TOXICOLOGICAL PROFILE FOR

ETHION

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

Agency for Toxic Substances and Disease Registry

September 2000
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DISCLAIMER

The use of company or product name(s) is for identification only and does not imply endorsement by the

Agency for Toxic Substances and Disease Registry.
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UPDATE STATEMENT

Toxicological profiles are revised and republished as necessary, but no less than once every three years. 

For information regarding the update status of previously released profiles, contact ATSDR at:

Agency for Toxic Substances and Disease Registry

Division of Toxicology/Toxicology Information Branch

1600 Clifton Road NE, E-29

Atlanta, Georgia 30333



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QUICK REFERENCE FOR HEALTH CARE PROVIDERS

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation of

available toxicologic and epidemiologic information on a substance. Health care providers treating

patients potentially exposed to hazardous substances will find the following information helpful for fast

answers to often-asked questions.

Primary Chapters/Sections of Interest

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating

patients about possible exposure to a hazardous substance. It explains a substance’s relevant

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of

the general health effects observed following exposure.

Chapter 2: Health Effects: Specific health effects of a given hazardous compound are reported by route

of exposure, by type of health effect (death, systemic, immunologic, reproductive), and by length

of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the

clinical setting. Please refer to the Public Health Statement to identify general health

effects observed following exposure.

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health

issues:

Section 1.6 How Can Ethion Affect Children?

Section 1.7 How Can Families Reduce the Risk of Exposure to Ethion?

Section 2.7 Children’s Susceptibility

Section 5.6 Exposures of Children

Other Sections of Interest:

Section 2.8 Biomarkers of Exposure and Effect

Section 2.11 Methods for Reducing Toxic Effects

ATSDR Information Center 

Phone: 1-888-42-ATSDR or (404) 639-6357 Fax: (404) 639-6359

E-mail: atsdric@cdc.gov Internet: http://www.atsdr.cdc.gov

The following additional material can be ordered through the ATSDR Information Center:

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an

exposure history and how to conduct one are described, and an example of a thorough exposure

history is provided. Other case studies of interest include Reproductive and Developmental

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide

Toxicity; and numerous chemical-specific case studies.
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Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene

(prehospital) and hospital medical management of patients exposed during a hazardous materials incident. 

Volumes I and II are planning guides to assist first responders and hospital emergency department

personnel in planning for incidents that involve hazardous materials. Volume III—Medical Management

Guidelines for Acute Chemical Exposures—is a guide for health care professionals treating patients

exposed to hazardous materials.

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances.

Other Agencies and Organizations

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease,

injury, and disability related to the interactions between people and their environment outside the

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, GA 30341-

3724 • Phone: 770-488-7000 • FAX: 770-488-7015.

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational

diseases and injuries, responds to requests for assistance by investigating problems of health and

safety in the workplace, recommends standards to the Occupational Safety and Health

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains

professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue,

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch,

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998

• Phone: 800-35-NIOSH.

 The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for

biomedical research on the effects of chemical, physical, and biologic environmental agents on

human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive,

Research Triangle Park, NC 27709 • Phone: 919-541-3212.

Referrals

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics

in the United States to provide expertise in occupational and environmental issues. Contact:

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 •

FAX: 202-347-4950 • e-mail: aoec@dgs.dgsys.com • AOEC Clinic Director: http://occ-envmed.mc.duke.edu/oem/aoec.htm.

The American College of Occupational and Environmental Medicine (ACOEM) is an association of

physicians and other health care providers specializing in the field of occupational and

environmental medicine. Contact: ACOEM, 55 West Seegers Road, Arlington Heights, IL

60005 • Phone: 847-228-6850 • FAX: 847-228-1856.
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CONTRIBUTORS

CHEMICAL MANAGER(S)/AUTHORS(S):

Nickolette Roney, M.P.H.

ATSDR, Division of Toxicology, Atlanta, GA

Mark R. Osier, Ph.D.

Syracuse Research Corporation, North Syracuse, NY

Armando D. Avallone, B.S.

Syracuse Research Corporation, North Syracuse, NY

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS:

1. Health Effects Review. The Health Effects Review Committee examines the health effects

chapter of each profile for consistency and accuracy in interpreting health effects and classifying

end points.

2. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to

substance-specific minimal risk levels (MRLs), reviews the health effects database of each

profile, and makes recommendations for derivation of MRLs.

3. Data Needs Review. The Research Implementation Branch reviews data needs sections to assure

consistency across profiles and adherence to instructions in the Guidance.

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PEER REVIEW

A peer review panel was assembled for ethion. The panel consisted of the following members: 

1. Dr. Robert Coppock, DABT, DABVT, P.O. Box 2031, Vegreville, Alberta T9C 1T2, Canada;

2. Dr. Frederick Oehme, Comparative Toxicology Laboratories, Kansas State University,

Manhattan, Kansas, 66506; and

3. Dr. James Withey, 49 Wilton Crescent, Ottawa, Ontario K1S 2T6, Canada.

These experts collectively have knowledge of ethion's physical and chemical properties, toxicokinetics,

key health end points, mechanisms of action, human and animal exposure, and quantification of risk to

humans. All reviewers were selected in conformity with the conditions for peer review specified in

Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as

amended.

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer

reviewers' comments and determined which comments will be included in the profile. A listing of the

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their

exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and

a list of unpublished documents cited are also included in the administrative record.

The citation of the peer review panel should not be understood to imply its approval of the profile's final

content. The responsibility for the content of this profile lies with the ATSDR.

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CONTENTS

FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v

QUICK REFERENCE FOR HEALTH CARE PROVIDERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

CONTRIBUTORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

PEER REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

LIST OF FIGURES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

LIST OF TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix

1. PUBLIC HEALTH STATEMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.1 WHAT IS ETHION? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.2 WHAT HAPPENS TO ETHION WHEN IT ENTERS THE ENVIRONMENT? ........... 2

1.3 HOW MIGHT I BE EXPOSED TO ETHION? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

1.4 HOW CAN ETHION ENTER AND LEAVE MY BODY? ........................... 4

1.5 HOW CAN ETHION AFFECT MY HEALTH? .................................... 4

1.6 HOW CAN ETHION AFFECT CHILDREN? ...................................... 6

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ETHION? . . . . . . . . . . . . 7

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED 

TO ETHION? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO

PROTECT HUMAN HEALTH? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

1.10 WHERE CAN I GET MORE INFORMATION? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

2. HEALTH EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

2.1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE . . . . . . . . . . . . . . . . . 13

2.2.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.1 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.2 Systemic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.3 Immunological and Lymphoreticular Effects . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.4 Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.5 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.6 Developmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.7 Genotoxic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.1.8 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

2.2.2.1 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

2.2.2.2 Systemic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

2.2.2.3 Immunological and Lymphoreticular Effects . . . . . . . . . . . . . . . . . . . . . . 36

2.2.2.4 Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

2.2.2.5 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

2.2.2.6 Developmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

2.2.2.7 Genotoxic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

2.2.2.8 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
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2.2.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

2.2.3.1 Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

2.2.3.2 Systemic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

2.2.3.3 Immunological and Lymphoreticular Effects . . . . . . . . . . . . . . . . . . . . . . 42

2.2.3.4 Neurological Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2.2.3.5 Reproductive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2.2.3.6 Developmental Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2.2.3.7 Genotoxic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2.2.3.8 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2.3 TOXICOKINETICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

2.3.1 Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

2.3.1.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

2.3.1.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

2.3.1.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

2.3.2 Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

2.3.2.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

2.3.2.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

2.3.2.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

2.3.2.4 Other Routes of Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

2.3.3 Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

2.3.4 Elimination and Excretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

2.3.4.1 Inhalation Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

2.3.4.2 Oral Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

2.3.4.3 Dermal Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

2.3.4.4 Other Routes of Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

2.3.5 Physiologically based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) 

Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

2.4 MECHANISMS OF ACTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

2.4.1 Pharmacokinetic Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

2.4.2 Mechanisms of Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

2.4.3 Animal-to-Human Extrapolations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

2.5 RELEVANCE TO PUBLIC HEALTH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

2.6 ENDOCRINE DISRUPTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

2.7 CHILDREN’S SUSCEPTIBILITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

2.8 BIOMARKERS OF EXPOSURE AND EFFECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

2.8.1 Biomarkers Used to Identify or Quantify Exposure to Ethion . . . . . . . . . . . . . . . . . . 75

2.8.2 Biomarkers Used to Characterize Effects Caused by Ethion . . . . . . . . . . . . . . . . . . . 76

2.9 INTERACTIONS WITH OTHER CHEMICALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

2.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE . . . . . . . . . . . . . . . . . . . . . . . 78

2.11 METHODS FOR REDUCING TOXIC EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

2.11.1 Reducing Peak Absorption Following Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

2.11.2 Reducing Body Burden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

2.11.3 Interfering with the Mechanism of Action for Toxic Effects . . . . . . . . . . . . . . . . . . . 79

2.12 ADEQUACY OF THE DATABASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

2.12.1 Existing Information on Health Effects of Ethion . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

2.12.2 Identification of Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

2.12.3 Ongoing Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

3. CHEMICAL AND PHYSICAL INFORMATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

3.1 CHEMICAL IDENTITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

3.2 PHYSICAL AND CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
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4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

4.1 PRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

4.2 IMPORT/EXPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

4.3 USE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

4.4 DISPOSAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

5. POTENTIAL FOR HUMAN EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

5.1 OVERVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

5.2 RELEASES TO THE ENVIRONMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

5.2.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

5.2.2 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

5.2.3 Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

5.3 ENVIRONMENTAL FATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

5.3.1 Transport and Partitioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

5.3.2 Transformation and Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

5.3.2.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

5.3.2.2 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

5.3.2.3 Soil Transformation and Degradation . . . . . . . . . . . . . . . . . . . . . . . . . . . 108

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT . . . . . . . . . . . . . . . 109

5.4.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

5.4.2 Water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

5.4.3 Sediment and Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

5.4.4 Other Environmental Media . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE . . . . . . . . . . . . . . . . . . 119

5.6 EXPOSURES OF CHILDREN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES . . . . . . . . . . . . . . . . . . . . . . 128

5.8 ADEQUACY OF THE DATABASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

5.8.1 Identification of Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

5.8.3 Ongoing Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

6. ANALYTICAL METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

6.1 BIOLOGICAL SAMPLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

6.2 ENVIRONMENTAL SAMPLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

6.3 ADEQUACY OF THE DATABASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

6.3.1 Identification of Data Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

6.3.2 Ongoing Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

7. REGULATIONS AND ADVISORIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

8. REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

9. GLOSSARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

APPENDICES

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A-1

B. USER'S GUIDE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B-1

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C-1
ETHION xvi

LIST OF FIGURES

2-1 Levels of Significant Exposure to Ethion — Oral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

2-2 Proposed Mammalian Pathways of Ethion Biotransformation . . . . . . . . . . . . . . . . . . . . . . . . . 45

2-3 Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model 

for a Hypothetical Chemical Substance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

2-4 Existing Information on Health Effects of Ethion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

5-1 Frequency of NPL Sites with Ethion Contamination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

5-2 Transformation of Ethion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

ETHION xviii

LIST OF TABLES

2-1 Levels of Significant Exposure to Ethion — Oral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

2-2 Levels of Significant Exposure to Ethion — Dermal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

2-3 Genotoxicity of Ethion In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

3-1 Chemical Identity of Ethion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

3-2 Physical and Chemical Properties of Ethion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

5-1 Percentage of Ethion Remaining in Various Types of Tropical Soils over Time . . . . . . . . . 110

5-2 Ethion Intakes from Foods for Infants, Children, and Adults in the U.S. Population (in

mg/kg/day) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

6-1 Analytical Methods for Determining Ethion and Metabolites in Biological Samples . . . . . . 136

6-2 Analytical Methods for Determining Ethion in Environmental Samples . . . . . . . . . . . . . . . . 138

7-1 Regulations and Guidelines Applicable to Ethion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148

ETHION 1

1. PUBLIC HEALTH STATEMENT

This public health statement tells you about ethion and the effects of exposure. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for

long-term federal cleanup activities. Ethion has been found in at least 9 of the 1,577 current or

former NPL sites. However, the total number of NPL sites evaluated for this substance is not

known. As more sites are evaluated, the sites at which ethion is found may increase. This

information is important because exposure to this substance may harm you and because these

sites may be sources of exposure.

When a substance is released from a large area, such as an industrial plant, or from a container,

such as a drum or bottle, it enters the environment. This release does not always lead to

exposure. You are exposed to a substance only when you come in contact with it. You may be

exposed by breathing, eating, or drinking the substance, or by skin contact.

If you are exposed to ethion, many factors determine whether you’ll be harmed. These factors

include the dose (how much), the duration (how long), and how you come in contact with it. 

You must also consider the other chemicals you’re exposed to and your age, sex, diet, family

traits, lifestyle, and state of health.

1.1 WHAT IS ETHION?

Ethion is a chemical used in agriculture as a pesticide. Ethion does not occur naturally in the

environment but is manufactured by industry. Pure ethion is a clear-to-yellowish liquid with an

unpleasant sulfur type of smell. Most of the ethion used in pest control is diluted with other

liquids and used as a spray. It is also sometimes used as a liquid adsorbed on dust or granules. 

Ethion is sold under many trade names including Bladan®, Rodicide®, and Nialate®. The ethion 
ETHION 2

1. PUBLIC HEALTH STATEMENT

present at hazardous waste sites will most likely be in a liquid solution or adsorbed on solid 

granules.

Ethion is a member of a group of pesticides known as organophosphates. Diazinon and

chlorpyrifos (Dursban®) are other members of this group.

In 1989, about one million pounds of ethion were used in the United States. In 1992, about

868,218 pounds of ethion were used in the United States in farming. The main use of ethion is for

insect control on citrus trees. It is also used on cotton, fruit and nut trees, and a variety of

vegetables. Ethion may also be used on lawns and turf grasses. Ethion is not used in the home

for pest control.

You will find further information on the properties and uses of ethion in Chapters 3 and 4 of this

profile.

1.2 WHAT HAPPENS TO ETHION WHEN IT ENTERS THE ENVIRONMENT?

Ethion enters the air, water, and soil during its manufacture and use. Wastes containing ethion

that are generated during its manufacture and use are sometimes disposed of in landfills. Ethion

can enter the environment from these landfills. Ethion also enters the environment from

accidental spills during transport and leaks from storage containers.

Ethion evaporates only slightly into the air. Ethion that does evaporate can react with oxygen in

the air. Ethion in air is estimated to break down in a day or two. These breakdown products are

not believed to be harmful.

If ethion is spilled into a lake or river, a small portion will dissolve, but most of it will bind to

particles in the water. Ethion can react with water and be broken down. In a test in an irrigation

canal, one-half of the ethion broke down in 26 days. Laboratory experiments show that the less

acidic the water is, the more rapidly ethion is broken down.
ETHION 3

1. PUBLIC HEALTH STATEMENT

Ethion binds tightly to soil. This means it will not move through soil. Bacteria and other

microorganisms (microscopic plants and animals) in the soil break down ethion. The breakdown

in soil is less rapid than in air or water. Depending on the temperature and type of soil, it can take

anywhere from 1 month to 1 year for half of the ethion in soil to break down.

Ethion does not seem to be stored or concentrated in the bodies of people or most animals. It is

not known if ethion is stored or concentrated by plants or fish.

You will find further information about what happens to ethion in the environment in Chapter 5

of this profile.

1.3 HOW MIGHT I BE EXPOSED TO ETHION?

The general population may be exposed to very small amounts of ethion by eating or drinking. 

Ethion has been found only rarely in drinking water in the United States. Ethion has been found

on raw foods (fruits, vegetables) at very low concentrations. These concentrations are usually far

below the maximum limits established by the EPA.

People living near hazardous waste sites containing ethion or near its manufacturing, processing,

or storage facilities could potentially be exposed. Because of the chemical properties of ethion,

the most likely way a person would be exposed is by skin contact with soil contaminated by

ethion.

You are most likely to be exposed to ethion if you are involved in manufacturing or using it. 

Chemical plant workers, transport workers, and pesticide applicators are the major occupational

groups that might be exposed to ethion. People in these groups are mainly exposed by skin

contact, but some exposure can also occur by breathing in air containing ethion.

You will find further information on the potential for exposure to ethion in Chapter 5.
ETHION 4

1. PUBLIC HEALTH STATEMENT

1.4 HOW CAN ETHION ENTER AND LEAVE MY BODY?

Ethion can enter your body through your lungs if it is in the air you breathe. It can also enter your

body through your stomach if it is in your drinking water or food. It can also enter through your

skin. How much ethion enters your body depends on how long you are exposed and the amount

to which you are exposed.

Once ethion enters your body, it goes into your bloodstream and is carried to all the organs in

your body. Ethion is converted by an enzyme in your liver to its active form, called ethion

monoxon. There are other enzymes in your liver and blood that rapidly break down both ethion

and ethion monoxon. These breakdown products are less harmful than ethion. Most of these

breakdown products quickly leave your body in the urine. Ethion and its breakdown products are

not stored in your body.

You will find further information on how ethion enters and leaves your body in Chapter 2. 

1.5 HOW CAN ETHION AFFECT MY HEALTH?

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people

who have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and

released by the body; for some chemicals, animal testing may be necessary. Animal testing may

also be used to identify health effects such as cancer or birth defects. Without laboratory animals,

scientists would lose a basic method to get information needed to make wise decisions to protect

public health. Scientists have the responsibility to treat research animals with care and

compassion. Laws today protect the welfare of research animals, and scientists must comply with

strict animal care guidelines.
ETHION 5

1. PUBLIC HEALTH STATEMENT

Ethion is a member of a group of chemicals called organophosphates. Some of these chemicals

can kill insects and are widely used as insecticides. At higher doses than those used to kill

insects, these chemicals can also be harmful to people. Ethion can chemically react with an

important enzyme in your brain and nerves called acetylcholinesterase and stop it from working

properly. When this happens, signals sent between your nerve cells and to your muscles are

disrupted.

We do not know how much ethion is necessary to cause harmful effects in people. This is

because few people have been exposed to enough ethion to cause symptoms of poisoning. If you

have been poisoned by ethion, you will suddenly feel nauseated, anxious, and restless. You may

also vomit, have tearing of the eyes, and heavy sweating. If this happens, you should seek

medical attention immediately. Emergency rooms have drugs that stop the harmful effects of

ethion. Further symptoms can include loss of bladder control, blurring or dimness of vision,

muscle tremors, and labored breathing. Severe poisoning can result in coma, inability to breathe,

and death.

Poisoning cases have occurred in people who accidentally drank ethion or who got it on their

skin. If you use ethion in your work, it is extremely important that you follow all directions

printed on the container.

People who have survived poisoning by ethion make a complete recovery, although this can

sometimes take several months. Ethion poisoning does not appear to cause permanent damage to

the nerves (a condition called "delayed neuropathy").

Volunteers who took capsules containing 0.15 milligrams ethion per kilogram of body weight

(0.15 mg/kg) daily for 21 days showed no harmful effects. In studies where animals (rats and

mice) have been fed ethion, about half the animals died when given approximately 100 mg/kg. 

Before the animals died, they showed signs of harmful effects to their nervous systems similar to

those seen in human poisoning cases.
ETHION 6

1. PUBLIC HEALTH STATEMENT

It is not known if exposure to ethion can affect fertility in people. Results of experiments done in

animals that were fed ethion did not show any effect on fertility.

There is no evidence that exposure to ethion increases the risk of cancer in people. Rats and mice

that were fed ethion for 2 years had the same rate of cancer as rats and mice that did not receive

ethion. Ethion has not been classified for carcinogenicity by the Department of Health and

Human Services (DHHS), the International Agency for Research on Cancer (IARC) or the EPA. 

You will find further information on how ethion may affect your health in Chapter 2.

1.6 HOW CAN ETHION AFFECT CHILDREN?

This section discusses potential health effects from exposures during the period from conception

to maturity at 18 years of age in humans.

Children playing on or near hazardous waste sites may be exposed to ethion in soil by skin

contact, accidentally putting soil into their mouths, through hand to mouth activity, or eating dirt

on purpose. They can also be exposed through food and drink. Since children have more fruit

and fruit drinks in their diets, their exposure to ethion may be higher than for adults when you

adjust for the difference in weight.

One case of ethion poisoning occurred in a 6-month-old boy. He had symptoms of harmful

effects on his nervous system (muscle twitching, lack of coordination, pinpoint pupils, difficulty

breathing). These symptoms are the same as those seen in adults and can be treated with drugs. 

It is not known if there are health effects in adults who were exposed as children. There is not

enough information to tell if ethion is more harmful to young animals than adult animals.

We do not know whether children differ from adults in their susceptibility to health effects from

ethion.
ETHION 7

1. PUBLIC HEALTH STATEMENT

Newborn babies of pregnant animals that were exposed to very high doses of ethion showed a

delayed development of the skeleton. Animals that were fed ethion at doses that did not cause

symptoms of poisoning did not show significant effects on the health or development of their

newborn babies. It is not known if ethion exposure to parents can affect development of the fetus

in the womb or the newborn child.

Ethion and one of its metabolites (a substance created when something is changed in the body,

soil, or water), ethion monoxon, can probably cross the placenta; however, no measurements have

been made in people or animals. Ethion and ethion monoxon can appear in breast milk. Ethion

appeared in goat milk after skin exposure in an animal experiment. Additional information about

ethion in breast milk can be found in Chapters 2 and 5.

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ETHION?

If your doctor finds that you have been exposed to significant amounts of ethion, ask whether

your children might also be exposed. Your doctor might need to ask your state health department

to investigate.

It may be possible to carry ethion from work on your clothing, skin, hair, tools, or other objects

removed from the workplace. This might happen if you work as a pesticide applicator in

agriculture, but no actual incidents where this has happened have been observed before. You

might contaminate your car, home, or other locations outside work where children might be

exposed to ethion. You should know about this possibility if you work with ethion. 

Your occupational health and safety officer at work can and should tell you whether chemicals

you work with are dangerous and likely to be carried home on your clothes, body, or tools, and

whether you should be showering and changing clothes before you leave work, storing your street

clothes in a separate area of the workplace, or laundering your work clothes at home separately

from other clothes. Material safety data sheets (MSDS) should be found at your place of work for

many of the chemicals used there, as required by the Occupational Safety and Health 
ETHION 8

1. PUBLIC HEALTH STATEMENT

Administration (OSHA). MSDS information should include chemical names and hazardous

ingredients, and important properties, such as fire and explosion information, potential health

effects, how you get the chemical(s) in your body, how to handle the materials properly, and what

to do in the case of emergencies. Your employer is legally responsible for providing a safe

workplace and should freely answer your questions about hazardous chemicals. OSHA or your

state OSHA-approved occupational safety and health program can answer any further questions

and help your employer identify and correct problems with hazardous substances. Your state

OSHA-approved occupational safety and health program or OSHA will listen to your formal

complaints about workplace health hazards and inspect your workplace when necessary. 

Employees have a right to safety and health on the job without fear of punishment.

If you buy over-the-counter pesticide products to apply yourself, be sure that the products are in

unopened pesticide containers that are labeled and contain an EPA registration number. Carefully

follow the instructions that are labeled on the pesticide container. In the case of ethion, it is not

intended for indoor use except in greenhouses. The use of ethion is only permitted for use by

proper personnel and it is illegal for the general public to use this compound at their residence. 

Pesticides and household chemicals should be stored out of reach of young children to prevent

unintentional poisonings. Always store pesticides and household chemicals in their original

labeled containers. Never store pesticides or household chemicals in containers children would

find attractive to eat or drink from, such as old soda bottles. 

Your children may be exposed to ethion if unqualified people apply pesticides around your home. 

In some cases, the improper use of pesticides banned for use in homes has turned homes into

hazardous waste sites. Make sure that any person you hire is licensed and, if appropriate,

certified to apply pesticides. Your state licenses each person qualified to apply pesticides using

EPA standards and further certifies each person qualified to apply “restricted use” pesticides. Ask

to see the license and certification. Also ask for the brand name of the pesticide, an MSDS, the

name of the product's active ingredient(s), and the EPA registration number. Ask whether EPA

has designated the pesticide “for restricted use” and what the approved uses are. If you feel sick

after the use of ethion, consult your doctor or local poison control center.
ETHION 9

1. PUBLIC HEALTH STATEMENT

Children can be exposed to pesticides by playing on a lawn too soon after a pesticide has been

applied. Carefully read and follow the directions on the pesticide label about how long to wait

before re-entering the treated area.

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN

EXPOSED TO ETHION?

Two blood tests are available that can determine whether you have been exposed to significant

amounts of ethion. These tests can be performed by any hospital or clinical laboratory. These

tests measure the activity of two enzymes (called plasma cholinesterase and erythrocyte [red

blood cell] acetylcholinesterase) that are affected by ethion. Ethion affects these enzymes at

lower levels of exposure than are necessary to produce harmful effects. This means that if these

enzymes have been affected, you will not necessarily have effects on your health. Many other

insecticides also affect these enzymes. To determine whether you have been exposed specifically

to ethion, a laboratory test must measure its breakdown products in your urine. Tests of this type

are not routinely done in hospital laboratories, and your doctor will have to send a sample to a

special laboratory. Both the blood and urine tests are most accurate if done within a few days of

exposure. These tests cannot tell you if you have been exposed to ethion if the exposure took

place more than 2–3 months before the test is done. 

You will find further information on how you can be tested for exposure to ethion in Chapter 2.

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO

PROTECT HUMAN HEALTH?

The federal government develops regulations and recommendations to protect public health. 

Regulations can be enforced by law. Federal agencies that develop regulations for toxic

substances include the Environmental Protection Agency (EPA), the Occupational Safety and

Health Administration (OSHA), and the Food and Drug Administration (FDA). 

Recommendations provide valuable guidelines to protect public health but cannot be enforced by

law. Federal organizations that develop recommendations for toxic substances include the
ETHION 10

1. PUBLIC HEALTH STATEMENT

Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for

Occupational Safety and Health (NIOSH).

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or

food that are usually based on levels that affect animals; then they are adjusted to help protect

people. Sometimes these not-to-exceed levels differ among federal organizations because of

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal

studies, or other factors.

Recommendations and regulations are also periodically updated as more information becomes

available. For the most current information, check with the federal agency or organization that

provides it. Some regulations and recommendations for ethion include the following:

Regulations for maximum limits of ethion on food products, ranging from 0.1 to 14 parts per

million (ppm), have been established by EPA.

NIOSH recommends that ethion concentrations in workplace air not exceed 0.4 milligrams per

cubic meter (mg/m3

) for a 10-hour time-weighted average (TWA).

1.10 WHERE CAN I GET MORE INFORMATION?

If you have any more questions or concerns, please contact your community or state health or

environmental quality department or

Agency for Toxic Substances and Disease Registry

Division of Toxicology

1600 Clifton Road NE, Mailstop E-29

Atlanta, GA 30333

* Information line and technical assistance

Phone: 1-888-42-ATSDR (1-888-422-8737)

Fax: (404) 639-6359
ETHION 11

1. PUBLIC HEALTH STATEMENT

ATSDR can also tell you the location of occupational and environmental health clinics. These

clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to

hazardous substances.

* To order toxicological profiles, contact

National Technical Information Service

5285 Port Royal Road

Springfield, VA 22161

Phone: (800) 553-6847 or (703) 605-6000

ETHION 13

2. HEALTH EFFECTS

2.1 INTRODUCTION

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and

other interested individuals and groups with an overall perspective on the toxicology of ethion. It contains

descriptions and evaluations of toxicological studies and epidemiological investigations and provides

conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile.

2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE

To help public health professionals and others address the needs of persons living or working near

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation,

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive,

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more).

Levels of significant exposure for each route and duration are presented in tables and illustrated in

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or

lowest-observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the

studies. LOAELS have been classified into "less serious" or "serious" effects. "Serious" effects are

those that evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute

respiratory distress or death). "Less serious" effects are those that are not expected to cause significant

dysfunction or death, or those whose significance to the organism is not entirely clear. ATSDR

acknowledges that a considerable amount of judgment may be required in establishing whether an end

point should be classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some

cases, there will be insufficient data to decide whether the effect is indicative of significant dysfunction. 

However, the Agency has established guidelines and policies that are used to classify these end points. 

ATSDR believes that there is sufficient merit in this approach to warrant an attempt at distinguishing

between "less serious" and "serious" effects. The distinction between "less serious" effects and "serious"

effects is considered to be important because it helps the users of the profiles to identify levels of 
ETHION 14

2. HEALTH EFFECTS

exposure at which major health effects start to appear. LOAELs or NOAELs should also help in

determining whether or not the effects vary with dose and/or duration, and place into perspective the

possible significance of these effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and

figures may differ depending on the user's perspective. Public health officials and others concerned with

appropriate actions to take at hazardous waste sites may want information on levels of exposure

associated with more subtle effects in humans or animals (LOAEL) or exposure levels below which no

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike.

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been

made for ethion. An MRL is defined as an estimate of daily human exposure to a substance that is likely

to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of

exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of

effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. 

MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs

can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. 

Appropriate methodology does not exist to develop MRLs for dermal exposure.

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990),

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an

example, acute inhalation MRLs may not be protective for health effects that are delayed in development

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic

bronchitis. As these kinds of health effects data become available and methods to assess levels of

significant human exposure improve, these MRLs will be revised.

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs.

Ethion is a pesticide, and its use is regulated under the Federal Insecticide, Fungicide, and Rodenticide

Act (FIFRA). Virtually all of the toxicity information on ethion is from unpublished studies performed
ETHION 15

2. HEALTH EFFECTS

by the manufacturer and submitted for review to the EPA. A few of these studies were unable to be

retrieved by ATSDR. In these cases, NOAEL and LOAEL values were taken from study summaries in

“Guidance for the Reregistration of Pesticide Products Containing Ethion as the Active Ingredient” (EPA

1989d) and are so cited in the text.

2.2.1 Inhalation Exposure

2.2.1.1 Death

Male and female rats (number and strain not specified) were exposed to technical ethion via inhalation

and the LC50 (lethal concentration, 50% kill), was calculated. The acute inhalation LC50 was 2.31 mg/m3

for male rats and 0.45 mg/m3 for females (Feiser 1983 as cited in EPA 1989d).

No studies were located regarding the following effects in humans or animals after inhalation exposure

to ethion:

2.2.1.2 Systemic Effects

2.2.1.3 Immunological and Lymphoreticular Effects

2.2.1.4 Neurological Effects

2.2.1.5 Reproductive Effects

2.2.1.6 Developmental Effects

2.2.1.7 Genotoxic Effects

Genotoxicity studies are discussed in Section 2.5.

2.2.1.8 Cancer

No studies were located regarding cancer in humans or animals afer inhalation exposure to ethion.
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2. HEALTH EFFECTS

2.2.2 Oral Exposure

2.2.2.1 Death

No studies were located regarding death in humans after oral exposure to ethion.

Several acute lethality studies have demonstrated the high toxicity of ethion by the oral route. In a study

reporting results for 98 (single dose) pesticides, (Gaines 1969) LD50 (lethal dose, 50% kill) values for

ethion via gavage were 65 mg/kg for male and 27 mg/kg for female Sherman rats. The minimum

survival time was 3 hours for males and 4 hours for females. The maximum time to death was 9 days for

males and 6 days for females. The lowest dose to kill a rat was 50 mg/kg for males and 20 mg/kg for

females. LD1 (lethal dose, 1% kill) values were calculated at 27 mg/kg/males and 15 mg/kg for females. 

In a toxicokinetic study in Sprague-Dawley rats (Selim 1985a), two of seven males died after a gavage

dose of 100 mg/kg; clinical signs of toxicity preceding death included salivation, tremors, diarrhea, and

convulsions. Five of seven females died after receiving 25 mg/kg. Female rats appear to be more

susceptible to ethion than males, but no explanations have been proposed.

Multiple oral exposures to ethion at lower doses in animals have generally not resulted in fatalities. For

example, no deaths occurred in pregnant Charles River rats receiving up to 2.5 mg/kg/day ethion by

gavage over gestation days (Gd) 6–15 (Hoberman et al. 1983a) or pregnant New Zealand rabbits

receiving up to 9.6 mg/kg/day over Gd 6–18 (Hoberman et al. 1983b).

In an intermediate-duration exposure to ethion in feed to groups of albino rats (25/dose/sex), survival

was similar after 96 days at doses of #9 mg/kg/day in males and 10 mg/kg/day in females (Keller and

Paynter 1958). No deaths occurred in the parental generation (F0) in a three-generation reproductive

study in CD rats (Enloe and Salamon 1985). Exposure to ethion in feed was #1.25 mg/kg/day for

236–238 days. One of a group of four female Beagle dogs was sacrificed in a moribund condition after

90 days of exposure to ethion in feed at a dose of 8.25 mg/kg/day (Bailey 1988). Clinical signs included

emesis, dehydration, and thin body mass. The other females in the group and the males exposed at

#6.9 mg/kg/day survived.

In a 2-year feeding study in Sprague-Dawley rats and CF1 mice (Morrow 1985a, 1985b), survival was

similar between control and treated groups. Exposures in rats were #2 mg/kg/day (80/dose/sex) and

#1.2 mg/kg/day in mice (10–50/dose/sex).
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2. HEALTH EFFECTS

All reliable LD50 values and LOAELs for death in each species and duration category are recorded in

Table 2-1 and plotted in Figure 2-1.

2.2.2.2 Systemic Effects

Most, if not all, of the systemic effects observed after oral exposure to ethion are the result of the

neurological effects of this chemical (see Section 2.2.2.4).

The highest NOAEL values and all LOAEL values from each reliable study for each systemic effect in

each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1.

Respiratory Effects. A 6-month-old boy who accidentally ingested 15.7 mg/kg ethion from a

contaminated milk bottle presented with diaphragmatic respiration with shallow excursions and

intercostal retraction (Comstock et al. 1967). Respiratory rate was 60/minute. Auscultation revealed

generalized rales and rhonchi and inspiratory and expiratory wheezes. Symptoms appeared one hour

following ingestion and were treated with atropine and Protopam® (pralidoxime). Approximately

5 hours after ingestion, respiratory arrest occurred and mechanical ventilation was necessary for the next

3 hours. Treatment with atropine and pralidoxime continued for 5 days until symptoms ceased. Followup examinations after 1 week, 1 month, and 1 year indicated that a complete recovery was made by this

patient. The respiratory effects seen in this case are consistent with cholinergic overstimulation caused

by ethion (see Section 2.2.2.4).

Histopathological examinations of respiratory tract tissues after oral exposure to ethion in animals have

shown no effect of treatment. Doses and durations include 96 days in male and female albino rats at

#10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats

at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day

(Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Cardiovascular Effects. Tachycardia was reported in a 6-month-old boy who accidentally ingested

15.7 mg/kg ethion (Comstock et al. 1967).

Blood pressure and pulse rate were measured in a group of 6 male volunteers (age range, 23–43 years)

who were given ethion in corn oil solutions in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) via














ETHION 32

2. HEALTH EFFECTS

gelatin capsule (Palazzolo 1970). Doses were 0.05 mg/kg/day for 21 consecutive days, 0.075 mg/kg/day

for the next 21 days, 0.10 mg/kg/day for the next 21 days, and 0.15 mg/kg/day for the next 3 days. 

Controls (n=4; age range, 22–40 years) received gelatin capsules containing corn oil. No differences

were noted between the control and test groups or between individual pre-treatment, treatment, or posttreatment results for blood pressure or pulse rate.

Histopathological examinations of cardiovascular tissues (heart, aorta) after oral exposure to ethion in

animals have shown no effect of treatment. Doses and durations include 96 days in male and female

albino rats at #10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female

Sprague-Dawley rats at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at

#1.2 mg/kg/day (Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day

(Bailey 1988).

Gastrointestinal Effects. Gastrointestinal effects reported in a 6-month-old boy who accidentally

ingested 15.7 mg/kg ethion (Comstock et al. 1967) included frothy saliva 1 hour after ingestion and a

watery bowel movement at 90 minutes. Bowel sounds were hyperactive and an episode of emesis

occurred 5 hours after ingestion.

Diarrhea was reported in Sprague-Dawley rats exposed to ethion by gavage at 10 mg/kg in females and

100 mg/kg in males (Selim 1985a). Severe signs of neurotoxicity (convulsions) were also present. The

gastrointestinal effects seen in both cases are consistent with cholinergic overstimulation of the

gastrointestinal tract.

Histopathological examinations of gastrointestinal tract tissues after oral exposure to ethion in animals

have shown no effect of treatment. Doses and durations include 96 days in male and female albino rats

at #10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley

rats at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day

(Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Hematological Effects. Significant hematological effects have not been observed in two cases of

human exposure to ethion. In a poisoning case of a 6-month-old boy who accidentally ingested

15.7 mg/kg ethion, hematocrit, hemoglobin level, and red blood cell (RBC) and platelet counts were
ETHION 33

2. HEALTH EFFECTS

normal (Comstock et al. 1967). White blood cell (WBC) counts were initially slightly depressed but

returned to normal after 1 day.

Similar results were seen for intermediate-duration oral exposure in a group of 6 male volunteers (age

range, 23–43 years) who were given ethion in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) via

gelatin capsule (Palazzolo 1970). Doses were 0.05 mg/kg/day for 21 consecutive days, 0.075 mg/kg/day

for the next 21 days, 0.1 mg/kg/day for the next 21 days, and 0.15 mg/kg/day for the next 3 days. 

Controls (n=4; age range, 22–40 years) received gelatin capsules containing corn oil. Blood studies

(hemoglobin concentration, hematocrit, RBC, and total and differential leukocyte counts) were

performed on days -15 and -1 of the pretreatment period, at the end of each of the 4 treatment periods,

and after a 19-day recovery period after dosing ended. No differences were noted between the control

and test groups or between individual pre-treatment, treatment, or post-treatment results for any of the

parameters.

Analysis of hematological parameters after oral exposure to ethion in animals has shown no effect of

treatment. Doses and durations include 96 days in male and female albino rats at #10 mg/kg/day in feed

(Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats at #2 mg/kg/day

(Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day (Morrow 1985b), and

13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Musculoskeletal Effects. Oral exposure to ethion can result in muscle tremors and fasciculations. 

These effects are discussed in Section 2.2.2.4, Neurological Effects.

The effect of intermediate-duration oral exposure to ethion on muscle tone was assessed in a group of

6 male volunteers (age range, 23–43 years) who were given ethion in 3 divided doses (9:00 a.m., noon,

and 5:00 p.m.) via gelatin capsule (Palazzolo 1970). Doses were 0.05 mg/kg/day for

21 consecutive days, 0.075 mg/kg/day for the next 21 days, 0.1 mg/kg/day for the next 21 days, and

0.15 mg/kg/day for the next 3 days. Controls (n=4; age range, 22–40 years) received gelatin capsules

containing corn oil. Muscle tone was assessed at the beginning and end of each treatment period. No

differences were noted between the control and test groups or between individual pre-treatment,

treatment, or post-treatment results.
ETHION 34

2. HEALTH EFFECTS

Histopathological examinations of musculoskeletal tissues (bone, skeletal muscle) after oral exposure to

ethion in animals have shown no effect of treatment. Doses and durations include 96 days in male and

female albino rats at #10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female

Sprague-Dawley rats at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at

#1.2 mg/kg/day (Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day

(Bailey 1988).

Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to

ethion.

Histopathological examinations of the liver after oral exposure to ethion in animals have shown no effect

of treatment. Doses and durations include 96 days in male and female albino rats at #10 mg/kg/day in

feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats at #2 mg/kg/day

(Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day (Morrow 1985b), and

13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Renal Effects. Proteinurea and increased urinary WBC counts were observed in a severely

intoxicated 6-month-old boy who accidentally ingested 15.7 mg/kg ethion (Comstock et al. 1967).

An increased incidence of orange-colored urine was observed in pregnant New Zealand rabbits receiving

ethion by gavage at 2.4, or 9.6 mg/kg/day during Gd 6–18 (Hoberman et al. 1983b). This effect was not

observed at 0.6 mg/kg/day. Urinalysis was not performed.

Histopathological examinations of the kidney and bladder after oral exposure to ethion in animals have

shown no effect of treatment. Doses and durations include 96 days in male and female albino rats at

#10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats

at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day

(Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Endocrine Effects. No studies were located regarding endocrine effects in humans after oral

exposure to ethion.
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2. HEALTH EFFECTS

Histopathological examinations of endocrine tissues (pituitary, thyroid, parathyroid, thymus, adrenals)

after oral exposure to ethion in animals have shown no effect of treatment. Doses and durations include

96 days in male and female albino rats at #10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months

in male and female Sprague-Dawley rats at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and

female CF1 mice at #1.2 mg/kg/day (Morrow 1985b), and 13 weeks in male and female Beagle dogs at

#8.25 mg/kg/day (Bailey 1988).

Dermal Effects. No studies were located regarding dermal effects in humans after oral exposure to

ethion.

Histopathological examinations of the skin after oral exposure to ethion in animals have shown no effect

of treatment. Doses and durations include 96 days in male and female albino rats at #10 mg/kg/day in

feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats at #2 mg/kg/day

(Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day (Morrow 1985b), and

13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Ocular Effects. Histopathological examinations of the eye after oral exposure to ethion in animals

have shown no effect of treatment. Doses and durations include 96 days in male and female albino rats

at #10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley

rats at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day

(Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).

Body Weight Effects. No studies were located regarding body weight effects in humans after oral

exposure to ethion.

An unspecified body weight decrease occurred in New Zealand rabbit does receiving 2.4 mg/kg/day

ethion via gavage over Gd 6–18. No effect on body weight was seen at 0.6 mg/kg/day (Hoberman et al.

1983b). No effect was observed on body weight in male and female dogs receiving #0.71 mg/kg/day in

the diet for 13 weeks (Bailey 1988).

Body weight decreases accompanied by reduced food consumption have been observed in New Zealand

rabbit does receiving 9.6 mg/kg/day ethion via gavage over Gd 6–18 (Hoberman et al. 1983b) and in

male and female Beagle dogs receiving 6.9 and 8.25 mg/kg/day, respectively, in feed (Bailey 1988). In
ETHION 36

2. HEALTH EFFECTS

other studies where doses were low enough that overt signs of cholinergic toxicity were not observed,

body weight was unaffected (Keller and Paynter 1958; Morrow 1985a, 1985b).

2.2.2.3 Immunological and Lymphoreticular Effects

No studies were located regarding immunological/lymphoreticular effects in humans after oral exposure

to ethion.

Histopathological examinations of immunological/lymphoreticular tissues after oral exposure to ethion

in animals have shown no effect of treatment. Doses and durations include 96 days in male and female

albino rats at #10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female

Sprague-Dawley rats at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at

#1.2 mg/kg/day (Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day

(Bailey 1988).

2.2.2.4 Neurological Effects

Ethion exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. This

enzyme, which is present at cholinergic synapses throughout the central and peripheral nervous systems, 

is responsible for hydrolyzing acetylcholine released from the pre-synaptic terminal. If this enzyme is

inhibited, acetylcholine accumulates in the synapse, resulting in increased firing of the post-synaptic

neuron or increased neuroeffector activity. The consequences of increased cholinergic activity in the

parasympathetic autonomic nervous system (muscarinic receptors) can include increased salivation,

lacrimation, perspiration, miosis, nausea, vomiting, diarrhea, excessive bronchial secretions, bradycardia,

frequent micturition, and incontinence. The effects of increased neuroeffector activity on skeletal

muscles (nicotinic receptors) can include muscle fasciculations, cramps, muscle weakness, and

depolarization-type paralysis. Effects on cholinergic synapses in the central nervous system

(predominantly muscarinic) can result in drowsiness, fatigue, mental confusion, headache, convulsions,

and coma. These classical symptoms of organophosphate neurotoxicity increase in severity and rapidity

of onset in a dose-dependent manner (Ecobichon 1991).

Acetylcholinesterase is also present in erythrocytes where it is referred to as erythrocyte acetylcholinesterase. Both forms of acetylcholinesterase are produced by the same gene (Taylor et al. 1993). In
ETHION 37

2. HEALTH EFFECTS

in vitro assays, erythrocyte and neural acetylcholinesterase are inhibited to roughly the same extent by

exposure to organophosphate compounds with insecticide activity (Hayes 1982). Measurement of

erythrocyte acetylcholinesterase is used as a surrogate for the inhibition of neural acetylcholinesterase. 

A cholinesterase capable of hydrolyzing acetylcholine is also produced by the liver and circulates in the

blood. This enzyme, called plasma cholinesterase, is also inhibited by ethion and other

organophosphates and can be used as a marker for exposure. The endogenous substrate of this enzyme

is unknown. Experiments in both humans and animals show that this enzyme is inhibited by ethion at

lower levels of exposure than required to inhibit neural or erythrocyte acetylcholinesterase (Bailey 1988;

Palazzolo 1970).

A case report of a 6-month-old boy who accidentally ingested 15.7 mg/kg ethion from a contaminated

milk bottle illustrates the toxic neurological effects of ethion (Comstock et al. 1967). Symptoms

appeared one hour following ingestion. The child awoke crying and choking on frothy saliva. He was

unable to control his head and limbs and subsequently had a watery bowl movement, and became limp

(depolarization-type paralysis). Occasional twitching movements of the hands and around the mouth

were noted. Upon admission to the hospital, he was slightly cyanotic with a generalized flaccid paralysis

and areflexia. Respiration was increased (60/min) as was heartbeat (200/min). Pupils were pinpoint and

nonreactive to light, and eye movements were purposeless. Salivation was excessive but not copious. 

Respiration was diaphragmatic with shallow respiratory excursions and intercostal retraction. 

Generalized rales and rhonchi and inspiratory and expiratory wheezes were noted. The liver and spleen

were palpable. Bowel sounds were hyperactive. There were no abnormal heart sounds. Treatment with

atropine and pralidoxime was started immediately. Approximately 5 hours after ingestion, respiratory

arrest occurred and mechanical ventilation was necessary for the next 3 hours. Laboratory and

roentgenologic studies showed protein in the urine and increased WBC in the urine. Treatment with

atropine and pralidoxime continued for 5 days until symptoms ceased. Follow-up examinations after

1 week, 1 month, and 1 year indicated that a complete recovery was made by this patient.

A study with male volunteers established oral levels of exposure to ethion that had no adverse effect in

humans (Palazzolo 1970). Male volunteers (n=6; age range, 23–43 years) were given ethion in corn oil

solutions in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) of 0.05, 0.075, 0.1, and 0.15 mg/kg/day via

gelatin capsule. Controls (n=4; age range, 22–40 years) received gelatin capsules containing corn oil. 

Medical histories and baseline plasma cholinesterase and erythrocyte acetylcholinesterase activities were

determined prior to the start of the study (days -15, -11, -8, -4, and -1). Blood samples were taken prior
ETHION 38

2. HEALTH EFFECTS

to dose administration. Subjects received 0.05, 0.075, and 0.1 mg/kg/day for 3 weeks each. 

Cholinesterase determinations were conducted on days 1, 3, 7, 14, and 21 for these dose levels. Subjects

received 0.15 mg/kg for 3 days and cholinesterase determinations were made on days 1 and 3. A 19-day

recovery period followed, and cholinesterase determinations were made on days 7, 12, and 19. At the

beginning and end of each treatment period, pupil size, light reflex, eye accommodation, muscle tone,

knee jerk, tongue tremor, and finger tremor were measured.

No effect on erythrocyte acetylcholinesterase was observed at any time during the study. No effect on

plasma cholinesterase were observed at the 0.05 mg/kg/day dose level. Statistically significant decreases

from pretreatment values were observed for all plasma cholinesterase determinations during the 0.075,

0.1, and 0.15 mg/kg/day treatment periods. A 16% decrease in plasma cholinesterase activity was seen

in the 0.075 mg/kg/day group. Decreases of 23 and 31% were seen at the 0.1 and 0.15 mg/kg/day levels. 

A partial recovery of plasma cholinesterase levels was seen after 7 days of recovery, and a complete

recovery was seen after 12 days. No clinical signs of adverse neurological effects were observed.

Severe neurological effects have also been observed in rats after a single oral exposure to ethion. Male

Sprague-Dawley rats receiving 100 mg/kg ethion in corn oil by gavage had cholinergic signs, including

salivation, tremors, nose bleeding, urination, diarrhea, and convulsions (Selim 1985a). Female rats

exhibited these same signs at a 10-fold lower dose (10 mg/kg). In another acute oral exposure to ethion,

groups of pregnant Charles River rats (n=25) were administered ethion via gavage at doses of 0, 0.2, 0.6,

and 2.5 mg/kg from Gd 6 to 15 (Hoberman et al. 1983a). An increased incidence of hyperactivity was

observed in dams in the 2.5 mg/kg group. Incidence was 2/25 in control, 3/25 at 0.2 mg/kg/day, 1/26 at

0.6 mg/kg/day, and 11/25 at 2.5 mg/kg/day (p<0.01). No other statistically significant physical signs

were observed.

No reports were located describing organophosphate-induced delayed neurotoxicity (OPIDN) in humans

after oral exposure to ethion. This is a syndrome observed in humans and some animal models after

recovery from the acute cholinergic effects of certain organophosphorus compounds, for example

tri-o-cresyl phosphate (Ecobichon 1991). The characteristic signs are disturbances of gait and ataxia

beginning 7–14 days after exposure, progressing to severe muscular weakness and paralysis. 

Histological analysis reveals a "dying-back" type degeneration of motor fibers. This condition can be

produced in chickens and cats but not in other test species. In a test to determine the potential of ethion

to cause delayed neurotoxicity, 4 groups of 10 chickens received a single gavage dose of 2,792 mg/kg
ETHION 39

2. HEALTH EFFECTS

ethion in corn oil after protection from acute cholinergic effects with 10 mg/kg atropine given

intramuscularly (Roberts et al. 1986). Preliminary experiments determined that this dose is equal to the

LD50 for ethion in chickens with atropine prophylaxis. A positive control group received 500 mg/kg of

the known delayed neurotoxic agent tri-o-cresyl phosphate in corn oil, the control group received vehicle

only. As expected, acute cholinergic signs were observed (inability to stand or walk, unsteadiness,

lethargy) in the treated groups including deaths in 14 of the 40 chickens dosed. However, after recovery

from the acute effects, no clinical or histopathological signs of delayed neurotoxicity were observed in

the ethion groups. These signs were observed in the tri-o-cresyl phosphate group. 

In an intermediate-duration feeding study in albino rats (Keller and Paynter 1958) significant inhibition

of cholinesterase activities was observed at and above ethion doses of 3 mg/kg/day. Plasma

cholinesterase was most sensitive to inhibition, followed by erythrocyte and then brain

acetylcholinesterase. For example, for males receiving 9 mg/kg/day in the diet for 93 days, brain

acetylcholinesterase was inhibited 22%, erythrocyte acetylcholinesterase 87%, and plasma cholinesterase

100%. This study also examined recovery of blood cholinesterases by putting the rats on a normal diet

for 14 days after the 93 day exposure to ethion. Plasma cholinesterase recovered completely over this

period while erythrocyte acetylcholinesterase recovered 63%. The no-effect level in this study was

1 mg/kg/day. In longer-term experiments in animals, groups of Sprague-Dawley rats (n=80/sex/group)

were fed diets resulting in ethion consumption of 0, 0.1, 0.2, and 2 mg/kg/day; no effect on erythrocyte

acetylcholinesterase was observed at 6, 12, or 18 months (Morrow 1985a). Significant neurological

effects were observed in dogs receiving higher doses of ethion (Bailey 1988). Groups of dogs

(n=4/sex/group) received ethion in the diet for 90 days, the average consumed was 0, 0.01, 0.06, 0.71,

and 6.9 mg/kg/day for males and 0, 0.012, 0.07, 0.71, and 8.25 mg/kg/day for females. Clinical signs

included ataxia, emesis, miosis, and tremors in the highest-dose groups. Strong inhibition of both brain

(61–64%) and erythrocyte acetylcholinesterase (93–94%) was observed in the highest-dose groups. A

reduction of 23% in brain acetylcholinesterase was observed in males at 0.71 mg/kg/day and 64% at

6.9 mg/kg/day, no effect was seen at 0.06 and 0.01 mg/kg/day. Plasma cholinesterase activity was

inhibited in all groups except the low-dose males and females and was dose-related. No compoundrelated histopathological changes were observed in nervous system tissues (brain [with medulla/pons,

cerebellar cortex, and cerebral cortex], sciatic nerve, or spinal cord [cervical, thoracic, lumbar]). Based

on the NOAEL of 0.06 mg/kg/day for inhibition of brain acetylcholinesterase observed in this study, an

MRL of 0.002 mg/kg/day for oral exposure for the acute and intermediate durations was calculated, as
ETHION 40

2. HEALTH EFFECTS

well as a chronic-duration MRL of 0.0004 mg/kg/day. More information on this MRL and how it was

derived is located in footnote b of Table 2-1, in Section 2.5, and in Appendix A of this profile.

In chronic-duration experiments, a 3-generation reproduction study in albino rats that consumed ethion

in feed at 0, 0.1, 0.2, and 1.25 mg/kg/day, showed that plasma cholinesterase was inhibited in F1 and F2

females in the high-dose group. No effect was observed on erythrocyte acetylcholinesterase in any

group (Enloe and Salamon 1985). In 2-year carcinogenicity bioassay experiments, no effect on

erythrocyte acetylcholinesterase was observed at daily exposures of #2 mg/kg/day in rats and

#1.2 mg/kg/day in mice (Morrow 1985a, 1985b).

2.2.2.5 Reproductive Effects

No studies regarding reproductive effects in humans after oral exposure to ethion were located.

In a 3-generation reproduction study, ethion was administered to F0, F1, and F2 male (n=15) and female

(n=30) rats in the diet at concentrations of 0, 0.1, 0.2, and 1.25 mg/kg/day. No effect on reproduction

was observed (Enloe and Salamon 1985). Indices measured were: mating index (number of

copulations/number of estrus cycles utilized), fertility index (number of pregnancies/number of

copulations), gestation (number of parturitions/number of pregnancies), female fertility (number of

pregnancies/number of females mated), and male fertility (number of sires/number of males mated).

Histopathological examinations of reproductive tissues after oral exposure to ethion in animals have

shown no effect of treatment. Doses and durations include 96 days in male and female albino rats at

#10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats

at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF1 mice at #1.2 mg/kg/day

(Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988)

2.2.2.6 Developmental Effects

No studies regarding developmental effects in humans after oral exposure to ethion were located.

Three studies examining the effects of ethion on development in animals are available. Groups of

pregnant Charles River rats (n=25) were administered ethion in a corn oil vehicle via gavage at doses of
ETHION 41

2. HEALTH EFFECTS

0, 0.2, 0.6, and 2.5 mg/kg from Gd 6 to 15 (Hoberman et al. 1983a). Dams were observed and skeletal

examinations were performed on the fetuses. Fetuses from the 2.5 mg/kg group had an increased

incidence of delayed ossification of pubes. Groups of pregnant New Zealand rabbits (n=17) received

ethion via gavage at doses of 0, 0.6, 2.4, and 9.6 mg/kg from Gd 6 to 18 (Hoberman et al. 1983b). Does

were observed for clinical signs. Does in the 2.4 and 9.6 mg/kg/day groups had an increased incidence

of orange-colored urine; however, this was not considered to be a toxic effect. Additionally, does in

these groups had decreased body weights (not specified). Food consumption was also reduced in the

9.6 mg/kg/day females. Fetuses in the 9.6 mg/kg/day group had an increased incidence of fused sterna

centra.

In a 3-generation reproduction study, ethion was administered to F0, F1, and F2 male (n=15) and female

(n=30) rats in the diet at concentrations of 0, 0.1, 0.2, and 1.25 mg/kg/day. No effect was observed on

pup viability, survival, body weight, or structural development (Enloe and Salamon 1985).

2.2.2.7 Genotoxic Effects

No studies were located regarding genotoxic effects in humans after oral exposure to ethion. Twentyfour hours after a single oral dose (2 mg/kg), ethion induced a small, but statistically significant, increase

in the frequency of sister chromatid exchanges in white Leghorn chicks (Bhunya and Jena 1994). No

other studies on the genotoxicity of ethion following oral exposure in animals were located.

Genotoxicity studies are discussed in Section 2.5.

2.2.2.8 Cancer

No studies regarding carcinogenicity in humans after oral exposure to ethion were located.

In 2-year carcinogenicity bioassays, groups of Sprague-Dawley rats (n=80/sex/group) receiving diets

containing ethion at 0, 0.1, 0.2, and 2 mg/kg/day had similar tumor incidences (Morrow 1985a). Similar

results were observed in CF1 mice receiving 0, 0.113, 0.225, and 1.2 mg/kg/day (Morrow 1985b).
ETHION 42

2. HEALTH EFFECTS

2.2.3 Dermal Exposure

2.2.3.1 Death

No studies were located regarding death in humans following dermal exposure to ethion.

In a study comparing LD50 values for 98 pesticides, including ethion, groups of 80 male and 60 female

adult Sherman rats were dermally dosed with technical-grade ethion dissolved in xylene (Gaines 1969). 

The calculated LD50 value was 245 mg/kg for males and 62 mg/kg for females. The minimum survival

time was 3 hours for males and 6 hours for females. The maximum time to death was 7 days for males

and 3 days for females. The lowest dose to kill a rat was 150 mg/kg for males and 50 mg/kg for females. 

LD1 values were calculated at 100 mg/kg for males and 34 mg/kg for females. The LD50 values for death

in rats are shown in Table 2-2.

2.2.3.2 Systemic Effects

No studies were located regarding systemic effects in humans following dermal exposure to ethion. The

only systemic effects reported in animals after dermal exposure to ethion are dermal effects in rabbits.

Dermal Effects. Groups of rabbits (n=6/sex/dose) received dermal applications of technical-grade

ethion at doses of 0, 1, 3, 25, and 250 mg/kg for 21 days (Weiner 1985a as cited in EPA 1989d). An

increased incidence of erythema and desquamation was observed at the application sites in both male

and females of the 25 and 250 mg/kg group.

2.2.3.3 Immunological and Lymphoreticular Effects

No studies regarding immunological and lymphoreticular effects in humans after dermal exposure to

ethion were located. 

Groups of guinea pigs (number and sex not specified) were dermally exposed to technical-grade ethion

in a skin sensitization test (Freeman 1984 as cited in EPA 1989d). Ethion caused slight erythema which

cleared within 48 hours. Ethion was determined not to be a skin sensitizer.

ETHION 44

2. HEALTH EFFECTS

2.2.3.4 Neurological Effects

No studies regarding neurological effects in humans after dermal exposure to ethion were located. 

Inhibition of brain acetylcholinesterase was observed in rabbits after dermal exposure to ethion for

21 days at 1 mg/kg/day, (Weiner 1985a, 1985b as cited in EPA 1989d). The NOAEL in these studies

was 0.8 mg/kg/day.

No studies were located regarding the following health effects after dermal exposure to ethion:

2.2.3.5 Reproductive Effects

2.2.3.6 Developmental Effects

2.2.3.7 Genotoxic Effects

Genotoxicity studies are discussed in Section 2.5.

2.2.3.8 Cancer

2.3 TOXICOKINETICS

Ethion is a small (MW 384), lipid-soluble molecule that can be absorbed by passive diffusion through the

lungs, gastrointestinal tract, or skin. Absorption appears to be rapid by the oral and dermal routes; the

time course of absorption is inferred from the onset of clinical signs within 1 hour after accidental

ingestion of ethion in a 6-month-old boy (Comstock et al. 1967) and deaths within 3–6 hours in dermally

exposed Sherman rats (Gaines 1969). Ethion is desulfurated by cytochrome P-450 enzymes in the liver to

its active form, ethion monoxon, which causes toxicity due to its potent inhibition of neural acetylcholinesterase. Ethion and its oxon form can be detoxified by the action of esterases in the blood and liver,

producing diethyl phosphate, diethyl thiophosphate, diethyl dithiophosphate, and other metabolites that

have not been characterized. A proposed pathway for ethion metabolism is presented in Figure 2-2. 

Information on other aspects of toxicokinetics (distribution, metabolism, elimination/excretion) is limited

by the nature of the studies available. Most toxicokinetic studies using ethion were designed to assess the

persistence of ethion and its metabolites in meat or milk in the event that livestock were exposed to

ethion-contaminated feed. Animals were exposed to [14C-methylene]ethion and tissues harvested at
H5C2O

P

S

S C

H2

S P

S OC2H5

H OC2H5 5C2O

desulfuration cytochrome P-450

H5C2O

P

S

S C

H2

S P

O OC2H5

H OC2H5 5C2O

 esterases

(Ethion Monooxon)

(P-S bond) (C-S bond)

H5C2O

P

S

S

H5C2O

CH2

SH

HO

P

O OC2H5

OC2H5

+

H5C2O

P

S

S

H5C2O

S P

O OC2H5

OC2H5 CH2 + HO

DEDTP

H5C2O

P

S

S

H5C2O

CH3

H5C2O

P

O

S

H5C2O

CH3

(Ethion)

DEP

furthermetabolism,conjugation?

urine urine

furthermetabolism,conjugation

urine

1 2

urine

mice

Figure 2-2. Proposed Mammalian Pathways of Ethion Biotransformation

Source: Mahajna et al. 1996; Nigg et al. 1993; Rao and McKinley 1969DEP = diethylphosphate; DEDTP = diethyldithiophosphateâ O,O-diethyl-S-mercaptomethyldithiophosphateã O,O-diethyl-S-hydroxymethylphosphate
ETHION 46

2. HEALTH EFFECTS

various times after exposure, and radioactivity was measured by liquid scintillation in ashed samples and

expressed as ethion "equivalents." These experiments show that ethion and its metabolites are not stored

in the body; however, since chemical characterization of the residues was not performed, no distinction

can be made between the kinetics of the parent compound, active metabolite, and nontoxic metabolites.

2.3.1 Absorption

No information is available for any route as to whether absorption of ethion is different between children

and adults or between juvenile and adult animals.

2.3.1.1 Inhalation Exposure

Absorption of ethion after inhalation exposure can be inferred from lethality reported in rats in an LC50

test (Feiser 1983 as cited in EPA 1989d). Time to death is not available from this summary, so no

inference can be drawn as to how rapidly the ethion was absorbed.

2.3.1.2 Oral Exposure

Rapid absorption of ethion by the oral route in humans can be inferred from the onset of clinical signs

within 1 hour after accidental ingestion of ethion in a 6-month-old boy (Comstock et al. 1967). 

Gastrointestinal absorption of ethion appears to be $80% in the rat based on residue studies performed

with [14C-methylene]ethion (Selim 1985a). In these studies, 75–85% of the total label was excreted in

urine and 4–8% in feces. This pattern was the same whether labeled ethion was administered as a single

dose or as the last dose after 14 days of dosing with unlabeled ethion.

2.3.1.3 Dermal Exposure

Dermal absorption of ethion has been measured in humans (Feldman and Maibach 1974). Radiolabeled

ethion ([14C]-specific activity not reported) was applied to the ventral forearm of 6 male volunteers at a

concentration of 4 μg/cm2

 in acetone. The authors stated that this was equivalent to a thin film of a 0.25%

solution. The skin sites were not protected, and the subjects were asked not to wash the area for 24 hours. 

All urine was collected for 5 days in a total of 8 samples (0–4, 4–8, 8–12, 12–24 hours, and the

4 subsequent 24-hour periods). Radioactivity in the urine was determined by combustion and liquid
ETHION 47

2. HEALTH EFFECTS

scintillation counting. Results were calculated as percentage of applied dose corrected for incomplete

urinary excretion using results from a parallel experiment where labeled ethion was administered

intravenously. Over 24 hours, 3.3% of the dose was absorbed as calculated from urinary excretion of

radioactivity.

In a study in goats dermally exposed with one application of 100 mg/kg ethion over a 600–700 cm2

 area,

ethion in the blood was measured for 14 days (Mosha et al. 1990b). Unchanged ethion appeared in blood

throughout the study and the t1/2 for absorption was calculated as 85 hours, indicating that dermally

applied ethion stays in the epidermis and is absorbed for a prolonged period.

2.3.2 Distribution

No information is available for any route as to whether distribution of ethion is different between children

and adults or between juvenile and adult animals. Similarly, no information is available on whether

ethion or its metabolites cross the placenta. However, given the high lipophilicity of ethion and ethion

monoxon, it is probable that placental transfer occurs.

2.3.2.1 Inhalation Exposure

No studies were located regarding distribution of ethion after inhalation exposure in humans or animals.

2.3.2.2 Oral Exposure

No studies were located regarding distribution of ethion after oral exposure in humans.

Seven days after rats received a single gavage dose of radiolabeled ethion, less than 1% of the radiolabel

was detected in the body (blood, brain, heart, pancreas, leg muscle, lungs, adipose, spleen, bone, skin,

hair, kidney, liver, gonads [uterus and ovaries for females, testes, seminal vesicle, and prostate for males])

(Selim 1985a). Total residues ranged from 0.21 to 0.34% of the original dose for females; and

0.18–0.28% for males. Similar results were obtained in a study where the radioactive dose was given

after 14 consecutive daily doses of unlabeled ethion (Selim 1985a).
ETHION 48

2. HEALTH EFFECTS

In a study designed to assess the presence of ethion in milk after oral exposure, two lactating goats (40 kg,

strain not stated) were orally administered [14C-methylene]ethion by capsule twice daily for

7 consecutive days (Jobsis and Zeitlow 1985). Test animals were sacrificed 4 hours after the final dose

and the animals dissected. Tissues (blood, adductor muscle, pectoral muscle, liver, heart, kidney,

peritoneal fat, and renal fat) along with daily milk samples taken during the test period were assayed for

residues by combustion and liquid scintillation counting. Total daily dose was 1.12 mg/kg/day. The

authors stated that this was comparable to a dietary level of 45–70 ppm in feed. Highest residue levels

(radioactivity as ethion equivalents) were in liver (13–14 ppm) and kidney (7–9 ppm). Levels in muscle

and heart tissues were approximately 1 ppm, and levels in fat were approximately 0.2 ppm. Levels in

milk were approximately 1.2 ppm.

Unchanged ethion (the monoxon was not measured) was detected in goat milk after oral (~1.4% of

administered activity) exposure to ethion. Equilibrium dialysis indicated that ethion was >99% bound to

plasma proteins (Mosha et al. 1990b). Radioactivity derived from labeled ethion was present in goat milk

after oral exposure (Jobsis and Zeitlow 1985); however, the chemical identity of the radioactivity was not

determined. 

2.3.2.3 Dermal Exposure

No studies were located regarding distribution of ethion after dermal exposure in humans. One animal

study (Mosha et al. 1990b) examined the levels of ethion in goat milk following dermal exposure,

reporting 0.04–0.05% of the total dose to be found in the milk. No other animal studies on the

distribution of ethion following dermal exposure were located.

2.3.2.4 Other Routes of Exposure

A study by Mosha (1990b) examined the distribution of [14C-methylene]ethion following a single

intravenous administration in male and female goats. All tissues examined (kidney, liver, muscle, fat,

heart, lung, and brain) had 14C levels similar to or higher than the corresponding concentration in plasma,

with the highest concentrations found in liver, kidney, and fat. No differences in distribution between

male and female goats were noted.
ETHION 49

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2.3.3 Metabolism

While the basic features of ethion metabolism are known, detailed information is lacking. Like other

organothiophosphate insecticides (chlorpyrifos, parathion), ethion is converted via desulfuration in the

liver by cytochrome P-450 enzymes to its active oxygen analogue, ethion monoxon (Rao and McKinley

1969) (see Figure 2-2). It is not known if ethion monoxon can then be desulfurated to ethion dioxon. 

Ethion monoxon is a potent inhibitor of cholinesterases and exerts toxicity by reacting with and inhibiting

neural acetylcholinesterase. The breakdown of ethion and ethion monoxon has not been characterized but

is presumed to be by esterases in the blood and liver. Cleavage of the monoxon at the P-S bond would

result in diethyl phosphate and a transient intermediate (O,O-diethyl-S-mercaptomethyldithiophosphate). 

Cleavage can occur in humans at both the P-S bond and the S-C bond, based on the detection of diethyl

phosphate (P-S cleavage of the monoxon), diethyl thiophosphate (P-S cleavage of ethion or S-C cleavage

of the monoxon), and diethyl dithiophosphate (S-C cleavage of ethion) in the urine of pest control

workers using ethion (Nigg et al. 1993). Relative amounts were not reported. Evidence in mice for

cleavage at the S-C bond and subsequent methylation of the sulfur has also been presented (Mahajna et al.

1996). Further metabolism of the product(s) of the esterase reaction continues but how it happens is

unknown. Elimination from the body is mainly through excretion of water-soluble metabolites in the

urine. Conjugation may occur, this is inferred from experiments where [14C-methylene]ethion was

administered orally to rats and the radioactivity in urine analyzed (Selim 1985b). Samples were extracted

with ethyl acetate; the aqueous and organic phases were analyzed by high-performance liquid

chromatography (HPLC). More than 99% of the urine radioactivity was in the aqueous phase. Another

sample was acidified (presumably to hydrolyze conjugates) and also extracted with ethyl acetate. 

Acidification converted about 30% of the radioactivity in the aqueous phase to an organosoluble form,

which may indicate that some of the products of ethion metabolism are present in urine as conjugates. 

Four to six radiolabeled metabolites were detected by HPLC, none migrated with standards for ethion,

ethion monoxon, or ethion dioxon. None of the metabolites were specifically identified.

No information is available for any route as to whether the metabolism of ethion is different between

children and adults or between juvenile and adult animals.
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2.3.4 Elimination and Excretion

No information is available for any route as to whether elimination and excretion of ethion is different

between children and adults or between juvenile and adult animals.

2.3.4.1 Inhalation Exposure

No studies were located regarding elimination or excretion following inhalation exposure to ethion in

humans or animals.

2.3.4.2 Oral Exposure

No studies were located regarding elimination or excretion following oral exposure to ethion in humans.

Ethion and its metabolites were readily excreted from male and female Sprague-Dawley rats exposed to

single and multiple dosing regimens of [14C-methylene]ethion (Selim 1985a). A majority of the

administered dose (75–85%) was excreted in urine. Most of the elimination occurred within 24 hours of

dosing. Elimination also occurred by feces (4–8%) and respiratory gases (CO2) (3–4%). Following oral

exposure to 10 mg/kg [14C]ethion in goats, 64% was excreted in the urine, 14% in the feces, and 1.7% in

the milk (total recovery was 80%) (Mosha et al. 1990b).

2.3.4.3 Dermal Exposure

Excretion in urine accounted for 3.3% (SD +1.1%) of the [14C]ethion radioactivity applied to the skin of

volunteers for 24 hours over the 5 days following application (Feldman and Maibach 1974). Diethyl

phosphate, diethyl thiophosphate, and diethyl dithiophosphate were detected in the urine of pest control

workers using ethion and the carbamate pesticide, benomyl (Nigg et al. 1993). Total ethion metabolites

(benomyl does not contain phosphorus) ranged from 0.30 to 7.0 ppm/day in a group of six workers;

metabolites were not detected in two control workers not directly engaged in spraying. Relative amounts

of the metabolites were not reported. Exposure is presumed to be primarily dermal. Unchanged ethion

(the monoxon was not measured) was detected in goat milk after dermal exposure to ethion (Mosha et al.

1990b). A total of 0.04–0.05% of the dose appeared in the milk.
ETHION 51

2. HEALTH EFFECTS

2.3.4.4 Other Routes of Exposure

Mosha (1990b) reported that following a single intravenous exposure to 2 mg/kg of [14C-methylene]ethion in goats, one third of the administered activity was excreted in the urine within the first

24 hours. Two weeks following administration, a total of 66% of the administered activity was excreted

in the urine, with another 8% found in the feces, and 4% in the milk (total recovery for the study was

78%). The identities of the excreted compounds were not determined. After intravenous exposure of

2 mg/kg [14C] ethion to goats in another study, the peak of ethion in milk was 1.2 ppm (Mosha 1991).

2.3.5 Physiologically based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and

disposition of chemical substances to quantitatively describe the relationships among critical biological

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to

delineate and characterize the relationships between: (1) the external/exposure concentration and target

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al.

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from

route to route, between species, and between subpopulations within a species. The biological basis of

PBPK models results in more meaningful extrapolations than those generated with the more conventional

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen
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2. HEALTH EFFECTS

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The

numerical estimates of these model parameters are incorporated within a set of differential and algebraic

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations

provides the predictions of tissue dose. Computers then provide process simulations based on these

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is

adequately described, however, this simplification is desirable because data are often unavailable for

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of

PBPK models in risk assessment.

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 2-3 shows a conceptualized representation of a PBPK model.

If PBPK models for ethion exist, the overall results and individual models are discussed in this section in

terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations.

No PBPK models exist for ethion. Toxicokinetic information is insufficient for modeling.

2.4 MECHANISMS OF ACTION

2.4.1 Pharmacokinetic Mechanisms

The pharmacokinetics of ethion have not been extensively studied. Ethion appears to be rapidly absorbed

by the oral route. It is less well absorbed by the dermal route, but absorption may be prolonged as a

consequence of using the epidermis as an intermediate storage depot (Feldman and Maibach 1974; 
ETHION 53

2. HEALTH EFFECTS

Skin

Kidney

Richly

perfused

tissues

Slowly 

perfused

tissues

Fat

Liver

Lungs

A

R

T

E

R

I

A

L

B

L

O

O

D

V

E

N

O

U

S

B

L

O

O

D

GI

Tract

Vmax Km

Urine

Chemicals in air

contacting skin

Inhaled chemical Exhaled chemical

Ingestion

Feces

Figure 2-3. Conceptual Representation of a Physiologically Based

Pharmacokinetic (PBPK) Model for a Hypothetical Chemical Substance

Source: adapted from Krishnan et al. 1994

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by

inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation.
ETHION 54

2. HEALTH EFFECTS

Mosha et al. 1990b). Ethion is a small, lipophilic molecule and would be expected to be absorbed rapidly

across cell membranes. Ethion is absorbed by passive diffusion from the gut, lungs, and skin to the

blood. Ethion is desulfurated in the liver to its active metabolite, ethion monoxon. Some ethion

monoxon and ethion can be inactivated by plasma cholinesterase or erythrocyte and neural acetylcholinesterase, but based on total esterase activity in the body, the liver is probably the major site of

metabolism. The toxicity of a given dose of ethion depends on how rapidly neural acetylcholinesterase is

inhibited; if this occurs before metabolic processes can reduce the blood level of ethion and ethion

monoxon, significant toxicity will take place.

The reversibility of the reaction between ethion monoxon and neural acetylcholinesterase has not been

studied. Based on studies with other diethyl organophosphates, it is probable that recovery of activity

will depend on de novo synthesis of acetylcholinesterase rather than spontaneous reactivation (Ecobichon

1991).

2.4.2 Mechanisms of Toxicity

Ethion exerts its toxicity by inhibiting the neural acetylcholinesterase enzyme. Ethion is converted in the

liver to ethion monoxon, a chemical form with an electrophilic phosphorus that is predisposed to

nucleophilic attack. One potential nucleophile is the serine hydroxyl group located at the active site of

acetylcholinesterase. The result of this reaction is a diethoxyphosphorylated acetylcholinesterase

molecule. Over a time period of minutes to hours, a phenomenon known as “aging” can occur, whereby

the diethoxyphosphorylated acetylcholinesterase molecule undergoes a spontaneous dealkylation,

resulting in a monoethoxyphosphorylated acetylcholinesterase molecule, which is resistant to hydrolysis

of the oxygen-phosphorus bond that would result in the regeneration of function of the enzyme. (The

influence of the “aging” phenomenon on therapeutic interventions is discussed in section 2.11.3.) Neither

the monoethoxyphosphorylated nor the diethoxyphosphorylated forms of acetylcholinesterase are capable

of hydrolyzing acetylcholine. If this enzyme is inhibited, acetylcholine accumulates in the synapse and

can interfere with neuron functioning. The parasympathomimetic consequences include lacrimation,

perspiration, miosis, nausea, vomiting, diarrhea, excessive bronchial secretions, bradycardia, increased

salivation, and increased urinary frequency and incontinence. Effects on motor nerve fibers in the

skeletal muscles can include muscle fasciculations, cramps, muscle weakness, and flaccidity. Effects on

cholinergic synapses in the central nervous system result in drowsiness, fatigue, mental confusion,

headache, convulsions, and coma.
ETHION 55

2. HEALTH EFFECTS

The nervous system can accept a certain amount of acetylcholinesterase inhibition without overt toxic

effects. In humans and animals, toxic signs are generally not seen until at least 20% of this enzyme

(erythrocyte acetylcholinesterase used as a marker) has been inhibited (Ecobichon 1991). In an animal

study, brain acetylcholinesterase after a 2-year inhalation exposure to another organophosphate,

dichlorvos, was inhibited more than 90% compared to control animals (Blair et al. 1976), yet signs of

cholinergic overstimulation were not observed. With ethion and other organophosphate compounds, the

best predictor of toxicity is not necessarily the actual percentage inhibition of acetylcholinesterase, but

rather how rapidly this inhibition has occurred. Rapid inhibition does not give the nervous system time to

adapt to acetylcholinesterase inhibition. This adaptation appears to involve desensitization and downregulation of muscarinic receptors (Fitzgerald and Costa 1993).

There is no information available suggesting that the mechanism of toxicity of ethion is different between

children and adults. Symptoms of toxicity in a 6-month-old boy poisoned by ethion (Comstock et al.

1967) were similar to those seen in adults acutely intoxicated by other organophosphates. 

2.4.3 Animal-to-Human Extrapolations

Rats, dogs and goats all show clinical signs similar to those of humans after acute exposure to high doses

of ethion. Information is insufficient to make any extrapolations from animal toxicokinetics to humans.

2.5 RELEVANCE TO PUBLIC HEALTH

Overview. 

Ethion is an organophosphorus insecticide that has been in use in the United States and elsewhere since

the mid-1960s. Like other insecticides in this class, ethion is not only extremely toxic to insects, but also

can be toxic to humans if high enough doses are received. The toxicity of ethion results from its

inhibition of neural acetylcholinesterase. This enzyme is necessary to hydrolyze acetylcholine and

terminate its action at synapses and ganglionic and neuromuscular junctions. The clinical signs of ethion

toxicity are the result of overstimulation of the parasympathetic autonomic nervous system, somatic

nerve fibers, and cholinergic pathways in the brain. After acute exposure to high concentrations of

ethion by any route, signs such as lacrimation, perspiration, miosis, nausea, vomiting, diarrhea, bronchial

secretion, dyspnea, increased salivation, and urinary frequency and incontinence can result from 
ETHION 56

2. HEALTH EFFECTS

overstimulation of the parasympathetic autonomic nervous system. The actions of ethion at

neuromuscular junctions can result in muscle fasciculations (especially in fine facial muscles), cramps,

muscle weakness, and paralysis. Ethion can also act in the central nervous system to produce

drowsiness, fatigue, mental confusion, headache, convulsions, coma, and depression of respiratory

centers in the brain.

There is limited information on the toxicity of ethion to humans. The potential hazards of this chemical

were well known before it came into use because of experience with other organophosphorus

compounds. Exposure to levels of ethion high enough to cause clinical symptoms of organophosphorus

poisoning has been very rare in the United States. Clinical and biochemical signs of ethion toxicity in

humans can be reproduced in animals. The metabolites of ethion are polar compounds that are excreted

into the urine; thus, no potential for bioaccumulation exists. Laboratory studies in animals have not

shown adverse reproductive or adverse developmental effects at doses that did not cause maternal

toxicity. Ethion exposure has not been associated with organophosphate-induced delayed neurotoxicity

(OPIDN) in humans and did not cause this condition in the preferred test species, the domestic hen.

Ethion has tested negative for mutagenicity in a number of in vitro test systems. Evaluation using in

vivo test systems is limited to a single positive test for sister chromatid exchange in chickens (Bhunya

and Jena 1994). Two-year oral exposure studies with ethion in rats and mice showed no evidence of

carcinogenicity. Ethion has not been assessed for potential carcinogenicity in humans by the DHHS, the

IARC, or the EPA.

The most likely population to be exposed to ethion is pesticide applicators. Exposure occurs during

and/or after pesticide application. The National Institute of Occupational Safety and Health (NIOSH)

recommends that ethion concentrations in workplace air not exceed 0.4 mg/m3

 for a 10-hour timeweighted average (TWA). Health effects could occur in workplaces if proper industrial hygiene and

safety precautions are not followed. The exposure of the general population to ethion appears to be very

low. Ethion has not been detected in drinking water in the United States and rarely detected in outdoor

air (only at agricultural sites). Monitoring of the food supply by the U.S. Food and Drug Administration

(FDA) and other government agencies has detected ethion, but levels are very rarely above tolerance

levels set by the EPA. Thus, the risk of adverse health effects in the general population from ethion

exposure appears to be negligible.
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2. HEALTH EFFECTS

For people living near hazardous waste sites, the potential for adverse health effects would depend on the

amount of ethion to which they were exposed. Ethion has been detected in at least 9 of the 1,577

hazardous waste sites that have been proposed for inclusion on the EPA National Priorities List (NPL)

(HazDat 2000). However, the number of sites evaluated for ethion is not known. The most likely routes

of exposure for people living near hazardous waste sites would be by breathing ethion-contaminated air,

drinking ethion-contaminated water, or skin contact with ethion-contaminated soil. Monitoring of the

air, drinking water, and soil levels of ethion at these sites is necessary to predict the possibility of

adverse health effects.

Issues relevant to children are explicitly discussed in Sections 2.7, Children’s Susceptibility, and 5.6,

Exposures of Children.

Minimal Risk Levels for Ethion. 

Inhalation MRLs.

No MRLs have been derived for inhalation exposure to ethion. No studies in humans on the effects of

inhalation exposure to ethion were identified. The only animal study located (Fieser 1983 as cited in

EPA 1989d) did not establish effect levels for neurological effects.

Oral MRLs.

• An MRL of 0.002 mg/kg/day has been derived for intermediate-duration oral exposure

(15–364 days) to ethion. This MRL is also applicable to acute-duration (14 days or less)

oral exposure to ethion.

• An MRL of 0.0004 mg/kg/day has been derived for chronic-duration (365 days or more)

oral exposure to ethion.

These MRLs are based on a NOAEL of 0.06 mg/kg/day for brain acetylcholinesterase activity observed

in dogs (Bailey 1988). To derive the intermediate-duration oral MRL, the NOAEL was adjusted by a

factor of 30, 3 for extrapolation of an animal study to humans and 10 for human variability. The purpose

of this study (Bailey 1988) was to evaluate the toxicity of ethion administered orally to dogs for

13 weeks. 
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Groups of Beagle dogs (n=4/sex/group, 20–28 weeks old) received ethion (purity 93.4%) in the diet at

target concentrations of 0, 0.5, 2.5, 25, and 300 ppm for 90 days. Food was available for 2 hours a day,

water was available ad libitum. The average amount of ethion consumed was 0, 0.01, 0.06, 0.71, and

6.9 mg/kg/day for males and 0, 0.012, 0.07, 0.71, and 8.25 mg/kg/day for females. All dogs were

observed twice daily for mortality and moribundity. Animals were observed once daily for clinical

signs. Body weights were recorded during acclimation and quarantine, on day 0 (one day prior to

initiation and during week 13. Clinical pathology parameters were evaluated for all dogs prior to

initiation of treatment (day -16) and during weeks 5, 9, and 13 and included cholinesterase activities

(plasma, erythrocyte, brain), hematology, and clinical chemistry. All surviving animals were sacrificed

following the 13-week treatment period. Histopathological examination of the following tissues was

conducted: lesions, brain (with medulla/pons, cerebellar cortex, and cerebral cortex), gallbladder,

pituitary, thyroid (parathyroid), thymus, lungs, trachea, heart, bone (femur), salivary glands

(mandibular), bone marrow (sternum), kidneys, uterus adrenals, liver, spleen, pancreas, testes (with

epididymides), ovaries, aorta, esophagus, stomach, duodenum, jejunum, ileum, colon, cecum, rectum,

urinary bladder, mesenteric lymph node, sciatic nerve, spinal cord (cervical, thoracic, lumbar), skin,

mammary gland, and eyes.

One female dog in the 8.25 mg/kg/day group was sacrificed on day 90 (1 day before schedule). Clinical

signs exhibited by this animal prior to sacrifice included emesis, dehydration, and thin body mass. All

other animals survived until terminal sacrifice. In the highest dose group (6.9 mg/kg/day for males,

8.25 mg/kg/day for females) clinical signs included miosis (all animals), emesis (all animals),

dehydration (3 males, 2 females), salivation (2 males, 2 females), and tremors (3 males, 4 females). 

Animals in this group appeared to be in generally poor condition at the end of the study. Erythrocyte

acetylcholinesterase was inhibited at weeks 5 (94% M, 96% F), 9 (95% M, 93% F), and 13 (94% M,

93% F) in the highest dose groups, but not in any of the other groups. Mean percent brain

acetylcholinesterase activity inhibition at termination was 64% in males and 61% in females at the

highest dose. Male brain acetylcholinesterase was inhibited 23% at 0.71 mg/kg/day but no inhibition of

brain acetylcholinesterase occurred in females at this dose. Plasma cholinesterase inhibition was doserelated in both males and females. No significant differences in absolute organ weights were observed

between treated and control animals. No compound-related Histopathological effects were observed in

any organ, including brain, sciatic nerve and spinal cord. The NOAEL for inhibition of brain

acetylcholinesterase is 0.06 mg/kg/day.

This study was chosen for MRL derivation because it identifies both a NOAEL and LOAELs for

inhibition of neural acetylcholinesterase, the target for ethion toxicity in humans. A study in albino rats
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fed ethion for 93 days established a NOAEL for brain acetylcholinesterase inhibition of 1 mg/kg/day

(Keller and Paynter 1958), which is higher than that used to derive the MRL. Neither erythrocyte nor

brain acetylcholinesterase activities were inhibited in rats (up to 2 mg/kg/day) or mice (up to

1.25 mg/kg/day) receiving ethion in the diet for 6 or 12 months (Morrow et al. 1985a, 1985b).

This MRL should be protective against adverse health effects in individuals potentially exposed to ethion

at hazardous waste sites. A study in volunteers (Palazzolo 1970) has determined the sensitivity of

humans to the effects of ethion on blood cholinesterase activities. A group of six male volunteers were

given ethion in corn oil solutions in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) of 0.05, 0.075, 0.1,

and 0.15 mg/kg/day via gelatin capsule. Subjects received 0.05, 0.075, and 0.1 mg/kg/day for 3 weeks

each and then 0.15 mg/kg/day for 3 days. No adverse clinical signs (blood pressure, pulse rate, pupil

size, light reflex, eye accommodation, chest sound, muscle tone, knee jerk, tongue tremor and finger

tremor) or effects on erythrocyte acetylcholinesterase were observed at any time during the study. 

Absorption of ethion by the volunteers was confirmed by a decrease in plasma cholinesterase levels. 

While no effect on plasma cholinesterase was observed at the 0.05 mg/kg/day dose level, a 16% decrease

was seen in the 0.075 mg/kg/day group. Decreases of 23 and 31% were seen in the 0.1 and

0.15 mg/kg/day groups.

To derive the intermediate oral MRL, the NOAEL of the Bailey (1988) study for inhibition of brain

acetylcholinesterase was adjusted by a factor of 10 for human variability and a factor of 3 for

extrapolation of an animal study to humans. A factor of 3 was used for extrapolation rather than the full

uncertainty factor of 10 because the results of the Palazzolo (1970) study indicated that dogs appear to

be at least as sensitive to the neurological effects of ethion as humans when exposed to comparable

doses.

The MRL value of 0.002 mg/kg/day for intermediate-duration oral exposure to ethion was extended to

acute oral exposure based on the toxicokinetics of ethion. Cholinesterase inhibition occurs quickly and

there are no indications of progressive inhibition over time at a given dose in either the Palazzolo (1970)

study in humans or the Bailey (1988) study in dogs. A similar lack of progression of inhibition was seen

in 2-year studies in rats and mice where brain and erythrocyte acetylcholinesterase and plasma

cholinesterase were measured at 6-month intervals (Morrow et al. 1985a, 1985b). The toxicity database

indicates no change in ethion toxicity over time (i.e., toxicity is dependent on the dose, not the duration

of exposure). Because the toxicological effects of ethion are due to a series of repeated acute exposures,

it is proposed that the intermediate-duration oral MRL should be protective for the acute exposure
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duration. For chronic duration, an additional modifying factor of 5 was applied to protect against

possible long-term effects, seen in structurally-related cholinesterase inhibitors, which might be the

result of mechanisms other than cholinesterase inhibition, and to protect against possible susceptibility in

children. Application of this factor resulted in a chronic-duration oral MRL of 0.0004 mg/kg/day.

Death. No studies were located describing death in humans after exposure to ethion. However,

without prompt medical attention, it is likely that a 6-month-old boy who ingested 15.7 mg/kg ethion

from a contaminated milk bottle would have died (Comstock et al. 1967).

Animal studies show that ethion is highly toxic by the oral route; reported LD50 values in the rat range

from 21 to 191 mg/kg. Deaths have also occurred by the inhalation and dermal route in animal studies.

Reported LD50 values for dermal exposure in rats range from 62 to 838 mg/kg while inhalation LC50

values range from 0.45 to 2.31 mg/m3 (Gaines 1969; Fieser 1983 as cited in EPA 1989d).

Systemic Effects. Ethion exerts its toxicity by inhibiting neural acetylcholinesterase in the central

and peripheral nervous systems. Some of these effects occur in different organ systems but are

ultimately the result of neurological effects. In animal studies where tissues have been examined

histopathologically, ethion does not appear to have direct effects on organ systems.

Respiratory Effects. Respiratory effects have been reported in humans after oral exposure to ethion. A

6-month-old boy who accidentally ingested 15.7 mg/kg ethion from a contaminated milk bottle

presented with diaphragmatic respiration with shallow excursions and intercostal retraction (Comstock et

al. 1967). Respiratory rate was 60/minute. Auscultation revealed generalized rales and rhonchi and

inspiratory and expiratory wheezes; all signs of increased secretions in the respiratory tract. Symptoms

appeared one hour following ingestion and were treated with atropine and pralidoxime. Approximately

5 hours after ingestion respiratory arrest occurred and mechanical ventilation was necessary for the next

3 hours. It is not known if respiratory arrest was due to muscular paralysis. The respiratory effects seen

in this case are consistent with cholinergic overstimulation caused by ethion.

Longer-term oral exposure at lower doses in animal experiments did not show effects on the respiratory

system. Histopathological examination of the lungs and trachea revealed no treatment-related lesions

several animal studies where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958;

Morrow et al. 1985a, 1985b). 
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Cardiovascular Effects. Tachycardia was reported in a 6-month-old boy who accidentally ingested

15.7 mg/kg ethion (Comstock et al. 1967).

Blood pressure and pulse rate were measured in a group of 6 male volunteers (age range, 23–43 years)

who were given ethion in corn oil solutions in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) via

gelatin capsule (Palazzolo 1970). Doses were 0.05 mg/kg/day for 21 consecutive days, 0.075 mg/kg/day

for the next 21 days, 0.1 mg/kg/day for the next 21 days, and 0.15 mg/kg/day for the next 3 days. 

Controls (n=4; age range, 22–40 years) received gelatin capsules containing corn oil. No differences

were noted between the control and test groups, or between individual pre-treatment, treatment, or posttreatment results for blood pressure or pulse rate.

Studies on the effects of ethion on electrical activity of the heart were not found in the literature.

Histopathological examination of the heart and aorta revealed no treatment-related lesions in several

animal studies where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et

al. 1985a, 1985b). 

Gastrointestinal Effects. Gastrointestinal effects reported in a 6-month-old boy who accidentally

ingested 15.7 mg/kg ethion (Comstock et al. 1967) included frothy saliva 1 hour after ingestion and a

watery bowel movement at 90 minutes. Bowel sounds were hyperactive and an episode of emesis

occurred 5 hours after ingestion.

Diarrhea was reported in Sprague-Dawley rats exposed to ethion by gavage at 10 mg/kg in females and

100 mg/kg in males (Selim 1985a). Severe signs of neurotoxicity (convulsions) were also present. The

gastrointestinal effects seen in both cases are consistent with cholinergic overstimulation of the

gastrointestinal tract.

Histopathological examination of gastrointestinal tissues (esophagus, stomach, duodenum, jejunum,

ileum, colon, cecum, rectum) revealed no treatment-related lesions in several animal studies where

exposure was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et al. 1985a, 1985b). 

Hematological Effects. Significant hematological effects have not been observed in two cases of human

exposure to ethion. In a poisoning case of a 6-month-old boy who accidentally ingested 15.7 mg/kg
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ethion, hematocrit, hemoglobin level, and RBC and platelet counts were normal (Comstock et al. 1967). 

WBC counts were initially slightly depressed but returned to normal after one day.

Similar results were seen for intermediate-duration oral exposure in a group of 6 male volunteers (age

range, 23–43 years) who were given ethion in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) via

gelatin capsule (Palazzolo 1970). Doses were 0.05 mg/kg/day for 21 consecutive days, 0.075 mg/kg/day

for the next 21 days, 0.1 mg/kg/day for the next 21 days, and 0.15 mg/kg/day for the next 3 days. 

Controls (n=4; age range, 22–40 years) received gelatin capsules containing corn oil. Blood studies

(hemoglobin concentration, hematocrit, RBC and total and differential leukocyte counts) were performed

on days -15 and -1 of the pretreatment period, at the end of each of the 4 treatment periods, and after a

19-day recovery period after dosing ended. No differences were noted between the control and test

groups, or between individual pre-treatment, treatment, or post-treatment results for any of the

parameters.

Hematological parameters (leukocyte count, erythrocyte count, hemoglobin, corrected leukocyte count,

hematocrit, platelet count, differential leukocyte count) were unaffected by treatment in several animal

studies where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et al.

1985a, 1985b).

Musculoskeletal Effects. Oral exposure to ethion can result in muscle tremor and fasciculations. These

effects are discussed under Neurological Effects.

The effect of oral exposure to ethion on muscle tone was assessed in a group of 6 male volunteers (age

range, 23–43 years) who were given ethion in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) via

gelatin capsule (Palazzolo 1970). Doses were 0.05 mg/kg/day for 21 consecutive days, 0.075 mg/kg/day

for the next 21 days, 0.1 mg/kg/day for the next 21 days, and 0.15 mg/kg/day for the next 3 days. 

Controls (n=4; age range, 22–40 years) received gelatin capsules containing corn oil. Muscle tone was

assessed at the beginning and end of each treatment period. No differences were noted between the

control and test groups or between individual pre-treatment, treatment, or post-treatment results.

Histopathological examination of the bone and skeletal muscle revealed no treatment-related lesions in

several animal studies where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958;

Morrow et al. 1985a, 1985b). 
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Hepatic Effects. No studies were located regarding hepatic effects in humans after oral exposure to

ethion.

Histopathological examination of the liver revealed no treatment-related lesions in several animal studies

where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et al. 1985a,

1985b).

Endocrine Effects. No studies were located regarding endocrine effects in humans after oral exposure to

ethion.

Histopathological examination of endocrine tissues (pituitary, thyroid, parathyroid, thymus and adrenals)

revealed no treatment-related lesions in several animal studies where exposure was via the oral route

(Bailey 1988; Keller and Paynter 1958; Morrow et al. 1985a, 1985b).

Renal Effects. Proteinuria and increased urinary WBC counts were observed in a severely intoxicated

6-month-old boy who accidentally ingested 15.7 mg/kg ethion (Comstock et al. 1967).

An increased incidence of orange-colored urine was observed in pregnant New Zealand rabbits receiving

2, 4, or 9.6 mg/kg/day during Gd 6–18 (Hoberman et al. 1983b). This effect was not observed at

0.6 mg/kg/day. The urine was not examined by chemical analyses.

Histopathological examination of the urinary bladder and kidneys revealed no treatment-related lesions

in several animal studies where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958;

Morrow et al. 1985a, 1985b).

Dermal Effects. No studies were located regarding dermal effects in humans after oral exposure to

ethion.

Histopathological examination of the skin revealed no treatment-related lesions in several animal studies

where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et al. 1985a,

1985b).

Ocular Effects. No studies were located regarding ocular effects in humans after oral exposure to

ethion. 
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Histopathological examination of the eyes revealed no treatment-related lesions in several animal studies

where exposure was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et al. 1985a,

1985b).

Body Weight Effects. No studies were located regarding body weight effects in humans after oral

exposure to ethion.

An unspecified body weight decrease occurred in New Zealand rabbit does receiving 2.4 mg/kg/day

ethion via gavage over Gd 6–18. No effect on body weight was seen at 0.6 mg/kg/day (Hoberman et al.

1983b). No effect was observed on body weight in male and female dogs receiving #0.71 mg/kg/day in

the diet for 13 weeks (Bailey 1988).

Body weight decreases accompanied by reduced food consumption have been observed in New Zealand

rabbit dams receiving 9.6 mg/kg/day ethion via gavage over Gd 6–18 and in male and female Beagle

dogs receiving 6 and 8.25 mg/kg/day, respectively, in feed (Bailey 1988).

Immunological and Lymphoreticular Effects. No studies were located regarding

immunological/lymphoreticular effects in humans after exposure to ethion.

Histopathological examination of immunological/lymphoreticular tissues (mesenteric lymph node,

thymus, bone marrow) revealed no treatment-related lesions in several animal studies where exposure

was via the oral route (Bailey 1988; Keller and Paynter 1958; Morrow et al. 1985a, 1985b). 

Neurological Effects. Ethion exerts its toxic effects in humans and animals by inhibiting neural

acetylcholinesterase. This enzyme is present at cholinergic synapses throughout the central and

peripheral nervous systems and is responsible for hydrolyzing acetylcholine released from the presynaptic terminal. If this enzyme is inhibited, acetylcholine accumulates in the synapse, resulting in

increased firing of the post-synaptic neuron or increased neuroeffector activity. The consequences of

increased cholinergic activity in the parasympathetic autonomic nervous system (muscarinic receptors)

can include increased salivation, lacrimation, perspiration, miosis, nausea, vomiting, diarrhea, excessive

bronchial secretions, bradycardia, frequent micturition, and incontinence. The effects of increased

neuroeffector activity on skeletal muscles (nicotinic receptors) can include muscle fasciculations,

cramps, muscle weakness, and depolarization-type paralysis. Effects on cholinergic synapses in the
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2. HEALTH EFFECTS

central nervous system (predominantly muscarinic) can result in drowsiness, fatigue, mental confusion,

headache, convulsions, and coma. These classical symptoms of organophosphate neurotoxicity increase

in severity and rapidity of onset in a dose-dependent manner (Ecobichon 1991).

Acetylcholinesterase is also present in erythrocytes where it is referred to as erythrocyte acetylcholinesterase. Both forms of acetylcholinesterase are produced by the same gene (Taylor et al. 1993). In

in vitro assays, erythrocyte and neural acetylcholinesterase are inhibited to roughly the same extent by

exposure to organophosphate compounds with insecticide activity (Hayes 1982). Measurement of

erythrocyte acetylcholinesterase is used as a surrogate of the inhibition of neural acetylcholinesterase. A

cholinesterase capable of hydrolyzing acetylcholine is also produced by the liver and circulates in the

blood. This enzyme, called plasma cholinesterase, is also inhibited by ethion and other organophosphates and can be used as a marker for exposure. The endogenous substrate of this enzyme is

unknown. Experiments in both humans and animals show that this enzyme is inhibited by ethion at

lower levels of exposure than required to inhibit neural or erythrocyte acetylcholinesterase (Bailey

1988).

A case study of a 6-month-old boy who accidentally ingested 15.7 mg/kg ethion from a contaminated

milk bottle illustrates the toxic neurological effects of ethion (Comstock et al. 1967). Symptoms

appeared one hour following ingestion. The child awoke crying and choking on frothy saliva. He was

unable to control his head and limbs and subsequently had a watery bowl movement and became limp. 

Occasional twitching movements of the hands and around the mouth were noted. Upon admission to the

hospital, he was slightly cyanotic with a generalized flaccid paralysis and areflexia. Respiration was

increased (60/minute) as was heartbeat (200/minute). Pupils were pinpoint and nonreactive to light, and

eye movements were purposeless. Salivation was excessive but not copious. Respiration was

diaphragmatic with shallow respiratory excursions and intercostal retraction. Generalized rales and

rhonchi and inspiratory and expiratory wheezes were noted. The liver and spleen were palpable. Bowel

sounds were hyperactive. There were no abnormal heart sounds. Treatment with atropine and

pralidoxime was started immediately. Approximately 5 hours after ingestion, respiratory arrest occurred

and mechanical ventilation was necessary for the next 3 hours. Laboratory and roentgenologic studies

showed protein in the urine and increased WBC in the urine. Serum WBC count was decreased and

treated with atropine and pralidoxime. Treatment with atropine and pralidoxime continued for 5 days

until symptoms ceased. Follow-up examinations after 1 week, 1 month, and 1 year indicated that a

complete recovery was made by this patient.
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2. HEALTH EFFECTS

A study with male volunteers established oral levels of exposure to ethion that had no adverse effect in

humans (Palazzolo 1970). Male volunteers (n=6; age range, 23-43 years) were given ethion in corn oil

solutions in three divided doses (9:00 a.m., noon, and 5:00 p.m.) of 0.05, 0.075, 0.1, and 0.15 mg/kg/day

via gelatin capsule. Controls (n=4; age range, 22-40 years) received gelatin capsules containing corn oil.

Medical histories and baseline plasma cholinesterase and erythrocyte acetylcholinesterase activities were

determined prior to the start of the study (days -15, -11, -8, -4, and -1). Blood samples were taken prior

to dose administration. Subjects received 0.05, 0.075, and 0.1 mg/kg/d for 3 weeks each. Cholinesterase

determinations were conducted on days 1, 3, 7, 14, and 21 for these dose groups. Subjects received

0.15 mg/kg for 3 days and cholinesterase determinations were made on days 1 and 3. A 19-day recovery

period followed, and cholinesterase determinations were made on days 7, 12, and 19. At the beginning

and end of each treatment period, pupil size, light reflex, eye accommodation, muscle tone, knee jerk,

tongue tremor, and finger tremor were measured.

No effect on erythrocyte acetylcholinesterase was observed at any time during the human exposure study.

No effect on plasma cholinesterase were observed at the 0.05 mg/kg/day dose level. Statistically

significant decreases from pretreatment values were observed for all plasma cholinesterase determination

periods during the 0.075, 0.1, and 0.15 mg/kg/day treatment periods. A significant 16% decrease in

plasma cholinesterase activity was seen in the 0.075 mg/kg/day group. When compared to pretreatment

values, decreases of 23 and 31% were seen in the 0.1 and 0.15 mg/kg/day groups, respectively. A partial

recovery of plasma cholinesterase levels were seen after 7 days of recovery, while a complete recovery

was seen after 12 days. No clinical signs of adverse neurological effects were observed.

Severe neurological effects have also been observed in rats after a single oral exposure to ethion. Male

Sprague-Dawley rats receiving 100 mg/kg ethion by gavage had cholinergic signs including salivation,

tremors, nose bleeding, urination, diarrhea, and convulsions (Selim 1985a). Female rats exhibited these

same signs at a 10-fold lower dose (10 mg/kg). In another acute oral exposure to ethion, groups of

pregnant Sprague-Dawley rats (n=25) were administered ethion via gavage at doses of 0,0.2,0.6, and

2.5 mg/kg from Gd 6 to 15 (Hoberman et al. 1983a). An increased incidence of hyperactivity was

observed in dams in the 2.5 mg/kg group. In a test of ethion in chickens for potential to cause delayed

neurotoxicity, an oral dose of 2,792 mg/kg caused neither clinical or histopathological signs of this

condition (Roberts et al. 1986).
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2. HEALTH EFFECTS

In longer-term experiments in animals, groups of Sprague-Dawley rats (n=80/sex/group) fed diets

resulting in ethion consumption of 0, 0.1, 0.2, and 2 mg/kg/day, no effect on erythrocyte acetylcholinesterase was observed at 6, 12, or 18 months (Morrow 1985a). Significant neurological effects were

observed in dogs receiving higher doses of ethion (Bailey 1988). Groups of dogs (n=4/sex/group)

received ethion in the diet for 90 days, the average consumed was 0, 0.01, 0.06, 0.71, and 6.9 mg/kg/day

for males and 0, 0.012, 0.07, 0.71, and 8.25 mg/kg/day for females. Clinical signs included ataxia,

emesis, miosis, and tremors in the high-dose groups. Ethion inhibited brain and erythrocyte acetylcholinesterase activity in a dose-related manner. A reduction of 23% in brain acetylcholinesterase was

observed in males at 0.71 mg/kg/day and 64% at 6.9 mg/kg/day; no effect was seen at 0.07 and

0.012 mg/kg/day. Plasma cholinesterase activity was inhibited in all groups except the low-dose males

and females and was dose-related. No compound-related histopathological changes were observed in

nervous system tissues (brain [with medulla/pons, cerebellar cortex, and cerebral cortex], sciatic nerve,

spinal cord [cervical, thoracic, lumbar]).

In chronic-duration experiments, a 3-generation reproduction study in albino rats that consumed ethion

in feed at 0, 0.1, 0.2, and 1.25 mg/kg/day, showed that plasma cholinesterase was inhibited in F1 and F2

females in the high-dose group. No effect was observed on erythrocyte acetylcholinesterase in any

group (Enloe and Salamon 1985). In 2-year carcinogenicity bioassay experiments, no effect on

erythrocyte acetylcholinesterase was observed at daily exposures of #2 mg/kg/day in rats and

1.12 mg/kg/day in mice (Morrow 1985a, 1985b).

Inhibition of brain acetylcholinesterase was observed in rabbits after dermal exposure to ethion for

21 days at 1 mg/kg/day, (Weiner 1985a, 1985b as cited in EPA 1989d). The NOAEL in these studies

was 0.8 mg/kg/day.

Histopathological examination of nervous system tissues (brain, spinal cord, peripheral nerve) showed

no treatment-related effects in several animal studies where exposure was via the oral route (Bailey

1988; Keller and Paynter 1958; Morrow et al. 1985a, 1985b). 

Reproductive Effects. In a 3-generation reproduction study, ethion was administered to F0, F1, and

F2 male (n=15) and female (n=30) rats in the diet at concentrations of 0, 0.1, 0.2, and 1.25 mg/kg/day. 

No effect on reproduction was observed (Enloe and Salamon 1985). Indices measured were: mating

index (number of copulations/number of estrus cycles utilized), fertility index (number of
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2. HEALTH EFFECTS

pregnancies/number of copulations), gestation (number of parturitions/number of pregnancies), female

fertility (number of pregnancies/number of females mated), and male fertility (number of sires/number of

males mated).

Histopathological examination of reproductive tissues (uterus, ovaries, testes) revealed no treatmentrelated lesions in several animal studies where exposure was via the oral route (Bailey 1988; Keller and

Paynter 1958; Morrow et al. 1985a, 1985b).

Developmental Effects. Three studies examining the effects of ethion on development are

available. Groups of pregnant Sprague-Dawley rats (n=25) were administered ethion via gavage at doses

of 0, 0.2, 0.6, and 2.5 mg/kg from Gd 6 to 15 (Hoberman et al. 1983a). Dams were observed and

skeletal examinations were performed on the fetuses. Fetuses from the 2.5 mg/kg group had an

increased incidence of delayed ossification of pubes. Groups of pregnant New Zealand rabbits (n=17)

received ethion via gavage at doses of 0, 0.6, 2.4, and 9.6 mg/kg from Gd 6 to 18 (Hoberman et al.

1983b). Does were observed for clinical signs. Maternal toxicity was noted, does in the 2.4 and

9.6 mg/kg/day groups had an increased incidence of orange-colored urine and decreased body weights

(not specified). Food consumption was also reduced in the 9.6 mg/kg/day females. Fetuses in the

9.6 mg/kg/day group had an increased incidence of fused sterna centra. In a 3-generation reproduction

study, ethion was administered to F0, F1, and F2 male (n=15) and female (n=30) rats in the diet at

concentrations of 0, 0.1, 0.2, and 1.25 mg/kg/day. No effect was observed on pup viability, survival,

body weight, or structural development (Enloe and Salamon 1985).

Genotoxic Effects. Ethion has shown no evidence of genotoxicity in several in vitro tests (see

Table 2-3). Ethion was negative in tests for point mutations (Kada et al. 1974; Waters et al. 1980), DNA

repair (Shirasu et al. 1976; Waters et al. 1980), recombination (Waters et al. 1980), sister chromatid

exchange (Sobti et al. 1982), and unscheduled DNA synthesis (Waters et al. 1980). An increase in the

frequency of sister chromatid exchanges was observed in white Leghorn chicks following a single oral

(2 mg/kg) or intraperitoneal (20 mg/kg) dose of ethion (Bhunya and Jena 1994). No other in vivo tests of

ethion genotoxicity were located.

Cancer. In 2-year carcinogenicity bioassays, groups of Sprague-Dawley rats (n=80/sex/group)

receiving diets containing ethion at concentrations of 0, 0.1, 0.2, and 2 mg/kg/day had similar tumor

incidences (Morrow 1985a). Similar results were observed in mice receiving 0, 0.113, 0.225, and 
Table 2-3. Genotoxicity of Ethion In Vitro

Results

System End points With activation Without activation Refe

Prokaryotes:

S. typhimurium (Strains TA 98, TA 100,TA 1535, TA 1537, TA 1538)

Point mutation All negative All negative EPA 

1984

S. typhimurium (Strains TA 1535,TA 1536, TA 1537, TA 1538)

Point mutation No data All negative Kada 

S. typhimurium (Strains TA 100,TA 1535, TA 1537, TA 1538)

Point mutation All negative All negative Wate

E. coli (Strain WP2 (urvA-)) Point mutation All negative All negative Wate

E. coli (Strains W3110, P3478) DNA repair No data All negative Wate

B. subtilis (Strains H17 , M45) DNA repair No data All negative WateB. subtilis (Strains H17, M45) DNA repair No data All negative Shira

S. cerevisiae (Strain D3) Recombination Negative Negative Wate

Eukaryotes 

Human lymphoid cells (LAZ-007)

Sister chromatidexchange

No data Negative Sobt

Human fetal lung fibroblasts (WI-38) Unscheduled DNA

synthesis

No data Negative Wate
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1.2 mg/kg/day (Morrow 1985b). Ethion has not been classified for carcinogenicity by DHHS, IARC or

EPA.

2.6 ENDOCRINE DISRUPTION

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine

system because of the ability of these chemicals to mimic or block endogenous hormones, or otherwise

interfere with the normal function of the endocrine system. Chemicals with this type of activity are most

commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to

disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. 

Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in

light of the fact that hormone mimics exist in the natural environment. Examples of natural hormone

mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). 

These compounds are derived from plants and are similar in structure and action as endogenous

estrogen. While there is some controversy over the public health significance of endocrine disrupting

chemicals, it is agreed that the potential exists for these compounds to affect the synthesis, secretion,

transport, binding, action, or elimination of natural hormones in the body that are responsible for the 

maintenance of homeostasis, reproduction, development, and/or behavior (EPA 1997c). As a result,

endocrine disruptors may play a role in the disruption of sexual function, immune suppression, and

neurobehavioral function. Endocrine disruption is also thought to be involved in the induction of breast,

testicular, and prostate cancers, as well as endometriosis (Berger 1994; Giwercman et al. 1993; Hoel et

al. 1992).

No studies were located regarding endocrine disruption in humans or animals after exposure to ethion. 

No in vitro studies were located regarding endocrine disruption by ethion.

2.7 CHILDREN’S SUSCEPTIBILITY

This section discusses potential health effects from exposures during the period from conception to

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential

effects on offspring resulting from exposures of parental germ cells are considered, as well as any

indirect effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed.
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Children are not small adults. They differ from adults in their exposures and may differ in their

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the

extent of their exposure. Exposures of children are discussed in Section 5.6 Exposures of Children.

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less

susceptible than adults to health effects, and the relationship may change with developmental age

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are

critical periods of structural and functional development during both prenatal and postnatal life and a

particular structure or function will be most sensitive to disruption during its critical period(s). Damage

may not be evident until a later stage of development. There are often differences in pharmacokinetics

and metabolism between children and adults. For example, absorption may be different in neonates

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in

infants and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for

example, infants have a larger proportion of their bodies as extracellular water and their brains and livers

are proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and

Brozek 1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier

(Adinolfi 1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites

1975). Many xenobiotic metabolizing enzymes have distinctive developmental patterns. At various

stages of growth and development, levels of particular enzymes may be higher or lower than those of

adults, and sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990;

Leeder and Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism

make the child more or less susceptible also depends on whether the relevant enzymes are involved in

activation of the parent compound to its toxic form or in detoxification. There may also be differences in

excretion, particularly in newborns who all have a low glomerular filtration rate and have not developed

efficient tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al.

1948). Children and adults may differ in their capacity to repair damage from chemical insults. 

Children also have a longer remaining lifetime in which to express damage from chemicals; this

potential is particularly relevant to cancer.

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others

may decrease susceptibility to the same chemical. For example, although infants breathe more air per
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kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by

their alveoli being less developed, which results in a disproportionately smaller surface area for alveolar

absorption (NRC 1993).

The toxicological database for the effects of ethion on humans is sparse. Ethion is not used in the home,

and no toxicological studies on individuals likely to have significant exposure (formulators and

applicators) are available in the literature. One well documented case report of a poisoning incident in

an infant has been published (Comstock et al. 1967). The only other human study located at this time is

an unpublished study that established no-effect levels for oral exposure to ethion in adult males

(Palazzolo 1970).

The effects of ethion have not been thoroughly studied in children, but they would likely experience the

same health effects seen in adults exposed to ethion. Effects observed in an infant accidentally poisoned

by ethion (Comstock et al. 1967) were similar in onset, severity, and duration to those seen in adults

poisoned by other organophosphate insecticides (Ecobichon 1991). Symptoms observed in the infant

(muscular twitching, lack of coordination, flaccid paralysis and areflexia, excessive salivation, pinpoint

pupils, watery bowel movement, proteinurea, increased urinary white cell count, emesis, tachycardia) are

classic symptoms of organophosphate poisoning in adults. Five days of treatment with atropine and

pralidoxime were necessary before recovery; this is comparable to clinical courses seen in poisoned

adults. Recovery appeared to be complete at a 1-year follow-up; this is also the case in adults (assuming

that the organophosphate does not cause delayed neurotoxicity). These same effects are seen in animal

studies. In the only animal study that directly compared weanling and adult animals (Brodeur and

DuBois 1963), the LD50 for weanling male Holtzman rats after intraperitoneal injection was 100 mg/kg

(95% confidence limits 92–109). For adult male Holtzman rats, the LD50 was 128 mg/kg (95%

confidence limits 110–149). This indicates that weanlings may be slightly more susceptible to the lethal

effects of ethion.

Specific information on whether children differ from adults in their susceptibility to the effects of ethion

is not available. Animal studies do not provide any further information. Two areas of concern for

exposure of children to ethion and other organophosphates have been identified. First, the target tissue

for ethion is the peripheral and central nervous system. The central nervous system continues to develop

after birth and it is not known if, or at what point, neural acetylcholinesterase inhibition can affect this

process and result in permanent effects. It is possible that effects could occur with inhibition levels that
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cause no clinical effects. Secondly, infants and children receive approximately 2–3 times more ethion in

their diets per unit body weight than adults due to higher consumption of fruits and fruit drinks (See

Chapter 5).

Ethion has not caused teratogenic effects in animal models (rats, rabbits), although some skeletal

abnormalities have been reported (delayed ossification, fused sterna centra). These effects occurred at

maternally toxic doses (Hoberman et al. 1983a, 1983b). Observation of the offspring after birth to

maturity was not performed. No developmental effects were observed in progeny in a 3-generation rat

reproduction study (Enloe and Salamon 1985). Ethion has not been tested in in vitro developmental

systems.

The pharmacokinetics of ethion are not well understood in animal models, and no information is

available on human adults or children. Studies in animals are limited by the fact that chemical

characterization of radiolabeled ethion and its metabolic products in tissues was not performed. Ethion

and its active metabolite ethion monoxon are highly lipophilic molecules so there should be no

significant barrier to crossing the placenta. No studies have been done in animal models to confirm

whether this occurs. Similarly, passage into breast milk is also possible. This has been examined in

animal models. Radioactivity derived from labeled ethion was present in goat milk after oral exposure

(Jobsis and Zeitlow 1985); however, the chemical identity of the radioactivity was not determined. 

Unchanged ethion (the monoxon was not measured) was detected in goat milk after oral (1.4% of

administered activity) and dermal (0.04–0.05% of administered activity) exposure to ethion (Mosha et al.

1990b).

The toxicity of ethion is determined by two biotransformations, a desulfuration by a cytochrome P-450

enzyme yielding the active metabolite ethion monoxon and detoxication by an ester cleavage catalyzed

by an esterase. Some, but not all, P-450 isozymes are regulated differently during development than

during adulthood (Leeder and Kearns 1997); without knowing the specific isozymes involved in ethion

metabolism it is impossible to predict whether its metabolism would vary developmentally. 

Comparisons of juvenile and adult animal toxicokinetics have not been made. There are no PBPK

models for ethion available for children, adults, or animal models. The toxicokinetic database is

insufficient for modeling purposes.
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There is no evidence that the mechanism of ethion toxicity is different between children and adults. The

symptoms of severe neural acetylcholinesterase inhibition observed in a 6-month-old infant were similar

to those seen in adult poisonings with other organophosphate insecticides. The acetylcholinesterase

molecule is believed to be the same at all stages of development (there is no evidence for a “fetal”

acetylcholinesterase).

The biomarkers of exposure and effect (plasma cholinesterase and erythrocyte acetylcholinesterase in

blood) are similar between adults and children. However, less is known about how much inhibition of

these enzymes is associated with health effects in children than in adults. Information is not available

for infants and children on the relationship between dietary intake and the activity of blood

cholinesterases.

Interactions of ethion with other chemicals have not been reported in children or adults. There is not

enough information from animal studies to determine if juvenile animals have unique interactions. As

with adults, it is reasonable to expect interactions with compounds that inhibit acetylcholinesterases.

Methods for reducing the toxic effects of ethion in children are similar to those used in adults. Doses of

the antidotes atropine and pralidoxime, adjusted for body weight, have been shown to be effective

treatment for acute poisoning (Comstock et al. 1967).

There is no information on whether parental exposure to ethion can cause transgenerational effects in

children. No effects were noted in a 3-generation rat reproduction study (Enloe and Salamon 1985). 

Ethion has tested negative for genotoxicity in a number of in vitro tests.

2.8 BIOMARKERS OF EXPOSURE AND EFFECT

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They

have been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC

1989).

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of

biomarkers as tools of exposure in the general population is very limited. A biomarker of exposure is a

xenobiotic substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and

some target molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC
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1989). The preferred biomarkers of exposure are generally the substance itself or substance-specific

metabolites in readily obtainable body fluid(s), or excreta. However, several factors can confound the

use and interpretation of biomarkers of exposure. The body burden of a substance may be the result of

exposures from more than one source. The substance being measured may be a metabolite of another

xenobiotic substance (e.g., high urinary levels of phenol can result from exposure to several different

aromatic compounds). Depending on the properties of the substance (e.g., biologic half-life) and

environmental conditions (e.g., duration and route of exposure), the substance and all of its metabolites

may have left the body by the time samples can be taken. It may be difficult to identify individuals

exposed to hazardous substances that are commonly found in body tissues and fluids (e.g., essential

mineral nutrients such as copper, zinc, and selenium). Biomarkers of exposure to ethion are discussed in

Section 2.8.1.

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within

an organism that, depending on magnitude, can be recognized as an established or potential health

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital

epithelial cells), as well as physiologic signs of dysfunction such as increased blood pressure or

decreased lung capacity. Note that these markers are not often substance specific. They also may not be

directly adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of

effects caused by are discussed in Section 2.8.2.

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic

or other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in

the biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are

discussed in Section 2.10, Populations That Are Unusually Susceptible.

2.8.1 Biomarkers Used to Identify or Quantify Exposure to Ethion

Ethion at high doses will cause clinical symptoms of organophosphate toxicity, such as miosis, tremor,

increased salivation, lacrimation, and respiratory distress. If these symptoms occur together and the

individual has recently been in contact with pesticides containing ethion, it is highly likely that exposure

to ethion has occurred.
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Exposure to ethion can also be confirmed by blood tests; however, these tests are not specific for ethion. 

Ethion can inhibit the activity of two enzymes in the blood, plasma cholinesterase and erythrocyte

acetylcholinesterase. Plasma cholinesterase is more sensitive to inhibition by ethion than erythrocyte

acetylcholinesterase in both humans and animals. Plasma cholinesterase activity recovers more rapidly

from inhibition than erythrocyte acetylcholinesterase because of the higher turnover rate of plasma

cholinesterase proteins compared to erythrocytes. Exposures that occurred two weeks or more before

testing probably would not be reflected in an inhibition of plasma cholinesterase. Because of the human

variability in activity of these enzymes, follow-up determinations showing a rise back to a constant

activity are more reliable evidence than a single determination that exposure has taken place. Many

other organophosphate and carbamate insecticides can cause inhibition of blood cholinesterases.

Ethion has been detected in saliva of pest control applicators (Nigg et al. 1993). Diethyl phosphate

metabolites of ethion were also detected in the workers’ urine. The correlation between urinary

metabolites and saliva ethion was 0.55, indicating that saliva ethion was not a good predictor of absorbed

ethion. The authors stated that mouth contamination may have influenced the results. Further

development of this method may result in a specific biomarker of exposure for ethion.

2.8.2 Biomarkers Used to Characterize Effects Caused by Ethion

The toxic effects of ethion are caused by its inhibition of neural acetylcholinesterase in the peripheral

and central nervous systems. This inhibition is reflected by the level of depression of erythrocyte acetylcholinesterase activity in the blood. 

The nervous system can accept a certain amount of acetylcholinesterase inhibition without overt toxic

effects. In humans and animals, toxic signs are generally not seen until at least 20% of this enzyme

(measured as erythrocyte acetylcholinesterase) has been inhibited (Ecobichon 1991). Adaptation can

also occur. In an animal study, brain acetylcholinesterase was inhibited 90% after a 2-year inhalation

exposure to the organophosphate dichlorvos (Blair et al. 1976), yet no symptoms of cholinergic

overstimulation were observed. With ethion and other organophosphate compounds, the best predictor

of toxicity is not necessarily the actual percentage of inhibition of acetylcholinesterase, but rather how

rapidly this inhibition has occurred. Rapid inhibition does not give the nervous system time to

physiologically adapt to acetylcholinesterase inhibition. This adaptation appears to involve

desensitization and down-regulation of muscarinic receptors (Fitzgerald and Costa 1993).
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For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC

Subcommittee Report on Biological Indicators of Organ Damage (1990) and for information on

biomarkers for neurological effects see OTA (1990).

2.9 INTERACTIONS WITH OTHER CHEMICALS

Reports on specific interactions of ethion with other chemicals are limited. Ethion administered orally at

25 mg/kg in rats did not increase the lethality of 53.5 mg/kg of the organophosphate bromophos-ethyl

(Muacevic 1973). Several of the other organophosphates tested (parathion, chlorfenvinphos) increased

the toxicity of bromophos-ethyl in this study. Pretreatment with phenobarbital to induce cytochrome

P-450 enzymes significantly reduced the lethality of ethion in Holtzman rats after intraperitoneal

injection (LD50 without pretreatment, 25.9 mg/kg; with phenobarbital pretreatment, 302.6 mg/kg). 

However, lethality in CF1 mice in the same study was unaffected by pretreatment with phenobarbital

(DuBois and Kinoshita 1968).

The major interaction of concern for ethion would be with chemicals that have the same mechanism of

action (i.e., organophosphate and carbamate pesticides). Simultaneous exposure to ethion and one of

these chemicals could possibly have an additive effect on inhibition of neural acetylcholinesterase.

Whether a toxic interaction would occur with a particular chemical depends on how it affects the

toxicokinetics of ethion. The toxicity of a given dose of ethion could conceivably be potentiated by

interactions with chemicals that interfere with its detoxication; however, no such interactions have been

reported. This effect has occurred with other organophosphates, e.g., the potentiation of malathion by

the carboxylesterase inhibitor EPN (ethyl p-nitrophenyl benzenethiophosphonate) in rats and dogs

(Frawley et al. 1957). Some chemicals can induce the synthesis of cytochrome P-450 enzymes

(polysubstrate mixed function oxidases) in the liver (e.g., organochlorines). Whether this would increase

or decrease the toxicity of ethion in humans is not known. While mixed function oxidases are

responsible for the activation of ethion (via desulfuration), it is not known if they play any role in

detoxication since specific metabolic pathways are unknown. For the same reason, interactions of ethion

with inhibitors of mixed function oxidases cannot be predicted. These effects are species specific;

induction decreased the lethality of ethion in rats but had no effect in mice (DuBois and Kinoshita 1968). 
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2.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

A susceptible population will exhibit a different or enhanced response to ethion than will most persons

exposed to the same level of ethion in the environment. Reasons may include genetic makeup, age,

health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These

parameters result in reduced detoxification or excretion of ethion, or compromised function of organs

affected by ethion. Populations who are at greater risk due to their unusually high exposure to ethion are

discussed in Section 5.7, Populations With Potentially High Exposures.

Individuals with impaired respiratory function or diseases of the central or peripheral nervous systems

may be more susceptible to the effects of ethion since these sites are the main targets for toxicity. People

with impaired esterase production would be unusually susceptible to ethion exposure because of a

reduced ability to metabolize ethion absorbed by the body. This population would include people

suffering from liver diseases (hepatitis, cirrhosis). Pregnant women have lower levels of plasma

cholinesterase and are more susceptible to agents such as succinylcholine, which is metabolized by this

enzyme. Ethion can bind stoichiometrically to this enzyme and inhibit its activity, so pregnant women

are at least hypothetically more susceptible to ethion exposure than other populations. A similar effect

could be expected in individuals with inherited abnormally low plasma cholinesterase levels. 

Individuals may not know if they have decreased plasma cholinesterase and other esterases and,

therefore, may not know that they are more susceptible to the effects of ethion.

2.11 METHODS FOR REDUCING TOXIC EFFECTS

This section will describe clinical practice and research concerning methods for reducing toxic effects of

exposure to ethion. However, because some of the treatments discussed may be experimental and

unproven, this section should not be used as a guide for treatment of exposures to ethion. When specific

exposures have occurred, poison control centers and medical toxicologists should be consulted for

medical advice. The following texts provide specific information about treatment following exposures

to ethion:

"Cholinesterase inhibitor pesticides" in Handbook of Poisoning, 1987, Appleton and Lange,

Norwalk, CT; R.H. Dreisbach and Robertson, WO 
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"Organophosphates and other insecticides" in Clinical Management of Poisoning and Drug

Overdose, 2nd edition, 1990, W.B. Saunders, Philadelphia; L.M. Haddad and J.F. Winchester, eds.

"Insecticides: Organophosphates and carbamates" in Goldfrank's Toxicologic Emergencies, 5th

ed., 1994, Norwalk; C.K. Aaron and M.A. Howland.

2.11.1 Reducing Peak Absorption Following Exposure

If exposure has occurred by the oral route, gastric lavage would reduce peak absorption if the treatment

is given shortly after exposure. Treatment with activated charcoal would probably also be effective. If

exposure has occurred by the dermal route, rinsing the exposed skin with large amounts of flowing water

and soap would greatly reduce exposure.

2.11.2 Reducing Body Burden

Because ethion does not accumulate in the body and appears to be rapidly metabolized, specific efforts

to reduce the body burden would not appear to be necessary.

2.11.3 Interfering with the Mechanism of Action for Toxic Effects

Ethion has the same mechanism of action as other organophosphorus insecticides. Poisonings with these

types of chemicals are common enough that specific and effective medical interventions have been

developed. The life-threatening effects of ethion poisoning are related to its effects on the respiratory

system (respiratory depression, bronchospasm, increased bronchial secretions, pulmonary edema,

muscular weakness). If these symptoms are present, artificial respiration and suctioning are performed

via an endotracheal tube. Atropine is used to counteract the muscarinic effects of ethion, with care being

taken that symptoms of atropine overdose do not occur (dry mouth, dilatation of the pupils). 

Pralidoxime (2-PAM or Protopam), a cholinesterase reactivator, can be used as an antidote for

organophosphate poisoning, and is typically given in conjunction with atropine. Enzyme reactivation,

accomplished by hydrolysis of the oxygen-phosphorus bond, occurs most markedly at the neuromuscular

junction, restoring skeletal muscle response and, importantly, normalizing diaphragm excursion and

respiratory effort. Pralidoxime must be administered as rapidly after organophosphate exposure as

possible, as its efficacy is inhibited by the “aging” phenomenon. The “aging” involves a chemical
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change in the organophosphate-enzyme complex and occurs within minutes to hours (see Section 2.4.2

for more details). The resulting compound, a monoethoxyphosphorylated acetycholinesterase molecule,

is very stable and resistant to the effects of pralidoxime.

2.12 ADEQUACY OF THE DATABASE

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether

adequate information on the health effects of ethion is available. Where adequate information is not

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure

the initiation of a program of research designed to determine the health effects (and techniques for

developing methods to determine such health effects) of ethion.

The following categories of possible data needs have been identified by a joint team of scientists from

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean

that all data needs discussed in this section must be filled. In the future, the identified data needs will be

evaluated and prioritized, and a substance-specific research agenda will be proposed.

2.12.1 Existing Information on Health Effects of Ethion

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

are summarized in Figure 2-4. The purpose of this figure is to illustrate the existing information

concerning the health effects of ethion. Each dot in the figure indicates that one or more studies provide

information associated with that particular effect. The dot does not necessarily imply anything about the

quality of the study or studies, nor should missing information in this figure be interpreted as a “data

need”. A data need, as defined in ATSDR’s Decision Guide for Identifying Substance-Specific Data

Needs Related to Toxicological Profiles (ATSDR 1989), is substance-specific information necessary to

conduct comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly

as any substance-specific information missing from the scientific literature.

As shown in Figure 2-4, information on health effects of ethion in humans is limited to systemic and

neurological effects. A case report of a poisoning incident (Comstock et al. 1967) and an unpublished 
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intermediate-duration oral exposure study in volunteers (Palazzolo 1970) are available. No studies

describing health effects in humans after inhalation or dermal exposure for any duration or chronicduration oral exposure were located.

Information on health effects in animals after exposure to ethion is far more extensive (see Figure 2-4). 

However, almost all of these studies were performed to satisfy EPA pesticide registration requirements

and have not been published in the open literature.

2.12.2 Identification of Data Needs

Acute-Duration Exposure. Populations in the vicinity of hazardous waste sites may be exposed to

ethion for brief periods. Exposure would most likely occur by contact with contaminated soil, but

drinking contaminated water is also possible. The central and peripheral nervous systems are the major

target organs for ethion toxicity by the oral and dermal routes. The specific target of ethion is the

enzyme that catalyzes the hydrolysis of the neurotransmitter acetylcholine, neural acetylcholinesterase. 

High doses of ethion can be extremely toxic by the oral route as demonstrated by a case report of a

6-month-old boy where a single oral dose of 15.7 mg/kg would have been fatal without aggressive

medical intervention (Comstock et al. 1967). Threshold doses for clinical effects and/or

cholinesterase/acetylcholinesterase inhibition after oral exposure to ethion are available for several

species including humans, rats, mice, dogs and rabbits. Threshold doses for acetylcholinesterase

inhibition after dermal exposure in the rabbit are also available (Weiner 1985a, 1985b cited in EPA

1989d).

The intermediate-duration oral MRL of 0.002 mg/kg/day derived for ethion based on a NOAEL of 

0.06 mg/kg/day for inhibition of brain acetylcholinesterase in Beagle dogs (Bailey 1988) is applicable to

acute-duration exposures as well. The acute-duration oral toxicity of ethion is well understood, and no

further studies appear necessary. Inhalation exposure at hazardous waste sites to levels that produce

detectable toxic effects is unlikely. Since the most likely route of exposure to ethion at hazardous waste

sites is dermal contact with contaminated soil, a study that establishes a threshold value for acetylcholinesterase inhibition in a second species may be useful for risk assessment. 

Intermediate-Duration Exposure. An intermediate-duration oral MRL of 0.002 mg/kg/day was

derived for ethion based on a NOAEL of 0.06 mg/kg/day for inhibition of brain acetylcholinesterase in
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dogs (Bailey 1988). A well conducted study in humans is available on the effects of intermediateduration oral exposure to ethion (Palazzolo 1970). Results in animal studies indicate that the toxic

effects of intermediate-duration exposure to ethion are similar to those for the acute-duration by both the

oral and dermal routes. No further intermediate-duration studies in animals would appear to be

necessary. 

Chronic-Duration Exposure and Cancer. There is limited information regarding the potential

toxic effects of chronic, low-level exposure to ethion. A chronic-duration oral MRL of 0.0004

mg/kg/day was derived for ethion based on a NOAEL of 0.06 mg/kg/day for inhibition of brain

acetylcholinesterase in Beagle dogs in an intermediate-duration study (Bailey 1988). A chronic-duration

(2-year) oral study has been done in rats and mice and produced no evidence of carcinogenicity by this

route (Morrow 1985a, 1985b). No neurological or systemic effects were found at the doses

(1.12–2 mg/kg/day) used in this study. Chronic-duration exposure is the most likely type of exposure

that would be experienced by people living near hazardous waste sites containing ethion. This exposure

is most likely to be by dermal contact with contaminated soil, although drinking contaminated water or

soil ingestion by children could cause oral exposure. Exposure to ethion contaminated dust is not likely

to cause intoxication.

Genotoxicity. Ethion has been tested for genotoxicity in several in vitro test systems and has tested

uniformly negative both with and without metabolic activation. A single in vivo study in chickens

showed an increase in sister chromatid exchanges following oral ethion exposure (Bhunya and Jena

1994). Further in vivo tests in rats or mice are needed to confirm these results.

Reproductive Toxicity. No information on reproductive toxicity in humans after ethion exposure is

available. Ethion did not cause reproductive toxicity by the oral route in a 3-generation study in rats or

histopathological evidence for damage to reproductive tissues in intermediate- or chronic-duration

studies. Ethion is not known to be an endocrine disruptor. Further studies on reproduction in animals

after exposure to ethion would not appear to be necessary.

Developmental Toxicity. No information on developmental toxicity in humans after ethion

exposure is available. Ethion did not cause teratogenicity in rats or rabbits, although skeletal

abnormalities were seen at maternally toxic doses. Additional animal studies in which neurobehavioral,

immunological, and reproductive end points are assessed up through sexual maturity following pre- and

postnatal exposure may be helpful to determine if developmental effects become apparent after birth. 
ETHION 84

2. HEALTH EFFECTS

Immunotoxicity. Ethion has tested negative in a skin sensitization study in guinea pigs. No reports

of allergic contact dermatitis after exposure to ethion in humans were located. It appears that further

immunotoxicity studies are not necessary.

Neurotoxicity. The neurotoxicity of ethion via acetylcholinesterase inhibition is understood. A no

effect level is available for humans and threshold doses for acetylcholinesterase inhibition have been

established for several species. A delayed neurotoxicity test was negative in chickens for ethion. 

Additional animal studies do not seem to be warranted at this time. 

Epidemiological and Human Dosimetry Studies. Epidemiological/occupational studies would

be useful for adequately assessing risk of exposure to ethion. At the present time, very few people are

exposed to ethion outside occupational groups. The major group potentially exposed, pest control

workers, generally use several different pesticides, and it may be difficult to identify a group exposed

primarily to ethion. However, well designed epidemiological studies of exposed workers that examine

the effects of ethion on the nervous system would be useful for establishing cause/effect relationships.

Biomarkers of Exposure and Effect. 

Exposure. Reliable biomarkers for exposure to ethion already exist (plasma cholinesterase, erythrocyte

acetylcholinesterase, and clinical symptoms of neurotoxicity). However, reliable methods to distinguish

ethion intoxication from that caused by other organophosphorus compounds do not exist.

Effect. Reliable biomarkers for the effect of ethion exist (cholinergic symptoms of neurotoxicity and

erythrocyte acetylcholinesterase).

Absorption, Distribution, Metabolism, and Excretion. The toxicokinetics of ethion are not

well understood. Two major data needs were identified. Studies should be done where ethion and

ethion monoxon are measured in tissues rather than radioactivity derived from labeled ethion. The

metabolites of ethion (besides diethyl phosphate) have not been identified beyond their solvent

extraction behavior. Without this information, the potential toxicity of metabolites cannot be assessed.

Comparative Toxicokinetics. No data needs have been identified for comparative toxicokinetics.
ETHION 85

2. HEALTH EFFECTS

Methods for Reducing Toxic Effects. Further studies on retarding gastrointestinal absorption of

ethion and the effectiveness of absorbents would be useful in the treatment of poisoning. No methods

exist for increasing the excretion of ethion and the active metabolite ethion monoxon. The medical

management of the toxic effects of ethion (respiratory support, atropine treatment, reactivation of neural

acetylcholinesterase with oximes) is similar to that for poisoning by other organophosphate insecticides. 

Any improvements in the management of organophosphate poisoning would apply to ethion. 

Children’s Susceptibility There are no populations of children identified that are specifically

exposed to ethion. Poisonings of children by this chemical appear to be exceedingly rare since only one

case report could be found in the literature (Comstock et al. 1967). The clinical course for this 6-monthold was very similar to that seen in adults poisoned by other organophosphate insecticides, and his

recovery appeared to be complete as late as one year post-exposure. In future incidents of ethion

poisoning of children and adults, better estimates should be made of exposure level, exposure route, and

metabolite levels relative to the observed symptoms of toxicity. The only animal study comparing

effects of ethion between juveniles and adults showed marginally greater toxicity (lower LD50) in

juvenile rats after intraperitoneal injection (Brodeur and DuBois 1963). Additional animal studies

examining nonlethal end points in juvenile and adult animals following ethion exposure are needed. In

particular, studies examining the dermal and oral routes of exposure would be the most useful.

It is conceivable that children, particularly very young children, may be more susceptible to the effects

of ethion than adults, due to suspected differences in metabolic activities. However, comparative

metabolic data for ethion in children and adults is lacking, specifically data regarding cytochrome P450

and esterase activities. Data are also lacking as to whether there are differences in absorption,

distribution, or excretion of ethion between children and adults. Additional animal pharmacokinetic and

metabolic studies comparing fetal, juvenile and adult animals, preferably supplemented with studies

utilizing human tissues where appropriate, will be needed to clarify these issues. Biomarkers of

exposure need to be further studied in order to better estimate human exposure at all age levels following

acute or chronic exposure to ethion. Also, developmental studies in animals are needed to quantitatively

measure placental transfer of ethion and its metabolites and to determine whether ethion and its

metabolites can be metabolized by placental tissue.

Child health data needs relating to exposure are discussed in Section 5.8.1 Identification of Data Needs:

Exposures of Children.
ETHION 86

2. HEALTH EFFECTS

2.12.3 Ongoing Studies

No ongoing studies on ethion were located.
ETHION 87

3. CHEMICAL AND PHYSICAL INFORMATION

3.1 CHEMICAL IDENTITY

Information regarding the chemical identity of ethion is located in Table 3-1.

3.2 PHYSICAL AND CHEMICAL PROPERTIES

Information regarding the physical and chemical properties of ethion is located in Table 3-2.
ETHION 88

3. CHEMICAL AND PHYSICAL INFORMATION

Table 3-1. Chemical Identity of Ethion

Characteristic Information Reference

Chemical name Ethion HSDB 1998

Synonym(s) Phosphorodithioic acid; S,S’-methylene

O,O,O’,O’-tetraethyl ester; ethyl methylene

phosphorodithioate; O,O,O’,O’-tetraethyl

S,S’-methylenediphosphorodithioate;

bis[-(diethoxyphosphinothioyl)mercapto]methane

Merck 1989

Registered trade name(s) NIA1240, Ethanox, Nialate, RP8167, Rodocide,

and others

HSDB 1998

Chemical formula C9H22O4P2S4 Merck 1989

Chemical structure

Identification numbers:

CAS Registry

NIOSH RTECS

EPA Hazardous Waste

OHM/TADS/DOT/UN/NA/IMCO

HSDB

NCI

563-12-2

TE455000

7800010

IMO 6.1; UN 3018; NA 2783

399

No data

HSDB 1998

HSDB 1998

HSDB 1998

HSDB 1998

HSDB 1998

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; HSDB =

Hazardous Substance Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for Occupational

Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; RTECS =

Registry of Toxic Effects of Chemical Substances
ETHION 89

3. CHEMICAL AND PHYSICAL INFORMATION

Table 3-2. Physical and Chemical Properties of Ethion

Property Information Reference

Molecular weight 384.48 Merck 1989

Color White/colorless to amber Tomlin 1994

Physical state Liquid Tomlin 1994

Melting point -12 to -13 Merck 1989

Boiling point 164–165 at 0.3 mm Hg EPA 1989b

Density at 19 EC 1.220 at 20 EC Merck 1989

Odor Odorless in pure form; technical

product has a disagreeable odor

HSDB 1998

Odor threshold:

Water

Air

No data

No data

Solubility:

Fresh water at 25 EC

Salt water at 25 EC

Organic solvent(s)

0.6 mg/L

No data

Xylene, chloroform, acetone, kerosene

plus 1% methyl ethyl ketone, benzene

Most organic solvents

Sharom et al. 1980a

Merck 1989

HSDB 1998

Partition coefficients:

Log Kow

Log Koc

5.073

4.189 (average in four soils)

3.810 (organic soil)

3.936 (beverly sandy loam)

4.004 (plainsfield sand)

Bowman and Sans 1983 

HSDB 1998

Sharom et al.1980b

Vapor pressure at 20 EC 1.5x10-6 mm Hg EPA 1989b; Merck 1989

Henry's law constant:

at 25 EC

6.9x10-7 atm m3

/mole HSDB 1998
ETHION 90

3. CHEMICAL AND PHYSICAL INFORMATION

Table 3-2. Physical and Chemical Properties of Ethion (continued)

Property Information Reference

Hydrolysis half-life

 30 EC (sterile water)

 30 EC (non-sterile 

 drainage water)

 25 EC (Water with 1% 

 ethanol)

pH 4 & 7 146 days

pH 8 62 days

pH 10 1 day

 26 days

pH 4.5 99 weeks

pH 5 63 weeks

pH 6 58 weeks

pH 7 25 weeks

pH 8 8.4 weeks

Dierberg and Pfeuffer 1983 

Chapman and Cole 1982

Autoignition temperature No data

Flashpoint No data

Flammability limits

at 25 EC

May burn but does not ignite readily HSDB 1998

Reactivity Hydrolyzed by acids and alkalies

Emits toxic oxides of sulfur and

phosphorous (T$150 EC)

Slowly oxidized in air

Tomlin 1994

Sax 1984

Tomlin 1994

Conversion factors

(25 EC)

Explosive limits

1 ppm = 15.7 mg/m3

1 mg/m3 = 0.064 ppm

Tends to decompose with violence

above 150 EC 

Calculated

HSDB 1998
ETHION 91

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

4.1 PRODUCTION

Ethion is the FMC Corporation trademark name for the active ingredient O,O,O’,O’-tetraethyl

S,S’-methylene bis (phosphorodithioate) (SRI 1997; Tomlin 1994). This insecticide is produced

commercially by reacting dibromomethane with O,O-diethyl hydrogen phosphorodithioate in ethanol

under controlled pH conditions (HSDB 1998). The FMC Corporation, the only U.S. manufacturer of

this chemical, produces ethion at its Agricultural Chemical Group in Baltimore, Maryland (SRI 1991,

1992, 1993, 1995, 1996, 1997). 

Ethion production in the United States for 1972 was estimated to be 1.36 million kg (2.97 million

pounds) (HSDB 1998). No more recent production estimates for ethion were located. As with many

toxic chemicals, especially those whose production or use involves proprietary information, quantitative

estimates of production are virtually impossible to obtain (Bason and Colborn 1992). 

No current information is available from the Toxics Release Inventory (TRI) database on facilities that

manufacture or process ethion, the intended use, or the range of maximum amounts of ethion that are

stored on-site because ethion is not one of the chemicals that facilities were required to report (EPA

1995e).

4.2 IMPORT/EXPORT

No historic or recent estimates are available on the volume of ethion imported into the United States

(HSDB 1998). No information was located on either past or current volumes of ethion exported from

the United States. Data on past and/or current import and export volumes are not adequate to assess

trends in import and export volumes of this pesticide. While the import and export volume for pesticides

as a group are often available, the data are not typically broken down by individual pesticide (Bason and

Colborn 1992). 
ETHION 92

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

4.3 USE

Ethion is an organothiophosphate member of the organophosphate pesticide family that was first

registered for use in the United States in 1965 (EPA 1989b, 1989d). This pesticide was first developed

as a nonsystemic insecticide and acaricide for use on fruit trees, including citrus fruits (grapefruit,

lemons, limes, oranges, tangelos, and tangerines), other fruit trees (apples, apricots, cherries, nectarines,

peaches, pears, plums, and prunes), nut trees (almonds, chestnut, filberts, pecans, and particularly

walnuts), fiber crops (cotton), and seed and forage crops (alfalfa, corn, and sorghum). as well as a wide

variety of fruits and vegetables (beans, cucumbers, eggplants, grapes, melons, onions, peanuts, peppers,

pimentos, summer squash, strawberries, and tomatoes) (EPA 1989b, 1989d). Ethion is used in

conjunction with petroleum oils on dormant trees to kill eggs and scale insects (HSDB 1998). It is also

used for control of aphids, spider mites, scale insects, thrips, lepidopterous larvae, leafhoppers, maggots,

suckers, and soil-dwelling insects on a wide variety of food, fiber, and ornamental crops, including

grapes, fruits, vegetables, and nuts (Farm Chemicals Handbook 1993; Tomlin 1997). Other uses include

applications as a topically applied pesticide agent on livestock to control biting flies and other insects or

skin parasites, such as ticks (EPA 1989b, 1989d).

With the steady elimination of older organochlorine pesticides from the market, the use of ethion and

other organophosphates has replaced many of the functions once filled by organochlorine pesticides

(Mosha et al. 1990a, 1990b, 1991). In addition to its registered applications in agriculture, ethion is also

used in terrestrial nonfood crops (Bermuda grass, junipers, ornamental evergreens, pine trees, lawns,

ornamental turf, and ornamental plants), in greenhouse nonfood crops including ornamental plants, and

in domestic outdoor uses associated with domestic dwellings and lawns (EPA 1989b, 1989d; Farm

Chemicals Handbook 1993). The methods of application for ethion include: ground and aerial foliar

applications, furrow treatments by ground equipment, and seed treatments (EPA 1989b, 1989d). Several

different types of ethion formulations are produced including: an emulsifiable solution (500 g/L),

wettable powders (25%), dusts (2, 3, and 4%), emulsifiable concentrates (4 and 8 lbs/gal), granules

(5 and 10%), and seed treatments (EPA 1989b; 1989d; Farm Chemicals Handbook 1993; Tomlin 1997). 

Estimated ethion use in the United States was 0.32 million kg (0.70 million pounds) in 1974 (HSDB

1998). Estimated ethion use in the United States increased slightly to 1.255 million pounds

(0.570 million kg) of the active ingredient in the early 1980s (Gianessi 1986). This volume appears to

have remained steady through the late 1980s as EPA (1989d) estimated that between 1.2 and 1.5 million
ETHION 93

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

pounds (0.55–0.68 million kg) of active ingredient of ethion were used in the United States annually. By

1992, the estimated annual use of ethion by agriculture was 868,218 pounds (USGS 1992). No more

recent information on ethion use was located in the literature.

With respect to its use application in 1974, 70% of the ethion applied was used as an insecticide and

acaricide on citrus fruit and 30% was used on other fruit and nut crops and cotton (HSDB 1998). In a

study of use application, EPA (1989d) estimated that from 86 to 89% of the ethion used in the United

States was applied to citrus crops, and the remaining 11–14% was applied to cotton, a variety of fruit and

nut trees, and vegetables. No more recent information on use applications for this pesticide was located.

4.4 DISPOSAL

Ethion is listed as a toxic substance under Section 313 of the Emergency Planning and Community Right

to Know Act (EPCRA) under Title III of the Superfund Amendments and Reauthorization Act (SARA)

(EPA 1995a, 1995b). Disposal of wastes containing ethion is controlled by a number of federal

regulations (see Chapter 7).

There are two primary recommendable methods for the disposal of ethion and ethion-containing wastes

including hydrolysis with subsequent disposal in a landfill and incineration by a variety of methods in a

unit with effluent scrubbing (EPA 1981; IRPTC 1985). Ethion undergoes rapid chemical hydrolysis

under alkaline (>pH 8) conditions (Dierberg and Pfeuffer 1983; IRPTC 1985). IRPTC (1985)

recommends that ethion or ethion-containing wastes be mixed with excess calcium oxide or sodium

hydroxide and sand or other adsorbent in a pit or trench at least 0.5 m deep in a clay soil. Sodium

hydroxide (or sodium carbonate) can also be added to the mixture to help speed the reactions when

calcium oxide is used as the primary alkali agent. The amount of calcium oxide or sodium hydroxide

used depends on the amount of pesticide to be disposed of and, to some extent, the concentration of

active ingredient in the pesticide, and the actual chemical nature of the active ingredient. A practical

guideline, in the absence of specific directions, is to use an approximate volume or weight of alkali from

50 to 100% that of the pesticide. For dilute formulations, such as a 1% solution or dust formulations of

ethion, the amount of calcium oxide or sodium hydroxide can be reduced by one-half. For very

concentrated ethion formulations (over 80% active ingredient), the amount of calcium oxide or sodium

hydroxide can be doubled, but the concentrate should be mixed first with water (or soapy water) before

reaction with the alkali. For safety, a preliminary test should be conducted in which very small amounts
ETHION 94

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL

of ethion and alkali are mixed to ensure that the mixture does not react too vigorously. For added safety,

sizable quantities of ethion can be disposed of in several smaller batches, rather than all at once (IRPTC

1985).

For ultimate disposal, large amounts of ethion residuals can be incinerated in a unit with effluent gas

scrubbing (IRPTC 1985) or by fluidized bed, rotary kiln, or liquid injection incineration (EPA 1981). 

Ethion is a potential candidate for fluidized bed incineration at a temperature range of 450–980 EC and

residence times of seconds for liquids and gases and longer for solids. Ethion is also a potential

candidate for rotary kiln incineration at a temperature range of 820–1,600 EC and residence times of

seconds for liquids and gases and hours for solids. Ethion is also a potential candidate for liquid injection

incineration at a temperature range of 650 to 1,600 EC and a residence time of 0.1–2 seconds (EPA

1981).

Currently, empty pesticide containers should be triple-rinsed with water and then transferred to a proper

hazardous waste disposal facility. On February 11, 1994, the EPA proposed container design

requirements for nonrefillable and refillable pesticide containers. This Federal Insecticide, Fungicide

and Rodenticide Act (FIFRA) authorized action also includes standards on pesticide removal from

containers before disposal, standards for containment of bulk pesticide containers, and procedures for

container refilling operations (EPA 1994). No information was located on past or current volumes of

ethion or ethion-contaminated wastes disposed of by any of the disposal method described. Facilities

involved in the production or processing of ethion are not required to report the amount of ethion wastes

disposed of by any disposal method (EPA 1995e).
ETHION 95

5. POTENTIAL FOR HUMAN EXPOSURE

5.1 OVERVIEW

Ethion is released to the environment solely by human activities. Atmospheric emissions result from

volatilization of the chemical during manufacturing and formulation, from soil and vegetation resulting

from its use as an insecticide and acaricide or from drift during pesticide application or careless mixing

and cleanup procedures during or after application. Ethion can be released to surface waters directly by

point source dischargers, from drift during pesticide applications, and by nonpoint source runoff from

agricultural and urban areas. Ethion is released to soils directly by pesticide application to the soil, from

dripping off sprayed vegetation, when used as a seed treatment, and from careless mixing and cleanup

procedures during and after application. No current information is available on total environmental

releases of ethion from production and processing facilities to air, water, and soil because these facilities

are not required to report releases to the Toxics Release Inventory (TRI) (EPA 1995e).

Although ethion is found in most environmental compartments, the compound shows a pronounced

tendency to partition to soil and sediment. By using an equation for estimating the bioconcentration

factor (BCF) of a chemical derived from its physical and chemical properties, it was determined that

ethion has the potential to bioaccumulate in aquatic organisms (Kenaga 1980). However, no

experimentally measured BCF values for ethion were located for fish, shellfish, or other aquatic

organisms. The half-life of ethion in three tropical soils ranged from 9–15.5 days (Mithyantha and

Agnihothrodu 1984), while in temperate sandy loam and organic soils of Ontario, Canada, the half-life

values ranged from 7 to 8 weeks (49–56 days) (Miles et al. 1979). Given adequate time, ethion will be

degraded by physical, chemical, and biological processes, however, the parent compound can persist at

low concentrations from one growing season to the next (25% carryover), and these concentrations can

build up slowly in the soil over several growing seasons (Chapman et al. 1984; Miles et al. 1978). 

If released to the atmosphere, ethion can exist in both the vapor-phase and adsorbed-phase, although the

adsorbed-phase will predominate (Eisenreich et al. 1981). In the vapor-phase, ethion will react with

photochemically produced hydroxyl radicals at an estimated half-life (first-order kinetics) of

40.13 minutes (Meylan and Howard 1993; SRC 1995). Ethion in the adsorbed-phase will be subject to

washout from the atmosphere by wet and dry deposition.
ETHION 96

5. POTENTIAL FOR HUMAN EXPOSURE

Ethion released to surface waters is subject to hydrolysis, volatilization, photolysis, and biodegradation. 

Volatilization, photolysis, and biodegradation are minor degradation processes that can remove small

amounts of ethion in water. Hydrolysis, however, appears to be the most important mechanism for

degradation, particularly in high alkaline conditions (pH >9) in water. Ethion is susceptible to very slow

hydrolysis in water with half-lives ranging from 63 to 8.4 weeks at pH values ranging from 5 to 8. 

Hydrolysis becomes relatively rapid at alkaline pHs (pH 9 and above), resulting in half-life values of

1 day (Dierberg and Pfeuffer 1983). If released to water, this pesticide has the potential to

bioaccumulate, assuming that rapid degradation of the compound by hydrolysis does not occur. Ethion

has been detected only rarely in both surface water and groundwater monitoring studies typically at

concentrations below 0.5 ppb. 

If released to soils and sediments, microbial degradation of ethion is the most important process for the

removal of the compound based on degradation studies with sterile versus nonsterile soils. The half-life

of ethion in sterile sandy soil loam and organic soil was found to be greater than 24 weeks, while the

half-life in these same nonsterile soils was 7–8 weeks (Miles et al. 1979). This suggests that microbial

degradation is an important fate process. Ethion is generally only slightly mobile in some sandy soils

with a low organic matter content (<3%). However, based on the compound's measured Koc value in

soils with moderate-to-high levels of organic matter, ethion is relatively immobile and does not leach

into groundwater. 

Although some historic information is available from large scale environmental monitoring efforts

conducted in the 1970s, and 1980s (Carey et al. 1978; Cohen 1986; Gilliom 1985), recent monitoring

efforts under national or regional programs have not analyzed for ethion in air, water, soil, sediment, or

fish. This makes it difficult to provide current quantitative estimates on the fate, transport, and

bioaccumulation of ethion in various environmental compartments. No information was located on

measurement of ethion or of its oxons in the atmosphere. In addition, no information was located on

ethion concentrations in air samples from rural or urban areas or in ambient indoor air. Ethion was

detected in indoor air at a pesticide production facility, but not a pesticide storage area (Lewis and Lee

1976). This pesticide has been detected rarely in surface water and in groundwater, but little quantitative

information is available. It has also been detected in soil and sediment in areas where it is extensively

used in agriculture typically at concentrations less than 8 ppm (Miles and Harris 1978a). Current

information is lacking on the total amount of ethion released to the environment and on the amount of

ethion that partitions into each environmental compartment. 
ETHION 97

5. POTENTIAL FOR HUMAN EXPOSURE

The best-documented concern over ethion relates to acute exposures of humans during or immediately

following pesticide applications. This concern is warranted, since ethion is used for some applications in

urban areas (lawns and gardens) that increase the possibilities of general population exposure. Ethion

and its major oxygen analog, ethion monoxon, have significant acute toxicity to humans. The

predominant exposure pathway for the general population appears to be via consumption of small

amounts of the chemical in ethion-contaminated food, particularly fruits and root vegetables, and via

inhalation both during or immediately following application in agricultural areas where this pesticide is

extensively used (e.g., citrus crops). Relative to inhalation, oral exposure probably accounts for a major

portion of the exposure of the general population. 

In addition to small quantities of ethion that are ingested via ethion-contaminated food, infants and

young children may be at increased risk via oral exposure if they put unwashed fingers, toys or other

objects, or soil contaminated with ethion in their mouths. Children may also receive dermal exposure if

they come in contact with freshly treated vegetation or soil around domestic structures, or if they

unknowingly enter ethion-treated agricultural areas before appropriate reentry intervals have elapsed. 

Children living in households of farmers or agricultural workers that apply ethion or work in fields or

orchards treated with ethion may be indirectly exposed if they come in contact with shoes and other

contaminated clothing of their parents, or if these clothing articles are not separately washed and stored

from other domestic laundry.

Occupational exposure may occur through inhalation and dermal exposure routes associated with the

manufacture, formulation, and application of ethion. The magnitude of exposure is greatest for those

individuals occupationally exposed to ethion, particularly those involved in production and

manufacturing of ethion, those involved in its mixing and application for agricultural and commercial

uses, and those workers involved in its disposal at hazardous waste sites. It should be noted that the

amount of ethion detected by chemical analysis is not necessarily the amount that is bioavailable.

Ethion has been identified in at least 9 of the 1,577 hazardous waste sites that have been proposed for

inclusion on the EPA National Priorities List (NPL) (HazDat 2000). However, the number of sites

evaluated for ethion is not known. The frequency of these sites can be seen in Figure 5-1.


















 

 





 1

 





 4

Frequency of

NPL Sites

Derived from HazDat 2000

Figure 5-1. Frequency of NPL Sites with Ethion Contamination
ETHION 99

5. POTENTIAL FOR HUMAN EXPOSURE

5.2 RELEASES TO THE ENVIRONMENT

The TRI data should be used with caution because only certain types of facilities are required to report. 

This is not an exhaustive list. Facilities involved in the production or processing of ethion are not

required to report the amount of releases of ethion to various environmental matrices (EPA 1995e,

1995f). 

Ethion has been identified in a variety of environmental media (air, surface water, groundwater, soil, and

sediment) collected at 9 of the 1,577 EPA National Priorities (NPL) hazardous waste sites (HazDat

2000). 

5.2.1 Air

Ethion is released into the atmosphere solely by human activities associated with its production and use

as a insecticide and acaricide. These releases include releases to ambient air from production and

packaging facilities or agricultural applications. It appears that ethion, once field-applied, can undergo

volatilization to the atmosphere. However, based on the vapor pressure for ethion (see Table 3-2), this

appears to be a relatively minor fate process (Eisenreich et al. 1981; Thomas 1990).

There is no information on releases of ethion to the atmosphere from manufacturing and processing

facilities because these releases are not required to be reported to the TRI Database (EPA 1995e). 

Ethion was detected in indoor air at a formulation plant in south Florida in 1974 at 4 μg/m3

 (Lewis and

Lee 1976). By contrast, ethion was not detected in indoor air of a storage shed where ethion was stored

in sealed containers.

Ethion has been identified in 1 outdoor air sample collected from 9 NPL hazardous waste sites where it

was detected in some environmental media (HazDat 2000). The TRI data should be used with caution

because only certain types of facilities are required to report. This is not an exhaustive list.
ETHION 100

5. POTENTIAL FOR HUMAN EXPOSURE

5.2.2 Water

Ethion can reach surface waters directly from point source discharges associated with its production and

from nonpoint source inputs introduced from agricultural applications associated with spray drift or

careless applications near water (Braun and Frank 1980; Frank et al. 1982; Miles and Harris 1978a,

1978b). Frank et al. (1982) found evidence in a study of 11 agricultural watersheds in the Canadian

Great Lakes Basin from 1975 to 1977 that residues of ethion and other pesticides could reach surface

waters from deposition close to or directly into stream water during the process of drawing water, mixing

the pesticide, spraying, or by cleaning pesticide spraying equipment and by seepage from discarded

containers in or around the spray site. In addition, heavy rainfall within a few days of a field application

often led to the runoff of the pesticide and deposition in streams. In the Frank et al. (1982) study, ethion

was only rarely (0.4% of the samples) found in surface waters during the 1975–1976 study and was not

detected during the 1976–1977 study. Ethion was typically found in surface waters samples

immediately after application. The oxons of ethion were not detected in any surface water samples. 

These authors estimated that ethion unit-area loadings (losses) to streams draining these watersheds

totaled 10 mg/hectare (ha) with the mean and maximum unit-area loading in 1975–1976 of 0.1 and

0.6 mg/ha, respectively, and the mean and maximum in 1976–1977 of 0.0 and 0.0 mg/ha, respectively. 

For ethion, all spray-season losses of ethion were attributed to spills, drift, or direct application in

surface waters rather than to runoff events. The overall mean concentration of ethion in water collected

from these watersheds was <0.01 ppb (minimum [not detected] to maximum [0.4 ppb]) for 1975–1976,

and the overall mean was not detected (minimum [not detected] to maximum [not detected]) for

1976–1977. In a study of the Holland Marsh drainage basin in Ontario, Canada, Miles and Harris

(1978a) reported that the rate of ethion transfer was highest in the spring during maximum runoff

periods. 

In another study in the Great Lakes region, ethion was qualitatively identified in tributary stream feeding

into Lake Ontario, Lake St. Clair, and Lake Huron (Great Lakes Water Quality Board 1983). Gilliom

(1985) also reported that as part of the U.S. Geological Survey (USGS) and EPA Pesticide Monitoring

Network conducted between 1975 and 1980, ethion was monitored in surface water at 174 stations

nationwide, but was detected at only 0.6% of the stations sampled (detection limit=0.25 ppb). 

Based on its Koc value (see Table 3-2), ethion is moderately to highly immobile in soils under most

typical soil conditions and is not likely to migrate through the soil and contaminate groundwater (Swann

et al. 1983). Although detected only rarely, ethion has been found in some groundwater wells in
ETHION 101

5. POTENTIAL FOR HUMAN EXPOSURE

agricultural areas in the United States (Cohen 1986). However, no quantitative information on

groundwater concentrations were located for the United States. It has not been possible to obtain

quantifiable estimates of ethion loadings to groundwater.

There is no information on releases of ethion to surface water from manufacturing and processing

facilities because ethion releases are not required to be reported to the TRI Database (EPA 1995e).

Ethion has been identified in 1 surface water and 4 groundwater samples collected from 9 NPL

hazardous waste sites, where it was detected in some environmental media (HazDat 2000).

The TRI data should be used with caution because only certain types of facilities are required to report. 

This is not an exhaustive list.

5.2.3 Soil

Ethion is released into soils primarily from its registered uses on various agricultural crops, as an

acaricide in veterinary applications against various sucking insects of domestic stock, and as a seed

treatment, or via spills directly to soils associated with the process of mixing the pesticide, spraying, or

by cleaning pesticide spraying equipment and by seepage from discarded containers in or around the

spray site. Because of its affinity for binding to organic matter, soils are the ultimate repository for the

majority of ethion applications. 

In agricultural areas, ethion may also be transferred to aquatic sediments through drift or spillage or via

improper disposal of the chemical after application (Frank et al. 1982; Miles and Harris 1978b; Miles et

al. 1978). Miles and Harris (1978b) reported that ethion residues in bed sediments from the Holland

Marsh agricultural drainage system, an area where ethion was extensively used, ranged from

0.043–0.073 ppm. Since ethion undergoes various chemical and biological degradation reactions in the

course of time ranging from days to months, these loadings to soils and sediments typically are a

temporary phenomena (Dierberg and Pfeuffer 1983; Miles et al. 1979); however, carryover from one

year to the next can result in a build-up of ethion residues under some field conditions (Chapman et al.

1984; Miles et al. 1978). The lack of environmental data makes it difficult to estimate the actual buildup of ethion in basins that receive drainage waters from ethion-treated agricultural lands.
ETHION 102

5. POTENTIAL FOR HUMAN EXPOSURE

There is no information on releases of ethion to soil from manufacturing and processing facilities

because these releases are not required to be reported to the TRI Database (EPA 1995e).

Ethion has been identified in 8 soil and 2 sediment samples collected from 9 NPL hazardous waste sites,

where it was detected in some environmental media (HazDat 2000). 

The TRI data should be used with caution because only certain types of facilities are required to report. 

This is not an exhaustive list.

5.3 ENVIRONMENTAL FATE

Ethion can move into various environmental compartments (air, surface water, groundwater, soil,

sediment, and biological organisms). For this chemical, the primary environmental reservoir or sink is

soil and sediment. The compound is retained in soil for moderate periods of time, depending on soil

temperature and the amount of organic matter content in the soil. Ethion can potentially bioaccumulate

in aquatic food chains, although little quantitative information on concentrations in edible fish and

shellfish was located.

5.3.1 Transport and Partitioning

Based on its vapor pressure (see Table 3-2), if ethion is released to the atmosphere, it will be expected to

exist both in the vapor-phase and particulate phase, although the particulate phase will predominate 

(Kenaga 1980; Eisenreich et al. 1981). Ethion in the adsorbed particulate form will be subject to

washout from the atmosphere by both wet and dry deposition. In the atmosphere, the kinetic motion of

the pesticide molecules as well as air currents will cause their distribution (Haque and Freed 1974). The

molecules will distribute vertically with the heavier molecules having the highest concentration at the

bottom and the lighter molecules at the top. Vapor-phase ethion is heavier than air and will consequently

concentrate on the bottom. The vapor pressure of a chemical can give a good estimate of air transport as

long as the chemical is in the free state or is evaporating from an inert surface (Haque and Freed 1974).

When the chemical is bound to a soil surface, the vapor pressure cannot be used to accurately predict

vapor transport. The vapor pressure of ethion will be greatly attenuated by its strong sorption to soil

surfaces (Sharom et al. 1980a; Swann et al. 1983). Therefore, ethion is not expected to exist in the vaporphase at an appreciable level above soil surfaces.
ETHION 103

5. POTENTIAL FOR HUMAN EXPOSURE

Ethion released to water from both point and nonpoint sources may be emitted to the atmosphere by

volatilization, sorbed to soils and sediments, or accumulated in aquatic organisms. Evaporation may not

be significant based upon the Henry's law constant (see Table 3-2), and volatilization of ethion is not

likely to be an important transport process (Racke 1992; Thomas 1990). Ethion released to water also

may be adsorbed significantly by soils and sediments based on its Koc values measured in soil (Sharom et

al. 1980a; Swann et al. 1983). These authors reported that after 10 successive washes with distilled

water, 13.9% of the ethion had leached from sandy soil, while only 1.2% had leached after 10 successive

washes from organic soil. Because this pesticide is significantly adsorbed by soils with high organic

content, leaching into groundwater is unlikely to occur to any significant extent except in soils with

relatively low organic content (Miles et al. 1979). 

Using the method of Kenaga (1980) to estimate the BCF value of ethion based on the compound’s

physical-chemical properties, ethion was found to have the potential to significantly bioaccumulate in

aquatic organisms. The estimated BCF for ethion ranged from 418 to 1,300, based on water solubility

data and the Koc value, respectively. The BCF value estimated from the log Koc suggests that

bioconcentration can be potentially significant for this compound. However, there were no

experimentally measured BCF values located in the scientific literature to verify that bioaccumulation

occurs in any fish, shellfish, or other aquatic organism. Despite the high lipid solubility of ethion,

distribution studies in rats (Selim 1985a), goats (Mosha 1991), and chickens (Mosha et al. 1990a) have

shown no preferential distribution to adipose tissue. The high lability of ethion to esterases in the blood

and liver may explain these findings.

Ethion and its metabolites have not been widely monitored in aquatic species such as fish and shellfish. 

Since ethion and its metabolite ethion monoxon are toxic, a measure of caution may still be in order in

cases where there is reason to believe edible fish or shellfish have had recent exposure to ethion. This is

partially the basis for the EPA recommendation that states consider routine monitoring for ethion in

edible fish and shellfish species as part of their state toxics monitoring programs, particularly in those

watersheds where extensive use of ethion is identified (EPA 1995g). 

Ethion released in soil from its registered uses partitions slightly to the atmosphere through volatilization,

slightly to surface water via runoff, and only slightly to groundwater as a result of leaching. According to

Kenaga (1980), chemical compounds with a Koc of <100 are considered moderately to highly mobile;

ethion with a Koc value of 15,435, therefore, would be considered almost immobile. Additional 
ETHION 104

5. POTENTIAL FOR HUMAN EXPOSURE

parameters influencing the leaching potential of this chemical include the soil type (e.g., clay, organic

matter, or sand), the amount of rainfall, the depth of the groundwater, and the extent of degradation. In

laboratory tests of sand and organic soil, Sharom et al. (1980b) found that (after 5 successive 200 mL

rinses with distilled water) 0.00, 0.4, 0.6, 1.0, and 1.5% of ethion leached from sand, respectively, and a

total of only 13.9% of ethion added to the sand was leached after 10 successive 200 mL rinses with

distilled water. In organic soil, however, (after 5 successive 200 mL rinses with distilled water) 0.0, 0.0,

0.03, 0.09, 0.11, and 1.2% of ethion leached from soil, respectively; and only 1.2% of ethion added to the

organic soil was leached after 10 successive 200 mL rinses with distilled water. The amount leached

from the sandy soil was over 10 times greater than that leached from the organic soil, although the

leachability of ethion was far less than for many of the other organophosphates tested. While ethion can

show high sorption in soils with high organic content (>3%), in most other soil types (sands), ethion has

properties suggesting only a slight potential for leaching into groundwater (Sharom et al. 1980b). 

In a study of groundwater contamination in California, ethion was detected, but not quantified in 5 out of

an unspecified number of groundwater well samples (Cohen 1986). In the Great Lakes region of Ontario,

Canada, Frank et al. (1982) reported that ethion was detected in only 0.4% of all surface water samples

collected from 11 agricultural watersheds from 1975 to 1976 at a maximum concentration of 0.05 ppb. 

Ethion was not detected, however, during the 1976–1977 monitoring season (Frank et al. 1982).

5.3.2 Transformation and Degradation

Ethion is subject to a variety of physical, chemical, and biological degradation processes in all

environmental compartments. Some of these transformation pathways are shown in Figure 5-2.

5.3.2.1 Air

Ethion, once released to the atmosphere, may be subject to direct photolysis; however, because ethion

does not absorb light in the spectrum above 290 nm (Gore et al. 1971), direct photolysis is likely to be

only a minor fate process. In the vapor-phase, ethion can react rapidly, however, with photochemically

produced hydroxyl radicals. The half-life (first-order kinetics) for the vapor-phase reaction of ethion with

hydroxyl radicals in the atmosphere is estimated to be 40.13 minutes, assuming an atmospheric

concentration of containing 5x105

 hydroxyl radicals/m3 at 25 EC (Meylan and Howard 1993; SRC 1995). 

No other information on the transformation processes of ethion in the atmosphere was located.
ETHION 105

5. POTENTIAL FOR HUMAN EXPOSURE

H5C2O

P

O

S C

H2

S P

O OC2H5

H OC2H5 5C2O

(Ivey and Mann 1975)

H5C2O

P

S

S C

H2

S P

O OC2H5

H OC2H5 5C2O

 mammals

(Ivey and Mann 1975)

H5C2O

P

S

S C

H2

S P

S OC2H5

H OC2H5 5C2O

humans (Nigg et al. 1993)

Diethyl phosphate

Diethyl thiophosphate

Diethyldithiophosphate

(Dierberg and Pfeuffer 1983)

pH 4-7

H2O+ OHpH>7

H5C2O

P

S

OH

H5C2O

P

S OC2H5

OC2H5

+

H5C2O

P

S

SH

H5C2O

S P

S OC2H5

OC2H5

C

H2

-

S + HO

 mice

(Mahajna et al. 1966)

H5C2O

P

S

S

H5C2O

CH3

(Mahajna et al. 1966)

H5C2O

P

O

S

H5C2O

CH3

+

H H

S

C

Figure 5-2. Transformation of Ethion
ETHION 106

5. POTENTIAL FOR HUMAN EXPOSURE

5.3.2.2 Water

Ethion released to water may be subject to both abiotic degradation (i.e., hydrolysis and photolysis) and

biotic degradation by microorganisms. The rate of abiotic degradation is influenced strongly by pH and

temperature. Cowart et al. (1971) studied the rate of hydrolysis of 7 organophosphate pesticides, 

including ethion in distilled water samples at a pH of 6. Over a 6-week study period, these authors

reported that the percentage of undegraded ethion was 92, 84.2, 71.3, 38.9, 37.9, 31.2, 13.4, 6, and 5.2%

at 2 hours, 1 day, 2 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, and 6 weeks post-application,

respectively. These authors found that ethion and parathion were the two most persistent organophosphates tested, and that as a general rule, the rate of hydrolysis in distilled water increases with

decreasing sulfur content of the organophosphate tested. Chapman and Cole (1982) also studied the

influence of pH on the degradation of ethion in sterile water at 25±3 EC. These authors reported

estimated half-life values (first-order kinetics) for ethion of 99, 63, 58, 25, and 8.4 weeks at pH values of

4.5, 5, 6, 7, and 8, respectively. The lower temperature conditions of this study may account for the much

slower ethion degradation rates in the acidic pH range. In a laboratory study, Dierberg and Pfeuffer

(1983) reported that the hydrolysis half-life of ethion in buffered distilled water at 30 EC was 20.8 weeks

at a pH ranging from 4 to 7 (first-order kinetics and independent of pH), 8.9 weeks at pH 8 (second-order

kinetics), and 1 day at pH 10 (second-order kinetics). Degradation of ethion was most rapid under

alkaline conditions. 

Available studies conducted using natural water and sterilized natural water suggest that hydrolysis 

rather than microbial degradation is the most important degradation process for ethion in water. Dierberg

and Pfeuffer (1983) reported that the half-life of ethion in natural and sterilized Florida canal water was

very similar, between 24 and 26 days over a 12-week study period, which suggested that hydrolysis 

rather than microbial degradation was a significant mechanism of loss from Florida surface waters. This

contrasts sharply with results obtained by Sharom et al. (1980a) using sterile and unsterile Ontario,

Canada marsh water where half-lives of greater than 16 weeks were calculated. The incubation

temperature of the Dierberg and Pfeuffer (1983) study was 4 EC higher and the initial ethion

concentrations were lower; however, the similarity of the half-lives for the sterile and unsterile distilled

water controls between the two investigations suggests that these differences were minor in accounting

for the degradation rates in the two surface waters. Degradation was more affected by temperature,

suggesting that hydrolysis was the primary mode of degradation. In contrast to the half-life of 26 days

reported by Dierberg and Pfeuffer (1983) for unsterile canal water, is the half-life value (>8 weeks) given 
ETHION 107

5. POTENTIAL FOR HUMAN EXPOSURE

by Eichelberger and Lichtenberg (1971) for water from the Little Miami River, Florida incubated under

similar laboratory conditions (except for the presence of light). The inclusion of light in the latter study

demonstrates that photolysis may not be a competitive degradation pathway for ethion compared to

hydrolysis. 

Gore et al. (1971) reported that ethion in a hexane solvent did not absorb ultraviolet light above 260 nm,

which suggests that direct photolysis does not readily occur. Frank et al. (1991) investigated the

degradation of ethion in surface and groundwater samples for 164 days, but found little difference in the

rate of ethion degradation in light and dark conditions, indicating that photolysis was not a major fate

process. The half-life (first-order kinetics) of ethion of 51 days (light) and 58 days (dark) suggests that

photolysis was not a major factor in degradation. The ambient temperature during this degradation

experiment ranged from -3.8 to 37.0 EC. These authors also compared the degradation of ethion in

two controlled temperature regimes of 4 and 21 EC at a pH of 8. These authors calculated a half-life

(first-order kinetics) for ethion of 34 days at 21 EC as compared to 84 days at 4 EC. 

Sharom et al. (1980a) studied the degradation of ethion under laboratory conditions using both distilled

water and natural water samples. The rate of degradation was comparable (half-life >16 weeks) in natural

water (pH 7.7), sterilized natural water, sterilized distilled water, or distilled water, suggesting

biodegradation of ethion was not occurring. Under these experimental microcosm conditions, hydrolysis

appears to be the major transformation process operative in the natural water system. Discrepancies in the

rates of ethion degradation in water reported in the literature appear to be influenced by both abiotic and

biotic factors.

Although ethion has been detected in groundwater samples only rarely in the United States (Cohen 1986;

HazDat 2000), no studies were identified dealing with ethion transformation and degradation processes

within aquifers. Based on theoretical considerations, abiotic hydrolysis mechanisms would be expected

to degrade ethion within a few months to years (99 weeks to 8.4 weeks at a pH of 4.5 and 8, respectively)

(Chapman and Cole 1982).
ETHION 108

5. POTENTIAL FOR HUMAN EXPOSURE

5.3.2.3 Soil Transformation and Degradation

Once released to soils and sediments, ethion can be degraded by hydrolysis, photolysis, and

biodegradation. Hydrolysis may be a significant degradation process under alkaline soil conditions. 

Photolysis, while possible, is not likely to be a significant degradation process because ethion does not

absorb ultraviolet (UV) light above 260 nm (Gore et al. 1971). Microbial degradation appears to be the

major pathway for the degradation of ethion in soils (Miles et al. 1979). Ethion degraded with a half-life

of 69–102 days in an aerobic soil metabolism study (EPA 1989b).

Miles et al. (1979) studied the persistence of 8 organophosphate pesticides including ethion in sterile and

nonsterile mineral (sandy loam) and organic soils. Ethion was the most persistent of the organophosphates tested. These authors reported that 50% of the initial concentration of ethion still remained at

>24 weeks in sterile sandy loam and sterile organic soil. In nonsterile soil, however, 50% of the initial

concentration remained after 7 and 8 weeks in sandy loam and organic soil, respectively. Ethion was

slightly more persistent in organic soil than in the sandy loam. These authors concluded that microbial

degradation played a major role in the degradation of ethion from the soils tested. 

Miles et al. (1978) studied the use of ethion as a seed furrow treatment for the control of onion maggots in

the Holland Marsh in Ontario, Canada from 1972 to 1975. These authors reported that a 25% carryover

of ethion residues in the soil occurred from one yearly application to the next. Ethion soil residues were

1.83±1.42 ppm (dry weight basis) in 1972, 6.93±8.31 ppm in 1973, 5.75±4.98 ppm in 1974, and

3.47±2.83 ppm in 1975. Chapman et al. (1984) also reported that concentrations of ethion in field

microplots over a 3-year period suggested that some carryover was occurring. These authors reported that

in the fall of 1977, concentrations of ethion in soil treated with a granular formulation to control onion

maggots were 4.36 ppm. Soil concentrations in the spring and fall of 1978 were 1.85 and 3.06 ppm,

respectively. Ethion residues in the spring of 1979 were not analyzed, and the fall concentrations were

7.77 ppm, and fell only slightly to 7.6 ppm in the spring of 1980 indicating slow degradation in winter. 

Sherman et al. (1974) studied iron sulfide production from ethion-enriched soils by bacteria found in

lagoonal sediments of the Indian River-Banana River in Florida. These authors reported that ethion

enriched sediment samples from the Indian River were used as the source of sulfur-utilizing bacteria

(probably Clostridium) in culture tube experiments. Inoculated media that contained both an iron wire
ETHION 109

5. POTENTIAL FOR HUMAN EXPOSURE

and ethion gave evidence of darkening of the wire; but more significantly, they gave evidence of iron

sulfide (FeS) production at the stab-line of the inoculation, after 12 hours of incubation. Upon further

incubation, the FeS discoloration spread from the inoculation stab-line throughout the culture tube. The

authors also concluded that this reaction was an anaerobic process because no FeS was found at the

surface of the media slant. Inoculated media that contained iron wire, but had no ethion added, supported

bacteria growth, but FeS was not produced. In uninoculated cultures containing both an iron wire and

ethion, there was evidence of a chemical reaction of ethion with the wire as indicated by a darkening of

the surface of the wire. However, there was no FeS production throughout the medium.

Mithyantha and Agnihothrodu (1984) studied the persistence of ethion in red, black, and laterite tropical

soils under 2 moisture conditions (field capacity vs. submergence) using 2 application rates (25 and

50 ppm). These authors reported that ethion degraded more slowly in the acidic laterite soils followed by

the red and black soils. Ethion degraded faster as the pH of the soil increased. The pH for the laterite,

red, and black soils was 4.6, 6, and 7.8, respectively. Degradation rates for the 2 concentrations of ethion

used were similar in each test. The half-life values (first-order kinetics) for ethion in these tropical soils

ranged from 9 to 15.5 days when incubated at a temperature of 24±2 EC throughout the test period. The

persistence of ethion in three different soil types at two treatment levels of ethion (25 and 50 ppm) is

summarized in Table 5-1.

In a study of the fate of ethion in canals draining a Florida citrus grove, Dierberg and Pfeuffer (1983)

reported that ethion adsorption to the sandy canal sediments was negligible following ethion applications

to the citrus grove, and that ethion concentrations never exceeded 0.03 μg/g (ppm) (dry weight). Sharom

et al. (1980b) reported that pesticides were desorbed to a greater degree from a sandy soil than a highly

organic soil. 

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT

Most information on ethion concentrations in various environmental media derived from large-scale

monitoring networks dates from before the mid-1980s and no longer reflects current environmental

conditions. There is a noticeable lack of recent national or regional monitoring studies that would allow

meaningful estimation of current ethion concentrations associated with various environmental media.
ETHION 110

5. POTENTIAL FOR HUMAN EXPOSURE

Table 5-1. Percentage of Ethion Remaining in Various Types 

of Tropical Soils over Time

Soil type (pH) 

treatment level 

% Ethiona

10 Days 22 Days 35 Days 45 Days 57 Days

Laterite soils (pH 4.6)

 25 ppm

66 

(16.26)

30 

(7.46)

13 

(3.36)

7.6 

(1.91)

3.3 

(0.83)

Laterite soils (pH 4.6)

 50 ppm

69 

(34.70)

39 

(19.25)

20 

(10.05)

7.7 

(3.87)

2.1 

(1.03)

Submerged laterite soils (pH 4.6) 

 25 ppm

59 

(14.82)

35 

(8.83)

20 

(5.08)

7.2 

(1.98)

3.3 

(0.83)

Submerged laterite soils (pH 4.6) 

 50 ppm

48 

(24.22)

26 

(13.11)

15 

(7.32)

4.3 

(2.16)

2 

(0.98)

Red soils (pH 6)

 25 ppm

65 

(16.22)

42

(10.61)

17 

(4.32)

2.6 

(1.03)

3.3 

(0.83)

Red soils (pH 6)

 50 ppm

67 

(33.62)

39 

(19.28)

18 

(9.10)

6.4 

(3.18)

2.1

(1.03)

Submerged red soils (pH 6)

 25 ppm

58 

(14.60)

32 

(8.00)

16 

(3.96)

3.6 

(0.90)

3.3 

(0.83)

Submerged red soils (pH 6)

 50 ppm

53 

(26.26)

28 

(14.13)

16 

(7.98)

5.2 

(2.16)

2.1 

(1.03)

Black soils (pH 7.8)

 25 ppm

50 

(12.60)

28 

(7.11)

16 

(4.00)

3.3 

(0.83)

2.4 

(0.59)

Black soils (pH 7.8)

 50 ppm

48 

(24.22)

24 

(11.82)

12 

(5.88)

2.6 

(1.03)

0.8 

(0.41)

Submerged black soils (pH 7.8) 

 25 ppm

42 

(10.48)

20 

(5.10)

10 

(2.58)

2 

(0.52)

1.8 

(0.45)

Submerged black soils (pH 7.8) 

 50 ppm

48 

(24.22)

25 

(12.66)

12 

(5.88)

2.6 

(1.03) 

1.7 

(0.83)

a

Values in paratheses are ethion soil concentrations in ppm

Source: Mithyantha and Agnihothrodu 1984
ETHION 111

5. POTENTIAL FOR HUMAN EXPOSURE

5.4.1 Air

Ethion concentrations or concentrations of its metabolite, monoxon, in the atmosphere were not

monitored in several major national and regional study (Glotfelty et al. 1990; Schomberg et al. 1991;

Whitmore et al. 1994). Ethion also was not an analyte included in the National Pesticide Monitoring

Program during the early 1970s (Kutz et al. 1976). No quantitative information was located on air

samples collected either in rural or urban areas, near production or formulation facilities, or in indoor air

associated with its use for pest control in greenhouses.

However, ethion was detected at 4 μg/m3

 in indoor air at a formulation plant in south Florida in 1974

(Lewis and Lee 1976). By contrast, ethion was not detected in indoor air of a storage shed where ethion

was stored in sealed containers at the same pesticide formulation plant.

Ethion has been identified in air samples (outdoor air) collected at 1 of the 9 NPL hazardous waste sites

where it was detected in some environmental media (HazDat 2000).

5.4.2 Water

Although ethion is considered an extremely hazardous substance under Title III of the Superfund

Amendments and Reauthorization Act (SARA) of 1986, also known as the Emergency Planning and

Community Right-To-Know Act and is subject to reporting under the Comprehensive Environmental

Response, Compensation, and Liability Act (CERCLA) of 1980, it has not been widely monitored in the

United States in routine surface water or groundwater monitoring networks. Gilliom (1985) reported that

as part of the USGS and EPA Pesticide Monitoring Network conducted between 1975 and 1980, ethion

was monitored in surface water at 174 stations nationwide but was detected at only 0.6% of the stations

sampled (detection limit=0.25 ppb). 

In the Great Lakes region, ethion was detected in surface waters in several river basins in southern

Ontario, Canada. Frank et al. (1982) monitored agricultural pesticide use and surface water

concentrations in 11 agricultural watersheds in southern Ontario. All watersheds drained into the Great

Lakes. During 1975, ethion use was estimated to range from 1 to 10 kg/ha. Ethion residues as a result of

field use were detected rarely (0.4%) and were detected immediately during the spray season rather than

throughout the year. The overall mean concentration of ethion in water collected from these watersheds
ETHION 112

5. POTENTIAL FOR HUMAN EXPOSURE

was <0.01 ppb (minimum [not detected] to maximum [0.4 ppb]) for 1975–1976 and the overall mean was

not detected (minimum [not detected] to maximum [not detected]) for 1976–1977. In another study in the

Great Lakes region, ethion was qualitatively identified in tributary stream feeding into Lake Ontario,

Lake St. Clair, and Lake Huron (Great Lakes Water Quality Board 1983). In a study of the occurrence of

pesticides in Spanish surface waters, ethion was detected in 1 out of 6 water samples from the Segre River

Basin (west of Catalonia) at an estimated concentration of 0.01 μg/L (Planas et al. 1997). A group of

research scientists recently completed a study of pesticide concentrations in the Arno river which supplies

over 90% of the drinking water to Florence, Italy (Griffini et al. 1997). Water samples were collected

from the river entering the drinking water treatment plant of Florence and from the finished drinking

water. Of the 167 water samples analyzed from 1992 to 1995, none contained any detectable amount of

ethion (detection limit = 0.010 μg/L).

In a groundwater contamination study of 28 of California's 58 counties that evaluated over 50 pesticides

(from both point and nonpoint sources), ethion was detected (but not quantified) in 5 samples out of an

unspecified number of groundwater samples (detection limit not specified) (Cohen 1986). Ethion

however, was not included as an analyte of interest in the EPA Pesticides in Ground Water Database

(EPA 1989c). This database was developed to compile the results of monitoring studies conducted by

pesticide registrants, universities and government agencies and identified the pesticides that have been

looked for in groundwater, the areas monitored, and the pesticides that have been detected. 

Ethion has been identified in 1 surface water and 4 groundwater samples collected from the 9 NPL

hazardous waste sites where it was detected in some environmental media (HazDat 2000).

5.4.3 Sediment and Soil

Ethion has not been the focus of many recent national soil or sediment monitoring programs in the

United States, but has been monitored in regional studies associated with agricultural applications in

both the United States and Canada. Ethion was one of the organophosphate pesticides monitored in soils

collected from 37 states as part of 1971 National Soils Monitoring Program (Carey et al. 1978). These

authors reported that of 1,141 soil samples collected from 4 hectare sites throughout the US, ethion was

detected in only 2 samples (0.2% positive detections) at concentrations ranging from 0.06 to 0.24 ppm.

Ethion was detected only in samples collected in two states, California and Florida. Ethion was not

detected in any crop samples that were analyzed for this study (detection limits 0.01–0.03 ppm). 
ETHION 113

5. POTENTIAL FOR HUMAN EXPOSURE

Possibly because of its lack of detection in the 1971 National Soils Monitoring Program, ethion was not

one of the 9 organophosphate pesticides monitored in soils collected as part of 1972 National Soils

Monitoring Program (Carey et al. 1979). 

Miles et al. (1978) reported on results of a regional study conducted on agricultural soils of high organic

content in Holland Marsh, Ontario, Canada. These authors reported that ethion was used as a seed

furrow treatment for control of first generation onion maggots and its use comprised 80% of the total

organophosphate soil residues. Ethion was detected in soil at all 13 farms in the Holland Marsh study

area from 1972 to 1975. Mean soil residues were 1.83±1.42 ppm, 6.93±8.31 ppm, 5.75±4.98 ppm, and

3.47±2.83 ppm (dry weight) for 1972, 1973, 1974, and 1975 respectively. The authors also

demonstrated both in field and laboratory studies an ethion carryover rate of 25% from one planting

season to the next when ethion was applied in a granular form. 

Winterlin et al. (1984) reported that ethion was detected in soil collected from a lined evaporation bed

used for disposal of pesticide wastes in California. Ethion was not detected in the soil horizon from the

surface to a depth of 1 inch but was detected at concentrations of 4.1 to 4.6 ppm in the 1–6-inch soil

horizon and was not detected in soil samples from the 6- to 12-inch soil horizon. 

Gilliom (1985) reported that, as part of the USGS and EPA Pesticide Monitoring Network conducted

between 1975 and 1980, ethion was monitored in bed sediments at 163 stations nationwide, but was

detected at only 0.6% of the station (detection limit=0.25 ppb). Ethion has been detected in organic mud

of the Holland Marsh drainage system in southern Ontario, Canada (Miles and Harris 1978b). Ethion

was detected in these sediments at concentrations ranging from 0.043 to 0.073 ppm. Miles and Harris

(1978a) also reported that ethion was detected in soil collected from 23 of 28 vegetable farms in

southwestern Ontario, Canada. Soil concentrations ranged from trace amounts (<0.02 ppm) to 7.81 ppm

at a maximum. On 15 of the farms, the ethion concentration in the soil was > 1.0 ppm and ethion was

the major organophosphate residue reported. 

Ethion has been identified in 8 soil and 2 sediment samples collected from the 9 NPL hazardous waste

sites, where it was detected in some environmental media (HazDat 2000). 
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5. POTENTIAL FOR HUMAN EXPOSURE

5.4.4 Other Environmental Media

Nigg et al. (1988) conducted a study of the distribution of ethion in Valencia oranges grown in Florida. 

The purpose of the study was to determine the distribution of ethion, ethion monoxon, and ethion dioxon

between the peel and pulp of Florida Valencia oranges, and whether the concentration for the entire fruit

was representative of ethion concentrations in the consumed portion (peeled orange). These authors

found that ethion levels in whole mature fruit declined from 1.8 ppm at 3 days post-spraying to 0.6 ppm

35 days thereafter. The mature fruit samples collected prior to spraying ethion, contained ethion in the

peel at 1.6 ppm. This mature harvestable crop, treated 9 months prior to sampling, contained ethion pulp

residues below 0.02 ppm (unquantifiable trace level) and no detectable ethion monoxon or ethion

dioxon. From these data, the authors concluded that the pulp (edible portion) contains a very small

percentage of the whole fruit ethion.

MacNeil and Hikichi (1976) studied the degradation of ethion on pears and pear and grape foliage. 

Ethion concentration on pears treated with 8 lb/acre ethion (wettable powder–25%) decreased from

3.96±0.31 ppm at day 0 to 2.54±0.12 ppm, 1.95±0.08 ppm, 1.18±0.26 ppm, 1.19±0.01 ppm and

0.67±0.01 ppm after 1, 2, 3, 4, and 5 weeks, respectively. Pear leaves were treated with 8 lb/acre ethion

(wettable powder–25%). Ethion concentrations on pear leaves declined from 3.34±0.56 ppm at day 0 to

3.41±1.78 ppm, 2.43±0.72 ppm, 1.21±0.26 ppm, 1.46±0.18 ppm, 0.40±0.19 ppm, 0.34±0.07 ppm, and

0.27±0.09 ppm at day 1, 3, 6, 14, 21, 28, and 35, respectively. Grape leaves were treated with 1 lb/acre

ethion (wettable powder–25%). Ethion residues were 0.59±0.07 ppm on day 0 and declined to

0.40±0.07 ppm, 0.20±0.14 ppm, 0.10±0.06 ppm, 0.10±0.11, 0.02±0.01 ppm, 0.02±0.02 ppm, and

0.01±0.01 ppm at day 1, 3, 6, 14, 21, 28, and 35, respectively. 

Ethion was found in 6 of 30 composite samples of fruit (at a maximum concentration of 0.265 ppm)

collected from 30 markets in 24 different cities from June 1968 through April 1969. Corneliussen

(1970) reported that average residues of ethion on fruit could be reduced from 0.024 ppm before

processing to 0.014 ppm after processing. Furthermore, this author calculated the average retention of

ethion residues on the fruit samples to be 58% after processing.

The FDA conducted a total diet study to determine dietary intake of selected pesticides, industrial

chemicals, and heavy metals, including radionuclides, in 20 cities from October 1978 to September 1979

(Gartrell et al. 1985a). These authors reported that the average ethion concentrations (ppm) were
ETHION 115

5. POTENTIAL FOR HUMAN EXPOSURE

<0.0001 and 0.0014 for garden fruits and fruits, respectively, and that ethion exposures (μg/day) from

garden fruits, fruits, and all groups of foods combined were 0.0018, 0.312 and 0.314, respectively. In a

similar study conducted from October 1979 to September 1980, Gartrell et al. (1985b), reported that

ethion was detected in root vegetables and fruits. The average ethion concentration (ppm) was 0.0008

and 0.0003, respectively, and the ethion exposures (μg/day) from root vegetables, fruits, and all foods

combined were 0.0263, 0.0658, and 0.0921, respectively. Similarly, Gartrell et al. (1986) reported that

ethion was detected in root vegetables, garden fruits, and fruits at 0.0001, 0.0007, and 0.0014 ppm,

respectively. The average ethion exposures (μg/day) from root vegetables, garden fruits, fruits, and all

groups of foods combined were 0.0021, 0.0482, 0.031, and 0.36, respectively, which rose slightly over

the previous years.

Almost 20,000 samples of food and feed commodities were evaluated as part of a 5-year study from

1981 to 1986 conducted by the FDA Los Angeles District Laboratory to determine pesticide residues in

domestic and imported foods and animal feeds (Hundley et al. 1988). These authors reported that ethion

was detected in a wide variety of domestic foods: grapefruit, grapes, romaine lettuce, strawberries, and

tomatoes; however, none of the samples exceeded EPA tolerance limits. Ethion was also detected in the

following imported foods: apples, green beans, limes, cucumbers, pickling cucumbers, eggplant,

Japanese eggplant, cantaloupe, honeydew melon, watermelon, nectarines, Chinese peas, peppers

(Anaheim, bell, caribe, fresco, jalapeno, poblano, yellow) Italian squash, tomatoes, and cherry tomatoes;

however, only residues in Chinese peas, bell peppers, and Serrano peppers exceeded the EPA tolerance

limits. The overall violation rates for domestic and imported samples collected on a surveillance basis

were 3.0 and 2.6%, respectively.

Luke et al. (1988) reported on a study of 19,851 samples of domestic and imported foods that were

analyzed for pesticide residues by the FDA Los Angeles District Laboratory from 1982 through 1986. 

The authors reported that ethion was detected in 425 food samples; however, in only 2 of these samples

did the concentrations of ethion exceed the 2 ppm tolerance limit.

Concentrations of ethion in ready-to-eat foods were monitored for 10 years from 1982 to 1991 through

the FDA's Revised Market Basket Survey (KAN-DO Office and Pesticides Team 1995). Ethion was

detected in 199 samples of 31 different foods at a mean concentration of 0.0053 μg/g (5.3 ppb), and the

ethion oxygen analogue was detected eight times in five different foods at a mean concentration of

0.0029 μg/g (2.9 ppb). Ethion was detected in apples, cantaloupe, cherries, donuts, frankfurters, fruit
ETHION 116

5. POTENTIAL FOR HUMAN EXPOSURE

cocktail, grapefruit and grapefruit juice, grape jelly, oranges, orange juice, orange drink, tomatoes,

tomato juice, plums, prunes, raisins, and summer squash, and was also detected in the following baby

foods: apple sauce, Dutch apple Betty, meat, beef and vegetables, orange and orange pineapple juice,

pears or pears and pineapples. The ethion oxygen analogue was detected in the following adult foods:

grapefruit juice, orange juice, and pears and in the following baby foods: orange or orange-pineapple

juice.

Minyard and Roberts (1991) reported pesticide residue data for 27,065 samples of foods collected and

analyzed in 10 state food laboratories from 1988 to 1989. They reported in 1988, that ethion was

detected in 15 of 13,980 samples analyzed with an occurrence frequency of 0.107%, but in only 1

sample was the residue at a significant level. Likewise in the 1989 study, ethion was detected in 25 of

13,085 samples for a frequency of occurrence of 0.0191%, but in only 2 of the samples were the residues

at a significant level.

Schattenberg and Hsu (1992) reported on results of a pesticide screening program conducted for 111

different pesticides and performed on 6,970 produce samples collected from 1989 to 1991 at a major

food chain in San Antonio, Texas. Ethion concentrations were detected (detection limit of 0.100 ppm) in

3.3% of apples, 0.5% of grapes, 1.8% of oranges, 0.6% of peppers, and 1.3% of strawberries tested. The

actual concentrations of ethion detected were not specified. 

More recently, Roy et al. (1995) evaluated ethion residues in domestic and imported pears and tomatoes. 

Ethion was found in <1% of the domestic pears sampled and the maximum concentration detected was

0.03 ppm. Ethion was not detected on any of the imported pears tested. With respect to tomatoes,

ethion was detected in <1% of domestic tomatoes at a maximum concentration of 0.21 ppm, and it was

also detected in 7% of the imported tomatoes at a maximum concentration of 0.09 ppm. The EPA

tolerance limit for both pears and tomatoes is 2 ppm. 

Most recently, Berry et al. (1997) conducted a study of human exposures in the lower Rio Grande Valley

(in and around the city of Brownsville, Texas) to a variety of pollutants including ethion derived from

the consumption of foods and beverages. Ethion was detected in only 1 food sample, at a concentration

of 0.009 ppm, during the spring of 1993; and ethion was not detected in any food or beverage samples

during the fall of 1993. 
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5. POTENTIAL FOR HUMAN EXPOSURE

The frequency of detection of ethion was 3% in both the FDA adult total diet study conducted from 1978

to 1982 (Yess et al. 1991) and the FDA adult total diet study from 1982 to 1984 (Gunderson 1988). 

More recently, the frequency of occurrence of ethion detections in the FDA total diet study has remained

relatively constant from 2% in 1987 (FDA 1988), 2% in 1988 (FDA 1989), 3% in 1989 (FDA 1990), 2%

in 1990 (FDA 1991), 2% in 1991 (FDA 1992), averaged 2% from 1986 to 1991 (FDA 1993), averaged

2% from 1991 to 1993 (FDA 1994), and was 2% in 1994 (FDA 1995). 

Gelardi and Mountford (1993) analyzed for the presence of 34 pesticides, including ethion in infant

formula. The detection limit range for ethion was <0.001–0.016 ppm. These authors reported that of

110 milk-based formulae and of 59 soy-based formulae analyzed, ethion was not detected in any samples

of either formula.

Pesticide residues were evaluated in infant and toddler total diet samples from August 1976 to

September 1977 (Johnson et al. 1984). These authors reported that of 117 infant foods tested, ethion was

detected in 2 samples in trace amounts, while ethion was detected in only 2 of 132 toddler foods at a

concentration of 0.001 ppm. Positive detections were made only in foods in the fruit or fruit juice

category. 

Yess et al. (1993) summarized the results of a study to monitor pesticide residues in infant and adult foods

eaten by infants and children. With respect to surveillance monitoring of domestic foods, these authors

reported that ethion (total) was detected in 22 of 2464 apple samples at a maximum concentration of

1.7 ppm, in 1 of 13 orange juice samples at a maximum concentration of 0.03 ppm, in 42 of 862 samples

of oranges at a maximum concentration of 1.1 ppm and in 7 of 571 pear samples at a maximum

concentration of 0.22 ppm. The concentration of ethion (total), however, did not exceed the EPA

tolerances level (2.0 ppm) for any of the domestic foods tested which might be eaten by infants and

children. With respect to surveillance monitoring of imported foods, these authors reported that ethion

(total) was detected in 9 of 735 apple samples at a maximum concentration of 0.23 ppm, in 1 of 64 orange

juice samples at a maximum concentration of 0.02 ppm, in 89 of 474 samples of oranges at a maximum

concentration of 0.61 ppm and in 1 of 816 pear samples at a maximum concentration of 0.17 ppm. The

concentration of ethion (total), however, did not exceed the EPA tolerances level (2 ppm) for any of the

imported foods tested which might be eaten by infants and children. With regard to prepared foods for

infants and children, Yess et al. (1993) also reported that the maximum concentrations of ethion (total)

detected in Dutch apple Betty were 0.001 ppm, in 3 samples of applesauce or applesauce with other fruits

were 0.002 ppm, in 21 samples of orange or orange pineapple juice were 0.01 ppm, in 
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5. POTENTIAL FOR HUMAN EXPOSURE

3 samples of pears or pears and pineapples were 0.003 ppm, in 24 samples of frozen orange juice were

0.008 ppm, and in 6 samples of raw pears were 0.280 ppm. Again, all of the adult foods that might be

consumed by infants and children that were tested contained ethion residues well below the EPA

tolerance level of 2 ppm.

Ethion residues have also been detected in a variety of fish species in two studies conducted during the

1970s; however, no more recent data on tissue concentrations of ethion were located. Butler and

Schutzmann (1978) summarized results of the National Pesticide Monitoring Program conducted from

July 1972 through June 1976, that analyzed residues of pesticides in 1,524 samples of juvenile fish

collected semi-annually in 144 estuaries nationwide. Composite samples of 25 whole fish were screened

for 20 pesticides and PCBs. Ethion was detected in composite samples of juvenile fish collected in two

states. Ethion was detected at a mean concentration of 0.169 ppm in 19 of 140 samples collected in

Maryland and at a concentration of 0.083 ppm in 1 of 51 samples collected in Texas. Ethion residues

were also detected in a regional study of fish collected from 1972 to 1975 from the Holland Marsh,

Ontario, Canada (Miles and Harris 1978a). These authors reported that ethion was only detected in fish

collected during 1974 at 0.01 ppm in silver bass, 0.01 ppm in catfish, 0.02 ppm in whitefish, and

0.05 ppm in carp. All of the ethion detections were made in fish collected in the agricultural drainage

system associated with Holland Marsh, and not in the fish collected downstream in Lake Simcoe. 

Ethion residues have also been reported in honey from the northwestern portion of Spain (Garcia et al.

1995). These authors reported that 177 honey samples collected from 1988 to 1990 contained residues

of 6 pesticides, including ethion. These pesticides were detected in 69 of the 177 samples tested;

however, ethion was detected in only 23 (13%) of the samples at a mean concentration of 3 ppb (range,

1–8 ppb).

Because ethion has been used in veterinary application as a dip to control ticks and other skin parasites,

there is the potential for residues to occur in some animal products (Mosha et al. 1990a, 1990b, 1991). 

Lino and da Silveira (1994) detected ethion residues in the muscle and skin tissue of chickens sampled in

Portugal. Ethion concentrations in muscle tissue ranged from 31.32 to 51.37 ppb, and concentrations in

skin tissue ranged from 361.3 to 1,796.8 ppb. These authors reported that chickens could be exposed to

ethion and other pesticides via feeds or the direct treatment of ethion on the chickens by external

application of dusts or sprays, by oral administration in the feed, and/or use of ethion in the chicken

houses. Ivey et al. (1975) reported on tissue residues of ethion and its metabolites (ethion monoxon and
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5. POTENTIAL FOR HUMAN EXPOSURE

dioxon) in the body tissues of domestic turkeys reared in pens on soil treated with an emulsion of ethion

(4 lb/gal effective concentration) at a rate of 4, 12, and 40 pounds active ingredient/acre or 4.48, 13.4, and

44.8 kg/ha, respectively. The maximum residues detected in turkey fat and skin, respectively, at 1 week

post-application were 0.022 ppm (22 ppb) and 0.080 ppm (80 ppb)for the 4 lb/acre, 0.031 ppm (31 ppb)

and 0.410 ppm (410 ppb)for the 12 lb/acre, and 0.295 ppm (295 ppb) and 0.666 ppm (666 ppb) for the

30 lb/acre application rates. Small residues of ethion monoxon were detected at 1–3 weeks postapplication in the skin of turkeys only at a rate of 40 lb/acre, but no ethion dioxon was detected in any

tissues. In an FDA study, Heikes and Craun (1992) reported the detection of 19 ppm ethion in 1 of 10

anhydrous lanolin samples analyzed in 1991. No ethion residues were detected in any lanolin samples

analyzed in 1989. These same authors also detected ethion residues in two lanolin-containing

pharmaceutical preparations: 0.28 ppm (280 ppb) in diaper rash ointment and 0.30 ppm (300 ppb) in

ophthalmic ointment sampled in 1992. In an earlier 1988 study of the same pharmaceutical preparations,

no ethion residues were detected. 

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE

While no quantitative information is available on the percentage of ethion released to each environmental

compartment, ethion can be emitted to any or all environmental media (air, surface water, groundwater,

soil, and sediment), depending on the source of the release, formulation used, and prevailing

environmental conditions. General population exposure to ethion typically occurs through two major

routes; inhalation and ingestion of contaminated food or drinking water. The major route of exposure to

ethion for the general population is through ingestion of foods contaminated with small residues of ethion

or consumption of ethion-contaminated drinking water. The general population may also be exposed to

ethion through inhalation of contaminated ambient (outdoor) air, specifically in agricultural areas where

ethion is extensively used to control some agricultural pests or in veterinary applications to control

external parasites (Lewis and Lee 1976). 

A comparison of ethion intakes for various age groups of children and adults derived from FDA total diet

studies over the past 25 years are summarized in Table 5-2. Johnson et al. (1984) reported ethion intakes

in mg/kg body weight/day for the total diet analysis conducted (1976 and 1977) for infants as trace

amounts and 1.1x10-6, respectively; and for toddlers, trace amounts and 1.1x10-6, respectively. Ethion

intakes, in mg/kg body weight/day, estimated for total diet analyses (1982–1984) were 6.4x10-6,

1.15x10-5, 2.2x10-6, 2.7x10-6, 2.5x10-6, 2.0x10-6, 3.1x10-6, and 2.2x10-6 for 6–11-month-old infants, 
Table 5-2. Ethion Intakes from Foods for Infants, Children, and Adults in the U.S. Population (in 

Period ofthe TotalDiet Study

6–11-month-oldinfants

2-yearoldchildren

14–16-year-oldfemales 

14–16-year-oldmales

25–30-year-oldfemales

25–30-year-oldmales

60–65-year-oldfemales

60–65-yearold males 

1976 Trace Trace No data No data No data No data No data No data 1977 1.1x10-6 1.0x10-6 No data No data No data No data No data No data 

1982–1984 6.4x10-6 1.15x10-5 2.2x10-6 2.7x10-6 2.5x10-6 2.0x10-6 3.1x10-6 2.2x10-6 

1987 1.68x10-5 No data No data 6.3x10-6 No data No data 7.0x10-6 No data 

1988 1.19x10-5 No data No data 3.9x10-6 No data No data 3.3x10-6 No data 1989 1.67x10-5 No data No data 6.0x10-6 No data No data 6.0x10-6 No data 1990 1.44x10-5 No data No data 5.9x10-6 No data No data 5.1x10-6 No data 1991 1.28x10-5 No data No data 3.4x10-6 No data No data 3.5x10-6 No data 1992 1.46x10-5 2.22x10-5 4.0x10-6 5.0x10-6 4.5x10-6 3.9x10-6 4.9x10-6 3.5x10-6 
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5. POTENTIAL FOR HUMAN EXPOSURE

2-year-old children, 14–16-year-old females, 14–16-year-old males, 25–30-year-old females, 25–30-yearold males, 60–65-year-old females, and 60–65-year-old males, respectively (Gunderson 1988). Ethion

intakes in mg/kg body weight/day, estimated for the total diet analyses for 1987–1992 also increase from

intakes estimated in the 1982–1984 analysis and were 1.68x10-5, 6.3x10-6, and 7.0x10-6 in 1987 (FDA

1988); 1.19x10-5, 3.9x10-6, and 3.3x10-6 in 1988 (FDA 1989); 1.67x10-5, 6.0x10-6, and 6.0x10-6 in 1989

(FDA 1990); 1.44x10-5, 5.9x10-6, and 5.1x10-6 in 1990 (FDA 1991); and 1.28x10-6, 3.4x10-6, and 3.5x10-6

in 1991 (FDA 1992) for 6–11-month-old infants, 14–16-year-old males, and 60–65-year-old females,

respectively. Ethion intakes in mg/kg body weight/day, estimated for the total diet study were 1.46x10-5,

2.22x10-5, 4.0x10-6, 5.0x10-6, 4.5x10-6, 3.9x10-6, 4.9x10-6, and 3.5x10-6 for 6–11-month-old infants,

2-year-old children, 14–16-year-old females, 14–16-year-old males, 25–30-year-old females, 25–30-yearold males, 60–65-year-old females, and 60–65-year-old males, respectively (FDA 1993).

No information was located on the levels of ethion or its oxygen analogs in human tissues, adipose tissue,

blood, urine, or breast milk in members of the general population. Ethion was not one of the pesticides

monitored as part of the NHANES study (Needham et al. 1990), in the National Adipose Tissue Study

(EPA 1986; Phillips and Birchard 1991), or in urine of the general population of the U.S. (Kutz and Cook

1992).

In occupational settings, dermal exposure and subsequent absorption through intact skin represent the

most important route of exposure, while inhalation exposure is generally less important (Jeyaratnam and

Maroni 1994). Inhalation of ethion depends on its volatility, the type of formulation used, and the

application technique employed. Occupational ingestion may occur as a result of poor work practices

and/or lack of personal hygiene. Workers employed in industries that manufacture, formulate, package,

or apply ethion and workers involved in the disposal of ethion or ethion-containing wastes may be

exposed to the highest concentrations of ethion.

Except for professional pesticide manufacturers, formulators, applicators, or farm workers, the exposure

risks from ethion appear relatively minor as long as label instructions are followed and safeguards are

taken to avoid extensive dermal contact (e.g., use of protective clothing). Studies of dermal exposure

typical of ethion suppliers and applicators (spray crews) in Florida citrus spray operations were reported

by Wojeck et al. (1981). These authors reported dermal and respiratory exposures for workers mixing

and loading ethion for application and for those applying ethion to citrus trees. The suppliers’ mean

exposures were 1,799±3,793.2 mg/hour and 0.005±0.004 mg/hour for dermal and inhalation exposure,
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5. POTENTIAL FOR HUMAN EXPOSURE

respectively. The applicators’ mean exposures were 1,972.5±244.6 mg/hour and 0.004±0.002 mg/hour

for dermal and respiratory exposure, respectively. Dermal exposure accounted for 99% of total exposure,

while respiratory exposure represented <1% for both the suppliers and applicators. For both suppliers and

applicators, the hands received the highest exposures to ethion. These authors reported that dermal

exposure of the hands represented 42% of the total body exposure for applicators and 76% for suppliers,

and there were no significant differences in exposures to other areas of the body. A significant amount of

variability existed between the groups of supplier and applicators tested, based on the procedures used. 

Ethion monoxon was detected in most samples, but did not exceed 5% of the total amount of toxicant.

This study also points out that management of protective clothing worn by ethion applicators is important

in reducing dermal exposures.

Kahn (1976) reported pesticide-related illness in California farm workers exposed to pesticide residues on

the foliage of treated crops and in dusty soils of orchards, fields, and vineyards. Of the reported pesticide

poisonings from 1949 to 1970, ethion was implicated in 4 separate incidents involving 46 farm workers;

however, the incidence always involved ethion and 1 or more other pesticides.

Wolfe et al. (1978) conducted a study to determine the potential dermal and respiratory exposure of

workers to ethion at an ethion formulating plant. The studies were conducted during the formulation of

25% water-wettable powder with adsorbed ethion. In order to determine the potential exposure in

different work situations, exposure pad studies were carried out on (1) workers who inserted the proper

proportions of ingredients into the formulating mixer (mixer), (2) workers who filled bags with the ethion

formulation at the filler spout (bagger), and (3) workers who performed a combination of jobs such as

packing bags into cartons for shipment or working at the mixing and bagging stations (mixer-baggercarton packer). Dermal contamination was measured primarily by attaching absorbent pads to various

parts of the workers' body and allowing them to be exposed during a timed period of work. Respiratory

exposure was estimated from the contamination of special filter pads used in place of the usual outer

absorbent filter pads which cover the filter cartridges of the respirators worn by the subjects. The authors

calculated that the exposure to ethion for all workers was 126 mg/hour for dermal exposure and

1.71 mg/hour for respiratory exposure. However, the authors reported that dermal exposure at the

bagging station (mean 116±234 mg/hour) was greater than at the mixing station (70±121 mg/hour), and

exposure of the mixer-bagger-carton package was the highest exposure of all (237±324 mg/hour). 

Inhalation exposure followed a similar pattern whereby respiratory exposure at the bagging station (mean

1.63±1.56 mg/hour) was greater than at the mixing station (1.15±1.60 mg/hour), and exposure of the
ETHION 123

5. POTENTIAL FOR HUMAN EXPOSURE

mixer-bagger-carton package was the highest exposure of all (2.67±2.32 mg/hour). Dermal exposure of

all workers typically represented 98.7% of the total exposure, while inhalation exposure represented 1.3%

of the total exposure. Again, this study points out that management of clothing and respirators is

important in reducing exposures.

Several studies have tested the use of various protective clothing or have made recommendations for

reducing total dermal exposure to ethion. Wojeck et al. (1981) reported that exposure to the hands

represented the largest percentage of total exposure to ethion in workers (suppliers and applicators) and

recommended that the use of elbow-length vinyl gloves, washed inside and out with a strong alkaline

detergent on a regular basis, would eliminate much of the potential hazard from dermal exposure. Davies

et al. (1982) also reported that pesticide illness in agricultural workers often resulted from excessive

dermal exposure to pesticides. These authors assessed the protection afforded by changing daily into

freshly laundered 100% cotton coveralls. They reported that coveralls provided significantly greater

protection from ethion exposure than did regular clothing and the use of respirators. Nigg et al. (1992)

conducted a field evaluation of various coverall fabrics to assess heat stress and pesticide penetration. 

These authors reported that lighter weight, untreated fabrics marginally ameliorated heat stress under

severe summer time temperatures in Florida citrus groves, but they also allowed more ethion penetration.

According to the National Institute for Occupational Safety and Health (NIOSH 1994), the Occupational

Safety and Health Administration (OSHA), proposed an 8-hour time-weighted average (TWA)

permissible exposure level (PEL) for ethion of 0.4 mg/m3

 for skin. However, this standard was vacated 

by a court decision. Two other organizations, however, adopted the proposed OSHA value. The National

Institute for Occupational Safety and Health (NIOSH) recommends that the occupational exposure level

not exceed 0.4 mg/m3

 (skin) for a 10-hour TWA workday (NIOSH 1997). In addition, the American

Conference of Governmental Industrial Hygienists has recommended a TWA limit (TWA-TLV) of

0.4 mg/m3

 (skin) for occupational exposure to ethion (ACGIH 1997b ).

5.6 EXPOSURES OF CHILDREN

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from

adults in susceptibility to hazardous substances are discussed in 2.7 Children’s Susceptibility.
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5. POTENTIAL FOR HUMAN EXPOSURE

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths,

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993).

Information on the effects of ethion on humans is limited, and information on the effects of ethion on

children is even more limited. One well documented case report of an acute poisoning incident was

reported by Comstock et al. (1967) in which a 6-month-old infant received 6 ounces of milk from an

8-ounce bottle used previously to measure a concentrated solution of ethion in kerosene. The child’s

exposure represented a dose of 15.7 mg/kg. Ethion is not a pesticide that is used in the home, and no

exposure studies on individuals likely to have significant exposure (formulators and applicators) are

available in the literature. No information was located on measurements of ethion or its metabolite levels

in amniotic fluid, meconium, cord blood, or neonatal blood that indicate prenatal exposure. Ethion and its

active metabolite ethion monoxon are highly lipophilic molecules so there should be no significant barrier

to crossing the placenta. 

In addition, no information was located on measurements of ethion or its metabolite levels in breast milk

that might result in post-natal exposure of an infant. Ethion and its active metabolite ethion monoxon are

highly lipophilic molecules so their passage into breast milk is possible. This has been examined in

animal models. Radioactivity derived from labeled ethion was present in goats’ milk after oral exposure

(Jobsis and Zeitlow 1985); however, the chemical identity of the radioactivity was not determined. 

Unchanged ethion (the monoxon was not measured) was detected in goats’ milk after oral and dermal

exposure to ethion (Mosha et al. 1990b). A total of 0.04–0.05% of the dose appeared in milk, after

dermal exposure, and 1.4% after oral exposure.

Children may receive higher ethion doses from dermal exposures if they play on freshly treated grass or

soil, or enter a treated agricultural area prematurely (Youngren et al. 1991). It is important that children

not be allowed entry into ethion treated areas until the sprays have dried, dusts have settled, or vapors

have dispersed to perform hand labor or to play. The reentry intervals described for farm workers should
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5. POTENTIAL FOR HUMAN EXPOSURE

be strictly adhered to with respect to all human exposures (EPA 1989d). In addition, children may receive

potentially higher oral doses from ingestion of ethion treated soils from their hands while playing in

contaminated areas. Because soil may be a reservoir for ethion in the environment, consumption of

contaminated soil from unwashed hands during hand to mouth activity or from putting contaminated toys

or other objects in their mouths could be a major source of ethion-contamination for children. Dermal

absorption of ethion is not likely, however, to be significant based on the relatively low amount (3.3%)

that is absorbed through the skin (Feldman and Maibach 1974). The vapor pressure of ethion is

1.5x10-6 mmHg (EPA 1989b; Merck 1989) suggesting that some of it may volatilize from soil surfaces.

However, due to its high Koc value, vapor pressure is expected to be greatly attenuated (Haque and Freed

1974). Thus, children’s exposure to vapor-phase ethion while playing outdoors on the ground is not

expected to be significant. As time goes by, ethion is expected to degrade in the environment through

both biodegradation and hydrolysis. Ethion degraded to 50% of its initial concentration after 7 and 8

weeks in nonsterile sandy loam and organic soils, respectively (Miles et al. 1979). Hydrolysis in moist

soils may also contribute to the decrease in ethion concentration. Estimated half-life values for the firstorder hydrolysis of ethion in sterile water at 25±3 EC was 99, 63, 58, 25, and 8.4 weeks at pH values of

4.5, 5, 6, 7, and 8, respectively (Chapman and Cole 1982). Based on these degradative processes, ethion

concentrations in soil are not expected to persist unless there is a continuous source of ethion

contamination.

Ethion is not intended for indoor use except within greenhouses (EPA 1989b, 1989d). Therefore, children

are not expected to be exposed to ethion indoors unless it is transported inside through contaminated

materials or applied illegally indoors. 

It is important that children of occupational users of pesticides, not be exposed to the contaminated work

clothes or shoes of their parent (NIOSH 1995). Worker protection statements for pesticides state that

workers should take off all work clothes and shoes and shower using soap and water, and then put on

clean clothes. Personal clothing worn during work must be laundered and stored separately from personal

family clothing. Heavily contaminated clothing should be destroyed according to state and local

regulations (EPA 1989b). Since some ethion is applied as a dust formulation (see Section 4.3) (liquid

ethion adsorbed to a particle matrix), children may be exposed dermally, orally via hand to mouth

activities, or via inhalation of dust particles while playing on contaminated floors or carpeting where

ethion-contaminated particles may have fallen from contaminated work clothes. However, no literature
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5. POTENTIAL FOR HUMAN EXPOSURE

could be located documenting ethion’s transfer to the home from contaminated work clothes or other

articles.

Levels of ethion concentrations in infant and toddler foods and in baby formula are discussed in

Section 5.4.4. Gelardi and Mountford (1993) analyzed for the presence of 34 pesticides including ethion

in infant formula. The detection limit range for ethion was <0.001–0.016 ppm. These authors reported

that of 110 milk-based formula and of 59 soy-based formula analyzed, that ethion was not detected in any

samples of either formula. Similarly, pesticide residues were evaluated in infant and toddler total diet

samples from August 1976 to September 1977 (Johnson et al. 1984). These authors reported that of 117

infant foods tested, ethion was detected in 2 samples in trace amounts, while ethion was detected in only 2

of 132 toddler foods at a concentration of 0.001 ppb. Positive detections were made only in foods in the

fruit or fruit juice category. Yess et al. (1993) summarized the results of a study to monitor pesticide

residues in infant and adult foods eaten by infants and children. These authors reported that ethion (total)

was detected in 22 of 2,464 apple samples (maximum concentration of 1.7 ppm), in 1 of 13 orange juice

samples (maximum concentration of 0.03 ppm), in 42 of 862 samples of oranges (maximum

concentration of 1.1 ppm), and in 7 of 571 pear samples (maximum concentration of 0.22 ppm). These

authors also reported that ethion (total) was detected in several imported foods including 9 of 735 apple

samples (maximum concentration of 0.23 ppm), in 1 of 64 orange juice samples (maximum concentration

of 0.02 ppm), in 89 of 474 samples of oranges (maximum concentration of 0.61 ppm), and in 1 of 816

pear samples (maximum concentration of 0.17 ppm). The concentration of ethion (total), however, did

not exceed the EPA tolerances level (2 ppm) for any of the domestic or imported foods tested which

might be eaten by infants and children. 

With regard to prepared foods for infants and children, Yess et al. (1993) also reported that the

maximum concentrations of ethion (total) detected in Dutch apple Betty were 0.001 ppm, in 3 samples of

applesauce or applesauce with other fruits were 0.002 ppm, in 21 samples of orange or orange pineapple

juice were 0.010 ppm, in 3 samples of pears or pears and pineapples were 0.003 ppm, in 24 samples of

frozen orange juice were 0.008 ppm, and in 6 samples of raw pears were 0.280 ppm. Again, all of the

adult foods that might be consumed by infants and children that were tested contained ethion residues

well below the EPA tolerance level of 2 ppm. Concentrations of ethion in ready-to-eat foods were

monitored for 10 years from 1982 to 1991 through the FDA's Revised Market Basket Survey (KAN-DO

Office and Pesticides Team 1995). Ethion was detected in 199 samples of 31 different foods at a mean

concentration of 0.0053 μg/g (5.3 ppb) and the ethion oxygen analogue was detected 8 times in 5 
ETHION 127

5. POTENTIAL FOR HUMAN EXPOSURE

different foods at a concentration of 0.0029 μg/g (2.9 ppb). Ethion was detected in the following baby

foods: apple sauce, Dutch apple Betty, meat, beef and vegetables, orange and orange pineapple juice,

pears or pears and pineapples. The ethion oxygen analogue was detected in the following baby foods:

orange or orange-pineapple juice. Based on these studies, it appears to be unlikely that food containing

ethion residues will pose a major health risk to infants and young children except in those instances

where the infants and children live on farms where large amounts of ethion are used and they consume

large amounts of farm-raised fruits and vegetables. 

A comparison of ethion intakes for various age groups of children and adults derived from FDA total

diet studies over the past 25 years are summarized in Table 5-2. Trends for adults are discussed

specifically in Section 5.5. Johnson et al. (1984) reported ethion intakes in mg/kg body weight/day for

the total diet analysis conducted (1976 and 1977) for infants as trace amounts and 1.1x10-6, respectively;

and trace amounts and 1.0x10-6 for toddlers, respectively. Ethion intakes, in mg/kg body weight/day,

estimated for total diet analyses (1982–1984) increased and were 6.4x10-6 and 1.15x10-5, respectively,

for 6–11-month-old infants, and 2-year-old children. Ethion intakes in mg/kg body weight/day,

estimated for the total diet analyses for 1987–1992 also increased from intakes estimated in the 1982–84

analysis and were 1.68x10-5, in 1987 (FDA 1988); 1.19x10-5 in 1988 (FDA 1989); 1.67x10-5 in 1989

(FDA 1990); 1.44x10-5 in 1990 (FDA 1991); and 1.28x10-5 in 1991 (FDA 1992) for 6–11-month-old

infants. Ethion intakes in mg/kg body weight/day, estimated for the total diet study were 1.46x10-5 and

2.22x10-5 for 6–11-month-old infants and 2-year-old-children, respectively (FDA 1993). 

In comparison, ethion intakes for older children were more comparable to adult intakes and were

2.2x10-6 and 2.7x10-6 for 14–16-year-old females and 14–16-year-old males, respectively (see Table 5-2)

(Gunderson 1988). Ethion intakes in mg/kg body weight/day, estimated for the total diet analyses for

1987–1992 also increased slightly from intakes estimated in the 1982–1984 analysis and were 6.3x10-6

in 1987 (FDA 1988); 3.9x10-6 in 1988 (FDA 1989); 6.0x10-6 in 1989 (FDA 1990); 5.9x10-6 in 1990

(FDA 1991); and 3.4x10-6 in 1991, (FDA 1992) and 5.0x10-6 in 1992 for 14–16-year-old males (FDA

1993). Ethion intakes in mg/kg body weight/day, estimated for the total diet study also increased in

1992 and were 4.0x10-6 for 14–16-year-old females (FDA 1993).
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5. POTENTIAL FOR HUMAN EXPOSURE

Infants and children receive approximately 2–3 times more ethion in their diets per unit body weight

than adults due to higher consumption of fruits and fruit drinks (FDA 1993). Studies have not been done

in infants and children on the relationship between dietary intake and the activity of cholinesterases in

red blood cells and plasma.

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES

In addition to individuals who are occupationally exposed to ethion during its production, formulation,

packaging, distribution, use or disposal (see Section 5.5), there are several groups within the general

population that have potentially high exposures (higher than background levels) to ethion. These

populations include individuals living in proximity to sites where ethion is produced or processed or

sites where ethion was disposed, and individuals living near one of the 9 NPL hazardous waste sites

where ethion has been detected in some environmental media (HazDat 2000). Other populations at risk

of exposure to ethion and its oxygen analogs include recreational and subsistence fishers who may fish

in ethion-contaminated waters and who typically consume larger amounts of locally caught fish and

shellfish than the general population. However, no fish consumption advisories are currently in effect in

the United States for ethion (EPA 1995g). Subsistence farmers and their families living in areas where

ethion is heavily used in agriculture who may consume their own farm-raised fruits and vegetables or

who may unknowingly consume drinking water from a ethion-contaminated well are at greater risk of

exposure. 

5.8 ADEQUACY OF THE DATABASE

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether

adequate information on the health effects of ethion is available. Where adequate information is not

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure

the initiation of a program of research designed to determine the health effects (and techniques for

developing methods to determine such health effects) of ethion. 

The following categories of possible data needs have been identified by a joint team of scientists from

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean

that all data needs discussed in this section must be filled. In the future, the identified data needs will be

evaluated and prioritized, and a substance-specific research agenda will be proposed. 
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5. POTENTIAL FOR HUMAN EXPOSURE

5.8.1 Identification of Data Needs

Physical and Chemical Properties. While the principal properties of ethion are well

characterized (Bowman and Sans 1983; Chapman and Cole 1982; Dierberg and Pfeuffer 1983; EPA

1989b; HSDB 1998; Merck 1989; Sax 1984; Sharom et al. 1980a, 1980b; Tomlin 1994), there are data

gaps for odor thresholds, flammability limits, autoignition temperature, and flash point for the

compound. Additional information on these properties would be helpful in assessing the compound's

environmental fate. There are also data gaps for some spontaneously produced degradation products,

some of which may be as toxic or more toxic than ethion.

Production, Import/Export, Use, Release, and Disposal. As with most pesticide agents, no

current information was found on production or import and export volumes for ethion (FASE 1996). 

This lack of current information seriously compromises efforts to design monitoring programs to study

fate and transport and can seriously jeopardize proper assessments of exposure opportunities and their

associated health risks for this compound. Information on current production, import/export volumes,

uses, releases to various environmental matrices, and disposal methods is needed to conduct a more

accurate assessment of exposure pathways. 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. 

Section 11023, industries are required to submit chemical release and off-site transfer information to the

EPA. The Toxics Release Inventory (TRI), which contains this information for 1996, will become

available in May of 1998. This database will be updated yearly and should provide a list of industrial

production facilities and emissions. No information was available on facilities involved in the

production or processing of ethion because it is not one of the chemicals that facilities are required to

report to the TRI (EPA 1995e).

Environmental Fate. In the atmosphere, ethion is subject to only minor degradation due to photolysis

(Gore et al. 1971), however, reactions with hydroxyl radicals result in an estimated half-life of less than an

hour (SRC 1995). No information was located on ethion’s reaction with ozone in the air. In water, ethion

is subject primarily to hydrolysis, with photolysis and biodegradation being minor fate processes (Dierberg

and Pfeuffer 1983; Eichelberger and Lichtenberg 1971; Frank et al. 1991; Gore et al. 1971). The rate of

degradation of ethion in water is strongly influenced by pH (Chapman and Cole 1982; Dierberg and

Pfeuffer 1983; Frank et al. 1991; Sharom et al. 1980a) and temperature (Dierberg and 
ETHION 130

5. POTENTIAL FOR HUMAN EXPOSURE

Pfeuffer 1983; Gore et al. 1971; Sharon et al. 1980a). The rate of ethion degradation increases in alkaline

pH and at higher temperatures. Ethion can be degraded in soils and sediment by hydrolysis (Chapman and

Cole 1982) and by biodegradation by microorganisms (Miles et al. 1979; Sherman et al. 1974). Ethion is

moderately to highly immobile in most soil types, particularly those with moderate amounts of organic

matter (Kenaga 1980; Sharom et al. 1980b). Information on the mobility of ethion is available (Sharom et

al. 1980b); however, no information was located on mobility of its major degradation products in various

soil types. Additional information on the persistence and mobility of major degradation products of ethion

would be useful. Additional information on environmental parameters governing the degradation rate of

ethion in soil also would be helpful in evaluating the environmental fate of ethion and its degradation

products. 

Bioavailability from Environmental Media. Ethion can be absorbed following inhalation, dermal,

or oral exposures. Absorption through the skin is of major concern for occupational exposures of

manufacturers and formulators, farmers, farm workers, commercial applicators or homeowners related to

the use of ethion as an insecticide or acaricide (Jeyaratnam and Maroni 1994; Kahn 1976; Wojeck and

Nigg 1980; Wojeck et al. 1981; Wolfe et al. 1978). Additional information on the bioavailability of

concentrations of ethion in soils, surface water, groundwater, and fish and shellfish, particularly from

environments near hazardous waste sites, is needed to determine the bioavailability of ethion in these

media. 

Food Chain Bioaccumulation. Ethion has an estimated high bioconcentration potential

(BCF=1,300) (Kenaga 1980) in aquatic organisms; however, there is little experimental or environmental

monitoring data to confirm that bioaccumulation occurs in edible fish and shellfish species (Butler and

Schutzmann 1978; Miles and Harris 1978a). Additional information on measured BCF values for edible

fish and shellfish would be helpful, as would information on tissue residues of ethion and its major

degradation products in edible tissues of livestock and poultry. Little information was found on studies

associated with plant uptake (Leffingwell et al. 1975; Nigg et al. 1988), but ethion is rarely detected

above EPA tolerance limits (Berry et al. 1997; Corneliussen 1970; FDA 1988, 1990, 1991, 1992, 1993,

1994, 1995; Gelardi and Mountford 1993; Gunderson 1988; Hundley et al. 1988; Johnson et al. 1984;

KAN-DO Office of Pesticide Team 1995; Minyard and Roberts 1991; Roy et al. 1995; Schattenberg and

Hsu 1992; Yess et al. 1991, 1993). Bioaccumulation of ethion in aquatic food chains appears to be

potentially important. Based on results obtained from a BCF estimating equation using the compound’s

chemical and physical properties, a substantial BCF value as high as 1,300 was calculated (Kenaga 
ETHION 131

5. POTENTIAL FOR HUMAN EXPOSURE

1980). However, experimental data on bioaccumulation and biomagnification of ethion in aquatic species

are needed to verify that the estimated theoretical BCF values are actually attained.

Exposure Levels in Environmental Media. Ethion is distributed in all environmental media and

has been detected in ambient air (HazDat 2000; Lewis and Lee 1976), indoor air at a manufacturing plant

(Lewis and Lee 1976), surface water (Frank et al. 1982), groundwater (Cohen 1986; HazDat 2000), and

sediment (Carey et al. 1978; HazDat 2000; Miles et al. 1978). While some information is available on

historic levels of ethion in environmental media, current levels of ethion in air, water, groundwater, soil,

and sediment in the United States have not been well documented. There is a need for more information

from national or large regional studies on current exposure levels in these environmental matrices. 

Adequate information from the late 1960s through to the present time are available for various raw and

prepared foods as ethion has been monitored in many FDA total diet studies as well as compliance and

surveillance monitoring programs (Berry et al. 1997; Corneliussen 1970; FDA 1988, 1990, 1991, 1992,

1993, 1994, 1995; Gelardi and Mountford 1993; Gunderson 1988; Hundley et al. 1988; Johnson et al.

1984; KAN-DO Office of Pesticide Team 1995; Minyard and Roberts 1991; Roy et al. 1995;

Schattenberg and Hsu 1992; Yess et al. 1991; Yess et. al. 1993). Additional information on tissue

residues of ethion and on its major degradation products in edible fish and shellfish species would be

particularly helpful in quantifying health risk from consumption of contaminated species.

Reliable monitoring data for the levels of ethion in contaminated media at hazardous waste sites are

needed so that the information obtained on levels of ethion in the environment can be used in combination

with the known body burden of ethion to assess the potential risk of adverse health effects in populations

living in the vicinity of hazardous waste sites. Monitoring information from piezometer and producing

water wells around hazardous waste sites for ethion and monitoring of water wells in areas that have high

agricultural usage of ethion are considered essential. 

Exposure Levels in Humans. Recent and historic data regarding levels of ethion in human tissues

(adipose tissue, blood, urine, breast milk) from environmental exposures of members of the general

population, populations living near hazardous waste sites, or occupationally exposed groups are not

available. It is arguable that these levels are knowable because of the rapid metabolism and clearance of

ethion after it enters the body. Studies are needed to determine ethion and ethion monoxon residues in

breast milk from women with high exposure risks (e.g., individuals that live near hazardous waste sites

where ethion has been detected or in agricultural areas of high ethion use (particularly citrus-growing
ETHION 132

5. POTENTIAL FOR HUMAN EXPOSURE

regions). Data on the relationship between environmental exposure to ethion and effects on biomarkers

(blood cholinesterases) are needed to estimate the extent of exposure to ethion. This information is

necessary for assessing the need to conduct health studies on these populations.

Exposures of Children. Children may be exposed to ethion primarily from consumption of small

amounts of ethion in contaminated fruits, by consumption of ethion-contaminated dirt and soil from

unwashed hands or other contaminated objects put into the mouth, or via ingestion of ethioncontaminated well water. Exposure and body burden studies for children would be helpful. There is no

information on ethion residues in breast milk of members of the general population nor in women residing

in areas of high ethion usage in agriculture and in areas near hazardous waste sites. Well water surveys

should be conducted in areas of high ethion usage. These pathways via ingestion of ethion- contaminated

breast milk or drinking water could be important routes of exposure in children.

Young children might be exposed to ethion through both pica and hand-mouth activity if they play in or

around contaminated vegetation and soil. Soil and sediment may be contaminated with ethion and there

are no studies of the transfer of ethion via both oral and dermal routes of exposure in children nor are

there studies of the bioavailability of the chemical from soil and sediment. 

Current information on whether children are different in their weight-adjusted intake of ethion via oral

and dermal exposures was not located; however, information from older studies was available. Children,

specifically 6–10-month-old infants and 2-year-old toddlers, are different in their weight-adjusted intake

of ethion from food as compared to 14-year-olds as demonstrated by intake data (FDA 1988, 1989, 1990,

1991, 1992, 1993; Gunderson 1988; Johnson et al. 1984). The highest intakes were for 2-year-oldtoddlers and 6–11-month-old-infants respectively (FDA 1993; Gunderson 1988). Intakes for children

(14-year-olds) were lower than in infants and toddler and were more comparable to data from 25-yearolds and 65-year-old adults (FDA 1993; Gunderson 1988).

Child health data needs relating to susceptibility are discussed in Section 2.12.2 Identification of Data

Needs: Children’s Susceptibility.

Exposure Registries. No exposure registries for ethion were located. This substance is not

currently one of the compounds for which a subregistry has been established in the National Exposure

Registry. The substance will be considered in the future when chemical selection is made for 
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5. POTENTIAL FOR HUMAN EXPOSURE

subregistries to be established. The information that is amassed in the National Exposure Registry

facilitates the epidemiological research needed to assess adverse health outcomes that may be related to

exposure to this substance.

5.8.2 Ongoing Studies

No additional information was located on current studies that would fill existing data needs for ethion

(FEDRIP 1998).

ETHION 135

6. ANALYTICAL METHODS

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring ethion, its metabolites, and other biomarkers of exposure and effect to

ethion. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to

identify well-established methods that are used as the standard methods of analysis. Many of the

analytical methods used for environmental samples are the methods approved by federal agencies and

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). 

Other methods presented in this chapter are those that are approved by groups such as the Association of

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower

detection limits and/or to improve accuracy and precision.

6.1 BIOLOGICAL SAMPLES

Methods for the analysis of ethion and its metabolites in human biological samples are given in

Table 6-1. Ethion can be recovered from saliva, urine, and plasma by extraction and analysis by gas

chromatography with flame photometric detection (GC/FPD), or GC in conjunction with mass

spectrometry (GC/MS) (Nigg et al. 1993; Singh et al. 1986). The metabolites of ethion for which

methods have been developed include diethylphosphate (DEP), diethylthiophosphate (DETP), and

diethyldithiophosphate (DEDTP). These metabolites are recovered from urine and saliva via extraction,

solid phase extraction (SPE), and derivatization with tetrabutylammonium hydroxide before analysis

using GC/FPD (Nigg et al. 1993). Ethion is also metabolized to form the oxygen analogs (monoxon,

dioxon) but no methods for these compounds were found for biological samples of human origin. A

method for the oxygen analogs in animal tissues has been described (Ivey and Mann 1975) and would

serve as a good starting point for methods to be validated for human samples. A recent publication

(Mahajna et al. 1996) has shown that O,O-dialkyl phophosphorodithioate insecticides (such as ethion)

can undergo cleavage at the S-R (S-CH3 of ethion) and be methylated. However, no methods have been

described for human samples.
Table 6-1. Analytical Methods for Determining Ethion and Metabolites in Biological Sa

Samplematrix Preparation method

Analyticalmethod

Sampledetection limit

Percentrecovery 

Saliva (Ethion,DEP, DETP,DEDTP)

Ethion: Extraction with hexane and addition ofmethanol followed by centrifugation (repeat 3times); evaporation of solvent to dryness with redissolution in hexane just prior to analysis.Metabolites: Addition of NaOH to aqueousresidue from ethion extraction; addition ofmethanol and removal of water; acidification andaddition of ammonium sulfate; isolation usingSPE; addition of tetrabutylammonium hydroxidejust prior to GC analysis.

GC/FPD Ethion: <1 ppm

Metabolites:<260 ppb

80±10% at1 ppmDEP: 68±3%DETP: 77±2%DEDTP: 69±at 260 ppb

Urine (DEP,DETP,DEDTP)

Acidification and addition of ammonium sulfate;isolation using SPE; addition of 20% methanol inacetone to eluate; addition oftetrabutylammonium hydroxide just prior to GCanalysis.

GC/FPD <260 ppb DEP: 81±3%

DETP: 92±2%DEDTP 51±5

Plasma Extraction with ethyl acetate followed by

centrifugation; water removal and evaporation ofsolvent; re-dissolution in small volume of ethylacetate

GC/MS(selected ionmonitoring)

no data 57% at

200 ng/mL

Urine Adjustment of pH to 7.4; centrifugation; extraction

with ethyl acetate; centrifugation; evaporation ofethyl acetate, re-dissolution in small volume

GC/MS(selected ionmonitoring)

<10 ng/mL 7,580% at

10 ng/mL

DEDTP = diethyl dithiophosphate; DEP = diethyl phosphate; DETP = diethyl thiophosphate; FPD = Flame photometric detector; GC = gas 

mass spectrometry; NaOH = sodium hydroxide; SPE = solid phase extraction
ETHION 137

6. ANALYTICAL METHODS

6.2 ENVIRONMENTAL SAMPLES

A variety of methods for the analysis of ethion, and to a lesser extent, ethion oxidation products (oxygen

analogs), in environmental samples have been described. Ethion has limited volatility, so it is not

typically measured in air. Methods have been reported for water (EPA 1992; EPA 1997c; Lopez-Avila et

al. 1997; Valor et al. 1997) and are based on solvent extraction or solid phase microextraction (SPME).

SPME is a technique in which a polymer-coated fiber is placed into the water and organic compounds

adsorb to the film. The organic compounds are subsequently released via thermal desorption in the GC.

The choice of fiber coating (polar vs. non-polar) can have a large impact on the recovery of the target

analytes (Lopez-Avila et al. 1997) and is thus an important consideration in methods utilizing SPME.

Since ethion is used on plants, it is not surprising that analytical methods have been developed for many

types of vegetative material, including many used as foods (see Table 6-2). The majority of methods are

based on solvent extraction during or following homogenization of the sample (e.g., FDA 1997; Johnson

et al. 1997; Sicbaldi et al. 1997; Torres et al. 1996) followed by GC with some form of selective

detection. Supercritical fluid extraction (SFE) has also been reported as a means to isolate ethion from

the plant matrix (Lehotay and Valverde-Garcia 1997; Pearce et al. 1997). The applicability of SFE has

been reviewed by Lehotay (1997).

Foods of animal origin have also been investigated for ethion and some of its metabolites/decomposition

products. Methods have been developed, for milk (Erney et al. 1997; Di Muccio et al. 1996); beef,

turkey, and chicken (Ivey and Mann 1975; Lino and da Silveira 1994); and fatty foods, including dairy

and meats (FDA 1997).

As with any analytical method, it is important to verify that the method blanks are free of interfering

compounds; it is also important to be certain that the matrix does not have an impact on the recovery of

the target analytes relative to solvent standards. Erney et al. (1997) have described how co-extracted

matrix components can have a protective effect on the analytes. That is, these matrix components can

reduce any thermal decomposition in the injector port and give rise to recoveries well in excess of 100%

relative to solvent standards. The use of spiked matrix samples during method development and

validation can bring such interferences to light.
Table 6-2. Analytical Methods for Determining Ethion in Environmental Sample

Sample matrix Preparation method

Analyticalmethod

Sample detectionlimit

Percentrecovery 

Milk Precipitation of protein using

acetone and acetonitrile followedby extraction of the aqueousphase with dichloromethane.

GC/FPD No data No data 

Milk Extraction with acetonitrile and

acetone, cleanup using SPE;extract taken to dryness followedby redissolution in 1 mL acetone.

GC/FPD 0.005 mg/kg 90 

Water Adjustment of pH of sample to 9,

liquid-liquid extraction with hexaneand water removal using sodiumsulfate.

GC/MS <10 ppt 113 at 10 ppt 

Water SPME from aqueous phase GC/TSD No data 82 (18%RSD) Water, wastewater SPME from aqueous phase GC/NPD 30 ng/L Tap water:

108±2%;Sea water:98±2%;Wastewater:103±8%

Leaves Addition of water and wetting

agent to pre-weighed leafsections; extraction with hexane;water removal.

GC/FPD 0.5 ng No data 

Oranges Addition of water and wetting

agent to pre-weighed leafsections; extraction with hexane;water removal.

GC/ECD 0.5 ng No data 
Table 6-2. Analytical Methods for Determining Ethion in Environmental Samples (con

Sample matrix Preparation method

Analyticalmethod

Sample detectionlimit

Percentrecovery 

Oranges Homogenization of oranges;

addition of C18 to 0.5 g of

homogentae, mixing (Matrix SolidPhase Dispersion). Introduce tocolumn and elute with ethylacetate; volume reduction 

GC/ECD 95 μg/kg 93±7% at

539 μg/kg

Oranges, sweetpotatoes, andgreen beans

Homogenization of sample withdrying agent. Supercritical fluidextraction.

GC/ion trap MS 4 ng/g 74–77 

Fruits andvegetables

Maceration of sample in presenceof acetone; filtration and additionof sodium sulfate followed byextraction with hexane; extractionwith ethyl acetate and cleanupusing Florisil.

GC/ThermionicNPD

<0.1 mg/kg peaches

88 at 0.2 mg/kg

Grass Homogenization with acetone;

filtration; extraction withdichloromethane; evaporation toless than 1 mL, dilution to 5.0 m;filtration clean up using GPC.

GC/MS 2 μg/kg 87±2% 

Vegetation Homogenization followed by

mixing with diatomaceous earth;extraction with ethyl acetate;filtration; vaporization to drynessthen redissolution in acetone.

GC/NPD 0.001 μg/g Apples 90–95 at

1 μg/g

Rice grains Using supercritical fluid extraction,

ethion is extracted using CO2 + 5%

methanol, 45EC, 315 bar, anddynamic flow.

SFE/GC-AED 0.01 mg/kg 75-120% 
Table 6-2. Analytical Methods for Determining Ethion in Environmental Samples (con

Sample matrix Preparation method

Analyticalmethod

Sample detectionlimit

Percentrecovery 

Strawberries Homogenization of sample and

mixing with Extralute; supercriticalfluid extraction and expansion intoacetone

GC/FPD;GC/NPD

0.1 mg/kg 82–117 

(3–12% RSD)

Beef and turkeyfat, skin, muscle,liver, kidney, heart,gizzard;(ethion, ethionmono-oxon, ethiondi-oxon)

Fat: Blending of fat with sodiumsulfate and 5% acetone in hexane;mixing with celite, heating;filtration; partitioning withacetonitrile; solvent evaporation;redissolution and column cleanup.Other tissue: blending of tissuewith acetone followed by stirringwith celite and filtration; residueextracted with hexane; volumereduction and combining ofextracts, volume reduction; waterremoval. Partitioning withacetonitrile and clean up as for fat.

GC/FPD Ethion: 0.002 ppm; 

ethion mono-oxon:0.002 ppm; ethiondioxin: 0.005 ppm

Ethion: 86–100%ethion monooxon: 79–107%ethion dioxon:63–98%

Chicken muscleand skin

Blending with acetonitrile followedby filtration; re-homogenizationwith acetonitrile-water; addition ofzinc acetate, addition of sodiumchloride and extraction withdichloromethane; removal of waterfrom dichloromethane layerfollowed by extraction with hexaneand cleanup using Florisil column.

GC/NPD 4.4–4.5 μg/kg Mscle: 82±8.5%

RSD at 39 μg/kg(ppb)skin: 91±8.5%RSD at 100 μg/kg(ppb)
Table 6-2. Analytical Methods for Determining Ethion in Environmental Samples (con

Sample matrix Preparation method

Analyticalmethod

Sample detectionlimit

Percentrecovery 

Orange leaves(ethion, ethionmonooxon, ethiondioxon)

Addition of wetting agent andextraction with methylene chloride,water removal, evaporation todryness; re-dissolution in benzene.

GC/FPD,GC/ECD

No data Ethion: 98±3%

ethionmonooxone:95±2%ethion dioxon:90±2%

Wastewater Extraction with 15% methylene

chloride in hexane, water removal,solvent exchange to hexane.Clean-up using columnchromatography if needed. (EPAMethod 614.1)

GC/NPD,GC/MS

0.1 μg/L (ppb) 89±4.5% RSD at

1.8 mg/L (ppm)

Water, soil,sediment, sludge

Less than 1% solids: continuousextraction with methylene chloride; Greater than 1% solids: If solids#30%, dilution with water andsonication prior to continuousextraction with methylene chloride. If solids >30%, extraction withmethylene chloride:acetone oracetonitrile followed by methylenechloride using sonication; volumereduction followed by GPC of SPEcleanup. (EPA Method 1657)

GC/FPD 13 ng/L (ppt) with no

interferences

47–149 (15% RSD)

Fatty foods(Ethion)

Extraction of fat and residuesusing sodium sulfate/petroleumether; column clean-up if needed(FDA PAM Method 304).

GC/FPD No data (sub-ppm) >80% 
Table 6-2. Analytical Methods for Determining Ethion in Environmental Samples (con

Sample matrix Preparation method

Analyticalmethod

Sample detectionlimit

Percentrecovery 

Non-fatty foods(Ethion, ethionoxygen analog)

Extraction using acetone/water;filtration; extraction into organicsolvent; column clean-up asneeded depending on matrix (FDAPAM Method 302)

GC/FPD No data (sub-ppm) >80% 

FPD = flame photometric detector; GC = gas chromatography; GPC = gel permeation chromatography; ECD = electron capture detector; 

spectrometry; NPD = nitrogen phosphorus detector; SPE = solid phase microextraction; SPE = solid phase extraction; TSD = thermionic s
ETHION 143

6. ANALYTICAL METHODS

6.3 ADEQUACY OF THE DATABASE

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with

the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether

adequate information on the health effects of ethion is available. Where adequate information is not

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure

the initiation of a program of research designed to determine the health effects (and techniques for

developing methods to determine such health effects) of ethion. 

The following categories of possible data needs have been identified by a joint team of scientists from

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean

that all data needs discussed in this section must be filled. In the future, the identified data needs will be

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.3.1 Identification of Data Needs

Methods for Determining Biomarkers of Exposure and Effect. Methods exist for the

determination of ethion in saliva (Nigg et al. 1993; LOD <1 ppm, 10% RSD) and urine (Singh et al.

1986; LOD <100 ng/mL). In the absence of a clear relationship between exposure concentrations and

concentrations in biological samples, a definitive statement about the adequacy of the methods available

is not possible. Methods for metabolites DEP, DETP, and DEDTP have also been described for saliva

and urine (Nigg et al. 1993), but these compounds are not specific to ethion exposure. In addition,

cholinesterase activity in plasma and red blood cells can be related to exposure to organophosphorus

pesticides, but a decrease in activity is not unique to ethion effect. 

Methods for Determining Parent Compounds and Degradation Products in

Environmental Media. Methods for the determination of ethion in water have limits of detection of

0.1 μg/L (EPA 1992), 13 ng/L (EPA 1997c), and 10 ppt (0.01 μg/L; Termonia and Termonia 1997). 

Assuming a 2 L/day consumption of water, an exposure via drinking water of 0.02 μg/day could be

quantified. The oral MRLs derived by ATSDR are 0.002 mg/kg/day for oral exposure in acute and

intermediate conditions, and 0.0004 mg/kg/day for oral exposure in chronic conditions. These methods

are adequate for determination of ethion at levels well below the MRL. Methods exist for the
ETHION 144

6. ANALYTICAL METHODS

determination of ethion in milk (DiMuccio et al. 1996; Erney et al. 1997, LOD=0.005 mg/kg), oranges,

sweet potatoes, fruits and vegetables, strawberries, and meats (FDA 1997; Ferreira and Fernandes 1980;

Ivey and Mann 1975; Lehotay and Valverde-García 1997; Lino and da Silveira 1994; Pearce et al. 1997;

Torres et al. 1996). Sensitivities are as low as 4 μg/kg (ppb) (Lehotay and Valverde-García 1997). 

Assuming a total ingestion of 2 kg of food per day, potential exposures as low as 8 μg per day could be

measured. Current methods are adequate to detect ethion in foods at the MRL levels. However,

methods must be validated for other matrices before they can be used.

6.3.2 Ongoing Studies

No ongoing studies in which new methods for the measurement of ethion or its metabolites/breakdown

products were identified.
ETHION 145

7. REGULATIONS AND ADVISORIES

The international, national, and state regulations and guidelines regarding ethion in air, water, and other

media are summarized in Table 7-1. 

ATSDR has derived a Minimal Risk Level (MRL) of 0.002 mg/kg/day for oral exposure to ethion over

the acute and intermediate durations based on a NOAEL of 0.06 mg/kg/day for inhibition of brain

acetylcholinesterase in Beagle dogs (Bailey 1988). This same study was used to derive a chronicduration MRL of 0.0004 mg/kg/day.

The Environmental Protection Agency (EPA) has not established a reference concentration (RfC) for

ethion. The reference dose (RfD) for ethion is 0.0005 mg/kg/day. This RfD is based on a study in

humans conducted by Palazzolo (1970) for the FMC Corporation (IRIS 1999).

Ethion has not been classified for carcinogenicity by the Department of Health and Human Services

(DHHS), the International Agency for Research on Cancer (IARC), or the EPA. The National

Toxicology Programs (NTP) Management Status Report does not list ethion as a candidate for general

toxicology studies (NTP 1998).

Between June 27, 1974 and January 18, 1989, the Occupational Safety and Health Administration

(OSHA) had promulgated protective, permissible exposure limits (PELs) for approximately 264 toxic

substances (OSHA 1993). The OSHA PELs were established to protect workers against adverse health

effects resulting from exposure to hazardous substances. An employer must ensure that an employee’s

exposure to a toxic substance in any 8-hour work shift of a 40-hour week does not exceed the 8-hour

time-weighted average (TWA) established for the substance (OSHA 1993). On January 18, 1989,

OSHA promulgated more protective PELs for approximately 376 toxic substances. Ethion was included

among 164 toxic substances not previously regulated (OSHA 1989). The newly established PEL for

ethion was set at 0.4 mg/m3

 (OSHA 1989). OSHA also provided a “skin designation” for ethion. The

skin designation would indicate a potential for dermal absorption and the need for employers to

implement the use of good work practices including providing workers with gloves, coveralls, goggles,

and other appropriate equipment in order to prevent skin exposures (NIOSH 1997). Because the 1989

promulgation was rescinded by the 11th Circuit Court Appeals in July 1992, only those PELs in place

prior to the 1989 rule are currently enforced by OSHA. On June 30, 1993, OSHA published in the
ETHION 146

7. REGULATIONS AND ADVISORIES

Federal Register a final rule announcing the revocation of the 1989 exposure limits, including the newly 

established limits for ethion (OSHA 1993). Currently, there is no OSHA PEL for ethion. However, the 

National Institute for Occupational Safety and Health (NIOSH) and approximately twenty-five states

have adopted the 0.4 mg/m3

 exposure limit for ethion that was initially promulgated by OSHA (NIOSH

1992, 1997; OSHA 1993). The American Conference of Governmental Industrial Hygienists (ACGIH)

also adopted the 0.4 mg/m3

 exposure limit for ethion (ACGIH 1998). 

Ethion has been designated as a hazardous substance pursuant to the Comprehensive Environmental

Response, Compensation, and Liability Act (CERCLA) of 1980 (EPA 1995a, 1996a). The statutory

source for this designation is section 311(b)(4) of the Clean Water Act (CWA) (EPA 1995a). The owner

and operator of any facility that produces, uses, or stores a CERCLA hazardous substance in an amount

exceeding the “threshold planning quantity” are required to immediately report any release to any

environmental media, if the amount released is equal to or exceeds the specified “reportable quantity”

assigned to the substance. The threshold planning quantity for ethion is 1,000 pounds, and the reportable

quantity is 10 pounds (4.54 kg) (EPA 1999c). 

Under the authority of the CWA ethion is regulated as a wastewater pollutant in discharges from new

and existing facilities that formulate, package, and repackage pesticide products. Facilities of this type

make up two subcategories of the Pesticide Chemicals Point Source Category—Subcategory C: Pesticide

Formulating, Packaging and Repackaging which includes facilities that also manufacture pesticide active

ingredients (PAIs) and Subcategory E: Repackaging of Agricultural Pesticides Performed at Refilling

Establishments (EPA 1996c). As of January 6, 1997, the regulatory limit for Subcategory C facilities on

the discharge of wastewater pollutants into navigable waters and into publicly owned treatment works

(POTWs) is a choice between zero discharge or compliance with the pollution prevention alternative

provided in Table 8 of 40 CFR 455 (EPA 1996c). Subcategory E facilities are required to achieve the

“zero” criterium for discharge of wastewater pollutants (EPA 1996c). Some of the PAIs to which these

effluent guidelines and standards do not apply are sanitizers, including pool chemicals; microorganisms,

such as Bacillus thuringiensis; and certain liquid chemical sterilants that are used on critical or semicritical medical devices (EPA 1996c). Complete listings of PAIs that are not required to meet the

Subcategory C and E guidelines and standards can be found in 40 CFR 455.40 and 40 CFR 455.60,

respectively. As a pesticide, ethion is regulated under the section 408 of the Federal Food, Drug, and 
ETHION 147

7. REGULATIONS AND ADVISORIES

Cosmetics Act as amended by the Food Quality Protection Act (EPA 1998a). The EPA has set tolerance

limits for the amount of ethion residue that can be found raw agricultural products and animal feeds

(EPA 1997a, 1998a).
ETHION 148

7. REGULATIONS AND ADVISORIES

Table 7-1. Regulations and Guidelines Applicable to Ethion

Agency Description Information Reference

International

Guidelines:

IARC

Cancer classification None IARC 1997

National

Regulations and

Guidelines:

a. Air

ACGIH Threshold limit value (TLV) 0.4 mg/m3 ACGIH 1999

NIOSH Exposure limit (TWA)—skin 0.4 mg/m3 NIOSH 1999

OSHA Permissible exposure limit (PEL) 

8-hour time weighted average

(TWA)

None 

0.4 mg/m3 was the

vacated 1989 PEL

OSHA 1989a

NIOSH 1997a

b. Water

No available data

c. Food

EPA Pesticide classification for ethion Cholinesterase

inhibiting pesticide

40 CFR 180.3

EPA 1999a

Tolerances for ethion residues in or

on raw agricultural commodities

0.2-10 ppm 40 CFR 180.173

EPA 1999b

d. Other

ACGIH Biological exposure indices (BEI)

organophosphorus cholinesterase

inhibitors

70% of individual’s

baseline

ACGIH 1999

EPA RfD

Cancer classification

5x10-4 mg/kg/day

Not determined

IRIS 1999

Reportable quantities of hazardous

substances

Ethion—designated CERCLA

hazardous substance under

sections 311(b)(4) Clean Water

Act

10 lbs. 40 CFR 302.4

EPA 1999c

Statutory source for designation as

a CERCLA hazardous substance

Yes Clean Water Act

U.S. Congress

1977
ETHION 149

7. REGULATIONS AND ADVISORIES

Table 7-1. Regulations and Guidelines Applicable to Ethion (continued)

Agency Description Information Reference

EPA (cont.) Designated hazardous substance

in accordance with section

311(b)(2)(a) of the act

Yes 40 CFR 116.4

EPA 1998a

Included in the list of organic

pesticide active ingredients

Yes 40 CFR 455

Sub E

EPA 1998b

STATE

Regulations and

Guidelines:

a. Air

Colorado 5 CCR1001-5 Regulation No. 3-Air

contaminant emissions notices for

HAP

Yes BNA 1998

Connecticut 8-hour

30-minute

8 μg/m3

40 μg/m3

Idaho Screening emissions level

Emissions in pounds per hour

0.4 mg/m3

0.0267

Acceptable concentration

Occupational exposure level

0.02 mg/m3

0.4 mg/m3

Idaho

Department of

Health and

Welfare 1999

Maryland Toxic air pollutants for existing

sources

Yes BNA 1998

New Mexico Screening emissions levels

Emissions in pounds per hour

0.4 mg/m3

0.0267

Washington Toxic air pollutants and acceptable

source impact levels

1.3 μg/m3

Wisconsin Air contaminant emission inventory

reporting requirements

147 pounds/year

Acceptable emission levels

<25 feet

25 feet

3.4x10-2 lbs/hour

0.14 lbs/hour

Wisconsin

Department of

Natural

Resources 1997

b. Water

Arizona Human health based guidance

levels (HBGLS)for ingestion of

contaminants in drinking water—

Oral HBGL

3.5 μg/L

Arizona

Department of

Health Services

1999

c. Other

Hawaii Restricted use pesticide Yes BNA 1998
ETHION 150

7. REGULATIONS AND ADVISORIES

Table 7-1. Regulations and Guidelines Applicable to Ethion (continued)

Agency Description Information Reference

Indiana Restricted use pesticide All products 80% or

greater

Vermont Restricted use pesticide All products

Washington Pesticide regulations Not for distribution to

home and garden

users

a

Prior to setting a protective PEL of 0.4 mg/m3 for ethion in 1989, OSHA had not established a protective level for

this substance. In July 1992, the 11th Circuit Court Appeals rescinded the 1989 PELs promulgated by OSHA for 212

substances, including ethion. Only PELs in place prior to the 1989 rule are currently allowed.

ACGIH = American Conference of Governmental Industrial Hygienists; CERCLA = Comprehensive Environmental

Response, Compensation, and Liability Act of 1980; CFR = Code of Federal Regulations; EPA = Environmental

Protection Agency; IARC = International Agency for Research On Cancer; NIOSH = National Institute for

Occupational Safety and Health; NPDES = National Pollutant Discharge Elimination System; ODW = Office of

Drinking Water; OERR = Office of Emergency and Remedial Response; OSHA = Occupational Safety and Health

Administration; PEL = Permissible Exposure Limit; RfD = Reference Dose; TLV = Threshold Limit Value; TWA =

Time-Weighted Average; USDA = United States Department of Agriculture; WHO = World Health Organization
ETHION 151

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ETHION 155

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*Sobti RC, Krishan A, Pfaffenberger CD. 1982. Cytokinetic and cytogenetic effects of some

agricultural chemicals on human lymphoid cells in vitro: organophosphates. Mutat Res 102:89-102.

South Dakota Department of Environment and Natural Resources. 1998. Drinking water regulations. 

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environmental parameters octanol/water partition coefficient, soil sorption constant, water to air ratio,

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*Taylor P, Li Y, Camp S, et al. 1993. Structure and regulation of expression of the acetylcholinesterase

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*Termonia A, Termonia M. 1997. Full scan gc-ms quantitation of pesticides in spring water at the 10

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Toxicol 5(1):55-61.

*Tomlin C. 1994. Ethion. In: The pesticide manual: Incorporating the agrochemicals handbook. 10th ed.

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Protection Council Publications and the Royal Society of Chemistry. 480-482.

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hypermethylation control of gene expression during the neonatal period. European Journal of

Biochemistry 238:476-483.

*Waters MD, Simmon VF, Mitchell AD, et al. 1980. An overview of short term tests for the mutagenic

and carcinogenic potential of pesticides. J Environ Sci Health B15(6):867-906.

*Weiner M. 1985a. Twenty-one day repeated dose dermal toxicity study in rabbits with FMC 1240

technical (ethion): study no. A84-1369. Unpublished study prepared by FMC Corp. EPA MRID No,

00155498. (information taken from EPA 1989d)

*Weiner M. 1985b. Twenty-one day repeated dose dermal toxicity study in male rabbits with FMC 1240

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00155499. ( information taken from EPA 1989d)

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*Whitmore RW, Immerman FW, Camann DE, et al. 1994. Non-occupational exposures to pesticides

for residents of two U.S. cities. Arch Environ Contam Toxicol 26:47-59.

WHO. 1996. Guidelines for drinking-water quality. Second Edition. Volume 2. Health criteria and

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*Winterlin WL, Schoen SR, Mourer CR. 1984. Disposal of Pesticide Wastes in Lined Evaporation

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*Wisconsin Department of Natural Resources. 1997. Ethion. Regulation & Licensing. Environmental

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http://www.dnr.state.wi.us/org/aw/air/index.htm
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Environ Contam Toxicol 10:725-735.

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*Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr

Res 12:29-34.
ETHION 169

9. GLOSSARY

Absorption—The taking up of liquids by solids, or of gases by solids or liquids.

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the

Toxicological Profiles.

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to

the surfaces of solid bodies or liquids with which they are in contact.

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase)

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at

a fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil

or sediment.

Benchmark Dose (BMD)—is usually defined as the lower confidence limit on the dose that produces a

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would

be 10%. The BMD is determined by modeling the dose response curve in the region of the dose response

relationship where biologically observable data are feasible. 

Benchmark Dose Model—is a statistical dose-response model applied to either experimental

toxicological or epidemiological data to calculate a BMD.

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms

at a specific time or during a discrete time period of exposure divided by the concentration in the

surrounding water at the same time or during the same period.

Biomarkers—are broadly defined as indicators signaling events in biologic systems or samples. They

have been classified as markers of exposure, markers of effect, and markers of susceptibility.

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces

significant increases in the incidence of cancer (or tumors) between the exposed population and its

appropriate control.

Carcinogen—A chemical capable of inducing cancer.

Case-Control Study—A type of epidemiological study which examines the relationship between a

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is

identified and compared to a similar group of people without outcome.

Case Report—describes a single individual with a particular disease or exposure. These may suggest

some potential topics for scientific research but are not actual research studies.
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9. GLOSSARY

Case Series—describes the experience of a small number of individuals with the same disease or

exposure. These may suggest potential topics for scientific research but are not actual research studies.

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously.

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological

Profiles.

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed

group.

Cross-sectional Study—A type of epidemiological study of a group or groups which examines the

relationship between exposure and outcome to a chemical or to chemicals at one point in time.

Data Needs—substance-specific informational needs that if met would reduce the uncertainties of

human health assessment.

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may

result from exposure to a chemical prior to conception (either parent), during prenatal development, or

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any

point in the life span of the organism.

Dose-Response Relationship—the quantitative relationship between the amount of exposure to a

toxicant and the incidence of the adverse effects.

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to

a chemical; the distinguishing feature between the two terms is the stage of development during which

the insult occurs. The terms, as used here, include malformations and variations, altered growth, and 

in utero death.

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking

water levels for a chemical substance based on health effects information. A health advisory is not a

legally enforceable federal standard, but serves as technical guidance to assist federal, state, and local

officials.

Epidemiology—refers to the investigation of factors that determine the frequency and distribution of

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—a specific adverse effect on the genome of living cells that, upon the duplication of

affected cells, can be expressed as a mutagenic, clastogenic or carcinogenic event because of specific

alteration of the molecular structure of the genome.

Half-life—a measure of rate for the time required to eliminate one half of a quantity of a chemical from

the body or environmental media.

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or

irreversible health effects.
ETHION 171

9. GLOSSARY

Incidence—The ratio of individuals in a population who develop a specified condition to the total

number of individuals in that population who could have developed that condition in a specified time

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15-364 days, as specified in the

Toxicological Profiles.

Immunological Effects—are functional changes in the immune response.

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from

exposure to environmental agents such as chemicals.

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube.

In Vivo—Occurring within the living organism.

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air which has been

reported to have caused death in humans or animals.

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for

a specific length of time is expected to cause death in 50% of a defined experimental animal population.

Lethal Dose(LO) (LDLO)—The lowest dose of a chemical introduced by a route other than inhalation that

has been reported to have caused death in humans or animals.

Lethal Dose(50) (LD50)—The dose of a chemical which has been calculated to cause death in 50% of a

defined experimental animal population.

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical

is expected to cause death in 50% of a defined experimental animal population.

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study,

or group of studies, that produces statistically or biologically significant increases in frequency or

severity of adverse effects between the exposed population and its appropriate control.

Lymphoreticular Effects—represent morphological effects involving lymphatic tissues such as the

lymph nodes, spleen, and thymus.

Malformations—Permanent structural changes that may adversely affect survival, development, or

function.

Minimal Risk Level (MRL) —An estimate of daily human exposure to a hazardous substance that is

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and

duration of exposure.

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a minimal risk

level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty

factors. The default value for a MF is 1.
ETHION 172

9. GLOSSARY

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a

specific population.

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time.

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s

DNA. Mutations can lead to birth defects, miscarriages, or cancer.

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of

death or pathological conditions.

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a

chemical.

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no

statistically or biologically significant increases in frequency or severity of adverse effects seen between

the exposed population and its appropriate control. Effects may be produced at this dose, but they are

not considered to be adverse.

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical

in n-octanol and water, in dilute solution.

Odds Ratio—a means of measuring the association between an exposure (such as toxic substances and a

disease or condition) which represents the best estimate of relative risk (risk as a ratio of the incidence

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not

exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk of

disease in the exposed group compared to the unexposed.

Organophosphate or Organophosphorus Compound—a phosphorus containing organic compound

and especially a pesticide that acts by inhibiting cholinesterase.

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA)

allowable exposure level in workplace air averaged over an 8-hour shift of a 40 hour workweek.

Pesticide—general classification of chemicals specifically developed and produced for use in the control

of agricultural and public health pests.

Pharmacokinetics—is the science of quantitatively predicting the fate (disposition) of an exogenous

substance in an organism. Utilizing computational techniques, it provides the means of studying the

absorption, distribution, metabolism and excretion of chemicals by the body.

Pharmacokinetic Model—is a set of equations that can be used to describe the time course of a parent

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based

and physiologically-based. A data-based model divides the animal system into a series of compartments

which, in general, do not represent real, identifiable anatomic regions of the body whereby the

physiologically-based model compartments represent real anatomic regions of the body.
ETHION 173

9. GLOSSARY

Physiologically Based Pharmacodynamic (PBPD) Model—is a type of physiologically-based doseresponse model which quantitatively describes the relationship between target tissue dose and toxic end

points. These models advance the importance of physiologically based models in that they clearly

describe the biological effect (response) produced by the system following exposure to an exogenous

substance. 

Physiologically Based Pharmacokinetic (PBPK) Model—is comprised of a series of compartments

representing organs or tissue groups with realistic weights and blood flows. These models require a

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar

ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical

information such as air/blood partition coefficients, and metabolic parameters. PBPK models are also

called biologically based tissue dosimetry models.

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study--a type of cohort study in which the pertinent observations are made on events

occurring after the start of the study. A group is followed over time.

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and

μg/m3

 for air).

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health

(NIOSH) time-weighted average (TWA) concentrations for up to a 10-hour workday during a 40-hour

workweek.

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups)

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately

expressed in units of mg/m3 or ppm.

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the

daily exposure of the human population to a potential hazard that is likely to be without risk of

deleterious effects during a lifetime. The RfD is operationally derived from the No-Observed-AdverseEffect Level (NOAEL- from animal and human studies) by a consistent application of uncertainty

factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which

is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable

to nonthreshold effects such as cancer.

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a

24-hour period.

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related
ETHION 174

9. GLOSSARY

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior,

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of

this system.

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed

at some time in the past. Data are collected from routinely recorded events, up to the time the study is

undertaken. Retrospective studies are limited to casual factors that can be ascertained from existing

records and/or examining survivors of the cohort.

Risk—the possibility or chance that some adverse effect will result from a given exposure to a chemical.

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or

inherited characteristic, that is associated with an increased occurrence of disease or other health-related

event or condition.

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed

group compared to the unexposed.

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 min

continually. No more than four excursions are allowed per day, and there must be at least 60 min

between exposure periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA)

may not be exceeded.

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited

exposure to those assumed over a lifetime of exposure to a chemical.

Teratogen—A chemical that causes structural defects that affect the development of an organism.

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit

(STEL), or as a ceiling limit (CL).

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal

8-hour workday or 40-hour workweek.

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation,

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population.

Toxicokinetic—The study of the absorption, distribution and elimination of toxic compounds in the

living organism.

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to

account for (1) the variation in sensitivity among the members of the human population, (2) the

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from
ETHION 175

9. GLOSSARY

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using LowestObserved-Adverse-Effect Level (LOAEL) data rather than No-Observed-Adverse-Effect Level

(NOAEL) data. A default for each individual UF is 10; if complete certainty in data exists, a value of

one can be used; however a reduced UF of three may be used on a case-by-case basis, three being the

approximate logarithmic average of 10 and 1.

Xenobiotic—any chemical that is foreign to the biological system.

ETHION A-1

APPENDIX A

ATSDR MINIMAL RISK LEVELS AND WORKSHEETS

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C.

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L.

99–499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly

with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous

substances most commonly found at facilities on the CERCLA National Priorities List (NPL); prepare

toxicological profiles for each substance included on the priority list of hazardous substances; and assure

the initiation of a research program to fill identified data needs associated with the substances.

The toxicological profiles include an examination, summary, and interpretation of available toxicological

information and epidemiologic evaluations of a hazardous substance. During the development of

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are

used by ATSDR health assessors to identify contaminants and potential health effects that may be of

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up

or action levels.

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty

factor approach. They are below levels that might cause adverse health effects in the people most

sensitive to such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate

(15–364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of

exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not

yet identified a method suitable for this route of exposure. MRLs are generally based on the most

sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects

(such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for

establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will

occur.
ETHION A-2

APPENDIX A

MRLs are intended only to serve as a screening tool to help public health professionals decide where to

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants,

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public

health principle of prevention. Although human data are preferred, MRLs often must be based on

animal studies because relevant human studies are lacking. In the absence of evidence to the contrary,

ATSDR assumes that humans are more sensitive to the effects of hazardous substance than animals and

that certain persons may be particularly sensitive. Thus, the resulting MRL may be as much as a

hundredfold below levels that have been shown to be nontoxic in laboratory animals.

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the

Division of Toxicology, expert panel peer reviews, and agency wide MRL Workgroup reviews, with

participation from other federal agencies and comments from the public. They are subject to change as

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs

in the most recent toxicological profiles supersede previously published levels. For additional

information regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances

and Disease Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333.
ETHION A-3

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical name: Ethion

CAS number: 563-12-2

Date: June 14, 2001

Profile status: Third Draft Post-Public Comment

Route: [ ] Inhalation [x] Oral

Duration: [x] Acute [ ] Intermediate [ ] Chronic

Key to figure: 24

Species: Dog

MRL: 0.002 [x] mg/kg/day [ ] ppm [ ] mg/m3

Reference: Bailey DE. 1988. 90-day subchronic toxicity study of ethion technical in dogs. 

Unpublished revised final report dated June 21, 1988 by Hazelton Laboratories America, Inc., Vienna

VA, for FMC Corporation, Princeton NJ. Hazelton Study No. 104-229, FMC Study No. A86-1990,

EPA MRID No. 40773301. [Available from EPA. Write to FOI, EPA, Washington, DC 20460] 

Experimental design: See MRL Worksheet for intermediate-duration oral exposure, page A-5. 

Effects noted in study and corresponding doses: See MRL Worksheet for intermediate-duration oral

exposure, page A-5.

Dose end point used for MRL derivation: 0.06 mg/kg/day; brain acetylcholinesterase inhibition

[x] NOAEL [ ]LOAEL

Uncertainty factors used in MRL derivation:

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)

[ ] 1 [x] 3 [ ] 10 (for extrapolation from animals to humans)

[ ] 1 [ ] 3 [x] 10 (for human variability)

The acute oral MRL for ethion is derived as follows:

MRL = NOAEL ÷ UF

MRL = 0.06 mg/kg/day ÷ 30

MRL = 0.002 mg/kg/day

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Dose was calculated

using mean daily compound consumption reported in the study (Table 5).

Was a conversion used from intermittent to continuous exposure? If so, explain: Not applicable

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not

applicable

Other additional studies or pertinent information that lend support to this MRL: This MRL should be

protective against health effects in individuals potentially exposed to ethion at hazardous waste sites. A 
ETHION A-4

APPENDIX A

study in volunteers (Palazollo 1970) has determined the sensitivity of humans to the effects of ethion on

blood cholinesterase activities. A group of six male volunteers were given ethion in corn oil solutions in

three divided doses (9:00 a.m., noon, and 5:00 p.m.) of 0.05, 0.075, 0.1, and 0.15 mg/kg/day via gelatin

capsule. Subjects received 0.05, 0.075 , and 0.1 mg/kg/day for 3 weeks each and then 0.15 mg/kg/day

for 3 days. No adverse clinical signs (blood pressure, pulse rate, pupil size, light reflex, eye

accommodation, chest sound, muscle tone, knee jerk, tongue tremor and finger tremor) or effects on

erythrocyte acetylcholinesterase were observed at any time during the study. Absorption of ethion by

the volunteers was confirmed by a decrease in plasma cholinesterase levels. While no effect on plasma

cholinesterase was observed at the 0.05 mg/kg/day dose level, a 16% decrease was seen in the

0.075 mg/kg/day group. Decreases of 23 and 31% were seen in the 0.1 and 0.15 mg/kg/day groups.

The NOAEL of the Bailey study for inhibition of brain acetylcholinesterase was adjusted by a factor of

10 for human variability and a factor of 3 for extrapolation of an animal study to humans. A factor of 3

was used for extrapolation rather than the full uncertainty factor of 10 because the results of the

Palazzollo (1970) study indicated that dogs appear to be at least as sensitive to the neurological effects of

ethion as humans when exposed to comparable doses. 

The MRL value of 0.002 mg/kg/day for intermediate-duration oral exposure to ethion was extended to

acute-duration oral exposure based on the toxicokinetics of ethion. Cholinesterase inhibition occurs

quickly and there are no indications of progressive inhibition over time at a given dose in either the

Palazzollo (1970) study in humans or the Bailey (1988) study in dogs. A similar lack of progression of

inhibition was seen in 2-year studies in rats and mice where brain and erythrocyte acetylcholinesterase

and plasma cholinesterase were measured at 6-month intervals (Morrow et al. 1985a, 1985b). The

toxicity database indicates no change in ethion toxicity over time, i.e., toxicity is dependent on the dose,

not the duration of exposure. Because the toxicological effects of ethion are due to a series of repeated

acute exposures, the intermediate-duration oral MRL should be protective for this endpoint for acute

exposure durations.

Agency Contact (Chemical Manager): Nickolette Roney
ETHION A-5

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical name: Ethion

CAS number: 563-12-2

Date: June 14, 2001

Profile status: Third Draft Post-Public Comment

Route: [ ] Inhalation [x] Oral

Duration: [ ] Acute [x] Intermediate [ ] Chronic

Key to figure: 24

Species: Dog

MRL: 0.002 [x] mg/kg/day [ ] ppm [ ] mg/m3

Reference: Bailey DE. 1988. 90-day subchronic toxicity study of ethion technical in dogs. 

Unpublished revised final report dated June 21, 1988 by Hazelton Laboratories America, Inc., Vienna

VA, for FMC Corporation, Princeton NJ. Hazelton Study No. 104-229, FMC Study No. A86-1990,

EPA MRID No. 40773301. [Available from EPA. Write to FOI, EPA, Washington, DC 20460] 

Experimental design: The purpose of this study was to evaluate the subchronic toxicity of Ethion

Technical when administered orally to dogs for 13 weeks. Groups of Beagle dogs (n=4/sex/group, 20-28

weeks old) received ethion (purity 93.4%)in the diet at target concentrations of 0, 0.5, 2.5, 25.0, and 300

ppm for 90 days. Food was available for 2 hours a day, water was available ad libitum. The average

compound consumed was 0, 0.01, 0.06, 0.71 and 6.9 mg/kg/day for males and 0, 0.012, 0.07, 0.71 and

8.25 mg/kg/day for females. All dogs were observed twice daily for mortality and moribundity. 

Animals were observed once daily for clinical signs. Body weights were recorded during acclimation

and quarantine, on day 0 (one day prior to treatment initiation), and weekly thereafter. Food

consumption was measured weekly. Detailed physical exams were performed at each weighing interval. 

Ophthalmoscopic examinations were performed prior to initiation and during week 13. Clinical

pathology parameters were evaluated for all dogs prior to initiation of treatment (day -16) and during

weeks 5, 9, and 13 and included the following: cholinesterase (plasma, erythrocyte, brain) activity,

hematology (leukocyte count, erythrocyte count, hemoglobin, corrected leukocyte count, hematocrit,

platelet count, differential leukocyte count), and clinical chemistry (sodium, potassium, chloride, total

protein, albumin, calcium, phosphorus, total bilirubin, urea nitrogen, creatinine, glucose, alanine

aminotransferase, aspartate aminotransferase, globulin). All surviving animals were sacrificed following

the 13-week treatment period. Necropsies were performed, terminal body weights taken, and liver (with

drained gallbladder), kidneys, testes (with epididymides), thyroid (with parathyroid) and brain weights

were taken. Histopathological examination of the following tissues was conducted: lesions, brain (with

medulla/pons, cerebellar cortex, and cerebral cortex), gallbladder, pituitary, thyroid (parathyroid),

thymus, lungs, trachea, heart, bone (femur), salivary glands (mandibular), bone marrow (sternum),

kidneys, uterus, adrenals, liver, spleen, pancreas, testes (with epididymides), ovaries, aorta, esophagus,

stomach, duodenum, jejunum, ileum, colon, cecum, rectum, urinary bladder, mesenteric lymph node,

sciatic nerve, spinal cord (cervical, thoracic, lumbar), skin, mammary gland, and eyes.

Effects noted in study and corresponding doses: One female dog in the 8.25 mg/kg/day group was

sacrificed on day 90 (one day before schedule). Clinical signs exhibited by this animal prior to sacrifice

included emesis, dehydration, and thin body mass. All other animals survived until terminal sacrifice. 

In the highest dose group (6.9 mg/kg/day for males, 8.25 mg/kg/day for females) clinical signs included

miosis (all animals), emesis (all animals), dehydration (3M, 2F), salivation (2M, 2F), and tremors (3M,

4F). Animals in this group appeared to be in generally poor condition at the end of the study. 

Erythrocyte acetylcholinesterase was strongly inhibited at weeks 5 (94%M, 96%F), 9 (95%M, 93%F),
ETHION A-6

APPENDIX A

and 13 (94%M, 93%F) in the highest dose groups, but not in any of the other groups. Mean percent

brain acetylcholinesterase activity inhibition at termination was 64% in males and 61% in females at the

highest dose. Male brain acetylcholinesterase was inhibited 23% at 0.71 mg/kg/day but no inhibition of

brain acetylcholinesterase occurred in females at this dose. Plasma cholinesterase inhibition was doserelated in both males and females. No significant differences in absolute organ weights were observed

between treated and control animals. No compound-related histopathological effects were observed in

any organ, including brain, sciatic nerve and spinal cord. The no-observed-adverse-effect level for

inhibition of brain acetylcholinesterase is 0.06 mg/kg/day.

Cholinesterase Inhibition vs. Control at 13 Weeks (In Percentages)

Dose (mg/kg/day)

Plasma

cholinesterase

Erythrocyte

acetylcholinesterase Brain acetylcholinesterase

0.01 (M) 3 4 10

0.012 (F) 5 0 0

0.06 (M) 15* 5 1

0.07 (F) 13 0 0

0.71 (M) 58* 12 23*

0.71 (F) 52* 5 2

6.9 (M) 84* 94* 64*

8.25 (F) 84* 93* 61*

* significantly different from control (p<0.05).

Dose end point used for MRL derivation: 0.06 mg/kg/day; brain acetylcholinesterase inhibition

[x] NOAEL [ ]LOAEL

Uncertainty factors used in MRL derivation:

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)

[ ] 1 [x] 3 [ ] 10 (for extrapolation from animals to humans)

[ ] 1 [ ] 3 [x] 10 (for human variability)

The intermediate oral MRL for ethion is derived as follows:

MRL = NOAEL ÷ UF

MRL = 0.06 mg/kg/day ÷ 30

MRL = 0.002 mg/kg/day

Was a conversion factor used from ppm in food or water to a mg/body weight dose? If so, explain: Dose

was calculated using mean daily compound consumption reported in the study (Table 5).

Was a conversion used from intermittent to continuous exposure? If so, explain: Not applicable.
ETHION A-7

APPENDIX A

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not

applicable.

Other additional studies or pertinent information that lend support to this MRL: This MRL should be

protective against health effects in individuals potentially exposed to ethion at hazardous waste sites. A

study in volunteers (Palazollo 1970) has determined the sensitivity of humans to the effects of ethion on

blood cholinesterase activities. A group of six male volunteers were given ethion in corn oil solutions in

3 divided doses (9:00 a.m., noon, and 5:00 p.m.) of 0.05, 0.075, 0.1, and 0.15 mg/kg/day via gelatin

capsule. Subjects received 0.05, 0.075 , and 0.1 mg/kg/day for 3 weeks each and then 0.15 mg/kg/day

for 3 days. No adverse clinical signs (blood pressure, pulse rate, pupil size, light reflex, eye

accommodation, chest sound, muscle tone, knee jerk, tongue tremor and finger tremor) or effects on

erythrocyte acetylcholinesterase were observed at any time during the study. Absorption of ethion by

the volunteers was confirmed by a decrease in plasma cholinesterase levels. While no effect on plasma

cholinesterase was observed at the 0.05 mg/kg/day dose level, a 16% decrease was seen in the

0.075 mg/kg/day group. Decreases of 23 and 31% were seen in the 0.1, and 0.15 mg/kg/day groups.

The NOAEL of the Bailey study for inhibition of brain acetylcholinesterase was adjusted by a factor of

10 for human variability and a factor of 3 for extrapolation of an animal study to humans. A factor of 3

was used for extrapolation rather than the full uncertainty factor of 10 because the results of the

Palazzollo (1970) study indicated that dogs appear to be at least as sensitive to the neurological effects of

ethion as humans when exposed to comparable doses. 

The MRL value of 0.002 mg/kg/day for intermediate-duration oral exposure to ethion was extended to

acute-duration oral exposure based on the toxicokinetics of ethion. Cholinesterase inhibition occurs

quickly and there are no indications of progressive inhibition over time at a given dose in either the

Palazzollo (1970) study in humans or the Bailey (1988) study in dogs. A similar lack of progression of

inhibition was seen in 2-year studies in rats and mice where brain and erythrocyte acetylcholinesterase

and plasma cholinesterase were measured at 6 month intervals (Morrow et al. 1985a, b). The toxicity

database indicates no change in ethion toxicity over time, i.e. toxicity is dependent on the dose, not the

duration of exposure. Because the toxicological effects of ethion are due to a series of repeated acute

exposures, the intermediate-duration oral MRL should be protective for this endpoint for acute exposure

durations.

Agency Contact (Chemical Manager): Nickolette Roney
ETHION A-8

APPENDIX A

MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical name: Ethion

CAS number: 563-12-2

Date: June 14, 2001

Profile status: Third Draft Post-Public Comment

Route: [ ] Inhalation [x] Oral

Duration: [ ] Acute [ ] Intermediate [x] Chronic

Key to figure: 24

Species: Dog

MRL: 0.0004 [x] mg/kg/day [ ] ppm [ ] mg/m3

Reference: Bailey DE. 1988. 90-day subchronic toxicity study of ethion technical in dogs. 

Unpublished revised final report dated June 21, 1988 by Hazelton Laboratories America, Inc., Vienna

VA, for FMC Corporation, Princeton NJ. Hazelton Study No. 104-229, FMC Study No. A86-1990,

EPA MRID No. 40773301. [Available from EPA. Write to FOI, EPA, Washington, DC 20460] 

Experimental design: See MRL Worksheet for intermediate-duration oral exposure, page A-5. 

Effects noted in study and corresponding doses: See MRL Worksheet for intermediate-duration oral

exposure, page A-5. 

Dose end point used for MRL derivation: 0.06 mg/kg/day; brain acetylcholinesterase inhibition

[x] NOAEL [ ]LOAEL

Uncertainty factors used in MRL derivation:

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)

[ ] 1 [x] 3 [ ] 10 (for extrapolation from animals to humans)

[ ] 1 [ ] 3 [x] 10 (for human variability)

[ ] 1 [x] 5 [ ] 10 (Modifying Factor)

The chronic oral MRL for ethion is derived as follows:

MRL = NOAEL ÷ (UF * MF)

MRL = 0.06 mg/kg/day ÷ (30 * 5)

MRL = 0.0004 mg/kg/day

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Dose was calculated

using mean daily compound consumption reported in the study (Table 5).

Was a conversion used from intermittent to continuous exposure? If so, explain: Not applicable

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not

applicable

Other additional studies or pertinent information that lend support to this MRL: This MRL should be

protective against health effects in individuals potentially exposed to ethion at hazardous waste sites. A

study in volunteers (Palazollo 1970) has determined the sensitivity of humans to the effects of ethion on
ETHION A-9

APPENDIX A

blood cholinesterase activities. A group of six male volunteers were given ethion in corn oil solutions in

3 divided doses (9:00 a.m., noon, and 5:00 p.m.) of 0.05, 0.075, 0.1, and 0.15 mg/kg/day via gelatin

capsule. Subjects received 0.05, 0.075 , and 0.1 mg/kg/day for 3 weeks each and then 0.15 mg/kg/day

for 3 days. No adverse clinical signs (blood pressure, pulse rate, pupil size, light reflex, eye

accommodation, chest sound, muscle tone, knee jerk, tongue tremor and finger tremor) or effects on

erythrocyte acetylcholinesterase were observed at any time during the study. Absorption of ethion by

the volunteers was confirmed by a decrease in plasma cholinesterase levels. While no effect on plasma

cholinesterase was observed at the 0.05 mg/kg/day dose level, a 16% decrease was seen in the

0.075 mg/kg/day group. Decreases of 23 and 31% were seen in the 0.1, and 0.15 mg/kg/day groups.

The NOAEL of the Bailey study for inhibition of brain acetylcholinesterase was adjusted by a factor of

10 for human variability and a factor of 3 for extrapolation of an animal study to humans. A factor of 3

was used for extrapolation rather than the full uncertainty factor of 10 because the results of the

Palazzollo (1970) study indicated that dogs appear to be at least as sensitive to cholinesterase inhibition

by ethion as humans when exposed to comparable doses. An additional modifying factor of 5 was

applied to the chronic duration to protect against possible long-term effects, seen in structurally-related

cholinesterase inhibitors, which might be the result of mechanisms other than cholinesterase inhibition,

and to protect against possible susceptibility in children.

Agency Contact (Chemical Manager): Nickolette Roney

ETHION B-1

APPENDIX B

USER'S GUIDE

Chapter 1

Public Health Statement

This chapter of the profile is a health effects summary written in non-technical language. Its intended

audience is the general public especially people living in the vicinity of a hazardous waste site or

chemical release. If the Public Health Statement were removed from the rest of the document, it would

still communicate to the lay public essential information about the chemical.

The major headings in the Public Health Statement are useful to find specific topics of concern. The

topics are written in a question and answer format. The answer to each question includes a sentence that

will direct the reader to chapters in the profile that will provide more information on the given topic.

Chapter 2

Tables and Figures for Levels of Significant Exposure (LSE)

Tables (2-1, 2-2, and 2-3) and figures (2-1 and 2-2) are used to summarize health effects and illustrate

graphically levels of exposure associated with those effects. These levels cover health effects observed

at increasing dose concentrations and durations, differences in response by species, minimal risk levels

(MRLs) to humans for noncancer end points, and EPA's estimated range associated with an upperbound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures

for a quick review of the health effects and to locate data for a specific exposure scenario. The LSE

tables and figures should always be used in conjunction with the text. All entries in these tables and

figures represent studies that provide reliable, quantitative estimates of No-Observed-Adverse- Effect

Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels

(CELs).

The legends presented below demonstrate the application of these tables and figures. Representative

examples of LSE Table 2-1 and Figure 2-1 are shown. The numbers in the left column of the legends

correspond to the numbers in the example table and figure.

LEGEND

See LSE Table 2-1

(1) Route of Exposure One of the first considerations when reviewing the toxicity of a substance

using these tables and figures should be the relevant and appropriate route of exposure. When

sufficient data exists, three LSE tables and two LSE figures are presented in the document. The

three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and

dermal (LSE Table 2-1, 2-2, and 2-3, respectively). LSE figures are limited to the inhalation (LSE

Figure 2-1) and oral (LSE Figure 2-2) routes. Not all substances will have data on each route of

exposure and will not therefore have all five of the tables and figures.
ETHION B-2

APPENDIX B

(2) Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15–364 days),

and chronic (365 days or more) are presented within each relevant route of exposure. In this

example, an inhalation study of intermediate exposure duration is reported. For quick reference to

health effects occurring from a known length of exposure, locate the applicable exposure period

within the LSE table and figure.

(3) Health Effect The major categories of health effects included in LSE tables and figures are death,

systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and

LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are

further defined in the "System" column of the LSE table (see key number 18).

(4) Key to Figure Each key number in the LSE table links study information to one or more data

points using the same key number in the corresponding LSE figure. In this example, the study

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL (also

see the 2 "18r" data points in Figure 2-1).

(5) Species The test species, whether animal or human, are identified in this column. Section 2.5,

"Relevance to Public Health," covers the relevance of animal data to human toxicity and Section

2.3, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although

NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent human doses

to derive an MRL.

(6) Exposure Frequency/Duration The duration of the study and the weekly and daily exposure

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from

different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via

inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the

dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e.,

Nitschke et al. 1981.

(7) System This column further defines the systemic effects. These systems include: respiratory,

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. 

"Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these

systems. In the example of key number 18, 1 systemic effect (respiratory) was investigated.

(8) NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which

no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of

3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation

MRL of 0.005 ppm (see footnote "b").

(9) LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study

that caused a harmful health effect. LOAELs have been classified into "Less Serious" and

"Serious" effects. These distinctions help readers identify the levels of exposure at which adverse

health effects first appear and the gradation of effects with increasing dose. A brief description of

the specific endpoint used to quantify the adverse effect accompanies the LOAEL. The respiratory

effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. MRLs are not

derived from Serious LOAELs.

(10) Reference The complete reference citation is given in chapter 8 of the profile.
ETHION B-3

APPENDIX B

(11) CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report

doses not causing measurable cancer increases.

(12) Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in

the footnotes. Footnote "b" indicates the NOAEL of 3 ppm in key number 18 was used to derive

an MRL of 0.005 ppm.

LEGEND

See Figure 2-1

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the

reader quickly compare health effects according to exposure concentrations for particular exposure

periods.

(13) Exposure Period The same exposure periods appear as in the LSE table. In this example, health

effects observed within the intermediate and chronic exposure periods are illustrated.

(14) Health Effect These are the categories of health effects for which reliable quantitative data exists. 

The same health effects appear in the LSE table.

(15) Levels of Exposure concentrations or doses for each health effect in the LSE tables are graphically

displayed in the LSE figures. Exposure concentration or dose is measured on the log scale "y"

axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in mg/kg/day.

(16) NOAEL In this example, 18r NOAEL is the critical endpoint for which an intermediate inhalation

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates

to a NOAEL for the test species-rat. The key number 18 corresponds to the entry in the LSE table. 

The dashed descending arrow indicates the extrapolation from the exposure level of 3 ppm (see

entry 18 in the Table) to the MRL of 0.005 ppm (see footnote "b" in the LSE table).

(17) CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to

the entry in the LSE table.

(18) Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the

upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are

derived from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of

the cancer dose response curve at low dose levels (q1*).

(19) Key to LSE Figure The Key explains the abbreviations and symbols used in the figure.
SAMPLE

1 6 TABLE 2-1. Levels of Significant Exposure to [Chemical x] – Inhalation

Key tofigurea Species

Exposurefrequency/duration System

NOAEL(ppm)

LOAEL (effect)

Less serious (ppm) Serious (ppm)

2 6 INTERMEDIATE EXPOSURE

5 6 7 8 9 

3 6 Systemic 9 9 9 99 

4 6 18 Rat 13 wk

5d/wk6hr/d

Resp 3b 10 (hyperplasia) 

CHRONIC EXPOSURE

11

Cancer 938 Rat 18 mo

5d/wk7hr/d

20 (CEL, multiple

organs)

39 Rat 89–104 wk

5d/wk6hr/d

10 (CEL, lung tumo

nasal tumors)

40 Mouse 79–103 wk

5d/wk6hr/d

10 (CEL, lung tumo

hemangiosarcom

a The number corresponds to entries in Figure 2-1.

12 6 b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent 

an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability).

ETHION B-6

APPENDIX B

Chapter 2 (Section 2.5)

Relevance to Public Health

The Relevance to Public Health section provides a health effects summary based on evaluations of

existing toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to present

interpretive, weight-of-evidence discussions for human health end points by addressing the following

questions.

1. What effects are known to occur in humans?

2. What effects observed in animals are likely to be of concern to humans?

3. What exposure conditions are likely to be of concern to humans, especially around hazardous

waste sites?

The section covers end points in the same order they appear within the Discussion of Health Effects by

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data

are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In

vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also

considered in this section. If data are located in the scientific literature, a table of genotoxicity

information is included.

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if

derived) and the end points from which they were derived are indicated and discussed.

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to

public health are identified in the Data Needs section.

Interpretation of Minimal Risk Levels

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These

MRLs are not meant to support regulatory action; but to acquaint health professionals with exposure

levels at which adverse health effects are not expected to occur in humans. They should help physicians

and public health officials determine the safety of a community living near a chemical emission, given

the concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely

on toxicological studies in animals and on reports of human occupational exposure.

MRL users should be familiar with the toxicologic information on which the number is based. Chapter

2.5, "Relevance to Public Health," contains basic information known about the substance. Other

sections such as 2.8, "Interactions with Other Substances,” and 2.9, "Populations that are Unusually

Susceptible" provide important supplemental information.

MRL users should also understand the MRL derivation methodology. MRLs are derived using a

modified version of the risk assessment methodology the Environmental Protection Agency (EPA)

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 
ETHION B-7

APPENDIX B

To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement,

represents the most sensitive human health effect for a given exposure route and duration. ATSDR

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is

available for all potential systemic, neurological, and developmental effects. If this information and

reliable quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the most

sensitive species (when information from multiple species is available) with the highest NOAEL that

does not exceed any adverse effect levels. When a NOAEL is not available, a lowest-observed-adverseeffect level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 must be

employed. Additional uncertainty factors of 10 must be used both for human variability to protect

sensitive subpopulations (people who are most susceptible to the health effects caused by the substance)

and for interspecies variability (extrapolation from animals to humans). In deriving an MRL, these

individual uncertainty factors are multiplied together. The product is then divided into the inhalation

concentration or oral dosage selected from the study. Uncertainty factors used in developing a

substance-specific MRL are provided in the footnotes of the LSE Tables.

ETHION C-1

APPENDIX C

ACRONYMS, ABBREVIATIONS, AND SYMBOLS

ACGIH American Conference of Governmental Industrial Hygienists

ADI Acceptable Daily Intake

ADME Absorption, Distribution, Metabolism, and Excretion

AFID alkali flame ionization detector

AFOSH Air Force Office of Safety and Health

AML acute myeloid leukemia

AOAC Association of Official Analytical Chemists

atm atmosphere

ATSDR Agency for Toxic Substances and Disease Registry

AWQC Ambient Water Quality Criteria

BAT Best Available Technology

BCF bioconcentration factor

BEI Biological Exposure Index

BSC Board of Scientific Counselors

C Centigrade

CAA Clean Air Act

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency

CAS Chemical Abstract Services

CDC Centers for Disease Control and Prevention

CEL Cancer Effect Level

CELDS Computer-Environmental Legislative Data System

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act

CFR Code of Federal Regulations

Ci curie

CL ceiling limit value

CLP Contract Laboratory Program

cm centimeter

CML chronic myeloid leukemia

CNS central nervous system

CPSC Consumer Products Safety Commission

CWA Clean Water Act

d day

Derm dermal

DHEW Department of Health, Education, and Welfare

DHHS Department of Health and Human Services

DNA deoxyribonucleic acid

DOD Department of Defense

DOE Department of Energy

DOL Department of Labor

DOT Department of Transportation

DOT/UN/ Department of Transportation/United Nations/

NA/IMCO North America/International Maritime Dangerous Goods Code

DWEL Drinking Water Exposure Level

ECD electron capture detection
ETHION C-2

APPENDIX C

ECG/EKG electrocardiogram

EEG electroencephalogram

EEGL Emergency Exposure Guidance Level

EPA Environmental Protection Agency

F Fahrenheit

F1 first-filial generation

FAO Food and Agricultural Organization of the United Nations

FDA Food and Drug Administration

FEMA Federal Emergency Management Agency

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FPD flame photometric detection

fpm feet per minute

ft foot

FR Federal Register

g gram

GC gas chromatography

Gd gestational day

gen generation

GLC gas liquid chromatography

GPC gel permeation chromatography

HPLC high-performance liquid chromatography

hr hour

HRGC high resolution gas chromatography

HSDB Hazardous Substance Data Bank 

IDLH Immediately Dangerous to Life and Health

IARC International Agency for Research on Cancer

ILO International Labor Organization

in inch

IRIS Integrated Risk Information System 

Kd adsorption ratio

kg kilogram

kkg metric ton

Koc organic carbon partition coefficient

Kow octanol-water partition coefficient

L liter

LC liquid chromatography

LCLo lethal concentration, low

LC50 lethal concentration, 50% kill

LDLo lethal dose, low

LD50 lethal dose, 50% kill

LT50 lethal time, 50% kill

LOAEL lowest-observed-adverse-effect level

LSE Levels of Significant Exposure

m meter

MA trans,trans-muconic acid

MAL Maximum Allowable Level

mCi millicurie

MCL Maximum Contaminant Level

MCLG Maximum Contaminant Level Goal

mg milligram
ETHION C-3

APPENDIX C

min minute

mL milliliter

mm millimeter

mm Hg millimeters of mercury

mmol millimole

mo month

mppcf millions of particles per cubic foot

MRL Minimal Risk Level

MS mass spectrometry

NAAQS National Ambient Air Quality Standard

NAS National Academy of Science

NATICH National Air Toxics Information Clearinghouse

NATO North Atlantic Treaty Organization

NCE normochromatic erythrocytes

NCI National Cancer Institute

NIEHS National Institute of Environmental Health Sciences

NIOSH National Institute for Occupational Safety and Health

NIOSHTIC NIOSH's Computerized Information Retrieval System

NFPA National Fire Protection Association

ng nanogram

NLM National Library of Medicine

nm nanometer

NHANES National Health and Nutrition Examination Survey

nmol nanomole

NOAEL no-observed-adverse-effect level

NOES National Occupational Exposure Survey

NOHS National Occupational Hazard Survey

NPD nitrogen phosphorus detection

NPDES National Pollutant Discharge Elimination System

NPL National Priorities List

NR not reported

NRC National Research Council

NS not specified

NSPS New Source Performance Standards

NTIS National Technical Information Service

NTP National Toxicology Program

ODW Office of Drinking Water, EPA

OERR Office of Emergency and Remedial Response, EPA

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System

OPP Office of Pesticide Programs, EPA

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA

OPPT Office of Pollution Prevention and Toxics, EPA

OSHA Occupational Safety and Health Administration

OSW Office of Solid Waste, EPA

OTS Office of Toxic Substances

OW Office of Water

OWRS Office of Water Regulations and Standards, EPA

PAH Polycyclic Aromatic Hydrocarbon

PBPD Physiologically Based Pharmacodynamic 

PBPK Physiologically Based Pharmacokinetic 
ETHION C-4

APPENDIX C

PCE polychromatic erythrocytes

PEL permissible exposure limit

PID photo ionization detector

pg picogram

pmol picomole

PHS Public Health Service

PMR proportionate mortality ratio

ppb parts per billion

ppm parts per million

ppt parts per trillion

PSNS Pretreatment Standards for New Sources

REL recommended exposure level/limit

RfC Reference Concentration

RfD Reference Dose

RNA ribonucleic acid

RTECS Registry of Toxic Effects of Chemical Substances

RQ Reportable Quantity

SARA Superfund Amendments and Reauthorization Act

SCE sister chromatid exchange

sec second

SIC Standard Industrial Classification

SIM selected ion monitoring

SMCL Secondary Maximum Contaminant Level

SMR standard mortality ratio

SNARL Suggested No Adverse Response Level

SPEGL Short-Term Public Emergency Guidance Level

STEL short-term exposure limit

STORET Storage and Retrieval

TD50 toxic dose, 50% specific toxic effect

TLV threshold limit value

TOC Total Organic Compound

TPQ Threshold Planning Quantity

TRI Toxics Release Inventory

TSCA Toxic Substances Control Act

TRI Toxics Release Inventory

TWA time-weighted average

U.S. United States

UF uncertainty factor

VOC Volatile Organic Compound

yr year

WHO World Health Organization

wk week

> greater than > greater than or equal to

= equal to

< less than < less than or equal to

% percent α alpha
ETHION C-5

APPENDIX C

β beta γ gamma δ delta

μm micrometer

μg microgram q1* cancer slope factor

– negative

+ positive

(+) weakly positive result

(–) weakly negative result