TROPODEGRADABLE BROMOCARBON EXTINGUISHANTS – 

COMPOUND SELECTION AND TESTING ISSUES 

J. Douglas Mather Robert E. Tapscott 

Center for Global Environmental Technology Vice President - GlobeTech, Inc., 

901 University Boulevard S.E. 8200 Montgomery Blvd, NE, #218 

Albuquerque, NM 87106-4339 Albuquerque, NM 87109 

Tel: 505-272-7259 Tel: 505-883-9397 

Mather@nmeri.unm.edu GlobeTech@speakeasy.net 

INTRODUCTION 

In work sponsored by the Next-Generation Fire Suppression Technology Program, the Center for 

Global Environmental Technology at University of New Mexico and GlobeTech, Inc. are 

identifying promising tropodegradable bromocarbons and evaluating their performance as 

replacements for Halon 1301. While a number of candidate tropodegradable compounds have 

been identified from the alkene, ether, and amine families the current interest is primarily on 

bromofluoroalkenes and bromofluoro-ethers. The current project, though only partially 

complete, is focused on improving the methods for estimating the cardiac sensitization properties 

of chemicals of interest to the halon replacement effort and has identified some potentially 

promising approaches. 

The recently announced results of a cardiac sensitization study by the Advanced Agent Working 

Group (AAWG) on 2-bromo-3,3,3-trifluoropropene indicate that its LOAEL and NOAEL are 

respectively, 1.0% and 0.5% by volume. Though there remain some questions that will be 

resolved once the final test report is made available, these values indicate that 2-bromo-3,3,3-

trifluoropropene is equivalent to Halon 1211 insofar as cardiac sensitization is concerned. As 

the goal of the NGP program is to identify a replacement compound for Halon 1301, additional 

compounds must be selected from the promising chemical families. 

The equivalence of 2-bromo-3,3,3-trifluoropropenes' cardiac sensitization to that of Halon 1211 

does provide some promise of eventual success for the search for halon replacements in the 

bromofluoro-alkene family of compounds, Table 1. While several bromofluoroalkenes have 

been prepared only one has been subject to a standard cardiac sensitization test. It is expected 

that differences in fluorine and bromine substitution patterns as well as the overall degree of 
fluorination represented within the bromofluoro-propenes' family of compounds will exhibit a 

wide range of cardiac sensitization responses in dog exposure studies. 

Table 1. Representative LOAEL and NOAEL values for fire suppressing agents. 

CHEMICAL FORMULA LOAEL (V%) NOAEL (V%)

Halon 1301 CF3Br 7.5 5.0

Halon 1211 CF2ClBr 1.0 0.5

Trifluoromethyl Iodide CF3I 0.4 0.2

2-Bromo-3,3,3-trifluoropropene C3F3H2Br 1.0 0.5

Currently no method exists for the estimation of cardiac sensitization performance and a single 

test costs approximately $70,000, not including the chemical. This cost effectively prohibits the 

testing of more than a few compounds by the established method and leaves the halon 

replacement research community with limited options. The inability to efficiently screen 

compounds using the established dog exposure test method also precludes the ready 

development of useful trends to guide in compound selection and requires that new cardiac 

sensitization performance estimation methods be identified or developed to fill this role. These 

new methods of ranking compounds may utilize the results of single test protocols or 

combinations of test methods. Regardless, short of a dramatic increase in the resources for 

toxicity testing, a new approach to the estimation and ranking of a compound's estimated cardiac 

sensitization properties is essential to continued progress in the area of halon replacement. 

Past work on toxicological assessments of halon replacement compounds employed QSAR 

studies to predict toxicity, identified trends based on limited data relating composition and 

structure as well as substitution patterns to toxicity, and in limited cases employed chemical 

reactivity estimates[1]. All of these methods have in the past proven useful in estimating 

unknown toxicological, biological or physical properties of chemicals from known information 

on related chemicals or chemical families. QSAR approaches often employ correlation 

equations, determined by linear regression analysis techniques using general, steric, 

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hydrophobic, electronic, and molecular structure properties of known chemicals, to form the 

basis of the toxicity analysis. 

Molecular connectivity based QSAR’s require that indices reflecting structure be determined, 

and generally the amount of data needed is less than that for property-activity QPAR’s. In both 

cases, sufficient toxicity data must be available with which to develop correlations capable of 

providing toxicity estimates of unknown substances. 

Toxicity estimation methods involving in vitro test protocols are now in widespread use. 

Methods for evaluating the impacts of chemicals on target organs (kidney, liver, skin, heart, etc.) 

have in many cases become well developed. The potential for employing a modified in vitro 

method as a means for evaluating the relative potential of a series of chemicals to induce 

arrhythmia is readily apparent. As such, the identification of an existing in vitro (cell or tissue) 

based protocol or the development of a new protocol enabling the ranking of compounds with 

respect to induction of cardiac arrhythmia could greatly enhance the selection of optimal 

compounds. 

GOALS: IDENTIFICATION OF IMPROVED SCREENING METHODS 

This project is intended to address the need for improvements in existing methods and 

development of new methods and approaches to the estimation of cardiac sensitization. The 

approaches being taken in this project to improving the existing QSAR methods, locating 

additional exposure information, and identifying promising in vitro approaches are described 

briefly below. 

a) A review of compound attributes and physical properties not currently 

employed in QSAR predictions of cardiac sensitization. 

b) A review of anesthesiology research to identify and collate relevant test data, 

SAR methods and any attributes that might be employed in evaluating the 

cardiac sensitization properties or establishing a relative ranking of the cardiac 

sensitization properties of a series of brominated fluorocarbons. 

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c) A search for possible in vitro methods applicable to the low cost assessment of 

the cardiac sensitization potential (or relative performance) of a candidate halon replacement 

chemical or series of such chemicals. This effort will identify and list existing research centers 

employing in vitro methods to study cardiac muscle and involve contacts with medical 

researchers to determine additional sources of information on cardiac sensitization related topics. 

IN VITRO METHODS 

In vitro methods represent a very promising approach to the screening of chemical candidates of 

interest to the halon replacement research community. The in vitro method refers to the use of 

tissue or cells derived from living organisms. In general, cell lines are grown in a manner 

analogous to the growth of bacterial cultures. The cells and tissues employed come from a wide 

range of donor species including humans, rats, mice, and monkeys. 

There are several phenomena which can be monitored in in vitro studies at present. In myocytes 

(heart cells) cell cultures and single cell suspensions as well as tissue samples or isolated 

muscle, rhymic cellular contraction occurs naturally. Observations of changes in rhythm or the 

onset of arrhythmia following chemical exposure have been reported in many research papers. 

A prior review of in vitro methods and their limitations provides a useful summary of this 

technology and a good indication of its potential for providing a means to give ranking 

information useful to the research community[2]. 

Dog ventricular myocytes isolation methods [3], based on procedures for preparing adult rat 

heart cells [13] have been reported. Subcellular organelles have been used to investigate 

mechanisms of cardiac function [4] and may lend themselves to the development of a ranking 

method. Human heart tissue preparations have been used in studies of in-situ signal conduction 

[14]. Preparations of rat and guinea pig atrial tissues have been described by a number of 

researchers [5-8]. 

Each of these methods yield unique observations, have specific limitations and inherent 

difficulties. In the final analysis it is not unreasonable to employ not one but several of these in 

vitro methods in a testing program involving an establishment of a baseline response to existing 

halons and compounds whose cardiac sensitization are documented. 

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Table 2. In vitro Cardiac Cell Systems. 

Model Life stage Species Reference

Myocardial cells Fetal Human Goldman (9) 

Cardiomyocytes Neonatal Rat Mark and Strasser (10) 

Ventricular Cardiomyocytes Neonatal Rat Schanne (11) 

Ventricular Cardiomyocytes Neonatal Dog Liu (12) 

Cardiomyocytes Adult Rat Vahouny (13)

Cardiomyocytes Adult Rabbit Dani (14)

Cardiomyocytes Adult Dog Youker (15)

Cardiomyocytes Adult Feline Woosley (16)

Ventricular Cardiomyocytes Adult Guinea Pig Failli (17) 

Ventricular Cardiomyocytes Adult Rat Eid (18) 

The results of such a study will help establish the repeatability of the method, give confidence in 

the ability of the method to "rank" compounds, as well as provide further information useful to 

the eventual understanding ofthe mechanism of cardiac sensitization. This method must be: 

•Sensitive to variations in air concentrations in the range of interest (1% to 7.5%) 

•Reflect the cardiac sensitization results of known compounds (Halons 1211 & 1301, 

CF3I, HFC’s, etc.) 

•Result in a ranking of compounds by air concentration 

QUANTITATIVE STRUCTURE PROPERTY RELATIONSHIPS (QSAR) 

QSPR-based estimates of the compound properties of potential halon replacement compounds 

have been performed and reported by Mainstream Engineering Corporation[1]. This effort 

modeled boiling point, flame extinguishment, global warming potential (GWP), ozone depletion 

potential (ODP), tropospheric lifetime, cardiac sensitization, and LC50 values. A major 

hindrance to all QSAR efforts is the lack of known toxicity data points for related compounds or 

chemical fragments. Without data upon which to establish relationships between structure and 

toxicity, the basis for subsequent predictions become tenuous at best. In this regard, in vitro 

studies may well help by providing data for the onset of adverse effects for specific chemical 

concentrations under a variety of in vitro methods. Incorporating the results of in vitro exposure 

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studies on cardiac myocytes, tissues, perfused organs, and associated nerve tissues into existing 

QSPR could prove of great value to the identification of predictive trends. 

CHEMICAL STRUCTURES OF INTEREST 

Tropodegradable chemical structures of greatest interest incorporate unsaturated carbon-carbon 

bonds. These sites of unsaturation are vulnerable to attack by OH radicals and ozone with the 

result that the compound decomposes into polar species that “rain out” of the atmosphere. While 

the simplest unsaturated species are those based on the ethene molecule, Figure 1, the propenes, 

Figure 2, represent the greatest hope for the eventual identification of a Halon 1301 replacement. 

Figure 1. Flat structure of ethene molecule 

Figure 2. Flat structure of propene molecule. 

The bromofluoro propenes of greatest interest are the bromo-difluoropropenes, bromotrifluoropropenes, and the bromo-tetrafluoropropenes. Together these compounds represent a 

very large number of unique structural isomers. For example, the site of the bromine in the 

general group of bromodifluoropropenes can be on any of the three carbons. 

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In addition, for those structural isomers where bromine is bonded to the terminal carbon of the 

ethene fragment, there are several unique bonding patterns for the two fluorines; i.e. 1-Bromo3,3-difluoropropene*, 1-Bromo-2,3-difluoropropene*, 1-Bromo-1,3-difluoropropene*, and 1-

Bromo-1,2-difluoropropene (* indicates “cis” or “trans” isomers possible). Each of these seven 

structures will exhibit differences in chemical reactivity, polarity, solubility, and stereo 

chemistry (shape). Likely structural isomerism effects on the properties of a specific chemical 

are listed below 

 Polarity of the compound – Solubility 

 Boiling Point 

 Reactivity 

 - Chemical 

- “Lock and Key” reactivity - blocking enzymatic sites 

- Decomposition in vivio 

 Toxicity (inhalation, cardiac etc.) 

The bromofluoro propene, trans-1-bromo-3,3,3-trifluoropropene, induced notable muscular 

effects (tremor) in the tissues of the exposed rats following acute inhalation toxicity tests. These 

effects were noted during post exposure necropsy. The tested compound's structure was 

assigned based on proton-to-fluorine NMR spin coupling as the “trans” isomer shown below 

with the “cis” isomer of this compound, Figure 3. These two isomers are expected to differ in 

reactivity and polarity due to the relative positions of the bromine and CF3 group and are not 

therefore expected to neccessarily have the same effect on muscle. 

 

Figure 3. “Trans” and “Cis” structural isomers of 1-bromo-3,3,3-trifluoropropene. 

Similarly, 2-bromo-1,3,3,3-tetrafluoropropene exists as "cis" and “trans” structural isomers, 

Figure 4, and again its cis and trans structural isomers would be expected to have distinctly 

different toxicity and physical properties. 

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Figure 4. Cis and trans 1-bromo-1,3,3,3- tetrafluoropropene 

CUP-BURNER METHOD IMPROVEMENTS 

Typically, to test a chemicals cup-burner extinguishment performance using a full scale 

cupburner requires approximately 500g to 1000g of the test chemical. Where research chemicals 

are concerned this is usually prohibitively expensive. Costs for the synthesis of new compounds 

for which viable syntheses and occasionally purification processes must be developed are 

typically in the range of $2,500 for 10g to 50g. This situation lead to the early development of 

the NMERI Standard cup-burner which requires only approximately 50g to run a modified cupburner test and provide a minimum of three tests of extinguishment. As research into the 

synthesis of new compounds continues, costs per gram are increasing, in some cases quite 

dramatically. This has necessitated an effort to further refine the sample introduction methods 

being employed in the cup-burner method. NMERI tested and now employs a sample 

introduction and dispersion method based on well established nebulizer technology widely 

employed by inductively coupled plasma (ICP) analytical instruments, Figure 5. In the 

analytical application the nebulizer aspirates the sample and disperses it as a very fine mist into 

the hot torch of the ICP. In our cup-burner, we have replaced aspiration with a syringe pump 

and 2.5cc Gastight syringe. In addition, because we have found that higher boiling 

compounds condense onto cool surfaces resulting in loss of agent from the air stream and 

elevated cup-burner extinguishment values, we employ a pre-heater column, Figure 6. In 

practice, the entire cupburner base and the evaporation/mixing column are wrapped with heating 

tape and insulating material to prevent the condensation loss of agents under test due to cool 

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glass surfaces. Some experimentation is required to develop the heating required to prevent 

condensation while not overheating the apparatus. 

The nebulizer as supplied requires a nominal air flow of 1L/min. - this is established using a 

regulated pressure source for air and appropriate valving. As the NMERI Standard cupburner 

requires a nominal 10L/min. total flow a "make-up" stream of air is introduced around the 

nebulizer tip. 

This modified sample introduction method allows three sequential extinguishment tests to be run 

on the same sample. Sample may be introduced over a period of several minutes and the flow 

rate ramped up in a very reproducible and controlled fashion. 

Advantages and additional details of this method are itemized below. 

•ICP Nebulizer – liquid agents uniformly misted, wide range of flow rates. ~5gm

of agent needed. 

•Heated nebulizer zone and cup-burner base prevents condensation, vaporizes 

higher boiling compounds; low BP compounds are chilled. 

•Syringe pump accurately controls liquid agent flow rate. 

•Air flow monitored via mass flow meter. 

•Barometric pressure and room temperature corrections applied to calculate actual 

air concentrations. 

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Figure 5. Cup-Burner (ICP) Nebulizer 

Figure 6. Evaporation/Mixing Column for Cup-Burner. 

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CONCLUSIONS 

The prospects for developing a screening method based on in vitro toxicity testing methods are 

promising. However, such a screening method will be of limited use and will potentially fail to 

lead to the identification of the ideal candidate if only a few halon replacement candidate 

compounds can be tested. Therefore both compound acquisition efforts and cardiac sensitization 

screening method development need to proceed in parallel. 

ACKNOWLEDGMENTS

The authors gratefully acknowledge the sponsorship of this research by the US Department of 

Defense’s Next Generation Fire Suppression Technology Program funded by the DoD Strategic 

Environmental Research and Development Program. 

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Mainstream Engineering Corporation, Rockledge, Florida, March 1997. 

2 Stephanie R. Skaggs, Robert E. Tapscott, and Everett W. Heinonen, Advanced Agent 

Program: Toxicological Screening Methods, NMERI 95/48/31882, Wright Laboratory 

Infrastructure Technology Section, Tyndall Air Force Base, Florida, December 1996. 

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