Modeling Cardiac Sensitization Potential 

of Humans Exposed to Halon 1301 

or Halon 1211 aboard Aircraft 

ALLEN VINEGAR, M.S., PH.D. 

VINEGAR A. Modeling cardiac sensitization potential of humans 

exposed to Halon 1301 or Halon 1211 aboard aircraft. Aviat Space 

Environ Med 2001; 72928-36. 

Background: Halon 1301 and Halon 121 1 are being replaced because they contribute to the depletion of ozone. Many of the potential 

candidate chemicals for replacing them are, like them, halogenated 

hydrocarbons. These chemicals have the potential to cause cardiac 

sensitization at high enough exposure concentrations. Methods: A physiologically based pharmacokinetic model, which mathematically describes the uptake, distribution, metabolism, and elimination of chemicals, was used to relate exposure to these chemicals with arterial blood 

concentrations resulting from the exposure. This information was then 

used to evaluate the potential for the occurrence of a cardiac-sensitizing 

event. The model was used to analyze the exposures to Halon 1301 and 

Halon 1211 in three aircraft (Navy E-28, Cessna-4218, and Cessna21 OC). Results: Halon 1301 exposures were shown to be safe, but Halon 

12 1 1 resulted in arterial concentrations in exposed individuals that 

reached levels that could potentially cause cardiac sensitization. Conclusions: Use of the model for evaluating the risk from exposure to 

Halon 1301 and Halon 121 1 is a moot point since both chemicals are 

being replaced. However, demonstration of the validity of the approach 

provides a tool for the evaluation of the health safety of replacement 

candidates. The National Fire Protection Association has approved use 

of this model for assessing times for safe egress from situations where 

agents are used to flood an area to extinguish a fire. 

Keywords: cardiac sensitization, halon, physiologically based pharmacokinetic model, fire extinguishant. 

ALONS, USED AS FIRE extinguishants, have been H banned from production because of international 

concern for the depletion of stratospheric ozone. Only 

existing stocks are available for essential application 

use in aircraft fire and explosion suppression systems. 

Constantly changing political pressure puts these stocks 

at risk for elimination, increasing the need to make 

halon alternatives available for aircraft use. Most chemicals being considered as replacements for Halon 1301 

and 1211 are halogenated hydrocarbons which, as a 

class, are regulated by the U.S. Environmental Protec- tion Agency (6). 

Cardiac sensitization is the acute toxic endpoint of 

concern. Dogs are monitored continually for electrocar- diographic changes indicative of the appearance of a 

burst of multifocal ventricular ectopic activity or ventricular fibrillation. They are given an epinephrine challenge after 5 min of exposure to the test chemical. The 

test is performed at several chemical concentrations to 

determine a no observable adverse effect level 

(NOAEL) and a lowest observable adverse effect level 

(LOAEL). The LOAEL and NOAEL values are used 

directly for establishing human exposure limits because 

of the sensitive nature of the test (6). 

Recently, a mathematical tool was developed which 

allows the quantitative evaluation of short-term exposure to halogenated hydrocarbons (10). This tool is a 

physiologically based pharmacokinetic (PBPK) model, 

which can relate chemical exposure to concentrations in 

the body. It has been proposed that the model be used 

to relate external exposure of halon replacement chemicals to arterial blood concentration. Arterial blood concentration can then be compared with a target arterial 

blood concentration associated with cardiac sensitization. The methodology for doing this has been proposed (7) and described in detail (8). The National Fire 

Protection Association (3) has approved use of this 

model for assessing times for safe egress from situations 

where agents are used to flood an area to extinguish a 

fire. 

The PBPK model can be used both retrospectively to 

evaluate previous actual exposure scenarios and prospectively to evaluate potential exposure scenarios. An 

example of a retrospective evaluation was given in 

Vinegar et al. (10) where they evaluated an accidental 

exposure to Halon 1211 that had occurred in an Israeli 

Army battle tank during a military exercise (2). In this 

instance, model predictions were consistent with the 

outcome where the gunner, having only brief exposure, 

successfully escaped without incident but the driver, 

with prolonged exposure, reached levels adequate for 

cardiac sensitization. The driver, in fact, was observed 

to be in ventricular fibrillation, never regained consciousness and died as a result of the incident. A prospective application of the model was demonstrated by 

Vinegar et al. (9). In order to evaluate the potential 

hazard to ground crews of an accidental release of CFJ 

From ManTech Environmental Technology, Inc. at Wright-Patterson AFB, OH. 

This manuscript was received for review in July 2000. It was 

revised in March 2001. It was accepted for publication in April 2001. 

Address reprint requests to: Allen Vinegar, Ph.D., P.O. Box 1398, 

Placitas, NM 87043; tokens@myranch.com 

Reprint & Copyright 0 by Aerospace Medical Association, Alexandria, VA. 

928 Aviation, Space, and Environmental Medicine Vol. 72, No. 10 October 2001 
HALON EXPOSURE ABOARD AIRCRAFT-VINEGAR 

Fig. 1. Halon 1301 - Ground Test 

(equipment cooling System ON) for 

Navy E-2b. Concentrations of Halon 

1301 measured at four locations are 

shown in the left-hand column. Simulated arterial concentrations for each 

of the four locations are shown in the 

right-hand column. The straight line 

shown at 25.7 mg - L-' for each of the 

arterial simulations represents the target concentration for cardiac sensitization. 

Personnel Area 

0 60 120 180 240 300 0 60 120 180 240 300 

d 0 

N p? 

Head Level 

Equipment Area a 

m 

0 

0 60 120 180 240 300 0 60 120 180 240 300 

Floor Level 

Equipment Area 

0 60 120 180 240 300 0 60 120 180 240 300 

Aft Equipment 

Area 

0 60 120 180 240 300 0 60 120 180 240 300 

SECONDS 

a discharge test was conducted on an F-15 jet to record 

CF,I concentration time histories at various locations 

near the aircraft. These exposure data were used with 

the PBPK model to simulate the potential blood levels 

of workers at various locations around the aircraft during the release. The blood levels were compared with 

the target arterial blood concentration associated with 

cardiac sensitization. Results showed that at some locations the target was not reached but at the open nacelle 

the blood concentrations could potentially reach double 

the target. This information was put in perspective with 

a hrther retrospective simulation of individuals who 

had actually inhaled CF,I and whose blood concentrations were simulated and estimated to be 100 times the 

target. These individuals experienced no apparent effect of their exposures, thus indicating the intended 

conservative nature of the cardiac sensitization test. 

Further prospective application of the model was demonstrated in Vinegar et al. (8). Here a method was 

demonstrated for establishing safe duration for exposure to potential halon replacements at different flood- ing concentrations. 

An issue of health concern is that of the intentional 

use of fire extinguishers in aircraft cabins with passen- gers aboard. No data were available for any of the 

potential halon replacements. However, there have 

929 Aviation, Space, and Environmental Medicine Vol. 72, No. 10 October 2001 
HALON EXPOSURE ABOARD AIRCRAFT-VINEGAR 

Personnel Area 

0 60 120 180 240 300 

Head Level 

Equipment Area 

z 

U 

z 

0 VI 

0 60 120 180 240 300 

Floor Level 

Equipment Area 

0 60 120 180 240 300 

0 60 120 180 240 300 

3 

3 

W 

E 

u 

z 

u 

-. 0 60 120 180 240 300 

-I 

0 60 120 180 240 300 

d N- N mAft Equipment d Fig. 2. Halon 1301 - Flight Test e - Area m- 00 

(Nozzle Jets Mixing Agent) for Navy 

2- 2- E-2B. Concentrations of Halon 1301 

measured at four locations are shown 

in the left-hand column. Simulated ar- terial concentrations for each of the a - m - 

four locations are shown in the rightat 25.7 mg - L-’ for each of the arterial 0 60 120 180 240 300 0 60 120 180 240 300 

simulations represents the target concentration for cardiac sensitization. 

1 

hand column. The straight line shown 0. 0 1 

SECONDS 

been several published reports on measurements taken 

in aircraft cabins during the release of Halon 1301 and 

Halon 1211. These data were used with the PBPK model 

to see if any of the described scenarios could put passengers or crew at potential risk for cardiac sensitization. Results of these simulations are reported herein. 

METHODS 

Three publications were found that presented data on 

releases of Halon 1211 and/or Halon 1301 in aircraft. 

The first study (5) used a fleet configured Navy E-2B 

“Hawkeye” airplane. Concentrations of Halon 1301 

were measured at head level in areas occupied by flight 

crewmembers, and in airplane locations where fire hazard potential posed the greatest threat. Halon 1301 was 

monitored using a Statham Laboratories Model GA-2A 

gas recorder and accessories. 

The second study (1) used a Cessna Model C421B, a 

small pressurized aircraft. Halon 1211 and Halon 1301 

were measured using factory field modified Beckman 

Model 865 infrared gas analyzers. Measurements were 

made at three locations: 

1. Test area -Actual fire extinguisher discharge location. 

2. Knee area -20 in above the floor at the area of 

discharge. Discharge area for pilot’s and copilot’s 

930 Aviation. Sauce. and Environmental Medicinp 9 Vnl. 73. Nn. 70 OrfnhPr 7001 
h 

s 

7 

W 

p! 

z 

z 

0 

rn 

3 clr 

z 

w 

u 

z 

0 

u 

,-- 

NN -- 

e. 

a. 

c, 

07' 

O 18 36 54 72 90 

, 

0 18 36 54 72 90 

c. 

N- - 

c\- 

w. 

VI07 , ~ 

c 

0 18 36 54 72 90 

N- - 

c\- 

w. 

VI07 , ~ 

c 

2- 

- N. 

m - 

a - 

2- 

- N. 

m - 

a - 

Test Area 

Knee Area 

Nose Area 

* 

t 

SECONDS 

Test Area 

Knee Area 

Nose Area 

SECONDS 

0 18 36 54 72 90 

0 18 36 54 72 90 

0 18 36 54 72 90 

.. 0 18 36 54 72 90 

0 18 36 54 72 90 

0 18 36 54 72 90 

Fig. 3. Halon 1301 - Concentrations 

Cabin Area Last Vent Before Door Left 

Side for Cessna C-4218. Concentrations of Halon 1301 measured at three 

locations are shown in the left-hand 

column. Simulated arterial concentrations for each of the three locations are 

shown in the right-hand column. The 

straight line shown at 25.7 mg * L-' for 

each of the arterial simulations represents the target concentration for cardiac sensitization. 

Fig. 4. Halon 1301 - Concentrations 

Cabin Area Last Vent Right Side for 

Cessna C-42 1 B. Concentrations of 

Halon 1301 measured at three locations are shown in the left-hand column. Simulated arterial concentrations 

for each of the three locations are 

shown in the right-hand column. The 

straight line shown at 25.7 mg - L-' for 

each of the arterial simulations represents the target concentration for cardiac sensitization. 

Aviation, Space, and Environmental Medicine Vol. 72, No. 10 9 October 2001 931 
--. . . . . 

0 18 36 54 72 90 

8- 

%- 

0- 

0 18 36 54 72 90 

8- 

8- 

sFi0 18 36 54 72 90 

0 

8- 

0 

ON -. 

4. 

o-),,,, 

0 18 36 54 72 90 

0 

8- 

0 

ON -. 

0 18 36 54 72 90 

o-),,,, 

Test Area 

Knee Area 

Nose Area 

t * 

SECONDS 

Test Area 

Knee Area 

Nose Area 

0 18 36 54 72 90 

SECONDS 

0 18 36 54 72 90 

0 18 36 54 72 90 

-, , . . . . 0 18 36 53 72 90 

0 18 36 54 72 90 

Fig. 5. Halon 121 1 - Concentrations 

Copilot’s Seat for Cessna C-4218. 

Concentrations of Halon 1211 measured at three locations are shown in 

the left-hand column. Simulated arterial concentrations for each of the 

three locations are shown in the righthand column. The straight line shown 

at 21 .O mg - L-’ for each of the arterial 

simulations represents the target concentration for cardiac sensitization. 

Fig. 6. Halon 121 1 - Concentrations 

Cabin Side Of Grill Under Copilot’s 

Seat for Cessna C-4218. Concentrations of Halon 12 1 1 measured at three 

locations are shown in the left-hand 

column. Simulated arterial concentrations for each of the three locations are 

shown in the right-hand column. The 

straight line shown at 21 .O mg L-’ for 

each of the arterial simulations represents the target concentration for cardiac sensitization. 

932 Aviation, Space, and Environmental Medicine Vol. 72, No. 10 October 2001 
Pilot-copilot 

Belt Level 

N. 

-tN 

0 20 40 60 80 100 0 20 40 60 80 100 

m. 

Pilot’s Nose 

Level 

0 

N. 

x- 

‘0- 

00. 

0 20 40 60 80 100 

N 

Under Instrument 

I Panel Pilot’s Side 3 

‘0 

0 20 40 60 80 100 

0 20 40 60 &80 100 0 20 40 60 80 100 

SECONDS 

Pilot-copilot 

BeltLevel 

, 1 !& m 

0 

Pilot-copilot 1 Belt Level 

0 20 40 60 80 100 0 20 40 60 80 100 

0 20 40 60 80 100 0 20 40 60 80 100 

Fuel And 

Hydraulic 

Selector Valve 

0 0 20 40 60 80 100 20 40 60 80 100 

SECONDS 

Fig. 7. Halon 1301-3-Ib Extinguisher Directed To Copilot’s Door - 

Overhead Vents Closed for Cessna 

21 OC. Concentrations of Halon 1301 

measured at three locations are shown 

in the left-hand column. Simulated arterial concentrations for each of the 

three locations are shown in the righthand column. The straight line shown 

at 25.7 mg- L-’ for each of the arterial 

simulations represents the target concentration for cardiac sensitization. 

Fig. 8. Halon 1301-3-lb Extinguisher Directed To Fuel And Hydraulic Selector Valves - Overhead Vents 

Open for Cessna 210C. Concentrations of Halon 1301 measured at three 

locations are shown in the left-hand 

column. Simulated arterial concentrations for each of the three locations are 

shown in the right-hand column. The 

straight line shown at 25.7 rng - L-’ for 

each of the arterial simulations represents the target concentration for cardiac sensitization. 

Aviation, Space, and Environmental Medicine Vol. 72, No. 10 October 2001 933 
HALON EXPOSURE ABOARD AIRCRAFT-VINEGAR 

Pilotcopilot 

Belt Level 

0 20 40 60 80 100 

Pilot’s Nose 

Level 

0 20 40 60 80 100 0 20 40 60 80 100 

r! 

0 20 40 60 80 100 0 20 40 60 

SECONDS 

seat tests was at knee level where the seat cushion 

meets the seat back. 

Nose area -37 in above the floor at the area of 

discharge. 

The last study (4) used a Cessna Model 210C, a small 

non-pressurized aircraft. Halon 1211 and Halon 1301 

were measured using modified Beckman Model 865 

infrared gas analyzers. Measurements were made at the 

point of release and at two other selected sites during 

each test. 

In all three publications there are diagrams showing 

the specific locations monitored. The data were presented in graphic form. Results reaching the highest 

peak exposure concentrations were used from each paper. The data were digitized and converted to ASCII so 

that they could be used with the PBPK model. Exposure 

scenarios selected were used to simulate the arterial 

concentration using the model described by Vinegar 

et al. (10). Arterial concentrations were compared 

with target arterial concentrations for cardiac sensitization (8). 

RESULTS 

Representative results for the Navy E-2B are shown 

in Figs. 1 and 2. A ground test is illustrated in Fig. 1. 

Concentrations of Halon 1301 measured at four locations are shown in the left-hand column. Simulated 

arterial concentrations for each of the four locations are 

80 100 

Fig. 9. Halon 1211-2.5-lb Extinguisher Directed Under Instrument 

Panel Pilot’s Side - Overhead Vents 

Open for Cessna 210C. Concentrations of Halon 121 1 measured at three 

locations are shown in the left-hand 

column. Simulated arterial concentrations for each of the three locations are 

shown in the right-hand column. The 

straight line shown at 21 .O mg * L-’ for 

each of the arterial simulations represents the target concentration for cardiac sensitization. 

shown in the right-hand column. The straight line 

shown at 25.7 mg L-’ for each of the arterial simulations represents the target concentration for cardiac 

sensitization. None of the simulated concentrations 

reached the target. An example of a flight test is shown 

in Fig. 2. Under these conditions at floor level in the 

equipment area the concentrations of Halon 1301 in 

arterial blood exceeded the target concentration at 

about 40 s into the exposure and remained above the 

target for the duration of the measurements. Arterial 

concentration simulations remained below target at the 

other measured sites. 

Results for representative releases aboard the Cessna 

C-421B are shown in Figs. 3 to 6. Halon 1301 releases at 

the last vent before the left side door (Fig. 3) or at the 

last vent on the right side of the cabin (Fig. 4) resulted 

in simulated arterial concentrations well below the target concentration. Both releases of Halon 1211 resulted 

in simulated arterial concentrations that surpassed the 

target concentration of 21.0 mg L-’ (Figs. 5 and 6). The 

target was exceeded at both sites of release. The release 

at the copilot’s seat (Fig. 5) had measurements at nose 

level, which exceeded the target after about 45 s of 

exposure. Release at the cabin side of grill under the 

copilot’s seat resulted in simulated arterial concentration at the knee area exceeding the target after about 

16 s and peaking at more than three times the target at 

about 26 s (Fig. 6). However, nose area concentrations 

remained below the target. 

934 Aviation, Space, and Environmental Medicine 9 Vol. 72, No. 10 October 2001 
HALON EXPOSURE ABOARD AIRCRAFT-VINEGAR 

Pilot-copilot 

Belt Level 

0 20 40 60 80 100 0 20 40 60 80 100 

2 *1-1 

Pilot’s Nose 

Level 31 

0 20 40 60 80 100 0 20 40 60 80 100 

0 20 40 60 80 100 0 20 40 60 

SECONDS 

Halon 1301 arterial concentrations remained below 

the target concentration for releases, in the Cessna 210C, 

directed to the copilot’s door with overhead vents 

closed (Fig. 7) and directed to fuel and hydraulic selector valves with overhead vents open (Fig. 8). Halon 

1211 arterial concentrations exceeded the target level at 

all measured locations when the extinguisher was directed under the instrument panel on the pilot’s side 

with overhead vents open (Fig. 9) or closed (Fig. 10). 

DISCUSSION 

The use of Halon 1301 for several decades has occurred 

with an excellent safety record. Retrospective modeling of 

scenarios such as those illustrated above show that 

generally under normal use there has been little to no 

opporhnity for the occurrence of exposure situations 

where individuals have been put at potential risk of having blood levels of Halon 1301 ever reach a target concentration that might predispose for the onset of a cardiac 

sensitization response. Halon 1211, when used as a 

streaming agent under open conditions, likewise has 

posed little risk. However, when used under more confined situations the potential for cardiac sensitization exists. Several scenarios illustrated above showed situations 

where arterial concentrations of Halon 1211 exceeded the 

target associated with a potential for cardiac sensitization. 

The report of an incident involving exposure in an army 

battle tank by Lerman et al. (2) (see introduction) demonstrates that the risk is real if Halon 1211 is used under 

80 100 

Fig. 10. Halon 1211-2.5-lb Extinguisher Directed Under Instrument 

Panel Pilot’s Side - Overhead Vents 

Closed for Cessna 2 1 OC. Concentrations of Halon 121 1 measured at three 

locations are shown in the left-hand 

column. Simulated arterial concentrations for each of the three locations are 

shown in the right-hand column. The 

straight line shown at 21 .O mg - L-’ for 

each of the arterial simulations represents the target concentration for cardiac sensitization. 

confined situations where the exposure concentration can 

get high enough to result in hghly elevated blood concentrations. 

The discussion with reference to Halons 1301 and 

1211 is perhaps a moot point with both of them being 

replaced with other agents. However, the use of PBPK 

modeling to evaluate exposure scenarios with replacement agents should be considered. Prospective modeling of potential scenarios can forewarn against situations such as that reported by Lerman et al. (2) for army 

battle tanks. 

ACKNOWLEDGMENTS 

Support for this work was provided partially by the Department of 

Defense’s Next Generation Fire Suppression Technology Rogram, 

funded by the DoD Strategic Environmental Research and Development 

Program (SERDP); through an Interagency Agreement between the U.S. 

EPA and the Department of the Air Force; and through Department of 

the Air Force Contract No. F41624-96-c-9010. The manuscript has been 

reviewed by the Office of Public Affairs and assigned the following 

journal article number, AFRL-HFST-WP-JA-2000OOOl. 

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f 

936 Aviation, Space, and Environmental Medicine Vol. 72, No. 10 October 2001