Skin Notation (SK) Profile

2-Hydroxypropyl acrylate (HPA)

[CAS No. 999-61-1]

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: 2-Hydroxypropyl acrylate. 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
iii

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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 2-hydroxypropyl 

acrylate (HPA). 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

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) .............................................................................................4

5.0 SUMMARY............................................................................................................................................................5

REFERENCES ............................................................................................................................................................6

APPENDIX: CALCULATION OF THE SI RATIO FOR HPA.............................................................................8

OVERVIEW.................................................................................................................................................................8

APPENDIX REFERENCES .........................................................................................................................................10
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agency determination or policy.

Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists 

CIB Current Intelligence Bulletin

cm2squared centimeter(s)

cm/hour centimeter(s) per hour

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

HPA 2-hydropropyl acrylate 

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/kg milligram(s) per kilogram body weight

mg/m3 milligram(s) per cubic meter

mL milliliter(s)

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

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
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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.

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

w/w weight by weight percentage
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.
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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, Paul Siegel, Ph.D., and Mark Toraason, 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 

Clayton B’Hymer, Ph.D. 

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

Matt Dahm, M.Sc. 

Todd Niemeier, M.Sc.

Loren Tapp, M.D. 

Education and Information Division 

Devin Baker, M.Ed.

Charles L. Geraci, Ph.D.

Thomas J. Lentz, Ph.D.

Richard Niemeier, Ph.D.

Sudha Pandalai. M.D., Ph.D. 

Health Effects Laboratory Division

Stacey Anderson, Ph.D. 

H. Fredrick Frasch, Ph.D. 

Vic Johnson, Ph.D.

Michael Luster, 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 Protection Technology Laboratory

Heinz Ahlers, JD, M.Sc.

Gregory Day, Ph.D.

Angie Shepherd

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
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policy.

1.0 Introduction 

1.1 General Substance Information

Chemical: 2-Hydroxypropyl acrylate 

CAS No: 999-61-1

Molecular weight (MW): 130.2

Molecular formula: CH2=CHCOOCH2CH(CH3)OH

Structural formula:

Synonyms: HPA; beta-Hydroxypropyl acrylate; Propylene glycol monoacrylate; Acrylic acid, 2-

hydroxypropyl ester; 1,2-Propanediol,1-acrylate

Uses: HPA is a monomer used in the manufacture of thermosetting resins for surface coatings [OSHA 

2010a], adhesives and sealants, textiles, paper coatings, fibers, and plastic copolymers.

1.2 Purpose 

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

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

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

September 2012 to identify information on HPA, 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 

HPA. 
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policy.

1.3 Overview of SK Assignment

HPA 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 HPA: SK: SYS(FATAL)-DIR 

(COR)-SEN. Table 1 provides an overview of the critical effects and data used to develop the SK 

assignment for HPA. 

Table 1. Summary of the SK Assignment for HPA

Skin Notation Critical

Effect

Available

Data

SK: SYS (FATAL) Acute toxicity Limited animal data

SK: DIR (COR) Skin corrosion Limited human and animal data

SK: SEN Skin allergy Sufficient human and limited animal data

2.0 Systemic Toxicity from Skin Exposure (SK: SYS)

No toxicokinetic studies following dermal exposure to HPA were identified in humans or animals. The 

potential of HPA to pose a skin absorption hazard was not evaluated with 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 

(OEL). The ratio of the skin dose to the inhalation dose (SI ratio) could not be calculated on the basis 

that the OEL was not based on systemic effects. As such, the potential for skin absorption could not be 

determined using the SI ratio. More information about the SI ratio can be found in the appendix.

No dermal lethal concentrations (LDLo) for humans were identified. A dermal LD50 (lethal dose in 50% 

of exposed animals) value of 0.16 milliliters per kilogram of bodyweight (mL/kg) [corresponding to 168 

milligrams per kilograms of bodyweight (mg/kg)] was reported for rabbits [Smyth et al. 1969]. Because 

the reported acute dermal LD50 values for the rabbit is lower than the critical dermal LD50 value of 200 

mg/kg that identifies chemical substances that are potentially fatal at relatively low doses following 

dermal exposure [NIOSH 2009], HPA is considered potentially fatal following acute dermal exposure.

No epidemiological studies or case reports were identified that evaluated the toxic effects of HPA. No 

reliable repeat-dose, sub-chronic, or chronic toxicity studies following dermal exposure were identified 

in humans or animals. No standard toxicity or specialty studies evaluating biological system/function 

specific effects (including genotoxicity, reproductive and developmental effects and immunotoxicity) 

following dermal exposure to HPA were identified. No studies were identified that evaluated the 

potential of HPA to be carcinogenic in animals following dermal exposure. Table 2 summarizes 

carcinogenic designations of multiple governmental and nongovernmental organizations for HPA. 
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policy.

Table 2. Summary of the carcinogenic designations* for HPA 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 [2014] 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.

* The listed cancer designations were based on data from nondermal (such as oral or inhalation) exposure since studies using 

the dermal route of exposure were unavailable..

†Date accessed.

No dermal absorption data for HPA were identified, thereby preventing the assessment of hazards of the 

substance following contact with the skin. However, acute toxicity data [Smyth et al. 1969] suggest that 

HPA is dermally absorbed, systemically available, and has the potential to cause systemic effects 

including fatality. Therefore, on the basis of these data, HPA is assigned the SK: SYS(FATAL) notation. 

3.0 Direct Effects on Skin (SK: DIR)

No human or animal in vivo studies on corrosivity of HPA or in vitro tests for corrosivity using human 

or animal skin models or in vitro tests of skin integrity using cadaver skin were identified. Limited 

information was available on irritant contact dermatitis potential of HPA in occupationally-exposed 

workers. A case report exists for 11 workers who developed irritation immediately after contact and 2 

patients developed blisters 5-6 hours after exposure to HPA while employed in the manufacturing 

process of an acrylate chemical [Lovell et al. 1985]. Kanerva et al. [1988] conducted patch tests with 28 

commercial (meth) acrylates (derivitatives of methacrylic acid that are common monomers in polymer 

plastics) on 24 patients and reported that 6 patients who showed irritation but were not sensitized to 

HPA. 

Smyth et al. [1969] noted severe irritation on uncovered rabbit belly. In a study by BP Chemicals, Inc. 

[1981], a 0.25 milliliter (mL) aliquot of HPA was applied to the abraded and non-abraded occluded 

dorsal skin of rabbits for 24 hours. The authors found the substance to be a severe irritant producing 

necrosis, subcutaneous hemorrhaging, and pitting edema over a wide area of skin. The structure activity 

relationship model, Deductive Estimation of Risk from Existing Knowledge (DEREK) for Windows, 

predicted HPA to be a plausible skin irritant.
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Although occupational case reports [Lovell et al. 1985; Kanerva et al. 1988]1suggest that HPA is a 

skin irritant, there are limited animal data [Smyth et al. 1969; BP Chemicals, Inc. 1981] that suggest 

HPA is a severe irritant and corrosive to the skin. Therefore, on the basis of the data for this assessment, 

HPA is assigned the SK: DIR (COR) notation. 

4.0 Immune-mediated Responses (SK: SEN)

There is sufficient information available to conclude that HPA is a human skin sensitizer based on 

several human patch tests and a number of case reports. In human patch tests conducted by Kanerva et 

al. [1988], three out of 24 patients with irritation upon initial exposure to (meth) acrylates including 

HPA were sensitized to HPA, with sensitization to HPA being confirmed in re-testing in 2 patients. A 

diagnostic patch test conducted on a maintenance technician at a manufacturing plant of HPA and 

methacrylate indicated that this worker was sensitized by HPA, and the subject also developed crosssensitivity to methacrylates to which he was previously exposed [Lovell et al. 1985]. Kanerva [1992b] 

described a case in which an orthodontist developed recurrent pharyngitis at work without any skin 

symptoms or reactions. However, the orthodontist developed a positive allergic reaction in a diagnostic 

patch test with 0.1% (w/w) HPA. Kanerva [1992a] also reported a woman who became sensitized with 

acrylates including HPA, which was confirmed upon retesting. After the retesting, however, the woman 

developed further positive acrylate patch reactions indicating that the second patch test session 

sensitized her. Jordan [1975] reported that 5 people developed allergic contact dermatitis to 

component(s) used in a commercial adhesive tape, of which 2 were strongly positive to HPA. Jolanki et 

al. [1995] reported that a patient who was occupationally exposed and sensitized to BIS-GA (2,2-bis[4-

(2-dydroxy-3-acryloxypropoxy)phenyl]-propane), 1,6-hexanediol diacrylate (HDDA), and tripropylene 

glycol diacrylate (TRPGDA) may have developed cross-sensitiziation to HPA.

Several studies were identified that evaluated the skin sensitization potential of HPA in animals. In a 

guinea pig maximization test, all guinea pigs (12/12) reacted positively to a dermal challenge with 0.3% 

HPA after dermal induction with a 5% aqueous 2-hydroxy-1-propyl acrylate solution and a 48-hour 

occlusive application of 0.4 mL of a 25% 2-hydroxypropyl acrylate solution [Clemmensen 1984]. 

However, Rao et al. [1981] observed no skin sensitization response in a guinea pig maximization study 

when nine guinea pigs were induced and challenged with the substance. Other skin sensitization tests 

investigated the cross-reactivity potential of HPA with other acrylates and methacrylate esters. In guinea 

pig maximization studies in which animals were induced with hydroxymethyl methacrylate followed by 

a challenge with HPA, two out of 15 guinea pigs reacted positively in one study [Clemmensen 1984] 

whereas no skin sensitization was observed in another study [Bjorkner 1984]. Clemmensen [1984] also 

reported that induction with hydroxyethyl acrylate followed by a challenge with HPA resulted in skin 

sensitization in all 12 animals. DEREK predicted HPA to be a skin sensitizer.

The human patch tests [Kanerva et al. 1988, 1992a,b; Lovell et al. 1985] and the weight of evidence in 

animals [Clemmensen 1984] sufficiently demonstrated the skin sensitization potential of HPA. 

Therefore, on the basis of the data for this assessment, HPA is assigned the SK: SEN notation. 

 

1References in bold text indicate studies that serve as the basis of the SK assignments.
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5.0 Summary

No studies that evaluated the dermal absorption of HPA were identified in humans or animals. However, 

acute toxicity data [Smyth et al. 1969] suggest that HPA is dermally absorbed, systemically available, 

and potentially fatal. Occupational case reports [Lovell et al. 1985; Kanerva et al. 1988] and animal 

data [Smyth et al. 1969; BP Chemicals, Inc. 1981] demonstrate that HPA is an irritant and corrosive to 

the skin. Human patch tests [Lovell et al. 1985; Kanerva et al. 1988, 1992a, b] and the weight of 

evidence in animals [Clemmensen 1984] sufficiently demonstrate the skin sensitization potential of 

HPA. Therefore, on the basis of these assessments, HPA is assigned a composite skin notation of SK: 

SYS(FATAL)-DIR (COR)-SEN. 

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

organizations. The equivalent dermal designations for HPA, according to the Globally Harmonized 

System (GHS) of Classification and Labelling of Chemicals, are Acute Toxicity Category 3 (Hazard 

statement: Toxic in contact with the skin), Skin Corrosion Category 1B (Hazard statement: Causes 

severe skin burns and eye damage) and Skin Sensitization Category 1 (Hazard statement: May cause an 

allergic skin reaction) [European Parliament 2008]. 

Table 3. Summary of previous skin hazard designations for HPA

Organization Skin hazard designation 

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

OSHA [2015]* None assigned

ACGIH [2014] [skin]: Based on dermal LD50 values reported for rabbits

DSEN notation: Based on animal data indicating that HPA may be a 

potential, but weak, skin sensitizer

EC [2013]* R24 - Toxic in contact with skin

R34 - Causes burns

R43 - May cause sensitization by skin contact

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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References

ACGIH (American Conference of Governmental Industrial Hygienists) [2014]. 2-hydroxypropyl 

acrylate. In: TLVs and BEIs, Based on the documentation of threshold limit values for chemical 

substances and physical agents and biological exposure indices. Cincinnati, OH: American Conference 

of Governmental Industrial Hygienists.

Bjorkner B [1984]. Contact allergy to 2-Hydroxypropyl-Methacrylate (2-HPMA) in an ultraviolet 

curable ink. Acta Derm.-Venerol 64(3):264-267.

BP Chemicals, Inc. [1981]. Irritation and mutagenicity tests of hydroxyethyl methacrylate. BP Group 

Occupational Health Centre, Toxicology report 25-09-0044. On file with the U.S. Environmental 

Protection Agency under TSCA Section 8D. OTS #0556083. Document #88-920010901.

Clemmensen S [1984]. Cross-reaction patterns in guinea pigs sensitized to acrylic monomers. Drug and 

Chemical Toxicology 7(6):527-540.

EC (European Commission) [2011]. 2-Hydroxypropyl acrylate. In: EINICS (European Inventory of 

Existing Commercial Chemical Substances), http://esis.jrc.ec.europa.eu/. Accessed: 01-25-13.

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: 01-27-15.

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: 01-27-15.

Jolanki R, Kanerva L, Estlander T [1995]. Occupational allergic contact dermatitis caused by epoxy 

diacrylate in ultraviolet-light-cured paint, and bisphenol A in dental composite resin. Contact Dermatitis 

33(2): 94-99.

Jordan WP Jr. [1975]. Cross-sensitization patterns in acrylate allergies, Contact Dermatitis 1:13-15.

Kanerva L, Estlander T, Jolanki R [1988]. Sensitization to patch test acrylates. Contact

Dermatitis 18:10-15.

Kanerva L, Estlander T, Jolanki R [1992a]. Double active sensitization caused by acrylics. American 

Journal of Contact Dermatitis 3(1):23 – 26.

Kanerva L, Estlander T, Jolatiki R, Pekkarinen E [1992b]. Occupational pharyngitis associated with 

allergic patch test reactions from acrylics, Allergy 47(5):571-573.
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 Occupational 

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

policy.

Lovell CR, Rycroft RJ, Williams DM, Hamlin JW [1985]. Contact dermatitis from the irritancy 

(immediate and delayed) and allergenicity of hydroxypropyl acrylate. Contact Derm 12:117-118.

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: 01-27-15.

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: 01-27-15.

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: 01-27-15.

OSHA (Occupational Safety and Health Administration) [ND]. 2-Hydroxypropyl acrylate. In: OSHA 

occupational chemical database, https://www.osha.gov/chemicaldata/chemResult.html?recNo=327. 

Accessed: 01-27-15.

Rao KS, Betso JE, Olson KJ [1981]. A collection of guinea pig sensitization test results - grouped by 

chemical class. Drug and Chemical Toxicology 4(4):331-351.

Smyth HF, Carpenter CP, Weil CS, Pozzani UC, Striegel JA, Nycum JS [1969]. Range-finding toxicity 

data: List VII. Am Ind Hyg Assoc J 30(5); 470-476.

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

(IRIS), http://www.epa.gov/ncea/iris/. Accessed: 01-27-15.
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 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 

This appendix presents an overview of the SI ratio. 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].
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.

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/hour) × Sw (mg/cm3) × 360 cm2× 8 hours

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.
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 [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: 03-08-11.