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policy. 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



## D IKETENE 15

16

17



## [CAS N O



## . 674-82-8] 18

19

20

21

22

23

24

Department of Health and Human Services 25

Centers for Disease Control and Prevention 26

National Institute for Occupa tional Safety and Health 27

28

29External Review Draft

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policy. 

## Disclaimer 1

2

Mention of any company or product does not constitute endorsement by the National Institute for Occupational 3

Safety and Health (NIOSH). In add ition, citations to Web sites extern al to NIOSH do not constitute NIOSH 4

endorsement of the sponsoring organizations or thei r programs or products. Furthermore, NIOSH is not 5

responsible for the content of these Web sites. 6

7



## Ordering Information 8

9

To receive this document or information about other o ccupational safety and health topics, contact NIOSH: 10

11

Telephone: 1-800-CDC-INFO (1-800-232-4636) 12

TTY: 1-888-232-6348 13

E-mail: cdcinfo@cdc.gov 14

Or visit the NIOSH Web site: www.cdc.gov/niosh 15

16

For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting www.cdc.gov/niosh/eNews. 17

18

DHHS (NIOSH) Publication No. XXX 19

20

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policy. 

## 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 IDLH value for diketene (CAS # 674-82-8). The scientific 28

basis, toxicologic data and risk assessment approach u sed to derive the IDLH valu e are summarized to ensure 29

transparency and scientific credibility. 30

31

John Howard, M.D. 32

Director 33

National Institute for Occupa tional Safety and Health 34External Review Draft

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policy. Centers for Disease Control and Prevention 1External Review Draft

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policy. 

## Table of Contents 1

FOREWORD

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

ABBREVIATIONS

............................................................................................................................... ........................ VI 3

GLOSSARY

............................................................................................................................... .................................. VII 4

ACKNOWLEDGMENTS

............................................................................................................................... .............. XI 5

1.0 INTRODUCTION

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

1.1 O VERVIEW OF THE IDLH V ALUE FOR D IKETENE

..................................................................................................................... 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

............................................................................................................................... .................. 6 11

4.0 SUMMARY

............................................................................................................................... ......................... 6 12

5.0 REFERENCES

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

14

15

16

17

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policy. 

## 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

IDLH immediately dangerous to life or health 11

kPa kilopascal 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 33External Review Draft

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

policy. 

## 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 levels used during rare events or single once-in-a8

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

threshold exposure limits are designed to protect the ge neral 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 duration (24 hours or less) of the human population 14

(including sensitive subgroups) that is likely 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 limitations 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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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. 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 sign 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 e xposure is likely to cause death or imme diate 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 concentr ation 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 concentration of a substa nce 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 the deaths resulting from acute toxicity studies. May 33

also be used in lethality threshold to describe the point of sufficient subs tance concentration to begin to cause 34

death. 35

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

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

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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. Mode of Action : The sequence of significant events and processes that describes how a substance causes a toxic 1

outcome. Mode of action is distinguished from the more detailed mechanism of action, which implies a more 2

detailed understanding on a molecular level. 3

No Observed Adverse Effect Level (NOAEL) : The highest tested dose or concen tration of a substance that has 4

been reported to cause no harmful (adverse) health effects in people or animals. 5

Occupational Exposure Limit (OEL) : Workplace exposure recommendations developed by governmental 6

agencies and non-governmental organizations. OELs ar e intended to represent the maximum airborne 7

concentrations of a chemical substance below wh ich workplace exposures should not cause adverse health 8

effects. OELs may apply to ceiling, short-term (STELs), or time-weighted average (TWA) limits. 9

Peak Concentration : Highest concentration of a substance record ed during a certain period of observation. 10

Permissible Exposure Limit (PEL) : Occupational exposure limits deve loped by OSHA (29 CFR 1910.1000) or 11

MSHA (30 CFR 57.5001) for allowable occupational air borne exposure concentra tions. PELs are legally 12

enforceable and may be designated as ceiling, STEL, or TWA limits. 13

14

Point of Departure (POD) : The point on the dose–response curve from which dose extrapolation is initiated. 15

This point can be the lower bound on dose for an estima ted incidence or a change in response level from a 16

concentration-response model (BMC), or it can be a NOAEL or LOAEL for an observed effect selected from 17

a dose evaluated in a health e ffects or toxicology study. 18

RD 50 : The statistically determined concentration of a substa nce in the air that is est imated to cause a 50% (one 19

half) decrease in the respiratory rate. 20

Recommended Exposure Limit (REL) : Recommended maximum exposure limit to prevent adverse health 21

effects based on human and animal studies and establishe d for occupational (up to 10-hour shift, 40-hour 22

week) inhalation exposure by NIOSH. RELs may be designated as ceiling, STEL, or TWA limits. 23

Short-Term Exposure Limit (STEL) : A worker’s 15-minute time-weighted average exposure concentration that 24

shall not be exceeded at any time during a work day. 25

Target Organ : Organ in which the toxic injury manifests in terms of dysfunction or overt disease. 26

Threshold Limit Values (TLVs®) : Recommended guidelines for occupational exposure to airborne 27

contaminants, published by the American Conference of Governmental Industrial Hygienists (ACGIH). TLVs 28

refer to airborne concentrations of chemical subs tances and represent conditions under which it is believed 29

that nearly all workers may be rep eatedly exposed, day after day, over a working lifetime, without adverse 30

effects. TLVs may be designated as ceiling, short-term (STELs), or 8-hr TWA limits. 31

Time-Weighted Average (TWA) : A worker’s 8-hour (or up to 10-hour) time-weighted average exposure 32

concentration that shall not be exceeded during an 8-hour (or up to 10-hour) work shift of a 40-hour week. 33

The average concentration is weighted to take into ac count the duration of different exposure concentrations. 34

Toxicity : The degree to which a substance is able to ca use an adverse effect on an exposed organism. 35

36

Uncertainty Factors (UFs) : Mathematical adjustments applied to th e POD when developing IDLH values. The 37

UFs for IDLH value derivation are determined by consid ering the study and effect used for the POD, with 38

further modification based on the overall database. 39External Review Draft

May 2015

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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. Workplace Environmental Exposure Levels (WEELs) : Exposure levels developed by the American Industrial 1

Hygiene Association (AIHA) that provide guidance for protecting most workers from adverse health 2

effects related to occupational chemical exposures expressed as a TWA or ceiling limit. 3External Review Draft

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Safety and 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

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

25External Review Draft

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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. 

## 1.0 Introduction 1



### 1.1 Overview of the IDLH Value for Diketene 2

3

IDLH Value: 7.6 ppm 4

5

Basis for IDLH Value: The IDLH value for diketene is based on the rat BMCL 05 of 181 ppm for lethality in a 1- 6

hour exposure [Katz 1987]. The duration adjusted BMCL 05 for a 30-minute exposure is 228 ppm. A composite 7

uncertainty factor of 30 was applied to account for extrapol ation from a lethal concentration threshold in animals, 8

animal to human differences, human variability, and da tabase uncertainties, resulting in an IDLH value of 7.6 9

ppm

. 10

11



### 1.2 Purpose 12

13

This IDLH Value Profile presents (1) a brief summary of technical data associated with acute inhalation 14

exposures to diketene and (2) the rati onale behind the Immediately Dangerous to Life or Health (IDLH) value for 15

diketene. IDLH values are developed based on the scientific rationale and logic outlined in the NIOSH Current 16

Intelligence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or Health (IDLH) values [NIOSH 17

2013]. As described in CIB 66, NIOSH performs in-depth lite rature searches to ensure that all relevant data from 18

human and animal studies with acute exposures to the subs tance are identified. Information included in CIB 66 on 19

the literature search includes pertinent databases, key terms, and guides for evaluating data quality and relevance 20

for the establishment of an IDLH value. The information that is identified in the in -depth literature search is 21

evaluated with general considerations that include description of studies (i.e., species, study protocol, exposure 22

concentration and duration), health endpoint evaluated, and critical eff ect levels (e.g., NOAELs, LOAELs, LC 50 23

values). For diketene, the in-depth literatu re search was conducted through February 2014. 24



### 1.3 General Substance Information 25

26

Chemical: Diketene 27

CAS No: 674-82-8 28

Synonyms: Acetyl ketene; 4-Methylene-2-oxeta none; But-3-en-3-olide; Dimer ketene * 29

Chemical category: Lactones † 30External Review Draft

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policy. 1

Structural formula: 2

3

4

5

6

Table 1 highlights selected physiochemical properties of diketene relevant to IDLH conditions. Table 2 provides 7

alternative exposure guidelines for diketene. Table 3 summarizes the Acute Exposure Guidelines Level (AEGL) 8

values for diketene. 9

10

Table 1: Physiochemical Properties of Diketene 11

12

Property Value

Molecular weight 84.04 ‡

Chemical formula C 4 H 4 O 2 Description Colorless to light-colored liquid

Odor Pungent

Odor Threshold Not available

UEL 11.7% †

LEL 2% †

Vapor pressure 1.07 kPa at 20°C (68°F) ‡

Flash point 34°C (93.2°F) ‡

Ignition temperature 275°C (527°F) †

Solubility Hydrolysis †

Abbreviation: °C – Celsius; °F – Fahrenheit; kPa – kilopascal; LEL – lower explosive limit; UEL – upper explosive limit 13

* NLM [2014] 14

† IFA [2014] 15

‡ HSDB [2014] 16

17

Table 2: Alternative Exposure Guidelines for Diketene 18

19

Organization Value

Original (SCP) IDLH value None

NIOSH REL Not available

OSHA PEL [2014] Not available

ACGIH TLV [2014] Not available

AIHA ERPG [2010] ERPG-1: 1 ppm; ERPG-2: 5 ppm; ERPG-3: 20 ppm

AIHA WEEL [2010] Not available

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 20

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 21

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 22

REL – recommended exposure limit; SCP – Standard Completion Program; WEEL – workplace e nvironmental exposure level 23 O CH 2 OExternal Review DraftMay 20153This 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.Table 3: AEGL Values for Diketene12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 NR NR NR NR NR Insufficient dataAEGL-2 11 ppm38.0 mg/m37.7 ppm26.0 mg/m36.0 ppm21.0 mg/m31.5 ppm5.2 mg/m30.77 ppm2.6 mg/m3AEGL-3 reduced byfactor of 3AEGL-3 33.0 ppm110.0 mg/m323.0 ppm79.0 mg/m318.0 ppm62.0 mg/m34.5 ppm15.0 mg/m32.3 ppm7.9 mg/m3BMCL05for lethality[Katz 1987]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; NR – not recommended due to insufficient data; ppm – parts per million3*References: NAS [2008]4External Review Draft

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

policy. 

## 2.0 Animal Toxicity Data 1

2

The available acute lethality database for diketene is limited to one rat study [Katz 1987] and one multi-species 3

study [Wooster et al. 1947]. Katz [1987] exposed rats to 0, 250, 500, or 750 ppm diketene for one hour with a 14- 4

day post-exposure period. Clinical signs providing evid ence of severe irritation included excessive tearing and 5

gasping at all exposure levels, and porphyrin discharge fro m the nose at the two highest concentrations. No gross 6

lesions were identified during necropsy. Mortality occurred at all concentrations except 250 ppm. Modeling of the 7

mortality responses yielded an LC 50 of 612 ppm. The lethality threshol ds were estimated using benchmark 8

concentration modeling, resulting in a BMCL 05 (lower bound estimate of the concentration associated with a 9

benchmark response of 5%) of 181 ppm for lethality. The 30-minute duration adjusted equivalent value of the 10

BMCL 05 is 228 ppm. 11

12

Wooster et al. [1947] exposed mice to 194, 580, or 870 ppm diketene in an acetone solvent for 10 minutes with a 13

15-day post-exposure period. Clinical signs were not repor ted. Pathological examination revealed proteinaceous 14

edematous fluid in the alveoli and in the perivascula r connective tissue of the bronchi. Only the highest 15

concentration (870 ppm) resulted in mortality, one mouse di ed. Wooster et al. [1947] also exposed guinea pigs to 16

194 ppm diketene for 10 minutes with a 15-day post-e xposure observation period. No clinical signs were 17

reported. The authors implied that the gross pathology fi ndings indicated pulmonary edema as the cause of death. 18

All guinea pigs in 194 ppm group died. Wooster et al. [1947] also exposed rats and ra bbits to 194 ppm diketene 19

for 10 minutes. No lethality, clinical signs, or gross pathology findings were noted. 20

21

Table 4 summarizes the LC data identified in animal st udies and provides 30-minute equivalent derived values for 22

diketene. Information in these tables includes species of test animals, toxicological metrics (i.e., LC, NOAEL, 23

LOAEL), adjusted 30-minute concentration, and the justifi cation for the composite uncertainty factors applied to 24

calculate the derived values. 25

26External Review DraftMay 20155This 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.Table 4: Lethal Concentration Data for Diketene12Reference Species(sex)LC50(ppm)Other lethalityconcentration(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Katz [1987] Rats (male and female) 612 -- 60 771 30±25.7Katz [1987] Rats 370^60 466 30+15.5Katz [1987] Rats 181‡60 228 30+7.63Abbreviation: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 were7available, therefore the default 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-minute concentration divided by the composite uncertainty factor.9±Composite uncertainty factor to account for adjustment of LC50values to LC01values, use of lethal concentration threshold in animals, interspecies differences and10human variability.11^LC1012+Composite uncertainty factor to account for adjustment from a lethal concentration threshold inanimals, interspecies differences, human variability and and database13uncertainties.14‡Lower bound estimate of the concentration associated with a benchmark response of 5% for lethality.15161718External Review Draft

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

policy. 

## 3.0 Human Data 1

Only very limited information on human effects and eff ect levels was available. Occupational exposure to 2

diketene was reported to cause mild irritation to the conjunctiva and mucosa of the nose and throat at a 3

concentration of 0.58 ppm for one minute [Fel’dman 1967] . These studies were not appropriate for an IDLH 4

value derivation due to the very short duration and limited details available. 5



## 4.0 Summary 6

The IDLH value for diketene is based on the rat BMCL 05 of 181 ppm for lethality in a 1-hour exposure [Katz 7

1987]. The duration adjusted BMCL 05 for a 30-minute exposure is 228 ppm. Application of composite 8

uncertainty factor of 30 to account for extrapolation from a lethal concentration threshold in animals, animal to 9

human differences, human variability, and database uncerta inties, including uncertainty regarding the threshold 10

for severe irritation, yielded an IDLH value of 7.6 ppm

. 11External Review Draft

May 2015

7

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. 

## 5.0 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 (American Industrial Hygiene Association) [2009]. AIHA Emergency Response Planning (ERP) 6

Committee procedures and responsibilities. Fairfax, VA: American Industrial Hygiene Association. 7

8

AIHA (American Industrial Hygiene Association) [2010] . Emergency response planning guidelines (ERPG) and 9

workplace environmental exposure levels (WEEL) handbo ok. Fairfax, VA: American Industrial Hygiene 10

Association Press. 11

12

Fel’dman YG [1967]. The experimental determination of the maximum permissible one-time concentration for 13

diketene in the atmosphere. Hygiene Sanit 32 :9–14. 14

15

HSDB [2014]. Hazardous Substances Data Bank [http://toxn et.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB1]. Date 16

accessed: August 1, 2014. 17

18

IFA (Institut für Arbeitsschutz der Deutschen Gesetzli chen Unfallversicherung) [2014]. GESTIS: database on 19

hazardous substances. 20

[http://gestis-en.itrust.de/nxt/gateway.dll?f=templates&f n=default.htm&vid=gestiseng: sdbeng]. Date accessed: 21

March 17, 2014. 22

23

Katz GV [1987]. Acute inhalati on toxicity and one-hour LC 10 value of diketene in the rat. Rochester, NY: 24

Eastman Kodak Company. Study No. TX-86-265. 25

26

NAS (National Academy of Sciences) [2008]. Interim Ac ute Exposure Guideline Levels (AEGLs) for diketene, 27

CAS No. 674-82-8. Washington, DC: National R esearch Council, Commission of Life Sciences. 28

[http://www.epa.gov/oppt/aegl/pubs/diketene_interim_ornl_j un_2008c.pdf]. Date acce ssed: August 1, 2014. 29

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NIOSH (National Institute for Occupational Safety an d Health) [2004]. NIOSH respirator selection logic. 31

Cincinnati, OH: U.S. Department of Health and Huma n Services, Centers for Disease Control and Prevention, 32

National Institute for Occupati onal Safety and Health, DHHS (N IOSH) Publication No. 2005-100. 33

[http://www.cdc.gov/niosh/docs/2005-100/pdfs/2005-100. pdf]. Date accessed: March 17, 2014. 34

35

NIOSH [2013]. NIOSH Current Intelligence Bulletin 66: Deri vation of Immediately Dangero us to Life or Health 36

(IDLH) Values. Cincinnati, OH: U.S. Department of H ealth and Human Services, Centers for Disease Control 37

and Prevention, National Institute fo r Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014- 38

100. 39

[http://www.cdc.gov/niosh/docs/2014-100/pdfs/2014- 100.pdf]. Date accessed : March 17, 2014. 40

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NIOSH [2014]. NIOSH pocket guide to chemical hazards . Cincinnati, OH: U.S. Department of Health and 42

Human Services, Centers for Disease Control and Preven tion, National Institute for Occupational Safety and 43

Health, DHHS (NIOSH) Publication No. 2005-149. [http://www.cdc.gov/niosh/npg/]. Date accessed: March 17, 44

2014. 45

46External Review Draft

May 2015

8

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. NLM (National Library of Medicine) [2014]. ChemIDplus lite [http://chem.sis.nlm.ni h.gov/chemidplus/]. Date 1

accessed: August 1, 2014. 2

3

OSHA (Occupational Safety and Health Administration) [2014]. Occupational Safety and Health Standards. 29 4

CFR 1910. Subpart Z -- Toxic and Hazardous Substances. OSHA; Washington, DC 5

[http://www.osha.gov/pls/oshaweb/owadisp.show_docum ent?p_table=standards&p_i d=9992]. Date accessed: 6

August 1, 2014. 7

8

ten Berge WF, Zwart A, Appelman LM [1986]. Concentra tion-time mortality response relationship of irritant and 9

systematically acting vapors and gases. J Haz Mat 13 :301–309. 10

11

Wooster HA, Lushbaugh CC, Redemann CE [1947]. The inhala tion toxicity of ketene and ketene dimer. J Ind 12

Hyg Toxicol 29 :56–57. 13