than plants grown in limed soil. This lower plant yield in acid soil becomes noticeable after addtiion of 200 ppm of fluoride of which 24 ppm are water-soluble. The fixation of the added fluoride not exceeding 500 ppm can be described by the Langmuir isotherm. This relation only applies to the acid soil.

Illite, the main component of the clay fraction of the Liebefeld soil, reacts solely with a pH 47 acid solution of sodium fluoride at a temperature of 50¼C. After an initial exchange of surface OH-groups against fluoride the crystal lattice of the illite is gradually decomposed forming cryolite and amorphous silica.

Long-term effects of fluoride administration - an experimental study. ii) Effect on serum proteins.

Civil Hospital, Jullandar (R.K.), and the Government Medical College, Department of Anatomy, Patiala, India

Summary: Thirty rabbits were given subcutaneously daily for 12 months sodium fluoride in doses ranging from 0.5 mg/kg to 5 mg/kg and the serum electrophoretic patterns were studied. There was a significant fall in the total serum proteins. An inversion of the albumin/globulin ratio was found, namely a decrease of albumin and a rise of globulin.

Summary: Fluorotic change in bones and joints were evaluated in 105 aluminum workers and 20 residents of an endemic fluorosis region in India. The age of the workers averaged 51.2 years, and the duration of their exposure 18.2 years. The skeletal changes in the aluminum workers exhibited the same characteristics as those of endemic fluorosis. In industrial fluorosis the changes were less advanced than in endemic fluorosis. Generalized sclerosis, alterations in the bone structure and periosteal reactions are the most tpical features of skeletal fluorosis; ossification of the interosseous membranes and muscle attachments, are less characteristic.

Department of Neurology, Osmania Medical College, Hyderabad, India;
Department of Neurosurgery, Gandhi Medical College, Hyderabad
District Headquarters Hospital, Nalgonda, Andhra Pradesh

Summary: In thirty-six cases (32 males, 4 females) with advanced fluorosis electromyograms were taken and motor nerve conduction was measured. In 19 patients the findings were abnormal. The motor nerve conduction in fluorosis was found to be within normal limits unless compressed by bony spurs. A fairly good correlation occurred beteen the electromyographical findings and those of clinical neurological examination. The findings of this electrophysiological study of endemic fluorsis are not in accord with the concept of fluorotic myopathy reported by others. Unequivocal evidence of neurogenticatrophy in the EMG leads us to conclude that the traditional concept of compression myeloradiculopathy of fluorosis is correct.

As abstracted in Fluoride 1978; 11(1):38-39:
Fluoride concentrations in soils of the United States are generally in the range of < 100 ug/g to > 1000 ug/g. The author examined the levels of total soil fluoride near the site of an aluminum manufacturing facility in order to determine:
1) the possible influence of an important airborne fluoride source on geographical soil fluoride distribution;
2) seasonal and annual trends in total soil fluoride concentrations as related to the fluoride source; and
3) the distribution of fluoride in the soil profile in relation to the fluoride source.

During the two years in which the soil data were collected the aluminum production averaged 218,000 metric tons per year. The area under study is situated on the Ohio river where ridges of the Ohio valley rise 150 to 200 m above the river. Soil samples were derived from pastures or grassland at 14 sites in the environs of the fluoride source. The sites were selected from data on the amounts of fluorides present in pasture grass and hay. In the forage the high and low fluoride sites averaged 46 to 16 ug/g fluoride, respectively, during the 2 years of the study. The kind of soil was described as deep, well-drained silt loam commmon on upper slopes and ridgetops.

At each of the 14 locations, 6 to 8 soil cores at different depths up to 30 cm were extracted with a standard soil sampler in spring and early fall of 1973 and 1974. A sulfuric acid steam distillation fluoride specific ion electrode technique was developed for the total soil fluoride determinations.

At the depth of 0 to 5 cm, the fluoride level ranged from 311 +- 56 to 371 +- 88 ppm; at 5 to 15 cm, from 304 +- 48 to 357 +- 80 ppm; at 15 to 30 cm depth, it ranged from 315 +- 53 to 379 +- 92 ppm. The highest levels were found in spring 1973. The total soil fluoride differed from one location to another and at different sampling depths. Seasonal trends also accounted for considerable differences between the high and low atmospheric fluoride sites. In the less polluted areas, the fluoride concentrations in soil increased with depth. However, this profile was inverted in the high airborne fluoride sites with the most superficial soil showing larger amounts of fluoride than at lower levels. The fluoride content of the soil decreased with increasing distance from the factory. No data were available at distances greater than 10 km.

The authors found no correlation between the average soil surface fluoride levels and the average fluoride levels in pasture. They conclude that the polluting source increased the fluoride content of nearby soils and changed its distribution in the soil. Its fluoride content decreased with increasing depth and as the distance from the source lengthened. At 3 km northeast of the source, the nearest agricultural land in this direction, the gain of fluoride amounted to as much as 180 ug/g in surface soil. This increase is believed to have less impact on forage fluoride than direct absorption of the halogen from the air.

A three-year-old male child was given prophylactic fluoride treatment to the teeth by a dental technician with a mixture of a 4% stannous fluoride solution and pumice. This mixture was applied to the teeth with a cotton swab. Shortly thereafter the pumice adhering to the teeth was removed with a cotton swab dipped in the fluoride solution. The child was instructed to rinse his mouth with the 4% stannous fluoride solution. Within five minutes the child vomited, developed a convulsive seizure and shock. He was promptly admitted to the intensive care unit of a pediatric ward where it was determined that he had swallowed a 1/2 cup of fluoride solution. He died approximately three hours after the topical application of the solution.

Morphometric measurements in the diagnosis of fluorotic changes in the long bones. Part I. The forearm

Summary: The fluorotic changes in the long bones of 95 aluminum workers were calculated by morphometric measurements. The workers' age averaged 51.2 years and their exposure to atmospheric fluorides 18.1 years. The forearms were x-rayed in supination and compared with measurement of a control group of 30 non-exposed workers. The maximum cortical thickness of the radius and ulna was determined by the author's method. The cortical indices were then calculated.

The mean values of the indices of the radius and ulna in the group of aluminum workers were significantly higher than those in the control groups. Morphometric measurements of the bones of the forearm may facilitate the diagnosis of osteofluorosis.

Morphometric measurements in the diagnosis of fluorotic changes in the long bones. Part II. The lower leg.

Summary: Radiograms of the legs, including the knee joint, were made of 50 aluminum workers (average age 50.1 years) whose aveage duration of exposure to fluoride was 18.2 years. A control group consisted of 40 workers not exposed to fluoride. The maximum cortical thickness in selected sites of the metaphysis and diaphysis of the tibia was determined. The cortical indices of the metaphysis and diaphysis were calculated. The measurements of the fibula were not taken into consideration on account of the great variability in the diameters.

The mean values of the cortical indices of the metaphysis and diaphysis of the tibia were significantly higher in the aluminum workers compared with the control group. The diagnostic value of measurements of the tibia in evaluating fluorotic changes in the long bones is emphasized.

Comparison of the biochemical mechanisms of growth retardation caused by fluoride and ozone

United States Department of Agriculture, Western Cotton Research Laboratory, Phoenix, Arizona

Summary: The biochemical alterations induced by fluoride are the disintegration of polysomes into smaller particles. This results in the formation of heterogeneous ribonsomal components including a decrease in ribosomal RNA particles. These changes are caused by the enhanced specific activity of ribosomal ribonuclease. The findings supply evidence for the destruction of messenger RNA as one of the factors responsible for the loss of polysomes, the site of protein synthesis.

In contrast, ozone specifically decreases the population of chloroplast ribosomes including polysomes and the level of 23S ribosomal RNA. The reduction in chloroplast ribosomes is caused by the reaction of ozone with sulfhydryl groups of the ribosomal proteins.

Both fluoride and ozone cause growth retardation by influencing the site of protein synthesis and the amount of ribosomal RNA. However, the mode by which each of these air pollutants modifies these metabolic constituents at the site of action differ.

The effect of fluoride on the mineral composition of polluted fir needles (Abies alba mill.)

Laboratoire de Biologie Vegetale, Department de Recherche Fondamentale, Centre d'Etudes Nucleaires, Grenoble, France

Summary: The chemical composition of fir needles is altered by the accumulation of fluoride. Our data indicate that fluoride pollution tends to reduce the concentration of Mg and Mn and to increase the concentration of Ca and F. They also indicate that the fluoride level has no consistent effect on levels of other major nutrient elements, such as N, F and K. Nevertheless, when the content of fluoride in needles reaches 400 ppm, no further depletion of Mg and Mn occur. Above 400 ppm fluoride has no significant effect on the levels of the remaining elements. Moreover, a similar depletion of Mg and Mn in relation to fluoride accumulation is observed and a distinct correlation may be found between these two elements.

Uptake and translocation of fluoride in Helianthus annus L. grown in sand culture

Biology Department, Sunderland Polytechnic, Sunderland UK;
Botany Department, The University, Liverpool;
Department of Plant Biology, The University, Newcastle

Summary: In Helianthus annus seedlings grown in sand culture for five weeks the concentration of fluoride in the root and shoot was generally proportional to the concentration in the substance. Highest concentrations were present in the roots and the concentrations in the leaves decreased acropetally. In a more detailed six week study the dynamics of uptake and translocation differed markedly. Whereas the total fluoride in the plant increased steadily in proportion to increased root dry weight, the amount translocated to the shoot each week was reduced to almost zero after four weeks. The fluoride in the shoot accumulated initially in the most physiologically active leaves. It appears, therefore, that the acropetal pattern of leaf accumulation is a function of leaf age rather than of position on the stem. The dynamics of accumulation in leaves suggested that a portion of the fluoride in a senescing leaf was retranslocated to younger leaves. Thus although there was an increase in the immobility of the fluoride in the root over the study period, a portion of the fluoride in the shoot could be translocated from older to younger leaves.

Some physiological and ultrastructural changes of Vicia faba L. after fumigation with hydrogen fluoride

Summary: Fourteen day old plants of Vicia faba L. cultivar Inovec were fumigated by 50 ppb HF concentrations and the efects of HF on photosynthesis, respiration and growth were observed during continual fumigation for the whole testing period (7 days). Preliminary observations on the dynamics of changes in the chloroplast ultrastructure were made as well.

Continuous fumigation of plants by HF resulted in strong inhibition of the photosnthetic activity, and of the growth processes during the whole teting period, even though no visible symptoms of injury were observed on the plants. The ultrastructural observations showed that the inhibition of the photosnthetic activity was accompanied by a step by step destruction of the granal and lamellar membrane system of the chloroplasts.

Observations made 24 hours after stopping the HF fumigation (50 ppb) showed a syamic repairing of the processes studied. Based on their repair processes, respiration was found to be relatively the most stable process. An average increase of 7.1% in the respiration rate over the whole test period together with a 8.7% decrease in the growth processes, indicated that treated plants compensated in such a way for the increased energy and material demands necessary for the repair processes, within the frame of autoregulation.

Plasma fluoride, 25-hydroxycholecalciferol, immunoreactive parathyroid hormone and calcitonin in patients with endemic skeletal fluorosis

Department of Medicine, Institute of Medical Sciences, Osmania Medical College, Hyderabad, India

Summary: Rabbits were administered sodium fluoride, 50 mg/kg body weight, through intragastric route at 24 hour intervals. The protein content of soft tissues was estimated using a spectrophotometric method. These estimations were carried out on day 158, 165, 225 and 265 after fluoride administration. A reduction in the protein content of the tissues which were studied, ranged from 10 to 46 percent. The current study also revealed three different patterns of tissue protein response to fluoride ions. Fluoride ions exert an inhibitory influence on the majority of the tissues. Whether similar changes take place in humans after excessive ingestion of sodium fluoride is not known.

Summary: Corn plants grow in fluoride-polluted areas show considerable differences in the fluoride content of their organs. Furthermore, the fluoride levels vary at the different stages of development. Alterations of fluoride concentrations are due to exposure, dilution effect by intensive biomass synthesis, and translocation phenomena. The results obtained should be taken into account in cattle nutrition.

The use of infrared aerial photography in determining fluoride damage to forest ecosystems near an aluminum plant in northwestern Montana, U.S.A.

US Department of Agriculture, Forest Service, Region I, Forest Insect and Disease Management, Missoula, Montana

Summary: A vertical stud Soderberg aluminum plant consisting of 600 pots emitting between 1150-1800 kg fluoride per day in western Montana, U.S.A. has caused serious injury and damage to nearby forest ecosystems. The fluorides have drastically stressed coniferous trees, causing considerable diameter growth loss and mortality. Aerial infrared photograpy, with a Fairchild KA-2 30.4 cm focal length camera and 24x24 cm format, at a scale of 1:4000 with complete stereo coverage, and transect stereo photography at 1:1200, and with Kodak ektachrome infrared aero type 2443 was most effective in delination of stressed stands and in computation of mortality. Trees on nearly 75,000 ha were in various stages of decline, and diameter growth loss attributable to the fluoride problem was about 30% of the predicted normal growth. Up to 50% mortality of coniferous treees, primarily western whie pine (Pinus monticola), Douglas-fir (Pseudotsuga menziesii), and lodgepole pine (Pinus contorta v. latifolia) occurred in stands 2-5 km from the aluminum plant.

The measurement of fluoride, with special reference to milk, using a fluoride ion-selective electrode, and an investigation of the interferences caused by certain ionic species

Department of Applied Biology and Food Science, Polytechnic of the South Bank, London, UK

Summary: The effects of sodium, calcium and magnesium on the apparent fluoride concentration of aqueous solutions, as measured by the fluoride ion-selective electrode, have been investigated. These effects have been lessened by the addition of 1% (m/V) solutions of citric, tartaric and oxalic acids. The response of the electrode with respect to pH, temperature of solution and statistical reproducibility of readings has been examined and suggestions have been made to explain the apparent low readings obtained in milk containing known amounts of fluoride.

The second annual Symposium of CEMO, Centre d'Etude des Maladies Osteo-articulaires, Geneve, was entirely devoted to the subject of "Fluoride and Bone." The three-day scientific program was divided into the following sessions:
I) Fundamental Aspects
II) Fluoride and Diagnosis
III) Fluoride and Kidney
IV) Fluoride and Prevention
V) Endemic and Industrial Fluorosis
VI) Fluoride and Therapy: Otospongiosis
VII) Fluoride and Therapy: Osteoporosis
In all, 42 contributions were presented. This report will be restricted to a short account of the individual sessions.

Department of Medicine, Institute of Medical Sciences, Osmania Medical College, Hyderabad, India

Determination of fluoride content in plants near the Tarnobrzeg Sulfur Basin

Summary: Fluoride levels were determined in plants growing in the Tarnobrzeg Sulfur Basin, where sulfur processing facilities pollute the air. The determinations were performed by means of Holub's method and Obrink type chambers. As complexon-forming material alizarin-complexone of lanthanum was used.

The highest fluoride levels, approached 200 ppm, at a radius of 1.5-2 km from the source of emission. The need for establishing a protective zone around industrial sources of fluoride emissions is emphasized.

Fluoride tolerance in grasses with particular reference to fluorspar mine waste

Biology Department, Sunderland Polytechnic, Sunderland, Tyne & Wear and the Botany Department, University of Liverpool, Merseyside, UK

Summary: A bioassay experiment on fluorspar mine waste comparing the performance of the native waste populations and non-native populations of Festuca rubra suggested that the native plants grew better. In further experiments using solutions of sodium fluoride, percentage germination and root extension growth was greater in plants native to fluorspar sites.

In a sand culture experiment, populations of Deschampsia cespitosa and Agrostis tenuis native to fluorspar sites showed a greater overall increase in dry weight in 9 weeks than did non-mine plant populations when watered with sodium fluoride solution.

These experiments suggest that grass populations native to fluorspar sites have a certain degree of tolerance to the elevated fluoride concentrations in the substrate. The ecological significance of this, with particular regard to reclamation of these wastes, is difficult to assess at this time.

Fluoride, calcium and aging in healthy and polluted fir trees (Albies alba mill.)

Laboratoire de Biologie Vegetale, Department de Recherche Fondamentale, Cenre d'Etudes Nucleaires de Grenoble, France

Fluoride content in eggs of wild birds (Parus major L. and Strix aluco L.) and the common house-hen (Gallus domesticus)

Summary: The fluoride levels in eggs of different species of birds, namely house hen, Parus major and Strix aluco were measured. There were no significant differences in fluoride levels in the yolk and the white. Probably because of the inconsistency in nutrition, levels of fluoride varied between species and significantly in egss from industry-contaminated zones compared with those from non-polluted areas. No definite conclusion can be drawn concerning the health effects of fluoride on the overall bird population but it is possible that the number of different species may be reduced.

Magnesium-fluoride interrelationships in man. II. Effect of magnesium on fluoride metabolism

Fluoride induced impact in a coniferous forest near the Anaconda aluminum plant in northwestern Montana

The effect of fluorine and lead ions on the chromosomes of human leukocytes in vitro

As abstracted in Fluoride 1979; 12(4):212-213
(correction noted in Fluoride 1980; 13(1):44 has been incorporated)
The authors studied human leukocytes in vitro to which they added lead ions at concentrations of 10-3M (19 ppm) and 10-5M (0.19 ppm) and fluoride at concentrations of 3.15 - 10-3M (59.85 ppm), 3.15 - 10-4M (5.98 ppm), 3.5 - 10-5M (.598 ppm). Both agents induced structural and quantitative aberrations in the chromosomes of the kind indicative of the mutgenic property of fluoride and lead. The lowest concentrationo fluoride (3.15 - 10-5M or .598 ppm) was equal to that in the water supply of the city of Szczecin, Poland where water if fluoridated for the prevention of tooth decay. The authors expressed concern about the suitability of this measure.

[Bone fluorosis without occupational exposure in chronic renal insufficiency]

[Article in German]

Schmidt CW, Kunze P, Funke U, Auermann E.

Report on a 70-year-old male with bone fluorosis which was ascertained radiologically, by section and fluor analysis in the bone ash. With empty professional anamnesis as cause was found the presence of a chronic renal insufficiency with simultaneously increased fluor content of drinking water. The decreased renal excretion of fluoride might have led to the pathological development in the bones. It is referred to the significance of extra-medical fluor load and the knowledge of the renal function when halogen is therapeutically used.

PMID: 746676 [PubMed - indexed for MEDLINE]

Organic fluorides: implications for psychiatry.

Guynn RW, Faillace LA.

The widespread use of synthetic organic fluorides has recently received attention as a potential health hazard. There are a number of organic fluorides which have become important considerations in psychiatry. Therapeutically the organic fluorides include the neuroleptics trifluoperazine, fluphenazine, triflupromazine, and haloperidol, the benzodiazepine flurazepam and the polyfluorinated inhalant convulsant indoklon. On the negative side, deliberate inhalation of fluorocarbon aerosol propellants has become a modern form of drug abuse among the young. A review is presented on the biochemistry and toxicology of organic fluorides with special emphasis on implications to the field of psychiatry.

Publication Types:

Retention of fluoride from diets containing materials produced during aluminium smelting.

Wright DA, Thompson A.

1. Using male rats, the availability of fluoride from five by products of the aluminium smelting industry was tested. This was done by considering the balance between fluoride administered in controlled diets and the total fluoride content of waste products eliminated over an experimental period of 1 week.
2. Results indicated that yields of available fluoride expressed as percentage weight of original material were cryolite (Na3ALF6), 45.9%; sodium fluoride (NaF), 41.7%; aluminium fluoride (AFL3.H20), 9.1%; mist eliminator grid solids (with CaF2), 9.4%; reclaimed alumina with adsorbed F, 0.27%.
3. Of the various tissues analysed for fluoride content, only the kidney and femur showed any significant correlation with the amounts of fluoride absorbed or retained.

PMID: 666997 [PubMed - indexed for MEDLINE]

Chinese hamster cell lines resistant to the cytotoxic action of fluoride.

Mankovitz R, Kisilevsky R, Florian M.

The proliferation and efficiency of colony formation of a Chinese hamster ovary cell line, CHO, was found to be inhibited by concentrations of fluoride greater than or equal to 10(-3) M. From mutagenized populations of CHO cells, clones were isolated that were from 1.6 to 13 times more resistant than the wild-type to the cytotoxic action of fluoride. The resistant clones were found to be stable in the absence of selection. The fluoride sensitivity of wild-type and fluoride resistant clones was not altered by changes in the pyruvate concentration in the culture medium, indicating that the cytotoxic effect of fluoride is not due to the action of fluoride on the glycolytic pathway. On the other hand, both the incorporation of 3H-leucine into acid precipitable material and the distribution of polyribosomes were sensitive only to fluoride concentrations that were cytotoxic, suggesting that the molecular basis of fluoride induced cytotoxicity in both wild-type and fluoride resistant cells is the sensitivity of protein synthesis to fluoride. At concentrations of fluoride at which the wild-type cells are inhibited but fluoride resistant cells are not, the intracellular concentration of fluoride in the fluoride resistant cells was found to be 1/5 to 1/10 that of the wild-type, suggesting that fluoride exclusion is the basis for resistance in the resistant lines.

PMID: 657004 [PubMed - indexed for MEDLINE]

Dental fluorosis as related to the concentration of fluoride in teeth and bone.

Brudevold F, Bakhos Y, Aasenden R.

Rats (N = 58), given a diet low in fluoride, were stomach-fed solutions of NaF and (NH4)3AIF6 in amounts corresponding to 3.3, 8.3, and 16.5 microgram of fluoride per gram of body weight. After five weeks, the incisors were scored for fluorosis and samples of the incisors and mandibles were analyzed for fluoride. Less fluoride was deposited in teeth and bone from AIF6, than from NaF at all dosage levels. Less fluorosis also developed from AIF6, except at the lowest dosage level, which produced very little fluorosis in either group. Both incisor fluoride and fluorosis scores increased with increases in ingestion of fluoride. In a larger group of rats (N = 101) that had been on different fluoride regimens, the fluoride concentrations of the incisors were grouped according to the fluorosis scroes. There was a consistent trend of increase in fluoride with increase in fluorosis scores, but each score had a wide range and overlap in fluoride concentrations.

PMID: 272428 [PubMed - indexed for MEDLINE]

The monovalent anions chloride and azide as potent activators of NaF- and p(NH)ppG-stimulation of pancreatic adenylate cyclase.

Svoboda M, Christophe J.

PMID: 624406 [PubMed - indexed for MEDLINE]

Hyaluronidase release from guinea pig spermatozoa as affected by reproductive tract secretions and metabolic inhibitors.

Lewin LM, Nevo Z, Marcus Z, Gabsu A, Nebel L.

Cauda epididymal sperm of mature guinea pigs were incubated (37 degrees, 5% CO2 in air). 10% of the total enzyme activity was released into the medium in 4 hr, 30% in 24 hr. Addition of lysolecithin resulted in rapid release of hyaluronidase. Vitamin C (0.54 mM), sodium fluoride (0.02 M), and cholesterol increased the rate of release whereas citrate (20 mM) diminished it. No effect upon hyaluronidase release was noted upon addition of KCN (10(-2)M), progesterone (250 microgram/ml), testosterone (500 microgram/ml), spermine (1.15 mg/ml), inositol (5.6 mM), or chloroquine phosphate (0.54 mM).

PMID: 736670 [PubMed - indexed for MEDLINE]

Stabilization and solubilization of bovine corpus-luteum adenylate cyclase. The effects of guanosine triphosphate, guanosine 5'-[beta,gamma-imido]triphosphate, sodium fluoride and Tris/hydrochloric acid concentration on enzyme activity.

Young JL, Stansfield DA.

PMID: 564693 [PubMed - indexed for MEDLINE]

LD50 of SnF2, NaF, and Na2PO3F in the mouse compared to the rat.

Lim JK, Renaldo GJ, Chapman P.

PMID: 272954 [PubMed - indexed for MEDLINE]

Histamine release by calcium from sodium fluoride-activated rat mast cells. Further evidence for a secretory process.

Patkar SA, Kazimierczak W, Diamant B.

PMID: 76611 [PubMed - indexed for MEDLINE]

Iatrogenic fluorosis.

Grennan DM, Palmer DG, Malthus RS, Matagni MF, de Silva RT.

A 69-year-old spinster presented with a history of generalised bone pains in September 1977. She was asthmatic and had been treated with 60 mg sodium fluoride and three Calcium Sandoz tablets daily for three years in an attempt to minimize steroid-induced osteoporosis. She was subsequently found to have fluorosis as shown by radiological osteosclerosis in vertebrae and pelvis with histological changes of osteomalacia on bone biopsy and a high bone fluoride content. A trial regimen for osteoporosis which is currently being assessed in various centres includes fluoride along with supplementary calcium and Vit D to prevent the production of osteomalacia which may occur with the fluoride salt alone. The case described here emphasises the potential toxicity of therapeutic dosages of fluoride when prescribed with calcium alone and emphasises the need for careful clinical and biochemical monitoring in all patients receiving therapeutic dosages of fluoride.

PMID: 283775 [PubMed - indexed for MEDLINE]

Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme.

Ross EM, Howlett AC, Ferguson KM, Gilman AG.

Adenylate cyclase can be resolved into at least two proteins, a thermolabile, N-ethylmaleimide-sensitive component and a second protein (or proteins) that is more stable to either of these treatments. Neither component by itself catalyzes the formation of cyclic AMP using MgATP as substrate. However, mixture of the two reconstitutes MgATP-dependent fluoride- and guanyl-5'-yl imidodiphosphate (Gpp(NH)p)-stimulatable adenylate cyclase activity. The more stable component can be resolved from the first in various tissues or cultured cells by treatment of membrnes or detergent extracts with heat or N-ethylmaleimide. The two proteins have also been resolved genetically in two clonal cell lines that are deficient in adenylate cyclase activity. An adenylate cyclase-deficient variant of the S49 lymphoma cell (AC-) contains only the thermolabile activity, while the activity of the more stable protein is found in a complementary hepatoma cell line (HC-1). In addition, AC-S49 cell plasma membranes contain MnATP-dependent adenylate cyclase activity. The protein that catalyzes this reaction appears to be the same as that which can combine with the thermostable component to reconstitute Mg2+-dependent enzyme activity because both activities co-fractionate by gel exclusion chromatography and sucrose density gradient centrifugation, both activities have identical denaturation kinetics at 30 degrees C, and both activities are stabilized at 30 degrees C and labilized at 0 degree C by various nucleotides and divalent cations with similar specificity. It is thus hypothesized that the thermolabile factor is the catalytic subunit of the physiological adenylate cyclase and that the Mn2+-dependent activity is a nonphysiological expression of the catalytic protein. The thermostable moiety of the enzyme, which is proposed to serve a regulatory function, appears to consist of two functional components, based upon differential thermal lability of its ability to reconstitute hormone-, NaF-, or Gpp(NH)p-stimulated adenylate cyclase activity. These components have not, however, been physically separated. The thermolabile and thermostable components can interact in detergent solution or in a suitable membrane. Mixing of the detergent-solubilized regulatory component with AC-membranes that contain only the catalytic protein and beta-adrenergic receptors reconstitutes catecholamine-stimulatable adenylate cyclase activity; however, addition of the catalytic protein to membranes that contain receptor and the regulatory component yields MgATP-dependent enzymatic activity that is unresponsive to hormone.

PMID: 210183 [PubMed - indexed for MEDLINE]

S49 lymphoma wild type and variant clones contain normal calcium dependent regulator.

Burgess WH, Howlett AC, Kretsinger RH, Gilman AG.

Calcium dependent regulator is present in wild-type S49 lymphoma cells, in the variant that is deficient in adenylate cyclase activity (AC-), and in the uncoupled variant (UNC). The electrophoretic mobility and the ability to stimulate cyclic nucleotide phosphodiesterase of the calcium dependent regulator from each of these three clones are indistinguishable from those of the modulator protein isolated from bovine brain. Calcium dependent regulator does not appear to be involved in the defect responsible for the UNC or AC- variants.

PMID: 214461 [PubMed - indexed for MEDLINE]

Adenylate cyclase in polyacrylamide gel electrophoresis: solubilized but active.

Newby AC, Rodbell M, Chrambach A.

PMID: 708065 [PubMed - indexed for MEDLINE]

[ Incidence of atmospheric fluoride upon the state of health of a population in the hydrogeochemical province of Bucak ]

Excerpts: The author carried out studies in six different areas of the province of USSR in Bucak of the Ukraine, the part of the USSR where water contains the highest levels of fluoride naturally in water.

... The effect on bones was studied in six localities with varying fluoride levels in the drinking water. Six hundred x-ray films were taken of the hands of 9-year old children and 600 of the cervical spine of 50-year olds. In addition, chemical and histological studies were carried out.

At 1.0 - 2.5 ppm the density of the bones had increased compared with the controls. At 4.0 - 4.2 ppm the density appeared to be reduced and at 8.2 -10.3 ppm there was a distinct decrease in density to the extent that osteoporosis occurred. In the last-mentioned group, a delay in ossification was observed. Among the 50-year old subjects, "old age" changes of the cervical spine appeared to be more frequent and more pronounced than in controls. Histologically, no clear-cut changes were found in the bones of individuals who had expired as a result of assicdents. The citrate content of their bones decreased when the drinking water contained 2 ppm fluoride. At 2 - 2.5 ppm and above in drinking water, children showed an increase in the threshold for sensitivity of the eye to red color. At the highest concentration of 8.2 - 10.3 ppm the degree of this deficiency was similar to that among workers in fluoride industries.