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policy.

i 1

2

3

4

5

6



## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

9

10



### FOR 11

12

13

14



## C HLORINE 

## P ENTAFLUORIDE 

## [CAS NO



## . 13637-63-3] 15

16



### AND 17

18



## B ROMINE 

## P ENTAFLUORIDE 

## [CAS NO



## . 7789-30-2] 19

20

21

22

23

24

25

Department of Health and Human Services 26

Centers for Disease Control and Prevention 27

National Institute for Occupa tional Safety and Health 28External Review Draft

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policy.

ii 

## 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. 14

15

16External Review Draft

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policy.

iii 

## 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 the ID LH values for chlorine pentafluoride (CAS # 13637-63-3) 28

and bromine pentafluoride (CAS #7789-30-2). The scien tific basis, toxicologic data and risk assessment 29

approach used to derive the IDLH value are summarized to ensure transparency a nd 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

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policy.

iv 

## Contents 1

FOREWORD

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

ABBREVIATIONS

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

GLOSSARY

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

ACKNOWLEDGMENTS

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

1.0 CHLORINE PENTAFLUORIDE

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

1.1 I NTRODUCTION

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

1.1.1 Overview of the IDLH Value for Chlorine Pentafluoride

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

1.1.2 Purpose

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

1.1.3 General Substance Information

......................................................................................................................... 1 10

1.2 A NIMAL T OXICITY D ATA

............................................................................................................................... ............. 4 11

1.3 H UMAN D ATA

............................................................................................................................... .............................. 7 12

1.4 S UMMARY

............................................................................................................................... .................................... 7 13

2.0 BROMINE PENTAFLUORIDE

........................................................................................................................ 8 14

2.1 I NTRODUCTION

............................................................................................................................... ............................ 8 15

2.1.1 Overview of the IDLH Valu e for Bromine Pentafluoride

.................................................................................. 8 16

2.1.2 Purpose

............................................................................................................................... ............................... 8 17

2.1.3 General Substance Information

......................................................................................................................... 9 18

2.2 A NIMAL T OXICITY D ATA

............................................................................................................................... ........... 12 19

2.3 H UMAN D ATA

............................................................................................................................... ............................ 13 20

2.4 S UMMARY

............................................................................................................................... .................................. 13 21

3.0 REFERENCES

............................................................................................................................... ................. 14 22

23

24

25

26

27External Review Draft

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v 

## 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

BrF 5 bromine pentafluoride 8

C° Celsius 9

C ceiling 10

CAS chemical abstract service 11

ClF 5 chlorine pentafluoride 12

ERPG Emergency Response Planning Guidelines 13

IDLH immediately dangerous to life or health 14

LC 50 median lethal concentration 15

LC Lo lowest concentration of a chemical that caused death in humans or animals 16

LEL lower explosive limit 17

LOAEL lowest observed adverse effect level 18

mg/m 3 milligram(s) per cubic meter 19

mmHg millimeter(s) of mercury 20

NAC National Advisory Committee 21

NAS National Academy of Sciences 22

NIOSH National Institute for O ccupational Safety and Health 23

NOAEL no observed adverse effect level 24

OSHA Occupational Safety and Health Administration 25

PEL permissible exposure limit 26

ppm parts per million 27

RD 50 concentration of a chemical in the air that is estimated to cause a 50% decrease in the respiratory 28

rate 29

REL recommend exposure limit 30

SCP Standard Completion Program 31

STEL short term exposure limit 32

TLV threshold limit value 33

TWA time weighted average 34

UEL upper explosive limit 35

WEEL workplace environmental exposure level 36External Review Draft

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policy.

vi 

## Glossary 1

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

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policy.

vii 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

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policy.

viii 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 effects 38

related to occupational chemical expos ures expressed as a TWA or ceiling limit. 39

40External Review Draft

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policy.

ix 

## 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

Michael S. Bisesi, Ph.D., R.E.H.S., C.I.H., Senior Asso ciate Dean for Academic Affairs; Director, Center 18

for Public Health Practice; Interim Chair & Asso ciate Professor, Division of Environmental Health 19

Science, College of Public H ealth, Ohio State University 20

21

Mary A. Fox, Ph.D., Assistant Professor; Co-Direct or, Risk Sciences and Public Policy Institute; 22

Department of Health Policy and Management, Bl oomberg School of Public Health, Johns Hopkins 23

University 24

25

Richard B. Schlesinger, Ph.D., Fellow A.T.S., Senior Associate Dean for Academic Affairs and Research 26

Professor of Biology, Dyson College of Arts and Sciences, Pace University 27External Review Draft

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policy.

1 

## 1.0 Chlorine Pentafluoride 1



## 1.1 Introduction 2



### 1.1.1 Overview of the IDLH Value for Chlorine Pentafluoride 3

4

IDLH Value: 1.7 ppm 5

6

Basis for IDLH Value: The IDLH value for chlorine pentafluoride is based on a 10-minute mouse LOAEL of 7

30 ppm associated with severe respiratory irritation in multiple species, which represents potentially escape8

impairing effects [MacEwen and Vernot 1972]. Duration adju stment yielded a 30-minute equivalent of 17.3 ppm. 9

Application of a composite uncertainty factor of 10 to account for extrapolation from an escape-impairing effect, 10

interspecies differences and human variability results an IDLH value for chlorine pentafluoride of 1.7 ppm

. 11

12



### 1.1.2 Purpose 13

14

This IDLH Profile presents (1) a brief summary of technical data associated with acute inhalation exposures to 15

chlorine pentafluoride and (2) the rationale behind the I mmediately Dangerous to Life or Health (IDLH) value for 16

chlorine pentafluoride. IDLH values are developed based on the scientific rationale and logic outlined in the 17

NIOSH Current Intelligence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or Health (IDLH) 18

values [NIOSH 2013]. As described in CIB 66, NIOSH perfo rms in-depth literature searches to ensure that all 19

relevant data from human and animal studies with acute exposures to the substance are identified. Information 20

included in CIB 66 on the literature search includes per tinent databases, key terms, and guides for evaluating data 21

quality and relevance for the establishment of an IDLH value. The information that is identified in the in-depth 22

literature search is evaluated with ge neral considerations that include d escription of studies (i.e., species, study 23

protocol, exposure concentration and duration), health endpoint evaluated, and criti cal effect levels (e.g., 24

NOAELs, LOAELs, LC 50 values). For chlorine pentafluoride, the in-depth literature search was conducted 25

through February 2014. 26

27



### 1.1.3 General Substance Information 28

29

Chemical: Chlorine pentafluoride (ClF 5 ) * 30

CAS No: 13637-63-3 31

Synonyms: Chlorine fluoride 32External Review Draft

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policy.

2 Chemical category: Inorganic fluorine compounds; Inorgani c chlorine compounds; Inorganic gases † 1

2

Structural formula: 3

4

5

Table 1 highlights selected physiochemical properties of chlorine pentafluoride relevant to IDLH conditions. 6

Table 2 provides alternative exposure guidelines for ch lorine pentafluoride. Table 3 summarizes the Acute 7

Exposure Guidelines Level (AEGL) values for chlorine pentafluoride. 8

9

Table 1: Physiochemical Properties of Chlorine Pentafluoride 10

11

Property Value

Molecular weight 130.45 †

Chemical formula ClF 5 Description Colorless or yellow gas

Odor Suffocating, pungent

Odor Threshold Not available

UEL Not available

LEL Not available

Vapor pressure 3.4 bar at 20°C

Flash point Noncombustible †

Ignition temperature Noncombustible †

Solubility Hydrolysis †

Abbreviation: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 12

* AEGL [2010a]; † IFA [2014] 13

14

Table 2: Alternative Exposure Guidelines for Chlorine Pentafluoride 15

16

Organization Value

Original (SCP) IDLH value None

NIOSH REL Not available

OSHA PEL [2011] Not available

ACGIH TLV [2014] Not available

AIHA ERPG [2010] Not available

AIHA WEEL [2010] Not available

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 17

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 18

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 19

REL – recommended exposure limit; SCP – Standard Completion Program; WEEL – workplace e nvironmental exposure level 20

21

22 

## Cl F F F

F FExternal Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination 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.3Table 3: AEGL Values for Chlorine Pentafluoride12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 0.3 ppm1.6 mg/m30.3 ppm1.6 mg/m30.3 ppm1.6 mg/m3NRNRNo observed irritation - rat[MacEwen and Vernot 1973]AEGL-2 3.0 ppm16.0 mg/m32.0 ppm10.1 mg/m31.0 ppm5.3 mg/m30.48 ppm2.6 mg/m30.33 ppm1.8 mg/m3Sensory irritation, mild lung congestion –monkey, dog, rat, and mouse[MacEwen and Vernot 1972; 1973]AEGL-3 21.0 ppm112.0 mg/m312.0 ppm64.0 mg/m38.0 ppm42.7 mg/m33.9 ppm20.8 mg/m32.7 ppm14.4 mg/m3Highest 1-hour non-lethal concentrationin rats[Darmer et al. 1972]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; NR – not recommended due to inadequate data; ppm – parts per million3*References: NAS [2010a]4External Review Draft

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policy.

4 

## 1.2 Animal Toxicity Data 1

2

Chlorine pentafluoride penetrates the lungs, causing edema and destruction of lung tissue at lethal concentrations 3

leading to pneumonia. It is also a potent irritant of the eyes and respiratory tract at non-lethal concentrations 4

[Darmer et al. 1972; MacEwen and Vernot 1972, 1973]. Darmer et al. [1972] repor ted signs of moderate 5

irritation (lacrimation, sneezing, and salivation) at the lo west concentrations tested for dogs and monkeys at 30 6

minutes, 102 ppm for dogs (one death at this level) and 198 ppm for monkeys (no deaths at this level). 7

8

MacEwen and Vernot [1972] exposed rats, mice, and monkeys to 10, 20, or 30 ppm for 60, 30, or 10 minutes, 9

respectively. Lacrimation was observed in rats and mice , and rats also experienced salivation in all exposure 10

groups. In monkeys, lacrimation and nausea were observe d in all the exposure groups almost immediately after 11

onset of exposure; all exposure groups also experienced tr ansient depression of weight gain when observed for 28 12

days after exposure. Monkeys exposed to 10 ppm for 60 minutes exhibited congested lungs; however, no gross 13

lung lesions were observed in monkeys exposed to 30 ppm for 10 minutes. 14

15

MacEwen and Vernot [1973] followed up with another st udy exposing mice, monkeys and dogs to 5, 10, or 30 16

ppm for 60, 30, or 10 minutes, respectively. Immediate sa livation, eye irritation, lacrimation, and rhinorrhea were 17

observed in all species with the most severe irritation in the 30 ppm dose group, but no gross lung lesions were 18

seen in any of the exposure groups. These effects were judged not to be of sufficient severity to be escape 19

impairing. In addition, rats were exposed to 3, 7, or 30 ppm for 10 minut es. Slight eye irritation was noted in rats 20

exposed to 7 ppm for 10 minutes, but there was no eye irritation in rats exposed to 3 ppm for 10 minutes 21

[MacEwen and Vernot 1973]. 22

23

Table 4 summarizes the LC data identified in animal st udies and provides 30-minute equivalent derived values for 24

chlorine pentafluoride. Table 5 provides non-lethal da ta reported in animal studies with 30-minute equivalent 25

derived values. Information in these tables includes species of test animals, toxicological metrics (i.e., LC, 26

NOAEL, LOAEL), adjusted 30-minute concentration, and th e justification for the composite uncertainty factors 27

applied to calculate the derived values. 28External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination 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.5Table 4: Lethal Concentration Data for Chlorine Pentafluoride12Reference SpeciesLC50(ppm)LC10(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Darmer et al. [1972] Dog 156 -- 30 156 30‡5.2Darmer et al. [1972] Monkey 218 -- 30 218 30‡7.3Darmer et al. [1972] Mouse 105 -- 30 105 30‡ 3.5Darmer et al. [1972] Rat 194 -- 30 194 30‡6.5Weinberg and Goldhamer [1967] Rat -- 200 10 115 10±12Abbreviation:LC – lethal concentration; LC10– concentration estimated to cause a 10% mortality rate; LC50– median lethal concentration; LCLo– lowest concentration of a chemical that3caused death in humans or animals; min – minute; ppm – parts per million45*For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for adjustment (Cnx t = k); NAS [2010a] empirically estimated a n value of 1.9 that6was used for extrapolating from all exposure times.7†The derived value is the result of the adjusted 30-minute LC value divided by the composite uncertainty factor.8‡Composite uncertainty factor to account for adjustment of LC50values to LC01values, use of lethal concentration threshold in animals, interspecies differences and9human variability.10±Composite uncertainty factor to account forlethal concentration threshold in animals,interspecies differences and human variability.111213141516External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination 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.6Table 5: Non-lethal Concentration Data for Chlorine Pentafluoride12Reference Species(reference)NOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†MacEwen and Vernot [1972] Monkey, Dog, Mouse 10^30 10 3‡3.3MacEwen and Vernot [1972]€Monkey, Dog, Mouse, Rat 30±10 17.3 10+1.7MacEwen and Vernot [1972] Rat 3 10 1.7 3‡00.6MacEwen and Vernot [1972] Rat 7**10 4 3‡1.3MacEwen and Vernot [1972] Rat 20††30 20 3‡6.7Abbreviation: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 adjustment (Cnx t = k); NAS [2010a] empirically estimated a n value of 1.9 that5was used for extrapolating from all exposure times.6†The derived value is the result of the adjusted 30-min value divided by the composite uncertainty factor.7^Concentration associated with immediate salivation, eye irritation, lacrimation, and rhinorrhea in multiple species.8‡Composite uncertainty factor assigned to account for interspeciesdifferences and human variability.9€Identified study is the primary basis of the IDLH value for chlorine pentafluoride.10±Concentration associated with severe irritation in multiple species.11+Composite uncertainty factor to account for adjusting from adjustment to an escape-impairing effect, interspecies differencesand human variability.12**Concentration associated with slight irritation.13††Concentration associated with immediate salivation, eye irritation, lacrimation, and rhinorrhea.14External Review Draft

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policy.

7 

## 1.3 Human Data 1

2

No human toxicity data were found, with the exception of a single case report. In this report, a researcher who 3

had taken a single breath of 30 ppm chlorine pentafluorid e in an exposure chamber while conducting an animal 4

toxicity study [MacEwen and Vernot 1973], reported a m ild “burning” of the lungs, mild nausea, an unpleasant 5

taste in the mouth, and headache. The persistence of these symptoms was not reported [MacEwen and Vernot 6

1973]. 7



## 1.4 Summary 8

9

In the absence of adequate human data, the IDLH value is based on potentially escape-impairing effects including 10

severe respiratory irritation in multiple species [MacEwen and Vernot 1972]. Test animals (i.e., monkey, dog, 11

mouse, and rat) exposed to chlorine pentafluoride at c oncentrations ranging from 10 to 30 ppm for durations up to 12

30 minutes experienced immediate salivation, eye irritation, lacrimation, rhinorrhea and respiratory irritation. 13

More specifically, exposures to 30 ppm chlorine pentafluor ide for 10 ppm was associated with severe respiratory 14

irritation, which is considered escape-impairing. Durati on adjusting yielded a 30-minute equivalent value of 17.3 15

ppm. Application of a composite uncertainty factor to account for adjusting from an escape-impairing effect, 16

interspecies differences and human vari ability results in an IDLH value of 1.7 ppm for chlorine pentafluoride. 17External Review Draft

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policy.

8 

## 2.0 Bromine Pentafluoride 1



## 2.1 Introduction 2



### 2.1.1 Overview of the IDLH Value for Bromine Pentafluoride 3

4

IDLH value : 3.5 ppm 5

Basis for IDLH Value: 6

Data were inadequate to directly de rive an IDLH value for bromine pentafluoride. For this reason, data from 7

studies with chlorine pentafluoride were used to devel op an IDLH value for bromine pentafluoride because their 8

structures, reaction mechanisms, and potencies are simila r. Therefore, deriving an IDLH value based on the 9

toxicity data for chlorine pentafluoride is appropriately health-protective. 10

11

The IDLH value for bromine pentafluoride is based on the 10-minute mouse LOAEL associated with severe 12

escape-impairing effects including respiratory irritation re ported in multiple species exposed to 30 ppm chlorine 13

pentafluoride [MacEwen and Vernot 1972]. Duration adju stment yielded a 30-minute equivalent of 17.3 ppm. 14

Application of a composite uncertainty factor of 10 to account for extrapolation from an escape-impairing effect, 15

interspecies differences and human variability results an IDLH value for bromine pentafluoride of 1.7 ppm

. 16

17



### 2.1.2 Purpose 18

19

This IDLH Profile presents (1) a brief summary of technical data associated with acute inhalation exposures to 20

bromine pentafluoride and (2) the rationale behind the Imme diately Dangerous to Life or Health (IDLH) value for 21

bromine pentafluoride. IDLH values are developed based on the scientific rationale and logic outlined in the 22

NIOSH Current Intelligence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or Health (IDLH) 23

values [NIOSH 2013]. As described in CIB 66, NIOSH perfo rms in-depth literature searches to ensure that all 24

relevant data from human and animal studies with acute exposures to the substance are identified. Information 25

included in CIB 66 on the literature search includes per tinent databases, key terms, and guides for evaluating data 26

quality and relevance for the establishment of an IDLH value. The information that is identified in the in-depth 27

literature search is evaluated with ge neral considerations that include d escription of studies (i.e., species, study 28

protocol, exposure concentration and duration), health endpoint evaluated, and criti cal effect levels (e.g., 29

NOAELs, LOAELs, LC 50 values). For bromine pentafluoride, the in-depth literature search was conducted 30

through February 2014. 31

32External Review Draft

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9 2.1.3 

### General Substance Information 1

2

Chemical: Bromine pentafluoride (BrF 5 ) 3

CAS No: 7789-30-2 4

Synonyms: Bromine fluoride * 5

Chemical category: Inorganic fluoride compounds; inorganic bromine compounds † 6

Structural formula: 7

8

9

Table 5 highlights selected physiochemical properties of bromine pentafluoride relevant to IDLH conditions. 10

Table 6 provides alternative exposure guidelines for br omine pentafluoride. Tabl e 7 summarizes the Acute 11

Exposure Guidelines Level (AEGL) values for bromine pentafluoride. 12

13

Table 5: Physiochemical Properties of Bromine Pentafluoride 14

15

Property Value

Molecular weight 174.89 ‡

Chemical formula BrF 5 Description Colorless to pale yellow liquid

Odor Pungent

Odor Threshold Not available

UEL Not available §

LEL Not available §

Vapor pressure 328 mmHg at 20°C §

Flash point Noncombustible ‡

Ignition temperature Noncombustible ‡

Solubility Decomposes in water †

Abbreviation: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 16

* NLM [2014]; † IFA [2014]; ‡ HSDB [2014]; 17

18

19

20

21

22

23

24 

## Br F F

F

F FExternal Review Draft

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10 Table 6: Alternative Exposure Guidelines for Bromine Pentafluoride 1

2

Organization Value

Original (SCP) IDLH value None

NIOSH REL 0.1 ppm (0.7 mg/m 3 ), TWA

OSHA PEL [2014] 0.1 ppm, TWA 8-hour

ACGIH TLV [2014] 0.1 ppm, TWA

AIHA ERPG [2010] Not available

AIHA WEEL [2010] Not available

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 3

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 4

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 5

REL – recommended exposure limit; SCP – Standards Completion Program; TWA – time-weighted average; WEEL – workplace 6

environment exposure level 7

8

9External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination 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.11Table 7: AEGL Values for Bromine Pentafluoride*12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 NR NR NR NR NR No dataAEGL-2 3.0 ppm21.5 mg/m32.0 ppm14.3 mg/m31.0 ppm7.2 mg/m30.48 ppm3.4 mg/m30.33 ppm2.4 mg/m3Based on analogy with chlorinepentafluorideAEGL-379.0 ppm565.1 mg/m355.0 ppm393.4 mg/m333.0 ppm236.0 mg/m38.3 ppm59.4 mg/m34.2 ppm30.0 mg/m3Highest non-lethal concentrationin the rat[Dost et al. 1970]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; NR – not recommended due to insufficient data; ppm – parts per million3References: NAS [2010b]4*Values based on analogy with chlorine pentafluoride5External Review Draft

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12 

## 2.2 Animal Toxicity Data 1

2

Bromine pentafluoride is corrosive to eyes, mucous memb ranes, respiratory tract and exposed skin. No deaths 3

were reported in rats exposed to bromine pentafluorid e at 500 ppm for 40 minutes, or to 1000 ppm for 20 minutes 4



### [Dost et al. 1968] . The impact of exposure scenario on toxicity a ppears to be large, at least in this exposure 5

duration, since slightly longer durations resulted in very high lethality. Exposure to 500 ppm for 60 minutes 6

resulted in 95% mortality, and 12/12 rats died after e xposure to 1000 ppm for 25 minutes [Dost et al. 1968]. 7

Because of the apparently large impact of exposure dura tion, with large implications of small differences in 8

measurements or between studies, it would be useful to have additional supporting studies on bromine 9

pentafluoride. In the absence of additional studies, these data were considered insufficient for derivation of an 10

IDLH value. 11

12

The toxicity of halogen fluorides appears to be consiste nt with their relative reactivity. The mechanism of 13

toxicity is the same as that of the other halogen causing lo calized irritation and tissue damage at the site of contact 14

[AEGL 2010b]. In studies with rats , one found no lethality after exposure to 500 ppm bromine pentafluoride for 15

30 minutes [Dost et al. 1970], while Darmer et al. [1972] reported a 30-minute LC 50 value of 194 ppm for 16

chlorine pentafluoride. This suggests that bromine pentafluor ide is less toxic than chlorine pentafluoride. Dost et 17

al. [1970] also found similar signs of toxicity for chlorine trifluroide and bromine pentafluoride. There was 18

however, a greater severity of respiratory tract damage following bromine pentafluoride exposure, but this may 19

have been due to the somewhat higher concentrations test ed for this chemical (e.g., 500 ppm vs. 400 ppm). Based 20

on these considerations and the limited empirical data fo r bromine pentafluoride, this assessment uses chlorine 21

pentafluoride as a surrogate. 22

23

LC 50 data and information on nonlethal effects of chlorine pentafluoride are available in multiple species, with the 24

results showing respiratory and ocular irritation, leading to edema and tissue destruction at lethal levels [Darmer 25

et al. 1972; MacEwen and Vernot 1972, 1973]. In monkeys, dogs, rats and mice, sensory irritation and reversible 26

mild lung congestion were observed following chlorine pentafluoride exposures to 30 ppm for 10 minutes, 20 27

ppm for 30 minutes or 10 ppm for 60 minutes [MacEwen and Vernot 1972, 1973]. Table 4 summarizes the LC 28

data, while Table 5 summarizes non-lethal data, presented in animal studies and provides 30-minute equivalent 29

derived values for chlorine pentafluoride. 30

31External Review Draft

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13 

## 2.3 Human Data 1

2

No human toxicity data were located. 3

4



## 2.4 Summary 5

6

Inadequate toxicity data were available for bromine pentaf luoride. The data on chlorine pentafluoride are used to 7

derive an IDLH value for bromine pentafluoride because their structures, reaction mechanisms, and potencies are 8

similar. Therefore, deriving an IDLH value based on the toxicity data for chlorine pentafluoride is appropriately 9

health-protective. In the absence of adequate hum an data, the IDLH value is based on potentially escape10

impairing effects including severe respiratory irritation in multiple species [MacEwen and Vernot 1972]. Test 11

animals (i.e., monkey, dog, mouse, and rat) exposed to chlorine pentafluoride at concentrations ranging from 10 12

to 30 ppm for durations up to 30 minutes experienced immedi ate salivation, eye irritation, lacrimation, rhinorrhea 13

and respiratory irritation. More specifically, exposur es to 30 ppm chlorine pentafluoride for 10 ppm was 14

associated with severe respiratory irritation, which is c onsidered escape-impairing. Duration adjusting yielded a 15

30-minute equivalent value of 17.3 ppm. Application of a composite uncertainty factor to account for adjusting 16

from an escape-impairing effect, interspecies differences and human variability results in an IDLH value of 1.7 17

ppm for chlorine pentafluoride. 18External Review Draft

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policy.

14 

## 3.0 References 1

2

ACGIH (American Conference of Gove rnmental Industrial Hygienists) [ 2014]. Annual TLVs® (Threshold Limit 3

Values) and BEIs® (Biological Exposure Indices) booklet . Cincinnati, OH: ACGIH Signature Publications. 4

5

AIHA [2006]. AIHA Emergency Response Planning (ERP) Committee procedures and responsibilities. Fairfax, 6

VA: American Industrial Hygiene Association. [https://www.aiha.org/get7

involved/AIHAGuidelineFoundation/EmergencyResponseP lanningGuidelines/Documents/ERP-SOPs2006.pdf]. 8

Date accessed: March 17, 2014. 9

10

AIHA (American Industrial Hygiene Association) [2009]. AIHA Emergency Response Planning (ERP) 11

Committee procedures and responsibilities. Fairfax, VA: American Industrial Hygiene Association. 12

13

AIHA (American Industrial Hygiene Association) [2010] . Emergency response planning guidelines (ERPG) and 14

workplace environmental exposure levels (WEEL) handbo ok. Fairfax, VA: American Industrial Hygiene 15

Association Press. 16

17

AIHA [2010a]. AIHA Emergency Response Planning (ERP) Committee procedures and responsibilities. Fairfax, 18

VA: American Industrial Hygiene Association. 19

20

AIHA [2010b]. Emergency response planning guidelines (E RPG) and workplace environmental exposure levels 21

(WEEL) handbook. Fairfax, VA: American Industrial Hygiene Association Press 22

23

Darmer KI Jr., Haun CC, Mac Ewen JD [1972]. The acute inhalation toxicology of chlorine pentafluoride. Hyg 24

Assoc J 33 (10):661–668. 25

26

Dost FN, Reed DJ, Finch A, Wang CH [1968]. Meta bolism and pharmacology of inorganic and fluorine 27

containing compounds. AMRL-TR-67-224, AD 681 161, Availa ble from National Technical Information Center, 28

Springfield, VA. 29

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Dost FN, Reed DJ, Cooper TD, Wang CH [1970]. Fluorine distribution in rats following acute intoxication with 31

nitrogen and halogen fluorides and with sodium fluoride. Toxicol Appl Pharmacol 17 :573–584. 32

33

HSDB (Hazardous Substances Data Bank) [2014]. [http://to xnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB]. Date 34

accessed: March 17, 2014. 35

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IFA (Institut für Arbeitsschutz der Deutschen Gesetzli chen Unfallversicherung) [2014]. GESTIS: database on 37

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[http://gestis-en.itrust.de/nxt/gateway.dll?f=templates&f n=default.htm&vid=gestiseng: sdbeng]. Date accessed: 39

March 17, 2014. 40

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information quality guidelines. It has not been formally di sseminated 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.

15 MacEwen JD, Vernot EH [1972]. Toxic hazards research un it annual technical report. Wright-Patterson Air Force 1

Base, OH: Aerospace Medical Research Laboratory, Ai r Force Systems Command, Report No. AMRL-TR-72-62, 2

NTIS AD755-358. 3

4

MacEwen JD, Vernot EH [1973]. Toxic hazards research un it annual technical report. Wright-Patterson Air Force 5

Base, OH: Aerospace Medical Research Laboratory, Ai r Force Systems Command, Report No. AMRL-TR-73-83, 6

NTIS AD771-025. 7

8

NAS (National Academy of Science) [2001]. Standing operating procedures for developing Acute Exposure 9

Guidelines Levels for hazardous chemicals. NAS, National Research Council (NRC), Committee on Toxicology, 10

Subcommittee on Acute Exposure Gu ideline Levels. National Academy Press: Washington, DC. IBSN: 0-309- 11

07553-X. [http://www.epa.gov/oppt/aegl/pubs/sop. pdf]. Date accessed : March 17, 2014. 12

13

NAS (National Academy of Sciences) [2010a]. Interim Acute Exposur e Guideline Levels (AEGLs) for chlorine 14

p entafluoride (CAS No. 13637-63-3). NAS, National Research Council (NRC), Committee on Toxicology, 15

Subcommittee on Acute Exposure Guideline Leve ls. National Academy Press: Washington, DC. 16

[ http://www.epa.gov/oppt/aegl/pubs/chlorine_pentafluorid e_interim_ornl_src_may2010c.pdf]. Date accessed: 17

March 17, 2014. 18

19

NAS (National Academy of Sciences) [2010b]. Interim Ac ute Exposure Guideline Levels (AEGLs) for bromine 20

pentafluoride (CAS No. 7789-30-2). NAS, National Research Council (NRC), Committee on Toxicology, 21

Subcommittee on Acute Exposure Guideline Leve ls. National Academy Press: Washington, DC. 22

[http://www.epa.gov/oppt/aegl/pubs/bromine_pentafluoride_ interim_ornl_apr2010c.pdf]. Date accessed: March 23

17, 2014. 24

25

NIOSH (National Institute for Occupational Safety an d Health) [2004]. NIOSH respirator selection logic. 26

Cincinnati, OH: U.S. Department of Health and Huma n Services, Centers for Disease Control and Prevention, 27

National Institute for Occupati onal Safety and Health, DHHS (N IOSH) Publication No. 2005-100. 28

[http://www.cdc.gov/niosh/docs/2005-100/pdfs/2005-100. pdf]. Date accessed: March 17, 2014. 29

30

NIOSH [2013]. NIOSH Current Intelligence Bulletin 66: Deri vation of Immediately Dangero us to Life or Health 31

(IDLH) values. Cincinnati, OH: U.S. Department of Hea lth and Human Services, Centers for Disease Control and 32

Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-100. 33

[http://www.cdc.gov/niosh/docs/2014-100/pdfs/2014- 100.pdf]. Date accessed : March 17, 2014. 34

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Human Services, Centers for Disease Control and Preven tion, National Institute for Occupational Safety and 37

Health, DHHS (NIOSH) Publication No. 2005-149. [http://www.cdc.gov/niosh/npg/]. Date accessed: March 17, 38

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accessed: March 17, 2014. 42

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

information quality guidelines. It has not been formally di sseminated 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.

16 OSHA (Occupational Safety and Health Administration) [2014]. Occupational Safety and Health Standards. 29 1

CFR 1910. Subpart Z -- Toxic and Hazardous Substances. OSHA; Washington, DC 2

[http://www.osha.gov/pls/oshaweb/owadisp.show_docum ent?p_table=standards&p_i d=9992]. Date accessed: 3

August 1, 2014. 4

5

ten Berge WF, Zwart A, Appelman LM [1986]. Concentrati on-time mortality response relationship of irritant and 6

systematically acting vapours and gases. J Haz Mat 13 :301–309. 7

8

USEPA (U.S. Environmental Protection Agency) [2014]. Integrated Risk Information System (IRIS). 9

[http://www.epa.gov/IRIS/]. Date accessed: Marc h 17, 2014. 10

11

Weinberg MS, Goldhamer RE [1967]. Pharmacology and metabolism of Compound A. ADA286095; Available 12

from National Technical Information Service, Springfield, VA. 13

14