Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 8 (2010) / Chapter Skim
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5 Fluorine
5 Fluorine
Pages 230-273
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Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Subcommittee on Acute Exposure Guideline Levels.
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Although the AEGL values represent threshold levels for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL. SUMMARY Fluorine is a reactive, highly irritating and corrosive gas used in the nuclear energy industry, as an oxidizer of liquid rocket fuels, and in the manufacture of various fluorides and fluorocarbons.
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The resulting value of 1.7 ppm was used across all AEGL-1 exposure durations because, at mildly irritating concentrations, adaptation to slight sensory irritation occurs. As noted, this value is supported by limited workplace monitoring data: workers exposed to fluorine at average yearly concentrations up to 1.2 ppm (range, 0.0-17 ppm)
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Because of the similar species sensitivity in the key study, based on both irritant effects and lethality, an interspecies uncertainty factor of 1 was considered sufficient to account for interspecies variability. The values were divided by an uncertainty factor of 3 to protect sensitive individuals (fluorine is a highly reactive, corrosive gas whose effect on respiratory tract tissues is not expected to differ greatly among individuals)
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a The characteristic, pungent odor of fluorine will be noticeable at this concentration. b The same value was used across all time periods because, at mildly irritating concentrations, adaptation to sensory irritation occurs.
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Nonlethal Toxicity No human studies documenting specific fluorine exposure levels and time of exposure were found for acute, irreversible effects. Limited data are available on reversible, non-disabling effects of fluorine gas to humans.
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; slightly irritating to the skin 100-200 Not stated Reaction with skin and body hair Belles 1965
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The subjects did not inhale at the 100 ppm concentration; inhalation exposure to 78 ppm caused coughing. The 100 ppm concentration caused slight irritation of the skin and a "sticky" feeling.
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ANIMAL TOXICITY DATA 3.1. Acute Lethality Data on acute lethal concentrations of fluorine for exposure durations of 5 min to 7 h are available for the rat, mouse, guinea pig, and rabbit.
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In short-term, repeated exposures, groups of five dogs (sex and strain unspecified) were administered fluorine at concentrations of 0.5, 2, 5, and 16 ppm for up to 35 days (Stokinger 1949)
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Autopsy results indicated that fluorine gas was severely corrosive to the respiratory tract as shown by bronchial and alveolar necrosis. Death was attributed to respiratory failure resulting from acute pulmonary damage involving edema, emphysema, and hemorrhage.
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and Stokinger (1949) exposed guinea pigs (sex and strain unspecified)
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Keplinger and Suissa (1968) exposed groups of five New England guinea pigs (sex unspecified)
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Data are presented for the dog, rat, mouse, guinea pig, and rabbit. The latter four species were exposed to concentrations approximating 50, 25, and 12.5% of their respective LC50 values for exposure durations of 5, 15, 30, and 60 min.
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TABLE 5-5 Summary of Sublethal Effects in Laboratory Animals 244 Species Concentration (ppm) Exposure Time Effecta Reference Dog 93 1h irritation, cough, slight labored breathing, Keplinger and Suissa 1968 vomiting, small areas of hemorrhage in lungs 93 15 min slight lung congestion 68 1h eye irritation 38 1h no effect 5 min marked signs of intoxication, Keplinger and Suissa 1968; Keplinger Rat 500 severe changes in lungs 1969 moderate lung congestion 350 5 min moderate lung congestion 325 5 min labored breathing; mild lung congestion 175 5 min very mild lung congestion 150 5 min no effect 88 5 min irritation, labored breathing, moderate diffuse Keplinger and Suissa 1968 Rat 195 15 min congestion very mild lung congestion 98 15 min 49 15 min no effect 30 min irritation of eyes and nose, slight labored Keplinger and Suissa 1968; Keplinger Rat 140 breathing, moderate diffuse lung congestion 1969 68, 70 30 min very mild lung congestion no effect 35 30 min Rat 140 1h severe diffuse lung congestion, Keplinger and Suissa 1968; kidney and liver changes Keplinger 1969 eye irritation and labored breathing; mild diffuse Keplinger and Suissa 1968; Rat 93 1h lung congestion Keplinger 1969 mild diffuse lung congestion 75 1h very mild diffuse lung congestion 47 1h no effect 28 1h
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Keplinger and Suissa 1968; marked irritation of eyes and respiratory tract, 5 min Mouse 467 Keplinger 1969 labored breathing, severe diffuse lung congestion moderate diffuse lung congestion 5 min 321 eye irritation and labored breathing; moderate 5 min 300 diffuse lung congestion slightly labored breathing; very mild diffuse 5 min 174 lung congestion very mild lung congestion 5 min 130 no effect 5 min 79 severe diffuse lung congestion to congestion Keplinger and Suissa 1968; Mouse 350, 359 15 min with hemorrhages Keplinger 1969 moderate diffuse lung congestion 265, 285 15 min 15 min eye irritation and labored breathing; moderate 188 diffuse lung congestion very mild diffuse lung congestion 87 15 min 65 15 min no effect eye irritation and labored breathing; Keplinger and Suissa 1968; Mouse 113 30 min mild diffuse lung congestion Keplinger 1969 64, 67 30 min very mild lung congestion no effect 32 30 min eye irritation and labored breathing, severe Keplinger and Suissa 1968; Mouse 75 1h diffuse lung congestion Keplinger 1969 very mild lung congestion 55 1h 50 1h labored breathing; mild diffuse lung congestion very mild diffuse lung congestion 30 1h no effect 15 1h eye irritation and labored breathing; mild diffuse Keplinger and Suissa 1968 Guinea pig 198 15 min lung congestion 70 15 min no effect (Continued)
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TABLE 5-5 Continued 246 Species Concentration (ppm) Exposure Time Effecta Reference Guinea pig 135 1h eye irritation and labored breathing; Keplinger and Suissa 1968 mild diffuse lung congestion 73 1h no effect Guinea pig 100 7h severe damage to the respiratory system Eriksen 1945; Stokinger 1949 eye irritation and labored breathing; Keplinger and Suissa 1968 Rabbit 410 5 min moderate diffuse lung congestion slightly labored breathing 134 5 min no effect 51 5 min Keplinger and Suissa 1968 Rabbit 135 30 min eye irritation, very mild diffuse congestion 71 30 min no irritation, very mild diffuse congestion 32 30 min no effect a Measured up to 45 days post exposure; serial sacrifice revealed that effects did not become worse with time and, in some cases, lung changes showed some regression starting 7 days post-exposure.
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. Rats exposed to these concentrations experienced eye irritation, slightly labored breathing and very mild to mild diffuse congestion of the lungs.
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, signs of eye and respiratory irritation and labored breathing and gross lung changes of mild diffuse congestion were present. At exposures to concentrations of 100 and 70 ppm for 5 min, mild effects were occasionally observed.
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3.6. Summary LC50 concentrations for the mouse, rat, guinea pig, and rabbit from the study of Keplinger and Suissa (1968)
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. The only experimental data available for longer-term exposures was the 7h exposure of rats, mice, guinea pigs and rabbits to 100 ppm which resulted in an over-all mortality of 60% (Eriksen 1945; Stokinger 1949)
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Source: Keplinger and Suissa 1968. Reprinted with permission; copyright 1968, Journal of Industrial Hygiene and Toxicology.
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The available studies show that damage to the respiratory tract, particularly the lung (edema, emphysema, and hemorrhage) , is the major pathology associated with acute exposure to fluorine (Eriksen 1945; Stokinger 1949; Keplinger and Suissa 1968; Keplinger 1969)
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. The only available data for scaling across time are LC50 data for the rat, mouse, and guinea pig for 5, 15, 30, and 60-min exposure durations.
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Guinea pigs succumbed more rapidly than the other three species at the three highest exposure levels (10,000, 1000, and 500 ppm) , but showed less mortality at the 200 ppm level and no mortality at the 100 ppm level.
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5.2. Summary of Animal Data Relevant to AEGL-1 The animal data indicated that at 25% of the LC50, there were mild signs of intoxication characterized by slight labored breathing and closed eyes (Keplinger and Suissa 1968)
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because at mildly irritating concentrations there is accommodation to irritating gases. This value is supported by limited workplace monitoring data: workers exposed to fluorine at average yearly concentrations up to 1.2 ppm (range, 0.0-17 ppm)
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The 8-h-AEGL-2 value was set equal to the 4-h value because at low concentrations the hygroscopic fluorine would react with and/or be scrubbed by the nasal passages, and because at mildly irritating concentrations, adaptation to sensory irritation occurs. Although human exposure for durations longer than 1 min were to concentrations below the definition of the AEGL-2, a comparison of the human data with the derived values can be made.
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. At 50% of the 15-min LC50, guinea pigs showed signs of respiratory irritation and labored breathing and gross changes in the lungs of mild diffuse congestion.
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The AEGL-1 was based on a study with human volunteers in which a concentration of 10 ppm administered for 15 min produced no irritation of the eyes, nose, or respiratory tract.
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Because accommodation to the irritant effects of irritant gases occurs at mildly irritating concentrations, the derived value of 1.7 ppm was applied across all AEGL-1 time intervals. In the absence of relevant human data, animal data were used to derive the AEGL-2 and AEGL-3 values.
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Data from animal studies used five species and encompassed a wide range of exposure concentrations and exposure durations, but none of the durations was for longer than 1 h for less than lethal effects. The animal studies were undertaken 27-47 years ago and analytical techniques have improved since then.
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The ERPG-2 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing irreversible or other serious health effects or symptoms that could impair an individual's ability to take protective action. The ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing lifethreatening health effects.
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f TLV-TWA (Threshold Limit Value - Time Weighted Average, American Conference of Governmental Industrial Hygienists)
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Although most of the experimental exposures were of short duration, at least one additional experimental value is consistent with the derived time-scaling relationship. Application of an intraspecies uncertainty factor of 3 to the human data, an interspecies uncertainty factor of 1 to the animal data, and a modifying factor of 2 to reasonably consistent but limited human and animal data is appropriate to insure the safety of the values.
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2004. Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol.
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2005. Occupational Exposure Limit Value and Measures Against Air Contaminants.
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Reprinted with permission; copyright 1968, Journal of Industrial Hygiene and Toxicology. Time (minutes)
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Calculation: 10 ppm/6 = 1.7 ppm Derivation of AEGL-2 Key Study: Keplinger and Suissa 1968 Toxicity end point: Very mild diffuse lung congestion in mice exposed to 67 ppm for 30 min and 30 ppm for 1 h. C1.77 × t = k (ten Berge et al.
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(75 ppm/6) 1.77 × 60 min = 5244.23 ppm1.77Amin Calculations: C1.77 × 10 min = 5244.23 ppm1.77Amin 10-min AEGL-3 C = 36 ppm C1.77 × 30 min = 5244.23 ppm1.77Amin 30-min AEGL-3 C = 19 ppm 60-min AEGL-3 75 ppm/6 = 13 ppm C1.77 × 240 min = 5244.23 ppm1.77Amin 4-h AEGL-3 C = 5.7 ppm 8-h AEGL-3 Because of accommodation to low concentrations of irritant gases, the 8-h value was set equal to the 4-h value.
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APPENDIX C 270 Category Graph of Toxicity Data and AEGL Values for Fluorine FIGURE C-1 Category graph of toxicity data and AEGL values for fluorine.
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Uncertainty Factors/Rationale: Total uncertainty factor: 3 Interspecies: Not applicable, human subjects were tested Intraspecies: 3- The effect was a NOAEL for sensory irritation. Limited workplace monitoring data showed that workers exposed to fluorine at average yearly concentrations up to 1.2 ppm (range, 0.0-17 ppm)
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13 ppm: irritation and labored breathing, mild diffuse lung congestion 225 ppm: LC50 1-h exposures: 15 ppm: no toxic signs, no gross lung pathology 30 ppm: no toxic signs, very mild diffuse lung congestion (basis for AEGL-2) 50 ppm: labored breathing, mild diffuse lung congestion 75 ppm: irritation and labored breathing, severe diffuse lung congestion 150 ppm: LC50 End Point/Concentration/Rationale: 67 ppm for 30 min and 30 ppm for 1 h resulted in very mild diffuse lung congestion.
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, 10/exposure group Exposure Route/Concentrations/Durations: Inhalation: 38, 79, 174, 300, 467, 600 ppm for 5 min 32, 65, 87, 188, 375 ppm for 15 min 16, 32, 67, 113, 225 ppm for 30 min 5, 30, 50, 75, 150 ppm for 1 h Effects: The 1-h substudy using the mouse was considered 15 ppm: no toxic signs, no gross lung pathology 30 ppm: no toxic signs, very mild diffuse lung congestion (basis for AEGL-2) 50 ppm: labored breathing, mild diffuse lung congestion 75 ppm: irritation and labored breathing, severe diffuse lung congestion 150 ppm: LC50 End Point/Concentration/Rationale: 75 ppm for 1 h resulted in irritation and labored breathing and severe diffuse lung congestion in the mouse.
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