EPA/600/8-89/002F 

December 1988 

Summary Review of Health Effects 

Associated with Hydrogen Fluoride 

and Related Compounds 

Health Issue Assessment 

Environmental Criteria and Assessment Office 

Office of Health and Environmental Assessment 

Office of Research and Development 

U.S. Environmental Protection Agency 

Research Triangle Park, NC 27711 

For eale by the Superintendent of Docments, U.S. Government u 

Printing Office, Washington, D.C. 20402 
Disclaimer 

This document has been reviewed in accordance with U.S. Environmental 

Protection Agency policy and approved for publication. Mention of trade 

names or commercial products does not constitute endorsement or 

recommendation for use. 
Preface 

The Office of Health and Environmental Assessment has prepared this 

health assessment to serve as.a source document for use by the Office of Air 

Quality Planning and Standard ~ to support decision making regarding possible 

regulation of hydrogen fluoride as a hazardous air pollutant. 

In the development of this assessment document, the scientific literature 

through January 1987 has been inventoried, key studies have been evaluated, 

and summary/conclusions have been prepared so that the chemical's toxicity 

and related characteristics are qualitatively identified. Observed effect levels 

and other measures of dose-response relationships are discussed, where 

appropriate, so that the nature of the adverse health responses is placed in 

perspective with observed environmental levels. 

Any information regarding sources, emissions, ambient air concentrations, 

and public exposure has been included only to give the reader a preliminary 

indication of the potential presence of this substance in the ambient air. While 

the available exposure information is presented as accurately as possible, it is 

acknowledged to be limited and dependent in some instances on assumption 

rather than specific data. This exposure information is not intended, nor should 

it be used, to support any conclusions regarding risk to public health. 

If a review of the health information indicates that the Agency should 

consider regulatory action for this substance, a considerable effort will be 

undertaken to obtain appropriate information regarding sources, emissions, 

and ambient air concentrations. Such data will provide additional information 

for drawing regulatory conclusions regarding the extent and significance of 

public exposure to this substance. 

Table of Contents 

Page 

Preface ............................................... ui ~~~ 

Tables ................................................ vi 

Authors and Contributors .................................. vu " 

1. Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1 

2. Introduction .......................................... 2-1 

3. Air Quality and Environmental Fate . . . . . . . . . . . . . . . . . . . . . 3-1 

3.1 Sources ....................................... 3-1 

3.2 Distributrion and Fate . . . . . . . . . . . . . . . . . . . . . . . . : . . . 3-3 

3.3 Ambient Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-4 

3.4 Exposure ..................................... 3-5 

4. Pharmacokinetics ...... ....... . . .. ...... ........ . .... 4-1 

4.1 Absorption .................................... 4-1 

4.2 Retention and Distribution . . . . . . . . . . . . . . . . . . . . . . . . 4-2 

4.3 Excretion .......:.............................. 4-3 

5. Mutagenicity and Carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . 5-1 

5.1 Mutagenicity .................................. 5-1 

5.2 Carcinogenicity ................................ 5-2 

6. Developmental and Reproductive Toxicity . . . . . . . . . . . . . : . . . . 6-1 

7. Other Toxic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1 

7.1 Acute Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-1 

7.2 Chronic Toxicity . . . . . . . . . : . . . . . . . . . . . . . . . . . . . . . . 7-4 

7.3 Biochemical Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7-6 

8. Beneficial Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-1 

9. References ........................................ :. 9-1 

u 
List of Tables 

No. Page 

1-1 Summary of.human fluoride intake from various sources 1-5 

1-2 Summary of effects on humans of various levels of ffuoride 

intake ..................:.................... 1=6 

1-3 Summary of official standards and human toxicity limits for 

airborne hydrogen fluoride, fluorine, and fluorides ..... 1-7 

2-1 Physical and chemical properties of'hydrogen fluoride .... 2-2 

2-2 Physical properties of aqueous seventy percent 

hydrogen fluoride . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 2-6 

2-3 U.S. hydrogen fluoride consumption . . . . . . . . . . . . ..: . .. `. 2-8 

2-4 U.S. fluorine sources and consumption . . . . . . . . . . . .... . . . 2-9 

3-1 Fluoride emissions to the atmosphere by industrial 

sources in the United States . . . . . . . . . . . . . . . . . . . ... . 3-2 

7-1 Summary of lethal concentration (LC) estimates for HF. 

inhalation .................................... 7-3 

vi 
Authors `and Contributors 

The'author of this document is Kathleen M. Thiessen, Ph.D., Chemical."' 

Effects lnformation Branch, lnformation Research and Analysis Division, Oak 

Ridge National Laboratory„P.O. Box X; Oak Ridge, Tennessee 37831.: - ~ 

The U.S. EPA project manager for this document js David E. Weil, Ph.D., 

Environmental Criteria and Assessment Office, Office of Health and 

Environmental Assessment, MD-52, Research Triangle, Park, Nor.th Carolina, 

27711. 

PEER REVIEWERS 

Earlier drafts of this document were reviewed by the following indiv,iduals": : 

Dr. John Morris 

University of Connecticut 

Storrs, CT 

Dr. John Drury 

Oak Ridge, TN 

Dr. Frank Smith 

Rochester, NY 

"Peer reviewers were selected on the basis of their recognized expertise 

and contributions to the scientific literature on hydrogen fluoride and 

related compounds. 

vi i 

1. Summary and Conclusions 

Anhydrous hydrogen fluoride (HF) is a colorless, fuming corrosive liquid 

or gas at room temperature and is one of the strongest acids known; aqueous 

HF, or hydrofluoric acid, isi a weak acid. Hydrogen fluoride is highly reactive 

with a number of materials. Some HF is produced naturally by volcanic 

activity; commercial production is by the reaction of sulfuric acid with 

fluorspar. Hydrogen fluoride is probably the most important of the many 

fluorine-containing compounds, because it is used in the production of most of 

the other fluorine compounds. 

The major uses of hydrogen fluoride are in the aluminum and 

fluorocarbon industries. Steel production is a major user of solid inorganic 

fluoride (F') in the form of fluorspar. Hydrogen fluoride and other inorganic 

fluoride compounds are also important for a number of other uses (e.g., 

uranium processing, petroleum alkylation, manufacturing fluoride salts, and 

metal pickling and fluxing operations). Total HF and fluorspar consumption has 

decreased since 1974, and an increasing proportion of the HF and fluorspar 

used in the United States is imported. 

The major natural sources of airborne HF and other airborne fluorides are 

volcanic activity, ocean spray, and dust from the weathering of fluoridecontaining rocks or soils. Anthropogenic sources include emissions from 

industrial operations consuming HF or fluorspar and from the combustion of 

coai for power; these sources may contribute as much as 150 thousand metric 

tons of airborne fiuoride per year in the United States and 3.6 million metric 

tons per year worldwide. Twenty to forty percent of industrial fluoride 

emissions are in gaseous form, the rest are particulate. Many of the gaseous 

fluorides, including HF, are hydrolyzed and dispersed in the atmosphere; 

particulate fluorides generally seftle to the ground as dusts. The major route 

for removal of airborne fluoride is atmospheric precipitation, and most of the 

fluoride in precipitation is thought to be of anthropogenic origin. 

At least 300,000 workers in the United States may have potential 

exposure to HF or to other inorganic fluorides. Occupational HF and fluoride 

(as F) exposure limits are set at 2.5 mg/m 3(3 ppm HF) for an 8-hour working 

day. A maximum of 10 to 25 mg fluoride per day could be inhaled by a worker 

under these exposure limits. Exposure of the general public to airborne 

fluorides, inciuding HF, is greatest in the vicinity of point sources such as 

factories; average total fluoride concentrations near industrial operations in the 

United States and Canada are normally below 8.2 pg/m 3 . People living in 

highiy poiluted industrial areas probably inhale at most 0.2 mg of fluoride per 

day. Fluoride intake from food and water is probably about 2 to 3 mg/day 

(normal range, 0.25 to 5.4 mg/day) per person, depending on individual diet 

and whether or not the local water supply is fluoridated. Cigarette smokers 

may inhale as much as 0.8 mg fluoride per day. Fluoride intake may also 

occur from other sources such as fluoridated dentifrices. Most of the toxic 

effects of hydrogen fluoride to humans are attributable to the fluoride ion, and 

fluoride exposure from all sources must be assessed in the determination of 

the health effects of HF or fluoride on the human population. 

1-1 
AbsorQtion of fluoride in mammals is dependent primarily on the s.olubility 

of the specific compound: NaF is readily absorbed in the gastrointestinal tract, 

CaF2much less so. Hydrogen fluoride is rapidly absorbed via the lungs, skin, 

or gastrointostinal tract. Not al1 particulate fluorides are actually deposited in or 

absorbed from the respiratory tract; some are exhaled without ever being 

deposited on the surface of the respiratory tract. As much as one half of 

absorbed fluoride may be retained in the human body, niost of it in the 

skeleton. The plasma concentration of ionic fluoride is directly relate,d to fhe 

fluoride content of the drinking vvater and is normally in the range of 10 to 20 

pg/L. Clearance from the blood is by uptake into bones or teeth (especially in 

children), where it replaces hydroxyl ions in the apatite lattice,, and by 

excretion via the kidneys. Urinary excretion is the main route of removal of 

fluoride from the body, and fluoride levels in urine are correlated with fluoride 

intake. People with renal dysfunction will excrete less than normal amounts of 

fluoride; oecause of the increased retention of fluoride, these people are at a 

higher risk for toxic effects caused by ffuoride. 

Some studies have suggested that HF and NaF are genotoxic in plants, 

Drosophila, or mammals, primarily by causing chromosome breakage. The 

fluoride concentrations used, to induce genotoxic effects in many in vivo 

experiments are several hundred to several thousand times higher'than the 

blood fluoride levels expected in humans. Epidemiological studies have not 

provided evidence for an association between fluoride in drin{cing water and an 

increased risk of cancer mortality. Increased rates of cancer have been 

reported for workers in several occupations involving possible fluoride 

exposure; however, all these situations involved mixed exposures to several 

chemicals, and fluoride could not be specifically implicated as the cause of the 

cancers. No animal bioassays have been reported on the potential 

carcinogenicity of inhaled fluorides, and tests of sodium fluoride administered 

orally to mice have been inconclusive. The available evidence is thought to be 

inadequate to support or refute a carcinogenic potential for inhalation exposure 

to fluorides. The United States Environmental Protection Agency has not 

classified fluo'ride or hydrogen fluoride with respect to potential 

carcinogenicity. 

Fluoride can cross the placenta and be deposited in the calcified tissues 

of the fetus; fetal exposure is proportional to maternal exposure. High levels of 

fluoride have caused impaired reproduction or malformation of fetal bones and 

teeth in some mammalian species, but no adverse effects on human reproduction or fetal development are expected at fluoride levels likely to be 

encountered by humans. 

The major developmental risk to humans from fluoride is dental mottling 

or fluorosis. This occurs in individuals receiving excess fluoride (usually in the 

drinking water) during the period of tooth mineraiization (prior to birth for 

deciduous teeth and up to age 12 for the last of the permanent teeth). Mild to 

moderate dental fluorosis (from water fluoride levels up to 4 mg/L) is ` 

considered a'cosmetic effect rather than a health effect. 

Acute exposure to gaseous fluoride is rare in a nonoccupational setting. ' 

Hydrogen fluoride and fluorine are extremely toxic, with IDLH ("immediately 

dangerous to life and health") levels of 16.4 and 50 mg/m 3(20 and 25 ppm), 

respectively. Both gases can cause• severe respiratory damage or skin burns 

on contact. Aqueous hydrofluoric acid also causes severe burris. The skin 

burns and respiratory damage caused by hydrogen fluoride are the only toxic 

effects of hydrogen fluoride which are not attributable solely to the action of 

the fluoride ion, and •systemic fluoride poisoning usually does occur from HF 

absorbed via the lungs or the skin. Ingested fluorides also cause systemic 

1-2 
fluoride poisoning. Symptoms of acute fluoride poisoning include.convulsions 

and cardiac arrhythmias, and death is usually from cardiac or respiratory 

failure and occurs within 24 hours. An acute dose of 8 to 16 mg fluoride per kg 

body weight can be safely tolerated by humans; a dose of 32 to 64 mg/kg is 

lethal. No. acute effects of fiydrogen' fluoride or other inorganic fluorides are 

noticed at air fluoride levels of 2.6 mg/m3. 

The bones and teeth are the tissues most sensitive to long-term fluoride 

intake. Chronic fluoride exposure to 0.1 to 0.35 mg/kg/day during childhood 

can result ,in dental fluorosis or mottling. Skeletal fluorosis requires a higher 

fluoride intake (0.2 to 1.0 mg/kg/day or more) over many more years. The , 

earliest observable effect of fiuoride deposition in the skeleton is an increased 

opacity of the bone to X-rays, known as osteosclerosis, which is first 

noticeable when the fluoride level reaches 5000 to 6000 mg/kg of dry, fat-free 

bone.. Skeletal fluorosis increases in severity with increased fluoride intake and 

increased tirne. Crippling fluorosis is characterized by pain, stiffness, irregular 

bone growth, and caicification of ligaments and tendons; this occurs only when 

occupational fluoride exposure has been very high (resulting in an intake of 20 

to 80 mg/day for 10 to 20 years) or when drinking water contains 10 to 40 

mg/L fluoride. Other effects of chronic fluoride exposure on humans have been 

reported, including hypersensitivity and dermatological reactions, but none has, 

been convincingly established. The United States Environmental Protection 

Agency (1986) has established an oral Reference Dose (RfD) of 0.06 

mg/kg/day for children (corresponding to a water fluoride level of 1, mg/L) 

which is adequate to prevent dental and skeletal fluorosis. An inhalation RfD is 

not available. 

Fluoride toxicity involves at least four major effects: inhibition of various . 

enzymes, . hypocalcemia, cardiovascular coliapse, and damage to specific 

organs such as the brain and the kidneys, The major chronic effects of filuoride may be caused by the action of the fluoride ion on various enzymes and 

thereby on metabolic pathways. Many of the acute toxic effects of fluoride, 

such as the cardiac arrhythmias, may be caused by hypocalcemia, and most 

methods of treatment of acute fluoride poisoning or HF burns include 

immediate replacement of calcium. 

It is generally accepted that fluoride has a significant cariostatic effect on 

human teeth, particularly 'for individuals who receive it during childhood. 

Fluoride acts systemically in ,the formation of teeth by being built into the, 

crystal structure of the enamel,-making it harder and more resistant to decay; 

fluoride aiso acts topically on erupted teeth by promoting remineralization and 

by inhibiting acid production by bacteria. In many communities, fluoride is 

administered to the population via the water supply, typically at a level of 1 

ppm fluoride, depending on the average local temperature. A few reports 

suggest that at least some of the decline in tooth decay attrib.uted to 

fluoridated water may in fact be due to other causes, such as changes in 

immune status, changes in dietary patterns, and use of topical fluorides. 

The use of fluoride has also been suggested as a means of preventing or 

treating osteoporosis, or premature bone loss. Some evidence exists which 

indicates that people living in an area with a high natural level of fluoride in the 

water (4 to 8 mg/L) have a lower incidence of osteoporosis, but medical use of 

high fluoride doses is still under investigation. Fluoridated water may also be 

correlated with a lower incidence of cardiovascular disease. The beneficial 

effects and the adverse effects of fluoride must be weighed in determining the 

optimal dose for humans, and in particular for the optimal fluoride level to be 

maintained in public water supplies. 

1-3 
In summary, most of the toxic effects of hydrogen fluoride are attributable 

to the effects of fluoride ion. Acute inhalation of HF or skin contact with HF or 

hydrofluoric acid results in respiratory damage or skin burns, as well as 

systemic fluoride effects. Average air fluoride concentrations near industrial 

operations are usually less than 8.2 Vg/m 3and exposure of thE: general public 

to airborne fluorides is normally less than 0.2 mg/day per person in industrial 

areas and even less in rural areas. For most people, exposure to airborne 

fluorides is considerably less than exposure to fluoride frorn other sources 

such as food and water; nevertheless exposure to fluoride from all `sources 

must be assessed in the accurate determination of the health effects on the 

human population. Most people probably ingest 0.25 to 5.4 mg fluoride per 

day, depending on individual diet and the fluoride content of local water 

supplies; smoke.rs may inhale another 0.8 mg fluoride per day. Table 1-1 

contains a summary of human fluoride intake from various sources. 

Some fluoride intake, about 0.06 mg/kg/day (1.2 mg/day in a 20-kg child 

or 4.2 mg/day in a 70-kg adult) has a beneficial effect in the prevention of 

dental caries, particularly for those receiving it during childhood. A fluoride 

intake of 0.2 to 0.35 mg/kg/day (4 to 7 mg/day for a child) during childhood 

commonly causes dental fluorosis. Long-term fluoride intake of 0.2 to 1.0 

mg/kg/day (14 to 70 mg/day for an adult) or more will .result iri severe skeletal 

fluorosis. An acute fluoride intake of 8 to 16 mg/kg can be safely tol2rated by 

humans; a dose of 32 to 64 mg/kg is lethal. Tabte 1-2 summarizes the effects 

on humans of various levels of fluoride intake, and Table 1-3 summarizes the 

existing official standarcis and human toxicity limits for airborne hydrogen 

fluoride, fluorine, and inorganic compounds of fluoride. 

1-4 
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1-5 
Tabie 1-2. Summaiy of Effects on Humans of Various Levels of 

Fluoride Intake 

Description Averaging Time Intake or Exposure 

4000-5000 ppm fluoride in 60 years 0.02-0.04 mg/kg/day 

bones 1 mg/L (water) 

NOAEL (oral), RfD (oral) 0-12 years of age 0.06 mg/kg/day 

cariostatic effect, very mild 1 mg/L (water) 

dental fluorosis in about 1 in 5 

people 

LOAEL (oral) dental mottling, 0-12 years of age 0.11 mg/kg/day 

mild dental fluorosis 2 mg/L (water) 

dental fluorosis common, 0-12 years of age 0.2-0.35 mg/kg/day 

sometimes severe > 4 mg/L (water) 

6000 ppm fluoride in bone, 2-35 years, 0.2-1.0 mg/kg/day 

osteosclerosis, skeletal average of 8 years 8 mg/L (water) 

fiuorosis 0.14-3:43 mg/m3 (air) 

crippling skeletal fluorosis 20 years; 0.2-10+ mg/kg/day 

> 2 years, dose > 10 mg/L (water) 

dependant 12-26 mg/m3(air) 

no effect (oral) acute 8-16 mg/kg 

lethal (oral) acute 32-64 mg`/kg 

a The information above is from human data. The estimates of f.luoride intake and 

fluoride exposure levels are those reported in the cited publications; they were 

not derived by use of conversion factors. If an air concentration is not given in 

the table, assume that no information was found associating that effect with a 

particular airborne fiuoride concentration. 

Abbreviations: NOAEL - No Observed Adverse Effect Level 

RfD - Reference Dose 

LOAEL - Lowest Observed Adverse Effect Level 

Sources: Heifetz and Horowitz, 1986; United States Environmental Protection 

Agency, 1986; Federal Register, 1985b; World Health Organization, 

1984; Hayes, 1982; Drury et al., 1980. 

W. 
Table 1-3. Summary of Official Standards and Human ToxiCity Limits for 

Airborne Hydrogen Fluoride, Fluorine, and Fluorides 

Hydrogen Fluorides 

` Fluoride Fluorine as F 

Standard or Effect , mg/m3 mg/m3 mg/m3 . Sources 

Detection by smeli 0.034a 0.28 na B 

ACGIH - TWA (8-hr) 2.5 2 2.5 A 

- STEL (15-min) (ceiling) 

na 4 na A 

NIOSH - TWA (8-hr) 2.5 na 2.5 F, G 

- STEL (15-min) 5.0 na na F 

OSHA - TWA (8-hr) , 2.5° 0.2 2.5 C 

No acute effect 2.6 (<8 h) 15 na E 

Irritation (>10 min) 13 na na E 

(< 10. min) . 26 25-40 na , E 

IDLH 16.4d 50e 500 H 

Breathing impossible na 75 na E 

Lethal (LCLo, 5 min) 41-205f na na D 

Lethal (LCIoo, 60 min) 877f na na E 

na - data not available. 

aGiven as 0.042 ppin in the cited publication. 

bGiven as 0.14 ppm in the cited publication. 

cGiven aS 3 ppm..in the cited publication. 

dGiven as 20 ppm in the cited publication. 

eGiven as 25 ppm in the, cited. publication. 

fSee Table 7-1 for other LC values. 

Abbreviations: ACGiH.- American Conference of Governmental Industrial Hygienists; IDLH 

- Immediately Dangerous to Life and Health; LCL O - lowest lethal concentration for the 

exposed population (estimated); LC 100 -- lethal concentration for 100 percent of the exposed 

population (estimated); NIOSH - National Institute for Occupational•Safety and Health; 

OSHA - Occupational Safety and Health Administration; STEL Short Term Exposure 

Limit; TWA - Time Weighted Average.,. 

Sources: A) American Conference of Governmental Industrial Hygienists, 1986. 

B) Amoore and Hautala, 1983. 

C) Code of Federal Regulations, 1985. 

D) Halton et al., 1984. 

E) Just and Emler, 1984. 

F) National Institute for Occupational Safety and Health, 1976; 1975. 

G) National Institute for Occupational Safety and Health, 1976. 

H) Siftig, 1985. 

1-7 

2. Introduction 

This report is intended to provide a brief review of the available 

information on the potential health effects associated with exposure to 

hydrogen fluoride and related compounds. Emphasis is placed on the potential 

health effects on the general public from exposure to ambient airborne 

concentrations. Sources, distribution, fate, and ambient levels of hydrogen 

fluoride and other inorganic fluorides are reviewed. Because most of the toxic 

effects of hydrogen fluoride are attributable to the fluoride ion, data concerning 

the pharmacokinetics, mutagenicity, carcinogenicity, teratogenicity, acute and 

chronic toxicity, and beneficial effects of both hydrogen fluoride and fluoride in 

general are discussed. 

Fluorine {F) is the 13th most abundant element (Hodge and Smith, 1972). 

It is the most electronegative of all the elements, combining with almost all 

other elements (Stokinger, 1981); elemental fluorine is therefore not found in 

nature. Most naturally occurring fluorine is in the form of minerals, primarily 

fluorspar (fluorite, CaF2), phosphate rock (fluorapatite, CaFz 3Ca(PO4) 2), and 

natural cryolite (Na 3AIF6 ; Levenson et al., 1982). Hydrogen fluoride is probably 

the most important of the numerous fluorine compounds, as' it is used in the 

production of elemental fluorine (F2) and in the synthesis of many other 

fluorine compounds, both organic and inorganic. Some HF is produced 

naturally by volcanic activity (Stokinger, 1981); most commercially used HF is 

produced by the reaction of sulfuric acid (H2SO4) with fluorspar to give HF and 

calcium sulfate (gypsum, CaSO4; Levenson et al., 1982). Hydrogen fluoride is 

also produced as a by-product in industries using phosphate rock or cryolite. 

Anhydrous hydrogen fluoride (HF) is a colorless, fuming, corrosive liquid 

or gas at room temperatures (boiling point, 19.54°C). Hydrogen fluoride is 

readily soluble in water and in a number of other solvents; aqueous HF is 

usually referred to as hydrofluoric acid. Anhydrous HF is one of the most 

acidic substances known, with a Hammet acidity function of -10.98 (Windholz 

et al., 1983); in aqueous solution, HF is a weak acid (Ka = 6.46 x 10- 4 

moles/liter). Hydrogen fluoride will attack glass, concrete, and certain metals, 

especially those containing silica (Weiss, 1980). Anhydrous HF actively 

dehydrates many organic materials, charring wood and paper on contact (Gall, 

1980). Although not flammable itseif, HF in contact with some metals may 

generate flammable hydrogen gas (Weiss, 1980). Polymerization of HF 

molecules due to hydrogen bonding occurs in the solid, liquid, and gaseous 

states (Gall, 1980). The strength of the hydrogen-fluorine bond, the hydrogen 

bonding and polymeric association of HF molecules, the strong acidity of 

anhydrous HF in contrast to its weak acidity in aqueous solution, and the 

absence of oxidation states of fluorine other than -1 are the most significant 

features of the chemistry of hydrogen fluoride (see Gall, 1980, for a review ofi 

hydrogen fluoride chemistry). Important chemical and physical properties of 

hydrogen fluoride and aqueous 70 percent hydrogen fluoride are summarized 

in Tables 2-1 and 2-2, respectively. 

• Hydrogen fluoride and hydrofluoric acid are used in a number of 

industries; since the 1930's, the two major uses of HF have been in aluminum 

2-1 
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2-5 
Table 2-2. Ptiysical Properties of. Aqueous Sewenty 

Percent Hydrogen Fluoride . 

Boiling, Point: 66.4°C ° 

Freezing Point: -69°C (solid phas.e is HF•H20 , 

Vapor Pressure:'• 150 mm Hg (20 kPa ;2.9 psia) af25?C: '•` 

Density: 1.22 glcm3 at 25°C 

Source: Gall (1980) I 

manufacture and fluorocarbon production (Levenson et al., 1982; Gall, 1980; 

Stuewe, 1958). Other important uses for HF include uranium processing, 

petroleum alkylation, stainless steel pickling, etching of glass and 

semiconductor components, and the production of synthetic cryolite, fluorine 

gas, fluoride salts, fluorine-containing plastics, and special metals. End uses of 

other fluoride compounds include water fluoridation (for prevention of dental 

caries), ore flotation, wood preservation, electroplating, and chemical cleaning. 

The consumption of hydrogen fluoride by the major U.S. industries is given in 

Table 2-3 for the years 1957 (near the beginning of rapid growth in HF usage), 

1974 (at the peak of HF usage in the aluminum and fluorocarbon industries), 

and 1981 (more typical of recent HF consumption following the effects of the 

economic recession on aluminum production and of environniental legislation 

on fluorocarbon production). Total HF consumption in the U.S. was between 

320 and 340 thousand metric tons from 1975 to 1981 (Levenson et al., 1982); 

HF consumption was 277 thousand metric tons in 1985 anci is expected to 

reach 318 thousand metric tons) by 1989 (Chemical Marketing Reporter, 

1986). U. S. fluorspar and hydrogen fluoride production have: been generally 

decreasing since 1974 (Table 2-4). The decrease in HF production has been 

larger than the decrease in HF consumption; imports of HF to the U. S. have 

been showing a corresponding increase. Mexico and Canada are the principal 

sources of imported HF. Most of the fluorspar used in the U. S. is also 

imported, primarily from Mexico and the Republic of South Africa (Levenson et 

al., 1982). About fifty to seventy percent of U. S. fluorspar consumption is for 

HF production; most of the rest of the fluorspar goes directly to steei 

production (Table 2-4), where it is used to increase the fluidity of the slag. The 

steel industry, and therefore the consumption of fluorspar by the steel 

industry, is highly dependent on economic factors. Steel-making processes 

have also been changing, from mostly open hearth production to mostly basic 

oxygen or electric processes, and this also affects fluorspar consumption by 

the industry (Levenson et al., 1982). 

Total industrial emission of soluble fluoride in the Uniteci States (around 

1964-1970) was an estimated 140 to 150 thousand metric tons per year (Smith 

and Hodge, 1979; Krook and Maylin, 1979a), and in Canada (1972) about 14 

thousand metric tons per year (Krook and Maylin, 1979a). Ttie emission rate 

for hydrogen fluoride in the U.S. in 1980 from HF inanufacture, aluminum 

production, phosphate processing, and coal combustion was an estimated 

81.5 thousand metric tons per year (MisenMeimer et al., 1985). Volcanic and 

fumarolic activity (throughout the world) is estimated to contribute up to 7.3 

million metric tons of fluoride per year to the atmosphere (Ban:els, 1972; 

Carpenter, 1969). 

Several comprehensive reviews exist on occupational exposure to and 

risks from fluorides or HF, the effects of HF or fluorides on plants and animals, 

and health and environmental effects of fluorides (see for instance Smith, 

1986b; World Health Organization, 1984; gJahr, 1983; Smith et al., 1982; van 

2-6 ' 
Haut and Krause, 1982; Drury et al., 1980; Safe Drinking 'Water Committee, 

1980; 1977; Smith and Hodge, 1979; Hodge and Smith, 1977; National 

Institute for Occupational Safety and Health, 1976; 1975; National Research 

Council, 1974; 1971; Hodge and Smith, 1965). This report seeks to 

concentrate on the effects of human health that can be expected from ambient 

airborne concentrations, of hjidrogen fiuoride and other fluorides. 

2-7 
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2-9 

3. Air Quality and Environmental Fate 

3.1. Sources 

The only known natural source of hydrogen fluoride is volcanic activity 

(Stokinger, 1981). Masaya Volcano in Nicaragua, for instance, emits 5 metric 

tons of HF per day during its active degassing phase (Baxter et al., 1982). The 

kinds and amounts of gases emitted vary between volcanoes, and in most 

cases HF is not the major component of the emissions. A number of other 

inorganic fluoride compounds are also present in volcanic emissions, including 

F2 , NH4F, KF, NaF, CaF2 , MgF2 , SiF4 , (NH4)2SiF6 , Na2SiF6 , K2SiF6 , and KBFA 

(Smith and Hodge, 1979); trace amounts of a few fluorine-containing organic 

compounds have also been identified in the emissions. Fluorine or fluoride 

compounds have been found in the emissions of volcanoes in Alaska, Hawaii, 

Central America, Iceland, New Zealand, ,the Azores, the Canary Islands, 

Martinique, and several places in Europe and Asia. Total fluoride 

concentrations in fumarole condensates of several Central American volcanoes 

range from <0.1 to 200 mg/kg (Smith and Hodge, 1979); the total worldwide 

contribution of fluoride to the atmosphere by volcanic and fumarolic activity 

has been estimated to be 1 million metric tons of fluoride per year (Carpenter, 

1969; Bartels, 1972, estimates it to be 7.3 million metric tons per year). 

Natural sources of other airborne fluoride compounds include ocean spray 

and dust from the weathering of fluoride-containing rocks or soils (Smith and 

Hodge, 1979). Fluoride concentrations in rocks range from 80 to 4700 mg/kg 

and in soils from traces to 7070 mg/kg with means around 200 to 300 mg/kg. 

Fresh water sources in North America contain 0 to 16 mg/L fluoride, 

depending on the minerals the water comes in contact with and several other 

factors such as temperature and pH (Smith and Hodge, 1979). Airborne dust 

collected at sea is thought. to derive from continental or volcanic rocks, since 

its fluoride content, which ranges from 330 to 875 mg/kg, approximates that of 

crustal rocks. Seawater itself typically contains 1.2 to 1.4 mg/L dissolved 

fluoride, about half of which is thought to be present as MgF (Carpenter, 

1969). Essentially all of the fluoride-containing dust is thought to remain in a 

particulate form, eventually settling out on land or over water, where it 

sediments (Carpenter, 1969). Sea salt may contribute a variable amount of 

dissolved fluoride to the air (see Carpenter, 1969; Mahadevan et al., 1986), but 

it does not appear to be a major source of airborne fluoride (Barnard and 

Nordstrom, 1982). 

Anthropogenic sources of hydrogen fluoride and other fluorides include 

coal-burning facilities and industries which produce or consume hydrogen 

fluoride or other fluorides, especially the steel, aluminum, and phosphate rock 

(fertilizer) industries (Table 3-1). Total sotuble fluoride emissions from 

industrial sources were 140 to 150 thousand metric tons per year in the U. S. 

around 1970 (Krook and Maylin, 1979a; Smith and Hodge, 1979); the U. S. 

emission rate for hydrogen fluoride from HF inanufacture, aluminum 

production, phosphate processing, and coal combustion was an estimated 

81.5 thousand metric tons per year in 1980 (Misenheimer et al., 1985; this 

3-1 
, 

Table 3-1. Fluoride Emissions to the Atmosphere by Industrial Sburces in 

the United Statesa 

Total Fluoride HF 

Source (1968-1970) (1980) 

Coal combustion for power 24.1 63.2 

St®el 58.6 b 

Phosphate rock processing 19.3 6:2 

Aluminum processing 14.7 12.1 

HF production 0.6 0.02 

Miscellaneous sources 32.9 b 

Total 150.2 81.5 

Sources: Boscak (1978); Krook and Maylin (1979a); Smith and Hodge (1979); 

Misenheimer et al. (1985). 

aData given in thousands of inetric tons per year. 

bData not available. 

report assumes that all the fluorine emitted from coal combustion is in the 

form of HF but admits that this has not yet been demonstrated). Hydrogen 

fluoride production is a minor source of fluoride emission when compared with 

the aluminum, phosphate, or steel industries, or with coal cornbustion (Table 

3-1). Steel production is one of the major sources of fluoride emissions 

(mostly particulate fluorides from the fluorspar in the flux), although fluorides 

are not the major emission from steel plants (United States Environmental 

Protection Agency, 1977). Coal combustion is probably the other major source 

of fluoride emission (various coals contain up to 141 mg/kg fluorine with a, 

mean of 74 mg/kg; Misenheimer et al., 1985), aithough again, HF (or other 

fluoride compounds) is not the major emission from coal burning facilities. 

Total worldwide fluoride (soluble and particulate) emissions from industrial 

sources were estimated to have been 3.6 million metric tons irl'1972 (Barnard 

and Nordstrom, 1982). 

Emission factors for HF, particulate fluorides, or SiF4 are available.for coal 

combustion, HF inanufacture, frit manufacturing, phosphate processing, and 

the various methods and steps of aluminum and steel production 

(Misenheimer et al., 1985; United States Environmental Protection Agency, 

1984; 1983; 1980a; 1980b; 1977). These give an emi"ssiori rate for a poilutant 

in terms of amount of a substance consumed or produced. F6r instance, the 

emission factor for HF production in the absence of any emission controls is 

12.5 kg HF emitted per metric ton of HF produced (25.0. Ibs/ton; Misenheimer 

et al., 1985); when emission control (a caustic scrubber) is used, the emission 

factor is 0.1 kg/metric ton of acid produced (0.2 Ibs/ton). By using a production 

figure for HF of 193 thousand metric tons per'"year (the amount of_ HF 

produced and withdrawn from the system in the United States in 1980; 

Levenson et al., 1982; see Table 2-4, p. 2-9) togetfier with the emission factors 

given above, estimates of 2.4 and 0.02 thousand metric tons FiF peP year are 

obtained for uncontrolled and controlled emissions, respectively, from HF 

production in the United States. Actual HF emissions from Hl= production iri 

1980 are in fact estimated to be 0.02 thousand metric tons (21.3 tons; 

Misenheimer et al., 1985; see Table 3-1). Actual amounts of U. S. fluoride 

(including HF) emissions have been changing in recent years due to changes 

3-2 
iri industrial methodoiogy (from primarily open hearth to basic oxygen 

processes in steel production, for instance), ihcreasing efficiency of emission 

controls, and various economic considerations.. The steel and aluminum 

industries in particular are:highly dependent pn economic conditions in terms 

of total production; it is also becoming econqmically desirable to recycle as 

much fluorine or fluoride as possible in the aluminum and petroleum alkylation 

industries (Levenson et al., 1982). i 

Gaseous fluorides commonly make up ~ 20 to 40 percent bf industrial 

fluoride emissions (Barnard and Nordstrom, 1982; both Alary et al., 1981, and 

Krook and Maylin, 1979a, give around 50 per ~ent for specific factories). Most 

of these gaseous fluorides are in the form of HF or SiF A , but H2SiF6 , BF3 , and 

F2may also be emitted from the .glass and phosphate industries (Smith and 

Hodge, 1979) and UF6from uranium processi6g facilities (Bostick et al., 1985). 

Common particulate fluorides released from industrial sources include 

Na3AIF6 , AIF3 , Na5A1.3 F,14 , CaF2 ; NaF, Na2 oiF6 , PbF2 , and Ca jo(PO4 )6F2 

(Smith and Hodge, 1979). 

Hydrogen fluoride is found in the stratosphere (about 12 km altitude) at a 

latitude-dependent column amount of about 1.4 to 5.4 x 10 14molecules per 

square cm (Mankin and Coffey, 1983). Thi;s HF is almost entirely from 

decomposition of chlorofluoromethanes of anthropogenic origin, and seems to 

be increasing at a rate of about 12 percent por year. Unlike chlorine, fluorine 

does not react with ozone, so that HF in thei stratosphere is stable. The HF 

gradually diffuses to the troposphere, where it is rained out (Mankin and 

Coffey, 1983). I 

, , 

3.2 Distribution and Fate 

The major gaseous fluorides released to! the environment, HF and SiF 4 , 

are both readily ,hydrolyzed and dispersed ib the atmosphere (Barnard and 

Nordstrom, 1982). Anhydrous HF combines w ~ th water vapor in the air to form 

aqueo`us hydrofluoric acid ,(National Research Council, 1971). Several volatiie 

inorganic fluorides;including SF4 , S2F2 , and ~ fluorine gas and other halogen 

fluorides, as well as SiF4, give rise to hydrolysis products which are less 

v.olatile and which are eventually removed from the atmosphere by 

condensation or nucleation processes (DruCy et al., ,1980; see National 

Research Council, .1971, for a discussionj of fluoride cherriistry in the 

atmosphere), Uranium hexafluoride, UF 6 , also hydrolyzes to form a less 

volatile product; UO 2 1`2; plus HF (Bostick et.;al., 1985): Uranium compounds 

pose a greater health haza,rd in terms of their radioactivity than their f.luoride 

content; for that reason stringent controls, arejpracticed and emissions of UF 6 

and related compounds:are` normally very small (Drury et al., 1980; see also 

Bostick . et al., 1985), although accidental rel4ses do occur (see for instance 

Murphy, 1986).. . 

Most particulate.fluorides of industrial origin are stable compounds and do 

not hydrolyze (Drury et al., 1980); most of the'se settle to the ground as dusts. 

The availability of the fluoride in tfiese compounds to plants or to herbivores is 

dependent on the solubili.ty of. the .comp'ourids, which varies between 

compounds and also betv!ieen solvents. NaF ts readily soluble in water, while 

CaF2is essentially insoluble. Fluorapatite is insoluble in Water, but it is at least 

somewhat soluble in the gastrointestinal tracts of animals which ingest it as 

dust on their forage (National Research Counc'il, 1971). 

Atmospheric precipitatiori is probably the main route for removal of 

airborne fluoride compounds. (Mahadevan et al., 1986; Barnard and Nordstrom, 

1982). Total inorganic fluoride concentrations (including all F from hydrogen 

fluoride or other fluoride compounds) up to 14 1 mg/L, depending on proximity 

3-3 
to industrial activities, have been measured in rain- and snowfall (Smith and 

Hodge, 1979). Mahadevan et al. (1986) found an average fluoride 

concentration in precipitation of 3 to 5lig/L (range, 1 to 12 jig/L) for 

background (nonindustrialized) sites in India and 20 pg/L or more for industrial 

areas. The calculated contribution of soil fluoride to precipital:ion was 0.6 pg/L. 

A variable amount of fluoride contribution from sea salt was demonstrated for 

coastal and marine areas; the total fluoride in the precipitation in these areas 

was still much less than for the industrial areas. 

Barnard and Nordstrom (1982) obtained a mean background fluoride 

concentration in precipitation of 8.1 lig/L (range, 0 to 18 ug/L) for nonindustrial 

sites in the eastern United States. They were unable to demonstrate.a fluoride 

contribution from sea salt. From their estimate of 3.6 million metric tons of 

fluoride released to the atmosphere from industrial sources (worldwide) in 

1972, they calculate a fluoride concentration in rainfall of 7.6 ug/L. If maximum 

fluoride contributions from dust (1 ug/L) and volcanic activity (2 to 3 μg/L) are 

added to that figure, a maximum rainfall fluoride concentration of 11.6 lig/L is 

obtained. Because there is no volcanic activity in the eastern United States 

(and therefore the maximum expected concentration of fluoride in the rainfall 

is 8.6 ug/L), Barnard and Nordstrom conclude .that most fluoride in 

atmospheric precipitation is of anthropogenic origin. Fluoride in precipitation 

eventually ends up in the soil and the ground water. 

3.3. Ambient Levels 

Ambient air concentrations of total inorganic fluoride (including fluoride 

from HF and any other fluoride compounds) or of gaseous and particulate 

fluorides have been measured at various industrial and nonindustrial sites. 

Similar measurements for hydrogen fluoride alone are generally not available. 

In rural air, away from any industrial sources of fluoride; only traces (<< 1 

11g/m3) of fluoride are found (Hodge and Smith, 1972). The amount of airborne 

fluoride is higher in urban areas, due both to industrial pollution and to the 

burning of coal and other fluoride-containing fuels; the increased burning of 

fuels in the winter months can cause additional increases, in the fluoride 

content of urban air (World . Health Organization, 1984). Even so, the 

atmospheric fluoride concentrations in urban areas rarely reach 2 μg/m 3 

(World Health Organization, 1984). In several studies of urban communities in 

the U.S. and Europe, fluoride concentrations up to 3.8 jig/m 3were measured; 

most samples contained less than 2.0 jig F/m 3(World Health Organization, 

1984; Drury et al., 1980). 

Air in the immediate vicinity of industrial operations can contain larger 

amounts of fluoride (World Health Organization, 1984; Drury et al., 1980). 

Local airborne fluoride concentrations of 140 to 220 jzg/m 3have been 

measured near European aluminum plants (Drury et al., 1980). Near som.e 

other industrial locations (priniarily aluminum or phosphate processing plants), 

in communities in which fluoride effects have been reported or studied, 

airborne fluoride concentrations (when reported) ranged from 2.5 to 14,000 ug 

F/m3(Smith and Hodge, 1979), although in most of these cases 

concentrations were less than 100 pg/m3. Smith and Hodge (1979) list more 

recent ambient air fluoride concentrations near industrial operations of several 

types and state that mean concentrations were nearly always less than 8.2 

tlg/m3(1 0 ppb)• 

Ambient air fluoride concentrations measured 1.5 km downwind from an 

aluminum processing plant in New York averaged 0.36 11g/m 3gaseous fluoride 

and 0.71 jig/m3total fluoride over a six month period (Krook and Maylin, 

3-4 
•1979a). T,he maximum fluoride concentrations. measured for a twelve-hour 

.period were 6.41 μg/m 3gaseous and 11.94 pg/m 3total fluoride. At a location 4 

km from the plant, the six-month ,averages were 0.28 11g/m3 gaseous and 0.43 

μg/m3total fluoride; the twelve-hour maximums were 2.05 μg/m 3gaseous and 

5.26 11g/m3total fluoridec,=.Air fluoride concentrations. in the vicinity of the 

Paducah (Kentucky) Gaseous Diffusion Plant r.eached a maximum of 1.5•11g/m 3 

:HF (1.8 ppb; from weekly measurements) in 1984 (Martin Marietta . Energy 

Systems, Inc., 1985); average fluoride concentrations at most sampling sites 

were less than 0.082 11g/m 3 . in general, fluoride concentrations near industrial 

sources are probably decreasing due to improved emission , control. standards 

and technoiogy (World Health Organization, 1984). , 

3.4. Exposure 

)n the middle 1970s in the United States, an estimated .22,000 workers in 

57 occupations were potentially exposed to hydrogen fluoride (National Institute for Occupational Safety and Health, 1976), and 350,0.00 workers in 92 

occupations were potentially exposed to various inorganic fluorides (National 

Institute for Occu,pational Safety and Health, 1975). Although recent figures are 

not available, the number of workers exposed to fluorides or hydrogen fluoride 

is probably somewhat smaller now because of the general decrease in the 

major industries which produce or use HF or other fluoride compounds. 

The Occupational Safety and Health Administration (OSHA) gives a 

federal occupational exposure standard for hydrogen fluoride of 2:5 mg/m 3 

(stated as 3 ppm) for an 8-hour time-weighted-average (TWA); the 8-hour 

TWA is 2.5 mg F/m3air for fluoride in generai, including fluoride in dust, and 

0.2 mg/m3 (0.1 ppm) for elemental fluorine (Code of Federal Regulations, 

1985). The American Conference of Governmental Industriai Hygienists (1986) 

recommends threshold limit values (TLVs) of 2.5 mg/m 3(3 ppm; this is' a 

ceilinq value, not to be exceeded at any time) for hydrogen fluoride, 2.5 

mg/m3(TWA) for fluorides as F, and 2 mg/m 3(1 ppm) for fluorine. A short 

term exposure limit (STEL, a 15-minute TWA) of 4 mg/m 3(2 ppm) . is also 

4ven` for fluorine. The National Institute for Occupational Safety and Health 

(1976; 1975) lists similar exposure limits for both hydrogen fluoride and 

fluorides, with the addition of a ceiling on short term exposure to HF of 5.0 mg 

F/m3' (6 ppm) for 15 minutes. Current occupational expos.ure limits in other 

countries are comparable to or lower than the iimits in the United' States 

(lnternational Labour Office, 1984). Occupational exposure to fiuoride has been 

much higher in the past than now, and much of the available information 

concerning the effects .of fluoride on humans has come from studies of 

occupational fluoride exposure. Under current exposure limits, a maximum of 

10 to 25 mg of fluoride could be inhaled in a working day (World Health 

Organization, 1984). Occupational exposure to fluoride or hydrogen fluoride is 

treated at length by the National Institute for Occupational Safety and Health 

(1976; 1975) and by Hodge and Smith (1977; see also Smith and Hodge, 

1979). 

Exposure of the general public to hydrogen fluoride or other airborne 

-fluorides is greatest in the vicinity of point sources such as active volcanoes, 

HF inanufacturing plants, plants which use HF or fluorspar (including 

aluminum, steel, and petroleum alkylation plants), and coal-burning facilities. 

An estimated 1,075,000 people live within 8 km of 11 HF-manufacturing plants 

in the United States (Boscak, 1978); the figure naturally is higher when the 

other fluoride or HF sources are consideretl. Average total fluoride 

concentrations in the vicinity of industrial operations in the U. S. and Canada 

3-5 
are normally less than 8.2 pg/m 3(10 ppb) (Smith and Hodge, 1979; see. also 

Krook and Maylin, 1979a). Several states have ambient air= standards for 

fluorides (Chester et al., 1979); these range from 0.8 gg/m 3(Montana) to 5 

jig/m3(Pennsylvania) over a 24-hour period for fluoride as HF. The American 

Industrial Hygiene Association in 1969 recommended a Community Air Quality 

Guide for HF of 2.8 pg/m 3(3.5 ppb) for 24 hours (Chester et al., 1979). These 

standards were established to protect vegetation and livestock; cattle health 

may not in fact be adequately protected by these standards (Krook and 

Maylin, 1979a), but these fluoride levels are well below those thought to cause 

adverse health effects in humans (Chester et al., 1979). 

People living in rural locations away from sites of indusi:rial operations are 

exposed to only trace amounts of airborne fluoride; people living in cities or in 

industrial areas are exposed to proportionately more airbor -ne fluoride. It has 

been estimated that an individual living in London might inhale 0.001 to 0.004 

mg of fluoride per day, possibly 5 to 10 times higher on an extremely foggy 

day with high pollution (Mart'in and Jones, 1971, as cited in Smith and Hodge, 

1979); in heavily industrialized areas, a person might inhale at most 0.01 to 

0.04 mg of fluoride per day (0.0025 and 0.06 mg/day in two other studies; see 

Smith and Hodge, 1979; World Health Organization, 1984). Near one 

aluminum plant an estimated 0.4 to 0.7 mg fluoride per day was inhaled per 

person (Smith and Hodge, 1979), but this was probably an extreme situation. If 

one assumes a high value of 2pg F/m 3air (see section 3.3 above) in urban 

areas, and an inhalation volume for an adult of 20 m 3air per day, the amount 

of fluoride inhaled would be 0.04 mg/day (Wo.rld Health Organization, 1984). If 

the airborne fluoride concentration near an industrial site were 8jig/m 3(about 

10 ppb), an adult could expect to inhale as much as 0.16 mg fluoride per day. 

Acute exposure to gaseous HF rarely occurs in a nonoccupational setting, but 

HF is one of several potentially toxic gases which may be encountered in fires 

(Hilado and Cumming, 1978; Hilado and Furst, 1976). 

The general population probably receives more fluoride via food and 

drinking water than from the air. Most food items contain traces of fluoride, 

and some items, particularly tea and seafood, can contain substantially more. 

Fluoride intake from food ranges from 0.25 to 1.5 mg per day (Smith and 

Hodge, 1079; see also Anonymous, 1986); leafy vegetabfes grown near 

industrial fluoride sources may increase dietary fluoride by 1 to 1.7 percent. 

Water sources in the United States may contain from 0.1 to 4 or more mg/L 

fluoride (Safe Drinking Water Committee, 1980; Smith and Hodge, 1979). In 

1980, 120 million Americans lived in areas with artificially fluoridated water 

supplies (Anonymous, 1986); this water typically contains 1 mg/L fluoride in 

temperate regions. Estimates for total fluoride intake from food, water, and 

other beverages for people in fluoridated areas range from 1 to 5.4 mg per 

day (World Health Organization, 1984; Safe Drinking Water Committee, 1980; 

Smith and Hodge, 1979); 2 to 3 mg per day is probably typical, although 

individual and population variations in fluoride intake probably exist. 

Some individuals will also be exposed to as much as 0.8 mg of fluoride 

per day from heavy cigarette smoking (Drury et al., 1980). Other potential 

sources of fluoride to humans include fluoridated dentifrices and mouthwashes 

(average about 0.25 mg/day); accidental intake, especially by children, of 

dentifrices (see Heifetz and Horowitz, 1986) or of sodium fluoride pesticides; 

exposure to fluoride-containing anaesthetic gases; and medically prescribed 

use of fluoride in the treatment of osteoporosis (World Health Organization, 

1984). For most people (those who do not have occupational exposure to 

fluorides or hydrogen fluoride), the major source of fluoride is their food and 

water. The average daily fluoride intake for people who are not in the 

3-6 
immediate vicinity of industrial operations is on the order of 2 to 3 mg per day 

: from food,-and water and fess than 0.1 mg fluoride per day from inhaled 

; fluoride. 

3-7 

4. Pharmacokinetics 

4.1. Absorption 

Inhaled fluorides consist primarily of HF and particulate fluorides, both of 

which can be deposited in the respiratory tract (World Health Organization, 

1984). Hydrogen fluoride, most of which is probably deposited in the upper 

respiratory tract, is rapidly absorbed into the system, either directly from the 

respiratory tract or following translocation to the gastrointestinal tract via nasal 

mucus (Morris and Smith, 1982). Close to 100 percent of inhaled HF is 

absorbed (Machle and Largent, 1943). Depending on the size and nature of 

the particles, fluoride-containing particles may be exhaled without being 

deposited on the surface of the respiratory tract, or they may be deposited in 

the nasopharynx, the tracheobronchial tree, or the alveoli (World Health 

Organization, 1984). Absorption of these fluorides and of ingested fluorides is 

dependent on several factors, including the chemical nature of the fluorides 

and what other substances have also been ingested. Fluoride from inhaled 

dust is absorbed as rapidly as fluoride from inhaled HF, but for a given 

airborne fluoride concentration, less total fluoride is absorbed from fluoridecontaining dust than from gaseous fluoride compounds (Collings et al., 1951). 

Soluble fluoride salts (e.g., fluorides in fluoridated water) are absorbed very 

rapidly by the gastrointestinal tract. The presence of fluoride-binding cations 

such as calcium or aluminum will result in greatly reduced fluoride absorption 

in the gastrointestinal tract (World Health Organization, 1984; Drury et al., 

1980; Spencer et al., 1980), thereby increasing fluoride excretion in the feces. 

In experiments with human subjects, Machle and Largent (1943) observed 

approximate gastrointestinal absorptions of 97 percent for NaF and 95 percent 

for CaF2administered in solution. Only 60 percent of solid CaF2was absorbed 

in the gastrointestinal tract, the rest being excreted in the feces. The low pH of 

the stomach permits some otherwise insoluble fluoride compounds to be 

dissolved, causing generation of HF gas in the stomach (World Health 

Organization, 1984). Hydrogen fluoride is rapidly absorbed from the 

gastrointestinal tract, as from the respiratory tract; absorption of HF through 

the skin has also been observed in workers suffering hydrofluoric acid burns in 

accidents (World Health Organization, 1984; Tepperman, 1980; Burke et al., 

1973). 

Absorption of any fluoride appears to be a passive process (Drury et al., 

1980). Fluoride from any source is thought to be transported across biological 

membranes primarily as molecular HF (Whitford and Pashley, 1984; 

Gutknecht and Walter, 1981; Whitford et al., 1976). At physiologicat pH (in 

blood, intracellular fluid, or mucus), fluoride from any source exists primarily 

as fluoride ion (F-), although a small amount of molecular HF exists in 

equilibrium with the ion. The fate or effects of absorbed inorganic fluoride are 

essentially independent of the fluoride source. 

4-1 
4.2. Retention and Clistribution 

Approximately 35 to 50 percent of absorbed fluoride from any source is 

retained in the human body (World Health Organization, 1984;.. Hodge and 

Smith, 1965); the (human) subjects of Machle. and Largent (1943) 

demonstrated about 60 percent retention of absorbed fluoride (total, daily 

intake, >6.0 mg/day). At low fluoride intakes (non-occupational, <4.0. to 5.0 

mg/day), there may be very little cumulative storage of fluoride (McClure,et al., 

1945). About 99 percent of retained fluoride is found in the s4celeton, the rest in 

the blood and in other tissues (World Health Organization, 1984). Fluoride is 

transported through the body Yia the bloodstream. About three-fourths of the 

blood fluoride is in the plasma; the remainder is in or on the red blood cells 

(World Health Organization, 1984). At least one-half of the fluoride in human 

serum may be nonionic fluoride; this includes both organic fluoride 

(perfluorinated fatty acid derivatives) and nonionizable fluoride formed from F' 

or HF, and the amount of nonionic fluoride is related to the total fluoride intake 

(World Health Organization, 1984; Morris and Smith, 1983; Ophaug and 

Singer, 1977). 

For the general population at a steady-state exposure -to fluoride,, the 

plasma concentration of inorganic (ionic) fluoride is directly related to the 

inorganic fluoride content of the drinking water (World Health Organization, 

1984; Drury et al., 1980). The normal range of plasma fluoride concentrations 

is about 10 to 20pg/L in areas with low water fluoride levels (less than or 

equal to 1 mg/L; World Health Organization, 1984; Drury et al., 1980; Smith 

and Hodge, 1979). An average blood fluoride concentration of about 82 ug/L 

was found in a community with 5.6 mg/L fluoride in the drinking water (Drury 

et al., 1980; Smith and Hodge, 1979). Blood fluoride levels in fatal cases of 

acute fluoride poisoning have ranged from 3.5 to 15.5 mg/L (Gosselin et al., 

1984). Plasma concentrations of fluoride increase with age, possibly because 

clearance from the blood via uptake into bone is slower in adults than in 

children. Clearance of fluoride from the blood occurs rapidly by incorporation 

into bone and by renal absorption and excretion. Young bone (i.e., in c.hildren), presumably.because it is less saturated with fluoride, appears to take 

up fluoride more rapidly than does bone in older individuafs; children therefore excrete less fluoride in the urine than do adults. 

The fluoride ion taken up by bone replaces hydroxyl ioris in bone apatite 

(World Health Organization, 1984). The precise mechanism of fluoride 

incorporation into bone is still under investi.gation (see World Health 

Organization, 1984; Rioufol et al., 1983; Drury et a1.,.1980); the overall result is 

that absorbed fluoride is incorporated into the hard tissue s primarily by an 

exchange process (the displacement of hydroxyl groups) and by incorporation 

into the apatite lattice during bone mineralization. The amount of fluoride in 

bone is dependent on an individual's age, sex, fluoride intake, and the specific 

type and part of bone being examined. Fluoride accumulates in the bone with 

increasing age, although the rate of incorporation decreases; hi.gher bone 

fluoride concentrations are also found in individuals or groups with greater 

fluoride exposure. Long-term (60 years) intake. of i mg/L fluoride in water can 

cause a fluoride level of 4000 mg/kg of dry f,at-free bone (Drury et al., 1980). 

An intake of 8 mg/L for 35 years would cause a bone fluor'ide level of 6000 

mg/kg, the level necessary for detection of osteosclerosis, which is defined as 

an increased opacity of the bone to X-rays. , Surface regions of bones 

incorporate fluoride more rapidly than interior. r.egions, and cancellous 

(spongy) bone more than cortical (compact) bone. Fluoride can be released 

from bone (when intake decreases), and has a removal half-life of 8 to 10 

4-2 
years (Grandjean, 1982; Drury et al., 1980; Forbes et al., 1978). If fluoride 

intake is decreased following a period of fluoride storage, the urinary fluoride 

level may exceed the current fluoride intake, resulting in a net loss of fluoride 

. from the body (Grandjean; - 1982; `Largent, 1952). Fluoride is incorporated into 

teeth in a similar" manner to its incorporation into bone (World Health 

Organization; 1984), Unlike bone, which can continue to take up fluoride 

throughout an individual's lifetime, teeth incorporate fluoride only during their 

period of calcification (up to about age 12 in humans; Drury et al., 1980). 

Only very smali amounts of fluoride are found in the soft tissues of the 

body (with levels generally highest in the kidneys; Heifetz and Horowitz, 1986, 

Hodge and Smith, 1965), and these levels do not increase with age (World 

Health Organization, 1984; Drury et a1., 1980; see also Knaus et al., 1976). 

Tissue fluoride ooncentrations are approximately in equilibrium with plasma 

fluoride concentrations. Sites of ectopic calcification of soft tissues, such as 

tendons, cartilage, aorta, or placenta, may accumulate fluoride. 

4.3: Excretion 

Approximately half of the absorbed fluoride is excreted in the urine (World 

Health Organizatiori, 1984; Drury et al., 1980); this is the major route of fluoride 

clearance from the blood and from the body. Renal fluoride excretion involves 

glomerular filtration followed by pH-dependent tubular reabsorption. 

Reabsorption occurs by nonionic diffusion of HF (see Whitford et al., 1976); 

and therefore is greater in acidic uri'ne than in alkaline urine (i.e., fluoride 

`removal from the body is greater in alkalosis than in acidosis; see Smith, 

1986b; Whitford et ai., 1979; Reynolds et al., 1978). Urinary fluoride is an 

important indicator of fluoride exposure, and it is routinely used to measure 

occupational fluoride absorption (Jackson and Hammersley, 1981; National 

Institute for Occupational Safety and Health, 1976; 1975). For the general 

population, a good correlation exists between urinary fluoride concentrations 

and fluoride concentrations in drinking water (World Health Organization, 

1984). For one group of'people drinking low-fluoride water (<0.2 mg/L) and 

receiving no occupational exposure to fluor•ide, the average urinary fluoride 

level was found to be 0.61 mg/L (upper limit, 2.00 mg/L; after correction for a 

specific gravity for the urine of 1.024, the average fluoride level was 0.74 mg/L 

and the upper limit was 3.9 mg/L; Massmann, 1981). Urinary fluoride 

concentrations of 9 mg/L or greater (corresponding to occupational exposure 

to more than 2.5 mg/m 3 fluoride in the air or to exposure to 8 mg/L fluoride in 

the drinking water) are associated with a higher incidence of osteosclerosis 

(Smith and Hodge, 1979): Preshift urinary fluoride levels below 5.3 mg/L have 

not been associated with` osteosclerosis in workers, and a preshift level of 4 

mg/L is thought to provide an adequate margin of protection (National Institute 

for Occupational Safety and Health; 1976; Derryberry et al., 1963; Largent, 

1961). Non-occupationally exposed people whose drinking water contains less 

than 4 mg/L fluoride are also considered not to be at risk of developing 

osteosclerosis (National Institute for Occupational Safety- and Health, 1976). 

Urinary excretion of fluoride is decreased in cases of renal failure "or 

disfunction, and retention (i:e:, bone deposition) of fluoride increases 

accordingly (Kono et al., 1984a; 1984b; Gerster et al:; 1983). People with 

renal disfunction are therefore at a higher risk of adverse health effects due to 

fluoride. 

Some fluoride is also excreted in the feces; sweat, saliva, and milk (World 

Health Organization, 1984): Fluoride in the feces is primarily ingested fluoride 

that was not absorbed; arnd' fluori de excreted into the gastrointestinal tract 

4-3 
does not appear to be a major source of fecal fiuoride (Machle and Largent, 

1943). That some fluoride can be excreted into the gastrointestinal tract is 

suggested by the findings of Largent (1961), in which the fecal fluoride content 

of human volunteers increased (2.5- to 6.7-fold, highest value was 0.700 

mg/day) during a period (2 to 4 weeks) of HF inhalation (0.74 to 6.6 mg/m 3), 

average individual exposures between 1.2 and 3.9 mg/m 3 , 6 hours per day). 

No coincident increase in oral fluoride intake (food or water) was noted which 

might have accounted for the observations. Sweat can be an important route 

of fluoride removal in people who are very active or live in hot climates and 

whose water intake is therefore very high, but normally only very small 

amounts of fluoride are found in sweat, saliva, or milk. Fluoride concentrations 

in sweat of 0.3 to 1.8 mg/L were reported in humans ingesting up to 4.0 to, 5.0 

mg fluoride per day; 2 weeks after termination of the experiment (returning to 

normal dietary fluoride intake), the measured fluoride in the subjects' sweat 

was 0.2 to 0.3 mg/L (McClure et al., 1945). Salivary fluoride concentrations are 

proportional to plasma fluoride concentrations, while the fluoride concentration 

in human milk is independent of the plasma fluoride level and therefore of 

maternal fluoride intake (Ekstrand et al., 1981). Observed fluori.de levels in 

human milk are between 2 and 8jig/L, less than those in most milk substitutes. 

4-4 
5. Mutagenicity and Carcinogenicity 

5.1. Mutagenicity ' 

Several 'authors have suggested the potential mutagenicity of either 

hydrog"eh fluoride ~ or sodium fluoride to plants, Drosophila, 'or mammals (see 

for instance Caspary et al., •1987; Cole et al.; 1986; TSutsui et al., 1984a; 

1984b; 1984c; Mohamed, 1977; Voroshilin et al., 1975; 1973; Gerdes,''1971; 

Gerdes et al., 1971; Mohamed and Kemner, 1969). On the other hand, 

Leonard et al. (1977) found no increase Jn chromosome -aberrations in 'the 

leukocytes of caftle with chronic fluoride poisoning, nor did Voroshilin et-al. 

(1973) in human- leukocytes treatedc in vitro with sodium fluoride. Temple and 

Weinstein (1978) -were unable to demonstrate mutagenicity of HF in tdmato 

plarits. Martin et al: (1979) found no 'evidence for increased chromosome 

aberrations in m'rco following - exposure to. sodium fluoride, nor' did they fi'nd 

sodiurn fluoride to be mutagenic in a bacterial (Sa/mone//a) mutagenesis 

assay. A review by the International Agency for Research on Cancer (1982) 

did not find sodium fluoride mutagenic in Salmonella or Drosophila, and both 

the United States Environmental Protection Agency (Federal Register, 1985b) 

and the National Research Council (Safe Drinking Water Committee, 1977) 

conclude that the mutagenicity of fluoride to man has not been demonstrated. 

Tsutsui et al. (1984a; 1984b; 1984c) found evidence for DNA damage in 

cultured human or Syrian hamster cells, including both chromosome 

aberrations and unscheduled DNA synthesis, following treatment with 50 to 

400 mg/L sodium fluoride in the extracellular medium. Cole et al. (1986) 

concluded that at high (and highly toxic) concentrations (up to 500 mg/L), 

sodium fluoride caused a small increase in mutation frequency in cultured 

mouse lymphoma cells, mainly as a result of chromosome breakage; at 10 

mg/L fluoride in the medium there was no significant effect. Caspary et al. 

(1987) demonstrated mutagenic effects in mouse lymphoma cells of both 

sodium fluoride and potassium fluoride, at concentrations in the range of 300 

to 700 mg/L. Tsutsui et al. (1984c) point out that genotoxicity of sodium 

fluoride has been demonstrated in many in vitro studies but in very few in vivo 

studies. The fluoride concentrations used to induce genotoxic effects in these 

experiments (50 to 700 mg/L) are 2,500 to 70,000 times greater than the 

normal blood fluoride range (10 to 20 vg/L in humans; World Health 

Organization, 1984; Drury et al., 1980; Smith and Hodge, 1979). A blood 

fluoride concentration of 80 lig/L (corresponding to a drinking water level of 5.6 

mg/L; Drury et al., 1980; Smith and Hodge, 1979) would still be 600 to 6,000 

times lower than the concentrations shown to cause chromosome damage. 

Martin et al. (1979) studied chromosome aberrations in bone marrow and 

testis cells of mice exposed to sodium fluoride. They found no evidence for an 

increased frequency of chromosome aberrations in mice with a fluoride intake 

of 50 mg/L in the drinking water for several generations or in mice with an 

intake of 100 mg/L for 6 weeks. Oral doses of sodium fluoride (up to 84 mg/kg) 

did not induce DNA-strand breaks in the testicular cells of rats, even when 

plasma fluoride reached (temporary) concentrations of 11 to 12 mg/L at 2 

hours, after dosing (Skare et al., 1986a); testicular fluoride levels did not 

exceed 1 mg/L; suggesting that sodium fluoride does not pose a heritable 

genetic hazard. 

5`1 
Sodium fluoride has been shown to cause a dose-dependent decrease in 

the amount of DNA replication in cultured WI-38 (human) cells (Skare et al., 

1986b). Fluoride ion is known to inhibit many enzymes, and any effects of 

fluoride on DNA or chromosomes are more likely the result of fluoride inhibition of DNA repair or replication enzymes than of interaction of fluoride with 

DNA itself (Co1e et al., 1986; Skare et al., 1986b). 

5.2. Carcinogenicity 

No specific epidemiofogical ~ evidence is available for the evaluation of the 

potential carcinogenicity to humans of hydrogen fluoride or other inhaled 

fluorides. Increased rates of cancer have been reported for workers in several 

occupations involving possible fluoride exposure, including aluminum production, fluorspar mining, and stainless steel pickling (Grandjean et al., 1985; 

World Health Organization, 1984; Ahlborg et al., 1981; de Villiers and Windish, 

1964). However, all these situations involved mixed exposures to several 

chemicals (e.g., radon in fluorspar mining, polycyclic aromatic hydrocarbons in 

aluminum production, and metal compounds and irritating acids in the 

stainless steel picl(ling house), and fluoride could not be specifically implicated 

as the cause of the cancers (Grandjean et al., 1985; World Health 

Organization, 1984; Ahlborg: et al., 1981; Drury et al., 1980; de Villiers and 

Windish, 1964). Correlation has also been demonstrated between cancer rates 

and industrial pollution from steel mills, which emit fluoride among other 

things; again, no specific pollutant could be identified as the major cause of 

the increased cancer rates (Drury et al., 1980). 

The possible carcinogenic potential of fluoride in drinkirig water has been 

investigated by comparing rates of cancer in areas with artificially or naturally 

high fluoride levels in drinking water with the corresponding rates in low 

fluoride areas. The International Agency for Research on Cancer (1982) 

concluded that when "proper account was taken of the differences among 

population units, in demographic composition, and in some cases also in their 

degree of industrialization and other social factors, none of the studies 

provided any evidence that an increased level of fluoride in water. was 

associated with an increase in cancer mortality." The National Research 

Council (Safe Drinking Water Committee, 1977) and the United States 

Environmental Protection Agency (Federal Register, 1985b) also agree that the 

available information does not suggest that fluoride in the drinking water has 

increased the rate of cancer mortality. The United States Envirorimental 

Protection Agency (Federal Register, 1985b) states that "there is not enougfi 

information to conclude that fluoride presents a cancer risk to humans" but 

has not officially classified fluoride or hydrogen fluoride with respect to 

carcinogenicity. 

No animal bioassays have been reported on the potential carcinogenicity 

of inhaled fluorides. The International Agency for Research on Cancer (1982) 

reviewed tests of sodium fluoride administered orally to mice and found the 

data insufficient to permit evaluation. Hydrogen f uoride has been suggested 

as a contributing factor in the production. of lung cancer from cigarette 

smoking (Sutton, 1986), but no specific evidence is available in support of this 

idea. The available evidence .is thought to be inadequate to support or refute a 

carcinogenic potential for inhalation exposure to fluorides. 

5-2 
6. Developmental and Reproductive Toxicity 

Few reports are available concerning women with industrial fluoride 

exposure (Smith and Hodge, 1979; Hodge and Smith, 1977). The one available 

Fepidemiological study of female workers in a superphosphate plant found a 

higher incidence of gynecological problems (e.g., menstrual irregularities, 

vaginal ;and uterine inflammation, toxicosis during pregnancy, untimely discharge of amniotic fluid) in production workers than in the control group of 

office workers and housewives (Smith and Hodge, 1979; Hodge and Smith, 

1977). The production workers were exposed to dust concentrations of 5 to 57 

mg/m3and fluoride concentrations of 0.3 to 2.8 mg/m 3 . The menstrual 

irregularities wer.e correlated with dust concentrations, but specific information 

is not available on possible correlation of gynecological problems with fluoride 

concentrations in the workplace air or in the urine of the workers. No 

difference between groups was found in the numbers of pregnancies, 

miscarriages, or births. No reports of increased incidence of either 

spontaneous abortions or births of abnormal fetuses have- come from 

communities in the United States with natural fluoride levels of 4 mg/L or more 

in the drinking water (Smith and Hodge, 1 -979; Hodge and Smith, 1977). The 

United States Environmental Protection Agency (Federal Register, 1985b) 

concludes that there is inadequate evidence to support an association 

between fluoride in U.S. drinking water and either reproductive or teratogenic 

effects. 

Fluoride is known to cross the placenta and to be deposited in the calcified tissues of the fetus (see Smith et al., 1982; Crissman et al., 1980; 

Maduska et al., 1980; Rioufol et a1., 1980; Krook and Maylin, 1979a; 1979b; 

Smith and Hodge, 1979). Although fetal exposure is proportional to maternal 

exposure, the fluoride level in umbilical cord blood increases more slowly than 

the level in maternal blood; the fetal blood level of fluoride is only about 75 

percent of the level in maternal blood. Largent cities a case report of acute 

fluoride poisoning (ingestion of 50 to 80 g NaF) in a sixteen-year-old girl who 

was in her 6th week (approximately) of pregnancy (Peters, 1948, cited in 

Largent, 1961). She was in serious condition at first, but received adequate 

treatment and recovered within a week; she eventually gave birth to a normal, 

full-term son. Blood fluoride concentrations were not measured at the time of 

the poisoning or at the birth of the child. 

Excess fluoride in the air; water, or food has caused impaired reproduction in Drosophila (Gerdes et al., 1971), mice (Messer et al., 1973), rats (Smith 

and Hodge, 1979; Hodge and Smith, 1977), and cattle (Crissman et al., 1980; 

Krook and Maylin, 1979a; 1979b; Safe Drinking Water Committee, 1977). 

Fluoride doses of 2.5 mg/kg body weight caused cessation of the estrus cycle 

in rats, and intake of 10 and 150-300 mg/kg caused endocrine malfunction in 

guinea pigs and rats, respectively (Smith and Hodge, 1979; Hodge and Smith, 

1977). Too low a fluoride intake also caused decreased reproductive 

performance in mice (Messer et al., 1973), but although the essentiality of' 

fluoride to humans has not been satisfactorily demonstrated, fluoride 

deficiency is not likely to occur in man because of the ubiquity of fluoride in 

C.'1Si 
normal humans diets (Smith, 1986b). Fluoride doses of 1 mg/kg or more have 

caused bone and tooth malformations in dog, rat, and mouse fetuses (Drury et 

al., 1980; Hodge and Smith, 1977), and embryo and fetal toxicity from high 

doses of fluoride (3 to 50 mg/kg/day, dependent on species) have been 

reported in experimental mammals (Smith and Hodge, 1979). If a 50 kg female 

worker were exposed to 2.5 ,mg F/m3 (the maximum permitted under current 

occupational standards), she would inhale an estimated 25 mg fluoride per 

day. If all the inhaled fluoride were actually absorbed (which is not the case), 

she would receive a maximum of 0.5 mg F/kg/day, which is still less than the 

fluoride doses necessary 'to cause toxic effects on reproduction or 

development in experimental animals. Hodge and Smith (1977) estimate that 

the toxic doses in animals are 10 to 200 times greater than the total 

occupational fluoride intake of the 50 kg female worker, and they conclude that 

the occupational standard is adequate to protect the pregnant woman and her 

fetus. Machle and Kitzmiller (1935) reported that a rabbit exposed to 15.2 mg 

HF/m3 (about 6 times the occupational exposure standard) for 309 hours (6-7 

hours per day over about 10 weeks) became pregnant during the exposure 

period and gave birth to 3 apparently normal offspring 13 days after the 

exposure ended. The human data that is available at this time does not 

suggest that HF poses a developmental risk. 

Some reports have suggested an increased risk of Down's syndrome 

associated with fluoridated water (Rapaport, 1963; 1959; 1956; cited in World 

Health Organization, 1984), but the current consensus is that fluoride has no 

influence on the incidence of Down's syndrome (World Health Organization, 

1984; Shepard, 1983; Smith et al., 1982; Drury et al., 1980; Safe Drinking 

Water Committee, 1977; Hodge and Smith, 1965). One study does suggest 

that fluoride has some effect, probably beneficial, on fetal growth in humans 

(see World Health Organization, 1984). 

The major developmental risk to humans from fluoride from any source is 

dental mottling or fluorosis (staining or pitting of the -teeth caused by 

hypomineralization of the enamel; Heifetz and Horowitz, 1986). Fluorosis 

occurs in individuals receiving excess fluoride during the period of tooth 

calcification: prior to birth for the deciduous teeth and up to age 12 for the last 

of the permanent teeth. The discoforation and pifting are the result of a 

disturbance affecting the formation of the enamel; damage occurs before the 

eruption of the teeth (World Health Organization, 1984). Fluorosis can occur in 

the deciduous teeth of a child when the mother's fluoride intake during 

pregnancy is high (Grandjean, 1982; Smith and Hodge, 1979); most fluorosis 

occurs in the permanent teeth and is caused by the child's own high fluoride 

intake. Fluorosis of the deciduous teeth is naturally of lesser concern than 

fluorosis of the permanent teeth. The severity of dental fluorosis increases with 

increased fluoride dose; mild fluorosis occurs at fluoride 9evels of 1.5 to 2 

mg/L in the drinking water (World Health Organization, 1984). 

The United States Environmental Protection Agency (1986) gives a No 

Observed Adverse Effect Level (NOAEL) and Lowest Observed Adverse Effect 

Level (LOAEL) of 1 and 2 mg/L (1 and 2 ppm) fluoride in the drinking water, 

respectively, using dental fluorosis as the endpoint. 'The Agency has 

established a Reference Dose (RfD) for oral exposure to fluoride of 0.06 

mg/kg/day (U.S. Environm,ental Protection Agency, 1986). This level 

corresponds to the fluoride intake expected for a 20-kg child if the water 

fluoride level is 1 mg/L (the NOAEL). Fluoride intake at this level does not 

cause dental fluorosis in the sensitive population (children), nor does it cause 

skeletal fluorosis in adults (United States Environmental Protection Agency, 

1986). The Agency does, however, consider dental fluorosis to be a cosmetic 

6-2 
effect rather than a health effect (Federal Register, 1985b), and permits 

(natural) fluoride levels in the drinking water up to 4 mg/L (4 ppm), a level at 

which fluorosis, but not in its severest form, does occur. 

F 

6-3 

7. Other Toxic Effects 

7.1. Acute Toxicity 

Acute exposure to hydrogen fluoride, fluorine, or other gaseous fluorides 

is rare outside of an occupational sefting, although some solutions cQntaining 

hydrofluoric acid (usually less than 20 percent) are available to the public 

(Jordan, 1982). The toxicity of some gaseous fluorine compounds decreases 

in the following order: F ZO, F2 , FiF, BF3 , and H2SiF6(World Health 

Organization, 1984); these compounds can severely damage the skin and 

respiratory tract of individuals exposed to them. Hydrogen fluoride can be 

detected by smell at concentrations of less than 1 mg/m 3(Amoore and 

Hautala, 1983), and no health effects are observed at 2.6 mg/m 3 , but irritation 

of eyes and respiratory passages is noticed in less than 10 minutes at 26 

mg/m3br at 13.33 mg/m3if exposure is longer than 10 miinutes (Just and 

Emler, 1984; Just, 1984). The Immediately Dangerous to Life or Health (IDLH) 

level is 16.4 mg/m3(20 ppm; Sittig, 1985). [The IDLH level is "the maximum 

level from which one could escape within 30 minutes without any esCapeimpairing symptoms or any irreversible health effects" (Just and Emler, 

1984).] Machle et al. (1934) reported that the highest concentration of HF 

tolerated by human volunteers for more than 1 minute was 100 mg/m3; at this 

level conjunctival and respiratory irritation was marked, the taste af the gas 

pronounced, and definite sman.ing of the skin noted. Irritation and taste were 

noted also at 50 mg/m3 . There was discomfort at 26 mg/m3, but the 

atmosphere could be tolerated for several minutes (Machle et al., 1934). 

Williams (1942) repori.ed irritation and a runny nose (with occasional bloody 

discharge after 20 minutes) at concentrations above 10 mg/m 3 . Fluorine gas 

causes almost immediate nasal and eye irritation at a concentration of 25 to 40 

mg/m3and is intolerable at 40 mg/m3(Just and Emler, 1984); the IDLH level is 

50 mg/m3(25 ppm; Sittig, 1985). Symptoms ot HF and F2inhalation are 

similar and include irritation, coughing, and choking followed eventually by 

symptoms of pulmonary edema (World Health Organization, 1984). Death from' 

hemorrhagic pulmonary edema and destruction of lung tissue may occur 

(Braun et al., 1984; Gosselin et al., 1984; Kleinfeld, 1965; Mayer and Guelich, 

1963). Most available case reports of HF inhalation describe death from 

pulmonary edema or cardiac and respiratory failure, and no information on 

long-term pulmonary damage in patients surviving acute HF inhalation is 

available. In a case of inhalation exposure to mixed hydrofluoric and sulfuric 

acid, described by Braun et al. (1984), the ' surviving patient exhibited no 

obvious pulmonary impairment, but he did continue to have upper respiratory 

tract problems (hoarseness, coughing, pain, npse bleeds) one year after the 

exposure. 

Machle et al. (1934) reported that exposure to 1,000 to 1,500 mg HF/m3 

for 5 minutes produced death in a significant proportion of rabbits and guinea 

pigs. Damage to liver, kidney, and lungs was observed in animals exposed to 

as little as 24.5 mg HF/m3(41 hours total exposure, 6 hours/day, autopsied 18 

hours post-exposure; no deaths occurred in animals with similar exposure 

7-1 
observed for 1 year following exposure; Machle and Kitzmiller, 1935; Machl,e 

et al., 1934). Rosenholtz et al. (1963) reported LC5 0 (lethal concentration for 50 

percent of the exposed population) values for rats of 4,060, 2,200, 1,670, and 

1,070 mg HF/m3 for 5, 15, 30, and 60 minutes, respectively, and for guinea 

pigs of 3,540 mg/m3 for 15 minutes. Inhalation of 25 mg/m3 HF for 166 hours 

total produced 100 percent mortality in rats and mice, but no mortality in 

guinea pigs, rats, or dogs (Hodge and Smith, 1965). No deaths occurred in 

any species at 7.2 mg HF/m3. Exposure to fluorine (F 2) at concentrations as 

low as 315 mg/m3for 3 hours killed all exposed animals (several species) 

within 14 days. At lower concentrations, guinea pigs appeared to be less 

susceptible than rats, mice, aind rabbits. For 170 hours exposure to 25 mg/m 3 

F2, both rats and guinea pigs e><hibited 50 percent mortality (Hodge and 

Smith, 1965; Stokinger, 1949). 

LC50 values for mice and rats (without any aftempt to estimate human 

values) have been reported by Vernot et al. (1977) and MacEwen and Vernot 

(1971). For a 5 minute exposure to HF gas and a 7 day observation period, 

LC50 values of 5,120 mg/m 3(6,247 ppm; 95% confidence limits of 4,789 and 

8,149 ppm) and 14,900 mg/m3(18,200 ppm; 95% confidence limits of 15,965 

and 20,748 ppm) were obtained for mice and rats, respectively (MacEwen and 

Vernot, 1971). For a 60 minute exposure, the LC 50 values for mice and rats, 

respectively, were 374 mg1m3 (456 ppm; 95% confidence limits of 426 and 

489 ppm) and 792 mg/ms (966 ppm; 95% confidence limits of 785 and 1,190 

ppm) (Vernot et al., 1977). MacEwen and Vernot report that, following a 5 

minute exposure to HF, most of the exposed animals experienced pulmonary 

edema of varying severity, and pulmonary hemorrhage was a common finding 

in animals which died during or shortly after exposure to HF concentrations 

above the L050 value. The available LC values for HF inhalation are 

summarized in Table 7-1. 

Contact of HF or hydrofluoric acid with the skin results in deep, severe 

burns (Gosselin et al., 1984; V1/orld Health Organization, 1984; Mackison et al., . 

1981; Stokinger, 1981; Drury et al., 1980; Jordan, 1982; Loriot et al., 1981; 

Greendyke and Hodge, 1964). Fluorine causes thermal burns on the skin (from 

reaction with the skin) rather than the deep necrosis characteristic of HF burns 

(World Health Organization, 1984). Solutions of less than 60 percent 

hydrofluoric acid probably do not pose an inhalation hazard, but skin burns 

can occur even from low concentrations of hydrofluoric acid (Jordan, 1982). 

Burns from solutions of less than 20 percent HF inay not be noticed for up to 

24 hours following skin contact, while solutions greater than 50 percent HF 

cause immediate pain and tissue damage. Death from systemic fluoride 

poisoning may occur from HF absorbed via the lungs or the skin (Gosselin et 

al., 1984; Kono et al., 1982; Tepperman, 1980; Burke et al., 1973). Derelanko 

et al. (1985) found that dilute (2 percent) concentrations of HF - were corrosive 

to rabbit skin following exposures as short as 5 minutes and that significant 

absorption of fluoride occurred through the skin. Serum fluoride levels were 

elevated by 3-fold and 5- to 6-fold following exposure to 2 percent HF for 1 

and 4 hours, respectively, and were still significantly elevated 48 hours postexposure. In rats, systemic fluoride poisoning and death occurred following 

exposure of 1.7 percent of the body surface to 50 percent HF for 5 minutes 

(Kono et al., 1982; inhalation of HF by the test.,animals was prevented). The 

mortality rate was about 80 percent within 24 hours of treatment. In animals 

dying within 4 hours of treatment, serum fluoride .levels varied from about 80 

to 200 times the control level, while serum iortic calcium levels were one-third 

to one-fiftieth of the control level. Tepperman (1980) and Burke et al. (1973) 

7-2 
Table 7-1. =Summary of Lethal Concentration (LC) Estimates for HF Inhalation 

Concentration Type 

LC ' Concentration Tim z Time of 

Level mg/m3 min mg/m3 x min Data Source 

LC50, 5,120. 5a 25,600 mouse ,M4cEwen 

14,900' ' 5a 74,500 rat " and 

Vernot (1971), . . 

LC50 374 60 22,440 mouse . Vernot et al. 

792 60 47,500 rat (1977) 

LCioo 148 ` 360 _ 53,280 rat Morris and 

Smith (1982)' 

LC10 6 105,000 0.5 52;500 estimate 'Just (1984); 

26,000 2 for humanb Just and 

10,500 5 Elmer (1984) 

5;250 10 52,000 estimate ` 

877 60 for humanb 

52,500 estimate 

for humanb, 

52,500 estimate, 

for humanb 

52,620 estimate 

for humanb 

aLC values determined for 5 minute exposure, 7 day observation for mortality. , 

bEstimated directly from animal (rat) data without any adjustment. 

report cases of fatal' or near fatal systemic poisoning' in humans following HF 

burns of only 2.5 percent of the body surface. 

Ingested fluorides (sodium fluoride, for instance) are fethal at a dose of 32' 

to 64 mg fluoride per kg body weight, or about 2.2 to" 4.5 g.'for an adult 

(Heifetz and Horowitz, 1986; Drury et al., 1980). This corresponds to'a, dose of 

5 to 10 g(70 to 140 mg/kg) of NaF (Heifetz and Horowitz, 1986; Gosselin et 

al., 1984; Wor1d Health Organization, 1984; Drury et al., 1980). This is in 

keeping with the findings of Lu et al. (1965) of acute lethal doses of fluoride, 

administered by intravenous infusion at 1 mg/kg/min,"of 26.6, 60.0, and 65:8 

mg/kg for squirrel monkeys.; albino rats, and Rhesus monkeys, 'respectively. 

An acute dose of 8 to 16 mg fluoride per kg body weight can be safely ' 

tolerated by humans (Heifetz and Horowitz, 1986). The toxicity of specific 

fluoride compounds varies primarily with their ease of absorption (Drury 'et al.,' 

1980). Symptoms of acute toxicity following the ingestion 'of fluoride include 

nausea and vomiting; caused by local irritation of the gastrointestinal tract 

(Heifetz and Horowitz, 1986). High doses result in systemic poisoning, with ' 

symptoms including °corivul`sions' and cardiac arrhythmias (Heifetz and 

Horowitz, 1986; , Baltazar (it al., 1980; Abukurah et al., 1972). One report' 

suggests that pulmonary damage due to inhibition of surfactant synthesis may 

also result from systemic fluoride poisoning, even 'if the fluoride was not 

irihaled'(Gaugl and' Wooldridge, 1983). Death from acute fluoride poisoning, 

whether from HF inhalation or burns or from ingestion of fluoride salts; is 

usually from cardiac or respiratory failure and generally occurs within 24 hours 

(Heifetz'and Horowitz, 1986; Stokinger, 1981). 

7-3 
Serum fluoride concentrations of 3 to 15.5 mg/L have been associated 

with fatal cases of fluoride poisoning, both from oral ingestion of fluorides and 

from skin burns or inhalation of HF (Gosselin et al., 1984; Tepperman, 1980; 

Yolken et al., 1976; Hodge and Smith, 1965; Greendyke and Hodge, 1964), 

although one case has been. reported in which the serum fluoride level at 

autopsy was only 67 lig/L (Braun et al., 1984). Most instances of survival of 

fluoride or HF poisoning are associated with serum fluoride levels below 3 

mgiL (Burke et al., 1973), aithough one victim of oral fluoride (Na 2SiF6) 

poisoning survived despite a serum fluoride of 14 mg/L 6 hours after ingestion 

of the poison (Yolken et al., 1976). The major route of clea.rance of excess 

fluoride from the body following poisoning is the urinary system, and urinary 

fluoride levels as high as 87 mg/L (3-1/2 hours after the accident) have been 

reported in survivors (Burke et al., 1973; Yolken et al., 1976). Fluoride 

concentrations are also increased in soft tissues following fatal intoxication. 

Levels of 10.6 mg/kg, 4.6 to 11.6 mg/kg, 4.4 to 11.2 mg/kg, and 12.4 to 15.6 

mg!kg have been reported in heart, kidney, liver, and lung tissue, respectively, 

following fatal intake of sodium fluoride (Hodge and Smith, 1965). 

7.2. Chronic Toxicity 

Chronic exposure to low concentrations (level not spec:ified, but in the 

context of occupational exposure) of hydrofluoric acid vapors may produce 

chronic irritation and congestion of the nose, throat, and bronchi (Evans, 1965; 

cited in Hodge and Smith, 1965). Most other manifestations of chronic fluoride 

toxicity are dependent solely on the intake of fluoride ion, independent of the 

source or route of exposure (e.g., HF vs. NaF, airborne vs. waterborne) (Hodge 

and Smith, 1965). The bones and teeth are the tissues most sensitive to longterm fluoride intake. Dental mottling or fluorosis occurs in humans when 

fluoride intake is high during the years of tooth calcification to age 12, usually 

before age 8; see section 6 for discussion). Mild fluorosis c:an occur with a 

fluoride intake of about 0.1 mg/kg/day (corresponding to a level of 1.5 to 2 

mg/L fluoride in the drinking water); fluorosis (in some cases severe) is 

common when fluoride intake is 0.2 to 0.35 mg/kg/day (>4 mg/L fluoride in 

drinking water; see United States Environmental Protection Agency, 1986; 

Federal Register, 1985a; 1985b; World Health Organization, 1984; Hayes, 

1982). 

Long-term fluoride irrtake of 0.2 to 1.0 mg/kg/day or more can result in 

skeletal fluorosis (Hayes, 1982); this amount corresponds to a level of 4 mg/L 

or greater in the drinking water or an air concentration of 12 to 26 mg/m 3 

(most likely an occupational exposure; Federal Register, 1985a; Hayes, 1982). 

Kaltreider et al. (1972) reported skeletal fluorosis, with no physical impairment, in a majority of potroom workers in an aluminum plant following 

exposure to "high concentrations" (2.4 to 6.0 mg/m 3 , 8-hr TWA; urinary 

fluoride ? 8.7 mg/L) for 10 years. Others workers exposed up to 40 years to 

lower fluoride concentrations (post-shift urinary fluoride <_ 4.6 mg/L, pre-shift 

fluoride <_ 1.6 mg/L) did not show any evidence of skeletal fluorosis. . 

Skeletal fluorosis is defined as an accumulation of fluoride in the skeletal 

tissues associated with pathological bone formation (World Health 

Organization, 1984). The earliest observable effect of fluoride deposition in the 

skeleton is an increased opacity of the bone to X-rays, known as osteosclerosis (Federal Register, 1985a, 1985b; World Health Organization, 1984; 

Hayes, 1982). Osteosclerosis is first noticeable when the fluor - ide level reaches 

5000 to 6000 mg/kg of dry, fat-free bone (World Health Organization, 1984), a 

level which corresponds to an intake of 8 mg/L ,fluoride in the drinking water 

7-4 
for 35 years (Drury et al., 1980). Skeletal fluorosis increases in severity with 

increased fluoride intake, and increased time. Prolonged high fluoride intake 

can cause "crippling fluorosis," which is characterized by pain, stiffness, 

irregular bone growth (e.g., exostoses), and calcification of ligaments and 

tendons. Most cases of crippling fluorosis have occurred in people with a high 

occupational f,luoride:<exposure (20 to 80 mg/day for 10 to 20 years) or in 

populations (not in ahe United States) with drinking water containing 10 to 40 

mg/L fluoride (Federal Register, 1985a; 1985b; World Health Organization, 

1984; Hayes, :1982; Mackison et al., 1981; see also Schmidt, 1983; 

Anonymous, 1981a; White, 1980; Smith and Hodge, 1979; Hodge and Smith, 

1977). The pain and other symptomt of crippling fluorosis occur as a result of 

abnormal bone •growth, which in turn occurs when the normal metabolism and 

remodeling of the bone are disrupted by high levels of fluoride. Deposition of 

fluoride into the bone. apatite lattice does not in itself cause harm, nor does the 

existence of a high fluoride level in the bone. A high bone fluoride level does 

indicate that fluoride exposure is or has been high, and high fluoride levels will 

disrupt bone metabolism and can thereby eventually cause crippling. 

Similar effects on bones and teeth occur in other mammals subjected to 

chronic fluoride poisoning, whether from contamination of forage by fluoride.. 

emissions from nearby factories (Krook and Maylin, 1979a; 1979b; Gruender, 

1972a; 1972b; Oelschlaeger et al., 1972), accidental fluoride contamination of 

feed (Eckerlin et al., 1986a; 1986b; Parsonson et al., 1975; Hard and Atkinson, 

1967a; 1967b; Atkinson and Hard, 1966), or in controlled studies (Grigorenko 

et al., 1986; Hard and Atkinson, 1967b; Shupe et al., 1963). Severe symptoms 

can result from extremely high fluoride intake; dairy caftle are probably the 

most susceptible animals, because of the high calciurri turnover and high feed 

intake associated with lactation (see Eckerlin et al., 1986b). 

Machle and Kitzmiller (1935) reported that no externally obvious adverse 

effects were noted in .aniinals (rabbits, guinea pigs, and Rhesus monkeys) 

exposed to 15.2 mg/m3HF for a total of 309 hours (6 to 7 hours per day over 

about 10 weeks, foliowed for up to 8 more months post-exposure). Two guinea 

pigs sickened and died after 134 and 160 hours exposure. Both of these 

animals showed liver and lung damage (one had pulmonary hemorrhage), and 

one had kidney damage. The surviving animals were normal in behavior and 

appearance but had slower-than-normal growth rates. Some had lower-thannormal erythrocyte counts. These animals upon necropsy exhibited varying 

degrees of lung, liver, and kidney damage (except the Rhesus monkey, which 

had kidney damage only). Stokinger (1949) reported pulmonary damage of 

varying degrees in dogs, rabbits, and rats exposed to 3 to 25 mg/m 3F2for 95 

to 176 hours (total, over 3:to 5 weeks) or to 21.1 mg/m 3HF' (7.2 mg/m3 for 

dogs) for 166 hours (total, over 5 weeks). The dogs also exhibited 

degenerative testicular changes. Deposition of fluoride inosseous tissues 

occurred with either FZor HF exposure. 

Other effects of chronic fluoride exposure in humans have been reported 

occasionally, including pulmonary effects, renal injury, thyroid injury, anemia, 

hypersensitivity, and dermatological reactions (Waldbott, 1981; 1980; 1973; 

1961; 'Waldbott' and Lee, 1978; McLaren, 1976; Hodge, 1960; Spira, 1944, 

cited in Princi, 1960). None of these effects has been convincingly established, particularly for fluoride concentrations'likely to be encountered by the 

general public (Federal Register, 1985b; World Health Organization, 1984; 

Smith and Hodge, 1979; Safe 'Drinking Water Commiftee, 1977; Kaltreider et 

al., 1972; Princi, 1960). The U.S. Environmental Protection Agency (1986) has 

established an oral Reference`Dose (RfD) for fluoride of 0.06 mg/kg/day for 

children, an intake which corresponds to a water fluoride level of 1 mg/L (1 

7-5 
ppm). Neither dental nor skeletal fluorosis occurs at this level. An inhalation 

RfD is not available.. 

7.3. Biochemical Effects 

Fluoride toxicity involves at least four major effects (Gosselin et al., 1984): 

(1) inhibition of enzymes controlling glycolysis or other vital path ways, (2) 

hypocalcemia resulting from binding or precipitation of calcium by fluoride, (3) 

cardiovascular collapse caused by hypotension and circulatory shock, and (4) 

damage to specific organs, primarily the brain and the kidneys. 

Fluoride inhibits a number of enzymes, in some cases by complexing with 

a metal (e.g., Ca2 ` or Mg2 ') associated with the enzyme, in other cases by a 

direct action of fluoride (as F-or as undissociated HF) on the enzyme itself 

(Anonymous, 1985; World Health Organization, 1984; Edwards et al., 1984). 

Inhibition of many enzymes will occur at high serum fluoride concentrations, at 

least 300 t,g/L (World Health Organization, 1984). Serum fluoride concentrations this high generally occur only with acute high fluoride intake (normal 

serum fluoride values are much less than 100 g/L, dependerit on the fluoride 

content of the drinking water). Among the results of enzyme inhibition by 

fluoride are hyperkalemia (incYeased potassium levels) and metabolic acidosis 

(Gosselin et al., 1984; World Health Organization, 1984). Fluoride at lower 

concentrations (about 180 pg/L in serum, still much higher than normal) can 

activate some other enzymes, most notably adenyl cyclase (World Health 

Organization, 1984). Fluoride has been shown to affect the metabolism of 

glucose, lipids and cholesterol, and collagen in mammals, as well as the 

formation of bones and teeth, and many of these metaboltc effects are 

probably due to the effects of fluoride on the enzymes involved (see for 

instance Den Besten, 1986; Aitbaev, 1984; Dousset et al., 1984a; 1984b; 

Drozdz et al., 1984; 1981; Watanabe et al., 1975; serum fluoride levels when 

reported were at least 50 tag/L). 

Hypocalcemia in cases of acute fluoride poisoning will often result in 

tetany--severe involuntary muscle contractions (Gosselin et al., 1984). Many of 

the other toxic effects of flu'oride (including cardiac arrhythmias and other 

effects often associated with acute systemic fluoride poisoning) are thought to 

be caused by hypocalcemia (Heifetz and Horowitz, 1986; Kono et al., 1982; 

Tepperman, 1980; Abkurah et al., 1972), although the evidence for that is not 

entirely clear (Gosselin et al., 1984). Most methods of treatment of HF burns 

or NaF poisoning include immediate replacement of calcium and often also of 

magnesium (see for instance Bracken et al., 1985; Gosselin et al., 1984; 

Trevino et al., 1983; Browne, 1982; Carney et al., 1974; Abkurah et al., 19.72; 

Klauder et al., 1955). 

Cardiovascular collapse ,is one of the two most common immediate 

causes of death in cases of acute fluoride poisoning (Gosselin et al., 1984). 

The hypotension and circulatory shock which are involved result from a 

combination of factors such as fluid and electrolyte losses (due to vomiting 

and diarrhea or intragastric bleeding) and central vasomotor depression. Brain 

damage from acute fluoride poisoning can cause such symptoms as 

convulsions, although more commonly lethargy, stupor, and coma are the 

result. Respiratory failure (the other leading cause of death in fluoride 

poisoning) is thought to be of central nervous system origin (Gosselin et al., 

1984). Renal injury, including trarisient diabetes insipidus, may also result from 

acute fluoride poisoning (it is probably not a major concern in cases of chronic 

fluoride exposure), although renal failure does not appear to be a cause of 

death (Gosselin et al., 1984). More severe nephrotoxicity, also 

NEI 
including d+abetes insipidus, may occur from exposure to fluorine-containing 

anesthetic agents such as methoxyflurane or enflurane (World Health 

Organization, 1984). 

7-7 

8. Beneficial Effects 

It is generally accepted that fluoride as fiuoride ion has a significant 

cariostatic (cavity-inhibiting) effect (American Academy of Pediatrics, 1986; 

World Health Organization, 1984; Drury et al., 1980), particularly for individuals who receive it during the years of tooth mineralization (prior to age 6). 

Fluoride acts systemically in the formation of teeth by being built into the 

crystal structure of the enamel, making it harder and more resistant to decay; 

it acts topicaily on erupted teeth by promoting remineralization (American 

Academy of Pediatrics, 1986). The acids produced by various oral bacteria 

contribute to tooth decay by dissolving enamel; fluoride on the tooth surface 

has a bacteriostatic effect, resulting in a decrease in acid production and 

ultimately a decrease in tooth decay (Drury et al., 1980). 

The most effective way to administer fluoride to the population is via the 

water suppiy, and a number of communities throughout the world now have 

artificially fluoridated municipal water supplies. The typical fluoride level for an 

artificially fluoridated water source in a temperate climate is 1 mg/L (1 ppm; 

Safe Drinking Water Committee, 1977); the recommended fluoride level 

changes with the average temperature of a region, due to differences in 

expected water consumption (Hayes, 1982). Other means of fluoride delivery 

include fluoride-containing tablets, drops, toothpastes, and mouthwa.shes 

(American Academy of Pediatrics, 1986). A few reports suggest that at least 

some of the decline in tooth decay attributed to fluoridated water may in fact 

be due to other causes, such as changes in immune status, changes in dietary 

patterns, and use of topical fluorides (Diesendorf, 1986; Smith, 1986a; 1986c). 

The increased bone density found in individuals with a high long-term 

fiuoride . intake suggests a possible use for fluoride in the prevention or 

treatment of such diseases as osteoporosis, characterized by an accelerated 

decrease in bone mass and strength (Smith, 1986b; World Health 

Organization, 1984). Some evidence exists that people living in an area with a 

high natural level of fluoride in the water (4 to 8 mg/L) have a lower incidence 

of osteoporosis (World Health Organization, 1984). Medical use of high 

fluoride doses (50 + mg/day, usually given with calcium and vitamin D 

supplements; Drury et al., 1980) is still under investigation (see Dambacher et 

al., 1986; Frey, 1986; Smith, 1986b; World Health Organization, 1984; Drury et 

al., 1980). In at least some cases, bone density seems to be increased without 

a concommitant increase in bone strength--bone formation is stimulated by 

fluoride, and fluoride is incorporated into the bone structure, but the overall 

bone structre is not entirely normal and is not necessarily stronger (Frey, 

1986; Smith, 1986b; see also Dambacher et al., 1986; Snow and Anderson, 

1986). Some side effects such as gastrointestinal bleeding (Frey, 1986) or 

osteoarticular side effects (Dambacher et al., 1986) can occur from treatment 

with large amounts of fluoride, and severe fluorosis can result if a patient with 

renal insufficiency is given fluoride for treatment of osteoporosis (Gerster et 

al., 1983). 

Some epidemiological studies have suggested a correlation between 

increased fluoride levels in drinking water (the high level in one study was 2.57 

:ID 
mg/L) and a decrease in mortality due to heart disease (World Health 

Organization, 1984; Luoma et al., 1973). The details of the relationship 

between fluoride and cardiovascular disease remain to be worked out, 

although one possibility is that fluoride may reduce soft tissue calcification 

such as atherosclerosis. 

The beneficial effects and the adverse effects of fluoride must be weighed 

in determining the optimal fluoride level in drinking water supplies. The most 

effective level for the prevehtion of caries seems to be about 1.0 to 1.2 mg/L; 

higher amounts (at least 4 to 5 mg/L) may be necessary for the prevention of 

osteoporosis. Some cases of milO dental fluorosis are found when the water 

contains 1 to 2 mg/L fluoride; fluorosis is common and occasionally severe at 

4 mg/L.- Although dental fluorosis is treated as a cosmetic effect and not a 

health effect, some people do consider it objectionable (Federal Register, 

1985b). 

Fluoride is usually added to water in the form of sodium fluoride (NaF), 

sodium fluosilicate (Na 2SiF6 ), fluosilicic acid (H 2 SiF6), or ammonium 

fluosilicate [(NH4 )2SiF6 ] (Safe Drinking Water Committee, 1977). Sodium 

fluoride, stannous fluoride (SnF2 ), acidulated phosphate fluoride, and 

monofluorophosphate are the fluorides most commonly added to dentifrices 

and mouthwashes (Heifetz and Horowitz, 1986). Sodium fluoride is also the 

main fluoride used in treatriment of osteoporosis (Frey, 1986; Smith, 1986b), 

although at least one fluorine-containing organic compound, niflumic acid (2- 

[3-(trifluoromethyl)anilino]nicotinic acid), has been suggested as a possible 

drug for this use (Meunier et al., 1980). Hydrogen fluoride is not used in these 

capacities, although it is important as an intermediate in the production of 

some of these other fluoride compounds. 

8-2 
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