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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. 1

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## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

9

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### FOR 11

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13

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## C HLOROACETYL 

## C HLORIDE 15

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## [CAS N O



## . 79-04-9] 19

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25

Department of Health and Human Services 26

Centers for Disease Control and Prevention 27

National Institute for Occupa tional Safety and Health 28

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## 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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## Foreword 1

2

Chemicals are a ubiquitous component of the modern wo rkplace. Occupational exposures to chemicals have the 3

potential to adversely affect the health and lives of workers. Acute or short-term exposures to high concentrations 4

of some airborne chemicals have the ability to quickly overwhelm workers, resulting in a spectrum of undesirable 5

health outcomes that may inhibit the ability to escape from the exposure envi ronment (e.g., irritation of the eyes 6

and respiratory tract or cognitive impairment), cause severe irreversible effects (e.g., damage to the respiratory 7

tract or reproductive toxicity), and in extreme cases, cause death. Airborne concentrations of chemicals capable 8

of causing such adverse health effects or of impeding escape from high-risk conditions may arise from a variety of 9

non-routine workplace situations , including special wo rk procedures (e.g., in confined spaces), industrial 10

accidents (e.g., chemical spills or explosions), and chemical releases into the community (e.g., during 11

transportation incidents or other uncontrolled-release scenarios). 12

13

The “immediately dangerous to life or health air concen tration values (IDLH values)” developed by the National 14

Institute for Occupational Safety a nd Health (NIOSH) characterize these high-risk exposure concentrations and 15

conditions [NIOSH 2013]. IDLH values are based on a 30-minute exposure duration and have traditionally 16

served as a key component of the decision logic for the selection of respiratory protection devices [NIOSH 2004]. 17

Occupational health professionals have employed these values beyond their initial purpose as a component of the 18

NIOSH Respirator Selection Logic to assist in developi ng Risk Management Plans for non-routine work practices 19

governing operations in high-risk envi ronments (e.g., confined spaces) and the development of Emergency 20

Preparedness Plans. 21

22

The approach used to derive IDLH values for high priority chemicals is outlined in the NIOSH Current 23

Intelligence Bulletin (CIB) 66: Derivation of Immediately Da ngerous to Life or Health Values [NIOSH 2013]. 24

CIB 66 provides 1) an update on the scientific basis a nd risk assessment methodology used to derive IDLH 25

values, 2) the rationale and derivati on process for IDLH values, and 3) a demonstration of the derivation of 26

scientifically credible IDLH values using available data resources. 27

28

The purpose of this technical report is to present the IDLH value for chloroacetyl chloride (CAS # 79-04-9). The 29

scientific basis, toxicologic data and risk assessment appr oach used to derive the ID LH value are summarized to 30

ensure transparency and scientific credibility. 31

32

John Howard, M.D. 33

Director 34

National Institute for Occupa tional Safety and Health 35External Review Draft

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Health. It does not represent and should not be construed to represent any agency determination or policy. Centers for Disease Control and Prevention 1External Review Draft

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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 of Contents 1

FOREWORD

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

ABBREVIATIONS

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

GLOSSARY

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

ACKNOWLEDGMENTS

............................................................................................................................... ............... X 5

1.0 INTRODUCTION

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

1.1 IDLH V ALUE FOR C HLOROACETYL C HLORIDE

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

1.2 P URPOSE

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

1.3 G ENERAL S UBSTANCE I NFORMATION

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

2.0 ANIMAL TOXICITY DATA

............................................................................................................................. 5 10

3.0 HUMAN DATA

............................................................................................................................... .................. 9 11

4.0 SUMMARY

............................................................................................................................... ......................... 9 12

REFERENCES

............................................................................................................................... .............................. 10 13

14

15

16

17

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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

HCl hydrochloric acid 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 33External Review Draft

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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 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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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

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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 effects 38

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

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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

24

25

26

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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 Ch loroacetyl Chloride 2

3

IDLH Value: 1.3 ppm (66 mg/m 3 ) 4

5

Basis for IDLH Value: The IDLH value for chloroacetyl chloride is based on potentially escape-impairing 6

effects including clinical signs of severe ocular and resp iratory irritation in rats exposed to 32 ppm for one hour 7

[Dow 1986]. The equivalent 30-minut e exposure duration value is 40 ppm. Applying a composite uncertainty 8

factor of 30 to account for extrapolation from a potentially escape impairing effect in animals, animal to human 9

differences and human variability, result s in an IDLH value of 1.3 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 chloroacetyl chloride a nd (2) the rationale behind the Immediat ely Dangerous to Life or Health 15

(IDLH) value for chloroacetyl chloride. IDLH values are developed based on the scientific rationale and logic 16

outlined in the NIOSH Current Intellig ence Bulletin (CIB) 66: Derivation of Immediately Dangerous to Life or 17

Health (IDLH) values [NIOSH 2013]. As described in CI B 66, NIOSH performs in-depth literature searches to 18

ensure that all relevant data from human and animal st udies with acute exposures to the substance are identified. 19

Information included in CIB 66 on the literature search includes pertinent databases, key terms, and guides for 20

evaluating data quality and relevance for the establishment of an IDLH value. The information that is identified 21

in the in-depth literature sear ch is evaluated with general considerations that include description of studies (i.e., 22

species, study protocol, exposure concentration and duration) , health endpoint evaluated, and critical effect levels 23

(e.g., NOAELs, LOAELs, LC 50 values). For chloroacetyl chloride, the in-depth literature search was conducted 24

through February 2014. 25

26



### 1.3 General Substance Information 27

28

Chemical: Chloroacetyl chloride 29

CAS No: 79-04-9 30

Synonyms: Chloroacetic acid chloride; Chloroacetic chloride; Monochloroacetyl chloride * 31

Chemical category: Substituted carboxylic acid halides; Organic chlorine compounds † 32External Review Draft

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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. Structural formula: 1

2

3

4

5

6

Table 1 highlights selected physiochemical properties of ch loroacetyl chloride relevant to IDLH conditions. Table 7

2 provides alternative exposure guidelines for chloroacet yl chloride. Table 3 summarizes the Acute Exposure 8

Guidelines Level (AEGL) valu es for chloroacetyl chloride. 9

10

Table 1: Physiochemical Properties of Chloroacetyl Chloride 11

12

Property Value

Molecular weight 112.94 ‡

Chemical formula C 2 H 2 Cl 2 O

Description Colorless to yellow liquid

Odor Pungent

Odor Threshold Strongly detectable at 0.140 ppm;

barely detectable at 0.023 ppm;

undetectable at 0.011 ppm, ‡

UEL Not available §

LEL Not available §

Vapor pressure 25.2 mmHg at 25°C (77°F) ‡

Flash point Non-combustible †

Ignition temperature Non-combustible †

Solubility Violent decomposition in water †

Abbreviation: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 13

* NLM [2014] 14

† IFA [2014] 15

‡ HSDB [2014] 16

§ OSHA [2014] 17 Cl

Cl OExternal Review Draft

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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 2: Alternative Exposure Guid elines for Chloroacetyl Chloride 1

2

Organization Value

Original (SCP) IDLH value [NIOSH 2014] None

NIOSH REL [2014] 0.05 ppm (0.23 mg/m 3 ), TWA

OSHA PEL [2014] 0.05 ppm (0.23 mg/m 3 ), TWA 8-hour

ACGIH TLV [2014] 0.05 ppm (0.23 mg/m 3 ), TWA

0.15 ppm (0.69 mg/m 3 ) STEL

AIHA ERPG [2010] ERPG-1: 0.05 ppm

ERPG-2: 0.5 ppm

ERPG-3: 10 ppm

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 Progr am; STEL – short-term exposur e limit; TWA – time-weighted 6

average; WEEL – workplace environmental exposure level 7

8

9External Review DraftMarch 20154This 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 Chloroacetyl Chloride12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 0.04 ppm0.19 mg/m30.04 ppm0.19 mg/m30.040 ppm0.19 mg/m30.04 ppm0.19 mg/m30.04 ppm0.19 mg/m3NOEL for conjunctivitis inrats [Dow 1982]AEGL-2 2.9 ppm13.0 mg/m32.0 ppm9.2 mg/m31.6 ppm7.4 mg/m30.40ppm1.8 mg/m30.20 ppm0.92 mg/m3NOEL for inability toescape due to eye irritationin rats [Dow 1986]AEGL-3 95.0 ppm440.0 mg/m366.0 ppm300.0 mg/m352.0 ppm240.0 mg/m313.0 ppm60.0 mg/m36.5 ppm30.0 mg/m3Threshold for lethality inmale rats [Dow 1986]Abbreviation: AEGL – acute exposure guideline levels; mg/m3– milligrams per cubic meter; min – minute; ppm – parts per million3*References: NAS [2007]4External Review Draft

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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

2

Chloroacetyl chloride decomposes in wa ter to produce chloroacetic acid and hydrochloric acid (HCl), releasing 3

heat in the process. Both chloroacetyl chloride and its hydrolysis products ar e irritants. Several modern studies 4

[Dow 1982, 1986] reported analytical concentrations substa ntially lower than nominal concentrations (analytical 5

concentrations about 25-50% of nominal). This difference has been attributed to both hydrolysis and incomplete 6

volatilization of the test chemical. Since the total concentr ation of irritant chemicals in the air (including HCl) 7

may have been higher than the anal ytical concentration of chloroacetyl chloride, use of the analytical 8

concentration is a conservative approach. In light of the difference between nominal and analytical 9

concentrations, the true concentrations (and associated LC 50 values) in some of the older acute studies may have 10

been lower than the reported nominal concentrations. 11

12

In a static-exposure study, Carpenter et al . [1949] reported an approximate 4-hour LC 50 value of 1,000 ppm in 13

rats. No further experimental resu lts were provided. Younger Labs [ 1969] exposed rats to “concentrated” 14

chloroacetyl chloride; all died within two hours. The exposure concentration was not specified, although 15

information suggested a saturated atmosphere (25,000 ppm at 20°C) [AIHA 2000]. Immediately upon exposure, 16

the rats showed signs of irritation in cluding pawing at the face and mouth, and tightly shut eyes. Within 10 17

minutes, rats had reddened eyes with nasal and salivary excretion and gasping, and within 30 minutes they had 18

opaque corneas, and death occurred after 90 (3/4 rats) or 120 (4/4) minutes. Severely hemorrhaged lungs were 19

seen at necropsy [Younger Labs 1969]. 20

21

Studies conducted by Dow Chemical Company in rats [Dow 1986] provide the most informative data for deriving 22

the IDLH value. F344 rats were exposed whole-body to 32, 208, 522, or 747 ppm chloroacetyl chloride for 1 23

hour, followed by observation for 14 days. Clinical signs observed during exposure included squinting and 24

lacrimation at all concentrations (32 to 747 ppm), a nd shallow or labored breathing at 208 ppm and higher. 25

Stress-related clinical signs were also observed at the higher concentrations; these included lethargy ( ≥ 208 ppm), 26

salivation, and stained eyes and face. Gross pathological examination of the rats that died during the 2-week post 27

exposure period showed lung and nasal tissue congestion. Death occurred only at 747 ppm, in 5/6 males and 1/6 28

females, yielding an LC 50 value of 645 ppm for males. The LC 50 value for females could not be calculated, but 29

was greater than 747 ppm. The effects at 32 ppm were c onsidered potentially escape impairing. Results in mice 30

and guinea pigs [Herzog 1959] support the determination that respiratory tract irritation is the key effect from 31

exposure to chloroacetyl chloride, but the results are lim ited by the use of a static exposure protocol and the 32External Review Draft

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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. absence of monitoring of analytical concentrations. Results from a 2-minute exposure study by Herzog [1959] 1

support the conclusion that the onset of irritation is rapid. 2

3

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

chloroacetyl chloride. Table 5 provides non-lethal data reported in animal studies with 30-minute equivalent 5

derived values. Information included in these tables includ es species of test animals, toxicological metrics (i.e., 6

LC, BMCL, NOAEL, LOAEL), adjusted 30-minute concentr ation, and the justification for the composite 7

uncertainty factors applied to calculate the derived values. 8

9External Review DraftMarch 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 4: Lethal ConcentrationData for Chloroacetyl Chloride12Reference Species(sex)LC50(ppm)LCLo(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Herzog [1959] Mouse 1,066 -- 120 1,69230‡56Dow [1986] Rat(female)-- 747 60 941 10±94Dow [1986] Rat(male)645 -- 60 81330‡273Abbreviation: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-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, interspeciesdifferences and human variability.10±Composite uncertainty factor toaccount for lethal concentration threshold in animals, interspecies differences and human variability.11121314External Review DraftMarch 20158This 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 Chloroacetyl Chloride12Reference Species(reference)NOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Dow [1986]+Rat -- 32 60 40 30±1.3Abbreviation: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 (Cn x t = k); noempirically 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-minute concentration divided by the composite uncertainty factor.7+Identified study is the primary basis of the IDLH value for chloroacetyl chloride.8±Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, interspecies differences, human variability and extrapolation to an escape-impairing effect.9External Review Draft

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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. 

## 3.0 Human Data 1

2

No reports of human deaths resulting from inhalation of chloroacetyl chloride were located. Exposure for an 3

undefined time period (likely a few minutes) to an air concentration of 0.011 ppm chloroacetyl chloride was 4

undetectable by odor; 0.023 ppm was “barely detectable,” and 0.14 ppm was considered a “strong” odor to an 5

industrial hygienist [Dow 1988a]. Ocular irritation w as not experienced at these concentrations, but 0.91 ppm 6

was painful to the eyes and cau sed lacrimation [Dow 1988a]. This study is not appropriate as the basis for an 7

IDLH value because insufficient information was provi ded about the exposure conditions, but the study does 8

provide information on the range of ex posure levels that are irritating. 9

10

The medical department of a chemical company repor ted that six workers who received “mild” inhalation 11

exposures of chloroacetyl chloride (exposures not stated) experienced dyspnea and cough, and that three workers 12

that received “moderate” inhalation exposu res had cyanosis a nd cough [Dow 1988b]. 13



## 4.0 Summary 14

15

Available human and animal data demonstrated the abilit y of chloroacetyl chloride to act as a potent irritant, 16

causing ocular and respiratory tract irritation, respiratory tract pathology and death depending on the exposure 17

concentration and duration. C oncentrations that induce potentially escape-im pairing and significant irritant effects 18

appear to be well below the estimated LC 50 values summarized in Table 4. Studies reporting non-lethal effects, 19

such as Dow [1988a], provide evidence that painful eye i rritation and lacrimation occurred in humans exposed to 20

0.91 ppm for an undisclosed duration. Dow [1986] reported significant irritation at 32 ppm as a LOAEL in rats. 21

Taking into account the potential for significant irrita nt effects at concentrations well below reported LC 50 values, 22

the LOAEL of 32 ppm in rats is an appropriate basis for deriving the IDLH value. Duration adjustment to a 30- 23

minute equivalent concentration yields a concentration of 40 ppm. Application of a composite uncertainty factor 24

to account for extrapolation from a potentially escape-impair ing effect in animals, animal to human differences 25

and human variability results in an IDLH value for chloroacet yl chloride of 1.3 ppm. This value is expected to 26

protect against both lethality and severe ocular and respiratory irritation that might impair escape. 27External Review Draft

March 2015

10

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. 

## References 1

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

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Dow (Dow Chemical Company) [1982]. Dow Chemical Company initial submission: chloroacetyl chloride: a 16

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(sanitized). Study report written by Henck JW, Nitschke KD, Jersey GC, et al., issued 6/28/82. Midland, MI: 18

Dow Chemical Company, NTIS/OTS 0536493, EPA Doc. #88-920002593S. 19

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Dow (Dow Chemical Company) [1986]. Chloroacetyl chlori de: an acute vapor inhalation study with rats. Final 21

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Dow (Dow Chemical Company) [1988a]. Subjective respon se to chloroacetyl chloride . February 18, 1988 memo 25

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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. National Institute for Occupati onal Safety and Health, DHHS (N IOSH) Publication No. 2005-100. 1

[http://www.cdc.gov/niosh/docs/2005-100/pdfs/2005-100. pdf]. Date accessed: March 21, 2014. 2

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[http://www.cdc.gov/niosh/docs/2014-100/pdfs/2014- 100.pdf]. Date accessed : March 21, 2014. 7

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