Skin Notation (SK) Profile

Sodium fluoroacetate (SFA)

[CAS No. 62-74-8]

Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
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Suggested Citation

NIOSH [20XX]. NIOSH skin notation profile: Sodium fluoroacetate (SFA). 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 sodium 

fluoroacetate (SFA). 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, policyand decision-makers, employers, and workers in potentially hazardous workplaces—so that 

improved risk-management 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.................................................................................................................. 2

2.0 Systemic Toxicity from Skin Exposure (SK: SYS).................................................................................. 2

3.0 Direct Effects on Skin (SK: DIR)........................................................................................................... 3

4.0 Immune-mediated Responses (SK: SEN)............................................................................................. 3

5.0 Summary............................................................................................................................................ 3

References............................................................................................................................................... 5

Appendix: Calculation of the SI Ratio for SFA........................................................................................... 7

Overview .................................................................................................................................................... 7

Calculation ................................................................................................................................................. 9

Appendix References................................................................................................................................ 10
v

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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 

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

(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

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit

OSHA Occupational Safety and Health Administration

ppm parts per million
vi

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agency determination or policy.

REL recommended exposure limit

RF retention factor 

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

exposure of the skin

SFA sodium fluoroacetate

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, Clayton B’Hymer, Ph.D., and John Snawder, 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 Respiratory Disease Studies 

Gregory A. Day, Ph.D. 

Aleksander Stefaniak, Ph.D. 

Division of Surveillance, Hazard Evaluations, and Field Studies

Matt Dahm, M.Sc.

Todd Niemeier, M.Sc.

Aaron Sussell, Ph.D.

Loren Tapp, M.D. 

Education and Information Division 

Devin Baker, M.Ed.

Charles L. Geraci, Ph.D.

Thomas J. Lentz, Ph.D.

Richard Niemier, Ph.D.

Ralph Zumwalde, M.Sc.

Health Effects Laboratory Division

Stacey Anderson, Ph.D.

H. Fredrick Frasch, Ph.D. 

Michael Luster, Ph.D. 

Anna Shvedova, Ph.D.

Paul Siegel, Ph.D.

Berran Yucesoy, Ph.D.

National Personal Protective Technology Laboratory

Heinz Ahlers, J.D., M.Sc.

Angie Shepherd
ix

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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.

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

acknowledgment is given to the following CDC personnel:

Office of Surveillance, Epidemiology and Laboratory Services/Epidemiology and Analysis 

Program Office 

Barbara Landreth, M.A.

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, M.D., Ph.D., Division of Dermatology, Vanderbilt School of Medicine, 

Nashville, TN 

 Jennifer Sahmel, M.Sc., CIH, ChemRisk, Boulder, CO

 James Taylor, M.D., Industrial Dermatology, The Cleveland Clinic, Cleveland, OH
1

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policy.

1.0 Introduction 

1.1 General Substance Information 

Chemical: Sodium fluoroacetate (SFA)

CAS No: 62-74-8

Molecular weight (MW): 100.3

Molecular formula: FCH2COONa

Structural formula:

Synonyms: SFA; sodium monofluoroacetate

Uses: SFA is an organofluorine compound used primarily as a predacide [USEPA 1995]. No estimate of 

the annual volume produced or used in the United States was identified during this assessment. 

1.2 Purpose 

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

associated with skin contact with SFA and (2) the rationale behind the hazard-specific skin notation 

(SK) assignment for SFA. 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 SFA. A literature search was conducted through 

February 2013 to identify information on SFA, including but not limited to data relating to its 

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 

SFA. 
2

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policy.

1.3 Overview of SK Assignment

SFA may potentially be capable of causing adverse health effects following skin contact. A critical 

review of available data has resulted in the following SK assignment for SFA: ID(SK). Table 1 provides 

an overview of the critical effects and data used to develop the SK assignment for SFA. 

Table 1. Summary of the SK Assignment for SFA

Skin Notation Critical

Effect

Available

Data

ID(SK)- -

2.0 Systemic Toxicity from Skin Exposure (SK: SYS)

No in vivo or in vitro toxicokinetic studies were identified that estimated the degree of absorption of 

SFA through the skin of humans or animals following dermal exposure. The potential of SFA to pose a 

skin absorption hazard was also evaluated, with use of a predictive algorithm for estimating and 

evaluating the health hazards of dermal exposure to substances [NIOSH 2009]. The evaluation method 

compares an estimated dose accumulated in the body from skin absorption and an estimated dose from 

respiratory absorption associated with a reference occupational exposure limit. On the basis of this 

algorithm, a ratio of the skin dose to the inhalation dose (SI ratio) of 161.7 was calculated for SFA. An 

SI ratio of ≥0.1 indicates that skin absorption may significantly contribute to the overall body burden of 

a substance [NIOSH 2009]; therefore, SFA is considered to be absorbed through the skin following 

dermal exposure. Additional information on the SI ratio and the variables used in its calculation are 

included in the appendix.

No estimate of the human dermal lethal dose (LDLo) was identified for SFA, and no dermal LD50 (the 

dose resulting in 50% mortality in the exposed animals) values were identified for SFA. 

No epidemiological, occupational exposure studies, or case reports and no repeat-dose, subchronic or 

chronic toxicity studies in animals were identified that evaluated the potential for SFA to cause to 

systemic toxicity following dermal exposure. Burns and Connolly [1995] reported that lambs wearing 

punctured livestock protection collars (LPC) for 7 days, exposing them to SFA, did not exhibit dermal 

erythema or edema but died after ingesting the product.

No standard toxicity or specialty studies were identified that evaluated the potential for SFA to cause 

biological system/function specific effects (including reproductive and developmental effects and 

immunotoxicity) following dermal exposure. No epidemiological studies or animal bioassays were 

identified that evaluated the carcinogenic potential of SFA following dermal exposure. Table 2 

summarizes carcinogenic designations of multiple governmental and nongovernmental organizations for 

SFA. 
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Table 2. Summary of the carcinogenic designations for SFA by numerous governmental and 

nongovernmental organizations

Organization Carcinogenic designation 

NIOSH [2005] No designation

NTP [2014] No designation

USEPA [2015] No designation 

European Parliament [2008] No GHS designation

IARC [2012] No designation

EC [2013]* No designation

ACGIH [2001] No designation

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.

*Date accessed.

Although the mathematical model predicted sodium fluoroacetate to be dermally absorbed through the 

skin following dermal exposure, no toxicokinetic studies or acute toxicity studies were identified that 

estimated the degree of absorption of SFA, or toxicity following dermal exposure. Therefore, on the 

basis of the data for this assessment, SFA is not assigned the SK: SYS notation. 

3.0 Direct Effects on Skin (SK: DIR)

No human or animal in vivo studies were identified that evaluated the skin corrosivity of SFA or in vitro

tests for corrosivity using human or animal skin models or in vitro tests of skin integrity using cadaver 

skin. Additionally, no case reports or standard skin irritation tests were identified that evaluated the 

potential of SFA to be corrosive or irritating to the skin of humans or animals. Therefore, on the basis of 

the data for this assessment, SFA is not assigned the SK: DIR (IRR) notation.

4.0 Immune-mediated Responses (SK: SEN)

No diagnostic (human patch) tests or predictive tests in animals (for example, guinea pig maximization 

tests, Buehler tests, murine local lymph node assays, or mouse ear swelling tests) or any other studies 

that were identified that evaluated the potential for SFA to cause skin sensitization. However, the 

USEPA [1995] has waved the requirement for dermal sensitization study for SFA due to severe acute 

toxicity of the compound (oral LD50 values reported in rats were 0.22 mg/kg, 0.055 mg/kg for dogs, and 

0.34 mg/kg for rabbits), and the restriction of its use in a livestock protection collar. Therefore, on the 

basis of the data for this assessment, SFA is not assigned the SK: SEN notation.

5.0 Summary

Although the mathematical model predicted sodium fluoroacetate to be dermally absorbed through the 

skin following dermal exposure, no toxicokinetic studies or acute toxicity studies were identified that 
4

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estimated the degree of absorption of SFA, or toxicity following dermal exposure. No epidemiological 

or occupational exposure studies or case reports and no repeat-dose, subbchronic or chronic toxicity 

studies were identified that evaluated the potential for SFA to be systemically toxic. No studies were 

identified that evaluated the skin corrosivity or potential for skin irritation after dermal exposure to SFA. 

Although no diagnostic (human patch) tests or predictive tests in animals were identified that evaluated 

the potential of the compound to be a skin sensitizer, the USEPA [1995] waived the requirement for 

dermal sensitization study for SFA due to severe acute toxicity of the compound and the restriction of its 

use in a livestock protection collar. Therefore, on the basis of these assessments, SFA is assigned a skin 

notation of ID(SK).

Table 3 summarizes the skin hazard designations for SFA previously issued by NIOSH and other 

organizations. The equivalent dermal designation for SFA, according to the Global Harmonization 

System (GHS) of Classification and Labelling of Chemicals, is Acute Toxicity Category 1 (Hazard 

statement: Fatal in contact with the skin) [European Parliament 2008]. 

Table 3. Summary of previous skin hazard designations for SFA

Organization Skin hazard designation 

NIOSH [2005] [skin]: Potential for dermal absorption

OSHA [2015]

*

[skin]: Potential for dermal absorption

ACGIH [2001] [skin]: Based on rapid absorption through intact and abraded or cut 

skin

EC [2013]* R27: Very toxic in contact with 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.
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policy.

References

ACGIH [2001]. Sodium fluoroacetate. In: Documentation of threshold limit values and biological 

exposure indices 7th ed., Vol. 3. Cincinnati, OH: American Conference of Governmental Industrial 

Hygienists.

Burns RJ, Connolly GE [1995] Toxicity of Compound 1080 Livestock Protection Collars to Sheep. 

Arch. Environ. Contam. Toxicol. 28: 141-144.

EC (European Commission) [ND]. Acrylic acid. In: EINICS (European Inventory of Existing 

Commercial Chemical Substances), 

http://ecb.jrc.ec.europa.eu/esis/index.php?GENRE=CASNO&ENTREE=79-10-7. Accessed: 08-15-13.

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, labelling 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: 01-28-15. 

IARC (International Agency for Research on Cancer) [2012]. Agents reviewed by the IARC 

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

http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php. Accessed: 01-28-15.

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/npgd0211.html. Accessed: 01-28-15.

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: 01-28-15.

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: 01-28-15.

OSHA [ND]. Sodium fluoroacetate. In: OSHA Occupational chemical database, 

https://www.osha.gov/chemicaldata/chemResult.html?recNo=458. Accessed: 01-28-15.

USEPA [1995]. Reregistration eligibility decision (RED) for sodium fluoroacetate. Washington, DC: 

United States Environmental Protection Agency, EPA 738-R-95-025.
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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.

USEPA [2015]. Sodium fluoroacetate. In: Integrated risk information system, 

http://www.epa.gov/iris/subst/0469.htm. Accessed: 01-28-15.
7

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

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policy.

Appendix: Calculation of the SI Ratio for SFA

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

1,3-D. 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 outlined in Table A1. Other model-based estimates of kp may also be used 

[NIOSH 2009].
8

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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.
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Calculation 

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

1,3-D. The calculated SI ratio was 161.7. On the basis of these results, 1,3-D is predicted to represent a 

skin absorption hazard.

Table A1. Summary of Data used to Calculate the SI Ratio for 1,3-D 

Variables Used in Calculation Units Value 

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path(kpsc) cm/hr 3.808 x 10-6

Permeation coefficient of the protein fraction of the stratum 

corneum (kpol) cm/hr 1.517 x 10-5

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.25

Molecular weight (MW)

*

amu 100.3

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

* None -3.78

Calculated skin permeation coefficient (kp) cm/hr 1.897 x 10-5

Skin dose

Water solubility (Sw)

* mg/cm3

1110

Calculated skin permeation coefficient (kp) cm/hr 1.897 x 10-5

Estimated skin surface area (palms of hand) cm2360

Exposure time hr 8

Calculated skin dose mg

Inhalation Dose

Occupational exposure limit (OEL)† mg/m30.05

Inhalation volume m

3

10

Retention factor (RF) None 0.75

Inhalation dose mg 0.375

Skin dose–to–inhalation dose (SI) ratio None 161.7

*

Variables identified from SRC [ND].

†

The OEL used in calculation of the SI ratio for 1,3-D was the NIOSH recommended exposure limit (REL) [NIOSH 

2005].
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.

Appendix References 

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: 01-28-15. 

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: 01-28-15.

SRC [2009]. Interactive PhysProp database demo, 

http://esc.syrres.com/fatepointer/webprop.asp?CAS=62748. Accessed: 01-28-15.