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2

3

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## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

9



## F OR 10

11

12

13

14



## 1,1-D ICHLORO 

## -1- FLUOROETHANE 

## (HCFC-141 B 

## ) 15

16

17

18

19



# [CAS No. 1717-00-6] 20

21

22

23

24

25

26

Department of Health and Human Services 27

Centers for Disease Control and Prevention 28

National Institute for Occupa tional Safety and Health 29

30

31External Review Draft Document

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## D ISCLAIMER 1

Mention of any company or product does not constitute endorsement by the National Institute for Occupational 2

Safety and Health (NIOSH). In add ition, citations of Web sites extern al to NIOSH do not constitute NIOSH 3

endorsement of the sponsoring organizations or thei r programs or products. Furthermore, NIOSH is not 4

responsible for the content of these Web sites. 5

6



## O RDERING 

## I NFORMATION 7

This document is in the public domain and may be freely copied or reprinted. To receive NIOSH documents or 8

other information about occupational safet y and health topics, contact NIOSH at 9

Telephone: 1-800-CDC-IN FO (1-800-232-4636) 10

TTY: 1-888-232-6348 11

E-mail: cdcinfo@cdc.gov 12

13

or visit the NIOSH Web site at www.cdc.gov/niosh. 14External Review Draft Document

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## Foreword 1

Chemicals are a ubiquitous component of the modern wo rkplace. Occupational exposures to chemicals have the 2

potential to adversely affect the health and lives of workers. Acute or short-term exposures to high concentrations 3

of some airborne chemicals have the ability to quickly overwhelm workers, resulting in a spectrum of undesirable 4

health outcomes that may inhibit the ability to escape from the exposure envi ronment (e.g., irritation of the eyes 5

and respiratory tract or cognitive impairment), cause severe irreversible effects (e.g., damage to the respiratory 6

tract or reproductive toxicity), and in extreme cases, cause death. Airborne concentrations of chemicals capable 7

of causing such adverse health effects or of impeding escape from high-risk conditions may arise from a variety of 8

non-routine workplace situations , including special wo rk procedures (e.g., in confined spaces), industrial 9

accidents (e.g., chemical spills or explosions), and chemical releases into the community (e.g., during 10

transportation incidents or other uncontrolled-release scenarios). 11

12

The “immediately dangerous to life or health air concen tration values (IDLH values)” developed by the National 13

Institute for Occupational Safety a nd Health (NIOSH) characterize these high-risk exposure concentrations and 14

conditions [NIOSH 2013]. IDLH values are based on a 30-minute exposure duration and have traditionally 15

served as a key component of the decision logic for the selection of respiratory protection devices [NIOSH 2004]. 16

Occupational health professionals have employed these values beyond their initial purpose as a component of the 17

NIOSH Respirator Selection Logic to assist in developi ng Risk Management Plans for non-routine work practices 18

governing operations in high-risk envi ronments (e.g., confined spaces) and the development of Emergency 19

Preparedness Plans. 20

21

The approach used to derive IDLH values for high priority chemicals is outlined in the NIOSH Current 22

Intelligence Bulletin (CIB) 66: Derivation of Immediately Da ngerous to Life or Health Values [NIOSH 2013]. 23

CIB 66 provides 1) an update on the scientific basis a nd risk assessment methodology used to derive IDLH 24

values, 2) the rationale and derivati on process for IDLH values, and 3) a demonstration of the derivation of 25

scientifically credible IDLH values using available data resources. 26

27

The purpose of this technical report is to present th e IDLH value for HCFC-141 B (CAS # 1717-00-6). The 28

scientific basis, toxicologic data and risk assessment appr oach used to derive the ID LH value are summarized to 29

ensure transparency and scientific credibility. 30

31

John Howard, M.D. 32

Director 33

National Institute for Occupa tional Safety and Health 34

Centers for Disease Control and Prevention 35External Review Draft Document

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## Table of Contents 1

FOREWORD

............................................................................................................................... ................................. III 2

ABBREVIATIONS

............................................................................................................................... ......................... V 3

GLOSSARY

............................................................................................................................... ................................... VI 4

ACKNOWLEDGMENTS

............................................................................................................................... .............. IX 5

1.0 INTRODUCTION

............................................................................................................................... ............... 1 6

1.1 IDLH V ALUE FOR 1,1-D ICHLORO -1- FLUOROETHANE (HCFC-141 B )

.......................................................................... 1 7

1.2 P URPOSE

............................................................................................................................... ...................................... 1 8

1.3 G ENERAL S UBSTANCE I NFORMATION

......................................................................................................................... 1 9

2.0 ANIMAL TOXICITY DATA

............................................................................................................................. 4 10

3.0 HUMAN DATA

............................................................................................................................... .................. 8 11

4.0 SUMMARY

............................................................................................................................... ......................... 8 12

5.0 REFERENCES

............................................................................................................................... .......................... 9 13

14

15

16

17

18External Review Draft Document

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## Abbreviations 1

2

ACGIH American Conference of Gove rnmental Industrial Hygienists 3

AEGL Acute Exposure Guideline Levels 4

AIHA American Industrial Hygiene Association 5

BMC benchmark concentration 6

BMCL benchmark concentra tion lower confidence limit 7

C ceiling 8

CAS chemical abstract service 9

ERPG Emergency Response Planning Guidelines 10

HCFC-141b 1,1-dichloro-1-fluoroethane 11

IDLH immediately dangerous to life or health 12

LC 50 median lethal concentration 13

LC Lo lowest concentration of a chemical that caused death in humans or animals 14

LEL lower explosive limit 15

LOAEL lowest observed adverse effect level 16

mg/m 3 milligram(s) per cubic meter 17

NAC National Advisory Committee 18

NAS National Academy of Sciences 19

NIOSH National Institute for O ccupational Safety and Health 20

NOAEL no observed adverse effect level 21

OSHA Occupational Safety and Health Administration 22

PEL permissible exposure limit 23

ppm parts per million 24

RD 50 concentration of a chemical in the air that is estimated to cause a 50% decrease in the respiratory 25

rate 26

REL recommended exposure limit 27

SCP Standard Completion Program 28

STEL short term exposure limit 29

TLV threshold limit value 30

TWA time weighted average 31

UEL upper explosive limit 32

WEEL workplace environmental exposure level 33

μ g/kg microgram(s) per kilogram of body weight 34External Review Draft Document

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## Glossary 2

Acute Exposure : Exposure by the oral, dermal, or inhalation route for 24 hours or less. 3

Acute Exposure Guideline Levels (AEGLs) : Threshold exposure limits for the general public applicable to 4

emergency exposure periods ranging from 10 minutes to 8 hours. AEGL-1, AEGL 2, and AEGL-3 are 5

developed for five exposure periods (10 and 30 minutes, 1 hour, 4 hours, and 8 hours) and are distinguished 6

by varying degrees of severity of toxic effects ranging fro m transient, reversible effects to life-threatening 7

effects [NAS 2001]. AEGLs are intended to be guideline le vels used during rare events or single once-in-a8

lifetime exposures to airborne concentrations of acu tely toxic, high-priority chemicals [NAS 2001]. The 9

threshold exposure limits are designed to protect the general population, including the elderly, children or 10

other potentially sensitive groups that are generally not considered in the development of workplace exposure 11

recommendations (additional information av ailable at http://www.epa.gov/oppt/aegl/). 12

Acute Reference Concentration (RfC) : An estimate (with uncertainty spa nning perhaps an order of magnitude) 13

of a continuous inhalation exposure for an acute dur ation (24 hours or less) of the human population 14

(including sensitive subgroups) that is li kely to be without an appreciable risk of deleterious effects during a 15

lifetime. It can be derived from a NOAEL, LOAEL, or benchmark concentration, with uncertainty factors 16

(UFs) generally applied to reflect li mitations of the data used. Generally used in USEPA noncancer health 17

assessments [USEPA 2014]. 18

Acute Toxicity : Any poisonous effect produced within a short period of time following an exposure, usually 24 19

to 96 hours. 20

Adverse Effect : A substance-related biochemical change, functional impairment, or pathologic lesion that affects 21

the performance of an organ or system or alters the ab ility to respond to additional environmental challenges. 22

Benchmark Dose/Concentration (BMD/BMC) : A dose or concentration that produces a predetermined change 23

in response rate of an effect (called the benchmar k response, or BMR) compared to background [USEPA 24

2014] (additional information available at http://www.epa.gov/ncea/bmds/). 25

Benchmark Response (BMR) : A predetermined change in response rate of an effect. Common defaults for the 26

BMR are 10% or 5%, reflecting study design, da ta variability, and sensitivity limits used. 27

BMCL : A statistical lower confidence limit on th e concentration at the BMC [USEPA 2014]. 28

Bolus Exposure : A single, relatively large dose. 29

Ceiling Value (“C”) : U.S. term in occupational exposure indicati ng the airborne concentration of a potentially 30

toxic substance that should never be exceeded in a worker’s breathing zone. 31

Chronic Exposure : Repeated exposure for an extended period of time. Typically exposures are more than 32

approximately 10% of life span for humans and >90 days to 2 years for laboratory species. 33

Critical Study : The study that contributes most significantly to the qualitative and quantitative assessment of risk 34

[USEPA 2014]. 35

36

Dose : The amount of a substance available for interactions with metabolic processes or biologically significant 37

receptors after crossing the outer boundary of an organism [USEPA 2014]. 38

ECt 50 : A combination of the effective concentration of a s ubstance in the air and the exposure duration that is 39

predicted to cause an effect in 50% (one half) of the experimental test subjects. 40External Review Draft Document

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quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and

Health. It does not represent and should not be construed to represent any agency determination or policy. Emergency Response Planning Guidelines (ERPGs) : Maximum airborne concentrations below which nearly all 1

individuals can be exposed without experiencing health effects for 1-hour exposure. ERPGs are presented in a 2

tiered fashion with health effects ranging from mild or transient to serious, irreversible, or life threatening 3

(depending on the tier). ERPGs are developed by the Am erican Industrial Hygiene Association [AIHA 2006]. 4

Endpoint : An observable or measurable biological event or si gn of toxicity ranging from biomarkers of initial 5

response to gross manifestations of clinical toxicity. 6

Exposure : Contact made between a chemical, physical, or biological agent and the outer boundary of an 7

organism. Exposure is quantified as the amount of an agent available at the exchange boundaries of the 8

organism (e.g., skin, lungs, gut). 9

Extrapolation : An estimate of the response at a point outside the range of the experimental data, generally 10

through the use of a mathematical model, although qualitative extrapol ation may also be conducted. The 11

model may then be used to extrapolate to res ponse levels that cannot be directly observed. 12

Hazard : A potential source of harm. Hazard is distinguished from risk, which is the probability of harm under 13

specific exposure conditions. 14

Immediately Dangerous to Life or Health (IDLH) condition : A situation that poses a threat of exposure to 15

airborne contaminants when that exposure is likely to cause death or immediate or delayed permanent adverse 16

health effects or prevent escape from such an environment [NIOSH 2004, 2013]. 17

IDLH value : A maximum (airborne concentration) level above which only a highly reliable breathing apparatus 18

providing maximum worker protection is permitted [NIOSH 2004, 2013]. IDLH values are based on a 30- 19

minute exposure duration. 20

LC 01 : The statistically determined concentra tion of a substance in the air that is estimated to cause death in 1% of 21

the test animals. 22

LC 50 : The statistically determined concentr ation of a substance in the air that is estimated to cause death in 50% 23

(one half) of the test animals; median lethal concentration. 24

LC

LO : The lowest lethal concentration of a substance in the air reported to cause death, usually for a small 25

percentage of the test animals. 26

27

LD 50 : The statistically determined lethal dose of a substance that is estimated to cause death in 50% (one half) of 28

the test animals; median lethal concentration. 29

LD LO : The lowest dose of a substance that causes death, usua lly for a small percentage of the test animals. 30

LEL : The minimum concentration of a gas or vapor in air, below which propagation of a flame does not occur in 31

the presence of an ignition source. 32

Lethality : Pertaining to or causing death; fatal; referring to th e deaths resulting from acute toxicity studies. May 33

also be used in lethality threshold to describe the poi nt of sufficient substance concentration to begin to cause 34

death. 35

Lowest Observed Adverse Effect Level (LOAEL) : The lowest tested dose or concentration of a substance that 36

has been reported to cause harmful (adverse) health effects in people or animals. 37

Mode of Action : The sequence of significant events and processes that describes how a substance causes a toxic 38

outcome. Mode of action is distinguished from the more detailed mechanism of action, which implies a more 39

detailed understanding on a molecular level. 40External Review Draft Document

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quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and

Health. It does not represent and should not be construed to represent any agency determination or policy. No Observed Adverse Effect Level (NOAEL) : The highest tested dose or concentration of a substance that has 1

been reported to cause no harmful (adverse) health effects in people or animals. 2

Occupational Exposure Limit (OEL) : Workplace exposure recommendations developed by governmental 3

agencies and non-governmental organizations. OELs are intended to represent the maximum airborne 4

concentrations of a chemical substance below wh ich workplace exposures should not cause adverse health 5

effects. OELs may apply to ceiling, short-term (STELs), or time-weighted average (TWA) limits. 6

Peak Concentration : Highest concentration of a substance record ed during a certain period of observation. 7

Permissible Exposure Limit (PEL) : Occupational exposure limits devel oped by OSHA (29 CFR 1910.1000) or 8

MSHA (30 CFR 57.5001) for allowable occupational air borne exposure concentr ations. PELs are legally 9

enforceable and may be designated as ceiling, STEL, or TWA limits. 10

11

Point of Departure (POD) : The point on the dose–response curve fro m which dose extrapolation is initiated. 12

This point can be the lower bound on dose for an estim ated incidence or a change in response level from a 13

concentration-response model (BMC), or it can be a NOAEL or LOAEL for an observed effect selected from 14

a dose evaluated in a health e ffects or toxicology study. 15

RD 50 : The statistically determined concentr ation of a substance in the air that is estimated to cause a 50% (one 16

half) decrease in the respiratory rate. 17

Recommended Exposure Limit (REL) : Recommended maximum exposure limit to prevent adverse health 18

effects based on human and animal studies and established for occupational (up to 10-hour shift, 40-hour 19

week) inhalation exposure by NIOSH. RELs may be designated as ceiling, STEL, or TWA limits. 20

Short-Term Exposure Limit (STEL) : A worker’s 15-minute time-weighted average exposure concentration that 21

shall not be exceeded at any time during a work day. 22

Target Organ : Organ in which the toxic injury manifests in terms of dysfunction or overt disease. 23

Threshold Limit Values (TLVs®) : Recommended guidelines for occupa tional exposure to airborne 24

contaminants, published by the American Conference of Governmental Industrial Hygienists (ACGIH). TLVs 25

refer to airborne concentrations of chemical substa nces and represent conditions under which it is believed 26

that nearly all workers may be repeatedly exposed, da y after day, over a working lifetime, without adverse 27

effects. TLVs may be designated as ceiling, short-term (STELs), or 8-hr TWA limits. 28

Time-Weighted Average (TWA) : A worker’s 8-hour (or up to 10-hour) time-weighted average exposure 29

concentration that shall not be exceeded during an 8- hour (or up to 10-hour) work shift of a 40-hour week. 30

The average concentration is weighted to take into ac count the duration of different exposure concentrations. 31

Toxicity : The degree to which a substance is able to ca use an adverse effect on an exposed organism. 32

33

Uncertainty Factors (UFs) : Mathematical adjustments applied to th e POD when developing IDLH values. The 34

UFs for IDLH value derivation are determined by consid ering the study and effect used for the POD, with 35

further modification based on the overall database. 36

Workplace Environmental Exposure Levels (WEELs) : Exposure levels developed by the American Industrial 37

Hygiene Association (AIHA) that provide guidance for protecting most workers from adverse health 38

effects related to occupational chemical exposures expressed as a TWA or ceiling limit. 39External Review Draft Document

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Health. It does not represent and should not be construed to represent any agency determination or policy. 

## Acknowledgments 1

2

This document was developed by the Education and Info rmation Division (Paul Schulte, Ph.D., Director). G. 3

Scott Dotson, Ph.D., was the project officer and lead NIOS H author for this technical report. The basis for this 4

document was a report contracted by NIOSH and prepar ed by Andrew Maier, Ph.D., Ann Parker, and Lynn 5

Haber, Ph.D. (Toxicology Excellen ce for Risk Assessment [TERA]). 6

7

Education and Information Division 8

Devin Baker, M.Ed. 9

Charles L. Geraci, Ph.D. 10

Thomas J. Lentz, Ph.D. 11

Richard Niemeier, Ph.D. 12

Chris Sofge, Ph.D. 13

14

NIOSH would like to acknowledge the contribution of th e following subject matter experts for their critical 15

technical review of this report. 16

17

Mary A. Fox, Ph.D., Assistant Professor; Co-Direct or, Risk Sciences and Public Policy Institute; 18

Department of Health Policy and Management, Bl oomberg School of Public Health, Johns Hopkins 19

University 20

21

Richard B. Schlesinger, Ph.D., Fellow A.T.S., Senior Associate Dean for Academic Affairs and Research 22

Professor of Biology, Dyson College of Arts and Sciences, Pace University 23

24External Review Draft Document

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Health. It does not represent and should not be construed to represent any agency determination or policy. 

## 1.0 Introduction 1



## 1.1 IDLH Value for 1,1-Dich loro-1-fluoroethane (HCFC-141b) 2

3

IDLH Value: 1,667 ppm (7,974 mg/m 3 ) 4

5

Basis for IDLH Value: Cardiac sensitization is the most sensitive indicator of toxicity and is an appropriate non6

lethal endpoint to serve as the basis for the IDLH value for 1,1-dichloro-1-fluoroethane (HFCF-141b), This effect 7

was reported in monkeys exposed to 5,000 ppm for 10 minut es [Hardy et al. 1989] and in a dog exposed to 5,200 8

ppm for 10 minutes [Mullin 1977]. No time scaling factor was applied, based on data that the threshold for this 9

effect is constant for durations longer than 5-10 minutes. Using the concentration of 5,000 ppm reported in Hardy 10

et al. [1989] as the point of departure and applying a com posite uncertainty factor of 3 to account for extrapolation 11

from a severe effect threshold in animals, animal to hum an differences and human variability, results in an IDLH 12

value for HCFC-141b of 1,667 ppm

. 13

14



## 1.2 Purpose 15

16

This IDLH Value Profile presents (1) a brief summary of technical data associated with acute inhalation 17

exposures to HCFC-141b and (2) the rationale behind the I mmediately Dangerous to Life or Health (IDLH) value 18

for HCFC-141b. IDLH values are developed based on the scientific rationale and logic outlined in the NIOSH 19

Current Intelligence Bulletin (CIB) 66: Derivation of Imme diately Dangerous to Life or Health (IDLH) values 20

[NIOSH 2013]. As described in CIB 66, NIOSH performs in -depth literature searches to ensure that all relevant 21

data from human and animal studies with acute exposures to the substance are identified. Information included in 22

CIB 66 on the literature search includes pertinent databases, key terms, and guides for evaluating data quality and 23

relevance for the establishment of an IDLH value. The in formation that is identified in the in-depth literature 24

search is evaluated with general consid erations that include description of studies (i.e., species, study protocol, 25

exposure concentration and duration), health endpoint evaluated, and cr itical effect levels (e.g., NOAELs, 26

LOAELs, LC 50 values). For HCFC-141b, the in-depth literatu re search was conducted th rough February 2014. 27



### 1.3 General Substance Information 28

29

Chemical: 1,1-Dichloro-1-fluoroethane 30

CAS No: 1717-00-6 31

Synonyms: HCFC-141b; Freon-141; CFC 141b * 32External Review Draft Document

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quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and

Health. It does not represent and should not be construed to represent any agency determination or policy. Chemical category: Aliphatic, saturated, halogenated hydrocar bons; Organic chlorine compounds; Organic 1

fluorine compounds † 2

Structural formula: 3

4

5

6

7

Table 1 highlights selected physiochemical properties of HCFC-141b relevant to IDLH conditions. Table 2 8

provides alternative exposure guidelines for HFC-141b. Table 3 summarizes the Acute Exposure Guidelines 9

Level (AEGL) values for HFC-141b. 10

11

Table 1: Physiochemical Properties of HCFC-141b 12

13

Property Value

Molecular weight 116.95 ‡

Chemical formula C 2 H 3 Cl 2 F

Description Colorless liquid

Odor Weak ethereal odor

Odor Threshold 250 ppm +

UEL 17.7% †

LEL 5.6% †

Vapor pressure 600 mmHg at 25°C (77°F) ‡

Flash point Not available

Ignition temperature Not available

Solubility Slightly soluble in water †

Abbreviation: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 14

+ Hardy et al. [1989] 15

* NLM [2014] 16

† IFA [2014] 17

‡ HSDB [2014] 18

19

Table 2: Alternative Exposure Guidelines for HCFC-141b 20

21

Organization Value

Original (SCP) IDLH value [NIOSH 2014] None

NIOSH REL [NIOSH 2014] Not available

OSHA PEL Not available

ACGIH TLV [2014] Not available

AIHA ERPG [2010] Not available

AIHA WEEL [2010] 500 ppm, 8 hr TWA

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 22

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 23

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Program; PEL – permissible exposure limit; REL – 24

recommended exposure limit; SCP – Standards Completion Program; TWA – time-weighted average; WE EL – workplace environmental 25

exposure level 26 Cl

CH 3 F

ClExternal Review Draft DocumentMarch 20153This information is distributed solely for the purpose of predissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.Table 3: AEGL Values for HCFC-141b12Classification 10-min 30-min 1-hour 4-hour 8-hourAEGL-1 1,000 ppm(4,850 mg/m3)1,000 ppm(4,850 mg/m3)1,000 ppm(4,850 mg/m3)1,000 ppm(4,850 mg/m3)1,000 ppm4,850 mg/m3)No effect in humans[Utell et al. 1997]AEGL-2 1,700 ppm(8,245 mg/m3)1,700 ppm(8,245 mg/m3)1,700 ppm(8,245 mg/m3)1,700 ppm(8,245 mg/m3)1,700 ppm8,245 mg/m3)Threshold for cardiacarrhythmia in the dog[Mullin 1977]AEGL-3 3,000 ppm(14,550 mg/m3)3,000 ppm(14,550 mg/m3)3,000 ppm(14,550 mg/m3)3,000 ppm(14,550 mg/m3)3,000 ppm(14,550 mg/m3)Threshold for severecardiac response in the dog[Hardy et al. 1989a]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; ppm – parts per million3*References: NAS [2002]45External Review Draft Document

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Health. It does not represent and should not be construed to represent any agency determination or policy. 

## 2.0 Animal Toxicity Data 1

Acute inhalation toxicity tests were perf ormed in rats and mice. A 4-hour rat LC 50 value was reported for male 2

and female rats at 58,931 and 64,991 ppm, respectively, with a combined LC 50 of 61,647 ppm [de Rooij 1989; 3

Brock et al. 1995]. Brock et al. [1995] also reported a 6-hour LC 50 value of 56,700 ppm in rats. Both studies 4

reported reduced motor activity, shallow breathing with rapi d respiration, and anesthesia at concentrations greater 5

than 29,000 ppm; tremors, incoordination, and convulsi ons were noted in some animals above 50,000 ppm. 6

7

A 30-minute LC 50 value of 100,000 ppm in mice was reported by Davies et al. [1976] with effects including 8

narcosis. In a second study in mice [Vlachos 1988], the authors reported a 60% mortality in mice exposed to 9

80,000 ppm for 6 hours. No clinical signs of exposu re were observed up to 30,000 ppm. Lethargy and tremors 10

were observed at 41,000 ppm, and narcos is occurred within 15 minutes at 80,000 ppm. Deaths were attributed to 11

deep anesthesia. 12

13

Cardiac sensitization tests were conduc ted in rats, dogs and monkeys. A response in this cardiac sensitization 14

assay is considered a sensitive measure of a severe effect. Arrhythmia in these cases is not produced by HCFC15

141b; rather, it is the result of the potentiation of endogenous epinephrine (adrenalin) by the chemical. NAS 16

[2014] described an unpublished study in which Sprague-D awley rats were exposed to 5,000, 10,000, or 20,000 17

ppm of HCFC-141b for 30 minutes and administered 12 μg/kg epinephrine. NAS [2014] reported that marked 18

arrhythmia was observed in 4/11 animals at 5,000 ppm. 19

20

Mullin [1977] exposed dogs to 2,600, 5,200, 10,000, or 21,600 ppm for 5 minutes followed by an intravenous 21

dose of 8 μ g/kg epinephrine. Cardiac sensitization was induced in 1/10 dogs at 5,200 ppm; deaths occurred at 22

higher concentrations. The authors also reported a no-eff ect level at 2,600 ppm. In a second cardiac sensitization 23

study, dogs were exposed to 9,000, 12,000, 13,000, 14,000, 15,000, 18,000, 19,000, or 20,000 ppm for 5 minutes 24

followed by challenge with 10 μ g/kg of intravenous epinephrine [Hardy et al. 1989]. A marked cardiac response 25

was reported in 1/2 dogs at 9,000 ppm, but there was no r esponse in eight other trials at 9,000 – 13,000 ppm. The 26

one dog exposed to 20, 000 ppm and then challenged with epinephr ine developed severe ventricular fibrillation 27

and died. Monkeys were exposed to 0, 3,000, 5,000, or 10,000 ppm for 10 minutes [Hardy et al. 1989]. After 5 28

minutes of exposures, the monkeys received epinephrine. No electrocardiogram effects were seen in the monkey 29

exposed to 3,000 ppm, but the authors reported a marked cardiac response at 5,000 ppm. 30

31External Review Draft Document

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quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and

Health. It does not represent and should not be construed to represent any agency determination or policy. Table 4 summarizes the LC data identified in animal st udies and provides 30-minute equivalent derived values for 1

HCFC-141B. Table 5 provides non-lethal data reported in animal studies with 30-minute equivalent derived 2

values. Information included in these tables includes species of test animals, toxicological metrics (i.e., LC, 3

NOAEL, LOAEL), adjusted 30-minute concentration, and th e justification for the composite uncertainty factors 4

applied to calculate the derived values. 5External Review Draft DocumentMarch 20156This information is distributed solely for the purpose of predissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.Table 4: Lethal Concentration Data for HCFC-141b12Reference SpeciesLC50(ppm)LCLo(ppm)Time(min)Adjusted30-min LCvalue*CompositeUncertaintyFactorDerivedValue(ppm)†Davies et al. [1976] Mouse 100,000 -- 30 100,000 30‡ 3,333Brock et al. [1995] Rat 56,700 -- 360 128,739 30‡ 4,291Brock et al. [1995]Rat(M+F)±61,647 -- 240 123,294 30‡ 4,1013Abbreviation:LC – lethal concentration; LC50– median lethal concentration; LCLo– lowest concentration of a chemical that caused death in humans or animals; min – minute; ppm – parts4per million56*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cnx t = k); no empirically estimated n values were available, therefore the7default values were used, n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes.8†The derived value is the result of the adjusted 30-min valuedivided by the composite uncertainty factor. The composite uncertainty factor used varies for each study based on the nature9and severity of the endpoint observed.10‡Composite uncertainty factor toaccount for adjustment of LC50 values to LC01values, use of lethal concentration threshold inanimals, interspecies differences and human variability.11±M+F – males and females combined12131415External Review Draft DocumentMarch 20157This information is distributed solely for the purpose of predissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.Table 5: Non-lethal Concentration Data for HCFC-141b12Reference SpeciesNOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minConcentration*CompositeUncertaintyFactorDerivedValue(ppm)†Mullin [1977] Dog 5,200 -- 10 5,200‡3± 1,733Hardy et al. [1989] Monkey 5,000 -- 10 5,000‡3± 1,667Abbreviation:NOAEL – no observed adverse effect level;min – minute; LOAEL – lowest observed adverse effect level; ppm– parts per million34*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cnx t = k); no empirically estimated n values were available, therefore the5default values were used, n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes.6†The derived value is the result of the adjusted 30-min valuedivided by the composite uncertainty factor. The composite uncertainty factor used varies for each study based on the nature7and severity of the endpoint observed.8‡The cardiac sensitization response is a concentration-dependent threshold effect; dogsexposed to similar chemicals for longerdurations responded in a similar manner, so no time9adjustment was applied.10±Composite uncertainty factor assigned to account for extrapolation from a severe effectthreshold in animals, animal to human differences and human variability.11External Review Draft Document

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8

This information is distributed solely for the purpose of pre dissemination peer review under applicable information

quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and

Health. It does not represent and should not be construed to represent any agency determination or policy. 

## 3.0 Human Data 1

Information regarding lethality in huma ns is limited to a single case report. Astier and Paraire [1997] reported a 2

worker was found dead with a bluish-purple coloration and edema of the face inside a degreasing tank in which 3

pure HCFC-141b was used as the degreasing solvent. The con centration and exposure duration were not reported. 4

In an experimental study [Utell et al. 1997] eight volunt eers were exposed to 0, 250, 500, or 1,000 ppm for 4 5

hours with three 20 minute exercise periods. Endpoints eval uated included clinical chemistry, hematology, EKG, 6

and spirometry. No effects were reported on these sens itive measures during exposures (aside from the expected 7

response to exercise). In addition, two of the volunteers were exposed at 0 or 500 ppm for 6 hours and one 8

volunteer was exposed to 1,000 ppm for 6 hours, and perfo rmed computerized neurobehavioral testing during the 9

last 2 hours of exposure. No effects were seen. 10



## 4.0 Summary 11

Limited human data are available on HCFC-141b. Multip le animal studies revealed the onset of cardiac 12

sensitization to HCFC-141b. This non-lethal and potentially irreversible effect is the basis of the IDLH value. 13

Monkeys exposed to 5,000 ppm for 10 minutes [Hardy et al. 1989] and a dog exposed to 5,200 ppm for 10 14

minutes [Mullin 1977] both demonstrated cardiac responses. NAS [2002] determined that the cardiac 15

sensitization response is a concentration-dependent thres hold effect; animals exposed to similar chemicals for 16

longer durations responded in a similar manner. Therefore, a duration adjustment for time scaling is not applied, 17

thus the reported exposure concentration is used instead of a 30-minute equivalent. The 5,000 ppm concentration 18

reported by Hardy et al. [1989] is used as the point of departure and basis of the IDLH value for HCFC-141b. 19

Application of an uncertainty factor of 3 to account fo r extrapolation given consideration of animal to human 20

differences and human variability results in an IDLH value of 1,667 ppm. 21

22External Review Draft Document

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9

This information is distributed solely for the purpose of pre dissemination peer review under applicable information

quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and

Health. It does not represent and should not be construed to represent any agency determination or policy. 

## 5.0 References 1

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Aster A, Paraire F [1997]. Fatal intoxication w ith 1,1-dichloro-1-fluoroethane. N Engl J Med 33 7:940. 20

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Brock WJ, Trochimowicz HJ, Millischer RJ, Farr C, Kawa no T, Rusch GM [1995]. Acute and subchronic toxicity 22

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Hardy JC, Sharman IJ, Chanter DO [1989]. Assessment of cardiac sensitization potential in dogs and monkeys. 32

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07553-X. [http://www.epa.gov/oppt/aegl/pubs/sop. pdf]. Date accessed : March 17, 2014. 49External Review Draft Document

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Health. It does not represent and should not be construed to represent any agency determination or policy. 1

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