2-Diethylaminoethanol

[CAS No. 100-37-8]

NIOSH Skin Notation (SK) Profiles

Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
ii Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE)

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Suggested Citation

NIOSH [2014]. NIOSH skin notation profiles: 2-diethylaminoethanol 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. 2014-140.

DHHS (NIOSH) Publication No. 2014-140

August 2014

Safer • Healthier • PeopleTM

This document is in the public domain and may be freely 

copied or reprinted.
Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 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 2-diethylaminoethanol (2-DAE). 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 | 2-Diethylaminoethanol (2-DAE) 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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

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

Appendix: Calculation of the SI Ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Appendix References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
vi Skin Notation Profiles | Diethylaminoethanol

Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists

CIB Current Intelligence Bulletin

cm2 square centimeter(s)

cm/hour centimeter(s) per hour

2-DAE 2-diethylaminoethanol

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

g/L grams per liter

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)

mg milligram(s)

mg/cm2 milligram(s) per square centimeter

mg/kg milligram(s) per kilogram body weight

mg/m3 milligram(s) per cubic meter

mL/kg milliliter(s) per kilogram body weight

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit

OSHA Occupational Safety and Health Administration

REL ecommended exposure limit

RF retention factor 
Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 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 | 2-Diethylaminoethanol (2-DAE)

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 | 2-Diethylaminoethanol (2-DAE) 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, Todd Niemeier, M.Sc., and Berran 

Yucesoy, 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. 

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.

National Personal Protection Technology Laboratory

Heinz Ahlers, M.Sc.

Angie Shephard
x Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE)

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:

Phil Bigelow, B.Sc., M.H.Sc., Ph.D., University of Waterloo, School of Public Health 

and Health Systems, Waterloo, ON, Canada

Youcheng Liu, M.D., Sc.D., M.P.H., M.S., University of North Texas Health Science 

Center, Fort Worth, TX

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 | 2-Diethylaminoethanol (2-DAE) 1

Diethylaminoethanol

Chemical: 2-Diethylaminoethanol (2-DAE)

CAS No: 100-37-8

Molecular weight (MW): 117.2

Molecular formula: (C2H5)

2

NCH2CH2OH

Structural formula:

Synonyms:

2-DAE; Diethylaminoethanol; 2-Diethylaminoethyl alcohol; N,N-Diethylethanolamine; Diethyl-(2-hydroxyethyl)amine; 

2-Hydroxytriethylamine

Uses:

2-DAE is used primarily as a chemical intermediate and as an emulsifying agent, in 

addition during the extraction of hydrogen 

sulfide and carbon dioxide from natural gas. 

[ACGIH 2001].

1.2 Purpose 

This skin notation profile presents (1) a brief 

summary of epidemiological and toxicological data associated with skin contact with 

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

2-DAE. 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 2-DAE. A literature 

search was conducted through April 2014 to 

identify information on 2-DAE, 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 2-DAE. 

1.3 Overview of SK Assignment 

2-DAE 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 

2-DAE: SK: SYS-DIR (COR). Table 1 provides an overview of the critical effects and 

data used to develop the SK assignment for 

2-DAE. 

2 Systemic Toxicity from Skin 

Exposure (SK: SYS)

No quantitative estimates of absorption of 

2-DAE were identified following dermal exposure in humans or animals. However, based 

on the physical properties of a saturated aqueous 2-DAE solution, Fiserova-Bergerova 

[1990] estimated a dermal penetration rate of 

3.44 milligrams per square centimeter (mg/

cm2) for human skin, with the rate described 

as being high. 2-DAE was also predicted to 

have significant skin absorption and potential 

toxicity through human skin based on a physico-chemical model of skin penetration [Guy 

and Potts 1993]. Some evidence for dermal 

1 Introduction 

1.1 General Substance Information
2 Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE)

Diethylaminoethanol

absorption of 2-DAE in humans is provided 

by two case reports that indicated that workers 

who were likely exposed repeatedly through 

both inhalation and dermal routes to 2-DAE 

developed nausea, vomiting, dizziness, chest 

tightness and/or headache [NIOSH 1981, 

1983]. The potential of 2-DAE to pose a skin 

absorption hazard could not be evaluated by 

the 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 

with an estimated dose from respiratory absorption associated with a reference occupational exposure limit. Additional information 

on the SI ratio and the variables used in its 

calculation are included in the appendix. 

While no dermal lethal dose (LDLo) for humans has been identified, the reported dermal 

LD50 value (the dose resulting in 50% mortality in the exposed animals) was reported as 

1.0 milliliters per kilogram bodyweight (mL/

kg) (corresponding to 892 milligrams per kilogram body weight, mg/kg) for the guinea 

pig [Smyth and Carpenter 1944]. The LD50

value is lower 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, 2-DAE is acutely toxic following dermal 

exposure. 

No epidemiological studies in workers following dermal exposure or dermal repeatdose, subchronic, or chronic toxicity studies 

in animals were identified that evaluated the 

systemic toxic effects of 2-DAE. No repeatdose studies were identified in humans or 

animals that evaluated standard biological 

system or function specific effects (including 

reproductive and developmental effects and 

immunotoxicity) following dermal exposure to 2-DAE. No epidemiology studies or 

standard rodent cancer bioassays that evaluated the potential of 2-DAE to be carcinogenic following dermal exposure were 

identified. Table 2 summarizes carcinogenic 

designations of multiple governmental and 

nongovernmental organizations for 2-DAE. 

Although information from human evidence 

is limited, modeled skin penetration rates for 

human skin [Fiserova-Bergerova 1990; Guy 

and Potts 1993]* and an acute dermal toxicity study in animals [Smyth and Carpenter 

1944] provide evidence that 2-DAE is absorbed through the skin, systemically available, and acutely toxic. Therefore, on the basis of the data for this assessment, 2-DAE is 

assigned the SK: SYS notation. 

3 Direct Effects on Skin (SK:DIR)

No human or animal in vivo studies on corrosivity of 2-DAE or in vitro tests for corrosivity 

using human skin models or in vitro tests of 

skin integrity using cadaver skin were identified. However, skin irritation or dermatitis 

was reported in two case reports following 

exposure to 2-DAE [NIOSH 1981, 1983]. 

In one of these reports, NIOSH [1981] suggested that a condensation or reaction product 

of 2-DAE present in the air was responsible 

for the primary irritation of exposed skin, and 

the response possibly involved a phototoxic 

skin reaction. Studies conducted according to 

the Organization for Economic Cooperation 

*References in bold text indicate studies that serve 

as the basis of the SK assignments.

Table 1. Summary of the SK assignment for 2-DAE

Skin notation Critical effect Available data

SK: SYS Acute toxicity Limited animal data

SK: DIR (COR) Skin corrosion Sufficient animal data
Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 3

Diethylaminoethanol

and Development (OECD) Guideline 404 

indicated that 2-DAE was corrosive to the 

skin of rabbits. For example, in two studies 

2-DAE applied to shaved skin of rabbits under occlusive or semi-occlusive conditions for 

1 hour or 4 hours was corrosive to the skin 

[Potokar et al. 1985; Union Carbide, 1990]. 

Smyth and Carpenter [1944] observed necrosis, edema and erythema when 2-DAE was 

applied to the skin of a rabbit. Corrosivity of 

2-DAE to the skin is expected since the pH 

measured at 20°C was 11.5 [100 grams per liter (g/L)] [OECD 2002]. The structure activity relationship model, Deductive Estimation 

of Risk from Existing Knowledge (DEREK) 

for Windows, predicted 2-DAE to be a skin 

irritant. 

Based on case reports of skin irritation following accidental dermal exposure to 2-DAE 

in humans [NIOSH 1981, 1983], and corrosivity observed in experimental animals 

[Smyth and Carpenter 1944; Potokar et al. 

1985; Union Carbide, 1990], this assessment 

concludes that undiluted 2-DAE is corrosive 

to the skin. The diluted substance produced 

concentration-related irritation effects when 

evaluated in rabbits. Therefore, on the basis of 

the data for this assessment, 2-DAE is assigned 

the SK: DIR (COR) notation. 

4 Immune-mediated 

Responses (SK: SEN)

Occupational exposure experiences or standard studies in humans that involved skin 

sensitization following dermal exposure to 

2-DAE were not identified. However, the 

substance was not a skin sensitizer in guinea 

pig sensitization tests performed according to 

the Magnusson and Kligman method [Nakamura et al. 1994; Leung and Blaszcak 1998]. 

DEREK predicted 2-DAE to be negative regarding skin sensitization potential. 

Based on the negative responses from two 

guinea pig maximization tests [Nakamura et 

al. 1994; Leung and Blaszcak 1998], sufficient 

data exist to conclude that the substance is 

not a skin sensitizer. Therefore, on the basis 

of the data for this assessment, 2-DAE is not 

assigned the SK: SEN notation. 

5 Summary

Studies that evaluated the potential of 2-DAE 

to be absorbed through the skin or to be systemically toxic in humans were limited to models of human skin penetration based on physico-chemical properties [Fiserova-Bergerova 

Table 2. Summary of the carcinogenic designations* for 2-DAE by numerous 

governmental and nongovernmental organizations

Organization Carcinogenic designation

NIOSH [2005] No designation

NTP [2011] No designation

USEPA [2014] No designation

European Parliament [2008] No designation

IARC [2012] No designation

EC [2014]† No designation

ACGIH [2001] No designation

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 nondermal (such as oral or inhalation) exposure rather than dermal exposure.

†

Date accessed
4 Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE)

Diethylaminoethanol

1990; Guy and Potts 1993]. However, these 

predictions are supported by an acute dermal 

toxicity study [Smyth and Carpenter 1944]; 

therefore, this assessment assigns a skin notation of SK: SYS for 2-DAE. Taken together, 

there is limited data in humans and animals to 

demonstrate that 2-DAE is absorbed through 

the skin, is systemically available, and is acutely toxic. Based on case reports of skin irritation following accidental dermal exposure to 

2-DAE in humans [NIOSH 1981, 1983] and 

corrosivity observed in experimental animals 

[Smyth and Carpenter 1944; Potokar et al. 

1985; Union Carbide, 1990], sufficient information exists to conclude that 2-diethylaminoethal is corrosive, and that dilute solutions 

of the substance may irritate the skin. No 

standard studies conducted in humans were 

identified that evaluated the potential of the 

substance to be a skin sensitizer. However, 

guinea pig maximization tests [Nakamura 

et al. 1994; Leung and Blaszcak 1998] show 

that 2-DAE was not a skin sensitizer. Therefore, on the basis of these assessments, 2-DAE 

is assigned a composite skin notation of 

SK: SYS-DIR (COR). 

Table 3 summarizes the skin hazard designations for 2-DAE previously issued by NIOSH 

and other organizations. The equivalent dermal designations for 2-DAE, according to 

the Global Harmonization System (GHS) of 

Classification and Labeling of Chemicals, are 

Acute Toxicity Category 4 (Hazard statement: 

Harmful in contact with the skin) and Skin 

Corrosion Category 1B (Hazard statement: 

Causes severe skin burns and eye damage) 

[European Parliament 2008].

References

ACGIH (American Conference of Governmental 

Industrial Hygienists) [2001]. 2-diethylaminoethanol. In: Documentation of threshold limit 

values and biological exposure indices 7th ed., 

Vol. 1. Cincinnati, OH: American Conference 

of Governmental Industrial Hygienists.

EC (European Commission) [ND]. 2-diethylaminoethanol. In: EINICS (European Inventory 

of Existing Commercial Chemical Substances), 

http://esis.jrc.ec.europa.eu/.Accessed: 04-30-14.

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, 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:2008:3

53:0001:1355:EN:PDF]. Accessed: 04-30-14.

Fiserova-Bergerova V, Pierce JT, and Droz PO. 

[1990]. Dermal absorption potential of industrial chemicals: Criteria for skin notation. Am J 

Ind Med 17(5):617–636.

Guy RH, Potts RO [1993]. Penetration of industrial chemicals across the skin: a predictive 

model. Am J Ind Med 23(5):711-719.

Table 3. Summary of previous skin hazard designations for 2-DAE

Organization Skin hazard designation

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

OSHA [2014]* [skin]: Potential for dermal absorption

ACGIH [2001] [skin]: Based on reported dermal LD50 in rabbits

EC [2014]* R21: Harmful if in contact with skin

R34: Causes burns

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 | 2-Diethylaminoethanol (2-DAE) 5

Diethylaminoethanol

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: 04-30-14.

Leung HW, Blaszcak DL [1998]. The skin Sensitization potential of four alkylalkanolamines. 

Vet Hum Toxicol 40: 65 – 67.

Nakamura A, Momma J, Sekiguchi H, Nodat T, Yamano T, Kaniwa MA, Kojima S, Tsuda M, and 

Kurokawa Y. [1994]. A new protocol and criteria 

for quantitative determination of sensitization 

potencies of chemicals by guinea pig maximization test. Contact Dermatitis 31: 72-85.

NIOSH [1981]. Health hazard evaluation report: 

Boehringer Ingelheim Ltd., Ridgefield CT. Cincinnati, OH: Department of Health and Human 

Services, Centers for Disease Control, National 

Institute for Occupational Safety and Health, 

NIOSH HETA Report No. 81-247-958.

NIOSH [1983]. Health hazard evaluation report: 

Johnson Museum, Cornell, NY. Cincinnati, 

OH: Department of Health and Human Services, Centers for Disease Control, National 

Institute for Occupational Safety and Health, 

NIOSH HETA Report No. 83-020-1351.

NIOSH [2005]. 2-Diethylaminoethanol. 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: 04-30-14.

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: 05-29-13.

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 04-30-14.

OECD (Organization for economic co-operation 

and development) [2002]. SIDS initial assessment profile. In: inChem, http://www.inchem.

org/documents/sids/sids/DIETHYLAMINOETHAN.pdf. Accessed: 04-30-14.

OSHA [ND]. 2-diethylaminoethanol. In: OSHA/

EPA occupational chemical database, http://

www.osha.gov/chemicaldata/chemResult.

html?recNo=11. Accessed: 04-30-14.

Potokar M, Grundler OJ, Heusener A, Jung R, 

Mürmann P, Schöbel C, Suberg H, and Zechel 

HJ [1985]. Studies on the design of animal 

tests for the corrosiveness of industrial chemicals. Food Chem Toxico 23:615–617.

Smyth HF, and Carpenter CP [1944]. The place of 

range-finding test in the industrial toxicology 

laboratory. J Ind Hyg Toxicol 26:269–273.

Union Carbide [1990]. Diethylethanolamine Primary skin irritancy studies in the rabbit. Export, 

PA: Union Carbide Corporation, Bushy Run 

Research Center. On file with the U.S. Environmental Protection Agency under TSCA Section 

8e. Project Report 53-21.

USEPA (United States Environmental Protection 

Agency) [2011]. Integrated Risk Information 

System (IRIS), http://www.epa.gov/ncea/iris/. 

Accessed: 04-30-14.
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Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 7

Diethylaminoethanol

Appendix: Calculation of the SI Ratio 

This appendix presents an overview of the SI 

ratio and a summary of the calculation of the 

SI ratio for 2-DAE. Although the SI ratio 

is considered in the determination of a substance’s hazard potential following skin contact, it is intended only to serve as supportive 

data during the assignment of the NIOSH 

SK. An in-depth discussion on the rationale 

and calculation of the SI ratio can be found 

in Appendix B of the Current Intelligence Bulletin (CIB) 61: A Strategy for Assigning New 

NIOSH Skin Notations [NIOSH 2009]. 

Overview 

The SI ratio is a predictive algorithm for estimating and evaluating the health hazards of 

skin exposure to substances. The algorithm is 

designed to evaluate the potential for a substance to penetrate the skin and induce systemic toxicity [NIOSH 2009]. The goals for 

incorporating this algorithm into the proposed strategy for assigning SYS notation are 

as follows:

1. Provide an alternative method to evaluate 

substances for which no clinical reports or 

animal toxicity studies exist or for which 

empirical data are insufficient to determine systemic effects.

2. Use the algorithm evaluation results to 

determine whether a substance poses a 

skin absorption hazard and should be labeled with the SYS notation.

The algorithm evaluation includes three steps:

1. Determining a skin permeation coefficient 

(kp) for the substance of interest.

2. Estimating substance uptake by the skin 

and respiratory absorption routes.

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 kp, which represents the 

overall diffusion of the substance through the 

stratum corneum and into the blood capillaries of the dermis, is estimated from the compound’s molecular weight (MW) and base-10 

logarithm of its octanol–water partition coefficient (log KOW). In this example, k

p

is determined for a substance with use of Equation 1. 

Other model-based estimates of k

p

 may also 

be used [NIOSH 2009].

Equation 1: Calculation of Skin Permeation 

Coefficient (kp)

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 Kpsc = −1.326 + 0.6097 × log Kow − 

0.1786 × MW 0.5

Kpol = 0.0001519 × MW−0.5

 Kaq = 2.5 × MW−0.5

The second step is to calculate the biologic 

mass uptake of the substance from skin absorption (skin dose) and inhalation (inhalation dose) during the same period of exposure. 

The skin dose is calculated as a mathematical 

product of the kp, the water solubility (SW) of 
8 Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE)

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 

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.

Appendix References 

NIOSH [2009]. Current intelligence bulletin 61: 

a strategy for assigning new NIOSH skin notations. Cincinnati, OH: U.S. Department of 

Health and Human Services, Centers for Disease Control and Prevention, National Institute 

for Occupational Safety and Health, DHHS 

(NIOSH) Publication No. 2009-147, http://

www.cdc.gov/niosh/docs/2009-147/pdfs/2009-

147.pdf. Accessed: 04-30-14.
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