NIOSH Skin Notation Profile

IDSK

[SK]

SYS

DIR

DIR (IRR)

SYS (FATAL)

DIR (COR)

SEN

Cyclohexanol

Centers for Disease Control

and Prevention

National Institute for Occupational 

Safety and Health
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NIOSH Skin Notation Profile

Cyclohexanol

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 Profile | Cyclohexanol

This document is in the public domain and may be freely 

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Suggested Citation

NIOSH [2020]. NIOSH skin notation profile: cyclohexanol. 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. 

2021-101.

DHHS (NIOSH) Publication No. 2021-101

DOI: https://doi.org/10.26616/NIOSHPUB2021101

October 2020
Skin Notation Profile | Cyclohexanol 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 cyclohexanol. 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 Profile | Cyclohexanol v

Contents

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

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

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

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

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

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

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

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

2 Systemic Toxicity from Skin Exposure (SK: SYS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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 Cyclohexanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

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

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

Appendix References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
vi Skin Notation Profile | Cyclohexanol

Abbreviations

ACGIH® American Conference of Governmental Industrial Hygienists 

AMU atomic mass unit

ATSDR Agency for Toxic Substances and Disease Registry

CIB Current Intelligence Bulletin

ChE cholinesterase

cm2 square centimeter(s)

cm/hr centimeter(s) per hour

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

to the skin following exposure 

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

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

during dermal absorption

GHS Globally Harmonized System of 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

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

LOAEL lowest-observed-adverse-effect level 

log KOW base-10 logarithm of a substance’s octanol–water partition

M molar

m3 cubic meter(s)

mg milligram(s)

mg/cm3 milligram(s) per cubic centimeter

mg/kg milligram(s) per kilogram body weight

mg/min milligram(s) per minute

mL milliliter(s)

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

NOAEL no-observed-adverse-effect level
Skin Notation Profile | Cyclohexanol vii

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

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 

w/v weight/volume
viii Skin Notation Profile | Cyclohexanol

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 Profile | Cyclohexanol ix

Acknowledgments

This document was developed by the Division of Science Integration (Paul Schulte, Ph.D., 

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

Special appreciation is expressed to the following individuals for serving as independent, 

external reviewers:

• Shane Que Hee, Ph.D., Professor, Environmental Health Sciences Director, UCLA Industrial Hygiene Program Director, UCLA Fielding School of Public Health, Los Angeles, CA

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

Medicine, Rockville, MD

Special appreciation is expressed to the following individuals for serving as internal reviewers 

by use of an Intergovernmental Personnel Agreement:

• Ronald E. Baynes, D.V.M., Ph.D., College of Veterinary Medicine, North Carolina State 

University, Raleigh, NC

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

Fort Worth, TX

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, 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
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Skin Notation Profile | Cyclohexanol 1

Cyclohexanol

1 Introduction

1.1 General Substance Information

Chemical: Cyclohexanol

CAS No: 108-93-0

Molecular weight (MW): 100.2

Molecular formula: C6H11OH

Structural formula:

HO

Image: National Center for Biotechnology Information [2020]

Synonyms: Anol, Cyclohexyl alcohol, 

Hexahydrophenol, Hexalin, Hydralin, 

Hydroxycyclohexane

Uses: With a melting point of 25.93 o

C, cyclohexanol can be a solid or a viscous liquid at 

25 o

C. Some producers use a mixture containing 2.25% methanol to keep cyclohexanol 

in a liquid state [HSDB 2011]. Cyclohexanol 

is used primarily as a chemical intermediate 

in the manufacturing of nylon, as a stabilizer, 

and a homogenizer for soap and detergent; an 

estimated >500 to 1 billion pounds (390 million kilograms) of the substance was produced 

in 2002 [HSDB 2019].

1.2 Purpose

This skin notation profile presents (1) a brief 

summary of epidemiological and toxicological data associated with skin contact with 

cyclohexanol and (2) the rationale behind the 

hazard-specific skin notation (SK) assignment 

for cyclohexanol. 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 cyclohexanol. A 

search of all available relevant literature was 

conducted through January 2020 to identify 

information on cyclohexanol 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 in humans, animals, or appropriate modeling systems that 

are relevant to assessing the effects of dermal 

exposure to cyclohexanol. 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

Cyclohexanol 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 cyclohexanol: SK: SYS-DIR (IRR). Table 

1 provides an overview of the critical effects 

and data used to develop the SK assignment 

for cyclohexanol.
2 Skin Notation Profile | Cyclohexanol

Cyclohexanol

Table 1. Summary of the SK assignment for cyclohexanol

Skin notation Critical effect Available data

SK: SYS Central nervous and/or peripheral 

system effects (tremors, narcosis, 

hypothermia); acute toxicity

Sufficient animal data

SK: DIR(IRR) Skin irritancy Sufficient animal data

2 Systemic Toxicity from Skin 

Exposure (SK: SYS)

No in vivo or in vitro toxicokinetic studies were 

identified in humans or animals that evaluated 

dermal exposure to cyclohexanol. Walker et al. 

[2003] estimated a skin absorption rate of 6.10 

× 10-3 centimeters per hour (cm/h) for cyclohexanol based on a quantitative structure-activity 

relationship prediction. The potential of cyclohexanol to pose a skin absorption hazard was 

also evaluated using the NIOSH [2009] predictive algorithm for estimating and evaluating the 

health hazards of dermal exposure to chemical 

substances. Based on this algorithm, the ratio 

of skin dose to inhalation dose (the SI ratio) of 

0.34 was calculated for cyclohexanol. An SI ratio 

of ≥0.1 indicates that skin absorption may significantly contribute to the overall body burden 

of a substance [NIOSH 2009]; therefore, cyclohexanol is considered to be a skin absorption 

hazard following dermal exposure. 

No estimated dermal lethal dose (LDLo) in 

humans was identified. The dermal LD50 (lethal 

dose in 50% of exposed animals) values in 

rabbits were reported to be greater than 501 

milligrams per kilogram body weight (mg/

kg) but less than 794 mg/kg [Monsanto 1978]. 

Because the reported acute dermal LD50 value 

for rabbits is lower than the critical dermal LD50

value of 2,000 mg/kg that identifies chemical 

substances with the potential for acute dermal 

toxicity [NIOSH 2009], cyclohexanol is considered acutely toxic following dermal exposure.

No epidemiological studies, human case reports, 

or subchronic/chronic toxicity studies in animals 

were identified that evaluated the potential of 

cyclohexanol to cause systemic effects following 

dermal exposure. Treon et al. [1943] applied 10 

milliliters (mL) (in two 5 mL portions at 0.5- 

hour intervals) of cyclohexanol for one hour a 

day for 10 days to the clipped abdominal skin 

of rabbits. Treon et al. [1943] reported that the 

second and successive dose of cyclohexanol 

resulted in narcosis, central nervous system 

effects such as tremor, athetoid movement 

(inability to maintain body parts in a stable 

position), and hypothermia, which became 

more marked with successive exposures. Hypothermia and narcosis were observed in rabbits 

that received 35 to 130 mL (approximately 29 to 

130 grams/animal) of cyclohexanol applied to 

the clipped skin of the abdomen in 5-mL portions at 20-minute intervals for a total of 160 

minutes to 9 hours, in addition to involuntary 

jerking and twitching of the forelegs and chest 

muscles in the rabbit given the highest dose. 

The animals receiving the highest dose of cyclohexanol died [Treon et al. 1943]. These results 

indicate that high doses of liquid cyclohexanol 

applied to the skin can result in tremors, narcosis, hypothermia, and death.

No standard toxicity or specialty studies were 

identified that evaluated biological system/

function specific effects (including reproductive 

and developmental effects and immunotoxicity) 

following dermal exposure to cyclohexanol.

No epidemiological studies or animal studies 

were identified that evaluated the potential 

of cyclohexanol to be a carcinogen following 

dermal exposure. Table 2 summarizes the 

carcinogenic designations of multiple governmental and nongovernmental organizations 

for cyclohexanol.
Skin Notation Profile | Cyclohexanol 3

Cyclohexanol

Table 2. Summary of the carcinogenic designations for cyclohexanol 

by governmental and nongovernmental organizations

Organization Carcinogenic designation

NIOSH [2005] No designation

NTP [2014] No designation

US EPA [2020]* No designation

European Parliament [2008] No GHS designation

IARC [2012] 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; NTP = National Toxicology Program; US EPA = United States Environmental Protection Agency.

*Date accessed 

Although no toxicokinetic data were identified 

that estimated the percent dermal absorption of 

cyclohexanol in humans or animals, the mathematical model predicts that cyclohexanol may 

be absorbed through the skin following dermal 

exposure. Acute and repeat-dose [Monsanto 

1978; Treon et al. 1943] toxicity studies with 

rabbits provide limited data indicating that 

cyclohexanol can be absorbed through the 

skin and may be acutely toxic and produce 

central nervous and/or peripheral nervous systems effects (tremors, narcosis, hypothermia) 

including death at high doses. Therefore, this 

assessment assigns a skin notation of SK: SYS 

for cyclohexanol.

3 Direct Effects on Skin (SK: DIR)

No human or animal in vivo studies on corrosivity or in vivo tests for corrosivity using 

human or animal skin models or in vitro 

tests of skin integrity using cadaver skin were 

identified. Limited skin irritation tests were 

identified in animals for cyclohexanol. Mild 

irritation was observed at 24 and 72 hours in 

a skin irritation test after 0.5 mL of undiluted 

cyclohexanol was applied to the skin of rabbits for 24 hours [Monsanto 1978]. Skin began 

to flake off after seven to ten days, but there 

was no corrosivity reported [Monsanto 1978]. 

Smyth et al. [1962] also reported mild irritation following application of cyclohexanol to 

clipped rabbit skin, with an irritation score 

of 2 out of 6 (where 1 is no irritation and 6 is 

necrosis). Repeated cutaneous application of 

cyclohexanol at high doses (10 mL of cyclohexanol for 10 days for a total of 94.4 g/kg) to 

the skin of rabbits resulted in slight local erythema, localized ulcers, and thickening of the 

skin [Treon et al. 1943]. Animals that received 

smaller doses of cyclohexanol (35-130 mL) 

experienced local erythema of the skin [Treon 

et al. 1943].

Using human keratinocytes, Muller-Decker 

et al. [1994] measured in vitro proinflammatory eicosanoid and interleukin 1-alpha 

(IL-1α) release as indicators of skin irritancy. Cyclohexanol was observed to induce a 

delayed (greater than 4 hour) stimulation of 

arachidonic acid release, leading the authors 

to estimate a half-maximum stimulation concentration (SC50) of 2.8 to 3.2 x 10-2 molar (M). 

A 10-fold stimulatory (ED10) concentration of 

IL-1α was observed at a dose of 5.3 x 10-2 M 

of cyclohexanol [Muller-Decker et al. 1994]. 

These mechanistic studies support the in vivo 

studies that suggest that cyclohexanol has the 

potential to cause skin irritation. 

The structure activity relationship model, 

DEREK®, predicted cyclohexanol to be negative 

*

References in bold text indicate studies that serve 

as the basis of the SK assignments.
4 Skin Notation Profile | Cyclohexanol

Cyclohexanol

for skin irritation, indicating that the chemical 

does not have structural alerts for skin irritation.

Although DEREK® predicted cyclohexanol to 

be negative for skin irritation, skin irritation 

tests in rabbits [Treon et al. 1943; Smyth et al. 

1962; Monsanto 1978] and the in vitro data 

using human keratinocytes [Muller-Decker 

et al. 1994] indicate that cyclohexanol has the 

potential to cause mild skin irritation, including 

localized ulcers and thickening of the skin at 

high doses. Therefore, this assessment assigns 

an SK: DIR(IRR) notation for cyclohexanol.

4 Immune-mediated 

Responses (SK: SEN)

No occupational exposure studies or diagnostic 

patch tests in humans or predictive tests (guinea 

pig maximization tests, Buehler test, murine local 

lymph node assays, etc.) that evaluated the potential of the cyclohexanol to cause skin sensitization 

were identified. The structure activity relationship model, DEREK®, predicted cyclohexanol to 

be negative for skin sensitization, indicating that 

the chemical does not have structural alerts for 

skin sensitization. 

Lack of case reports or diagnostic patch tests in 

humans or predictive tests in animals precludes 

adequate evaluation of the skin sensitization 

potential of cyclohexanol. Therefore, this assessment does not assign an SK: SEN notation for 

cyclohexanol.

5 Summary

Although no toxicokinetic data were identified 

that estimated the percent dermal absorption 

of cyclohexanol in humans or animals, the 

mathematical model predicts that cyclohexanol 

may be absorbed through the skin following 

dermal exposure. Acute and repeat-dose [Monsanto 1978; Treon et al. 1943] toxicity studies 

with rabbits provide limited data indicating 

that cyclohexanol can be absorbed through 

the skin and may be acutely toxic and produce 

central nervous and/or peripheral nervous systems effects (tremors, narcosis, hypothermia), 

including death at high doses. Results from a 

skin irritation test in rabbits [Smyth et al. 1962; 

Monsanto 1978] and in vitro data using human 

keratinocytes [Muller-Decker et al. 1994] provide evidence that cyclohexanol has the potential 

to cause skin irritation, including the potential 

to cause localized ulcers and thickening of the 

skin at high doses. No case reports or diagnostic patch tests in humans or predictive tests 

in animals were identified upon which the skin 

sensitization potential of cyclohexanol can be 

evaluated. Therefore, this assessment assigns a 

composite skin notation of SK: SYS-DIR (IRR) 

for cyclohexanol. 

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

other organizations. The equivalent dermal 

designation for cyclohexanol according to the 

Globally Harmonized System (GHS) of classification and labeling of chemicals is Skin 

Table 3. Summary of the previously issued skin hazard designations for 

cyclohexanol from NIOSH and other organizations

Organization Skin hazard designation

NIOSH [2005] [skin]: Based on the potential for dermal absorption

OSHA [2018]* No designation

ACGIH® [2001] [skin] Based on the studies with rabbits in which

narcosis, tremors, hypothermia, and death ensued

following dermal application of cyclohexanol

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

Health; OSHA = Occupational Safety and Health Administration.

*Year accessed.
Skin Notation Profile | Cyclohexanol 5

Cyclohexanol

Irritation Category 2 (Causes skin irritation) 

[European Parliament 2008].

References

Note: Asterisks (*) denote sources cited in 

text; daggers (†) denote additional resources.

*ACGIH® [2001]. Documentation of threshold limit 

values and biological exposure indices. 7th Ed. 

Cincinnati, OH: American Conference of Governmental Industrial Hygienists.

†Clayton GD, Clayton FE, eds [1981–1982]. Patty's industrial hygiene and toxicology, volumes 

2A, 2B, 2C: toxicology. 3rd ed. New York: John 

Wiley Sons, p. 4646. 

†Draize JH, Alvarez E, Whitesell MF, Woodard G, 

Hagan EC, Nelson AA [1948]. Toxicological 

investigations of compounds proposed for use 

as insect repellents. A. Local and systemic effects 

following topical skin application. B. Acute oral 

toxicity. C. Pathological examination. J Pharmacol Exper Therapeutics 93:26–39. 

†Epstein WL [1974]. Report to RIFM. Woodcliff Lake, 

NJ: Research Institute for Fragrance Materials.

*ECHA [2020]. Classification and labelling inventory: table of harmonised entries in Annex VI 

to CLP. European Chemicals Agency, https://

pubchem.ncbi.nlm.nih.gov/compound/7966. 

Accessed 01-21-2020. 

*HSDB [2011]. Cyclohexanol. In: Hazardous Substances Data Bank, https://pubchem.ncbi.nlm.

nih.gov/compound/7966. Accessed: 06-07-19.

*IARC [2012]. Agents reviewed by the IARC monographs. In: IARC monographs on the evaluation of 

carcinogenic risks to humans. Lyon, France: World 

Health Organization, International Agency for 

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

fr/monographs-available/. Accessed 12-06-17.

†Mraz J, Galova E, Nohova H, Vitkova D [1994]. 

Uptake, metabolism and elimination of cyclohexanone in humans. Intl Arch Occup Environ 

Health 66(3):203–208. 

*Monsanto Company [1978]. Toxicity studies on 

cyclohexanol. South Windsor, CT: Younger Laboratories, OTS 0538617.

*Muller-Decker K, Furstenberger G, Marks F [1994]. 

Keratinocyte-derived proinflammatory key mediators and cell viability as in vitro parameters of 

irritancy: a possible alternative to the Draize skin 

irritation test. Toxicol Appl Pharmacol 127: 99–108. 

*National Center for Biotechnology Information 

[2020]. PubChem Database. Cyclohexanol, 

CID=7966, https://pubchem.ncbi.nlm.nih.

gov/compound/Cyclohexanol. Accessed on 

01-22-2020.

*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/. Accessed 01-28-2020. 

*NIOSH [2009]. Current intelligence bulletin 61: 

a strategy for assigning the new NIOSH skin 

notations for chemicals. 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/docs/2009-147/

pdfs/2009-147.pdf. Accessed 01-28-2020.

*NTP [2014]. Report on carcinogens, 13th edition. 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. Accessed 01-22-2020.

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

Occupational Safety and Health Administration, 

https://www.osha.gov/chemicaldata/chemResult.html?recNo=92. Accessed 01-22-2020.

†Schroder J [1986]. Cutaneous absorption of chemicals. OORSIG 57:169–176. 

*Smyth HP Jr, Carpenter CP, Weil CS, Pozzani UC, 

Striegel JA [1962]. Range-finding toxicity data: 

List VI. Am Ind Hyg Assoc J 23:95–107.

†Takeuchi A, Ogawa Y, Endo Y, Kawai T, Namera 

A, Yamamuro K, Sumino K, Endo G [2015]. 

Evaluation of urinary cyclohexanediols and cyclohexanol as biomarkers of occupational exposure 

to cyclohexane. J Occup Health 57(4):365–370.

*Treon JF, Crutchfield WE, Kitzmiller KV [1943]. 

The physiological response of rabbits to cyclohexane, methylcyclohexane, and certain 

derivatives of these compounds. I. Oral administration and cutaneous application. J Ind Hyg 

Toxicol J 25(6):199–214. 

*US EPA (United States Environmental Protection 

Agency) [ND]. Integrated Risk Information 

System. Washington, DC: United States Environmental Protection Agency, https://www.epa.

gov/iris. Accessed 01-21-2020.

*Walker JD, Rodford R, Patlewicz G [2003]. 

Quantitative structure-activity relationships 

for predicting percutaneous absorption rates. 

22:1870–1884. 
6 Skin Notation Profile | Cyclohexanol

Cyclohexanol

Appendix: Calculation of the SI Ratio for Cyclohexanol

This appendix presents an overview of the 

SI ratio and a summary of the calculation of 

the SI ratio for cyclohexanol. 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 centimeters per hour (cm/

hr), outlined in Table A1. Other model-based 

estimates of kp may also be used [NIOSH 2009].

 = 1

1

kpsc + kpol kaq

1 +

kp

Equation 1: Calculation of Skin Permeation 

 Coecient (kaq)

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 

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 
Skin Notation Profile | Cyclohexanol 7

Cyclohexanol

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 cyclohexanol. The calculated SI ratio 

was 0.34. On the basis of these results, cyclohexanol 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/. Accessed 01-28-2020. 

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. Accessed 

01-28-2020.

NLM [ND]. Toxnet, ChemIDplus: cyclohexanol. 

Bethesda, MD: National Institutes of Health, 

National Library of Medicine, https://chem.

nlm.nih.gov/chemidplus/rn/108-93-0. Accessed 

01-28-2020.
8 Skin Notation Profile | Cyclohexanol

Cyclohexanol

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

Variables used in calculation Units Value

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path (kpsc) cm/hr 0.0043

Permeation coefficient of the protein fraction of the 

stratum corneum (kpol)

cm/hr 1.5178 × 10-5

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.2498

Molecular weight (MW)* amu 100.16

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

*

None 1.23

Calculated skin permeation coefficient (kp) cm/hr 0.00427

Skin dose

Water solubility (Sw)

* mg/cm3 42

Calculated skin permeation coefficient (kp) cm/hr 0.00427

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

Exposure time hr 8

Calculated skin dose mg 516.21

Inhalation dose

Occupational exposure limit (OEL)† mg/m3 200

Inhalation volume m3 10

Retention factor (RF) None 0.75

Inhalation dose mg 1500

Skin dose–to–inhalation dose (SI) ratio None 0.3441

*

Variables identified from NLM [ND].

†

The OEL used in calculation of the SI ratio for cyclohexanol 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. 2021-101

DOI: https://doi.org/10.26616/NIOSHPUB2021101