4
Hydrogen Fluoride

This chapter summarizes the relevant epidemiologic and toxicologic studies of hydrogen fluoride. It presents selected chemical and physical properties, toxicokinetic and mechanistic data, and inhalation-exposure levels from the National Research Council and other agencies. The committee considered all that information in its evaluation of the U.S. Navy’s 1-h, 24-h, and 90-day exposure guidance levels for hydrogen fluoride. The committee’s recommendations for hydrogen fluoride exposure levels are provided at the end of this chapter with a discussion of the adequacy of the data for defining the levels and the research needed to fill the remaining data gaps.

PHYSICAL AND CHEMICAL PROPERTIES

Hydrogen fluoride is a corrosive, colorless gas that may fume in air (Budavari et al. 1989). Odor thresholds have been reported to range from 0.04 to 3 ppm (HSDB 2008). Like hydrogen chloride, hydrogen fluoride is highly soluble in water. Hydrofluoric acid is the term used to describe aqueous solutions of hydrogen fluoride. Selected physical and chemical properties are shown in Table 4-1.

OCCURRENCE AND USE

Hydrogen fluoride is used primarily to produce aluminum fluoride, synthetic cryolite, fluoropolymers, and chlorofluorocarbons (Lindahl and Mahmood 2005). It is also used in inorganic fluoride production, uranium enrichment, and fluorine production. Fluoride is found in some foods and beverages, particularly fish, seafood, gelatin, and tea; and many public water sources are fluoridated



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4 Hydrogen Fluoride This chapter summarizes the relevant epidemiologic and toxicologic stud- ies of hydrogen fluoride. It presents selected chemical and physical properties, toxicokinetic and mechanistic data, and inhalation-exposure levels from the Na- tional Research Council and other agencies. The committee considered all that information in its evaluation of the U.S. Navy’s 1-h, 24-h, and 90-day exposure guidance levels for hydrogen fluoride. The committee’s recommendations for hydrogen fluoride exposure levels are provided at the end of this chapter with a discussion of the adequacy of the data for defining the levels and the research needed to fill the remaining data gaps. PHYSICAL AND CHEMICAL PROPERTIES Hydrogen fluoride is a corrosive, colorless gas that may fume in air (Budavari et al. 1989). Odor thresholds have been reported to range from 0.04 to 3 ppm (HSDB 2008). Like hydrogen chloride, hydrogen fluoride is highly solu- ble in water. Hydrofluoric acid is the term used to describe aqueous solutions of hydrogen fluoride. Selected physical and chemical properties are shown in Table 4-1. OCCURRENCE AND USE Hydrogen fluoride is used primarily to produce aluminum fluoride, syn- thetic cryolite, fluoropolymers, and chlorofluorocarbons (Lindahl and Mahmood 2005). It is also used in inorganic fluoride production, uranium enrichment, and fluorine production. Fluoride is found in some foods and beverages, particularly fish, seafood, gelatin, and tea; and many public water sources are fluoridated 70

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71 Hydrogen Fluoride TABLE 4-1 Physical and Chemical Properties of Hydrogen Fluoride Synonyms Anhydrous hydrofluoric acid CAS registry number 7664-39-3 Molecular formula HF Molecular weight 20.01 Boiling point 19.51°C Melting point –83.55°C Flash point NA Explosive limits NA Specific gravity 1.002 at 0°C/4°C Vapor pressure 917 mmHg at 25°C Solubility Very soluble in water and alcohol; slightly soluble in ether; soluble in many organic solvents 1 ppm = 0.82 mg/m3; 1 mg/m3 = 1.22 ppm Conversion factors Abbreviation: NA, not available or not applicable. Sources: Budavari et al. (1989) and HSDB (2008). (ATSDR 2003). Ambient air concentrations of hydrogen fluoride are typically below the detection limit, although concentrations may be higher near industrial facilities that use or produce hydrogen fluoride (ATSDR 2003). Hydrogen fluoride has been measured on board submarines. NRC (1988) listed hydrogen fluoride as a potential contaminant of submarine air and re- ported a concentration of 0.3 ppm. No information was provided on sampling protocol, location, operations, or duration. Trials conducted on three nuclear- powered attack submarines did not detect hydrogen fluoride; the level of detec- tion was about 3 ppb (Hagar 2008). Whether the reported results are representa- tive of the submarine fleet is not known; few details were provided about the conditions on the submarines when the samples were taken. No other exposure data were located. Hydrogen fluoride emissions aboard submarines are thought to arise from decomposition of halogenated hydrocarbons and refrigerants (Hagar 2008). SUMMARY OF TOXICITY Hydrogen fluoride and its aqueous solutions present an acute hazard by inhalation or dermal exposure. The primary target of airborne gaseous hydrogen fluoride is the respiratory tract; however, injury to distant organs may also occur because of absorption of substantial amounts of fluoride. Acute effects of hydro- fluoric acid include damage to skin and lungs, including severe burns, and sys-

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72 Exposure Guidance Levels for Selected Submarine Contaminants temic effects, such as cardiac arrhythmias and acute renal failure (see, for exam- ple, Sanz-Gallén et al. 2001; Björnhagen et al. 2003; Horton et al. 2004; Hol- stege et al. 2005; Mitsui et al. 2007; Vohra et al. 2008). Some of the systemic effects may be due to depletion of calcium and magnesium or hyperkalemia. The critical effects of inhalation exposure to hydrogen fluoride are respira- tory tract irritation and the induction of respiratory disease. Respiratory tract irritation is documented in animal models and has been observed in controlled human exposure studies. Marked sensory irritation can occur at exposures greater than 3 ppm for 1 h (Lund et al. 1997). Prolonged respiratory tract effects can occur after short-term exposure. To evaluate longer-term exposures or sys- temic effects, the total fluoride intake from all exposure routes (inhalation, der- mal, and ingestion) must be considered (EPA 1988; NRC 2006). Chronic expo- sure to hydrogen fluoride (with particulate fluorides) in the aluminum industry is associated with increased risk of asthma (Taiwo et al. 2006). The literature on the systemic toxicity of fluoride is voluminous and is not addressed in full detail here. NRC (2006) recently reviewed fluoride toxicity with an emphasis on chronic toxicity. Fluoride-induced effects include hormonal disturbances; renal damage; reproductive toxicity; skeletal changes, including fluorosis; and possible genotoxicity and cancer. Effects in Humans Accidental Exposures Several case reports of death after acute accidental exposure to hydrogen fluoride are available and have been extensively reviewed by ATSDR (2003) and NRC (2004). Most of the reports stem from accidents involving spills of hydrofluoric acid. Because of its high volatility, inhalation exposure to hydrogen fluoride results from spills of hydrofluoric acid. The degree to which hydroflu- oric acid-induced burns or dermal absorption of fluoride may have contributed to the death is not known. Nonetheless, the case reports indicate that lung injury, including pulmonary edema (with or without hemorrhage), is common after such accidents. An informative case report describes the delayed and prolonged chemical pneumonitis that developed in a woman after use of large amounts of 8% hydro- fluoric acid as a cleaner in an unventilated bathroom (Bennion and Franzblau 1997). Airborne hydrogen fluoride concentrations were unknown. Symptoms developed slowly in the days after the exposure and eventually necessitated oxygen therapy (100% O2; 10 cm H2O peak end-expiratory pressure) because of hypoxemia. Chest radiography indicated a lung infiltrate, and signs included diffuse rhonchi and wheezing in both lungs. Another case report describes a woman who used 8-9% hydrofluoric acid as a cleaner in a ventilated bathroom (Franzblau and Sahakian 2003). It was estimated that hydrogen fluoride in the bathroom may have exceeded 170 ppm.

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73 Hydrogen Fluoride She developed breathing problems, such as persistent wheezing and difficulty taking a deep breath, over the 1-2 months after exposure. Examination at that time revealed a mild obstructive pattern. Several months after the exposure, she was diagnosed with reactive airways dysfunction syndrome (RADS); her inter- mittent wheezing on exertion persisted for at least 3 years. An industrial accident in Texas in 1987 resulted in the release of 24,000 kg of hydrogen fluoride and about 3,000 kg of isobutane over a small commu- nity (population, 41,000; Wing et al. 1991). The airborne hydrogen fluoride concentration 1 h after the accident was reported to be 10 ppm; 2 h after the ac- cident, concentrations were “minimal.” The report indicates that air sampling was performed at those times but provides no information on the analytic meth- ods used to determine hydrogen fluoride concentrations. A total of 939 people sought emergency care; common symptoms were eye irritation, throat irritation (burning), headache, and shortness of breath. Of those who sought care, 94 were hospitalized. Forced expiratory volume in 1 s (FEV1) was less than 80% of pre- dicted in one-third of the people who sought medical care and were not hospital- ized compared with half the people who were hospitalized. A follow-up study revealed that respiratory symptoms persisted in some people for at least 2 years, although much reduced (Dayal et al. 1992). The degree to which psychologic factors influenced the symptoms is unknown, but it is thought that the symptoms could not be explained entirely on the basis of psychologic stress (Dayal et al. 1994). In summary, respiratory tract injury appears to be the predominant re- sponse to accidental exposure to hydrogen fluoride. Respiratory tract effects include irritation, airway obstruction (as assessed with FEV1), and airway in- flammation. Upper airway symptoms may have occurred in some situations and gone unreported because they were overshadowed by the lower airway effects. There are suggestions that long-term respiratory tract effects may occur after exposure to hydrogen fluoride at high concentrations as indicated by the devel- opment of RADS in one subject and the presence of persistent respiratory symp- toms in the general population after the release of hydrogen fluoride during an industrial accident. The studies indicate that the respiratory tract may be a criti- cal target of hydrogen fluoride in the general population but do not provide in- formation on concentration-response relationships. Fluoride ion is rapidly and efficiently absorbed into the circulation after inhalation of hydrogen fluoride or airborne fluorides as indicated by increased blood or urinary fluoride concentrations (see, for example, Collings et al. 1951, 1952; Largent et al. 1951). Therefore, the possibility of systemic fluoride- induced injury after accidental exposure to hydrogen fluoride is important to consider. Little information is available on systemic effects after accidental in- halation exposure to fluoride, but accidental ingestion has been followed by itch- ing, rash, gastrointestinal symptoms, and numbing or tingling of extremities or the face (reviewed by NRC 2006).

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74 Exposure Guidance Levels for Selected Submarine Contaminants Experimental Studies Upper Airway Irritation There are several published controlled studies of short-term inhalation ex- posure to hydrogen fluoride in humans (Table 4-2). The exposure durations in the studies spanned from 1 min to 6 h/day for multiple days. All studies report upper airway irritation as the predominant symptom. The degree of upper airway irritation was reported as intolerable at 122 ppm for more than 1 min, marked at 61 ppm for several minutes, and mild at 32 ppm for several minutes (Machle et al. 1934). Lund et al. (1997) described a 1-h exposure with exercise at low concen- tration (0.2-0.7 ppm), intermediate concentration (0.9-2.9 ppm), and high con- centration (3.1-6.3 ppm). Exercise consisted of a fixed workload of 75 W on a bicycle ergometer for the last 15 min of exposure. There were no air-exposed control subjects, but baseline reporting of symptoms was conducted for all sub- jects before exposure. Subjects were men, 21-44 years old; persons with asthma or recent respiratory tract infection were excluded from the study, but the study group did include people with “hay fever.” Symptoms, including upper airway (nose or throat) itching and soreness, were reported during exposure on a scale of 0-5 (1 was very mild, and 5 was severe). More detail was not provided on the scaling; the authors report ratings of 1-3 as representing a “low” degree of irrita- tion and greater than 3 as representing a “high” degree of irritation. It seems reasonable to assume that low corresponds to mild irritation and high corre- sponds to moderate to marked irritation. In the low-concentration group, four of nine subjects reported mild upper airway irritation. In the intermediate- concentration group, six of seven reported mild irritation. In the high- concentration group, three of seven reported moderate to severe irritation, and the other four reported mild irritation. Thus, a clear concentration-response rela- tionship was observed in the study. Only mild irritation was reported at concen- trations as high as 2.9 ppm, whereas marked irritation was reported in some sub- jects at concentrations as low as 3.1 ppm. Thus, 3 ppm appears to reflect the demarcation between minimal and marked irritation, at least as determined by the small number of subjects in this study. In a later study with high concentra- tion (4.0-4.8 ppm), six of 10 subjects reported mild irritation, and one of 10 re- ported marked irritation (Lund et al. 2002)—essentially the same response pat- tern observed in their earlier study (Lund et al. 1997). There were no air- exposed control subjects, but baseline reporting of symptoms was conducted for all subjects before exposure. Largent (1961) performed a study with multiple 6-h exposures to hydro- gen fluoride 5 days/week for a total of 10-50 exposures. Again, upper airway irritation was experienced. One subject exposed at 1.4 ppm reported no symp- toms, and all five subjects exposed at 2.6-4.7 ppm reported the perception of

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TABLE 4-2 Effects of Hydrogen Fluoride in Controlled Human Studies Concentration (ppm) Duration Subjects and Effects Reference 32, 61,122 1 to several min Two healthy subjects, smoking status unknown Machle et al. Maximum tolerable level (1 min) at 122 ppm; marked conjunctival, nasal, and large 1934 airway irritation at 61 ppm (several minutes); mild conjunctival, nasal, and large airway irritation at 32 ppm (several minutes); sour taste detected at all concentrations 1.4, 2.6-4.7 6 h/day Five healthy subject, smoking status unknown Largent 1961 5 days/week No reported airway irritation in one subject exposed at average of 1.4 ppm; slight 10-50 days cutaneous (facial), ocular, and nasal irritation in all subjects at average concentration of 2.6-4.7 ppm daily for a total of 10-50 days; cutaneous erythema frequent (requiring face-cream application); increased symptoms in one subject who developed an upper respiratory tract infection during the protocol 0.2-6.3 1 h (with Twenty healthy, nonsmoking men (21-44 years old); persons with airway infection Lund et al. exercise) or history of asthma excluded; three exposure groups (low, 0.2-0.7 ppm; middle, 1997 0.9-2.9 ppm; high, 3.1-6.3 ppm); symptom scores reported as “low,” presumably mild (1-3 on scale of 0-5), and “high,” presumably moderate to marked (>3 on scale of 0-5). Mild upper airway irritation was reported in four of nine subjects in low- concentration group, six of seven in middle concentration group, four of seven in high-concentration group; moderate to severe upper airway irritation reported in three of seven in high-concentration group; mild lower airway irritation reported in two of seven and moderate to severe irritation in one of seven in high-concentration group; eye irritation (mild) reported in two subjects in each concentration group (Continued) 75

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76 TABLE 4-2 Continued Concentration (ppm) Duration Subjects and Effects Reference 0.2-6.3 1 h (with Nineteen healthy, nonsmoking men (21-44 years old); persons with airway Lund et al. exercise) infection or history of asthma excluded; three exposure groups (low, 0.2-0.7 ppm; 1999 middle, 0.9-2.9 ppm; high, 3.1-6.3 ppm). Publication presumably provides BAL results in subjects described in Lund et al. (1997); BAL performed 24 h after exposure; percentage of lymphocytes increased in both bronchial and bronchoalveolar portions of BAL with no apparent concentration-response relationship; increases appeared to be present in middle- and high-concentration groups; no observed changes in any other cell type; myeloperoxidase increased in bronchial portion of BAL with no apparent concentration-response relationship 4.0-4.8 1 h (with Ten healthy, nonsmoking men (21-44 years old); persons with airway infection or Lund et al. exercise) history of asthma excluded; all exposed at 4.0-4.8 ppm for 1 h with exercise; nasal 2002 irritation symptoms reported as “low,” presumably mild (1-3 on scale of 0-5), and “high,” presumably moderate to marked (>3 on a scale of 0-5). Mild irritation reported by six of 10 and marked irritation by one of 10 subjects; nasal lavage performed immediately and 90 min after exposure; lavage neutrophil count and lavage proteins (TNF-α, PGE2, LTB4, peptide LT) significantly increased; symptom score and lavage neutrophil counts correlated with each other 4.0-4.8 1 h (with Ten healthy, nonsmoking men (21-44 years old); persons with airway infection or Lund et al. exercise) history of asthma excluded; all exposed at 4.0-4.8 ppm for 1 h with exercise; nasal 2005 symptomology not measured; BAL performed 2 h after exposure No increase observed in differential cell count or in numerous mediators (interleukins, myeloperoxidase, eicosanoids, others); several significantly decreased. Abbreviations: BAL, bronchoalveolar lavage; LTB4, leukotriene B4; PGE2, prostaglandin E2; TNF-α, tumor-necrosis factor-alpha; peptide LT, peptide leukotriene.

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77 Hydrogen Fluoride slight irritation. One subject developed an “upper airway cold” during the proto- col, at which time exposure at 3.4 ppm produced “considerable discomfort.” All subjects completed the multiple-exposure regimen—an indication that the de- gree of irritation was not sufficient to cause withdrawal from the study. Al- though a quantitative scaling of symptoms was not reported, comparison of the data with the symptoms reported in the studies of Lund et al. (1997, 2002) sug- gests that repeated exposure to hydrogen fluoride does not result in exacerbation of the irritation response and may actually lead to some degree of habituation. In summary, symptoms of upper airway irritation were uniformly reported in clinical studies. The threshold for mild irritation may be 0.5 ppm or less in some people. Given that the studies used small numbers of subjects, the database suggests that a significant fraction of subjects experience moderate to marked irritation at concentrations over 3 ppm but only mild irritation at lower concen- trations. Lower Airway Irritation Lower airway irritation has been reported in human subjects exposed to hydrogen fluoride but is generally of less magnitude than upper airway irritation. In the intermediate-concentration group (0.9-2.9 ppm) of the study of Lund et al. (1997), one of seven subjects reported mild lower airway irritation (chest tight- ness and soreness, coughing, expectoration, or wheezing) during the 1-h expo- sure (compared with six of seven reporting mild upper airway irritation). In the high-concentration group (3.1-6.3 ppm), two of seven reported mild lower air- way symptoms, and one of seven reported moderate to marked lower airway symptoms compared with three of seven reporting upper airway symptoms of this degree. A concentration-response relationship may be apparent, but the changes in the lower airway symptoms did not achieve statistical significance, and this led the study authors to conclude that lower airway symptoms were not reported to a significant degree in relation to exposure to hydrogen fluoride. The study design included forced expiration to assess lower airway physiologic changes. No consistent change was observed in forced vital capacity (FVC) or FEV1. Thus, mild symptoms of lower airway irritation occur at exposures as high as 2.9 ppm, and more marked symptoms may occur in some people ex- posed at higher concentrations, but such changes occurred in the absence of al- terations in airway function as assessed by forced expiration. Airway Inflammation Hydrogen fluoride exposure for 1 h results in airway inflammation as as- sessed by increases in inflammatory cells in nasal lavage or bronchoalveolar lavage (BAL) fluid. Exposure at 4.4 ppm for 1 h (range, 4.0-4.8) results in a significant increase in nasal lavage neutrophils and proinflammatory mediators,

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78 Exposure Guidance Levels for Selected Submarine Contaminants including tumor-necrosis factor-alpha, prostaglandin E2, and leukotriene B4 (Lund et al. 2002). Although hydrogen fluoride clearly induced upper airway inflammation, the exposure was not debilitating, nor would any long-term ef- fects be expected to result from a response of this nature. Exposure to hydrogen fluoride for 1 h also results in inflammatory cell changes in the lower airways as assessed by BAL (Lund et al. 1999). A significant correlation between increases in BAL lymphocyte numbers (but not neutrophil or eosinophil numbers) and increased exposure concentrations was observed 24 h after exposure (Lund et al. 1999, which involved the same subjects described in Lund et al. 1997). It is dif- ficult to discern precisely the concentration-response relationships from the data presented, but apparently no alteration occurred in the low-concentration (0.2- 0.7 ppm) group; increases in BAL lymphocyte number occurred only in the in- termediate (0.9-2.9 ppm) and high (3.1-6.3 ppm) groups. The changes were ob- served 24 h but not 2 h after the 1-h exposure (Lund et al. 1999, 2005). Al- though lavage neutrophil numbers were not significantly increased, a slight increase in the myeloperoxidase content in the bronchial portion of the BAL fluid was observed; this suggests that subtle recruitment or activation of neutro- phils occurred. The absence of an overt increase in neutrophils or overt symp- toms suggests that the responses would not result in short-term or long-term health impairment. Other Irritation Effects Cutaneous irritation and ocular irritation have been reported in subjects exposed to hydrogen fluoride. In the study of Machle et al. (1934), two subjects exposed to hydrogen fluoride at 32 ppm or higher for several minutes reported cutaneous, ocular, and respiratory tract irritation. Ocular irritation was reported during 1-h exposures in the study of Lund et al. (1997), but the degree of ocular irritation was less than that of upper airway irritation. Largent (1961) used mul- tiple 6-h exposures and found that cutaneous irritation was experienced at 2.6- 4.7 ppm. Subjects applied cream to alleviate symptoms. Cutaneous erythema was common in the five subjects although reported to be without discomfort. One subject experienced peeling of the skin in the third week of exposure. It should be noted that the sour, pungent taste of hydrogen fluoride can be detected during exposure at above 3 ppm. Amoore and Hautala (1983) reported the odor threshold at below 1 ppm. Systemic Effects Exposure to hydrogen fluoride or other airborne fluorides may result in absorption of fluoride ion (see, for example, Collings et al. 1951, 1952; Largent et al. 1951; Waldbott and Lee 1978); thus, the potential for fluoride-induced systemic effects should be considered. For example, given a ventilation rate of

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79 Hydrogen Fluoride 15 m3/day (EPA 1997) for a 70-kg man and 100% deposition and absorption, a 1-h exposure to hydrogen fluoride at 3 ppm results in systemic absorption of 1.5 mg of fluoride (0.02 mg/kg).1 Few experimental studies involving human expo- sure to hydrogen fluoride or inhaled fluorides are available; experimental studies and case reports involving ingestion of fluoride have reported antithyroid effects (0.03-0.14 mg/kg-day for 20-245 days; Galletti and Joyet 1958) and hypersensi- tivity or reduced tolerance to fluoride (0.02 mg/kg-day for short-term exposures; Grimbergen 1974; Waldbott 1956, 1958). One study reported a threshold of hydrogen fluoride for the light-adaptive reflex2 of 0.04 ppm (Sadilova et al. 1965) in three subjects exposed to hydrogen fluoride at 0.02, 0.04, or 0.07 ppm (exposure duration not available), but it is difficult to evaluate the underlying experimental work (Smith and Hodge 1979), and the toxicologic relevance of the response is unknown (ATSDR 2003). The absorbed doses at those exposures are likely to be so low that it is difficult to attribute the neurologic effect to absorbed fluoride itself. Occupational and Epidemiologic Studies A variety of occupational and epidemiologic studies of airborne and in- gested fluoride have been conducted; many of them have been reviewed by NRC (2006) and ATSDR (2003). The following paragraphs discuss respiratory symptoms (asthma), renal damage, endocrine effects, increased risk of bone fracture, and bone and joint pain (skeletal fluorosis). In the workplace, exposure to hydrogen fluoride rarely occurs in the absence of exposure to other particu- lates (such as calcium fluoride [CaF2] or sodium aluminum fluoride [Na3AlF6]) or gaseous fluoride-containing materials (such as tetrafluorosilane [SiF4]); this confounds interpretation of the results with respect to the effects of hydrogen fluoride. That is particularly true of possible effects of systemic fluoride absorp- tion because the source of the fluoride is not known with certainty. Many studies of worker health in the aluminum industry have found an as- sociation between occupational exposure to fluoride in aluminum “potrooms” and respiratory disease or asthma (see, for example, Kaltreider et al. 1972; Soy- seth and Kongerud 1992; Kongerud et al. 1994). Most studies, however, did not reveal potential etiologic agents. In aluminum potrooms, workers are exposed to particulate fluoride, gaseous fluoride (presumably hydrogen fluoride), sulfur dioxide, and other irritants. A recent study of the health of workers in the alumi- num industry suggests that exposure to airborne fluorides is associated with an increased incidence of asthma (Taiwo et al. 2006). Analysis of records on 1 The calculation is as follows: (15 m3/day)(1 day/24 h)(3 ppm)(0.82 mg/m3 per ppm)(19/20 mg fluoride per mg hydrogen fluoride) = 1.5 mg of fluoride for 1-h exposure, assuming 100% absorption. 2 The light-adaptive reflex is defined as reflex changes in ocular sensitivity to light based on dark adaptation. It is measured as a marker of neurologic effects.

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80 Exposure Guidance Levels for Selected Submarine Contaminants 12,000 workers (about 10% of whom worked in potrooms) found an increased risk of asthma in workers exposed to gaseous fluoride at 0.27 ± 0.53 ppm (mean ± SD) for an average of 16 ± 10.8 years. The study included only people who had a new diagnosis of asthma after two or more asthma-free years in the work- place; thus, anyone who developed occupationally related asthma in the first 2 years of employment was excluded. The average age of the potroom workers was 43.7 ± 10.1 years. Using a multivariate generalized linear model relating the natural logarithm of predicted asthma rate, the authors concluded that asthma risk was significantly associated with exposure to hydrogen fluoride and current smoking but not to other contaminants in the workplace, such as particulate fluoride and sulfur dioxide. The relative risk for development of asthma was estimated by the model to be 1.18 per 0.1 mg/m3 change in hydrogen fluoride (95% confidence interval [CI], 1.09-1.3), which corresponds to a relative risk of 1.18 per 0.12 ppm. Although documentation of an association does not indicate cause and effect, a 1-h exposure to hydrogen fluoride does cause increased BAL lymphocytes (Lund et al. 1999), and persistent respiratory symptoms were re- ported in the general community after exposure to hydrogen fluoride in an in- dustrial accident (Wing et al. 1991). Those facts raise concern that the increased incidence of asthma in potroom workers may reflect a response to hydrogen fluoride. It is important to note that the presence of high dust concentrations and other irritants and occasional short-term (15-min) high-exposure excursions to hydrogen fluoride may have contributed to the response (Taiwo et al. 2006). Waldbott and Lee (1978) reported a case of systemic fluoride toxicity from repeated exposures to hydrogen fluoride gas in the alkylation unit of an oil company. Estimated exposures over the worker’s 10 years of employment were often above 3 ppm, on the basis of odor detection, and were thought to have been very high (25-200 ppm) during some procedures. Chronic symptoms in- cluded reduction in pulmonary function, gastrointestinal problems, and severe back and leg pains. Fluoride measured in bone 10 years after the maximal expo- sures was significantly above normal. Given a hydrogen fluoride concentration of 3 ppm, an 8-h workday, a ventilation rate of 15 m3/day, and complete absorp- tion, the worker’s minimum systemic fluoride dose was 8 mg/day, averaged over the entire week, or about 0.08 mg/kg-day for his reported weight of 230 lb (105 kg).3 Derryberry et al. (1963) reported a significantly higher frequency of albu- minuria in a group of workers exposed to airborne fluoride in a phosphate- fertilizer plant than in nonexposed controls (12.2% vs 4.5%) and suggested a relationship between fluoride excretion and renal function. Urinary fluoride ex- cretion averaged 4.6 mg/L (range, 2.1-14.7 mg/L) in the exposed group and 1.15 mg/L (range, 0.15-3.2 mg/L) in the controls. Two studies of aluminum potroom workers did not yield similar findings (reviewed by Hodge and Smith 1977). 3 The calculation is as follows: (15 m3/day)(1 day/24 h)(3 ppm)(0.82 mg/m3 per ppm)(19/20 mg fluoride per mg hydrogen fluoride)(8 h/day)(5/7) = 8 mg/day, assuming 100% absorption and dose averaged over the entire week.

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99 Hydrogen Fluoride 1991), 25% mortality was observed in male rats exposed to hydrogen fluoride at 10 ppm. Neither mortality nor histologic lesions were observed at 0.1 or 1 ppm for 90 days, but it is not clear that the critical regions of the nose were examined (Placke and Griffin 1991; Rosenholtz et al. 1963). On the basis of body-weight reductions, the study authors considered 1 ppm to represent a NOAEL. The sub- chronic animal exposure study of Stokinger (1949) included only a small num- ber of animals, and complete histopathologic evaluation was not performed, so use of the results is problematic. In that study, one of five dogs exposed to hy- drogen fluoride at 8.6 ppm 6 h/day, 5 days/week for 10 weeks exhibited focal pulmonary hemorrhage that was observable during necropsy, but no histologic examinations of the nose or lungs were included. Thus, the committee consid- ered the animal studies as inadequate for establishing a CEGL. If a human NOAEL were derived from the animal NOAEL of 1 ppm by applying an interspecies uncertainty factor of 3-10, the resulting value would not differ markedly from a NOAEL derived from occupational epidemiology in which a relative risk of asthma for hydrogen fluoride of 1.18 per 0.12 ppm was estimated. Given the weaknesses of the animal database and the weight that hu- man data should receive for risk assessment, it is appropriate to base the 90-day CEGL on the human occupational epidemiologic data. Because the other agents in the workplace (such as particulate fluorides and sulfur dioxide) and the short- term high-exposure excursions may have contributed to the asthma risk in the workers, the relative risk for hydrogen fluoride of 1.18 per 0.12 ppm may over- estimate the health risk. Therefore, 0.12 ppm is a reasonable point of departure for CEGL derivation. A concentration-time extrapolation of the data is problem- atic; workers in the study of Taiwo et al. (2006) were exposed 8 h/day, 5 days/week for at least 2 years compared with submariners’ exposure 24 h/day for 90-day durations. The two scenarios may represent similar exposure concen- trations on an annualized basis; therefore, a concentration-time extrapolation is not proposed. The worker population in the epidemiologic study most likely included people who had rhinitis or were otherwise sensitive, so an interindi- vidual uncertainty factor is not suggested here. Although the occupational epi- demiologic study of Taiwo et al. (2006) was well performed, uncertainties are associated with using this study, particularly the uncertainty introduced by ex- cluding people who had a new diagnosis of asthma within 2 years of beginning work. On the basis of that uncertainty and the difficulty of extrapolating a typi- cal 5 days/week occupational exposure to the submarine setting, a database un- certainty factor of 3 was applied. The resulting 90-d CEGL is 0.04 ppm. Sensory irritation is not expected at this exposure level on the basis of the 1-h and multi- ple 6-h human studies by Lund et al. (1997) and Largent (1961). The proposed 90-d CEGL of 0.04 ppm most likely protects against sys- temic fluoride-induced toxicity if airborne hydrogen fluoride is the only impor- tant source of fluoride exposure. At a ventilation rate of 15 m3/day, it corre- sponds to a total absorbed dose of 0.5 mg/day (0.007 mg/kg-day for a 70-kg person). However, for systemic effects, it is necessary to consider fluoride expo- sure from all sources (EPA 1988; NRC 2006). Furthermore, it is necessary to

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100 Exposure Guidance Levels for Selected Submarine Contaminants consider effects that could occur within a 90-day exposure and long-term effects due to cumulative exposures, of which 90-day exposures on a submarine would be a part. Health end points that require long-term exposure or accumulation of fluoride include effects on bones (increased risk of fracture and of skeletal fluorosis). Other effects (such as endocrine effects) do not necessarily require accumulation or long-term exposure but may depend on current physiologic fluoride concentrations. In particular, subchronic thyroid effects have been re- ported in animals—an indication that altered concentrations of thyroid hormones do not necessarily require long exposure. Impaired glucose tolerance and male reproductive effects have also been reported in animals exposed to fluoride for 28-100 days. Table 4-8 summarizes systemic fluoride effects and corresponding esti- mated intakes in humans. For most end points, systemic effects in generally healthy people have been reported in situations corresponding to estimated aver- age chronic intakes of around 0.05 mg/kg-day or higher. Long-term fluoride exposure would include exposure to airborne and in- gested fluoride on board a submarine and on shore. Table 4-9 summarizes the estimated average fluoride intake (by source and total from all sources) based on information provided to the committee by the U.S. Navy (LCDR D. Martin, U.S. Navy, personal commun., July 8, 2008). The proposed 90-d CEGL of 0.04 ppm based on chronic respiratory effects would lead to a systemic fluoride intake of 0.5 mg/day (0.007 mg/kg-day) at an inhalation rate of 15 m3/day (EPA 1997) and an average body weight of 70 kg. That value would correspond to an esti- mated average total systemic fluoride intake (from all sources) of 0.023 or 0.026 mg/kg-day for normal or high activity levels, respectively (Table 4-9). That es- timated total daily fluoride intake is less than 0.05 mg/kg-day, the lowest dose associated with the potential for fluoride-induced systemic toxicity (Table 4-8). Persons who have fluoridated water on shore will have total systemic fluoride intakes on board a submarine that will be lower than those on shore. TABLE 4-8 Summary of Systemic Effects in Humans Associated with Chronic Intake of Fluoride from All Sources Typical Fluoride Intake Estimated NOAEL Associated with Effects Effects (mg/kg-day) (mg/kg-day) Endocrine effects 0.01-0.03 0.05 Increased risk of bone fracture NA ~0.05 Skeletal fluorosis (stage II) NA 0.05 Reduced testosterone concentrations <0.03 0.05 NA, not available.

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101 Hydrogen Fluoride TABLE 4-9 Estimated Fluoride Intakes (mg/kg-day) for Specified Exposure Situationsa Source of Fluoride Exposure On Board Submarine On Shore b Fluoridated source:c Drinking water (normal 0.0024 0.0173 Nonfluoridated source:c 0.0024 activity) Drinking water (high 0.005 Fluoridated source: 0.05 activity)d Nonfluoridated source: 0.005 Food and beveragese 0.0114 0.0114 f Pesticides 0.0007 0.0007 Toothpasteg 0.0014 0.0014 h Air 0.007 0.0006 Totals: Normal activity 0.023 Fluoridated source: 0.031 Nonfluoridated source: 0.017 High activity 0.026 Fluoridated source: 0.064 Nonfluoridated source: 0.019 a Based on NRC (2006) estimates for U.S. adults 20-49 years old unless otherwise indi- cated. b Assumes that drinking water on submarine is primarily from reverse-osmosis unit. Puri- fied water is expected to have low fluoride concentrations (<0.15 mg/L; NRC 2006). c Drinking water on shore could be from fluoridated sources (around 1 mg/L) or non- fluoridated sources (defined as <0.7 mg/L; assumed here to be 0.5 mg/L). Two types of sources are considered separately. d Assumes a drinking-water intake of 50 mL/kg of body weight per day (Table 2-4, NRC 2006) and fluoride concentrations of 1 mg/L (fluoridated source) or 0.1 mg/L (on board submarine or nonfluoridated source on shore). e Food on board submarine includes fresh and frozen ingredients, canned soups and vege- tables, and canned fruits and fruit juices. Commercial beverages (such as soft drinks and bottled tea) are available. Tea, coffee, and Kool-Aid are available. Tea is prepared from tea bags. This diet is considered comparable with average diet of adults in United States with respect to fluoride intake. f Exposure to fluoride from pesticides is considered typical for adults in United States. g Toothpaste use and inadvertent ingestion of toothpaste are considered typical for adults in United States. h Based on proposed 90-d CEGL of 0.04 ppm, inhalation rate of 15 m3/day, and average body weight of 70 kg. DATA ADEQUACY AND RESEARCH NEEDS NRC (2006) identified a number of research needs regarding fluoride toxi- cology for various health end points. In particular, nearly all human studies re- quire improved characterization of fluoride exposure, including individual fluo- ride intake. There are very few subchronic or short-term studies of humans with any route of exposure. There have been occupational studies and studies of ex-

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102 Exposure Guidance Levels for Selected Submarine Contaminants posures to airborne fluoride from coal combustion in China, but most of the lit- erature on effects in humans comes from ingestion exposures, primarily to fluo- ride in drinking water. Although many health end points (such as effects on bones) require long-term exposure or accumulation of fluoride, others (such as endocrine effects, low tolerance or hypersensitivity, and asthma) do not. A criti- cal research need for animal studies would be a 90-day continuous-inhalation bioassay for hydrogen fluoride. Studies that use multiple 90-day exposures that mimic the exposure of the submarine crew may be needed to examine fully the potential for the induction of asthma. A species appropriate for examination of induction of allergic airway disease and measures of airway function would be critical for such a study. REFERENCES Aardema, M.J., and T. Tsutsui. 1995. Sodium fluoride-induced chromosome aberrations in different cell cycle stages. Mutat. Res. 331(1):171-172. Aardema, M.J., D.P. Gibson, and R.A. LeBoeuf. 1989. Sodium fluoride-induced chromo- some aberrations in different stages of the cell cycle: A proposed mechanism. Mu- tat. Res. 223(2):191-203. ACGIH (American Conference of Governmental Industrial Hygienists). 2005. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs) for 2005. American Conference of Governmental Hy- gienists, Cincinnati, OH. Alarie, Y. 1973. Sensory irritation by airborne chemicals. CRC Crit. Rev. Toxicol. 2(3):299-363. Alexeeff, G.V., D.C. Lewis, and N.L. Ragle. 1993. Estimation of potential health effects from acute exposure to hydrogen fluoride using a “benchmark dose” approach. Risk Anal. 13(1):63-69. Amoore, J.E., and E. Hautala. 1983. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. J. Appl. Toxicol. 3(6):272-290. Ando, M., M. Tadano, S. Yamamoto, K. Tamura, S. Asanuma, T. Watanabe, T. Kondo, S. Sakurai, R. Ji, C. Liang, X. Chen, Z. Hong, and S. Cao. 2001. Health effects of fluoride pollution caused by coal burning. Sci. Total Environ. 271(1-3):107-116. Araibi, A.A., W.H. Yousif, and O.S. Al-Dewachi. 1989. Effect of high fluoride on the reproductive performance of the male rat. J. Biol. Sci. Res. 20(1):19-30. ATSDR (Agency for Toxic Substances and Disease Registry). 2003. Toxicological Pro- file for Fluorides, Hydrogen Fluoride, and Fluorine. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. September 2003 [online]. Available: http:// www.atsdr.cdc.gov/toxprofiles/tp11-p.pdf [accessed Mar. 27, 2009]. ATSDR (Agency for Toxic Substances and Disease Registry). 2008. ATSDR Minimal Risk Levels (MRLs). U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry, Atlanta, GA. December 2008 [online]. Available: http://www.atsdr.cdc.gov/mrls/pdfs/atsdr_mrls_december_2008.pdf [accessed Mar. 27, 2009].

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103 Hydrogen Fluoride Bachinskii, P.P., O.A. Gutsalenko, N.D. Naryzhniuk, V.D. Sidora, and A.I. Shliakhta. 1985. Action of the body fluorine of healthy persons and thyroidopathy patients on the function of hypophyseal-thyroid the system [in Russian]. Probl. Endokrinol. 31(6):25-29. Baud, C.A., R. Lagier, G. Boivin, and M.A. Boillat. 1978. Value of bone biopsy in the diagnosis of industrial fluorosis. Virchows Arch. A Pathol. Anat. Histol. 380(4):283-297. Bennion, J.R., and A. Franzblau. 1997. Chemical pneumonitis following household expo- sure to hydrofluoric acid. Am. J. Ind. Med. 31(4):474-478. Björnhagen, V., J. Höjer, C. Karlson-Stiber, A.I. Seldén, and M. Sundbom. 2003. Hydro- fluoric acid-induced burns and life-threatening systemic poisoning: Favorable out- come after hemodialysis. J. Toxicol. Clin. Toxicol. 41(6):855-860. Black, A., and R.F. Hounam. 1968. Penetration of iodine vapour through the nose and mouth and the clearance and metabolism of deposited iodine. Ann. Occup. Hug. 11(3):209-225. Bobek, S., S. Kahl, and Z. Ewy. 1976. Effect of long-term fluoride administration on thyroid hormones level in blood in rats. Endocrinol. Exp. 10(4):289-295. Buckley, L.A., X.Z. Jiang, R.A. James, K.T. Morgan, and C.S. Barrow. 1984. Respira- tory tract lesions induced by sensory irritants at the RD50 concentration. Toxicol. Appl. Pharmacol. 74(3):417-429. Budavari, S., M.J. O’Neil, A. Smith, and P.E. Heckelman, eds. 1989. Hydrogen fluoride. P. 760 in The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologi- cals, 11th Ed. Rahway, NJ: Merck. Collings, G.H., Jr., R.B. Fleming, and R. May. 1951. Absorption and excretion of inhaled fluorides. AMA Arch. Ind. Hyg. Occup. Med. 4(6):585-590. Collings, G.H., Jr., R.B. Fleming, R. May, and W.O. Bianconi. 1952. Absorption and excretion of inhaled fluorides; further observations. AMA Arch. Ind. Hyg. Occup. Med. 6(4):368-373. Dalbey, W., B. Dunn, R. Bannister, W. Daughtrey, C. Kirwin, F. Reitman, M. Wells, and J. Bruce. 1998. Short-term exposures of rats to airborne hydrogen fluoride. J. Toxicol. Environ. Health Part A 55(4):241-275. Das (Sarkar), S., R. Maiti, and D. Ghosh. 2006. Management of fluoride induced testicu- lar disorders by calcium and vitamin-E co-administration in the albino rat. Reprod. Toxicol. 22(4):606-612. Dayal, H.H., M. Brokwick, R. Morris, T. Baranowski, N. Trieff, J.A. Harrison, J.R. Lisse, and G.A. Ansari. 1992. A community-based epidemiologic study of health sequelae of exposure to hydrofluoric acid. Ann. Epidemiol. 2(3):213-230 (as cited in ATSDR 2003). Dayal, H.H., T. Baranowski, Y.H. Li, and R. Morris. 1994. Hazardous chemicals: Psy- chological dimensions of the health sequelae of a community exposure in Texas. J. Epidemiol. Community Health 48(6):560-568. de Lopez, O.H., F.A. Smith, and H.G. Hodge. 1976. Plasma fluoride concentrations in rats acutely poisoned with sodium fluoride. Toxicol. Appl. Pharmacol. 37(1):75- 83. Derryberry, O.M., M.D. Bartholomew, and R.B. Fleming. 1963. Fluoride exposure and worker health. The health status of workers in a fertilizer manufacturing plant in relation to fluoride exposure. Arch. Environ. Health 6:503-514. Dominok, G., K. Siefert, J. Frege, and B. Dominok. 1984. Fluoride content of bones of retired fluoride workers. Fluoride 17(1):23-26.

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104 Exposure Guidance Levels for Selected Submarine Contaminants Dvoráková-Hortová, K., M. Sandera, M. Jursová, J. Vasinová, and J. Pecknicová. 2008. The influence of fluorides on mouse sperm capacitation. Anim. Reprod. Sci. 108(1-2):157-170. EPA (U.S. Environmental Protection Agency). 1988. Summary Review of Health Effects Associated with Hydrogen Fluoride and Related Compounds: Health Issue As- sessment. EPA/600/8-89/002F. Environmental Criteria and Assessment Office, Of- fice of Health and Environmental Assessment, Office of Research and Develop- ment, U.S. Environmental Protection Agency, Research Triangle Park, NC. December 1988 [online]. Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.. cfm?deid=47539 [accessed Mar. 27, 2009]. EPA (U.S. Environmental Protection Agency). 1989. Fluorine (Soluble Fluoride) (CASRN 7782-41-4). Integrated Risk Information System, U.S. Environmental Protection Agency [online]. Available: http://www.epa.gov/ncea/iris/subst/0053. htm [accessed June 22, 2009]. EPA (U.S. Environmental Protection Agency). 1994. Methods for Derivation of Inhala- tion Reference Concentrations and Application of Inhalation Dosimetry. EPA/600/8-90/066F. 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. October 1994 [online]. Available: http://www.epa.gov/raf/publications/pdfs/RFC METHODOLOGY.PDF [accessed Mar. 27, 2009]. EPA (U.S. Environmental Protection Agency). 1997. Exposure Factors Handbook, Vol. 1. General Factors. EPA/600/P-95/002Fa. National Center for Environmental As- sessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington DC. August 1997 [online]. Available: http://www.epa. gov/ncea/efh/report.html [accessed Mar. 27, 2009]. Franke, J., and E. Auermann. 1972. Significance of iliac crest puncture with histological and microanalytical examination of the obtained bone material in the diagnosis of fluorosis [in German]. Int. Arch. Arbeitsmed. 29(2):85-94. Franke, J., F. Rath, H. Runge, F. Fengler, E. Auermann, and G.L. Lenart. 1975. Industrial fluorosis. Fluoride 8(2):61-85. Franzblau, A., and N. Sahakian. 2003. Asthma following household exposure to hydro- fluoric acid. Am. J. Ind. Med. 44(3):321-324. Gadhia, P.K., and S. Joseph. 1997. Sodium fluoride induced chromosome aberrations and sister chromatid exchange in cultured human lymphocytes. Fluoride 30(3):153- 156. Galletti, P.M., and G. Joyet. 1958. Effect of fluorine on thyroidal iodine metabolism in hyperthyroidism. J. Clin. Endocrinol. Metab. 18(10):1102-1110. Grandjean, P., and J.H. Olsen. 2004. Extended follow-up of cancer incidence in fluoride- exposed workers. J. Natl. Cancer Inst. 96(10):802-803 (as cited in NRC 2006). Grandjean, P., and G. Thomsen. 1983. Reversibility of skeletal fluorosis. Br. J. Ind. Med. 40(4):456-461. Grandjean, P., M. Hørder, and Y. Thomassen. 1990. Fluoride, aluminum, and phosphate kinetics in cryolite workers. J. Occup. Med. 32(1):58-63. Grandjean, P., J.H. Olsen, O.M. Jensen, and K. Juel. 1992. Cancer incidence and mortal- ity in workers exposed to fluoride. J. Natl. Cancer Inst. 84(24):1903-1909 (as cited in NRC 2006). Grimbergen, G.W. 1974. A double blind test for determination of intolerance to fluori- dated water. (Preliminary Report). Fluoride 7(3):146-152. Guan, Z.Z., Z.J. Zhuang, P.S. Yang, and S. Pan. 1988. Synergistic action of iodine-

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105 Hydrogen Fluoride deficiency and fluorine-intoxication on rat thyroid. Chin. Med. J. 101(9):679-684. Hagar, R. 2008. Submarine Atmosphere Control and Monitoring Brief for the COT Committee. Presentation to the First Meeting on Emergency and Continuous Ex- posure Guidance Levels for Selected Submarine Contaminants, June 17, 2008, Washington, DC. Hara, K. 1980. Studies on fluorosis, especially effects of fluoride on thyroid metabolism [in Japanese]. Koku Eisei Gakkai Zasshi 30(1):42-57 (as cited in NRC 2006). Hodge, H.C., and F.A. Smith. 1977. Occupational fluoride exposure. J. Occup. Med. 19(1):12-39. Holstege, C., A. Baer, and W.J. Brady. 2005. The electrocardiographic toxidrome: The ECG presentation of hydrofluoric acid ingestion. Am. J. Emerg. Med. 23(2):171- 176. Horton, D.K., Z. Berkowitz, and W.E. Kaye. 2004. Hydrofluoric acid releases in 17 states and the acute health effects associated, 1993-2001. J. Occup. Environ. Med. 46(5):501-508. HSDB (Hazardous Substances Data Bank). 2008. Hydrogen Fluoride (CASRN: 7664-39- 3). TOXNET, Specialized Information Services, U.S. National Library of Medi- cine, Bethesda, MD [online]. Available: http://toxnet.nlm.nih.gov/ [accessed Mar. 27, 2009]. IARC (International Agency for Research on Cancer). 1987. Fluorides (Inorganic, Used in Drinking Water)/ Supplement 7, IARC [online]. http://www.inchem.org/ documents/iarc/suppl7/fluorides.html [accessed June 22, 2009]. Jooste, P.L., M.J. Weight, J.A. Kriek, and A.J. Louw. 1999. Endemic goitre in the ab- sence of iodine deficiency in schoolchildren of the Northern Cape Province of South Africa. Eur. J. Clin. Nutr. 53(1):8-12. Kaltreider, N.L., M.J. Elder, L.V. Cralley, and M.O. Colwell. 1972. Health survey of aluminum workers with special reference to fluoride exposure. J. Occup. Med. 14(7):531-541. Kongerud, J., J. Boe, V. Soyseth, A. Naalsund, and P. Magnus. 1994. Aluminum potroom asthma: The Norwegian experience. Eur. Respir. J. 7(1):165-172. Kishi, K., and T. Ishida. 1993. Clastogenic activity of sodium fluoride in great ape cells. Mutat. Res. 301(3):183-188. Largent, E.J. 1961. Pp. 34-39, 43-48 in Fluorosis: The Health Aspects of Fluorine Com- pounds. Columbus, OH: Ohio State University Press. Largent, E.J., P.G. Bovard, and F.F. Heyroth. 1951. Roentgenographic changes and uri- nary fluoride excretion among workmen engaged in the manufacture of inorganic fluorides. Am. J. Roentgenol. Radium Ther. 65(1):42-48. Lasne, C., Y.P. Lu, and I. Chouroulinkov. 1988. Transforming activities of sodium fluo- ride in cultured Syrian hamster embryo and BALB/3T3 cells. Cell Biol. Toxicol. 4(3):311-324. Lestari, F., A.J. Hayes, A.R. Green, and B. Markovic. 2005. In vitro cytotoxicity of se- lected chemicals commonly produced during fire combustion using human cell lines. Toxicol. In Vitro 19(5):653-663. Lindahl, C.B., and T. Mahmood. 2005. Fluorine compounds, inorganic. Pp. 852-858 in Kirk-Othmer Encyclopedia of Chemical Technology, Vol. 11, A. Seidel et al. eds. Hoboken, NJ: Wiley-Interscience. Liu, J.L., T. Xia, Y.Y. Yu, X.Z. Sun, Q. Zhu, W. He, M. Zhang, and A. Wang. 2005. The dose-effect relationship of water fluoride levels and renal damage in children [in Chinese]. Wei Sheng Yan Jiu 34(3):287-288.

OCR for page 70
106 Exposure Guidance Levels for Selected Submarine Contaminants Lund, K., J. Ekstrand, J. Boe, P. Sostrand, and J. Kongerud. 1997. Exposure to hydrogen fluoride: An experimental study in humans of concentrations of fluoride in plasma, symptoms, and lung function. Occup. Environ. Med. 54(1):32-37. Lund, K., M. Refsnes, T. Sanstrom, P. Sostrand, P. Schwarze, J. Boe, and J. Kongerud. 1999. Increased CD3 positive cells in bronchoalveolar lavage fluid after hydrogen fluoride inhalation. Scand. J. Work Environ. Health 25(4):326-334. Lund, K., M. Refsnes, I. Ramis, C. Dunster, J. Boe, P.E. Schwarze, E. Skovlund, F.J. Kelly, and J. Kongerud. 2002. Human exposure to hydrogen fluoride induces acute neutrophilic, eicosanoid, and antioxidant changes in nasal lavage fluid. Inhal. Toxicol. 14(2):119-132. Lund, K., C. Dunster, I. Ramis, T. Sandström, F.J. Kelly, P. Sostrand, P. Schwarze, E. Skovlund, J. Boe, J. Kongerud and M. Refsnes. 2005. Inflammatory markers in bronchoalveolar lavage fluid from human volunteers 2 hours after hydrogen fluo- ride exposure. Hum. Exp. Toxicol. 24(3):101-108. Machle, W.F., and K. Kitzmiller. 1935. The effects of the inhalation of hydrogen fluo- ride. II. The response following exposure to low concentration. J. Ind. Hyg. 17:223-229. Machle, W.F., F. Thamann, K. Kitzmiller, and J. Cholak. 1934. The effects of the inhala- tion of hydrogen fluoride. I. Response following exposure to high concentrations. J. Ind. Health 16(2):129-145. Meng, Z., and B. Zhang. 1997. Chromosomal aberrations and micronuclei in lympho- cytes of workers at a phosphate fertilizer factory. Mutat. Res. 393(3):283-288. Meng, Z., H. Meng, and X. Cao. 1995. Sister-chromatid exchanges in lymphocytes of workers at a phosphate fertilizer factory. Mutat. Res. 334(2):243-246. Mihashi, M., and T. Tsutsui. 1996. Clastogenic activity of sodium fluoride to rat vertebral body-derived cells in culture. Mutat. Res. 368(1):7-13. Mitsui, G., T. Dote, K. Adachi, E. Dote, K. Fujimoto, Y. Shimbo, M. Fujihara, H. Shi- mizu, K. Usuda, and K. Kono. 2007. Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats. Toxicol. Ind. Health 23(1):5-12. Morris, J.B. 1979. The Absorption, Distribution and Excretion of Inhaled Hydrogen Fluo- ride in the Rat. Ph.D. Thesis, University of Rochester, Rochester, NY. 293 pp. Morris, J.B. 2006. Nasal toxicology. Pp. 349-371 in Inhalation Toxicology, 2nd Ed., H. Salem, and S.A. Katz, eds. Boca Raton: CRC/Taylor and Francis. Morris, J.B., and F.A. Smith. 1982. Regional deposition and absorption of inhaled hydro- gen fluoride in the rat. Toxicol. Appl. Pharmacol. 62(1):81-89. Morris, J.B., P.T. Symanowicz, J.E. Olsen, R.S. Thrall, M.M. Cloutier, and A.K. Hub- bard. 2003. Immediate sensory-nerve mediated respiratory responses to irritants in healthy and allergic airway diseased mice. J. Appl. Physiol. 94(4):1563-1571. NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH). No. 2005-149. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Cincinnati, OH [online]. Available: http://www.cdc.gov/niosh/npg/ [accessed Mar. 30, 2009]. NRC (National Research Council). 1988. Submarine Air Quality: Monitoring the Air in Submarines. Washington, DC: National Academy Press. NRC (National Research Council). 2004. Hydrogen fluoride. Pp. 123-197 in Acute Expo- sure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: The National Academies Press.

OCR for page 70
107 Hydrogen Fluoride NRC (National Research Council). 2006. Fluoride in Drinking Water: A Scientific Re- view of EPA’s Standards. Washington, DC: The National Academies Press. NTP (National Toxicology Program). 1990. Toxicology and Carcinogenesis Studies of Sodium Fluoride (CAS No. 7681-49-4) in F344/N Rats and B6C3F1 Mice. NTP Technical Report No. 393. NIH Publication No. 91-2848. U.S. Department of Health and Human Services, National Toxicology Program, Research Triangle Park, NC. OEHHA (Office of Environmental Health Hazard Assessment). 2003. Chronic Toxicity Summary: Fluorides including Hydrogen Fluoride. Determination of Noncancer Chronic Reference Exposure Levels. August 2003 [online]. Available: http://www. oehha.ca.gov/air/chronic_rels/pdf/2ApnA_Fluoride_Final.pdf [accessed September 19, 2008]. Oguro, A., J. Cervenka, and K. Horii. 1995. Effect of sodium fluoride on chromosomal ploidy and breakage in cultured human diploid cells (IMR-90): An evaluation of continuous and short-time treatment. Pharmacol. Toxicol. 76(4):292-296. Ortiz-Pérez, D., M. Rodríguez-Martínez, F. Martínez, V.H. Borja-Aburto, J. Castelo, J.I. Grimaldo, E. de la Cruz, L. Carrizales, and F. Díaz-Barriga. 2003. Fluoride- induced disruption of reproductive hormones in men. Environ. Res. 93(1):20-30. Placke, M.E., and S. Griffin. 1991. Subchronic Inhalation Exposure Study of Hydrogen Fluoride in Rats. Battelle Memorial Institute, Columbus, OH. Submitted by Bat- telle Washington Environmental Program, Arlington VA. January 4, 1991. Placke, M.E., M. Brooker, R. Persing, J.Taylor, and M. Haterty. 1990. Final Report on Repeated-Exposure Inhalation Study of Hydrogen Fluoride in Rats. Battelle Me- morial Institute, Columbus, OH. Submitted by Battelle Washington Environmental Program, Arlington VA. September 1990. Rees, D., D.B. Rama, and V. Yousefi. 1990. Fluoride in workplace air and in urine of workers concentrating fluorspar. Am. J. Ind. Med. 17(3):311-320. Rigalli, A., J.C. Ballina, and R.C. Puche. 1992. Bone mass increase and glucose tolerance in rats chronically treated with sodium fluoride. Bone Miner. 16(2):101-108. Rigalli, A., R. Alloatti, I. Menoyo, and R.C. Puche. 1995. Comparative study of the effect of sodium fluoride and sodium monofluorophosphate on glucose homeostasis in the rat. Arzneimittel-Forschung. 45(3):289-292. Roholm, K. 1937. Fluorine Intoxication: A Clinical-Hygienic Study, with a Review of the Literature and Some Experimental Investigations. London: H.K. Lewis. Romundstad, P., A. Andersen, and T. Haldorsen. 2000. Cancer incidence among workers in six Norwegian aluminum plants. Scand. J. Work Environ. Health 26(6):461-469 (as cited in NRC 2006). Rosenholtz, M.J., T.R. Carson, M.H. Weeks, F. Wilinski, D.F. Ford, and F.W. Oberst. 1963. A toxicopathologic study in animals after brief single exposures to hydrogen fluoride. Am. Ind. Hyg. Assoc. J. 24:253-261. Sadilova, M.S., K.P. Selyankina, and O.K. Shturkina. 1965. Experimental studies on the effect of hydrogen fluoride on the central nervous system [in Russian]. Gig. Sanit. 30(5):155-160. Sanz-Gallén, P., S. Nogué, P. Munné, and A. Faraldo. 2001. Hypocalcaemia and hypo- magnesaemia due to hydrofluoric acid. Occup. Med. 51(4):294-295. Schlegel, H.H. 1974. Industrial skeletal fluorosis: Preliminary report on 61 cases from aluminum smelter [in German]. Soz. Praventiv. Med. 19:269-274. Shusterman, D., A. Tarun, M.A. Murphy, and J. Morris. 2005. Seasonal allergic rhinitic and normal subjects respond differentially to nasal provocation with acetic acid vapor. Inhal. Toxicol. 17(3):147-152.

OCR for page 70
108 Exposure Guidance Levels for Selected Submarine Contaminants Singh, P.P., M.K. Barjatiya, S. Dhing, R. Bhatnagar, S. Kothari, and V. Dhar. 2001. Evi- dence suggesting that high intake of fluoride provokes nephrolithiasis in tribal populations. Urol. Res. 29(4):238-244 (as cited in NRC 2006). Smith, F.A., and H.C. Hodge. 1979. Airborne fluorides and man: Part II. Crit. Rev. Env. Contr. (1):1-25. Soyseth, V., and J. Kongerud. 1992. Prevalence of respiratory disorders among aluminum potroom workers in relation to exposure to fluoride. Br. J. Ind. Med. 49(2):125- 130. Stavert, D.M., D.C. Archuleta, M.J. Behr, and B.E. Lehnert. 1991. Relative acute toxici- ties of hydrogen fluoride, hydrogen chloride and hydrogen bromide in nose- and pseudo-mouth-breathing rats. Fundam. Appl. Toxicol. 16(4):636-655. Stokinger, H.E. 1949. Toxicity following inhalation of fluorine and hydrogen fluoride. Pp. 1021-1057 in Pharmacology and Toxicology of Uranium Compounds, Vol. 1, C. Voegtlin, and H.C. Hodge, eds. New York: McGraw-Hill. Susheela, A.K., and P. Jethanandani. 1996. Circulating testosterone levels in skeletal fluorosis patients. J. Toxicol. Clin. Toxicol. 34(2):183-189. Susheela, A.K., M. Bhatnagar, K. Vig, and N.K. Mondal. 2005. Excess fluoride ingestion and thyroid hormone derangements in children living in Delhi, India. Fluoride 38(2):98-108. Taiwo, O.A., K.D. Sircar, M.D. Slade, L.F. Cantley, S.J. Vegso, P.M. Rabinowitz, M.G. Fiellin, and M.R. Cullen. 2006. Incidence of asthma among aluminum workers. J. Occup. Environ. Med. 48(3):275-282. ten Berge, W.F., A. Zwart, and L.M. Appelman. 1986. Concentration-time mortality response relationship of irritant and systemically acting vapours and gases. J. Haz- ard. Mater. 13(3):151-162. Teotia, S.P., M. Teotia, R.K. Singh, D.R. Taves, and S. Heels. 1978. Endocrine aspects of endemic skeletal fluorosis. J. Assoc. Physicians India 26(11):995-1000. Tokar, V.I., and O.N. Savchenko. 1977. Effect of inorganic fluorine compounds on the functional state of the pituitary-testis system [in Russian]. Probl. Endokrinol. 23(4):104-107. Trivedi, N., A. Mithal, S.K. Gupta, and M.M. Godbole. 1993. Reversible impairment of glucose tolerance in patients with endemic fluorosis. Fluoride Collaborative Study Group. Diabetologia 36(9):826-828. Turner, C.H., L.P. Garetto, A.J. Dunipace, W. Zhang, M.E. Wilson, M.D. Grynpas, D. Chachra, R. McClintock, M. Peacock, and G.K. Stookey. 1997. Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. Calcif. Tissue Int. 61(1):77-83. Turner, C.H., W.R. Hinckley, M.E. Wilson, W. Zhang, and A.J. Dunipace. 2001. Com- bined effects of diets with reduced calcium and phosphate and increased fluoride intake on vertebral bone strength and histology in rats. Calcif. Tissue Int. 69(1):51- 57 (as cited in ATSDR 2003). Vohra, R., L.I. Velez, W. Rivera, F.L. Benitez, and K.A. Delaney. 2008. Recurrent life- threatening ventricular dysrhythmias associated with acute hydrofluoric acid inges- tion: Observations in one case and implications for mechanism of toxicity. Clin. Toxicol. 46(1):79-84. Waldbott, G.L. 1956. Incipient chronic fluoride intoxication from drinking water. II. Distinction between allergic reactions and drug intolerance. Int. Arch. Allergy Appl. Immunol. 9(5):241-249. Waldbott, G.L. 1958. Allergic reactions from fluorides. Int. Arch. Allergy Appl. Immu- nol. 12(6):347-355.

OCR for page 70
109 Hydrogen Fluoride Waldbott, G.L., and J.R. Lee. 1978. Toxicity from repeated low-grade exposure to hy- drogen fluoride—case report. Clin. Toxicol. 13(3):391-402. Wang, A.G., T. Xia, Q.L. Chu, M. Zhang, F. Liu, X.M. Chen, and K.D. Yang. 2004. Effects of fluoride on lipid peroxidation, DNA damage and apoptosis in human embryo hepatocytes. Biomed. Environ. Sci. 17(2):217-222. Wing, J.S., J.D. Brender, L.M. Sanderson, D.M. Perrotta, and R.A. Beauchamp. 1991. Acute health effects in a community after a release of hydrofluoric acid. Arch. En- viron. Health 46(3):155-160. Wu, D.Q., and Y. Wu. 1995. Micronucleus and sister chromatid exchange frequency in endemic fluorosis. Fluoride 28(3):125-127. Xiong, X., J. Liu, W. He, T. Xia, P. He, X. Chen, K. Yang, and A. Wang. 2007. Dose- effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environ. Res. 103(1):112-116. Yamamoto, S., K. Katagiri, M. Ando, and X.Q. Chen. 2001. Suppression of pulmonary antibacterial defenses mechanisms and lung damage in mice exposed to fluoride aerosol. J. Toxicol. Environ. Health A 62(6):485-494. Yokoyama, E., R. Yoder, and N.R. Frank. 1971. Distribution of 35S in blood and its ex- cretion in urine of dogs exposed to 35SO2. Arch. Environ. Health 22(3):389-395. Young, J.T. 1981. Histopathologic examination of the rat nasal cavity. Fundam. Appl. Toxicol. 1(4):309-312. Zhao, W., H. Zhu, Z. Yu, K. Aoki, J. Misumi, and X. Zhang. 1998. Long-term effects of various iodine and fluorine doses on the thyroid and fluorosis in mice. Endocr. Regul. 32(2):63-70 (as cited in NRC 2006).