# 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 Healthii 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) Publica

tion 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 spec

trum of adverse health effects ranging from localized damage (e.g., irritant contact dermatitis and corrosion) to induction of immune-mediated responses (e.g., allergic contact dermatitis and pulmonary responses), or systemic toxicity (e.g., neurotoxicity and hepatoxicity). Under

standing the hazards related to skin contact with chemicals is a critical component of modern occupational safety and health programs. In 2009, the National Institute for Occupational Safety and Health (NIOSH) published Cur

rent 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 ef

fects, 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 ana

lytical or numerical methods. This Skin Notation Profile provides the SK assignments and supportive data for 2-diethylami

noethanol (2-DAE). In particular, this document evaluates and summarizes the literature de

scribing 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 PreventionSkin 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

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

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

cm 2 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 k

pol coefficient in the protein fraction of the stratum corneum k

psc permeation coefficient in the lipid fraction of the stratum corneum LD 50 dose resulting in 50% mortality in the exposed population LD Lo dermal lethal dose LLNA local lymph node assay LOAEL lowest-observed-adverse-effect level log K OW base-10 logarithm of a substance’s octanol–water partition M molarity

m 3 cubic meter(s) mg milligram(s) mg/cm 2 milligram(s) per square centimeter mg/kg milligram(s) per kilogram body weight mg/m 3 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 factorSkin 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 S W solubility SYS skin notation indicating the potential for systemic toxicity following exposure of the skin USEPA United States Environmental Protection Agencyviii 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 Assess

ment [TERA] ) contracted by NIOSH and prepared by Bernard Gadagbui, Ph.D., and Andrew Maier, Ph.D. For their contribution to the technical content and review of this document, special acknowl

edgment is given to the following NIOSH personnel:


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

### Division of Applied Research and Technology 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 Shephardx Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) For their contribution to the technical content and review of this document, special acknowl

edgment is given to the following CDC personnel: 

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

pendent, external reviewers and providing comments that contributed to the development or improvement of this document: 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 Environ

mental 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, OHSkin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 1 Chemical: 2-Diethylaminoethanol (2-DAE) CAS No: 100-37-8 Molecular weight (MW): 117.2 Molecular formula: (C 2 H 5 ) 2 NCH 2 CH 2 OH Structural formula: Synonyms: 2-DAE; Diethylaminoethanol; 2-Dieth

ylaminoethyl alcohol; N,N-Diethyletha

nolamine; Diethyl-(2-hydroxyethyl)amine; 2-Hydroxytriethylamine Uses: 2-DAE is used primarily as a chemical in

termediate 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 toxicologi

cal data associated with skin contact with 2-DAE and (2) the rationale behind the haz

ard-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 Strat

egy for Assigning New NIOSH Skin Notations [NIOSH 2009]. The summarized informa

tion 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 toxicokinet

ics, acute toxicity, repeated-dose systemic tox

icity, carcinogenicity, biological system/func

tion–specific effects (including reproductive and developmental effects and immunotox

icity), irritation, and sensitization. Informa

tion 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 nu

merous 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 pro

vides 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 ex

posure in humans or animals. However, based on the physical properties of a saturated aque

ous 2-DAE solution, Fiserova-Bergerova [1990] estimated a dermal penetration rate of 3.44 milligrams per square centimeter (mg/
cm 2 ) 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 physi

co-chemical model of skin penetration [Guy and Potts 1993]. Some evidence for dermal 

# 1 Introduction
1.1 General Substance Information2 Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 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 expo

sure to substances [NIOSH 2009]. The evalu

ation method compares an estimated dose ac

cumulated in the body from skin absorption with an estimated dose from respiratory ab

sorption associated with a reference occupa

tional 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 (LD Lo ) for hu

mans has been identified, the reported dermal LD 50 value (the dose resulting in 50% mor

tality in the exposed animals) was reported as 1.0 milliliters per kilogram bodyweight (mL/ kg) (corresponding to 892 milligrams per ki

logram body weight, mg/kg) for the guinea pig [Smyth and Carpenter 1944]. The LD 50 value is lower than the critical dermal LD 50 value of 2000 mg/kg body weight that identi

fies chemical substances with the potential for acute dermal toxicity [NIOSH 2009]. There

fore, 2-DAE is acutely toxic following dermal exposure. No epidemiological studies in workers fol

lowing dermal exposure or dermal repeatdose, subchronic, or chronic toxicity studies in animals were identified that evaluated thesystemic 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 expo

sure to 2-DAE. No epidemiology studies or standard rodent cancer bioassays that evalu

ated the potential of 2-DAE to be carci

nogenic 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 toxic

ity study in animals [Smyth and Carpenter 1944] provide evidence that 2-DAE is ab

sorbed through the skin, systemically avail

able, and acutely toxic. Therefore, on the ba

sis 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 corro

sivity of 2-DAE or in vitro tests for corrosivity using human skin models or in vitro tests of skin integrity using cadaver skin were iden

tified. 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] sug

gested 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 dataSkin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 3 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 un

der 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 necro

sis, 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 li

ter (g/L)] [OECD 2002]. The structure activ

ity 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 fol

lowing accidental dermal exposure to 2-DAE in humans [NIOSH 1981, 1983] , and cor

rosivity 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 stan

dard 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 [Naka

mura et al. 1994; Leung and Blaszcak 1998]. DEREK predicted 2-DAE to be negative re

garding 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 sys

temically toxic in humans were limited to mod

els of human skin penetration based on physi

co-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 Occu

pational 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 accessed4 Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 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 nota

tion 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 acute

ly toxic. Based on case reports of skin irrita

tion 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 infor

mation exists to conclude that 2-diethylami

noethal 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. There

fore, 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 designa

tions for 2-DAE previously issued by NIOSH and other organizations. The equivalent der

mal 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 Corrosi on Category 1B (Hazard statement: Causes severe skin burns and eye damage) [ European Parliament 2008]. 

# References ACGIH (American Conference of Governmental Industrial Hygienists) [2001]. 2-diethylamino

ethanol. 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-diethylami

noethanol. 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, label

ling and packaging of substances and mixtures, amending and repealing Directives 67/548/ EEC and 1999/45/EC, and amending Regu

lation (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 indus

trial chemicals: Criteria for skin notation. Am J Ind Med 17 (5):617–636. Guy RH, Potts RO [1993]. Penetration of in

dustrial 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 LD 50 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 accessedSkin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 5 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/Mono

graphs/PDFs/index.php]. Accessed: 04-30-14. Leung HW, Blaszcak DL [1998]. The skin Sen

sitization potential of four alkylalkanolamines. Vet Hum Toxicol 40: 65 – 67. Nakamura A, Momma J, Sekiguchi H, Nodat T, Ya

mano 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 maximiza

tion test. Contact Dermatitis 31 : 72-85. NIOSH [1981]. Health hazard evaluation report: Boehringer Ingelheim Ltd., Ridgefield CT. Cin

cinnati, 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 Ser

vices, 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 Con

trol and Prevention, National Institute for Occu

pational 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 no

tations. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National In

stitute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009-147, http://www.cdc.gov/niosh/docs/2009-147/ pdfs/2009-147.pdf. Accessed: 05-29-13. NTP [2011]. Report on Carcinogens. Twelfth Edition; U.S. Department of Health and Hu

man Services, Public Health Service. National Toxicology Program, [ http://ntp.niehs.nih.gov/ ntp/roc/twelfth/roc12.pdf ]. Accessed 04-30-14. OECD (Organization for economic co-operation and development) [2002]. SIDS initial assess

ment profile. In: inChem, http://www.inchem. org/documents/sids/sids/DIETHYLAMI

NOETHAN.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 chemi

cals. 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 Pri

mary skin irritancy studies in the rabbit. Export, PA: Union Carbide Corporation, Bushy Run Research Center. On file with the U.S. Environ

mental 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.Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) 7 

# 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 sub

stance’s hazard potential following skin con

tact, 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 Bul

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


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

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

stance to penetrate the skin and induce sys

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

posed strategy for assigning SYS notation are as follows: 1. Provide an alternative method to evaluate substances for which no clinical reports or animal toxicity studies exist or for which empirical data are insufficient to deter

mine systemic effects. 2. Use the algorithm evaluation results to determine whether a substance poses a skin absorption hazard and should be la

beled with the SYS notation. The algorithm evaluation includes three steps: 1. Determining a skin permeation coefficient (k

p ) 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 require

ment and can operate entirely on the basis of the physicochemical properties of a substance and the relevant exposure parameters. Thus, the algorithm is independent of the need for biologic data. Alternatively, it can function with both the physicochemical properties and the experimentally determined permeation coefficient when such data are available and appropriate for use. The first step in the evaluation is to deter

mine the k p for the substance to describe the transdermal penetration rate of the substance [NIOSH 2009]. The k p , which represents the overall diffusion of the substance through the stratum corneum and into the blood capillar

ies of the dermis, is estimated from the com

pound’s molecular weight (MW) and base-10 logarithm of its octanol–water partition coef

ficient (log K OW ). In this example, k p is deter

mined 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)

aq pol psc p 

## k k k k 1 1 1

+ + =

where k psc is the permeation coefficient in the lipid fraction of the stratum corneum, k

pol is the coefficient in the protein fraction of the stratum corneum, and k aq is the coef

ficient in the watery epidermal layer. These components are individually estimated by log K psc = −1.326 + 0.6097 × log K
ow − 0.1786 × MW 0.5
K

pol = 0.0001519 × MW −0.5
K aq = 2.5 × MW −0.5 The second step is to calculate the biologic mass uptake of the substance from skin ab

sorption (skin dose) and inhalation (inhala

tion dose) during the same period of exposure. The skin dose is calculated as a mathematical product of the k p , the water solubility (S W ) of8 Skin Notation Profiles | 2-Diethylaminoethanol (2-DAE) the substance, the exposed skin surface area, and the duration of exposure. Its units are mil

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


### Equation 2: Determination of Skin Dose Skin dose = K p × S
w × Exposed skin surface area × Exposure time
= K p (cm/hour) × S
w (mg/cm 3 ) × 360 cm 2 × 8 hours The inhalation dose (in mg) is derived on the basis of the occupational exposure limit (OEL) of the substance—if the OEL is de

veloped to prevent the occurrence of systemic effects rather than sensory/irritant effects or direct effects on the respiratory tract. Assume a continuous exposure of 8 hours, an inhala

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

tion of the airborne substance in the lungs during respiration (retention factor, or RF). 

### Equation 3: Determination of Inhalation Dose Inhalation dose = OEL × Inhalation volume × RF = OEL (mg/m 3 ) × 10 m 3 × 0.75 The final step is to compare the calculated skin and inhalation doses and to present the result as a ratio of skin dose to inhalation dose (the SI ratio). This ratio quantitatively indi

cates (1) the significance of dermal absorp

tion as a route of occupational exposure to the substance and (2) the contribution of dermal uptake to systemic toxicity. If a substance has an SI ratio greater than or equal to 0.1, it is considered a skin absorption hazard. 

## Appendix References NIOSH [2009]. Current intelligence bulletin 61: a strategy for assigning new NIOSH skin no

tations. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Dis

ease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2009-147, http:// www.cdc.gov/niosh/docs/2009-147/pdfs/2009- 147.pdf. Accessed: 04-30-14.