Skin Notation (SK) Profile

Dichlorvos

[CAS No. 62-73-7]

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: Dichlorvos (PCP). 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 dichlorvos. 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 ..........................................................................................................................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 DICHLORVOS ........................................................10

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

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

APPENDIX REFERENCES...........................................................................................................................................13
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Abbreviations

ACGIH American Conference of Governmental Industrial Hygienists 

ATSDR Agency for Toxic Substances and Disease Registry

CIB Current Intelligence Bulletin

ChE cholinesterase

cm2squared centimeter(s)

cm/hour centimeter(s) per hour

DEREK Deductive Estimation of Risk from Existing Knowledge

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

contact with a chemical

EC European Commission 

GHS Globally Harmonized System for Classification and Labelling of Chemicals

GPMT guinea pig maximization test

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

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/cm3 milligram(s) per cubic centimeter

mg/kg milligram(s) per kilogram body weight

mg/min milligram(s) per minute

MW molecular weight

NIOSH National Institute for Occupational Safety and Health

NOAEL no-observed-adverse-effect level

NTP National Toxicology Program

OEL occupational exposure limit

OSHA Occupational Safety and Health Administration

REL recommended exposure limit

RF retention factor 

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

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

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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 
vii

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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.

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.
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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.

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 Neimeier, M.Sc., and Sudha Pandalai, M.D., 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. 

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.

Health Effects Laboratory Division

Stacey Anderson, Ph.D.

H. Fredrick Frasch, Ph.D.

Vic Johnson, Ph.D.

Michael Luster, 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 Protection Technology Laboratory

Heinz Ahlers, 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: Dichlorvos

CAS No: 62-73-7

Molecular weight (MW): 221.0

Molecular formula: (CH3O)2P(O)OCH=CCl2

Structural formula:

Synonyms: 2,2-Dichlorovinyl dimethyl phosphate; Phosphoric acid, 2,2-dichloroethenyl dimethyl ester; 

2,2 -Dichloroethenyl phosphoric acid dimethyl ester; 2,2 - Dichlorovinyl dimethyl phosphoric acid ester; 

DDVP

Uses: Dichlorvos is used primarily as a broad spectrum organophosphate pesticide [ATSDR 1997].

1.2 Purpose 

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

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

notation (SK) assignment for dichlorvos. 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 dichlorvos. A literature search was 

conducted through February 2013 to identify information on dichlorvos, 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 

dichlorvos. 
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1.3 Overview of SK Assignment

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

assignment for dichlorvos. 

Table 1. Summary of the SK Assignment for Dichlorvos

Skin Notation Critical Effect Available Data

SK: SYS Histopathological changes in male 

reproductive system, lungs, liver, 

lymphatic glands, thymus, and heart; 

neurotoxicity; inhibition of 

cholinesterase activity

Sufficient animal data

SK: DIR (IRR) Skin irritation Sufficient human and 

animal data

SK: SEN Skin allergy, photoallergy Sufficient human and 

animal data

2.0 Systemic Toxicity from Skin Exposure (SK: SYS)

Quantitative estimates of dermal absorption in humans were not identified, but the potential for 

significant dermal absorption is indicated by cases of systemic effects including neurotoxicity resulting 

from cholinesterase (ChE) activity inhibition after a single episode of dermal exposure [Bisby and 

Simpson 1975; Mathias 1983] and cholinesterase inhibition-associated symptoms following dermal 

exposures in animals [Durham et al. 1957; Gajewski and Katkiewicz 1981; Tos-Luty et al.1994]. An 

animal study was identified that reported skin penetration of dichlorvos. Tos-Luty et al. [1994] applied 

0.3%, 0.62%, and 1.5% of dichlorvos in ethanol to the tails of rats for 4 hours. The highest penetration 

of dichlorvos in the rat tail skin (2.91% absorbed) was at the lowest concentration (0.3%), and 2.02% 

and 2.23% absorbed reported for concentrations of 0.62% and 1.5% dicholorvos, respectively [Tos-Luty 

et al. 1994]. The potential of dichlorvos 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 

2.55 was calculated for dichlorvos. An SI ratio of ≥0.1 indicates that skin absorption may significantly 

contribute to the overall body burden of a substance [NIOSH 2009]; therefore, dichlorvos 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. 

No quantitative estimates of the lethal dermal dose (LDLo) in humans have been identified. In animals, 

dermal LD50 values (the dose resulting in 50% mortality in the exposed animals) were influenced by the 
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purity of dichlorvos tested, the vehicle used, and condition of the skin. LD50 values for rats were 

reported to range from 75 milligrams per kilogram body weight (mg/kg) to 107 mg/kg [Gaines 1969; 

Durham et al. 1957]. Gajewski and Katkiewicz [1981] reported an LD50 in a negative logarithm of 3.49 

mols/kg in rats. Because the reported acute dermal LD50 values for experimental animals are all lower

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

the potential for acute dermal toxicity [NIOSH 2009], dichlorvos is considered systemically toxic by the 

dermal route.

Dermal application of dichlorvos to several animal species, including the monkey and rat, over a few 

days, resulted in significant inhibition of brain, erythrocyte, or serum ChE activity [Durham et al. 1957; 

Moriearty et al. 1993]. Symptoms of neurotoxicity have been reported within 20 minutes in monkeys 

after single or repeated dermal exposure to doses of dichlorvos in xylene at doses as low as 50 mg/kg or 

in rats topically exposed to 75 mg/kg [Durham et al. 1957]. These studies indicate that dichlorvos is a 

potent cholinesterase (ChE) inhibitor, significantly reducing blood plasma, red blood cell and brain ChE 

following dermal exposure. 

No repeat-dose dermal toxicity studies have been identified that quantified the dose to which humans 

were exposed. Although no chronic toxicity studies were identified in animals, the potential of 

dichlorvos to cause systemic toxicity has been evaluated in two repeat-dose and two subchronic dermal 

toxicity studies. Dermal application of dichlorvos over shorter durations, e.g. daily doses of 50 mg/kg, 

75 mg/kg, and 100mg/kg resulted in death in monkeys after 8, 10, and 4 doses, respectively, while 

cholinergic signs (incoordination, muscle fasciculation, excessive salivation, labored breathing, miosis, 

and eventually inability or indisposition to move), and significant inhibition of cholinesterase activities 

in the plasma and red blood cells were qualitatively similar at all dosage levels [Durham et al. 1957]. 

Luty et al. [1998] also reported dose-dependent histopathological changes in multiple organs (lungs, 

lymphatic glands and thymus, liver, kidneys and heart muscle) and stimulation of the bactericidal and 

phagocytic activity of neutrophils in rats exposed for 4 hours/day to 7.5 and 37.5 mg/kg-day dichlorvos 

for 4 weeks. In a subchronic study, dermal painting of rats with dichlorvos at a dose of 30 mg/kg per day 

(mg/kg-day) for 90 days did not elicit any symptoms of intoxication or mortality [Ali and Abdalla 

1992]. However, histopathological examination revealed changes in testicular and liver tissues, with the 

cellular damage being prominent in animals treated for 30 days or more [Ali and Abdalla 1992]. 

Degenerative seminiferous tubules and fewer Leydig cells were observed in the testis, while congestion, 

atrophy, and cells at different stages of necrobiotic changes were observed in the liver [Ali and Abdalla 

1992]. In an earlier 90-day subchronic dermal painting study, rats exposed to 21.4 mg/kg-day for 5 

days/week exhibited few clinical symptoms or histopathology changes in the skin or testes [Dikshith et 

al. 1976]. Histopathologic changes in the testes occurred in one control animal, however, the power to 

detect a difference between the cases and controls was low, thus the possibility of an effect of the 

compound at 21.4 mg/kg-day cannot be fully ruled out. The dose of 21.4 mg/kg-day can be regarded as 

the Lowest Observed-Adverse-Effect Level (LOAEL) for the testicular and hepatic effects. These 

studies demonstrate that dermal exposure to dichlorvos is systemically toxic, causing histopathological 

changes in internal organs, ChE inhibition, and central nervous system effects at doses significantly 

lower than the critical dermal LOAEL value of 1,000 mg/kg for repeat-dose toxicity that identifies 

chemical substances with the potential for subchronic dermal toxicity [NIOSH 2009]. 
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No standard toxicity or specialty studies evaluating biological system/function-specific effects 

(including developmental effects) following dermal exposure to dichlorvos were identified in humans or 

animals. However, reproductive system effects were identified when histopathology examination 

following a 90-day subchronic dermal exposure to 30 mg/kg/day observed testicular effects [Ali and 

Abdalla 1992]. The study by Luty et al. [1998] also demonstrates the potential of dichlorvos to affect 

immune system components (including lymphatic glands and thymus) following dermal exposure. 

No studies that evaluated the potential of dermally-applied dichlorvos to cause cancer in humans or 

animals were identified. Table 2 summarizes carcinogenic designations of multiple governmental and 

nongovernmental organizations for dichlorvos. 

Table 2. Summary of the carcinogenic designations*for dichlorvos by numerous governmental 

and nongovernmental organizations

Organization Carcinogenic designation 

NIOSH [2005] No designation

NTP [2014] No designation

USEPA [2014] B2: probable human carcinogen 

European Parliament [2008] No GHS designation 

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

EC [2013]† No designation

ACGIH [2014] A4: not classifiable as a human carcinogen

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.

Taken together, the toxicokinetic data in animals [Tos-Luty et al. 1994]1, results from the predictive 

mathematical algorithm, acute toxicity studies in animals [Gaines 1969; Durham et al. 1957], and 

subchronic dermal toxicity in animals [Durham et al. 1957; Dikshith et al. 1976; Ali and Abdalla 

1992; Luty et al. 1998] are sufficient to demonstrate the potential of dichlorvos to be absorbed through 

the skin and be systemically toxic, causing histopathological changes in testis, lungs, liver, lymphatic 

glands, thymus, and heart; neurotoxicity; and inhibition of cholinesterase activity following dermal 

exposure. Therefore, this assessment assigns a skin notation of SK: SYS for dichlorvos.

3.0 Direct Effects on Skin (SK: DIR)

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

human or animal skin models or in vitro tests of skin integrity using cadaver skin were identified. 

However, cases of irritant contact dermatitis have been reported in humans who came into direct contact 

 

1References in bold text indicate studies that serve as the basis of the SK assignments.
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with 1% to 10% solutions of, or mixtures containing, dichlorvos [Bisby and Simpson 1975; Cronce and 

Alden 1968; Mathias 1983]. Flea collar dermatitis – a primary irritant contact dermatitis – has been 

described in cats and dogs wearing dichlorvos-impregnated PVC flea collars [Breen and Conroy 1971; 

Fox et al. 1969a, 1969b]. In guinea pigs, Ueda et al. [1994] reported a threshold irritation concentration 

of 1% dichlorvos, while 0.5% was reported to produce discrete erythema [Fujita 1985]. The structureactivity relationship model, Deductive Estimation of Risk from Existing Knowledge (DEREK), 

predicted dichlorvos to be negative for skin irritation.

Case reports of irritant contact dermatitis in humans [Bisby and Simpson 1975; Cronce and Alden 

1968; Mathias 1983] and animals [Breen and Conroy 1971; Fox et al. 1969a, 1969b] provide 

sufficient evidence that dilute solutions are irritating to the skin. Therefore, on the basis of the data for 

this assessment, dichlorvos is assigned the SK: DIR (IRR) notation. 

4.0 Immune-mediated Responses (SK: SEN)

There is evidence from occupational exposures that dichlorvos has the potential to cause skin 

sensitization. For example, human diagnostic patch tests of occupational flower growers or tea growers 

with a history of pesticide dermatitis have shown allergic contact dermatitis response to dichlorvos 

[Fujita 1985; Ueda et al. 1994]. Horiuchi and Ando [1978] reported light-induced hypersensitization to 

dichlorvos in photosensitizing patch tests of workers presenting with dermatitis caused by agricultural 

pesticides. Dichlorvos has been implicated as a causative agent in contact dermatitis in a case-control 

study conducted by Matsushita et al. [1985], and may also cause skin sensitization in animals. A positive 

response was reported in a guinea pig maximization test (GPMT) [Ueda et al. 1994]. Fujita [1985] rated 

the allergenicity of dichlorvos as moderate using the guinea pig maximization test. DEREK also 

predicted dichlorvos to be a plausible skin sensitizer. 

Human diagnostic patch tests conducted on agricultural workers presenting with contact dermatitis show 

that dichlorvos has the potential to be a skin sensitizer [Fujita 1985; Matsushita et al. 1985; Ueda et 

al. 1994] and a photosensitizer [Horiuchi and Ando 1978]. Predictive tests in animals (for example, 

guinea pig maximization tests) [Fujita 1985; Ueda et al. 1994] demonstrate that dichlorvos causes skin 

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

notation. 

5.0 Summary

No quantitative estimates of dermal absorption in humans were identified. However, toxicokinetic data 

[Tos-Luty et al. 1994], acute toxicity studies [Gaines 1969; Durham et al. 1957], and repeat-dose and 

subchronic dermal toxicity in animals [Durham et al. 1957; Dikshith et al. 1976; Ali and Abdalla 

1992; Luty et al. 1998], and results from the predictive mathematical algorithm sufficiently demonstrate 

the potential of dichlorvos to be absorbed through the skin and be systemically toxic, causing diverse 

effects including histopathological changes in testis, lungs, liver, lymphatic glands, thymus, and heart; 

neurotoxicity; and inhibition of cholinesterase activity following dermal exposure. Although cases of 

skin corrosivity were not identified, case reports of irritant contact dermatitis in humans [Bisby and 
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Simpson 1975; Cronce and Alden 1968; Mathias 1983] and animals [Breen and Conroy 1971; Fox 

et al. 1969a, 1969b] provide sufficient evidence that dilute solutions of dichlorvos are irritating to the 

skin. Human diagnostic patch tests conducted on agricultural workers presenting with contact dermatitis 

show that dichlorvos has the potential to be a skin sensitizer [Fujita 1985; Matsushita et al. 1985; 

Ueda et al. 1994] and a photosensitizer [Horiuchi and Ando 1978]. Predictive tests in animals (for 

example, guinea pig maximization tests) [Fujita 1985; Ueda et al. 1994] demonstrate that dichlorvos 

causes skin sensitization. Therefore, on the basis of these assessments, dichlorvos is assigned a 

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

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

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

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

Category 3 (Hazard statement: Toxic in contact with the skin) and Skin Sensitization Category 1 

(Hazard statement: May cause an allergic skin reaction) [European Parliament 2008]. 

Table 3. Summary of previous skin hazard designations for dichlorvos

Organization Skin hazard designation 

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

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

ACGIH [2014] [skin]: symptoms of organophosphate poisoning have been seen in 

humans and animals following dermal contact.

DSEN: based upon positive patch-test responses in humans and 

positive responses in the guinea pig maximization test.

EC [2013]* R24: Toxic in contact with skin

R43: May cause sensitization by skin contact

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.

*Ali FA, Abdalla MH [1992]. Pathological changes in testes and liver of male albino rats after dermal 

exposure to DDVP insecticide. J Egypt Public Health Assoc 67(5-6):565-78. 

*ACGIH (American Conference of Governmental Industrial Hygienists) [2002]. Dichlorvos. In: TLVs 

and BEIs: Based on the documentation of threshold limit values for chemical substances and physical 

agents and biological exposure indices. Cincinnati, OH: American Conference of Governmental 

Industrial Hygienists.

*ATSDR [1997]. Toxicological profile for dichlorvos. Atlanta, GA: U.S. Department of Health and 

Human Services, Public Health Service, Agency for Toxic Substance and Disease Registry (ATSDR), 

http://www.atsdr.cdc.gov/toxprofiles/tp88.pdf. Accessed: 01-27-15. 

*Bisby JA, Simpson GR [1975]. An unusual presentation of systemic organophosphate poisoning. Med 

J Aust 2:394-395. 

*Breen PT, Conroy JD [1971]. Flea-collar contact dermatitis. Vet. Med. Small Anim Clin 66(12): 1181-

1183. 

*Cronce PC, Alden HS [1968]. Flea-collar dermatitis. J Am Med Assoc 206(7):1563-1564. 

*Dikshith TS, Datta KK, Chandra P [1976]. 90 day dermal toxicity of DDVP in male rats. Bull Environ 

Contam Toxicol 15(5):574-80. 

* Durham WF, Gaines TB, McCauley RH Jr., Sedlak VA, Mattson AM, Hayes WJ Jr. [1957]. Studies 

on the toxicity of O,O-dimethyl-2-2-dichlorovinyl phosphate (DDVP). AMA Arch Ind Health 15:340–

349. 

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

Commerical Chemical Substances), http://esis.jrc.ec.europa.eu/. Accessed: 04-24-13. 

*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: 01-27-15. 

*Fox I, Bayona IG, Armstrong JL [1969a]. Cat flea control through use of dichlorvos - impregnated 

collars. J Am Vet Med Assoc 155(10):1621-3.
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.

*Fox I, Rivera GA, Bayona IG [1969b]. Controlling cat fleas with dichlorvos-impregnated collars. J 

Econ Entomol 62(5):1246-1249.

*Fujita Y [1985]. Studies on contact dermatitis from pesticides in tea growers. Acta Med Univ 

Kagoshima 27(1):17-37. 

*Gaines TB [1969]. Acute toxicity of pesticides. Toxicol Appl Pharmacol 14:515–534. 

*Gajewski D, Katkiewicz M [1981]. Activity of certain enzymes and histomorphological changes in 

subacute intoxication of rats with selected organophosphates. Acta Physiol Pol 32(5):507-520. 

*Horiuchi N, Ando Y [1978]. Photosensitivity Caused by Pesticides. Proceedings of the VII 

International Congress of Rural Medicine, September 17-21, Salt Lake City, Utah, International 

Association of Agricultural Medicine, Grant No. R13-OH-00694, pages 279-284.

†HSDB (Hazardous Substances Data Bank) [2009]. Dichlorvos. In: HSDB (Hazardous Substances Data 

Bank), http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. Accessed: 01-27-15.

*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: 01-27-15.

*Luty S, Latuszynska J, Halliop J, Tochman A, Obuchowska D, Przylepa E, Korczak E, Bychawski E

[1998]. Toxicity of dermally absorbed dichlorvos in rats. Ann Agric Environ Med 5(1):57-64. 

*Mathias CGT [1983]. Persistent contact dermatitis from the insecticide dichlorvos. Contact Dermatitis 

9:217–218. 

*Matsushita T, Aoyama K, Yoshimi K, Fujita Y, Ueda A [1985]. Allergic contact dermatitis from 

organophosphorus insecticides. Ind Health 23:145-153. 

*Moriearty PL, Thornton SL, Becker RE [1993]. Transdermal patch delivery of acetylcholinesterase 

inhibitors. Meth Find Exp Clin Pharmacol 15(6):407-412. 

†Muller GH [1970]. Flea collar dermatitis in animals. J Am Vet. Med. Assoc 157(11):1616-1626. [Cited 

in IPCS 1989].

*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: 01-27-15.
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.

*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: 01-27-15.

*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: 01-27-15.

*OSHA [ND]. Dichlorvos. In: OSHA Occupational Chemical Database, 

http://www.osha.gov/chemicaldata/chemResult.html?recNo=457. Accessed: 01-27-15. 

*Shellenberger TE [1980]. Organophosphorus pesticide inhibition of cholinesterase in laboratory 

animals and man and effects of oxime reactivators. J Environ Sci Health B15(6):795-822. 

*Shellenberger TE, Newell GW, Okamoto SS, Sarros A [1965]. Response of rabbit whole blood 

cholinesterase in vivo after continuous intravenous infusion and percutaneous application of dimethyl 

organophosphate inhibitors. Biochem Pharmacol 14:943-952.

*Tos-Luty S, Latuszynska J, Halliop J, Tochman A, Przylepa E, Bychawski E, Obuchowska D [1994]. 

Skin penetration of selected pestidices. Ann Agric Environ Med 1:57-67. 

*Ueda A, Aoyama K, Manda F, Ueda T, Kawahara Y [1994]. Delayed-type allergenicity of triforine 

(Saprol®). Contact Dermatitis 31:140–145. 

†Ueda K, Shiyo K, Iizuka Y, Kitahara E, Ohashi A [1960]. [The toxicity of organic phosphate “DDVP" 

for small animals and man.] Igaku Seibutsugaku (Med. Biol.) 57(3):98-101 (in Japanese). 

*USEPA [2014]. Integrated Risk Information System: dichlorvos. In: Integrated Risk Information 

System, http://www.epa.gov/iris/subst/0151.htm. Accessed: 01-27-15.
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 Dichlorvos

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

dichlorvos. Although the SI ratio is considered in the determination of a substance’s hazard potential 

following skin contact, it is intended only to serve as supportive data during the assignment of the 

NIOSH SK. An in-depth discussion on the rationale and calculation of the SI ratio can be found in 

Appendix B of the Current Intelligence Bulletin (CIB) 61: A Strategy for Assigning New NIOSH Skin 

Notations [NIOSH 2009]. 

Overview 

The SI ratio is a predictive algorithm for estimating and evaluating the health hazards of skin exposure 

to substances. The algorithm is designed to evaluate the potential for a substance to penetrate the skin 

and induce systemic toxicity [NIOSH 2009]. The goals for incorporating this algorithm into the 

proposed strategy for assigning SYS notation are as follows:

(1) Provide an alternative method to evaluate substances for which no clinical reports or animal 

toxicity studies exist or for which empirical data are insufficient to determine systemic effects.

(2) Use the algorithm evaluation results to determine whether a substance poses a skin absorption 

hazard and should be labeled with the SYS notation.

The algorithm evaluation includes three steps:

(1) determining a skin permeation coefficient (kp) for the substance of interest,

(2) estimating substance uptake by the skin and respiratory absorption routes, and 

(3) evaluating whether the substance poses a skin exposure hazard.

The algorithm is flexible in the data requirement and can operate entirely on the basis of the 

physicochemical properties of a substance and the relevant exposure parameters. Thus, the algorithm is 

independent of the need for biologic data. Alternatively, it can function with both the physicochemical 

properties and the experimentally determined permeation coefficient when such data are available and 

appropriate for use.

The first step in the evaluation is to determine the kp for the substance to describe the transdermal 

penetration rate of the substance [NIOSH 2009]. The kp, which represents the overall diffusion of the 

substance through the stratum corneum and into the blood capillaries of the dermis, is estimated from 

the compound’s molecular weight (MW) and base-10 logarithm of its octanol–water partition coefficient 

(log KOW). In this example, kp is determined for a substance with use of Equation 1. A self-consistent set 

of units must be used, such as outlined in Table A1. Other model-based estimates of kp may also be used 

[NIOSH 2009].
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/hour) × Sw (mg/cm3) × 360 cm2× 8 hours

The inhalation dose (in mg) is derived on the basis of the occupational exposure limit (OEL) of the 

substance—if the OEL is developed to prevent the occurrence of systemic effects rather than 

sensory/irritant effects or direct effects on the respiratory tract. Assume a continuous exposure of 8 

hours, an inhalation volume of 10 cubic meters (m3) inhaled air in 8 hours, and a factor of 75% for 

retention of the airborne substance in the lungs during respiration (retention factor, or RF).

Equation 3: Determination of Inhalation Dose

Inhalation dose = OEL × Inhalation volume × RF

 = OEL (mg/m3) × 10 m3× 0.75

The final step is to compare the calculated skin and inhalation doses and to present the result as a ratio of 

skin dose to inhalation dose (the SI ratio). This ratio quantitatively indicates (1) the significance of 

dermal absorption as a route of occupational exposure to the substance and (2) the contribution of 

dermal uptake to systemic toxicity. If a substance has an SI ratio greater than or equal to 0.1, it is 

considered a skin absorption hazard.
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 

dichlorvos. The calculated SI ratio was 2.55. On the basis of these results, dichlorvos is predicted to 

represent a skin absorption hazard.

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

Variables Used in Calculation Units Value 

Skin permeation coefficient

Permeation coefficient of stratum corneum lipid path(kpsc) cm/hour 8.2281 × 10-4

Permeation coefficient of the protein fraction of the stratum 

corneum (kpol) cm/hour 1.0218 × 10-5

Permeation coefficient of the watery epidermal layer (kaq) cm/hour 0.1682

Molecular weight (MW)

*

amu 220.98

Base-10 logarithm of its octanol–water partition coefficient 

(Log Kow)

* None 1.47

Calculated skin permeation coefficient (kp) cm/hour 8.2892 × 10-4

Skin dose

Water solubility (Sw)

* mg/cm3

8

Calculated skin permeation coefficient (kp) cm/hour 8.2892 × 10-4

Estimated skin surface area (palms of hand) cm2360

Exposure time hour 8

Calculated skin dose mg 19.1

Inhalation Dose

Occupational exposure limit (OEL)† mg/m31

Inhalation volume m

3

10

Retention factor (RF) None 0.75

Inhalation dose mg 7.5

Skin dose–to–inhalation dose (SI) ratio None 2.55

*

Variables identified from SRC [ND].

†

The OEL used in calculation of the SI ratio for dichlorvos 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: 01-27-15.

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: 01-27-15. 

SRC [2009]. Interactive PhysProp database demo, 

http://esc.syrres.com/fatepointer/webprop.asp?CAS=62737. Accessed: 01-27-15.