RISK ASSESSMENT FOR ALTERNATIVE REFRIGERANT HFO-1234yf 

PREPARED FOR: 

SAE INTERNATIONAL 

Cooperative Research Program 1234 

PREPARED BY: 

GRADIENT CORPORATION 

600 Stewart Street 

Seattle, WA 98101 

February 26, 2008 (Original Report Date) 

April 3, 2009 (General Release Date) 
 

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Table of Contents

Executive Summary............................................................................................................ vi

1 Introduction .............................................................................................................. 1

1.1 European Union F-Gas Regulation..................................................................................... 1

1.2 U.S. EPA Significant New Alternatives Program (SNAP)................................................. 1

1.3 U.S. EPA Sponsored Risk Assessment of R-152a and R-744 (CO2).................................. 2

1.4 SAE Cooperative Research Program (CRP) 150................................................................ 3

1.5 SAE Cooperative Research Program 1234 (CRP1234)...................................................... 3

2 Conducting Risk Assessment for Alternative Refrigerants...................................... 5

2.1 Approach............................................................................................................................. 5

2.2 Evaluating Potential AR Toxicity....................................................................................... 6

2.2.1 Criteria for Evaluating Manufacturer-Supplied Toxicity Data.............................. 6

2.2.2 Acute Toxicity ....................................................................................................... 7

2.2.2.1 Acute Toxicity - Lethality...................................................................... 7

2.2.2.2 Anesthetic Potency................................................................................. 8

2.2.2.3 Cardiac Sensitization.............................................................................. 9

2.2.3 Subacute, Sub-Chronic and Chronic Toxicity (Repeated Dose Studies)............. 12

2.2.4 Genotoxicity ........................................................................................................ 12

2.2.5 Carcinogenesis..................................................................................................... 13

2.2.6 Reproductive/Developmental Toxicity................................................................ 13

2.2.7 Ecotoxicity........................................................................................................... 14

2.2.8 Toxicity Criteria Used for Risk Assessment........................................................ 15

2.3 Evaluating Flammability of ARs ...................................................................................... 17

2.3.1 Relevant Flammability Properties........................................................................ 18

2.4 Exposure Assessment........................................................................................................ 19

2.4.1 Passenger Compartment Scenario........................................................................ 20

2.4.2 Potential AR Concentrations in Vehicle Passenger Compartment ...................... 21

2.4.2.1 CFD Modeling ..................................................................................... 21

2.4.2.2 Field Testing ........................................................................................ 22

2.4.3 Potential AR Concentrations After a Leak in the Engine Compartment ............. 23

2.4.4 Potential AR Concentrations Associated with Leaks in Vehicle Repair 

Areas .................................................................................................................... 24

2.4.4.1 Professional Service Technician Scenario ........................................... 25

2.4.4.2 DIY Scenarios ...................................................................................... 27

2.5 Risk Characterization........................................................................................................ 29

2.5.1 Health Risks for Passengers and Vehicle Repair Workers .................................. 29

2.5.2 Ignition Risks for Passengers and Vehicle Repair Workers ................................ 30

2.5.3 Ecological Risks .................................................................................................. 30

2.5.4 Risks for Other Exposure Scenarios .................................................................... 31

2.6 Fault Tree Analysis for Evaluating Potential Risks.......................................................... 32

2.6.1 Fault Tree Assumptions for Passenger Compartment Scenario........................... 33

2.6.1.1 Fault Tree Assumptions Related to Health Risks for Vehicle 

Passengers ............................................................................................ 33

2.6.1.2 Fault Tree Assumptions Related to AR Ignition Risks for 

Vehicle Passengers............................................................................... 35

2.6.2 Fault Trees for Engine Compartment AR Ignition Scenario ............................... 38
 

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2.6.3 Fault Trees for Vehicle Repair Scenarios ............................................................ 39

2.6.3.1 Fault Trees Related to Health Risks for Vehicle Repair Workers........ 39

2.6.3.2 Fault Trees Related to AR Ignition Risks for Vehicle Repair 

Workers................................................................................................ 40

2.6.4 Interpretation of FTA Results .............................................................................. 41

2.7 Sources of Uncertainty in the Risk Assessment................................................................ 42

3 Summary of R-12 Risk Assessment....................................................................... 44

3.1 General Properties............................................................................................................. 44

3.2 Toxicity Assessment ......................................................................................................... 45

3.2.1 Summary of Toxicological Findings ................................................................... 45

3.2.2 Toxicity Criteria Used for Risk Assessment........................................................ 48

3.3 Results of Exposure Assessment ...................................................................................... 48

3.4 Risk Characterization........................................................................................................ 49

3.5 FTA................................................................................................................................... 50

3.6 Conclusions Regarding R-12 ............................................................................................ 51

4 Risk Assessment – HFO-1234yf............................................................................ 52

4.1 General Properties............................................................................................................. 52

4.2 Toxicity Assessment ......................................................................................................... 52

4.2.1 Evaluation of Available Toxicity Data from Manufacturer................................. 52

4.2.3 Summary of Toxicological Findings ................................................................... 54

4.2.4 Toxicity Criteria Used for Risk Assessment........................................................ 56

4.3 Flammability Properties.................................................................................................... 56

4.4 Results of Exposure Assessment ...................................................................................... 57

4.4.1 Results for Passenger Compartment Scenarios – CFD Modeling ....................... 57

4.4.2 Results for Passenger Compartment Scenarios – Field Measurements ............... 59

4.4.3 Results for Engine Compartment AR Ignition Scenario – Field 

Measurement........................................................................................................ 60

4.4.4 Results for Repair Worker Scenarios – Perfect Mixing Model ........................... 60

4.5 Risk Characterization........................................................................................................ 61

4.5.1 Health Hazard Indices for HFO-1234yf for Passenger Compartment and 

Repair Worker Scenarios ..................................................................................... 61

4.5.2 Ignition Risks for HFO-1234yf for Passenger Compartment, Engine 

Compartment and Repair Worker Scenarios ....................................................... 63

4.5.3 Ecological Risks .................................................................................................. 65

4.5.4 Potential Risks to Other Receptors ...................................................................... 66

4.5.5 Degradation Products........................................................................................... 67

4.6 FTA................................................................................................................................... 68

4.6.1 Toxicity FTAs...................................................................................................... 68

4.6.2 Flammability FTAs.............................................................................................. 68

4.6.3 Comparative Risks............................................................................................... 69

4.7 Conclusions Regarding HFO-1234yf ............................................................................... 70

5 References .............................................................................................................. 72
 

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LIST OF TABLES 

Table 1 LC50s of Select Refrigerants 

Table 2 Anesthetic Concentrations of Select Refrigerants

Table 3 Results of Cardiac Sensitization Studies for Different Fluorocarbons 

Table 4 Inputs for Passenger Scenario Fault Trees Addressing Health Effects – Normal Operation 

Table 5 Inputs for Passenger Scenario Fault Trees Addressing Health Effects – Collision Scenario 

Table 6 Inputs for Passenger Scenario Fault Trees Addressing Flammability 

Table 7 Inputs for Passenger Scenario (Collision) Fault Trees Addressing Flammability 

Table 8 Inputs for Engine Compartment Scenario Fault Trees Addressing Flammability 

Table 9 Generic Inputs for Repair Worker Fault Trees Addressing Health Effects 

Table 10 Generic Inputs for Repair Worker Fault Trees Addressing Flammability 

Table 11 Summary of Available Toxicity Data for R-12 

Table 12 Comparison of Toxicity of R-12 to the Toxicity of R-134a 

Table 13 Passenger Modeling Scenarios for R-12 Evaluation (R-12 Simulation Key)

Table 14 Predicted Passenger Compartment R-12 Concentrations 

Table 15 Results of Air Modeling for Repair Worker Scenarios, R-12

Table 16 Hazard Indices Associated with Different Exposure Scenarios, R-12

Table 17 Summary of Available Toxicity Data for HFO-1234yf 

Table 18 Comparison of Toxicity of HFO-1234yf to the Toxicity of R-134a 

Table 19 Flammability of HFO-1234yf Relative to Other Refrigerants 

Table 20 CFD Modeling Scenarios 

Table 21 Results of Air Modeling Simulations for Passenger Scenarios, HFO-1234yf 

Table 22 Results of Field Measurements for Passenger Compartment Scenarios, HFO-1234yf 

Table 23 Results of Air Modeling for Repair Worker Scenarios, HFO-1234yf 

Table 24 Hazard Indices Associated with Passenger Exposure Scenarios, HFO-1234yf 

Table 25 Hazard Indices Associated with Vehicle Repair Scenarios, HFO-1234yf 

Table 26 Ignition Risk Associated with Passenger Compartment Scenarios, HFO-1234yf 

Table 27 Ignition Risk Associated with Passenger Compartment Scenarios, HFO-1234yf 

Table 28 Ignition Risk Associated with Repair Scenarios, HFO-1234yf 

Table 29 Ecological Toxicity Data for Selected Chemicals Compared to HFO-1234yf 

Table 30 Acute Exposure Limits for Fluorocarbon Decomposition Products 

Table 31 Risks of Injury or Fatality from Various Events Compared to Risks Associated with 

Leaks of HFO-1234yf 
 

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LIST OF FIGURES

Figure 1 Example Fault Tree 

Figure 2 R-12 Fault Tree – Summary 

Figure 3 R-12 Fault Tree – Small Leak Scenario 

Figure 4 R-12 Fault Tree – Medium Leak Scenario 

Figure 5 R-12 Fault Tree – Large Leak Scenario 

Figure 6 R-12 Fault Tree – Collision Scenario 

Figure 7 R-12 Fault Tree – Vehicle Repair Scenarios 

Figure 8 Aggregate risk of potentially adverse exposure due to HFO-1234yf release 

Figure 9 Fault tree describing risk of potentially adverse exposure associated with a small HFO1234yf leak into passenger compartment 

Figure 10 Fault tree describing risk of potentially adverse exposure associated with a medium HFO1234yf leak into passenger compartment 

Figure 11 Fault tree describing risk of potentially adverse exposure associated with a large HFO1234yf leak into passenger compartment 

Figure 12 Fault tree describing risk of potentially adverse exposure associated with a HFO-1234yf 

leak due to vehicle collision 

Figure 13 Fault tree describing risk of potentially adverse exposure associated with a HFO-1234yf 

leak during vehicle repair 

Figure 14 Aggregate ignition risk due to HFO-1234yf release 

Figure 15 Fault tree describing ignition risk associated with a small HFO-1234yf leak into 

passenger compartment 

Figure 16 Fault tree describing ignition risk associated with a medium HFO-1234yf leak into 

passenger compartment 

Figure 17 Fault tree describing ignition risk associated with a large HFO-1234yf leak into 

passenger compartment 

Figure 18 Fault tree describing ignition risk associated with a HFO-1234yf leak in passenger 

compartment caused by collision 

Figure 19 Fault tree describing ignition risk associated with a HFO-1234yf leak in engine 

compartment 

Figure 20 Fault tree describing ignition risk associated with a HFO-1234yf leak during vehicle 

repair by professional service technicians 

Figure 21 Fault tree describing ignition risk associated with a HFO-1234yf leak during vehicle 

repair by DIYers 
 

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LIST OF ATTACHMENTS 

Attachment A Ignition Source Table 

Attachment B Modeling Results for Repair Worker Scenarios: R-12 

Attachment C Modeling Results for Repair Worker Scenarios: HFO-1234yf 

Attachment D List of Technical Terms and Acronyms Used in the Risk Assessment
 

 

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Executive Summary 

 Due to concerns about global warming, the use of refrigerant R-134a (i.e., 1,1,1,2-

tetrafluoroethane), will be banned for air conditioning systems for new vehicle platforms throughout the 

European Union (EU) on January 1, 2011. Use of R-134a will be banned in the EU for all new vehicles 

by January 1, 2017 (European Fluorocarbon Technical Committee, 2007). Regulations developed by the 

European Union require that any refrigerant(s) intended to replace R-134a have a global warming 

potential less than or equal to 150 based on a 100-year time horizon. The replacement(s) will also have to 

be acceptable in terms of human and ecological toxicity, environmental effects, effectiveness, and 

compatibility with other air conditioning components. No regulatory scheme equivalent to that adopted 

by the EU exists in the U.S. or Japan, but the global automobile market creates an incentive for each 

manufacturer to use a single refrigerant for all vehicle designs. Because the automotive companies are 

already engaged in design for the 2011 model year, the evaluation and selection of an alternative 

refrigerant (AR) involves considerable urgency. 

 To assist member companies with selection of a R-134a replacement, the Society of Automotive 

Engineers (SAE), in co-operation with E.I. du Pont de Nemours and Company (DuPont) and Honeywell 

International (Honeywell), has undertaken an evaluation of the DuPont/Honeywell alternative refrigerant 

2,3,3,3-Tetrafluoropropene (HFO-1234yf, IUPAC nomenclature).1

 The evaluation is intended to address 

risks to passengers and potential vehicle repair workers based on toxicology and flammability data 

obtained for this chemical. 

 The current risk assessment follows the approach of the U.S. EPA-sponsored risk assessment of 

R-152a and R-744 (CO2) (Blackwell et al., 2006) so as to employ a consistent methodology and generate 

a product familiar to regulatory agencies. The approach is also consistent with a more recent risk 

assessment of other ARs prepared by Gradient for SAE Cooperative Research Project (CRP) 150 

(Gradient, 2008). In a number of cases, the current risk assessment also considers additional scenarios or 

input values which are believed to provide a more robust or realistic estimate of passenger or repair 

worker risks. 

 

1

 ASHRAE is currently reviewing a proposal to accept the refrigerant designation nomenclature for this hydro-fluoro-olefin 

(HFO) as R-1234yf. In this report, we will use the DuPont/Honeywell recommended designation of HFO-1234yf for this 

chemical. 
 

 

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The SAE CRP150 risk assessment was initially conducted using R-12 as a study example, both to 

resolve any questions about risk assessment methodology and to provide a comparison for the actual ARs. 

The R-12 section of the SAE CRP150 risk assessment has been carried forward into the present risk 

assessment to provide a similar frame of reference. However, because R-12 is non-flammable, the R-12 

risk assessment only addressed health risks. Air modeling for the R-12 analysis indicated that passengers 

could be exposed to R-12 concentrations above health-based limits in the event of a large leak while the 

vehicle was operated in recirculation mode. The results also suggested exposures above health-based 

limits in the event of a vehicle collision although this was not explicitly modeled. For all other scenarios 

evaluated (involving vehicle passengers and vehicle repair personnel), the predicted air concentrations did 

not exceed the health-based limits. When these findings were incorporated in a fault tree analysis (FTA), 

Gradient estimated that in both Europe and the U.S., use of R-12 as an automotive refrigerant could result 

in 11 exposures per year above health-based limits (equivalent to 1 such exposure every 50 years). This 

is less than or equal to the level of risk tolerated by the general public with many commonly accepted 

activities (e.g., airplane travel, riding in elevators). 

The risk assessment for HFO-1234yf incorporated various types of data including toxicity data, 

vehicle design and use characteristics, bench scale testing results (i.e., flammability metrics), modeled air 

concentrations (vehicle cabin concentrations), and vehicle measurements (i.e., measurements of vehicle 

cabin and engine compartment concentrations and subsequent ignition tests). These data were generated 

by CRP1234 members. Toxicity testing reports were reviewed by a Gradient toxicologist in order to 

confirm the appropriateness of the methodology employed and to verify the reported health effect levels. 

All other data that we received from CRP1234 team members were assumed to be accurate and complete 

for the purposes of the risk assessment. 

The DuPont/Honeywell AR, HFO-1234yf, offers equivalent or lower toxicity compared to R134a or R-12 in terms of both human health effects and ecological effects. The material also has an ozone 

depletion potential (ODP) of 0 and a global warming potential (GWP) of 4 based on a 100-year time 

horizon, which meets the European Union F-gas requirements. HFO-1234yf is considered flammable (by 

definitions applied to mobile air-conditioning systems i.e., ASTM E681-01, E681-85, etc.), although 

testing conducted by DuPont and Honeywell indicates the ignition potential of this chemical is far less 

than that of other flammable refrigerants (e.g., R-152a, which is also considered flammable using the 

same definitions). Nonetheless, due to the flammability of HFO-1234yf, the risk assessment addressed 

both health effects and potential ignition risks for this chemical. 
 

 

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Based on a review of toxicity data developed by the manufacturers as well as the results of air 

modeling to predict exposure concentrations, potential HFO-1234yf exposures of vehicle passengers in 

the event of small, medium and large system leaks are expected to be below levels associated with 

potential health risk. Similarly, HFO-1234yf exposures of vehicle repair workers (both professional 

technicians and do-it-yourselfers) are expected to be below levels associated with potential health risk. In 

the event of a vehicle collision and refrigerant release, air concentrations could potentially exceed healthbased limits. However, the health-based limit for acute exposure used in this risk assessment for 

exposures involving stress, such as a collision, was 120,000 ppm. This is approximately four times the 

concentration measured in a test vehicle after release of HFO-1234yf in a large (0.5 mm) leak. In 

addition, the frequency of collision related releases is quite small and results in a very low overall 

estimate of health risk. Across the entire vehicle fleet in Europe or the U.S., use of HFO-1234yf could 

result in 0.02 exposures per year above limits protective of human health for acute exposures. This 

frequency is equivalent to 1 such exposure every 50 years. This level of risk is several orders of 

magnitude less than the comparable risks estimated for R-12. The estimated level of health risk 

associated with use of HFO-1234yf as an AR is also substantially less than the level of risk tolerated by 

the general public as part of every day life and less than the risk inherent in many commonly accepted 

activities (e.g., airplane travel, riding in elevators). 

Potential ignition hazards of HFO-1234yf were evaluated though both CFD modeling and field 

testing. Together, these evaluations suggested a lack of ignition risk in the event of small, medium or 

large leaks into the passenger cabin or leaks in repair worker areas. Consideration of the large leak data 

suggests that an HFO-1234yf release associated with a severe vehicle collision could potentially result in 

passenger compartment concentrations which could pose an ignition risk. However, data from laboratory 

experiments suggest that the flame stability and propagation potential in such an event would be very 

limited. In addition, the frequency of this event is expected to be extremely small, amounting to 0.004

events per year across the entire vehicle fleet in either the U.S. or Europe (equivalent to 1 such event 

every 250 years). CRP1234 also evaluated potential ignition risks from leaks of HFO-1234yf in the 

engine compartment via vehicle testing. The results of this study indicated that concentrations of HFO1234yf could be detected in the flammable range in highly conservative field conditions. However, an 

attempt to ignite HFO-1234yf after a release in the engine compartment was unsuccessful. Additional 

testing by CRP1234 to support this finding is now underway. 
 

 

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1 Introduction 

1.1 European Union F-Gas Regulation 

 On June 14, 2006, the F-Gas Regulation and Mobile Air Conditioning (MAC) Directive were 

published in the official journal of the European Union. The objective of these regulations is to contain, 

prevent, and thereby reduce emissions of fluorinated greenhouse gases covered by the Kyoto Protocol. 

The measures became effective as of July 4, 2007. The F-gas regulation covers the use of 

hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), and SF6 (sulfur hexafluoride) in all their 

applications, except Mobile Air Conditioning, which is covered by the MAC Directive (European 

Fluorocarbon Technical Committee, 2007). 

 The MAC Directive covers the use of HFCs in Mobile Air Conditioning for passenger cars only 

(Directive 2006/40/EC). The main objectives of the Directive are the control of leakage of certain 

fluorinated greenhouse gases with a global warming potential (GWP) higher than 150 in MAC systems 

and the prohibition of MAC systems using those gases after a certain date (Kozakiewicz, 2007). R-134a 

will be banned for air conditioning systems for new vehicle models by January 1, 2011, and for all new 

vehicles by January 1, 2017 (European Fluorocarbon Technical Committee, 2007). No equivalent 

regulatory scheme exists in the U.S. or Japan, but the global automobile market creates an incentive for 

each manufacturer to use just one refrigerant for all vehicle designs. 

1.2 U.S. EPA Significant New Alternatives Program (SNAP) 

 Section 612 of the U.S. Clean Air Act (CAA) requires the U.S. Environmental Protection Agency 

(EPA) to establish a program to identify alternatives to Class I (CFCs, halons, carbon tetrachloride, 

methyl chloroform, methyl bromide, and HBFCs) and Class II (HCFCs) ozone-depleting substances and 

to publish lists of acceptable and unacceptable substitutes. U.S. EPA implements these requirements 

through the Significant New Alternatives Policy (SNAP) Program. The purpose of the program is to 

allow a safe, smooth transition away from ozone-depleting compounds by identifying substitutes that 

offer lower overall risks to human health and the environment. SNAP evaluates substitutes for ozonedepleting compounds in a number of industrial sectors including the automotive industry. Although R134a is not an ozone depleting substance, U.S. EPA will have jurisdiction over the evaluation of the R134 replacements because these chemicals are, in terms of the regulations, substitutes for R-12 as well as 
 

 

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R-134a. Substitutes are reviewed based on their effects on human health and the environment, and 

assessed based on the potential for human exposure, toxicity, flammability, ozone depletion, impact on 

global warming, and other environmental effects. The final rulemaking describing the process for 

administering the SNAP program and issuing the first acceptability lists for substitutes was published on 

March 18, 1994. Under the rule it is illegal to replace a Class I or Class II substance with any substitute 

which U.S. EPA determines may produce adverse effects on human health or the environment where 

other substitutes have been identified that reduce overall risk and are currently or potentially available 

(U.S. EPA, 2007). 

1.3 U.S. EPA Sponsored Risk Assessment of R-152a and R-744 (CO2) 

 Blackwell et al. (2006) presented a risk assessment for alternative MAC systems employing 

either R-152a (1,1-difluoroethane) or R-744 (CO2). The risk assessment was sponsored by U.S. EPA, the 

Australian Greenhouse Gas Office; the European Commission; the Japanese Ministry of Environment; the 

Japanese Ministry of Economy, Trade and Industry; and Environment Canada. In order to examine these 

risks, U.S. EPA identified AR release scenarios with the highest risks of an adverse outcome. These 

scenarios were the potential for a moderate to large leak into the passenger compartment, and the potential 

for technicians to be exposed during vehicle AC system service. For R-152a, unacceptable exposures 

were defined as those exposures above 3.5% in air, which is slightly less than the lower flammability 

limit of 3.7%. Potential toxic effects of R-152a were not addressed because the thresholds for these 

effects are above the lower flammability limit. For CO2, unacceptable exposures were defined as those 

above 4% for a period of an hour, or above 6% for exposures of one to two minutes or more.2

 These 

levels were selected because human exposure to CO2 at and above these levels can reduce a driver’s 

capacity to handle a vehicle in a safe manner. Computational fluid dynamic (CFD) modeling simulated a 

reasonable worst-case scenario leak into the passenger compartment and the potential for passenger 

exposures. The simulated exposure concentrations were then used in a fault tree analysis to estimate and 

broadly quantify the potential for passenger exposure and technician exposure in a range of scenarios. 

 Taken together, the fault tree analysis and the CFD consequence modeling indicated that a 

reasonable worst-case scenario leak for both R-152a and CO2 systems resulted in unacceptable exposures 

to vehicle occupants. For R-152a, U.S. EPA estimated 50 events per year where flammable 

 

2

 In the September 21, 2006 SNAP notice concerning the use of CO2 as a mobile air conditioning refrigerant, U.S. EPA 

stipulated an exposure limit of 3% averaged over 15 minutes (Federal Register, Vol. 71, No. 183). The 3% concentration limit is 

identical to the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL) for CO2 and 

the American Conference of Governmental Industrial Hygienists (ACGIH) short-term exposure limit (STEL). 
 

 

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concentrations of R-152a might be present in the passenger compartment along with an ignition source. 

U.S. EPA also estimated 1,600 events per year where flammable concentrations of R-152a might be 

present in repair areas along with an ignition source. For CO2, U.S. EPA estimated 4,300 passenger 

exposures per year above the health-based limit and 2,400 repair worker exposures above the healthbased limit.3

 The authors found that proper engineering to reduce the amount of refrigerant that can leak 

into the passenger compartment would reduce estimated exposures to acceptable levels. For example, a 

directed release system (squib valve) where the refrigerant charge is released outside the passenger 

compartment in the event of a large leak was modeled and shown to effectively reduce potential 

passenger exposure to below levels of concern for both CO2 and R-152a. Other risk mitigation strategies 

were also described. 

1.4 SAE Cooperative Research Program (CRP) 150 

 The Society of Automotive Engineers (SAE), in conjunction with the German Association of the 

Automotive Industry (VDA), requested that Gradient Corporation (Gradient) conduct a risk assessment of 

alternative refrigerants from several different chemical manufacturers (SAE CRP150). An assessment of 

potential risks associated with the use of R-12 as an automotive refrigerant was also included as a 

baseline evaluation. The risk assessment followed the approach of the U.S. EPA-sponsored risk 

assessment of R-152a and R-744 (Blackwell et al., 2006) so as to allow comparison with the risks from 

the other alternatives. In a number of cases, the SAE CRP150 risk assessment also considered additional 

scenarios or input values which were believed to provide a more robust or realistic estimate of passenger 

or worker risks. Because the risk assessment included proprietary information from a number of chemical 

manufacturers, the details of the SAE CRP150 risk assessment remain confidential to CRP150 members. 

However, because the R-12 evaluation did not involve proprietary information, the R-12 portion of the 

CRP150 risk assessment is included in this report. 

1.5 SAE Cooperative Research Program 1234 (CRP1234) 

 The SAE, in conjunction with E.I. DuPont de Nemours and Company (DuPont) and Honeywell 

International Inc. (Honeywell), is undertaking an additional risk assessment of a new AR, HFO-1234yf. 

 

3

 Note that the results of U.S. EPA’s analysis of R-152a and CO2 cannot be directly compared to the results of the CRP150 and 

CRP1234 analyses due to some differences in fault tree parameters. In addition, U.S. EPA assumed that all repair worker 

exposures would be above concentrations of concern and did not conduct modeling to confirm that this was the case. Modeling 

for repair worker exposures in CRP150 and CRP1234 consistently indicated exposures were below concentrations of concern. 
 

 

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This current risk assessment generally follows the approach used in the U.S. EPA-sponsored risk 

assessment of R-152a and R-744 (Blackwell et al., 2006) and the assessment conducted for CRP150. 

This facilitates comparison with the risks determined for the other alternatives. In a number of cases, the 

most recent SAE risk assessment also considers additional scenarios (i.e., those associated with material 

flammability) or input values which are believed to provide a more robust or realistic estimate of 

passenger or worker risks. The details of this assessment are described in the following sections of this 

report. It should be noted that the risk assessment for HFO-1234yf incorporated various types of data 

including toxicity data, vehicle design and use characteristics, bench scale testing results (i.e., 

flammability metrics), modeled air concentrations, and vehicle measurements (i.e., measurements of 

vehicle cabin and engine compartment concentrations and subsequent ignition tests). These data were 

generated by CRP1234 members. Toxicity testing reports were reviewed by a Gradient toxicologist in 

order to confirm the appropriateness of the methodology employed and to verify the reported health effect 

levels. All other data that we received from CRP1234 team members were assumed to be accurate and 

complete for the purposes of the risk assessment. 
 

 

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2 Conducting Risk Assessment for Alternative Refrigerants 

2.1 Approach 

 Like all risk assessments, the risk assessment of a potential AR is a multi-step process in which 

different types of data are reviewed and then brought together to develop a mathematical estimate of 

potential health risk. The risk assessment procedure employed in this evaluation consisted of the 

following steps: 

1. A review of toxicity studies sponsored by the AR manufacturers to ensure they were 

conducted appropriately. Our review included evaluating the study design, the results, 

any deviations noted from the study protocol, and the conclusions drawn by the testing 

laboratory from the data. 

2. Determining the most significant toxicological effects for potential AR exposures, the 

levels at which these occur, and any human health criteria related to these effects, 

including any safety factors considered to be necessary. 

3. An evaluation of ecological toxicity data in the context of limits developed by regulatory 

agencies for classifying chemicals of ecological concern. 

4. Based on the available toxicity data, an evaluation of the absolute toxicity as well as the 

relative toxicity of the AR compared to R-134a, the refrigerant to be replaced. The 

toxicity relative to R-134a is expected to be a criterion used by U.S. EPA in their SNAP 

evaluation. 

5. An assessment of the flammability of the potential AR, including determining the upper 

and lower flammable limits, the minimum ignition energy, the autoignition temperature, 

and the fundamental burning velocity. 

6. An assessment of potential concentrations in the event of an AR release in the passenger 

compartment, engine compartment, or vehicle repair areas. 

7. Estimation of probabilities of specific risks (toxicological and flammability-related) from 

AR releases through the use of fault tree analysis (FTA). The risks of the proposed ARs 

were then compared to the risks that would be expected from the use of R-12. 

8. A qualitative evaluation of the potential risks of AR breakdown products. 

9. A characterization of risks in the context of other commonly encountered life events 

which may involve adverse effects. 

Methods and issues related to each stage of the risk assessment process are described in generic form 

below. The specific assessment of individual ARs is then described in successive chapters of this report. 
 

 

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This approach was taken so that proprietary information can be readily removed from the report in case 

distribution of the methodology outside CRP1234 is desired. 

2.2 Evaluating Potential AR Toxicity 

 Potential AR toxicity is a primary consideration for the evaluation. There are a number of 

toxicological tests that are employed, each of which relates to a different type of toxicological endpoint. 

These are described below. The goal of these studies is to define a No Observed Adverse Effect Level 

(NOAEL), a dose that did not produce any observable indications of toxicity. In some instances, a 

Lowest Observed Adverse Effect Level (LOAEL) is also defined. A LOAEL may be important in cases 

where the experiment did not include a dose at which no toxicological effects were observed or where it is 

useful to understand the margin of safety between the NOAEL and LOAEL. Note that because only 

discrete doses are tested in these experiments, the "true" no effect level may be between the observed 

NOAEL and the LOAEL. 

2.2.1 Criteria for Evaluating Manufacturer-Supplied Toxicity Data 

 Valid data on the toxicity of the potential AR are critical to the risk assessment. To ensure that 

the available toxicity data for the AR were of acceptable quality, Gradient obtained laboratory test reports 

from the chemical manufacturers (or published studies where relevant) for each toxicological endpoint of 

interest. Gradient then reviewed the study reports for the following elements: 

1. Gradient considered each contract laboratory involved in terms of their reputation for producing 

quality data and their ability to carry out the work described. 

2. Gradient reviewed each study report in detail, including the methods employed, the results (both 

as summarized in text and in tabular form), the conclusions drawn from the data, any notes of 

deviations from the established study protocol, and all report backup such as measurements of 

exposure concentrations. 

3. Gradient ensured that the study used standard methods (if such exist) or if the methods used were 

non-standard, that the rationale for their use was sound and was not simply intended to produce a 

more favorable outcome. 

4. Overall, Gradient considered the completeness of the assembled data package to ensure that it 

fully addressed all questions about the potential toxicity of the proposed refrigerant. 
 

 

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 The following sections describe the types of toxicity data evaluated, indicate how these endpoints 

are studied, and give some background information on the relevant toxicity of existing refrigerants. 

2.2.2 Acute Toxicity 

 Acute toxicity describes the adverse effects of a substance which result either from a single 

exposure or from multiple exposures in a short space of time (usually less than 24 hours). It suggests the 

possible risk levels for the consequences of accidental releases, such as from a spill or rupture. To be 

described as acute toxicity, the adverse effects should be noticeable within 14 days of the administration 

of the substance. Because it is generally unethical to test for acute (or chronic) toxicity in humans, most 

acute toxicity data are obtained from animal testing. Some acute toxicity data also come from studies of 

accidental human exposures. 

2.2.2.1 Acute Toxicity - Lethality 

A key measure of acute toxicity is the median lethal concentration (LC50), which is the 

concentration that is lethal to half of the test animals, typically during a 4-hour exposure (OECD Test 

Method 4034

). It is a very gross measure of toxicity but is often the first test conducted in order to 

establish the appropriate doses in more extended studies. LC50s for refrigerants are generally very high 

(i.e., indicating a relatively low toxicity). Table 1 shows LC50s for several refrigerants. For comparison, 

the 4-hr LC50 for the common industrial solvent xylene (found in paints and adhesives) is reported to be 

5,000 ppm in the rat. 

 

4

 The Organization for Economic Cooperation and Development (OECD) has published a list of standard test protocols for 

evaluating product chemistry and toxicity. The full list of tests can be found at 

www.oecd.org/department/0,3355,en_2649_34377_1_1_1_1_1,00.html 
 

 

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Table 1. LC50s of Select Refrigerants

Haloalkane LC50 (ppm)b

 Source 

R-12 >600,000; 800,000 (2-h) Ritchie et al., 2001 

R-23 663,000 Tsai, 2005 

R-32 520,000 Tsai, 2005 

R-113 110,000 (rats); 

95,000 (mice) (2-h) 

Trochimowicz et al., 

1988 

R-123 32,000 Trochimowicz, 1993 

R-124 262,500 Trochimowicz, 1993 

R-125 800,000 Tsai, 2005 

R-134a 567,000 Ritchie et al., 2001 

R-152a 383,000 Tsai, 2005 

R-227ea 789,000 Tsai, 2005 

R-236ea 85,000 Tsai, 2005 

R-236fa 457,000 Tsai, 2005 

a

 Based on 4-hour exposure unless otherwise noted. 

b

 Some of these values are considered approximate LC50s. 

ppm = parts per million. 

All of the refrigerants identified above are haloalkanes (i.e., compounds containing only single bonds). 

Acute lethality data for fluoroalkenes (that is, fluorinated hydrocarbons containing at least one double 

bond) are more limited than data for fluoroalkanes. Data are publicly available for one fluoroalkene, 

hexafluoropropene. The LC50 for hexafluoropropene has been reported to be in the range of 1,800 to 

3,000 ppm for rats and 750 ppm for mice (IUCLID database, 2007). 

2.2.2.2 Anesthetic Potency 

An anesthetic effect is the impairment of the ability to perceive pain and other sensory 

stimulation or reduced coordination (ISO, 2007). Halogenated hydrocarbons such as chloroform were 

among the first general anesthetics and certain forms (particularly fluorinated hydrocarbons) are still 

widely used for clinical purposes. There is no single mandated test method for evaluating anesthetic 

potency. In experimental animals, anesthetic effects can be tested by measuring changes in coordination 

or posture, such as the loss of righting ability of mice or rats, or loss of balance in a rotating apparatus. 

More commonly, anesthetic effects are evaluated as part of acute or subchronic studies where the activity 

level of the animals (locomotion, inquisitiveness, breathing rates) are tracked by the investigators and 

compared to those in control animals. Table 2 identifies concentrations associated with anesthetic effects 

for a number of well known refrigerants. 
 

 

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Table 2. Anesthetic Concentrations of Select Refrigerants 

Refrigerant NOEL(ppm) Source 

R-11 50,000 

12,500* 

Lester and Greenberg, 1950 

ASHRAE, 2007 

R-12 22,700** ASHRAE, 2007 

R-32 86,000 

250,000* 

Ellis et al. 1996 

ASHRAE, 2007 

R-134a 81,000 Silber and Kennedy 1979 

R-152a 100,000# Limperos and Zapp, 1951 

R-227ea 105,000 DuPont, 2006 

R-744 (CO2) <75,000 Blackwell et al., 2006 

*ASHRAE values may differ because ASHRAE has access to unpublished manufacturer data 

** Value adapted from a human study which indicated escape impairment potential. 

# The Lowest Observed Effect Levels (LOEL)

All values from studies with rats unless otherwise noted 

ppm = parts per million 

2.2.2.3 Cardiac Sensitization 

 An increased sensitivity of the heart to endogenous epinephrine (also called adrenaline), a 

phenomenon referred to as cardiac sensitization, has long been recognized as a risk during exposure to 

refrigerants and related chemicals (Brock et al., 2003). In the early 1900s, Levy and Lewis (1911; as 

cited in Brock et al., 2003) reported that cats lightly anesthetized with chloroform were unexpectedly 

sensitive to injected epinephrine. Based on this observation and further studies, the potential hazard 

associated with administering hydrocarbon anesthetic agents followed by epinephrine became clearly 

recognized. In the 1960s when CFCs were increasingly being used as aerosol propellants, numerous 

sudden deaths from their abuse to achieve a light anesthesia (a "high") led to further investigation of the 

phenomenon of cardiac sensitization. It should be noted that these deaths were due to extreme exposures, 

doses sufficient to cause central nervous system effects. 

 The first detailed description of a method for determining the cardiac sensitization potential of 

compounds was published by Reinhardt and colleagues (1971) of DuPont. The method used a fixed 

epinephrine dose protocol. Briefly, a beagle dog was exposed to various concentrations of the test 

compound in air and given an intravenous epinephrine injection before and during exposure to the 

potential sensitizing agent. The electrocardiogram (ECG) response was continuously monitored over the 

course of the 17-minute protocol. If the compound at a given concentration was a cardiac sensitizer, a 

life-threatening arrhythmia was seen on the ECG. The dose of epinephrine used in the Reinhardt et al. 

protocol was 8 μg/kg, which provides a dose rate that is about 10-times higher than the dose rate 

calculated to occur in humans during times of stress (Brock et al., 2003). Using this protocol, nearly 100 
 

 

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halocarbons and hydrocarbons were tested for the purpose of ranking the potency of the test compounds. 

Nearly all were capable of sensitizing the beagle heart to an epinephrine challenge, resulting in a serious 

arrhythmia. Of the CFCs, R-11 and R-113 (trichlorotrifluoroethane) were the most potent, each with a 

lowest-observed-adverse-effect level (LOAEL) of 5,000 ppm. 

 In the 1980s and early 1990s, there was a significant amount of toxicological investigation 

undertaken to evaluate the toxicity of HCFCs and HFCs as CFC replacements. The protocol for cardiac 

sensitization studies was similar to that of Reinhardt et al. (1971), except that the dose of epinephrine 

used was adjusted for each experimental animal (i.e., the titration protocol). That is, prior to testing the 

refrigerant chemical, a dose of epinephrine was established for each individual dog that would be 

minimally arrythmiogenic. Once the dose of epinephrine was established, that dose would be used when 

the dog was exposed to the test compound following the same 17-minute protocol described above. 

Hardy et al. (1994) reported that titration of the dose for each dog with epinephrine at doses of 2-12 μg/kg 

was more sensitive for detecting cardiac sensitization than when using the fixed epinephrine dose 

protocol. Results from cardiac sensitization studies for a number of fluorocarbon compounds studied 

with the earlier and later methodologies are presented in Table 3. 

Table 3. Results of Cardiac Sensitization Studies for Different Fluorocarbonsa 

Compound LOAEL (ppm) NOAEL (ppm) Epinephrine Dose (μg/kg)b

Fixed epinephrine dose 

CFC-11 25,000 1,000 8 

CFC-12 50,000 25,000 8 

CFC-114 25,000 Not determined 8 

CFC-115 150,000 Not determined 8 

CFC-113 5,000 2,500 8 

Titrated epinephrine dose 

HCFC-141b 9,000 Not determined 10, 12 

HCFC-225cb 20,000 15,000 8, 12 

HFC-125 100,000 75,000 12, 12 

HFC-134a 75,000 50,000 4, 8 

HFC-143a 300,000 250,000 4, 12 

HFC-236fa 150,000 100,000 8, 12 

HFC-32 Not determined 350,000 8, 12 

a

 Results adapted from Brock et al., 1999, 2003 b

 For titrated doses, the first number is the lowest dose used in the study to elicit a cardiac sensitization response, the 

LOAEL. The second number is the highest epinephrine dose used in the study at the NOAEL. 

 In the protocols discussed above, exogenous doses of epinephrine were expected to result in 

blood levels that were greater than physiological levels attained in humans under stress conditions. 

Therefore, endogenous epinephrine studies were conducted to determine the exposure concentrations 
 

 

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needed to induce sensitization without the administration of exogenous epinephrine. In one approach 

(Reinhardt et al., 1971), dogs were exposed to 80% test compound while simultaneously being subjected 

to "fright stimuli" (e.g., sirens, gongs, and jet engines) with the intention of stimulating the release of 

endogenous epinephrine. In this study, a cardiac sensitization response could not be elicited with any 

dose of R-12 in the 12 dogs being tested, even at a dose of 800,000 ppm, which is sixteen times higher 

than the R-12 concentration found to produce cardiac sensitization with injected epinephrine. In the other 

endogenous epinephrine approach (Mullin et al., 1972), dogs were exposed to specific inhaled 

concentrations of test compounds for approximately 20 minutes while they ran on a treadmill to generate 

their own adrenaline. In this study, the dose of R-12 producing cardiac sensitization was 100,000 ppm, or 

twice that producing such an effect with injected epinephrine. These studies indicated the conservative 

nature of the test result from studies involving injected adrenalin. 

 Investigators have also examined how dose metric (e.g., peak dose, cumulative dose, dose over a 

specific time period) affects cardiac sensitization. A series of studies in dogs (summarized in Brock et al., 

2003) found that blood fluorocarbon concentrations generally increase rapidly during the first 5 minutes 

of inhalation exposure and more slowly or not at all for the remaining minutes of exposure. At the end of 

exposure, there is a rapid decline in blood concentration for the first few minutes which then levels off 

substantially. Trochimowicz et al. (1974) found that tissue concentrations of fluorocarbon were directly 

correlated with the blood and inhaled concentrations of fluorocarbon associated with cardiac sensitization. 

There was no evidence of retention of fluorocarbon in tissues after a 10-minute acute inhalation exposure. 

Beck et al. (1973) demonstrated that the peak blood concentration of the test compound is the most 

important factor regarding the timing of the epinephrine challenge, and that it does not matter whether the 

peak concentration is reached quickly or gradually. 

 Concerns have been raised about the protectiveness of results from the dog studies for particularly 

susceptible human populations, such as individuals with pre-existing heart conditions (Trochimowicz et 

al., 1976). Trochimowicz and colleagues conducted a study in which they compared the thresholds for 

cardiac sensitization in dogs with recent artificially induced myocardial infarctions (i.e., heart attacks) to 

those thresholds in normal dogs (Trochimowicz et al., 1976). The authors reported that dogs with recent 

myocardial infarctions were not more susceptible to cardiac sensitization by R-11 or Halon 1301 

(bromotrifluoromethane) than normal dogs, and concluded that there was "no greater potential for cardiac 

sensitization among dogs having recovered from myocardial infarction as compared to normal, healthy 

animals" (Trochimowicz et al., 1976). It should also be noted that the United States National Research 

Council (NRC) (2004) concluded that no uncertainty factors are necessary when the normal cardiac 
 

 

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sensitization protocol is used, because the doses of exogenous epinephrine achieve plasma concentrations 

that are 10 times greater than those achieved during physiologic stress, such as exercise or loud noise. 

Therefore the dog cardiac-sensitization test, when performed using the standard methodology, is believed 

to be sufficiently conservative to compensate for uncertainties related to dog-to-human extrapolation or 

inter-individual sensitivity. 

2.2.3 Subacute, Sub-Chronic and Chronic Toxicity (Repeated Dose Studies) 

 As opposed to acute toxicity, sub-chronic and chronic toxicity refer to adverse effects resulting 

from continuous or repeated exposures of intermediate (sub-chronic) or long-term (chronic) duration. 

Sub-chronic and chronic toxicity tests are performed to assess the cumulative toxicity of chemicals. Tests 

are generally conducted in rodents for reasons of cost and space. Subacute studies involve exposing 

animals to test materials for either 14 or 28 days (OECD 412). Subchronic studies involve exposure of 

the test animals to the test chemical for a period of 90 days (for inhalation studies, this usually involves 

exposure 6 hours per day, 5 days per week), followed by detailed examination of tissues for signs of 

damage (OECD 413). Chronic studies follow a similar approach but the exposure period is one to two 

years (if rodents are used) (OECD 452/453). The studies are usually conducted in series, with results of 

the shorter term studies informing the design of the longer term studies. Because the risk of exposure to 

refrigerants will be due to accidental discharges in high concentrations over an acute time frame, 

subchronic and chronic effects are not specifically addressed in the risk assessment. These types of 

effects could be significant for automotive or chemical manufacturing workers who may be exposed to 

low concentrations of refrigerant over extended periods of time. 

2.2.4 Genotoxicity 

Genotoxicity refers to potentially harmful effects on the hereditary material (DNA) and on the 

genetic processes of living things. Such effects can be assessed directly by measuring the interaction of 

agents with DNA or more indirectly through the assessment of DNA repair or the production of gene 

mutations or chromosome alterations. A number of assays are used to screen for possible mammalian 

mutagens and carcinogens. These tests include the Ames assay (OECD 471), the chromosomal aberration 

assay (OECD 473), the micronucleus assay (OECD 474), the sister chromatid assay, and the unscheduled 

DNA synthesis assay. The first two of these assays are conducted using isolated cells (i.e., in vitro) 

whereas the latter three tests involve exposure of whole animals. All evaluate changes in some part of the 

DNA replication process. In general, regulatory agencies give greater credence to tests results obtained in 
 

 

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whole animal assays and in tests using mammalian cells (e.g., the chromosomal aberration and 

micronucleus assays) rather than tests using bacteria (i.e., the Ames assay). 

2.2.5 Carcinogenesis 

Chronic toxicity tests often include a consideration of the carcinogenic potential of chemicals so 

that a separate lifetime feeding study that addresses carcinogenicity does not have to be performed. These 

studies are usually performed in rats and mice and extend over the lifetime of the species (18 months to 2 

years for mice; 2 to 2.5 years for rats) (OECD 451/453). Recognizing that lifetime studies are both very 

costly and slow to provide needed data, regulatory agencies have recently begun considering 

carcinogenicity screening tests. Such tests can involve exposures of genetically susceptible animals, 

which may evidence early signs of carcinogenicity (e.g., molecular or microscopic alterations) in 

substantially shorter timeframes. 

Although the possible carcinogenicity of most refrigerant chemicals has not been studied in 

detail, those studies which have been conducted (primarily on the haloalkanes) have suggested a lack of 

carcinogenic potency relevant for humans. For example, in two chronic studies of R-134a in rats, inhaled 

concentrations of up to 50,000 ppm for 6 hr/day for up to 2 years did not result in any tumors relevant to 

humans (NRC, 1996). In a chronic inhalation study of HCFC-123 at exposure levels up to 5,000 ppm, 

rats at the end of the 24-month exposure period showed an increased incidence of microscopic, benign 

tumors of the liver, pancreas, and testes. There was evidence that these tumors were caused by nongenotoxic mechanisms and would not be relevant to humans, but a more in-depth understanding of these 

findings needs to be developed (Dekant, 1996; Trochimowicz, 1993). Two-year cancer studies of 

chlorotetrafluoroethane (HCFC-124) and 1,1-dichloro-1-fluoroethane (HCFC-141b) conducted in rats 

also yielded findings indicating a lack of carcinogenic potential in humans (Malley et al., 1998, 

Millischer et al., 1995). 

2.2.6 Reproductive/Developmental Toxicity 

Several types of animal tests are utilized to examine the potential of an agent to alter development 

and reproductive capacity (e.g. OECD 414,422,423). Developmental toxicity refers to adverse effects on 

the developing organism occurring anytime during the life span of the organism that may have resulted 

from exposure to chemical or physical agents before conception (either parent), during prenatal 

development, or postnatally until the time of puberty. Tests are generally conducted in rats and/or rabbits. 
 

 

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Reproductive toxicity refers to adverse effects on the male or female reproductive system that may result 

from exposure to chemical or physical agents (OECD 415,416). Examples of reproductive and 

developmental toxicity studies for some haloalkanes are presented below. 

In three inhalation studies (two in rats and one in rabbits) conducted to examine the 

developmental effects of R-134a, high concentrations (10,000 ppm and greater) resulted in developmental 

effects, including maternal toxicity, reduction in fetal weight, and delays in skeletal ossification. No 

treatment-related effects were seen at lower concentrations (NRC, 1996). NRC (1996) identified a 

developmental NOAEL of 2,500 ppm from these studies. In reproductive studies of R-134a in rats, there 

was an increase in testicular weight from exposure to 50,000 ppm for 6 hr/day, 5 days/wk for 2 years, but 

no such effects at lower concentrations or for shorter durations (NRC, 1996). NRC (1996) did not 

consider the increase in testicular weight to be an adverse effect by itself, and thus identified a 

reproductive NOAEL of 50,000 ppm. 

2.2.7 Ecotoxicity 

 Ecotoxicity (or ecological toxicity) studies measure the effects of chemicals on fish, wildlife, 

plants, and other wild organisms. Due to their physiochemical properties, CFCs, HFCs, and HCFCs are 

expected to have a low potential for ecotoxicity and bioaccumulation (Dekant, 1996). These properties 

include low octanol/water coefficients and high volatility. Most are gases and have very low solubility in 

water at room temperature and thus are unlikely to remain in water (Dekant, 1996; Tsai, 2005). 

 Ecological toxicity is typically tested in a few indicator species including the algae Selenastrum 

capricornutum (OECD 201), the invertebrate Daphnia magna (OECD 210), and fish such as the small 

head minnow (Pimephales promelas) or carp (Cyprinus carpio) (OECD 211). In these studies the test 

organism is exposed to the agent of interest dissolved in water for relatively short durations (e.g., 96-

hours in the fish test) and measures of gross toxicity are evaluated. For algae, the concentration which 

causes 50% inhibition of growth relative to a control group is calculated. For animals, measures such as 

immobility or mortality are recorded. The value recorded is generally the concentration producing a 50% 

effect (e.g., 50% mortality). 

 

 Most CFC replacements have been only partly tested for toxic effects on organisms in the 

environment. Berends et al. (1999) tested R-134a, HCFC-123, HCFC-141b, and HCFC-225ca for effects 

on algae, Daphnia, and fish. R-134a showed the lowest toxicity, with LC50 values ranging from 450 to 
 

 

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980 mg/L, indicating a classification of “not dangerous to the environment” according to EC regulations 

(EC Directive 67/548/EEC). The low toxicity of R-134a in acute aquatic toxicity tests is said to be in 

agreement with results from mammalian toxicity testing and could be related to its low bioaccumulation 

potential (Berends et al., 1999). Some of the acute aquatic LC50 values for HCFC-123, HCFC-141b, and 

HCFC-225ca were less than 100 mg/L, but all were greater than 10 mg/L, indicating a classification of 

“harmful” under European Union regulations (i.e., R52/R53) However, because these compounds are 

volatile and will disappear from aquatic ecosystems rapidly, they do not constitute a long-term danger to 

the environment (Berends et al., 1999). 

2.2.8 Toxicity Criteria Used for Risk Assessment 

 In considering how to relate the toxicity data described in the proceeding sections to potential 

risks for humans exposed to ARs, we followed the approach developed by the American National 

Standards Institute (ANSI) and American Society of Heating, Refrigerating and Air-Conditioning 

Engineers (ASHRAE) in their joint standard 34-2007, Designation and Safety Classification of 

Refrigerants. An nearly identical standard (ISO 817) is also under review by the International Standards 

Organization (ISO, 2007). 

 The ANSI/ASHRAE standard describes the process of establishing a refrigerant concentration 

limit (RCL) which is defined as a concentration limit "intended to reduce the risks of acute toxicity, 

asphyxiation, and flammability hazards in normally occupied, enclosed spaces." With respect to acute 

toxicity, the standard specifies that an Acute Toxicity Exposure Limit (ATEL) is determined from the 

lowest of several values: 

1. A fraction of the animal LC50. 

2. The cardiac sensitization NOAEL. 

3. A fraction of the concentration producing anesthetic or central nervous system effects in 

animals. 

4. Eighty percent of the lowest concentration reported to cause effects in humans which 

would impair the ability to escape or which causes irreversible health effects. 

For criteria 1 and 3, the specific fraction employed is dependent on the type of data available. For 

example, criterion 3 allows for 50% of the 10-minute EC50 in rodents for loss of righting ability in the 

rotating apparatus test, 50% of the lowest effect level for signs of anesthetic or CNS effects in any acute 
 

 

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study, or 80% of the no effect level for signs of anesthetic or CNS effects in any acute, subchronic, or 

chronic study. For refrigerant blends, the ATEL is calculated by weighting the critical value for each 

component by its mole fraction in the blend, according to the following formula: 

. 2

% 2

1

% 1

1

etc

Toxicity Value Component

Mole Component

Toxicity Value Component

Mole Component Toxicity Value for Blend

+ +

=

 Once the ATEL is calculated, the RCL is then selected as the lowest concentration among the 

ATEL, the oxygen deprivation limit (140,000 ppm), or 25% of the LFL. The ANSI/ASHRAE RCL is 

meant to be a generic standard applicable to all situations where exposure to refrigerants may occur. The 

ANSI/ASHRAE use of a single RCL does not allow one to consider various aspects of product safety 

which are important in selecting an AR. Because the scenarios addressed in this risk assessment are fairly 

specific, the ANSI/ASHRAE methodology was adapted in the following ways to derive a modified RCL 

(mRCL): 

• In exposure scenarios where an element of fright/stress is possible, the exposure 

concentration is compared to the cardiac sensitization NOAEL, unless some other healthbased criterion produces a lower value. Stress may be induced by sudden, lifethreatening events (e.g.. vehicle accidents) or sudden and strong auditory or visual stimuli 

(e.g., a high pressure leak which produces an audible sound). 

• In exposure scenarios which are unlikely to produce stress, the exposure is considered in 

comparison to an "mRCL"5

 based on a set of criteria that do not include cardiac 

sensitization (i.e., acute toxicity or anesthetic/CNS effects). Because the cardiac 

sensitization endpoint required both chemical exposure and an element of significant 

stress to produce an adverse outcome, applying the toxicity criteria based on cardiac 

sensitization to non-stress situations would be inappropriate. 

Flammability concerns were addressed by calculating a separate Flammability Hazard value (Section 

2.5.2). Oxygen deprivation concerns were not relevant to the present case since flammability and healthbased values were always more restrictive. With respect to the mRCL, note that subchronic/chronic 

effects are only relevant for on-going, non-episodic exposures. Because potential exposures of vehicle 

passengers or vehicle repair personnel are acute in nature, subchronic or chronic toxicity health effects are 

not quantitatively addressed in the risk assessment. However, effects such as subchronic, chronic, 

reproductive and developmental toxicity; genotoxicity; and carcinogenesis may be of concern for 

 

5

 Because RCL as defined by ANSI/ASHRAE is a comprehensive term incorporating both toxicity and flammability concerns 

and also does not distinguish between stressful and non-stressful situations, the term mRCL is used to describe separate healthbased values for stressful and non-stressful situations. 
 

 

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chemical company production workers or automotive lab technicians who may have repeated exposures. 

These effects are evaluated qualitatively. 

 The ANSI/ASHRAE standard also describes a process for classifying refrigerants into "safety 

groups" based on both toxicity and flammability. Refrigerants are given an alphanumeric code (A1, A2, 

A3, B1, B2, or B3) where the letter indicates toxicity class and the number indicates flammability. 

Refrigerants where the occupational exposure limit is at or above 400 ppm are designated class A, 

whereas refrigerants where the occupational exposure limit is below 400 ppm are designated class B. 

Refrigerants which are not flammable according to the ASHRAE specified tests are designated class 1, 

whereas flammable refrigerants are designated class 2 or class 3 depending on factors such as the lower 

flammable limit (LFL) and heat of combustion, as determined using specified test methods and 

conditions. It should also be noted that the draft ISO refrigerant standard (ISO 817) includes within the 

“class 2” flammability designation, an additional subclass, 2L, which applies to refrigerants with a 

burning velocity of less than or equal to 0.1 meter per second, when evaluated under ISO specified test 

conditions. Thus, under the proposed ISO standard A2L and B2L are also possible safety designations 

(ISO, 2007). The 2L flammability classification category was proposed by ISO participating member 

countries in recognition of the substantially lower fire damage and fire spread risk associated with low 

burning velocity refrigerants (i.e., those with burning velocities less than 0.1 meters per second) relative 

to Class 2 or Class 3 refrigerants with higher burning velocities. 

Finally, in addition to the alphanumeric code, the ANSI/ASHRAE standard assigns the term 

"toxic" to refrigerants with rodent LC50 values between 200 ppm and 2,000 ppm, and the term "very 

toxic" to refrigerants with LC50 values less than or equal to 200 ppm. This terminology does not appear 

to be part of the draft ISO 817 standard. 

2.3 Evaluating Flammability of ARs 

Flammability of refrigerants is a long-standing issue. Some of the earliest refrigerant gases were 

flammable and the development of R-12 was in part driven by a desire to avoid fire risks. The discovery 

that the highly unreactive and largely non-flammable CFCs and HCFCs pose ozone depletion and global 

warming risks has forced a reconsideration of refrigerants that are slightly to moderately flammable. 

Thus, U.S. EPA conducted a risk assessment of R-152a (1,1-difluoroethane) that specifically addressed 

risk of fire and potential methods for mitigation (Blackwell et al., 2006). 
 

 

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2.3.1 Relevant Flammability Properties 

To evaluate the potential flammability of an AR, one must know the flammability characteristics 

of the chemical, including the lower and upper flammable limits, the minimum ignition energy, the 

autoignition temperature, and the burning velocity. Since these parameters can depend on the test 

apparatus and criteria used, the actual method used to determine each value should be identified. Wellestablished testing methodologies (e.g., ASTM E681 for flammable limits) should be employed where 

possible. 

Definitions of the key flammability properties are given below : 

• The upper and lower flammable limits (LFL and UFL). The minimum and maximum 

concentrations of a substance between which it is possible to propagate a flame through a 

homogeneous mixture of the substance and air under specified test conditions (based on 

ASHRAE, 2007). Below the LFL, there is insufficient fuel to support combustion. 

Above the UFL, the material dilutes the oxygen required for combustion. 

• Minimum Ignition Energy (MIE). Energy is required to initiate the reaction of the 

gaseous fuel with atmospheric oxygen. The MIE is the minimum amount of external 

energy that must be added to the system to start the self-sustaining reaction. The MIE is 

determined at the optimal mixture of the gas and air that supports combustion. 

• Autoignition Temperature (AIT). Contact with a hot surface may potentially increase the 

energy of the gas molecules to a level where combustion (combination with oxygen) can 

occur in the absence of an ignition source. Note that the gas needs to be exposed to the 

hot surface for a long enough time to acquire sufficient energy to self-ignite. In the U.S. 

the AIT is generally determined at atmospheric pressure using ASTM E659, “Standard 

Test Method for Autoignition Temperature of Liquid Chemicals.” While the ASTM 

standard states that the method is to be used for liquid and solid phase materials, it is 

often used for vapor-phase chemicals as well. The test method involves injecting a 

known concentration of flammable vapor/air mixture into a 500 cc flask maintained at 

constant temperature. Visual observations are made to determine whether ignition occurs 

within 10 minutes of exposure. Both concentration and temperature are varied until a 

temperature is reached at which no ignition is found for any concentration tested. It 

would be more correct to refer to this value as the minimum AIT, since autoignition will 

also occur for richer or leaner concentrations of the refrigerant, but at higher 

temperatures. AIT is not an intrinsic property of a refrigerant, but rather dependent upon 
 

 

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system volume, pressure, boundary conditions for heat transfer, and time of contact 

(induction time) between the hot environment and gas mixture. This is clearly stated in 

ASTM E659. 

• Fundamental Burning Velocity (Burning Velocity). The maximum speed at which a 

laminar flame propagates through a stationary optimal fuel/air mixture under specified 

conditions. This is a fundamental parameter of the potential damage a propagating flame 

may cause. As a fuel/air mixture burns, hot gases are produced and the expansion of 

these hot gases causes an increase in local air pressure. The rate of this pressure increase 

can be determined from the burning velocity, the volume change of combustion and the 

area of the flame front. The combustion rate (i.e., the burning velocity multiplied by the 

area of the flame front) combined with the rate the fuel material is vented into the system 

determines the maximum pressure obtained. The maximum pressure and the rate of 

pressure change are related to the resulting structural damage. 

These properties are generally tested in a laboratory setting using well-established methodologies (e.g., 

ASTM E681 for determining the upper and lower flammable limits). The results of these studies provide 

a baseline indication of whether a material has the potential to initiate and/or sustain a fire. These tests 

are highly conservative, however, and do not accurately simulate real world conditions. Field testing, 

where the gas is introduced in a likely release scenario and brought into contact with an ignition source, 

can provide a better idea of the real world flammability potential. Field testing carried out as part of this 

evaluation is described in Section 2.4.2.2. 

2.4 Exposure Assessment 

 Determining potential exposure is a critical element in any risk assessment. Even the most 

inherently toxic chemical will pose no risk if there is no exposure. Similarly, even the most flammable 

chemical will not pose a risk if the concentration is not within the flammable range. In order to evaluate 

the risks of potential AR exposures, we first developed a set of potential exposure scenarios, based largely 

on U.S. EPA's prior risk assessment of R-152a and CO2 (e.g., Blackwell, 2006). SAE CRP1234 then 

conducted air modeling and field testing to determine the air concentrations of the AR in each scenario. 
 

 

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2.4.1 Passenger Compartment Scenario 

 A primary concern for the automotive industry is the potential risks for vehicle passengers in the 

case of a system failure or accidental release of refrigerant from the vehicle AC system. Under normal 

operating conditions, the systems are self-contained and no release of refrigerant is expected to occur. 

However, leaks in system piping may occur over time (e.g., as a result of corrosion) and could cause a 

release of refrigerant into the passenger compartment. In addition, in a vehicle collision the AC system 

may be damaged in such a way as to cause release of a large portion of the refrigerant charge into the 

vehicle cabin. Both types of leaks were considered in this risk assessment. 

 Information solicited from CRP1234 team members indicated that leaks generally fall into four 

categories: small, medium, large, and very large leaks. The first three categories would involve 

corrosion-type leaks of the system piping whereas the very large leak would be associated with rupture of 

the evaporator tube from the condenser, as could occur in a severe vehicle collision. The size of the leak 

is critical to the exposure assessment because the diameter of the leak hole not only affects the amount of 

material that can be discharged but also the pressure and rate of the leak. Based on consultation with SAE 

CRP1234 members, three leak sizes considered were quantitatively evaluated in the risk assessment: 0.01, 

0.1, and 0.5 mm. The very large leak (associated with rupture of the evaporator tube near the condenser) 

was not evaluated via modeling but was considered in the FTA assuming the resulting passenger cabin 

concentrations would be greater than those associated with the large leak. 

 Assuming a release does occur, passengers may be affected if they inhale the refrigerant above a 

health-based limit (i.e., in this case the mRCL). Passengers may also be adversely affected if the 

refrigerant is flammable (per definitions associated with the mobile air-conditioning application, i.e. 

ASTM E681, E582, etc.), if it is present in a flammable concentration, and if there are ignition sources 

within the flammable concentration zone. A review by CRP1234 members considered possible ignition 

sources which could be expected to be present in the passenger compartment and which could possibly 

have sufficient energy to ignite a material such as HFO-1234yf. A table summarizing the review of 

potential automotive ignition sources is included as Attachment A. The review identified three possible 

worst-case ignition sources: a butane lighter or match used to light a cigarette6

, a spark generated by a 

 

6

 Studies by Arthur D. Little (1982) indicated that filament cigarette lighters such as those present in automotive vehicles will not 

ignite a mixture of methane and air. Since the methane-air mixture would be more flammable than HFO-1234yf, this potential 

ignition source was not considered in the risk assessment. 
 

 

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short of an internal vehicle battery, and a mechanical short from a PTC heater present within the vehicle 

air ducts. Each of these potential ignition sources was evaluated in the risk assessment. 

 In its evaluation of R-152a and CO2, the U.S. EPA considered the potential of a large leak to 

startle the passenger to the extent that they loose control of the vehicle and have an accident. U.S. EPA's 

analysis showed that the probability of this outcome (i.e., passenger or bystander injury from accident) 

was approximately 40-times less than the probability of a corresponding adverse health effect of exposure 

of vehicle passengers. In addition, risks of chemical exposure or ignition and risks of being injured by an 

out-of-control vehicle represent different types of outcomes and combining these into an overall risk 

estimate is questionable. We therefore did not include the startled driver accident-related injury scenario 

in the current risk assessment. 

2.4.2 Potential AR Concentrations in Vehicle Passenger Compartment 

2.4.2.1 CFD Modeling 

 Air modeling for the passenger exposure consisted of a two step process: estimation of the mass 

of refrigerant released through the leak over time followed by dispersion modeling to estimate refrigerant 

concentrations in the passenger compartment. The predicted emission leak rates were determined based 

on empirical leak data collected by Honeywell (Honeywell, 2008). Honeywell measured the leak rate of 

HFO-1234yf using a cylinder discharge system (simulating leak through evaporator) with a specific hole 

diameter of 0.5 mm. 

 The predicted emission rates were used as input for CFD modeling in order to estimate chemical 

concentrations in the passenger compartment. CFD modeling is a powerful tool that can predict localized 

refrigerant concentrations in the passenger compartment. In the CFD model the passenger cabin was 

represented by a set of several hundred thousand cells, each cell representing a small discrete air space. 

The refrigerant concentration in each cell is then simulated over time, taking into account air flow 

patterns within the vehicle. 

 CFD modeling was conducted by DuPont, using a virtual vehicle with the same dimensions as the 

vehicle model used by the U.S. EPA in its evaluation of R-152a and CO2 (R-744). Specific details 

pertaining to the passenger cabin modeling are described in the DuPont document CFD Modeling of a 

Large Car (DuPont, 2008). Honeywell also conducted modeling using a smaller vehicle (2.5 m3

 internal 
 

 

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volume vs. 3.1 m3) in order to understand the potential impacts of a refrigerant release on another segment 

of the vehicle fleet (Honeywell, 2008). Because same vehicle specifications were used as the model for 

earlier CFD efforts (i.e., the U.S. EPA assessment of CO2 and R-152a as well as the work of CRP150), 

the Honeywell results were not used in the risk assessment. The Honeywell study nonetheless reached 

conclusions similar to the DuPont study and provide confidence in the use of the DuPont data in the risk 

assessment. 

 

 To evaluate modeled concentrations of the AR in the passenger compartment we calculated three 

values. To evaluate the potential risks of cardiac sensitization, we calculated the maximum 5-minute 

Time Weighted Average (TWA) concentration. This represents the highest 5-minute exposure the 

passenger might experience. Note that the animals in the cardiac sensitization studies are exposed to a 

steady concentration whereas the passenger would be exposed to a variable concentration. While it is true 

that the actual peak exposure (i.e., the highest level reached over any time frame) may be higher than the 

5-minute TWA, studies of cardiac sensitization suggest that a 5-minute exposure is most comparable with 

the data obtained with the experimental animals. 

 To evaluate other health effects (e.g., anesthetic effects, acute lethality), we calculated the 

maximum 30-minute TWA concentration. This is because the ASHRAE criteria specify human 

exposures of 30 minutes which involve escape-impairing effects. As regards animal data, the ASHRAE 

RCL criteria specify lethality in 4-hour studies or anesthetic effects from acute exposures (again, likely to 

be at least 4 hours in duration). Thus a 30-minute TWA is conservative. 

 To evaluate potential ignition risks, we looked at the peak AR concentration in the passenger 

compartment (i.e., the maximum concentration occurring at any second). This is also conservative 

because it assumes that the peak occurs in the same time frame as the ignition source and that the 

concentration of AR stays above the LFL for a sufficient time for the passenger to be injured or other 

materials in the passenger cabin to be ignited. 

2.4.2.2 Field Testing 

 To supplement and confirm the CFD results, potential AR concentrations and ignition risks 

associated with a leak of refrigerant into the passenger and engine compartments were field tested using 

an actual vehicle by Exponent, Inc. (Exponent). Obviously, the amount of testing (i.e., the combination 
 

 

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of operating and environmental conditions that can be considered) is constrained by cost and vehicle 

availability. The testing done was intended to reflect a worst-case situation. 

 Briefly, a commercial vehicle was obtained and equipped with six mannequins encased in Nomex 

suits. The vehicle was located inside a temporary shed to minimize the effect of wind. During the test, 

the refrigerant was released into the air conditioning system air distribution system. The release 

simulated a 0.5 mm hole in the evaporator (the “large” leak considered in the CFD modeling) with 

refrigerant leaking into the passenger compartment. During the refrigerant release (full system charge 

was released) and a significant time after the full refrigerant release, refrigerant concentrations were 

determined at different locations in the vehicle interior (driver and front seat passenger breathing zones, 

driver and passenger lap areas, driver and passenger foot areas, AC vents, and inside the AC ductwork). 

Concentrations were monitored for approximately 1,600 seconds as the refrigerant concentration 

dissipated. The vehicle fan was operated at low speed, using an outside source of electric power. A 

separate test was also conducted in an attempt to ignite the refrigerant using a butane lighter. The lighter 

was placed near the location having the highest refrigerant concentration in the preceding concentration 

studies. Pressure transducers and video cameras were used to monitor potential refrigerant combustion. 

Other variables (e.g., temperature inside vehicle, wind speed, humidity) were also measured. More detail 

regarding the field testing is provided in the Exponent report HFO-1234yf Refrigerant Concentrations 

and Ignition Tests in Full-Scale Vehicle Passenger Cabin and Engine Compartment (Exponent, 2008). 

2.4.3 Potential AR Concentrations After a Leak in the Engine Compartment 

 CFD modeling was not conducted to determine potential AR concentrations in the engine 

compartment. Given the complex and variable geometry of the engine compartment, developing such a 

model would have been both time consuming and of questionable validity. Instead, field testing was used 

to estimate AR concentrations and ignition risks from a refrigerant release within the engine 

compartment. The leak involved a 12.4 g/s refrigerant leak rate, mimicking a leak at the compressor 

outlet hose. This leak rate is approximately ten times the large leak rate used in the CFD modeling. The 

refrigerant was released into the engine space through a 1⁄4” nylon tube. After the complete release of the 

charge (approximately 691 grams), measurements of the refrigerant concentration were recorded at 

locations in the engine compartment near the exhaust manifold, the anticipated location of highest 

temperature. As with the passenger compartment study, the potential to ignite the refrigerant was also 

evaluated by introducing a heating element into the engine compartment at the location of highest 

concentration. Pressure transducers were used to characterize the potential combustion. Other variables 
 

 

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(e.g., the temperature inside the vehicle, wind speed, humidity) were also measured. Greater detail on the 

field testing can be found in the Exponent report HFO-1234yf Refrigerant Concentrations and Ignition 

Tests in Full-Scale Vehicle Passenger Cabin and Engine Compartment (Exponent, 2008). 

2.4.4 Potential AR Concentrations Associated with Leaks in Vehicle Repair Areas 

 There are an estimated 20 to 25 million vehicle AC system service events annually performed by 

repair workers in the U.S. (Carley, 2004). Of these, approximately 75% involve work with the refrigerant 

loop. Persons engaged in AC system repair could be exposed to refrigerants in the event of a release from 

the vehicle or from service equipment. In their "Risk Analysis for Alternative Refrigerant in Motor 

Vehicle Air Conditioning," U.S. EPA addressed repair worker risks qualitatively, but not quantitatively 

(Blackwell et al., 2006). We have conducted modeling analyses in order to address these release 

scenarios quantitatively. We have specifically addressed two sets of scenarios – professional service 

technicians and DIY non-professionals. 

 For all repair scenarios air modeling was conducted using a simple perfect mixing model (also 

called a box model). The box model is the simplest model type for estimating concentrations of a 

released or leaking chemical in an air space. It assumes the air space is in the shape of a box and that the 

air pollutants inside the box are homogeneously distributed. Air concentrations are calculated iteratively 

assuming a constant emission rate over the time of the release (i.e., the total amount of refrigerant 

involved in the release is divided by the time of the release). The following formula was used in the 

calculations: 

( ) C AER t

V

ER t Ct C ⎟ − Δ ⎠

⎞ ⎜

⎝

⎛ Δ = + * *

*

Where 

Ct = the concentration at time point of interest (g/m3

) 

C = the air concentration of the chemical at the proceeding time step (g/m3

) 

ER = the emission or release rate of the chemical (g/minutes) 

V = the volume of the room or airspace of interest (m3

) 

AER = the air exchange rate for the room or space of interest (minutes-1) 

Δ t = the time step interval (minutes) 

For situations involving an instantaneous release of material (i.e., the professional repair scenario 

involving a system rupture), the air concentration is initially set by dividing the entire charge amount by 
 

 

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the available air volume and then calculating the changing air concentration over time based on 

exponential decay. 

AER t Ct Ce − Δ = *

Although these models are very simple and thus limited in their ability to accurately predict complex air 

dispersion patterns, the approach is reasonable for small spaces such as those likely to be encountered in 

vehicle repair. Furthermore, unlike the passenger compartment of an automobile, where an individual is 

confined to one position, individuals conducting repair are likely to move about within the "box" and thus 

experience exposures that are closer to an average chemical concentration. 

2.4.4.1 Professional Service Technician Scenario 

 Using professional service equipment (e.g., Snap-on Dual II, Kool Kare, and ECO-12), the 

refrigerant in the AC system is first removed and stored in the service unit reservoir. After any necessary 

repair, the system is then recharged to ensure that a full refrigerant charge is present. Data from various 

equipment manufactures indicate that it takes approximately 15 minutes to remove the refrigerant from 

the system and 10 minutes or less to recharge the system with fresh refrigerant. 

 Two potential AR release scenarios were evaluated for the professional repair situation: an 

instantaneous AC system rupture during repair which vents the entire vehicle charge to repair area, and an 

equipment leak during refrigerant removal and recharging. In the first scenario, one might envision a case 

where some repair activity places stress on a damaged AC system which causes the system to rupture and 

vent the entire refrigerant charge (691 grams, consistent with the CFD modeling) to the repair room 

atmosphere. To address this as worst case, we assumed that the rupture caused an instantaneous release 

rather than a slow release over several minutes. In the second scenario considered, leaks in the service 

equipment hoses could allow for a leak of refrigerant of various magnitudes, depending on the size of the 

hole in the hoses. This scenario requires that the service technician fails to monitor the equipment or note 

that the equipment is malfunctioning. This would be possible if the service technician were to hook up 

the equipment and then leave to perform other tasks while the system was being evacuated and/or 

recharged. If system monitoring were neglected for a sufficient duration, the entire draining and 

recharging cycle could be involved in a release. For this scenario, we assumed that 15% of the transferred 

refrigerant would be released, theorizing that a higher release rate would produce a sound that would be 

noticed by service personnel. 
 

 

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 The professional service technician exposure scenario is assumed to occur in a small service 

station with only two service bays, where the doors and windows are closed. This results in a relatively 

small air space with limited ventilation. A review of property sales records suggested that a typical 

volume for the service area of a small station is approximately 1,000 square feet (approximately 93 m2

). 

Assuming an interior area height of 9.5 feet (approximately 2.9 m), the total work area volume would be 

270 m3

. If the estimated volumes of two vehicles (16 m3) and miscellaneous equipment (8 m3) are 

deducted, this leaves an open air volume of approximately 230 m3

. We assumed an air exchange rate of 1 

room volume per hour (0.017/minute), which is a low-end estimate for a commercial facility (U.S. EPA, 

2002). It should be noted that many professional repair shops have good ventilation by design and are 

often open to outside air during much of the year. Finally, we assumed that only one vehicle is having the 

AC system serviced at a time and that the time between different vehicles being serviced is such that 

accumulation of refrigerant does not occur. 

 Two other theoretically possible professional repair scenarios were not evaluated in the risk 

assessment because they were judged to be implausible. One of these would involve a release which 

could occur if an improper seal were made between the vehicle and the service equipment, allowing the 

refrigerant charge to escape. Most, if not all, service units are equipped with auto shut-off 

adapters/couplers which prevent release of refrigerant during connection/disconnection and also ensure a 

locked seal to the vehicle AC system. Thus we judged this scenario to be implausible. In addition, this 

scenario is unlikely to result in greater exposure than the system rupture scenario described above. The 

other implausible scenario involved release of residual refrigerant from the 30-pound storage canisters 

once they were changed out of the charging equipment. Results from the Disposable Container Heel 

Testing Study Report [Heel Study] (Perrin Quarles, 2007) showed that only minimal residual refrigerant 

remained in the 30 pound canisters after charging. Further, due to the design of recharge systems, a 

release from the canister itself is unlikely. Therefore, this type of release was not included in the risk 

assessment. 

 It should be noted that visits to facilities where AC systems were being evaluated and discussions 

with industry professionals indicated that refrigerant exposures to professional service technicians are 

likely to be very rare. Most service shops are well ventilated and, as noted above, AC service equipment 

is designed to provide a tight seal between the service unit and the vehicle AC system. The scenarios 

evaluated should therefore be considered worst-case and unlikely to occur in the vast majority of service 

locations. 
 

 

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2.4.4.2 DIY Scenarios 

 Some individuals may not use professional service technicians to service their MAC systems and 

instead may attempt to perform repairs themselves. Because MAC systems are now better built, need less 

refrigerant, and are more complicated, there are fewer DIYers now than in the past. However, it is 

estimated that 3% of MAC service work is done by DIYers (MACS, 2003). These individuals could be at 

an increased risk of injury because they may not know the appropriate precautions to take and would not 

have access to specialized tools and safety equipment. 

 

 In the DIY scenarios, the amount of refrigerant will be more limited than in the professional 

repair technician scenario. DIYers are not assumed to have access to professional service equipment 

(units which cost several thousand dollars) and instead are assumed to use commercially available 

recharge cans. These cans involve much smaller volumes (e.g., one may purchase 350 gram cans of R134a, which constitutes slightly more than one-half the normal R-134a system charge). 

 The potential for release of refrigerant from small recharge cans was evaluated by Perrin Quarles 

Associates for U.S. EPA in 2007 (Perrin Quarles Associates, 2007). In their document, "Disposable 

Container Heel Testing Study Report," Perrin Quarles Associates described the varying use conditions 

under which recharge cans are employed and the impact of these recharge conditions on the AC system 

charging time and the residual volume left in the can. They reported that the most efficient charging 

method involved turning the can upside down. After five minutes of system charging in this position, 

98.6% of the can's contents were transferred, leaving only 1.4% residual (i.e., heel). In contrast, when AC 

system charging was performed holding the cans in an upright position, only 25.3% of the can contents 

was transferred within 5 minutes, and only 42.7% was transferred within 15 minutes. They reported that 

it would take approximately 90 minutes to empty the remainder of the can contents into the room 

atmosphere. In an intermediate condition, in which the can is rotated while charging, 79.6 percent of the 

can contents were transferred in the first 5 minutes and 98.4% were transferred in the first 15 minutes (see 

Perrin Quarles Associates, 2007, Table 4). Despite the fact that charging in the upside down position was 

the most efficient in terms of refrigerant transfer, a survey conducted at a training institute (Universal 

Technical Institute, Avondale Arizona) revealed that only approximately 25% of respondents indicated 

using the upside down method whereas 75% indicated they held the can upright (Perrin Quarles 

Associates, 2007). This is consistent with directions printed on the can which instruct users to hold the 

can upright. All survey respondents also indicated they would charge a system with a single can for 
 

 

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either less than 5 minutes (41%) or 5 to 10 minutes (59%). None reported that they would charge for a 

longer time (Perrin Quarles Associates, 2007). Perrin Quarles also reported that charge kits, used to 

connect the refrigerant cans to the vehicle AC system, were prone to leaks, at either the service port 

adaptor or the can tap. The magnitude of the leaks from these locations was not measured. 

 In the upright can position scenario, the DIYer uses 2 cans of refrigerant and charges the vehicle 

AC system with cans in the upright position. This results in a limited amount of transfer of refrigerant to 

vehicle AC and 75% remaining in cans (see Perrin Quarles Associates, 2007, Table 4). The Perrin 

Quarles study was conducted with 134a and we assumed results would be similar for a future AR (lacking 

specific information on future retail plans, we also assumed the mass of AR in each can would be the 

same the current situation with R-134a, i.e., 350 grams). The cans are set out and slowly release the 

remaining refrigerant to the garage air over 90 minutes (i.e., the time it reportedly took for cans in this 

position to empty). Note that charging the system with the can in other orientations (e.g., upside down, 

sideways, with shaking) causes more refrigerant to be transferred to the vehicle AC system and thus less 

to be released to room air. 

 In the upside down position scenario, the DIYer uses 2 cans of refrigerant and charges the vehicle 

AC system with cans in the upside down position. This results in the most rapid and complete transfer of 

refrigerant to vehicle. We assumed that due to a leak in the charge kit hook up or an improper 

connection, 15% of the refrigerant escapes and enters room air. The leakage is assumed to occur over the 

10 minutes it takes to transfer most of the contents of the two cans to the vehicle (see Heel Study, Table 

4). Note that in reality a small amount of time (0.5 to 2 minutes) would be required to hook up the second 

can. This additional amount of time is not included in the modeling since the time will vary among 

individuals and its exclusion is more conservative (i.e., a shorter time for material release results in 

greater air concentrations). 

 For the DIY scenario involving a heel release, we assumed a small garage volume of 36 m3

 (4m x 

3m x 3m). We deducted the estimated volumes of a typical vehicle (8 m3

) and miscellaneous garage 

equipment (5 m3

). An air exchange rate of 0.1 room air volumes/hour was used, which is likely to be 

excessively low for a home garage, which would tend to be poorly insulated. At least one recent study 

has reported that air exchange rates in garages averaged 0.77 per hour (Batterman et al., 2007). These 

assumptions are meant to represent a worst-case scenario when the garage door is closed (e.g., in winter). 

With the garage door open, it is likely that there would be sufficient ventilation to substantially reduce 

risk. 
 

 

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 For the DIY scenario involving leak from the charge kit assembly while charging a vehicle, we 

assumed a very small volume of 0.5 m3

, which characterizes the amount of air volume surrounding the 

engine with the hood raised. In charging the vehicle, we assumed the DIYer would be stationary at the 

side of the car, leaning over the engine area until charging is complete. This small air space will clearly 

be overly conservative if air currents (e.g., those generated by the leak itself) are sufficient to rapidly 

disperse the released refrigerant beyond the immediate vicinity of the hood area. 

2.5 Risk Characterization 

 Risk characterization represents the step in the analysis where data on toxicity, flammability and 

anticipated air concentrations are brought together to quantify the potential risks of the AR. The results 

of the risk characterization contribute to the FTA and allow a final estimate of the number of adverse 

events. 

2.5.1 Health Risks for Passengers and Vehicle Repair Workers 

 The first step in the characterization of potential health risks is to compare the predicted air 

concentrations for the passenger compartment and repair areas to the mRCL. This is done using a Hazard 

Index approach wherein the Hazard Index is calculated as: 

( )

( ) ( ) mRCL value ppm

Exposure Concentration ppm Hazard Index HI =

For situations where the HI is less than 1.0, we conclude that the potential exposure is not of concern 

from the standpoint of potential health effects. In addition, the magnitude of the HI (e.g., 0.1, 0.001, 

0.0001) gives a sense of the margin of safety between the exposure and the concentration at which 

adverse health effects might be expected. This may be useful in evaluating ARs where there is some 

disagreement regarding the adequacy of the data or the need to apply additional safety factors to data 

obtained in experimental animals. Note that for chemicals where the HI exceeds 1.0 (that is, the exposure 

concentration is higher than the mRCL) there is no guarantee that adverse effect will occur because the 

assessment employs conservative assumptions. A HI greater than 1.0 only indicates that the exposure in 

question should be of concern and should be looked at more carefully. 
 

 

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2.5.2 Ignition Risks for Passengers and Vehicle Repair Workers 

The evaluation of potential ignition risks involves a two step process. First, one determines 

whether the AR concentration in the location of interest (i.e., passenger compartment, engine 

compartment, repair area) exceeds the LFL7

. A formula analogous to that used to calculate the hazard 

index may be used: 

( )

( )

LFL ppm

Exposure Concentration ppm Flammability Hazard =

 

The resulting value should indicate some reasonable margin below the LFL (e.g., 90% of the LFL 

or 0.9) to provide an adequate margin of safety and account for uncertainties in measurement or model 

predictions. Note that this calculation is a screening step, intended to address the question: “is the 

estimated concentration in the passenger compartment sufficiently below the LFL”. If the answer is yes 

(e.g., Flammability hazard <0.9) then the fault tree branch for the scenario in question is “zeroed out”. If 

the answer is no (e.g.,Flammability hazard ≥ 0.9) then the fault tree analysis continues and we consider 

how frequently an ignition source might be in the flammable area. Once it is determined whether or not a 

potentially flammable concentration was present in the passenger compartment, it is then necessary to 

consider whether an ignition source is present in the same point in time and space where the refrigerant 

exists in the flammable range. This latter step was considered in the FTA (Section 2.6). 

2.5.3 Ecological Risks 

 As stated above, ecological risks associated with refrigerants are not anticipated to be substantial 

due to the low water solubility of these chemicals and their tendency not to accumulate in biological 

tissues. Nevertheless an evaluation of ecological risks is required in order to fully understand the 

potential environmental impacts of each AR. This evaluation is conducted qualitatively, by comparing 

the ecotoxicity test results for the AR with comparable results for other industrial chemicals, including 

common solvents and materials used in the automotive industry (e.g., gasoline components, brake fluid 

components, anti-freeze). The data from ecological toxicity studies are also considered in terms of the 

European ecological toxicity classifications and risk phrases (as set forth in EC directive 67/548/EEC). 

 

7

 Technically, the air concentration is compared to both the LFL and UFL to determine if it lies within the flammable range. In

this assessment, predicted concentrations were all well below the UFL. 
 

 

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2.5.4 Risks for Other Exposure Scenarios 

 Three other potential scenarios of concern to the automotive industry involve vehicle assembly 

workers, workers at scrap yards who may be involved in disassembling automotive vehicles, and risks for 

the general public from AC system leaks which may occur while a leaking vehicle is parked in a public 

parking garage. 

 Regarding vehicle assembly workers, data from one OEM (General Motors) indicate that 

refrigerant concentrations (in this case R-134a) in assembly plants is generally in the single digit parts per 

million (ppm) range (M. Anticoli, 2007). These data are based on both personal and area sampling. It is 

reasonable to assume that exposures to any future AR would be of the same order of magnitude (i.e., 0 to 

10 ppm). This level of exposure is well below occupational exposure limits for known refrigerants which 

are established as safe levels of chronic exposure (i.e., 8 hours per day, 5 days per week for multiple 

years). It is also several orders of magnitude below the LFL of any likely refrigerant (LFLs for 

refrigerants are measured in percentages in air, 1% is equal to 10,000 ppm). Based on this large margin 

of safety, we concluded that risks for automotive assembly plant workers did not need to be addressed in 

the risk assessment. 

 Regarding exposures of scrap yard workers who may disassemble automotive AC systems, 

current U.S. EPA regulations require that these workers use the same equipment used by repair workers to 

drain and reclaim refrigerant prior to crushing or scrapping the vehicle. The risk assessment conducted 

for repair workers should therefore address the risks of these workers as well. It should be noted that 

scrap yard operations would be expected to be even less enclosed than vehicle repair facilities and the 

potential for build of released AR material to levels of concern is therefore unlikely. As a result, risks for 

scrap yard workers also were not quantitatively addressed in the risk assessment. 

 Finally, with respect to the parking garage scenario, the leak situations that could be considered 

(e.g., slow leak over time or instantaneous rupture) are identical to those that are being evaluated for 

repair workers (Section 2.4.4). However, while the repair worker scenarios involve relatively small air 

spaces and small air exchange rates, a parking garage would have a much greater air volume and much 

higher rates of air exchange (either due to large windows or active ventilation). The potential risks 

associated with release of ARs from a leak in a parking garage will therefore be lower than those 

associated with vehicle repair and we did not deem it necessary to quantitatively address the former 

situation. 
 

 

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2.6 Fault Tree Analysis for Evaluating Potential Risks 

In order to quantify the potential adverse effects associated with a refrigerant release, we used 

Fault Tree Analysis (FTA). FTA is a methodology that graphically presents the sequences and 

combinations of failures that lead to a particular outcome. It utilizes a "top-down" approach, starting with 

the undesired effect as the top event of a tree of logic. Each situation that could cause that effect is added 

to the tree as a series of logic expressions. This technique analyzes the potential combinations or 

sequences of events by which an undesired event may occur. FTA can consider such causal effects as 

human error, equipment failure, and operating and maintenance procedures, though it cannot cover those 

causes of system failure that cannot be envisioned by risk analysts (Blackwell et al., 2006). 

FTA provides insight on failure sequences and serves as a guide for identifying system 

components, use patterns, or failure modes that are most likely to contribute to an undesirable outcome. 

Though fault trees can be labeled with quantitative failure probabilities, not all fault trees are quantified. 

When quantified, absolute accuracy is often secondary to the identification of failure sequences and the 

determination of the effectiveness of various mitigation measures, particularly in daily safety management 

activities (Blackwell et al., 2006). 

FTAs consist of various event "boxes", which reflect the probability or frequency of key events 

leading up to a system failure. The event boxes are linked by connectors ("gates") which describe how 

the contributing events may combine to produce the failure. Events may be combined in different ways: 

in cases where a series of events must all occur in order to produce an outcome (e.g., ignition source and 

sufficient oxygen to support combustion), the probabilities or frequencies of the individual contributing 

events are multiplied via an "AND" gate; in cases where only one of a series of events is needed to 

produce an outcome (e.g., a spark, a lighted cigarette, a hot surface all possibly leading to ignition), the 

probabilities are added via an "OR" gate.8

 More complex combinations are possible (e.g., conditional 

situations in which a series of contributing events must occur in a specific order in order to produce a 

failure) but these are not required by the present analysis. An example fault tree illustrating these 

principals is shown in Figure 1. 

 

8

 In the special case when the inputs to an OR gate are probabilities of vents that could occur simultaneously (e.g., driver 

fatigued/vehicle operated at night) and which can each by themselves cause the failure, the math is A+B-A*B. When the 

probabilities are mutually exclusive (vehicle stationary/vehicle moving) the math is A+B. 
 

 

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 To construct the fault trees and conduct the FTA analysis, we used the software program 

FaultrEASETM (ICF Consulting Services, 2003). This software package is the same as that used by U.S. 

EPA in the prior evaluation of R-152a and CO2 (Blackwell et al., 2006). 

2.6.1 Fault Tree Assumptions for Passenger Compartment Scenario 

For both the health and flammability risk evaluations, the fault trees for the passenger 

compartment scenarios include 3 branches, each branch reflecting a different leak size (i.e., small, 

medium and large leaks). In addition, a fourth branch is included to address risks related to a vehicle 

collision which damages the AC system to an extent that a refrigerant release occurs. 

 The fault tree branches corresponding to the different leak sizes are identical in terms of the 

events, gates, and multipliers involved; the primary difference is in the assigned probability of each type 

of release (small leaks being the most common, large leaks being the least common). The other critical 

difference between the different fault tree branches is the determination whether the modeled air 

concentration exceeds the relevant criterion (i.e., mRCL or LFL). Note that in this FTA, the value of an 

exceedance event is either 0 or 1, meaning that the air concentration either exceeds the limit (1.0) or it 

does not (0.0). The value for this input is Boolean in nature because the air modeling or field 

measurement result is based on a single set of conditions (e.g., fan speed, air infiltration rate). In order to 

generate a probability of an exceedance (i.e., a value between 0 and 1.0), different conditions would need 

to be considered in a large number of simulations or field measurements to yield an overall distribution of 

results. This level of effort is outside the scope of the current project. Note that the consequence of the 

"0 or 1" value for this input is that in cases where the air concentration does not exceed the relevant limit, 

the value of "0" causes the risks of that fault tree branch to become zero. 

2.6.1.1 Fault Tree Assumptions Related to Health Risks for Vehicle Passengers 

Input values for the FTAs addressing toxicity concerns are given in Tables 4 and 5 below. These input 

values were selected based on the values identified by Jetter et al. (2001), Blackwell et al. (2006) as well 

as additions from the CRP150 analysis. Where possible, data from the Jetter et al. and Blackwell et al. 

analysis were updated with newer information. The most significant changes to values from these earlier 

assessments involve the frequency of various sizes of leak as well as changes to the series of events 

required for the collision scenario. Regarding leak sizes, the CRP1234 members decided to model 

different sizes of evaporator corrosion leaks (0.01, 0.1, 0.5 mm) in lieu of U.S. EPA's approach of only 
 

 

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considering the rupture of the evaporator tube with a resulting leak orifice diameter of 1.8 mm. The 

CRP1234 members felt that this type of leak was highly unlikely and the risk assessment would be better 

directed at evaluating risks of leaks that are more realistic. As regards the collision scenario, the earlier 

CRP150 analysis required that the collision damage no other AC system components such that refrigerant 

would be vented away from the passenger compartment. This assumption was retained in the present 

analysis. This more realistic scenario results in a lower probability of exposure. 

Table 4. Inputs for Passenger Scenario Fault Trees Addressing Health Effects – Normal Operation 

Input Parameter Value 

USA Europe 

Basis 

Passenger vehicles in fleet 230,000,000 241,200,000 U.S. National Transportation Statistics, 2002. 

For the U.S. we assume all vehicles have AC. 

In Europe, it anticipates that about 90% of the 

fleet will have AC. These values reflect the 

2027-2032 timeframe when the new ARs are 

fully in use. 

Number of hours per year car is in 

use 

340 340 Blackwell et al., 2006 

Number of occupants in vehicle 1.59 1.59 Average value, Jetter et al., 2001 

Frequency of sudden leak from AC 

system. 

4E-4/yr 4E-4/yr Conservative VDA field data indicates 4E-4 is 

the probability of a leaking evaporator. The 

field data average is approximately 100ppm. A 

factor of 4 is applied to account for lifetime 

influence. 

Factor accounting for impact of 

inadequate repair on leak frequency 

1.5 1.5 Expert judgment. 

Probability of leak of specific size: 

- sudden large leak 

- sudden medium leak 

- sudden small leak 

0.01 

0.05 

0.94 

0.01 

0.05 

0.94 

Based on OEM expert opinion and 

understanding of the corrosion process. Also 

based on Jetter et al., 2001 which indicated that 

leaks of a significant size (1-3 grams per 

minute) are exceptionally rare. 

Probability leak not detected by 

occupants: 

- sudden large leak 

- sudden medium leak 

- sudden small leak 

0.4 

0.6 

0.8 

0.4 

0.6 

0.8 

Based on OEM expert opinion. Jetter et al. 

(2001) indicated that leaks bigger than 0.05g/s 

are clearly noticeable by passengers. 

Probability system is in recirculation 

mode when AC is in use 

0.32 0.16 OEM updating of Jetter et al. 2001 value (0.2) 

based on expert opinion. 

Probability fresh air flap is open 

when AC in use 

0.68 0.84 OEM updating of Jetter et al. 2001 value (0.8) 

based on expert opinion. 

Probability windows are closed 

when AC is in use. 

0.95 0.95 OEM estimate based on field observation. 

Probability passenger air 

compartment concentration exceeds 

health-based limit. 

0 or 1 0 or 1 Based on results of air modeling/field 

measurements 
 

 

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Table 5. Inputs for Passenger Scenario Fault Trees Addressing Health Effects – Collision Scenario 

Input Parameter Value 

USA Europe 

Basis 

Number of occupants in 

vehicle 

1.59 1.59 Average value, Jetter et al., 2001 

Frequency of serious 

collision (every crash 

involving an injury of 

whatever severity) 

5.60E-3/yr 5.60E-3/yr Five times the national transportation statistics 

fatal crash rate multiplied by 12,000 miles driven 

per year. Consistent with 2.5% of all crashes (3E6/mile) involving vehicle towing (9E-4/yr). 

Probability collision deforms 

A pillar > 35cm in serious 

collision. 

0.0187 0.0187 BMW Accident Research data (Severe crashes 

involving BMW vehicles in Bavaria 1976-2007) 

Probability evaporator piping 

fails in a collision. 

0.05 0.05 Expert judgment. 

Probability occupant 

survives a collision severe 

enough to deform A pillar > 

35 cm 

0.9 0.9 Jetter et al., 2001. 

Probability that only

evaporator piping fails while 

side crash. 

0.1 0.1 Estimate from DOE. In case of side crash> 35cm 

there’s always danger to destroy piping. Risk is 

higher if no other parts in engine compartment 

are destroyed. OEM estimation. 

Probability that collision 

does not break any windows 

0.0001 0.0001 BMW Accident Research data (Severe crashes 

involving BMW vehicles in Bavaria 1976-2007). 

Data suggest true likelihood is near zero. 

Probability passenger air 

compartment concentration 

exceeds health-based limit. 

0 or 1 0 or 1 Based on results of air modeling. 

2.6.1.2 Fault Tree Assumptions Related to AR Ignition Risks for Vehicle Passengers 

 A key step in evaluating potential ignition or flammability hazards is the determination whether 

potential ignition sources are present. If no ignition source is present which can produce sufficient energy 

(either via open flames, hot surfaces or electrical sparks) then there is no ignition hazard. Furthermore, it 

is necessary that the ignition source be present in the same location as that where the refrigerant is within 

the flammable range. In order to evaluate the potential ignition sources for the exposure scenarios of 

interest, SAE CRP1234 relied on the expert opinion of team members. The results of the deliberations 

are provided in Attachment A. The members of CRP1234 concluded that the most credible ignition 

sources capable of igniting an automotive refrigerant were butane lighters or matches that might be used 

to light cigarettes or cigars, sparks generated by the short of a vehicle battery located on the floor of the 

passenger compartment, and sparks generated by a short of a PTC heater located within the dashboard. 
 

 

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These were believed to be the worst-case ignition sources. Based on previous reports, a number of other 

ignition sources (e.g., lit cigarettes/cigars, electrical cigarette lighters, vehicle clocks and radios) do not 

have the potential to ignite the flammable AR under consideration. 

Input values for the passenger-associated flammability FTAs are given in Tables 6 and 7 below. 

Many of the values are shared with the toxicity fault trees but a number of parameters, particularly those 

relating to smoking and other possible ignition sources, are novel. Input values for these scenarios were 

taken from the studies of Jetter et al. (2001), Blackwell et al. (2006) and CRP150 or were based on input 

from CRP1234 members. 

Table 6. Inputs for Passenger Scenario Fault Trees Addressing Flammability 

Parameter Value Basis 

Average time vehicle is operated per 

year 

340 Blackwell et al., 2006 

Probability passenger smokes 0.21 Percentage of adults in U.S. who smoke. MMWR, 

2005. 

Fraction of time spent in vehicle 

lighting cigarette 

0.003 The average smoker consumes 17 cigarettes per day 

(MMWR, 2005) or 6,205 per year. Assuming 1/8th 

of cigarettes are consumed while driving (Blackwell 

et al., 2006), this is 776 cigarettes per year smoked in 

the car. Assuming 5 seconds to light each cigarette, 

the fraction of the total yearly amount of time spent 

in the vehicle that involves lighting a cigarette is 

776*5 seconds/340 hr = 0.003. 

Probability cigarette is lit with 

butane lighter or match (i.e., not 

electric lighter) 

0.5 Blackwell et al., 2006 

Sudden leak in passenger 

compartment 

4.6E-8 per hr VDA field data indicate 4E-4 is the probability of a 

leaking evaporator. The field data average is 

approximately 1E-4 and a factor of 4 was applied to 

account for lifetime influence. This value is divided 

by 8,760 hr/yr. 

Probability leak size is 

Small 0.94 

Medium 0.05 

Large 0.01 

Based on OEM expert opinion and understanding of 

the corrosion process. Also based on Jetter et al., 

2001 which indicated that leaks of a significant size 

(1-3 grams per minute) are exceptionally rare. 

Probability doors and windows are 

closed when AC system is in use 

0.95 OEM estimate based on field observation. 

Probability vehicle is in recirculation 

mode when AC system in use 

0.32 OEM updating of Jetter et al. 2001 value (0.2) based 

on expert opinion. 

Probability vehicle is in outside air 

mode when AC system in use 

0.68 OEM updating of Jetter et al. 2001 value (0.8) based 

on expert opinion. 

Number of occupants per vehicle 1.59 Average value, Jetter et al. 2001 

Probability smoking related ignition 

source (i.e., lighter, match) is within 

flammable zone 

Small leak = 0.2 

Med. leak = 0.4 

Large leak = 0.6 

Preliminary value. Refined for specific AR based on 

modeling results. 
 

 

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Table 6. Inputs for Passenger Scenario Fault Trees Addressing Flammability 

Parameter Value Basis 

Probability vehicle has interior 

battery 0.05 This value currently does not include hybrid vehicles that will come into service in the future. 

Probability of external short with a 

battery located inside vehicle * 1E-7 Does not include “jumper cable” situations where vehicle door will be opened. 

Probability sufficient energy 

released in battery system short 1.0 OEMs agreed to assume such a short will exceed minimum ignition energy. 

Probability battery short occurs 

within flammable zone 

Small leak = 0.0 

Med. leak = 0.1 

Large leak = 0.5 

Preliminary value. Refined for specific AR based on 

modeling results. 

Probability that vehicle has a PTC 

heater 0.30 Value for Europe, value for U.S. would be much lower (currently <1%). 

Probability that PTC heater is in use 0.1 The PTC heater is used 6 months of the year (factor 

=0.5) and only during cold starts (factor=0.2). 

Frequency of fault from PTC heater 1E-5 Based on OEM opinion. 

Probability sufficient energy 

released during interior PTC heater 

fault 

1.0 OEMs agreed to assume such a short will exceed 

minimum ignition energy. 

Probability PTC heater short is 

within flammable zone 

Small leak = 1.0 

Med. leak = 1.0 

Large leak = 1.0 

Based on location of PTC heater. 

AR concentration in passenger 

compartment exceeds LFL 0 or 1 Determined from CFD and/or field measurements. 

*Applies to design intent electrical circuits and excludes any after market alteration of the vehicle 

 For the collision scenario involving leaks into the passenger cabin it should be noted that the 

CRP1234 members assumed that any sparks associated with a collision (e.g., from grinding or rubbing 

metals parts either within the cabin or the AC ductwork) would have sufficient energy to ignite the 

material and would occur in the same time frame in which a release reaches the flammable range. 

CRP1234 team members acknowledged that this is a highly conservative assumption that would be 

expected to overestimate potential risks in this scenario. 
 

 

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Table 7. Inputs for Passenger Scenario (Collision) Fault Trees Addressing Flammability 

Parameter Value Basis 

Number of occupants per vehicle 1.59 Average value, Jetter et al. 2001 

Occupant survives collision 0.9 Jetter et al., 2001 

Probability occupant does not 

escape vehicle 

0.2 OEM members felt the value should be between 0.1 and 

0.2 and elected to use the more conservative value of 

0.2 in the analysis. 

Probability evaporator piping 

fails and refrigerant is released 

0.05 Based on OEM expert opinion 

Probability collision deforms Apillar >6“ 0.0187 OEM data. 

Frequency of serious collision 5.6E-3 per 

yr 

Blackwell et al., (2006) value of 8E-4 per year updated 

with VDA data from Statistisches Bundesamt 

Probability collision does not 

break windows and windows not 

already open 

1E-4 Based on OEM expert opinion. Actual data suggest the 

value is near zero. 

Probability collision does not 

break any other component in 

refrigerant cycle 

0.1 Estimate from U.S. Department of Energy. 

Probability collision produces 

sparks with sufficient energy to 

ignite material 

1.0 It was conservatively assumed that sparks associated 

with a collision (i.e., collision-related sparks located 

inside passenger compartment) would be sufficient to 

ignite the material. The likelihood of a collision 

producing such sparks within the passenger 

compartment may in reality be quite low. In addition, 

this assumption may be overly conservative for 

refrigerants with very high minimum ignition energies. 

2.6.2 Fault Trees for Engine Compartment AR Ignition Scenario 

With respect to the engine compartment scenario, there is only one fault tree, corresponding to 

risk of AR ignition (since passengers are not present in the engine compartment the release is not 

evaluated in terms of human health risk). Input values for this scenario are given in Table 8. Input values 

were taken from the studies of Jetter et al. (2001), Blackwell et al. (2006) and CRP150 or were based on 

new input from CRP1234 members. 
 

 

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Table 8. Inputs for Engine Compartment Scenario Fault Trees Addressing Flammability

Parameter Value Comment 

Number of occupants per vehicle 1.59 Average value, Jetter et al. 2001. 

Average time vehicle is operated 

per year 340 hr/yr Blackwell et al., 2006. 

Frequency of a large leak in the 

engine compartment 

6.8E-10 /yr 

Based on the frequency of a leak (4.6E-8 per hr) 

multiplied by the probability the leak is large and 

the factor accounting for the effect of inadequate 

repair. 

Probability of battery cable short* 1E-5 

This was the scenario OEM representatives felt 

had sufficient energy to be a possible ignition 

source. 

Probability sufficient energy 

released from battery cable short to 

ignite material. 

1.0 Based on OEM expert opinion. 

Probability battery cable short 

occurs within flammable 

concentration zone 

0 or 1 Based on field data. 

Probability manifold temperature 

exceeds autoignition temperature 0.05 

Exhaust manifold temperature only reaches 

autoignition temperature (405°C) during high 

work phases (e.g., climbing hills) . 

Probability hot component is within 

flammable concentration zone 0 or 1 Based on field data. 

Probability the refrigerant is 

actually ignited by the hot engine 

component 

0 or 1 Based on field data. 

Probability HFO-1234yf 

concentration in underhood area 

exceeds LFL 

0 or 1 Based on field data. 

*Applies to design intent electrical circuits and excludes any after market alteration of the vehicle. 

2.6.3 Fault Trees for Vehicle Repair Scenarios 

2.6.3.1 Fault Trees Related to Health Risks for Vehicle Repair Workers 

 The fault tree for repair workers is very similar to that used by U.S. EPA in their 2005 evaluation 

of R-152a and CO2 in terms of the professional repair workers. With respect to the DIY workers, the 

fault tree is similar although the exposure variable is based on modeling results for the two exposure subscenarios. As with the passenger fault trees, a value of either 0 or 1 is used to indicate whether the 

predicted air concentration in the repair area exceeds the mRCL. 

 Input values for the FTAs are given in Table 9 below. As with the passenger scenario FTAs, 

input values for these scenarios were taken from the studies of Jetter et al. (2001), Blackwell et al. (2006) 

and CRP150 or were based on input from CRP1234 members. 
 

 

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Table 9. Generic Inputs for Repair Worker Fault Trees Addressing Health Effects

Input Parameter Value 

USA Europe 

Basis 

Vehicle AC systems 

serviced annually 

22,000,000 7,236,000 Estimates suggest 20 to 25 million AC systems 

are serviced annually in U.S. (Carley, 2004). 

OEM data used for EU estimate. 

Probability work is carried 

out by a trained technician 

0.97 0.99 MACs meeting, August 2003. 

Probability work is carried 

out by a DIYer 

0.03 0.01 MACs meeting, August 2003. 

Frequency of sudden leak 

from vehicle system during 

service 

0.005/yr 0.005/yr Jetter et al. (2001) survey for U.S. data. In EU, 

it assumed to be the same as USA. 

Sudden leak from AC 

service equipment 

0.001/serviced 

vehicle/yr 

0.001/serviced 

vehicle/yr 

Jetter et al. (2001). Only applicable for amount 

of serviced vehicles, not complete fleet. 

Probability of inadequate 

ventilation in professional 

shop 

0.10 0.10 Expert opinion based on discussions at the 

MACS meeting, 2008. 

Probability of inadequate 

ventilation in DIY location 

0.20 0.20 Expert opinion based on discussions at the 

MACS meeting, 2008. 

Probability air 

concentration exceeds 

health-based limit. 

0 or 1 0 or 1 Based on results of modeling. 

2.6.3.2 Fault Trees Related to AR Ignition Risks for Vehicle Repair Workers 

 The fault tree used to assess flammability risks for repair workers is very similar to that used to 

assess health risks but contains unique inputs relating to potential ignition sources (i.e., smoking and 

equipment sparks). FTA input values are given in Table 10 below. As with the passenger scenario FTAs, 

input values for these scenarios were taken from the studies of Jetter et al. (2001), Blackwell et al. (2006) 

and CRP150 or were based on new input from CRP1234 members. 
 

 

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Table 10. Generic Inputs for Repair Worker Fault Trees Addressing Flammability

Input Parameter Value Basis 

Vehicle AC systems serviced 

annually 

22,000,000 

(U.S.) 

7,236,000 

(Europe) 

Estimates suggest 20 to 25 million AC systems 

are serviced annually in U.S. (Carley, 2004). 

OEM data used for EU estimate. 

Probability work is carried out 

by a trained technician 

0.97 MACs meeting, August 2003. 

Probability work is carried out 

by a DIYer 

0.03 MACs meeting, August 2003. 

Frequency of sudden leak from 

vehicle system during service 

0.005/yr Jetter et al. (2001) survey for U.S. data. In EU, 

this is not relevant: Technicians wear gloves and 

goggles and all pressure testing is done with 

vacuum or nitrogen. 

Sudden leak from AC service 

equipment 

0.001/serviced 

vehicle/yr 

Jetter et al. (2001). Only applicable for amount 

of serviced vehicles, not complete fleet. 

Probability of inadequate 

ventilation in professional shop 

0.10 OEM opinion. 

Probability of inadequate 

ventilation in DIY location 

0.20 Value agreed upon during Team 1 call on June 

12, 2007 

Probability that high energy 

generating activities are 

occurring in a professional repair 

shop. 

1E-3 OEMs agreed to assume that these activities 

could produce sufficient energy to ignite the 

material if the source was in the flammable 

Probability that welding, 

grinding, or other high energy 

generating activities are 

occurring at a given time in a 

DIY location 

1E-5 OEMs agreed to assume that these activities 

could produce sufficient energy to ignite the 

material if the source was in the flammable 

region. 

Probability employees smoke in 

a professional repair shop 

0.01 OEM opinion. 

Probability smoking occurs in a 

DIY location 

0.10 OEM opinion. 

2.6.4 Interpretation of FTA Results 

Risk estimates from FTA by themselves are of little value unless they can be placed in proper 

context. Clearly, in an idealized world we would all opt for situations which present no risk whatsoever. 

Unfortunately, all facets of life involve some element of risk. Life involves the identification and 

selection of activities that present an acceptable level of risk, based on the knowledge available about the 

risk involved. With this in mind, the risks associated with AR exposure developed in the FTA analysis 

are compared to common risks of death and injury reported in the literature. This allows the automotive 
 

 

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manufacturers not only to weigh risks of one AR against another, but also to consider the significance of 

individual AR risks in an appropriate context. 

2.7 Sources of Uncertainty in the Risk Assessment 

As with any risk assessment, the present work contains a number of sources of uncertainty that make 

the resulting risk estimates themselves are uncertain. However, in each area of uncertainty, an effort was 

made to err on the side of over predicting rather than under predicting actual risks since the goal of this 

risk assessment is to ensure the chosen AR does not pose a threat to human health or the environment. 

Areas of uncertainty present in the risk assessment include the following: 

• Modeling Uncertainty – Both the CFD and perfect mixing models require simplification of the 

real world situation. It is possible that details not included in the models could affect processes 

such as airflow patterns and cause inaccurate results. While such errors may be possible, the 

magnitude of their effect is likely to be small relative to the margin of safety present in the 

Hazard Indices calculated in the risk assessment. That is, one would not expect inclusion of such 

details in the models to cause a 50% increase in the predicted air concentration. In addition, with 

respect to the passenger compartment modeling, it should be noted that the work involved a 

worst-case vehicle situation. Because the results of the modeling were applied across the entire 

vehicle fleet, the final risk estimates can be expected to be unrealistically high. 

• Measurement Uncertainty – Measurement uncertainty concerns the ability of test instruments or 

protocols to accurately detect the parameter of interest. This type of uncertainty is present in both 

the bench top testing of flammability parameters and in the field assessment of AR concentrations 

and ignition potential. In both cases, tests were designed to reflect worst-case situations. For 

example, in the field testing, the vehicle was stationary and shielded from external airflow, both 

factors which minimized dilution of the released material and maximized contact with the 

potential ignition source. As noted in the Exponent report HFO-1234yf Refrigerant 

Concentrations and Ignition Tests in Full-Scale Vehicle Passenger Cabin and Engine 

Compartment (Exponent, 2008), there was also some degree of measurement bias in the sensor 

measurements of HFO-1234yf in those cases where sensors were used more than once. However, 

the level of error associated with this phenomenon is believed to be small and relatively minor 

compared to test-to-test variability and the overall conservativeness of the vehicle test relative to 
 

 

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real-world conditions. Thus, in this risk assessment, the measurement uncertainty was generally 

biased towards overestimation rather than underestimation of real world risks. 

• Parameter Uncertainty – A number of the parameters used in the FTA were based on expert 

judgment and only limited data. In many cases, the values reflect conservative assumptions that 

are likely to result in overestimates of the actual risks. For example, OEM data suggest that the 

probability of a vehicle sustaining sufficient damage in a collision such that the evaporator tube is 

rupture but the windows remain unbroken is close to zero. The fact that this probability was 

assumed to be 1 x 10-4 reflects a desire on the OEMs to err on the side of being conservative 

when data are lacking. Similarly, air exchange rates used in the repair scenario modeling (for 

both the professional shop and DIY location) are likely unrealistically low for most facilities. 

Since the results of that analysis were used to represent risks associated with all vehicle AC repair 

operations, the predicted risks are again likely to be overly high. 

• Toxicological Uncertainty – There are a number of uncertainties involved in applying 

toxicological data obtained with experimental animals in a risk assessment of human health risks. 

Studies typically involve a limited number of animals per dose group, the species involved may 

not be as sensitive as humans, and specially sensitive subpopulations may exist in the human 

population which are not addressed by the uniform strains of animals used for experimental 

testing. These uncertainties are addressed by again being cautious in the application of the 

toxicological data. For example, endpoints based acute toxicity are obtained from animal studies 

which generally involve 4 hours of continuous exposure to the test compound whereas human 

exposures would be expected to be substantially shorter based on the modeling results. 

Furthermore, human health-based exposure criteria used in the risk assessment were based on 

either a No Observed Adverse Effect Level (NOAEL) from the animal study (e.g., for cardiac 

sensitization) or an effect level divided by a safety factor (e.g., for acute toxicity or anesthetic 

potency). These values are biased towards the conservative. For example, exposures somewhat 

above the NOAEL may not produce any adverse effects, the NOAEL is simply the highest dose 

tested where effects were not seen. 

Based on the rationale stated above, it can be reasonably expected that the risks associated with AR 

exposures developed in this risk assessment are likely to be greater than risks experienced by real world 

vehicle passengers or repair personnel. This is appropriate if one goal of the risk assessment is to ensure 

health and safety. 
 

 

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3 Summary of R-12 Risk Assessment 

To validate the risk assessment methodology (and in particular the air modeling component) we 

first conducted an assessment of R-12, the refrigerant in use prior to R-134a. We evaluated R-12 as if it 

were a potential AR, even though the ODP of this material renders this impossible. R-12 was chosen over 

R-134a for this purpose because it has longer history of use in mobile air conditioning. This analysis 

allowed us to refine the air modeling and fault trees and optimize modeling and data collection when we 

turned to evaluation of the actual ARs. Because R-12 is not flammable, the risk assessment only dealt 

with potential health risks and did not include an analysis of the risks of potential AR ignition. 

3.1 General Properties 

Dichlorodifluoromethane (R-12, CFC-12) has primarily been used as a refrigerant and aerosol 

propellant and, to a lesser extent, as a blowing agent in the production of foam products (NRC, 2000). 

R-12 is a gas at standard temperature and pressure with a boiling point of -29.8°C (NRC, 2000; ACGIH, 

2001). Like most other refrigerants, R-12 is fairly stable but may decompose into toxic and corrosive 

gases (hydrogen chloride, phosgene, hydrogen fluoride, carbonyl fluoride) when in contact with hot 

surfaces or flames (NIOSH, 2002; ACGIH, 2001). The ODP of R-12 has been designated as 1.0, the 

same value as assigned to R-11 (U.S. EPA, 2007). The GWP of R-12 has been reported to be 10,600, 

relative to CO2 (U.S. EPA, 2007). R-12 is non-flammable according to ASHRAE test requirements 

(NRC, 2000). 

Reacting to the environmental threat of ozone depletion from CFCs, the 1987 Montreal Protocol 

established requirements that began the worldwide phaseout of ozone-depleting CFCs. All developed 

countries agreed to phase out production of most ozone-depleting substances, including CFCs, by the end 

of 1995. The 1990 Clean Air Act Amendments in the U.S. incorporated this production end date and 

directed U.S. EPA to develop regulations to maximize recycling, ban nonessential uses, develop labeling 

requirements and examine safe alternatives for ozone-depleting substances. On December 31, 1995, R-12 

production essentially ended in the US. Production in the European Union countries was phased out in 

the same time frame. Limited production of R-12 for “essential uses” (e.g., for use in medical inhalers) is 

permitted under U.S. and E.U. regulations until suitable replacements are developed (IPCC, 2005). 
 

 

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3.2 Toxicity Assessment 

3.2.1 Summary of Toxicological Findings 

The toxicology of R-12 has been extensively discussed in a number of publications (WHO, 1975; 

NRC, 1984, 2000; U.S. EPA, 1987) and therefore only the key studies are described in this section. 

When inhaled, R-12 has very low acute toxicity and acts like a weak narcotic (ACGIH, 2001). 

The inhalation lethal concentrations (LC50) of R-12 in rats after 30-minute and 2-hour exposures are 

800,000 ppm (Ritchie et al., 2001) and 600,000 ppm (Scholz, 1962), respectively. In guinea pigs exposed 

to R-12 at concentrations ranging from 21,000 to 304,000 ppm for time durations of between 5 and 120 

minutes, 51,000 ppm was found to be a NOAEL for all times up to 2 hours (Nuckolls, 1933). Ritchie et 

al. (2001) also evaluated neurobehavioral toxicity in rats exposed for up to 30 minutes to R-12. Rats 

were exposed while performing in either a rotarod/motorized running wheel apparatus (rotawheel) or in 

an operant chamber. The results indicated that 3 to 20 minutes of exposure to R-12 at concentrations 

ranging from 140,000 to 470,000 ppm induced acute neurobehavioral effects ranging from operant 

performance deficits to anesthesia with occasional convulsions. A NOAEL was not defined in this study 

because the authors increased concentrations across the dose range during the course of the experiment 

rather than evaluating specific concentrations. The finding of increasingly severe effects starting at 

140,000 ppm is consistent with the NOAEL of 51,000 ppm reported by Nuckolls (1933). As regards 

data in humans, Azar et al. (1972) exposed two human volunteers to concentrations of 1,000 and 10,000 

ppm of R-12 for 2.5 hours. There were no adverse effects resulting from exposure to 1,000 ppm. 

Exposures to 10,000 ppm resulted in an apparent slight reduction in some standardized test scores (a card 

sorting and clerical test), although the data are difficult to interpret given that there were only two 

subjects and considerable inter- and intra-subject variability in test performance. 

 Cardiac sensitization to epinephrine, resulting in multiple ventricular beats or cardiac arrest, has 

been observed in dogs inhaling R-12 at 50,000 ppm for 5 minutes (LOAEL) but not at 25,000 ppm 

(NOAEL) (Reinhardt et al., 1971; Trochimowicz and Reinhardt, 1975). It should also be noted that 

Kehoe (1943, as cited in NRC, 2000) reported a "significant degree of cardiac arrhythmia" in a single 

human volunteer exposed to 110,000 ppm R-12 for 10 minutes. This single case report in a human does 

not provide sufficient data to establish a safe exposure level but is consistent with the reported findings in 

dogs. 
 

 

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As regards longer term studies, Scholz reported that 4 weeks of 3.5-hour exposures at 100,000 

ppm R-12 produced no pathologic changes in guinea pigs, rats, cats, or dogs (Scholz, 1962). In another 

study, rats, monkeys, dogs, rabbits, and guinea pigs were exposed to 810 ppm R-12 twenty-four 

hours/day for 90 days (Prendergast et al., 1967). There were no treatment-related adverse effects in rats, 

monkeys, dogs or rabbits. Some microscopic effects were seen in the livers of treated guinea pigs but the 

authors expressed uncertainty that the effects were treatment related. A 90-day NOAEL from a later 

study conducted in rats was reported to be 10,000 ppm (Leuschner et al., 1983). Stewart et al. (1978) 

found that repetitive exposures (8 hours per day, 5 days per week, for 3.5 weeks) of eight human 

volunteers at 1,000 ppm were without adverse cardiac, respiratory, or CNS effects. 

R-12 was found to be negative for genotoxicity in various experimental systems: the Ames assay, 

the BHK21 cell-transformation assay, the CHO/HPRT assay, and the dominant lethal assay (Longstaff et 

al. 1984; Longstaff 1988; Krahn et al. 1980; ACGIH, 2001). 

Regarding the potential carcinogenicity of R-12, a study by Maltoni et al. (1988) found no 

exposure-related cancers in rats or mice exposed to R-12 at 0, 1,000, and 5,000 ppm repeatedly for 104 

(rats) and 78 weeks (mice). The NRC (2000) noted that the highest tested concentration (5,000 ppm) 

might not have been sufficient to firmly establish R-12 as noncarcinogenic. However, given the absence 

of genotoxicity and the lack of carcinogenicity of related compounds, it appears highly unlikely that R-12 

is carcinogenic. 

 

The available data concerning the toxicity of R-12 are summarized in Table 7. The acute and 

chronic toxicities of R-12 are low and the occupational exposure limit is correspondingly high. The 

compound does not appear to pose any significant specialized toxicological risks such as genotoxicity or 

carcinogenicity. Studies have not been conducted to indicate whether R-12 exhibits developmental 

toxicity. 
 

 

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Table 11. Summary of Available Toxicity Data for R-12 

Endpoint R-12 Reference 

Acute (LC50) (ppm) 600,000 Scholz, 1962 

Anesthetic effect level (ppm) 51,000* Nuckolls, 1933 

Cardiac sens. No effect level (ppm) 25,000 Reinhardt et al., 1971 

Worker exposure limit (ppm) 1,000 OSHA, MAK 

28-day no effect level (ppm) 100,000 Scholz, 1962 

90-day no effect level (ppm) 10,000 Leuschner et al., 1983 

Developmental toxicity no effect level No data 

Genotoxicity Negative NRC, 2000 

Carcinogenicity Negative NRC, 2000 

mRCL (ppm) 

40,800 (based on 

anesthetic effects) 

25,000 (based on cardiac 

sensitization) 

ODP 1.0 Montreal Protocol 

GWP 10,600 U.S. EPA, 2007 

*The value from the Nuckolls (1933) study is a no effect level. For calculating the mRCL, 80% of this value 

was used, as described in the ASHRAE/ANSI standard. 

** This was the only dose tested in a 90-day study. The true no effect level is likely to be much higher.

 According to the U.S. EPA SNAP regulations, each new AR will also be evaluated in terms of 

potential health risk relative to the current MAC refrigerant, R-134a. We therefore also compared key 

toxicity indices for R-12 to those associated with R-134a in Table 12 below. 

Table 12. Comparison of Toxicity of R-12 to the Toxicity of R-134a 

Endpoint R-12 R-134a

Acute (LC50) (ppm) 600,000 >500,000 

Anesthetic effect level (ppm) 51,000* 81,000 

Cardiac sensitization no effect level (ppm) 25,000 50,000 

Worker exposure limit (ppm) 1000 1000 

28-day no effect level (ppm) 100,000 50,000 

90-day no effect level (ppm) 10,000 50,000 

Developmental toxicity no effect level (ppm) No data 50,000 

Genotoxicity Negative Negative 

Carcinogenicity Negative Negative 

mRCL (ppm)** 

40,800 (based on 

anesthetic effects) 

25,000 (based on cardiac 

sensitization) 

50,000 (cardiac 

sensitization) 

ODP 1 0 

GWP 10,600 1410 

Flammability Not Flammable Not Flammable 

Shading highlights values indicating greater toxicity/environmental hazard compared to R-134a. 

* This value is a no effect level. 
 

 

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3.2.2 Toxicity Criteria Used for Risk Assessment 

 As indicated in Section 2.2.8, we have adapted the ANSI/ASHRAE RCL methodology for use in 

this risk assessment. The mRCL values for R-12 are 25,000 ppm based on cardiac sensitization potential 

and 40,800 ppm based on anesthetic properties. As indicated in Section 2.2.8, these will be compared to 

the 5-minute and 30-minute TWA air concentrations, respectively, based on whether the exposure 

scenario in question involves potential stress. 

 Based on the available toxicological data and lack of flammability, R-12 is classified as a "A1" 

refrigerant in terms of the ANSI/ASHRAE safety groups. 

3.3 Results of Exposure Assessment 

For the passenger exposure scenarios, air modeling was conducted using various leak sizes, 

vehicle speeds, system pressures, etc., as described in Table 13 below. 

Table 13. Passenger Modeling Scenarios for R-12 Evaluation (R-12 Simulation Key)

Sim #

Vehicle 

Condition

Blower 

Status

Leakage Condition - 

Evaporator hole 

diameter

Air 

Exchange 

Rate

Mode Temperature 

Behind 

Orifice or 

Behind Evap 

Leak Hole. 

Venting to 

Atmospheric 

Pressure 

Sim 1 1.8 ACH Recirc 

Sim 2 

Small leak (0.01 mm) 

34.3 ACH Outside air 

Sim 3 1.8 ACH Recirc 

Sim 4 

Medium leak (0.1 mm) 

34.3 ACH Outside air 

Sim 5 1.8 ACH Recirc 

Sim 6 

All at 

Idling 

All at 

Low 

(60 

cfm) Large leak (0.5 mm) 

34.3 ACH Outside air 

All at 0.5 

MPa 

At 15 C 

Quality = 0.5 

All outlet flow through rear package shelf. 

Charge=833g, Unoccupied 270 g/m3

, Occupied 298 g/m3

Results of the air modeling are shown in Table 14 below. More detail concerning the passenger exposure 

modeling for R-12 may be found in the CRP150 risk assessment. 
 

 

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Table 14. Predicted Passenger Compartment R-12 Concentrations

Sim # Simulation Conditions Peak 5-minute 

TWA (ppm)

Peak 30-minute 

TWA (ppm)

Sim 1 Vehicle idling, low fan, small leak (0.01 mm orifice), 1.8 

ACH, 0.5 mPa pressure behind leak, recirc mode 

55 55 

Sim 2 Vehicle idling, low fan, small leak (0.01 mm orifice), 1.8 

ACH, 0.5 mPa pressure behind leak, outside air mode 

2.9 2.9 

Sim 3 Vehicle idling, low fan, medium leak (0.1 mm orifice), 

1.8 ACH, 0.5 mPa pressure behind leak, recirc mode 

5,490 5,490 

Sim 4 Vehicle idling, low fan, medium leak (0.1 mm orifice), 

1.8 ACH, 0.5 mPa pressure behind leak, outside air mode 

289 289 

Sim 5 Vehicle idling, low fan, large leak (0.5 mm orifice), 1.8 

ACH, 0.5 mPa pressure behind leak, recirc mode 

35,000 28,720 

Sim 6 Vehicle idling, low fan, large leak (0.5 mm orifice), 1.8 

ACH, 0.5 mPa pressure behind leak, outside air mode 

7,067 2,867 

Air modeling for repair workers (both professionals and DIYers) who may be exposed to R-12 was 

carried out as described in Section 2.3.3. Results of the air modeling simulations are summarized in 

Table 15. 

Table 15. Results of Air Modeling for Repair Worker Scenarios, R-12

Scenario Predicted R-12 Concentration (ppm)

Professional repair – complete charge loss 

due to rupture (5-minute TWA) 

708 

Professional repair – hose leak during system 

drain and recharge (30-minute TWA) 

139 

DIY – Scenario 1, slow loss of heel from 2 

cans of R-12 (30-minute TWA) 

2,182 

DIY – Scenario 2, leak from charge kit while 

charging system (30-minute TWA) 

30,896 

 A series of graphs, indicating the predicted air concentrations over time that are associated with 

each repair scenario are included as Attachment B. 

3.4 Risk Characterization 

 Results of the air modeling for passenger exposures indicated that refrigerant releases associated 

with a large leak in recirculation mode would result in an unacceptable level of risk (i.e., HI>1.0). 

Predicted exposure levels were below the mRCL for all small and medium leak scenarios, and for the 

large leak scenario involving a vehicle operated in outside air mode. Modeling was not conducted for the 
 

 

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collision scenario. However, the leak involved in a rupture of the AC piping (as envisioned in the 

collision scenario) would be greater than that considered by the large leak, and thus a leak associated with 

a serious collision would result in air concentrations above the health-based limit. 

 For the vehicle repair scenarios, none of the modeled air concentrations exceeded the relevant 

mRCL. As a result, the vehicle repair scenarios did not contribute to risks calculated in the FTA. 

 The calculated HIs for all of the R-12 scenarios are shown in Table 16, below. 

Table 16. Hazard Indices Associated with Different Exposure Scenarios, R-12 

Scenario Predicted R-12 

Concentration 

(ppm) 

Health-Based 

Comparison Value 

(ppm) 

Hazard Index 

Passenger Exposure Scenarios 

Small leak, recirc mode 55 40,800* 0.001 

Small leak, outside air 2.9 40,800* 0.00007 

Medium leak, recirc mode 5,490 40,800* 0.13 

Medium leak, outside air 289 40,800* 0.007 

Large leak, recirc mode 35,000 25,000** 1.4 

Large leak, outside air 7,067 25,000** 0.28 

Collision not modeled 25,000** >1.4 

Repair Worker Exposure Scenarios 

Professional repair – system rupture 708 25,000** 0.03 

Professional repair – hose leak 

during system drain and recharge 

139 40,800* 0.003 

DIY – slow loss of heel from 2 cans 2,182 40,800* 0.05 

DIY – charge kit leak while charging 

system 

30,896 40,800* 0.76 

* Based on anesthetic properties. 

** Based on cardiac sensitization potential because the exposure scenario involves potential stress. 

3.5 FTA 

Fault trees related to the risk assessment of R-12 are shown in Figures 4 through 9. As indicated 

in these figures, for the small and medium leak situations, concentrations of R-12 in the passenger 

compartment are not predicted to exceed health-based limits. The FTA risks associated with these fault 

tree branches are therefore zero. With respect to the large leak scenarios, the fault tree involving the 

vehicle in recirculation mode is associated with an air concentration above the health-based limit, whereas 

the vehicle with a large leak while in outside air mode does not achieve an air concentration above the 

limit. With respect to the vehicle collision scenario, air modeling data are not directly available to 
 

 

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evaluate the potential risks with certainty. However, given that the HI for the large leak (0.5 mm) 

scenario (recirculation mode) substantially exceeds the health based limit, and given the larger leak size 

contemplated by the collision scenario (i.e., 1.45 or 2.3 mm), R-12 concentrations in the passenger cabin 

can be expected to exceed health-based limits, at least in the event of the extreme collision scenario as 

described. The risks associated with this fault tree branch were therefore retained in the FTA. HI values 

for vehicle repair scenarios never exceeded 1.0 and therefore the contribution of these exposure scenarios 

to overall risk is zero. The final estimated risks from the FTA are 11 per year, in both the U.S. and 

Europe. These risks are largely due to the large leak scenario associated with the vehicle in recirculation 

mode. The collision scenario contributes negligibly to the overall risk. 

3.6 Conclusions Regarding R-12 

 The overall result of the FTA was an estimate of 11 refrigerant exposures above health-based 

limits per year to R-12 in the U.S. and in Europe. While the number of vehicles in the fleet in Europe is 

somewhat higher, the difference when multiplied against the low frequency is less than 1 exposure per 

year. To place this number in perspective, if divided by the number of drivers currently registered in the 

U.S. (200 million), the annual risk per driver would be 5.5 x 10-8 per year. This value is comparable to 

the reported risk of being injured in an elevator ride (2x10-7) and substantially less than the risk of dying 

during a 5,000-mile plane trip (2x10-6).
 

 

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4 Risk Assessment – HFO-1234yf 

4.1 General Properties 

 The joint DuPont Honeywell product is 2,3,3,3-tetrafluoropropene (HFO-1234yf). HFO-1234yf 

is a new proprietary chemical being developed by the companies and has been subjected to an extensive 

battery of evaluations. HFO-1234yf is slightly flammable; the LEL is 6.5% (65,000 ppm) at 21°C and the 

minimum ignition energy is greater than 1,000 mJ (DuPont/Honeywell, 2007). Thus, in addition to 

toxicity, the potential flammability of HFO-1234yf is a concern for the risk assessment. 

 The occupational exposure limit established by Honeywell for HFO-1234yf is 1,000 ppm. 

Studies by Honeywell have indicated that the ODP of HFO-1234yf is zero (Dupont/Honeywell, 2007). 

The GWP of the HFO-1234yf has been estimated to be 4 (Nielsen et al., 2007). Thus, the chemical will 

satisfy the EU F-gas directive. 

4.2 Toxicity Assessment 

4.2.1 Evaluation of Available Toxicity Data from Manufacturer 

 Honeywell has provided results for a large number of studies conducted on HFO-1234yf. These 

consisted of the following laboratory reports: 

Mammalian Toxicity

 4-hour inhalation range finding study in the mouse (Huntingdon Life Sciences, March 11, 2004) 

 4-hour inhalation screening study with micronucleus assay in rats and mice (Huntingdon Life 

Sciences, March 30, 2004) 

 14-day inhalation study in rats (TNO, November 4, 2005) 

 Chromosomal aberration test in cultured human lymphocytes (TNO, November 8, 2005) 

 Bacterial reverse mutation test (Ames Assay) (TNO, November 15, 2005) 

 Micronucleus test in bone marrow cells of mice treated via inhalation (TNO, November 23, 2005) 

 4-hour inhalation toxicity test in rats (TNO, January 17, 2006) 
 

 

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 Toxicogenomic assessment of carcinogenic potential (Hamner Institutes for Health Sciences, May 

26, 2006) 

 Cardiac sensitization study in dogs (WIL Research Laboratories, August 23, 2006) 

 4-week (28-day) inhalation toxicity study in rats, including unscheduled DNA synthesis and 

micronucleus test results (TNO, September 5, 2006) 

 Prenatal developmental inhalation toxicity study in rats (TNO, April 17, 2007) 

 13-week (90-day) inhalation toxicity test in rats (TNO, May 11, 2007) 

Ecological Toxicity

 Preliminary experiment for developing methods to maintain test concentrations in aquatic toxicity 

tests (TNO, May 5, 2006) 

 Freshwater algal growth inhibition test (TNO, May 8, 2006) 

 Acute toxicity study in Daphnia magna (TNO, May 8, 2006) 

 96-hour acute toxicity study in carp (TNO, June 15, 2006) 

At the time of this report, Honeywell has completed a full range of toxicity testing on HFO-1234yf. 

Honeywell is currently conducting an optional developmental toxicity test in a second species (i.e., 

rabbits), and is starting a 2-generation reproductive toxicity test which would be required by European 

authorities when commercial imports reach certain size limits. In lieu of a full 2-year carcinogenicity 

study, Honeywell has conducted a 13-week inhalation exposure in rats and mice followed by a genomic 

carcinogenicity examination. Honeywell has reviewed the study design with both the U.S. EPA and with 

a European (i.e., Belgian) regulatory agency before initiating the toxicology program, and has not 

received any objections to the approach. Honeywell has indicated it would perform a 2-year 

carcinogenicity study if required by regulatory authorities; however, given the lack of activity in the 

mammalian mutagenicity assays, the lack of specific organ toxicity in the 13-week inhalation study, and 

the lack of a positive carcinogenic response in the genomic assays, the probability that HFO-1234yf 

would show a positive response is considered by the Honeywell Director of Toxicology to be low. 

 Honeywell's toxicity testing was conducted primarily at TNO Laboratories in the Netherlands. 

TNO is one of the largest toxicology research laboratories and has a solid reputation. Some work 

(including the cardiac sensitization study of HFO-1234yf) was conducted at WIL Research Laboratories 

in the U.S. WIL is another well recognized toxicological testing laboratory with experience in cardiac 

sensitization testing (Chengelis, 1993; 1997). The final research laboratory used, the Hamner Institutes 
 

 

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for Life Sciences, conducted the genomics study. Hamner (formerly the Chemical Industry Institute of 

Toxicology) is also well regarded and specializes in cutting edge research. 

 For each of the toxicity studies identified above, Gradient was able to obtain the final and 

complete laboratory report and reviewed the methodology, data generated, and conclusions. Based on the 

information provided in the study reports, most of the studies appear to have been conducted 

appropriately, using standard methodology. The only exception may be the cardiac sensitization study. 

The Honeywell cardiac sensitization study appears to have several design elements that may be less 

conservative than the standard test. The study used baseline epinephrine doses in some dogs that did not 

produce any arrythmiogenic effect ["the highest dose level tested during the pre-study evaluation that did 

not elicit significant ECG findings (e.g., PVC)"] rather than a minimally arrythmiogenic effect (the 

standard method). In addition, Honeywell/WIL used the criterion of eleven or more premature ventricular 

contractions in 10 seconds to identify an adverse effect. This particular criterion has not been cited 

elsewhere. These study design differences would be expected to have fairly limited effects on the final 

outcome of the study. Given that the cardiac sensitization NOAEL of HFO-1234yf is 120,000 ppm (the 

highest dose tested), these study design differences should not be a barrier to adoption of the chemical. 

 It should be noted that in discussions with Honeywell about the cardiac sensitization study, the 

company indicated that the study was conducted in the same manner as previous studies and that 

differences in terminology ("minimally arrythmiogenic" vs "no significant ECG findings") do not indicate 

differences in study design. 

4.2.3 Summary of Toxicological Findings 

 The available data concerning the toxicity of HFO-1234yf are summarized in Table 17. Overall 

the acute and chronic toxicity of HFO-1234yf appear to be low. Based on the toxicological data provided 

by Honeywell, as well as the flammable nature of the chemical, HFO-1234yf would be placed into the 

"A2" ANSI/ASHRAE safety group and into the A2L ISO 817 safety group. 
 

 

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Table 17. Summary of Available Toxicity Data for HFO-1234yf 

Endpoint HFO-1234yf

Acute (LC50) (ppm) >405,800 (TNO, 2006a)* 

Anesthetic effect (ppm) >405,800 (TNO, 2006a)* 

Cardiac sens. No effect level (ppm) 120,000 (WIL, 2006) 

Worker exposure limit (ppm) 1,000 (Honeywell 8-hr value) 

28-day NOAEL (ppm) 50,000 (TNO, 2006f) 

90-day NOAEL (ppm) 50,000 (TNO, 2007b) 

Developmental toxicity NOAEL (ppm) 50,000 (TNO, 2007a) 

Genotoxicity Negative (Huntingdon, 

2004;2005b,c,d; 2006f) 

Carcinogenicity Screen Negative (Hamner, 2006) 

Aquatic toxicity (mg/L) Acceptable (TNO 2006c,d,e) 

mRCL (ppm)* 120,000 (based on card. sens.) 

115,000 (based on acute toxicity) 

ODP 0 (Dupont/Honeywell, 2007) 

GWP 4 (Nielsen et al., 2007) 

* Based on the highest dose tested 

According to the U.S. EPA SNAP regulations, each new AR will also be evaluated in terms of potential 

health risk relative to the current MAC refrigerant, R-134a, a comparison of key health indices for HFO1234yf relative to R-134a is included in Table 18, below. 

Table 18. Comparison of Toxicity of HFO-1234yf to the Toxicity of R-134a 

Endpoint 1234yf R-134a

Acute (LC50) (ppm) >405,800 >500,000 

Anesthetic effect (ppm) >405,800 81,000 

Cardiac sensitization no effect level 

(ppm) 120,000 50,000 

Worker exposure limit (ppm) 1,000 (Honeywell 8-hr value) 1,000 (PEL) 

1,000 (MAK) 

28-day NOAEC (ppm) 50,000 50,000 

90-day NOAEL (ppm) 50,000 50,000 

Developmental toxicity NOAEL (ppm) 50,000 50,000 

Genotoxicity Negative Negative 

Carcinogenicity Screen Negative Negative 

Aquatic toxicity (mg/L) >83 (Daphnia) 450 

mRCL (ppm) 120,000 (based on card. sens.) 

115,000 (based on acute toxicity) 

50,000 (cardiac sensitization) 

141,000 (acute toxicity) 

64,800 (anesthetic effects) 

ODP 0 0 

GWP 4 1,410 

Like R134a, HFO-1234yf displays low acute and chronic toxicity. In fact, for each of the toxicological 

measures listed in Table 12, HFO-1234yf evidences equal or lesser toxicity compared to R-134a. The 
 

 

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Honeywell suggested worker exposure limit for HFO-1234yf (1,000 ppm) is identical to the exposure 

limits for R-12 and R134a. HFO-1234yf also appears to be a good substitute for R134a in terms of ODP 

and GWP. 

4.2.4 Toxicity Criteria Used for Risk Assessment 

 As indicated in Section 2.2.8, we have adapted the ANSI/ASHRAE RCL methodology for use in 

this risk assessment. We have therefore estimated mRCL values for HFO-1234yf as follows: 

 For exposure scenarios involving potentially stressful stimuli we will use a mRCL of 120,000 

ppm, based on the cardiac sensitization NOAEL for Honeywell's study of HFO-1234yf (WIL 

Research Laboratories, 2006). 

 For exposure scenarios not involving potentially stressful stimuli we will use a mRCL of 115,000 

ppm, which was calculated as 28.3% of the maximum dose of HFO-1234yf from the acute 

toxicity study in rats (TNO, January 17, 2006). Note that no lethality was observed at this dose. 

Note that the mRCL for non-stress involving exposures is slightly less than the mRCL based on cardiac 

sensitization. The cardiac sensitization value is nonetheless more conservative to use in stress-related 

situations because this value will be compared to the peak 5-minute TWA concentration rather than the 

peak 30-minute TWA. 

4.3 Flammability Properties 

As noted previously, the manufacturers of HFO-1234yf have conducted considerable research to 

understand its potential for combustion. These properties are summarized in Table 19, along with 

comparative data for some other common refrigerants. ASHRAE Standard 34 testing indicates that the 

flammable range lies between 6.5 and 12.3 percent (i.e., 65,000 ppm and 123,000 ppm). This range is 

narrower than that for R-152a and the LFL is substantially higher, indicating a higher accumulation of gas 

is required before ignition is possible. The minimum ignition energy of HFO-1234yf appears to be 

exceptionally high among refrigerants that would be assigned to ASHRAE Classification 2. Tests using a 

1000 mJ ignition spark were not able to ignite the material. In contrast, the minimum ignition energy of 

R-152a is below 1 mJ (i.e, more than 1,000 times less than HFO-1234yf). The autoignition temperature 

of HFO-1234yf is similar to that of R-152a and well below that of R-32. However tests run by 
 

 

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Honeywell on ignition of HFO-1234 vapors on hot steel surfaces up to 800C, as reported to CRP1234 

members, have not shown an indication of ignition (Honeywell, 2008). It should also be noted that the 

inability to ignite HFO-1234yf on hot surfaces was demonstrated in engine compartment ignition tests 

conducted by Exponent (Exponent, 2008). Finally, the heat of combustion and burning velocity of HFO1234yf are both fairly low, particularly in comparison to R-152a. This suggests HFO-1234yf has a weak 

potential to sustain a serious fire if the gas were to be ignited. HFO-1234yf has not yet received a safety 

classification from ASHRAE or ISO, but the known flammability properties would result in a 

flammability classification of 2L. A toxicity classification of A would be expected given that the current 

recommended occupational exposure limit is 1,000 ppm. 

Table 19. Flammability of HFO-1234yf Relative to Other Refrigerants 

Property 1234yf R-12 R-134a R-152a R-32 

LFL (% volume in air) 6.5 NA NA 3.9 14.4 

UFL (% volume in air) 12.3 NA NA 16.9 29.3 

Minimum Ignition Energy (mJ) >1,000 NA NA 0.38 >30, <100 

Autoignition temperature (oC) 405 >750# >743 454 648 

Heat of combustion (kJ/g) 9.5 -0.8* 4.2 16.5 9.4 

Burning velocity (cm/s) 1.5 NA NA 23 6.7 

Safety Classification A2L† A1 A1 A2 A2 

NA – Property not relevant for this material. 

Source: DuPont/Honeywell presentation 12/13/2007. 

* U.S. EPA, 2007. http://www.epa.gov/ozone/snap/refrigerants/safety.html #

 DuPont MSDS for R-12 

† Anticipated ISO safety classification based on known properties.

4.4 Results of Exposure Assessment 

4.4.1 Results for Passenger Compartment Scenarios – CFD Modeling 

 Earlier modeling conducted as part of the SAE CRP150 effort indicated that modeling of the 

recirculation and outside air use conditions were most important to the FTA. Therefore, recirculation and 

outside air scenarios were evaluated for each of the three leak sizes (0.01, 0.1, and 0.5 mm holes in the 

evaporator face). For each simulation, the vehicle was assumed to be idling and the fan was operated at 

low speed. Previous modeling from CRP150 indicated that these were the most conservative options; i.e., 

moving vehicles and vehicles with the fan operating at high speed yielded lower concentrations in the 

passenger compartment. The various CFD simulation conditions used by DuPont are shown in Table 20. 
 

 

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Table 20. CFD Modeling Scenarios 

Sim 

Number

Conditions Leak Rate 

(g/s)

1 Vehicle idling, low fan, large leak (0.5 mm 

orifice), recirc mode 

1.14 

2 Vehicle idling, low fan, medium leak (0.1 

mm orifice), outside air mode 

0.04 

3 Vehicle idling, low fan, small leak (0.01 mm 

orifice), recirc mode 

0.00036 

4 Vehicle idling, low fan, large leak (0.5 mm 

orifice), outside air mode 

1.14 

5 Vehicle idling, low fan, medium leak (0.1 

mm orifice), recirc mode 

0.04 

6 Vehicle idling, low fan, small leak (0.01 mm 

orifice),outside air mode 

0.00036 

According to DuPont, CFD modeling was only conducted for the first 200 seconds of the leak. In the 

case of the large leaks with the vehicle in recirculation mode and outside air mode, linear extrapolation 

was then used to calculate the maximum concentration that would be reached at the end of the leak (at 

606 seconds). From this data we were able to estimate the maximum, 5-minute, and 30-minute TWA 

concentrations. The 5-minute TWA values were based on the results of the CFD modeling for 200 

seconds plus linear extrapolation for the remaining time period, assuming linear decay of concentrations 

after the end of the leak. 

For the small and medium leak conditions (both recirculation and outside air), maximum, 5- and 30-

minute TWA were not calculated due to the long time required to reach the end of the leak. For these 

situations, it was assumed that because results for the large leak did not exceed the health-based limit, 

results for the smaller leaks would also be acceptable. 
 

 

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Table 21. Results of Air Modeling Simulations for Passenger Scenarios, HFO-1234yf 

Sim 

Number

Conditions Maximum 

Concentration 

(ppm)

Peak 5-

minute 

TWA*

Peak 30-

minute 

TWA*

1 Vehicle idling, low fan, large leak (0.5 

mm orifice), recirc mode 

65,000 63,000 51,000 

2 Vehicle idling, low fan, medium leak 

(0.1 mm orifice), recirc air mode 

Will not exceed relevant criterion based on 

results for large leak 

3 Vehicle idling, low fan, small leak 

(0.01 mm orifice), recirc mode 

Will not exceed relevant criterion based on 

results for large leak 

4 Vehicle idling, low fan, large leak (0.5 

mm orifice), outside air mode 

34,000 32,000 21,000 

5 Vehicle idling, low fan, medium leak 

(0.1 mm orifice), outside air mode 

Will not exceed relevant criterion based on 

results for large leak 

6 Vehicle idling, low fan, small leak 

(0.01 mm orifice),outside air mode 

Will not exceed relevant criterion based on 

results for large leak 

* Data for measurement point P4, which yields the highest results. 

4.4.2 Results for Passenger Compartment Scenarios – Field Measurements 

In addition to CFD modeling, field measurements of HFO-1234yf concentration are available 

from the Exponent field study (Exponent, 2008). Although Exponent collected data from multiple 

locations in the vehicle cabin, 3 locations are used in the risk assessment. Data for the driver’s side 

breathing area are used to evaluate potential health effects. The driver’s side breathing zone estimate is 

used to assess the risks of an AR ignition from smoking, the floor value is used to assess the risks 

associated with a short from an internal battery, and the duct value is used to assess the risks of a short in 

a PTC heater. In all cases, the maximum detected concentration is used. Data for each of these scenarios 

is shown in Table 22. 
 

 

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Table 22. Results of Field Measurements for Passenger 

Compartment Scenarios, HFO-1234yf

Test Maximum Measured Concentration (ppm)

Driver’s Breathing Area 

PCC1 28,721

PCC3 28,993 

PCI1 22,001

Duct Location 

PCC1 23,270

PCC3 20,431

PCI1 28,254

Driver’s Floor Area 

PCC1 17,717 

PCI1 29,774

Data from Exponent (2008). 

PCC= Passenger cabin test 

PCI = Passenger cabin ignition test (concentrations of HFO-1234yf were also 

measured in this test)

4.4.3 Results for Engine Compartment AR Ignition Scenario – Field Measurement 

Exponent also measured HFO-1234yf concentrations and attempted ignition after a release in the 

engine compartment. Two tests were conducted to evaluate reproducibility. Results of measurements in 

the engine compartment were more variable than results for the passenger compartment, which is not 

surprising given that the engine compartment is more open to outside air and has a more complicated 

geometry. The highest value measured in the engine compartment (87,000 ppm, engine compartment 

test 1, sensor 5) suggests a potential ignition hazard. However, the engine compartment field test also 

showed that it was not possible to ignite the released refrigerant with the high temperature source. This 

suggests that, while theoretically possible, ignition and propagation of a HFO-1234yf fire in the engine 

compartment during normal vehicle operation is extremely unlikely 

4.4.4 Results for Repair Worker Scenarios – Perfect Mixing Model 

 Air modeling for repair workers (both professionals and DIYers) who may be exposed to HFO1234yf was carried out as described in Section 2.3.3. Results of the air modeling simulations are 

summarized in Table 23.
 

 

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Table 23. Results of Air Modeling for Repair Worker Scenarios, HFO-1234yf 

Scenario Predicted HFO1234yf 

Concentration 

(Maximum, 

ppm)

Predicted HFO1234yf 

Concentration 

(5-minute TWA, 

ppm)

Predicted HFO1234yf 

Concentration 

(30-minute TWA, 

ppm)

Professional repair – complete charge loss 

due to rupture (5-minute TWA) 

590 566 464 

Professional repair – hose leak during system 

drain and recharge (30-minute TWA) 

146 141 122 

DIY – Scenario 1, slow loss of heel from 2 

cans of HFO-1234yf (30-minute TWA) 

2,670 2,636 2,493 

DIY – Scenario 2, leak from charge kit while 

charging system (30-minute TWA) 

38,900 37,800 32,800 

 A series of graphs, indicating the predicted air concentrations over time which are associated with 

each repair scenario are included as Attachment C. 

4.5 Risk Characterization 

4.5.1 Health Hazard Indices for HFO-1234yf for Passenger Compartment and Repair Worker 

Scenarios 

 Results of the air modeling and risk characterization (Table 24) indicate that none of the modeled 

HFO-1234yf releases would result in an unacceptable level of health risk (HI<1.0). Note that the 

measurement from the field test of the large leak results in a substantially lower HI than the CFD 

modeling. Also note that the collision scenario was not modeled for HFO-1234yf, and it seems unlikely 

that air concentrations in this scenario would exceed the health-based limits given the large margin of 

safety present with the large leak, particularly as relates to the field measurements. However, lacking 

specific data to support this conclusion, the collision scenario will be evaluated in the FTA. 
 

 

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Table 24. Hazard Indices Associated with Passenger Exposure Scenarios, HFO-1234yf 

Scenario

Predicted HFO1234yf Concentration 

(ppm)

Health Based 

Comparison Value 

(ppm)

Hazard Index 

(HI)

Results of CFD Modeling 

Large leak, recirc 

mode (CFD Sim 1) 63,000 120,000 (mRCLcs) 0.53 

Medium leak, recirc 

mode (CFD Sim 2) NA 115,000 (mRCLat) NA 

Small leak, recirc 

mode (CFD Sim 3) NA 115,000 (mRCLat) NA 

Large leak, outside air 

(CFD Sim 4) 32,000 120,000 (mRCLcs) 0.27 

Medium leak, outside 

air (CFD Sim 5) NA 115,000 (mRCLat) NA 

Small leak, outside air 

(CFD Sim 6) NA 115,000 (mRCLat) NA 

Results of Field Measurement 

Large leak, recirc 

mode <29,000* 120,000 (mRCLcs) <0.24 

Collision Scenario – imputed from CFD results for large leak (recirc condition) 

Collision >63,000 120,000 (mRCLcs) Possibly >1 

NA – value must be less than value for the relevant large leak and therefore well below 1.0. 

MRCLcs = health criterion based on cardiac sensitization. 

MRCLat = health criterion based on acute toxicity. 

* The maximum measured value, the 5-minute TWA would be less than this value.

The risk characterization indicates that HFO-1234yf releases associated with all of the vehicle repair 

scenarios (Table 25) are associated with HI values < 1.0, indicating exposures that are below levels of 

concern. The highest HI value, associated with the charge kit leak, was 0.29. This particular scenario 

results in a substantially higher HI value because the air volume under consideration is extremely small 

(i.e., 0.5 m3

). The air volumes associated with the other repair worker scenarios are substantially greater 

and allow for greater dispersion of the leaked material into the room. 

Table 25. Hazard Indices Associated with Vehicle Repair Scenarios, HFO-1234yf 

Scenario Predicted HFO1234yf 

Concentration (ppm) 

Health Based 

Comparison 

Value (ppm)

Hazard 

Index (HI)

Professional repair – 

complete charge loss 

566 120,000 

(mRCLcs) 

0.005 

Professional repair – hose 

leak during system drain 

and recharge 

122 115,000 

(mRCLat) 

0.001 

DIY – Scenario 1 (slow 

loss of heel from 2 cans) 

2,493 115,000 

(mRCLat) 

0.022 

DIY – Scenario 2 (leak 

while charging) 

32,800 115,000 

(mRCLat) 

0.29 
 

 

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4.5.2 Ignition Risks for HFO-1234yf for Passenger Compartment, Engine Compartment and 

Repair Worker Scenarios 

Results from the CFD modeling and vehicle testing pertaining to the potential ignition hazard of 

HFO-1234yf in the passenger compartment are shown in Table 26 below. With respect to ignition from 

a potential smoking-related ignition source, the CFD modeling indicated that maximum HFO-1234yf 

concentrations in the passenger compartment resulting from the small and medium leaks (both 

recirculation and outside air) as well as the large leak (outside air only) did not approach the LFL. These 

situations therefore do not present a potential smoking related ignition hazard. The CFD modeling did 

indicate that passenger compartment concentrations may exceed the LFL in the case of the large leak with 

the vehicle operating in recirculation mode. This suggests a potential ignition hazard if a smoking-related 

ignition source is present, as indicated in Table 26. Note however, that field test results indicated that 

HFO-1234yf concentrations in the passenger compartment do not reach the LFL, indicating a lack of 

ignition hazard. Because the Exponent field test results are derived from a more realistic situation than 

the results of the DuPont CFD modeling, the overall conclusion should be that a large leak (0.5 mm) 

while the vehicle is operating in recirculation mode will not result in a potential ignition hazard. This 

conclusion is also supported by the CFD modeling work conducted by Honeywell and Fluent with a 

smaller vehicle. In the Honeywell/Fluent simulations (conducted for the full leak duration of 600 

seconds), the peak concentration associated with the large 0.5 mm leak was well below the LFL (53,000 

ppm versus 65,000 ppm) (Honeywell, 2008). In addition, actual concentration measurements made 

during and after a simulated 0.5 mm leak in a mock-up vehicle also confirmed that the passenger 

compartment concentration of HFO-1234yf remained below the LFL (Honeywell, 2008).

With respect to ignition from a short from an internal battery, the DuPont CFD modeling results 

show that in the event of a large leak, concentrations of HFO-1234yf at the floor of the passenger cabin 

do not exceed the LFL. This is confirmed by the results of the Exponent vehicle testing (Table 26). As 

with the smoking-related ignition source scenario, the Exponent vehicle test measurements of HFO1234yf concentrations were substantially lower than concentrations estimated by CFD modeling. 

CFD modeling was not conducted to evaluate the risks of a short from a PTC heater located in the 

AC duct system. Vehicle testing for this scenario indicated that HFO-1234yf concentrations would not 

exceed the LFL (Table 26). Thus, this scenario also does not present an ignition risk. 
 

 

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 Neither the DuPont CFD modeling nor the Exponent field measurements addressed the vehicle 

collision scenario. Results from the DuPont CFD modeling of the large leak suggest that, in the event of 

a collision and complete rupture of the evaporator tubing, the HFO-1234yf concentration in the passenger 

compartment would likely exceed the LFL. It is not clear how the results of vehicle testing can contribute 

to this speculation. Lacking specific data to address the collision scenario, we will assume the LFL is 

exceeded and will include this scenario in the FTA.9

Table 26. Ignition Risk Associated with Passenger Compartment Scenarios, HFO-1234yf 

Scenario Maximum 

Concentration 

(ppm)

LFL 

(ppm)

Ratio: 

Concentration 

to LFL 

Conclusion 

Passenger Compartment Smoking Scenario (CFD Modeling) 

Large leak, recirc mode (Sim 1) 65,000 65,000 1.0 Possible ignition risk* 

Medium leak, recirc mode (Sim 2) <65,000† 65,000 <1.0 No ignition risk 

Small leak, recirc mode (Sim 3) <65,000† 65,000 <1.0 No ignition risk 

Large leak, outside air (Sim 4) 34,000 65,000 0.52 No ignition risk 

Medium leak, outside air (Sim 5) <34,000† 65,000 <0.52 No ignition risk 

Small leak, outside air (Sim 6) <34,000† 65,000 <0.52 No ignition risk 

Passenger Compartment Internal Batter Scenario (CFD Modeling) 

Concentration on vehicle floor 56,500 65,000 0.87 No ignition risk 

Passenger Compartment Scenarios (Vehicle Test) 

Driver’s Breathing area 29,000 65,000 0.45 No ignition risk

Driver’s side floor 27,500 65,000 0.42 No ignition risk

Duct Location 29,500 65,000 0.45 No ignition risk

Passenger Compartment Collision Scenario 

(Data imputed from CFD results for large leak during recirculation mode)

Collision >65,000 65,000 >1 Potential ignition risk 

* Possible ignition risk from CFD modeling is countered by results of vehicle test. 

† The maximum concentration was not determined because the leak duration is greater than the time frame addressed by 

CFD modeling. However, the leak rate in the small and medium leaks is lower than that in the large leak case and thus 

more affected by cabin leakage to the exterior air. Thus, the maximum concentration in the event of small and 

medium leaks must be less than that observed with the corresponding large leaks. 

Results from the CFD modeling and vehicle testing pertaining to the potential ignition hazard of 

HFO-1234yf in the engine compartment are shown in Table 27 below. The results of the vehicle test 

indicate that while the LFL was exceeded in one location (near the exhaust manifold), the investigators 

were unable to ignite the material. Thus, the conclusion for this scenario is that a very large leak such as 

that simulated would not result in a potential engine compartment ignition hazard. 

 

9

 Note that CFD modeling and mock-up measurements by Honeywell for the smaller size vehicle (Honeywell, 2008) indicate 

that a very large leak such as might occur in a collision could produce concentrations above the LFL. However, Honeywell also 

found that it was not possible to ignite the HFO-1234yf in such cases using either a butane lighter or an electrical arc welder. 

Thus, the decision of the CRP1234 team to retain the collision scenario in the fault tree analysis is conservative. 
 

 

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Table 27. Ignition Risk Associated with Passenger Compartment Scenarios, HFO-1234yf 

Scenario Maximum 

Concentration 

(ppm)

LFL 

(ppm)

Ratio: 

Concentration 

to LFL 

Conclusion 

Engine Compartment AR Ignition Scenario (Vehicle Test) 

Engine compartment 87,000 65,000 1. 3 Failed to ignite, no 

ignition risk 

 

 Results from the CFD modeling and vehicle testing pertaining to the potential ignition hazard of 

HFO-1234yf in vehicle repair areas are shown in Table 28 below. None of the modeled HFO-1234yf 

concentrations in the repair areas approached the LFL. In most instances, the concentrations were 

extremely low. Only in the charge kit leak scenario was the modeled peak air concentration a sizeable 

fraction of the LFL (i.e., 60%). Recall that this scenario conservatively assumed the refrigerant was 

released and remains over the course of release (10 minutes) in a 0.5 m3 volume around the engine 

compartment. 

Table 28. Ignition Risk Associated with Repair Scenarios, HFO-1234yf 

Scenario Maximum 

Concentration 

(ppm)

LFL 

(ppm)

Ratio: 

Concentration 

to LFL 

Conclusion 

Repair Scenarios (Modeling) 

Professional repair – 

complete charge loss 

590 65,000 0.009 No ignition risk 

Professional repair – 

hose leak during system 

drain and recharge 

146 65,000 0.002 No ignition risk 

DIY – Scenario 1 (slow 

loss of heel from 2 cans) 

2,670 65,000 0.04 No ignition risk 

DIY – Scenario 2 (leak 

while charging) 

38,900 65,000 0.60 No ignition risk 

 

4.5.3 Ecological Risks 

 Honeywell has completed a set of ecological aquatic toxicity tests for HFO-1234yf. All test 

results appear to be at levels which would preclude a designation of "very toxic", "toxic" or "harmful" to 

aquatic organisms under the EU Directive. Although results for the Daphnia and algal tests, expressed as 

"greater than" values, are not clearly above the threshold of 100 mg/L (for designation as "harmful to 

aquatic organisms") the testing laboratory laboratory's opinion, in which we concur, is that because no 

effects at all were observed at the maximum tested concentrations, the EC50s must be above the 100 

mg/L criterion. A comparison of toxicity values is provided in Table 29. 
 

 

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Table 29. Ecological Toxicity Data for Selected Chemicals Compared to HFO-1234yf 

Chemical Usage EC50 algal 

growth 

inhibition in 96-

hr test (mg/L) 

EC50 

Daphnia in 

48-hr test 

(mg/L) 

LC50 fish 

in 96-hr test 

(mg/L) 

Source 

1234yf Potential AR >75 >83 >197 (carp) Honeywell 

Comparison Chemicals 

Benzene Gasoline 

component 

> 1,360 356-390 5.3 (salmon) ESIS 

Toluene Gasoline 

component 

>433 11.5L 26 (minnow) 

24 (trout) 

ESIS 

Xylenes Gasoline 

component 

10* no data 26.7 (minnow) 

>780 (carp) 

ESIS 

Pentane Gasoline 

component 

no data 9.74 no data ESIS 

Gasoline Fuel 4,700 (72-hr test) no data no data ESIS 

Ethylene glycol Antifreeze 

component 

6,500-7,500 >10,000 17,800 (trout) ESIS 

Triethylene 

glycol 

monobutyl ether 

Brake fluid 

component 

>500** 1740 -2,802 2,400 (minnow) ESIS 

Chlorine Disinfectant 

gas 

no data 0.017-0.085 0.08 (minnow) 

0.014 (trout) 

ESIS 

Chloroform Water 

disinfection 

by-product 

950** 66-90 18 (trout) 

71 (minnow) 

ESIS 

Malathion Pesticide 4.06 (72-hr test) 0.0009 0.04 (minnow) ESIS 

2,4-D Herbicide 33.2 417 (72 hr 

test) 

128-217 

(silverside) 

ESIS 

R-134a Current 

automotive 

refrigerant 

no data 980 450 (trout) DuPont 

ESIS – European Chemical Substances Information System, http://ecb.jrc.it/esis 

Unless otherwise noted, algal tests were conducted with Selenastrum capricornutum. Where more than one test result 

was available in the ESIS database, the most representative number was chosen. 

* Test conducted with Cricosphaera carterae

** Test conducted with Scenedesmus subspicatus 

4.5.4 Potential Risks to Other Receptors 

 As indicated in Section 2.5.3, risks for automotive assembly workers are anticipated to be 

insignificant. Data from GM indicate that R-134a levels measured in assembly plants were consistently 

below 10 ppm (i.e., 100 times less than the Occupational Exposure Limit of 1,000 ppm). Although there 

is some uncertainty in extrapolating results for R-134a to HFO-1234yf, it would be reasonable to expect 

that HFO-1234yf levels would be generally similar to levels of R-134a. The no effect level for HFO1234yf, based on the 90-day animal studies of the components is 38,500 ppm. This concentration is 
 

 

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almost 4,000 times higher than the R-134a concentration measured in the GM assembly plants, which 

provides a sufficient margin of safety for assembly workers. 

4.5.5 Degradation Products 

 Although fluorocarbons such as the components of refrigerants are generally perceived to be 

chemically stable, under extreme conditions, such as a fire, they may decompose. For example, the 

decomposition temperature of R-134a is reported to be greater than 340oC (>700oF), a temperature which 

may be reached in a vehicle fire but not under normal operating conditions. The products of the 

decomposition of hydrofluorocarbons include hydrogen fluoride (HF), carbon dioxide (CO2), carbon 

monoxide (CO), and carbonyl fluoride (COF2). The toxicity of HF and COF2 is of an irritant or caustic 

nature as these gases are highly reactive and water soluble. The respiratory tract and mucous membranes 

will be the primary organ systems affected. The irritancy properties of HF is a means to warn occupants 

to evacuate the area if HF is formed or released at detection levels similar to its exposure limits. The air 

odor threshold for hydrogen fluoride is 0.04 ppm (OSHA, 2008) and if levels substantially above the odor 

threshold are present, the car occupant would likely seek outside air circulation or open windows, 

providing mitigation measures. Acute exposure limits for HF and COF2 are summarized in Table 30. 

Table 30. Acute Exposure Limits for Fluorocarbon Decomposition Products 

Chemical Exposure 

Limit 

(ppm) 

Basis 

Hydrogen Fluoride (HF) 1 AEGL1 – a level without adverse effect. Value for 10 minutes to 8 

hours of exposure. U.S. EPA acute exposure guideline. 

Carbonyl Fluoride 

(COF2) 

5 TEEL1 – a level expected to produce only mild or transient health 

effects. NOAA guideline 

 Decomposition of HFO-1234yf in a fire scenario might, in theory, pose a significant acute health 

risk to passengers or firemen. But in the event of a fire, other toxic chemicals will be produced by 

combustion of other automotive components and thus decomposition of the refrigerant may increase the 

risk for fire fighters and would not introduce an entirely new type of hazard. It is also anticipated that 

only a small portion of the refrigerant charge will be converted to these decomposition products. In U.S. 

EPA's assessment of risk of R-152a and CO2 (R-744), the agency cited a study by Southwestern 

Laboratories which indicated that a 100% R-134a atmosphere only produced an HF concentration of 10 

ppm when passed through a tube heated to 1,000 oF (Blackwell et al., 2006). A search of the medical 

literature also did not reveal any published reports of injuries to fire fighters or vehicle passengers 

resulting from exposures to COF2 or HF produced in fires involving refrigerants. 
 

 

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 With respect to risk of HF, use of HFO-1234yf would not be expected to create a significantly 

greater risk than that which exists with refrigerants such as R-12 or R-134a. HFO-1234yf contains four 

moles of fluorine per mole of chemical, the same value as R-134a. However, when one accounts for the 

molecular weights of R-134a (102 grams per mole) and HFO-1234yf (114 grams per mole), the amount 

of HF that could be produced by complete decomposition of 1 kilogram of material is less for HFO1234yf (702 grams per kilogram) relative to R-134a (784 grams per kilogram).10 As noted above, the 

Southwestern Laboratories study of R-134 decomposition suggests the actual amount of HF produced by 

decomposition of HFO-1234yf in a fire would be substantially less than this theoretical estimate. 

4.6 FTA 

4.6.1 Toxicity FTAs 

 Fault trees related to the toxicity of HFO-1234yf are shown in Figures 8 through 13. As indicated 

in these figures, for the small, medium and large leak situations, concentrations of HFO-1234yf in the 

passenger compartment are not predicted to exceed health-based limits. The FTA risks associated with 

these fault tree branches are therefore zero. With respect to the vehicle collision scenario, air modeling 

data are not available to evaluate the potential risks with certainty. However, the HI for the large leak 

(0.5 mm) scenario (recirculation mode) was <0.56 and the earlier R-12 scenario suggests that with the 

larger leak size contemplated by the collision scenario (i.e., 1.45 or 2.3 mm), HFO-1234yf concentrations 

in the passenger cabin could possibly exceed health-based limits. The risks associated with this fault tree 

branch were therefore retained in the FTA. HI values for vehicle repair scenarios never exceeded 1.0 and 

therefore the contribution of the repair fault tree to overall risk is zero. The final estimated risks from the 

FTA are 0.02 per year, in both the U.S. and Europe. These risks are entirely due to the collision scenario. 

Note that this risk level is several orders of magnitude less than the equivalent risks estimated for R-12 

(11 exposures of concern per year). 

4.6.2 Flammability FTAs 

 Fault trees related to the potential flammability of HFO-1234yf are shown in Figures 14 through 

21. As indicated in these figures, the probability of reaching the LFL and having a potential ignition 

 

10 A similar analysis can be conducted for R-12, which consists of two moles of fluorine and two moles of chlorine per mole of 

R-12. Complete decomposition of R-12 would produce 332 grams of HF and also 606 grams of HCl. 
 

 

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situation is zero for small and medium HFO-1234yf leaks into the vehicle compartment and all leaks 

involving worker repair areas. As noted above, neither large leak scenario involving the passenger 

compartment (i.e., vehicle in recirculation or outside air mode) is expected to result in a potential ignition 

hazard based on the results of the field testing. With respect to the engine compartment, while field 

measurements did indicate the LFL was exceeded in one test/measurement location, it did not prove 

possible to ignite the material after an engine compartment release. This also suggests that the possibility 

of ignition in the engine compartment is negligible. Thus, as shown in the fault trees, the only scenario 

which contributes to a potential ignition risk is the vehicle collision scenario. Including this scenario in 

the analysis results in a very small risk of ignition, 0.004 per year, which translates into once per 250 

years. 

4.6.3 Comparative Risks 

 The risk of exposure to HFO-1234yf above human health-based criteria is estimated in the FTA 

to be 0.02 per year and the risk of HFO-1234yf ignition is estimated to be 0.004 per year. Both values are 

solely attributable to the collision scenario, the only scenario for which neither modeling nor field 

measurement has been conducted. Because the values represent different types of outcome, they should 

not be added but considered individually. An event frequency of 0.02 per year is equivalent to one 

occurrence every 50 years whereas an event frequency of 0.004 per year is equivalent to one occurrence 

every 250 years. These event frequencies compare very favorably to the risks estimated for R-12, which 

were 11 exposures above the human health-based criterion per year. 

To place these estimated risks in better perspective, they can be compared to annual risks of other 

adverse outcomes. If the risk estimates for HFO-1234yf derived from the FTA are divided by the number 

of drivers currently registered in the U.S. (200 million) the annual risk per driver of an exposure above 

the mRCL would be 1 x 10-10 and the risk of an HFO-1234yf release leading to an ignition event and an 

injury would be 2 x 10-11. Similar values can be derived based on European statistics. As shown in 

Table 31, these risks are far below those associated with other commonly encountered and accepted risks 

and are in fact smaller than risks of events that are considered extremely unlikely. 
 

 

G:\Projects\206703\1234yf\Deliverable\Risk Assessment_final.doc 70 Gradient CORPORATION

Table 31. Risks of Injury or Fatality from Various Events Compared to Risks 

Associated with Leaks of HFO-1234yf 

Risk Risk per 

individual per 

year 

Citation 

Risk of stroke 2.7 x 10-3 Rhys Williams, 2001 

Fatal accident in the home 1.1x 10-4 Wilson and Crouch, 1987 

Serious injury while using a chainsaw# 2.2 x 10-4 CDC, 2004#

Fatal accident while climbing mountains (if mountaineer) 6 x 10-4 Wilson and Crouch, 1987 

Risk of being injured as a pedestrian 2.1 x 10-5 NSC, 2004 

Fatal injury at work (all occupations) 3.6 x 10-5 NSC, 2004 

Injury during use of fireworks 3.6 x 10-5 Hall, 2007§

Risk of catastrophic asteroid impact with the earth 1 x 10-6 Chapman and Morrison, 1994* 

Injury from lightning strike 1 x 10-6 NWS, undated** 

Risk of dying during a 5000-mile plane trip 3x10-6 Wilson and Crouch, 1987 

Fatal electrocution 5.3 x 10-6 Wilson and Crouch, 1987 

Risk of being fatally injured in an elevator ride 2x10-7 McCann and Zalesky, 2006 

Risk of being struck by airplane while on the ground 6 x 10-8 Goldstein et al., 1992 

Risk of exposure to HFO-1234yf above health based 

limits resulting from a collision 

1 x 10-10 Current analysis&

Risk of being injured by an HFO-1234yf ignition 

resulting from a collision 

2 x 10-11 Current analysis&

*Risk cited is 1 in 10,000 over the next century 

# Injury sufficiently serious to require hospital visit. Based on number of injuries per year divided by U.S. adult population. 

§ Total number of injuries requiring hospital visit per year divided by the total U.S. population. 

** Total number of documented injuries from lightning strikes per year, divided by total U.S. population. & Number of FTA predicted events divided by the number of estimated drivers in the U.S.

4.7 Conclusions Regarding HFO-1234yf 

The DuPont/Honeywell AR, HFO-1234yf, offers equivalent or lower toxicity compared to R134a or R-12 in terms of both human health effects and ecological effects. The material also has an ODP 

of 0 and a GWP of 4 which meets the European Union F-gas requirements. HFO-1234yf is flammable, 

although testing conducted by DuPont and Honeywell indicates the ignition potential of this chemical is 

far less than that of other flammable refrigerants (e.g., R-152a). Nonetheless, due to the flammability of 

HFO-1234yf, the risk assessment addressed both health effects and potential ignition. Based on a review 

of toxicity data developed by the manufacturers as well as the results of air modeling to predict exposure 

concentrations, potential exposures of vehicle passengers and repair workers are expected to be below 

levels associated with health risk. In the event of a vehicle collision and refrigerant release, air 

concentrations could potentially exceed health-based limits. However, the frequency of collision related 

releases is quite small and results in a very low overall estimate of health risk. Evaporator failures are not 

found to occur in the case of frontal impact based on OEM experience. In the case of side impact, the 
 

 

G:\Projects\206703\1234yf\Deliverable\Risk Assessment_final.doc 71 Gradient CORPORATION

probability of evaporator rupture is very small and if they do fail, the passenger compartment will 

damaged such that it will no longer be sealed as a result of the same side impact. Consideration of the 

large leak data suggests that an HFO-1234yf release associated with a severe vehicle collision could result 

in passenger compartment concentrations that could pose an ignition hazard. However, the frequency of 

this event is expected to be extremely small, amounting to 0.009 events per year across the entire vehicle 

fleet in either the U.S. or Europe (equivalent to 1 such event every 111 years). 

Across the entire vehicle fleet in Europe or the U.S., use of HFO-1234yf could result in 0.02 

exposures per year above health-based limits as evaluated for the USA and European vehicle fleet, a 

value protective of human health for acute exposures. This frequency is equivalent to 1 such exposure 

every 50 years. This level of risk is several orders of magnitude less than the comparable risks estimated 

for R-12. The estimated level of health risk associated with use of HFO-1234yf as an AR is also 

substantially less than the level of risk tolerated by the general public as part of every day life and less 

than the risk inherent in many commonly accepted activities (e.g., airplane travel, riding in elevators). 

Potential ignition hazards of HFO-1234yf were evaluated through laboratory testing, CFD 

modeling, and vehicle testing. Together, these evaluations suggested an absence of potential ignition 

hazards in the event of small, medium or large leaks into the passenger cabin or repair worker areas. 

CRP1234 also evaluated potential ignition risks from leaks of HFO-1234yf in the engine compartment via

vehicle testing. The issues of collision that are discussed above also apply to the additional risks of 

flammability following a collision. The results of this study indicated that concentrations of HFO-1234yf 

could be detected in the flammable range in highly conservative vehicle conditions. However, an attempt 

to ignite HFO-1234yf after a release in the engine compartment was unsuccessful. Additional testing by 

CRP1234 to support this finding is now underway. 
 

 

G:\Projects\206703\1234yf\Deliverable\Risk Assessment_final.doc 72 Gradient CORPORATION

5 References 

American Conference of Industrial Hygienists (ACGIH). 2001. 7th Edition Documentation of the Threshold Limit 

Values for Chemical Substances. ACGIH Worldwide. Cincinnati, OH. 

American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE). 2007. ANSI/ASHRAE 

Standard 34-2007, Designation and Safety Classification of Refrigerants. American Society of Heating, 

Refrigerating, and Air-Conditioning Engineers. Atlanta, GA. 

Anticoli, M. General Motors Corporation. 2007. Personal communication regarding testing results for R-134a in 

General Motors Corporation assembly plants. August 11. 

Arthur D. Little Company. 1982. Ignition sources of LNG [liquefied natural gas] vapor clouds. Project for the Gas 

Research Institute (GRI-80/0108), January. 

Azar A, Reinhardt CF, Maxfield ME, Smith PE Jr, Mullin LS.1972. Experimental human exposures to fluorocarbon 

12 (dichlorodifluoromethane). AIHA Journal. April 

Batterman S, Jia C, Hatzivasilis G. 2007. Migration of volatile organic compounds from attached garages to 

residences: a major exposure source. Environ Res. 104(2):224-40. 

Beck, PS; Clark, DG; Tinston, DJ. 1973. The pharmacologic actions of bromochlorodifluoromethane (BCF).

Toxicol. Appl. Pharmacol. 24 (1) :20-29. 

Berends, AG; de Rooij, CG; Shin-ya, S; Thompson, RS. 1999. Biodegradation and ecotoxicity of HFCs and HCFCs. 

Arch Environ Contam Toxicol. 36(2):146-51

Blackwell, N; Bendixen, L; Birgfeld, E. 2006. Risk Analysis for Alternative Refrigerant in Motor Vehicle Air 

Conditioning. September. 

Brock WJ, Shin-Ya S, Rusch GM, Hardy CJ, Trochimowicz HJ. 1999. Inhalation toxicity and genotoxicity of 

hydrochlorofluorocarbon (HCFC)-225ca and HCFC-225cb. J Appl Toxicol. 19(2):101-12. 

Brock, WJ; Rusch, GM; Trochimowicz, HJ. 2003. Cardiac sensitization: methodology and interpretation in risk 

assessment. Reg. Tox. Pharmacol. 38:78-90. 

Carley, L. 2004. Automatic Climate Control. Counterman. March 01, 2004. Available at: 

www.aftermarketnews.com/default.aspx?type=wm&module=4&id=3&state=DisplayFullText&item=5368 

Centers for Disease Control (CDC). 2004. Preventing Chain Saw Injuries During Tree Removal After a Disaster. 

Available at: http://www.bt.cdc.gov/disasters/chainsaws.asp 

Centers for Disease Control (CDC). 2004. Cigarette smoking among adults – United States, 2004. MMWR Weekly. 

54(44):1121-1124. Available at: http://www.cdc.gov/MMWR/preview/mmwrhtml/mm5444a2.htm 

Chapman, C.R. and Morrison, D., 1994. Impacts on the Earth by asteroids and comets: assessing the hazard, Nature, 

v. 367, p. 33-40. 

Chengelis, C.P., (1993). Acute cardiac sensitization study in dogs with FM-200 by inhalation. WIL Research 

Laboratories, unpublished data. Cited in Brock et al., 2003. 

Chengelis, C.P. 1997. Epinephrine sensitivity of the canine heart: A useful test. In R. Snyder, K.S. Bakshi, and B. 

M. Wagner, Abstracts of the Workshop on Toxicity of Alternatives to 34 Chlorofluorocarbons. Inhalat. Toxicol. 

9:775-810. 

Dekant, W. 1996. Toxicology of chlorofluorocarbon replacements. Env. Health Perspect. 104(Suppl. 1): 75-83. 

DuPont. 2008. CFD modeling of a large car. DRAFT. January 25. 

DuPont/Honeywell. 1234yf: A Low GWP Refrigerant For MAC. [Meeting Presentation]. September 28, 2007 

European Fluorocarbon Technical Committee. 2007. F-Gas Regulation. Obtained online at: 

http://www.fluorocarbons.org/en/debate/regulatory_developments/f_gas_regulation.html. 
 

 

G:\Projects\206703\1234yf\Deliverable\Risk Assessment_final.doc 73 Gradient CORPORATION

Exponent Inc. 2008. HFO-1234yf Refrigerant Concentrations and Ignition Tests in Full-Scale Vehicle Passenger 

Cabin and Engine Compartment. February 

Goldstein BD, Demak M, Northridge M, Wartenberg D. 1992. Risk to groundlings of death due to airplane 

accidents: a risk communication tool. Risk Anal. 12(3):339-41. 

Gradient Corporation. 2008. Risk Assessment For Alternative Refrigerants. Prepared for the Society of 

Automotive Engineers (SAE) Cooperative Research Project 150. Confidential. February. 

Hall, JR. 2007. Fireworks. Fire Analysis and Research Division, National Fire Protection Association, Quincy MA. 

Available at: http://www.nfpa.org/assets/files/pdf/os.fireworks.pdf 

Hamner Institutes for Health Sciences. 2006. Toxicogenomic assessment of the carcinogenic potential of 2,3,3,3-

tetrafluoropropene. Final Report. MA-RR-07-3454 

Hardy CJ, Kieran PC, and Sharman IJ. 1994. Assessment of the cardiac sensitization potential (CSP) of a range of 

halogenated alkanes. Toxicologist. 14:378 

Honeywell International. 2008. Evaluation of Leak Rates, CFD Modeling of a Typical European Size Vehicle, and 

Flammability Testing in a Passenger Compartment Mock-up and on Hot Surfaces. February. 

Huntingdon Life Sciences. 2004. Final Report. Study No. 03-5471. Trans HFO-1234: An Acute (4-hour) Inhalation 

Range finding study in the mouse via whole-body exposure. 

Huntingdon Life Sciences. 2004. Trans HFO-1234: an acute (4-hour) inhalation toxicity screening study with a 

micronucleus assay in the mouse and rat via nose-only exposure. MA-RR-04-2768.

ICF Consulting. FaultrEASETM software. www.icfi.com. 

Intergovernmental Panel on Climate Change (IPCC). 2005. Special Report on Safeguarding the Ozone Layer and 

the Global Climate System: Issues Related to Hydrofluorocarbons and Perfluorocarbons. Special Report of the 

Intergovernmental Panel on Climate Change. Bert Metz, Lambert Kuijpers, Susan Solomon, Stephen O. Andersen, 

Ogunlade Davidson, José Pons, David de Jager, Tahl Kestin, Martin Manning, and Leo Meyer (Eds.). Cambridge 

University Press, UK. pp 478. Obtained online at: http://arch.rivm.nl/env/int/ipcc/docs/full-reports/SROCFullVolumev2.pdf 

International Standards Organization (ISO). 2007. Refrigerants – Designation and safety classification. Committee 

Draft. International Organization for Standardization. ISO/CD 817:2007. 

International Uniform Chemical Information Database (IUCLID). 2007. Database file for hexafluoropropene. 

Jetter JJ, Forte R Jr, Rubenstein R. 2001. Fault tree analysis for exposure to refrigerants used for automotive air 

conditioning in the United States. Risk Anal. 21(1):157-70 

Kozakiewicz, A. 2007. Update on Legal Situation on Greenhouse Gas Emissions of MACs. European Commission 

presentation at VDA Alternative Refrigerant Winter Meeting. Saalfelden. February 14. 

Krahn DF, Barsky FC, McCooey KT. 1980. CHO/HGPRT Mutation Assay: Evaluation of Gases and Volatile 

Liquids. Pp. 91-103 in Genotoxic Effects of Airborne Agents, R.R. Tice, D.L. Costa, and K.M. Schaich, eds. New 

York: Plenum Press. 

Leuschner F, Neumann W, Hübscher F. 1983. Report on subacute toxicological studies with several fluorocarbons 

in rats and dogs by inhalation. Arzneimittelforschung. 33(10):1475-6 

Longstaff E, Robinson M, Bradbrook C, Styles JA, Purchase IF. 1984. Genotoxicity and carcinogenicity of 

fluorocarbons: assessment by short-term in vitro tests and chronic exposure in rats. Toxicol Appl Pharmacol. 

72(1):15-31. 

Longstaff E.1988. Carcinogenic and mutagenic potential of several fluorocarbons. Ann N Y Acad Sci. 1988;534:283-

98. 

Malley LA, Frame SR, Elliott GS, Bentley KS, Brock WJ, Trochimowicz HJ, Rusch GM. 1998. Chronic toxicity, 

oncogenicity, and mutagenicity studies with chlorotetrafluoroethane (HCFC-124). Drug Chem Toxicol. 21(4):417-

47. 

Maltoni C, Lefemine G, Tovoli D, Perino G. 1988. Long-term carcinogenicity bioassays on three 

chlorofluorocarbons (trichlorofluoromethane, FC11; dichlorodifluoromethane, FC12; chlorodifluoromethane, FC22) 

administered by inhalation to Sprague-Dawley rats and Swiss mice. Ann N Y Acad Sci. 534:261-82. 
 

 

G:\Projects\206703\1234yf\Deliverable\Risk Assessment_final.doc 74 Gradient CORPORATION

Millischer RJ, de Rooij CG, Rush GM, Farr CH, Ben-Dyke R, Hardy CJ, Lewis DJ, Hodson-Walker G. 1995. 

Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC141b). Food Chem Toxicol. 33(6):491-500. 

Mobile Air Conditioning Society (MACS). 2003. Presentations at Worldwide convention. Jan. 30 to Feb. 1. New 

Orleans, LA. 

McCann, M., Zalesky, N. 2006. Deaths and Injuries Involving Elevators and Escalators. The Center to Protect 

Workers’ Rights, Silver Spring, MD. http://www.cpwr.com/pdfs/pubs/research_pubs/elevatorconstructors2006.pdf 

Mullin, LS; Azar, A; Reinhardt, CF; Smith, PE; Fabryka, EF. 1972. Halogenated hydrocarbon-induced cardiac 

arrhythmias associated with release of endogenous epinephrine. Am. Ind. Hyg. Assoc. J. 33 (6) :389-396. 

National Institute for Occupational Safety and Health (NIOSH) [U.S.A.] 2002. International Chemical Safety Cards. 

Dichlorodifluoromethane. ICSC: 0048. http://www.cdc.gov/niosh/ipcsneng/neng0048.html 

National Research Council (NRC). 1984. Emergency and continuous exposure limits for selected airborne 

contaminants. Vol. 2. National Academy Press. Washington, DC. 

National Research Council (NRC) [U.S.A.]. 1996. Toxicity of Alternatives to Chlorofluorocarbons: HFC-134a and 

HCFC-123. Commission on Life Sciences (CLS). The National Academies Press. Washington, D.C. 

National Research Council (NRC) [U.S.A.]. 2000. Spacecraft Maximum Allowable Concentrations for Selected 

Airborne Contaminants: Volume 4. Commission on Life Sciences (CLS). Obtained online at: 

http://books.nap.edu/openbook.php?record_id=9786&page=R1 

National Safety Council (NSC) [U.S.A]. 2004. Website. www.nsc.org. Accessed on December 23, 2007.

National Weather Service [U.S.A.] undated. Thunderstorms, Tornadoes, Lightning, Natures most violent storms. 

www.nws.noaa.gov/os/brochures/ttl.pdf 

Nielsen, OJ; Javadi, MS; Sulbaek Andersen, MP; Hurley, MD; Wallington, TJ; Singh, R. 2007. Atmospheric 

chemistry of CF3CF@CH2: Kinetics and mechanisms of gas-phase reactions with Cl atoms, OH radicals, and O3. 

Chemical Physics Letters 439: 18–22 

Nuckolls, A.H. 1933. Underwriter's Laboratories' Report on the Comparative Life, Fire, and Explosion Hazards of 

Common Refrigerants. Miscellaneous Hazard No. 2375. Underwriter's Laboratories. Chicago, IL. 

Occupational Safety and Health Administration (OSHA). 2008. Occupational Safety and Health Guideline for 

Hydrogen Fluoride. http://www.osha.gov/SLTC/healthguidelines/hydrogenfluoride/recognition.html. Accessed 

2/8/2008. 

Perrin Quarles Associates. 2007. Disposable Container Heel Testing Study Report. Prepared for U.S. EPA, 

Stratospheric Protection Division. March 21, 2007. 38 p. 

Prendergast JA, Jones RA, Jenkins LJ, Siegel J. 1967. Effects on experimental animals of long-term inhalation of 

trichloroethylene, carbon tetrachloride, 1,1,1-trichloroethane, dichlorodifluoromethane, and 1,1-dichloroethylene. 

Toxicol. Appl. Pharmacol. 10:270–289 

Reinhardt, CF; Azar, A; Maxfield, ME; Smith, PE; Mullin, LS. 1971. Cardiac arrhythmias and aerosol sniffing. 

Arch. Environ. Health. 22:265-279. 

Rhys Williams, G. 2001. Incidence and Characteristics of Total Stroke in the United States. BMC Neurol. 2001; 1: 

2.. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=32314 

Ritchie et al. 2001. Acute neurobehavioral effects in rats from exposure to HFC 134a or CFC 12. NeuroToxicology. 

22:233-248. 

Scholz J. 1962. New toxicologic investigations of freons used as propellants for aerosols and sprays. Translation of: 

Fortschr. Biol. Aerosol-Forsch. Jahren 1957–1961, Ber. Aerosol-Kongr. 4:420–429 

Silber, L.S., and G.L. Kennedy. 1979. Acute Inhalation Toxicity of Tetrafluoroethane. Rep. No. 422-79. Haskell 

Laboratory , Wilmington, Del. (as cited in NRC, 1996) 

Stewart RD, Newton PE, Baretta ED, Herrmann AA, Forster HV, Soto RJ. 1978. Physiological response to aerosol 

propellants. Environ Health Perspect. 26:275-85. 

TNO. 2005a. Sub-acute (2-week) inhalation toxicity study with HFO-1234yf in rats. Study code 6394. November 4. 
 

 

G:\Projects\206703\1234yf\Deliverable\Risk Assessment_final.doc 75 Gradient CORPORATION

TNO. 2005b. Chromosomal aberration test with HFO-1234yf in cultured human lymphocytes. Study code 6202/07. 

November 8. 

TNO. 2005c. Bacterial reverse mutation test with HFO-1234yf. Study code 6205/09. November 15. 

TNO. 2005d. .Micronucleus test in bone marrow cells of mice treated with HFO-1234yf, administered by inhalation. 

Study code 6204/03. November 23. 

TNO. 2006a. Acute (4-hour) inhalation toxicity study with HFO-1234yf in rats. Study code 6201/06. January 17. 

TNO. 2006b. Preliminary experiment for development of a method for optimal maintenance of test concentration in 

aqueous media as used in aquatic toxicity tests with HFO-1234yf. Study code 6472/01. May 5. 

TNO. 2006c. Acute toxicity study in Daphnia magna with HFO-1234yf. Study code 6472/03. May 8. 

TNO. 2006d. Freshwater algal growth inhibition test with HFO-1234yf. Study code 6472/02. May 8. 

TNO. 2006e. 96-hour acute toxicity study in carp with HFO-1234yf (static). Study code 6472/04. June 15. 

TNO. 2006f. Sub-acute (4-week) inhalation toxicity study (including Unscheduled DNA Synthesis and 

Micronucleus test) with 2-week recovery period, with HFO-1234yf in rats. Study code 6872/02. September 5. 

TNO. 2007a. Prenatal developmental inhalation toxicity study with HFO-1234yf in rats. Study code 6986. April 17. 

TNO. 2007b. Sub-chronic (13-week) inhalation toxicity study with HFO-1234yf in rats. Study code 6872/01. May 

11. 

Trochimowicz, HJ. 1993. Industrial research on alternative fluorocarbons. Toxicology Letters. 68:25-30. 

Trochimowicz HJ, Azar A, Terrill JB, Mullin LS. 1974. Blood levels of fluorocarbon related to cardiac 

sensitization: II. Am Ind Hyg Assoc J. 35(10):632-9. 

Trochimowicz HJ, Reinhardt CF. 1975. Studies clarify potential toxicity of aerosol propellants. DuPont Innovation

6(3):12-16 

Trochimowicz, HJ; Reinhardt, CF; Mullin, LS; Azar, A; Karrh, BW. 1976. The effect of myocardial infarction on 

the cardiac sensitization potential of certain halocarbons. J. Occup. Med. 18(1): 26-30. 

Trochimowicz, HJ; Rusch, GM; Chiu, T; Wood, CK. 1988. Chronic inhalation toxicity/carcinogenicity study in rats 

exposed to Fluorocarbon 113 (FC-113). Fundam. Appl. Toxicol. 11:68-75. 

Tsai, WT. 2005. An overview of environmental hazards and exposure risk of hydrofluorocarbons (HFCs). 

Chemosphere. 61: 1539-47. 

United States Environmental Protection Agency (U.S. EPA). 1987. Integrated Risk Information System (IRIS) file: 

Dichlorodifluoromethane. www.epa.gov/iris/subst/0040.htm. Accessed 1/10/08. 

United States Environmental Protection Agency (U.S. EPA). 2002. A guide to selected algorithms, distributions, 

and databases used in exposure models developed by the office of air quality planning and standards. Office of 

Research and Development. Prepared by Ted Johnson, TRJ Environmental, Inc. EPA Grant No. CR827033. 

Obtained online at: http://www.epa.gov/ttn/fera/data/human/report052202.pdf. 

United States Environmental Protection Agency (U.S. EPA). 2007. Ozone Depletion. Obtained online at: 

www.epa.gov/ozone/strathome.html 

World Health Organization (WHO). 1978. Toxicological evaluation of some food colours, thickening agents, and 

certain other substances. Who Food Additives Series No. 8. World Health Organization, Geneva 

WIL Research Laboratories, LLC. 2006. Acute cardiac sensitization study of <redacted name> and HFO-1234yf in 

dogs. WIL study number-447008. Final Report. 

Wilson R, Crouch EA. 1987. Risk assessment and comparisons: an introduction. Science. 236(4799):267-70. 
FIGURES 
Figure 1. Example Fault Tree 

Sufficient oxygen 

present to support 

combustion

0.90

Concentration of 

flammable material 

sufficient

0.1

Conditions favorable to a 

fire

0.09

Open flame 

present

0.001

Ignition Source 

0.031

Combustion Event

0.0028

&

&

OR

Lighted 

cigarette 

present

0.01
Figure 2. R-12 Fault Tree – Summary 

Exposure due to small leak

0 /yr 

Exposure due to leak caused 

by collision

7.5 x 10-11 /yr 

Total number of passenger exposures 

to refrigerant concentration exceeding 

exposure limits (per vehicle and year) 

4.5 x 10-8 /yr 

Exposure due to medium leak

0 /yr 

Exposure due to large leak

4.5 x 10-8 /yr 

Number of vehicles in U.S. 

and Europe 

230 million (U.S.) 

241 million (Europe) 

Number of exposures to 

refrigerant concentration 

exceeding exposure limit 

11 /yr (U.S.) 

11 /yr (Europe) 

Number of exposures of 

technicians/DIYer

0 /yr (U.S.) 

0 /yr (Europe) 

OR 

& 

Number of vehicles 

U.S. and Europe 

230 million (U.S.) 

241 million (Europ

Exposure above limit 

during vehicle service 

(per serviced vehicle) 

0 /yr

& 

A B C D

E 
Figure 3. R-12 Fault Tree – Small Leak Scenario 

Exposure due to sudden 

small leak 

3.26 x 10-9 /h 

Doors and windows 

closed 

0.95 

Exposure to refrigerant concentration 

exceeding exposure limit due to 

medium leak 

0 /yr 

Size of leak is small 

(0.01 mm) 

0.05 

Sudden leak in 

passenger compartment 

(400 ppm/yr / 8,760 h/yr) 

4.6 x 10-8 /h 

Leakage is not detected 

by passenger 

0.80 

& 

Number of occupants 

per vehicle 

1.59 

Additional exposures due 

to inadequate repair in 

service (plus 50%) 

1.5 

Air control in 

outside air mode 

0.68 

& 

Probability of exceeding 

exposure limits in 

recirculation mode 

0 

P

Probability of exceeding 

exposure limits 

0 

OR 

A

Air control in 

recirculation mode 

0.32 

Refrigerant concentration in passenger 

compartment exceeds exposure limit 

for small leak recirculation mode 

0 (CFD Sim 1) 

& 

Note: Simulation numbers refer to CFD modeling conducted for CRP150 and not the current CRP1234 risk assessment. 
Figure 4. R-12 Fault Tree – Medium Leak Scenario 

Exposure due to sudden 

medium leak 

6.5 x 10-10 /h 

Doors and windows 

closed 

0.95 

Exposure to refrigerant concentration 

exceeding exposure limit due to 

medium leak 

0 /yr 

Size of leak is medium 

(0.1 mm) 

0.01 

Sudden leak in 

passenger compartment 

(400 ppm/yr / 8,760 h/yr) 

4.6 x 10-8 /h 

Leakage is not detected 

by passenger 

0.60 

& 

Number of occupants 

per vehicle 

1.59 

Additional exposures due 

to inadequate repair in 

service (plus 50%) 

1.5 

Air control in 

outside air mode 

0.68 

Ref

com

for 

(

& 

Probability of exceeding 

exposure limits in 

recirculation mode 

0 

Proba

ex

ou

Probability of exceeding 

exposure limits 

0 

OR 

Av

B

& 

Note: Simulation numbers refer to CFD modeling conducted for CRP150 and not the current CRP1234 risk assessment. 

Air control in 

recirculation mode 

0.32 

Refrigerant concentration in passenger 

compartment exceeds exposure limit 

for medium leak recirculation mode 

0 (CFD Sim 3) 

& 
Figure 5. R-12 Fault Tree – Large Leak Scenario 

Exposure due to sudden 

large leak 

6.5 x 10-10 /h 

Doors and windows 

closed 

0.95 

Exposure to refrigerant concentration 

exceeding exposure limit due to 

large leak 

4.5 x 10-8/vehicle 

Size of leak is large 

(0.5 mm) 

0.01 

Sudden leak in 

passenger compartment 

(400 ppm/yr / 8,760 h/yr) 

4.6 x 10-8 /h 

Leakage is not detected 

by passenger 

0.40 

& 

Number of occupants 

per vehicle 

1.59 

Additional exposures due 

to inadequate repair in 

service (plus 50%) 

1.5 

Air control in 

outside air mode 

0.68 

& 

Probability of exceeding 

exposure limits in 

recirculation mode 

0.32 

P

Probability of exceeding 

exposure limits 

0.32 

OR 

C

Note: Simulation numbers refer to CFD modeling conducted for CRP150 and not the current CRP1234 risk assessment. 

Air control in 

recirculation mode 

0.32 

Refrigerant concentration in passenger 

compartment exceeds exposure limit 

for large leak recirculation mode 

1 (CFD Sim 5) 

& 
Figure 6. R-12 Fault Tree – Collision Scenario 

Leak in passenger 

compartment caused 

by collision 

5.2 x 10-6 /yr 

Exposure to refrigerant 

concentrations exceeding 

exposure limit due to collision 

7.5 x 10-11 /yr 

Occupant survives 

collision 

0.9 

Probability collision 

deforms A-pillar >6“

0.0187 

Frequency of serious 

collision 

5.6 x 10-3 /yr 

Probability evaporator 

piping fails 

0.05 

Probability collision does not 

break windows and windows 

not already open 

0.0001 

Probability collision does not 

break any other component 

in refrigerant cycle 

0.1 

Number 

& 

& 

D

Refrigerant 

compartme

in 

1 (lik

Note: Simulation numbers refer to CFD modeling conducted for CRP150 and not the current CRP1234 risk assessment. 
Figure 7. R-12 Fault Tree – Vehicle Repair Scenarios 

Air concentration is 

above health-based 

limit 

0 

Leak during 

service 

0.006 /yr 

Probability of 

inadequate 

ventilation in 

shop 

0.001 

Work is carried 

out by trained 

technician 

0.97 

Leak from vehicle 

system during 

service 

0.005 /yr 

Leak from AC 

service 

equipment 

during service 

0.001 /yr 

Trained Technician has 

exposure above limit 

0 /yr 

A

ab

Leak during service 

0.006 /yr 

Work is carried 

out by DIYer 

0.03 

Leak from 

vehicle system 

during service 

0.005 /yr 

Leak from AC 

can during 

service 

0.001 /yr 

DIYer has ex

above lim

0 /yr 

Exposure above limit 

during vehicle service 

(per serviced vehicle) 

0 /yr

& 

& 

OR 

OR 

OR 

E

Professional 

shop air 

concentration 

exceeds limit 

0 

& 
Exposure events due to small 

leak

0 /yr

Exposure events due to leak 

caused by collision

7.5 x 10-11 /yr

Total number of exposure events 

involving 1234yf (per vehicle and 

year)

7.5 x 10-11 /yr

Exposure events due to 

medium leak

0 /yr

Exposure events due to large 

leak

0 /yr

Number of vehicles in U.S. 

and Europe

230 million (U.S.)

241 million (Europe)

&

Number of veh

U.S. and Eu

230 million (

241 million (E

Number of exposure 

events associated with 

vehicle repair –

0 /serviced vehicle

&

a b c d

e

Potential exposure events 

related to 1234yf release 

associated with vehicle repair 

in Europe and U.S.

0 /yr

OR

Potential exposure events 

related to 1234yf release 

associated with vehicle use 

in Europe and U.S.

0.02 /yr (U.S.)

0.02 /yr (Europe)

Figure 8. Aggregate risk of potentially adverse exposure due to HFO-1234yf release
Exposure due to sudden 

small leak

6.16 x 10-8 /h

Doors and windows 

closed

0.95

Exposure to 1234yf concentration 

exceeding exposure limit due to 

small leak

0 /yr

Size of leak is 

small

0.94

Sudden leak in 

passenger compartment

(400 ppm/yr / 8,760 h/yr)

4.6 x 10-8 /h

Leakage is not detected 

by passenger 

0.8

“a”

Number of occupants

per vehicle

1.59

Air control in

outside air mode

0.68 (U.S.)

0.84 (Europe)

123

com

for 

&

&

Probability of exceeding

exposure limits in

recirculation mode

0

Probability of e

exposure lim

outside air 

0

Probability of exceeding

exposure limits

0

Average ti

per c

3

&

Air control in 

recirculation 

mode

0.32 (U.S.)

0.16 (Europe)

1234yf concentration in passenger 

compartment exceeds exposure limit

for small leak and recirculation mode

0

&

OR

Figure 9. Fault tree describing risk of potentially adverse exposure associated with a small HFO-1234yf leak into passenger compartment

Additional 

exposures due to 

inadequate repair in 

service 

1.5
Exposure due to sudden 

medium leak

3.3 x 10-9 /h

Doors and windows 

closed

0.95

Exposure to 1234yf concentration 

exceeding exposure limit due to 

medium leak

0 /yr

Size of leak is 

medium

0.05

Sudden leak in 

passenger compartment

(400 ppm/yr / 8,760 h/yr)

4.6 x 10-8 /h

Leakage is not detected 

by passenger 

0.6

“b”

Number of occupants

per vehicle

1.59

Air control in

outside air mode

0.68 (U.S.)

0.84 (Europe)

c

fo

&

&

Probability of exceeding

exposure limits in

recirculation mode

0

Probability o

exposure 

outside a

0

Probability of exceeding

exposure limits

0

Average 

pe

&

Air control in 

recirculation 

mode

0.32 (U.S.)

0.16 (Europe)

1234yf concentration in passenger 

compartment exceeds exposure limit

for medium leak and recirculation mode

0

&

OR

Figure 10. Fault tree describing risk of potentially adverse exposure associated with a medium HFO-1234yf leak into passenger compartment

Additional 

exposures due to 

inadequate repair in 

service 

1.5
Exposure due to sudden 

large leak

6.6 x 10-10 /h

Doors and windows 

closed

0.95

Exposure to 1234yf concentration 

exceeding exposure limit due to 

large leak

0 /yr

Size of leak is 

large

0.01

Sudden leak in 

passenger compartment

(400 ppm/yr / 8,760 h/yr)

4.6 x 10-8 /h

Leakage is not detected 

by passenger 

0.4

“c”

Number of occupants

per vehicle

1.59

Air control in

outside air mode

0.68 (U.S.)

0.84 (Europe)

c

&

&

Probability of exceeding

exposure limits in

recirculation mode

0

Probability o

exposure 

outside a

0

Probability of exceeding

exposure limits

0

Average 

pe

&

Air control in 

recirculation 

mode

0.32 (U.S.)

0.16 (Europe)

1234yf concentration in passenger 

compartment exceeds exposure limit

for large leak and recirculation mode

0

&

OR

Figure 11. Fault tree describing risk of potentially adverse exposure associated with a large HFO-1234yf leak into passenger compartment

Additional 

exposures due to 

inadequate repair in 

service 

1.5
Exposure to 1234yf 

concentration exceeding 

exposure limit due to 

collision

7.5 x 10-11 /yr

Probability collision 

deforms A-pillar >6“

0.0187

Frequency of 

serious collision

5.6 x 10-3 /yr

Probability evaporator 

piping fails

0.05

“d”

Leak in passenger 

compartment caused 

by collision

5.2 x 10-6 /yr

Occupant survives 

collision

0.9

Probability collision does not 

break windows and windows 

not already open

0.0001

Probability collision does not 

break any other component 

in refrigerant cycle

0.1

Nu

&

&

Figure 12. Fault tree describing risk of potentially adverse exposure associated with a HFO-1234yf leak due to vehicle collision
“e”

Air 

concentrations 

above LFL

0/yr

OR

Service carried out 

with inadequate 

ventilation

0.006 (U.S.)

0.002 (Europe)

Probability of 

inadequate 

ventilation

0.20

Work is carried 

out by DIYer

0.03 (U.S.)

0.01 (Europe)

&

Air concentrations 

above LFL due to 

system rupture

0/yr

Air concentrations 

above LFL due to 

equipment leak

0/yr

Shop air 

concentration 

exceeds mRCL

0

Rupture of 

vehicle system 

during service

0.005 /yr

&

Shop air 

concentration 

exceeds mRCL

0

Leak from AC 

service 

equipment 

during service

0.001 /yr

&

&

DIYer has exposure 

above mRCL

0 /yr

Exposure to 1234yf 

above limit during vehicle 

service

(per serviced vehicle)

0 /yr

OR

Wor

out 

te

0.9

0.99 

Air 

concentrations 

above mRCL

0/yr

Shop air 

concentration 

exceeds mRCL

0

Release of can 

heel contents 

during service

0.005 /yr

Release from 

charge kit while 

charging system

0.001 /yr

Air concentrations 

above mRCL due to 

heel release

0/yr

Air concentrations 

above mRCL due 

to charge kit leak

0/yr

OR

& &

&

Professional technician 

has exposure above 

mRCL

0 /yr

Figure 13. Fault tree describing risk of potentially adverse exposure associated with a HFO-1234yf leak during vehicle repair
Number of events of possible 

HFO-1234yf -associated fire 

from small leak

0 /yr

Number of events of possible 

HFO-1234yf-associated fire 

from leak caused by collision

1.5 x 10-11 /yr

Total number of events where a 1234yf 

fire injury associated with vehicle use 

is possible (per vehicle and year)

1.5 x 10-11 /yr

Number of events of possible 

HFO-1234yf -associated fire 

from medium leak

0 /yr

Number of events of possible 

HFO-1234yf -associated fire 

from large leak

0 /yr

Number of vehicles in U.S. 

and Europe

230 million (U.S.)

241 million (Europe)

&

Numb

U.S

230 

241 m

Number of events of 

possible 1234yfassociated fire, 

professional shop

0 /serviced vehicle

&

A B C D

F

Potential fire events related to 

1234yf release associated 

with vehicle repair in Europe 

and U.S.

0 /yr

Number of eve

HFO-1234yf -a

in engine co

0 /

E

OR

G

Number of events of 

possible 1234yfassociated fire, DIY 

location

0 /serviced vehicle

Potential injurious fire events 

related to 1234yf release 

associated with vehicle use 

in Europe and U.S.

0.004/yr (U.S.)

0.004/yr million (Europe)

Figure 14. Aggregate risk of fires due to HFO-1234yf release
Doors and 

windows closed

0.95

Potential injury from fire related to 

1234yf release via small leak

0 /yr

Probability 

size of leak 

is small

0.94

Frequency of 

evaporator 

leaks

4.57 x 10-8 /h

“A”

A

outs

0

0.

&

Probability 1234yf 

concentration exceeds L

in

recirculation mode

0

P

Air control 

recirculation 

0.32 (U.S

0.16 (Euro

Release due to 

sudden small leak

6.12 x 10-8 /h

Probability spark from 

internal battery will 

ignite material

0

Probability smoking-related 

ignition source 

(match/lighter) present

3.15 x 10-4

Probability sufficient ignition 

source present 

0

OR

OR

&

&

Battery spark is within 

flammable 

concentration area

0 (based on CFD)

Probability 

driver or passenger 

smokes

0.21

&

Ignition source is 

within flammable 

concentration area

0 (based on CFD)

&

Probability smoking

source will ignite 

material

0

Probability vehicle has 

internal battery

0.05

&

Number of hours 

vehicle is operated 

per year

340 hr/yr

Probability 

lighting is with 

flame source

0.5

Number of 

occupants

per vehicle

1.59

Factor to 

account for leaks 

due to improper 

repair

1.5

Probability 

vehicle has 

PTC heater

0.30

Probability PTC 

heater spark will 

ignite material

0

Probability of battery 

short

1 x 10-7

Battery short is of 

sufficient energy

1.0

Probability of PTC 

heater short

1 x 10-5

PTC heater spark is 

within flammable 

concentration area

0 (based on CFD)

PTC heater short 

is of sufficient 

energy

1.0

&

Probability PTC heater 

is powered on

0.1

Fraction of 

time spent in 

vehicle lighting 

cigarette

0.003

Figure 15. Fault tree describing risk of fire associated with a small HFO-1234yf leak into passenger compartment
Doors and 

windows closed

0.95

Potential injury from fire related to 

1234yf release via medium leak

0 /yr

Probability 

size of leak 

is medium

0.05

Frequency of 

evaporator 

leaks

4.57 x 10-8 /h

“B”

A

outs

0

0.

&

Probability 1234yf 

concentration exceeds L

in

recirculation mode

0

P

Air control 

recirculation 

0.32 (U.S

0.16 (Euro

Release due to 

sudden medium 

leak

3.26 x 10-9 /h

Probability spark from 

internal battery will 

ignite material

0

Probability smoking-related 

ignition source 

(match/lighter) present

3.15 x 10-4

Probability sufficient ignition 

source present 

0

OR

OR

&

&

Battery spark is within 

flammable 

concentration area

0 (based on CFD)

Probability 

driver or passenger 

smokes

0.21

&

Ignition source is 

within flammable 

concentration area

0 (based on CFD

&

Probability smoking

source will ignite 

material

0

Probability vehicle has 

internal battery

0.05

&

Number of hours 

vehicle is operated 

per year

340 hr/yr

Probability 

lighting is with 

flame source

0.5

Number of 

occupants

per vehicle

1.59

Factor to 

account for leaks 

due to improper 

repair

1.5

Probability 

vehicle has 

PTC heater

0.30

Probability PTC 

heater spark will 

ignite material

0

Probability of battery 

short

1 x 10-7

Battery short is of 

sufficient energy

1.0

PTC heater spark is 

within flammable 

concentration area

0 (based on CFD

&

Probability of PTC 

heater short

1 x 10-5

PTC heater short 

is of sufficient 

energy

1.0

Probability PTC heater 

is powered on

0.1

Fraction of 

time spent in 

vehicle lighting 

cigarette

0.003

Figure 16. Fault tree describing risk of fire associated with a medium HFO-1234yf leak into passenger compartment
Doors and 

windows closed

0.95

Potential injury from fire related to 

1234yf release via large leak

0 /yr

Probability 

size of leak 

is large

0.01

Frequency of 

evaporator 

leaks

4.57 x 10-8 /h

“C”

A

outs

0

0.

&

Probability 1234yf 

concentration exceeds L

in

recirculation mode

0

P

Air control 

recirculation 

0.32 (U.S

0.16 (Euro

Release due to 

sudden large leak

6.5 x 10-10 /h

Probability spark from 

internal battery will 

ignite material

0

Probability smoking-related 

ignition source 

(match/lighter) present

3.15 x 10-4

Probability sufficient ignition 

source present 

0

OR

OR

&

&

Battery spark is within 

flammable 

concentration area

0 (based on 

measurement)

Probability 

driver or passenger 

smokes

0.21

&

Fraction of 

time spent in 

vehicle lighting 

cigarette

0.003

Ignition source is 

within flammable 

concentration area

0 (based on CFD)

&

Probability smoking

source will ignite 

material

0

Probability vehicle has 

internal battery

0.05

&

Number of hours 

vehicle is operated 

per year

340 hr/yr

Probability 

lighting is with 

flame source

0.5

Number of 

occupants

per vehicle

1.59

Factor to 

account for leaks 

due to improper 

repair

1.5

Probability 

vehicle has 

PTC heater

0.30

Probability PTC 

heater spark will 

ignite material

0

Probability of battery 

short

1 x 10-7

Battery short is of 

sufficient energy

1.0

Probability of PTC 

heater short

1 x 10-5

PTC heater spark is 

within flammable 

concentration area

0 (based on 

measurement)

PTC heater short 

is of sufficient 

energy

1.0

&

Probability PTC heater 

is powered on

0.1

Figure 17. Fault tree describing risk of fire associated with a large HFO-1234yf leak into passenger compartment
Leak in passenger 

compartment 

caused by collision

5.24 x 10-6 /yr

Potential injury from fire 

related to 1234yf release in 

passenger compartment

via collision

1.5 x 10-11 /yr

Occupant 

survives 

collision

0.9

Probability collision does 

not break windows and 

windows not already open

0.0001

Probability collision does not 

break other components in 

refrigerant cycle

0.1

“D”

&

Probability collision 

produces ignition source 

with enough energy to 

ignite refrigerant

1.0

Probability collision 

deforms A-pillar >6“

0.0187

Frequency of 

serious collision

5.6 x 10-3 /yr

Probability evaporator 

piping fails and 

refrigerant is released

0.05

&

Probability 

concentration in 

passenger compartm

exceeds LFL

1.0

Surv

occupan

escape 

0

Figure 18. Fault tree describing risk of fire associated with a HFO-1234yf leak in passenger compartment caused by collision
Potential injury from fire related to 

1234yf release in under hood area

0 / yr

Probability sufficient 

ignition source present 

0

“E”

Number of occupants

per vehicle

1.59

Probability of LFL being 

exceeded in under 

hood area

1.0

Number o

oper

&

Frequency of leak in 

under hood area

6.8 x 10-10 /hr

Probability spark from 

battery will ignite 

material

TBD

OR

Battery spark is within 

flammable 

concentration zone

TBD

&

Probability hot 

manifold will ignite 

material

0

Probability of 

battery cable short

1 x 10-5

Battery short is of 

sufficient energy

1.0

&

Hot manifold is 

within flammable 

concentration zone

1.0

Probability manifold 

exceeds autoignition 

temperature

0.05

Probability gas is 

actually ignited

0

Figure 19. Fault tree describing risk of fire associated with a HFO-1234yf leak in engine compartment

Currently subject to further testing
“F”

Possibility of refrigerant 

related fire in 

professional shop

0 /yr

&

Air 

concentrations 

above LFL

0/yr

Air concentrations 

above LFL due to 

system rupture

0/yr

Air concentrations 

above LFL due to 

equipment leak

0/yr

OR

Sufficient igniti

presen

0.006

Probability smokingrelated source present 

with sufficient energy to 

ignite material

0.005

OR

Service carried out 

with inadequate 

ventilation

0.097 (U.S.)

0.099 (Europe)

Probability of 

inadequate 

ventilation

0.10

Work is carried 

out by trained 

technician

0.97 (U.S.)

0.99 (Europe)

&

Pro

lightin

flame 

Probability 

trained technician 

smokes while 

working

0.01

&

Shop air 

concentration 

exceeds LFL

0

Rupture of 

vehicle system 

during service

0.005 /yr

&

Shop air 

concentration 

exceeds LFL

0

Leak from AC 

service 

equipment during 

service

0.001 /yr

&

Figure 20. Fault tree describing risk of fire associated with a HFO-1234yf leak during vehicle repair by professional service technicians
“G”

Possibility of refrigerant 

related fire in DIY 

location

0 /yr

&

Air 

concentrations 

above LFL

0/yr

Air 

concentrations 

above LFL due 

to heel release

0/yr

Air concentrations 

above LFL due to 

charge kit leak

0/yr

OR

Sufficient igniti

presen

0.05

Probability smokingrelated source present 

with sufficient energy to 

ignite material

0.05

OR

Service carried out 

with inadequate 

ventilation

0.006 (U.S.)

0.002 (Europe)

Probability of 

inadequate 

ventilation

0.20

Work is carried 

out by DIYer

0.03 (U.S.)

0.01 (Europe)

&

Proba

lighting 

flame s

0

Probability 

trained technician 

smokes while 

working

0.1

&

Shop air 

concentration 

exceeds LFL

0

Release of can 

heel contents 

during service

0.005 /yr

&

Shop air 

concentration 

exceeds LFL

0

Release from 

charge kit while 

charging system

0.001 /yr

&

Figure 21. Fault tree describing risk of fire associated with a HFO-1234yf leak during vehicle repair by DIYers
ATTACHMENT A 

Ignition Source Table
Possible Ignition Sources for Passenger Compartment Scenarios 

Potential Ignition 

Source 

Is Source of Sufficient Energy to 

Ignite Refrigerant 

Ignition Energy 

(mJ) 

Source 

Temperature 

(C) 

Source Power 

(W) 

Conditions when sparking or 

(i.e., normal opera

Burning cigarettes/cigars 

Not likely based on 1982 ADL study and recent testing of 1234yf NA 400-780oC NA 

The ADL study evaluated ignition methane air mixture. The ADL sconservative for HFO-1234yf whflammable. Activity occurs in novery brief time of use 

Electrical cigarette lighter (nickelchromium heating element) 

Not likely based on 1982 ADL study and recent testing of 1234yf 

NA NA NA The ADL study evaluated ignition 

methane air mixture. The study conservative for HFO-1234yf whflammable. 

Activity occurs in normal use but 

of use 

Lit match Possibly ND 600-800oC ND Occurs in normal use but there is Butane lighter Possibly (heat of combustion: 

49 MJ/kg) 

1977oC NA Activity occurs in normal use but 

of use 

Electrical equipment in passenger compartment 

Not likely, ADL study found devices such as car radios and clocks did not ignite 7% methane atmosphere 

ND ND ND The ADL study evaluated norma

alternator, starter relay, distributohousing. Other passenger compa

power windows) presumably pre

 Starter/ignition Not likely based on 1982 ADL 

study 

ND ND ND OEMs felt other ignition sources 

worst case. 

 Radio Not likely based on 1982 ADL 

study 

NA NA NA ADL study suggests this source 

operation. 

 Passenger 

items 

Not likely, based on ADL study for clocks and radios, passenger items would be expected to produce a lesser hazard. 

ND ND ND 

Static spark from passengers in contact with carpet/upholstery 

No, an upper end value for a human static electricity discharge is given as 20 mJ, well below the ignition energy of 1234yf. 

approx. 20 mJ or 

less 

NA NA The value of 20 mJ is widely quo

documentation for this value. 

Internal battery Yes, OEM members felt that an 

external short of a battery located inside the vehicle could have sufficient energy 

ND NA 95/110 A 

800/950 A 

Data from Fiat for passenger trantruck 

PTC heaters Possibly, location of PTC heater 

in the duct could result in refrigerant contact with source at maximum concentration 

ND ND 1.5kw with 

30Amp fuse; 

1 kW with 13.5 

V. 

Data from two OEMs 

ND – no data available NA – not applicable to the source in question
Possible Ignition Sources for Repair Worker Scenarios 

Potential Ignition 

Source 

Is Source of Sufficient 

Energy to Ignite 

Refrigerant 

Ignition Energy 

(mJ) 

Source 

Temperature 

(C) 

Source Power 

(W) 

Comment 

Burning cigarettes/cigars 

Not likely (based on 1982 

ADL study and recent 

HFO-1234yf testing) 

NA 400-780oC NA Will containers of 1234yf display a flamma

Electrical cigarette lighter 

Not likely (based on 1982 

ADL study and recent 

HFO-1234yf testing) 

NA NA NA Are there any statistics for frequency of ele

versus butane lighters? 

Lit match Yes (based on recent 

testing) 

ND 600-800oC ND Will containers of 1234yf display a flamma

Butane lighter Yes (based on recent 

testing) 

(heat of 

combustion= 49 

MJ/kg) 

1977oC (heat of 

combustion: 49 

MJ/kg) 

NA Will containers of 1234yf display a flamma

AC service units No, equipment will be 

designed to be nonsparking 

NA NA NA 

Other AC service equipment (e.g., 

detectors) 

Possible, but ignition potential will be far less than activities such as welding, grinding, etc. 

ND ND ND 

Sparks from activities that may be performed on other vehicles (e.g., metal 

sanding, welding or grinding associated with body work) 

Possible, grinding, sanding or welding metal parts would generate sparks/arcs of very high energy 

1 to 1000 mJ 

(Eckhoff, 2003) 

Acetylene/O2

welding - 

3300oC 

NA A MACS survey indicated that most mobile 

shops use flammable gases in their operatwas in use in 82% of shops, propane in 18operations included brazing (47% of shopssoldering (14%), and welding (65%) (U.S. 

Report, Oct. 12, 2007). Not that these numrelevant for the small 2-vehicle shop used 

Lights used during repair, if these are of high wattage and pulled in towards the engine area 

Unlikely. Several incandescent or halogen lights would be required in contact with gas cloud. 

NA Tungstenhalogen: 600-

900oC Incandescent: 100-300oC 

NA 

ND – no data available NA – not applicable to the source in question 
Possible Ignition Sources for Engine Compartment Scenario 

Potential Ignition 

Source 

Is Source of Sufficient 

Energy to Ignite 

Refrigerant 

Ignition Energy 

(mJ) 

Source 

Temperature (C) 

Source Power (W) Conditions when sparks 

temperature occurs (norma

Equipment sparks from vehicle components while in operation 

Possible, broken wiring was able to ignite a 7% methane-air mixture in the 

ADL study. Unclear if the 

same would be true for 1234yf. 

ND NA ND This source is probably adequate

by considering the effect of a batshort. 

 Battery Possible with short across 

terminals 

ND NA 36 kW (12 V boat 

battery) 

Fault 

Hot surfaces in/near engine compartment (would need to exceed autoignition temperature of refrigerant)  Battery No NA 200oC NA Fault (when crushed)  Exhaust System Possible NA 600oC NA Under strenuous uphill climb  Catalytic conv. NA 200-900oC (internal 

temp) 

NA Carley, 2007

Fires generated from other automotive components (e.g., 

motor oil leaks) 

Possible ~2000oC (gasoline 

heat of combustion: 

47 mJ/kg) 

 Fault. 

DuPont/Honeywell test data suggpotential for HFO-1234yf to contsignificantly to a fire initiated by omaterials may be limited. 

ND – no data available NA – not applicable to the source in question 
ATTACHMENT B 

MODELING RESULTS FOR REPAIR WORKER SCENARIOS: R-12 
Plots of Concentration vs. Time for Professional Mechanic Exposure

Leak Due to Complete Evaporator Rupture During Service

0

100200300400500600700800

0 100 200 300 400 500 

Time in minutes

R-12 Concentration in ppm 5-minute TWA = 708 ppm
Plots of Concentration vs. Time for Service Technician Exposure

Leak from Service Equipment During Service

0

20406080

100120140160180

0 100 200 300 400 500 

Time in minutes

R-12 Concentration in ppm

30-minute TWA = 139 ppm
Plots of Concentration vs. Time for DIY Exposure

Release of Heel Contents of 2 Cans of R-12 Over 90 Minutes

0

500

1,0001,5002,0002,5003,000

0 100 200 300 400 500 

Time in minutes

R-12 Concentration in ppm

30-minute TWA = 2,182 ppm
Plots of Concentration vs. Time for DIY Exposure

Small Leak from 2 Cans of R-12 While Charging

0

5,000

10,00015,00020,00025,00030,00035,00040,000

0 100 200 300 400 500 

Time in minutes

R-12 Concentration in ppm

30-minute TWA = 30,896 ppm
ATTACHMENT C 

MODELING RESULTS FOR REPAIR WORKER SCENARIOS: HFO-1234yf
Plots of Concentration vs. Time for Service Technician Exposure

Leak Due to Complete Evaporator Rupture During Service

0

100200300400500600700

0 100 200 300 400 500 

Time in minutes

Maximum Concentration = 590 ppm

5-minute TWA = 566 ppm

30-minute TWA = 464 ppm

HFO-1234yf Concentration in ppm
Plots of Concentration vs. Time for Service Technician Exposure

Leak From Service Equipment During Service

0

20406080

100120140160

0 100 200 300 400 500 

Time in minutes

Maximum Concentration = 146 ppm

5-minute TWA = 141 ppm

30-minute TWA = 122 ppm

HFO-1234yf Concentration in ppm
Plots of Concentration vs. Time for DIY Exposure

Release of Heel Contents of 2 Cans of HFO-1234yf Over 90 Minutes

0

500

10001500200025003000

0 100 200 300 400 500 

Time in minutes

1234yf Concentration in ppm Maximum Concentration = 2,670 ppm 5-minute TWA =2,636 ppm 30-minute TWA = 2,493 ppm
Plots of Concentration vs. Time for DIY Exposure

Small Leak From 2 Cans of HFO-1234yf While Charging AC System

0

500

10000

15000200002500030000350004000045000

0 100 200 300 400 500 

Time in minutes

Maximum Concentration = 38,946 p

5-minute TWA = 37,800 ppm

30-minute TWA = 32,800 ppm

HFO-1234yf Concentration in ppm
ATTACHMENT D 

LIST OF TECHNICAL TERMS AND ACRONYMS USED IN THE RISK ASSESSMENT
G:\projects\206703\1234yf\Deliverables\Acronyms 1 

List of Technical Terms and Acronyms Used in the Risk Assessment 

Term or 

Acronym Full name Explanation 

ACGIH 

American Conference of 

Governmental Industrial 

Hygienists 

A not-for-profit organization of industrial health 

professionals. A key activity of this group is the 

setting of Threshold Limit Values (TLVs), which 

are health-based limits for worker exposures to 

chemicals and other agents (e.g., noise). 

Acute toxicity - Concerns adverse health effects that are related to

single or short-term (e.g., several hour) exposures. 

AEGL1 - 

Exposure levels developed by U.S. EPA to address 

once-in-a-lifetime or rare exposures to airborne 

chemicals. Level 1 indicates concentrations above 

which non-disabling, reversible discomfort may 

occur. 

Ames assay - 

A toxicological test for genotoxicity in which a 

material of concern is applied to specialized 

bacterial cultures which are subsequently evaluated

for signs of DNA mutation. 

ANSI American National Standards 

Institute 

A private institute in the U.S. that oversees the 

development of testing and production standards for

materials and devices. 

AR Alternative Refrigerant A new refrigerant intended to replace R-134a in 

mobile air conditioning systems. 

ASHRAE 

America Society of Heating, 

Refrigerating and AirConditioning Engineers 

An international organization which develops 

standards related to refrigeration processes and the 

design and maintenance of indoor environments 

Carcinogenicity,

Carcinogenic - 

Producing cancer, having the potential to produce 

cancer. 

Cardiac 

sensitization - 

The ability of certain chemicals to render the heart 

more sensitive to the effects of epinephrine (also 

called adrenalin). 

CFC Chlorofluorocarbons 

Hydrocarbons in which all of the hydrogen atoms 

have been replaced with chlorine or fluorine atoms,

for example, dichlorodifluoromethane. 

CFD Computational Fluid Dynamics 

A computational methodology which yields 

predictions of the flow of materials such as liquids 

or gases. 

Chromosomal 

aberration test - 

A toxicological test for genotoxicity which 

evaluates the potential for a material to cause 

damage to genetic material when a cell divides. 

Chronic toxicity - 

Concerns adverse health effects related to exposures 

lasting longer than 6 months and potentially as long 

as a lifetime. 

DIY Do It Yourselfer 

An individual who performs automotive repairs 

without using the services of a professional 

automotive repair technician. 

Epinephrine 

(also called 

adrenalin) 

- 

A natural hormone produced which mediates the 

body’s response to stress. 

FTA Fault Tree Analysis 

A methodology for studying the chain of events 

leading to system failures and for quantifying the 

resulting risks. 
G:\projects\206703\1234yf\Deliverables\Acronyms 2 

List of Technical Terms and Acronyms Used in the Risk Assessment 

Term or 

Acronym Full name Explanation 

Genotoxicity - 

Causing damage to the genetic material of the cell. 

Genotoxicity can be a possible indication of 

carcinogenic potential. 

GWP Global Warming Potential 

The potential of a particular chemical to contribute 

to the greenhouse gas effect measured over a 

specific time frame (e.g., 100 years) and often 

standardized to the effect of CO2. 

HCFC Hydrochlorofluorcarbons 

Hydrocarbons containing, in addition to hydrogen 

and carbon atoms, varying substitution with fluorine 

and chlorine atoms, for example 

chlorodifluoromethane. 

HFC Hydrofluorocarbons 

Hydrocarbons containing, in addition to hydrogen 

and carbon atoms, varying substitution with fluorine 

atoms (but no chlorine atoms), for example, 1,1-

difluoroethane. 

HFO Hydrofluoroolefin A fluorinated hydrocarbon which has at least 1 

carbon-to-carbon double bond. 

IPCC Intergovernmental Panel on 

Climate Change 

A scientific intergovernmental body established by 

the World Meteorological Organization (WMO) and 

the United Nations Environment Programme 

(UNEP). The IPCC studies aspects of climate 

change and makes recommendations for lessening 

human activities that may potentially alter the 

environment. 

ISO International Standards 

Organization 

An organization working to harmonize chemical 

and equipment testing standards that have been 

adopted by different countries. 

LC50 Lethal Concentration 50 

The concentration of a gas or vapor which kills 50%

of the test animal population after an acute (often 4-

hour) exposure. 

LOAEL Lowest Observed Adverse Effect 

Level 

The lowest dose evaluated in a toxicity study which 

produced signs of adverse effects in the test 

animals. By definition, the LOAEL represents a 

higher concentration than the NOAEL. 

Micronucleus 

test - 

A test for genotoxicity which evaluates the potential 

for a material to induce chromosome fragmentation 

when cells divide. 

mRCL Modified Recommended 

Concentration Limit 

A health-based exposure limit used in this risk 

assessment which differentiates between stressful 

and non-stressful exposure situations. 

NIOSH National Institute of 

Occupational Safety and Health 

A research branch of the U.S. Centers for Disease 

Control which establishes Recommended Exposure 

Limits (RELs), which are health-based guidelines 

for worker exposures to chemical agents. 

NOAEL No Observed Adverse Effect 

Level 

The highest dose tested in a toxicity study which 

does not produce signs of adverse effects. 

NOEL No Observed Effect Level 

The highest dose tested in a toxicity study which 

does not produce signs of any effects. Often used 

when the effect of interest may not necessarily be 

considered adverse. 
G:\projects\206703\1234yf\Deliverables\Acronyms 3 

List of Technical Terms and Acronyms Used in the Risk Assessment 

Term or 

Acronym Full name Explanation 

NRC National Research Council 

A unit of the U.S. National Academy of Sciences, 

consisting of scientists from different disciplines

who advise the U.S. government in matters of 

science policy. 

ODP Ozone Depletion Potential 

The potential of a particular chemical to cause 

stratospheric ozone depletion measured over a 

specific time frame (e.g., 100 years). 

OECD Organization for Economic 

Cooperation and Development 

In the context of this report, an international body 

which has developed standard chemical testing 

protocols. 

RCL Recommended Concentration 

Limit 

A health-based exposure limit developed in 

ANSI/ASHRAE Standard 34-2007 which is meant 

to be protective for acute exposures to refrigerants. 

SNAP Significant New Alternatives 

Program 

U.S. EPA program which evaluates new chemicals 

proposed as replacements for those with ozone 

depletion or global warming potential. 

Subacute 

toxicity - 

Concerns adverse health effects that are related to

exposures lasting several days to a few weeks. 

Subchronic 

toxicity - 

Concerns adverse health effects that are related to

exposures lasting a few weeks to several months. 

TEEL1 Temporary Emergency Exposure 

Limit, level 1 

An acute exposure level developed by the U.S. 

National Oceanic and Atmospheric Administration. 

Level 1 indicates a level which produces only 

minimal and transient health effects. 

TWA Time Weighted Average The average concentration over a specified time 

interval (e.g., 5 minutes or 8 hours).