Skin Notation (SK) Profile

Chlorinated Camphene

[CAS No. 8001-35-2]

Department of Health and Human Services

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
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Suggested Citation

NIOSH [20XX]. NIOSH skin notation profile: Chlorinated camphene. 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
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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 chlorinated 

camphene. 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 decisionmakers, employers, and workers in potentially hazardous workplaces—so that improved riskmanagement 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.................................................................................................................. 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 Chlorinated camphene........................................................... 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

CIB Current Intelligence Bulletin

cm2squared centimeter(s)

cm/hr centimeter(s) per hour

cm/s centimeter(s) per second

CNS central nervous system

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

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

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

OSHA Occupational Safety and Health Administration
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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.

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 microgram(s)

μg/cm2 microgram(s) per square centimeter

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

μL microliter(s)

μmol micromole(s)
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 aborption 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, Todd Niemeier, M.Sc., and Berran Yucesoy, Ph.D. The basis 

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

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

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

acknowledgment is given to the following NIOSH personnel:

Denver Field Office

Eric Esswein, M.Sc.

Division of Applied Research and Technology 

Clayton B’Hymer, Ph.D. 

John Snawder, Ph.D.

Mark Toraason, Ph.D.

Division of Respiratory Disease Studies 

Gregory A. Day, Ph.D. 

Aleksander Stefaniak, Ph.D. 

Division of Surveillance, Hazard Evaluations, and Field Studies

Matt Dahm, M.Sc.

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.
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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.

Health Effects Laboratory Division

Stacey Anderson, Ph.D.

H. Fredrick Frasch, Ph.D. 

Michael Luster, Ph.D. 

Anna Shvedova, Ph.D.

Paul Siegel, Ph.D.

Berran Yucesoy, Ph.D.

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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1.0 Introduction 

1.1 General Substance Information 

Chemical: Chlorinated camphene

CAS No: 8001-35-2

Molecular weight (MW): 413.8

Molecular formula: C10H10Cl8

Structural formula:

Synonyms: Chlorocamphene; Octachlorocamphene; Polychlorocamphene; Toxaphene

Uses: Chlorinated camphene was used primarily as an insecticide. The Agency for Toxic Substance and 

Disease Registry (ATSDR) reported that an estimated that 3.7 million pounds [less than 2 million 

kilograms (kg)] were produced in the United States in 1982 [ATSDR 1996]. The United States 

Environmental Protection Agency (USEPA) banned chlorinated camphene in 1990 [55 Fed. Reg. 31164 

(1990); ATSDR 2014].

1.2 Purpose 

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

associated with skin contact with chlorinated camphene and (2) the rationale behind the hazard-specific 

skin notation (SK) assignment for chlorinated camphene. 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 chlorinated camphene. A 

literature search was conducted through February 2013 to identify information on chlorinated camphene, 

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 chlorinated camphene.
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1.3 Overview of SK Assignment

Chlorinated camphene 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 chlorinated 

camphene: SK: SYS-DIR (IRR). Table 1 provides an overview of the critical effects and data used to 

develop the SK assignment for chlorinated camphene. 

Table 1. Summary of the SK Assignment for chlorinated camphene

Skin Notation Critical Effect Available Data

SK: SYS Central nervous system (CNS), 

liver, kidney, spleen, thyroid 

Limited human and animal data

SK: DIR (IRR) Skin irritation Limited animal data

2.0 Systemic Toxicity from Skin Exposure (SK: SYS)

No quantitative toxicokinetic data following dermal exposure to chlorinated camphene were identified 

for humans or animals. The potential of chlorinated camphene 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 0.01was calculated for chlorinated camphene. An SI ratio of ≥0.1 indicates 

that a chemical is capable of producing systemic toxicity from skin exposure [NIOSH 2009]; therefore, 

chlorinated camphene is not 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.

No estimate of the dermal lethal dose (LDLO) of chlorinated camphene for humans was identified. 

Dermal LD50 (lethal dose in 50% of exposed animals) values of 780 milligrams per kilogram body 

weight (mg/kg) to 1,075 mg/kg were reported for rats [Gaines 1969]. For rabbits, a dermal LD50 range of 

1,025 mg/kg to 1,075 mg/kg was reported using a non-standard acute dermal toxicity test that involved 

immersing the animals in water suspension of wettable chlorinated camphene powder for 2 minutes 

[Johnston and Eden 1953]. Dermal LD50 values ranging from 3,725 mg/kg when applied to skin burned 

with ultraviolet light to 4,556 mg/kg for intact skin areas have been reported for rabbits after dermal 

exposure to chlorinated camphene (90% weight/volume in xylene) for 24 hours (hr) [Industrial BioTest 

Labs 1973]. Because the reported acute dermal LD50 values for chlorinated camphene in rats and rabbits 

are lower than the critical dermal LD50 value of 2,000 mg/kg body weight that identifies chemical 

substances with the potential for systemic toxicity following dermal exposure [NIOSH 2009], 

chlorinated camphene has the potential to be absorbed through the skin and be systemically available. 

This is in contrast to the model prediction that indicated a low potential of chlorinated camphene for 

absorption through the skin.
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No epidemiological studies were identified that evaluated the potential of chlorinated camphene to cause 

systemic toxicity following dermal exposure. A case report by Pollock [1958] described severe systemic 

effects including generalized muscular aches and pain (particularly of the extremities) and stiffness, 

semi-consciousness, vomiting, and epigastric pain following a 2 hr contact with a lindane–chlorinated 

camphene solution. The worker handled the material while mixing the solution into the wool of sheep as 

a pesticide treatment; the contaminated skin was not washed and symptoms developed 10 hr after 

exposure. The doses of lindane or chlorinated camphene were not quantified, and it is unclear which 

chemical produced the systemic effects. Both chlorinated camphene and lindane produce similar 

symptoms, with the usual sequence of events after ingestion being central nervous system (CNS) 

stimulation, high temperature, convulsions, gastric irritation, vomiting, diarrhea, respiratory failure, and 

death [Pollock 1958]. The systemic CNS effects observed, secondary to cutaneous absorption, are 

similar to those reported following oral ingestion or inhalation exposure in humans [McGee et al. 1952] 

and animals [DiPietro and Haliburton 1979; Lawrence and Casida 1984], suggesting that chlorinated 

camphene has the potential to cause CNS effects following prolonged dermal exposure. 

No repeated-dose, sub-chronic, or chronic toxicity studies were identified that evaluated dermal 

exposure to chlorinated camphene in humans or animals. However, several oral exposure studies to 

chlorinated camphene identified the liver, kidney, spleen, and the immune system as target organs and 

systems [Agency for Toxic Substances and Disease Registry (ATSDR) 1996]. In a 13-week feeding 

study rats were given 0, 4.0, 20, 100, or 500 ppm chlorinated camphene [corresponding to 0, 4.0, 20, 

100, and 500 mg/kg] [Chu et al. 1986]. Chu et al. [1986] reported that rats receiving 20 mg/kg daily of 

chlorinated camphene only ingested approximately 1.8 milligrams per kilograms per day (mg/kg-day), 

and that those rats receiving doses of 20 mg/kg-day and greater had histological changes in liver, kidney 

and thyroid. Chu et al. [1986] also fed dogs 0.2 to 5.0 mg/kg-day of chlorinated camphene for 13 weeks, 

and reported increased relative liver weight and histological changes in the liver and thyroid. In a later 

study, Chu et al. [1988] reported that chlorinated camphene caused increased liver and kidney weights, 

elevated serum cholesterol, and histological changes in the liver, thyroid and kidney of adult rats in a 

generation 2 reproductive toxicity study following dietary exposure. These studies indicate that 

chlorinated camphene, in addition to inducing CNS effects, has the potential to be systemically available 

and may cause hepatic, liver, spleen and thyroid effects. 

No specialty studies were identified that evaluated biological system/function specific effects (including 

reproductive and developmental effects and immunotoxicity) following dermal exposure to chlorinated 

camphene. However, a reproductive toxicity study in which rats were administered chlorinated 

camphene in the diet observed no impairment in reproductive performance including the gestation index, 

survival indices, and litter size at doses up to 500 ppm, of which approximately 37 to 49 mg/kg-day was 

ingested [Chu et al. 1988]. 

No studies were identified that evaluated the carcinogenic potential of chlorinated camphene following 

dermal exposures. However, organizations and agencies have evaluated the carcinogenic potential of 

chlorinated camphene following other routes of exposure. Table 2 summarizes carcinogenic 

designations of multiple governmental and nongovernmental organizations for chlorinated camphene. 
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Table 2. Summary of the carcinogenic designations*for chlorinated camphene 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] B2: Probable human carcinogen

IARC [2012] 2B: Possibly carcinogenic to humans

European Parliament [2008] GHS Carcinogenicity Category 2: Suspected of causing 

cancer

EC [2013]† R40: Limited evidence of a carcinogenic effect 

ACGIH [2001] A3: Confirmed animal carcinogen with 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

No studies were identified that provided quantitative estimates of chlorinated camphene absorption 

through the skin. Although the percent absorption following dermal exposure has not been estimated and 

no epidemiological studies or repeated-dose, subchronic or chronic toxicity studies in animals were 

identified that evaluated the potential of chlorinated camphene to cause systemic effects following 

dermal exposure, standard acute dermal toxicity study in rats [Gaines 1969]1and a non-standard acute 

toxicity test in rabbits [Johnston and Eden 1953] suggest that chlorinated camphene is absorbed 

through the skin following dermal exposure and can be systemically toxic. The potential to cause CNS 

effects are supported by a human case study which was also exposed to the pesticide lindane [Pollock 

1958] and by oral and inhalation toxicity studies [DiPietro and Haliburton 1979; Lawrence and Casida 

1984], indicating the CNS effects are not route-specific. In addition, subchronic oral toxicity studies 

[Chu et al. [1986, 1988] have identified the liver, kidney, spleen, and thyroid as target organs for 

chlorinated camphene at doses up to 2 mg/kg-day. NIOSH [2005] has previously identified chlorinated 

camphene as a potential occupational carcinogen, but data are not available to assess the carcinogenic 

potential of dermal exposures. Therefore, on the basis of the data for this assessment, chlorinated 

camphene is assigned the SK: SYS notation.

3.0 Direct Effects on Skin (SK: DIR)

No human or animal in vivo studies that evaluated the corrosivity of chlorinated camphene or in vitro

tests for corrosivity using human or animal skin models or in vitro tests of skin integrity using cadaver 

skin were identified. A human case report of an individual exposed to a lindane-chlorinated camphene 

mixture for 2 hr reported itchy skin that was not accompanied by a rash [Pollock 1958], although it is 

unknown if the irritation was caused by chlorinated camphene or lindane. Standard irritation and 

 

1References in bold text indicate studies that serve as the basis of the SK assignments.
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corrosivity tests were conducted on albino rabbits using 500 mg of technical grade chlorinated 

camphene, 0.5 milliliter (mL) of a 90% solution or a formulation of chlorinated camphene – the diluents 

for the solution and the formulation were not reported– was applied to an area of clipped and abraded 

skin that was occluded for 4 h [International Research and Development Corporation (IRDC) 1973]. The 

technical grade chlorinated camphene caused slight to moderate erythema and edema at 24 and 72 hr 

later on both intact and abraded skin. Similar effects were observed for the 90% solution and the 

formulated preparation at 4, 24 and 72 hr on both intact and abraded skin. IRDC [1973] defined a 

primary irritant as a substance which was not corrosive, but which resulted in a score of 5 or more. 

Because an irritation score of 2.1 was reported for the technical grade, 3.2 for the 90% solution, and 2.6 

for the formulated preparation, IRDC [1973] concluded that the dosing regimens used did not result in 

skin irritation and that the irritation noted was due to the test articles to the skin. However, this 

assessment concludes that observations at the specified time points (24 and 72 h) show the potential of 

chlorinated camphene to cause skin irritation. Industrial BioTest [1973] reported moderate to severe 

edema and erythema, followed by severe desquamation in rabbits after dermal application of very high 

doses (3,038 mg/kg and greater) of chlorinated camphene (90% in xylene) under occlusion for 24 hr. It 

is possible that xylene may have contributed to the skin effects observed in the Industrial Bio Test 

[1973] study, given that xylene causes mild irritation in guinea pigs and rats with a Draize score of 1.2 

[Anderson et al. 1986; Chatterjee et al. 2005]. However, the dermal irritation score reported by 

Industrial Bio Test [1973] exceeds what we would expect to see from xylene alone, suggesting that 

chlorinated camphene has irritant properties. This is further supported by IRDC [1973], which reports 

slight to moderate erythema and edema following dermal exposure to technical grade chlorinated 

camphene. 

The standard skin irritation tests identified [IRDC 1973] and results from prolonged exposure 

[Industrial BioTest Labs 1973] indicate that chlorinated camphene has the potential to cause mild to 

moderate skin irritation, and prolonged dermal contact with very high doses may be irritating to the skin. 

Therefore, on the basis of the data for this assessment, chlorinated camphene is assigned the SK: DIR 

(IRR) notation.

4.0 Immune-mediated Responses (SK: SEN)

No reports of sensitization in humans, or predictive tests (for example, guinea pig maximization tests, 

Buehler tests, murine local lymph node assays, mouse ear swelling tests) or other tests were identified 

that evaluated the potential of chlorinated camphene to cause skin sensitization in animals Lack of data 

precludes adequate evaluation of chlorinated camphene to cause skin sensitization. Therefore, on the 

basis of the data for this assessment, chlorinated camphene is not assigned the SK: SEN notation.

5.0 Summary

Although no studies were identified that provided quantitative estimates of absorption of chlorinated 

camphene through the skin, a standard acute toxicity study in rats [Gaines 1969] ] and a non-standard 

acute toxicity test in rabbits [Johnston and Eden 1953] indicate that chlorinated camphene has the 

potential to be absorbed and be systemically toxic. Because neurotoxic effects have also been reported 
6

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by a human case study who was also exposed to the pesticide lindane [Pollock 1958] and by following 

inhalation and ingestion exposure in humans [McGee et al. 1952] and animals [DiPietro and Haliburton 

1979; Lawrence and Casida 1984] to chlorinated camphene, the limited dermal exposure data in animals 

[Chu et al. 1986; 1988] support the conclusion that chlorinated camphene causes CNS effects following 

exposure via skin contact. In addition, subchronic oral toxicity studies with chlorinated camphene have 

identified the liver, kidney, spleen, and thyroid as target organs at doses of chlorinated camphene up to 2 

mg/kg-day [Chu et al. 1986, 1988]. The standard irritation tests with a technical grade chlorinated 

camphene, a 90% solution of chlorinated camphene, and a commercially-available product [IRDC 

1973] and results from prolonged dermal contact with high doses [Industrial BioTest Labs 1973] are 

sufficient to indicate that the chlorinated camphene has the potential to cause skin irritation. No 

diagnostic tests in humans or predictive tests in animals were identified to adequately evaluate the 

potential of chlorinated camphene to cause skin sensitization. Therefore, on the basis of these 

assessments, chlorinated camphene is assigned a composite skin notation of SK: SYS-DIR (IRR). 

Table 3 summarizes the skin hazard designations for chlorinated camphene previously issued by NIOSH 

and other organizations. The equivalent dermal designations for chlorinated camphene, according to the 

Global Harmonization System (GHS) of Classification and Labelling of Chemicals, are Acute Toxicity 

Category 4 (Hazard statement: Harmful in contact with the skin), and Skin Irritation Category 2 (Hazard 

statement: Causes skin irritation) [European Parliament 2008]. 

Table 3. Summary of previous skin hazard designations for chlorinated camphene

Organization Skin hazard designation 

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

OSHA [2015]*[skin]: Potential for dermal absorption

ACGIH [2001] [skin]: Based on the absorption of chlorinated camphene through 

intact and abraded skin of treated rabbits leading to systemic effects 

and lethality

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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policy.

References

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

*55 Fed. Reg. 31164 [1990]. Environmental Protection Agency: notice to intent to remove certain active 

ingredients from reregistration List B and to cancel pesticides containing those ingredients.

*ACGIH [2001]. Chlorinated camphene. In: Documentation of threshold limit values and biological 

exposure indices 7th ed., Vol. 1. Cincinnati, OH: American Conference of Governmental Industrial 

Hygienists.

*Anderson C, Sundberg K, Groth O [1986]. Animal model for assessment of skin irritancy. Contact 

Dermatitis 15:143-151.

*ATSDR [2014]. Toxicological profile for toxaphene, http://www.atsdr.cdc.gov/toxprofiles/tp94.pdf. 

Atlanta: U.S. Department of Health and Human Services, Public Health Serice, Agency for Toxic 

Substances and Disease Registry. Accessed: 01-29-15.

*Chatterjee A, Babu RJ, Ahaghotu E, Singh M [2005]. The effect of occlusive and unocclusive exposure 

to xylene and benzene on skin irritation and molecular responses in hairless rats. Arch Toxicol 79(5): 

294-301.

*Chu I, Villeneuve DC, Sun CW, Secours V, Proctor B, Arnold EP, Clegg D, Reynolds L, Valli VE. 

[1986]. Toxicity of chlorinated camphene in the rat and beagle dog. Fund Appl Toxicol 7:406-418.

*Chu I, Secours V, Villeneuve DC, Valli VE, Nakamura A, Colin D, Clegg DJ, Arnold EP. [1988]. 

Reproduction study of toxaphene in the rat. J Environ Sci Health (B) 23:101-126.

*Dille JR, Smith PW [1964]. Central nervous system effects of chronic exposure to organophosphate 

insecticides. Aerospace Med 351475-478.

*DiPietro JA, Haliburton JC [1979]. Toxaphene toxicosis in swine. J Am Vet Med Assoc 175:452-453. 

*EC (European Commission) [ND]. Toxaphene. In: EINICS (European Inventory of Existing 

Commercial Chemical Substances), http://esis.jrc.ec.europa.eu/. Accessed: 08-21-13.

*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.

*Gaines, TB. [1969]. Acute Toxicity of Pesticides. Toxicology and Applied Pharmacology 14:515-534.
8

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.

*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.

*Industrial Biotest [1973]. Acute dermal toxicity studies with four samples in female albino rabbits. 

Northbrook, IL: Industrial Biotest Laboratories, Inc., Project No. 72-26.

*IRDC (International Research and Development Corporation) [1973]. Primary skin irritation study in 

the albino rabbit. International Research and Development Corporation. Report to Hercules, Inc. 

Wilmington, Delaware. Mattawon, Michigan.

*Johnston BL, Eden WG [1953]. The toxicity of aldrin, dieldrin and toxaphene to rabbits by skin 

absorption. Journal of Economic Entomology 46(4):702-703.

*Lawrence LJ, Casida JE [1984]. Interactions of lindane, toxaphene and cyclodienes with brain-specific 

tert-butylbicyclophosphorothionate receptor. Life Sci 35:171-178.

*McGee LC, Reed HL, Fleming JP. [1952]. Accidental poisoning by toxaphene: Review of toxicology 

and case reports. JAMA 149: 1124-l 126.

*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. 

*NTP [2014]. Report on Carcinogens. Thirteenth Edition; U.S. Department of Health and Human 

Services, Public Health Service. National Toxicology Program, 

http://ntp.niehs.nih.gov/pubhealth/roc/roc13/index.html. Accessed: 01-29-15.

*OSHA [ND]. Chlorinated camphene. In: OSHA Occupational chemical database, 

https://www.osha.gov/chemicaldata/chemResult.html?recNo=698. Accessed: 01-29-15.

*Pollock RW [1958]. Toxaphene-lindane poisoning by cutaneous absorption. Report of a case with 

recovery. Northwest Medicine March 1958 pp. 325-326.

†Prasada Rao KS, Trottman CH, Morrow W, Desaiah D [1986]. Toxaphene inhibition of calmodulindependent calcium ATPase activity in rat brain synaptosomes. Fundam Appl Toxicol 6(4): 648-653.
9

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.

†UNECE (United Nations Economic Commission for Europe) [2007]. Part 3: health hazards. In: 

Globally harmonized system of classification and labeling of chemical (GHS): third revised edition, 

http://www.unece.org/trans/danger/publi/ghs/ghs_rev02/English/03e_part3.pdf. Accessed: November 20 

2009. 

*USEPA [2014]. Chlorinated Camphene. In: Integrated risk information system, 

http://www.epa.gov/iris. Accessed: 01-28-15.
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 Chlorinated camphene

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

chlorinated camphene. 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

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.

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 hr, 

an inhalation volume of 10 cubic meters (m3) inhaled air in 8 s, 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 

chlorinated camphene. The calculated SI ratio was 0.01. On the basis of these results, chlorinated 

camphene is predicted not to represent a skin absorption hazard.

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

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 7.1745 × 10-6

Permeation coefficient of the watery epidermal layer (kaq) cm/hr 0.11808

Molecular weight (MW)

*

amu 448.26

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

* None 5.9

Calculated skin permeation coefficient (kp) cm/hr 0.02449

Skin dose

Water solubility (Sw)

* mg/cm3

5.5 × 10-4

Calculated skin permeation coefficient (kp) cm/hr 0.02449

Estimated skin surface area (palms of hand) cm2360

Exposure time hr 8

Calculated skin dose mg 0.0388

Inhalation Dose

Occupational exposure limit (OEL)† mg/m30.5

Inhalation volume m

3

10

Retention factor (RF) None 0.75

Inhalation dose mg 3.75

Skin dose–to–inhalation dose (SI) ratio None 0.01

*

Variables identified from SRC [ND].

†

The OEL used in calculation of the SI ratio for chlorinated camphene 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=8001352. Accessed: 01-29-15.