Skin Notation (SK) Profile

Catechol

[CAS No. 120-80-9]

Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
ii

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Suggested Citation

NIOSH [20XX]. NIOSH skin notation profile:Catechol. 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. XXX

DHHS (NIOSH) Publication No. XXX
iii

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information quality guidelines. It has not been formally disseminated by the National Institute for 

Occupational Safety and Health. It does not represent and should not be construed to represent any 

agency determination or policy.

Foreword

As the largest organ of the body, the skin performs multiple critical functions, such as serving as 

the primary barrier to the external environment. For this reason, the skin is often exposed to 

potentially hazardous agents, including chemicals, which may contribute to the onset of a 

spectrum of adverse health effects ranging from localized damage (e.g., irritant contact 

dermatitis and corrosion) to induction of immune-mediated responses (e.g., allergic contact 

dermatitis and pulmonary responses), or systemic toxicity (e.g., neurotoxicity and hepatoxicity). 

Understanding the hazards related to skin contact with chemicals is a critical component of 

modern occupational safety and health programs. 

In 2009, the National Institute for Occupational Safety and Health (NIOSH) published 

Current Intelligence Bulletin (CIB) 61 – A Strategy for Assigning New NIOSH Skin Notations

[NIOSH 2009-147]. This document provides the scientific rationale and framework for the 

assignment of multiple hazard-specific skin notations (SK) that clearly distinguish between the 

systemic effects, direct (localized) effects, and immune-mediated responses caused by skin 

contact with chemicals. The key step within assignment of the hazard-specific SK is the 

determination of the hazard potential of the substance, or its potential for causing adverse health 

effects as a result of skin exposure. This determination entails a health hazard identification 

process that involves use of the following:

 Scientific data on the physicochemical properties of a chemical

 Data on human exposures and health effects

 Empirical data from in vivo and in vitro laboratory testing

 Computational techniques, including predictive algorithms and mathematical models that 

describe a selected process (e.g., skin permeation) by means of analytical or numerical 

methods. 

This Skin Notation Profile provides the SK assignments and supportive data for catechol. 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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information quality guidelines. It has not been formally disseminated by the National Institute for 

Occupational Safety and Health. It does not represent and should not be construed to represent any 

agency determination or policy.

Contents

FOREWORD ............................................................................................................................................................III

ABBREVIATIONS.....................................................................................................................................................V

GLOSSARY .............................................................................................................................................................VII

ACKNOWLEDGMENTS..................................................................................................................................... VIII

1.0 INTRODUCTION ..........................................................................................................................................1

1.1 GENERAL SUBSTANCE INFORMATION ..................................................................................................................1

1.2 PURPOSE..............................................................................................................................................................1

1.3 OVERVIEW OF SK ASSIGNMENT FOR CATECHOL .................................................................................................2

2.0 SYSTEMIC TOXICITY FROM SKIN EXPOSURE (SK: SYS) ......................................................................2

3.0 DIRECT EFFECTS ON SKIN (SK: DIR)...........................................................................................................4

4.0 IMMUNE-MEDIATED RESPONSES (SK: SEN) .............................................................................................5

5.0 SUMMARY............................................................................................................................................................5

REFERENCES ............................................................................................................................................................7

APPENDIX: CALCULATION OF THE SI RATIO FOR CATECHOL.............................................................10

OVERVIEW...............................................................................................................................................................10

CALCULATION .........................................................................................................................................................12

APPENDIX REFERENCES...........................................................................................................................................13
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agency determination or policy.

Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists 

ATSDR Agency for Toxic Substances and Disease Registry

BaP benzo[a]pyrene 

BaP-7,8-diol 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene 

CIB Current Intelligence Bulletin

cm2squared centimeter(s)

cm/hr centimeter(s) per hour

cm/s centimeter(s) per second

DEREK Deductive Estimation of Risk from Existing Knowledge

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

contact with a chemical

EC European Commission 

GHS Globally Harmonized System for Classification and Labelling of Chemicals

GPMT guinea pig maximization test

hr hour(s)

IARC International Agency for Research on Cancer

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

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

m

3

cubic meter(s)

mg milligram(s)

mg/cm2 milligram(s) per square centimeter

mg/kg milligram(s) per kilogram body weight

mg/m3 milligram(s) per cubic meter

mL milliliter(s)

mL/kg milliliter(s) per kilogram body weight

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit
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agency determination or policy.

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

SW solubility in water

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

the skin

USEPA United States Environmental Protection Agency 

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

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information quality guidelines. It has not been formally disseminated by the National Institute for 

Occupational Safety and Health. It does not represent and should not be construed to represent any 

agency determination or policy.

Glossary 

Absorption—The transport of a chemical from the outer surface of the skin into both the skin 

and systemic circulation (including penetration, permeation, and resorption). 

Acute exposure—Contact with a chemical that occurs once or for only a short period of time. 

Cancer—Any one of a group of diseases that occurs when cells in the body become abnormal 

and grow or multiply out of control. 

Contaminant—A chemical that is (1) unintentionally present within a neat substance or mixture 

at a concentration less than 1.0% or (2) recognized as a potential carcinogen and present within a 

neat substance or mixture at a concentration less than 0.1%. 

Cutaneous (or percutaneous)—Referring to the skin (or through the skin). 

Dermal—Referring to the skin. 

Dermal contact—Contact with (touching) the skin. 

Direct effects—Localized, non-immune-mediated adverse health effects on the skin, including 

corrosion, primary irritation, changes in skin pigmentation, and reduction/disruption of the skin 

barrier integrity, occurring at or near the point of contact with chemicals. 

Immune-mediated responses—Responses mediated by the immune system, including allergic 

responses. 

Sensitization—A specific immune-mediated response that develops following exposure to a 

chemical, which, upon re-exposure, can lead to allergic contact dermatitis (ACD) or other 

immune-mediated diseases such as asthma, depending on the site and route of re-exposure. 

Substance—A chemical. 

Systemic effects—Systemic toxicity associated with skin absorption of chemicals after exposure 

of the skin.
viii

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information quality guidelines. It has not been formally disseminated by the National Institute for 

Occupational Safety and Health. It does not represent and should not be construed to represent any 

agency determination or policy.

Acknowledgments

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

Director). G. Scott Dotson, Ph.D., was the project officer for this document, assisted in great part 

by Naomi Hudson, Dr.P.H., MPH, Stacey Anderson, 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, Ph.D.

Loren Tapp, M.D. 

Education and Information Division 

Devin Baker, M.Ed.

Charles L. Geraci, Ph.D.

Thomas J. Lentz, Ph.D.

Richard Niemeier, Ph.D.

Ralph Zumwalde, M.Sc.

Health Effects Laboratory Division

H. Fredrick Frasch, Ph.D. 

Michael Luster, Ph.D. 

Anna Shvedova, Ph.D.

Paul Siegel, Ph.D.

Berran Yucesoy, Ph.D.
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information quality guidelines. It has not been formally disseminated by the National Institute for 

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agency determination or policy.

National Personal Protective Technology Laboratory

Heinz Ahlers, J.D., M.Sc.

Angie Shepherd

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:

 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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policy.

1.0 Introduction

1.1 General Substance Information

Chemical: Catechol

CAS No: 120-80-9

Molecular weight (MW): 110.1

Molecular formula: C6H4(OH)2

Structural formula:

Synonyms: 1,2-Benzenediol; o-Benzenediol; 1,2-Dihyroxybenzene; Pyrocatechol; Pyrocatechin; oDihydroxybenzene; 2-Hydroxyphenol

Uses: Catechol is used primarily as an antioxidant in rubber, dye fat, and oil industries and is used in 

pesticides, pharmaceutical ingredients, and aroma chemicals [ACGIH 2001]. 

1.2 Purpose 

This skin notation profile presents (1) a brief summary of epidemiological and toxicological data 

associated with skin contact with catechol and (2) the rationale behind the hazard-specific skin notation 

(SK) assignment for catechol. 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 catechol and the potential for direct skin injuries 

from catechol. A literature search was conducted through February 2013 to identify catechol 

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 

catechol.
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1.3 Overview of SK Assignment for Catechol

Catechol 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 catechol: SK: SYSDIR(IRR)-SEN. Table 1 provides an overview of the critical effects and data used to develop the SK 

assignment for catechol. 

Table 1. Summary of the SK assignment for catechol

Skin Notation Critical Effect Available Data

SK: SYS Acute toxicity Limited animal data

SK: DIR(IRR) Skin irritancy; skin 

depigmentation

Sufficient animal data

SK:SEN Skin allergy Limited human data

2.0 Systemic Toxicity from Skin Exposure (SK: SYS)

There were no in vivo toxicokinetic studies of humans or animals that evaluated the degree of skin 

absorption of catechol from dermal exposure that were identified. Rhodia Incorporated [2005] 

investigated the in vitro percutaneous penetration of [14C]-labeled catechol through human skin 

membranes. When an aqueous solution was applied at a concentration of 1 milligram per cubic 

centimeter (mg/cm3), corresponding to an area concentration of 0.1 mg/cm3, the author reported that 

0.04% and 0.22% of the applied dose penetrated through the skin membrane within 10 and 60 minutes, 

respectively [Rhodia Incorporated 2005]. Within 24 hours, 26.65% of the applied dose penetrated 

through the membrane [Rhodia Incorporated 2005]. Rhodia Incorporated [2005] also reported a 

penetration rate of 1.425 micrograms per square centimeter per hour (μg/cm2/hr) after a lag time of 6 

hours. In that study, the permeability constant, kp, was reported as 1.430 x 10-3cm/hr [Rhodia 

Incorporated 2005]. This kp is greater than the value of 0.001 cm/hr that identifies a chemical as readily 

absorbed by the skin [NIOSH 2009]; therefore, catechol is considered to be absorbed through the skin 

via dermal exposure. The potential of catechol 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 and 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 17.9 was calculated for catechol. An SI ratio of ≥0.1 indicates that skin absorption may 

significantly contribute to the overall body burden of a substance [NIOSH 2009]; therefore catechol is 

considered to be absorbed through the skin following dermal exposure. Additional information on the SI 

ratio and the variables used in its calculation are included in the appendix.
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No estimate of the human dermal lethal dose (LDLo) of catechol has been reported in the literature. A 

dermal LD50 (the dose resulting in 50% mortality in the exposed population) value of 800 milligrams per 

kilogram body weight (mg/kg) in rabbits was reported [Flickinger 1976]. Because the reported acute 

dermal LD50 value is lower than the critical dermal LD50 value of 2,000 mg/kg that identifies chemicals 

with the potential for acute dermal toxicity [NIOSH 2009], catechol is considered acutely toxic 

following dermal exposure.

No epidemiological or occupational exposure studies of humans and no repeated-dose, subchronic, or 

chronic exposure studies in animals have evaluated the potential of catechol to cause systemic effects 

following dermal exposure. In addition, no standard toxicity or specialty studies evaluating biological 

system/function–specific effects (including reproductive and developmental effects and immunotoxicity) 

following dermal exposure to catechol were identified in the literature. 

No epidemiological studies or standard animal bioassays have evaluated the carcinogenic potential of 

catechol. In two-stage carcinogenicity studies in mice, topically applied catechol did not exhibit tumorpromoting activity with benzo[a]pyrene (BaP) as an initiator [Van Duuren and Goldschmidt 1976], but 

co-application of the substance with the racemic mixture or either of the enantiomers of 7,8-dihydroxy7,8-dihydrobenzo[a]pyrene (BaP-7,8-diol) increased the tumor-initiating activity of racemic BaP-7,8-

diol [Melikian et al. 1989]. However, it had no statistically significant effect on the tumor-initiating 

activity of the (+)- or (-)-enantiomers in mouse skin [Melikian et al. 1989]. Catechol was a potent cocarcinogen when tested for co-carcinogenic activity by dermal application at doses of 0.01 to 2 mg to 

mouse skin three times per week with a low dose of BaP (3 μg) for 48 to 59 weeks [Van Duuren and 

Goldschmidt 1976; Hecht et al. 1982; Melikian et al. 1989] or with racemic and enantiomeric BaP-7,8-

diols for 48 weeks [Melikian et al. 1989]. Co-carcinogenesis is a process in which a co-carcinogen, 

applied repeatedly (in this case, on mouse skin) with low doses of a known carcinogen such as 

benzo[a]pyrene (BaP), enhances considerably the carcinogenic activity of the carcinogen [Van Duuren 

and Goldschmidt 1976]. Although these studies indicate a co-carcinogenetic effect of catechol, the lack 

of data precludes adequate evaluation of the underlying mode of action or of whether catechol itself has 

carcinogenic potential following skin contact. Table 2 summarizes carcinogenic designations of multiple 

governmental and nongovernmental organizations for catechol.
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Table 2. Summary of the carcinogenic designations*for catechol by governmental and 

nongovernmental organizations

Organization Carcinogenic Designation 

NIOSH [2005] No designation

NTP [2014] No designation

USEPA [2015] No designation

European Parliament 2008] No GHS designation 

IARC [2012] Group 2B: Possibly carcinogenic to humans

EC [2013]† No designation 

ACGIH [2001] Group A3: Confirmed animal carcinogen of 

unknown relevance to humans

ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint Research, 

Institute for Health and Consumer Protection; 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 nondermal (such as oral or inhalation) exposure since studies using 

the dermal route of exposure were unavailable.

†Date accessed.

Although no in vivo toxicokinetic data have been reported reflecting the degree of skin absorption 

following dermal exposure, an in vitro study [Rhodia 2005]1, supported by a model prediction and acute 

toxicity data from rabbits [Flickinger 1976], indicate that catechol has the potential to be absorbed 

through the skin and can cause acute toxicity following dermal exposure. No epidemiological or case 

studies of humans and no repeated-dose, subchronic, or chronic exposure studies or specialty studies of 

animals have investigated the potential of catechol to cause systemic effects following dermal exposure. 

Therefore, on the basis of this assessment, catechol is assigned the SK:SYS notation. 

3.0 Direct Effects on Skin (SK: DIR)

No human or animal in vivo data on the skin corrosivity of catechol and no data from in vitro tests for 

corrosivity in human or animal skin models or in vitro tests for skin integrity in cadaver skin were found 

in the literature. O’Malley et al. [1988] reported the finding of vitiligo (an acquired skin disease 

characterized by patches of unpigmented skin, often surrounded by a heavily pigmented border) in five 

of 200 workers who handled catecholic substances on a regular basis; however the authors did not find 

any evidence of para-substituted phenolic or catecholic derivatives in the rubber formulations and 

adhesive sprays, indicating that another substance caused the occupational cases of vitiligo. Gellin et al. 

[1979] noted moderate depigmentation following application of 5 and 10% of catechol to the clipped 

dorsal skin of guinea pigs. These authors also noted primary skin irritation following application of 

catechol [Gellin et al. 1979]. Bleehen et al. [1968] applied 1% to 10% catechol in creams once daily, 

five times a week, to wax-epilated skin of the back and the unepilated skin of the ear of black guinea 

pigs for up to 1 month. Catechol did not depigment or irritate rabbit skin at a concentration of 1.0%, but 

at 3.0% it induced depigmentation, and very strong depigmentation was induced at 7% to 10%. 

 

1 References in bold text indicate studies that served as the basis of the SK assignment.
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Flickinger et al. [1976] reported moderate erythema and slight edema on intact skin and necrosis on 

abraded skin of rabbits after exposure to 500 mg/kg of catechol on the abdomen.

Sufficient data in animals [Bleehen et al. 1968; Flickinger et al. 1976; Gellin et al. 1979] are available 

to indicate that repeated application of catechol is irritating to the skin and generates skin 

depigmentation. Therefore, the notation SK: DIR(IRR) is assigned to catechol.

4.0 Immune-mediated Responses (SK: SEN)

A limited number of diagnostic patch tests have investigated the skin sensitization potential of catechol 

in humans. Morelli et al. [1989] described a patient occupationally exposed to catechol as a 

radiographer, who presented with contact dermatitis of the hands. Patch tests showed strong positive 

reactions to 0.1%, 0.5%, and 2% catechol [Morelli et al. 1989]. In a nonoccupational exposure case, a 

patient presented with acute contact dermatitis around the eyes from treatment of the eyelashes and 

eyebrows with a permanent dye cream and had positive reactions when patch-tested with 0.1% to 2% 

catechol [Andersen and Carlsen 1988]. Keil [1962] reported that persons sensitive to resorcinol have 

mild cross-reactions to catechol. No predictive tests in animals (for example, guinea pig maximization 

tests, murine local lymph node assays, or mouse ear swelling tests) or any other studies have evaluated 

the potential of the substance to cause skin sensitization.

A limited number of patch tests [Keil 1962; Andersen and Carlsen 1988; Morelli et al. 1989] have 

indicated the potential of catechol to cause skin sensitization in humans. Although no predictive tests in 

animals have been reported, the notation SK: SEN is assigned to catechol on the basis of the limited 

number of human cases identified.

5.0 Summary

No in vivo toxicokinetic data have been reported on the degree of skin absorption of catechol via dermal 

exposure. However, the findings of an in vitro study [Rhodia 2005], supported by a model prediction 

and acute toxicity data in rabbits [Flickinger 1976], indicate catechol has the potential to be absorbed 

through the skin and can cause acute toxicity following dermal exposure. No epidemiological or case 

studies of humans or repeated-dose, subchronic, or chronic exposure studies or specialty studies of 

animals have investigated the potential of catechol to cause systemic effects via dermal exposure. 

Sufficient data are available in animals [Bleehen et al. 1968; Flickinger et al. 1976; Gellin et al. 1979]

to indicate that catechol has the potential to irritate and depigment the skin following repeated contact. 

No predictive tests have investigated the potential of catechol to cause skin sensitization in animals, but 

a limited number of case reports [Keil 1962; Andersen and Carlsen 1988; Morelli et al. 1989] have 

indicated that catechol has the potential to cause skin sensitization. On the basis of the available 

information, a composite skin notation of SK: SYS-DIR(IRR)-SEN is assigned to catechol.

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

organizations. The equivalent dermal designations for catechol, according to the Global Harmonization 

System (GHS) of Classification and Labelling of Chemicals, are Acute Toxicity Category 4 (Hazard 
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statement: Harmful in contact with the skin), and Skin Irritation Category 2 (Hazard statement: Causes 

skin irritation) [European Parliament 2008]. 

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

Organization Skin hazard designation 

NIOSH [2005] [skin]: Potential for dermal absorption; prevent skin contact

OSHA [2015]* None

ACGIH [2001] [skin]: Based on dermal studies of mice and data on dermally 

exposed workers with symptoms of illness resembling those 

associated with phenol as well as central nervous system effects

EC [2013]* R21: Harmful if in contact with skin

R38: Irritating to skin

ACGIH = American Conference of Governmental Industrial Hygienists; EC = European Commission, Joint Research, 

Institute for Health and Consumer Protection; NIOSH = National Institute for Occupational Safety and Health; OSHA = 

Occupational Safety and Health Administration.

*Date accessed.
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References

Note: Asterisks (*) denote sources cited in text; daggers (†) denote additional resources.

*ACGIH (American Conference of Governmental Industrial Hygienists) [2001]. TLVs and BEIs Based 

on the Documentation of threshold limit values for chemical substances and physical agents and 

biological expsoure indices. Cincinnati, OH: American Conference of Governmental and Industrial 

Hygienists.

*Andersen KE, Carlsen L [1988]. Pyrocatechol contact allergy from a permanent cream dye for 

eyelashes and eyebrows. Contact Dermatitis 18(5):306–307.

†Baer H, Dawson CR, Byck JS, Kurtz AP [1970]. The immunochemistry of immune tolerance: II. The 

relationship of chemical structure to the induction of immune tolerance to catechols. J Immunol. 

104(1):178–184.

*Bleehen SS, Pathak MA, Hori Y, Fitzpatrick TB [1968]. Depigmentation of skin with 4-

isopropylcatechol mercaptoamines, and other compounds. J Invest Dermatol 50(2):103–117.

†Elder R [1986]. Final report on the safety assessment of hydroquinone and pyrocatechol. J Am Coll 

Toxicol 15:123–165.

*EC (European Commission) [ND]. EINECS (European INventory of Existing Commercial Chemical 

Substances), http://esis.jrc.ec.europa.eu/. Accessed: 09-03-13.

*European Parliament, Council of the European Union [2008]. Regulation (EC) No 1272/2008 of the 

European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging 

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

amending Regulation (EC) No 1907/2006. OJEU, Off J Eur Union L353:1–1355, http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:EN:PDF. Accessed: 01-29-15. 

*Flickinger CW [1976]. The benzenediols: catechol, resorcinol and hydroquinone. a review of the 

industrial toxicology and current industrial exposure limits. Am Ind Hyg Assoc J 37:596–607.

†Forsyth WGC, Quesnel VA [1957]. Intermediated in the enzymic oxidation of catechol. Biochem 

Biophys Acta 25:155–160.

*Gellin GA, Maibach HI, Misiaszek MH, Ring M [1979]. Detection of environmental depigmenting 

substances. Contact Dermatitis 5(4): 201-213.

†Gellin GA, Maibach HI [1983]. Detection of environmental depigmenting chemicals. In: Marzulli FN, 

Maibach HI, eds. Dermatotoxicology, 2nd Ed. New York, NY: Hemisphere Publishing, pp. 443–459.
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information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy.

*Hecht SS, Carmella S, Furuya K, LaVoie EJ [1982]. Polynuclear aromatic hydrocarbons and catechol 

derivatives as potential factors in digestive tract carcinogenesis. In: Environmental mutagens and 

carcinogens. Proceedings of the 3rd International Conference on Environmental Mutagens. Tokyo: 

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†Hirosawa I, Asaeda G, Arizono H, et al. [1976]. Effects of catechol on human subjects: a field study. 

Int Arch Occup Environ Health 37:107–114.

*IARC (International Agency for Research on Cancer) [2012]. Agents reviewed by the IARC 

monographs. In: IARC monographs on the evaluation of carcinogenic risks to humans, 

http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php. Accessed: 01-29-15.

†Kavlock RJ [1990]. Structure-activity relationships in the developmental toxicity of substituted 

phenols: in vivo effects. Teratology 41(l):43–59.

*Keil H [1962]. Group reactions in contact dermatitis due to resorcinol. Arch Dermatol 86:212–234.

†Melikian AA, Leszcynska JM, Hecht SS, Hoffman D [1986]. Effects of the co-carcinogen catechol on 

benzo[a]pyrene metabolism and DNA adduct formation in mouse skin. Carcinogenesis 7(1):9–15.

*Melikian AA, Jordan, KG, Braley J, Rigotty J, Meschter CL, Hecht SS, Hoffman D [1989]. Effects of 

catechol on the induction of tumors in mouse skin by 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes. 

Carcinogenesis 10(10):1897–1900.

†Melikian AA, Bagheri K, Goldin BF, Hoffman D [1989]. Catechol-induced alterations in metabolic 

activation and binding of enantiometric and racemic 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes to DNA 

in mouse skin. Carcinogenesis 10(10):1863–1870

†Melikian AA, Bagheri K, Hoffman D [1990]. Oxidation and DNA binding of (+)-7,8-dihydroxy-7,8-

dihydrobenzo(a)pyrene in mouse epidermis in vivo and effects of coadministration of catechol. Cancer 

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*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/npgd0211.html. Accessed: 01-29-15.
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This information is distributed solely for the purpose of pre-dissemination peer review under applicable 

information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy.

*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: 01-29-15.

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†Yonemoto K, Gellin GA, Epstein WL, Fukuyama K [1983]. Glutathione reductase activity in skin 

exposed to 4-tertiary butyl catechol. Int Arch Occup Environ Health 51:341–345.
10

This information is distributed solely for the purpose of pre-dissemination peer review under applicable 

information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy.

Appendix: Calculation of the SI Ratio for Catechol

This appendix presents an overview of the SI ratio and a summary of the calculation of the SI ratio for 

catechol. 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].
11

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information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy.

Equation 1: Calculation of Skin Permeation Coefficient (kp)

psc pol aq

p

k k k

k

1 1

1







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 

continues for 8 hours to unprotected skin on the palms of both hands (a surface area of 360 squared 

centimeters [cm2]). 

Equation 2: Determination of Skin Dose

Skin dose = kp × Sw × Exposed skin surface area × Exposure time

 = kp(cm/hr) × Sw (mg/cm3) × 360 cm2× 8 hr

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.
12

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information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy.

Calculation 

Table A1 summarizes the data applied in the previously described equations to determine the SI ratio for 

catechol. The calculated SI ratio was 17.9. On the basis of these results, catechol is predicted to 

represent a skin absorption hazard.

Table A1. Summary of Data used to Calculate the SI Ratio for catechol 

Variables Used in Calculation Units Value 

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path(kpsc) cm/hr 0.0309

Permeation coefficient of the protein fraction of the stratum 

corneum (kpol) cm/hr 1.4477 × 10-5

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.23826

Molecular weight (MW)

*

amu 110.1

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

* None 0.88

Calculated skin permeation coefficient (kp) cm/hr 0.00216

Skin dose

Water solubility (Sw)

* mg/cm3

430

Calculated skin permeation coefficient (kp) cm/hr 0.00216

Estimated skin surface area (palms of hand) cm2360

Exposure time hr 8

Calculated skin dose mg 2680

Inhalation Dose

Occupational exposure limit (OEL)† mg/m320

Inhalation volume m

3

10

Retention factor (RF) None 0.75

Inhalation dose mg 150

Skin dose–to–inhalation dose (SI) ratio None 17.9

*

Variables identified from SRC [ND].

†

The OEL used in calculation of the SI ratio for catechol was the NIOSH recommended exposure limit (REL) 

[NIOSH 2005].
13

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information quality guidelines. It has not been formally disseminated by the National Institute for Occupational 

Safety and Health. It does not represent and should not be construed to represent any agency determination or 

policy.

Appendix References 

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: 01-29-15.

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: 01-29-15.

SRC [2009]. Interactive PhysProp database demo, 

http://esc.syrres.com/fatepointer/webprop.asp?CAS=120809. Accessed: 01-29-15.