# 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 Healthii

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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. 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 Occupational Safety and He alth. 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 expos ed 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 program s.

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 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 decision

makers, employers, and workers in potentially hazardous workplaces

— so that improved risk

mana gement 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

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- dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and He alth. It does not represent and should not be construed to represent any agency determination or policy. 

## Conte nts

FOREWORD

................................ ................................ ................................ ................................ ............................ III

ABBREVIATIONS

................................ ................................ ................................ ................................ ..................... V

ACKNOWLEDGMENTS

................................ ................................ ................................ ................................ ..... VIII

1.0 INTRODUCTION

................................ ................................ ................................ ................................ ................. 1

1.1 G ENERAL S UBSTANCE I NFORMATION

................................ ................................ ................................ ................. 1

1.2 P URPOSE

................................ ................................ ................................ ................................ ............................. 1

1.3 O VERVIEW OF SK A SSIGNMENT

................................ ................................ ................................ .......................... 2

2.0 SYSTEMIC TOXICIT Y FROM SKIN EXPOSURE (SK: SYS)

................................ ................................ ...... 2

3.0 DIRECT EFFECTS O N SKIN (SK: DIR)

................................ ................................ ................................ ........... 3

4.0 IMMUNE

- MEDIATED RESPONSES ( SK: SEN)

................................ ................................ ............................. 4

5.0 SUMMARY

................................ ................................ ................................ ................................ ............................ 5

REFERENCES

................................ ................................ ................................ ................................ ............................ 6

APPENDIX: CALCULAT ION OF THE SI RATIO FOR HPA

................................ ................................ ............. 8

O VERVIEW

................................ ................................ ................................ ................................ ................................ . 8

A PPENDIX R EFERENCES

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

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## Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists

CIB Current Intelligence Bulletin

cm 2 squared centimeter(s)

cm/hour centimeter(s) per hour

DEREK Deductive Estimation of Risk from Existing Knowledge

DIR skin notation indicating the potential fo r 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

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

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 d ose resulting in 50% mortality in the exposed population

LD Lo dermal lethal dose

LLNA local lymph node assay

LO AEL 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/kg milligram(s) per kilogram body weight 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 limit

OSHA Occupational Safety and Health Administration

REL recommended e xposure 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 dosevi

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 He alth. It does not represent and should not be construed to represent any 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 percentagevii

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- dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and He alth. 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 bot h 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 carcino gen and present within a

neat sub stance 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, oc curring at or near the point of contact with chemicals.

Immune

- mediated responses

— Respons es 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

- med iated diseases such as asthma, depending on the site and route of re

- exposure.

Substance

— A chemical.

Systemic effects

— Systemic toxicity associated with skin absorption of chemicals after exposure

of the skin.viii

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- dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and He alth. 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 Tor aason, 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

Gr egory 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.ix

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 He alth. 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, 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 Occupational Safety and He alth. 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: 2

- Hydroxypropyl acrylate

CAS No: 999

- 61

- 1 Molecular weight (

MW ): 130.2

Molecular formula: CH 2 =CHCOOCH 2 CH(CH 3 )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 I

ntelligence 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, includin g 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 s ensitization. Information was considered from studies of humans, animals, or appropriate modeling systems that are relevant to assessing the effects of dermal exposure to
HPA.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 Occupational Safety and He alth. It does not represent and should not be construed to represent any agency determination or policy. 

### 1.3 Overview of SK Assignment

HPA is potentially capable of causing numerous ad verse 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 assignm ent 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 subst ances [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.

N o dermal lethal concentrations (LD Lo ) for humans were identified. A dermal LD 50 (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 bodyweigh t (mg/kg)] was reported for rabbits [Smyth et al. 1969]. Because the reported acute dermal LD 50 values for the rabbit is lower than the critical dermal LD 50 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, o r 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.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 Occupational Safety and He alth. It does not represent and should not be construed to represent any agency determination or 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 derm ally 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 viv o 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 [L ovell 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 ( DERE K ) for Windows, predicted HPA to be a plausible skin irritant.4

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 He alth. It does not represent and should not be construed to represent any agency determination or policy. Although occupational case reports [Lovell et al. 1985; Kanerva et al. 1988] 1 suggest 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 co nclude 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 includin g 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 cross

sensitivity 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 commerc ial 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), a nd 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) reacte d 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 wi th 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]

where as 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.

1 References in bold text indicate studies that serve as the basis of the SK assignments.5

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- dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the National Institute for Occupational Safety and He alth. It does not represent and should not be construed to represent any agency determination or policy. 

## 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 NIO SH 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 C orrosi on 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 f or HPA

Organization Skin hazard designation
NIOSH [2005] [skin]: Potential for dermal absorption OSHA [2015] * None assigned ACGIH [2014] [skin]: Based on dermal LD 50 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.6

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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

o f 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 hydroxyethy l 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 pi gs 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://eur

lex.europa.eu/LexUriServ/LexUriServ.do ?uri=OJ:L:2008:353:0001:1355:EN:PDF. Accessed: 01

- 27

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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/EN G/Monographs/PDFs/index.php. Accessed: 01

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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, Jol anki 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 He alth. 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 hydroxypr opyl 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 (NIO SH) 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 Pro gram, http://ntp.niehs.nih.gov/pubhealth/roc/roc13/index.html. Accessed: 01

- 27

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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

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

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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

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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 He alth. 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 d uring 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].



### Overvi ew

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) determini ng 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 requi rement 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 physicochemic al 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 k p for the substance to describe the transdermal penetration rate of the subs tance [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 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].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 He alth. 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/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 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 (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.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 He alth. 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 (NIO SH) Publication No.

2009

- 147, http://www.cdc.gov/niosh/docs/2009

- 147/pdfs/2009

- 147.pdf. Accessed: 03

- 08

- 11.