SK

NIOSH Skin Notation Profiles

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

IDSK

[SK]

SYS

DIR

DIR (IRR)

SYS (FATAL)

DIR (COR)

SEN

Trichloroethylene (TCE)
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Naomi L. Hudson and G. Scott Dotson

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 

NIOSH Skin Notation (SK) Profile

Trichloroethylene (TCE)

[CAS No. 79-01-6]
ii Skin Notation Profiles | Trichloroethylene (TCE)

This document is in the public domain and may be freely 

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Suggested Citation

NIOSH [2017]. NIOSH skin notation profile: Tricholoroethylene (TCE). 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. 2017-192.

DHHS (NIOSH) Publication No. 2017-192

August 2017
Skin Notation Profiles | Trichloroethylene (TCE) 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 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 (SKs) 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 for trichloroethylene 

(TCE). 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 | Trichloroethylene (TCE) v

Contents

Foreword . .

Abbreviations . 

Glossary . . 

Acknowledgments . 

1 Introduction .

1.1 General Substance Information: .

1.2 Purpose .

1.3 Overview of SK Assignment .

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

3 Direct Effects on Skin (SK: DIR) .

4 Immune-mediated Responses (SK: SEN) .

5 Summary .

References .

Appendix: Calculation of the SI Ratio for TCE . 

Overview . 

Calculation . 

Appendix References . 
vi Skin Notation Profiles | Trichloroethylene (TCE)

Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists 

CIB Current Intelligence Bulletin

cm2 square centimeter(s)

cm/hour centimeter(s) per hour

DEREK Deductive Estimation of Risk from Existing Knowledge

DIR skin notation indicating the potential for direct effects to the skin following 

contact with a chemical

GHS Globally Harmonized System for Classification and Labelling of Chemicals

GPMT guinea pig maximization test

HPA 2-hydropropyl acrylate 

IARC International Agency for Research on Cancer

(IRR) subnotation of SK: DIR indicating the potential for a chemical to be a skin 

irritant following exposure to the skin

kaq coefficient in the watery epidermal layer 

kp skin permeation coefficient 

kpol coefficient in the protein fraction of the stratum corneum

kpsc 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/kg milligram(s) per kilogram body weight

mg/m3 milligram(s) per cubic meter

mL milliliter(s)

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit

OSHA Occupational Safety and Health Administration

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
Skin Notation Profiles | Trichloroethylene (TCE) vii

SK skin notation

SW solubility in water

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

the skin

USEPA United States Environmental Protection Agency

w/w weight by weight percentage
viii Skin Notation Profiles | Trichloroethylene (TCE)

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. 

Permeability coefficient (kp)–The transdermal penetration rate of a substance and is expressed 

in cm/hr and represents the overall diffusion of the substance through the stratum corneum and 

into the blood capillaries of the dermis.

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 | Trichloroethylene (TCE) ix

Acknowledgments

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

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

great part by G. Scott Dotson, Ph.D., Michael Luster, Ph.D., and Loren Tapp, M.D. The basis for 

this document was a report (Toxicology Excellence for Risk Assessment [TERA]) contracted by 

NIOSH and prepared by Bernard Gadagbui, Ph.D., and Andrew Maier, Ph.D.

For their contribution to the technical content and review of this document, special acknowledgment 

is given to the following NIOSH personnel:

Denver Field Office

Eric Esswein, M.Sc.

Division of Applied Research and Technology

Clayton B’Hymer, Ph.D. 

John Snawder, Ph.D.

Division of Respiratory Disease Studies

Gregory A. Day, Ph.D.

Aleksander Stefaniak, Ph.D.

Division of Surveillance, Hazard Evaluations, and Field Studies

Matt Dahm, M.Sc. 

Todd Niemeier, M.Sc.

Aaron Sussell 

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.

Berran Yucesoy, Ph.D. 

National Personal Protective Technology Laboratory

Heinz Ahlers, JD, M.Sc.

Gregory Day, Ph.D. 

Angie Shepherd
x Skin Notation Profiles | Trichloroethylene (TCE)

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:

Karin Pacheco, MD, MSPH, Associate Professor, Division of Environmental and Occupational 

Health Sciences, National Jewish Medical and Research Center, Denver, CO

Sean Semple, Ph.D., Senior lecturer, Scottish Centre for Indoor Air Division of Applied 

Health Sciences, University of Aberdeen, Aberdeen, Scotland

Glenn Sipes, Ph.D., Professor Emeritus, Department of Pharmacology, University of Arizona, 

Tucson, AZ

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 | Trichloroethylene (TCE) 1

Trichloroethylene (TCE)

1 Introduction

1.1 General Substance Information:

Chemical: Trichloroethylene (TCE) 

CAS No: 79-01-6

Molecular weight (MW): 131.39

Molecular formula: C2HCl3

Structural formula:

Synonyms: Ethylene trichloride; TCE; 

Trichloroethene; Trilene; TRI

Uses: Trichloroethylene (TCE) is a chlorinated organic compound used primarily as 

a solvent in metal degreasing operations and 

as a component of the refrigerant HFC-134a 

[ATSDR 2014; Bakke et al. 2007; EPA 2014]. 

TCE is also used as a spotting agent in dry 

cleaning operations [EPA 2014] and historically has been used as a general anesthetic or 

analgesic [ATSDR 2014; Bakke et al. 2007; 

EPA 2014]. 

1.2 Purpose

This skin notation profile presents (1) a brief 

summary of epidemiological and toxicological 

data associated with skin contact with TCE and 

(2) the rationale behind the hazard-specific 

skin notation (SK) assignment for TCE. 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 

TCE. A literature search was conducted through 

June 2017 to identify information on TCE, 

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 TCE. The criteria for 

the search strategy, evaluation, and selection of 

data are described in Appendix E in CIB 61: A 

Strategy for Assigning New NIOSH Skin Notations 

[NIOSH 2009].

1.3 Overview of SK Assignment

TCE 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 TCE: SK: SYS-DIR 

(IRR)-SEN. Table 1 provides an overview of the 

critical effects and data used to develop the SK 

assignment for TCE.

2 Systemic Toxicity from

Skin Exposure (SK: SYS)

Numerous studies of dermal absorption of TCE 

in humans have indicated that the substance can 

be absorbed following skin contact [Stewart and 

Dodd 1964; Sato and Nakajima 1978; Poet et al. 

2000; Kezic et al. 2001]. In a study conducted by 

Stewart and Dodd [1964], volunteers immersed 
2 Skin Notation Profiles | Trichloroethylene (TCE)

Trichloroethylene (TCE)

their thumbs in TCE for 30 minutes. Concentrations of TCE in exhaled air were determined 

during exposure and for 5 hours post-exposure; the mean peak breath concentration was 

reported to be 0.5 parts per million (ppm) 

[corresponding to 2.7 milligrams per kilogram 

(mg/kg)] and occurred within 15 minutes postexposure [Stewart and Dodd 1964]. The rate 

of dermal uptake of TCE was not determined, 

although the authors indicated that the amount 

dermally absorbed would be similar to the 

amount absorbed by the lung from inhalation at 

two to five times the peak breath concentration 

reported in this study [Stewart and Dodd 1964]. 

The authors noted that factors including integrity 

as well as thickness of the skin affected dermal 

penetration [Stewart and Dodd 1964]. Sato 

and Nakajima [1978] reported dermal absorption in four male volunteers who immersed one 

hand up to the wrist for 30 minutes in TCE in 

a covered jar to avoid inhalation exposure. For 

10 hours post-exposure, concentrations of TCE 

in breath and blood, and the concentration of 

metabolites in urine were measured at regular 

intervals [Sato and Nakajima 1978]. Sato and 

Nakajima [1978] indicated that the levels found 

in the breath and blood from exposure to TCE 

were similar to those noted after a 4 hour inhalation exposure to TCE (100 ppm; corresponding 

to 537.4 mg/kg); however, the rate of dermal 

uptake of TCE was not determined. Poet et al. 

[2000] estimated that in volunteers, the average 

dermal permeability coefficient (kp) values for 

TCE were 0.019 and 0.015 centimeters per 

hour (cm/hr) following water-patch and handimmersion studies, respectively and 0.015 cm/hr 

of TCE through the skin of volunteers when a 

fully occluded patch system was used. In another 

study, volunteers were exposed to neat TCE on 

the volar forearm over an area of 27 square centimeters (cm2

) for 1 minute [Kezic et al. 2001]. 

Kezic et al. [2001] noted fast dermal permeation 

through skin: a flux of 430 nanomoles/cm2 per 

minute (nmol/cm2/min). 

Several experimental studies of the dermal 

absorption of TCE in animals [Tsuruta 1978; 

Jakobson et al. 1982, Bogen et al. 1992, Nakai 

et al. 1999; Poet et al. 2000] were identified. 

Tsuruta [1978] exposed mice to undiluted 

liquid TCE for 5, 10, or 15 minutes to determine 

the rate of dermal absorption. The reported 

results indicated that the amount of TCE 

absorbed increased linearly, and the rate of 

dermal absorption through mouse abdominal 

skin was estimated to be 8 μg/cm2/min [Tsuruta 

1978]. Jakobsen et al. [1982] used guinea pigs to 

investigate the dermal absorption of undiluted 

TCE in occluded conditions. Blood samples 

were collected at intervals of 5 to 20 minutes 

during the 6-hour exposure period [Jacobsen et 

al. 1982]. The authors reported that peak blood 

levels of around 0.79 μg/mL occurred after 

30 minutes [Jacobsen et al. 1982]. Bogen et al. 

[1992], dermally exposed guinea pigs to aqueous 

diluted solutions (approximately 10 to 100 parts 

per billion [ppb]; corresponding to 0.05 to 0.54 

mg/kg) of TCE, and reported kp values of 0.21 to 

0.23 cm/hr. Poet et al. [2000] measured dermal 

absorption of TCE using physiologically based 

pharmacokinetic modeling in a water matrix 

in rats, and reported a kp of 0.31 cm/hr [Poet et 

al. 2000]. In vitro studies on dermal absorption 

Table 1. Summary of the SK assignment for TCE

Skin notation Critical effect Available data

SK: SYS Hepatotoxicity; nephrotoxicity; 

neurotoxicity

Sufficient human and animal data

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

SK: SEN Skin sensitization; liver damage 

associated with delayed-type 

hypersensitivity reaction

Limited human and sufficient 

animal data
Skin Notation Profiles | Trichloroethylene (TCE) 3

Trichloroethylene (TCE)

of TCE were identified. Using the aluminum 

dermal absorption block method reported by 

Moody et al. [1992], Nakai et al. [1999] reported 

a kp of 0.12 cm/hr for human abdomen and 

breast skin samples. 

The potential of TCE to pose a skin absorption 

hazard was also evaluated with use of a predictive algorithm for estimating and evaluating the 

health hazards of dermal exposure to substances 

[NIOSH 2009]. The evaluation method compares an estimated dose accumulated in the body 

from skin absorption with an estimated dose 

from respiratory absorption associated with a 

reference occupational exposure limit. On the 

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

the inhalation dose (SI ratio) of 0.02 was calculated for TCE. An SI ratio of ≥0.1 indicates that 

skin absorption may significantly contribute to 

the overall body burden of a substance [NIOSH 

2009]; therefore, TCE is not 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 the mathematical 

predictive model indicated that TCE is not 

readily absorbed by the skin, studies in humans 

and animals indicates that TCE is absorbed by 

the skin and may be similar to uptake via inhalation [Sato and Nakajima 1978]. 

Although no estimate of the dermal lethal dose 

(LDLo) for humans has been identified, dermal 

LD50 (lethal dose for 50% of exposed population) values of >10,000 milligrams per kilogram 

(mg/kg) have been reported for the rabbit [Dow 

Chemical Company 1956; Smyth et al.1969]. 

Because the reported acute dermal LD50 value 

is greater than the critical dermal LD50 value of 

2,000 mg/kg that identifies chemical substances 

with the potential for acute dermal toxicity 

[NIOSH 2009], TCE is not considered acutely 

toxic by the dermal route.

No health effects data were identified regarding 

dermal repeated-dose, subchronic, or chronic 

toxicity of TCE in humans or animals. However, Yu et al. [2012] evaluated renal impairment 

in TCE-sensitized guinea pigs. Animals were 

exposed to three pairs of 0.1 ml injections of 

5% TCE solution in olive oil followed by an 

application of 0.5 ml of 40% TCE solution 

applied to the skin with non-irritant tape for 

24 hours [Yu et al. 2012]. Yu et al. [2012] noted 

that metabolites of TCE caused the deposition 

of C3 and MAC renal epithelial cells, and may 

indicate that this mechanism accounts for TCE 

induced kidney and liver dysfunction. In a study 

that assesses liver injury associated with hypersensitive skin reactions in the GPMT, Tang et 

al. [2008] reported that serum alanine transaminase (ALT) and aspartate aminotransferase 

(AST), both indicative of liver injury, were significantly increased in guinea pigs exposed 

to 4,500 mg/kg TCE and 1,500 mg/kg TCE, 

respectively. Zhang et al. [2015] reported liver 

and kidney dysfunction after mice received an 

intradermal injection of 0.1 ml 50% TCE on the 

first day and 0.1 ml of 50% TCE on the back on 

days 4, 7 and 10 followed one week later with 

0.1 ml of 30% TCE applied on the back. In a 

later study, Al-Griw et al. [2016] divided Swiss 

albino mice into four groups: a vehicle control 

group exposed to corn oil, a sham control group, 

and 100μg and 400μg TCE in corn oil bi-weekly 

for three weeks. Hepatocellular apoptosis in 

the TCE groups, including histophathological 

changes such as congestion of hepatic blood vessels, perivascular cloudy swelling, and hydropic 

degeneration. Mice receiving 400μg TCE had 

significantly different liver weights (1.89g ± 

0.21g) than the control group (1.27g ± 0.13g) 

(p≤0.05) [Al-Griw et al. 2016]. Moreover, AlGriw et al. [2016] reported that TCE-treated 

mice had a statistically significant increase in the 

number of apoptotic hepatocytes (p < 0.05) and 

MDA levels (a marker for oxidative stress) in the 

liver (p ≤ 0.05).

Occupational exposure to an unquantified 

amount of TCE that involved both dermal and 

inhalation exposure for up to 20 years has been 

reported to cause dizziness, headache, insomnia, 

lethargy, forgetfulness, and loss of feeling in the 

hands and feet, or enlarged liver [Bauer and 

Rabens 1974; Kohlmuller and Kochen 1994]. 

In a case series, Liu [2009] reported the onset 

of dermatitis and systemic toxicity in workers 

(six males, one female) who used TCE to clean 

metal surfaces. Although the report did not precisely describe the exposure conditions, it can 
4 Skin Notation Profiles | Trichloroethylene (TCE)

Trichloroethylene (TCE)

be assumed that skin exposures were a primary 

pathway since there was onset of dermatitis in all 

cases, and the degree of liver and renal dysfunction was related to the degree of skin injury [Liu 

2009]. Liu [2009] reported that liver or kidney 

damage in five of the seven workers was attributed to TCE exposures, in addition to effects on 

the central nervous system (i.e., dizziness) and 

changes in blood chemistry (i.e., elevated white 

blood cell count). All five of the workers who 

had liver dysfunction developed liver steatosis 

(fatty liver) within 2 months, and one worker 

had kidney dysfunction with inflammation and 

swelling [Liu 2009]. Liu [2009] concluded that 

TCE is capable of causing both systemic and 

localized adverse health effects. Watanabe et al. 

[2010] reported a patient that had been exposed 

to TCE and was hospitalized with severe liver 

dysfunction. Xu et al. [2009] conducted a study 

with 21 patients with TCE-induced skin disorders that worked at 3 separate factories from 

2003-2005 with an average exposure duration 

of 38 days. These patients were exposed during 

cleaning and degreasing operations and did not 

wear gloves, and were also possibly exposed 

via inhalation [Xu et al. 2009]. The patients 

reported neurological symptoms (headache, 

dizziness), skin effects, and liver dysfunction 

[Xu, et al. 2009]. Gash et al. [2008] reported 3 

workers that were exposed to TCE both through 

chronic inhalation and dermal contact for 25 

years or greater had Parkinson’s disease (PD). 

Of these workers, 2 had no family history of 

PD. The workers shared the same work hours, 

including overtime, and cleaned parts directly 

in a vat of TCE without use of gloves or other 

protective equipment [Gash et al. 2008]. Other 

workers in the same factory, more distant from 

the source of TCE who were exposed via inhalation, reported neurological symptoms, such 

as significant motor slowing [Gash et al. 2008]. 

The neurotoxicity of TCE was supported by 

animal studies conducted by Gash et al. [2008], 

which demonstrated that oral exposure to TCE 

was accompanied by complex 1 mitochondrial 

impairment in the midbrain and loss of dopamine neurons, which is a hallmark of PD. 

No epidemiological investigations or experimental animal studies evaluating the potential 

for TCE to induce cancer following dermal 

exposure were identified; however, evidence that 

TCE is carcinogenic to humans has been found 

in multiple studies but the exposure route (i.e. 

inhalation, dermal, oral) is unknown [Hansen et 

al. 2013; Karami et al. 2013]. Hansen et al. [2013] 

found increased liver cancer 1.93 times more 

likely (confidence interval [CI] 1.19 to 2.95) and 

cervical cancer 2.31 times more likely (CI: 1.32 

to 3.75) in workers exposed to TCE; however, 

exposure routes are unknown and were likely a 

combination of multiple routes (inhalation and 

dermal). Karami et al. [2013] conducted a metaanalysis of published cohort and case control 

studies that assessed occupational exposure to 

TCE and five different cancers: non-Hodgkin’s 

lymphoma, Hodgkin’s lymphoma, multiple 

myeloma, leukemia, and chronic/small lymphocytic leukemia. Routes of exposure were 

unknown for these studies and cases were likely 

exposed via multiple routes. These authors 

reported a significantly raised summary estimate 

of non-Hodgkin’s lymphoma (relative risk=1.93; 

CI: 1.14 to 1.54) for all cohort and case-control 

studies [Karami et al. 2013]. Table 2 provides a 

summary of carcinogenic designations from 

multiple governmental and nongovernmental 

organizations for TCE.

Although the toxicokinetic studies indicate 

that TCE has limited dermal absorption 

potential, which is supported by the limited 

available animal data reporting low acute 

toxicity in rabbits [Dow Chemical Company 1956; Smyth et al.1969], case reports, 

case series, an occupational exposure study 

[Bauer and Rabens 1974; Kohlmuller and 

Kochen 1994; Liu 2009; Watanabe et al. 

2010], and animal studies [Tang et al. 2008; 

Yu et al. 2012; Zhang et al. 2015; Al-Griw et 

al. 2016] provide evidence of TCE-induced 

liver and kidney dysfunction following subchronic dermal exposures to the substance, 

and occupational studies [Gash et al. 2008; Liu 

2009; Xu et al. 2009] reported neurological 

effects. These human data provide evidence of 

its ability to cause systemic toxicity following 

*

References in bold text indicate studies that serve 

as the basis of the SK assignments.
Skin Notation Profiles | Trichloroethylene (TCE) 5

Trichloroethylene (TCE)

subchronic dermal exposure. Therefore, on 

the basis of these data, TCE is assigned the 

SK: SYS notation.

3 Direct Effects on Skin (SK: DIR)

No evidence of skin corrosivity of TCE, no in 

vitro tests for corrosivity in human or animal 

skin models, and no in vitro tests of skin integrity using cadaver skin were identified. Evidence 

of corrosivity and irritation in humans and animals were identified. Evidence of corrosivity 

in animals is limited to findings from a single 

acute toxicity study. In that study, high doses of 

TCE, ranging from 2,520 to 20,000 mg/kg, were 

administered to the skin of 16 rabbits under 

an impervious covering, resulting in burning, 

scabbing, and scarring [Dow Chemical Company 1956]. 

In occupational exposures that involved inhalation of the vapor, percutaneous penetration, 

or both, TCE caused skin irritation and rashes, 

central nervous system effects, and/or eye effects 

after repeated exposure [El Ghawabi et al. 1973; 

Bauer and Rabens 1974; Xu et al. 2009]. Xu et 

al. [2009] reported skin irritation in 21 patients 

diagnosed with a TCE-induced skin disorder, 

and symptoms included skin erythema, rashes, 

and blistering. Study volunteers have reported 

burning sensations, erythema, rashes, and dermatitis following exposure to TCE [Stewart 

and Dodd 1964; Sato and Nakajimi 1978]. Four 

volunteers who each immersed a single hand 

up to the wrist for 30 minutes in liquid TCE 

reported a burning sensation that increased 

with time and distinct pain toward the end of 

the exposure, as well as moderate erythema for 

over an hour post-exposure [Sato and Nakajima 1978]. Similar effects were seen in three 

volunteers who immersed their thumbs in TCE 

for 30 minutes [Stewart and Dodd 1964]. Kezic 

et al. [2001] noted intensive skin irritation, 

with burning sensation varying from “hardly 

noticed” to “unbearable pain” in six volunteers. 

Wahlberg [1984b] reported marked and persistent erythema in a healthy individual following 

excess application (1.5 mL) of neat TCE to the 

unoccluded volar forearm (3.1 cm2) for 5 minutes, and application for 1 or 3 minutes caused 

transient whitening and then erythema. Wahlberg [1984b] reported stinging and/or burning 

sensations after exposure to TCE in human volunteers. Liu [2009] investigated seven workers 

who all experienced erythema and were 

exposed to TCE when using it to clean metal 

surfaces. In six of the seven workers, dermatitis occurred within 1 month of exposure to 

TCE [Liu 2009]. Liu [2009] also reported that 

the workers experienced a variety of effects, 

Table 2. Summary of the carcinogenic designations* for TCE by 

numerous governmental and nongovernmental organizations

Organization Carcinogenic designation

NIOSH [2005] Potential occupational carcinogen

NTP [2014] Reasonably anticipated to be a human carcinogen

USEPA [2014] Carcinogenic to humans

European Parliament [2008] GHS Category 1B: May cause cancer

IARC [2014] Group 1: Carcinogenic to humans

ACGIH [2007] Group A2: Suspected human carcinogen

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; NTP = National Toxicology Program; USEPA = United States Environmental Protection Agency.

*

The listed cancer designations were based on data from non-dermal (such as oral or inhalation) exposure since studies using the 

dermal route of exposure were unavailable.
6 Skin Notation Profiles | Trichloroethylene (TCE)

Trichloroethylene (TCE)

including erythema with pruritus, rashes on 

the extremities, and systemic toxic effects 

attributed to exposures to TCE.

Several studies in rabbits and guinea pigs 

indicate that TCE caused severe irritation to 

the skin following occlusive and unocclusive 

dermal application [Smyth et al. 1969; Wahlberg 1984b]. Anderson et al. [1986] conducted 

a guinea pig irritant-contact reaction test in 

which 10 microliters (μL) TCE was applied 

under occlusion to 1 cm2 shaved skin on the 

flank three times daily for 3 days. Macroscopic 

assessment of erythema and edema as well as 

microscopic assessments of epidermal thickness and dermal inflammatory cell infiltration 

(total and differential cell responses) indicated that TCE was irritating to the guinea pig 

skin [Anderson et al. 1986]. Shen et al. [2008] 

investigated the effects of TCE on skin irritation and oxidative stress, using hairless mice 

under acute and cumulative exposure conditions. Mice were administered concentrations 

of TCE (20%, 40%, 80%, or 100% v/v) dissolved in olive oil [Shen et al. 2008]. In an 

acute irritation test, TCE administration for 1 

day resulted in mild to moderate irritation that 

was concentration dependent, and erythema 

and intracellular edema developed [Shen et al. 

2008]. Epidermal necrosis occurred in a few 

mice treated with 100% TCE. In a cumulative 

irritation test, mice underwent daily topical 

applications of TCE for 14 days, resulting in 

epidermal hyperplasia, hyperkeratosis, edema, 

and inflammation [Shen et al. 2008]. Kronevi 

et al. [1981] noted degenerative changes in the 

epidermis, including karyopyknosis, oedema, 

junctional separation and cellular infiltration 

in the dermis. The structure-activity relationship model (Deductive Estimation of Risk from 

Existing Knowledge, or DEREK, for Windows) 

predicted TCE to be negative for skin irritation, 

indicating that the chemical does not have a 

structural alert for skin irritation.

An epidemiological study concerning the potential of TCE to cause skin cancer was identified. 

Axelson et al. [1994] assessed the exposure of 

workers from a plant in central Sweden that produced TCE. Although the routes of exposure 

were unknown, the authors noted a doubled 

incidence of nonmelanocytic skin cancer; however there was no correlation with exposure 

categories [Axelson et al. 1994]. One dermal carcinogenicity study in animals was identified. Van 

Duuren et al. [1979] found no tumors in mice at 

the site of topical application of TCE (1 mg in 0.1 

mL acetone per application); in addition, there 

was no statistically significant difference in the 

incidence of distant tumors in this group versus 

no-treatment and vehicle control groups. The 

investigators also found no skin tumor–initiating 

activity in a mouse skin initiation promotion 

experiment [Van Duuren et al. 1970].

Results indicate that undiluted TCE is corrosive to the skin [Dow Chemical Company 

1956; Shen et al. 2008]. Evidence of skin whitening, erythema, and dermatitis in humans 

[Stewart and Dodd 1964; Bauer and Rabens 

1974; Sato and Nakajima 1978; Wahlberg 

1984 a,b; Kezic et al. 2001; Liu 2009; Xu et al. 

2009] and of erythema, edema, and changes in 

the epidermis in animals [Kronevi et al. 1981; 

Anderson et al.1986; Shen et al. 2008] indicates that TCE is a skin irritant when TCE is 

diluted. Therefore, on the basis of the data for 

this assessment, TCE is assigned the SK: DIR 

(COR) notation. 

4 Immune-mediated

Responses (SK: SEN)

Few reports were identified that suggest that 

TCE may be a skin sensitizer in humans. An 

occupational study on 19 patients hospitalized 

for generalized skin disorders and their healthy 

colleagues by Kamijima et al. [2008], indicated 

that TCE caused the hypersensitivity disorders. 

Watanabe et al. [2010] reported a case with 

generalized rash and liver dysfunction that had 

been exposed to TCE at work. This patient was 

patch tested for TCE and its metabolites trichlorethanol and chloral hydrate; the patient 

had positive reactions to the metabolites but 

not to TCE [Kamijima et al. 2008]. Similarly, 

Huang et al. [2015] reported fever, generalized 

rash, liver dysfunction, and superficial lymphadenopathy in workers exposed to TDI that 
Skin Notation Profiles | Trichloroethylene (TCE) 7

Trichloroethylene (TCE)

exhibited trichloroethylene hypersensitivity disorder. All of these patients developed positive 

skin reactions to TCE or the metabolites of TCE, 

including chloral hydrate, trichloroethanol, 

trichloroacetic acid. Chloral hydrate had the 

greatest positive response (100%) and 10.5% of 

patients had positive reactions to TCE [Huang et 

al. 2015]. Dai et al. [2009] compared 111 workers 

with hypersensitivity dermatitis and 154 healthy 

workers, all of whom were exposed to TCE, to 

determine if there was a gene polymorphism 

that influenced individual susceptibility to TCEinduced hypersensitivity dermatitis. All of the 

cases diagnosed with occupational hypersensitivity dermatitis by an occupational disease 

physician developed skin damage within 3 

months of exposure to TCE [Dai et al. 2009]. 

The authors concluded that a slow metabolic 

phenotype of N-acetyltransferases (NATs) and 

combined slow acetylator phenotypes of NAT1 

and NAT2, two isoenzymes of NAT that are 

encoded by separate genes, may be risk factors for TCE-induced hypersensitivity [Dai et 

al. 2009], In a case report, a worker developed 

severe dermal effects, including skin lesions and 

erythroderma with edematous face and eyelids, 

a combined inhalation and dermal exposure 

to TCE [Nakayama et al. 1988]. This subject 

had positive reactions to 10% and 25% TCE in 

olive oil (and to 0.005%, 0.05%, and 5% trichloroethanol, a metabolite of TCE) [Nakayama et 

al. 1988]. Nakayama et al. [1988] regarded this 

result to be due to delayed hypersensitivity to 

TCE. The findings in that case indicate that the 

subject was allergic to both TCE and its metabolite, trichloroethanol. In another reported case, a 

female worker developed erythematous lesions 

and had a positive reaction when patch tested 

with TCE (5% in olive oil) [Conde-Salazar et al. 

1983]. The worker developed the same lesions 

when challenged on many occasions, after exposure to TCE. Phoon et al. [1984] reported five 

cases in which individuals were occupationally 

exposed to TCE for periods ranging from 2 to 

5 weeks and subsequently presented with Stevens-Johnson syndrome (erythema multiforme 

major). Three of the cases had air exposure only, 

and the remaining two had air and direct skin 

contact [Phoon et al. 1984]. One individual 

exposed to fairly high levels of TCE vapor in the 

air and by direct skin contact was patch tested 

with TCE after the episode but tested negative. 

In spite of the negative reaction, Phoon et al. 

[1984] did not rule out the possibility of a hypersensitivity response.

Animal studies regarding the potential for TCE 

to induce immune-mediated responses following skin contact were identified. Yao et al. 

[2016] investigated the role of transforming 

growth factor-β activated kinase-1 (TAK1) on 

contact hypersensitivity in control mice and 

dendritic cell (DC)-specific TAK1 deletion mice 

who were exposed to 80% (v/v) TCE using the 

local lymph node assay (LLNA). Compared 

to the control mice, the TCE group had an 

inflammatory response in the ears, increased 

lymphocyte proliferation, and increased T-cells 

and interferon (IFN)-γ CD8(+) T cells in the 

draining lymph nodes [Yao et al. 2016]. Yu et al. 

[2012 ] conducted modified guinea pig maximization tests (GPMT), where animals were 

exposed to three pairs of 0.1 ml injections of 5% 

TCE solution in olive oil followed by application 

of 0.5ml of 40% TCE solution was applied to the 

skin with non-irritant tape for 24 hours [Yu et al. 

2012]. The investigators reported a sensitization 

rate of 63.16% compared to 100% for the positive control [Yu et al. 2012]. 

In an earlier study, Tang et al. [2002], using a 

modified GPMT, reported that TCE caused 

skin sensitization (i.e., edema and erythema) 

in guinea pigs. The authors reported a sensitization rate of 71.4% (10/14) for TCE and of 

58.3% trichloroacetic acid. Histopathological 

analysis revealed allergenic transformation in 

guinea pig skin exposed to TCE, and the authors 

concluded that TCE appeared to be a strong 

allergen following skin contact [Tang et al. 

2002]. In a subsequent investigation, Tang et al. 

[2008] attempted to characterize the liver injury 

associated with hypersensitive skin injuries in 

guinea pigs by using dermal patches containing 

TCE and performing a GPMT. The results of 

the study included sensitization rates of TCEinduced dermal allergy of 66%, accompanied by 

skin edema, and erythema [Tang et al. 2008]. In 

addition, elevated liver enzymes and the presence of lesions were reported [Tang et al. 2008]. 
8 Skin Notation Profiles | Trichloroethylene (TCE)

Trichloroethylene (TCE)

The GPMT revealed histopathologic evidence 

of fatty degeneration in the liver, hepatic sinusoid dilation, and inflammatory cell infiltration 

with an acute intradermal dose of 4,500 mg/kg 

[Tang et al. 2008]. Tang et al. [2008] concluded 

that TCE may be capable of inducing dermatitis 

and liver damage, on the basis of delayed-type 

hypersensitivity in guinea pigs. Wang et al. 

[2016] evaluated immune-mediated renal injury 

of TCE on BALB/c mice that received an intradermal injection of 100 μL of 50% TCE on day 

one, 100 μL of 50% TCE painted on clipped 

dorsal skin on days four, seven, and ten, and was 

challenged with 100 μL on clipped dorsal skin 

on days 17 and 19. The sensitization rate in mice 

exposed to TCE was 40% (48/120). TDI exposed 

mice had increased serum urea nitrogen (BUN) 

and creatinine (Cr) (an indication of how well 

the kidneys are working) and inflammatory cell 

infiltration and tubular epithelial cell vacuolar 

degeneration at 48 and 72 hours after the final 

challenge with TCE [Wang et al. 2016].

Predictions from structure-activity relationship 

models provide some information regarding 

the potential for sensitization. On the basis of its 

chemical structure, TCE is predicted by DEREK

to be negative for sensitization, indicating that 

the chemical does not have a structural alert for 

skin sensitization.

Although the mathematical model predicted 

TCE to be negative for sensitization, isolated 

reports of cases involving humans [CondeSalazar et al. 1983; Nakayama et al. 1988]

and an epidemiological study [Dai et al. 2009]

suggest that TCE may have sensitizing potential. Evidence of immune-mediated responses 

in workers is often confounded by exposures 

via both dermal and inhalation routes. Positive results from predictive tests (GPMTs and 

LLNAs) [Tang et al. 2002, 2008; Yu et al. 2012; 

Yao et al. 2016] demonstrate that TCE is capable 

of inducing dermatitis and liver damage via 

delayed-type hypersensitivity in guinea pigs. 

Therefore, on the basis of the data for this assessment, TCE is assigned the SK: SEN notation.

5 Summary

Although the toxicokinetic studies indicate that 

TCE has limited dermal absorption potential, 

which is supported by the limited available 

animal data reporting low acute toxicity 

in rabbits [Dow Chemical Company 1956; 

Smyth et al.1969], case reports, case series, 

an occupational exposure study [Bauer and 

Rabens 1974; Kohlmuller and Kochen 

1994; Liu 2009; Watanabe et al. 2010] and 

animal studies [Tang et al. 2008; Yu et al. 

2012; Zhang et al. 2015; Al-Griw et al. 2016]

provide evidence of TCE-induced liver and 

kidney dysfunction following subchronic 

exposures to the substance, and occupational 

studies [Gash et al. 2008; Liu 2009; Xu et al. 

2009] reported neurological effects. These 

limited human and animal data provide evidence of its ability to cause systemic toxicity 

following subchronic exposure. Results indicate that undiluted TCE is corrosive to the 

skin [Dow Chemical Company 1956; Shen 

et al. 2008]. Evidence of skin whitening, erythema, and dermatitis in humans [Stewart 

and Dodd 1964; Bauer and Rabens 1974; 

Sato and Nakajima 1978; Wahlberg 1984 a,b; 

Kezic et al. 2001; Liu 2009; Xu et al. 2009]

and of erythema, edema, and changes in the 

epidermis in animals [Kronevi et al. 1981; 

Anderson et al.1986; Shen et al. 2008] indicates that TCE is a skin irritant when diluted. 

Although the mathematical model predicted 

TCE to be negative for sensitization, isolated 

reports of cases involving humans [CondeSalazar et al. 1983; Nakayama et al. 1988]

and an epidemiological study [Dai et al. 

2009] suggest that TCE may have sensitizing 

potential. Positive results from predictive tests 

(GPMTs and LLNAs) [Tang et al. 2002, 2008; 

Yu et al. 2012; Yao et al. 2016] demonstrate 

that TCE is capable of inducing dermatitis and 

liver damage via delayed-type hypersensitivity 

in guinea pigs. Therefore, on the basis of these 

assessments, TCE is assigned a composite skin 

notation of SK: SYS-DIR (IRR)-SEN.

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

other organizations. The equivalent dermal 
Skin Notation Profiles | Trichloroethylene (TCE) 9

Trichloroethylene (TCE)

designations for TCE, according to the Globally 

Harmonized System (GHS) of Classification and 

Labelling of Chemicals, are Skin Irritation Category 2 (Hazard Statement: Causes skin irritation) 

and Mutagenicity Category 2 (Hazard Statement: 

Suspected of causing genetic defects) [European 

Parliament 2008].

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Organization Skin hazard designation

NIOSH [2005] No designation

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ACGIH [2007] No designation

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Health; OSHA = Occupational Safety and Health Administration.

*

Date accessed.
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Skin Notation Profiles | Trichloroethylene (TCE) 13

Trichloroethylene (TCE)

Appendix: Calculation of the SI Ratio for TCE

This appendix presents an overview of the SI 

ratio and a summary of the calculation of the 

SI ratio for TCE. 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, 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 kp 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, kp is determined for a 

substance with use of Equation 1. A self-consistent set of units must be used, such as outlined 

in Table A1. Other model-based estimates of kp

may also be used [NIOSH 2009].

Equation 1: Calculation of Skin Permeation 

Coefficient (kp)

where kpsc 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. 

The skin dose is calculated as a mathematical 
14 Skin Notation Profiles | Trichloroethylene (TCE)

Trichloroethylene (TCE)

product of the kp, the water solubility (SW) of 

the substance, the exposed skin surface area, 

and the duration of exposure. Its units are milligrams (mg). Assume that the skin exposure 

continues for 8 hours to unprotected skin on 

the palms of both hands (a surface area of 360 

square centimeters [cm2]). 

Equation 2: Determination of Skin Dose 

Skin dose = kp × Sw × Exposed skin surface

 area × Exposure time

= kp(cm/hour) × Sw (mg/cm3) 

 × 360 cm2 × 8 hours

The inhalation dose (in mg) is derived on 

the basis of the occupational exposure limit 

(OEL) of the substance—if the OEL is developed to prevent the occurrence of systemic 

effects rather than sensory/irritant effects or 

direct effects on the respiratory tract. Assume 

a continuous exposure of 8 hours, an inhalation volume of 10 cubic meters (m3

) inhaled 

air in 8 hours, and a factor of 75% for retention of the airborne substance in the lungs 

during respiration (retention factor, or RF).

Equation 3: Determination of Inhalation Dose

Inhalation dose = OEL × Inhalation volume

× RF

=OEL (mg/m3) × 10 m3

× 0.75

The final step is to compare the calculated skin 

and inhalation doses and to present the result 

as a ratio of skin dose to inhalation dose (the 

SI ratio). This ratio quantitatively indicates 

(1) the significance of dermal absorption 

as a route of occupational exposure to the 

substance and (2) the contribution of dermal 

uptake to systemic toxicity. If a substance has 

an SI ratio greater than or equal to 0.1, it is 

considered a skin absorption hazard.

Calculation

Table A1 summarizes the data applied in the 

previously described equations to determinethe SI ratio for TCE. The calculated SI ratio 

was 0.02. On the basis of these results, TCE is 

not predicted to represent a skin absorption 

hazard.

Appendix References

Hayes WA [2008]. Principles and Methods of Toxicology. Fifth Edition. Informa Healthcare USA, 

Inc. New York, NY. 

NIOSH [2005]. NIOSH pocket guide to chemical 

hazards. Cincinnati, OH: U.S. Department of 

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

for Occupational Safety and Health, DHHS 

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

www.cdc.gov/niosh/npg/. Accessed: 06-07-17.

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: 06-07-17.

SRC [ND]. Interactive PhysProp database demo, 

http://esc.syrres.com/fatepointer/webprop.

asp?CAS=79016. Accessed: 06-07-17.
Skin Notation Profiles | Trichloroethylene (TCE) 15

Trichloroethylene (TCE)

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

Variables used in calculation Units Value

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid 

path(kpsc)

cm/hr 0.01266

Permeation coefficient of the protein fraction of 

the stratum corneum (kpol)

cm/hr 1.32519 x 10-5

Permeation coefficient of the watery epidermal 

layer (kaq)

cm/hr 0.21810

Molecular weight (MW)* amu 131

Base-10 logarithm of its octanol–water partition 

coefficient (Log Kow)*

None 2.42

Calculated skin permeation coefficient (kp) cm/hr 0.01197

Skin dose

Water solubility (Sw)* mg/cm3 1.28

Calculated skin permeation coefficient (kp) cm/hr 0.01197

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

Exposure time hr 8

Calculated skin dose mg 44.14

Inhalation Dose

Occupational exposure limit (OEL)† mg/m3 268

Inhalation volume m3 10

Retention factor (RF) None 0.75

Inhalation dose mg 2010

Skin dose–to–inhalation dose (SI) ratio None 0.02

*

Variables identified from SRC [ND].

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

§

Hayes WA [2008]. Principles and Methods of Toxicology. Fifth Edition. Informa Healthcare USA, Inc. New York, NY. 
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