1 Proposed: April 2009

2 

3 

4 

5 ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 

6 FOR

7 PERFLUOROISOBUTYLENE (PFIB) 

8 

9 (CAS Reg. No. 382-21-8) 

10 

11 C4F8

12 

13 

14 

15 

16 PROPOSED 

17 

18 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 2 of 43 

1 

2 

3 

4 ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 

5 FOR 

6 PERFLUOROISOBUTYLENE (PFIB) 

7 (CAS Reg. No. 382-21-8) 

8 

9 

10 

11 

12 PROPOSED

13 

14 

15 

16 

17 

18 

19 

20 

21 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 3 of 43 

1 

2 

3 

4 PREFACE

5 

6 Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 

7 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous 

8 Substances (NAC/AEGL Committee) has been established to identify, review and interpret 

9 relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic 

10 chemicals. 

11 

12 AEGLs represent threshold exposure limits for the general public and are applicable to 

13 emergency exposure periods ranging from 10 minutes to 8 hours. Three levels – AEGL-1, 

14 AEGL-2 and AEGL-3 C are developed for each of five exposure periods (10 and 30 minutes, 1 

15 hour, 4 hours, and 8 hours) and are distinguished by varying degrees of severity of toxic effects. 

16 The three AEGLs are defined as follows: 

17 

18 AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per 

cubic meter [ppm or mg/m3 19 ]) of a substance above which it is predicted that the general 

20 population, including susceptible individuals, could experience notable discomfort, irritation, or 

21 certain asymptomatic, non-sensory effects. However, the effects are not disabling and are 

22 transient and reversible upon cessation of exposure. 

23 

AEGL-2 is the airborne concentration (expressed as ppm or mg/m3 24 ) of a substance above 

25 which it is predicted that the general population, including susceptible individuals, could 

26 experience irreversible or other serious, long-lasting adverse health effects or an impaired ability 

27 to escape. 

28 

AEGL-3 is the airborne concentration (expressed as ppm or mg/m3 29 ) of a substance above 

30 which it is predicted that the general population, including susceptible individuals, could 

31 experience life-threatening health effects or death. 

32 

33 Airborne concentrations below the AEGL-1 represent exposure levels that could produce 

34 mild and progressively increasing but transient and nondisabling odor, taste, and sensory 

35 irritation or certain asymptomatic, non-sensory effects. With increasing airborne concentrations 

36 above each AEGL, there is a progressive increase in the likelihood of occurrence and the 

37 severity of effects described for each corresponding AEGL. Although the AEGL values 

38 represent threshold levels for the general public, including susceptible subpopulations, such as 

39 infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized 

40 that individuals, subject to unique or idiosyncratic responses, could experience the effects 

41 described at concentrations below the corresponding AEGL. 

42 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 4 of 43 

1 TABLE OF CONTENTS 

2 PREFACE....................................................................................................................... 3

3 TABLE OF CONTENTS.................................................................................................. 4

4 LIST OF TABLES ........................................................................................................... 6

5 SUMMARY...................................................................................................................... 7

6 1. INTRODUCTION..............................................................................................................................................9

7 2. HUMAN TOXICITY DATA.............................................................................................................................9

8 2.1. Acute lethality ...........................................................................................................................................9

9 2.2 Nonlethal acute toxicity..........................................................................................................................10

10 2.3. Developmental/Reproductive Toxicity..................................................................................................10

11 2.4. Genotoxicity ............................................................................................................................................10

12 2.5. Summary .................................................................................................................................................10

13 3. ANIMAL TOXICITY DATA..........................................................................................................................10

14 3.1. Acute Lethality........................................................................................................................................10

15 3.1.1. Rats .....................................................................................................................................................10

16 3.1.2. Mice.....................................................................................................................................................15

17 3.1.3. Guinea pigs.........................................................................................................................................16

18 3.1.4. Rabbits................................................................................................................................................16

19 3.1.5. Cats.........................................................................................................................................................17

20 3.2. Nonlethal Acute Toxicity........................................................................................................................17

21 3.2.1. Rats .....................................................................................................................................................17

22 3.3. Repeat Dose Studies................................................................................................................................17

23 3.4. Developmental/Reproductive Toxicity..................................................................................................18

24 3.5. Genotoxicity ............................................................................................................................................18

25 3.6. Chronic Toxicity/Carcinogenicity .........................................................................................................18

26 3.7. Summary .................................................................................................................................................18

27 4. SPECIAL CONSIDERATIONS .....................................................................................................................21

28 4.1. Metabolism and Disposition...................................................................................................................21

29 4.2. Mechanism of Toxicity ...........................................................................................................................21

30 4.3. Other Relevant Information ..................................................................................................................23

31 4.3.1. Interspecies Variability .....................................................................................................................23

32 4.3.2. Intraspecies Variability .....................................................................................................................23

33 4.3.3 Structure Activity...............................................................................................................................24

34 4.3.4. Concentration-Exposure Duration Relationship.............................................................................24

35 5. DATA ANALYSIS FOR AEGL-1 ..................................................................................................................25

36 5.1. Summary of Human Data Relevant to AEGL-1 ..................................................................................25

37 5.2. Summary of Animal Data Relevant to AEGL-1...................................................................................25

38 5.3. Derivation of AEGL-1 ............................................................................................................................25

39 6. DATA ANALYSIS FOR AEGL-2 ..................................................................................................................25

40 6.1. Summary of Human Data Relevant to AEGL-2 ..................................................................................25

41 6.2. Summary of Animal Data Relevant to AEGL-2...................................................................................25

42 6.3. Derivation of AEGL-2 ............................................................................................................................25
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 5 of 43 

1 7. DATA ANALYSIS FOR AEGL-3 ..................................................................................................................26

2 7.1. Summary of Human Data Relevant to AEGL-3 ..................................................................................26

3 7.2. Summary of Animal Data Relevant to AEGL-3...................................................................................26

4 7.3. Derivation of AEGL-3 ............................................................................................................................26

5 8. SUMMARY OF AEGLs ..................................................................................................................................27

6 8.1. AEGL Values and Toxicity Endpoints..................................................................................................27

7 8.2. Comparison with Other Standards and Guidelines.............................................................................28

8 9. REFERENCES.................................................................................................................................................29

9 APPENDIX A: DERIVATION OF PFIB AEGLS........................................................... 33

10 APPENDIX B: TIME SCALING CALCULATIONS ....................................................... 36

11 APPENDIX C: DERIVATION SUMMARY FOR PFIB.................................................. 38

12 APPENDIX D: CATEGORY PLOT FOR PFIB.............................................................. 41

13 

14 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 6 of 43 

1 LIST OF TABLES 

2 

3 S 1. SUMMARY OF AEGL VALUES FOR PFIB...................................................................................................8

4 

5 TABLE 1. CHEMICAL AND PHYSICAL PROPERTIES.....................................................................................9

6 TABLE 2. SUMMARY OF MORTALITY DATA IN RATS EXPOSED TO PFIB FOR UP TO 6 HOURS. ..11

7 TABLE 3. SUMMARY OF MORTALITY DATA IN RATS EXPOSED TO PFIB FOR 4 HOURS. ...............11

8 TABLE 4. SUMMARY OF MORTALITY DATA IN RATS EXPOSED TO PFIB FOR 0.25 TO 10 

9 MINUTES.........................................................................................................................................................12

10 TABLE 5. SUMMARY OF MORTALITY DATA FOR ANIMALS EXPOSED TO HEAVY 

11 PRODUCTS/HIGH BOILERS FOR 2 HOURS............................................................................................15

12 TABLE 6. SUMMARY OF MORTALITY DATA IN MICE EXPOSED TO PFIB FOR 10 MINUTES.........15

13 TABLE 7. SUMMARY OF MORTALITY DATA IN MICE EXPOSED TO PFIB FOR 1 MINUTE..............16

14 TABLE 8. SUMMARY OF SELECTED ANIMAL INHALATION DATA ........................................................19

15 TABLE 9. COMPARISON OF PFIB LC50 VALUES FOR VARIOUS ANIMAL SPECIES............................23

16 TABLE 10. AEGL-1 VALUES FOR PFIB..............................................................................................................25

17 TABLE 11. AEGL-2 VALUES FOR PFIB..............................................................................................................26

18 TABLE 12. AEGL-3 VALUES FOR PFIB..............................................................................................................27

19 TABLE 13. SUMMARY OF AEGL VALUES........................................................................................................28

20 TABLE 14. STANDARDS AND GUIDELINES FOR PFIB..................................................................................28

21 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 7 of 43 

1 SUMMARY

2 

3 Perfluoroisobutylene (PFIB) is a colorless gas that is formed during the production of 

4 tetrafluoroethylene. It is also produced in relatively small amounts during the heated 

decomposition of polytetrafluoroethylene (PTFE or Teflon® 5 ) and some closely related plastics. 

6 It is also produced by the thermal decomposition of the fluorinated primary fluid in the 

7 condensation reflow soldering process. PFIB may be synthesized by atmospheric-pressure 

8 pyrolysis of tetrafluoroethylene dimer (i.e., octafluorocyclobutane), which gives a 50% yield of 

9 PFIB. 

10 

11 Data were insufficient for derivation of AEGL-1 values; therefore, AEGL-1 values are not 

12 recommended for PFIB. 

13 

14 In the absence of appropriate chemical-specific data, the AEGL-3 values were divided by 3 

15 to derive AEGL-2 values for PFIB (NRC, 2001). This approach is justified by the steep 

16 concentration-response curve observed in several animal studies. No rats died when exposed to 

17 0.25 ppm PFIB for 4 hours; whereas 100% lethality (6/6) was noted at 0.5 ppm for 4 hours 

18 (DuPont, 1966). No mortality was noted in rats exposed to 228 ppm PFIB for 0.25 min and 

19 100% mortality (10/10) was noted at 468 ppm. No mortality was noted in rats exposed to 20 

20 ppm PFIB for 5 min and 9/10 rats died at 32 ppm. In rats exposed for 10 minutes, no mortality 

21 was noted at 10 ppm and 8/10 rats died at 20 ppm (Smith et al., 1982). No mortality was noted 

22 in mice exposed to 98 ppm PFIB for 1 minute; whereas, 6/6 mice died at 116 ppm (Fusheng et 

23 al., 1992), and no mice died when exposed to 10 ppm for 10 minutes and 10/10 mice died at 65 

24 ppm (Bide et al., 2000). Finally, no mortality was noted in rats, mice, guinea pigs, and rabbits 

25 exposed to approximately 0.70 ppm PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 4/5 

26 guinea pigs, and 3/3 rabbits died when exposed to 1.5 ppm (Paulet and Bernard, 1968). 

27 

28 The highest concentration causing no mortality in rats exposed to PFIB for 4-hours (0.25 

29 ppm) was used as the point-of-departure for AEGL-3 values (DuPont, 1966). Clinical signs 

30 noted at this concentration included face washing, hyperemia, sneezing, hypernea, dyspnea, and 

31 decreased responsiveness. There was 100% mortality (6/6) at the next highest concentration 

32 tested (0.5 ppm). An interspecies uncertainty factor of 1 and an intraspecies uncertainty factor of 

33 3 were applied. The interspecies UF of 1 is considered sufficient because lethality data available 

34 for several animal species suggest little interspecies variability; LC50 values for given exposure 

35 durations are essentially equivalent (Table 9). Reported 1-min LC50 values are 107 ppm for mice 

36 (Fusheng et al., 1992) and 122 ppm for rats (Smith et al., 1982); 10-minute values are 11.8 ppm 

37 for mice (Bide et al., 2000) and 17 ppm for rats (Smith et al., 1982); 15 minute values are 6.1 

38 ppm for mice and 6.7 ppm for rats (Karpov, 1977); and reported 2-hour values are 0.98 ppm 

39 (Paulet and Bernard, 1968) and 1.6 ppm for mice (Karpov, 1977), 1.05 ppm for rats and guinea 

40 pigs (Paulet and Bernard, 1968), and 1.20 ppm for rabbits (Karpov, 1977). The intraspecies UF 

41 of 3 is supported by the steep concentration-response curve for PFIB (described above for 

AEGL-2), implying limited intraspecies variability. Values were scaled across time using the cn 42 

43 x t = k, relationship where the exponent, n, is the chemical-specific value of 1.0, derived from rat 

44 LC50 data ranging from 0.25 to 120 minutes. 

45 

46 The calculated values are listed in the table below. 

47 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 8 of 43 

S 1. Summary of AEGL Values for PFIB

Classification 10-min 30-min 1-h 4-h 8-h 

Endpoint 

(Reference) 

AEGLB1 

(Nondisabling) 

NR NR NR NR NR Insufficient data 

AEGLB2 

(Disabling) 

0.67 ppm 

(5.5 mg/m3

) 

0.22 ppm 

(1.8 mg/m3) 

0.11 ppm 

(0.90 mg/m3)

0.028 ppm 

(0.23 mg/m3) 

0.014 ppm 

(0.11 mg/m3) 

1/3 the AEGL-3 

values. 

AEGLB3 

(Lethal) 

2.0 ppm 

(16 mg/m3

) 

0.67 ppm 

(5.5 mg/m3) 

0.33 ppm 

(2.7 mg/m3) 

0.083 ppm 

(0.68 mg/m3) 

0.042 ppm 

(0.34 mg/m3) 

Highest concentration 

causing no lethality in 

rats (0.25 ppm; 4-hr). 

 100% mortality at 

next concentration 

(0.5 ppm) tested 

(DuPont, 1966) 

NR: Not Recommended due to insufficient data. Absence of an AEGL-1 value does not imply that concentrations 

below the AEGL-2 are without effect. 

1 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 9 of 43 

1 

2 1. INTRODUCTION

3 

4 Perfluoroisobutylene (PFIB) is a colorless gas that is formed during the production of 

5 tetrafluoroethylene (Kennedy, 1990; Gangal, 2004). It is also produced in relatively small 

amounts during the heated decomposition of polytetrafluoroethylene (PTFE or Teflon® 6 ) and 

7 some closely related plastics. It is also produced by the thermal decomposition of the fluorinated 

8 primary fluid in the condensation reflow soldering process (Shih et al., 1990). PFIB may be 

9 synthesized by atmospheric-pressure pyrolysis of tetrafluoroethylene dimer (i.e., 

10 octafluorocyclobutane), which gives a 50% yield of PFIB. No production information was 

11 located. Chemical and physical property data are limited; available information is presented in 

12 Table 1. 

13 

TABLE 1. Chemical and Physical Properties 

Parameter Value Reference 

Synonyms PFIB; Octafluoroisobutylene; Octafluoro-secbutylene; 1-Propene, 1,1,3,3,3-pentafluoro-2- 

(tri fluoromethyl) 

AIHA, 2000; ACGIH, 1991 

Chemical formula C4F8 ACGIH, 1991 

Molecular weight 200 AIHA, 2000 

CAS Reg. No. 382-21-8 AIHA, 2000 

Physical state Colorless gas AIHA, 2000 

Density 1.5922 g/ml at 0 oC (liquid) AIHA, 2000 

Boiling point 7oC at 760 mmHg AIHA, 2000 

Conversion factors 1 ppm = 8.2 mg/m3

1 mg/m3

 = 0.12 ppm 

AIHA, 2000 

14 

15 

16 2. HUMAN TOXICITY DATA 

17 2.1. Acute lethality 

18 

19 Makulova (1965) monitored 5 patients (2 men and 3 women) accidentally exposed to 

20 PFIB at work. Two were chemical plant operators and the other three were chemical engineer 

21 technologists involved in laboratory work. All but one [female] patient reported that the contact 

22 with PFIB lasted less than one minute during which time 2 to 5 breaths were taken. Immediately 

23 after exposure, all patients developed cough, difficulty breathing, and deep chest pains. 

24 Approximately 6 to 8 hours after exposure, these symptoms increased in severity. No ocular or 

25 upper respiratory irritation was noted. All patients ran fevers that lasted between 2 and 25 days, 

26 and all developed pulmonary edema. The duration of the in-patient stay of the three patients was 

27 13, 17, and 23 days. They were discharged as healthy, and follow-up checkups over 2 years 

28 revealed no complications in these patients. One [male] patient remained hospitalized for over 2 

29 months due to exudative pleuritis. Another [female] patient died two days after exposure; post30 mortem examination confirmed toxic fluid pneumonia and lung edema, hemorrhage into the left 

31 adrenal and full bloodiness of internal organs. 

32 

33 Five workers were accidentally exposed to a gas that contained 2% PFIB, and they 

34 reported irritation of the respiratory tract within 24 hours (DuPont, 1976). A majority developed 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 10 of 43 

1 a cough and exhibited choking or shortness of breath, and a few experienced wheezing. One of 

2 the five workers died 11 days after exposure, and another one died 13 days after exposure. 

3 Pathological examination revealed pulmonary congestion. 

4 

5 2.2 Nonlethal acute toxicity 

6 

7 A worker was exposed to PFIB for approximately 3 minutes after a spill of a 2% PFIB 

8 mixture (DuPont, 1976). He reported a bad odor, bad taste in the mouth, nausea, and weakness. 

9 After returning to fresh air, he recovered and experienced no more symptoms. A PFIB 

10 concentration of 0.04 ppm was measured one-half hour post-exposure, and it was estimated that 

11 the worker could have been exposed to more than 4 ppm PFIB (assumes 10 to 40 air 

12 changes/hour for a factory) (Kennedy and Geisen, 1985).

13 

14 2.3. Developmental/Reproductive Toxicity 

15 

16 One of the exposed workers in the Makulova (1965) study was 15-16 weeks pregnant at 

17 the time of exposure. The pregnancy ended in a normal, term delivery, the child was reportedly 

18 healthy. 

19 

20 2.4. Genotoxicity 

21 

22 No data were located. 

23 

24 2.5. Summary 

25 

26 Human data are limited to occupational exposures with no definitive concentration or 

27 duration parameters. Clinical signs included cough, difficulty breathing, wheezing, nausea, chest 

28 pain, weakness, and bad taste. Pulmonary edema and congestion were noted at autopsy. 

29 

30 

31 

32 3. ANIMAL TOXICITY DATA 

33 3.1. Acute Lethality 

34 

35 3.1.1. Rats

36 

37 Groups of two male albino rats were exposed whole-body for up to six hours to nominal 

38 concentrations of 0.3, 0.5, or 1.0 ppm of PFIB from a supply cylinder and diluted with an air 

39 stream in a mixing chamber (DuPont, 1956; 1961). Nominal concentrations were calculated 

40 from the flow rates of PFIB gas and air. Clinical signs of respiratory impairment were noted at 

41 0.5 and 1.0 ppm. At 0.5 ppm, slight dyspnea was noted at the end of the exposure period, and 

42 both of these rats died the following night. At 1.0 ppm clinical signs progressed from labored 

43 respiration noted during the first two hours of exposure, to gasping, cyanosis, and terminal 

44 convulsions, with both rats being dead by 5 hours and 25 minutes after the start of treatment. 

45 Pulmonary edema was noted in rats exposed to 0.5 and 1.0 ppm; rats in the 1.0 ppm group also 

46 exhibited congestion of the brain. The rats exposed to 0.3 ppm did not show any signs of 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 11 of 43 

1 toxicity during the exposure; however, a slight increase in respiration rate was noted on the first 

2 day after exposure. No treatment-related effects were noted at terminal sacrifice (10 days post3 exposure). Data are summarized in Table 2. 

4 

TABLE 2. Summary of mortality data in rats exposed to PFIB for up to 6 hours.

Concentration (ppm) Duration (hours) Mortality Clinical Signs Necropsy findings 

0.3 6 0/2 none none 

0.5 6 2/2 slight dyspnea Pulmonary edema 

1.0 4.25 2/2 dyspnea; cyanosis Pulmonary edema 

5 DuPont, 1956; 1961 

6 

7 Groups of six male ChR-CD rats were exposed whole body for up to 4 hours to 0.25, 

8 0.50, or 1.00 ppm PFIB (DuPont, 1966). Using a Harvard syringe drive, the gas was metered 

9 into a T-tube, and a stream of air carried the gas into the 16-liter exposure chamber for the 

10 treatment. Concentrations were measured by gas chromatography. All 6 rats exposed to 1.00 

11 ppm died. Clinical signs noted during exposure at 1.0 ppm included face washing, hyperemia, 

12 dyspnea, pale ears, rapid respiration, and convulsions (in one animal). All 6 rats exposed for 4 

13 hours at 0.50 ppm were found dead the following day. Clinical signs were similar to those 

14 described for the 1.0 ppm group except that no convulsions occurred. Two groups of 6 rats each 

15 were exposed to 0.25 ppm for 4 hours. None died from the exposure. No gross effects attributed 

16 to the treatment were seen at necropsy in these 12 rats. Clinical signs during exposure included 

17 face washing, hyperemia, sneezing, hyperpnea, dyspnea, and they were “mildly responsive”. 

18 Half of the rats experienced dyspnea, which lasted for 3 hours after the end of the exposure. 

19 Data are summarized in Table 3. 

20 

TABLE 3. Summary of mortality data in rats exposed to PFIB for 4 hours. 

Conc. 

(ppm) 

Mortality Fate Clinical signs 

 During exposure Post-exposure 

0.25 0/6 2/6 sacrificed 1-day post-exposure 

2/6 sacrificed 2days post-exposure 

2/6 sacrificed 7-days post-exposure 

Face washing, hyperemia, 

sneezing, hypernea, dyspnea, 

mildly responsive 

Dyspnea for 3 

hr (3/6) 

0.25 0/6 6/6 sacrificed 14-days post-exposure Same as above Same as above 

0.5 6/6 Found dead 1-day post-exposure Same as 1.0 ppm except no 

convulsions; mildly responsive 

- 

1.0 6/6 Found dead during exposure (1:36-

2:19 hrs elapsed) 

Face washing, hyperemia, 

hypernea, dyspnea, pale ears, rapid 

respiration, convulsions (1/6) 

- 

21 DuPont, 1966 

22 

 Groups of 10 male ChR-CD® 23 albino rats were exposed nose-only to varying 

24 concentrations of PFIB for 0.25, 0.50, 1, 2, 5, or 10 minutes, followed by a 14-day observation 

25 period (Smith et al., 1982). A metered flow of PFIB (>99% pure) from a compressed gas 

26 cylinder was dispersed into the small volume exposure chamber using a high rate of flow to 

27 rapidly achieve chamber equilibrium. It was diluted with houseline air at 15.6 liters per minute 

for dispersal into the exposure chamber. Rats were enclosed individually in sealed Parafilm® 28 -

29 wrapped wire-mesh restraining cages and were positioned in the portals so that only their snouts 

30 protruded into the chamber. Gross pathological examinations were given to at least two 

31 representative rats that died within 24 hours after each exposure. Two to three gas samples per 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 12 of 43 

1 exposure were collected from the different sampling ports and were analyzed by gas 

2 chromatography. There were no deaths or clinical signs noted during exposure; however, the 

3 lack of clinical observations may be due to the fact that animals were exposed in nose-only 

4 restraints. Most deaths occurred between eight and 24 hours after the exposure. Clinical signs 

5 24 hours after the exposures were similar for all exposure scenarios. Mild to moderate weight 

6 loss was observed, sometimes continuing up to 48 hours. At the higher concentrations there 

7 were also signs of respiratory impairment (wheezing and labored breathing), but those 

8 disappeared within 48 hours. Deaths were often accompanied by nasal and oral discharge of a 

9 clear yellow fluid. Pathological examination revealed heavy lungs that contained a foamy 

10 exudate characteristic of acute pulmonary edema. Mortality data are summarized in Table 4. 

11 

TABLE 4. Summary of mortality data in rats exposed to PFIB for 0.25 to 10 minutes. 

Exposure Duration (min) Average Concentration (ppm) Mortality LC50 (ppm) 

(±95%) 

228 0/10 

248 2/10 

318 5/10 

334 2/10 

430 6/10 

0.25 

468 10/10 

361 (321-415) 

144 0/10 

159 3/10 

216 6/10 

260 8/10 

0.5 

442 9/10 

214 (179-261) 

100 1/10 

102 0/10 

106 5/10 

130 6/10 

158 9/10 

1 

832 10/10 

122 (113-139) 

71 1/10 

81 1/10 

86 6/10 

92 7/10 

2 

100 9/10 

86 (82-91) 

20 0/10 

24 1/10 

27 7/10 

28 3/10 

5 

32 9/10 

28 (26-29) 

10 0/10 

15 2/10 

17 5/10 

10 

20 8/10 

17 (15-19) 

12 Smith et al., 1982 

13 

14 Danishevskii and Kochanov (1961) reported a 2-hour “maximal tolerance” 

15 concentration of 1.5 ppm and “absolute lethal” (assumed to be 100% lethality) concentration of 

16 1.8 ppm for albino rats. Histology showed pulmonary hemorrhages and edema, degenerative 

17 changes in the kidney, and fatty changes in the liver. No other details were provided. 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 13 of 43 

1 Karpov (1977) reported a 15-min LC50 of 6.7 ppm for rats. Karpov (1977) reported a 2-

2 hour LC50 of 11.6 ppm for white rats, and stated that rats exposed to 61-183 ppm PFIB died 

3 within 1 minute. Pulmonary edema was given as the cause of death. 

4 

5 Moore, Jaeger and Jaax (1991) studied the effect of exercise on the pulmonary toxicity of 

6 PFIB in male Sprague-Dawley rats. Groups of 12 rats trained to exercise on a treadmill were 

7 sham-exposed or exposed to 12.2 ppm of PFIB vapor for 10 minutes. They were then exercised 

8 on a treadmill until they were so exhausted that they refused to run when prodded with an 

9 electric shock. Following 24 hours of observation, they were sacrificed, weighed, and their 

10 livers, hearts and kidneys were examined for pathological changes. There was a significant 

11 (p<0.01) difference in the endurance times of the two groups, with the PFIB-exposed group 

12 having about 10 minutes more of endurance (64.71 vs 53.29 min for the PFIB and sham exposed 

13 rats, respectively). The PFIB-exposed group showed significantly decreased activity and 

14 piloerection starting 6 hours after exposure. Two of the 12 PFIB-exposed rats had breathing 

15 difficulty and died 14 and 17 hours after exposure. The PFIB-exposed rats had increased 

16 absolute and relative lung weights regardless of whether they had been exercised; however, the 

17 PFIB-induced edema was more severe in the exposed rats that had been exercised. No effects of 

18 the treatment were seen on the livers, hearts, or kidneys. 

19 Lehnert et al. (1995) also investigated the effects of exercise on PFIB-treated male Fischer 

20 344 rats exposed to 12 ppm for 10 minutes. This treatment regimen reportedly results in a 

21 latency period of approximately 8 hours before the occurrence of overt pulmonary edema. The 

22 study examined the effect of exercise on these animals during and after the latency period. 

23 Initial results indicated that exercise during the latency period did not potentiate the injurious 

24 response, as judged by conventional lung gravimetric and histopathologic criteria. However, 

25 when overt pulmonary edema was preexistent, exercise had a potentiating effect. 

26 

27 Brown and Rice (1991) conducted an electron microscopy study on female Porton rat lungs 

28 during the first 24 hours after a single 1.5-minute exposure to 78 ppm PFIB (96% purity). Rats 

29 were sacrificed within 5 minutes of exposure or at 1, 2, 3, 4, 6, 8, 12, 16, or 24 hours post30 exposure. Within five minutes after the head-only exposures, changes in the bronchioles and 

31 peribronchial alveoli were observed that took the form of alterations in cilial structure, increased 

32 pinocytosis and electron lucency. There was occasional vesicle formation of type I alveolar 

33 epithelial cells. Intercellular leakage was also noted with minimal fluid accumulation in the 

34 alveolar spaces. Gradually there was development of pulmonary edema, which was visible 

35 histologically between two and three hours after treatment. Deaths occurred starting at seven 

36 hours post-exposure. Rats that were killed for examination 24 hours after treatment had 

37 widespread pulmonary edema and interstitial infiltration by lympho-mononuclear cells and 

38 macrophages. 

39 

40 Lehnert et al. (1993) also studied damage to the lungs of PFIB-treated rats. Adult male 

41 Wistar rats were exposed for 10 minutes to 6.1, 10, 11, 13, or 24 ppm of PFIB. Groups of rats 

42 were killed at various times after the exposures for gravimetric and histopathological 

43 examination of the lungs. Gravimetric measurements included lung wet weight (LWW), right 

44 cranial lobe dry weight (RCLDW), and wet weight. In a second series that involved exposures 

45 to 12 and 24 ppm, lungs were examined by transmission electron microscopy. Body weight 

46 losses of about 3% were seen within the first 8 hours after exposure and continued for 48 to 72 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 14 of 43 

1 hours. No gravimetric increases or pathological changes were noted after exposures to PFIB at 

2 6.1 and 10 ppm. LWW and RCLDW values revealed the clear development of pulmonary 

3 edema. At exposure to 11 ppm, the lung injuries began to show up histologically, within hours 

4 after the exposure, and the latency periods were inversely proportional to the PFIB 

5 concentrations. Significant accumulations of edema fluid were not apparent until 9 hours 

6 following the exposure, in correspondence with the gravimetric data. At 18 to 24 hours after 

7 exposure, significant amounts of fibrin were detected in the alveolar spaces, but no fibrin was 

8 seen at 48 to 72 hours. At the highest concentration, there was no latency period. 

9 

10 An influx of polymorphonuclear neutrophils was not seen until 12 to 24 hours after exposure 

11 to 12 ppm of PFIB (Lehnert et al., 1993). Significant increases in alveolar macrophages were 

12 seen 10 hours after exposure, with peak increases between 24 and 48 hours. As revealed by 

13 transmission electron microscopy, the alveolar epithelial cells and endothelial cells showed 

14 abnormal vacuolization and blebbing already at one hour after exposure. The alveolar surface 

15 was progressively denuded, leading to the flooding of the alveolar area with vascular 

16 constituents including red blood cells. Alveolar macrophages seemed to be relatively insensitive 

17 to the toxic effects of PFIB. 

18 

19 Nold et al. (1991) conducted light and electron microscopy to morphologically characterize 

20 the development of lung injury following a 2-minute whole-body exposure of thirty-five Wistar 

21 Porton female rats to 64 ppm PFIB vapor. Concentrations in the exposure chamber were 

22 monitored by a Miran infrared spectrophotometer. Five rats each were necropsied at post23 exposure intervals of 5 minutes, 30 minutes, 90 minutes and 4, 12, 24, and 72 hours. At 5 

24 minutes, there was minimal, multifocal, perivascular edema with minimal to moderate 

25 eosinophilic pulmonary perivasculitis. By 90 minutes, all rats had mild multifocal perivascular 

26 edema in all lung lobes and mild, pulmonary, eosinophilic perivascular inflammation. By 12 

27 hours, and also at 24 hours, all rats showed diffuse severe alveolar edema with deposition of 

28 fibrin. The alveolar septa were thickened, and the alveoli contained increased numbers of 

29 macrophages as well as occasional eosinophils and neutrofils. There was significant resolution 

30 of the pulmonary edema and fibrin deposition by 72 hours. 

31 

32 

33 Paulet and Bernard (1968) exposed groups of ten rats to “heavy products/high boilers” for 

34 2 hours. The “heavy products/high boilers” are by-products formed at high temperatures 

35 (700°C) during the synthesis of tetrafluoroethylene from chlorodifluoromethane. Certain 

36 volatile and relatively inert by-products readily dissipate; however, other heavier more unstable 

37 by-products with high boiling points (above 40°C) accumulate at the base of the distillation 

38 column. The physical properties of these compounds lead to the name “heavy products/high 

39 boilers.” Analyses of these “heavy products/high boilers” suggested that PFIB (found in 

40 concentrations ranging from 0.1 to 3%) is responsible for the high toxicity of “heavy 

41 products/high boilers”. A concentration of 0.15% PFIB was assumed in this study. A 2-hr LC50

42 of 1.05 ppm was calculated for PFIB (the 2-hr LC50 was 700 ppm for heavy products/high 

43 boilers). Data are summarized in Table 5. 

44 

45 

46 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 15 of 43 

TABLE 5. Summary of mortality data for animals exposed to heavy products/high boilers for 2 hours 

“Heavy 

Product” 

(HP) 

Concentration 

(ppm) 

Estimated 

PFIB 

Concentration 

(ppm) 

Rat Mouse Guinea pig Rabbit 

 Mortality Average 

survival 

Mortality Average 

survival 

Mortality Average 

survival 

Mortality Average 

survival 

270 0.49 0/10 - 0/10 - 0/5 - 0/3 - 

480 0.70 0/10 - 0/10 - 0/5 - 0/3 - 

750 1.10 8/10 24 hr 10/10 - 7/10 - 1/5 - 

1000 1.50 10/10 15 hr 10/10 7 hr 4/5 24 hr 3/3 12 hr 

1530 2.30 10/10 - 10/10 3 hr 20 5/5 - 3/3 - 

2000 3.00 10/10 - 10/10 - 5/5 - 3/3 - 

3000 4.50 10/10 2 hr 10/10 2 hr 30 5/5 2 hr 3/3 2 hr 

3500 5.20 10/10 2 hr 10/10 3 hr 5/5 2 hr 15 3/3 2 hr 

5200 7.90 10/10 1 hr 20 10/10 1 hr 10 5/5 0 hr 50 3/3 1 hr 10 

PFIB LC50 1.05 ppm 0.98 ppm 1.05 ppm 1.20 ppm 

HP LC50 700 ppm 650 ppm 700 ppm 800 ppm 

1 Paulet and Bernard, 1968 

2 

3 

4 3.1.2. Mice

5 

6 As part of a study to examine inhalation toxicologic procedures in small laboratory animals, 

7 Bide et al. (2000) whole body exposed male and female CD-1 mice to PFIB for 10 minutes. 

8 Animals were observed for at least 20 days after the exposure. The 6 L exposure chamber was a 

9 Plexiglas box with conical ends. Concentrations were determined using a MIRAN Analyzer. 

10 The LC50 was estimated to be 11.8 ppm, with most deaths occurring between 24 and 48 hours 

11 after the treatment. In all cases lung edema was the cause of death. Data are summarized in 

12 Table 6. 

13 

TABLE 6. Summary of mortality data in mice exposed to PFIB for 10 minutes.

Concentration Number of deaths by day 

(ppm) 

Mortality 

1 2 3 4 

8.3 0/10 - - - - 

9.2 0/10 - - - - 

10* 0/10 - - - - 

10* 2/10 - 2 - - 

12* 2/5 - 2 - - 

12* 1/5 - 1 - - 

13* 5/5 1 1 2 1 

13* 4/5 - 3 1 - 

15* 9/9 5 4 - - 

15* 8/8 4 4 - - 

65 10/10 10 - - - 

14 Bide et al., 2000 

15 *Although not stated in the study report, it is assumed that the duplicate exposures represent males and 

16 females separately. 

17 

18 Fusheng et al. (1992) exposed groups of six Kunming mice whole body to 98, 104, 110, 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 16 of 43 

1 116, or 123 ppm PFIB (97.5% purity) for 1-minute. PFIB concentrations were determined by 

2 gas chromatography. The mice showed no clinical signs during the first 3 hours after exposure. 

3 After that they gradually showed a decrease in spontaneous movement, depressed respiration, 

4 staggering, inflammation of the eyes, prostration, and finally weakness and convulsions leading 

5 to death. Surviving animals appeared to recover fully. An LC50 value of 107 ppm (95% CI 104-

6 110 ppm) was reported. Mortality data are summarized in Table 7. 

7 

TABLE 7. Summary of mortality data in mice exposed to PFIB for 1 minute. 

Concentration (ppm) Mortality Death time after exposure (hr) 

98 0/6 - 

104 2/6 23, 26 

110 4/6 14, 16, 20, 26 

116 6/6 10, 27, 28, 29, 39, 40 

123 6/6 10, 16, 17, 8, 18, 18 

8 Fusheng et al., 1992 

9 

10 

11 

12 Danishevskii and Kochanov (1961) reported a 2-hour “maximal tolerance” 

13 concentration of 0.61 ppm, “minimal lethal” concentration of 1.2 ppm and “absolute lethal” 

14 (assumed to be 100% lethality) concentration of 1.8 ppm for albino mice. Histology showed 

15 pulmonary hemorrhages and edema, degenerative changes in the kidney, and fatty changes in the 

16 liver. No other details were provided. 

17 

18 Karpov (1977) reported a 15-min LC50 of 6.1 ppm for white mice. Karpov (1977) also 

19 reported a 2-hour LC50 of 1.6 ppm for white mice, and stated that mice exposed to 61-183 ppm 

20 PFIB died within 1 minute. Pulmonary edema was given as the cause of death. 

21 

22 Paulet and Bernard (1968) exposed groups of ten mice to “heavy products/high boilers” for 2 

23 hours as described in section 3.1.1. A 2-hr LC50 of 0.98 ppm was calculated for PFIB (the 2-hr 

24 LC50 was 650 ppm for heavy products/high boilers). Data are summarized in Table 5. 

25 

26 

27 3.1.3. Guinea pigs 

28 

29 Paulet and Bernard (1968) exposed groups of five or ten guinea pigs to “heavy 

30 products/high boilers” for 2 hours as described in section 3.1.1. A 2-hr LC50 of 1.05 ppm was 

31 calculated for PFIB (the 2-hr LC50 was 700 ppm for heavy products/high boilers). Data are 

32 summarized in Table 5. 

33 

34 

35 3.1.4. Rabbits 

36 

37 Karpov (1977) reported a 15-min LC50 of 12.2 ppm for rabbits. Karpov (1977) also 

38 reported a 2-hour LC50 of 4.3 ppm, and stated that rabbits exposed to 61-183 ppm PFIB died 

39 within 1 minute. Pulmonary edema was given as the cause of death. 

40 

41 Paulet and Bernard (1968) exposed groups of three or five rabbits to “heavy 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 17 of 43 

1 products/high boilers” for 2 hours as described in section 3.1.1. A 2-hr LC50 of 1.20 ppm was 

2 calculated for PFIB (the 2-hr LC50 was 800 ppm for heavy products/high boilers). Data are 

3 summarized in Table 5. 

4 

5 3.1.5. Cats 

6 

7 Karpov (1977) reported a 2-hour LC50 of 3.1 ppm for cats. Pulmonary edema was given 

8 as the cause of death. 

9 

10 

11 3.2. Nonlethal Acute Toxicity 

12 

13 3.2.1. Rats 

14 

15 Groups of white rats were exposed to 0, 0.12, 0.24, or 0.49 ppm PFIB for 4 hours (Karpov, 

16 1977). “Impairment of conditioned reflexive activity” was noted in animals exposed to 0.24 and 

17 0.49 ppm. Liver transaminase activity was also increased in these rats (33% and 55% increases 

18 for the 0.24 and 0.49 ppm groups, respectively). Pulmonary edema was reported in the 0.24 and 

19 0.49 ppm groups. No significant treatment-related effects were noted at 0.12 ppm. 

20 

21 

22 3.3. Repeat Dose Studies

23 

24 Four male albino rats were exposed to 0.1 ppm PFIB 6 hours/day for 10 days (DuPont, 

25 1956; 1961). Rats were sacrificed at the end of the exposure period. The PFIB gas was mixed 

26 with air in a carboy and then passed into a bell jar containing the rats. Nominal concentrations 

27 were calculated from the flow rates of PFIB gas and air. During the exposures, the rats were 

28 occasionally restless and had mild respiratory impairment that sometimes proceeded to cyanosis; 

29 two of the rats developed moist rales. Occasional body weight loss was noted in two rats during 

30 the first week of exposure only. There were no clinical observations or effects on weight gain. 

31 All rats survived the treatment period. There were no gross or histopathological effects or organ 

32 weight effects noted at necropsy. 

33 

34 In another study, ten male ChR-CD rats were exposed to 0 or 0.098 ppm of PFIB 6 

35 hours/day, 5 days/week for two weeks (DuPont, 1975). PFIB chamber concentrations were 

36 determined by gas chromatography using an electron capture detector. Five rats/concentration 

37 were sacrificed at 0 and 14-days post-exposure. No treatment-related gross or microscopic 

38 changes were observed at the end of the exposure period or after the14-day follow-up period. 

39 

40 McMaster et al. (1989) exposed ten male Sprague-Dawley rats to PFIB by inhalation. 

41 The rats had been trained to press a lever for a food reward under a multiple time-out fixed ratio 

42 of reinforcement. At certain times in this activity, 30 lever presses resulted in a reward pellet. 

43 Multiple 10-minute head-only exposures to PFIB starting at 1.2 ppm were administered at 

44 unspecified intervals of no less than one week. The exposures were increased in 2.4 ppm 

45 increments an unspecified number of times. During the experiment, all rats continued to respond 

46 within the range of their baseline levels at exposure concentrations below 180 ppm x minutes 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 18 of 43 

1 (presumably cumulative). As the cumulative exposure concentrations approached what would 

2 be the estimated LC50, performance deficits were seen in some animals. The animals with 

3 performance deficits showed pulmonary edema and histologically-damaged lungs. 

4 

5 3.4. Developmental/Reproductive Toxicity

6 

7 No data were located. 

8 

9 3.5. Genotoxicity 

10 

11 No data were located. 

12 

13 3.6. Chronic Toxicity/Carcinogenicity

14 

15 No data were located. 

16 

17 

18 3.7. Summary

19 

20 Animal lethality data are available for rats, mice, guinea pigs, rabbits, and cats, with the most 

21 robust data sets being for rats and mice. Clinical signs include dyspnea, cyanosis, face washing, 

22 hyperemia, sneezing, mild responsiveness, rapid respiration, and convulsions. Death is 

23 attributed to pulmonary edema which is a consistent necropsy finding. The concentration24 response curve is very steep for many species with regard to lethality. For example, no rats died 

25 when exposed to 0.25 ppm PFIB for 4 hours; whereas 100% lethality (6/6) was noted at 0.5 ppm 

26 for 4 hours (DuPont, 1966). No mortality was noted in rats exposed to 228 ppm PFIB for 0.25 

27 min and 100% mortality (10/10) was noted at 468 ppm. No mortality was noted in rats exposed 

28 to 20 ppm PFIB for 5 min and 9/10 rats died at 32 ppm. In rats exposed for 10 minutes, no 

29 mortality was noted at 10 ppm and 8/10 rats died at 20 ppm (Smith et al., 1982). No mortality 

30 was noted in mice exposed to 98 ppm PFIB for 1 minute; whereas, 6/6 mice died at 116 ppm 

31 (Fusheng et al., 1992), and no mice died when exposed to 10 ppm for 10 minutes and 10/10 mice 

32 died at 65 ppm (Bide et al., 2000). Finally, no mortality was noted in rats, mice, guinea pigs, and 

33 rabbits exposed to approximately 0.70 ppm PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 

34 4/5 guinea pigs, and 3/3 rabbits died when exposed to 1.5 ppm (Paulet and Bernard, 1968). No 

35 developmental/reproductive, genotoxicity, chronic toxicity, or carcinogenicity data were located. 

36 Selected animal data are summarized in Table 8. 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 19 of 43 

1 

TABLE 8. Summary of selected animal inhalation data 

Species Duration Concentration 

(ppm) 

Endpoint Reference 

Rat 0.25 minutes 228 No mortality. Weight loss (10)a Smith et al., 1982 

Rat 0.25 minutes 361 LC50 (10) Smith et al., 1982 

Rat 0.5 minutes 144 No mortality. Weight loss (10) Smith et al., 1982 

Rat 0.5 minutes 214 LC50 (10) Smith et al., 1982 

Mouse 1 minute 98 No mortality. Decreased 

movement, decreased 

respiration, staggering, ocular 

inflammation, prostration (6) 

Fusheng et al., 1992 

Rat 1 minute 100 10% mortality (10) Smith et al., 1982 

Mouse 1 minute 107 LC50 (6) Fusheng et al., 1992 

Rat 1 minute 122 LC50 (10) Smith et al., 1982 

Rat 2 minutes 71 10% mortality (10) Smith et al., 1982 

Rat 2 minutes 86 LC50 (10) Smith et al., 1982 

Rat 5 minutes 20 No mortality. Weight loss (10) Smith et al., 1982 

Rat 5 minutes 28 LC50 (10) Smith et al., 1982 

Mouse 10 minutes 9.2 No mortality. Clinical signs 

not reported (10) 

Bide et al., 2000 

Rat 10 minutes 10 No mortality. Weight loss (10) Smith et al., 1982 

Mouse 10 minutes 11.8 LC50 (10) Bide et al., 2000 

Rat 10 minutes 17 LC50 (10) Smith et al., 1982 

Mouse 15 minutes 6.1 LC50 Karpov, 1977 

Rat 15 minutes 6.7 LC50 Karpov, 1977 

Rabbit 15 minutes 12.2 LC50 Karpov, 1977 

Rat 2 hours 0.25 No mortality. Face washing, 

hyperemia, sneezing, 

hypernea, dyspnea, mildly 

responsive (6) 

DuPont, 1966 

Rat, mouse, 

guinea pig, 

rabbit 

2 hours 0.70b

 No mortality (3-10) Paulet and Bernard, 1968 

Mouse 2 hours 0.98b LC50 (10) Paulet and Bernard, 1968 

Rat 2 hours 1.05b LC50 (10) Paulet and Bernard, 1968 

Guinea pig 2 hours 1.05b LC50 (5-10) Paulet and Bernard, 1968 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 20 of 43 

Rabbit 2 hours 1.20b LC50 (3-5) Paulet and Bernard, 1968 

Mouse 2 hours 1.2 ALCa Karpov, 1977 

Mouse 2 hours 1.6 LC50 Karpov, 1977 

Mouse 2 hours 1.8 100% mortality Danishevskii and Kochanov, 1961

Rat 2 hours 1.8 100% mortality Danishevskii and Kochanov, 1961

Cat 2 hours 3.1 LC50 Karpov, 1977 

Rabbit 2 hours 4.3 LC50 Karpov, 1977 

Rat 2 hours 11.6 LC50 Karpov, 1977 

Rat 4 hours 0.50 100% mortality (6) DuPont, 1966 

Rat 4 hours 1.0 100% mortality (6) DuPont, 1966 

Rat 4.25 hours 1.0 100% mortality (2) DuPont, 1956; 1961 

Rat 6 hours 0.3 No effects (2) DuPont, 1956; 1961 

Rat 6 hours 0.50 100% mortality (2) DuPont, 1956; 1961 

1 a 2 Number in round brackets is the number of animals exposed/group, when this is known. b 3 PFIB Concentration estimated assuming 0.15% PFIB in Heavy Products/High Boilers c 4 ALC = Approximate Lethal Concentration, a concentration at which at least one animal died after a single inhalation 

5 exposure 

6 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 21 of 43 

1 4. SPECIAL CONSIDERATIONS

2 4.1. Metabolism and Disposition

3 

4 Essentially no information was located concerning the metabolism and disposition of 

5 PFIB. However, Maidment and Upshall (1992) studied retention of inhaled PFIB using female 

6 rats that were restrained by stocks at the neck in a head-out plethysmograph while being exposed 

7 for 2.25 minutes to 1.2, 6, or 30 ppm of PFIB in a number of repeated exposures. The total 

8 exposures amounted to 0.1, 0.5, and 2.5 times a reported LC50. There was no evidence of 

9 changes in minute volume or breathing rate that could be related to the repeated exposures. The 

10 uptake of PFIB at the tested concentrations was said to be an apparent first-order process in that 

11 the percentage of the inhaled PFIB that was retained remained constant, and the rate of uptake 

12 increased proportionately with the inhaled dosage. Early tissue damage, if any, did not influence 

13 retention in the respiratory tract. 

14 

15 

16 4.2. Mechanism of Toxicity 

17 

18 Arroyo (1997) studied the chemistry of PFIB by using electron paramagnetic resonance spin19 trapping techniques and concluded that this highly electrophilic chemical likely undergoes 

20 electron transfer that leads to several highly reactive intermediates. PFIB is reactive towards 

21 nucleophilic reagents to yield substitution and addition radical byproducts. PFIB reacts with 

22 almost all known nucleophiles. 

23 

24 Lailey et al. (1991) suggested that PFIB may exert its toxic effect by depletion of 

25 intracellular nucleophiles, including amines, thiols and alcohols. When a lethal concentration of 

26 PFIB (purity >96.1%) was inhaled by Porton strain rats, total non-protein thiol (NPSH) and 

27 glutathione (GSH) in the lung were reduced by between 30 and 49%, respectively (Lailey et al., 

28 1991). If rats were pretreated to reduce endogenous thiol levels in the lungs before PFIB 

29 treatment, the rats were more susceptible to the lethal effects of the gas. Treatments that raised 

30 levels of cysteine (CySH) in the lungs before treatment with PFIB protected rats from the lethal 

31 effects of PFIB. In a study of the effects of pretreatment of rats with oral N-acetylcyteine 

32 (Lailey, 1997), it was found that plasma levels of cysteine, glutathione, and N-acetylcystein were 

33 increased for up to seven hours following oral administration of N-acetylcysteine, and this 

34 treatment provided substantial protection for rats against the lethal effects of inhaling PFIB. 

35 

36 The pattern of pulmonary damage induced by PFIB is characteristic of highly hydrophobic 

37 gases that penetrate into the deep lung. The first sign of cellular damage is at the pulmonary 

38 epithelium. However, there is evidence of interstitial edema and increased lymph flow before 

39 there is alveolar filling, which suggests that damage to the endothelial cells is an early event. 

40 After exposure to an LC50 of PFIB, there is no increase in lung weight for up to six hours, after 

41 which there is a progressive filling of the alveoli. That filling may lead to death from pulmonary 

42 edema between eight and 12 hours after the exposure. No significant pathology is apparent 

43 outside the lung other than the congestion induced by flow resistance that is caused by the severe 

44 pulmonary edema (Lailey et al., 1991). 

45 

46 Maidment et al. (1994) also noted that there is little evidence of direct pathological damage 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 22 of 43 

1 to tissues outside the respiratory tract by PFIB. All PFIB-induced tissue damage appears to 

2 result from rapid interaction with cells that are either in, or in close proximity to, the respiratory 

3 airways. PFIB is a hydrophobic gas that induces a permeability-type edema. Maidment et al. 

4 (1994) stated that extensive unreported studies in rats of the toxicopathology of PFIB in their 

5 laboratory had “failed to reveal any significant macroscopic or microscopic pathology outside 

6 the respiratory system at a number of time points up to 14 days after exposure, when resolution 

7 of the initial pulmonary injury is complete.” 

8 

9 Gurley et al. (1991) used high-performance capillary electrophoresis to identify proteins 

10 from the fluid lining of the lungs of male rats given whole-body exposures to 12 ppm of PFIB for 

11 10 minutes. Comparisons were made with untreated controls. The PFIB concentration was 

12 measured using a dual-column gas chromatograph fitted with an electron-capture detector that 

13 was sensitive to 1 ppb of PFIB. The lung fluid was obtained using a bronchoalveolar lavage 

14 procedure. The edema that was induced involved the translocation of proteins from the blood 

15 compartment into the lung’s alveolar compartment. Three of the major proteins that were 

16 translocated in this way were albumin, transferrin and IgG. 

17 

18 Pathogen-free male Sprague-Dawley rats and pathogen-free male Kunming mice 

19 (5/group/species) were exposed whole-body to sublethal concentrations of PFIB in order to 

20 determine how PFIB causes lung injury (Wang et al., 2001). A separate group of rats and mice, 

21 made neutropenic by i.p. injection with cyclophosphamide, were exposed to PFIB to determine 

22 the effect of depleted polymorphonuclear leukocytes (PMN) on PFIB-induced lung injury. All 

23 exposures lasted five minutes, and measurement of lung myeloperoxidase (MPO) activity, and 

24 lung wet-to-dry ratio, lung lavage, and histopathological examinations were conducted over 

25 time. In the first experiment, rats were exposed to 16.8 ppm and mice were exposed to 15.6 ppm 

26 for five minutes. The rats were sacrificed 24 hours post exposure for ultrastructural examination. 

27 In rats, the total protein concentration in the bronchoalveolar lavage fluid was increased as early 

28 as two hours post exposure and reached a peak at 24 hours. A decrease in protein was found at 

29 48 and 72 hours post exposure, but still remained significantly higher than baseline. In mice, 

30 lung MPO activity increased as early as 1-hour post exposure and peaked at 20 hours, but it had 

31 returned to normal by 60 hours. The lung wet-to-dry weight increased drastically from 20 to 24 

32 hours and recovered slowly from 24-48 hours. In the PMN depletion study, mice were exposed 

33 to 22.8 ppm of PFIB for five minutes and followed for up to seven days post exposure. The rats 

34 were exposed to 16.8 ppm and sacrificed 24 hours post exposure. After 5 min of exposure, 10 of 

35 16 mice exposed to PFIB without depleted PMN died by 7 days after treatment compared to only 

36 1 of 16 in the PMN-depleted mice, with this difference being statistically significant. There was 

37 a lack of increase in MPO activity, but the lung wet-to-dry ratio was slightly increased in the 

38 mice. The total protein concentration in the bronchoalveolar lavage fluid of the PMN-depleted 

39 and PFIB-exposed rats was significantly increased compared to that of the controls but to a 

40 lesser degree in the rats exposed to PFIB only. Vascular congestion, interstitial and intra41 alveolar edema, alveolar hemorrhage, and increased numbers of inflammatory cells were 

42 observed in the lungs of the rats exposed only to PFIB. Ultrastructural examination showed 

43 severe damage to the alveolar structure, excessive vesiculation, exfoliated epithelial cells, and 

44 alveoli with exudated erythrocytes, fibrin, and inflammatory cells. The PMN-depleted and 

45 PFIB-exposed rats had moderate septal thickening, intra-alveolar edema, fibrin deposition, and 

46 macrophage accumulation in the alveolar spaces. The alveolar structures of the PMN-depleted 

47 and PFIB-exposed rats were intact, but vacuoles and blebs in endothelial and epithelial cells 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 23 of 43 

1 were seen. The authors concluded that neutrophil sequestration and accumulation in the lungs is 

2 a key factor in acute PFIB-induced lung injury and mortality. They indicated that 

3 polymorphonuclear leukocytes (PMN) are not the only contributor to PFIB inhalation-induced 

4 lung damage and edema, and suggested that the roles of other effector cells such as monocytes 

5 and macrophages should also be clarified. 

6 

7 

8 4.3. Other Relevant Information

9 4.3.1. Interspecies Variability

10 

11 Lethality data, available for several animal species, suggest little interspecies variability 

12 (Table 9). LC50 values for given exposure durations are essentially equivalent except for one 

13 two-hour rat value (Karpov, 1977) which is inconsistent with the overall data set. This value 

14 suggests that the rat is much less sensitive than would be expected from the other LC50 values. 

15 

16 

TABLE 9. Comparison of PFIB LC50 values for various animal species

Duration Species LC50 (ppm) Ratio of LC50

values (maximum) 

Reference 

1 minute Mouse 107 Fusheng et al., 1992 

Rat 122 

1.1 

Smith et al., 1982 

10 minutes Mouse 11.8 Bide et al., 2000 

Rat 17 

1.4 

Smith et al., 1982 

15 minutes Mouse 6.1 Karpov, 1977 

Rat 6.7 

1.1 

Karpov, 1977 

Mouse 0.98 

Rat 1.05 

Guinea pig 1.05 

Rabbit 1.20 

Paulet and Bernard, 

1968 

Mouse 1.6 Karpov, 1977 

 

2 hours 1.6 

Rat* 11.6* 11.8* Karpov, 1977 

17 *LC50 value inconsistent with overall data base (Karpov (1977) 15-minute rat value and reports from other authors). 

18 

19 

20 4.3.2. Intraspecies Variability

21 

22 Specific data concerning susceptible populations are not available; however the 

23 concentration-response curve for PFIB is very steep, thus, implying limited intraspecies 

24 variability. [Data showing steepness of the concentration response curve are as follows: No rats 

25 died when exposed to 0.25 ppm PFIB for 4 hours; whereas 100% lethality (6/6) was noted at 0.5 

26 ppm for 4 hours (DuPont, 1966). No mortality was noted in rats exposed to 228 ppm PFIB for 

27 0.25 min and 100% mortality (10/10) was noted at 468 ppm. No mortality was noted in rats 

28 exposed to 20 ppm PFIB for 5 min and 9/10 rats died at 32 ppm. In rats exposed for 10 minutes, 

29 no mortality was noted at 10 ppm and 8/10 rats died at 20 ppm (Smith et al., 1982). No mortality 

30 was noted in mice exposed to 98 ppm PFIB for 1 minute; whereas, 6/6 mice died at 116 ppm 

31 (Fusheng et al., 1992), and no mice died when exposed to 10 ppm for 10 minutes and 10/10 mice 

32 died at 65 ppm (Bide et al., 2000). No mortality was noted in rats, mice, guinea pigs, and rabbits 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 24 of 43 

1 exposed to approximately 0.70 ppm PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 4/5 

2 guinea pigs, and 3/3 rabbits died when exposed to 1.5 ppm (Paulet and Bernard, 1968).] 

3 

4 

5 

6 4.3.3 Structure Activity 

7 

8 Clayton (1977) reported that the susceptibility of fluoroalkenes to nucleophilic attack 

9 parallels the inhalation toxicity of these compounds: PFIB > hexafluoropropylene > 

10 tetrafluoroethylene. However, experimental data supporting this potential relationship are not 

11 available. 

12 

13 Clayton (1977) also compared the acute rat inhalation toxicity of several fluoroalkenes. 

14 While toxicity may appear to be inversely related to the number of fluorine atoms, there are no 

15 mechanistic data to support this assumption. It is more likely that toxicity is related instead to 

16 the double bond. 

17 

18 Jugg et al. (1999) investigated the differences in action between PFIB and phosgene, both 

19 of which produce pulmonary permeability-type edema. The study attempted to distinguish 

20 between damage to the surfactant system of alveoli and effects on type II pneumocytes in the rat 

21 lung. Alterations of the lung surfactant system were demonstrated. The progression of the 

22 injury was followed for 48 hours after exposure with one or the other of these gases at a 

23 concentration equal to the LC30 by analyzing the inflammatory cells and protein in 

24 bronchoalveolar lavage fluid. Six lung phospholipids were measured by high-performance 

25 liquid chromatography after solid phase extraction from lavage fluid. These two gases differed 

26 both with respect to the percentage composition of surfactant and the total amount of 

27 phospholipids present. PFIB produced increases in phosphatidylglycerol and 

28 phosphatidylcholine within the first hour, followed by a substantial decrease in these 

29 phospholipids. In contrast, phosgene caused a late increase in all phospholipids beginning 6 

30 hours after the exposure. These findings show that phosgene and PFIB have different 

31 mechanisms of action at the alveolar surface. PFIB also caused a large neutrophilia at 24 hours 

32 post-treatment, with large numbers of monocytes being present from then on. Phosgene 

33 exposure also led to a large neutrophilia between 24 and 48 hours after treatment. Both gases 

34 caused a significant reduction in the number of alveolar macrophages. 

35 

36 

37 4.3.4. Concentration-Exposure Duration Relationship

38 

39 The concentration-exposure time relationship for many irritant and systemically-acting 

vapors and gases has been described by the relationship cn 40 x t = k, where the exponent, n, 

41 typically ranges from 0.8 to 3.5 (ten Berge et al., 1986). When the rat 0.25 to 120 minute- LC50

42 values from Table 8 are considered in the derivation of the exponent, a value of 1.0 is obtained. 

43 When the mouse 1 to 120 minute- LC50 values from Table 8 are considered in the derivation of 

44 the exponent, a value of 1.1 is obtained (Appendix B). 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 25 of 43 

1 

2 5. DATA ANALYSIS FOR AEGL-1

3 5.1. Summary of Human Data Relevant to AEGL-1

4 

5 No human studies were available for development of AEGL-1 values. 

6 

7 5.2. Summary of Animal Data Relevant to AEGL-1

8 

9 No animal studies were available for development of AEGL-1 values. 

10 

11 5.3. Derivation of AEGL-1

12 

13 No human or animal data were available for derivation of AEGL-1 values for PFIB. 

14 Therefore, AEGL-1 values are not recommended (Table 10). 

15 

16 

TABLE 10. AEGL-1 Values for PFIB

10-min 30-min 1-h 4-h 8-hour 

NR NR NR NR NR 

17 NR: Not Recommended due to insufficient data. Absence of an AEGL-1 value does not imply that concentrations 

18 below the AEGL-2 are without effect. 

19 

20 

21 6. DATA ANALYSIS FOR AEGL-2

22 6.1. Summary of Human Data Relevant to AEGL-2

23 

24 No human studies were available for development of AEGL-2 values. 

25 

26 6.2. Summary of Animal Data Relevant to AEGL-2

27 

28 Animal data showing clinical signs consistent with the definition of AEGL-2 are available; 

29 however, mortality was observed at the next highest concentration tested. Therefore, these data 

30 are more appropriate for derivation of AEGL-3 values. 

31 

32 6.3. Derivation of AEGL-2

33 

34 In the absence of appropriate chemical-specific data, the AEGL-3 values will be divided by 3 

35 to derive AEGL-2 values for PFIB (NRC, 2001). This approach is justified by the steep 

36 concentration-response curve observed in several animal studies. No rats died when exposed to 

37 0.25 ppm PFIB for 4 hours; whereas 100% lethality (6/6) was noted at 0.5 ppm for 4 hours 

38 (DuPont, 1966). No mortality was noted in rats exposed to 228 ppm PFIB for 0.25 min and 

39 100% mortality (10/10) was noted at 468 ppm. No mortality was noted in rats exposed to 20 

40 ppm PFIB for 5 min and 9/10 rats died at 32 ppm. In rats exposed for 10 minutes, no mortality 

41 was noted at 10 ppm and 8/10 rats died at 20 ppm (Smith et al., 1982). No mortality was noted 

42 in mice exposed to 98 ppm PFIB for 1 minute; whereas, 6/6 mice died at 116 ppm (Fusheng et 

43 al., 1992), and no mice died when exposed to 10 ppm for 10 minutes and 10/10 mice died at 65 

44 ppm (Bide et al., 2000). Finally, no mortality was noted in rats, mice, guinea pigs, and rabbits 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 26 of 43 

1 exposed to approximately 0.70 ppm PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 4/5 

2 guinea pigs, and 3/3 rabbits died when exposed to 1.5 ppm (Paulet and Bernard, 1968). AEGL-2 

3 values are summarized in Table 11 and calculations are in Appendix A. 

4 

TABLE 11. AEGL-2 Values for PFIB

10-min 30-min 1-h 4-h 8-h 

0.67 ppm 

(5.5 mg/m3

) 

0.22 ppm 

(1.8 mg/m3) 

0.11 ppm 

(0.90 mg/m3) 

0.028 ppm 

(0.23 mg/m3) 

0.014 ppm 

(0.11 mg/m3) 

5 

6 

7 

8 7. DATA ANALYSIS FOR AEGL-3

9 7.1. Summary of Human Data Relevant to AEGL-3

10 

11 No human studies were available for development of AEGL-3 values. 

12 

13 7.2. Summary of Animal Data Relevant to AEGL-3

14 

15 Animal lethality data are available for rats, mice, rabbits, guinea pigs, and cats exposed to 

16 varying concentrations of PFIB for durations ranging from 0.25 minutes to 6 hours. Potential 

17 AEGL-3 points-of-departure include the following: the highest experimental concentration 

18 causing no mortality in rats exposed to PFIB for 4-hours (0.25 ppm analytical concentration); 

19 100% mortality was observed at the next highest concentration tested (0.5 ppm) (DuPont, 1966); 

20 or the highest experimental concentration causing no mortality in rats exposed to PFIB for 6-

21 hours (0.3 ppm nominal concentration); 100% mortality (2/2 animals) was observed at the next 

22 highest concentration tested (0.5 ppm) (DuPont, 1956; 1961). Calculated thresholds for lethality 

23 in rats (data in Tables 2, 3, 4, & 5) or mice (data in Tables 5, 6, & 7) using the probit-analysis 

24 dose-response program of ten Berge may also be used for derivation of AEGL-3 values. Use of 

25 the ten Berge approach would utilize both nominal and analytical data. The highest 

26 experimental concentration causing no mortality in rats, mice, guinea pigs, and rabbits exposed 

27 to PFIB for 2-hours (0.70 ppm) (Paulet and Bernard, 1968) is also a potential point-of-departure. 

28 Mortality was noted in all species at the next highest concentration tested (1.1 ppm); the PFIB 

29 concentrations in this study were estimated assuming 0.15% PFIB in heavy products/high 

30 boilers. 

31 

32 

33 7.3. Derivation of AEGL-3

34 

35 The highest concentration causing no mortality in rats exposed to PFIB for 4-hours (0.25 

36 ppm) will be used as the point-of-departure for AEGL-3 values (DuPont, 1966). This approach 

37 is chosen over the other approaches discussed in Section 7.2 because it is the only approach 

38 utilizing entirely analytical data. Clinical signs noted at this concentration included face 

39 washing, hyperemia, sneezing, hypernea, dyspnea, and decreased responsiveness. There was 

40 100% mortality (6/6) at the next highest concentration tested (0.5 ppm). 

41 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 27 of 43 

1 An interspecies uncertainty factor of 1 and an intraspecies uncertainty factor of 3 will be 

2 applied. The interspecies UF of 1 is considered sufficient because lethality data available for 

3 several animal species suggest little interspecies variability; LC50 values for given exposure 

4 durations are essentially equivalent (Table 9). Reported 1-min LC50 values are 107 ppm for mice 

5 (Fusheng et al., 1992) and 122 ppm for rats (Smith et al., 1982); 10-minute values are 11.8 ppm 

6 for mice (Bide et al., 2000) and 17 ppm for rats (Smith et al., 1982); 15 minute values are 6.1 

7 ppm for mice and 6.7 ppm for rats (Karpov, 1977); and reported 2-hour values are 0.98 ppm 

8 (Paulet and Bernard, 1968) and 1.6 ppm for mice (Karpov, 1977), 1.05 ppm for rats and guinea 

9 pigs (Paulet and Bernard, 1968), and 1.20 ppm for rabbits (Karpov, 1977). 

10 

11 The intraspecies UF of 3 is supported by the steep concentration-response curve for PFIB, 

12 implying limited intraspecies variability. No rats died when exposed to 0.25 ppm PFIB for 4 

13 hours; whereas 100% lethality (6/6) was noted at 0.5 ppm for 4 hours (DuPont, 1966). No 

14 mortality was noted in rats exposed to 228 ppm PFIB for 0.25 min and 100% mortality (10/10) 

15 was noted at 468 ppm. No mortality was noted in rats exposed to 20 ppm PFIB for 5 min and 

16 9/10 rats died at 32 ppm. In rats exposed for 10 minutes, no mortality was noted at 10 ppm and 

17 8/10 rats died at 20 ppm (Smith et al., 1982). No mortality was noted in mice exposed to 98 ppm 

18 PFIB for 1 minute; whereas, 6/6 mice died at 116 ppm (Fusheng et al., 1992), and no mice died 

19 when exposed to 10 ppm for 10 minutes and 10/10 mice died at 65 ppm (Bide et al., 2000). No 

20 mortality was noted in rats, mice, guinea pigs, and rabbits exposed to approximately 0.70 ppm 

21 PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 4/5 guinea pigs, and 3/3 rabbits died when 

22 exposed to 1.5 ppm (Paulet and Bernard, 1968). 

23 

Values will be scaled across time using the cn 24 x t = k, relationship where the exponent, n, is 

25 the chemical-specific value of 1.0, derived from rat LC50 data ranging from 0.25 to 120 minutes. 

26 

27 AEGL-3 values are summarized in Table 12 and calculations are in Appendix A. 

28 

TABLE 12. AEGL-3 Values for PFIB

10-min 30-min 1-h 4-h 8-h 

2.0 ppm 

(16 mg/m3

) 

0.67 ppm 

(5.5 mg/m3) 

0.33 ppm 

(2.7 mg/m3) 

0.083 ppm 

(0.68 mg/m3) 

0.042 ppm 

(0.34 mg/m3) 

29 

30 Time scaling from 4-hours to 10-minutes is justified based on the fact that no mortality was 

31 noted in rats exposed to 10 ppm PFIB (Smith et al., 1982) or mice exposed to 9.2 ppm PFIB 

32 (Bide et al., 2000) for 10-minutes. Applying a total uncertainty factor of 3 to these 

33 concentrations, yields 10-min AEGL-3 values of 3.3 and 3.1 ppm, suggesting that the derived 

34 10-min AEGL-3 value is reasonable. 

35 

36 8. SUMMARY OF AEGLs

37 8.1. AEGL Values and Toxicity Endpoints 

38 

39 AEGL-1 values are not recommended due to insufficient data. AEGL-2 values are one40 third of the AEGL-3 values, and AEGL-3 values are based on a 4-hour threshold for lethality in 

41 rats. AEGL values for PFIB are summarized in Table 13. 

42 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 28 of 43 

TABLE 13. Summary of AEGL Values

Exposure Duration

Classification 10-min 30-min 1-h 4-h 8-h

AEGL-1 

(Nondisabling) 

NR NR NR NR NR 

AEGL-2 

(Disabling) 

0.67 ppm 

(5.5 mg/m3

) 

0.22 ppm 

(1.8 mg/m3) 

0.11 ppm 

(0.90 mg/m3) 

0.028 ppm 

(0.23 mg/m3) 

0.014 ppm 

(0.11 mg/m3) 

AEGL-3 

(Lethal) 

2.0 ppm 

(16 mg/m3

) 

0.67 ppm 

(5.5 mg/m3) 

0.33 ppm 

(2.7 mg/m3) 

0.083 ppm 

(0.68 mg/m3) 

0.042 ppm 

(0.34 mg/m3) 

1 NR: Not Recommended due to insufficient data. Absence of an AEGL-1 value does not imply that concentrations 

2 below the AEGL-2 are without effect. 

3 

4 

5 8.2. Comparison with Other Standards and Guidelines 

6 

7 Extant standards and guidelines for PFIB are presented in Table 14. 

8 

TABLE 14. Standards and Guidelines for PFIB

Exposure Duration

Guideline 10-min 30-min 1-h 4-h 8-h 

AEGL-1 NR NR NR NR NR 

AEGL-2 0.67 ppm 0.22 ppm 0.11 ppm 0.028 ppm 0.014 ppm 

AEGL-3 2.0 ppm 0.67 ppm 0.33 ppm 0.083 ppm 0.042 ppm 

 

ERPG-1 (AIHA)a NA 

ERPG-2 (AIHA)a 0.1 ppm 

ERPG-3 (AIHA)a 0.3 ppm 

TLV-STEL (ACGIH)b 0.01 ppm (ceiling) 

MAC 

(The Netherlands)

c 0.01 ppm 

9 a 10 ERPG (Emergency Response Planning Guidelines, American Industrial Hygiene Association (AIHA 2008) 

11 The ERPG-1 is the maximum airborne concentration below which it is believed nearly all individuals could be 

12 exposed for up to one hour without experiencing other than mild, transient adverse health effects or without 

13 perceiving a clearly defined objectionable odor. The ERPG-1 for PFIB is not established due to lack of data. 

14 

15 The ERPG-2 is the maximum airborne concentration below which it is believed nearly all individuals could be 

16 exposed for up to one hour without experiencing or developing irreversible or other serious health effects or 

17 symptoms that could impair an individual=s ability to take protective action. The ERPG-2 for PFIB is just below 

18 the level at which pulmonary edema (0.24 ppm) and clinical signs of respiratory irritation (0.25 ppm) were 

19 observed in rats exposed for 4-hours. 

20 

21 The ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be 

22 exposed for up to one hour without experiencing or developing life-threatening health effects. The ERPG-3 for 

23 PFIB is based on CT product lethality data for animals. 

24 b 25 ACGIH TLV-STEL (American Conference of Governmental Industrial Hygienists, Threshold Limit Value - 

26 Short Term Exposure Limit) (ACGIH 2008) is for a 15-minute exposure, ceiling. Recommended to minimize 

27 the potential for acute pulmonary and adverse systemic effects in other organs. 

28 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 29 of 43 

c 1 MAC (Maximaal Aanvaarde Concentratie [Maximal Accepted Concentration]). SDU Uitgevers (under the 

2 auspices of the Ministry of Social Affairs and Employment), The Hague, The Netherlands 2000, is defined 

3 analogous to the ACGIH-TLV-TWA. 

4 

5 

6 

7 9. REFERENCES

8 

9 

10 ACGIH (American Conference of Government and Industrial Hygienists). 2008. TLVs and 

11 BEIs Based on the Documentation of the Threshold Limit Values for Chemical Substances and 

12 Physical Agents and Biological Exposure Indices: Perfluoroisobutylene. ACGIH, Cincinnati, 

13 OH. 

14 

15 ACGIH (American Conference of Government and Industrial Hygienists). 1991. 

16 Perfluoroisobutylene. Documentation of the Threshold Limit Values and Biological Exposure 

17 Indicies. Sixth Edition. Cincinnati, OH: ACGIH. 

18 

19 AIHA (American Industrial Hygiene Association). 2008. The AIHA 2008 Emergency Response 

20 Planning Guidelines and Workplace Environmental Exposure Level Handbook. Fairfax, VA. 

21 

22 AIHA (American Industrial Hygiene Association). 2000. Emergency Response Planning 

23 Guidelines for Perfluoroisobutylene. AIHA, Fairfax, VA. 

24 

25 Arroyo, CM. 1997. The chemistry of perfluoroisobutylene (PFIB) with nitrone and nitroso spin 

26 traps: an EPRpin trapping study. Chemico-Biological Interactions 105(2): 119-129. 

27 

28 Bide, R., D.J. Risk and D. Beifus. 2000. Inhalation toxicologic procedures for exposure of small 

29 laboratory animals to highly toxic materials: Part A: Exposures to gases with notes on the 

30 toxicity of PFIB. Technical Report DRES TR 2000-065. Defense Research Establishment 

31 Suffield, England. 

32 

33 Brown, R.F.R. and P. Rice. 1991. Electron microscopy of rat lung following a single acute 

34 exposure to perfluoroisobutylene (PFIB). A sequential study of the first 24 hours following 

35 exposure. Int. J. Exper. Path. 72(4): 437-450. 

36 

37 Clayton, J.W. 1977. Toxicology of the fluoroalkenes: review and research needs. Environ. 

38 Health Perspect. 21: 255-267. 

39 

40 Danishevskii, S.L. and M.M. Kochanov. 1961. [On the toxicology of some fluoro-organic 

41 compounds.] Gig. Truda Prof: Zabol. 5: 3-8. 

42 

43 DuPont (E.I. duPont de Nemours and Company, Inc.). 1956. Toxicity Studies of Pyrolysis 

44 Products of Fluorinated Polymers (Teflon Polytetrafluoroethylene) with Cover Letter Date 

45 101292: Initial Submission. Haskell Laboratory Report No. 18-56. DuPont Co., Haskell 

46 Laboratory, Newark. DE. 

47 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 30 of 43 

1 DuPont (E.I. duPont de Nemours and Company, Inc.). 1961. Initial submission: Inhalation 

2 toxicity studies on perfluoroisobutylene with cover letter dated 101592. Haskell Laboratory 

3 Report No. 1-61. DuPont Co., Haskell Laboratory for Toxicology and Industrial Medicine, 

4 Newark. DE. 

5 

6 Du Pont Company: “Acute Inhalation Toxicity (Haskell Laboratory Report Number 34-66)”. 

7 February 25, 1966. [Unpublished information.] E.I. DuPont de Nemours & Co., Haskell 

8 Laboratory, Elkton Rd, P.O Box 50, Newark, DE 19714. 

9 

10 DuPont (E.I. duPont de Nemours and Company, Inc.). 1975. Two week inhalation toxicity study. 

11 Haskell Laboratory Report No. 684-75. DuPont Co., Haskell Laboratory, Elkton Rd, P.O Box 

12 50, Newark, DE 19714. 

13 

14 Du Pont Company. 1976. Personal Communication to the ERP Committee. October 14, 1976. 

15 E.I. DuPont de Nemours & Co., Haskell Laboratory, Elkton Rd, P.O Box 50, Newark, DE 

16 19714. 

17 

18 Fusheng, L., L. Weigang, Y. Songmin, et al. 1992. Acute inhalation toxicology studies on three 

19 perfluoroorganic compounds. The Proceedings of the Fourth International Symposium on 

20 Protection Against Chemical Warfare Agents, pp. 183-190. 

21 Gangal, S.V. 2004. Perfluorinated Polymers. Kirk-Othmer Encyclopedia of Chemical 

Technology, 4th 22 Ed., M. Howe-Grant, ed. [Online] Available. 

23 http://www.mrw.interscience.wiley.com/ emrw/ 9780471238966/ kirk/article/ 

24 tetrgang.a02/current/html. 

25 

26 Gurley, L.R., Buchanan, J.S., J.E. London, et al. 1991. High-performance capillary 

27 electrophoresis of proteins from the fluid lining of the lungs of rats exposed to 

28 perfluoroisobutylene. Journal of Chromatography. 559(1-2): 411-429. 

29 

30 Jugg, B., J. Jenner and P. Rice. 1999. The effect of perfluoroisobutene and phosgene on rat 

31 lavage fluid surfactant phospholipids. Hum. Exp. Toxicol. 18(11): 659-668. 

32 

33 Karpov, B.D. 1977. Establishment of upper and lower toxicity parameters of 

34 perfluroisobutylene toxicity. Tr. Lenig. Sanit-Gig. Med. Inst. 111: 30-33. 

35 

36 Kennedy, G.L. and Geisen, R.J. 1985. Setting occupational exposure limits for 

37 Perfluoroisobutylene, a highly toxic chemical following acute exposure. J. Occup. Med. 

38 27:675. 

39 

40 Kennedy, G.L., Jr. 1990. Toxicology of fluorine-containing monomers. Critical Reviews in 

41 Toxicology 21:149-170. 

42 

43 Lailey, A.F., L. Hill, I.W. Lawston, et al. 1991. Protection by cysteine esters against chemically 

44 induced pulmonary edema. Biochem. Pharmacol. 42: S47-S54. 

45 Lailey, A.F. 1997. Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats. 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 31 of 43 

1 Human and Experimental Toxicology 16(4): 212-216. 

2 

3 Lehnert, B.E., D. Archuleta, M.J. Behr and D.M. Stavert. 1993. Lung injury after acute 

4 inhalation of perfluoroisobutylene: Exposure concentration-response relationships. Inhalation 

5 Toxicology 5(1): 1-32. 

6 Lehnert, B.E., D. Archuleta, L. Gurley, et al. 1995. Exercise potentiation of lung injury 

7 following inhalation of a pneumoedematogenic gas: perfluoroisobutylene. Exp. Lung Res. 21(2): 

8 331-348. 

9 Maidment, M.P. and D.G. Upshall. 1992. Retention of inhaled perfluoroisobutene in the rat. J. 

10 Appl. Toxicol. 12: 393-400. 

11 Maidment, M.P., P. Rice and D.G. Upshall. 1994. Retention of inhaled hexafluorocyclobutene in 

12 the rat. J. of Applied Toxicolgy 14(6): 395-400. 

13 Makulova, I.D. 1965. [Clinical picture of acute poisoning with perfluroisobutylene.] Gig. Tr. 

14 Prof. Zabol. 9:20-23. 

15 McMaster, S.B., K.G. Phillips, A.V. Finger and F. Feliciano. 1989. An analysis of potential 

16 behavioral effects of multiple sub-lethal exposures to perfluoroisobutylene. Proceedings of the 

17 1989 Medical Defense Biosciences Review. pp 175-178. 

18 

19 Moore, D.H., J.J. Jaeger and N.K. Jax. 1991. Effects of exercise following exposure to 

20 perfluoroisobutylene. Inhalation Toxicology 3(1): 113-122. 

21 

22 Nold, J.B., J.P. Petrali, H.G. Wall and D.H. Moore. 1991. Progressive pulmonary pathology of 

23 two organofluorine compounds in rats. Inhalation Toxicol. 3: 123-137. 

24 NRC (National Research Council). 2001. Standing operating procedures for developing acute 

25 exposure guideline levels for hazardous chemicals. Committee on Toxicology, Board on 

26 Toxicology and Environmental Health Hazards, Commission on Life Sciences, National 

27 Research Council. National Academy Press, Washington, DC. 

28 

29 Paulet, G. and J.P. Bernard. 1968. Heavy products appearing during the fabrication of 

30 polytetrafluorethylene: Toxicity-physiopathologic action; therapy. Biol-Med. (Paris) 57: 247-

31 301. 

32 SDU. 2000. MAC (Maximaal Aanvaarde Concentratie [Maximal Accepted Concentration]). 

33 SDU Uitgevers (under the auspices of the Ministry of Social Affairs and Employment), The 

34 Hague, The Netherlands 2000

35 Shih, M.L., J.R. Smith and J.D. McMonagle. 1990. Gas chromatographic analysis of toxic 

36 edemagenic inhalation compounds. Analytical Letters 23(9): 1711-1727.

37 Smith,W., R.J. Gardner and G.L. Kennedy. 1982. Short-term inhalation toxicity of 

38 perfluoroisobutylene. Drug and Chemical Toxicology 5: 295-303.
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 32 of 43 

1 ten Berge, W.F., A. Zwart and L.M. Appelman. 1986. Concentration-time mortality response 

2 relationship of irritant and systemically acting vapors and gases. J. Hazard. Mater. 13(3): 301-

3 310. 

4 Wang, H., Ding, R., Ruan, J., Yuan, B. Sun, X., Zhang X., Yu, S., Qu, W. 2001. Perfluoro5 isobutylene-induced acute lung injury and mortality are heralded by neutrophil sequestration and 

6 accumulation. J. Occup. Health 43: 331-338. 

7 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 33 of 43 

1 APPENDIX A: Derivation of PFIB AEGLs 

2 

3 Derivation of AEGL-1 Values

4 

5 

6 AEGL-1 values are not recommended due to insufficient data. Absence of AEGL-1 values does 

7 not imply that concentrations below AEGL-2 are without effect.
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 34 of 43 

1 

2 Derivation of AEGL-2 Values

3 

4 

5 Key Study: None. In the absence of appropriate data, the AEGL-2 values are derived by taking 

6 one-third of the respective AEGL-3 values. This approach is justified by a steep concentration7 response. [No rats died when exposed to 0.25 ppm PFIB for 4 hours; whereas 100% lethality 

8 (6/6) was noted at 0.5 ppm for 4 hours (DuPont, 1966). No mortality was noted in rats exposed 

9 to 228 ppm PFIB for 0.25 min and 100% mortality (10/10) was noted at 468 ppm. No mortality 

10 was noted in rats exposed to 20 ppm PFIB for 5 min and 9/10 rats died at 32 ppm. In rats 

11 exposed for 10 minutes, no mortality was noted at 10 ppm and 8/10 rats died at 20 ppm (Smith et 

12 al., 1982). No mortality was noted in mice exposed to 98 ppm PFIB for 1 minute; whereas, 6/6 

13 mice died at 116 ppm (Fusheng et al., 1992), and no mice died when exposed to 10 ppm for 10 

14 minutes and 10/10 mice died at 65 ppm (Bide et al., 2000). Finally, no mortality was noted in 

15 rats, mice, guinea pigs, and rabbits exposed to approximately 0.70 ppm PFIB for 2 hours; 

16 whereas, 10/10 rats, 10/10 mice, 4/5 guinea pigs, and 3/3 rabbits died when exposed to 1.5 ppm 

17 (Paulet and Bernard, 1968). ] 

18 

19 

20 

21 10-minute AEGL-2: 1⁄3 10-minute AEGL-3 = 2.0 ppm ÷ 3 = 0.67 ppm 

22 

23 30-minute AEGL-2: 1⁄3 30-minute AEGL-3 = 0.67 ppm ÷ 3 = 0.22 ppm 

24 

25 1-hour AEGL-2: 1⁄3 1-hour AEGL-3 = 0.33 ppm ÷ 3 = 0.11 ppm 

26 

27 4-hour AEGL-2: 1⁄3 4-hour AEGL-3 = 0.083 ppm ÷ 3 = 0.028 ppm 

28 

29 8-hour AEGL-2: 1⁄3 8-hour AEGL-3 = 0.042 ppm ÷ 3 = 0.014 ppm 

30 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 35 of 43 

1 

2 Derivation of AEGL-3 Values

3 

4 Key Study: DuPont, 1966 

5 

6 Toxicity endpoint: 0.25 ppm, 4-hours 

7 Highest concentration causing no mortality in rats; 100% mortality (6/6) at the next highest 

8 concentration tested (0.5 ppm) 

9 

Time scaling: cn 10 x t = k, where the exponent, n, is the chemical-specific value of 1.0, derived 

11 from rat LC50 data ranging from 0.25 to 120 minutes 

12 

C1.0 13 x t = k 

(0.25 ppm)1 14 x 4 hr = 1 ppm⋅hr 

15 

16 

17 Uncertainty factors: 1 for interspecies variability. Considered sufficient because lethality data 

18 available for several animal species suggest little interspecies variability; 

19 LC50 values for given exposure durations are essentially equivalent (Table 

20 9). 

21 

22 3 for intraspecies variability. Supported by the steep concentration23 response curve for PFIB, implying limited intraspecies variability. 

24 

25 

10-minute AEGL-3: C1.0 26 x 0.167 hr = 1 ppm⋅hr 

C1 27 = 5.9 ppm 

28 AEGL-3 = 5.9 ppm ÷ 3 = 2.0 ppm 

29 

30-minute AEGL-3: C1.0 30 x 0.5 hr = 1 ppm⋅hr 

C1 31 = 2 ppm 

32 AEGL-3 = 2 ppm ÷ 3 = 0.67 ppm 

33 

1-hour AEGL-3: C1.0 34 x 1 hr = 1 ppm⋅hr 

C1 35 = 1 ppm 

36 AEGL-3 = 1 ppm ÷ 3 = 0.33 ppm 

37 

38 4-hour AEGL-3: C = 0.25 ppm 

39 AEGL-3 = 0.25 ppm ÷ 3 = 0.083 ppm 

40 

8-hour AEGL-3: C1.0 41 x 8 hr = 1 ppm⋅hr 

C1 42 = 0.125 ppm 

43 AEGL-3 = 0.125 ppm ÷ 3 = 0.042 ppm 

44 

45 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 36 of 43 

1 APPENDIX B: Time Scaling Calculations 

2 

3 RAT DATA 

 Log Log 

Time Conc. Time Conc. Regression 

Output: 

 

0.25 361 -0.6021 2.5575 Intercept 2.0774

0.5 214 -0.3010 2.3304 Slope -0.9618

1 122 0.0000 2.0864 R Squared 0.9870

2 86 0.3010 1.9345 Correlation -0.9935

5 28 0.6990 1.4472 Degrees of 

Freedom 

 6

10 17 1.0000 1.2304 Observations 8

15 6.7 1.1761 0.8261

120 1.05 2.0792 0.0212

n = 1.04

k = 144.53

Minutes Conc. Hours Conc.

30 4.54 0.5 232.79

60 2.33 1.0 119.52

240 0.61 4.0 31.51

480 0.32 8.0 16.18

4 

5 

0 

0.5 

1 

1.5 

2 

2.5 

3 

Log Concentration

-1 -0.5 0 0.5 1 1.5 2 2.5 

Log Time

Best Fit Concentration x Time Curve

6 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 37 of 43 

1 

2 MOUSE DATA 

 Log Log 

Time Conc. Time Conc. Regression 

Output: 

 

1 107 0.0000 2.0294 Intercept 1.9844

10 11.8 1.0000 1.0719 Slope -0.9220

15 6.1 1.1761 0.7853 R Squared 0.9847

120 0.98 2.0792 -0.0088 Correlation -0.9923

120 1.6 2.0792 0.2041 Degrees of 

Freedom 

 3

Observations 5

n = 1.08

k = 142.03

Minutes Conc. Hours Conc.

30 4.19 0.5 182.80

60 2.21 1.0 96.48

240 0.62 4.0 26.87

480 0.33 8.0 14.18

3 

-0.5 

0 

0.5 

1 

1.5 

2 

2.5 

Log Concentration

0 0.5 1 1.5 2 2.5 

Log Time

Best Fit Concentration x Time Curve

4 

5 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 38 of 43 

1 

2 APPENDIX C: Derivation Summary for PFIB 

3 

4 

AEGL-1 VALUES FOR PFIB

10-min 30-min 1-h 4-h 8-hour 

NR NR NR NR NR 

Key Reference: 

Test Species/Strain/Number: 

Exposure Route/Concentration/Duration: 

Effects: 

Endpoint/Concentration/Rationale: 

Uncertainty Factors/Rationale: 

 Total uncertainty factor: 

 

Modifying Factor: 

Animal to Human Dosimetric Adjustment: 

Time Scaling: 

Data Adequacy: Data are insufficient for deriving AEGL-1 values for PFIB; therefore, AEGL-1 values are not 

recommended. Absence of an AEGL-1 value does not imply that concentrations below the AEGL-2 are without 

effect. 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 39 of 43 

AEGL-2 VALUES FOR PFIB

10 min 30 min 1 h 4 h 8 h 

0.67 ppm 

(5.5 mg/m3

) 

0.22 ppm 

(1.8 mg/m3) 

0.11 ppm 

(0.90 mg/m3) 

0.028 ppm 

(0.23 mg/m3) 

0.014 ppm 

(0.11 mg/m3) 

Reference: 

 

Test Species/Strain/Sex/Number: : 

Exposure Route/Concentrations/Durations: 

Effects: 

Endpoint/Concentration/Rationale : One-third the AEGL-3 values. Justified by a steep concentration-response. 

[No rats died when exposed to 0.25 ppm PFIB for 4 hours; whereas 100% lethality (6/6) was noted at 0.5 ppm for 

4 hours (DuPont, 1966). No mortality was noted in rats exposed to 228 ppm PFIB for 0.25 min and 100% 

mortality (10/10) was noted at 468 ppm. No mortality was noted in rats exposed to 20 ppm PFIB for 5 min and 

9/10 rats died at 32 ppm. In rats exposed for 10 minutes, no mortality was noted at 10 ppm and 8/10 rats died at 

20 ppm (Smith et al., 1982). No mortality was noted in mice exposed to 98 ppm PFIB for 1 minute; whereas, 6/6 

mice died at 116 ppm (Fusheng et al., 1992), and no mice died when exposed to 10 ppm for 10 minutes and 

10/10 mice died at 65 ppm (Bide et al., 2000). Finally, no mortality was noted in rats, mice, guinea pigs, and 

rabbits exposed to approximately 0.70 ppm PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 4/5 guinea pigs, 

and 3/3 rabbits died when exposed to 1.5 ppm (Paulet and Bernard, 1968). 

Uncertainty Factors/Rationale: 

 

Modifying Factor: 

Animal to Human Dosimetric Adjustment: 

Time Scaling: : 

Data Adequacy: Inadequate data set for AEGL-2 effects. 

1 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 40 of 43 

1 

AEGL-3 VALUES FOR PFIB

10 min 30 min 1 h 4 h 8 h 

2.0 ppm 

(16 mg/m3

) 

0.67 ppm 

(5.5 mg/m3) 

0.33 ppm 

(2.7 mg/m3) 

0.083 ppm 

(0.68 mg/m3) 

0.042 ppm 

(0.34 mg/m3) 

Reference: DuPont , 1966. Initial Submission: Acute inhalation toxicity of perfluoroisobutylene in rats with 

cover letter dated 101592. OTS0571231. 

Test Species/Strain/Sex/Number: rat/ChR-CD /male/6 per group 

Exposure Route/Concentrations/Durations: Rats exposed to 0.25, 0.5, or 1.0 ppm for 4-hours 

Effects: 

0.25 ppm: No mortality. Clinical signs included face washing, hyperemia, sneezing, hypernea, dyspnea, mildly 

responsive 

0.5 ppm: 100% Mortality (6/6; found dead 1-day post-exposure). Clinical signs same as 1.0 ppm except no 

convulsions. Mildly responsive 

1.0 ppm: 100% Mortality (6/6; found dead during exposure). Clinical signs included face washing, hyperemia, 

hypernea, dyspnea, pale ears, rapid respiration, convulsions (1/6) 

Endpoint/Concentration/Rationale: 0.25 ppm for 4-hr/ Highest concentration causing no mortality in rats; 100% 

mortality (6/6) at the next highest concentration tested 

Uncertainty Factors/Rationale: Total uncertainty factor adjustment was 3. 

Interspecies: 1 – Considered sufficient because lethality data available for several animal species suggest little 

interspecies variability; LC50 values for given exposure durations are essentially equivalent (Table 9). Reported 

1-min LC50 values are 107 ppm for mice (Fusheng et al., 1992) and 122 ppm for rats (Smith et al., 1982); 10-

minute values are 11.8 ppm for mice (Bide et al., 2000) and 17 ppm for rats (Smith et al., 1982); 15 minute 

values are 6.1 ppm for mice and 6.7 ppm for rats (Karpov, 1977); and reported 2-hour values are 0.98 ppm 

(Paulet and Bernard, 1968) and 1.6 ppm for mice (Karpov, 1977), 1.05 ppm for rats and guinea pigs (Paulet and 

Bernard, 1968), and 1.20 ppm for rabbits (Karpov, 1977). 

Intraspecies: 3 – Supported by the steep concentration-response curve for PFIB, implying limited 

intraspecies variability. No rats died when exposed to 0.25 ppm PFIB for 4 hours; whereas 100% lethality (6/6) 

was noted at 0.5 ppm for 4 hours (DuPont, 1966). No mortality was noted in rats exposed to 228 ppm PFIB for 

0.25 min and 100% mortality (10/10) was noted at 468 ppm. No mortality was noted in rats exposed to 20 ppm 

PFIB for 5 min and 9/10 rats died at 32 ppm. In rats exposed for 10 minutes, no mortality was noted at 10 ppm 

and 8/10 rats died at 20 ppm (Smith et al., 1982). No mortality was noted in mice exposed to 98 ppm PFIB for 1 

minute; whereas, 6/6 mice died at 116 ppm (Fusheng et al., 1992), and no mice died when exposed to 10 ppm for 

10 minutes and 10/10 mice died at 65 ppm (Bide et al., 2000). No mortality was noted in rats, mice, guinea pigs, 

and rabbits exposed to approximately 0.70 ppm PFIB for 2 hours; whereas, 10/10 rats, 10/10 mice, 4/5 guinea 

pigs, and 3/3 rabbits died when exposed to 1.5 ppm (Paulet and Bernard, 1968). 

 

Modifying Factor: NA 

Animal to Human Dosimetric Adjustment: Not applicable 

Time Scaling: Cn x t = k, where n=1.0, derived from rat LC50 data ranging from 0.25 to 120 minutes. Time 

scaling from 4-hours to 10-minutes is justified based on the fact that no mortality was noted in rats 

exposed to 10 ppm PFIB (Smith et al., 1982) or mice exposed to 9.2 ppm PFIB (Bide et al., 2000) 

for 10-minutes. Applying an uncertainty factor of 3 to these concentrations, yields 10-min AEGL3 values of 3.3 and 3.1 ppm, suggesting that the derived 10-min AEGL-3 value is reasonable.

Data Adequacy: Sufficient for AEGL-3 derivation. 

2 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 41 of 43 

1 APPENDIX D: CATEGORY PLOT FOR PFIB 

2 

3 

0.0 

0.1 

1.0 

10.0 

100.0 

1000.0 

ppm

0 60 120 180 240 300 360 420 480 

Minutes

Human - No Effect

Human - Discomfort

Human - Disabling

Animal - No Effect

Animal - Discomfort

Animal - Disabling

Animal - Some Lethality

Animal - Lethal

AEGL

Chemical Toxicity

PFIB

AEGL-3

AEGL-2

4 

5 

6 

7 

8 

9 

10 

11 

12 

13 

14 

15 

16 

17 

18 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 42 of 43 

1 

Source Species ppm Minutes Category 

 

NAC/AEGL-1 NR 10 AEGL 

NAC/AEGL-1 NR 30 AEGL 

NAC/AEGL-1 NR 60 AEGL 

NAC/AEGL-1 NR 240 AEGL 

NAC/AEGL-1 NR 480 AEGL 

 

NAC/AEGL-2 0.67 10 AEGL 

NAC/AEGL-2 0.22 30 AEGL 

NAC/AEGL-2 0.11 60 AEGL 

NAC/AEGL-2 0.028 240 AEGL 

NAC/AEGL-2 0.014 480 AEGL 

 

NAC/AEGL-3 2.0 10 AEGL 

NAC/AEGL-3 0.67 30 AEGL 

NAC/AEGL-3 0.33 60 AEGL 

NAC/AEGL-3 0.083 240 AEGL 

NAC/AEGL-3 0.042 480 AEGL 

 

 Rat 0.3 360 0 no effects (DuPont, 1956;1961) 

 Rat 0.5 360 3 Mortality: 2/2 (DuPont, 1956; 1961) 

 Rat 1 255 3 Mortality: 2/2 (DuPont, 1956; 1961) 

 Rat 0.25 240 2 Face washing, hyperemia, sneezing, 

dyspnea, mildly responsive (DuPont, 1966) 

 Rat 0.5 240 3 Mortality: 6/6 (DuPont, 1966) 

 Rat 1 240 3 Mortality: 6/6 (DuPont, 1966) 

 Rat 10 10 2 Wheezing, labored breathing (Smith et al., 1982) 

 Rat 15 10 pl Mortality: 2/10 (Smith et al, 1982) 

 Rat 17 10 pl Mortality: 5/10 (Smith et al, 1982) 

 Rat 20 10 pl Mortality 8/10 (Smith et al., 1982) 

 Rat 1.8 120 3 100% mortality (Danishevskii & Kochanov, 1961) 

 Rat 6.7 15 pl LC50 (Karpov, 1977) 

 Rat 11.6 120 pl LC50 (Karpov, 1977) 

 rat, 

mouse, 

GP, rabbit 

0.7 120 2 clinical signs (Paulet & Bernard, 1968) 

 rat, 

mouse, 

GP, rabbit 

1.1 120 pl Mortality: 8/10 rats, 10/10mice, 7/10 GP, 

1/5 rabbit (Paulet & Bernard, 1968) 

 rat, 

mouse, 

GP, rabbit 

1.5 120 3 100% mortality (Paulet & Bernard, 1968) 

 mouse 9.2 10 2 “Clinical signs" (Bide et al., 2000) 

 mouse 10 10 pl Mortality: 2/10(Bide et al, 2000) 

 mouse 15 10 3 Mortality: 17/17 (Bide et al., 2000) 

 mouse 98 1 2 Decreased movement, respiration, staggering, 

weakness (Fusheng, 1992) 

 mouse 104 1 pl Mortality: 2/6 (Fusheng, 1992) 

 mouse 116 1 3 Mortality: 6/6 (Fusheng, 1992) 

 mouse 1.8 120 3 100% mortality (Danishevskii & Kochanov, 1961) 
PERFLUOROISOBUTYLENE (PFIB) Proposed: April 2009/ Page 43 of 43 

 mouse 1.2 120 pl minimal lethality (Danishevskii & Kochanov, 1961) 

 mouse 6.1 15 pl LC50 (Karpov, 1977) 

 mouse 1.6 120 pl LC50 (Karpov, 1977) 

 rabbit 12.2 15 pl LC50 (Karpov, 1977) 

 rabbit 4.3 120 pl LC50 (Karpov, 1977) 

 Cat 3.1 120 pl LC50 (Karpov, 1977) 

 Rat 0.24 240 2 Impaired reflexes (Karpov, 1977) 

1