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1

2

3

4

5

6

7 IMMEDIATELY DANGEROUS TO LIFE OR HEALTH (IDLH) VALUE PROFILE

8

9

10

11 FOR

12

13

14 

15 METHYL ISOCYANATE

16

17

18

19 [CAS NO. 624-83-9] 

20

21

22

23

24

25

26 Department of Health and Human Services 

27 Centers for Disease Control and Prevention 

28 National Institute for Occupational Safety and Health 

29

30
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ii

1 Disclaimer

2

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

4 Safety and Health (NIOSH). In addition, citations to Web sites external to NIOSH do not constitute NIOSH 

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

6 responsible for the content of these Web sites. 

7

8 Ordering Information 

9

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

11

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

13 TTY: 1-888-232-6348 

14 E-mail: cdcinfo@cdc.gov 

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

16

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

18

19 DHHS (NIOSH) Publication No. XXX 

20

21
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iii

1 Foreword 

2

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

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

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

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

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

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

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

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

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

12 transportation incidents or other uncontrolled-release scenarios). 

13

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

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

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

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

18 In addition, occupational health professionals have employed these values beyond their initial purpose as a 

19 component of the NIOSH Respirator Selection Logic to assist in developing Risk Management Plans for non20 routine work practices governing operations in high-risk environments (e.g., confined spaces) and the 

21 development of Emergency Preparedness Plans. 

22

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

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

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

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

27 scientifically credible IDLH values using available data resources. 

28

29 The purpose of this technical report is to present the IDLH value for methyl isocyanate (CAS # 624-83-9). The 

30 scientific basis, toxicologic data and risk assessment approach used to derive the IDLH value are summarized to 

31 ensure transparency and scientific credibility. 

32 

33 John Howard, M.D. 

34 Director 

35 National Institute for Occupational Safety and Health 
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iv

1 Centers for Disease Control and Prevention
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v

1 Table of Contents 

2 FOREWORD ................................................................................................................................................................ III

3 ABBREVIATIONS .......................................................................................................................................................VI

4 GLOSSARY .................................................................................................................................................................VII

5 ACKNOWLEDGMENTS ..............................................................................................................................................X

6 1.0 INTRODUCTION.............................................................................................................................................. 1

7 1.1 IDLH VALUE FOR METHYL ISOCYANATE ...................................................................................................................1

8 1.2 PURPOSE .....................................................................................................................................................................1

9 1.3 GENERAL SUBSTANCE INFORMATION .........................................................................................................................1

10 2.0 ANIMAL TOXICITY DATA............................................................................................................................. 5

11 3.0 HUMAN DATA ................................................................................................................................................. 9

12 4.0 SUMMARY........................................................................................................................................................ 9

13 5.0 REFERENCES ................................................................................................................................................ 11

14

15

16

17

18
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vi

1 Abbreviations 

2

3 ACGIH American Conference of Governmental Industrial Hygienists 

4 AEGL Acute Exposure Guideline Levels 

5 AIHA American Industrial Hygiene Association 

6 BMC benchmark concentration 

7 BMCL benchmark concentration lower confidence limit 

8 C ceiling 

9 CAS chemical abstract service 

10 ERPG Emergency Response Planning Guidelines 

11 GD gestation day 

12 IDLH immediately dangerous to life or health 

13 LC50 median lethal concentration 

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

15 LEL lower explosive limit 

16 LOAEL lowest observed adverse effect level 

mg/m3 17 milligram(s) per cubic meter 

18 NAC National Advisory Committee 

19 NAS National Academy of Sciences 

20 NIOSH National Institute for Occupational Safety and Health 

21 NOAEL no observed adverse effect level 

22 OSHA Occupational Safety and Health Administration 

23 PEL permissible exposure limit 

24 ppm parts per million 

25 RD50 concentration of a chemical in the air that is estimated to cause a 50% decrease in the respiratory 

26 rate 

27 REL recommend exposure limit 

28 SCP Standard Completion Program 

29 STEL short term exposure limit 

30 TLV threshold limit value 

31 TWA time weighted average 

32 UEL upper explosive limit 

33 WEEL workplace environmental exposure level 
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vii

1 Glossary 

2

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

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

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

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

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

8 effects [NAS 2001]. AEGLs are intended to be guideline levels used during rare events or single once-in-a9 lifetime exposures to airborne concentrations of acutely toxic, high-priority chemicals [NAS 2001]. The 

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

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

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

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

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

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

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

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

18 assessments [USEPA 2014]. 

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

20 to 96 hours. 

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

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

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

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

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

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

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

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

29 Bolus Exposure: A single, relatively large dose. 

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

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

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

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

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

35 [USEPA 2014]. 

36

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

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

39 ECt50: A combination of the effective concentration of a substance in the air and the exposure duration that is 

40 predicted to cause an effect in 50% (one half) of the experimental test subjects. 
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viii

1 Emergency Response Planning Guidelines (ERPGs): Maximum airborne concentrations below which nearly all 

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

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

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

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

6 response to gross manifestations of clinical toxicity. 

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

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

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

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

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

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

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

14 specific exposure conditions. 

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

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

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

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

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

20 minute exposure duration. 

21 LC01: The statistically determined concentration of a substance in the air that is estimated to cause death in 1% of 

22 the test animals. 

23 LC50: The statistically determined concentration of a substance in the air that is estimated to cause death in 50% 

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

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

26 percentage of the test animals. 

27

28 LD50: The statistically determined lethal dose of a substance that is estimated to cause death in 50% (one half) of 

29 the test animals; median lethal concentration. 

30 LDLO: The lowest dose of a substance that causes death, usually for a small percentage of the test animals. 

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

32 the presence of an ignition source. 

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

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

35 death. 

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

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

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

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

40 detailed understanding on a molecular level. 
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ix

1 No Observed Adverse Effect Level (NOAEL): The highest tested dose or concentration of a substance that has 

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

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

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

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

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

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

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

9 MSHA (30 CFR 57.5001) for allowable occupational airborne exposure concentrations. PELs are legally 

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

11

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

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

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

15 a dose evaluated in a health effects or toxicology study. 

16 RD50: The statistically determined concentration of a substance in the air that is estimated to cause a 50% (one 

17 half) decrease in the respiratory rate. 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

33

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

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

36 further modification based on the overall database. 

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

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

39 effects related to occupational chemical exposures expressed as a TWA or ceiling limit.
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x

1 Acknowledgments 

2

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

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

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

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

7

8 Education and Information Division 

9 Devin Baker, M.Ed. 

10 Charles L. Geraci, Ph.D. 

11 Thomas J. Lentz, Ph.D. 

12 Richard Niemeier, Ph.D. 

13 Chris Sofge, Ph.D. 

14

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

16 technical review of this report. 

17

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

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

20 Science, College of Public Health, Ohio State University 

21

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

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

24

25 
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1

1 1.0 Introduction 

2 1.1 IDLH Value for Methyl Isocyanate 

3

IDLH Value: 0.12 ppm (0.28 mg/m3 4 ) 

5

6 Basis for IDLH Value: The IDLH value for methyl isocyanate is based on the LOAEL for severe reproductive 

7 and developmental effects, specifically fetal resorption and fetal skeletal malformations. Varma et al. [1987] 

8 reported a LOAEL of 2 ppm for these developmental and reproductive effects in dams exposed for 3 hours on 

9 gestation day (GD) 8. This represents a one-time acute exposure at a critical developmental time of the dam and 

10 fetuses. The LOAEL was adjusted to a 30-minute equivalent duration concentration of 3.6 ppm. A composite 

11 uncertainty factor of 30 was applied to account for extrapolation from a concentration that causes severe effects in 

12 animals, animal to human differences, human variability, and uncertainty about the threshold for escape-impairing 

13 effects, yielding an IDLH value of 0.12 ppm. 

14

15 1.2 Purpose 

16

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

18 exposures to acrylonitrile and (2) the rationale behind the Immediately Dangerous to Life or Health (IDLH) value 

19 for methyl isocyanate. IDLH values are developed based on the scientific rationale and logic outlined in the 

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

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

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

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

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

25 literature search is evaluated with general considerations that include description of studies (i.e., species, study 

26 protocol, exposure concentration and duration), health endpoint evaluated, and critical effect levels (e.g., 

27 NOAELs, LOAELs, LC50 values). For methyl isocyanate, the in-depth literature search was conducted through 

28 February 2014.

29 1.3 General Substance Information 

30

31 Chemical: Methyl Isocyanate 

32 CAS No: 624-83-9 
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2

Synonyms: Methyl ester isocyanic acid; Isocyanato-methane; MIC [Isocyanate]* 1

Chemical category: Organic isocyanates† 2

3 Structural formula: 

4

5

6

7

8 Table 1 highlights selected physiochemical properties of methyl isocyanate relevant to IDLH conditions. Table 2 

9 provides alternative exposure guidelines for methyl isocyanate. Table 3 summarizes the Acute Exposure 

10 Guidelines Level (AEGL) values for methyl isocyanate. 

11

12

13 Table 1: Physiochemical Properties of Methyl Isocyanate 

14

Property Value 

Molecular weight 57.06‡

Chemical formula C2H3NO 

Description Colorless liquid 

Odor Sharp, unpleasant

Odor Threshold 2.1 ppm+

UEL 26%†

LEL 5.3%†

Vapor pressure 348 mmHg at 20°C (68°F)‡

Flash point -7°C (19°F)‡

 - closed cup

Ignition temperature 534°C (994°F)‡

Solubility Hydrolysis†

Abbreviation: oC – Celsius; o 15 F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit * 16 NLM [2012] 

+ 17 AIHA [1989]

† 18 IFA [2012] 

‡ 19 HSDB [2012] 

§ 20 AIHA [1989]

21

22

23

24

25

26

27

28

29

30

31

32

N

H3C

C O
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3

1 Table 2: Alternative Exposure Guidelines for Methyl Isocyanate 

2

Organization Value 

Revised (1994) IDLH value* 3 ppm 

NIOSH REL [2014]† 0.02 ppm (0.05 mg/m3) 

OSHA PEL[2014]^

 0.02 ppm (0.05 mg/m3) [skin] 

ACGIH TLV [2014] ‡ TWA 0.02 ppm (0.05 mg/m3

) 

STEL 0.06 ppm (0.14 mg/m3

) 

AIHA ERPG [2010]+

 ERPG 1: 0.025 ppm 

ERPG 2: 0.5 ppm 

ERPG 3: 5 ppm 

AIHA WEEL [2010] § Not available 

3 Abbreviation: ACGIH – American Conference of Governmental Industrial Hygienists; AIHA – American Industrial Hygiene 

4 Association; ERPG – Emergency Response Preparedness Guidelines; IDLH – immediately dangerous to life or health; NIOSH – National 

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

6 REL – recommended exposure limit; SCP – Standards Completion Program; STEL - short term exposure limit; TWA - time weighted 

7 average; WEEL – workplace environmental exposure level

8 References: *NIOSH [1994]; ^OSHA [2014]; †NIOSH [2014]; ‡ ACGIH [2014]; AIHA [2010a]+; §AIHA [2010b]
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1 Table 3: AEGL Values for Methyl Isocyanate 

2

Classification 10-min 30-min 1-hour 4-hour 8-hour End Point [reference] AEGL-1 NR NR NR NR NR Insufficient data AEGL-2 0.40 ppm 

0.94 mg/m3

0.13 ppm 0.32 mg/m3

0.067 ppm 0.16 mg/m3

0.017 ppm 0.034 mg/m3

0.008 ppm 0.02 mg/m3

Decreased fetal body we[Varma 1987]; Cardiac arrhythmias [Tepper et al. 1987] 

AEGL-3 1.2 ppm 

2.8 mg/m3

0.40 ppm 0.95 mg/m3

0.20 ppm 0.47 mg/m3

0.05 ppm 0.12 mg/m3

0.025 ppm 0.06 mg/m3

Decreased pup survival dlactation [Schwetz et al. 1987] 

Abbreviation: AEGL – acute exposure guideline levels; mg/m3 3 – milligrams per cubic meter; min – minute; NR – not recommended due to insufficient da* 4 References: NAS [2003] 
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5

1 2.0 Animal Toxicity Data 

2

3 Methyl isocyanate is one of the most reactive isocyanates and rapidly degrades in water [Varma and Guest 1993; 

4 NAS 2003]. The reactive nature of methyl isocyanate contributes to its toxicological potential and ability to cause 

5 irritation and cytotoxicity in the respiratory tract. The database for acute lethality in animals consists of multiple 

6 studies in rabbits [Pant et al. 1987; Dow Chemical 1990], guinea pigs [Mellon Institute 1966, 1970; Dodd et al. 

7 1985, 1986, 1987; Kolb et al. 1987; Troup et al. 1987; Ferguson and Alarie 1991], rats [Mellon Institute 1963b, 

8 1970; IRDC 1964; Kimmerle and Eben 1964; Eastman Kodak 1966; Fait and Dodd 1981; Dodd et al. 1985, 1986, 

9 1987; Nemery et al. 1985a; Salmon et al. 1985; Bucher et al. 1987a,b; Dinsdale et al. 1987; Pant et al. 1987; 

10 Vijayaraghavan and Kaushik 1987; Dutta et al. 1988; Sethi et al. 1989; Dow Chemical 1990; Jeevaratnam et al. 

11 1990; Man Tech Environmental 1992; Jeevaratnam and Sriramachari 1994; Sriramachari and Jeevaratnam 1994], 

12 and mice [Dodd et al. 1985, 1986; Boorman et al. 1987a,b; Bucher et al. 1987a; Vijayaraghavan and Kaushik 

13 1987; Varma et al. 1988]. Based on histopathology and necropsy reports, lethality appears to be primarily caused 

14 by damage to the respiratory system. 

15

16 Multiple studies have reported varied non-lethal effects following acute exposure to methyl isocyanate. Studies in 

17 guinea pigs indicate that exposure to methyl isocyanate for 15 minutes causes hypoxia and metabolic acidosis at 

18 concentrations as low as 240 ppm [Fedde et al. 1987; Maginniss et al. 1987]. Rats acutely exposed to methyl 

19 isocyanate developed severe inflammation and erosion of the respiratory tract [Mitsumori et al. 1987] and 

20 hypoxia [Troup et al. 1987]. Studies that observed acutely exposed rats for extended periods of time reported 

21 evidence of pulmonary obstruction [Stevens et al. 1987; Bucher and Uriah 1989]. Tepper et al. [1987] reported an 

22 increase in cardiac arrhythmia in rats at 4-6 months post-exposure to a 2 hour exposure to 3 ppm methyl 

23 isocyanate. In mice, an RD50 value of 1.3 – 2.9 ppm and an RD50TC of 1.9 ppm have been estimated [Ferguson et 

24 al. 1986; James et al. 1987]. 

25

26 Developmental and reproductive studies have determined that acute exposure to methyl isocyanate significantly 

27 decreases maternal body, fetal, and placental weight and significantly increases the total number of resorptions 

28 and skeletal malformations in both rats and mice [Varma 1987; Varma et al. 1990; Singh et al. 1994]. Varma et al. 

29 [1987] reported a LOAEL of 2 ppm for developmental and reproductive effects, including increased fetal 

30 resorptions and increased skeletal malformations, in dams exposed for 3 hours on GD 8. This represents a one31 time acute exposure at a critical developmental time of the dam and fetuses. 

32
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6

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

2 methyl isocyanate. Table 5 provides non-lethal data reported in animal studies with 30-minute equivalent derived 

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

4 LOAEL), adjusted 30-minute concentration, and the justification for the composite uncertainty factors applied to 

5 calculate the derived values.

6 
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1 Table 4: Lethal Concentration Data for Methyl Isocyanate

2

Reference Species LC50

(ppm) 

LCLo

(ppm) 

Time (min) 

Adjusted 30-min Concentration* (ppm) 

Composite Uncertainty Factor 

Dodd et al. [1985, 1986] Guinea Pig 5.4 -- 360 12.4 10‡ Ferguson and Alarie [1991] Guinea Pig 26.5 -- 180 48.2 10‡ 

Vijayaraghavan and Kaushik [1987] Mouse 112.4 -- 30 112.4 10‡ Kimmerle and Eben [1964] Rat 5.0 -- 240 10.0 10‡ 

ManTech Environmental [1992] Rat 45.0 -- 60 56.7 10‡ 

34 Abbreviation: LC – lethal concentration; LC50 – median lethal concentration; LCLo – lowest concentration of a chemical that caused death in humans or a5 per million 

* For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn 6 x t = k); no empirically est

7 available, 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 LC50 values to LC01 values in animals, interspecies differences and human variab

10
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1 Table 5: Non-lethal Concentration Data for Methyl Isocyanate

2

Reference Species 

(reference) 

NOAEL (ppm) 

LOAEL (ppm) 

Time (min) 

Adjusted 30-min Concentration* (ppm) 

Composite Uncertainty Factor 

Mellon Institute [1970] Human 0.5 -- 10 0.2 3‡ Mellon Institute [1963a] Human -- 1 10 0.3 10± 

Kimmerle and Eben [1964] Human -- 4 5 0.7 10± Tepper et al. [1987] Rats -- 3 120 4.8 30^ Fedde et al. [1987] Guinea Pig -- 240 15 120 30^ 

Varma [1987] + Mouse -- 2 180 3.6 30^ Varma et al. [1990] Rat -- 9 180 16.4 30^ 

3 Abbreviation: NOAEL – no observed adverse effect level; min – minute; LOAEL – lowest observed adverse effect level; ppm – parts per million

* For exposures other than 30 minutes the ten Berge et al. [1986] relationship is used for duration adjustment (Cn 4 x t = k), with n=3 for exposures greater th

5 exposures less than 30 minutes. 

† 6 The derived value is the result of the adjusted 0.5-hour value divided by the composite uncertainty factor. The composite uncertainty factor used varies fo

7 and severity of the endpoint observed. 

‡ 8 Composite uncertainty factor assigned to account for interspecies differences and human variability.± 9 Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, interspecies differences and human variability.^ 10 Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, severe effects, interspecies differences, human variability, and 

11 escape-impairing effects 

+ 12 Identified study is the primary basis of the IDLH value for methyl isocyanate.
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9

1 3.0 Human Data 

2

3 An accidental release in Bhopal, India is the source of most information on human exposures to methyl 

4 isocyanate. Although actual exposure concentrations are unknown, Karlsson et al. [1985] estimated a 

5 concentration range of 10 to 3,000 ppm, with higher concentrations occurring closer to the site of release, based 

6 on dispersion calculations. Although multiple deaths were reported, most occurred 8-72 hours post-release 

7 [Varma 1989; Varma and Guest 1993]. Symptoms reported with the most frequency were ocular irritation, 

8 coughing, respiratory distress, pulmonary congestion, nausea, vomiting, muscle weakness, and hypoxia resulting 

9 in CNS involvement [Kamat et al. 1985; Misra et al. 1987; Lorin and Kulling 1986; Andersson et al. 1988; Weill 

10 1988; Kamat et al. 1992]. Most of these symptoms resolved within 2 weeks post-release, but many of those 

11 exposed, including adults and children, reported continued restrictive respiratory, ophthalmological, 

12 neuromuscular, and gastrointestinal symptoms for years after the accident [Andersson et al. 1984, 1985; Kamat et 

13 al. 1985; Irani and Mahashur 1986; Maskati 1986; Naik et al. 1986; Khurrum and Ahmad 1987; Andersson et al. 

14 1990; Kamat et al. 1992; Cullinan et al. 1997; Misra and Kalita 1997]. 

15

16 In addition to information from the Bhopal release, a case report and multiple experimental studies on human 

17 volunteers exist. Skin irritation and respiratory irritation were reported in workers exposed to unknown 

18 concentrations of methyl isocyanate for unknown durations [Union Carbide 1973]. In one experimental study, 

19 four volunteers were exposed to 0.4 to 21 ppm methyl isocyanate for 1-5 minutes [Kimmerle and Eben 1964]; 

20 minor irritation of the mucous membranes was reported at 2 ppm with more pronounced ocular irritation at 4 

21 ppm. Volunteers reported that exposure to 21 ppm was instantaneously intolerable. Another experimental study 

22 exposed 8 volunteers to 1.75 ppm for 1 minute and then re-exposed 6 of the 8 to 0.5 ppm for 10 minutes [Mellon 

23 Institute 1970]. All volunteers reported ocular irritation and multiple volunteers reported nose and throat irritation 

24 in both exposures. A third study exposed 7 male volunteers to 0.3 to 5.0 ppm for 1 minute or to 1 ppm for 10 

25 minutes [Mellon Institute 1963a]. Exposure to 2.5 and 5.0 ppm for 1 minute resulted in eye and nose irritation. 

26 One volunteer exposed to 5.0 ppm also reported throat irritation. Volunteers exposed to 1 ppm for 10 minutes 

27 reported eye, nose, and throat irritation. 

28 4.0 Summary 

29

30 Methyl isocyanate is one of the most reactive isocyanates and rapidly degrades in water [Varma and Guest 1993; 

31 NAS 2003]. The reactive nature of methyl isocyanate contributes to its toxicological potential and ability to cause 
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10

1 irritation and cytotoxicity in the respiratory tract. The IDLH value for methyl isocyanate is based on a LOAEL, 

2 which corresponds to severe reproductive and development effects in animals. Tepper et al. [1987] reported 

3 cardiac arrhythmia in rats at 4-6 months post-exposure to a 2-hour exposure to 3 ppm methyl isocyanate. Varma 

4 et al. [1987] reported a LOAEL of 2 ppm for developmental and reproductive effects, including increased fetal 

5 resorptions and increased skeletal malformations, in dams exposed for 3 hours on GD 8. This represents a one6 time acute exposure at a critical developmental time of the dam and fetuses. The reproductive and developmental 

7 effects occurred at lower concentrations than the cardiac effects and are identified as the most sensitive health 

8 endpoint. The LOAEL of 2 ppm when adjusted to a 30-minute equivalent duration concentration is 3.6 ppm. A 

9 composite uncertainty factor of 30 was applied to account for extrapolation from a concentration that causes 

10 severe effects in animals, animal to human differences, human variability, and uncertainty about the threshold for 

11 escape-impairing effects, yielding an IDLH value of 0.12 ppm for methyl isocyanate. This IDLH value should be 

12 protective against the reproductive, developmental and cardiac effects associated with methyl isocyanate 

13 exposure. Additionally, it is supported by duration-adjusted estimates of the irritation threshold in humans 

14 [Mellon Institute 1963a; Kimmerle and Eben 1964]. 
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11

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