NIOSH Skin Notation Profile

Diethylenetriamine (DETA)

Centers for Disease Control

and Prevention

National Institute for Occupational 

Safety and Health
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NIOSH Skin Notation Profile

Diethylenetriamine (DETA)

Naomi L. Hudson

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
ii Skin Notation Profiles | Diethylenetriamine (DETA)

This document is in the public domain and may be freely 

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Suggested Citation

NIOSH [2020]. NIOSH skin notation profile: diethylenetriamine (DETA). By Hudson NL. 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. 2021-102.

DHHS (NIOSH) Publication No. 2021-102

DOI: https://doi.org/10.26616/NIOSHPUB2021102

October 2020
Skin Notation Profiles | Diethylenetriamine (DETA) 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 (such as irritant contact dermatitis and corrosion) to induction of immune-mediated responses (such as allergic contact 

dermatitis and pulmonary responses) or systemic toxicity (such as neurotoxicity and hepatotoxicity). 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 (such as skin permeation) by means of analytical or 

numerical methods.

This Skin Notation Profile provides the SK assignments and supportive data for diethylenetriamine. 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
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Skin Notation Profiles | Diethylenetriamine (DETA) 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 for Diethylenetriamine . . . . . . . . . . . . . . . . . . . . . . . . . 1

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

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

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

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

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

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

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

Calculation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Appendix References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
vi Skin Notation Profiles | Diethylenetriamine (DETA)

Abbreviations

ACGIH® American Conference of Governmental Industrial Hygienists 

AMU atomic mass unit

ATSDR Agency for Toxic Substances and Disease Registry

CIB Current Intelligence Bulletin

cm2 squared centimeter(s)

cm/hr centimeter(s) per hour

cm/s centimeter(s) per second

COR subnotation of SK: COR indicating the potential for a chemical to be a skin corrosive following exposure to the skin

DEREK Deductive Estimation of Risk from Existing Knowledge

DETA diethylenetriamine

DIR skin notation indicating the potential for direct effects to the skin following contact with a chemical

FATAL subnotation of SK: SYS, indicating the potential for the chemical to be fatal during dermal absorption

g gram(s)

g/L gram(s)/liter

GHS Globally Harmonized System for Classification and Labelling of Chemicals

GPMT guinea pig maximization test

hr hour(s)

IARC International Agency for Research on Cancer

ID(SK) skin notation indicating that a chemical has been evaluated, but insufficient data 

exist to accurately assess the hazards of skin exposure

IPCS International Program for Chemical Safety 

IRR subnotation of SK: DIR indicating the potential for a chemical to be a skin irritant following exposure to the skin

kaq 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/hr milligram(s) per square centimeter per hour

mg/kg milligram(s) per kilogram body weight
Skin Notation Profiles | Diethylenetriamine (DETA) vii

mg/m3 milligram(s) per cubic meter

mL milliliter(s)

mL/kg milliliter(s) per kilogram body weight

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

nmol/cm2/hr nanomoles per square centimeter per hour

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit

OSHA Occupational Safety and Health Administration

ppm parts per million

REL recommended exposure limit

RF retention factor 

SEN skin notation indicating the potential for immune-mediated reactions following 

exposure of the skin

SI ratio ratio of skin dose to inhalation dose

SK skin notation

SK skin notation indicating that the reviewed data did not identify a health risk associated with skin exposure

SW solubility in water

SYS skin notation indicating the potential for systemic toxicity following exposure of 

the skin

US EPA United States Environmental Protection Agency 

μg microgram(s)

μg/cm2 microgram(s) per square centimeter

μg/cm2/hr microgram(s) per square centimeter per hour

μL microliter(s)

μmol micromole(s)

w/v weight/volume
viii Skin Notation Profiles | Diethylenetriamine (DETA)

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 occur 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 | Diethylenetriamine (DETA) ix

Acknowledgments

This document was developed by the Education and Information Division (Paul Schulte, Ph.D., 

Director). Naomi Hudson, Dr.P.H., was the project officer for this document and was assisted in 

great part by Loren Tapp, M.D., and Clayton B’Hymer, Ph.D. The basis for this document was a 

report (Toxicology Excellence for Risk Assessment [TERA]) contracted by NIOSH and prepared by 

Bernard Gadagbui, Ph.D., and Andrew Maier, Ph.D.

For their contribution to the technical content and review of this document, special acknowledgment is given to the following:

• M. Cecilia Aguila, D.V.M., Division of Human Food Safety, FDA, Center for Veterinary 

Medicine, Rockville, MD

• Emily N. Reinke, Ph.D., DABT, Biologist, Health Effects Division, Toxicology Directorate, 

U.S. Army Public Health Center

The following individuals contributed to the development or improvement of the skin notation 

profiles:

• 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, 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
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Skin Notation Profile | Diethylenetriamine (DETA) 1

Diethylenetriamine

1 Introduction

1.1 General Substance Information

Chemical: Diethylenetriamine

CAS No: 111-40-0

Molecular weight (MW): 103.2

Molecular formula: (NH2CH2CH2)2NH

Structural formula:

Image by National Center for Biotechnology Information [2020]

Synonyms: DETA; Aminoethylethanediamine; 2,2'-Diaminodiethylamine; 

N-(2-Aminoethyl)-1,2-ethanediamine; Bis(2-

aminoethyl)amine

Uses: Diethylenetriamine (DETA) is used as 

an additive in asphalt, chelating agents, corrosion inhibitors, drainage aids, epoxy curing 

agents, fabric softeners, and fuel.

1.2 Purpose

This skin notation profile presents (1) a brief 

summary of epidemiological and toxicological data associated with skin contact with 

diethylenetriamine (DETA) and (2) the rationale behind the hazard-specific skin notation 

(SK) assignment for DETA. 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 

DETA and the potential for direct skin injuries 

from DETA. A search of all available relevant 

literature was conducted through January 

2018 to identify DETA dermal absorption, 

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 DETA. The criteria for the search strategy, 

evaluation, and selection of data are described 

in Appendix E in the aforementioned CIB 61 

[NIOSH 2009].

1.3 Overview of SK Assignment for 

Diethylenetriamine (DETA)

DETA 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 DETA: SK: SYS-DIR(COR)-SEN. Table 1 

provides an overview of the critical effects and 

data used to develop the SK assignment for 

DETA.
2 Skin Notation Profile | Diethylenetriamine (DETA)

Diethylenetriamine

Table 1. Summary of the SK assignment for 

diethylenetriamine (DETA)

Skin notation Critical effect Available data

SK: SYS Acute toxicity Sufficient

SK: DIR(COR) Skin corrosivity Sufficient animal data

SK: SEN Skin allergy, crosssensitizationSufficient human and

animal data

2 Systemic Toxicity from Skin 

Exposure (SK: SYS)

No data from human or animal toxicokinetic 

studies that evaluated dermal absorption of 

DETA were identified. However, a study evaluating permeation of risedronate (RIS) through 

skin extracted from hairless mice looked at RIS 

dissolved in DETA [Nam et al. 2011]. The study 

authors found that RIS alone had a penetration 

rate as low as 4.13 micrograms per square centimeters (μg/cm2

) and the solution containing 

RIS and DETA at molar ratios of 1:1 and 1:2 

had a penetration rate of 511.21 μg/cm2 and 

504.73 μg/cm2

, respectively. However, Nam et 

al. [2011] did not evaluate the penetration rate 

of DETA alone. The potential of DETA to pose a 

skin absorption hazard was evaluated by means 

of the NIOSH [2009] predictive algorithm for 

estimating and evaluating the health hazards of 

dermal exposure to chemical substances. On 

the basis of this algorithm, a ratio of skin dose to 

inhalation dose (SI ratio) of 4.93 was calculated 

for DETA. Because this ratio is significantly 

higher than the SI ratio of ≥0.1 that indicates 

that skin absorption may significantly contribute to the overall body burden of a chemical 

[NIOSH 2009], DETA is considered to be a skin 

absorption hazard following dermal exposure. 

Additional information on the SI ratio and the 

variables used in its calculation are included in 

the appendix.

Although no dermal lethal dose (LDLo) values 

for humans were identified, the dermal LD50

(the dose resulting in 50% mortality in the 

exposed population) values have been reported 

for rabbits and guinea pigs. LD50 values of 0.707 

milliliter per kilogram body weight (mL/kg) 

(corresponding to 675.19 milligrams/kg [mg/

kg]) [Union Carbide Corporation 1977] and 

1.09 mL/kg (corresponding to 1040.95 mg/

kg) [Smyth et al. 1949] were reported for rabbits, and 170 mg/kg were reported for guinea 

pigs [Smyth and Carpenter 1944]. Because LD50

values for rabbits and guinea pigs are below the 

critical LD50 value of 2000 mg/kg that identifies 

chemical substances with potential for acute 

dermal toxicity [NIOSH 2009], DETA is considered acutely toxic by the dermal route.

No epidemiological studies that evaluated the 

potential of DETA to cause systemic effects 

have been identified. No standard toxicity 

studies have evaluated biological system/

function−specific effects of DETA (including 

reproductive effects, developmental effects, and 

immunotoxicity) following dermal exposure. 

However, a chronic study designed primarily to 

evaluate tumorigenicity has been conducted. In 

a study of male mice exposed dermally for their 

lifetime to 25 microliters (μL) of a 5% aqueous 

solution of DETA (corresponding to 1.25 mg/

day of high-purity [HP] grade [96.77% purity]) 

or the commercial preparation (90.8% purity) 

for 3 days per week applied on the shaved back, 

DePass et al. [1987] observed no evidence of 

skin tumors or internal tumors. Limited animal 

data show that DETA is not carcinogenic. Table 

2 summarizes the carcinogenic designations 

from NIOSH and other governmental and 

nongovernmental organizations.
Skin Notation Profile | Diethylenetriamine (DETA) 3

Diethylenetriamine

Table 2. Summary of the carcinogenic designations for diethylenetriamine 

(DETA) by governmental and nongovernmental organizations

Organization Carcinogenic designation

NIOSH [2005] No designation

US EPA [1988] No designation

NTP [2011] No designation

European Parliament [2008] No GHS designation

IARC [2009] No designation

ACGIH® [2001] No designation

ACGIH® = American Conference of Governmental Industrial Hygienists; GHS = Globally Harmonized System for Classification and 

Labelling of Chemicals; IARC = International Agency for Research on Cancer; NIOSH = National Institute for Occupational Safety 

and Health; US EPA = United States Environmental Protection Agency.

Although no toxicokinetic studies of humans 

or animals have involved estimating the extent 

of dermal absorption of DETA, a mathematical 

algorithm predicted its potential to be absorbed 

through the skin. Sufficient information was 

identified from acute toxicity studies [Smyth 

and Carpenter 1944; Smyth et al. 1949; Union 

Carbide Corporation 1977] to show that DETA 

is absorbed through the skin and is acutely 

toxic. Therefore, DETA is assigned the SK: SYS 

notation. 

3 Direct Effects on Skin (SK: DIR)

One study evaluated the effects of occupational 

exposure to ethylene amines, including DETA. 

In that study, Dernehl [1951] reported skin 

irritation, including dermatitis, erythema, and 

edema in 34% of 35 workers exposed to ethylene 

amines at a manufacturing plant. A majority 

of these workers had recurring episodes that 

became progressively more severe, but these 

reactions ceased when the workers were transferred to other units [Dernehl 1951]. Several 

studies using standard skin irritation test protocols in animals have evaluated the potential 

of DETA to cause skin corrosivity or irritation. 

Hine et al. [1958] reported that a single application of DETA to rabbit skin for 24 hours under 

patches of gauze or a repeated application to 

the skin for 1 hour per day for 2 days was corrosive to the skin. Another study reported that 

the concentrated material applied to the shaved 

abdomen of rabbits for 1 to 3 minutes produced 

minimal skin irritation, whereas application for 

6 to 12 minutes resulted in complete destruction 

of the skin, and a 1% aqueous solution applied 

repeatedly to the ears and shaven abdomens of 

rabbits for 10 days produced only slight irritation [Dow Chemical Company 1951]. Undiluted 

DETA was reported to be corrosive to the skin 

of rabbits following nonoccluded application 

[Union Carbide Corporation 1977; Smyth et 

al. 1949], and 0.5 mL of undiluted DETA for 24 

hours under occlusion was corrosive to rabbit 

skin [American Cyanamid Company 1969]. 

A 10% dilution of DETA in distilled water was 

corrosive to the skin of rabbits [Union Carbide 

Corporation 1977]. Studies conducted by the 

structure-activity relationship model (Deductive 

Estimation of Risk from Existing Knowledge, or 

DEREK, for Windows) predicted DETA to be 

negative for skin irritation. 

Dernehl [1951] reported the effects of occupational exposure to ethylene amines, including 

skin irritation, dermatitis, erythema, and edema. 

Sufficient animal data [Smyth et al. 1949; Dow 

Chemical Company 1951; Hine et al. 1958; 

American Cyanamid Company 1969; Union 

Carbide Corporation 1977] were identified to 

demonstrate that DETA is corrosive to the skin. 

*

References in bold text indicate studies that serve 

as the basis of the SK assignments.
4 Skin Notation Profile | Diethylenetriamine (DETA)

Diethylenetriamine

More-dilute solutions are likely to cause skin 

irritation. Therefore, on the basis of the data for 

this assessment, DETA is assigned the notation 

SK-DIR(COR).

4 Immune-mediated 

Responses (SK: SEN)

Data from studies of volunteers are sufficient 

to indicate that dermal exposure to DETA 

can result in sensitization. Kligman [1966] 

conducted a maximization test and reported 

extreme sensitization in 21 of 25 volunteers 

patch-tested with DETA at a concentration of 

10% at both induction and challenge. Booth et 

al. [1962] conducted a prophetic patch test on 

200 volunteers to evaluate the health hazards of 

Elcide 75, which is used in industrial cutting oils 

and contains DETA as a coupling agent. Patch 

tests revealed positive reactions in two subjects 

[Booth et al. 1962]. Upon further testing, one of 

the two workers reacted to 0.009% DETA, and 

the investigators concluded that the chemical 

has sensitizing properties [Booth et al. 1962]. 

Ormerod et al. [1989] reported allergy in 10 of 

800 patients due to oil-based drilling mud, a 

complex mixture containing amines in emulsifiers. Patch-testing of these 10 patients yielded a 

positive reaction to DETA (0.5% in petrolatum) 

in five patients and cross-reactivity between ethylenediamine, DETA, and triethylenetriamine 

in nine patients. Kydd [1960] reported that standard patch tests resulted in positive reactions, 

ranging from light to moderate, in 9 of 50 volunteers. However, the 9 volunteers did not have 

reactions when the patch was re-applied, but 

8 different volunteers had reactions to DETA 

ranging from light to moderate. One study 

showed no skin sensitization reaction in humans 

[Key et al. 1961]. 

Several guinea-pig maximization tests (GPMTs) 

revealed sensitization reactions. Thorgeirsson 

[1978] reported positive reactions in 93% of the 

animals patch-tested with a 2% solution after 

dermal exposure to 0.5% aqueous DETA solutions for 2 weeks. In another GPMT, Union 

Carbide Chemicals [1990] noted positive reactions in 16 of 20 guinea pigs exposed to HP 

DETA (98.8% pure) and in 11 of 20 guinea pigs 

exposed to commercial-grade DETA (90.8% 

pure). Leung and Auletta [1997] reported that 

80% of 20 guinea pigs had positive responses 

when 5% aqueous DETA solutions were used for 

intradermal induction, 50% solutions were used 

for epicutaneous induction, and 25% solutions 

were used for epicutaneous challenge. Basketter 

et al. [1994] conducted a murine local lymph 

node assay (LLNA) with DETA and reported 

skin sensitization. Union Carbide Chemicals 

[1990] reported that commercial-grade DETA 

induced cross-sensitization to the structurally similar amines ethylenediamine-UHP, 

diethylenetriamine-HP, aminoethylpiperazine, 

triethylenetetramine, aminoethylethanolamine, 

and tetraethylenepentamine, as well as probable slight cross-sensitization to piperazine. The 

structure-activity relationship model, DEREK, 

predicted DETA to be positive for skin sensitization, indicating that the chemical has structural 

alerts for skin sensitization.

There is sufficient evidence from diagnostic 

patch tests in humans [Booth et al. 1962; 

Kligman 1966; Ormerod 1989] and from predictive tests in animals (GPMTs and murine 

LLNAs) [Thorgeirssen 1978; Union Carbide 

Chemicals 1990; Basketter et al. 1994; Leung 

and Aulette 1997] to demonstrate that exposure 

to DETA causes skin sensitization. Therefore, 

DETA is assigned the notation SK-SEN.

5 Summary

Although there were no toxicokinetic studies 

that estimated the extent of dermal absorption 

of DETA identified in humans or animals, acute 

dermal toxicity studies [Smyth and Carpenter 

1944; Smyth et al. 1949; Union Carbide Corporation 1977] sufficiently demonstrate that 

DETA is absorbed through the skin and is acutely 

toxic. A limited number of human studies were 

identified that evaluated the potential of DETA 

to cause direct skin effects. However, sufficient 

evidence is provided by animal data [Smyth et 

al. 1949; Dow Chemical Company 1951; Hine 

et al. 1958; American Cyanamid Company 

1969; Union Carbide Corporation 1977] to 
Skin Notation Profile | Diethylenetriamine (DETA) 5

Diethylenetriamine

Table 3. Summary of previous skin hazard designations for 

diethylenetriamine (DETA)

Organization Skin hazard designation

NIOSH [2005] [skin]: Corrosive to the skin; repeated or prolonged contact may cause 

skin sensitization

ACGIH® [2001]* [skin]: [skin]: Based on the LD50 values for guinea pigs and rabbits 

following dermal application. Recommendation of a sensitizer (SEN) 

notation is deferred until additional evidence becomes available linking 

exposure and sensitization. 

OSHA [2018]* None

ACGIH® = American Conference of Governmental Industrial Hygienists; NIOSH = National Institute for Occupational Safety and 

Health; OSHA = Occupational Safety and Health Administration.

*

Year accessed

demonstrate that DETA is corrosive to the skin 

at high concentrations, whereas more-dilute 

solutions are likely to cause skin irritation. Information from diagnostic patch tests in humans 

[Booth et al. 1962; Kligman 1966; Ormerod 

1989] and from predictive tests in animals 

(GPMTs and murine LLNAs) [Thorgeirssen 

1978; Union Carbide Chemicals 1990; Basketter et al. 1994; Leung and Aulette 1997] is 

sufficient to show that exposure to DETA causes 

skin sensitization and can induce cross-sensitization with structurally similar amines. On 

the basis of the available data, a composite skin 

notation of SK-SYS-DIR(COR)-SEN is assigned 

to DETA.

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

other organizations. The equivalent dermal designations for DETA, according to the Globally 

Harmonized System (GHS) for Classification 

and Labelling of Chemicals, are Acute Toxicity 

Category 4 (Hazard statement: Harmful in contact with the skin), Skin Corrosion Category 1B 

(Hazard statement: Causes severe skin burns 

and eye damage), and Skin Sensitization Category 1 (May cause an allergic skin reaction) 

[European Parliament 2008].

References

Note: Asterisks (*) denote sources cited in 

text; daggers (†) denote additional resources.

ACGIH® [2001]. Diethylenetriamine. In: Documentation of threshold limit values and biological 

exposure indices. 7th ed., vol. 1. Cincinnati, OH: 

American Conference of Governmental and 

Industrial Hygienists.

*American Cyanamid Company [1969]. Diethylenetriamine toxicity data. NTIS Report No. 

OTS 206436.

*Basketter DA, Scholes EW, Kimber I [1994]. The 

performance of the local lymph node assay 

with chemicals identified as contact allergens 

in the human maximization test. Food Chem 

Toxicol 32:543–547.

*Booth BH, Gray HR, Wolf RL, Doneff RH [1962]. 

Prophetic patch-test study of a soluble cutting-oil antibacterial additive. J Occup Med 

4:367–369.

*DePass LR, Fowler EH, Weil CS [1987]. Dermal 

oncogenicity studies on various thyleneamines in male C3H mice. Fund Appl Toxicol 

9:807–811.

*Dernehl CU [1951]. Clinical experiences with 

exposures to ethylene amines. Ind Med Surg 

20(12):541–546.

*Dow Chemical Company [1951]. Results of range 

finding toxicological studies on diethylenetriamine. NTIS Report No. OTS 206407.

†Eastman Kodak Company [1979]. Classification: 

highly corrosive (causes severe burns). Data on 

file. Rochester, NY: Eastman Kodak Co., NTIS 

Report No. OTS 0206547.

*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 
6 Skin Notation Profile | Diethylenetriamine (DETA)

Diethylenetriamine

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.

†Greim H [2001]. Diethylenetriamine. In: Gesundheitsschädlicher Arbeitsstoffe. Toxikologischarbeitsmedizinische Begründungen von 

MAK-Werten (Maximale Arbeitsplatzkonzentrationen). Eds. 1 to 33. Weinheim, FRG: 

Wiley-VCH.

*Hine CH, Kodama JK, Anderson HH, Simonson 

DW, Wellington JS [1958]. The toxicology of 

epoxy resins. AMA Arch Ind Health 17:129–144.

*IARC [2009]. Agents reviewed by the IARC monographs, volumes 1-100A. Lyon, France: World 

Health Organization, International Agency for 

Research on Cancer, https://monographs.iarc.

fr/wp-content/uploads/2018/09/ClassificationsAlphaOrder.pdf. Accessed 02-27-13.

*Key MM, Perone VB, Birmingham DJ [1961]. 

Patch testing in dermatitis from the newer 

resins. J Occup Med 3:361–364.

*Kligman AM [1966]. The identification of contact 

allergens by human assay. III. The maximization 

test: a procedure for screening and rating contact sensitizers. J Invest Dermatol 47:393–409.

*Kydd WL [1960]. Toxicity evaluation of diethylenetriamine. J Dent Res 39(1):46–48.

*Leung HW, Auletta CS [1997]. Evaluation of skin 

sensitization and cross-reaction of nine alkyleneamines in the guinea pig maximization test. 

J Toxicol Cutan Ocul Toxicol 16:189–195.

*Nam SH, Xu YJ, Nam H, Jin G, Jeong, Y, An S, Park 

J [2011]. Ion pairs of risedronate for transdermal delivery and enhanced permeation rate on 

hairless mouse skin. Int J Pharm 419:114–120.

*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, https://www.cdc.gov/

niosh/npg/npgd0211.html. 

*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, https://www.cdc.gov/niosh/

docs/2009-147/pdfs/2009-147.pdf. 

*NTP [2011]. Report on carcinogens, 14th ed. 

Research Triangle, NC: U.S. Department of Health 

and Human Services, Public Health Service. 

National Toxicology Program, https://ntp.niehs.

nih.gov/whatwestudy/assessments/cancer/roc/

index.html.

*Ormerod AD, Wakeel RA, Mann TA, Main RA, 

Aldridge RD [1989]. Polyamine sensitization in 

offshore workers handling drilling muds. Contact Dermatitis 21(5):326–329. 

*OSHA [2018]. Diethylenetriamine. In: OSHA occupational chemical database. Washington, DC: 

Occupational Safety and Health Administration, 

https://www.osha.gov/chemicaldata/chemResult.html?recNo=125. Accessed 11-18-18.

*Smyth HF Jr, Carpenter CP [1944]. The place of the 

range finding test in the industrial toxicological 

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

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*Thorgeirsson A [1978]. Sensitization capacity of 

epoxy resin hardeners in the guinea pig. Acta 

Derm Venereol 58:332–336.

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maximization test. Bio/dynamics Project No. 

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Arch Exp Pathol Pharmacol 232:239–240.
Skin Notation Profile | Diethylenetriamine (DETA) 7

Diethylenetriamine

Appendix: Calculation of the SI Ratio for 

Diethylenetriamine (DETA)

This appendix presents an overview of the 

SI ratio and a summary of the calculation of 

the SI ratio for diethylenetriamine (DETA). 

Although the SI ratio is considered in the 

determination of a substance's hazard potential following skin contact, it is intended 

to serve only 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 its transdermal penetration rate [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 centimeters 

per hour (cm/hr), outlined in Table A1. Other 

model-based estimates of k

p

 may also be used 

[NIOSH 2009].

 = 1

1

kpsc + kpol kaq

1 +

kp

Equation 1: Calculation of Skin Permeation 

 Coecient (kaq)

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 × MW0.5)

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. 
8 Skin Notation Profile | Diethylenetriamine (DETA)

Diethylenetriamine

The skin dose is calculated as a mathematical 

product of the k

p

, 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

]).

Skin dose = kp × Sw × Exposed skin surface

area × Exposure time

= kp (cm/hr) × Sw (mg/cm3) × 

360 cm2 × 8 hr

Equation 2: Determination of Skin Dose

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).

Inhalation dose = OEL × Inhalation

volume × RF

= OEL (mg/m3

) × 10 m3 × 0.75

Equation 3: Determination of Inhalation Dose

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 DETA. The calculated SI ratio was 

4.93. On the basis of these results, DETA is predicted to represent a skin absorption hazard.

Appendix References

Hayes WA [2008]. Principles and methods of toxicology. 5th ed. New York: Informa Healthcare 

USA.

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, https://www.cdc.gov/

niosh/npg/. 

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, 

https://www.cdc.gov/niosh/docs/2009-147/

pdfs/2009-147.pdf. 

NLM [ND]. Toxnet, ChemIDplus: diethylenetriamine. Bethesda, MD: National Institutes of 

Health, National Library of Medicine, https://

chem.nlm.nih.gov/chemidplus/rn/111-40-0. 

Accessed 09-15-2020.
Skin Notation Profile | Diethylenetriamine (DETA) 9

Diethylenetriamine

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

diethylenetriamine (DETA)

Variables used in calculation Units Value

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path (kpsc) cm/hr 0.000364

Permeation coefficient of the protein fraction of the 

stratum corneum (kpol)

cm/hr 1.015 × 10-5

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.246129

Molecular weight (MW)* amu 103.17

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

*

None -2.13

Calculated skin permeation coefficient (kp) cm/hr 0.0000514

Skin dose

Water solubility (Sw)

* mg/cm3 1000

Calculated skin permeation coefficient (kp) cm/hr 0.000054

Estimated skin surface area (palms of hands)§ cm2 360

Exposure time hr 8

Calculated skin dose mg 147.91

Inhalation dose

Occupational exposure limit (OEL)† mg/m3 4

Inhalation volume m3 10

Retention factor (RF) None 0.75

Inhalation dose mg 30

Skin dose–to–inhalation dose (SI) ratio None 4.93

*

Variables identified from NLM [ND].

†

The OEL used in calculation of the SI ratio for diethylenetriamine was the NIOSH recommended exposure limit (REL) [NIOSH 2005].

§

Hayes WA [2008]. Principles and methods of toxicology. 5th ed. New York: Informa Healthcare USA.
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Promoting productive workplaces through safety and health research

DHHS (NIOSH) Publication No. 2021-102

DOI: https://doi.org/10.26616/NIOSHPUB2021102