# 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 Healthii

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

## Disclaimer

Mention of any company or product does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). In addition, citations to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organization s or their programs or products. Furthermore, NIOSH is not responsible for the content of these Web sites.



## Ordering Information

To receive this document or information about other occupational safety and health topics,

contact NIOSH:

Telephone: 1

- 800

- CDC

- INFO (1

- 800

- 232

- 4636)

TTY: 1

- 888

- 232

- 6348

E

- mail: cdcinfo@cdc.gov Or visit the NIOSH Web site: www.cdc.gov/niosh

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



## 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
(NIOS H) Publication No. XXX

DHHS (NIOSH) Publication No. XXXiii

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 Occupati onal 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 exp osed 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 progr ams.

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 respo nses 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 deter mination 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 sup portive 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, policy

and decision

- makers, employers, and workers in potentially hazardous workplaces

— so that improved risk

- manageme nt 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 Preventioniv

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 Occupati onal 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

................................ ................................ ................................ ................................ 10v

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 Occupati onal 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

cm 2 squared 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 G lobally 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

k aq coefficient in the watery epidermal layer

k p skin permeation coefficient

k pol coefficient in the protein fraction of the stratum corneum

k ps c permeation coefficient in the lipid fraction of the stratum corneum

LD 50 d ose resulting in 50% mortality in the exposed population

LD Lo dermal lethal dose

LLNA local lymph node assay

LOAEL lowest

- observed

- adverse

- effect level log K OW base

- 10 logarithm of a substance’s octanol

– water partition

M molarity

m 3 cubic meter(s)

mg milligram(s) mg/cm 2 /hr milligram(s) per square centimeter per hour mg/kg milligram(s) per kilogram body weight mg/m 3 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 millionvi

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 Occupati onal Safety and Health. It does not represent and should not be construed to represent any
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 s odium fluoroacetate

SI ratio ratio of skin dose to inhalation dose

SK skin notation

S W 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/cm 2 microgram(s) p er square centimeter μg/cm 2 /hr microgram(s) per square centimeter per hour μL microliter(s) μmol micromole(s)vii

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 Occupati onal 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% o r ( 2 ) recognized as a potential carcino gen 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 w ith (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, oc curring at or near the point of contact with chemicals.

Immune

- mediated responses

— Responses mediated by the immune system, in cluding allergic

responses.

Sensitization

— A specific immune

- mediated response that develops following ex posure to a chemical, which, upon re

- exposure, can lead to allergic contact derma titis (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 chem icals after exposure

of the skin.viii

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 Occupati onal 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 H udson, 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 thei r 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. Le ntz, 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 Protectiv e Technology Laboratory Heinz Ahlers, J.D., M.Sc. Angie Shepherdix

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 Occupati onal 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 pr oviding 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, Clevelan d, OH1

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 Occupati onal Safety and Health. It does not represent and should not be construed to represent any agency determination or
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: FCH 2 COONa

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 infor mation 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

immunotoxic ity), 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

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 Occupati onal Safety and Health. It does not represent and should not be construed to represent any agency determination or
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 assignme nt 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 estima ting 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 referenc e 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 b urden 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

.

N o estimate of the human dermal lethal dose (LD Lo ) was identified for SFA , and no d ermal LD 50 ( 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 (L PC) 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 specifi c 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.3

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 Occupati onal Safety and Health. It does not represent and should not be construed to represent any agency determination or
policy. Table 2. Summary of the carcinogenic designations for SFA by numerous governmental and nongovernmental organizati ons

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 = I nternational 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 huma ns 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 maxi mization 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 LD 50 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. Therefor e, 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 that4

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 Occupati onal Safety and Health. It does not represent and should not be construed to represent any agency determination or
policy. 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 toxicit y 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 sever e 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 s kin) [ 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.5

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 Occupati onal Safety and Health. It does not represent and should not be construed to represent any agency determination or
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. Toxico l. 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, Counc il 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://eur

lex.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/E NG/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, N ational 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

- 025.6

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 Occupati onal 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

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 Occupati onal 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 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 calc ulation 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 h azards 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 resul ts 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 ( k p ) 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 p roperties 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 coefficien t when such data are available and appropriate for use.

The first step in the evaluation is to determine the k p for the substance to describe the transdermal penetration rate of the substance [NIOSH 2009]. The k p , 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 K

OW ). In this example, k p is determined fo r 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 k p may also be used [NIOSH 2009].8

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 Occupati onal 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 ( k p )

where k

psc is the permeation coefficient in the lipid fraction of the stratum corneum, k pol is the coefficient in the protein fraction of the stratum corneum, and k aq is the coefficient in the watery epidermal layer.

These components are individually estimated by

log k psc = −1.326 + 0.6097 × log K

ow − 0.1786 × MW 0.5

k pol = 0.0001519 × MW −0.5

k aq = 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 k p , the water solub ility ( S

W ) 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

centi meters [cm 2 ]).

Equation 2: Determination of Skin Dose

Skin dose = k

p × S

w × Exposed skin surface area × Exposure time

= k p (cm/hr) × S

w (mg/cm 3 ) × 360 cm 2 × 8 hr

The inhalation dose (in mg) is derived on the basis of the occupational exposure li mit (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 mete rs (m 3 ) 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/m 3 ) × 10 m 3 × 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.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 Occupati onal 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 1,3

- 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 o f 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( k psc ) cm/hr 3.808 x 10 - 6
Permeation coefficient of the protein fraction of the stratum corneum ( k

pol ) cm/hr 1.517 x 10 - 5

Permeation coefficient of the watery epidermal layer ( k aq ) cm/hr 0.25 Molecular weight ( MW

) * amu 100.3
Base

- 10 logarithm of its octanol

– water partition coefficient (Log K

ow ) * None

- 3.78 Calculated skin permeation coefficient ( k p ) cm/hr 1.897 x 10 - 5

Skin dose

Water solubility ( S w ) * mg/cm 3 1110 Calculated skin permeation coefficient ( k p ) cm/hr 1.897 x 10 - 5

Estimated skin surface area (palms of hand) cm 2 360 Exposure time hr 8

Calculated skin dose mg
Inhalation Dose
Occupational exposure limit (OEL) † mg/m 3 0.05

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 Occupati onal 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 Inst itute 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?CA S=62748 . Accessed: 01

- 28

- 15

.