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policy.

i 1

2

3

4

5

6



## I MMEDIATELY 

## D ANGEROUS TO 

## L IFE OR 

## H EALTH 

## (IDLH) V ALUE 

## P ROFILE 7

8

9

10



### FOR 11

12

13

14



## I RON 

## P ENTACARBONYL 15

16

17



## [CAS N O



## . 13463-40-6] 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.

ii 

## 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 19External Review Draft

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iii 

## Foreword 1

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

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

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

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

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

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

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

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

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

transportation incidents or other uncontrolled-release scenarios). 11

12

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

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

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

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

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

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

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

Preparedness Plans. 20

21

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

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

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

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

scientifically credible IDLH values using available data resources. 26

27

The purpose of this technical report is to present the IDLH value for iron pentacarbon yl (CAS # 13463-40-6). 28

The scientific basis, toxicologic data and risk assessment approach used to derive the IDLH value are summarized 29

to ensure transparency a nd 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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iv Centers for Disease Control and Prevention 1External Review Draft

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policy.

v 

## 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 I RON P ENTACARBONYL

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

1.2 P URPOSE

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

1.3 G ENERAL S UBSTANCE I NFORMATION

......................................................................................................................... 2 9

2.0 ANIMAL TOXICITY DATA

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

3.0 HUMAN DATA

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

4.0 SUMMARY

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

5.0 REFERENCES

............................................................................................................................... ................. 11 13

14

15

16

17

18External Review Draft

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vi 

## 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

LC 50 median lethal concentration 12

LC Lo lowest concentration of a chemical that caused death in humans or animals 13

LEL lower explosive limit 14

LOAEL lowest observed adverse effect level 15

mg/m 3 milligram(s) per cubic meter 16

NAC National Advisory Committee 17

NAS National Academy of Sciences 18

NIOSH National Institute for O ccupational Safety and Health 19

NOAEL no observed adverse effect level 20

OSHA Occupational Safety and Health Administration 21

PEL permissible exposure limit 22

ppm parts per million 23

RD 50 concentration of a chemical in the air that is estimated to cause a 50% decrease in the respiratory 24

rate 25

REL recommended exposure limit 26

SCP Standard Completion Program 27

STEL short term exposure limit 28

TLV threshold limit value 29

TWA time weighted average 30

UEL upper explosive limit 31

WEEL workplace environmental exposure level 32External Review Draft

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vii 

## Glossary 1

2

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

assessments [USEPA 2014]. 18

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

to 96 hours. 20

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

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

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

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

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

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

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

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

Bolus Exposure : A single, relatively large dose. 29

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

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

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

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

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

[USEPA 2014]. 35

36

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

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

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

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

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policy.

viii 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. 37External Review Draft

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policy.

ix 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 concentration 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 are 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 devel oped by OSHA (29 CFR 1910.1000) or 11

MSHA (30 CFR 57.5001) for allowable occupational air borne exposure concentr ations. 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 fro m which dose extrapolation is initiated. 15

This point can be the lower bound on dose for an estim ated 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 concentr ation of a substance in the air that is estimated 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 established 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 occupa tional exposure to airborne 27

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

refer to airborne concentrations of chemical substa nces and represent conditions under which it is believed 29

that nearly all workers may be repeatedly exposed, da y 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

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policy.

x 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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policy.

xi 

## Acknowledgments 1

2

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

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

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

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

7



### Education and Information Division 8

Devin Baker, M.Ed. 9

Charles L. Geraci, Ph.D. 10

Thomas J. Lentz, Ph.D. 11

Richard Niemeier, Ph.D. 12

Chris Sofge, Ph.D. 13

14

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

technical review of this report. 16

17

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

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

University 20

21

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

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

24External Review Draft

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policy.

1 

## 1.0 Introduction 1



### 1.1 Overview of the IDLH Value for Iron Pentacarbonyl 2

3

IDLH Value: 0.4 ppm 4

5

Basis for IDLH Value: The IDLH value is based on a rat non-lethalit y concentration of 5.2 ppm in the 4-hour 6

Biodynamics [1988] study, which corresponds to a concentration of 10.4 ppm after a 30-minute duration 7

adjustment. Reported effects at this concentration incl uded lacrimation and nasal discharge, which are classified 8

as potentially escape-impairing. Applying a composite un certainty factor of 30 to account for adjusting from a 9

LOAEL to NOAEL, steep exposure-response relationship, interspecies differences and human variability yields 10

an IDLH value of 0.4 ppm

. 11

12



### 1.2 Purpose 13

14

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

exposures to iron pentacarbonyl and (2) th e rationale behind the Immediately Da ngerous to Life or Health (IDLH) 16

value for iron pentacarbonyl. IDLH values are developed based on the scientific rationa le and logic outlined in the 17

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

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

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

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

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

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

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

NOAELs, LOAELs, LC 50 values). For iron pentacarbonyl, the in-d epth literature search was conducted through 25

February 2014. 26

27

28

29External Review Draft

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policy.

2 

### 1.3 General Substance Information 1

2

Chemical: Iron pentacarbonyl 3

CAS No: 13463-40-6 4

Synonyms: Iron carbonyl; Pentacarbonyliron * 5

Chemical category: Iron compounds; metal carbonyls † 6

7

8

Structural formula: 9

10

11

12

13

Table 1 highlights selected physiochemical properties of iron pentacarbonyl relevant to IDLH conditions. Table 2 14

provides alternative exposure guidelines for iron pe ntacarbonyl. Table 3 summarizes the Acute Exposure 15

Guidelines Level (AEGL) values for iron pentacarbonyl. 16

17

Table 1: Physiochemical Properties of Iron Pentacarbonyl 18

19

Property Value

Molecular weight 195.99 ‡

Chemical formula C 5 FeO 5 Description Colorless to yellow to dark red, oily

liquid

Odor Moldy, musty

Odor Threshold Not available

UEL 12.5 †

LEL 3.7 †

Vapor pressure 40 mmHg at 30.56°C (87°F) §

Flash point -15°C (5°F) ‡

Ignition temperature 320°C (608°F) ‡

Solubility Very slightly soluble in water †

Abbreviation: o C – Celsius; o F – Fahrenheit; mmHg – millimeter mercury; LEL – lower explosive limit; UEL – upper explosive limit 20

* NLM [2014] 21

† IFA [2014] 22 Fe C

–

C

–

C

– C

– C

– O +

O +

O + + O O +External Review Draft

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policy.

3 ‡ HSDB [2014] 1

§ OSHA [1989] 2

3

4

5

Table 2: Alternative Exposure Guidelines for Iron Pentacarbonyl 6

7

Organization Value

Original (SCP) IDLH value [NIOSH 2014] None

NIOSH REL [2014] Not available

OSHA PEL [2014] 0.1 ppm TWA; 0.2 ppm STEL

ACGIH TLV [2014] Not available

AIHA ERPG [2013] Not available

AIHA WEEL [2013] Not available

Abbreviation: ACGIH – American Conference of Governmental I ndustrial Hygienists; AIHA – Am erican Industrial Hygiene 8

Association; ERPG – Emergency Re sponse Preparedness Guidelines; IDLH – immediatel y dangerous to life or health; NIOSH – Nationa l 9

Institute for Occupational Safety and Hea lth; OSHA – Occupational Safety and Health Administration; PEL – permissible exposure limit; 10

REL – recommended exposure limit; SCP – Standards Completion Program; WEEL – workplace e nvironmental exposure level 11External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.4Table 3: AEGL Values for Iron Pentacarbonyl12Classification 10-min 30-min 1-hour4-hour 8-hour Endpoint [reference]AEGL-1 NR NR NR NR NR Not recommended; insufficient dataAEGL-2 0.077 ppm0.61 mg/m30.077 ppm0.61 mg/m30.060 ppm0.48 mg/m30.037 ppm0.30 mg/m30.025 ppm0.20 mg/m3Based on a 3-fold reduction in theAEGL-3 values.AEGL-3 0.23 ppm1.8 mg/m30.23 ppm1.8 mg/m30.18 ppm1.4 mg/m30.11 ppm0.88 mg/m30.075 ppm0.60 mg/m3Estimated lethality threshold in rats(1.0 ppm determined by BMDanalysis [BASF 1995]. n = 1or 3; uncertainty factor = 10 (3 forboth interspecies variability, andindividual variability).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 [2010]45External Review Draft

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5 

## 2.0 Animal Toxicity Data 1

2

The majority of acute studies for iron pentacarbonyl provide d data on lethality, with little additional information 3

to assess potential escape-impairing effects. Using a dynami c exposure chamber without analytical monitoring, 4

Gage [1970] reported that a single 5.5 h our exposure to 33 ppm was lethal to 3 of 8 rats, but no effects were seen 5

in rats exposed for eighteen 5.5 hour periods at 7 ppm. Postmortem examination of the rats that died showed 6

pulmonary edema, indicating that lung effects are a criti cal target for this chemical. Sunderman et al. [1959] 7

conducted lethality studies with mice and rats with reported 30-minute LC50 values of 273 ppm and 114 ppm, 8

respectively. Biodynamics [1988] reported that rats expo sed to 5.2 ppm of iron pentacarbonyl for 4 hours showed 9

effects 1 to 2 hours post exposure, but essentially no toxicity during exposure. The observed effects included 10

lacrimation and nasal discharge at a slightly higher incide nce than controls. Necropsy of these rats revealed red 11

lungs in some of the rats, but the actual number was not reported, and the observation was considered of 12

equivocal significance on the basis of gross pathology only. Together, the studies of Gage [1970] and 13

Biodynamics [1988] show minimal irritant effects in the range of 5 to 7 ppm of iron pentacarbonyl even for single 14

acute exposure periods significantly longer than 30-minut es. BASF [1995] reported 1 of 10 rats died following a 15

single 6-hour exposure to 2.91 ppm of iron pentacarbonyl. A to tal of 5/10 rats died within 4 days after receiving 16

two 6-hour exposures. Because of the delayed mortality seen in this and other studies, it is not known whether 17

additional rats would have died following the singl e exposure if there had been additional post-exposure 18

monitoring. NAS [2010] calculated an LC 01 value of 1.9 ppm and a BMCL 05 for lethality of 0.8 ppm, assuming 19

that a single exposure would have killed 5/10 animals, as a worst case scenario in light of the delayed deaths. 20

However, rats exposed to 1.0 ppm for 5 days/week for 1 month did not exhibit any clinical signs, suggesting a 21

steep exposure-response curve, and that 1.0 ppm is a very conservative estimate of the lethality threshold from a 22

single exposure. 23

24

The acute toxicity studies show a significant difference in le thal concentrations in rats across the available studies. 25

It is convenient that the study by Sunderman et al. [1959] was for the duration of interest and included sufficient 26

information to calculate an LC 50 value, but a static exposure scenario was used, leading to significant uncertainty 27

in the actual exposure levels. The Biodynamics [1988] and BASF [1995] studies were conducted using modern 28

exposure methods and identified much lo wer effect levels, but involved great er time extrapolation, and the BASF 29

[1995] study includes the additional uncertainties due to the multiple exposures and inadequate information on 30External Review Draft

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6 post-exposure deaths following a single exposure. Thus, the appropriate IDLH value derivation would yield a 1

value generally near this exposure range. 2

3

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

iron pentacarbonyl. Table 5 provides no n-lethal data reported in animal studies with 30-minute equivalent 5

derived values. Information in these tables includes speci es of test animals, toxicological metrics (i.e., LC, 6

NOAEL, LOAEL), adjusted 30-minute concentration, and th e justification for the composite uncertainty factors 7

applied to calculate the derived values. 8

9

10External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.7Table 4: Lethal Concentration Data for Iron Pentacarbonyl12Reference SpeciesLC50(ppm)LCLo(ppm)Time(min)Adjusted30-minuteConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Sunderman et al. [1959] Mouse 273273 -- 30 273273 30‡9.11Armit [1980] Rabbit 250 -- 45 286 30‡9.5Sunderman et al. [1959] Rat 118 -- 30 118 30‡3.9Biodynamics [1988] Rat 10 -- 240 20 30‡0.7BASF [1995] Rat 3±-- 720 9 30‡0.3BASF [1995] Rat -- 3§360 7 10^0.7BASF [1995] Rat -- 1**360 2.3 10^0.23Abbreviation: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 greater than 30 minutes the ten Bergeet al. [1986] relationship is used for adjustment7(Cnx t = k); empirically estimated n values were not available, therefore the default values were used,8n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes.9†The derived value is the result of the adjusted 30-minute concentration divided by the composite uncertainty factor.10‡Composite uncertainty factor to account for adjustment of LC50values to LC01values, use of lethal concentration threshold in animals, interspecies differences and11human variability.12±5/10 rats died within 4 days after receiving two 6-hour exposures13§1/10 rats died after a single 6-hour exposure14^Composite uncertainty factor to account for lethal concentration threshold in animals, interspecies differences and human variability.15**Modified BMCL05for lethality after a single 6-hour exposure16171819202122232425External Review DraftMarch 2015This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not beenformally disseminated by the National Institute for Occupational Safety and Health. It does not represent and should not be construed to represent anyagency determination or policy.81234Table 5: Non-lethal Concentration Data for Iron Pentacarbonyl56Reference Species NOAEL(ppm)LOAEL(ppm)Time(min)Adjusted30-minuteConcentration*(ppm)CompositeUncertaintyFactorDerivedValue(ppm)†Biodynamics [1988]+Rat -- 5.2 240 10.4 30±0.4Abbreviation:NOAEL – no observed adverse effect level;min – minute; LOAEL – lowest observed adverse effect level; ppm– parts per million78*For exposures greater than 30 minutes the ten Bergeet al. [1986] relationship is used for adjustment9(Cnx t = k); empirically estimated n values were not available, therefore the default values were used,10n = 3 for exposures greater than 30 minutes and n = 1 for exposures less than 30 minutes.11†The derived value is the result of the adjusted 30-minute concentration divided by the composite uncertainty factor.12+Identified study is the primary basis ofthe IDLH value for iron pentacarbonyl.13±Composite uncertainty factor assigned to account for adjusting from a LOAEL to NOAEL, steep exposure-response relationship, interspecies differences and human14variability15External 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.

9 

## 3.0 Human Data 1

No information was identified that provided adequa te estimates of observed effects following exposure in 2

humans. Stokinger [1981] reported that the effects of hum an exposure to iron pentacarbonyl are similar to those 3

of nickel carbonyl exposure. Such effects are giddiness and headache, dyspnea, and vomiting that was alleviated 4

after removal from exposure. Symptoms such as fever, cyanosis and coughing lasti ng up 36 hours after exposure 5

have also been reported. Death may occur several days after exposure. 6



## 4.0 Summary 7

8

The assembled data on iron pentacarbonyl reveal a steep exposure-response relationshi p and a small gap between 9

concentrations associated with severe non-lethal effects a nd death in test animals. Reported effects of concern 10

include delayed onset of death following acute exposure. The IDLH value for iron pentacarbonyl is based on a rat 11

non-lethality concentration of 5.2 ppm in the 4-h our Biodynamics [1988] study, which corresponds to a 12

concentration of 10.4 ppm after a 30-minute duration adjust ment. Reported effects at this concentration included 13

lacrimation and nasal discharge, which are classified as potentially escape impairing. Applying a composite 14

uncertainty factor of 30 to account for extrapolation fr om a LOAEL to a NOAEL, severe effects in animals (i.e., 15

steep exposure-response relationship), in terspecies differences and human vari ability, results in an IDLH value of 16

0.4 ppm

. 17

18

It should be noted that the IDLH value for iron pentacarbon yl differs by more than an order of magnitude from 19

the AEGL-2 30-minute value, which is intended to repr esent an airborne concentration of a substance above 20

which it is predicted that the genera l population, including su sceptible individuals, could experience irreversible 21

or other serious, long-lasting adverse health effects or an impaired ability to escape [NAS 2001]. Data to 22

calculate an AEGL-2 value for iron pentacarbonyl were de emed insufficient resulting in the establishment of an 23

AEGL-2 equal to 1/3 of the calculated AEGL-3 value, wh ich is intended to represent an airborne concentration of 24

a substance above which it is predicted that the gene ral population, including susceptible individuals, could 25

experience life-threatening health effects or death [NAS 2001, 2010]. The AEGL-3 value for 30-minutes was set 26

at 0.23 ppm and was based on lethal threshold estimat es in rats reported in BASF [1995]. NIOSH used non27

lethality data reported in Biodynamics [1988] as the basis of the IDLH value of 0.4 ppm for iron pentacarbonyl. 28External Review Draft

March 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.

10 The small difference between the AEGL-3 value and IDLH value are caused by alternative primary data, selection 1

of the endpoints and duration adjustments. 2External Review Draft

March 2015

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.

11 

## 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) [2006]. AIHA Emergency Response Planning (ERP) 6

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

https://www.aiha.org/get8

involved/AIHAGuidelineFoundation/EmergencyResponseP lanningGuidelines/Documents/ERP-SOPs2006.pdf. 9

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AIHA (American Industrial Hygiene Association) [2013] . Emergency response planning guidelines (ERPG) and 11

workplace environmental exposure levels (WEEL) handbo ok. Fairfax, VA: American Industrial Hygiene 12

Association Press, https://www.aiha.org/get13

involved/AIHAGuidelineFoundation/EmergencyRespon sePlanningGuidelines/Pages/default.aspx. 14

15

Armit HW [1908]. The Toxicology of Nickel Carbonyl. Part II. J Hygiene 8 :565–600. 16

17

BASF [1995]. Study on inhalation toxic ity of eisenpentacarbonyl as a vapor in rats-28 day test. Ludwigshafen, 18

Germany: BASF (Badische Anilin & Soda Fabrik), Depa rtment of Toxicology. Environmental Protection 19

Agency, Office of Toxics Substances, Document #88-950000244. 20

21

Biodynamics [1988]. An acute inhalation toxicity study of iron pentacarbonyl in the rat. Final Report. 22

Environmental Protection Agency, Office of Toxic Substances. Document #88-920001300. 23

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EPA [2010]. Integrated Risk Information System (IRIS): glossary [http://www.epa.gov/iris/help_gloss.htm]. 25

26

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http://www.nap.edu/. 40

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Iron pentacarbonyl. National Academy of Science, Committee on Toxicology and Committee on Acute Exposure 43

Guideline Levels, Board on Environmental Studies and Toxicology, National Research Council. Washington, DC: 44

National Academy Press, http://www.epa.gov/oppt/aegl/pubs/iro 45

http://www.epa.gov/oppt/aegl/pubs/iron_pentacarbonyl_fin al_volume6_2007.pdfn_pent acarbonyl_final_volume6 46

_2007.pdf]. 47External Review Draft

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

information quality guidelines. It has not been formally di sseminated by the National Institute for Occupational

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

policy.

12 1

NIOSH [2004]. NIOSH respirator selection logic. Cinc innati, OH: U.S. Department of Health and Human 2

Services, Centers for Disease Control and Prevention, National Institute for Occupa tional Safety and Health, 3

DHHS (NIOSH) Publication No. 2005-100. 4

5

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Health, DHHS (NIOSH) Publication No. 2005-149. 8

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NIOSH [2014]. NIOSH Current Intelligence Bulletin 66: Deri vation of Immediately Dangero us to Life or Health 10

(IDLH) Values. Cincinnati, OH: U.S. Department of H ealth and Human Services, Centers for Disease Control 11

and Prevention, National Institute fo r Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014- 12

100. 13

14

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[http://chem.sis.nlm.nih.gov/chemidplus/chemid lite.jsp]. Date accessed: March 15, 2013. 16

17

OSHA [2013]. OSHA occupational chemical database: iron pentacarbonyl, as Fe 18

[http://www.osha.gov/chemicaldata/chemResult.html ?recNo=245]. Date accessed: March 15, 2013. 19

20

OSHA [2011]. OSHA PEL project documentation: ir on pentacarbonyl [http://www. cdc.gov/niosh/pel88/13463- 21

40.html]. Date accessed: June 21, 2013. 22

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CFR 1910. Subpart Z -- Toxic and Hazardous Substances. OSHA; Washington, DC 25

[http://www.osha.gov/pls/oshaweb/owadisp.show_docum ent?p_table=standards&p_i d=9992]. Date accessed: 26

February 14, 2013. 27

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Sunderman F, West B, Kincaid J [1959]. A toxicity study of iron pentacarbonyl. Arch Ind Health 19 :11–13. 32

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systematically acting vapors and gases. J Haz Mat 13 :301–309. 35