i

Skin Notation (SK) Profile

1-Bromopropane 

[CAS No. 106-94-5]

Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
ii

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Occupational Safety and Health. It does not represent and should not be construed to represent any 

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Suggested Citation

NIOSH [20XX]. NIOSH skin notation profile: 1-Bromopropane. By Hudson NL, Dotson GS. 

Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control 

and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) 

Publication No. XXX

DHHS (NIOSH) Publication No. XXX
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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.

Foreword

As the largest organ of the body, the skin performs multiple critical functions, such as serving as 

the primary barrier to the external environment. For this reason, the skin is often exposed to 

potentially hazardous agents, including chemicals, which may contribute to the onset of a 

spectrum of adverse health effects ranging from localized damage (e.g., irritant contact 

dermatitis and corrosion) to induction of immune-mediated responses (e.g., allergic contact 

dermatitis and pulmonary responses), or systemic toxicity (e.g., neurotoxicity and hepatoxicity). 

Understanding the hazards related to skin contact with chemicals is a critical component of 

modern occupational safety and health programs. 

In 2009, the National Institute for Occupational Safety and Health (NIOSH) published 

Current Intelligence Bulletin (CIB) 61 – A Strategy for Assigning New NIOSH Skin Notations

[NIOSH 2009-147]. This document provides the scientific rationale and framework for the 

assignment of multiple hazard-specific skin notations (SK) that clearly distinguish between the 

systemic effects, direct (localized) effects, and immune-mediated responses caused by skin 

contact with chemicals. The key step within assignment of the hazard-specific SK is the 

determination of the hazard potential of the substance, or its potential for causing adverse health 

effects as a result of skin exposure. This determination entails a health hazard identification 

process that involves use of the following:

 Scientific data on the physicochemical properties of a chemical

 Data on human exposures and health effects

 Empirical data from in vivo and in vitro laboratory testing

 Computational techniques, including predictive algorithms and mathematical models that 

describe a selected process (e.g., skin permeation) by means of analytical or numerical 

methods. 

This Skin Notation Profile provides the SK assignments and supportive data for 1-bromopropane 

(1-BP). In particular, this document evaluates and summarizes the literature describing the 

hazard potential of the substance and its assessment according to the scientific rationale and 

framework outlined in CIB 61. In meeting this objective, this Skin Notation Profile intends to 

inform the audience—mostly occupational health practitioners, researchers, policy- and decisionmakers, employers, and workers in potentially hazardous workplaces—so that improved riskmanagement practices may be developed to better protect workers from the risks of skin contact 

with the chemicals of interest.

John Howard, M.D.

Director

National Institute for Occupational Safety and Health

Centers for Disease Control and Prevention
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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.

Contents

FOREWORD ............................................................................................................................................................III

ABBREVIATIONS.....................................................................................................................................................V

GLOSSARY .............................................................................................................................................................VII

ACKNOWLEDGMENTS..................................................................................................................................... VIII

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

1.1 GENERAL SUBSTANCE INFORMATION ..................................................................................................................1

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

1.3 OVERVIEW OF SK ASSIGNMENT FOR 1-BROMOPROPANE.....................................................................................2

2.0 SYSTEMIC TOXICITY FROM SKIN EXPOSURE (SK: SYS) ......................................................................2

3.0 DIRECT EFFECTS ON SKIN (SK: DIR)...........................................................................................................5

4.0 IMMUNE-MEDIATED RESPONSES (SK: SEN) .............................................................................................6

5.0 SUMMARY............................................................................................................................................................6

REFERENCES ............................................................................................................................................................8
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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.

Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists 

ATSDR Agency for Toxic Substances and Disease Registry

CIB Current Intelligence Bulletin

cm2squared centimeter(s)

cm/hr centimeter(s) per hour

cm/s centimeter(s) per second

DEREK Deductive Estimation of Risk from Existing Knowledge

DIR skin notation indicating the potential for direct effects to the skin following 

contact with a chemical

EC European Commission 

g gram(s)

g/L gram(s)/liter

GHS Globally Harmonized System for Classification and Labelling of Chemicals

GPMT guinea pig maximization test

hr hour(s)

IARC International Agency for Research on Cancer

IPCS International Program for Chemical Safety 

(IRR) subnotation of SK: DIR indicating the potential for a chemical to be a skin irritant 

following exposure to the skin

kaq coefficient in the watery epidermal layer

kp skin permeation coefficient 

kpol coefficient in the protein fraction of the stratum corneum

kpsc permeation coefficient in the lipid fraction of the stratum corneum 

LD50 dose resulting in 50% mortality in the exposed population

LDLo dermal lethal dose

LLNA local lymph node assay

LOAEL lowest-observed-adverse-effect level 

log KOW base-10 logarithm of a substance’s octanol–water partition

M molarity

m

3

cubic meter(s)

mg milligram(s)

mg/cm2/hr milligram(s) per square centimeter per hour

mg/kg milligram(s) per kilogram body weight

mg/m3 milligram(s) per cubic meter

mL milliliter(s)

mL/kg milliliter(s) per kilogram body weight

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

nmol/cm2/hr nanomoles per square centimeter per hour
vi

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information quality guidelines. It has not been formally disseminated by the National Institute for 

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agency determination or policy.

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit

OSHA Occupational Safety and Health Administration

ppm parts per million

REL recommended exposure limit

RF retention factor 

SEN skin notation indicating the potential for immune-mediated reactions following 

exposure of the skin

SI ratio ratio of skin dose to inhalation dose

SK skin notation

SW solubility in water

SYS skin notation indicating the potential for systemic toxicity following exposure of 

the skin

USEPA United States Environmental Protection Agency 

μg microgram(s)

μg/cm2 microgram(s) per square centimeter

μg/cm2/hr microgram(s) per square centimeter per hour

μL microliter(s)

μmol micromole(s)
vii

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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.

Glossary 

Absorption—The transport of a chemical from the outer surface of the skin into both the skin 

and systemic circulation (including penetration, permeation, and resorption). 

Acute exposure—Contact with a chemical that occurs once or for only a short period of time. 

Cancer—Any one of a group of diseases that occurs when cells in the body become abnormal 

and grow or multiply out of control. 

Contaminant—A chemical that is (1) unintentionally present within a neat substance or mixture 

at a concentration less than 1.0% or (2) recognized as a potential carcinogen and present within a 

neat substance or mixture at a concentration less than 0.1%. 

Cutaneous (or percutaneous)—Referring to the skin (or through the skin). 

Dermal—Referring to the skin. 

Dermal contact—Contact with (touching) the skin. 

Direct effects—Localized, non-immune-mediated adverse health effects on the skin, including 

corrosion, primary irritation, changes in skin pigmentation, and reduction/disruption of the skin 

barrier integrity, occurring at or near the point of contact with chemicals. 

Immune-mediated responses—Responses mediated by the immune system, including allergic 

responses. 

Sensitization—A specific immune-mediated response that develops following exposure to a 

chemical, which, upon re-exposure, can lead to allergic contact dermatitis (ACD) or other 

immune-mediated diseases such as asthma, depending on the site and route of re-exposure. 

Substance—A chemical. 

Systemic effects—Systemic toxicity associated with skin absorption of chemicals after exposure 

of the skin.
viii

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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.

Acknowledgments

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

Director). G. Scott Dotson, Ph.D., was the project officer for this document, assisted in great part 

by Naomi Hudson, Dr.P.H., MPH, Stacey Anderson, and Clayton B’Hymer, Ph.D. The basis for 

this document was a report (Toxicology Excellence for Risk Assessment [TERA]) contracted by 

NIOSH and prepared by Bernard Gadagbui, Ph.D., and Andrew Maier, Ph.D.. 

For their contribution to the technical content and review of this document, special 

acknowledgment is given to the following NIOSH personnel:

Denver Field Office

Eric Esswein, M.Sc.

Division of Applied Research and Technology 

John Snawder, Ph.D.

Division of Respiratory Disease Studies 

Gregory A. Day, Ph.D. 

Aleksander Stefaniak, Ph.D. 

Division of Surveillance, Hazard Evaluations, and Field Studies

Kevin Dunn, M.S.

Todd Niemeier, M.Sc.

Loren Tapp, M.D.

Aaron Sussell, Ph.D. 

Education and Information Division 

Devin Baker, M.Ed.

Charles L. Geraci, Ph.D.

Thomas J. Lentz, Ph.D.

Richard Niemeier, Ph.D.

Ralph Zumwalde, M.Sc.

Health Effects Laboratory Division

Stacey Anderson, Ph.D.

H. Fredrick Frasch, Ph.D. 

Anna Shvedova, Ph.D.

Paul Siegel, Ph.D.

Berran Yucesoy, Ph.D.
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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.

National Personal Protective Technology Laboratory

Heinz Ahlers, JD, M.Sc.

Gregory Day, Ph.D.

Angie Shepherd

In addition, special appreciation is expressed to the following individuals for serving as 

independent, external reviewers and providing comments that contributed to the development or 

improvement of this document:

 G. Frank Gerberick, Ph.D., The Procter and Gamble Company, Cincinnati, OH

 Dori Germolec, Ph.D., National Toxicology Program, National Institute for 

Environmental Health Sciences, Research Triangle, NC

 Ben Hayes, MD, Ph.D., Division of Dermatology, Vanderbilt School of Medicine, 

Nashville, TN 

 Jennifer Sahmel, MSc, CIH, ChemRisk, Boulder, CO

 James Taylor, MD, Industrial Dermatology, The Cleveland Clinic, Cleveland, OH
1

SK Profile for Group C

Draft: Sept 2013

1.0 Introduction

1.1 General Substance Information

Chemical: 1-Bromopropane (1-BP)

CAS No: 106-94-5

Molecular weight (MW): 123.00

Molecular formula: CH3CH2CH2Br

Structural formula:

Synonyms: 1-BP; N-Propyl bromide; nPB; Propyl bromide; n-Propyl bromide; Propane, 1-

bromo

Uses: 1-Bromopropane (1-BP) is used primarily as a solvent in vapor degreasing and cold 

cleaning operations, as well as adhesive and coating spray applications [USEPA 2003]. An 

estimated 8.2 million pounds (3.8 million kilograms) of 1-BP was used in the US in 2002 [NTP 

2004].

1.2 Purpose 

This skin notation profile presents (1) a brief summary of epidemiological and toxicological data 

associated with skin contact with 1-BP and (2) the rationale behind the hazard-specific skin 

notation (SK) assignment for 1-BP. The SK assignment is based on the scientific rationale and 

logic outlined in the Current Intelligence Bulletin (CIB) 61: A Strategy for Assigning New 

NIOSH Skin Notations [NIOSH 2009]. The summarized information and health hazard 

assessment are limited to an evaluation of the potential health effects of dermal exposure to 1-BP

and the potential for direct skin injuries from 1-BP. A literature search was conducted through 

January 2013 to identify 1-BP toxicokinetics, acute toxicity, repeated-dose systemic toxicity, 

carcinogenicity, biological system/function–specific effects (including reproductive and 

developmental effects and immunotoxicity), irritation, and sensitization. Information was 

considered from studies of humans, animals, or appropriate modeling systems that are relevant to 

assessing the effects of dermal exposure to 1-BP.

Br

CH3
2

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information quality guidelines. It has not been formally disseminated by the National Institute for 

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agency determination or policy.

1.3 Overview of SK Assignment for 1-Bromopropane

1-Bromopropane is potentially capable of causing numerous adverse health effects following 

skin contact. A critical review of available data has resulted in the following SK assignment for 

1-BP: SK: SYS-DIR (IRR). Table 1 provides an overview of the critical effects and data used to 

develop the SK assignment for 1-BP. 

Table 1. Summary of the SK Assignment for 1-BP

Skin Notation Critical Effect Available Data

SK: SYS Neurotoxicity; reproductive 

and developmental toxicity

Human data and animal toxicity data 

from studies of alternative exposure 

routes (inhalation, oral, and 

subcutaneous injection)

SK: DIR(IRR) Skin irritation Limited animal data

2.0 Systemic Toxicity from Skin Exposure (SK: SYS)

There were no toxicokinetic studies involving humans identified; however an in vitro dermal 

penetration study was identified. Frasch et al. [2011] used heat-separated epidermal membranes 

from Caucasian female breasts or abdominal skin samples with 3 different dosing regimens. The 

skin samples were dosed with 10 microliters per square centimeter (μL/cm2), equivalent to 13.5 

milligrams per square centimeter (mg/cm2), in an non occluded environment to simulate splash 

exposures; had a transient exposure where 1-BP was applied to donor compartments in an 

occluded environment, and then removed after 10 minutes of exposure with the skin surfaces 

wiped to remove excess 1-BP; or were exposed to an infinite dose of 1-BP in an occluded 

environment for 3 hours [Frasch et al. 2011]. The authors noted that the total amount of 1-BP 

absorbed from the 13.5 mg/cm2dose was 22 μg/cm2, corresponding to an average penetration of 

0.16% of the applied dose [Frasch et al. 2011]. The total amount of 1-BP absorbed from transient 

and infinite exposures was 179 μg/cm2, and 1,322 μg/cm2, respectively [Frasch et al. 2011]. 

These data indicate that 1-BP has the potential for substantial dermal penetration dependent of 

type and duration of exposure. The potential of 1-BP to pose a skin absorption hazard has also 

been evaluated with use of a predictive algorithm for estimating and evaluating the health 

hazards of dermal exposure to chemical substances [NIOSH 2009]. The evaluation method 

compares the chemical dose accumulated in the body from skin absorption and the dose from 

respiratory absorption during the same period. The ratio of the skin dose to the inhalation dose 

(SI ratio) calculated for 1-BP by this alternative method was 17.02. An SI ratio of ≥0.1 indicates 

that skin absorption may significantly contribute to the overall body burden of a substance 
3

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[NIOSH 2009]; therefore, 1-BP is considered to be absorbed through the skin following dermal 

exposure. Additional information on the SI ratio can be found in the appendix.

No dermal lethal doses (LDLo) of 1-BP for humans have been identified. Only one acute dermal 

toxicity study was identified, in which 1-BP (2,000 milligrams per kilogram body weight 

[mg/kg]; 99.3% purity) was applied to the shaved dorsal skin of rats under semi-occlusive wrap 

for 24 hours [Elf Atochem 1995a]. In this study, no clinical signs of toxicity were observed, and 

the authors concluded that the dermal LD50 (the dose resulting in 50% mortality in the exposed 

population) was higher than 2,000 mg/kg, indicating that 1-BP is not acutely toxic upon dermal 

expsoure. However, 1-BP is highly volatile, and the use of semi-occlusive instead of occlusive 

wrap is likely to have resulted in evaporation of the chemical, leading to a less-than-optimal 

exposure period.

Because of a paucity of toxicokinetic and toxicity data concerning skin exposures to 1-BP, a 

review of data associated with alternative exposure pathways (e.g., inhalation, oral, and 

subcutaneous injections) was conducted. Numerous studies of rats revealed systemic effects, 

including neurotoxicity, hepatotoxicity, hematotoxicity, reproductive toxicity, and 

developmental toxicity, attributed to the inhalation of airborne 1-BP below 1,000 parts per 

million (ppm) [ClinTrials Bioresearch 1997; Ichihara et al. 2000a, b; WIL Research Laboratories 

2001; Wang et al. 2002, 2003; Yamada et al. 2003; NTP 2004; Banu et al. 2007; Fueta et al. 

2007]. Anderson et al. [2010] reported significant decreases in the spleen IgM responses to sheep 

red blood cells in mice (125-500 ppm) and rats (1000 ppm) after whole body inhalation exposure 

to 1-BP for 10 weeks. Lee et al. [2005, 2007] treated mice with a single dose of 1-BP at levels of 

200, 500, and 1,000 mg/kg via the oral route. At 500- and 1000-mg/kg treatment levels, the 

authors reported a significant increase in relative liver weight and changes in liver enzyme levels 

[Lee et al. 2005, 2007]. In another investigation, Zhao et al. [1999] treated rats with daily 

injections of 1-BP at treatment levels of 3.7 millimoles (mmol)/kg (corresponding to 455 mg/kg) 

and 11.0 mmol/kg (corresponding to 1,353 mg/kg) for 20 days. At both treatment levels, 

neurotoxic effects were reported. 

There were no human epidemiological studies or repeated-dose (subchronic or chronic) studies 

in animals that evaluated the potential of 1-BP to cause systemic toxicity following dermal 

exposure identified. However, occupational (presumably a combination of dermal and 

respiratory) exposure to 1-BP resulted in neuropathy in a male worker after he was exposed for 2 

months to a degreasing solvent (containing 95.5% 1-BP, less than 0.5% butylene oxide, less than 

2.5% 1,3-dioxolane, and less than 0.25% nitromethane) [Sclar 1999]. In addition, central nervous 

system effects were noted in a cohort of workers who had sprayed an adhesive (containing 70% 

1-BP, 0.3% 1,2-epoxybutane, 10% styrene-butadiene rubber, and 20% rosin ester) without 

proper personal protective equipment in a poorly ventilated area for 30 to 40 hours a week for 3 

months [Beck and Caravati 2003]. Other case reports also detailed nervous system effects 

[Ichihara et al. 2002, 2004a, 2004b; Majersik et al. 2007; Raymond and Ford 2007]. Hanley et al. 

[2006] assessed occupational exposures to 1-BP through air sampling and urinary testing for 

bromide (Br-) concentrations (a known biomarker of 1-BP exposure) in workers employed as 

either adhesive sprayers or nonsprayers at foam-fabricating plants that used a spray adhesive 
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containing within 1-BP during the manufacture of polyurethane seat cushions. One of the 

reported findings included a lower than expected correlation between urinary Brconcentration 

and time-weighted average (TWA) for sprayers. The authors stated that this disparity may be due 

to the absorption of 1-BP by the skin when the sprayers handled the wet adhesive with bare 

hands. The results of Hanley et al. [2006] indicate that 1-BP may be absorbed via the skin, thus 

contributing to the systemic dose. 

No standard toxicity or specialty studies evaluating biological system/function–specific effects 

(including reproductive and developmental effects and immunotoxicity) following dermal 

exposure to 1-BP were identified. Table 2 summarizes the carcinogenic designations for 1-BP 

from NIOSH and other governmental and nongovernmental organizations.

Table 2. Summary of the carcinogenic designations for 1-BP by numerous governmental 

and nongovernmental organizations

Organization Carcinogenic Designation 

NIOSH No designation

NTP [2014] Reasonably anticipated to be a human carcinogen

European Parliament [2008] No GHS designation

USEPA [2015] No designation

IARC [2012] No designation

ACGIH [2014] A3, Confirmed animal carcinogen with unknown relevance 

to humans

ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint 

Research, Institute for Health and Consumer Protection; GHS = Globally Harmonized System for Classification and 

Labelling of Chemicals; IARC = International Agency for Research on Cancer; NIOSH = National Institute for 

Occupational Safety and Health; NTP = National Toxicology Program; USEPA = United States Environmental 

Protection Agency.

Although the mathematical model predicted that 1-BP was not readily absorbed by the skin, 

there was an in vitro dermal penetration study identified that indicates that 1-BP has the potential 

for substantial dermal penetration dependent on type and duration of exposure [Frasch et al. 

2011]. Studies of workers exposed to 1-BP indicate that the solvent may be absorbed by the skin 

and contribute to systemic toxicity, but the results of these investigations are confounded by the 

inhalation of 1-BP vapors [Sclar 1999; Ichihara et al. 2002, 2004a, 2004b; Beck and Caravati 

2003; NTP 2004; Hanley et al. 2006; Majersik et al. 2007; Raymond and Ford 2007]. A review

of animal toxicity data from several non-dermal exposure routes indicated that 1-BP is capable of 

inducing a range of systemic effects, including neurotoxicity, hepatotoxicity, hematotoxicity, 

reproductive toxicity, and developmental toxicity in a dose-response manner [ClinTrials 

Bioresearch 1997; Zhao et al. 1999; Ichihara et al. 2000a, 2000b; WIL Research 

Laboratory 2001; Wang et al. 2002, 2003; Lee et al. 2005, 2007; Banu et al. 2007; Fueta et 

al. 2007]. Therefore, on the basis of these data, 1-BP is assigned the SK: SYS notation. 
5

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information quality guidelines. It has not been formally disseminated by the National Institute for 

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agency determination or policy.

3.0 Direct Effects on Skin (SK: DIR)

No evidence of skin corrosivity of 1-BP, no in vitro tests for corrosivity in human or animal skin 

models, and no in vitro tests of skin integrity using cadaver skin were identified. Frasch et al. 

[2011] evaluated the corrosivity of 1-BP using the EpiDerm human reconstructed epidermis 

model. Using this model, a chemical is classified as corrosive to skin if the cell viability after a 3 

minute exposure is less than 50% and less than 15% after a one hour exposure [Frasch et al. 

2011]. Frasch et al. [2011] found that after the 3 minute exposure, the viability for cells exposed 

to 1-BP was 101% compared to the water-exposed control and a one hour exposure of 1-BP had 

a cell viability of 22%, indicating that 1-BP is not considered corrosive to the skin. No studies on 

the skin-irritating potential of 1-BP in humans were identified, but there is limited evidence that 

the substance is a skin irritant in animals. Using a Draize scale, Jacobs et al. [1987] reported 1-

BP was a skin irritant, and observed a limit concentration (defined as the highest tested 

concentration at which the mean erythema score remains below 2) for skin irritation of 50% for 

1-BP solution in sweet almond oil in rabbits. In another test, performed according to the 

chemical testing guidelines of the Organization for Economic Co-operation and Development 

(OECD), topical application of 1-BP to rabbit skin produced erythema and edema and complete 

regeneration of the skin occurred within 8 days [Pálovics 2004]. Pálovics [2004] also tested the 

irritation potential of 1-BP on the chorioallantoic membrane of hen’s egg according to the 

ECVAM/INVITTIX Protocol. In this test, local application of 1-BP caused copious hemorrhage 

and moderate lysis of blood vessels in the chorioallantoic membrane, indicating severe irritation 

after exposure to 1-BP; however, this procedure is typically used to evaluate ocular irritancy. 

Although rats administered 2,000 mg/kg 1-BP covered by a semi-occlusive dressing for 24 hours 

exhibited no cutaneous reaction [Elf Atochem 1995a], use of the semi-occlusive rather than 

occlusive wrap in this study was likely to result in less-than-optimal exposure. This may explain 

the lack of irritation observed by those investigators. The structure–activity relationship model 

(Deductive Estimation of Risk from Existing Knowledge, or DEREK, for Windows) predicted 1-

BP to be negative for skin irritation.

A study using the EpiDerm human reconstructed epidermis model [Frasch et al. 2011] indicated 

that 1-BP is not corrosive to the skin following exposure to 1-BP. Two in vivo tests conducted 

with standard methods [Jacobs et al. 19871; Pálovics 2004], provide limited evidence that 1-BP 

is irritating to the skin of rabbits. Therefore, on the basis of the findings for this assessment, 1-BP 

is assigned a skin notation of SK: DIR (IRR).

 

1 References in bold text indicate studies that served as the basis of the SK assignment.
6

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4.0 Immune-mediated Responses (SK: SEN)

No diagnostic human patch tests that evaluated the potential of 1-BP to cause skin sensitization 

were identified. However, one study evaluated the skin sensitization potential of 1-BP with use 

of the guinea pig maximization test. In this study, Elf Atochem [1995b] intradermally injected 

0.1 ml of 1-BP solution at a concentration of 25% on day 1, and applied 0.5ml of 1-BP in 

occlusive conditions to the skin of guinea pigs for 48 hours on day 8. A challenge dose of 0.5 ml 

1-BP was given on day 12 on the left flank in occlusive conditions for 24 hours [Elf Atochem 

1995b]. The investigators did not observe any cutaneous reactions that can be attributed to the 

sensitization potential of 1-BP [Elf Atochem 1995b]. DEREK predicted 1-BP to have skin 

sensitization potential. However, because of the absence of human data and insufficient animal 

data, a skin notation of SK: SEN is not assigned to 1-BP. 

5.0 Summary

Although the mathematical model predicted that 1-BP was not readily absorbed by the skin, 

there was an in vitro dermal penetration study identified that indicates that 1-BP has the potential 

for substantial dermal penetration dependent of type and duration of exposure [Frasch et al. 

2011]. A review of the available literature indicates that 1-BP is capable of inducing a wide array 

of adverse systemic health effects, including neurotoxicity, hepatotoxicity, hematotoxicity, 

reproductive toxicity, and developmental toxicity, regardless of exposure route [ClinTrials 

Bioresearch 1997; Zhao et al. 1999; Ichihara et al. 2000a, 2000b; WIL Research 

Laboratory 2001; Wang et al. 2002, 2003; Lee et al. 2005, 2007; Banu et al. 2007; Fueta et 

al. 2007]. Although the exact systemic hazards associated with skin contact and absorption of 1-

BP are unknown, 1-BP is assigned the SK: SYS notation; this notation is based on the 

recognition of adverse health effects in test animals exposed via the inhalation, oral, and 

subcutaneous injection routes. Although a study using the EpiDerm human reconstructed 

epidermis model [Frasch et al. 2011] indicated that 1-BP is not corrosive to the skin following 

exposure to 1-BP, two in vivo tests, conducted with standard methods [Jacobs et al. 19872; 

Pálovics 2004], provide limited evidence that 1-BP is irritating to the skin of rabbits. Although 

no human patch tests that evaluated the sensitization potential of 1-BP were identified, one 

guinea pig maximization test [Elf Atochem 1995b] showed that the substance is not a skin 

sensitizer. Therefore, on the basis of this assessment, 1-BP is assigned the composite skin 

notation SK: SYS-DIR (IRR). 

Table 3 summarizes the skin designations for 1-BP from NIOSH and other organizations. The 

equivalent skin designation for 1-BP from the Globally Harmonized System (GHS) of 

Classification and Labelling is Reproductive Category 1B (Presumed human reproductive toxicant) 

and Skin Irritation Category 2 (Causes skin irritation) [European Parliament 2008].

 

2 References in bold text indicate studies that served as the basis of the SK assignment.
7

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Table 3. Summary of previous skin hazard designations for 1-BP

Organization Dermal Classification

NIOSH [2005] No designation

OSHA [2015]* No designation

ACGIH [2014] No designation

EC [2013]* R38: Irritating to skin

ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint 

Research, Institute for Health and Consumer Protection; NIOSH = National Institute for Occupational Safety and 

Health; OSHA = Occupational Safety and Health Administration.

*Date accessed.
8

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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

Note: Asterisks (*) denote sources cited in text; daggers (†) denote additional resources.

*ACGIH (American Conference of Governmental Industrial Hygienists) [2014]. 1-

Bromopropane. In: 2014 TLVs and BEIs: Based on the documentation of the threshold limit 

values for chemical substances and physical agents and biological exposure indices. Cincinnati, 

OH: American Conference of Governmental Industrial Hygienists.

*Anderson SE, Munson, AE, Butterworth LF, Germolec D, Morgan DL, Roycroft JA, Dill J, 

Meade BJ [2010]. Whole-body inhalation exposure to 1-bromopropane suppresses the IgM 

response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats. Inhal Toxicol 

22(1): 125-132.

*Banu S, Ichihara S, Huang F, Ito H, Inaguma Y, Furuhashi K, Fukunaga Y, Wang O, Kitoh J, 

Ando H, Kikkawa F, Ichihara G [2007]. Reversibility of the adverse effects of 1-bromopropane 

exposure in rats. Toxicol Sci 100(2):504–512.

*Beck BR, Caravati EM [2003]. Neurotoxicity associated with 1-bromopropane exposure: Utah 

Poison Control Center, University of Utah, Salt Lake City, UT. J Toxicol Clin Toxicol 

41(5):729. 

*ClinTrials BioResearch [1997]. A 28-day inhalation study of a vapor formulation of ALBTA1 

in the albino rat. Bio-Research Project No. 91189 (sponsored by Albermarle Corporation). 

Senneville, Quebec, Canada: ClinTrials BioResearch, H9X 3R3, EPA Docket A-91-42, 

Document X-A-4.

*EC (European Commission) [ND]. 1-Bromopropane. In: EINECS (European INventory of 

Existing Commercial Chemical Substances), http://esis.jrc.ec.europa.eu/. Accessed: 02-28-13.

*European Parliament, Council of the European Union [2008]. Regulation (EC) No 1272/2008 

of the European Parliament and of the Council of 16 December 2008 on classification, labeling 

and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 

1999/45/EC, and amending Regulation (EC) No 1907/2006. OJEU, Off J Eur Union L353:1–

1355, http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:EN:PDF. Accessed: 

01-29-15. 

*Elf Atochem [1995a]. Acute dermal toxicity in rats: n-propyl bromide. Study No. 13113 TAR. 

Document OAR-2002-0064, available from U.S. Environmental Protection Agency, 

Washington, DC.
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.

*Elf Atochem [1995b]. Skin sensitization test in guinea-pigs: n-propyl bromide. Study No. 

12094 TSG. Document OAR-2002-0064, available from U.S. Environmental Protection Agency, 

Washington, DC. 

*Frasch, HF, Dotson GS, Barbero AM [2011]. In vitro human epidermal penetration of 1-

bromopropane. J Toxicol Environ Health Part A 74(19):1249-1260.

* Fueta Y, Ishidao T, Ueno S, Yoshida Y, Kunugita N, Hori H [2007]. New approach to risk 

assessment of central neurotoxicity induced by 1-bromopropane using animal models. 

Neurotoxicology 28(2):270–273.

*Hanley KW, Petersen BD, Curwin BD, Sanderson ET [2006]. Urinary bromide and breathing 

zone concentrations of 1-Bromopropane from workers exposed to flexible foam spray adhesives. 

Ann Occup Hyg 50(6):599–607.

*IARC (International Agency for Research on Cancer) [2009]. Agents reviewed by the IARC 

monographs. In: IARC monographs on the evaluation of carcinogenic risks to humans, 

http://monographs.iarc.fr/ENG/Classification/ClassificationsAlphaOrder.pdf. Accessed: 01-29-

15.

*Ichihara G, Yu X, Kitoh J, Asaeda N, Kumazawa T, Iwai H, Shibata E, Yamada T, Wang H, 

Xie Z, Maeda K, Tsukamura H, Takeuchi Y [2000a]. Reproductive toxicity of 1-bromopropane, 

a newly introduced alternative to ozone layer depleting solvents, in male rats. Toxicol Sci 

54:416–423. 

*Ichihara G, Kitoh J, Yu X, Asaeda N, Iwai H, Kumazawa T, Kumazawa T, Shibata E, Yamada 

T, Wang H, Xie Z, Takeuchi Y [2000b]. 1-Bromopropane, an alternative to ozone depleting 

solvents, is dose dependently neurotoxic to rats in long-term inhalation exposure. Tox Sci 

55:116–123. 

*Ichihara G, Miller JK, Ziolkowska A, Itohara S, Takeuchi Y [2002]. Neurological disorders in 

three workers exposed to 1-bromopropane. J Occup Health 44:1–7. 

*Ichihara G, Li W, Ding X, Peng S, Yu X, Shibata E, Yamada T, Wang H, Itohara S, Kanno S, 

Sakai K, Ito H, Kanefusa K, Takeuchi Y [2004a]. A survey on exposure level, health status, and 

biomarkers in workers exposed to 1-bromopropane. Am J Ind Med 45:63–75. 

*Ichihara G, Li W, Shibata E, Ding X, Wang H, Liang Y, Peng S, Itohara S, Kamijima M, Fan 

O, Zhang Y, Zhong E, Wu X, Valentine WM, Takeuchi Y [2004b]. Neurological abnormalities 

in workers of 1-bromopropane factory. Environ Health Perspect 112(13):1319–1325.
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.

*Jacobs G, Martens M, Mosselmans G [1987]. Proposal of limit concentrations for skin irritation 

within the context of a new EEC directive on the classification and labeling of preparations. 

Regul Toxicol Pharmacol 7(4):370–378. 

*Lee SK, Jo SW, Jeon TW, et al. [2005]. Hepatotoxic effect of 1-bromopropane and its 

conjugation with glutathione in male ICR mice. Arch Pharm Res 28(10):1177–1182.

* Lee SK, Jo SW, Kim YB, et al. [2007]. Role of glutathione conjugation in the hepatotoxicity 

and immunotoxicity induced by 1-bromopropane in female BALB/c mice. J Appl Toxicol 

27(4):358–367.

*Majersik JJ, Caravati EM, Steffens JD [2007]. Severe neurotoxicity associated with exposure to 

the solvent 1-bromopropane (n-propyl bromide). Clin Toxicol 45:270–276.

*NIOSH [2005]. NIOSH pocket guide to chemical hazards. Cincinnati, OH: U.S. Department of 

Health and Human Services, Centers for Disease Control and Prevention, National Institute for 

Occupational Safety and Health, DHHS (NIOSH) Publication No. 2005-149, 

http://www.cdc.gov/niosh/npg/. Accessed: 01-29-15. 

*NIOSH [2009]. Current intelligence bulletin 61: a strategy for assigning new NIOSH skin 

notations. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease 

Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) 

Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/pdfs/2009-147.pdf. 

Accessed: 01-29-15.

*NTP (National Toxicology Program) [2004]. NTP-CERHR Expert Panel report on the 

reproductive and development toxicity of 1-bromopropane. Reproductive Toxicol 18:157–188.

*NTP [2014]. Report on Carcinogens. Thirteenth Edition; U.S. Department of Health and 

Human Services, Public Health Service. National Toxicology Program, 

http://ntp.niehs.nih.gov/pubhealth/roc/roc13/index.html. Accessed: 01-29-15.

*Occupational Safety and Health Administration (OSHA) [ND]. OSHA Occupational chemical 

database, https://www.osha.gov/chemicaldata/. Accessed: 01-29-15.

*Pálovics Á [2004]. Epithelial irritation effect of 1-bromopropane, an alternative solvent to 

chlorofluorocarbons. CEJOEM 10(4): 333–337.

*Raymond LW, Ford MD [2007]. Severe illness in furniture makers using a new glue: 1-

bromopropane toxicity confounded by arsenic. J Occup Environ Med 49(9): 1009–1019.

†RTI (Research Triangle Institute) [2005]. Report on uptake and metabolism of 1-bromopropane 

in rats and mice. Research Triangle Institute report for the National Toxicology Program, 

Documents EPA-HQOAR-2002-0064-0077, -0080, -0081, -0082, -0101, -0104, -0137, -0137.1.
11

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.

*Sclar G [1999]. Encephalomyeloradiculoneuropathy following exposure to an industrial 

solvent. Clin Neurol Neurosurg 101:199–202.

†UNECE (United Nations Economic Commission for Europe) [2005]. Globally harmonized 

system of classification and labeling of chemicals (GHS). ST/SG/AC.10/30. New York and 

Geneva: United Nations Economic Commission for Europe.

*USEPA (United States Environmental Protection Agency) [2003]. Protection of stratospheric 

ozone: listing of substitutes for ozone-depleting substances-n-propyl bromide: proposed rule. 

Federal Register, Part III, 40 CFR Part 82, Vol. 68, No. 106, June 3, 2003, pp. 33284–33316.

*USEPA (United States Environmental Protection Agency) [2015]. Integrated Risk Information 

System (IRIS), http://www.epa.gov/iris/. Accessed: 01-29-15. 

*Wang H, Ichihara G, Ito H, et al. [2002]. Biochemical changes in the central nervous system of 

rats exposed to 1-bromopropane for seven days. Toxicol Sci 67:114–120.

*Wang H, Ichihara G, Ito H, et al. [2003]. Dose-dependent biochemical changes in rat central 

nervous system after 12-week exposure to 1-BP. Neurotoxicology 24:199–206.

*WIL Research Laboratories [2001]. An inhalation two-generation reproductive toxicity study of 

1-bromopropane in rats. Study No. WIL-380001. Ashland, OH: Brominated Solvents Committee 

(sponsor). 

*Yamada T, Ichihara G, Wang H, et al. [2003]. Exposure to 1-bromopropane causes ovarian 

dysfunction in rats. Toxicol Sci 71:96–103.

*Zhao K, Xie AT, Misumi J [1999]. Electrophysiological changes induced by different doses of 

1-bromopropane and 2-bromopropane. J Occup Health 41:1–7.
12

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.

Appendix: Calculation of the SI Ratio for 1-Bromopropane

This appendix presents an overview of the SI ratio and a summary of the calculation of the SI 

ratio for 1-BP. Although the SI ratio is considered in the determination of a substance’s hazard 

potential following skin contact, it is intended only to serve as supportive data during the 

assignment of the NIOSH SK. An in-depth discussion on the rationale and calculation of the SI 

ratio can be found in Appendix B of the Current Intelligence Bulletin (CIB) 61: A Strategy for 

Assigning New NIOSH Skin Notations [NIOSH 2009]. 

Overview 

The SI ratio is a predictive algorithm for estimating and evaluating the health hazards of skin 

exposure to substances. The algorithm is designed to evaluate the potential for a substance to 

penetrate the skin and induce systemic toxicity [NIOSH 2009]. The goals for incorporating this

algorithm into the proposed strategy for assigning SYS notation are as follows:

(1) Provide an alternative method to evaluate substances for which no clinical reports or 

animal toxicity studies exist or for which empirical data are insufficient to determine 

systemic effects.

(2) Use the algorithm evaluation results to determine whether a substance poses a skin 

absorption hazard and should be labeled with the SYS notation.

The algorithm evaluation includes three steps:

(1) determining a skin permeation coefficient (kp) for the substance of interest,

(2) estimating substance uptake by the skin and respiratory absorption routes, and 

(3) evaluating whether the substance poses a skin exposure hazard.

The algorithm is flexible in the data requirement and can operate entirely on the basis of the 

physicochemical properties of a substance and the relevant exposure parameters. Thus, the 

algorithm is independent of the need for biologic data. Alternatively, it can function with both 

the physicochemical properties and the experimentally determined permeation coefficient when 

such data are available and appropriate for use.

The first step in the evaluation is to determine the kp for the substance to describe the transdermal 

penetration rate of the substance [NIOSH 2009]. The kp, which represents the overall diffusion of 

the substance through the stratum corneum and into the blood capillaries of the dermis, is 

estimated from the compound’s molecular weight (MW) and base-10 logarithm of its octanol–

water partition coefficient (log KOW). In this example, kp is determined for a substance with use of 

Equation 1. A self-consistent set of units must be used, such as centimeters per hour (cm/hr), 

outlined in Table A1. Other model-based estimates of kp may also be used [NIOSH 2009].
13

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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.

Equation 1: Calculation of Skin Permeation Coefficient (kp)

psc pol aq

p

k k k

k

1 1

1







where kpsc is the permeation coefficient in the lipid fraction of the stratum corneum, kpol is the 

coefficient in the protein fraction of the stratum corneum, and kaq is the coefficient in the watery 

epidermal layer. These components are individually estimated by

log kpsc = −1.326 + 0.6097 × log Kow − 0.1786 × MW0.5

kpol = 0.0001519 × MW−0.5

kaq = 2.5 × MW−0.5

The second step is to calculate the biologic mass uptake of the substance from skin absorption 

(skin dose) and inhalation (inhalation dose) during the same period of exposure. The skin dose is 

calculated as a mathematical product of the kp, the water solubility (SW) of the substance, the 

exposed skin surface area, and the duration of exposure. Its units are milligrams (mg). Assume 

that the skin exposure continues for 8 hours to unprotected skin on the palms of both hands (a 

surface area of 360 squared centimeters [cm2]). 

Equation 2: Determination of Skin Dose

Skin dose = kp × Sw × Exposed skin surface area × Exposure time

 = kp(cm/hr) × Sw (mg/cm3) × 360 cm2× 8 hr

The inhalation dose (in mg) is derived on the basis of the occupational exposure limit (OEL) of 

the substance—if the OEL is developed to prevent the occurrence of systemic effects rather than 

sensory/irritant effects or direct effects on the respiratory tract. Assume a continuous exposure of 

8 hours, an inhalation volume of 10 cubic meters (m3) inhaled air in 8 hours, and a factor of 75% 

for retention of the airborne substance in the lungs during respiration (retention factor, or RF).

Equation 3: Determination of Inhalation Dose

Inhalation dose = OEL × Inhalation volume × RF

 = OEL (mg/m3) × 10 m3× 0.75

The final step is to compare the calculated skin and inhalation doses and to present the result as a 

ratio of skin dose to inhalation dose (the SI ratio). This ratio quantitatively indicates (1) the 

significance of dermal absorption as a route of occupational exposure to the substance and (2) 

the contribution of dermal uptake to systemic toxicity. If a substance has an SI ratio greater than 

or equal to 0.1, it is considered a skin absorption hazard.
14

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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.

Calculation 

Table A1 summarizes the data applied in the previously described equations to determine the SI 

ratio for 1-BP. The calculated SI ratio was 8.43. On the basis of these results, 1-BP is predicted 

to represent a skin absorption hazard.

Table A1. Summary of Data used to Calculate the SI Ratio for 1-BP 

Variables Used in Calculation Units Value 

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path(kpsc) cm/hr 0.00941

Permeation coefficient of the protein fraction of the stratum 

corneum (kpol) cm/hr 1.3696 × 10-6

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.22542

Molecular weight (MW)

*

amu 123

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

* None 2.1

Calculated skin permeation coefficient (kp) cm/hr 0.00904575

Skin dose

Water solubility (Sw)

* mg/cm3

2.45

Calculated skin permeation coefficient (kp) cm/hr 0.00904575

Estimated skin surface area (palms of hand) cm2360

Exposure time hr 8

Calculated skin dose mg 63.8268

Inhalation Dose

Occupational exposure limit (OEL)† mg/m31.01

Inhalation volume m

3

10

Retention factor (RF) None 0.75

Inhalation dose mg 7.575

Skin dose–to–inhalation dose (SI) ratio None 8.42598

*

Variables identified from SRC [ND].

†

The OEL used in calculation of the SI ratio for 1-BP was the ACGIH threshold limit value (TLV) [ACGIH 

2014].
15

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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.

Appendix References 

ACGIH (American Conference of Governmental Industrial Hygienists) [2014]. 1-

Bromopropane. In: 2014 TLVs and BEIs, Based on the documentation of the threshold limit 

values for chemical substances and physical agents and biological exposure indices. Cincinnati, 

OH: American Conference of Governmental Industrial Hygienists.

NIOSH [2009]. Current intelligence bulletin 61: a strategy for assigning new NIOSH skin 

notations. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease 

Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) 

Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/pdfs/2009-147.pdf. 

Accessed: 01-29-15.

SRC [2009]. Interactive PhysProp database demo, 

http://esc.syrres.com/fatepointer/webprop.asp?CAS=106945. Accessed 01-29-15.