DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health 

# NIOSH Skin Notation (SK) Profiles

Ethyl Acrylate [CAS No. 140-88-5]ii Skin Notation Profiles | Ethyl acrylate 

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# Suggested Citation NIOSH [2014]. NIOSH skin notation profiles: ethyl acrylate. By Hudson NL, Dotson GS. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Con

trol and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-144 DHHS (NIOSH) Publication No. 2014-144 August 2014



### Safer • Healthier • PeopleTMSkin Notation Profiles | Ethyl acrylate iii 

# 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 spec

trum 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). Under

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

ern 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 de

termination 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 us e 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 ana

lytical or numerical methods. This Skin Notation Profile provides the SK assignments and supportive data for ethyl acrylate. In particular, this document evaluates and summarizes the literature describing the hazard po

tential 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-manage

ment 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 PreventionSkin Notation Profiles | Ethyl acrylate v 

# Contents
Foreword

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii Abbreviations

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Glossary

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Acknowledgments

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x 1 Introduction

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 General Substance Information

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Purpose

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.3 Overview of SK Assignment

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 Systemic Toxicity from Skin Exposure (SK: SYS)

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

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4 Immune-mediated Responses (SK: SEN)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 5 Summary

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 References

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Appendix: Calculation of the SI Ratio For Ethyl acrylate

. . . . . . . . . . . . . . . . . . . 10 Overview

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10vi Skin Notation Profiles | Ethyl acrylate 

# Abbreviations
ACGIH American Conference of Governmental Industrial Hygienists CIB Current Intelligence Bulletin

cm 2 square 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 EC3 Effective concentration inducing a 3-fold increase in proliferation of lymph node cells FCAT Freund’s complete adjuvant test GHS G lobally Harmonized System for Classification and Labelling of Chemicals GPMT guinea pig maximization test 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

psc permeation coefficient in the lipid fraction of the stratum corneum LD 50 dose 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) μmoles micromoles μL microliter(s) mg milligram(s) mg/kg milligram(s) per kilogram body weight mg/kg-day milligrams per kilogram body weight per day mg/m 3 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 limitSkin Notation Profiles | Ethyl acrylate vii 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 SK skin notation S W solubility SYS skin notation indicating the potential for systemic toxicity following exposure of the skin USEPA United States Environmental Protection Agency μmoles micromoles μL microlitersviii Skin Notation Profiles | Ethyl acrylate 

# 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.Skin Notation Profiles | Ethyl acrylate ix 

# 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, Matt Dahm, M.Sc., and Clayton B’Hymer, Ph.D. The basis for this document was a report ( Toxicology Excellence for Risk Assessment [TERA] ) contracted by NIOSH and prepared by Bernard Gadagbui, Ph.D., and Andrew Maier, Ph.D. For their contribution to the technical content and review of this document, special acknowl

edgment is given to the following NIOSH personnel: 

### Denver Field Office Eric Esswein, M.Sc. 

### Division of Applied Research and Technology John Snawder, Ph.D. Mark Toraason, Ph.D. 

### Division of Respiratory Disease Studies Gregory A. Day, Ph.D. Aleksander Stefaniak, Ph.D. 

### Division of Surveillance, Hazard Evaluations, and Field Studies 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 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. Anna Shvedova, Ph.D. Paul Siegel, Ph.D. Berran Yucesoy, Ph.D. 

### National Personal Protection Technology Laboratory Heinz Ahlers, M.Sc. Angie Shepherd For their contribution to the technical content and review of this document, special acknowl

edgment is given to the following CDC personnel: 

### Office of Surveillance, Epidemiology and Laboratory Services/Epidemiology and Analysis Program Office Barbara Landreth, M.A.x Skin Notation Profiles | Ethyl acrylate In addition, special appreciation is expressed to the following individuals for serving as inde

pendent, external reviewers and providing comments that contributed to the development or improvement of this document: Shane Stephen Que Hee, M.Sc., Ph.D., University of California at Los Angeles, School of Public Health, Los Angeles, CA Glenn Sipes, Ph.D., University of Arizona, College of Medicine, Tucson, AZ G. Frank Gerberick, Ph.D., The Procter and Gamble Company, Cincinnati, OH Dori Germolec, Ph.D., National Toxicology Program, National Institute for Environmen

tal Health Sciences, Research Triangle, NC Ben Hayes, M.D., Ph.D., Division of Dermatology, Vanderbilt School of Medicine, Nash

ville, TN Jennifer Sahmel, M.Sc., CIH, ChemRisk, Boulder, CO James Taylor, M.D., Industrial Dermatology, The Cleveland Clinic, Cleveland, OHSkin Notation Profiles | Ethyl acrylate 1 

## 1.2 Purpose This Skin Notation Profil e presents (1) a brief summary of epidemiological and toxicological data associated with skin contact with ethyl acrylate and (2) the rationale behind the haz

ard-specific skin notation (SK) assignment for ethyl acrylate. 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 Nota

tions [NIOSH 2009]. The summarized infor

mation and health hazard assessment are lim

ited to an evaluation of the potential health effects of dermal exposure to ethyl acrylate. A literature search was conducted through May 2014 to identify information on ethyl acrylate, 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 ef

fects of dermal exposure to ethyl acrylate.


## 1.3 Overview of SK Assignment Ethyl acrylate is potentially capable of caus

ing numerous adverse health effects following skin contact. A critical review of available data has resulted in the following SK assignment for ethyl acrylate: SK: SYS-DIR (COR)- SEN . Table 1 provides an overview of the critical effects and data used to develop the SK assignment for ethyl acrylate. 

# 1 Introduction

1.1 General Substance Information

Chemical: Ethyl acrylate CAS No: 140-88-5 Molecular weight (MW): 100.1 Molecular formula: CH2=CHCOOC2H2 Structural formula: Synonyms: Ethyl acrylate (inhibited); Ethyl ester of acrylic acid; Ethyl propenoate Uses: Ethyl acrylate is used primarily as a chemical intermediate during the production of poly

mers including resins, plastics, and rubber [HSDB 2010].



### Table 1. Summary of the SK assignment for ethyl acrylate
Skin notation Critical effect Data available SK: SYS Acute toxicity Sufficient animal data SK: DIR (COR) Skin corrosion Sufficient animal data SK: SEN Skin allergy Sufficient human and animal data2 Skin Notation Profiles | Ethyl acrylate 

# 2 Systemic Toxicity from Skin Exposure (SK: SYS)
No in vivo or in vitro toxicokinetic data that estimated the dermal absorption of ethyl ac

rylate following dermal exposure were iden

tified. Some evidence of absorption through the skin was provided by acute dermal toxic

ity studies in which dermal application of the substance resulted in the deaths of rats, mice, and rabbits [Pozzani 1949; Treon et al. 1949; Sokal et al. 1980; Rohm and Haas Company 1986]. The potential of ethyl acrylate to pose a skin absorption hazard was also evaluated, with use of a predictive algorithm for estimat

ing and evaluating the health hazards of der

mal exposure to substances [NIOSH 2009]. The evaluation method compares an estimat

ed dose accumulated in the body from skin absorption and an estimated dose from respi

ratory 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 1.09 was calcu

lated for ethyl acrylate. An SI ratio of ≥0.1 in

dicates that skin absorption may significantly contribute to the overall body burden of a substance [NIOSH 2009]; therefore, ethyl acrylate is considered to be absorbed through the skin following dermal exposure. Addi

tional information on the SI ratio and the variables used in its calculation are included in the appendix. No dermal lethal doses (LD Lo ) of ethyl acry

late for humans have been identified. How

ever, dermal LD 50 (the dose resulting in 50% mortality in the exposed animals) values of 1200-2000 milligrams per kilogram body weight (mg/kg) in rabbits [Pozzani et al. 1949; Dow Chemical Company 1957; Bio/dynam

ics Inc. 1990; Mellon Institute 1972; Soka et al. 1980], and 1800 mg/kg to greater than 5000 mg/kg in rats [Rohm and Haas Com

pany 1986; Soka et al. 1980] have been report

ed. Because the reported acute dermal LD 50 values for rabbits are lower than the critical dermal LD 50 value of 2000 mg/kg that identi

fies chemical substances with the potential for acute dermal toxicity [NIOSH 2009], ethyl acrylate demonstrates acute toxicity following dermal exposure. No systemic effects associated with occu

pational exposures to ethyl acrylate or stan

dard, repeat-dose studies in animals were identified. However, a mouse skin-painting study evaluated the systemic effects of ethyl acrylate. In this study, Nylander-French and French [1998] applied 60, 300 or 600 micro

moles (μmoles) of ethyl acrylate in 200 micro

liters (μL) acetone vehicle to the skin of fe

male transgenic mice, 3 times per week for 20 weeks. Although no statistical analysis of the systemic effects observed was provided, graph

ical representation indicated that the LowestObserved-Adverse-Effect Level (LOAEL) for ethyl acrylate that produced systemic toxicity, as evidenced by depression of body weights, was 60 μmoles/mouse [correspond

ing to 200 milligrams per kilogram per day (mg/kg-day)] [Nylander-French and French 1998]. Acetone has been noted as a mild skin irritant after long periods of exposure [Smyth et al. 1962], which may compromise the skin such that more ethyl acrylate may be absorbedthan if another vehicle had been used. A NoObserved-Adverse-Effect Level (NOAEL) of 300 μmoles/mouse [corresponding to 1000 mg/kg-day] was also identified in the study. Based on this study, ethyl acrylate is systemi

cally available and toxic because the LOAEL and NOAEL is at or lower than the critical dermal NOAEL value of 1000 mg/kg-day that identifies chemical substances with the potential for repeated-dose dermal toxicity [NIOSH 2009]. No standard toxicity or specialty studies evaluating biological system/function specific effects (including reproductive and develop

mental effects and immunotoxicity) following dermal exposure to ethyl acrylate were identi

fied. Few studies were identified that evalu

ated the carcinogenicity potential of ethyl acrylate following dermal exposure. Union Carbide Corporation [1982] and DePass et al. [1984] evaluated the dermal carcinogenic potential of ethyl acrylate by applying 25 μLSkin Notation Profiles | Ethyl acrylate 3 of the undiluted substance [corresponding to 23 mg] to the backs of male C3H/HeJ mice three times a week throughout the lifetime of the animals and observed no formation of skin tumors and reported no significant ef

fects on survival. Table 2 summarizes carci

nogenic designations of multiple governmen

tal and nongovernmental organizations for ethyl acrylate. No studies that evaluated the dermal absorp

tion of ethyl acrylate were identified. However, mathematical modeling, several dermal acute toxicity studies [Pozzani et al. 1949; Treon et al. 1949; Dow Chemical Company 1957; Sokal et al. 1980; Bio/dynamics Inc. 1990] , and a repeat-dose study [Nylander-French and French 1998] indicate that the substance is absorbed through the skin and can cause systemic toxicity including bodyweight de

pression. Therefore, on the basis of the data for this assessment, ethyl acrylate is assigned the SK: SYS notation. 

# 3 Direct Effects on Skin (SK: DIR)
No human or animal in vivo studies for cor

rosivity of ethyl acrylate or in vitro tests for corrosivity using human or animal skin mod

els or in vitro tests of skin integrity using ca

daver skin were identified. No standard irrita

tion studies were identified for humans upon which the skin corrosion or irritation potential of ethyl acrylate can be evaluated. Hazardous polymerization of ethyl acrylate may occur if it is subject to heat, light or peroxides, which may result in containers to violently, rupture or burst [HSDB 2010]. As such, ethyl acry

late may potentially have extensive contact with the skin. Several studies conducted according to stan

dard methods were identified in animals that show ethyl acrylate is corrosive or a skin irri

tant. An in vitro study was identified that as

sessed the irritating potential for ethyl acrylate using the MATREX LDM (Living Dermal Model) and TESTSKIN LSE (Living Skin Equivalent)-high human dermis models and also Tokumura reported an EC 50 (concentra

tion of the compound that caused death in half of the culture cells) of 6700–7500 parts per million (ppm) [corresponding to 6700–7500 mg/kg] in the LDM and LSE models, re

spectively. Rohm and Haas Company [1991] reported that ethyl acrylate was corrosive to the skin of rabbits following application of 0.5 milliliters (mL) [corresponding to 450 mg/ 

### Table 2. Summary of the carcinogenic designations * 

### for ethyl acrylate by numerous governmental and nongovernmental organizations Organization Skin hazard designation NIOSH [2005] Potential occupational carcinogen NTP [2011] No designation USEPA [2014] No designation European Parliament [2008] No designation IARC [2012] Group 2B: Possibly carcinogenic to humans EC [2014] † No designation ACGIH [2001] Group A4: Not classifiable as a human carcinogen
ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint Research, Institute for

Health and Consumer Protection; IARC = International Agency for Research on Cancer; NIOSH = National Institute for Occupa

tional 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 rather than dermal exposure. † Date accessed.4 Skin Notation Profiles | Ethyl acrylate kg] of undiluted ethyl acrylate to the shaved intact skin for 4 hours under occlusive condi

tions. Application of 25 μL [corresponding to 23 mg] of undiluted ethyl acrylate to the skin of mice three times per week for the life of the mouse caused epidermal necrosis, keratin necrosis, dermal fibrosis, and hyperkeratosis [Union Carbide Corporation 1982; DePass et al. 1984], indicating that prolonged and repeated exposure to the substance can lead to severe skin effects (skin corrosion). Earlier studies conducted by Pozzani et al. [1949] and Dow Chemical Company [1957] also showed that repeated, prolonged contact with the skin causes tissue damage. Other stud

ies reported that undiluted ethyl acrylate ap

plied occluded to rabbit skin was moderately to severely irritating [Treon et al. 1949; Dow Chemical Company 1957; Safepharm Labo

ratories Limited 1984]. Applications under unoccluded conditions were slightly irritat

ing [Pozzani et al. 1949]. However, Industrial Bio-Test Laboratories Inc. [1972] found ethyl acrylate applied undiluted under occlusive conditions to abraded or intact skin of rabbits to be non-corrosive after rabbits were exposed to ethyl acrylate for four hours. Ethyl acrylate at concentrations up to 30% did not induce significant irritancy as measured by ear swell

ing in mice [Hayes and Meade 1999]. Toku

mura et al. [2010] assessed dermal irritation, using the Draize method, after applying ethyl acrylate in occluded conditions to the shaved backs in rabbits for 24 hours. The lowest ery

thema dose (the concentration at which the compound caused very slight erythema) for ethyl acrylate was 1500 ppm [corresponding to 1500 mg/kg]. These studies indicate that the severity of irritation and tissue damage is dependent upon the concentration, dura

tion, and frequency of exposure. The structure activity relationship model, Deductive Es

timation of Risk from Existing Knowledge ( DEREK ) for Windows, predicted ethyl acry

late to be negative for skin irritation. In a short-term carcinogenicity skin-paint

ing study in female Tg.AC mice, NylanderFrench and French [1998] found no statisti

cally significant increase in skin papillomas when mice were administered doses of 60–600 μmoles/200 μL of ethyl acrylate in acetone(corresponding to 200 mg to 2000 mg/kgday) 3 times per week for 20 weeks compared to acetone controls. In another transgenic mice study, Tennant et al. [1995] found topi

cally applied ethyl acrylate (30 mg, 3 times per week for 20 weeks) to be inactive. These stud

ies suggest that ethyl acrylate is not carcino

genic under the conditions of the tests. Although human data were not located, suffi

cient data were identified from standard irrita

tion tests. There are sufficient data to indicate that ethyl acrylate is an irritant, and prolonged and repeated dermal exposure studies to the undiluted substance in animal’s causes skin corrosion [Pozzani et al. 1949; Treon et al. 1949; Dow Chemical Company 1957; Union Carbide Corporation 1982; DePass et al. 1984; Safepharm Laboratories Limited, 1984; Rohm and Haas Company 1991] . On the basis of the assembled data, ethyl acrylate is assigned the SK: DIR (COR) notation. 

# 4 Immune-mediated Responses (SK: SEN)
Several studies were identified that evalu

ated the potential of ethyl acrylate to cause skin sensitization in humans and animals. In humans, Kanerva et al. [1997] com

piled statistics on 10 years of patch test

ing with 30 (meth)acrylates and reported the frequency of allergic reactions caused by ethyl acrylate (0.1% ) as 16/192 (8.3%) during 1985–1995, 9/124 (7.3%) from 1985–1990, and 7/68 (10.3%) during 1991–1995. In an earlier study, Kanerva et al. [1988] reported that 3/24 patients were sensitized to ethyl acrylate (0.5% in petrolatum). Drucker and Pratt [2011] conducted a retrospective chart review of patients attending a contact dermatitis clinic in Ontario, Canada and reported 28 (64%) patients had positive reactions when patch tested to ethyl acrylate. Tuck

er and Beck [1999] patch tested patients with a history of exposure (occupationalSkin Notation Profiles | Ethyl acrylate 5 

### and non-occupational) to (meth) acrylates with Chemotechniqes series and to their own suspected products when possible. Out of 255 patients tested, 22 (8.6%) were sensitized to ethyl acrylate at a concentra

tion of 0.5%. Bjorkner et al. [1980] report

ed two of six patients patch tested with ethyl acrylate showed positive allergic re

actions. A manicurist who presented with dermatitis tested positive to ethyl acrylate and other acrylates when patch tested us

ing the International Contact Dermatitis Research Group (ICDRG) recommenda

tions [Torres et al. 2005]. Brandao [2001] described a nurse who, after developing skin lesions, edema, and erythema fromworking with bone cement, showed crossreactivity to (meth) acrylates, including ethyl acrylate. Pérez- Formoso et al. [2010] noted that 1 of 8 patients patch tested to acrylates had a positive reaction for ethyl acrylate. In guinea pigs, ethyl acrylate (greater than 99% pure) was reported to be a skin sensitizer in Freund’s complete adjuvant test (FCAT) [van der Walle et al. 1982a, 1982b], but not a sensitizer in the guinea pig maximization test. Warbrick et al. [2001] conducted murine local lymph node assays and reported a maximum stimulation index of 5.01 in response to ethyl acrylate when a concentration of 50% was applied, with indices of less than 3 reported when lower concentrations (10 and 25%) were applied. Based on these results, these investi

gators estimated the effective concentration (EC3) value (%) [the concentration of chemi

cal required to induce a stimulation index of three in LLNA] to be 28.7%. Dearman et al. [2007] reported an EC3 value of 36.8%, indicating ethyl acrylate is a skin sensitizer. However, in an earlier study, ethyl acrylate at concentrations up to 30% did not increase lymph node cell proliferation over controls in the LLNA [Hayes and Meade 1999]. The same concentrations of ethyl acrylate did not exhibit allergic potential as measured by the mouse ear swelling test [Hayes and Meade 1999]. These investigators also found no cross-reactivity between ethyl acrylate, n-butyl acrylate or trimethylol propane triac

rylate. DEREK predicted ethyl acrylate to be a plausible skin sensitizer. Based on numerous reports of sensitization in humans [Bjorkner et al. 1980; Kanerva et al. 1988, 1997; Tucker and Beck 1999; Drucker and Pratt 2011] , and the weight of evidence from standard skin sensitization tests in ani

mals including FCAT and LLNA [van der Walle 1982a, 1982b; Warbrick et al. 2001; Dearman et al. 2007] , supported by the pre

diction from structure-activity relationship model, this assessment concludes that suffi

cient data exist to conclude that ethyl acrylate is a skin sensitizer in humans and animals. Therefore, on the basis of the data for this as

sessment, ethyl acrylate is assigned the SK: SEN notation. 

# 5 Summary Although no studies that evaluated the der

mal absorption of ethyl acrylate were identi

fied, mathematical modeling, several acute dermal [Pozzani 1949; Treon et al. 1949; Dow Chemical Company 1957; Sokal et al. 1980; Bio/dynamics Inc. 1990] , and repeatdose [Nylander-French and French 1998] toxicity studies show that the substance is absorbed through the skin and can cause sys

temic toxicity including body weight depres

sion. No studies were identified that evaluated the potential of ethyl acrylate to cause skin effects in humans following dermal exposure. However, sufficient data were identified from standard skin irritation tests and prolonged and repeated-dose studies that showed that the undiluted substance is corrosive to the skin of rabbits and mice [Pozzani et al. 1949; Union Carbide Corporation 1982; DePass et al. 1984; Rohm and Haas Company 1991] , while the diluted substance tends to be irritat

ing. Numerous reports of skin sensitization in humans [Bjorkner et al. 1980; Kanerva et al. 1988, 1997; Tucker and Beck 1999; Drucker and Pratt 2011] , and the weight of evidence from standard skin sensitization tests in ani

mals (FCAT and LLNA) [van der Walle6 Skin Notation Profiles | Ethyl acrylate 1982a, 1982b; Warbrick et al. 2001; Dear

man et al. 2007] , supported by the prediction from structure-activity relationship model, demonstrate that ethyl acrylate is a skin sensi

tizer in both humans and animals. Therefore, on the basis of these assessments, ethyl acry

late is assigned a composite skin notation of SK: SYS-DIR (COR)-SEN

. Table 3 summarizes the skin hazard designa

tions for ethyl acrylate previously issued by NIOSH and other organizations. The equiva

lent dermal designations for ethyl acrylate, according to the Global Harmonization Sys

tem (GHS) of Classification and Labelling of Chemicals, are Acute Toxicity Category 4 (Hazard statement: Harmful in contact with skin), Skin Irritation Category 2 (Hazard statement: Causes skin irritation), and Skin Sensitization Category 1 (Hazard statement: May cause an allergic skin reaction) [ Euro

pean Parliament 2008]. 

# References ACGIH (American Conference of Governmental Industrial Hygienists) [2001]. Ethyl acrylate. In: Documentation of threshold limit values and biological exposure indices 7th ed., Vol. 2. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Bio/dynamics Inc. [1990]. Acute dermal toxic

ity study in rabbits with ethyl acrylate. Bio/ dynamics Inc., Project #4361-87 for Hoechst Celanese Corporation. Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D. OTS #0524345. Document #86- 900000468. Bjorkner B, Dahlquist I, Fregert S [1980]. Al

lergic Contact Dermatitis From Acrylates in Ultraviolet Curing Inks. Contact Dermatitis 6(6):405–409. Brandao FM [2001]. Palmar contact dermatitis due to (meth)acrylates. Contact dermatitis 44 (3):186–187. Dearman RJ, Betts CJ, Farr C, McLaughlin J, Ber

dasco N, Wiench K, Kimber I [2007]. Com

parative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay. Contact Dermatitis 57 (4):242–247. DePass LR [1984]. Dermal oncogenicity bioassays of acrylic acid, ethyl acrylate, and butyl acrylate. J Toxicol Environ Health 14 :115–120. Dow Chemical Company [1957]. Results of the range finding toxicological tests on ethyl acry

late. Midland, MI: Dow Chemical Company. On file with the U.S. Environmental Protec

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### Table 3. Summary of previous skin hazard designations for ethyl acrylate Organization Skin hazard designation NIOSH [2005] [skin] OSHA [2014] * [skin]: Potential for dermal absorption ACGIH [2001] No designation EC [2014]* R21: Harmful if in contact with skin R38: Irritating to skin 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.Skin Notation Profiles | Ethyl acrylate 7 of 16 December 2008 on classification, label

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ulation (EC) No 1907/2006. OJEU, Off J Eur Union L353:1–1355, http://eurex.europa.eu/ LexUriServ/LexUriServ.do?uri=OJ:L:2008:35 3:0001:1355:EN:PDF. Accessed: 05-01-14. Hayes BB, Meade BJ [1999]. Contact sensitivity to selected acrykate compounds in B6C3F1 mice: relative potency, cross reactivity, and comparison of test methods. Drug and Chemi

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mary skin irritation tests with eighteen materi

als in albino rabbits. Northbrook, IL: Industrial Bio-test Laboratories Inc., IBT #A1854, report to Celanese Chemical Company. On file with the U.S. Environmental Protection Agency un

der TSCA Section 8D. OTS #0520783. Docu

ment #86-890001277. Kanerva L, Estlander T, Jolanki R [1988]. Sensiti

zation to patch test acrylates. Contact Derma

titis 18 :10–15. Kanerva L, Jolanki R, Estlander T [1997]. 10 years of patch testing with the (meth)acrylate series. Contact Dermatitis 37 :255–258. Mellon Institute [1972]. (Methylcarbanyl)ethyl acrylate 1972-MCEA: range finding toxicity studies. Pittsburgh: Mellon Institute, Report 35-33 for Union Carbide Corporation. On file with the U.S. Environmental Protection Agen

cy under TSCA Section 8D. OTS #0537571. Document #88-920004590. NIOSH [2005]. Ethyl acrylate. In: NIOSH pock

et guide to chemical hazards. Cincinnati, OH: U.S. Department of Health and Human Ser

vices, Centers for Disease Control and Preven

tion, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2005-149, http://www.cdc.gov/niosh/npg/. Accessed: 05-01-14. 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 In

stitute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/ pdfs/2009-147.pdf. Accessed: 05-01-14. NTP [2011]. Report on Carcinogens. Twelfth Edition; U.S. Department of Health and Hu

man Services, Public Health Service. National Toxicology Program, http://ntp.niehs.nih.gov/ ntp/roc/twelfth/roc12.pdf . Accessed 05-01-14. Nylander-French, French [1998]. Tripropylene glycol diacrylate but no ethyl acrylate induces skin tumors in a twenty-week short-term tu

morigenesis study in Tg.AC (v-Ha-ras) Mice. Toxicologic Pathology 16 (4):476–483. OSHA [ND]. Ethyl acrylate. In: OSHA occupa

tional chemical database, http://www.osha.gov/ chemicaldata/chemResult.html?recNo=259. Accessed: 05-01-14.Pérez-Formoso JL, de Anca-Fernández J, MaravíCecilia R, Díaz-Torres JM [2010]. Contact dermatitis caused by acrylates among 8 work

ers in an elevator factor. Actas Dermosifilogr 101 (4):336–340. Pozzani U, Weil CS, Carpenter CP [1949]. Subacute vapor toxicity and range-finding data for ethyl acrylate. J Ind Hyg Toxicol 31 :311–316. Rohm and Haas Company [1986]. Acute toxicity report on ethyl acrylate monomer (final report). Spring House, PA: Rohm and Haas Company. On file with the U.S. Environmental Protec

tion Agency under TSCA Section 8D. OTS #0520999. Document #86-890001364S. Rohm and Haas Company [1991]. Ethyl acrylate (15 ppm MEHQ) skin irritation study in rab

bits. Spring House, PA: Rohm and Haas Com

pany. On file with the U.S. Environmental Pro

tection Agency under TSCA Section 8D. OTS #0529735. Document #88-910000100. Safepharm Laboratories Limited [1984]. Federal register skin irritation test: determination of the degree of primary cutaneous irritation caused by ethylacrylate in the rabbit. Derby, United Kingdom: Safepharm Laboratories Limited, experiment #657/8410 for Mitsubishi Petro

chemical Company Limited. On file with the U.S. Environmental Protection Agency under TSCA Section 8D. OTS #0557581. Document #86950000068.8 Skin Notation Profiles | Ethyl acrylate Smyth HF Jr, Carpenter CP, Weil CS, Pozzani UC, Striegel JA [1962]. Range-finding toxicity data: List VI. Am Ind Hyg Assoc J 23 :95–107. Sokal J , Barański B , Czajkowska T , Kyrsiak B, Ma

jka J, Szendzikowski S, Stetkiewicz J, Tarkowski S [1980]. Preliminary project of the standard minimal scope and methods of testing acute toxicity of industrial chemical substances. Pol J Pharmacol Pharm 32 (2):223–229 Tennant RW, French JE, Spalding JW [1995]. Identifying chemical carcinogens and assess

ing potential risk in short-term bioassays using transgenic mouse models. Environ Health Per

spect 103 (10):942–950. Tokumura F, Matsui T, Suzuki Y, Sado M, Tani

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mal irritating effect of residual (meth) acrylic monomers in pressure sensitive adhesive tapes. Drug Chem Toxicol 33 (1):1–7. Torres MC, Linares T, Hernandez MD [2005]. Acrylates induced rhinitis and contact derma

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droquinone and P-methoxyphenol in the guin

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# Appendix: Calculation of the SI Ratio For Ethyl acrylate This appendix presents an overview of the SI ratio and a summary of the calculation of the SI ratio for ethyl acrylate. 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 support

ive 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 Bul

letin (CIB) 61: A Strategy for Assigning New NIOSH Skin Notations [NIOSH 2009]. 

## Overview The SI ratio is a predictive algorithm for esti

mating and evaluating the health hazards of skin exposure to substances. The algorithm is designed to evaluate the potential for a sub

stance to penetrate the skin and induce sys

temic toxicity [NIOSH 2009]. The goals for incorporating this algorithm into the pro

posed strategy for assigning SYS notation are as follows:
1. Provide an alternative method to evalu

ate substances for which no clinical re

ports 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 la

beled with the SYS notation. The algorithm evaluation includes three steps: 1. determining a skin permeation coeffi

cient ( 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 require

ment 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 deter

mine 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 capil

laries of the dermis, is estimated from the compound’s molecular weight ( MW ) and base-10 logarithm of its octanol–water par

tition coefficient (log K OW

). In this example, k p 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 k p may also be used [NIOSH 2009].


### Equation 1: Calculation of Skin Permeation Coefficient (k p 

### )

aq pol psc p 

## k k k k 1 1 1

+ + =

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 ab

sorption (skin dose) and inhalation (inhalation10 Skin Notation Profiles | Ethyl acrylate dose) during the same period of exposure. The skin dose is calculated as a mathematical product of the k p , the water solubility ( S W ) of the substance, the exposed skin surface area, and the duration of exposure. Its units are mil

ligrams (mg). Assume that the skin exposure continues for 8 hours to unprotected skin on the palms of both hands (a surface area of 360 square centimeters [cm 2 ]).


### Equation 2: Determination of Skin Dose Skin dose

= k p × S
w × Exposed skin surface area × Exposure time

= k p (cm/hour) × S
w (mg/cm 3 ) × 360 cm 2 × 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 de

veloped 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 inhala

tion volume of 10 cubic meters (m 3 ) inhaled air in 8 hours, and a factor of 75% for reten

tion 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 indi

cates (1) the significance of dermal absorp

tion 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.


## Calculation Table A1 summarizes the data applied in the previously described equations to determine the SI ratio for ethyl acrylate. The calculated SI ratio was 1.09. On the basis of these results, ethyl acrylate is predicted to represent a skin absorption hazard. 

# Appendix References NIOSH [2005]. NIOSH pocket guide to chemical hazards. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Dis

ease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2005–149, http:// www.cdc.gov/niosh/npg/. Accessed: 05-01-14. 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 In

stitute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/ pdfs/2009-147.pdf. Accessed: 05-01-14. SRC [2009]. Interactive PhysProp database demo, http://www.srcinc.com/what-we-do/databas

eforms.aspx?id=386 . Accessed: 05-01-14.Skin Notation Profiles | Ethyl acrylate 11 

### Table A1. Summary of data used to calculate the SI ratio for ethyl acrylate

Variables used in calculation Units Value Skin permeation coefficient Permeation coefficient of stratum corneum lipid path( k psc ) cm/hr 4.043 × 10 -3 Permeation coefficient of the protein fraction of the stratum

corneum ( k pol

) cm/hr 1.152 × 10 -5 Permeation coefficient of the watery epidermal layer ( k aq ) cm/hr 0.2499 Molecular weight (MW)* amu 100.1 Base-10 logarithm of its octanol–water partition coefficient

(Log K
ow ) * None 1.18 Calculated skin permeation coefficient ( k p ) cm/hr 3.992 × 10 -3 Skin dose Water solubility ( S W ) * mg/cm 3 15 Calculated skin permeation coefficient ( k p ) cm/hr 3.992 × 10 -3 Estimated skin surface area (palms of hand) cm 2 360 Exposure time hr 8 Calculated skin dose mg 172.45 Inhalation Dose Occupational exposure limit (OEL) † mg/m 3 21 Inhalation volume m 3 10 Retention factor (RF) None 0.75 Inhalation dose mg 157.5 Skin dose–to–inhalation dose (SI) ratio None 1.09

* Variables identified from SRC [2009]. † The OEL used in calculation of the SI ratio for ethyl acrylate was the NIOSH recommended exposure limit (REL)

[NIOSH 2005].