NIOSH Skin Notation (SK) Profiles

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

Allyl Glycidyl Ether (AGE)

[CAS No. 106-92-3]
ii Skin Notation Profiles | Allyl glycidyl ether

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Suggested Citation

NIOSH [2014]. NIOSH skin notation profiles: allyl glycidyl ether (AGE). 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. 2014-143.

DHHS (NIOSH) Publication No. 2014-143

August 2014

Safer • Healthier • PeopleTM
Skin Notation Profiles | Allyl glycidyl ether 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 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 allyl glycidyl 

ether (AGE). 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-management practices may be developed to better protect workers from the risks of skin 

contact with the chemicals of interest.

John Howard, M.D.

Director, National Institute for 

 Occupational Safety and Health

Centers for Disease Control and Prevention

Skin Notation Profiles | Allyl glycidyl ether v

Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii

Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii

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

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

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

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

1.3 Overview of SK Assignment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2 Systemic Toxicity from Skin Exposure (SK: SYS) . . . . . . . . . . . . . . . . . . . . . . . 1

3 Direct Effects on Skin (SK: DIR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

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

5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Appendix: Calculation of the SI Ratio for AGE . . . . . . . . . . . . . . . . . . . . . . . . . . 6

 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Appendix References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
vi Skin Notation Profiles | Dichloropropene

Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists 

AGE allyl glycidyl ether 

CIB Current Intelligence Bulletin

cm2 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 

GHS Globally 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 

kpol coefficient in the protein fraction of the stratum corneum

k

psc 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

m3 cubic meter(s)

MEST mouse ear swelling test

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

pmol/g picomoles per gram 

REL recommended exposure limit

RF retention factor 
Skin Notation Profiles | Allyl glycidyl ether vii

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

SW solubility 

SYS skin notation indicating the potential for systemic toxicity following exposure

of the skin

USEPA United States Environmental Protection Agency 
viii Skin Notation Profiles | Allyl glycidyl ether

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 | Allyl glycidyl ether ix

Acknowledgments

This document was developed by the NIOSH 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, Vic Johnson, Ph.D., and Aaron Sussell, 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.

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

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. 

Michael Luster, Ph.D.

Anna Shevedova, 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 acknowledgment 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 | Allyl glycidyl ether

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:

Frank A Barile, Ph.D., St. John’s University, College of Pharmacy, Queens, NY

Phillip L. Williams, Ph.D., CIH, The University of Georgia, College of Public Health,

 Athens, GA

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
Skin Notation Profiles | Allyl glycidyl ether 1

Allyl glycidyl ether

1 Introduction 

1.1 General Substance Information: 

Chemical: Allyl glycidyl ether (AGE)

CAS No: 106-92-3

Molecular weight (MW): 114.2

Molecular formula: C6H10O2

Structural formula:

Synonyms: AGE; 1-Allyloxy-2,3-epoxypropane; Glycidyl allyl ether; [(2-Propenyloxy)

methyl] oxirane 

Uses: AGE is used primarily as a commercial 

chemical of as a resin intermediate, and is also 

used as a stabilizer of chlorinated compounds, 

vinyl resins, and rubber [Waechter et al. 2001]. 

Table 1. Summary of the SK assignment for AGE

Skin notation Critical effect Data available

SK: DIR (IRR) Skin irritation Limited human and animal data

SK: SEN Skin allergy Sufficient human data

1.2 Purpose 

This skin notation profile presents (1) a brief 

summary of epidemiological and toxicological 

data associated with skin contact with AGE 

and (2) the rationale behind the hazard-specific skin notation (SK) assignment for AGE. 

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 AGE. A literature search 

was conducted through April 2014 to identify information on AGE, 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 AGE. 

1.3 Overview of SK Assignment

AGE 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 

AGE: SK: DIR (IRR)-SEN. Table 1 provides 

an overview of the critical effects and data used 

to develop the SK assignment for AGE. 

2 Systemic Toxicity from Skin 

Exposure (SK: SYS)

There is paucity of data on the toxicokinetic 

studies of AGE following dermal exposure. A 

study that provided some evidence for dermal 

absorption was conducted by Perez and Osterman-Golker [2000] in which application 
2 Skin Notation Profiles | Allyl glycidyl ether

Allyl glycidyl ether

of 4 milligrams (mg) of AGE (99% pure) dissolved in acetone to the skin of mice for 5 or 

24 hours resulted in hemoglobin (AGE-Val) 

adduct levels of about 20 picomoles per gram 

(pmol/g) globin (median value) compared to 

undetected levels in control mice (detection 

limit 2 pmol/g globin). The potential of AGE 

to pose a skin absorption hazard was also evaluated, with use of a predictive algorithm for 

estimating and evaluating the health hazards 

of dermal exposure to substances [NIOSH 

2009]. The evaluation method compares an 

estimated dose accumulated in the body from 

skin absorption and an estimated dose from 

respiratory absorption associated with a reference occupational exposure limit. On the basis of this algorithm, a ratio of the skin dose 

to the inhalation dose (SI ratio) of 0.84 was 

calculated for AGE. An SI ratio of ≥0.1 indicates that skin absorption may significantly 

contribute to the overall body burden of a 

substance [NIOSH 2009]; therefore, AGE is 

considered to be absorbed through the skin 

following dermal exposure. Additional information on the SI ratio and the variables used 

in its calculation are included in the appendix. 

No dermal lethal doses (LDLo) of AGE for 

humans have been identified. The reported 

dermal LD50 value (the dose resulting in 50% 

mortality in the exposed animals) in rabbits 

was 2550 milligrams per kilogram (mg/kg) 

bodyweight [Hine et al. 1956]. Although no 

newer studies have been identified, the available acute dermal LD50 value for rabbits is 

higher than the critical dermal LD50 value 

of 2000 mg/kg body weight that identifies 

chemical substances with the potential for 

acute dermal toxicity [NIOSH 2009]. Therefore, AGE is not considered acutely toxic following dermal exposure. 

No epidemiological or occupational exposure studies in humans or standard repeatdose, subchronic, or chronic toxicity studies in animals were identified that evaluated 

systemic effects following dermal exposure. 

No studies that evaluated standard biological 

system or function specific effects (including 

reproductive and developmental effects and 

immunotoxicity) in humans or animals following dermal exposure to AGE were identified. No epidemiological studies or animal 

bioassays were identified that evaluated the 

carcinogenic potential of AGE following 

dermal exposure. No other organizations or 

agencies have classified AGE as a carcinogen 

by other routes of exposure. Table 2 summarizes carcinogenic designations of multiple 

governmental and nongovernmental organizations for AGE. 

Although the detection of hemoglobin adducts in mice dermally exposed to AGE indicates that the substance was absorbed through 

the skin, the available acute dermal toxicity 

study [Hine et al. 1956] indicated that the 

substance was not acutely toxic following dermal exposure until the applied dose exceeded 

2000 mg/kg. Lack of epidemiological studies 

in exposed workers or repeat-dose, subchronic, or chronic toxicity studies in humans or 

animals precludes adequate evaluation of the 

potential of the substance to cause systemic 

effects following dermal exposure. Therefore, 

on the basis of the available data for this assessment, AGE is not assigned the SK: SYS 

notation. 

3 Direct Effects on Skin 

(SK: DIR)

No human or animal in vivo studies on corrosivity of AGE 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 occupational exposure 

data were identified. Dermatitis, consisting of 

tenderness, itching, swelling, and blister formation, and whitish macules, were observed 

in 10 of 20 workers dermally exposed to AGE 

vapor and/or liquid [Hine et al., 1956]. In 

rabbits, a single application of 0.5 milliliter 

(mL) of undiluted AGE to the clipped skin 

for 24 hours, according to the Draize protocol, resulted in moderate skin irritation on intact skin and moderate to severe irritation on 

abraded skin [Hine et al. 1956; Dow Chemical Company 1957]. The structure activity 
Skin Notation Profiles | Allyl glycidyl ether 3

Allyl glycidyl ether

Table 2. Summary of the carcinogenic designations* for AGE 

by governmental and nongovernmental organizations

Organization Carcinogenic designation

NIOSH [2005] No designation

NTP [2011] No designation

US EPA [2012] No designation

European Parliament [2008] Carcinogenicity Category 2: Suspected of causing cancer

IARC [2011] No designation

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 Occupational Safety and Health; NTP = National Toxicology Program; USEPA = United States Environmental Protection Agency.

*The listed cancer designations were based on data from non-dermal (such as oral or inhalation) exposure rather than dermal exposure.

†

Date accessed.

relationship model, Deductive Estimation of 

Risk from Existing Knowledge (DEREK), 

predicted AGE to be a skin irritant. 

Results from a number of studies, including 

human experience [Hine et al. 1956]* and 

studies conducted using standard methods 

in animals [Hine et al. 1956; Dow Chemical Company 1957], with supporting information from a structure activity relationship 

model, demonstrate that AGE is a potential 

skin irritant. Therefore, on the basis of the data 

for this assessment, AGE is assigned the SK: 

DIR (IRR) notation. 

4 Immune-mediated 

Responses (SK: SEN)

A limited number of studies were identified that evaluated the potential of AGE to 

cause skin sensitization in both humans and 

animals. Hine et al. [1956] provided data that 

indicated that occupational exposure to AGE 

resulted in skin sensitization. Occupational exposure to a resin composed of epoxy resin and 

ortho-cresyl glycidyl ether produced contact 

*References in bold text indicate studies that serve 

as the basis of the SK assignments.

dermatitis and airborne contact dermatitis in 

10 of 22 workers after 20 days to 2 months 

of exposure [Angelini et al. 1996]. All 10 reacted to the diluent ortho-cresyl glycidyl ether 

(CGE), while only one of the 22 showed allergic reactions to AGE [Angelini et al. 1996]. 

Dooms-Goossens et al. [1995] also reported 

a case study in which a worker in the plastics 

industry who presented with dermatitis on 

his hands and forearms reacted positively to 

AGE after patch testing. Fregert and Rorsman 

[1964] conducted patch tests on people that 

presented with contact allergies to resins of diglycidyl ethers of bisphenol A. In this study, 

2 of 20 subjects were sensitized to AGE. No 

predictive tests [guinea pig maximization test 

(GPMT), Buehler test, local lymph node assays (LLNA), mouse ear swelling test (MEST) 

etc.] were identified. DEREK predicted AGE 

to be a skin sensitizer. 

A number of occupational exposure studies [Hine et al. 1956; Dooms-Goossens et 

al. 1995] and patch test studies [Fregert and 

Rorsman 1964; Angelini et al. 1996] demonstrate that AGE is a potential skin sensitizer. 

This conclusion is also supported by a structure activity relationship model. Therefore, on 

the basis of the data for this assessment, AGE 

is assigned the SK: SEN notation. 
4 Skin Notation Profiles | Allyl glycidyl ether

Allyl glycidyl ether

Table 3. Summary of previous skin hazard designations for AGE

Organization Skin hazard designation

NIOSH [2005] [skin]: Potential for dermal absorption; prevent skin contact

OSHA [2014]* No designation 

ACGIH [2001] No designation 

EC [2014]* 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.

5 Summary

No estimates of percent absorption of AGE 

following dermal exposure were identified. 

However, a mathematical model predicts that 

the chemical is poorly absorbed through the 

skin. Acute dermal toxicity data demonstrate 

that AGE has low systemic toxicity. No repeat-dose, subchronic or chronic dermal toxicity studies in animals or epidemiological or 

occupational exposure studies following dermal exposure that estimated systemic effect 

levels were identified. Occupational exposure 

information and standard skin irritation tests 

[Hine et al., 1956; Dow Chemical Company 

1957] provide sufficient evidence of the potential for AGE to cause skin irritation. Similarly, studies from occupational exposures and 

positive results from patch testing of individuals occupationally exposed to AGE [Hine 

et al. 1956; Fregert and Rorsman 1964; 

Dooms-Goossens et al. 1995; Angelini et al. 

1996] are sufficient to demonstrate that AGE 

is a potential skin sensitizer. Therefore, on 

the basis of these assessments, AGE is assigned a composite skin notation of SK: DIR 

(IRR)-SEN. 

Table 3 summarizes the skin hazard designations for AGE previously issued by NIOSH 

and other organizations. The equivalent dermal designations for AGE, according to the 

Global Harmonization System (GHS) of 

Classification and Labeling of Chemicals, are 

Skin Irritation Category 2 (Hazard statement: 

Causes skin irritation) and Skin Sensitization 

Category 1 (Hazard statement: May cause 

an allergic skin reaction) [European Parliament 2008]. In addition, AGE has been classified as a Mutagenicity Category 2 (Hazard 

Statement: Suspected of causing genetic defects) and a Reproductive Toxicity Category 

2 (Hazard Statement: Suspected of damaging 

fertility) [European Parliament 2008].

References

*ACGIH (American Conference of Governmental Industrial Hygienists) [2001]. Allyl glycidyl 

ether. In: Documentation of threshold limit 

values and biological exposure indices 7th ed., 

Vol. 1. Cincinnati, OH: American Conference 

of Governmental Industrial Hygienists.

*Angelini, G; Rigano, L; Foti, C; Grandolfo, M; 

Vena, GA;Bonamonte, D; Soleo; Scorpiniti, 

AA. [1996]. Occupational sensitization to epoxy resin and reactive diluents in marble workers. Contact Dermatitis. 35(1):11–16.

*Dooms-Goossens A, Bruze M, Buysse L, Fregert 

S, Gruvberger B, and Stals H [1995]. Contact 

allergy to allyl glycidyl ether present as an impurity in 3-glycidyloxypropyltrimethoxysilane, 

a fixing additive in silicone and polyurethane 

resins. Contact Dermatitis 33(1):17–19. 

*Dow Chemical Company [1957]. Results of 

range-finding toxicological tests on allyl glycidyl ether. Midland, MI: Dow Chemical Company. On file with the US Environmental Protection Agency under TSCA Section 8D. OTS 

#: 0206671.Document #: 878214852. 

*EC (European Commission) [ND]. Allyl 2,3-epoxypropyl ether. In: EINICS (European Inventory of Existing Commercial Chemical 
Skin Notation Profiles | Allyl glycidyl ether 5

Allyl glycidyl ether

Substances), http://esis.jrc.ec.europa.eu/. Accessed: 04-29-14.

*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, labeling 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://eurex.europa.eu/

LexUriServ/LexUriServ.do?uri=OJ:L:2008:35

3:0001:1355:EN:PDF. Accessed: 04-29-14.

*Fregert S; Rorsman H [1964]. Allergens in epoxy 

resins. Acta Allegrol. 19:296–299. 

*Hine CH, Kodama, JK, Kodama JK; Wellington 

JS, Dunlap MK, Anderson, HH [1956]. The 

toxicology of glycidol and some glycidyl ethers. 

Arch Ind Health 14:250–264

*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: 04-29-14.

*NIOSH [2005]. Allyl glycidyl ether. In: 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: 04-29-14.

*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 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: 04-29-14.

*NTP [2011]. Report on Carcinogens. Twelfth 

Edition; U.S. Department of Health and Human Services, Public Health Service. National 

Toxicology Program, http://ntp.niehs.nih.gov/

ntp/roc/twelfth/roc12.pdf. Accessed 05-29-13.

*OSHA [ND]. Allyl glycidyl ether. In: OSHA 

occupational chemical database, https://www

.osha.gov/chemicaldata/chemResult.html?

recNo=47. Accessed: 04-29-14.

*Perez HL, Osterman-Golkar S [2000]. Biotransformation of the double bond in allyl glycidyl 

ether to an epoxide ring. Evidence from hemoglobin adducts in mice. Chem-Biol. Interactions 125:17–28. 

*USEPA (United States Environmental Protection Agency) [2013]. Integrated Risk Information System (IRIS), http://www.epa.gov/ncea/

iris/. Accessed: 04-29-14.

*Waechter JM Jr., Pottenger LH, Veenstra GE 

[2001]. Epoxy compounds: olefin oxides, aliphatic glycidyl ethers and aromatic monoglycidyl ethers. In: Bingham E, Cohrssen B, Powell 

CH (Eds.), Patty’s toxicology 5th ed., Vol. 6. 

New York: John Wiley & Sons, Inc.
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Skin Notation Profiles | Allyl glycidyl ether 7

Allyl glycidyl ether

Appendix: Calculation of the SI Ratio for AGE

This appendix presents an overview of the SI 

ratio and a summary of the calculation of the 

SI ratio for allyl glycidyl ether. 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 

(k

p

) for the substance of interest,

2. estimating substance uptake by the skin 

and respiratory absorption routes, and 

3. evaluating whether the substance poses a 

skin exposure hazard.

The algorithm is flexible in the data requirement and can operate entirely on the basis of 

the physicochemical 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 k

p

 for the substance to describe the 

transdermal penetration rate of the substance 

[NIOSH 2009]. The k

p

, which represents the 

overall diffusion of the substance through the 

stratum corneum and into the blood capillaries of the dermis, is estimated from the 

compound’s molecular weight (MW) and 

base-10 logarithm of its octanol–water partition coefficient (log KOW). 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

)

psc pol aq

p

k k k

k 1 1

1

+

+

=

where k

psc 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 k

psc = −1.326 + 0.6097 × log Kow − 

0.1786 × MW 0.5

kpol = 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 
8 Skin Notation Profiles | Allyl glycidyl ether

Allyl glycidyl ether

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 

square centimeters [cm2]). 

Equation 2: Determination of Skin Dose 

= k

p

 × Sw × Exposed skin surface area 

 × Exposure time

= k

p

(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.

Calculation 

Table A1 summarizes the data applied in the 

previously described equations to determine 

the SI ratio for AGE. The calculated SI ratio was 0.837. On the basis of these results, 

AGE 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 Disease Control and Prevention, National Institute 

for Occupational Safety and Health, DHHS 

(NIOSH) Publication No. 2005–149, http://

www.cdc.gov/niosh/npg/. Accessed: 04-29-14.

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 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: 04-29-14.

SRC [2009]. Interactive PhysProp database demo 

http://www.srcinc.com/what-we-do/database

forms.aspx?id=386. Accessed: 04-29-14.
Skin Notation Profiles | Allyl glycidyl ether 9

Allyl glycidyl ether

Table A1. Summary of data used to calculate the SI ratio for AGE 

Variables used in calculation Units Value

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path(k

psc

) cm/hr 1.099 × 10-3

Permeation coefficient of the protein fraction of the stratum 

corneum (kpol)

cm/hr 1.4223 × 10-5

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.234089

Molecular weight (MW)

* amu 114.06

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

*

None 0.45

Calculated skin permeation coefficient (kp) cm/hr 1.1078 × 10-3

Skin dose

Water solubility (Sw)

* mg/cm3 43.3

Calculated skin permeation coefficient (k

p

) cm/hr 1.1078 × 10-3

Estimated skin surface area (palms of hand) cm2 360

Exposure time hr 8

Calculated skin dose mg 138.15

Inhalation Dose

Occupational exposure limit (OEL)† mg/m3 22

Inhalation volume m3 10

Retention factor (RF) None 0.75

Inhalation dose mg 165

Skin dose–to–inhalation dose (SI) ratio None 0.837

*

Variables identified from SRC [2009].

†

The OEL used in calculation of the SI ratio for allyl glycidyl ether was the NIOSH recommended exposure limit (REL) 

[NIOSH 2005].
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