B6

Perfluoropropane and Other Aliphatic Perfluoroalkanes

Chiu-Wing Lam, Ph.D., D.A.B.T.

Johnson Space Center Toxicology Group

Medical Operations Branch

Houston, Texas

PHYSICAL AND CHEMICAL PROPERTIES

Perfluoropropane (PFA3, octafluoropropane) is gaseous at room temperature. It is colorless and odorless. Some physical characteristics are as follows:

Formula:

CF3CF2CF3

CAS no.:

76-19-7

Synonyms:

Freon 218, FC-218, PF 5030 3M Performance Fluid

Molecular weight:

188.08

Boiling point:

–37°C

Vapor pressure:

114.8 psia at 21°C (3M 1995a)

Solubility in water:

Extremely low

Conversion factors:

1 ppm = 7.68 mg/m3

 

1 mg/m3 = 0.13 ppm (at 25°C)

OCCURRENCE AND USE

When compressed, gaseous PFA3 is easily condensed into liquid. PFA3 is currently used as a secondary coolant in refrigerators aboard the Russian space-station Mir. According to Russian toxicologists, if all the PFA3 were to escape from the cooling system into the Mir cabin, the cabin concentration could reach 5000 mg/m3 (G.I.Solomina and L.N.Mouakhamedieva, Institute of Biomedical Problems, Moscow, personal commun., 1996). PFA3 is not used in the U.S. space program, and to our knowledge, astronauts have not been exposed to



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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 B6 Perfluoropropane and Other Aliphatic Perfluoroalkanes Chiu-Wing Lam, Ph.D., D.A.B.T. Johnson Space Center Toxicology Group Medical Operations Branch Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES Perfluoropropane (PFA3, octafluoropropane) is gaseous at room temperature. It is colorless and odorless. Some physical characteristics are as follows: Formula: CF3CF2CF3 CAS no.: 76-19-7 Synonyms: Freon 218, FC-218, PF 5030 3M Performance Fluid Molecular weight: 188.08 Boiling point: –37°C Vapor pressure: 114.8 psia at 21°C (3M 1995a) Solubility in water: Extremely low Conversion factors: 1 ppm = 7.68 mg/m3   1 mg/m3 = 0.13 ppm (at 25°C) OCCURRENCE AND USE When compressed, gaseous PFA3 is easily condensed into liquid. PFA3 is currently used as a secondary coolant in refrigerators aboard the Russian space-station Mir. According to Russian toxicologists, if all the PFA3 were to escape from the cooling system into the Mir cabin, the cabin concentration could reach 5000 mg/m3 (G.I.Solomina and L.N.Mouakhamedieva, Institute of Biomedical Problems, Moscow, personal commun., 1996). PFA3 is not used in the U.S. space program, and to our knowledge, astronauts have not been exposed to

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 PFA3 in U.S. spacecraft. However, NASA has joined the Russian Space Agency in using the Mir space station. Mir-18 was the first mission that involved a U.S. astronaut living onboard the Russian spacecraft. For this mission, the cabin air samples showed that PFA3 was the trace contaminant present in the highest concentration; its concentrations in Mir ranged from 20 to 48 mg/m3 (Limero 1995). TOXICOKINETICS AND METABOLISM Toxicokinetics PFA3 is practically insoluble in water (3M 1995a). The air/blood/liver/fat partition coefficients (PCs) of PFA3 were 1/0.25/0.07/0.04 (Creech et al. 1995), as determined by the vial equilibration method of Gargas et al. (1986). For solubility comparison, the corresponding PCs of chloroform, determined by the same method, were 1/20.8/21.1/203 (Gargas et al. 1989). Those data suggest that at the same airbrone exposure concentration, the blood, liver, and fat would take up, respectively, 83, 300, and 5000 times more chloroform than PFA3 when the equilibrium is reached. Theoretical predictions showed that concentrations of very low water-soluble, volatile compounds in body water would approach steady state within 1 hof exposure (Goldstein 1974). Metabolism Perfluoroalkanes (PFAs) are very stable. They are not oxidized even by ozone to any appreciable extent; their atmospheric half-life greater than 5000 y (R.G. Perkins, 3M Company, personal commun., 1995). Creech et al. (1995) detected no increases in fluoride in urine of rats exposed to 1% PFA3 for 4 h. TOXICITY SUMMARY PFA3 is a low-molecular-weight PFA. PFAs are chemically inert; included in this family is Teflon (a polymeric, high-molecular-weight PFA). The major concern from exposure to high concentrations of gaseous PFAs is their potential for cardiac toxicity. Cardiac effects are known to occur when humans or animals are exposed to high concentrations of other fluorinated hydrocarbons (FCs), including Freons (Table 6-1). FCs, such as chlorofluorocarbons, could induce cardiac arrhythmias by sensitizing the heart to epinephrine (Aviado and

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 Micozzi 1981; Hanig and Herman 1991). The inertness of PFAs has attracted few attempts to investigate the toxic properties of these compounds. Only a few unpublished toxicological studies on PFA3 and other PFAs were found; none of them were conducted with human subjects. These studies revealed that PFAs are very low in toxicity (McHale 1972; 3M 1993a,b, 1995a,b,c) (Table 6-2). At very high concentrations, PFA3 could indeed induce cardiac effects (3M 1993a). However, the concentrations of PFA3 that produce cardiac effects are substantially higher than those of other halogenated compounds that are not fully fluorinated. A survey of the literature on fluorine-containing alkanes reveals that substituting fluorine for chlorine or hydrogen atoms in an FC decreases the compound's toxicity, including cardiac toxicity (Table 6-1). CNS toxicity that could impair cognitive performance is another concern associated with exposures to high concentrations of relatively biologically inert FCs (e.g., bromotrifluoromethane (NRC 1984a)). The extremely low solubility of PFA3 in water, blood, and tissues would imply that the PFA3 concentration in the brain would be low. Any CNS toxicity in humans due to PFA3, if it occurs, would likely manifest at only very high concentrations. That is likely to be true for other PFAs also. These speculations are indeed supported by the findings that rats exposed to 80% PFA1, PFA2, or PFA3 experienced only minimal effects (initial hyperactivity followed by hypoactivity (see Table 6-2)).

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 TABLE 6-1 Acute Inhalation Toxicity of Selected Fluorinated Alkanes Compound Namea Exposure, ppm × time Toxicity in Rats Epinephrineb + Exposure (ppm) Cardiac Toxicity in Dogs References CFCl3 FC 11 26,220 × 4 h LC 5000 Lowest concentration that elicited a marked response NRC 1984b CFCl2H FC 21 50,000 × 4 h LC 10,000 Affected 2/12 dogs NRC 1984c CF2ClH FC 22 300,000 × 2 h LC 50,000 Effects observed ACGIH 1991a CF2Cl2 FC 12 620,000 × 3 h LC 80,000 EC50 NRC 1984d CF3Br FC1301 560,000 × 1 h Mild-to-moderate CNS effects 200,000 EC50 McHale 1972 CF4 FC 14 (PFA1) 780,000 × 1 h Mild effects 600,000 Very mild effect McHale 1972 CF3CCl3 FC 113 50,000 × 4 h LC 5000 EC:20-35% NRC 1984e CF3CFCl2 FC 114 600,000 × 2 h LC 45,000 EC50 NRC 1984f CF3CF2Cl FC 115 800,000 × 4 h No clinic signs 150,000 Affected 1/13 dog ACGIH 1991b CF3CF3 FC 116 (PFA2) 800,000 × 1 h Very mild CNS effects, no deaths — — McHale 1972 CF3CF2CF3 FC 218 (PFA3) 800,000 × 1 h Very mild CNS effects, no deaths 400,000 1/8 dog: definite positive response; 1/8 dog: weak response McHale 1972 3M 1993a CF3(CF2)2CF3 (PFA4) 800,000 × 1 h No toxic signs, no deaths 400,000 No effects 3M 1995a CF3(CF2)3CF3 (PFA5) 280,000 × 4 h No effects, no deaths — — 3M 1993a CF3(CF2)4CF3 (PFA6) 381,000 × 1 h No clinical signs, no pathological changes or deaths 170,000 No or very mild effects 3M 1995b a PFAs are abbreviations for perfluoroalkanes used in this document. b Pretreated with epinephrine before inhalation exposure to the compound. LC, lethal concentration; EC, effect concentration; EC50 = concentration that produces an effect on 50% of exposed animals.

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 TABLE 6-2 Toxicity Summary of Perfluoroalkanes PFAs Exposure Concentration Exposure Length Animals Effects Reference PFA1 80% 1 h 10 rats Initial hyperactivity followed by hypoactivity, hyperemia McHale 1972   22.6% 10 d (24 h/d) 20 rats, 20 guinea pigs No clinical signs, no macroscopic or microscopic lesions McHale 1972   20% or 60% — 6 dogs/group (epinephrine-sensitized) Occasional preventricular contractions in three of the six dogs exposed to 60% McHale 1972 PFA2 80% 1 h 10 rats Initial hyperactivity followed by hypoactivity, hyperemia McHale 1972   12.1% 10 d (24 h/d) 20 rats, 20 guinea pigs No clinical signs, no macroscopic or microscopic lesions McHale 1972 PFA3 80% 1 h 10 rats Initial hyperactivity followed by hypoactivity, hyperemia McHale 1972   11% 4 h 10 rats No clinical signs, no macroscopic and microscopic lesions 3M 1993a   11.3% 10 d (24 h/d) 20 rats, 20 guinea pigs No clinic signs, no microscopic lesions McHale 1972   5%, 10%, 20%, 30%, and 40% — 6 dogs/group (epinephrine-sensitized) 1 positive cardiac response (multiple and multifocal ectopic beats), 1 weak positive response in the eight 40%-exposed dogs; no effects at ≤ 30% 3M 1993a PFA4 9.8% and 79% 4 h 10 rats/group No clinical signs, no macroscopic or microscopic lesions 3M 1993b   5%, 10%, 20%, 30%, or 40% — 6-8 dogs/group (epinephrine-sensitized) No cardiac effects 3M 1993b PFA6 38% (saturated vapor) 1 h Rats No clinical signs, no deaths; necropsy showed no gross pathological changes 3M 1995b

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 PFAs Exposure Concentration Exposure Length Animals Effects Reference PFA6 30.5% 30 exposures, 7 h/d, 5 d/w 26 rats Some clinical chemistry and hematological variables differed slightly from those of control rats, but were within biologically acceptable ranges; no macroscopic or microscopic lesions 3M 1995a   5% 2 w (6 h/d, 5 d/w) 20 rats No clinical signs; no macroscopic lesions 3M 1995a   0.5%, 1.5%, or 5% 90 d (6 h/d, 5 d/w) 10 rats/group No clinical signs; some clinical chemistry and hematological variables differed slightly from those of control rats, but were within biologically acceptable ranges; no macroscopic or microscopic lesions 3M 1995a   5%, 10%, or 17.5% — 6 dogs/group (epinephrine-sensitized) No cardiac toxicity 3M 1995a

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 Acute Exposures General Toxicity McHale (1972) evaluated the acute toxicity of inhaled perfluoromethane (PFA1), perfluoroethane (PFA2), and PFA3. Three groups of male rats (10 per group) were exposed for 1 h to 80% (target concentration) of these PFAs (with 20% oxygen) (Table 6-2). Two additional groups of rats were exposed to either air (control) or 56% bromotrifluoromethane (also with 20% oxygen). Bromotrifluoromethane, a compound of known toxicity, was used for comparison. During the exposures, all animals exposed to the PFAs exhibited initial hyperactivity and subsequent hypoactivity, hyperemia (redness of skin), and closed eyes. Rats exposed to bromotrifluoromethane also exhibited initial hyperactivity and subsequent hypoactivity, but also showed increases in respiration rate, abdominal breathing, slight-to-moderate ataxia (incoordination), and a slight bluish tint to the skin. All animals seemed normal during the 14-d post-exposure observation period, and none died. A study by the 3M Company (3M 1993a) on 10 rats (5 males, 5 females) exposed to 11% PFA3 for 4 h showed neither deaths nor clinical signs. Necropsy of these animals after a 15-d observation period revealed some lung congestion in one rat. Microscopic pathological examination of lungs, liver, and kidneys showed no abnormalities in any of the PFA-exposed rats. The higher molecular-weight PFAs also showed little or no biological activity even at high exposure concentrations. Groups of 10 rats (5 males, 5 females) were exposed to 9.8% or 79% perfluorobutane (PFA4) for 4 h or to 38.1% perfluorohexane (PFA6) for 1 h; neither deaths nor pharmacotoxic signs were observed during the exposure or during the 14-d post-exposure period. Necropsy revealed no gross pathological changes (3M 1993a, 1995c). Microscopic findings on animals exposed to PFA4 showed no abnormalities. No information was provided regarding whether tissues of rats exposed to PFA6 were examined microscopically. Cardiac Effects Cardiac sensitization was assessed in a study in which dogs (six to eight per group) were pretreated with epinephrine and exposed either to 5%, 10%, 20%, 30%, or 40% PFA3. One definite positive cardiac response (multiple and multifocal ectopic beats) and one questionable (weak) response were observed among the eight dogs exposed to 40% PFA3 (3M 1993a). However, exposures to PFA4 at the same concentrations produced no cardiac abnormalities (3M

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 1993b). No cardiac effects were observed in any of the dogs exposed to 5%, 10%, or 17.5% PFA6 after being injected with epinephrine (3M 1995c). Trichlorofluoromethane at 2%, used as a positive control, elicited 100% cardiac response in the dogs in all three 3M cardiac-sensitization studies. McHale (1972) also assessed cardiac sensitization in beagles injected intravenously with epinephrine (8 µg/kg) and exposed to 20% PFA1 (80% air) or 60% PFA1 (40% O2). No cardiac arrhythmias were observed; the only responses were occasional preventricular contractions in three of the six dogs exposed to 60% PFA1. These results showed that PFAs have very low cardiac-sensitizing activity. Short-Term and Subchronic Exposures McHale (1972) conducted a 10-d continuous (24 h/d) exposure study with PFA1, PFA2, PFA3, or bromotrifluoromethane. Each exposure group consisted of 10 male and 10 female rats, and 10 male and 10 female guinea pigs. The average analytical concentrations were 20.6% (PFA1), 12.1% (PFA2), 11.3% (PFA3), and 5.1% (bromotrifluoromethane). Parameters studied included toxicity signs, clinical chemistry, hematology, gross pathology of all organs, microscopic histopathology of selected organs (lungs, liver, heart, kidneys, and spleen), organ weights, and organ-to-body-weight ratios of these organs and adrenals. No overt signs of toxicity were present during the exposures. Clinical chemistry data were unremarkable. Hematological examinations of rats and guinea pigs revealed elevation of total leukocyte counts in some PFA-exposed groups (Table 6-3). However, all groups had pneumonitis and associated inflammation that could easily account for the mild elevation in leukocyte counts. Moreover, the elevation of leukocyte counts was not statistically significant for all three PFAs, and not considered an adverse effect of these compounds. Gross pathology showed no lesions associated with any particular group. Histopathological findings also revealed no differences between the FC-exposed animals and the controls. Another inhalation study was conducted with two groups of rats (10 males and 10 females per group) exposed to either air or 10% PFA4 for 2 w (6 h/d; 5 d/w) (3M 1993b). A similar study was also conducted with 5% PFA6 (3M 1995c). Clinical observations, body and organ weight measurements, and gross pathological examination were conducted. No deaths or exposure-related effects were observed for either compound except for a small increase in liver weight of the female rats and in kidney weight of the male rats in the PFA6-exposed group. Microscopic examination showed no difference between the exposed and control groups. 3M also conducted an inhalation study with 26 rats (16 males, 10 females) given 30 exposures (7h/d, 5 d/w) to ''near-satu-

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 rated" (30.5%) PFA6 vapor (3M 1995c). Mortality, abnormal weight patterns, and gross pathological changes were not observed. Microscopic examination of the lung and liver showed no significant histopathological changes. Blood chemistry revealed that some of the parameters in exposed animals were different from those of control animals. However, according to 3M, all of these blood results were within biologically acceptable ranges. A 90-d inhalation study (6 h/d, 5 d/w) conducted with groups of 10 rats (5 males, 5 females) exposed to 0, 5000, 15,000, or 50,000 ppm PFA6 produced no exposure-related deaths. Clinical signs were normal. Minor differences in several hematological and clinical-chemistry variables were observed, but according to 3M (1995b), the values from the exposed animals were within normal limits and were not considered toxicologically significant. Histopathological examination showed no exposure-related histological changes. Genotoxicity Vapors of PFA3, PFA4, PFA5, or PFA6 were tested for their potential mutagenic activity on Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98, and TA100) in the presence or absence of liver enzymes. The concentrations tested were 80% for PFA3 and PF4 and near-saturated vapors (> 10%) for PFA5 and PFA6. No mutagenic activity was observed (3M 1993a, b, 1995b, c). These results are not surprising given the extremely low water solubility and chemical inertness of these compounds. EXPOSURE LIMITS Exposure Limits Set by Other Organizations No exposure limits have been established for any PFAs by any organization in the United States, including 3M, the manufacturer of the products. The Russian Space Agency has set a maximum allowable concentration for PFA3 of 150 mg/m3 (G. I. Solomina and L. N. Mouakhamedieva, Institute of Biomedical Problems, Moscow, personal commun., 1996). Nasa Spacecraft Maximum Allowable Concentrations (SMACs) SMACs are derived in accordance with guidelines developed by the SMACs subcommittee of the Committee on Toxicology (NRC 1992). The SMACs (Table 6-3) are set by choosing the lowest values among the ACs (see Table 6-4).

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 TABLE 6-3 Spacecraft Maximum Allowable Concentrations (SMACs) of Perfluoropropane Exposure Duration Concentration, ppm Concentration, mg/m3 Target Toxicity 1 h 11,000 85,000 CNS effects 24 h 11,000 85,000 CNS effects 7 d 11,000 85,000 CNS effects 30 d 11,000 85,000 CNS effects 180 d 11,000 85,000 CNS effects RATIONALE FOR ACCEPTABLE CONCENTRATIONS (ACS) FOR EXPOSURES ACs Based on the CNS Effects of the Acute Exposure Studies PFA3 is not metabolized. The brain is a richly and fast-perfused organ. Thus, the CNS effects of PFA3 would be due solely to PFA3 concentration in the brain. For a given exposure concentration, the blood concentration of PFA3 would likely approach a steady state within 60 min, and the concentration in the brain will follow the blood in a comparable time. Thus, the possible CNS effects induced by PFA3 would be independent of exposure length of ≤ 60 min. Thus, one AC value is set for all exposure durations. McHale (1972) reported that a 1-h exposure of rats to 80% PFA3 resulted in only mild CNS responses. 3M reported that a 4-h exposure of rats to 11% PFA3 caused no clinical signs (3M 1993a). An AC of 1.1% is obtained by applying an animal-to-human extrapolation safety factor of 10 to the NOAEL of 11%. ACs Based on Cardiac Effects The heart, like the brain, is also a richly and fast-perfused organ. For the reasons presented above, one AC value could be set for all exposure durations. 3M (1993a) has reported that no cardiac effects were observed in epinephrine-treated dogs exposed to 30% PFA3. Therefore, using an uncertainty factor of 10 to account for interspecies variability, the AC is set at 3% (30% ÷ 10). The space factor of 5 is not used here because the epinephrine-treated dog model is a conservative test, and epinephrine is probably associated with cardiac arrhythmias observed in humans.

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 ACs Based on Subchronic Animal Exposure Data McHale (1972) showed that continuous inhalation exposure of rats to 11.3% PFA3 for 10 d (24 h/d) produced neither clinical signs nor microscopic lesions. Using an uncertainty factor of 10 for interspecies variability, ACs for 7 d, 30 d, and 180 d of exposure are set at 1.1% (11.3% ÷ 10). The AC derived from various toxicity end points are summarized in Table 6-4. The SMACs are set by choosing the lowest values among these ACs.

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 TABLE 6-4 Acceptable Concentrations of PFA3 End Point, Exposure Data, Reference   Uncertainty Factors Acceptable Concentrations, ppm Species Time Species Spaceflight 1 h 24 h 7 d 30 d 180 d CNS effects Rat 1 10 — 11,000 11,000 11,000 11,000 11,000 NOAEL, 11% (3M 1993a)                   Cardiotoxicity Dog 1 10 1a 30,000 30,000 30,000 30,000 30,000 NOAEL, 30% (3M 1993a)                   Subchronic toxicity Rat 1 10 — NS NS 11,000 11,000 11,000 NOAEL, 11.3% (McHale 1972)                   SMACs         11,000 11,000 11,000 11,000 11,000 —, not applicable. NS, not set. aSee text for explanation of not using the spaceflight factor 5.

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 SMACs for Other Volatile Perfluoroalkanes As discussed above, PFAs have extremely low solubility in water and are biologically inert and extremely low in toxicity. No evidence exists to suggest that increasing or decreasing the molecular weight of these compounds drastically changes their toxicity. Therefore, the SMACs for the other straight-chain PFAs are set at the same values as those of PFA3. A survey of perfluorocyclobutane toxicity indicates that this cyclic PFA is more cardiotoxic than the aliphatic PFAs discussed in this document. The generalization about the toxicity of aliphatic PFAs would not be applicable to the cyclic PFAs. Therefore, the SMACs set for PFAs in this document would not be applicable to cyclic PFAs. ACKNOWLEDGMENTS The author is grateful to Dr. Henry Trochimowicz of Haskell Laboratory (du Pont de Nemours & Co.), and Dr. Roger Perkins of 3M for kindly providing several unpublished reports. REFERENCES ACGIH. 1991a. Chlorodifluoromethane. Pp. 282-283 in Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th Ed. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio. ACGIH. 1991b. Chloropentafluoroethane. Pp. 297-298 in Documentation of the Threshold Limit Values and Biological Exposure Indices, 6th Ed. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio. Aviado, D.M., and M.S. Micozzi. 1981. Fluorine-containing organic compounds. Pp. 3071-3115 in Patty's Industrial Hygiene and Toxicology, Vol. II B, 3th Ed. G.D. Clayton and F.E. Clayton, eds. New York: John Wiley & Son. Creech, J.R., R.K. Black, S.K. Neurath, M.C. Caracci, R.J. William, and G.W. Jepson.. 1995. Inhalation Uptake and Metabolism of Halon 1301 Replacement Candidates, HFC 227, HFC-125, and FC-218. Interim Report: AL/OE-TR-1995-0022. Occupational and Environmental Health Directorate, Toxicology Division, Armstrong Laboratory, Wright-Patterson Air Force Base, Dayton, Ohio. Gargas, M.L. M.E. Andersen, and H.J. Clewell III. 1986. A physiologically based simulation approach for determining metabolic constants from gas uptake data. Toxicol. Appl. Pharmacol. 86:341-352. Gargas, M.L., R.J. Burgess, D.E. Voisard, G.H. Cason, and M.E. Anderson. 1989. Partition coefficients of low-molecular-weight volatile chemicals in various liquid and tissues. Toxicol. Appl. Pharmacol. 98:87-99. Goldstein, A., L. Aronow, and S.M. Kalman. 1974. The time course of drug action.

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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants: Volume 4 Pp. 338-355 in Principles of Drug Action, 2nd Ed. New York: John Wiley & Sons. Hanig, J.P., and E.H. Herman. 1991. Toxic responses of the heart and vascular systems. Pp. 442 in Casarett and Doull's Toxicology: The Basic Science of Poison, 4th Ed. M.O. Amdur, J. Doull, and C.D. Klaassen, eds. New York: Pergamon. Limero, T. 1995. Analysis of Mir-18 Flight Samples. An internal memo to John James, NASA Toxicology Monitor. Toxicology Laboratory, KRUG Life Sciences, Houston, Tex. McHale, E.T. 1972. Final Technical Report on Habitable Atmospheres Which Do Not Support Combustion. Report submitted to U.S. Army Research Office, Arlington, Va., by Atlantic Research Corporation, Alexandria, Va. NRC. 1984. Bromotrifluoromethane. Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 3. Washington, D.C.: National Academy Press. NRC. 1984a. Fluorocarbon 11. Pp. 26-33 in Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, D.C.: National Academy Press. NRC. 1984b. Fluorocarbon 21. Pp. 41-45 in Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, D.C.: National Academy Press. NRC. 1984c. Fluorocarbon 12. Pp. 34-40 in Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, D.C.: National Academy Press. NRC. 1984d. Fluorocarbon 113. Pp. 46-50 in Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, D.C.: National Academy Press. NRC. 1984e. Fluorocarbon 114. Pp. 51-57 in Emergency and Continuous Exposure Limits for Selected Airborne Contaminants, Vol. 2. Washington, D.C. : National Academy Press. NRC. 1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants. Washington, D.C.: National Academy Press. 3M. 1993a. Product Toxicity Summary Sheet on PF-5030 3M Brand Performance Fluid. 3M, St. Paul, Minn. 3M. 1993b. Product Toxicity Summary Sheet on PF-5040 3M Brand Performance Fluid. 3M, St. Paul, Minn. 3M. 1995a. Material Safety Data Sheet on PF-5030 3M Performance Fluid. 3M, St. Paul, Minn. 3M. 1995b. Product Toxicity Summary Sheet on PF-5050 3M Brand Performance Fluid. 3M, St. Paul, Minn. 3M. 1995c. Product Toxicity Summary Sheet on PF-5060 3M Brand Performance Fluid. 3M, St. Paul, Minn.