TOXICOLOGICAL PROFILE FOR 

DIAZINON 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry

September 2008 
DIAZINON ii 

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. 
DIAZINON iii 

UPDATE STATEMENT 

A Toxicological Profile for Diazinon, Draft for Public Comment was released in September 2006. This 

edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. For information regarding the update 

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch 

1600 Clifton Road NE 

Mailstop F-32 

Atlanta, Georgia 30333 
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DIAZINON v

FOREWORD

This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic 

Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary.

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects 

information for the hazardous substance described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a hazardous substance’s toxicologic properties. Other pertinent 

literature is also presented, but is described in less detail than the key studies. The profile is not intended 

to be an exhaustive document; however, more comprehensive sources of specialty information are 

referenced.

The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile 

begins with a public health statement that describes, in nontechnical language, a substance’s relevant 

toxicological properties. Following the public health statement is information concerning levels of 

significant human exposure and, where known, significant health effects. The adequacy of information to 

determine a substance’s health effects is described in a health effects summary. Data needs that are of 

significance to protection of public health are identified by ATSDR and EPA.

Each profile includes the following:

(A) The examination, summary, and interpretation of available toxicologic information and 

epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human 

exposure for the substance and the associated acute, subacute, and chronic health effects;

(B) A determination of whether adequate information on the health effects of each substance is 

available or in the process of development to determine levels of exposure that present a 

significant risk to human health of acute, subacute, and chronic health effects; and

(C) Where appropriate, identification of toxicologic testing needed to identify the types or levels 

of exposure that may present significant risk of adverse health effects in humans.

The principal audiences for the toxicological profiles are health professionals at the Federal, State, and 

local levels; interested private sector organizations and groups; and members of the public. 

This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been 

peer-reviewed. Staff of the Centers for Disease Control and Prevention and other Federal scientists have 

also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel 
DIAZINON vi

and was made available for public review. Final responsibility for the contents and views expressed in 

this toxicological profile resides with ATSDR.

Howard Frumkin M.D., Dr.P.H.

Director

National Center for Environmental Health/

Agency for Toxic Substances and

Disease Registry

Julie Louise Gerberding, M.D., M.P.H.

Administrator

Agency for Toxic Substances and 

Disease Registry

*Legislative Background

The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization 

Act (SARA) of 1986 (Public Law 99 499) which amended the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to 

prepare toxicological profiles for hazardous substances most commonly found at facilities on the 

CERCLA National Priorities List and that pose the most significant potential threat to human health, as 

determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous 

substances was announced in the Federal Register on December 7, 2005 (70 FR 72840). For prior 

versions of the list of substances, see Federal Register notices dated April 17, 1987 (52 FR 12866); 

October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17,1990 (55 FR 42067); 

October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); February 28, 1994 (59 FR 9486); 

April 29, 1996 (61 FR 18744); November 17, 1997 (62 FR 61332); October 21, 1999(64 FR 56792); 

October 25, 2001 (66 FR 54014) and November 7, 2003 (68 FR 63098). Section 104(i)(3) of CERCLA, 

as amended, directs the Administrator of ATSDR to prepare a toxicological profile for each substance on 

the list.
DIAZINON vii 

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: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, 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 (Chemical X) Affect Children? 

 Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? 

 Section 3.7 Children’s Susceptibility 

 Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-800-CDC-INFO (800-232-4636) or 1-888-232-6348 (TTY) Fax: (770) 488-4178 

E-mail: cdcinfo@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. 
DIAZINON viii 

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@AOEC.ORG • Web Page: http://www.aoec.org/. 

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, 25 Northwest Point Boulevard, Suite 700, Elk 

Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266. 
DIAZINON ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

G. Daniel Todd, Ph.D. 

Carolyn Harper, Ph.D. 

Paula Burgess, M.D. 

ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, GA 

David Wohlers, Ph.D. 

Michael H. Lumpkin, Ph.D. 

Christina Coley, B.S. 

Courtney M. Hard, 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 Applied Toxicology Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

4. Green Border Review. Green Border review assures the consistency with ATSDR policy. 
DIAZINON x 

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DIAZINON xi 

PEER REVIEW 

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

1. Douglas Crawford-Brown, Ph.D., Professor, Department of Environmental Sciences and 

Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 

27599, 

2. Bhupendra Kaphalia, Ph.D., Associate Professor, Department of Pathology, University of Texas 

Medical Branch, Galveston, Texas 77555, and 

3. Jim Riviere, D.V.M, Ph.D., Director, Center for Chemical Toxicology Research and 

Pharmacokinetics, Burroughs Wellcome Fund Distinguished Professor of Pharmacology, North 

Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina 27606. 

These experts collectively have knowledge of diazinon'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. 

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. 
DIAZINON xii 

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DIAZINON xiii 

CONTENTS 

DISCLAIMER .............................................................................................................................................. ii 

UPDATE STATEMENT ............................................................................................................................. iii 

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

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

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

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

CONTENTS ............................................................................................................................................... xiii 

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

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

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

1.1 WHAT IS DIAZINON? ................................................................................................................. 1 

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

1.3 HOW MIGHT I BE EXPOSED TO DIAZINON? ........................................................................ 2 

1.4 HOW CAN DIAZINON ENTER AND LEAVE MY BODY?...................................................... 3 

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

1.6 HOW CAN DIAZINON AFFECT CHILDREN? .......................................................................... 5 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO DIAZINON? ...................... 5 

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

TO DIAZINON? ............................................................................................................................. 6 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? .................................................................................................... 6 

1.10 WHERE CAN I GET MORE INFORMATION? .......................................................................... 7 

2. RELEVANCE TO PUBLIC HEALTH ................................................................................................... 9 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO DIAZINON IN THE 

UNITED STATES .......................................................................................................................... 9 

2.2 SUMMARY OF HEALTH EFFECTS ......................................................................................... 10 

2.3 MINIMAL RISK LEVELS (MRLs) ............................................................................................ 12 

3. HEALTH EFFECTS .............................................................................................................................. 29 

3.1 INTRODUCTION ........................................................................................................................ 29 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................... 30 

3.2.1 Inhalation Exposure .............................................................................................................. 31 

3.2.1.1 Death .............................................................................................................................. 31 

3.2.1.2 Systemic Effects ............................................................................................................. 32 

3.2.1.3 Immunological and Lymphoreticular Effects ................................................................ 37 

3.2.1.4 Neurological Effects ...................................................................................................... 38 

3.2.1.5 Reproductive Effects ...................................................................................................... 40 

3.2.1.6 Developmental Effects ................................................................................................... 40 

3.2.1.7 Cancer ............................................................................................................................ 40 

3.2.2 Oral Exposure ........................................................................................................................ 41 

3.2.2.1 Death .............................................................................................................................. 41 

3.2.2.2 Systemic Effects ............................................................................................................. 71 

3.2.2.3 Immunological and Lymphoreticular Effects ................................................................ 80 

3.2.2.4 Neurological Effects ...................................................................................................... 81 

3.2.2.5 Reproductive Effects ...................................................................................................... 85 

3.2.2.6 Developmental Effects ................................................................................................... 86 

3.2.2.7 Cancer ............................................................................................................................ 88 
DIAZINON xiv 

3.2.3 Dermal Exposure...................................................................................................................89 

3.2.3.1 Death..............................................................................................................................89 

3.2.3.2 Systemic Effects.............................................................................................................92 

3.2.3.3 Immunological and Lymphoreticular Effects ................................................................93 

3.2.3.4 Neurological Effects ......................................................................................................94 

3.2.3.5 Reproductive Effects......................................................................................................94 

3.2.3.6 Developmental Effects...................................................................................................94 

3.2.3.7 Cancer ............................................................................................................................94 

3.2.4 Other Routes of Exposure .....................................................................................................95 

3.3 GENOTOXICITY........................................................................................................................96 

3.4 TOXICOKINETICS.....................................................................................................................98 

3.4.1 Absorption.............................................................................................................................98 

3.4.1.1 Inhalation Exposure .......................................................................................................98 

3.4.1.2 Oral Exposure ................................................................................................................98 

3.4.1.3 Dermal Exposure ...........................................................................................................99 

3.4.2 Distribution ...........................................................................................................................99 

3.4.2.1 Inhalation Exposure .......................................................................................................99 

3.4.2.2 Oral Exposure ................................................................................................................99 

3.4.2.3 Dermal Exposure .........................................................................................................100 

3.4.3 Metabolism..........................................................................................................................100 

3.4.4 Elimination and Excretion...................................................................................................102 

3.4.4.1 Inhalation Exposure .....................................................................................................102 

3.4.4.2 Oral Exposure ..............................................................................................................102 

3.4.4.3 Dermal Exposure .........................................................................................................102 

3.4.4.4 Other Routes of Exposure............................................................................................103 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ...........103 

3.5 MECHANISMS OF ACTION ................................................................................................... 107 

3.5.1 Pharmacokinetic Mechanisms............................................................................................. 107 

3.5.2 Mechanisms of Toxicity......................................................................................................108 

3.5.3 Animal-to-Human Extrapolations.......................................................................................109 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS...........................110 

3.7 CHILDREN’S SUSCEPTIBILITY............................................................................................111 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT.....................................................................114 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Diazinon........................................115 

3.8.2 Biomarkers Used to Characterize Effects Caused by Diazinon ..........................................116 

3.9 INTERACTIONS WITH OTHER CHEMICALS ..................................................................... 117 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE................................................ 118 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................... 119 

3.11.1 Reducing Peak Absorption Following Exposure.............................................................120 

3.11.2 Reducing Body Burden ...................................................................................................120 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..........................................120 

3.12 ADEQUACY OF THE DATABASE ........................................................................................121 

3.12.1 Existing Information on Health Effects of Diazinon.......................................................121 

3.12.2 Identification of Data Needs............................................................................................123 

3.12.3 Ongoing Studies ..............................................................................................................132 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................133 

4.1 CHEMICAL IDENTITY............................................................................................................133 

4.2 PHYSICAL AND CHEMICAL PROPERTIES.........................................................................133 
DIAZINON xv 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................137 

5.1 PRODUCTION ..........................................................................................................................137 

5.2 IMPORT/EXPORT ....................................................................................................................139 

5.3 USE ............................................................................................................................................139 

5.4 DISPOSAL.................................................................................................................................140 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................143 

6.1 OVERVIEW...............................................................................................................................143 

6.2 RELEASES TO THE ENVIRONMENT...................................................................................146 

6.2.1 Air .......................................................................................................................................147 

6.2.2 Water...................................................................................................................................147 

6.2.3 Soil ......................................................................................................................................150 

6.3 ENVIRONMENTAL FATE ......................................................................................................150 

6.3.1 Transport and Partitioning...................................................................................................150 

6.3.2 Transformation and Degradation ........................................................................................154 

6.3.2.1 Air................................................................................................................................154 

6.3.2.2 Water............................................................................................................................154 

6.3.2.3 Sediment and Soil ........................................................................................................156 

6.3.2.4 Other Media .................................................................................................................159 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT..................................159 

6.4.1 Air .......................................................................................................................................160 

6.4.2 Water...................................................................................................................................163 

6.4.3 Sediment and Soil ...............................................................................................................167 

6.4.4 Other Environmental Media................................................................................................168 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE........................................169 

6.6 EXPOSURES OF CHILDREN..................................................................................................176 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ..............................................179 

6.8 ADEQUACY OF THE DATABASE ........................................................................................179 

6.8.1 Identification of Data Needs ...............................................................................................180 

6.8.2 Ongoing Studies ..................................................................................................................183 

7. ANALYTICAL METHODS ...............................................................................................................185 

7.1 BIOLOGICAL MATERIALS....................................................................................................185 

7.2 ENVIRONMENTAL SAMPLES ..............................................................................................188 

7.3 ADEQUACY OF THE DATABASE ........................................................................................198 

7.3.1 Identification of Data Needs ...............................................................................................198 

7.3.2 Ongoing Studies ..................................................................................................................200 

8. REGULATIONS AND ADVISORIES ...............................................................................................201 

9. REFERENCES ....................................................................................................................................207 

10. GLOSSARY ......................................................................................................................................237 
DIAZINON xvi 

APPENDICES 

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

B. USER’S GUIDE.................................................................................................................................. B-1 

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

D. INDEX ................................................................................................................................................D-1 
DIAZINON xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Diazinon - Inhalation ................................................................... 35 

3-2. Levels of Significant Exposure to Diazinon - Oral............................................................................. 66 

3-3. Putative Pathways of Diazinon Biotransformation...........................................................................101 

3-4. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance....................................................................................................105 

3-5. Existing Information on Health Effects of Diazinon........................................................................122 

6-1. Frequency of NPL Sites with Diazinon Contamination ...................................................................144 
DIAZINON xviii 

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DIAZINON xix 

LIST OF TABLES 

2-1. Effect of Aerosol Diazinon on Plasma ChE and RBC and Brain AChE Activity in Male and 

Female Rats Exposed for 6 Hours/Day, 5 Days/Week for 3 Weeks .................................................. 15 

2-2. Parameters Used to Calculate the Regional Deposited Dose Ratio (RDDRER) for 

Diazinon-induced Extrarespiratory Effects Using EPA’s Software (Version 2.3) ............................17 

2-3. NOAELs and LOAELs for RBC and Brain AChE Inhibition Following Intermediate-duration 

Dietary Exposure to Diazinon............................................................................................................20 

2-4. RBC AChE Data From Male and Female Rats Exposed to Diazinon in the Diet for 90 Days..........23 

2-5. RBC AChE Data From Female Rats Exposed to Diazinon in the Diet for 42 Days..........................25 

3-1. Levels of Significant Exposure to Diazinon – Inhalation................................................................... 33 

3-2. Levels of Significant Exposure to Diazinon – Oral............................................................................ 43 

3-3. Levels of Significant Exposure to Diazinon – Dermal ....................................................................... 90 

3-4. Genotoxicity of Diazinon In Vitro......................................................................................................97 

4-1. Chemical Identity of Diazinon..........................................................................................................134 

4-2. Physical and Chemical Properties of Diazinon.................................................................................135 

5-1. Facilities that Produce, Process, or Use Diazinon ............................................................................138 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Diazinon.....................148 

6-2. Bioconcentration Data for Diazinon.................................................................................................152 

6-3. Diazinon Residues in Various Foods from 1994 to 2000.................................................................170 

7-1. Analytical Methods for Determining Diazinon and Transformation Products in Biological 

Samples ............................................................................................................................................186 

7-2. Analytical Methods for Determining Diazinon and Transformation Products in Environmental 

Samples ............................................................................................................................................189 

8-1. Regulations and Guidelines Applicable to Diazinon........................................................................202 
DIAZINON xx 

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DIAZINON 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about diazinon and the effects of exposure to it. 

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

nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term 

federal clean-up activities. Diazinon has been found in at least 25 of the 1,699 current or former NPL 

sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility 

exists that the number of sites at which diazinon is found may increase in the future as more sites are 

evaluated. This information is important because these sites may be sources of exposure and exposure to 

this substance may be harmful. 

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

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

can be 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 diazinon, many factors will determine whether you will 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 any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and 

state of health. 

1.1 WHAT IS DIAZINON? 

Description Diazinon does not occur naturally in the environment. 

The pure chemical is an oil that is colorless and practically odorless. 

Commercial diazinon is a pale to dark brown liquid. 

Uses 

• Pesticide uses Diazinon is the common name of an organophosphorus insecticide used to 

control pest insects in soil, on ornamental plants, and on fruit and vegetable 

field crops. 

Diazinon is sold under common trade names including Alfatox, Basudin, 

AG 500, Dazzel, Gardentox, and Knoxout. 
DIAZINON 2 

1. PUBLIC HEALTH STATEMENT 

For more information on the physical and chemical properties of diazinon, and its production, disposal 

and use, see Chapters 4 and 5. 

1.2 WHAT HAPPENS TO DIAZINON WHEN IT ENTERS THE ENVIRONMENT? 

Sources Diazinon may enter the environment from agricultural and household 

application of the chemical to control insects. 

After diazinon has been applied, it may be present in the soil, surface waters 

(such as rivers and ponds), and on the surface of plants. 

How diazinon 

breaks down 

• Air 

• Water and 

soil 

• Plants and 

animals 

Diazinon is rapidly broken down to a number of different compounds. 

Diazinon is quickly broken down in a few hours to 2 weeks. 

Diazinon is rapidly broken down by most animals that eat it and is not likely to 

build up to high or dangerous levels in animals or plants that you might eat. 

For more information on diazinon in the environment, see Chapter 6. 

1.3 HOW MIGHT I BE EXPOSED TO DIAZINON? 

Food-primary 

source of 

exposure 

Small amounts of diazinon have been detected in foods sold to consumers, 

but studies by the U.S. Food and Drug Administration (FDA) have found that 

the levels in food are far below the level that might cause any harmful health 

effects. 

Air You may be exposed to diazinon in air in agricultural areas where diazinon is 

extensively used or in urban areas where it is applied to lawns and gardens. 

Drinking water You may be exposed to diazinon by drinking contaminated water. 

Recently sprayed 

plants 

You may be exposed to diazinon by touching diazinon-treated plant 

materials such as grass clippings. 

Workplace People who work in the manufacture and professional application of diazinon 

have the most significant exposure to this insecticide. 
DIAZINON 3 

1. PUBLIC HEALTH STATEMENT 

Consumer 

products 

Although diazinon was formerly used as the active ingredient in home and 

garden pest control products, sale of these home and garden products in the 

United States was stopped in 2004. However, previously purchased 

diazinon-containing home and garden products may still be in use and 

present the potential for exposure. 

For more information on human exposure to diazinon, see Chapter 6. 

1.4 HOW CAN DIAZINON ENTER AND LEAVE MY BODY? 

Enter your body 

 • Inhalation 

 • Ingestion 

 • Dermal contact 

If you breathe air containing diazinon, you may absorb it into your body 

through your lungs. 

Diazinon in food or water may also rapidly enter your body through the 

digestive tract. 

Diazinon may enter your body across the skin. 

Leave your body Once in the body, diazinon is rapidly broken down and eliminated from the 

body mainly in the urine. Diazinon has not been shown to accumulate in 

any tissues and most of the chemical is eliminated from the body within 

12 days. 

For more information on how diazinon enters and leaves the body, see Chapter 3. 
DIAZINON 4 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN DIAZINON AFFECT MY HEALTH? 

This section looks at studies concerning potential health effects in animal and human studies. 

Human exposure 

• High exposure 

• Very high 

exposure 

Short exposures to high levels of diazinon can affect the nervous system. 

Symptoms include: 

 • headache, dizziness, weakness 

 • feelings of anxiety 

 • constriction of the pupils of the eye 

 • not being able to see clearly 

Exposures to very high levels can cause more severe symptoms including: 

 • nausea, vomiting, abdominal cramps, and diarrhea 

 • slow pulse 

 • pinpoint pupils 

 • difficulty breathing 

 • passing out (coma) 

Signs or symptoms of nervous system damage may occur within 30–

60 minutes. If you experience these symptoms, you should seek medical 

attention immediately. Emergency rooms have drugs that stop the harmful 

effects of diazinon. 

Long-term 

exposure to low 

levels 

There is no evidence that long-term exposure to low levels of diazinon 

causes any harmful health effects in people. 

Cancer Diazinon has not been shown to cause cancer in people or animals. The 

International Agency for Research on Cancer (IARC) has not classified 

diazinon for carcinogenicity. EPA classified diazinon as a Group E 

chemical (evidence of noncarcinogenicity for humans). 

Further information on the health effects of diazinon in humans and animals can be found in 

Chapters 2 and 3. 
DIAZINON 5 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN DIAZINON AFFECT CHILDREN? 

This section discusses potential health effects in humans from exposures during the period from 

conception to maturity at 18 years of age. 

Effects in 

children 

It is likely that children would have the same health effects as adults. We do 

not know whether children would be more sensitive than adults to the effects of 

diazinon. 

One study found neurological and bone effects in young children living in a 

house were diazinon was misused to control a flea infestation. 

Birth defects There is no evidence that environmental exposure to diazinon causes birth 

defects or other developmental effects in people. 

In animals, levels of exposure to diazinon high enough to affect the health of 

pregnant mothers caused developmental effects in their newborn babies. 

Breast milk Animal studies have shown that diazinon and/or its breakdown products can be 

transferred from a pregnant mother to a developing fetus, but no human data 

were located regarding the transfer of diazinon from the mother to the fetus or 

nursing infant. 

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

Cautions for 

those who live 

in agricultural 

areas 

People who live near agricultural areas where diazinon is still used should stay 

away from the area that has been treated. Diazinon can be dispersed some 

distance from a spray zone by air currents and runoff water. 

If you are aware that diazinon is being sprayed in the vicinity, you may want to 

go indoors or leave the area for a short time. 

Agricultural workers who have come into contact with relatively large amounts 

of diazinon at work may need to remove and wash contaminated clothing 

before coming into contact with other family members. 

Wash fruits 

and vegetables 

To reduce the risk of exposure to diazinon residue on fresh fruits or vegetables, 

wash the foods prior to eating them. 

Properly use 

insect sprays 

Occasionally, diazinon may be improperly sprayed inside the home to kill 

insects. Make sure that any person who treats your home with pesticides is 

properly certified. Ask what chemical or chemicals are being used. Diazinon is 

a “restricted use” chemical and is no longer registered for residential indoor or 

garden use. 
DIAZINON 6 

1. PUBLIC HEALTH STATEMENT 

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

TO DIAZINON? 

Measuring effects Most of the signs and symptoms resulting from diazinon poisoning are due 

to the inhibition of an enzyme called acetylcholinesterase in the nervous 

system. This enzyme is also found in your red blood cells and a similar 

enzyme (plasma cholinesterase) is found in blood plasma. The most 

common test for exposure to many organophosphorus insecticides, 

including diazinon, is to determine the level of cholinesterase activity in the 

red blood cells or plasma. 

It takes time for this enzyme to completely recover to normal levels following 

exposure. Therefore, a valid test may be conducted a number of days 

following the suspected exposure. This test indicates only exposure to an 

insecticide of this type. It does not specifically show exposure to diazinon. 

Detecting 

exposure 

Specific tests are available to determine the presence of diazinon or its 

breakdown products in blood, body tissue, and urine. These tests are only 

useful if done within a few hours or days of exposure. This is because 

diazinon is rapidly broken down and excreted from the body. 

Information about tests for detecting diazinon in the body is given in Chapters 3 and 7. 

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. The EPA, the Occupational Safety and Health Administration (OSHA), and the 

Food and Drug Administration (FDA) are some federal agencies that develop regulations for toxic 

substances. Recommendations provide valuable guidelines to protect public health, but cannot be 

enforced by law. The Agency for Toxic Substances and Disease Registry (ATSDR) and the National 

Institute for Occupational Safety and Health (NIOSH) are two federal organizations that develop 

recommendations for toxic substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels, that is, levels of a toxic 

substance in air, water, soil, or food that do not exceed a critical value that is usually based on levels that 

affect animals; they are then adjusted to levels that will help protect humans. Sometimes these not-toexceed levels differ among federal organizations because they used different exposure times (an 8-hour 

workday or a 24-hour day), different animal studies, or other factors. 
DIAZINON 7 

1. PUBLIC HEALTH STATEMENT 

Recommendations and regulations are also updated periodically 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 diazinon include the following: 

Drinking water The EPA has determined that exposure to diazinon in drinking water at a 

concentration of 20 micrograms per liter (μg/L) for up to 10 days is not 

expected to cause any harmful effects in a child. 

The EPA has determined that lifetime exposure to 1 μg/L diazinon in 

drinking water is not expected to cause any harmful effects. 

Food The EPA has also set tolerances for residues of diazinon in various raw food 

products of 0.1–40 parts of diazinon per million parts of food (ppm). 

For more information on regulations and advisories, see Chapter 8. 

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 contact ATSDR at the address and phone number below. 

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

specialize in recognizing, evaluating, and treating illnesses that result from exposure to hazardous 

substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You may 

request a copy of the ATSDR ToxProfilesTM CD-ROM by calling the toll-free information and technical 

assistance number at 1-800-CDCINFO (1-800-232-4636), by e-mail at cdcinfo@cdc.gov, or by writing 

to: 

 Agency for Toxic Substances and Disease Registry 

 Division of Toxicology and Environmental Medicine 

 1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 
DIAZINON 8 

1. PUBLIC HEALTH STATEMENT 

Organizations for-profit may request copies of final Toxicological Profiles from the following: 

 National Technical Information Service (NTIS) 

 5285 Port Royal Road 

 Springfield, VA 22161 

 Phone: 1-800-553-6847 or 1-703-605-6000 

 Web site: http://www.ntis.gov/ 
DIAZINON 9 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO DIAZINON IN THE UNITED 

STATES 

Diazinon is an organophosphorus insecticide primarily used for agricultural purposes and is released to 

the environment through spraying on a wide variety of agricultural crops and at agricultural sites. Once 

diazinon is introduced into the environment, it may be activated by atmospheric photooxidation or 

degraded by hydrolysis or biodegradation mediated by microorganisms found in most sediment, soils, and 

water. Diazinon and diazoxon can be transported from the site of application by precipitation, fog, and 

wind to other areas. Since diazinon is moderately mobile in soils under certain conditions, it has the 

potential to migrate through the soil and into groundwater. Volatilization of diazinon from ground 

surfaces following aerial applications has been observed. Data from limited studies suggest that 

bioconcentration of diazinon does not occur to a significant extent in most aquatic organisms tested, and 

that it is rapidly metabolized when it is accumulated. 

Significant exposure of the general population to diazinon is not likely at present, due to the ban on 

residential uses. Diazinon was formerly used in household and garden products for pest control. 

However, manufacturing of indoor use products was discontinued on June 30, 2001 and production of 

non-agricultural outdoor use products containing diazinon was discontinued on June 30, 2003. As of 

December 31, 2004, sales of diazinon-containing products for residential use were discontinued, although 

numerous restricted-use commercial products that contain diazinon are still available. Because diazinoncontaining products are no longer sold for residential use, potential for significant exposure of the general 

population is expected to decrease as supplies that were obtained and stored before discontinuation are 

expended. General population exposure to diazinon may occur through ingestion of contaminated food or 

drinking water and inhalation. Ingestion of foods contaminated with small residues of diazinon is the 

most likely route of exposure for the general population not living in areas where diazinon is extensively 

used. The general population may also be exposed to diazinon through inhalation of contaminated 

ambient (outdoor) air. 

Populations living within or very near areas of heavy agricultural diazinon use would have an increased 

risk of exposure to relatively larger amounts of diazinon through dermal contact with contaminated 

plants, soils, surface waters, or artificial surfaces such as playground equipment and pavements; by 

inhalation of the mist formed from the applied insecticide; or by ingestion of water or food-borne 

residues. Those likely to receive the highest levels of exposure are those who are involved in the 
DIAZINON 10 

2. RELEVANCE TO PUBLIC HEALTH 

production, formulation, handling, and application of diazinon, farm workers who enter treated fields 

prior to the passage of the appropriate restricted entry intervals, and workers involved in the disposal of 

diazinon or diazinon-containing wastes. Dermal contact appears to be the major route of exposure for 

workers. Inhalation of diazinon in occupational settings depends on its volatility, the type of formulation 

used, and the application technique employed. 

Children are expected to be exposed to diazinon by the same routes that affect adults. Small children are 

more likely to come into contact with diazinon residues that may be present in soil and dust, due to 

increased hand-to-mouth activity and playing habits. Diazinon has been detected in foods found in infant 

and toddler diets at concentrations of up to 0.46 mg/kg food. No data were located regarding diazinon in 

breast milk; therefore, an adequate determination of the importance of this route of child exposure has not 

been made. 

See Chapter 6 for more detailed information regarding concentrations of diazinon in environmental 

media. 

2.2 SUMMARY OF HEALTH EFFECTS 

Diazinon is considered to be of moderate toxicity compared to other organophosphates. The principal 

toxic effect of diazinon in humans and laboratory animals is inhibition of acetylcholinesterase (AChE), 

which results in the accumulation of acetylcholine at acetylcholine receptors leading to cholinergic 

responses in the peripheral (muscarinic and nicotinic) and central nervous system and neuromuscular 

junctions. 

High-level acute exposure to diazinon causes severe AChE inhibition that often leads to cholinergic signs 

and symptoms, manifest as reversible neuromuscular dysfunction when treated or when exposure is 

terminated. These manifestations include muscarinic effects (bronchoconstriction, increased 

bronchosecretion, nausea and vomiting, diarrhea, bradycardia, hypotension, miosis, urinary incontinence), 

nicotinic effects (tachycardia, hypertension, muscular twitching and weakness, fasciculation, cramping), 

and central nervous system effects (anxiety, apathy, depression, giddiness, drowsiness, insomnia, 

nightmares, headaches, confusion, ataxia, depressed reflex, seizure, respiratory depression, coma). In 

sufficiently high exposures (accidental or intentional), respiratory and cardiac failure and death may result 

without timely treatment intervention. The cholinergic manifestations of high acute exposure to diazinon 

have also been reported in animals and include anorexia, ataxia, epistaxis, tremors, listlessness, gasping, 
DIAZINON 11 

2. RELEVANCE TO PUBLIC HEALTH 

convulsions, tachypnea, dyspnea, prostration, fasciculations, twitches, exophthalmos, diarrhea, salivation, 

diuresis, lacrimation, prostration, Straub tail reflex, and hypothermia. Clinical signs of diazinon 

neurotoxicity following repeated oral exposure in animals have been reported at doses ranging from 30 to 

300 mg/kg/day. Limited information is available regarding clinical signs of neurotoxicity in animals 

exposed to diazinon by inhalation. One study reported decreased activity and salivation responses in rats 

exposed to an aerosol of diazinon for 4 hours at an exposure level of 2,330 mg/m3

. 

As previously noted, the systemic toxicity of diazinon is mainly attributable to its action on the nervous 

system. Although AChE is intimately associated with neurotransmission within the central and peripheral 

nervous system, AChE is also found in erythrocytes (red blood cells [RBCs]). The blood plasma of 

humans and animals contains cholinesterases as well. Plasma cholinesterase (ChE) in humans is 

comprised almost entirely of butyrylcholinesterase (also known as pseudocholinesterase), whereas AChE 

constitutes a portion of the plasma ChE of animals, the relative amount of which is species dependent. In 

both humans and animals, measures of plasma ChE and RBC AChE activities have been used as 

indicators of exposure to cholinesterase inhibitors such as diazinon. Plasma ChE inhibition may often be 

observed at exposure levels lower than those inducing measurable RBC AChE inhibition. However, 

decreased activity of AChE is more indicative of a potential neurotoxic effect because RBC AChE is 

identical to neural AChE, whereas butyrylcholinesterase has not been demonstrated to play a role in the 

development or function of the central or peripheral nervous system. 

Numerous animal studies and limited controlled human studies identify levels of exposure to diazinon 

resulting in plasma ChE, RBC AChE, and/or brain AChE inhibition. RBC and/or brain AChE inhibition 

of 20–59% is considered to represent a less serious adverse neurological effect in the absence of more 

serious indicators of neurotoxicity. In this Toxicological Profile, “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. The animal studies identified exposure levels at which diazinon caused RBC AChE 

inhibition in the absence of more serious indicators of neurotoxicity, which indicates that RBC AChE 

inhibition at such exposure levels may represent the most sensitive effect for diazinon toxicity. For 

example, inhibition of RBC and/or brain AChE at magnitudes ranging from 20 to 60% (in the absence of 

clinical signs) was observed following repeated oral dosing in the range of 0.3–75 mg/kg/day. In a 

repeated-exposure inhalation study, exposure to an airborne concentration of 1.57 mg/m3

, 6 hours/day, 

5 days/week for 3 weeks resulted in 36–39% RBC AChE inhibition in rats. 
DIAZINON 12 

2. RELEVANCE TO PUBLIC HEALTH 

Plasma ChE inhibition can typically be observed at doses lower than those required to produce significant 

RBC and/or brain AChE inhibition; RBC AChE appears to be more sensitive than brain AChE to 

diazinon toxicity. Following single oral dosing, peak cholinesterase inhibition is typically observed at 6– 

12 hours. Results of longer-term oral studies indicate that diazinon-induced plasma ChE and RBC AChE 

inhibition increases in severity with exposure duration to a peak at approximately 35 days; after which the 

severity of the inhibition remains relatively constant. Rat and dog studies indicate that females may be 

more sensitive than males to diazinon-induced cholinesterase inhibition, particularly with respect to brain 

AChE inhibition. Diazinon-induced neurohistopathological effects have not been demonstrated. 

Diazinon does not appear to be a reproductive or developmental toxicant at exposure levels that do not 

result in maternal toxicity. There is limited evidence of morphological changes in spleen, thymus, and 

lymph nodes of animals following oral exposure to relatively high doses of diazinon, but no studies have 

demonstrated compromised immunological function. Predominantly negative results have been reported 

in testing of diazinon for genotoxicity. Two epidemiological studies reported weak associations between 

exposure to diazinon and lung cancer. Results of a few case-control studies have suggested possible links 

between diazinon exposure and non-Hodgkin’s lymphoma, multiple myeloma, and childhood brain 

cancer. However, all of these studies involved exposure to other pesticides as well. A 2-year oral cancer 

bioassay in rats and mice did not find evidence for diazinon-induced carcinogenicity. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for diazinon. 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 
DIAZINON 13 

2. RELEVANCE TO PUBLIC HEALTH 

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. 

Diazinon is one member of a class of organophosphates that share a common mechanism of action, 

namely inhibition of AChE. Although the Toxicological Profile for Diazinon presents MRLs derived for 

diazinon in particular, human exposure scenarios may include simultaneous exposure to multiple 

organophosphate AChE inhibitors. MRLs derived specifically for diazinon may not be adequately 

protective for exposure scenarios that include exposure to multiple similarly-acting organophosphate 

AChE inhibitors. 

Inhalation MRLs 

An acute-duration inhalation MRL for diazinon was not derived due to the lack of suitable acute-duration 

human or animal data. Available reports of neurotoxicity indicators in humans exposed to diazinon by 

the inhalation route of exposure do not include quantitative data regarding exposure levels (Coye et al. 

1987; Dahlgren et al. 2004; Kamha et al. 2005; Maizlish et al. 1987; Rayner et al. 1972; Richter et al. 

1992; Soliman et al. 1982; Stalberg et al. 1978). Some of these exposures included multiple exposure 

routes and exposures to other pesticides as well. Available acute-duration inhalation data in animals are 

restricted to a single report of nasal discharge, polyuria, decreased activity, and salivation in a group of 

five rats exposed to a diazinon aerosol at a concentration of 2,330 mg/m3

. This study was not suitable for 

MRL derivation because it included a single exposure level at which serious effects were observed and no 

supporting data were available. 

• An MRL of 0.01 mg/m3

 has been derived for intermediate-duration inhalation exposure (15– 

364 days) to diazinon. 

This MRL is based on a no-observed-adverse-effect level (NOAEL) of 1.57 mg diazinon/m3

 for RBC 

AChE inhibition (a critical target of diazinon toxicity) observed in a 21-day study in hybrid rats (Hartman 

1990). 

No human reports were located regarding intermediate-duration inhalation exposure to diazinon. A single 

animal study (Hartman 1990) was located in which toxic effects of intermittent exposure to aerosols of 

diazinon for 21 days were assessed. This study served as the principal study for deriving an intermediateduration inhalation MRL for diazinon. Support for the selection of diazinon-induced RBC AChE 
DIAZINON 14 

2. RELEVANCE TO PUBLIC HEALTH 

inhibition as the critical effect is provided by the results of numerous animal studies that employed the 

oral exposure route. In the principal inhalation study (Hartman 1990), groups of rats (10/sex) were 

exposed to control air or air containing four different concentrations of aerosolized diazinon (0.05, 0.46, 

1.57, or 11.6 mg/m3

) for 6 hours/day, 5 days/week for 3 weeks. No clinical signs of organophosphate 

neurotoxicity or effects on survival or body weight were observed. Histopathology of the nasal tract and 

lungs was normal in all groups; no histopathological effects were seen in spleen, heart, liver, kidney, and 

adrenal gland (examined only in the 11.6 mg/m3

 groups). Plasma ChE activity and RBC and brain AChE 

activity in the male and female rats are shown in Table 2-1. Significant reductions in plasma ChE 

(marker for exposure) were seen in males at exposure levels ≥1.57 mg/m3

 and in females at exposure 

levels ≥0.46 mg/m3

. Organophosphate-induced plasma ChE inhibition is typically observed at exposure 

levels lower than those inducing measurable RBC or brain AChE inhibition. Plasma ChE inhibition is 

used as an indicator of exposure, but does not serve as a reliable indicator of a neurotoxic effect. 

However, inhibition of RBC AChE and brain AChE represents a relevant neurological effect. In the 

principal study (Hartman 1990), significant reductions in RBC AChE activity (surrogate marker for 

neural AChE activity) were seen in male rats at 11.6 mg/m3

 and in female rats at 1.57 and 11.6 mg/m3 

(Table 2-1). Treatment-related 20–59% RBC or brain AChE inhibition is considered to represent a less 

serious adverse effect in the absence of more clear indicators of neurotoxicity (Chou and WilliamsJohnson 1998). The 10% RBC AChE inhibition observed in the 1.57 mg/m3

 group of female rats is 

below the level of inhibition considered to represent an adverse effect. Therefore, the 1.57 mg/m3 

exposure level is a NOAEL and the highest exposure level (11.6 mg/m3

) is the lowest-observed-adverseeffect level (LOAEL) for 36 and 39% RBC AChE inhibition in the male and female rats, respectively. 

There was no significant difference between brain AChE activity in any of the exposure groups of male 

rats and that of vehicle controls. All diazinon-exposed groups of female rats exhibited significantly 

decreased brain AChE activity, relative to vehicle controls. The report of significantly increased brain 

AChE inhibition in the female rats of all exposure levels is indicative of an inherent problem with the 

brain data set, perhaps related to tissue collection or quantitative analysis of enzymatic activity in the 

brain tissue of the female rats. Furthermore, results of repeated oral dosing (Singh 1988) indicate that the 

male and female rats are comparably sensitive to diazinon-induced effects on both RBC and brain AChE 

activity. Therefore, the report (Hartman 1990) of significant brain AChE inhibition in the female rats 

exposed to diazinon by inhalation at levels much lower than the LOAEL of 11.6 mg/m3

 for RBC AChE 

inhibition is questionable, and a clear LOAEL for brain AChE inhibition cannot be determined. 

Benchmark dose (BMD) analysis of the critical effect data sets for AChE inhibition from the principal 

study of Hartman (1990) was not possible. Although mean values for RBC and brain AChE activity were 
DIAZINON 15 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Effect of Aerosol Diazinon on Plasma ChE and RBC and Brain AChE 

Activity in Male and Female Rats Exposed for 6 Hours/Day, 5 Days/Week for 

3 Weeks 

Mean plasma ChE Mean RBC AChE Mean brain AChE 

activity in U/L activity in U/L activity in U/g 

(percent change from (percent change from (percent change from 

controls) controls) controls) 

Males 

Vehicle controls 368.9 894.2 3.893 

 0.05 mg/m3

 401.5 (+9%)a 908.6 (+2%) 3.855 (-1%) 

 0.46 mg/m3 351.4 (-5%) 849.5 (-5%) 3.898 (0%)

 1.57 mg/m3

 316.6 (-14%)

b 840.1 (-6%) 3.737 (-4%) 

 11.6 mg/m3

 297.9 (-19%)

b

 573.0 (-36%)

a

 3.883 (0%) 

Females 

Vehicle controls 631.8 887.7 3.742 

 0.05 mg/m3 615.5 (-3%) 882.7 (-1%) 2.838 (-24%)

a

 0.46 mg/m3

 506.0 (-20%)

b 943.0 (+6%) 3.106 (-17%)b

 1.57 mg/m3

 459.0 (-27%)

a

 798.6 (-10%)

b

 2.983 (-20%)

b

 11.6 mg/m3

 361.0 (-43%)

a

 545.0 (-39%)

a

 2.369 (-37%)

a 

a

statistically significantly different from control (p≤0.01) b

statistically significantly different from control (p≤0.05) 

AChE = acetylcholinesterase; ChE = cholinesterase; RBC = red blood cell 

Source: Hartman 1990 
DIAZINON 16 

2. RELEVANCE TO PUBLIC HEALTH 

reported, measures of variance (standard deviation or standard error) were not included in the report. The 

NOAEL of 1.57 mg/m3

 for RBC AChE activity in the male and female rats of the principal study 

(Hartman 1990) served as the point of departure for deriving an intermediate-duration inhalation MRL for 

diazinon. The NOAEL was adjusted for intermittent exposure as follows: 

NOAELADJ = 1.57 mg diazinon/m3

 x 6 hours/24 hours x 5 days/7 days = 0.28 mg diazinon/m3 

A regional deposited dose ratio (RDDRER) of 1.558 for extrarespiratory effects was used to extrapolate 

from rats to humans. The RDDRER was calculated using the parameters listed in Table 2-2 and EPA’s 

software (Version 2.3) (EPA 1994b) for calculating RDDRs. 

The human equivalent concentration was calculated using Equation 4-5 (EPA 1994b) as follows: 

NOAELHEC = NOAELADJ x RDDRER = 0.28 mg diazinon/m3

 x 1.558 = 0.44 mg diazinon/m3 

The NOAELHEC of 0.44 mg/m3

 was divided by an uncertainty factor of 30 (3 for extrapolation from 

animals to humans using dosimetric adjustment and 10 for human variability) resulting in an 

intermediate-duration inhalation MRL of 0.01 mg/m3

. 

No human or animal data were located regarding health effects from chronic-duration inhalation exposure 

to diazinon, precluding the derivation of a chronic-duration inhalation MRL for diazinon. 

Oral MRLs 

• An MRL of 0.006 mg/kg/day has been derived for acute-duration oral exposure (1–14 days) to 

diazinon. 

The acute-duration oral MRL is based on a NOAEL of 0.6 mg/kg/day and a LOAEL of 1.2 mg/kg/day for 

>20% RBC AChE inhibition in rats exposed to diazinon in the diet (Davies and Holub 1980a). 

Available information regarding health effects in humans following acute-duration oral exposure to 

diazinon is restricted to individual case reports of serious effects and death, which precludes derivation of 

an acute-duration oral MRL based on human data. Most acute-duration oral studies in animals involved 

diazinon doses that caused serious neurological effects. One single-dose oral gavage study (unpublished) 

identified a NOAEL of 2.5 mg/kg and a LOAEL of 25 mg/kg for 35% RBC AChE inhibition and 36% 
DIAZINON 17 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-2. Parameters Used to Calculate the Regional Deposited Dose Ratio 

(RDDRER) for Diazinon-induced Extrarespiratory Effects 

Using EPA’s Software (Version 2.3) 

Biological parametersa Rat Human 

Surface area 

Extrathoracic 15 cm2 200 cm2 

Tracheobronchial 22.5 cm2 3,200 cm2 

Pulmonary 0.34 m2 54 m2 

Minute ventilation 147.24 mL 13.8 L 

Body weight 196 g 70 kg 

a

Parameters are default values for rats and humans from the EPA software, except for the rat body weight, which 

was the mean body weight for the 1.57 mg/m3

 exposure group of female rats. 

Mass Median Aerodynamic Diameter (MMAD) = 0.85 μm from lower limit of 0.8 μm and upper limit of 0.9 μm for the 

1.57 mg/m3

 exposure group of female rats reported by Hartman (1990). 

Geometric Standard Deviation (GSD) = 1.3 μm from lower limit of 1.2 μm and upper limit of 1.4 μm reported by 

Hartman (1990). 

Source: Hartman 1990 
DIAZINON 18 

2. RELEVANCE TO PUBLIC HEALTH 

brain AChE inhibition (EPA 2000a). However, the single-dose gavage level of 2.5 mg/kg was the lowest 

dose tested in a similar study (unpublished) and represented a LOAEL for 40% RBC AChE inhibition 

(EPA 2000a). In yet another unpublished study (EPA 1996), rats were administered diazinon in the diet 

for 28 days and assessed for cholinesterase inhibition at weeks 1, 2, and 4. An estimated dose of 

2.4 mg/kg/day resulted in 38–59% RBC AChE inhibition, which was observed as early as week 1 and 

peaked at week 2. The next lower dose (0.02 mg/kg/day) represented a NOAEL. 

Results of repeated-dose oral animal studies indicate that diazinon-induced AChE inhibition progressively 

increases in magnitude with time. For example, in female Wistar rats administered diazinon (99.2% 

purity) in the diet for 92 days, RBC AChE activity was significantly depressed as early as day 8 (Davies 

and Holub 1980a). By day 12, the magnitude of RBC AChE inhibition was approximately 5 and 22% at 

dietary concentrations resulting in doses of approximately 0.6 mg/kg/day (NOAEL) and 1.2 mg/kg/day 

(LOAEL), respectively. The study of Davies and Holub (1980a) identified the lowest LOAEL for the 

critical effect (22% RBC AChE inhibition) associated with the highest NOAEL for acute-duration oral 

exposure to diazinon and was therefore selected as the principal study for deriving an acute-duration oral 

MRL for diazinon. 

In the principal study (Davies and Holub 1980a), female Wistar rats were administered diazinon (99.2% 

purity) in the diet at concentrations of 0, 5, 10, or 15 ppm for 92 days. Blood samples were collected on 

treatment days 3, 8, and 12 from 10 rats/group for assessment of plasma ChE and RBC AChE activity. 

Other groups of similarly-treated rats were sacrificed (n=6) for assessment of brain AChE activity. All 

rats were assessed daily for clinical signs of neurotoxicity and body weights and food intake were 

monitored throughout the treatment period. Based on reported food consumption and body weight data, 

calculated doses for the first 12 days of exposure were 0.6, 1.2, and 1.8 mg/kg/day for the 5- 10-, and 

15-ppm exposure groups, respectively. 

No clinical signs of toxicity were observed in any of the treated groups. At treatment day 12, treatmentrelated effects included 43, 70, and 73% plasma ChE inhibition and 5, 22, and 33% RBC AChE inhibition 

in the 0.6, 1.2, and 1.8 mg/kg/day dose groups, respectively. There was no significant effect on brain 

AChE activity. Plasma ChE inhibition is used as an indicator of exposure, but does not serve as a reliable 

indicator of a neurotoxic effect. Therefore, plasma ChE inhibition was not considered relevant to the 

selection of the critical effect for diazinon. However, inhibition of RBC AChE and brain AChE 

represents a relevant neurological effect. Treatment-related 20–59% RBC or brain AChE inhibition is 

considered to represent a less serious adverse effect in the absence of more clear indicators of 
DIAZINON 19 

2. RELEVANCE TO PUBLIC HEALTH 

neurotoxicity (Chou and Williams-Johnson 1998). The principal study (Davies and Holub 1980a) 

identified a NOAEL of 0.6 mg/kg/day and a LOAEL of 1.2 mg/kg/day for 22% RBC AChE inhibition at 

interim day 12 assessment of female rats administered diazinon in the diet for 92 days. 

BMD analysis of the critical effect data (RBC AChE inhibition) was not attempted because quantitative 

statistical data (mean and standard error or standard deviation) for the critical effect were presented only 

in graphical format (i.e., numerical values were not presented). The NOAEL of 0.6 mg/kg/day was 

divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human 

variability) resulting in an intermediate-duration inhalation MRL of 0.006 mg/kg/day. 

• An MRL of 0.002 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to diazinon. 

The intermediate-duration MRL is based on RBC AChE inhibition in female rats exposed to diazinon in 

the diet (Davies and Holub 1980a). 

Available human information regarding intermediate-duration oral exposure to diazinon is restricted to a 

controlled study in which four male volunteers were administered diazinon in gelatin capsules at a dose 

level of 0.03 mg/kg/day for up to 31 days (EPA 2001). There were no treatment-related clinical signs. 

Approximately 22–42% plasma ChE inhibition was noted as early as treatment day 8 and reached a 

maximum of 47–55% by day 20 or the end of treatment. Because there was no indication of treatmentrelated effects on RBC AChE activity or clinical signs of neurotoxicity, the 0.03 mg/kg/day dose level 

represents a free-standing NOAEL. 

Results of numerous oral studies in animals identify AChE inhibition as the most sensitive effect of 

diazinon toxicity following oral exposure. Table 2-3 presents a summary of NOAELs and LOAELs for 

RBC and brain AChE inhibition following intermediate-duration oral exposure to diazinon. These values 

were identified from publicly-available studies and unpublished studies submitted to EPA’s Office of 

Prevention, Pesticides, and Toxic Substances. Although dose spacing among these intermediate-duration 

oral studies is variable, and in some studies may be in excess of 100-fold for levels at or below identified 

LOAELs for AChE inhibition, these studies collectively indicate that the threshold for less serious AChE 

inhibition occurs in rats and dogs at repeated oral dose levels between 0.2 and 2 mg/kg/day. 

In selecting the principal study for deriving an intermediate-duration oral MRL for diazinon, one 6-week 

oral rat study (Trutter 1991) employed relatively narrow dose spacing in the region of 0.2–2 mg/kg/day 
DIAZINON 20 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-3. NOAELs and LOAELs for RBC and Brain AChE Inhibition Following 

Intermediate-duration Dietary Exposure to Diazinon 

Study type NOAEL LOAEL (mg/kg/day) 

estimated doses (mg/kg/day) (mg/kg/day) AChE inhibition Reference 

28-Day rat study 0.02 (M, F) 2.4; M, F: 38–59% RBC EPA 1996 

M, F: 0, 0.02, 2.4, 23, 213 

30-Day rat study ND 2.86; 58% RBC Davies and 

F: 0, 2.86 Holub 1980b 

35-Day rat study 0.2 ND Davies and 

F: 0, 0.009, 0.05, 0.09, 0.2 Holub 1980a 

42-Day rat study 0.18 0.27; 20% RBC Davies and 

F: 0, 0.09, 0.18, 0.27, 0.36 Holub 1980a 

6-Week rat study Trutter 1991 

M: 0, 0.018, 0.045, 0.19, 1.81, 9.08, 0.19 (M) 1.81; M: 46–55% RBC 

26.67 

F: 0, 0.02, 0.038, 0.20, 1.97, 9.78, 0.20 (F) 1.97; F: 50–61% RBC 

30.20 

6-Week rat study MakhteshimM: 0, 0.02, 0.04, 0.17, 1.68, 8.60, 0.17 (M) 1.68; M: 29–35% RBC Agan 1989 

25.76 

F: 0, 0.02, 0.05, 0.19, 1.82, 9.27, 0.19 (F) 1.82; F: 16–35% RBC 

28.95 

6-Week rat study 0.2 (M, F) 8.4; M: 21% RBC Singh 1988 

M: 0, 0.04, 0.2, 8.4, 150.8 

F: 0, 0.05, 0.2, 9.4, 198 9.4; F: 21% RBC and 24% brain 

90-Day rat study Singh 1988 

M: 0, 0.03, 0.3, 15, 168 0.3 (M) 15; M: 27% RBC 

F: 0, 0.04, 0.4, 19, 212 0.4 (F) 19; F: 41% RBC 

90-Day rat study 0.018 (M, F) 1.8; M, F: 37–75% RBC EPA 1996 

0, 0.018, 1.8, 18, 180 

92-Day rat study 0.4 0.8; 40% RBC Davies and 

F: 0, 0.4, 0.8, 1.2 Holub 1980a 

4-Week dog study Barnes 1988 

M: 0, 0.02, 0.073, 0.8, 14.68 0.8 (M) 14.68; M: 25% RBC; 31% brain 

F: 0, 0.023, 0.082, 0.75, 15.99 0.75 (F) 5.6; F: 31% RBC; 30% brain 

13-Week dog study 0.02 (M, F) Barnes 1988 

M: 0, 0.0034, 0.02, 5.9, 10.9 5.9; M: 26% RBC; 31% brain 

F: 0, 0.0037, 0.02, 5.6, 11.6 5.6; F: 31% RBC ; 30% brain 

AChE = acetylcholinesterase; F = female; LOAEL = lowest-observed-adverse-effect level; M = male; ND = not 

determined; NOAEL = no-observed-adverse-effect level; RBC = red blood cell 
DIAZINON 21 

2. RELEVANCE TO PUBLIC HEALTH 

and was initially considered as a candidate for deriving an intermediate-duration oral MRL for diazinon. 

However, the three lowest dose groups inadvertently received essentially no diazinon in the diet during 

treatment week 5, thus precluding the usefulness of the study results for purposes of quantitative risk 

assessment. The 90-day oral rat study of Singh (1988) was considered as a candidate for the principal 

study because (1) it identified the highest NOAEL (0.3 mg/kg/day for males and 0.4 mg/kg/day for 

females) below the lowest LOAELs identified in other repeated-dose oral studies, and (2) quantitative 

dose-response data for the critical effect (RBC AChE inhibition) were available for BMD analysis. The 

42-day oral rat study of Davies and Holub (1980a) was considered because the effects of diazinon on 

RBC AChE inhibition were assessed at several doses within the low-dose range (0.1–0.4 mg/kg/day). 

This study identified a NOAEL of 0.18 mg/kg/day and a LOAEL of 0.27 mg/kg/day for 20% RBC AChE 

inhibition. 

In the study of Singh (1988), groups of male and female Sprague-Dawley rats (15/sex) were administered 

diazinon MG-8 (purity 87.7%) in the diet at concentrations of 0, 0.5, 5, 250, or 2,500 ppm (after adjusting 

for purity) for 90 days. The corresponding doses were calculated by the study authors to be 0.03, 0.3, 15, 

and 168 mg/kg in males and 0.04, 0.4, 19, and 212 mg/kg in females. Clinical observations were made 

daily and body weight and food consumption were recorded weekly. Clinical laboratory measurements 

and physical, auditory, and ophthalmoscopic exams were performed prior to termination. Prior to 

necropsy, blood and urine samples were collected for hematology, clinical chemistry, and urinalysis. At 

necropsy, organ weights were recorded and comprehensive gross and microscopic examinations were 

performed on all rats. A portion of each brain was processed for assessment of AChE activity. All 

animals survived the 90-day dosing period. Treatment-related clinical symptoms were observed at the 

highest dose level and included hyperactivity and hypersensitivity to touch and sound in males and 

females and aggressive behavior in males. No treatment-related gross or microscopic abnormalities were 

seen in any of the treatment groups. Hematology and urinalysis were unremarkable, with the exception of 

decreased mean hemoglobin and hematocrit accompanied by an increase in reticulocytes in high-dose 

females. Statistically-significant (p<0.01) effects on ChE and AChE included decreased plasma ChE 

activity in males and females at doses ≥0.3 mg/kg/day, decreased RBC AChE activity at doses 

≥15 mg/kg/day in males and ≥0.4 mg/kg/day in females, and decreased brain AChE activity at the highest 

dose in males and doses ≥19 mg/kg/day in females. As discussed earlier, a 20–59% inhibition (reduction 

in measured activity) of neural or RBC AChE may be considered a less serious effect in the absence of 

more serious indicators of neurotoxicity (Chou and Williams-Johnson 1998). Treatment-related 

decreased RBC activity was noted at doses lower than those resulting in decreased brain AChE activity 
DIAZINON 22 

2. RELEVANCE TO PUBLIC HEALTH 

and was therefore selected as the critical effect for BMD analysis. Table 2-4 contains the data that were 

modeled. 

The linear model in the EPA Benchmark Dose Software (Version 1.3.2) was initially fit to the male rat 

data for RBC AChE activity shown in Table 2-4. A benchmark response (BMR) of 20% below the 

control mean RBC AChE activity was selected because 20–59% RBC or brain AChE inhibition is 

considered to represent a less serious effect in the absence of more serious indicators of neurotoxicity 

(Chou and Williams-Johnson 1998). 

Inadequate fit was provided by the linear model, as indicated by a p value <0.0001 for the test of mean fit 

(according to BMD technical guidance, a p value ≥0.1 indicates an adequate goodness-of-fit). The same 

result was obtained using the BMD software for the polynomial and power models. The BMD software 

for the Hill model calculated a BMD20 of 0.38 mg/kg/day for the male rat data, but failed to identify the 

lower 95% confidence limit (BMDL20) value (presumably due to a bad completion code in an 

optimization routine). Under the presumption that the highest dose may have been a major influence in 

the model output, the data from the highest dose were eliminated and the linear model was fit to the 

remaining data. In this case, a near-adequate fit was obtained, as indicated by a p value of 0.09294 for the 

test of mean fit. The polynomial and power model outputs from the male rat data set (minus the highest 

dose) were found to be clearly inadequate, based on p values of 0.02919 and 0.02928 for the test of mean 

fit. Without the high-dose data, the data set for RBC AChE activity in the male rats of the Singh (1988) 

study contained insufficient dose groups to accommodate the requirements for the Hill model. In 

summary, the results of BMD analysis of RBC AChE activity in the male rats of the Singh (1988) study 

were rejected due to inadequate fit from all available continuous data models in the EPA Benchmark 

Dose Software (Version 1.3.2). 

For the female rat data (see Table 2-4), inadequate fit was provided by the linear, polynomial, and power 

models, as indicated by p values <0.0001 for the test of mean fit. The Hill model provided the only 

adequate fit of the female data and resulted in a BMD20 of 0.56 mg/kg/day and a BMDL20 of 

0.38 mg/kg/day. Elimination of the RBC AChE activity data for the highest-dose female rats did not 

result in adequate fit for the linear, polynomial, or power models. Furthermore, this elimination resulted 

in insufficient dose groups to accommodate the requirements of the Hill model. In summary, BMD 

analysis of RBC AChE activity in the female rats of the Singh (1988) study resulted in a single adequate 

fit (Hill model output using all dose groups) and resulting BMD20 of 0.56 mg/kg/day and a BMDL20 of 

0.38 mg/kg/day. 
DIAZINON 23 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-4. RBC AChE Data From Male and Female Rats Exposed to Diazinon in 

the Diet for 90 Days 

Dose group Number RBC AChE activity Percent RBC AChE 

(mg/kg/day) of rats (mU/mL)a inhibition 

Males 

0 15 2093.333±44.150 

0.03 15 2186.667±68.220 – 

0.3 15 2000.000±59.362 4 

15 15 1526.667±58.119 27 

168 15 1540.000±60.788 26 

Females 

0 14 2300.000±58.366 

0.04 15 2213.333±46.667 4 

0.4 15 1913.333±45.635 17 

19 15 1353.333±40.079 41 

212 15 1346.667±33.618 41 

a

Mean±standard error 

Source: Singh 1988 
DIAZINON 24 

2. RELEVANCE TO PUBLIC HEALTH 

In the study of Davies and Holub (1980a), groups of female Wistar rats (16/group) were exposed to 

diazinon (99.2% purity) in the diet at concentrations of 0, 1, 2, 3, or 4 ppm for 42 days. Blood samples 

were collected periodically from 10 rats/group for assessment of plasma ChE and RBC AChE activity. 

Six rats per group were sacrificed on day 35 for assessment of brain AChE activity. All rats were 

assessed daily for clinical signs of neurotoxicity and body weights and food intake were monitored 

throughout the treatment period. Based on reported food consumption and body weight data, the doses to 

the 1-, 2-, 3-, and 4-ppm exposure groups were calculated to be 0.09, 0.18, 0.27, and 0.36 mg/kg/day. No 

clinical signs of toxicity were observed in any of the treated groups. Significant plasma ChE inhibition 

was observed at most timepoints in all diazinon-treated groups, relative to controls. The magnitude of 

inhibition in all treatment groups increased with time and appeared to peak around day 35, remaining near 

the peak level for the remaining 7 treatment days. Maximum plasma ChE inhibition in the 0.09, 0.18, 

0.27, and 0.36 mg/kg/day treatment groups was approximately 35, 50, 55, and >60%, respectively. 

Plasma ChE inhibition is used as an indicator of exposure, but does not serve as a reliable indicator of a 

neurotoxic effect. Therefore, plasma ChE inhibition was not considered relevant to the selection of the 

critical effect for diazinon. Through treatment day 35, there was no significant treatment-related effect on 

RBC AChE activity in any of the treatment groups. However, on treatment day 42, significant RBC 

AChE inhibition was observed at treatment levels of 0.18, 0.27, and 0.36 mg/kg/day (magnitude 9, 20, 

and 22%, respectively). There were no indications of treatment-related significant brain AChE inhibition 

at any timepoint during the 42 days of treatment. The results of RBC AChE activity in the female rats of 

the principal study (Davies and Holub 1980a) are presented in Table 2-5. Inhibition of RBC AChE and 

brain AChE represents a relevant neurological effect. Treatment-related 20–59% RBC or brain AChE 

inhibition is considered to represent a less serious adverse effect in the absence of more clear indicators of 

neurotoxicity (Chou and Williams-Johnson 1998). The principal study (Davies and Holub 1980a) 

identified a NOAEL of 0.18 mg/kg/day and a LOAEL of 0.27 mg/kg/day for 20% RBC AChE inhibition 

in female rats administered diazinon in the diet for 42 days. 

The linear model in the EPA Benchmark Dose Software (Version 1.3.2) was fit to the female rat data. As 

discussed previously, a BMR of 20% below the control mean RBC AChE activity was selected because 

20–59% RBC or brain AChE inhibition is considered to represent a less serious effect in the absence of 

more serious indicators of neurotoxicity (Chou and Williams-Johnson 1998). Initial BMD analysis using 

the linear model was performed using constant variance as one of the selected parameters. The model 

output indicated that a nonhomogeneous variance was more appropriate for the data set. Using a 

nonhomogeneous variance, the linear model provided adequate fit to the data from Table 2-5, as indicated 

by acceptable p values for tests for (1) differences in response and/or variances among dose levels, 
DIAZINON 25 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-5. RBC AChE Data From Female Rats Exposed to Diazinon in the Diet for 

42 Days 

Dose group Number RBC AChE activity (μmole/mL Percent RBC AChE 

(mg/kg/day) of rats packed cells/minute)a inhibition 

0 10 0.74±0.05 

0.09 10 0.68±0.07 8 

0.18 10 0.67±0.06 9 

0.27 10 0.59±0.04 20 

0.36 10 0.58±0.02 22 

a

Mean±standard error 

AChE = acetylcholinesterase; RBC = red blood cell 

Source: Davies and Holub 1980a 
DIAZINON 26 

2. RELEVANCE TO PUBLIC HEALTH 

(2) homogeneous or nonhomogeneous variance, and (3) model mean fit. The resulting BMD20 was 

0.36 mg/kg/day and the BMDL20 was 0.25 mg/kg/day. Because the simplest model, the linear model, 

provided adequate fit to the RBC AChE data from the 42-day rat study of Davies and Holub (1980a), the 

application of more complex continuous variable models was not considered necessary. 

BMD analysis identified two potential points of departure for deriving an intermediate-duration oral MRL 

for diazinon, the BMDL20 of 0.3267 mg/kg/day for RBC AChE activity in the female rats from the 90-day 

oral rat study of Singh (1988) and the BMDL20 of 0.2238 mg/kg/day for RBC AChE activity in the 

female rats from the 42-day oral study of Davies and Holub (1980a). The 42-day oral rat study of Davies 

and Holub (1980a) was selected as the principal study based on the fact that this study employed several 

dose groups in the low-dose region of threshold effect. Therefore, the BMDL20 of 0.2238 mg/kg/day 

from the RBC AChE data of Davies and Holub (1980a) was selected as the point of departure for deriving 

an intermediate-duration oral MRL for diazinon. The BMDL20 of 0.2238 mg/kg/day was divided by an 

uncertainty factor (UF) of 100 (10 for extrapolation from animals to humans and 10 for human 

variability) resulting in an intermediate-duration oral MRL of 0.002 mg/kg/day. 

• An MRL of 0.0007 mg/kg/day has been derived for chronic-duration oral exposure (365 days or 

more) to diazinon. 

The chronic-duration oral MRL is based on a NOAEL of 0.065 mg/kg/day and a LOAEL of 

5.5 mg/kg/day for >20% RBC AChE inhibition in female rats administered diazinon in the diet for 

98 weeks (Kirchner et al. 1991). 

No human data are available from which to evaluate the health effects associated with chronic-duration 

oral exposure to diazinon. The available chronic-duration oral database in animals consists of two 

unpublished studies, a 98-week feeding study in rats and a 52-week feeding study in dogs. These studies 

identified RBC AChE inhibition as the most sensitive effect of diazinon toxicity. 

The 52-week dog study (Rudzki et al. 1991) identified a NOAEL of 0.5 ppm (0.017 mg/kg/day) and a 

LOAEL of 150 ppm (4.6 mg/kg/day) for RBC AChE inhibition of 20% or more in both males and 

females at treatment day 359. The 98-week rat study (Kirchner et al. 1991) identified a NOAEL of 

0.065 mg/kg/day and a LOAEL of 5.5 mg/kg/day for RBC AChE inhibition of 20% or more in both 

males and females. The 98-week rat study (Kirchner et al. 1991) was selected as the principal study for 

deriving a chronic-duration oral MRL for diazinon because: (1) clinical chemistry results, including 

assessments of AChE inhibition, were available for a treatment period in excess of 364 days and (2) the 
DIAZINON 27 

2. RELEVANCE TO PUBLIC HEALTH 

study identified a slightly higher NOAEL (0.065 mg/kg/day) than the NOAEL (0.017 mg/kg/day) 

identified in the 52-week dog study (Rudzki et al. 1991). 

In the 98-week rat study (Kirchner et al. 1991), diazinon MG-8 (purity 87.7%) was dissolved in acetone 

vehicle and added to the diet of male and female Sprague-Dawley rats at concentrations of 0, 0.1, 1.5, 

125, or 250 ppm for up to 98 weeks. The study included both untreated and vehicle control groups. 

According to the study authors, the corresponding diazinon doses (adjusted for purity) were 0, 0.004, 

0.06, 5, and 10 mg/kg/day for males and 0, 0.005, 0.07, 6, and 12 mg/kg/day for females), which result in 

averaged doses of 0, 0.0045, 0.065, 5.5, and 11 mg/kg/day for both males and females. Twenty 

rats/sex/group were treated for the full 98 weeks. Ten rats/sex/group were treated for 52 weeks and 

sacrificed for interim assessment. Additional groups of 10 rats/sex were assigned to the untreated control, 

vehicle control, and 250 ppm groups and assessed for recovery 45 days following 52 weeks of treatment. 

Animals were observed daily for clinical signs of toxicity. Food consumption, water intake, and body 

weights were monitored. Ophthalmoscopic examinations were performed during weeks 2, 51, and 97 or 

98. Blood was collected on at several timepoints between days 88 and 684. Ten animals/sex/group from 

the 98-week treatment groups received clinical chemistry evaluation at treatment days 88, 181, 356, 390, 

552, and 684. Urinalysis was performed on all surviving rats of the 98-week treatment groups at 

treatment days 81, 189, 350, 545, and 679. All rats were subjected to comprehensive gross and 

microscopic pathologic examination at death or sacrifice. There were no apparent treatment-related 

effects on survival, food or water consumption, body weights, or hematological or urinalysis parameters 

examined. Due to mortality in all groups, including controls, the study was terminated at 97 weeks. 

Ophthalmoscopic and gross and microscopic examinations did not reveal evidence of dose-related effects. 

The major findings of this study were those of dose related decreased plasma ChE and RBC and brain 

AChE activity in both male and female rats. Significantly decreased plasma ChE activity (28–51% lower 

than controls) was noted in 0.065 mg/kg/day male rats at treatment days 88 and 684, but not at treatment 

days 181, 356, or 552 and in 0.065 mg/kg/day female rats (approximately 50% lower than controls) at 

most timepoints. High-dose male and female rats consistently exhibited significantly decreased plasma 

ChE activity, ranging from 80 to 97% lower than controls. In 0.065 mg/kg/day groups, RBC and brain 

AChE activity was not significantly decreased at any timepoint. The 5.5 mg/kg/day groups exhibited 

significantly decreased RBC AChE activity at all timepoints, ranging in magnitude from 15 to 28% and 

from 22 to 25% in males and females, respectively. At the 5.5 and 11 mg/kg/day levels, the magnitude of 

the effect did not appear to increase with either duration of treatment or increased dose. Following 

52 weeks of treatment and 45 days of recovery, RBC AChE activity had returned to control levels in 

high-dose male rats and to within 7% of control levels in high-dose female rats. Brain AChE activity was 
DIAZINON 28 

2. RELEVANCE TO PUBLIC HEALTH 

significantly decreased in 5.5 and 11 mg/kg/day male and female rats. In 5.5 and 11 mg/kg/day males, 

the magnitude of the effect was effect was 24 and 42%, respectively, after 684 days of treatment, but not 

significantly different from controls at 370 days. In 5.5 and 11mg/kg/day female rats, the effect was 

noted at both 370 and 684 day timepoints; the magnitude of the effect was >24% at 5.5 mg/kg/day and 

>40% at 11 mg/kg/day. 

All available continuous variable models in the EPA Benchmark Dose Software (Version 1.3.2) were fit 

to the male and female rat data for RBC AChE activity reported in the principal study (Kirchner et al. 

1991). A benchmark response (BMR) of 20% below the control mean RBC AChE activity was selected 

because 20–59% RBC or brain AChE inhibition is considered to represent a less serious effect in the 

absence of more serious indicators of neurotoxicity (Chou and Williams-Johnson 1998). Inadequate 

mean fit was provided by all models, as indicated by p values <0.05 for tests of mean fit (according to 

BMD technical guidance, a p value ≥0.1 indicates an adequate goodness-of-fit). Because BMD analysis 

provided inadequate mean fit to the RBC AChE data sets, a NOAEL/LOAEL approach was taken to 

derive a chronic-duration oral MRL for diazinon. The principal study (Kirchner et al. 1991) identified a 

NOAEL of 0.065 mg/kg/day (1.5 ppm of diazinon in the diet) and a LOAEL of 5.5 mg/kg/day (125 ppm 

of diazinon in the diet) for 22–28% decreased RBC AChE activity in male and female rats, which is 

considered the critical effect. The effect was observed as early as day 88 of treatment and did not appear 

to increase in magnitude with duration of treatment. The NOAEL of 0.065 mg/kg/day was divided by a 

total uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability) 

resulting in a chronic-duration oral MRL of 0.0007 mg/kg/day. 
DIAZINON 29 

3. HEALTH EFFECTS 

3.1 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 diazinon. 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. 

Systemic effects common to humans and laboratory animals exposed to diazinon by all natural exposure 

routes (inhalation, oral, dermal) are primarily attributable to the inhibition of acetylcholinesterase (AChE) 

by diazoxon, the active metabolite of diazinon. Inhibition of AChE at nerve terminals in central and 

peripheral nervous tissues triggers cholinergic signs and symptoms that are particularly apparent in 

respiratory, cardiovascular, and gastrointestinal systems. Although listed under specific systemic effects 

sections, many of the systemic effects listed are likely the direct result of AChE inhibition. Some cases of 

human exposure to diazinon may include mixed (inhalation, oral, and/or dermal) exposure routes; in such 

cases, a cumulative dose of diazinon would be expected to be the result of absorption by all relevant 

exposure routes. 

The Toxicological Profile for Diazinon deals with diazinon-induced health effects in humans and animals. 

Most controlled animal studies were performed using technical-grade diazinon (purity ranging from 87 to 

essentially 100%). Other ingredients in technical-grade diazinon were not typically specified. Some 

animal studies employed particular diazinon pesticide formulations such as 60EC (a 60% emulsifiable 

concentration of diazinon) or 25WP (a 25% wettable powder). Summaries of animal data in the 

Toxicological Profile for Diazinon focus on health effects in animals exposed to technical-grade diazinon. 

MRLs were derived from results of studies that employed technical-grade diazinon. Available controlled 

human studies were performed using technical-grade diazinon of high purity. However, most of the 

available human data derive from case reports of intentional or accidental exposure to various diazinon 

formulations. Exposure of pesticide applicators often included exposure to other pesticides as well. 

Thus, some signs and symptoms resulting from a particular exposure scenario may be at least partly 

attributable to compounds other than diazinon. Furthermore, the extent and rate of absorption of diazinon 

may vary greatly depending on the source of diazinon exposure (i.e., technical grade or particular 

formulation of an end-use product). 
DIAZINON 30 

3. HEALTH EFFECTS 

3.2 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 lowestobserved-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 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 (LOAELs) 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. 
DIAZINON 31 

3. HEALTH EFFECTS 

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. 

The principal toxic effect of diazinon in humans and laboratory animals is inhibition of 

acetylcholinesterase (AChE), which results in the accumulation of acetylcholine at acetylcholine receptors 

leading to cholinergic responses in the peripheral (muscarinic and nicotinic) and central nervous system 

and neuromuscular junctions. In this Toxicological Profile for Diazinon, AChE inhibition of magnitude 

20–59% is considered a less serious adverse effect in the absence of more serious signs of neurotoxicity. 

AChE inhibition ≥60% is considered a more serious effect independent of the presence or absence of 

other neurotoxicity indicators. 

3.2.1 Inhalation Exposure 

Diazinon has a low volatility; thus, inhalation exposure is likely to be to diazinon aerosols rather than 

vapor. In one of the studies described below, animals were exposed to diazinon in inhalation chambers 

(Holbert 1989). It is possible that some of the exposure under these conditions was by the dermal route 

and/or the oral route (grooming). 

3.2.1.1 Death 

There are no reports of deaths in humans or animals exposed by inhalation to diazinon alone. One case 

report described the death and autopsy results of a 51-year-old man who had been exposed to an 

insecticide mixture that contained diazinon and malathion, another anticholinesterase insecticide that is 

more acutely potent than diazinon (Wecker et al. 1985). The death was attributed to irreversible cardiac 

arrest, despite atropine therapy. Autopsy revealed mild pathologic changes in intercostal muscle tissue, 

including muscle fibers with subsarcolemmal grouped granular basophilic inclusions and scattered areas 

of necrosis. The victim's neuromuscular AChE activity was one-half that of muscle from unexposed 

persons. 

No deaths were reported in Sprague-Dawley rats (5/sex) exposed to 2,330 mg/m3

 diazinon for 4 hours in 

inhalation chambers and observed for a further 14 days (Holbert 1989), or in hybrid rats (10/sex/group) 

exposed to air concentrations of 0.05, 0.46, 1.57, or 11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 

5 days/week for 3 weeks (Hartman 1990). 
DIAZINON 32 

3. HEALTH EFFECTS 

3.2.1.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, hepatic, 

renal, endocrine, dermal, ocular, or body weight effects in humans after inhalation exposure to diazinon. 

A single study described mild degenerative changes in the muscles in a human acute-duration exposure to 

a mixture of diazinon and malathion (Wecker et al. 1985). No studies were located regarding 

gastrointestinal, musculoskeletal, or dermal effects in animals after inhalation exposure to diazinon. The 

systemic effects observed in humans and animals after inhalation exposure to diazinon are discussed 

below. The highest NOAEL and all LOAEL values from each reliable study for systemic end points in 

each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

Respiratory Effects. Nasal discharge was observed in Sprague-Dawley rats exposed to 2,330 mg/m3 

diazinon for 4 hours in an inhalation chamber (Holbert 1989). A statistically significant increase in lungto-body weight ratio was observed in hybrid female rats exposed to 0.46 and 1.57 mg/m3

 diazinon (noseonly) for 6 hours/day, 5 days/week for 3 weeks (Hartman 1990). This effect was not seen in male rats or 

in female rats exposed at 11.6 mg/m3

, so its toxicological significance is unclear. No gross or histological 

evidence of treatment-related damage to nasal tissues or the lungs was observed at the termination of this 

study. 

Cardiovascular Effects. No gross or histological evidence of treatment-related damage to the heart 

was observed in hybrid rats (10/sex) exposed to 11.6 mg/m3

 diazinon (nose-only) 6 hours/day, 

5 days/week for 3 weeks (Hartman 1990). 

Hematological Effects. No statistically significant effects on hematological parameters (erythrocyte 

count, hemoglobin, packed red cell volume) were seen in hybrid rats (10/sex/group) exposed to up to 

11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 5 days/week for 3 weeks (Hartman 1990). 

Musculoskeletal Effects. Mild pathologic changes in the intercostal muscle tissue, including muscle 

fibers with subsarcolemmal grouped granular basophilic inclusions and scattered areas of necrosis were 

reported in the autopsy of a 51-year-old man who died from high acute-duration exposure, via inhalation, 

to a commercial insecticide spray containing diazinon and malathion. Neuromuscular AChE activity was 

one-half that of muscle from unexposed persons (Wecker et al. 1985). 
443

23302330

2330

444

2330

447

11.611.611.611.611.611.611.611.6

448

11.6

Table 3-1 Levels of Significant Exposure to Diazinon - Inhalation 

Exposure/ LOAEL 

Duration/ 

a 

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/m3) (mg/m3) (mg/m3) Chemical Form 

ACUTE EXPOSURE Systemic 

1 Rat 

(SpragueDawley) 

4 hr Resp 2330 M (nasal discharge; 3/5) Holbert 1989 

Renal 2330 F (polyuria; 3/5) 

Neurological 

2 Rat 

(SpragueDawley) 

4 hr 

Bd Wt 2330 

2330 (decreased activity, 2/5; 

salivation, 2/5) 

Holbert 1989 

INTERMEDIATE EXPOSURE Systemic 

3 Rat 

(Hybrid) 

3 wk 5 d/wk 6 hr/d 

Resp 11.6 Hartman 1990 

Cardio 11.6 

Hemato 11.6 Hepatic 11.6 Renal 11.6 Endocr 11.6 Ocular 11.6 

Immuno/ Lymphoret 

4 Rat 

(Hybrid) 

3 wk 5 d/wk 6 hr/d 

Bd Wt 11.6 

11.6 Hartman 1990 
445

1.57

11.6

Table 3-1 Levels of Significant Exposure to Diazinon - Inhalation (continued) 

Exposure/ LOAEL 

Duration/ 

a 

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/m3) (mg/m3) (mg/m3) Chemical Form 

Neurological 

5 Rat b 1.57 11.6 (36-39% RBC AChE Hartman 1990 (Hybrid) inhibition) a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate-duration inhalation minimal risk level (MRL) of 0.01 mg/m3 for diazinon. The concentration (1.57 mg/m3) was adjusted for intermiconverted to a human equivalent concentration as described in detail in Appendix A. The resulting duration-adjusted human equivalent concentration was divided bfactor of 30 (3 for extrapolation from animals to humans using dosimetric adjustment and 10 for human variability). AChE = acetylcholinesterase; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; Gastro = gastrointestinal; Hemato = hem

hour(s); Immuno/Lymphoret = immunological/lymphoreticular; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect leveblood cell; Resp = respiratory; wk = week(s) 
1000

10000

Respiratory

1r

Renal

1r

Body Weight

1r

Neurological

2r

ppm

Figure 3-1 Levels of Significant Exposure to Diazinon - Inhalation

Acute (≤14 days)

c-Cat

d-Dog

r-Rat

p-Pig

q-Cow

 -Humans

k-Monkey

m-Mouse

h-Rabbit

a-Sheep

f-Ferret

j-Pigeon

e-Gerbil

s-Hamster

g-Guinea Pig

n-Mink

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

 LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

 LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

 Minimal Risk Level

 for effects

 other than

 Cancer

Systemic

DIAZINON

3. HEALTH EFFECTS

35
Respiratory 

Cardiovascular Hematological Hepatic Renal Endocrine Ocular Body Weight Immuno/Lymphor Neurological 

100 

Figure 3-1 Levels of Significant Exposure to Diazinon - Inhalation (Continued)

Intermediate (15-364 days)

Systemic

DIAZINON

ppm 

3r 3r 3r 3r 3r 3r 3r 3r 4r 5r 10 

5r 

1 

0.1 

0.01 

3. HEALTH EFFECTS

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow

 -Humans 

k-Monkey

m-Mouse 

h-Rabbit 

a-Sheep 

f-Ferret 

j-Pigeon

e-Gerbil 

s-Hamster 

g-Guinea Pig 

n-Mink 

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

LOAEL, Less Serious-Animals

NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

LOAEL, Less Serious-Humans

NOAEL - Humans

 LD50/LC50

Minimal Risk Level

 for effects

 other than

 Cancer 

36
DIAZINON 37 

3. HEALTH EFFECTS 

Hepatic Effects. No gross or histological evidence of treatment-related damage to the liver was 

observed in hybrid rats (10/sex) exposed to 11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 

5 days/week for 3 weeks (Hartman 1990). 

Renal Effects. Polyuria was observed in Sprague-Dawley rats exposed to 2,330 mg/m3

 diazinon for 

4 hours (Holbert 1989). No gross or histological evidence of treatment-related damage to the kidney was 

observed in hybrid rats (10/sex) exposed to 11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 

5 days/week for 3 weeks (Hartman 1990). 

Endocrine Effects. No gross or histological evidence of treatment-related damage to the adrenal 

gland was observed in hybrid rats (10/sex) exposed to 11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 

5 days/week for 3 weeks (Hartman 1990). 

Ocular Effects. Ptosis was observed in Sprague-Dawley rats exposed to 2,330 mg/m3

 diazinon for 

4 hours in an inhalation chamber (Holbert 1989). No evidence of treatment-related ophthalmoscopic 

lesions was observed in hybrid rats (10/sex/group) exposed to up to 11.6 mg/m3

 diazinon (nose-only) for 

6 hours/day, 5 days/week for 3 weeks (Hartman 1990). 

Body Weight Effects. No effect on body weight was observed in Sprague-Dawley rats (5/sex) 

exposed to 2,330 mg/m3

 diazinon for 4 hours and observed for 14 days (Holbert 1989) or in hybrid rats 

(10/sex/group) exposed to up to 11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 5 days/week for 

3 weeks (Hartman 1990). 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological or lymphoreticular effects in humans after inhalation 

exposure to diazinon. 

No gross or histological evidence of treatment-related damage to the spleen was observed in hybrid rats 

(10/sex) exposed to 11.6 mg/m3

 diazinon (nose-only) for 6 hours/day, 5 days/week for 3 weeks (Hartman 

1990). 

The NOAEL for immunological and/or lymphoreticular end points in hybrid rats for intermediateduration exposure is recorded in Table 3-1 and plotted in Figure 3-1. 
DIAZINON 38 

3. HEALTH EFFECTS 

3.2.1.4 Neurological Effects 

Diazinon, an anticholinesterase organophosphate, inhibits AChE in the central and peripheral nervous 

system. Inhibition of AChE results in accumulation of acetylcholine at muscarinic and nicotinic receptors 

leading to peripheral and central nervous system effects. These effects usually appear within a few 

minutes to 24 hours after exposure, depending on the extent of exposure. Most of the located reports of 

incidents of human exposure to diazinon involved occupational exposure via the inhalation route, 

although it is possible that significant exposure also took place via the dermal route. 

Cholinergic symptoms began within 15 minutes in 17 of 18 mushroom workers exposed to diazinon 

sprayed around the only entrance to a room in which they were working. The workers exhibited reduced 

plasma cholinesterase (ChE) and erythrocyte acetylcholinesterase (RBC AChE) levels (markers for 

diazinon exposure) within 48 hours; plasma ChE levels were inhibited 27–29% by diazinon exposure 

during 15 days postexposure (Coye et al. 1987). In another report, members of a family complained of 

signs and symptoms of insecticide poisoning (headache, vomiting, fatigue, chest heaviness) after moving 

into a house that had been treated with diazinon. Five months after the diazinon treatment, analysis of the 

family members' urine samples showed "very high urinary levels" (0.5–1.5 mg/L) of a diazinon 

metabolite, diethylphosphate (DEP), while plasma ChE levels were slightly depressed (79–94% of normal 

levels). Surface concentrations of diazinon in the home ranged from 126 to 1,051 μg/m2

, air 

concentrations were between 5 and 27 μg/m3

, and some clothing showed contamination (0.5–0.7 μg/g). 

After cleanup of the house, the signs and symptoms reported by family members promptly ceased, and the 

urinary excretion of DEP dropped to background levels (Richter et al. 1992). Another case study of 

99 individuals who were occupationally exposed to diazinon granules 8 hours/day for 39 days during an 

insecticide application program reported only slight neurological functional deficits (postshift symboldigit speed and pattern memory accuracy) as a result of the exposure. A dose of 0.02 mg/kg/day, 

considered a NOAEL, was estimated for the workers on the basis of measured diazinon concentration in 

passive dermal badges, hand rinses, and full-shift breathing-zone air samples. Thus, multiple exposure 

routes were implied, making it difficult to verify the dose calculated by the authors of the study. 

Adequate information regarding exposure time to onset and recovery (if any) from the slight neurological 

functional deficits described was not provided in the report (Maizlish et al. 1987). Other persons 

occupationally exposed to organophosphorus insecticides, including diazinon, showed no significant 

change in neurological function, although there was a reduction in plasma ChE levels indicating exposure 

(Stalberg et al. 1978). In contrast, organophosphate-induced increases in hyperreflexia were reported in 
DIAZINON 39 

3. HEALTH EFFECTS 

workers occupationally exposed to many insecticides, including diazinon. These workers, however, 

showed no overt signs of poisoning or of cholinergic signs and symptoms after spraying diazinon (Rayner 

et al. 1972). Two other insecticide sprayers developed cholinergic symptoms after spraying diazinon. 

Symptoms included nausea, vomiting, muscle twitching, difficulty breathing, and blurred vision. Plasma 

ChE and RBC AChE activities remained depressed for at least 18 days after exposure (Soliman et al. 

1982). In all of these cases of occupational exposure (Rayner et al. 1972; Soliman et al. 1982; Stalberg et 

al. 1978), no estimate of the exposure level to diazinon was made. 

A 42-year-old woman (26 weeks pregnant) in the country of Qatar was exposed when she used undiluted 

diazinon liquid insecticide (60EC) to clean a nonventilated bathroom (Kamha et al. 2005). Her symptoms 

included dizziness, vomiting, blurred vision, and increased salivation. Laboratory tests revealed plasma 

ChE activity of 161 U/L (normal range 5,400–13,200 U/L), which confirmed a clinical diagnosis of 

organophosphate poisoning. The patient was treated with the cholineaterase reactivators atropine and 

2-PAM (pralidoxime) and the symptoms of diazinon poisoning subsided. 

Decreased activity and salivation were noted in Sprague-Dawley rats exposed to 2,330 mg/m3

 diazinon 

for 4 hours in an inhalation chamber (Holbert 1989). No clinical signs of neurological effects except 

piloerection were observed in hybrid rats exposed to 0.05, 0.46, 1.57, or 11.6 mg/m3

 diazinon for 

6 hours/day, 5 days/week for 3 weeks (Hartman 1990). At study termination, plasma ChE activity (a 

marker for diazinon exposure) was significantly decreased in a dose-related manner in females. 

Decreases of 20, 27, and 43% were seen at airborne diazinon levels of 0.46, 1.57, and 11.6 mg/m3

, 

respectively. No change was seen at 0.05 mg/m3

. In males, no change was seen at 0.05 or 0.46 mg/m3, 

but decreases of 14 and 19% were seen at 1.57 and 11.6 mg/m3

, respectively. RBC AChE activity (a 

surrogate marker for neural AChE) was unaffected in females at 0.05 and 0.46 mg/m3

, but was decreased 

by 10 and 39% at 1.57 and 11.6 mg/m3

, respectively. In males, no change was seen at 0.05, 0.46, or 

1.57 mg/m3

, while a decrease of 36% was observed at 11.6 mg/m3. Brain AChE activity was unchanged 

in males at all exposure levels, but was decreased in females at 0.05 mg/m3

 (24%), 0.46 mg/m3 (17%), 

1.57 mg/m3

 (20%), and 11.6 mg/m3 (37%). The decreases in the females at the two lowest exposures are 

unusual in that no accompanying decrease in RBC AChE activity was observed. Diazinon exposure had a 

consistently greater effect on cholinesterase activities in females than in males in this study, although 

clinical signs of neurological effects (other than piloerection) were not observed in either sex. 

No studies were located regarding organophosphate-induced delayed neurotoxicity (OPIDN) in humans 

or in animals after inhalation exposure to diazinon. 
DIAZINON 40 

3. HEALTH EFFECTS 

The highest NOAEL and all LOAEL values from each reliable study for neurological end points in each 

species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans or animals after inhalation exposure to 

diazinon. 

3.2.1.6 Developmental Effects 

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

to diazinon. 

3.2.1.7 Cancer 

Several epidemiological studies have reported increased incidence of cancers in humans who were 

concurrently or sequentially exposed to a number of insecticides, including diazinon. Some of the 

exposure is presumed to have occurred by the inhalation route. Because epidemiological studies typically 

involve exposure to multiple pesticides, the carcinogenicity of diazinon itself has not been determined. 

A case-control study suggested a possible link between family gardening use of diazinon (and other 

insecticides) and increased incidence of childhood brain cancer (type unspecified). However, this report 

gave no indication of level, duration, or frequency of exposure to diazinon (or to other insecticides) 

(Davis et al. 1993). Another case-control study suggested a positive association between an increased 

incidence of non-Hodgkin's lymphoma in farmers as compared to nonfarmers. The report attributed the 

increased incidence of lymphomas to handling of organophosphorus insecticides, including diazinon 

(Cantor et al. 1992). A third case-control study suggested an association between an increased incidence 

of multiple myeloma and exposure to high concentrations of insecticides, including diazinon. Actual 

exposure to diazinon was reported in 2 (0.3%) of the cases and 5 (0.3%) of the controls (Morris et al. 

1986). 

No studies were located regarding cancer effects in animals after inhalation exposure to diazinon. 
DIAZINON 41 

3. HEALTH EFFECTS 

3.2.2 Oral Exposure 

3.2.2.1 Death 

In humans and animals, acute-duration oral exposure to high doses of diazinon induces cholinergic signs 

and symptoms. With sufficiently high doses of diazinon, extensive edema and hemorrhage in tissues and 

organs, as well as severe respiratory distress in the victims, have been reported. On some occasions, the 

respiratory effects progressed to respiratory failure and death preceded by coma. Treatment of test 

animals with anticholinesterase antagonists such as atropine and pralidoxime (2-PAM) significantly 

reduced the acute lethality of diazinon in rats, indicating that acute diazinon lethality is primarily 

attributable to AChE inhibition (Harris et al. 1969). 

A summary of autopsy findings of 76 cases of acute diazinon poisoning described cholinergic signs that 

included: congested, swollen, edematous brain with prominent dural and surface vasculature; livid, 

congested face; cyanosis; soft flabby heart with conspicuous vasculature on the pericardium and 

epicardium; cloudy swelling and hyperemia (upon histopathological examination); occasional and 

scattered petechial and ecchymotic hemorrhage; and occasional brain or spinal hemorrhage. In addition, 

the victims died with congested respiratory tract, sweating and frothing at the mouth, pulmonary edema 

and hyperemia, hypostatic congestion, and pneumonia. Generally, the cause of death was respiratory 

failure and, occasionally, cardiac arrest (Limaye 1966). Other reports of human deaths from diazinon 

exposure include descriptions of petechial hemorrhages throughout the stomach and gastric mucosa in a 

diazinon-poisoned 54-year-old female suicide victim who had ingested an estimated 293 mg/kg diazinon 

(Poklis et al. 1980). Accidental ingestion of an insecticide mixture containing diazinon, parathion, and 

chlordane resulted in the death of an 8-year-old girl from cardiac and respiratory arrest (DePalma et al. 

1970). The estimated dose of diazinon in this case was 20 mg/kg. The toxicity in this case may have 

been related to the additive effects of diazinon and parathion and/or a possible interaction with chlordane. 

The diazinon dose that causes death of experimental animals depends on the form of the test compound 

(pure, technical, or formulated preparations) as well as on the animal species, sex, age, and other 

modifying factors such as diet. It is likely that earlier formulations were more toxic to experimental 

animals than current ones due to the formation of toxic breakdown products (e.g., sulfotepp) in 

unstabilized diazinon (Hayes 1982). This section summarizes lethality in animals exposed to technicalgrade diazinon. 
DIAZINON 42 

3. HEALTH EFFECTS 

Single-dose oral (gavage) studies in rats identify lethality at dose levels ranging from approximately 75 to 

600 mg (Boyd and Carsky 1969; Boyd et al. 1969; Chow and Richter 1994; Enan et al. 1982; Gaines 

1960, 1969; Harris et al. 1969). Strain-specific differences in sensitivity to the lethal effects of diazinon 

are apparent. For example, acute oral LD50 values of 108 and 76 mg/kg were reported for male and 

female Sherman rats, respectively, whereas LD50 values of 415 and 466 mg/kg were noted in separate 

studies of male Wistar rats (Boyd and Carsky 1969; Boyd et al. 1969). A single 600 mg/kg oral dose of 

diazinon MG87% (88% purity; 528 mg diazinon/kg) to Sprague-Dawley rats resulted in 2/15 and 

1/15 deaths in males and females, respectively (Chow and Richter 1994). 

Death was noted in 6 of 8 pregnant New Zealand rabbits administered diazinon orally at a dose level of 

30 mg/kg/day on gestation days 5–15 (Robens 1969). In a similar rabbit study, a dose level of 

100 mg/kg/day on gestation days 6–16 resulted in 9/22 deaths (Harris and Holson 1981). No deaths were 

reported in pregnant CD-1 rats receiving 10, 20, or 100 mg/kg/day diazinon during gestation days 6–15 

(Infurna and Arthur 1985). 

Intermediate-duration oral administration of 10 or 20 mg/kg/day diazinon dissolved in corn oil in gelatin 

capsules for 8 months to Beagle dogs (3/sex/group) resulted in mortality (1/3 of each sex at the 20 mg/kg 

dose level). Toxic signs, which were not consistent in all the dogs at a given dose, did not show a doseresponse relationship. Generally, female dogs were less sensitive to diazinon toxicity than male dogs 

(Earl et al. 1971). Daily oral administration of diazinon capsules to Hormel-Hanford miniature swine 

(3/sex) at a dose of 10 mg/kg/day resulted in the deaths of 3/3 males and 2/3 females between treatment 

days 13 and 38 of a scheduled 8-month treatment period; no deaths were observed at dose levels of 1.25, 

2.5, or 5.0 mg/kg/day (Earl et al. 1971). 

No deaths were reported in male or female Sprague-Dawley rats receiving up to 183.2 mg/kg/day 

diazinon in feed for 6 weeks or up to 212 mg/kg/day for 13 weeks (Singh 1988) or in Beagle dogs 

(4/sex/group) receiving up to 15.99 mg/kg/day diazinon from feed for 4 weeks or up to 11.6 mg/kg/day 

diazinon for 13 weeks (Barnes 1988; EPA 2000a). Survival rates were similar to controls in SpragueDawley rats receiving up to 12 mg/kg/day diazinon from feed for 98 weeks (Kirchner et al. 1991). Daily 

doses as high as 8–9 mg/kg were not lethal to male and female Beagle dogs receiving diazinon in the diet 

for 52 weeks (Rudzki et al. 1991). 

The LD50 values and doses associated with death in each species and duration category are shown in 

Table 3-2 and plotted in Figure 3-2. 
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

ACUTE EXPOSUREDeath

1

32

293 F (death) Poklis et al. 1980

293

Human once

(IN)

2

33

466 M (LD50) Boyd and Carsky 1969

466

Rat(Wistar)

once(GO)

3

34

415 M (LD50) Boyd et al. 1969

415

Rat(Wistaralbino)

once(GO)

4

403

600 (2/15 males and 1/15 Chow and Richter 1994

females died)

600

Rat(SpragueDawley)

once(GO)

5

36

300 M (LD50) Enan et al. 1982 300 Rat (white) once (GO)

6

37

108 M (LD50) Gaines 1960

108

b

76 F (LD50)

76

Rat(Sherman)

once(GO)

7

38

Gaines 1969 b 250 M (LD50)

250

285 F (LD50)

285

Rat(Sherman)

once(GO)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

8

39

294 F (LD50) Harris et al. 1969 294 Rat (albino) once (GO)

9

402

100 F (9/22 died) Harris and Holson 1981

100

Rabbit(NewZealand)

Gd 6-181 x/d(G)

10

475

30 F (6/8 died) Robens 1969

30

Rabbit(NewZealand)

Gd 5-151 x/d(C)

Systemic

11

47

Resp Klemmer et al. 1978 b 240 M (tachypnea, cyanosis)

240

509 F (tachypnea, cyanosis)

509

Human once

(IN)

Cardio

b

240 M (bradycardia,

tachycardia)

240

509 F (bradycardia,

tachycardia)

509

Hemato

b

240 M

240

509 F

509

Metab

b

240 M (metabolic acidosis)

240

509 F (metabolic acidosis)

509
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

12

48

Resp 293 F (heavily congested lungs) Poklis et al. 1980

293

Human once

(IN)

Gastro 293 F (petechial hemorrhages

throughout the stomachand gastric mucosa)

293

13

412

Hemato 600 Chow and Richter 1994

600

Rat(SpragueDawley)

once(GO)

Ocular 600 (chromodacryorrhea)

600

Bd Wt

b

150 M

150

600 F

600

300 M (25% decrease in weight

gain)

300

14

422

Bd Wt 0.21 Davies and Holub 1980

0.21 Rat (Wistar) 7 d ad lib

(F)

15

407

Bd Wt 20 F Infurna and Arthur 1985 20 100 F (5.5-9.6% decrease in maternal weight, 26-30%

decrease in feedconsumption)

100

Rat(CD-1)

Gd 6-151 x/d(G)

16

53

Hemato 4.4 M (reduced platelet count, Lox 1983

altered coagulation factoractivities)

4.4

Rat(SpragueDawley)

once(GW)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

17

54

Hemato 52 F (reduced hematocrit, Lox 1987 altered clotting factor

activities)

52

Rat(SpragueDawley)

14 dad lib(W)

Bd Wt 52 F

52

18

55

Hepatic 300 (reduced hepatic Mihara et al. 1981

cytochrome P-450,aniline hydroxylase,aminopyrineN-demethylase)

300

Rat(SpragueDawley)

once(G)

19

408

Resp 100 F Harris and Holson 1981

100

Rabbit(NewZealand)

Gd 6-181 x/d(G)

Cardio 100 F

100

Gastro 25 F

25

100 F (7/9 stomach mucosal

hemorrhage, congestionand erosion)

100

Hepatic 100 F

100

Renal 100 F

100

Bd Wt 100 F

100
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

Neurological

20

63

Klemmer et al. 1978 b 240 M (stupor, profuse

diaphoresis, coma)

240

509 F (stupor, profuse

diaphoresis, coma)

509

Human once

(IN)

21

409

293 F (petechial hemorrhages Poklis et al. 1980

throughout the brain)

293

Human once

(IN)

22

425

2.5 Chow and Richter 1994

2.5

150 (82% decrease in

erythrocyte AChE, ataxia,alterations in functionalobservation battery tests9-11 hrs post-dosing)

150

Rat(SpragueDawley)

once(GO)

23

631

Davies and Holub 1980

c 0.6 F

0.6

1 F (22% RBC AChE

inhibition)

1

Rat(Wistar)

12 dad lib(F)

24

68

0.21 Davies and Holub 1980

0.21 Rat (Wistar) 7 d ad lib

(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

25

624

2.5 F (40% RBC AChE EPA 2000a

inhibition)

2.5

300 M (clinical signs of

neurotoxicity)

300

Rat(SpragueDawley)

once(GO)

26

626

2.5 F EPA 2000a

2.5

25 F (35% RBC and brain

AChE inhibition)

25

Rat(SpragueDawley)

once(GO)

27

70

235 F (78% brain AChE Harris et al. 1969 inhibition)

235

Rat(albino)

once(GO)

28

609

50 M Moser et al. 2005 50 75 M (35% brain AChE inhibition)

75

Rat(Long- Evans)

once(GO)

29

621

15 M (30% RBC AChE Timchalk et al. 2005 inhibition)

15

60 M (>60% RBC AChE

inhibition)

60

Rat(SpragueDawley)

once(GO)

30

472

0.125 F (diarrhea, salivation, Robens 1969

incoordination)

0.125

Hamster(GoldenSyrian)

Gd 6, 7 and/or 8

1 x/d(GO)

31

411

25 F Harris and Holson 1981

25

100 F (tremors, convulsion)

100

Rabbit(NewZealand)

Gd 6-181 x/d(G)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

32

474

7 F Robens 1969

7

30 F (ataxia)

30

Rabbit(NewZealand)

Gd 5-151 x/d(C)

Reproductive

33

481

100 F Infurna and Arthur 1985 100 Rat (CD-1) Gd 6-15 1 x/d

(G)

34

491

100 F Harris and Holson 1981

100

Rabbit(NewZealand)

Gd 6-181 x/d(G)

Developmental

35

482

20 F Infurna and Arthur 1985 20 100 F (increased incidence of rudimentary ribs at T-14

in fetuses)

100

Rat(CD-1)

Gd 6-151 x/d(G)

36

73

0.25 F Robens 1969

0.25

Hamster(GoldenSyrian)

Gd 6, 7 and/or 8

1 x/d(GO)

37

490

100 F Harris and Holson 1981

100

Rabbit(NewZealand)

Gd 6-181 x/d(G)

38

74

30 F Robens 1969

30

Rabbit(NewZealand)

Gd 5-151 x/d(C)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

INTERMEDIATE EXPOSUREDeath

39

76

10 (3/3 males and 2/3 Earl et al. 1971

females died)

10

Dog(Beagle)

8 mo1 x/d(C)

40

77

10 (3/3 males and 2/3 Earl et al. 1971

females died)

10

Pig(HormelHanford)

8 mo1 x/d(C)

Systemic

41

617

Hemato 0.03 M EPA 2001 0.03 Human 28-31 d (C)

42

78

Hepatic 0.5 M (lipid vacuolation) Anthony et al. 1986

0.5

Rat(Wistar)

7-28 wk2 x/wk(G)

Bd Wt 0.5 M (10% reduction in body

weight gain)

0.5

43

483

Bd Wt 1.2 F Davies and Holub 1980

1.2 Rat (Wistar) 92 d ad lib

(F)

44

629

Bd Wt 0.4 F Davies and Holub 1980

0.4 Rat (Wistar) 42 d ad lib

(F)

45

630

Bd Wt 0.2 F Davies and Holub 1980

0.2 Rat (Wistar) 35 d ad lib

(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

46

484

Bd Wt 2.86 Davies and Holub 1980

2.86 Rat (Wistar) 30 d ad lib

(F)

47

79

Hepatic 30 M (reduced serum Enan et al. 1982 beta-lipoproteins,

increased ALT, AST,GGT, LDH)

30

Rat(white)

4 wkad lib(F)

48

611

Bd Wt 18 M EPA 1996

18

180 M (20% reduced body

weight gain)

180

Rat(SpragueDawley)

90 d(F)

49

613

Bd Wt 23 EPA 1996

23

213 (muscle fasciculations in

forefoot; 26 and 39%decreased body weightgain in males andfemales, respectively)

213

Rat(SpragueDawley)

28 d(F)

50

638

Kalender et al. 2005 

Hepatic 10 M (40% increased serum

liver enzymes,hepatocellularmitochondrial swellingand breaking up ofcristae)

10

Rat(Wistar)

7 wk1x/d(GO)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

51

637

Kalender et al. 2006 

Hemato 10 M (significantly altered

hemoglobin; hematocrit;RBC, WBC, andthrombocyte counts,mean corpuscularvolume)

10

Rat(Wistar)

7 wk1x/d(GO)

52

80

Hemato 0.18 F Lox and Davis 1983

0.18

Rat(SpragueDawley)

6 moad lib(W)

Hepatic 0.18 F

0.18

Bd Wt 0.18 F

0.18

53

639

Ogutcu et al. 2006 

Bd Wt 10 M (22% lower mean body

weight)

10

Rat(Wistar)

7 d1x/d(GO)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

54

417

Resp Singh 1988 b 168 M

168

212 F

212

Rat(SpragueDawley)

13 wk7 d/wkad lib(F)

Cardio

b

168 M

168

212 F

212

Gastro 19 M

19

b

15 F

15

b

168 M (soft stools)

168

212 F (soft stools)

212

Hemato 168 M

168

b

19 F

19

212 F (decreased hemoglobin

and hematocrit; increasein reticulocytes)

212

Hepatic 168 M

168

b

19 F

19

212 F (increase in relative and

absolute liver weight,minimal centrolobularhepatocellularhypertrophy)

212

Renal

b

168 M

168

212 F

212

Endocr

b

168 M

168

212 F

212

Ocular

b

168 M

168

212 F

212

Bd Wt

b

168 M

168

212 F

212
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

55

418

Gastro Singh 1988 b 0.2 M

0.2

9.4 F

9.4

b

8.4 M (soft stools)

8.4

182.9 F (soft stools)

182.9

Rat(SpragueDawley)

6 wk7 d/wkad lib(F)

Bd Wt 8.4

8.4

150.8 M (15% decrease in body

weight)

150.8

56

415

Resp 11.6 Barnes 1988

11.6

Dog(Beagle)

13 wk7 d/wk(F)

Cardio 11.6

11.6

Gastro 11.6

11.6

Hemato 11.6

11.6

Hepatic 11.6

11.6

Renal 11.6

11.6

Endocr

b

5.6 M

5.6

11.6 F

11.6

10.9 M (atrophy of pancreatic

acini)

10.9

Ocular 11.6

11.6

Bd Wt 5.9 M

5.9

b

0.21 F

0.21

10.9 M (34% decreased weight

gain in males)

10.9

b

5.6 F (33% decreased weight

gain in females)

5.6
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

57

416

Hemato 15.99 Barnes 1988

15.99

Dog(Beagle)

4 wk7 d/wk(F)

Hepatic 15.99

15.99

Renal 15.99

15.99

Bd Wt 0.8

0.8

14.68 M (weight loss)

14.68

15.99 F (emaciation- 20% weight

loss)

15.99
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

58

81

Cardio Earl et al. 1971 b5 M

5

20 F

20

10 M (no pericardial fat,

cord-like heart vessels)

10

Dog(Beagle)

8 mo1 x/d(C)

Gastro 5

5

10 M (duodenal wall

thickening)

10

20 (duodenal and stomach

ruptures)

20

Hemato 10 F

10

b

10 M (peripheral anemia; bone

marrow hypocellularity,increased myeloidelement content,reticulocytopenia)

10

20 F (peripheral anemia; bone

marrow hypocellularity,increased myeloidelement content,reticulocytopenia)

20

Hepatic 2.5

2.5

5 (markedly elevated

serum AST and OCT)

5

10 M (yellow, fatty liver;

parenchymal atrophy,hepatocyte dissociation;moderate cirrhosis focalnecrosis, fibrousinfiltration elevatedserum LDH)

10

Renal

b

5 M

5

10 F

10

10 M (localized chronic

nephritis, tubular atrophy,glomeruli necrosis,fibrous infiltration,elevated serum LDH)

10

Endocr 5

5

10 M (pancreatic atrophy and

interstitial fibrosis)

10

Bd Wt

b

5 M

5

10 F

10

b

10 M (significant weight loss)

10

20 F (significant weight loss)

20
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

59

82

Gastro 1.25 Earl et al. 1971

1.25

2.5 (edema and serosal

seepage in the ileum)

2.5

10 (jejunal edema, localized

mucosal erosion intointestinal muscle layerswith marked serosalseepage; duodenalulceration)

10

Pig(HormelHanford)

8 mo1 x/d(C)

Hemato 2.5

2.5

5 (occasional transient

peripheal anemia,reticulocytopenia, bonemarrow hypocellulartiy,increased myeloidelement content)

5

Hepatic 1.25 (slight inflammation,

occasional lobularcongestion)

1.25

5

5

2.5 (interlobular connective

tissue thickening,degenerativehepatocytes, hepatichemorrhage)

2.5

Immuno/ Lymphoret

60

455

Singh 1988 b 168 M

168

212 F

212

Rat(SpragueDawley)

13 wk7 d/wkad lib(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

61

495

11.6 Barnes 1988

11.6

Dog(Beagle)

13 wk7 d/wk(F)

Neurological

62

616

0.03 M EPA 2001 0.03 Human 28-31 d (C)

63

627

Davies and Holub 1980

d 0.18 F

0.18

0.27 F (20% RBC AChE

inhibition)

0.27

Rat(Wistar)

42 dad lib(F)

64

628

0.2 F Davies and Holub 1980

0.2 Rat (Wistar) 35 d ad lib

(F)

65

83

0.4 F Davies and Holub 1980

0.4 0.8 F (40% RBC AChE inhibition)

0.8

Rat(Wistar)

92 dad lib(F)

66

84

2.86 (58% RBC AChE Davies and Holub 1980

inhibition)

2.86

Rat(Wistar)

30 dad lib(F)

67

610

0.018 EPA 1996

0.018

1.8 F (greater than 79-86%

RBC AChE inhibition)

1.8

Rat(SpragueDawley)

90 d(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

68

612

0.02 EPA 1996

0.02

2.4 (38-59% RBC AChE

inhibition)

2.4

Rat(SpragueDawley)

28 d(F)

69

469

7.63 F Giknis 1989

7.63

41.43 F (tremors in 3/30 and 4/30

F0 and F1 parentalfemales)

41.43

Rat(SpragueDawley)

133 d(F)

70

635

0.17 M Mahkteshim-Agan 1989

0.17

0.19 F

0.19

1.68 M (29-35% RBC AChE

inhibition)

1.68

1.82 F (16-35% RBC AChE

inhibition)

1.82

8.6 M (>59% RBC AChE

inhibition)

8.6

9.27 F (>59% RBC AChE

inhibition)

9.27

Rat(SpragueDawley)

42 d(F)

71

454

0.2 M Singh 1988

0.2

b

8.4 M (21% RBC AChE

inhibition)

8.4

9.4 F (24% brain AChE

inhibition)

9.4

b

150.8 M (58% decrease in brain

AChE in males, 61%

decrease in females)

150.8

182.9 F (61% decrease in brain

AChE in females)

182.9

Rat(SpragueDawley)

6 wk7 d/wk(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

72

459

0.4 Singh 1988

0.4

15 M (27% RBC AChE

inhibition)

15

Rat(SpragueDawley)

13 wk7 d/wkad lib(F)

73

634

0.19 M Trutter 1991

0.19

0.2 F

0.2

1.81 M (46-55% RBC AChE

inhibition)

1.81

9.08 M (>59% RBC AChE

inhibition)

9.08

1.97 F (>59% RBC AChE

inhibition)

1.97

Rat(SpragueDawley)

42 d(F)

74

427

0.021 Barnes 1988

0.021

5.9 (31% RBC and brain

AChE inhibition)

5.9

Dog(Beagle)

13 wk7 d/wk(F)

75

464

0.082 Barnes 1988

0.082

14.68 (30% RBC AChE

inhibition, 44% brain

AChE inhibition, emesis)

14.68

Dog(Beagle)

4 wk7 d/wk(F)

76

88

5 Earl et al. 1971

5

10 (fasciculation, diarrhea,

emesis)

10

Dog(Beagle)

8 mo1 x/d(C)

77

90

1.25 Earl et al. 1971

1.25

2.5 (emesis, diarrhea,

fasciculations)

2.5

Pig(HormelHanford)

8 mo1 x/d(C)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

Reproductive

78

636

1.5 M (increased sperm Abd El-Aziz et al. 1994 abnormalities, decreased

fertility)

1.5

Rat(albino)

65 d(GW)

79

467

41.43 F Giknis 1989

41.43

Rat(SpragueDawley)

133 d(F)

80

91

0.05 Green 1970 0.05 Rat (SpragueDawley) 60 d ad lib (F)

81

457

Singh 1988 b 168 M

168

212 F

212

Rat(SpragueDawley)

13 wk7 d/wkad lib(F)

82

498

0.18 F (14% reduced maternal Spyker and Avery 1977

weight gain, 20%reduced litter size)

0.18

Mouse(Hybrid)

Gd 1-181 x/d(F)

83

450

11.6 Barnes 1988

11.6

Dog(Beagle)

13 wk7 d/wk(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

84

92

5 M Earl et al. 1971

5

10 M (testicular atrophy,

aspermatogenesis)

10

Dog(Beagle)

8 mo1 x/d(C)

Developmental

85

468

0.77 F Giknis 1989

0.77

7.63 F (decreased F1 pup

survival)

7.63

Rat(SpragueDawley)

133 d(F)

86

95

0.18 Barnett et al. 1980

0.18

9 (significantly reduced

early weight gain bypups, increased mortalityat ppd 28)

9

Mouse(Hybrid)

Gd 1-181 x/d(F)

87

98

0.18 F (neuromuscular Spyker and Avery 1977

coordination deficits,reduced litter size,delayed contact placingand sexual maturity)

0.18

Mouse(Hybrid)

Gd 1-181 x/d(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

CHRONIC EXPOSURESystemic

88

606

Resp 11 Kirchner et al. 1991

11

Rat(SpragueDawley)

98 wk or 52 wk(F)

Cardio 11

11

Gastro 11

11

Hemato 11

11

Musc/skel 11

11

Hepatic 11

11

Renal 11

11

Endocr 11

11

Dermal 11

11

Ocular 11

11

Bd Wt 11

11

Metab 11

11

89

615

Hemato 8.4 Rudzki et al. 1991

8.4

Dog(Beagle)

52 wk(F)

Bd Wt 0.015 M

0.015

4.7 M (42% depressed body

weight gain)

4.7
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

Immuno/ Lymphoret

90

602

11 Kirchner et al. 1991

11

Rat(SpragueDawley)

98 wk or 52 wk(F)

Neurological

91

605

Kirchner et al. 1991 e 0.065

0.065

5.5 (22-29% RBC and brain

AChE inhibition)

5.5

Rat(SpragueDawley)

98 wk or 52 wk(F)

92

614

0.017 Rudzki et al. 1991

0.017

4.6 (21-35% RBC AChE

inhibition)

4.6

Dog(Beagle)

52 wk(F)
a

Key to

Figure

Table 3-2 Levels of Significant Exposure to Diazinon - Oral (continued)

Species

(Strain)

LOAEL

System 

NOAEL

(mg/kg/day)

Less Serious

(mg/kg/day)

Serious

(mg/kg/day)

ReferenceChemical Form

Exposure/

Duration/

Frequency

(Route)

Reproductive

93a The number corresponds to entries in Figure 3-2.b Differences in levels of health effects and cancer effects between male and females are not indicated in Figure 3-2. Where such differences exist, only the levels most sensitive gender are presented.c Used to derive an acute-duration oral minimal risk level (MRL) of 0.006 mg/kg/day for diazinon based on significant RBC AChE inhibition in female rats by treatme92-day study. The NOAEL of 0.6 mg/kg/day was divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability)d Study results used to derive an intermediate-duration oral minimal risk level (MRL) of 0.002 mg/kg/day for diazinon, as described in detail in Appendix A. Benchmanalysis was performed on RBC AChE activity to select a point of departure, which was divided by an uncertainty factor of 100 (10 for extrapolation from animals to for human variability).e Used to derive a chronic-duration oral minimal risk level (MRL) of 0.0007 mg/kg/day for diazinon. The NOAEL of 0.065 mg/kg/day was divided by an uncertainty for extrapolation from animals to humans and 10 for human variability).AChE = acetylcholinesterase; ad lib = ad libitum; ALT = alanine aminotransferase; AST = aspartate aminotransferase; Bd Wt = body weight; (C) = capsule; Cardio = 

= day(s); Endocr = endocrine; (F) = feed; F = Female; (G) = gavage; Gastro = gastrointestinal; gd = gestational day; (GO) = gavage in oil; GGT = gamma-glutamyl-= gavage in water; Hemato = hematological; hr = hour(s); Immuno/Lymphoret = immunological/lymphoreticular; (IN) = ingestion; LD50 = lethal dose, 50% kill; LDH dehydrogenase; LOAEL = lowest-observed-adverse-effect level; Metab = Metabolic; M = male; min = minute(s); mo = month(s); Musc/skel = musculoskeletal; NOAno-observed-adverse-effect level; OCT = ornithine carbamyl transferase; ppd = post-parturition day; RBC = red blood cell; Resp = respiratory; x = time(s); (W) = driweek(s); yr = year(s)

603

11 Kirchner et al. 1991

11

Rat(SpragueDawley)

98 wk or 52 wk(F)
0.001

0.01

0.1

1

10

100

1000

Death

1

2r 3r

4r

5r

6r

7r 8r

9h

10h

Respiratory

1112

19h

Cardiovascular

11

19h

Gastrointestinal

12

19h

19h

Hematological

11

13r

16r

17r

Hepatic

18r

19h

Renal

19h

Ocular

13r

Body Weight

13r

13r

14r

15r

15r

17r

19h

Metabolic

11

Neurological

30s

2021

22r

22r

23r

23r

24r

25r

25r

26r

26r

27r

28r

28r 29r

29r

31h

31h

32h

32h

Reproductive

33r

mg/kg/day

Figure 3-2 Levels of Significant Exposure to Diazinon - Oral

Acute (≤14 days)

c-Cat

d-Dog

r-Rat

p-Pig

q-Cow

 -Humans

k-Monkey

m-Mouse

h-Rabbit

a-Sheep

f-Ferret

j-Pigeon

e-Gerbil

s-Hamster

g-Guinea Pig

n-Mink

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

 LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

 LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

 Minimal Risk Level

 for effects

 other than

 Cancer

Systemic

DIAZINON

3. HEALTH EFFECTS

66
0.001

0.01

0.1

1

10

100

1000

Reproductive

34h

Developmental

36s

35r

35r

37h

38h

mg/kg/day

Figure 3-2 Levels of Significant Exposure to Diazinon - Oral (Continued)

c-Cat

d-Dog

r-Rat

p-Pig

q-Cow

 -Humans

k-Monkey

m-Mouse

h-Rabbit

a-Sheep

f-Ferret

j-Pigeon

e-Gerbil

s-Hamster

g-Guinea Pig

n-Mink

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

 LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

 LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer

Acute (≤14 days)

 Minimal Risk Level

DIAZINON

3. HEALTH EFFECTS

67
0.001

0.01

0.1

1

10

100

1000

Death

39d 40p

Respiratory

56d

54r

Cardiovascular

56d 58d

58d

54r

Gastrointestinal

56d

58d

58d

58d

54r

54r

55r

55r 59p

59p

59p

Hematological

56d

57d

58d 58d

41

51r

52r

54r

54r

59p

59p

Hepatic

56d

57d

58d

58d

58d

42r

47r

50r

52r

54r

54r

59p

59p

59p

Renal

56d

57d

58d

58d

54r

Endocrine

56d

56d

58d

58d

54r

mg/kg/day

c-Cat

d-Dog

r-Rat

p-Pig

q-Cow

 -Humans

k-Monkey

m-Mouse

h-Rabbit

a-Sheep

f-Ferret

j-Pigeon

e-Gerbil

s-Hamster

g-Guinea Pig

n-Mink

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

 LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

 LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer

 Minimal Risk Level

Systemic

Figure 3-2 Levels of Significant Exposure to Diazinon - Oral (Continued)

Intermediate (15-364 days)

DIAZINON

3. HEALTH EFFECTS

68
0.001

0.01

0.1

1

10

100

1000

Ocular

56d

54r

Body Weight

56d

56d

57d

57d

57d

58d

58d

42r

43r

44r

45r

46r

48r

48r

49r

49r

52r

53r

54r

55r

55r

Immuno/Lymphor

61d

60r

Neurological

74d

74d

75d

75d

76d

76d

62

63r

63r

64r

65r

65r

66r

67r

67r 68r

68r

69r

69r 70r 70r

70r 70r

70r 70r

71r

71r

71r

72r

72r

73r

73r

73r 73r

73r

77p

77p

Reproductive

83d 84d

84d

82m

78r

79r

80r

81r

Developmental

86m

86m 87m

85r

85r

mg/kg/day

c-Cat

d-Dog

r-Rat

p-Pig

q-Cow

 -Humans

k-Monkey

m-Mouse

h-Rabbit

a-Sheep

f-Ferret

j-Pigeon

e-Gerbil

s-Hamster

g-Guinea Pig

n-Mink

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

 LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

 LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer

 Minimal Risk Level

Systemic

Figure 3-2 Levels of Significant Exposure to Diazinon - Oral (Continued)

Intermediate (15-364 days)

DIAZINON

3. HEALTH EFFECTS

69
0.0001

0.001

0.01

0.1

1

10

100

Respiratory

88r

Cardiovascular

88r

Gastrointestinal

88r

Hematological

89d

88r

Musculoskeletal

88r

Hepatic

88r

Renal

88r

Endocrine

88r

Dermal

88r

Ocular

88r

Body Weight

89d

89d

88r

Metabolic

88r

Immuno/Lymphor

90r

Neurological

92d

92d

91r

91r

Reproductive

93r

mg/kg/day

c-Cat

d-Dog

r-Rat

p-Pig

q-Cow

 -Humans

k-Monkey

m-Mouse

h-Rabbit

a-Sheep

f-Ferret

j-Pigeon

e-Gerbil

s-Hamster

g-Guinea Pig

n-Mink

o-Other

 Cancer Effect Level-Animals

 LOAEL, More Serious-Animals

 LOAEL, Less Serious-Animals

 NOAEL - Animals

 Cancer Effect Level-Humans

 LOAEL, More Serious-Humans

 LOAEL, Less Serious-Humans

 NOAEL - Humans

 LD50/LC50

 for effects

 other than

 Cancer

 Minimal Risk Level

Systemic

Figure 3-2 Levels of Significant Exposure to Diazinon - Oral (Continued)

Chronic (≤365 days)

DIAZINON

3. HEALTH EFFECTS

70
DIAZINON 71 

3. HEALTH EFFECTS 

3.2.2.2 Systemic Effects 

No studies were located regarding musculoskeletal, dermal, or body weight effects in humans after oral 

diazinon exposure. No information was located regarding musculoskeletal or dermal effects in animals 

after oral exposure to diazinon. Autopsy findings in human acute diazinon poisonings and laboratory 

animal lethality studies, as well as findings from other human and laboratory animal nonlethal oral 

exposures, included respiratory impairment, cardiovascular, gastrointestinal, hematological, and 

endocrine (pancreas) effects. These effects were largely derived from cholinergic responses typical of 

high-level organophosphate poisoning. 

The highest NOAEL value and all LOAEL values for systemic effects in each reliable study for each 

species and duration category are shown in Table 3-2 and plotted in Figure 3-2. 

Respiratory Effects. Respiratory distress, a typical cholinergic sign of AChE inhibition, was 

reported in several human acute poisoning incidents and laboratory animal evaluations following oral 

diazinon exposure. In humans, acute-duration oral exposure to high doses of diazinon causes pulmonary 

distress with signs that include congested respiratory tract, copious airway secretions, and pulmonary 

edema (Balani et al. 1968; Hata et al. 1986; Kabrawala et al. 1965). An 18% incidence of pulmonary 

edema was found in diazinon-poisoned patients (Limaye 1966; Shankar 1967). An autopsy report of a 

diazinon-poisoned 54-year-old female suicide victim described heavy and congested (edematous) lungs 

(Poklis et al. 1980). Tachypnea and cyanosis were observed in a male who intentionally ingested 

240 mg/kg diazinon and in a female who ingested 509 mg/kg (Klemmer et al. 1978). Diazinon treatment 

also resulted in signs of respiratory effects in laboratory animals. Single oral diazinon doses of 50– 

700 mg/kg to rats resulted in respiratory distress from pulmonary inflammation, vascular congestion, 

venous stasis, and occasional extensive pneumonitis. Death generally resulted from respiratory failure 

that was usually preceded by coma (Boyd and Carsky 1969). Dyspnea was observed in male SpragueDawley rats given a single gavage dose of 264 mg/kg diazinon and impaired respiration was observed in 

females receiving a dose of 528 mg/kg (Chow and Richter 1994). 

No gross or histological evidence of treatment-related damage to the lungs was observed in New Zealand 

rabbit dams receiving up to 100 mg/kg/day diazinon during gestation days 6–18 (Harris and Holson 

1981), in male or female Sprague-Dawley rats receiving up to 212 mg/kg/day diazinon from feed for 

13 weeks (Singh 1988) or up to 12 mg/kg/day for 98 weeks (Kirchner et al. 1991), or in male or female 

Beagle dogs receiving up to 11.6 mg/kg/day diazinon for 13 weeks (Barnes 1988). 
DIAZINON 72 

3. HEALTH EFFECTS 

Cardiovascular Effects. Acute-duration oral, lethal human exposure to diazinon resulted in 

extensive congestion of the heart and blood vessels as reported in a summary of autopsy findings of 

76 cases of acute diazinon poisoning which described cardiovascular signs that included: livid, congested 

face; soft flabby heart with conspicuous vasculature on the pericardium and epicardium; occasional and 

scattered petechial/ecchymotic hemorrhage; and cloudy swelling and hyperemia (upon histopathological 

examination) (Limaye 1966). In a case study of 25 attempted suicides by diazinon ingestion, some 

patients showed hypertension and peripheral circulatory failure (Kabrawala et al. 1965). Other 

cardiovascular signs reported after acute oral exposure to high doses of diazinon in humans include 

tachycardia (Kabrawala et al. 1965; Klemmer et al. 1978; Shankar 1967), hypertension (Balani et al. 

1968; Hata et al. 1986), and bradycardia (Hata et al. 1986; Klemmer et al. 1978). 

One male dog given 10 mg/kg/day diazinon for 8 months exhibited an absence of pericardial fat on the 

heart, as well as a cord-like appearance of the heart vessels (Earl et al. 1971). Two other dogs, given 

10 or 20 mg/kg/day diazinon, exhibited markedly elevated serum lactate dehydrogenase (LDH). This is a 

nonspecific response that may be suggestive of either cardiac or skeletal muscle damage or some other 

unknown pathology. Pallor was reported in male Sprague-Dawley rats receiving a single oral dose of 

132 mg/kg diazinon (Chow and Richter 1994). Oral administration of 10 mg/kg/day diazinon to rats for 

7 weeks resulted in significantly increased malondialdehyde levels in heart tissue and histopathologic 

evidence of vacuolization and swelling of mitochondria in myocardial cells (Ogutcu et al. 2006). The 

biological significance of these results is uncertain because the diazinon-treated rats exhibited 22% lower 

mean body weight than controls. 

No gross or histological evidence of treatment-related damage to the heart was seen in New Zealand 

rabbit dams receiving up to 100 mg/kg/day diazinon during gestation days 6–18 (Harris and Holson 

1981), in male or female Sprague-Dawley rats receiving up to 212 mg/kg/day diazinon in feed for 

13 weeks (Singh 1988) or up to 12 mg/kg/day diazinon in feed for 98 weeks (Kirchner et al. 1991), or in 

male or female Beagle dogs receiving up to 11.6 mg/kg/day diazinon for 13 weeks (Barnes 1988). 

Gastrointestinal Effects. A summary of autopsy findings from 76 cases of acute diazinon poisoning 

describes gastrointestinal signs that include: dark, blood-stained stomach contents; congested stomach 

mucosa with submucosal petechial hemorrhage; and occasional erosion and ulceration (Limaye 1966). 

Petechial hemorrhages throughout the stomach and gastric mucosa were revealed in the autopsy report of 

a diazinon-poisoned 54-year-old female suicide victim who had ingested an estimated 293 mg/kg 
DIAZINON 73 

3. HEALTH EFFECTS 

diazinon (Poklis et al. 1980). Other signs of gastrointestinal toxicity seen in humans after acute exposure 

to high doses of diazinon include nausea, diarrhea and vomiting (Balani et al. 1968; Klemmer et al. 1978), 

and abdominal pain (Balani et al. 1968). A 16-year-old female who drank an estimated 1.5 mg/kg of a 

diazinon formulation (Tik-20) developed pancreatitis after being treated for cholinergic manifestations. 

The pancreatic effects may well have been secondary to the diazinon-induced cholinergic manifestations 

(Dagli et al. 1981). Acute pancreatitis was also found in two children poisoned with diazinon (Weizman 

and Sofer 1992). 

In male albino Wistar rats exposed to acute lethal doses of diazinon, lamina propria of the small intestine 

were congested, and occasional small areas of hemorrhage and necrosis at the mouth of gastric glands 

were observed. The digestive tract was dehydrated with small increases in organ wet weight except for 

the cecum, whose wet weight declined approximately 32%. Other effects included pyloric stomach 

ulceration and inflammation of the small intestine and cecum (Boyd and Carsky 1969). Similar effects 

were seen in an intermediate exposure of Beagle dogs given diazinon orally for 8 months. Marked 

edematous thickening of the intestinal wall was observed in 5/6 dogs at the lethal 20 mg/kg/day dose with 

one developing a duodenal rupture and subsequent peritonitis, and another rupture of the pyloric portion 

of the stomach. At the 10 mg/kg/day dose, the duodenal wall thickening was observed only in the solitary 

male dog that exhibited weight loss and other gross pathological changes. Elevated serum amylase levels 

were also found in dogs of both sexes at the 10 mg/kg/day dose, but apparently did not correlate with 

observable pancreatic pathology with the exception of one male dog. Either congestion or hemorrhage 

(or both) of the small intestines and colon was present in varying degrees among dogs receiving 5– 

100 mg/kg/day diazinon for various time periods in a preliminary dose-range study. Apparently, many of 

the effects described were not found uniformly in all of the dogs at a given dose, and a clear doseresponse relationship was not always present (Earl et al. 1971). Treatment of Hormel-Hanford miniature 

pigs with daily diazinon doses of 1.25–10 mg/kg/day for 8 months resulted in injury to the gastrointestinal 

tract. At 10 mg/kg/day, 4/5 pigs which died had edematous thickening of the walls of the jejunum, 

3/5 had ulcer formation in the duodenum, and one had localized mucosal erosion into the muscular layer 

with serosal seepage throughout the intestines. One pig at each of the 5.0 and 2.5 mg/kg/day dose levels 

displayed edema of the jejunum; serosal seepage of the ileum was noted at the lower dose. 

Histopathologically, slight thickening of the serosa, occasional focal hyperemia, and outer muscle 

hemorrhaging were observed in the intestines of swine exposed to 10 or 5 mg/kg/day diazinon. 

Abdominal ascites that clotted on exposure to air was reported without further description for one pig 

exposed to 2.5 mg/kg/day. This animal also suffered intestinal edema and serosal seepage, liver toxicity, 

and death on day 141 (Earl et al. 1971). 
DIAZINON 74 

3. HEALTH EFFECTS 

Stomach mucosal hemorrhage, congestion, and erosion were observed in 7/9 New Zealand rabbit dams 

that died while receiving 100 mg/kg/day diazinon during gestation days 6–18 (Harris and Holson 1981). 

No signs of gastrointestinal toxicity were seen in dams treated at 7 or 25 mg/kg/day. Diarrhea was 

observed in male Sprague-Dawley rats receiving a single oral dose of 528 mg/kg diazinon, but not in 

females receiving the same dose (Chow and Richter 1994). Soft stools were observed in male SpragueDawley rats receiving 8.4 mg/kg/day diazinon from feed for 6 weeks and in females receiving 

183.2 mg/kg/day (Singh 1988), as well as males receiving 168 mg/kg/day diazinon from feed for 

13 weeks and in females receiving 212 mg/kg/day (Singh 1988). Emesis was reported in male and female 

Beagle dogs receiving 14.68 mg/kg/day diazinon from feed for 4 weeks (EPA 2000a). Emesis, bloody 

feces, and diarrhea were observed in Beagle dogs receiving up to 11.6 mg/kg/day diazinon from feed for 

13 weeks (Barnes 1988). These signs were not dose-related and were considered by the authors to be 

unrelated to treatment. 

No histological evidence of treatment-related damage to gastrointestinal tissues was found in SpragueDawley rats receiving up to 12 mg/kg/day diazinon for 98 weeks (Kirchner et al. 1991), or up to 

212 mg/kg/day for 13 weeks (Singh 1988). Similar results were reported in Beagle dogs receiving up to 

11.6 mg/kg/day diazinon over a 13-week period (Barnes 1988). 

Hematological Effects. A report on five individuals (three males, two females) who intentionally 

ingested 60–180 mL of 25% diazinon solution (estimated to deliver a dose of 240–400 mg/kg for males 

and 509–986 mg/kg for females) found that leucocyte counts (3,700, 95% polymorphonuclear), 

hemoglobin (16.3 g), and hematocrit (47) were all within normal ranges (Klemmer et al. 1978). 

Diazinon-induced hematological effects have been reported in several animal studies. The hematological 

effects of a single oral dose of 4.4 mg/kg diazinon were studied in Sprague-Dawley rats 2 hours after 

treatment. Although diazinon exposure did not significantly alter hematocrit or factor VII activity, 

platelet count was significantly (p<0.05) reduced when compared with pre-exposure values 

(694x103

/mm3 as compared to 856x103/mm3). Similarly, small (6–14%) but significant (p<0.05) changes 

were observed in activities of the remaining clotting factors; fibrinogen activity was reduced, while 

prothrombin, partial thromboplastin, factor II, factor V, and factor X activities were increased. Since 

fibrinogen and factors II, V, VII, and X are synthesized in the liver, the associated alterations may reflect 

hepatic effects of diazinon exposure. The data indicate an overall diazinon-induced condition of hypercoagulability that, considered together with observations from other studies of various haemorrhagia, may 
DIAZINON 75 

3. HEALTH EFFECTS 

suggest that diazinon might affect hemostasis in general (Lox 1983). Other rats received 52 mg/kg/day 

diazinon from drinking water for 14 days and were monitored for hematocrit and platelet count, and 

various clotting factor times (prothrombin, partial thromboplastin, fibrinogen, and factors II, V, VII, X, 

and XII). Immediately after treatment, increased times for prothrombin, partial thromboplastin, and 

fibrinogen suggest an overall state of hypocoagulability, despite no consistent pattern for the other factors 

and parameters (decreased for VII and XII, no changes for II, V, VII, and X, or in hematocrit and platelet 

count). One week after treatment, partial thromboplastin time was shortened (indicating intrinsic pathway 

activation), as were the clotting times for factors VIII, X, and XII, although that for II was lengthened. 

Overall, this suggests a hypercoagulability of the intrinsic pathway. Also, hematocrit was decreased. 

These alterations may reflect a time-course in hepatic damage (at least for II, VII, X, and fibrinogen 

which are of liver origin) (Lox 1987). A group of 24 rats receiving approximately 0.18 mg/kg/day 

diazinon from drinking water for 6 months showed no changes compared with controls in the clotting 

activities associated with prothrombin, partial thromboplastin, fibrinogen, or the coagulation factors II, V, 

VII, and X (Lox and Davis 1983). Significantly (p<0.01) decreased hematocrit, hemoglobin, and RBC 

and thrombocyte counts, and increased white blood cell (WBC) count and mean corpuscular volume were 

observed in rats orally administered 10 mg/kg/day diazinon for 7 weeks (Kalender et al. 2006). One of 

six dogs treated with 20 mg/kg/day diazinon exhibited marked reductions in peripheral red blood cells, 

hematocrit, and hemoglobin. All six dogs displayed greatly elevated myeloid/erythroid (M/E) bone 

marrow ratios (114–183/1 as opposed to 1.1–1.9/1 for controls) with slight to moderate bone marrow 

hypocellularity, and a pronounced reticulocytopenia in two dogs (one male, one female) (Earl et al. 1971). 

Three of six Hormel-Hanford miniature pigs orally administered 5.0 mg/kg/day diazinon showed a 

transient drop in red blood cells, hematocrit, and hemoglobin content, but no indication of peripheral 

anemia. No peripheral anemia was present in any of five pigs in the 10 mg/kg/day group, but all the pigs 

exhibited reticulocytopenia, with three displaying elevated M/E ratios (Earl et al. 1971). 

Hematological parameters were normal in Sprague-Dawley rats (10–15/sex/group) receiving a single oral 

gavage dose of up to 528 mg/kg diazinon and examined 14 days later (Chow and Richter 1994). 

Decreased hemoglobin and hematocrit along with an increase in reticulocytes were observed in female 

Sprague-Dawley rats receiving 212 mg/kg/day diazinon from feed for 13 weeks. Hematological 

parameters were normal in female rats receiving up to 19 mg/kg/day and in males receiving up to 

168 mg/kg/day (Singh 1988). No changes in hematological parameters were observed in Beagle dogs 

receiving up to 11.6 mg/kg/day diazinon from feed for 13 weeks (Barnes 1988) or up to 9 mg/kg/day for 

52 weeks (Rudzki et al. 1991), or in Sprague-Dawley rats receiving up to 12 mg/kg/day for 98 weeks 

(Kirchner et al. 1991). 
DIAZINON 76 

3. HEALTH EFFECTS 

Hepatic Effects. A summary of autopsy reports from 76 human diazinon poisonings includes findings 

of congested liver (Limaye 1966). 

In laboratory animals, single oral doses of 300 mg/kg diazinon given to male and female Sprague-Dawley 

rats were followed by significant (p<0.001–0.05) reductions in hepatic microsomal cytochrome P-450 

content and aniline hydroxylase and aminopyrine N-demethylase activities, especially during the first 

24 hours. These effects largely disappeared within 72 hours to 2 weeks, with values often exceeding 

those of controls. No significant changes in mitochondrial respiratory function (respiratory control ratio, 

ADP/O ratio, and ATPase activity) were observed (Mihara et al. 1981). Oral administration of 

30 mg/kg/day diazinon for 4 weeks to white male rats reduced serum beta-lipoprotein, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase. Although elevated levels of 

these transaminases are generally associated with liver pathology, the toxicological implications of the 

significant reduction (13–67%) of these liver enzymes and its relevance to diazinon poisoning are unclear 

(Enan et al. 1982). In another rat study, normal lobular architecture was maintained in the livers, but 

small lipid droplets were observed in some hepatocytes after 7 weeks. In this study, male Wistar rats 

were treated with oral doses of 0.5 mg/kg twice a week for 28 weeks. Lipid accumulation became 

progressively more severe from 14 to over 28 weeks, but no cellular necrosis was observed (at least after 

14 weeks). This lipid accumulation could result from disturbed metabolism in the hepatocellular rough 

endoplasmic reticulum, increased lipid mobilization from peripheral tissue, or impaired lipoprotein 

release from liver cells. Electron microscopic examination revealed fat droplets near mitochondria, with 

abundant rough and smooth endoplasmic reticulum, mitochondria, and glycogen present in liver cells 

from both treated and control rats. No changes were observed in hepatocyte nuclei or nucleoli. But in 

another study, groups of rats exposed to approximately 0.18 mg/kg/day diazinon in the drinking water for 

6 months exhibited no adverse effects on the liver as determined by histopathological examination (Lox 

and Davis 1983). The autopsy of a male Beagle dog that died from exposure to 10 mg/kg/day diazinon 

for 8 months revealed fatty liver, markedly elevated serum aspartate aminotransferase, serum lactate 

dehydrogenase, and ornithine carbamyl transferase, parenchymal atrophy, and hepatocyte dissociation 

(Earl et al. 1971). Female dogs treated with 20 mg/kg/day diazinon showed moderate cirrhosis, focal 

necrosis, fibrous infiltration, and hepatocyte dissociation. In another study, hepatic effects noted in pigs 

treated with 1.25 mg/kg/day diazinon for 8 months included slight inflammation and occasional lobular 

congestion with degenerative hepatocytes (Earl et al. 1971). Animals treated with a daily dose of 

2.5 mg/kg exhibited interlobular connective tissue thickening and lobular congestion. In addition to the 

noted hepatic effects, all livers from swine exposed to 10 mg/kg/day were very firm to the touch and hard 
DIAZINON 77 

3. HEALTH EFFECTS 

to cut, and one liver from a pig treated with 5 mg/kg/day diazinon was described as “friable” and very 

gritty, with focal subscapular hemorrhages. 

An increase in relative and absolute liver weight was observed in female Sprague-Dawley rats receiving 

212 mg/kg/day diazinon from feed for 13 weeks (Singh 1988). This was accompanied by histological 

evidence of minimal centrilobular hepatocellular hypertrophy. Kalender et al. (2005) noted serum 

biochemical and hepatocellular structural changes in male Wistar rats administered diazinon by gavage at 

a dose of 10 mg/kg/day for 7 weeks. The observed effects included significantly (p<0.01) increased 

hepatic enzyme activity (ALP, ALB, AST), total protein, and albumin levels, increased total cholesterol 

and decreased low density lipoprotein cholesterol and triglycerides, and histopathologic evidence of 

pronounced mitochondrial swelling, structural changes in mitochondrial cristae, swelling of endoplasmic 

reticulum, and changes in the density of nuclear chromatin. 

No gross or histological evidence of treatment-related damage to the liver after oral exposure to diazinon 

was observed in Sprague-Dawley rats receiving up to 12 mg/kg/day diazinon for 98 weeks (Kirchner et 

al. 1991), in New Zealand rabbit dams receiving up to 100 mg/kg/day diazinon during gestation days 6– 

18 (Harris and Holson 1981), or in Beagle dogs (4/sex/group) receiving up to 11.6 mg/kg/day diazinon 

for 13 weeks (Barnes 1988) or up to 9 mg/kg/day diazinon for 52 weeks (Rudzki et al. 1991). 

Renal Effects. A summary of autopsy findings in 76 cases of acute diazinon poisoning described 

renal signs that included congested kidney and rare renal tract and kidney cortex submucosal petechiae 

and ecchymoses (Limaye 1966). 

A single oral dose of diazinon ranging from 50 to 700 mg/kg produced dose-dependent renal effects in 

rats. These effects were observed to varying degrees during the first 72 hours following diazinon 

exposure. Substituting a purified protein diet for Purina lab chow resulted in additional oliguria, in 

aciduria rather than alkalinuria, and in somewhat more severe hematuria. A low-protein purified diet 

exacerbated the aciduria. Other renal effects included tubular swelling, capillary loop congestion, 

glycosuria, proteinuria, and hematuria (Boyd and Carsky 1969). Beagle dogs treated with 5 mg/kg for 

8 months showed kidney corticomedullary congestion and capsular adhesions. One dog that died from 

exposure to 10 mg/kg/day diazinon exhibited localized chronic nephritis, tubular atrophy, and glomeruli 

with fibrous infiltrations (Earl et al. 1971). 
DIAZINON 78 

3. HEALTH EFFECTS 

No gross or histological evidence of treatment-related damage to the kidneys after oral exposure to 

diazinon was observed in New Zealand rabbit dams receiving up to 100 mg/kg/day diazinon during 

gestation days 6–18 (Harris and Holson 1981), in Sprague-Dawley rats receiving up to 212 mg/kg/day 

diazinon in feed for 13 weeks (Singh 1988), or up to 12 mg/kg/day for 98 weeks (Kirchner et al. 1991), or 

in Beagle dogs receiving up to 11.6 mg/kg/day diazinon for 13 weeks (Barnes 1988) or up to 9 mg/kg/day 

for 52 weeks (Rudzki et al. 1991). 

Endocrine Effects. A 16-year-old female who drank an estimated 10 mL of a diazinon formulation 

(Tik-20) developed pancreatitis after being treated for cholinergic manifestations. A dose could not be 

calculated because the concentration of diazinon in the liquid was not reported. The pancreatic effects 

may well have been secondary to the diazinon-induced cholinergic manifestations (Dagli et al. 1981). 

Acute pancreatitis was also found in two children poisoned with diazinon (Weizman and Sofer 1992). 

Pancreatic atrophy and interstitial fibrosis was reported in male Beagle dogs receiving 10 mg/kg/day 

diazinon in capsule form for 8 months (Earl et al. 1971), but not in females. Atrophy of the pancreatic 

acini was observed in male Beagle dogs receiving 10.9 mg/kg/day of diazinon from feed for 13 weeks, 

but not in similarly treated female dogs receiving 11.6 mg/kg/day diazinon (Barnes 1988). 

No gross or histological evidence of treatment-related damage to the adrenals after oral exposure to 

diazinon was observed in Sprague-Dawley rats (15/sex/group) receiving up to 212 mg/kg/day diazinon 

from feed for 13 weeks (Singh 1988). No gross or histological evidence of treatment-related damage to 

the adrenals, pituitary, or thyroid glands was observed in Sprague-Dawley rats receiving up to 

12 mg/kg/day diazinon for 98 weeks (Kirchner et al. 1991), or in Beagle dogs receiving up to 

11.6 mg/kg/day diazinon for 13 weeks (Barnes 1988). 

Ocular Effects. Miosis has been reported in humans admitted to the hospital with diazinon poisoning 

(Shankar 1967). 

Exophthalmos has been reported in male Wistar rats receiving single doses of 50–700 mg/kg diazinon by 

gavage (Boyd et al. 1969; Boyd and Carsky 1969). No ocular effects were reported in Sprague-Dawley 

rats receiving a single dose of up to 528 mg/kg diazinon and observed for a further 14 days (Chow and 

Richter 1994); in Sprague-Dawley rats receiving up to 212 mg/kg/day diazinon from feed for 13 weeks 

(Singh 1988), or up to 12 mg/kg/day for 98 weeks (Kirchner et al. 1991); or in Beagle dogs receiving up 
DIAZINON 79 

3. HEALTH EFFECTS 

to 11.6 mg/kg/day diazinon from feed for 13 weeks (Barnes 1988) or up to 9 mg/kg/day for 52 weeks 

(Rudzki et al. 1991). 

Body Weight Effects. Dogs administered diazinon by the oral route in an intermediate-duration 

study exhibited significant weight loss at doses >10 mg/kg/day. Reduced food intake, diarrhea, and 

emesis were also reported in this study (Earl et al. 1971). The body weight effects are probably a result of 

the emesis, diarrhea, generalized emaciation, and anorexia reported in the study. Significant (p<0.05) 

reductions in body weight gain were also found in male Wistar rats treated orally with 0.5 mg/kg diazinon 

twice a week for 28 weeks. Body weight was significantly greater in 28-week controls (602.5 g) than in 

diazinon-treated rats (542.0 g) despite the absence of significant deviations in average daily food intake 

(Anthony et al. 1986). Other male Wistar rats receiving 10 mg/kg/day diazinon by oral gavage for 

7 weeks exhibited 22% lower terminal mean body weight than vehicle controls (Ogutcu et al. 2006). 

Significant reductions in maternal weight (5.5–9.6%) and weight gain were seen in CD-1 rats receiving 

100 mg/kg/day diazinon by gavage during gestation days 6–15 (Infurna and Arthur 1985). This effect 

was most striking during gestation days 6–10 when the 100 mg/kg/day group lost on average 11 grams 

while the control group gained 14 grams. A 25% decrease in body weight gain was seen in male 

Sprague-Dawley rats receiving a single gavage dose of 264 mg/kg diazinon and observed for a period of 

14 days (Chow and Richter 1994). Male Sprague-Dawley rats receiving 150.8 mg/kg/day diazinon from 

feed had a 15% decrease in body weight compared to controls after 6 weeks (Singh 1988). Weight gain 

in females was unaffected. Emaciation was observed in female Beagle dogs receiving 15.99 mg/kg/day 

diazinon from feed for 4 weeks; less severe, but still significant, weight loss was observed in male Beagle 

dogs receiving 14.68 mg/kg/day (EPA 2000a). Significantly reduced rates of body weight gain were 

observed in male Beagle dogs receiving 10.9 mg/kg/day diazinon from feed (34%) and in females 

receiving 5.6 mg/kg/day (33%) for 13 weeks (Barnes 1988). Reduced body weight gain was also noted in 

male Beagle dogs receiving 4.7 mg/kg/day diazinon for 52 weeks (Rudzki et al. 1991). A clear doseresponse for body weight gain was not detected in similarly-treated female dogs, but the highest dose 

level (9.1 mg/kg/day) resulted in a 19% reduction in body weight gain (Rudzki et al. 1991). 

No effects on body weight were observed in New Zealand rabbit dams receiving 100 mg/kg/day diazinon 

by gavage during gestation days 6–18 (Harris and Holson 1981). No effect on body weight was observed 

in female Wistar rats receiving up to 1.35 mg/kg/day from feed for 92 days (Davies and Holub 1980a); in 

Wistar rats of both sexes receiving 0.21 mg/kg/day from feed for 7 days or 2.86 mg/kg/day for 30 days 

(Davies and Holub 1980b); and in Sprague-Dawley rats receiving up to 212 mg/kg/day from feed for 
DIAZINON 80 

3. HEALTH EFFECTS 

13 weeks (Singh 1988), 0.18 mg/kg/day from drinking water for 6 months (Lox and Davis 1983), or up to 

12 mg/kg/day for 98 weeks (Kirchner et al. 1991). No effects on body weight were observed in male 

Beagle dogs receiving 5 mg/kg/day and females receiving 10 mg/kg/day in capsules daily for 8 months 

(Earl et al. 1971). 

Metabolic Effects. Metabolic acidosis was reported in patients who had ingested 240–916 mg/kg 

diazinon (Klemmer et al. 1978). 

No effect on blood electrolytes was observed in Sprague-Dawley rats receiving up to 12 mg/kg/day 

diazinon orally for 98 weeks (Kirchner et al. 1991). 

3.2.2.3 Immunological and Lymphoreticular Effects 

A summary of autopsy findings of 76 cases of acute diazinon poisoning described signs that included 

congested spleen (Limaye 1966). 

Single oral administration of 50–700 mg/kg diazinon to male albino Wistar rats resulted in a reduction in 

spleen weight (35%) and splenic red pulp contraction, reduced thymus weight, and thymic atrophy 

ranging from minor to near total loss of thymocytes (Boyd and Carsky 1969). In an intermediate-duration 

study of dogs administrated oral doses of 2.5–20 mg/kg/day diazinon, the spleen of an anorexic and 

emaciated male dog given 10 mg/kg/day diazinon was markedly shrunken and pale in appearance with 

moderate atrophy in the splenic pulp prior to death after 232 days of exposure (Earl et al. 1971). The 

splenic atrophy reported in this study may be a result of the generalized emaciated condition of the dog 

due to diarrhea, emesis, and anorexia, as reported in the study. 

Repeated oral administration of diazinon to mice (50 mg/kg/day for 30 days) resulted in significantly 

increased levels of interleukin-10 in splenic lymphocyte subpopulations CD4+, CD8+, and B cells and 

significantly decreased levels of interferon-γ in B cells (Alluwaimi and Hussein 2007). These results 

indicate a diazinon-induced effect on cytokines involved in the regulation of cellular and humoral 

responses. 

No gross or histological evidence of treatment-related damage to the spleen or thymus was observed in 

Sprague-Dawley rats receiving up to 212 mg/kg/day diazinon from feed for 13 weeks (Singh 1988), or up 
DIAZINON 81 

3. HEALTH EFFECTS 

to 12 mg/kg/day for 98 weeks (Kirchner et al. 1991), or in Beagle dogs receiving up to 11.6 mg/kg/day 

diazinon for 13 weeks (Barnes 1988) or up to 9 mg/kg/day for 52 weeks (Rudzki et al. 1991). 

The highest NOAEL values and all reliable LOAEL values for immunological and lymphoreticular 

effects in each species and duration category are presented in Table 3-2 and plotted in Figure 3-2. 

3.2.2.4 Neurological Effects 

In humans, typical signs and symptoms of cholinesterase poisoning have been widely reported following 

intentional or accidental ingestion of diazinon (Balani et al. 1968; Bichile et al. 1983; Dagli et al. 1981; 

Hata et al. 1986; Jaksa and Palahniuk 1995; Kabrawala et al. 1965; Klemmer et al. 1978; Poklis et al. 

1980; Reichert et al. 1977; Wadia et al. 1974; Wedin et al. 1984). Reported signs and symptoms of 

diazinon poisoning included vomiting, abdominal pain, giddiness, excessive sweating, diarrhea, 

brachycardia, tachycardia, muscle fasciculations, hyperreflexia, restlessness, constricted pupils, miosis, 

clonus, weakness, bronchospasm, stupor, and coma. In a few of these reports, oral diazinon dose 

estimates ranged from approximately 200 to 1,000 mg/kg (Klemmer et al. 1978; Poklis et al. 1980). In 

one case, a neurological examination showed lateral nystagmus and gross incoordination (Bichile et al. 

1983). In some cases, measurements of plasma and blood ChE activities indicated significant reduction 

(Klemmer et al. 1978). Diazinon-poisoned patients responded well to ChE-reactivating agents such as 

atropine and pralidoxime (Dagli et al. 1981; Kamha et al. 2005; Klemmer et al. 1978). Autopsy findings 

in patients who died following acute diazinon poisoning include spinal hemorrhage and congestion, 

swelling, and hemorrhage of the brain (Limaye 1966; Poklis et al. 1980). 

As discussed in detail in Section 3.5. Mechanisms of Action, diazinon poisoning is characterized by the 

inhibition of AChE in the central and peripheral nervous system. AChE is also present in erythrocytes 

(RBCs). In in vitro assays, roughly equivalent inhibition of AChE in RBCs and neural tissues is produced 

by a given concentration of organophosphates such as diazinon (Iyaniwura 1991). Therefore, inhibition 

of RBC AChE can be used as a surrogate indicator of the extent of inhibition of neural AChE. Blood 

plasma also contains other cholinesterases. In humans, plasma ChE is almost exclusive composed of 

butyrylcholinesterase, which is capable of hydrolyzing acetylcholine and butyrylcholine in vitro. The 

in vivo substrate of plasma ChE is unknown. In general, plasma ChE can be inhibited by diazinon at 

lower levels of exposure than those required to inhibit neural or RBC AChE (Barnes 1988; Singh 1988). 

Plasma ChE activity is considered to be a sensitive indicator of exposure to organophosphates such as 

diazinon, but not an indicator of a neurologic effect. 
DIAZINON 82 

3. HEALTH EFFECTS 

Results of a few controlled studies of human subjects were submitted to the U.S. EPA Office of 

Prevention, Pesticides and Toxic Substances (OPPT) (EPA 2001). Inhibition of plasma ChE was 

observed following ingestion of gelatin capsules containing diazinon (EPA 2001). Single doses of 0.12 or 

0.2 mg diazinon/kg (purity not specified in the data evaluation record available to ATSDR) resulted in 

approximately 40 and 60 % inhibition of plasma ChE, respectively. Approximately 90% inhibition was 

observed in a single volunteer given a 0.3 mg/kg dose of diazinon. Maximum inhibition of plasma ChE 

in these volunteers was achieved between 4 and 8 hours postdosing. Recovery began 24 hours 

postdosing, but was only about 70% complete in some volunteers at 15 days postdosing. Although 

plasma ChE inhibition was noted, RBC AChE was not inhibited and there were no clinical signs of 

treatment-related neurotoxicity even at the highest dose tested. 

In a repeated-dose oral investigation, four male volunteers were administered 0.03 mg diazinon/kg/day 

(purity 99.5%) in gelatin capsules at breakfast for 28–31 days (EPA 2001). Maximum plasma ChE 

inhibition reached 47–56% near the end of the treatment period. Recovery was 86–92% by day 28 

following the cessation of treatment. There was no apparent treatment-related effect on RBC AChE 

activity. 

In another controlled human study, diazinon (purity not specified in the EPA summary review available to 

ATSDR) was administered to male volunteers (apparently three males per dose level) at doses of 0.02, 

0.025, or 0.05 mg/kg/day (EPA 2001). There was no indication of treatment-related effects on plasma 

ChE activity following dosing at 0.02 mg/kg for up to 37 days. At 0.025 mg/kg/day, a 23% plasma ChE 

inhibition was noted from day 12 through day 43. The 0.05 mg/kg/day dose level resulted in 40% plasma 

ChE inhibition after 5 days of treatment. No treatment-related effects on RBC AChE activity were seen 

at any of the dose levels. 

Results of animal studies support the findings in humans of diazinon-induced neurotoxicity. For 

example, single oral gavage doses in the range of 75–300 mg/kg, administered to rats (Boyd and Carsky 

1969; Chow and Richter 1994; EPA 1996, 2000a; Moser 1995; Moser et al. 2005) or rabbits (Harris and 

Holson 1981), resulted in signs of cholinergic stimulation such as muscle fasciculations, tremors, miosis, 

lacrimation, diarrhea, gait changes, and hypoactivity. Robens (1969) reported cholinergic signs in 

pregnant rabbits administered technical diazinon (purity unspecified) by daily oral gavage on gestation 

days 5–15 at a dose level of 30 mg/kg/day and in hamsters dosed on gestation days 6–8 at a level of 

0.125 mg/kg/day. However, no supporting studies were located to confirm clinical signs of diazinon-
DIAZINON 83 

3. HEALTH EFFECTS 

induced neurotoxicity at these relatively low acute dose levels. In a 92-day feeding study in rats, daily 

doses of 168 mg/kg/day (females) or 212 mg/kg/day (males) resulted in signs of cholinergic stimulation, 

but doses of 15 and 19 mg/kg/day, respectively, did not elicit clinical signs of neurotoxicity (Singh 1988). 

Cholinergic signs (muscle fasciculations, emesis, and/or diarrhea) were reported in 3/3 male and 

3/3 female dogs administered diazinon in the food at a concentration resulting in a calculated dose of 

20 mg diazinon/kg/day for 8 months; only 1/6 dogs in the next lower dose group (10 mg/kg/day) 

exhibited cholinergic signs (Earl et al. 1971). Similarly-treated swine exhibited clinical signs of 

neurotoxicity at a dose level of 10 mg/kg/day, but not at 5 mg/kg/day (Earl et al. 1971). In a chronicduration rat study, 98 weeks of diazinon treatment in the food resulted in no treatment-related clinical 

signs of neurotoxicity at doses up to approximately 12 mg/kg/day (the highest exposure level) (Kirchner 

et al. 1991). No clinical signs of neurotoxicity were observed in dogs administered diazinon in the diet 

for up to 52 weeks at concentrations resulting in doses as high as 9 mg/kg/day (Kirchner et al. 1991). 

In an extensive study of diazinon-induced neurological effects following single oral dosing, SpragueDawley rats of both sexes were treated by gavage with diazinon (88% purity) at doses of 0, 2.5, 150, 300, 

or 600 mg/kg and observed in a functional observation battery (FOB) of tests (Chow and Richter 1994). 

Signs of neurotoxicity were seen only at the expected time of peak effect (9–11 hours postdosing) and not 

at weeks 1 or 2 posttreatment. At the 150 mg/kg dose level, decreased rearing in a 2-minute period and 

suppressed maze activity (females only), repetitive opening and closing of the mouth, ataxia, and 

abnormal gait were noted. Additional treatment-related effects at the next higher dose (300 mg/kg) 

included altered fecal consistency, soiled fur, stained nose, impaired righting reflex and hindlimb extensor 

reflex, decreased rearing in a 2-minute period and suppressed maze activity (males), tremors, body twitch, 

and lowered arousal (females only). Treatment at 600 mg/kg resulted in impaired respiration, 

lacrimation, reduced forelimb and hindlimb grip strength, decreased hindlimb foot splay, abnormal 

hindlimb positioning, decreased tail pinch response, lowered arousal level (males), and reduced touch 

response (females). No treatment-related gross or histopathologic lesions were observed in brain, spinal 

cord, peripheral nerves, skeletal muscle, eyes, or optic nerve at doses up to and including the highest dose 

tested (600 mg/kg). 

Most available oral animal studies include assessments of diazinon-induced changes in RBC and/or 

neural AChE activity. Many of these studies were particularly designed to assess AChE activity at 

diazinon doses below those eliciting clinical signs of neurotoxicity. Diazinon-induced decreased AChE 

activity may be a sensitive indicator of neurotoxicity, and a 20–59% inhibition of neural or RBC AChE is 

considered a less serious effect in the absence of more serious indicators of neurotoxicity. Results of 
DIAZINON 84 

3. HEALTH EFFECTS 

several rat and dog studies identified diazinon-induced RBC and/or brain AChE inhibition of 20% or 

more following acute-, intermediate-, and chronic-duration oral exposure at doses in the range of 2– 

15 mg/kg/day (Barnes 1988; EPA 1996, 2000a; Makhteshim-Agan 1989; Trutter 1991). For example, 

single oral gavage dosing of rats at 2.5 mg/kg resulted in 40% RBC AChE inhibition (EPA 2000a). In a 

28-day feeding study, male and female rats receiving diazinon at 2.4 mg/kg/day exhibited 38% RBC 

AChE inhibition by the end of the first week of treatment (EPA 1996). Davies and Holub (1980a) 

reported 9, 20, and 22% RBC AChE inhibition in female rats receiving diazinon (99.2% purity) in the diet 

for 42 days at concentrations of 2, 3, and 4 ppm (0.18, 0.27, and 0.36 mg/kg/day), respectively. This 

study was specifically designed to assess low-dose cholinesterase responses to oral diazinon and serves as 

the principal study for deriving an intermediate-duration oral MRL for diazinon (see Appendix A). 

Administration of diazinon in the diet of male and female rats for 98 weeks at a concentration resulting in 

a dose level of approximately 5 mg/kg/day caused 26–28% RBC AChE inhibition and 24–29% brain 

AChE inhibition (Kirchner et al. 1991). The next lower dose level (0.07 mg/kg/day in the female rats) 

represented a NOAEL and serves as the basis for deriving a chronic-duration oral MRL for diazinon (see 

Appendix A). 

Available single and repeated-dose oral studies in animals demonstrate that significant diazinon-induced 

plasma ChE inhibition occurs at doses lower than those required to produce significant RBC AChE 

inhibition and that RBC AChE inhibition is a somewhat more sensitive indicator of effect than brain 

AChE inhibition (Barnes 1988; Davies and Holub 1980a; Kirchner et al. 1991; Rudzki et al. 1991; Singh 

1988; Timchalk et al. 2005). Peak cholinesterase inhibition is typically observed between 6 and 12 hours 

following single oral dosing (Chow and Richter 1994; Timchalk et al. 2005). In a longer-term (90-day) 

dietary rat study, diazinon-induced plasma ChE and RBC AChE inhibition increased in severity with 

exposure duration to a peak at approximately 35 days, after which the severity of the inhibition remained 

relatively constant (Davies and Holub 1980a). Available animal data indicate that females may be more 

sensitive than males to diazinon-induced cholinesterase inhibition, particularly with respect to brain 

AChE inhibition (Barnes 1988; Davies and Holub 1980b; EPA 1996, 2000a; Singh 1988; Trutter 1991). 

Limited animal data were located regarding potential for diazinon to elicit other neurophysiologic or 

neurohistopathologic effects. There were no indications of histopathologic lesions in central and 

peripheral nervous tissue samples from rats administered diazinon once by oral gavage at doses up to 

600 mg/kg (Chow and Richter 1994) or in rats administered diazinon in the diet for 90 days at 

concentrations resulting in doses as high as 212 mg/kg/day (Singh 1988). No clinical signs or 
DIAZINON 85 

3. HEALTH EFFECTS 

histopathologic evidence of diazinon-induced delayed neuropathy were seen in hens following oral 

administration of 11.3 mg diazinon/kg on 2 days (21 days apart) (Jenkins 1988). 

Refer to Section 3.2.2.6, Developmental Effects, for information regarding diazinon-induced 

neurodevelopmental effects. 

The highest NOAEL values and all reliable LOAEL values for neurological effects in each species and 

duration category are presented in Table 3-2 and plotted in Figure 3-2. 

3.2.2.5 Reproductive Effects 

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

Limited information is available regarding the reproductive toxicity of diazinon in orally-exposed 

laboratory animals. No adverse effects on reproduction were reported for four generations of female 

Sprague-Dawley rats fed diazinon in the diet at a concentration resulting in a dose of 0.05 mg/kg/day 

during gestation and lactation for 60 days prior to weaning (Green 1970). No adverse effect on fertility 

was observed, as all females became pregnant. Apparently, diazinon exposure increased the average 

number of pups per litter compared to undosed controls (9.7–11.1 as opposed to 6.2–8) for all 

five generations (F0–F4). Oral administration of diazinon to male albino rats at dose levels of 1.5 or 

3 mg/kg/day for 65 days resulted in significantly decreased reproductive tissue weights, increased 

percentage of dead and morphologically abnormal spermatozoa, decreased plasma testosterone levels, and 

decreased fertility as assessed by conception rates of untreated females mated to diazinon-treated males 

(Abd El-Aziz et al. 1994). In a study of hybrid mice, litter size was reduced by 20% at oral maternal 

diazinon doses of 0.18, but not at 9 mg/kg/day relative to controls (Spyker and Avery 1977). A 14% 

reduction in maternal weight gain was observed at both doses. Male and female Beagle dogs were given 

daily capsules containing diazinon in corn oil at doses ranging from 2.5 to 20 mg/kg/day for 8 months 

(Earl et al. 1971). Testicular atrophy with completely arrested spermatogenesis was observed in the one 

male dog of the 10 mg/kg/day group that lost weight and evidenced other gross pathological changes. All 

three male dogs in the 20 mg/kg/day group suffered similar effects (testicular atrophy observed in 2/3, 

arrested spermatogenesis observed in the other dog). 

Administration of diazinon at 10, 20, or 100 mg/kg/day by oral gavage during gestation days 6–15 in 

CD-1 rats had no significant effect on litter sizes or numbers of viable fetuses (Infurna and Arthur 1985). 

Maternal toxicity was noted at 100 mg/kg/day with a significant reduction in feed consumption and body 
DIAZINON 86 

3. HEALTH EFFECTS 

weight gain. In New Zealand rabbits dosed by gavage at 7, 25, or 100 mg/kg/day diazinon during 

gestation days 6–18, no treatment-related effects were seen in number of implantations, proportion of 

live, dead or resorbed fetuses, fetal weights, or fetal sex ratios (Harris and Holson 1981). The highest 

dose level (100 mg/kg/day) resulted in the death of 9/22 dams. 

No gross or histological evidence of treatment-related damage to reproductive tissues (ovaries, uterus, 

vagina, epididymides, seminal vesicles, testes) was observed in Sprague-Dawley rats exposed to up to 

168 mg/kg/day diazinon (males) or 212 mg/kg/day (females) for 13 weeks via feed (Singh 1988), or up to 

10 mg/kg/day (males), or 12 mg/kg/day (females) for 98 weeks (Kirchner et al. 1991), or in Beagle dogs 

exposed to up to 10.9 mg/kg/day (males) or 11.6 mg/kg/day (females) for 13 weeks (Barnes 1988). 

The highest NOAEL values and all reliable LOAEL values for reproductive effects in each species and 

duration category are presented in Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects of diazinon in orally-exposed humans. Mouse 

studies provide evidence that lactational exposure to diazinon does not cause developmental toxicity. 

Results of other studies in rats, mice, hamsters, and rabbits also have not demonstrated dose-response 

effects on the developing mammalian fetus or neonate. The adverse effects reported for pups have been 

suggested to derive from diazinon impairment of placental transport of nutrients or maternal regulation of 

fetal growth, or directly via antagonism to cholinergic development of the fetus. No significant effects 

were seen in rabbit offspring at maternally lethal doses. 

In a teratology study, mouse dams were administered doses of 0, 0.18, or 9 mg/kg/day diazinon (technical 

grade, purity not specified) in peanut butter throughout gestation. The study found no maternal toxicity at 

any of the doses tested. Significantly elevated (p<0.05) mortality (12%, 18 of 150) was observed in the 

high dose group at weaning (postpartum day 28), but not in the low dose group (2%, 3 of 134), when 

compared with controls (6%, 19 of 311). Histological examination indicated that the majority of these 

pups died from pulmonary congestion and mucosal infiltration consistent with acute bronchitis. Diazinon 

treatment did not adversely affect postweaning mortality. Lactational exposure to diazinon did not have 

any adverse effect (Barnett et al. 1980). A previous study using the same protocol and dose regimen 

exposed dams throughout gestation to doses of 0, 0.18, or 9 mg/kg/day diazinon in peanut butter (Spyker 

and Avery 1977). Dams exposed to either diazinon dose experienced reduced weight gain (86% that of 
DIAZINON 87 

3. HEALTH EFFECTS 

controls, p<0.05) during pregnancy, but gestation length was not significantly affected. Pup weight gain 

during the first 14 weeks after parturition was significantly (p<0.05) less at the 9 mg/kg/day dose than at 

the 0 and 0.18 mg/kg/day doses. With the exception of contact placing and sexual maturity, which were 

delayed with respect to controls (p<0.05) in the low dose pups, developmental ontogeny as measured by 

numerous parameters was not significantly affected by diazinon exposure. No teratological effects were 

evident. However, both diazinon groups displayed endurance and coordination deficits during 

neuromuscular function tests (rod cling and inclined plane), and 9 mg/kg/day offspring also displayed 

slower running speed in a Lashley III maze and reduced swimming endurance. Morphologically, the 

brains of 9 (but not 0.18) mg/kg/day offspring had focal abnormalities in the forebrain area, including 

dense aggregations of atypical chromatin-containing cells. Among the offspring of hybrid mouse dams 

exposed to 0.18 or 9 mg/kg/day diazinon during gestation days 1–18, females from the 9 mg/kg/day 

group showed a 33% decrease of serum IgG1 levels 101 days after birth (Barnett et al. 1980). These 

levels were normal at 400 and 800 days after birth, and no effects on serum Ig levels were observed in 

male offspring at either dose. Fetal exposure to low levels of diazinon may result in functional deficits in 

otherwise normal animals that can only be detected by systemic behavioral evaluation. These neural 

dysfunctions and pathologies might occur either indirectly through diazinon impairment of placental 

transport of nutrients or maternal regulation of fetal growth, or directly via antagonism to cholinergic 

development of the fetus (Spyker and Avery 1977). 

Pregnant Golden Syrian hamsters were orally exposed by gavage to diazinon during organogenesis 

(0.125 mg/kg/day to eight dams on gestation day 6, 7, and 8; 0.25 mg/kg/day to five dams on gestation 

day 7 or 8). All dams survived, but displayed cholinergic signs of diarrhea, salivation, and ataxia. No 

terata were observed at either dose, nor were average number of fetuses per litter, fetal mortality, or 

average fetal weight adversely affected. Thus, at maternally toxic doses, diazinon was not feto- or 

developmentally toxic to hamsters (Robens 1969). 

Diazinon was not fetotoxic or developmentally toxic to rabbits at maternally lethal doses. When pregnant 

New Zealand white rabbits were orally exposed by gel capsules to 7 or 30 mg/kg/day diazinon on day 15 

of gestation, 6/8 of the dams in the high dose group died. The dams in this dose group also exhibited 

severe cholinergic signs. However, no terata or dose-related embryotoxic effects (average number of 

fetuses per litter, fetal mortality, average fetal weight) were observed even at maternally toxic doses 

(Robens 1969). In a study of New Zealand rabbit does exposed by gavage to 7, 25, or 100 mg/kg/day 

diazinon during gestation days 6–18 and sacrificed on gestation day 25, no significant treatment-related 

fetal malformations or skeletal malformations were observed in the offspring (Harris and Holson 1981). 
DIAZINON 88 

3. HEALTH EFFECTS 

Nine of the 22 dams in the 100 mg/kg/day group died during the study, indicating that significant 

maternal toxicity occurred at this dose. 

An increased incidence of rudimentary ribs at T-14 was observed in CD-1 rats receiving 100 mg/kg/day 

diazinon during gestation days 6–15 (Infurna and Arthur 1985). This finding was accompanied by severe 

weight loss in the dams and this developmental effect was considered by the authors of this study to be 

secondary to maternal toxicity. 

The highest NOAEL values and all reliable LOAEL values for developmental effects in each species and 

duration category are presented in Table 3-2 and plotted in Figure 3-2. 

3.2.2.7 Cancer 

Several epidemiological studies have reported increased incidence of cancers in humans who were 

concurrently or sequentially exposed to a number of insecticides, including diazinon. Some degree of 

oral exposure is presumed to have occurred. However, it is not possible to attribute the increased cancer 

incidence exclusively to diazinon exposure. 

A case-control study suggested a possible link between family gardening use of diazinon (and other 

insecticides) and increased incidence of childhood brain cancer (type unspecified). However, this report 

gave no indication of level, duration, or frequency of exposure to diazinon (or to other insecticides) 

(Davis et al. 1993). Another case-control study suggested a positive association between an increased 

incidence of non-Hodgkin’s lymphoma in farmers compared to nonfarmers. The report attributed the 

increased incidence of lymphomas to handling of organophosphorus insecticides, including diazinon 

(Cantor et al. 1992). A third case-control study suggested an association between an increased incidence 

of multiple myelomas and high exposure to insecticides, including diazinon. Actual exposure to diazinon 

was reported in 2/698 (0.3%) of the cases and 5/1,683 (0.3%) of the controls (Morris et al. 1986). 

A cancer bioassay was conducted with groups of Fischer 344 rats (50/sex/group) exposed ad libitum to 

estimated dietary doses of 20 or 40 mg/kg/day diazinon for 103 weeks; groups of 25 rats/sex served as 

unexposed controls. Tissue masses were noted especially in high-dose males and low-dose females, and 

tachypnea incidence was elevated in exposed groups. A variety of neoplastic and nonneoplastic lesions 

was observed with approximately equal frequency in the control and dosed groups in both sexes. An 

increase in the common lesion of endometrial stromal polyps observed in female rats (control=2/23, low 
DIAZINON 89 

3. HEALTH EFFECTS 

dose=8/43, high dose=11/49) was considered unrelated to diazinon exposure. In male rats, lymphomas 

and leukemias were significantly (p<0.011) elevated in the low dose group (25/50), but not in the high 

dose group (12/50), relative to controls (5/25). The study concluded that diazinon was not carcinogenic 

under the conditions of this assay for either sex of Fischer 344 rats (NCI 1979). In another cancer 

bioassay, groups of B6C3F1 mice (50/sex/group) were exposed for 103 weeks to estimated dietary doses 

of 13 or 26 mg/kg/day diazinon; groups of 25 mice/sex served as unexposed controls. A number of 

neoplastic and nonneoplastic lesions, essentially considered nontreatment-related, were observed in both 

the control and treated mice. An elevation in hepatocellular adenomas and carcinomas was observed in 

low-dose (20/46), but not high-dose (13/48) male mice, relative to controls (5/21). The study concluded 

that diazinon was not carcinogenic under the conditions of this assay for either sex of B6C3F1 mice (NCI 

1979). 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located regarding death in humans after dermal exposure to diazinon. 

In laboratory animal studies, the acute dermal toxicity of diazinon and its formulations varies profoundly, 

largely as the result of sample aging and differences in purity of formulation, particular solvent, and area 

of exposed skin. In general, aged diazinon samples that contained more impurities were more toxic 

(Gaines 1960). The use of an occlusive dressing after dermal application usually increases dermal 

toxicity because it enhances sweating and dermal absorption. Dermal LD50 values were determined in 

Sherman rats of both sexes (Gaines 1960). Diazinon was applied to a shaved dermal area of 

approximately 13.5 cm2

. LD50 values were 900 and 455 mg/kg for males and females, respectively. 

Among New Zealand rabbits dermally exposed for 24 hours to 2,020 mg/kg diazinon, 2/5 females and 

0/5 males died within 2 days after exposure ceased (EPA 1990). 

The LD50 values and doses associated with death in each species and duration category are shown in 

Table 3-3. 
Table 3-3 Levels of Significant Exposure to Diazinon - Dermal

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System NOAEL Less Serious 

LOAEL

Serious

ReferenceChemical Form

ACUTE EXPOSURE

Death

(Sherman)Rat

151

once

900 M (LD50)

mg/kg

mg/kg

455 F (LD50)

mg/kg

mg/kg

Gaines 1960 

Systemic

Human

156

72 hr Dermal 1

Percent (%)

Percent (%)

Lisi et al. 1987 

(Hartley)Gn Pig

157

24 hr Dermal 5 F

Percent (%)

Percent (%)

10 F (erythema)

Percent (%)

Percent (%)

Matsushita et al. 1985 

(NewZealand)Rabbit

632

4 hr Dermal 0.5 B (erythema,

 slight edema)

colonies per 100 milliters

colonies per

100 milliters

EPA 1990 

Immuno/ Lymphoret

Human

456

once

1

Percent (%)

Percent (%)

Lisi et al. 1987 

Neurological

(SpragueDawley)Rat

622

(C)once

65 F (52% RBC AChE

inhibition)

mg/kg

mg/kg

Abu-Qare and Abou-Do

2001
Table 3-3 Levels of Significant Exposure to Diazinon - Dermal (continued)

Species

(Strain)

Exposure/

Duration/

Frequency

(Route) System NOAEL Less Serious 

LOAEL

Serious

ReferenceChemical Form

INTERMEDIATE EXPOSURE

Systemic

(dark agouti)Rat

162

12 wk7 d/wk1 x/d

Hepatic 114 F (elevated fecal

porphyrin)

mg/kg

mg/kg

Bleakley et al. 1979 

Immuno/ Lymphoret

(Hartley)Gn Pig

AChE = acetylcholinesterase; (C) = capsule; Cardio = cardiovascular; d = day(s); Endocr = endocrine; F = Female; Gn pig = guinea pig; hr = hour(s); Immuno/Lymp

immunological/lymphoreticular; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); mo = month(s); NOAEL =no-observed-adverse-effect level; RBC = red blood cell; x = time(s); wk = week(s)

163

24 hr

0.05 F (moderate delayed

contact sensitivity)

Percent (%)

Percent (%)

Matsushita et al. 1985 
DIAZINON 92 

3. HEALTH EFFECTS 

3.2.3.2 Systemic Effects 

No studies were located regarding musculoskeletal, renal, ocular, or body weight effects in humans after 

dermal exposure to diazinon. No studies were located regarding cardiovascular, hematological, 

musculoskeletal, renal, endocrine, or ocular effects in animals after dermal exposure to diazinon. 

Respiratory Effects. A 56-year-old female gardener, dermally exposed to spilled diazinon of 

unknown purity, developed respiratory distress as one of the cholinergic symptoms of AChE inhibition. 

The victim exhibited pulmonary edema with bilateral lung crepitations and tachypnea (Lee 1989). 

Nasal discharge was observed in New Zealand rabbits of both sexes following dermal exposure for 

24 hours to 2,020 mg/kg diazinon (EPA 1990). 

Cardiovascular Effects. A 56-year-old female gardener, dermally exposed to spilled diazinon of 

unknown purity, developed sinus tachycardia with no evidence of infarction and showed increased 

cardiac enzyme (serum glutamate oxalate transaminase, total lactate dehydrogenase creatine 

phosphokinase) levels. The victim was diagnosed on discharge with acute left ventricular failure (Lee 

1989). 

Gastrointestinal Effects. Two female gardeners, dermally exposed to spilled diazinon of unknown 

purity, developed signs of acute pancreatitis which included abdominal colic, diarrhea, nausea, vomiting, 

and epigastric pain, as well as elevated serum amylase and urinary diastase levels (Lee 1989). 

Both decreased defecation and diarrhea were observed in New Zealand rabbits of both sexes following 

dermal exposure for 24 hours to 2,020 mg/kg diazinon (EPA 1990). 

Hematological Effects. Two female gardeners, dermally exposed to spilled diazinon of unknown 

purity, developed hypokalemia and leucocytosis (Lee 1989). 

Hepatic Effects. Female dark Agouti rats received daily cutaneous doses of either 114 or 

229 mg/kg/day diazinon. Significant elevations in total fecal porphyrin excretion were observed at the 

114 mg/kg/day dose after 8–12 weeks (3–5-fold), and at the 229 mg/kg/day dose at least by week 12 

(4-fold). No concomitant rises in urinary porphyrin excretion were observed. Electrophoretic analysis 

revealed the presence of isocoporphyrin in the feces. Except for the unexplained lack of urinary 
DIAZINON 93 

3. HEALTH EFFECTS 

porphyrin, these findings were noted to be biochemically characteristic of human porphyria cutanea tarda, 

and indicative of disturbed hepatic porphyrin metabolism. However, oral administration of 46 mg/kg/day 

to another group of rats was without this effect (Bleakley et al. 1979). 

Endocrine Effects. Two female gardeners, 56 and 48 years old, dermally exposed to spilled diazinon 

of unknown purity, developed signs of acute pancreatitis, which included abdominal colic, diarrhea, 

nausea, vomiting, and epigastric pain, as well as elevated serum amylase and urinary diastase levels. One 

of the victims was diagnosed on discharge with organophosphate poisoning and diabetes mellitus. The 

authors of this study noted that acute pancreatitis is frequently a component of organophosphate 

intoxication, although it is often not recognized as such in the medical literature or by treating physicians 

(Lee 1989). 

Dermal Effects. Dermal exposure to diazinon resulted in contact dermatitis in farm workers 

(Matsushita et al. 1985). But, according to another report, a 1% diazinon solution in a skin patch did not 

elicit an irritation or cause sensitization in humans (Lisi et al. 1987). 

Skin erythema was noted in guinea pigs dermally exposed to 10 and 20% diazinon, but not at lower 

concentrations of 0.5–5.0% (Matsushita et al. 1985). Well defined erythema and slight edema were 

observed in New Zealand rabbits of both sexes following dermal exposure for 4 hours to 0.5 mL of 

diazinon (EPA 1990). 

Body Weight Effects. Body weight was unaffected in New Zealand rabbits dermally exposed to up 

to 2,020 mg/kg diazinon for 24 hours and observed for 14 days (EPA 1990). 

3.2.3.3 Immunological and Lymphoreticular Effects 

One percent diazinon in "pet" (presumably petroleum ether) has been tested for allergic reactions by patch 

tests in 294 volunteers examined after 48 and 72 hours of dermal contact (Lisi et al. 1987). The 1% 

diazinon solution on a skin patch did not elicit allergic reactions in any of the volunteers studied. 

Diazinon has also been tested for delayed contact hypersensitivity following skin application to guinea 

pigs. Induction concentrations of diazinon were reported as 5% (intradermal) and 25% (topical). At both 

24 and 48 hours after challenge in the guinea pig maximization test, response to a 0.05% diazinon 

challenge was scored as grade III (moderate, 30% sensitization rate), and to 0.5% diazinon as grade V 
DIAZINON 94 

3. HEALTH EFFECTS 

(extreme, 100% rate). When cross-sensitization was tested using a challenge of 0.2 or 2% benomyl, 

allergenicities were grade I (0%) and grade III (30%), respectively (Matsushita et al. 1985). Skin 

sensitization did not occur in Hartley guinea pigs treated 11 times over a 36-day period with 0.5 mL of 

diazinon (Kuhn 1989b). 

3.2.3.4 Neurological Effects 

Two female gardeners, 56 and 48 years old, dermally exposed to spilled diazinon of unknown purity, 

developed cholinergic organophosphate poisoning symptoms. The victims exhibited signs and symptoms 

which included cyanosis, frothing at the mouth, drowsiness, nausea, vomiting, abdominal colic, diarrhea, 

tachypnea, miosis, and sinus tachycardia with no evidence of infarction. One victim showed significantly 

depressed plasma ChE levels (Lee 1989). 

Tremors were reported in female (but not male) New Zealand rabbits after 24 hours of dermal exposure to 

2,020 mg/kg diazinon (EPA 1990). 

No studies were located regarding OPIDN in humans or in animals after dermal exposure to diazinon. 

3.2.3.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans or animals following dermal exposure 

to diazinon. 

3.2.3.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after dermal exposure to 

diazinon. 

3.2.3.7 Cancer 

Several epidemiological studies have reported increased incidence of cancers in humans who were 

concurrently or sequentially exposed to a number of insecticides, including diazinon. Some degree of 

dermal exposure is presumed to have occurred. However, it is not possible to attribute the increased 

cancer incidence exclusively to diazinon exposure. 
DIAZINON 95 

3. HEALTH EFFECTS 

A case-control study suggested a possible link between family gardening use of diazinon (and other 

insecticides) and increased incidence of childhood brain cancer (type unspecified). However, this report 

gave no indication of level, duration, or frequency of exposure to diazinon, or to other insecticides (Davis 

et al. 1993). Another case-control study suggested a positive association between an increased incidence 

of non-Hodgkin’s lymphoma in farmers compared to nonfarmers. The report attributed the increased 

incidence of lymphomas to handling of organophosphorus insecticides, including diazinon (Cantor et al. 

1992). A third case-control study suggested an association between an increased incidence of multiple 

myelomas and high exposure to insecticides, including diazinon. Actual exposure to diazinon was 

reported in 2/698 (0.3%) of the cases and 5/1,683 (0.3%) of the controls (Morris et al. 1986). 

No studies were located regarding cancer in animals after dermal exposure to diazinon. 

3.2.4 Other Routes of Exposure 

This section contains diazinon toxicity data from injection studies that reported effects not observed in 

studies using natural (inhalation, oral, or dermal) exposure routes. In vitro diazinon toxicity data are 

included as well. 

Slotkin and coworkers (Jameson et al. 2007; Slotkin et al. 2006a, 2006b, 2007) reported evidence of 

diazinon-induced neurodevelopmental effects in the forebrain and brainstem of neonatal rats at dose 

levels near or below those eliciting significant cholinesterase inhibition, the most commonly-observed 

indicator of diazinon toxicity. In these studies, newborn rats were subcutaneously injected with diazinon 

on postnatal days 1–4 at doses ranging from 0.5 to 2 mg/kg/day. Slotkin et al. (2006a) noted impaired 

neuritic outgrowth, evidenced by treatment-related decreased ratio of membrane protein to total protein, 

and a dose-dependent deficit in choline acetyltransferase activity (a constitutive marker of cholinergic 

projections) in the absence of an effect on hemicholinium-3 binding to the presynaptic choline transporter 

(an index of cholinergic neuronal activity). Diazinon-induced up-regulation of 5HT receptors and 5HT 

transporter was reported by Slotkin et al. (2006b). Diazinon-induced regional suppression of selected 

fibroblast growth factors, neurotrophic factors that play critical roles in neuronal development and 

recovery from injury, were reported by Slotkin et al. (2007). 

Diazinon inhibited the outgrowth of axon-like processes in mouse N2a neuroblastoma cells in vitro at a 

concentration (1 μM) causing slight AChE inhibition but not affecting cell viability (Flaskos et al. 2007). 
DIAZINON 96 

3. HEALTH EFFECTS 

3.3 GENOTOXICITY 

Chronic occupational exposure to multiple insecticides, including diazinon, has been associated with an 

increased incidence of chromosomal aberrations and increased sister chromatid exchanges in peripheral 

blood lymphocytes as compared with nonexposed populations (De Ferrari et al. 1991; Kiraly et al. 1979; 

See et al. 1990). Some of these exposures are presumed to be by inhalation. However, it is not possible 

to attribute the results of these studies to diazinon alone, as workers were exposed to up to 80 different 

insecticides in unknown amounts for variable durations. 

Limited information is available regarding the in vivo genotoxicity of diazinon. Significantly increased 

sister chromatid exchanges were noted in peripheral blood lymphocytes from a group of volunteers 

following exposure to diazinon in a sheep-dip formulation (approximately 45% diazinon); the magnitude 

of the increase in sister chromatid exchanges was approximately 2-fold greater than the pre-exposure 

sister chromatic exchange rate (Hatjian et al. 2000). However, the specific role of diazinon in the 

observed effect could not be determined because the sheep-dip formulation contained other ingredients as 

well. Diazinon (95% purity) induced mutations in a wing somatic mutation and recombination test 

(SMART) of Drosophila melanogaster (Çakir and Sarikaya 2005). Diazinon did not induce sister 

chromatid exchanges in the bone marrow of mice administered diazinon (88% purity) in single 100 mg/kg 

gavage dose (EPA 1990). 

Results of in vitro laboratory testing for diazinon-induced genotoxicity in mammalian cells and 

microorganisms are equivocal (see Table 3-4). Diazinon induced gene mutations in one Ames assay of 

Salmonella typhimurium in the presence (but not the absence) of metabolic activation (Wong et al. 1989). 

The chemical was not mutagenic in other Ames assays either with (Kubo et al. 2002) or without (Kubo et 

al. 2002; Marshall et al. 1976) metabolic activation. Diazinon did not induce gene mutation in the 

rec-assay utilizing strains of Bacillus subtilis tested without metabolic activation (Shirasu et al. 1976). In 

one mouse lymphoma mutagenicity assay, diazinon elicited a mutagenic response in the absence of 

metabolic activation (McGregor et al. 1988). However, mutagenicity was not indicated in a similar assay 

of mouse lymphoma cells either with or without metabolic activation (EPA 1988). Diazinon induced 

chromosomal aberrations in Chinese hamster cells with metabolic activation (Matsuoka et al. 1979), but 

tested negative for chromosomal aberrations in human peripheral blood lymphocytes (Lopez et al. 1986). 

Negative results were obtained in a test for sister chromatid exchanges in Chinese hamster V79 cells, both 

with and without metabolic activation (Chen et al. 1982) and in a test for micronuclei in cultured rat 

hepatocytes (Frölichstahl and Piatti 1996). A weakly positive result was obtained for micronuclei in 
DIAZINON 97 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Diazinon In Vitro 

Results 

With Without 

Species (test system) End point activation activation References 

Prokaryotic organisms: 

Bacillus subtilis (rec assay) Gene mutation Not done – Shirasu et al. 1976 

Salmonella typhimurium Gene mutation + – Wong et al. 1989 

S. typhimurium Gene mutation Not done – Marshall et al.1976 

S. typhimurium Gene mutation – – Kubo et al. 2002 

Eukaryotic organisms: 

Mammalian cells: 

Mouse lymphoma cells Gene mutation Not done + McGregor et al. 1988 

Mouse lymphoma cells Gene mutation – – EPA 1988 

Human peripheral blood Chromosomal aberration Not done – Lopez et al. 1986 

lymphocytes 

Chinese hamster cells Chromosomal aberrations + – Matsuoka et al. 1979 

Chinese hamster cells Sister chromatid – – Chen et al. 1982 

exchange 

Human peripheral blood Micronuclei Not done (+) Bianchi-Santamaria et 

lymphocytes al. 1997 

Rat hepatocytes Micronuclei – Not done Frölichstahl and Piatti 

1996 

Human primary nasal DNA damage Not done + Tisch et al. 2002 

mucosal cells 

Transformed PC12 Inhibition of DNA Not done + Qiao et al. 2001 

pheochromocytoma cells synthesis 

Transformed C6 glioma Inhibition of DNA Not done + Qiao et al. 2001 

cells synthesis 

Human 1321N1 Inhibition of DNA Not done + Guizzetti et al. 2005 

astrocytoma cells synthesis 

Fetal rat astrocytes Inhibition of DNA Not done + Guizzetti et al. 2005 

synthesis 

– = negative result; + = positive result; (+) = weakly positive; DNA = deoxyribonucleic acid 
DIAZINON 98 

3. HEALTH EFFECTS 

cultured human peripheral blood lymphocytes exposed to diazinon at concentrations ranging from 0.04 to 

4 μg/mL (Bianchi-Santamaria et al. 1997). Diazinon-induced deoxyribonucleic acid (DNA) damage was 

reported in a Comet assay using human primary nasal mucosal cells (Tisch et al. 2002). Diazinon 

inhibited DNA synthesis in transformed PC12 pheochromocytoma and C6 glioma cells (Qiao et al. 2001), 

as well as fetal rat astrocytes and human 1321N1 astrocytoma cells (Guizzetti et al. 2005). 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

No studies were located regarding absorption after inhalation exposure of diazinon in humans or animals. 

However, efficient absorption of inhaled diazinon is expected. 

3.4.1.2 Oral Exposure 

Diazinon is readily absorbed by the oral exposure route. Rapid and extensive absorption was noted 

following the ingestion of a 0.011 mg/kg dose of diazinon (94% purity) by a group of five volunteers, as 

evidenced by the excretion of approximately 60% of the administered dose as dialkyl phosphate 

metabolites in the urine, most (90%) of which was recovered within 14 hours postadministration (Garfitt 

et al. 2002). Diazinon was detected in several tissues from a woman who had ingested a lethal amount of 

an estimated 293 mg/kg diazinon formulation ("FERTI-LOME" bagworm spray) containing 10% 

diazinon suggesting rapid absorption from the gastrointestinal tract (Poklis et al. 1980). 

Animal studies also demonstrate rapid absorption of diazinon following oral administration. Wistar WU 

rats of both sexes were given either a single oral dose of 4 mg/kg or daily doses of 8.0 mg/kg 

[

14C]diazinon for 10 consecutive days. The rapid absorption of diazinon was indicated by the early 

excretion of radioactivity (Mücke et al. 1970). Similar results were obtained following a single oral dose 

of 4.0 mg/kg [

14C]diazinon to female Beagle dogs where absorption was determined to be at least 85% 

(Iverson et al. 1975). Within 30 minutes following the oral administration of an 80 mg/kg dose of 

diazinon (99.8% purity) to eight male Wistar rats, the mean plasma concentration of diazinon exceeded 

0.6 mg/L; by 2 hours postadministration, a peak plasma concentration of 1.22 mg/L was achieved (Wu et 

al. 1996a). In goats given daily oral doses of 0.5 or 5.0 mg/kg/day diazinon for 7 days or a single 150 or 

700 mg/kg dose, diazinon was detected in blood from the first day of treatment (Mount 1984). Other 
DIAZINON 99 

3. HEALTH EFFECTS 

studies demonstrated rapid absorption of orally administered diazinon in sheep (Janes et al. 1973; Machin 

et al. 1971, 1974) and cows (Abdelsalam and Ford 1986). 

3.4.1.3 Dermal Exposure 

Absorption of diazinon following dermal exposure has been demonstrated in humans. Volunteers were 

exposed for 24 hours to [14C]diazinon applied to either the forearm or abdomen in acetone or lanolin wool 

grease (Wester et al. 1993). Based on the excretion of 14C in the urine, absorption was determined to be 

3–4% of the applied dose with no difference related to vehicle or the area applied. In another study, 

8-hour occluded dermal application of 100 mg of diazinon (94% purity) on an 80 cm2

 area of the forearm 

of four volunteers resulted in approximately 0.5% absorption based on the recovery of urinary dialkyl 

phosphate metabolites (Garfitt et al. 2002). Greater than 90% of the administered dose was recovered 

from the application site. 

No studies were located regarding absorption of diazinon after dermal exposure in animals. 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

No studies were located regarding distribution of diazinon after inhalation exposure in humans or 

animals. 

3.4.2.2 Oral Exposure 

Samples of stomach contents, blood, bile, adipose tissue, liver, brain, and kidney were collected at 

autopsy of a woman who ingested a lethal dose estimated at 293 mg/kg of a diazinon formulation 

("FERTI-LOME" bagworm spray) containing 10% diazinon (Poklis et al. 1980). The highest 

concentrations of diazinon were found in the blood, followed by stomach contents and the bile. Lowest 

concentrations were found in the kidney, followed by adipose tissue and bile. Animal studies support the 

human data and demonstrate that diazinon is widely distributed in all analyzed tissues in rats (Mücke et 

al. 1970), sheep (Janes et al. 1973; Machin et al. 1971, 1974), and cows (Abdelsalam and Ford 1986). 

Although widely distributed via the circulation, it is generally understood that absorbed diazinon is 

rapidly metabolized and does not accumulate significantly in body tissues. However, Garcia-Repetto et 

al. (1996) reported detectable levels of diazinon in blood, adipose tissue, muscle, liver, and brain of rats 

following oral dosing at approximately 23 mg/kg. In blood, adipose tissue, and brain, the levels 
DIAZINON 100 

3. HEALTH EFFECTS 

decreased with time from 4 to 20 days postdosing. Levels in muscle and liver increased up to 12 and 

8 days postdosing, respectively, and decreased thereafter. By 30 days postdosing, detectable levels were 

no longer observed in blood, adipose tissue, muscle, liver, or brain. 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution of diazinon after dermal exposure in humans or animals. 

3.4.3 Metabolism 

Although diazinon (as parent compound) can elicit mild cholinergic stimulation, its oxygenated 

metabolite (diazoxon) is mainly responsible for these neurotoxic signs (Wilson 2001). A proposed 

metabolic scheme for diazinon is presented in Figure 3-3. The CYP450-catalyzed oxidation of diazinon 

(reaction 1 in Figure 3-3) results in an intermediate (phosphooxythiran), which in turn undergoes 

spontaneous desulfuration (reaction 2) to form diazoxon. Alternatively, phosphooxythiran may be 

deactivated via hydrolysis, desulfuration, and deoxygenation (reaction 3) to form metabolites 2-isopropyl4-methyl-6-hydroxypyrimidine (IMHP), diethylthiophosphate (DETP), and DEP, all of which are 

excreted in the urine. Detoxification of diazoxon (reaction 4) to IMHP and DEP occurs via hydrolysis 

catalyzed by hepatic and extrahepatic A-esterases (paraoxonase or PON1) and B-esterases 

(carboxylesterases) (Fabrizi et al. 1999; Poet et al. 2003; Yang et al. 1971). Results of several in vitro 

assays using human liver cells implicate CYP2C19 as a major P-450 isozyme involved in the formation 

of diazoxon from diazinon; other P-450 isozymes (e.g., CYP1A2, CYP2B6, CYP3A4, CYP3A5, 

CYP2D6) are also implicated (Buratti et al. 2003; Kappers et al. 2001; Mutch and Williams 2006; Sams 

et al. 2004). In rat liver, CYP2C11, CYPA2, and CYP2B1/2 appear to be the major catalyzing agents in 

the formation of diazoxon from the parent compound, diazinon. 

Available data indicate that absorbed diazinon is rapidly metabolized. Wu et al. (1996a) administered 

diazinon to male Wistar rats at a dose of 80 mg/kg and followed the timecourse of measurable plasma 

concentrations. Based on the rate of disappearance of diazinon from the plasma, an elimination half-time 

of 2.86 hours was estimated. These results provide suggestive evidence for the rapid metabolism of 

absorbed diazinon. 

Age-related differences in the detoxification of diazinon and its active metabolite, diazoxon, are apparent, 

as demonstrated in an in vitro assay of rat liver and plasma (Padilla et al. 2004). The results indicated a 

much lower degree of detoxification by liver and plasma from young rats compared to adult tissues. 
DIAZINON 101 

3. HEALTH EFFECTS 

Figure 3-3. Putative Pathways of Diazinon Biotransformation 

N 

O N

P 

S 

CH3CH2 O CH(CH3)

2 

CH3CH2 O 

CH3 

Diazinon 

CH2CH3

1 CYP450 O2 CH3CH2 

O 

O P O 

+ S H 

CH3CH2 O 

N CH(CH3) O 2 H [O][S] O 2O N CH(CH3)

2 Diethylthiophosphate P H (DETP) 

N 

CH3CH2 O 

N S O 

Spontaneous

CH3 CH2CH3 

3 

CH3 

CH3CH2 

O 

Phosphooxythiran 2-Isopropyl-4-methyl-6- OP O 

hydroxypyrimidine (IMHP) + O H 

2 Spontaneous Diethylphosphate 

(DEP) [S] 

CH3CH2 O N CH(CH3) P 

O 2 N CH(CH CH2CH3 3)

2 H2O O

CH H 3CH2 O CH3CH2 

O 

O N

N O P O 

A- + B-esterases + 

CH3 O H 

Diazoxon 4 CH3 

IMHP DEP 

IMHP, DEP, and DETP are urinary metabolites of diazinon 

Sources: Kappers et al. 2001; Poet et al. 2004 
DIAZINON 102 

3. HEALTH EFFECTS 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

No studies were located regarding excretion of diazinon after inhalation exposure in humans or animals. 

3.4.4.2 Oral Exposure 

Following oral dosing of diazinon (0.011 mg/kg) to four volunteers, rapid absorption, metabolism, and 

elimination was indicated as evidenced by the excretion of approximately 60% of the administered dose 

as dialkyl phosphate metabolites (DEP and DETP) in the urine, most (90%) of which was recovered 

within 14 hours postadministration (Garfitt et al. 2002). Unmetabolized diazinon was not detected. 

Following a single oral dose of 4.0 mg/kg 2-pyrimidinyl ring-labeled and 4-pyrimidinyl ring-labeled 

[

14C]diazinon to rats, approximately 50% of the dose was excreted within 12 hours of dosing (Mücke et 

al. 1970). Sixty-nine to 80% of the radioactivity was recovered in the urine and 18–25% was excreted in 

the feces. Only 5.6% of an ethyl-[14C]diazinon dose was recovered as 14CO2 in expired air. No 14CO2 

was expired from rats given an oral dose of 2-[14C] or 4-[14C]pyrimidine diazinon, indicating that 

complete degradation of the pyrimidine ring did not take place. Traces of unchanged diazinon were 

recovered in the feces. Three of the unidentified metabolites recovered in the urine and feces of treated 

rats accounted for 70% of the total administered dose. The half-life of the 14C-ring labeled diazinon was 

12 hours while that of [ethyl-14C]diazinon was 7 hours (Mücke et al. 1970). Recovery of radioactivity in 

the urine of female Beagle dogs 24 hours after receiving a single oral dose of [14C]diazinon was 85% 

(53% water-soluble fraction, and two metabolites that no longer had a phosphorothioate group, 

comprising 10 and 23%). No diazinon was detected in the feces (Iverson et al. 1975). Following oral 

administration of diazinon to lactating goats, DETP was detected in the urine but not in the milk (Mount 

1984). 

3.4.4.3 Dermal Exposure 

Diazinon urinary metabolites (DEP and DETP) were recovered from volunteers treated by occluded 

dermal application of 100 mg of diazinon (94% purity) on an 80 cm2

 area of the forearm for 8 hours 

(Garfitt et al. 2002). Most (90%) of the administered dose was recovered from the application site. 

Approximately 0.5% was recovered as urinary metabolites. In another human study, volunteers were 

exposed for 24 hours to 2-pyrimidinyl ring-labeled [14C]diazinon applied to either the forearm or 

abdomen in either an acetone solution or a lanolin wool grease at doses of approximately 15–20 μg for 

each application method to test the percutaneous absorption of diazinon (Wester et al. 1993). Daily 
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complete void urine samples were collected and analyzed for levels of radioactivity for 7 days after 

dosing. The percentage of the administered dose excreted in the urine was approximately 3–4%. 

3.4.4.4 Other Routes of Exposure 

Following an intravenous injection of [ethyl-14C]diazinon to female Beagle dogs, approximately 58% of 

the radioactivity was recovered in the urine within 24 hours as DETP (42%) and DEP (16%). No 

unchanged diazinon was excreted (Iverson et al. 1975). 

3.4.5 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 and 

Krishnan 1994; Andersen et al. 1987). 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 parameterization, (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 

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 
DIAZINON 104 

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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) are 

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 3-4 shows a conceptualized representation of a PBPK model. 

If PBPK models for diazinon 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. 

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model has been developed 

for predicting the absorption, distribution, metabolism, and elimination of diazinon and its metabolites, 

diazoxon and IMHP, in rats and humans (Poet et al. 2004). The model also quantifies the inhibition of 

B-esterases (AChE, butylcholinesterase [BuChE], ChE, and carboxylesterase) activities in blood, RBCs, 

liver, diaphragm, and brain. 

Description of the Model. The PBPK/PD model for diazinon (Poet et al. 2004) is based on the 

PBPK/PD model for chlorpyrifos in rats and humans (Timchalk et al. 2002). Represented tissues include 

the blood, liver, brain, diaphragm, fat, skin, and other rapidly and slowly perfused tissues connected via 

arterial and venous blood flows. Portals of entry include oral absorption from a two-compartment model 

of the gut (for gavage dosing) or zero-order absorption directly into the liver (for dietary exposure), firstorder dermal absorption into the skin compartment, and intravenous, and intraperitoneal injection. 
DIAZINON 105 

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Figure 3-4. Conceptual Representation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance 

Lungs 

Liver 

Fat 

Slowly 

perfused 

tissues 

Richly 

perfused 

tissues 

Kidney 

Skin 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

Vmax Km 

Ingestion 

Inhaled chemical Exhaled chemical 

GI 

Tract 

Feces 

Urine

 Chemicals in air 

contacting skin 

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. 
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Competing metabolism of diazinon to diazoxon or IMHP occurs exclusively in the liver via a CYP450 

Michaelis-Menten process. Elimination of parent diazinon is strictly by hepatic metabolism. 

Detoxification metabolism of diazoxon by the A-esterase, PON, occurs in the blood and liver 

compartments. A fraction of diazoxon is also eliminated as IMHP as part of the B-esterase inhibition 

pathway. IMHP is eliminated to urine via first-order transfer to a single compartment. Parameter 

estimates for physiological volumes and flow rates were taken from the literature (Brown et al. 1997). 

Metabolic constants were determined using in vitro rat data previously published (Poet et al. 2003). 

Physiological flow rates and metabolic constants were scaled to the 0.74 power of body weight. 

Diffusion of diazinon and diazoxon across tissues was based on the algorithm of Poulin and Krishnan 

(1996). Oral absorption and IMHP elimination parameter values were derived from fitting the model to 

rat and human blood and urine data. 

In the liver, brain, diaphragm, and blood, free esterase (resulting from net new esterase synthesized minus 

esterase degraded) may bind to free diazoxon to form an oxon-esterase complex that may be aged or 

reversed to yield free esterase and IMHP. The parameters governing these processes were taken from the 

PBPK/PD model for chlorpyrifos (Timchalk et al. 2002), with subsequent optimization to esterase 

inhibition data in rats (Poet et al. 2004). 

Risk Assessment. The model has not been used in risk assessment. It represents both 

pharmacokinetic disposition of diazinon and metabolites and pharmacodynamic effect (esterase activity 

inhibition) for diazoxon in target tissues of rats and humans for multiple routes of exposure. 

Validation of the Model. The model was calibrated against rat plasma levels of diazinon, plasma and 

urine levels of IMHP, ChE activity in blood and diaphragm, AChE activity in brain and RBCs, and 

BuChE levels in blood and diaphragm of rats given oral bolus doses of 15, 50, or 100 mg diazinon/kg in 

corn oil vehicle (Poet et al. 2004). The model was validated against observations of plasma, brain, and 

liver levels and inhibition of plasma ChE and RBC AChE in rats (Tomokuni et al. 1985; Wu et al. 1996a). 

The sole available human data set was for urinary metabolite levels in humans following single gavage or 

dermal exposures (Garfitt et al. 2002). For both oral and dermal routes of exposure, parameter values 

governing urinary excretion rate and dermal absorption, respectively, were modified to achieve visual fit 

of the model output to the data. The effect of these changes to blood and other target tissue levels was not 

reported. 
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Species Extrapolation. The model has been applied to rats and humans. The model structure for 

both species is identical, with species-specific parameter values used for physiological volumes and flow 

rates and model-optimized values used for oral absorption. Extrapolation to other species would require 

data for physiological parameters and oral absorption rates. 

High-Low Dose Extrapolation. The model has been evaluated for simulating oral, intravenous, and 

intraperitoneal doses in rats ranging from 15 to 100 mg/kg. For humans, it has been evaluated for a single 

oral dose level of 11 μg/kg and a dermal dose of 4 mg/kg. 

Interroute Extrapolation. The model is structured to simulate exposures from oral gavage and diet, 

dermal absorption, and intravenous and intraperitoneal injection. 

Strengths and Limitations. The model has been shown to make predictions that are quite similar to 

observations of blood and tissue levels of diazinon and metabolites from multiple routes of exposure in 

rats from multiple studies (Poet et al. 2004). The human model also makes predictions of blood, red 

blood cell, and tissue esterase inhibition, which are important toxicodynamic end points. In humans, the 

model predicts urine levels of diazinon metabolites from oral and dermal exposures that are very similar 

to observations; however, the ability of the model to accurately simulate levels of diazinon and diazoxon 

in human target tissues is unknown. Limitations include the lack of validation of model performance for 

human blood and tissue levels due to the absence of human data for these end points. An associated 

limitation is uncertainty in the model to accurately describe esterase inhibition in blood, RBCs, or tissues, 

including the peripheral and central nervous systems. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

No studies were located in which mechanisms of absorption were assessed for diazinon. It is expected 

that absorption is accomplished via passive diffusion. Limited information was located regarding 

mechanisms of distribution of absorbed diazinon. Results of in vitro assays indicate that plasma diazinon 

is predominantly (90%) bound to plasma proteins (Wu et al. 1996a). It is generally understood that 

diazinon does not appreciably accumulate in any specific body tissues and that absorbed diazinon is 

rapidly metabolized and eliminated. As discussed in Section 3.4.3, detoxification of diazoxon, the 

diazinon metabolite responsible for the cholinergic response, is catalyzed by A- and B-esterases. The 

efficacy of diazinon as an effective insecticide is attributed to deficiencies in these esterases, particularly 
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among target insects. No information was located regarding mechanisms of elimination and excretion of 

parent compound or metabolites of diazinon. 

3.5.2 Mechanisms of Toxicity 

Diazinon toxicity results predominantly from the inhibition of AChE in the central and peripheral nervous 

system. AChE is responsible for terminating the action of the neurotransmitter, acetylcholine, in the 

synapse of the pre- and postsynaptic nerve endings and in the neuromuscular junction. The action of 

acetylcholine does not persist long as it is hydrolyzed by AChE and rapidly removed. As an 

anticholinesterase organophosphate, diazinon inhibits AChE by reacting with the active site to form a 

stable phosphorylated complex incapable of destroying acetylcholine at the synaptic gutter between the 

pre- and postsynaptic nerve endings or neuromuscular junctions of skeletal muscles resulting in 

accumulation of acetylcholine at these sites. This leads to continuous or excessive stimulation of 

cholinergic fibers in the postganglionic parasympathetic nerve endings, neuromuscular junctions of the 

skeletal muscles, and cells of the central nervous system that results in hyperpolarization and receptor 

desensitization. These cholinergic actions involving end organs (heart, blood vessels, secretory glands) 

innervated by fibers in the postganglionic parasympathetic nerves result in muscarinic effects, which are 

manifested as miosis, excessive glandular secretions (salivation, lacrimation, rhinitis), nausea, urinary 

incontinence, vomiting, abdominal pain, diarrhea, bronchoconstriction or bronchospasm, increased 

bronchosecretion, vasodilation, bradycardia, and hypotension. Nicotinic effects are due to accumulation 

of acetylcholine at the skeletal muscle junctions and sympathetic preganglionic nerve endings. Nicotinic 

effects are manifested as muscular fasciculations, weakness, mydriasis, tachycardia, and hypertension. 

The central nervous system effects are due to accumulation of acetylcholine at various cortical, 

subcortical, and spinal levels (primarily in the cerebral cortex, hippocampus, and extrapyramidal motor 

system). The central nervous system effects are manifested as respiratory depression, anxiety, insomnia, 

headache, restlessness, tension, mental confusion, loss of concentration, apathy, drowsiness, ataxia, 

tremor, convulsion, and coma (Klaassen et al. 1986; Williams and Burson 1985). Although diazinon 

directly inhibits AChE, its oxidation product, diazoxon (Iverson et al. 1975; Yang et al. 1971) formed in 

the liver, is an even more potent inhibitor of the enzyme (Davies and Holub 1980a, 1980b; Enan et al. 

1982; Harris et al. 1969; Rajendra et al. 1986; Takahashi et al. 1991). 

The primary cause of death in acute diazinon poisoning is a depression of the neurons in the brainstem 

(medulla), collectively known as the respiratory center, resulting in loss of respiratory drive or, in the case 

of managed treatment, cardiac failure due to electrical impulse or beat conduction abnormalities in 
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cardiac muscles (fatal arrhythmias). Other effects, such as bronchoconstriction, excessive bronchial 

secretions, and paralysis of the respiratory muscles (intercostal muscles and diaphragm) may also 

contribute to respiratory insufficiency and death. Thus, death results from loss of respiratory drive and 

paralysis of the respiratory muscles, or cardiac failure, or both, with attendant asphyxia or cardiac arrest 

(Klaassen et al. 1986; Shankar 1967, 1978; Williams and Burson 1985). 

Oxidative stress has been proposed as an additional mechanism of action for organophosphorus pesticides 

such as diazinon, particularly with respect to chronic effects on the central nervous system (Ray 1998) 

and developmental toxicity (Garry 2004; Roy et al. 2005). Akturk et al. (2006) noted increased 

malondialdehyde levels and increased activities of superoxide dismutase and catalase, indicators of 

increased lipid peroxidation, in myocardial cells of rats administered diazinon in a single 235 mg/kg oral 

dose. Giordano et al. (2007) assessed the role of oxidative stress in the neurotoxicity of diazinon and its 

oxygen analog (diazoxon) to cerebellar granule neurons from wild type and glutathione-deficient mice. 

Glutathione-deficient cells exhibit increased sensitivity to agents that increase oxidative stress. 

Cytotoxicity was significantly higher in neurons from glutathione-deficient mice and was antagonized by 

a variety of antioxidants. Manipulated depletion of glutathione in neurons from wild type mice resulted 

in increased cytotoxicity. Diazinon caused increased intracellular levels of reactive oxygen species and 

lipid peroxidation, the magnitudes of which were greatest in neurons from the glutathione-deficient mice. 

Diazinon increased cellular levels of oxidized glutathione without altering levels of reduced glutathione. 

Whereas diazinon-induced cytotoxicity was not altered by cholinergic antagonists, it was decreased by the 

calcium chelator BAPTA-AM. Collectively, these results indicate that diazinon cytotoxicity includes 

glutathione-modulated generation of reactive oxygen species and may include intracellular homeostasis of 

calcium. 

3.5.3 Animal-to-Human Extrapolations 

The general pharmacokinetic behavior of diazinon is similar in humans and laboratory animals. 

Available comparative data derive mainly from oral exposure. Following oral exposure, diazinon is 

rapidly absorbed, widely distributed, and metabolized to reactive intermediates and other metabolites, 

which are primarily quickly eliminated in the urine (see Section 3.4). Although animals and humans 

share these similarities, potential differences in pharmacokinetic behavior and biotransformation in blood 

and target tissues, particularly at exposure levels of toxicity concern, have not been extensively studied. 

Therefore, extrapolation from animals to humans includes an appreciable degree of uncertainty. 
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3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

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. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view 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 chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

Information regarding the potential for diazinon-induced neuroendocrine effects is limited. No data are 

available regarding diazinon-induced hormonal effects. Results of available animal studies indicate that 

the reproductive system is not particularly sensitive to diazinon toxicity. No treatment-related 

morphological or functional effects on reproductive systems were seen in rats, mice, or rabbits 

administered diazinon orally at doses up to and including those eliciting maternal toxicity (Giknis 1989; 
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Green 1970; Harris and Holson 1981; Infurna and Arthur 1985; Spyker and Avery 1977). There was no 

histopathological evidence of diazinon-induced effects on reproductive organs of male or female rats or 

dogs chronically exposed to diazinon in the diet at doses up to and including those eliciting neurotoxic 

effects (Barnes 1988; Kirchner et al. 1991; Rudzki et al. 1991; Singh 1988). One study reported testicular 

atrophy and arrested spermatogenesis in 3 male dogs administered encapsulated diazinon at a dose level 

of 20 mg/kg/day for 8 months (Earl et al. 1971); however, one of these dogs died and there was 

significant weight loss, indicating that the testicular effects were likely secondary to primary neurotoxic 

effects. In another study, oral administration of diazinon to male albino rats at dose levels of 1.5 or 

3 mg/kg/day for 65 days resulted in significantly decreased reproductive tissue weights, increased 

percentage of dead and morphologically abnormal spermatozoa, decreased plasma testosterone levels, and 

decreased fertility as assessed by conception rates of untreated females mated to diazinon-treated males 

(Abd El-Aziz et al. 1994). 

Results of available in vitro assessments of diazinon estrogenicity indicate a potentially weak estrogenic 

effect at best. A positive estrogenic response was not elicited in a yeast two-hybrid assay at diazinon 

concentrations up to and including the highest concentration tested (1x10-4 M) (Nishihara et al. 2000). 

Results of the E-CALUX assay indicated a weakly positive response at a diazinon concentration of 

4.6x10-4 M (Kojima et al. (2005). 

Collectively, these limited data indicate that the endocrine system may not be particularly sensitive to 

diazinon toxicity. 

3.7 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. 

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 6.6, Exposures of Children. 
DIAZINON 112 

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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 

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). 
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It is not known whether children are more susceptible than adults to diazinon toxicity, although available 

human and animal data provide suggestive evidence of increased sensitivity during critical periods of 

development. 

A single human study reported neurophysiological and neuropsychological deficits and delayed bone 

growth in young children exposed at home to a formulation of diazinon that was misused to control an 

infestation of fleas (Dahlgren et al. 2004). These results provide suggestive evidence that children may be 

particularly susceptible to diazinon toxicity during critical periods of neural and skeletal development. 

Results of one animal study indicate that fetal exposure to low levels of diazinon may result in functional 

deficits that can only be detected by systemic behavioral evaluation (Spyker and Avery 1977). In the 

study, pregnant mice were exposed to diazinon (technical grade, purity not specified) in peanut butter at 

doses of 0, 0.18, or 9 mg/kg/day throughout gestation. When subjected to neuromuscular function tests 

(rod cling and inclined plane) as adults, the pups of both groups of diazinon-exposed dams exhibited 

endurance and coordination deficits. Offspring of the high-dose dams also displayed slower running 

speed in a Lashley III maze and reduced swimming endurance. Morphologically, focal abnormalities in 

the forebrain area, including dense aggregations of atypical chromatin-containing cells, were observed in 

the high-dose offspring. These neural dysfunctions and pathologies might occur either indirectly through 

diazinon impairment of placental transport of nutrients or maternal regulation of fetal growth, or directly 

via antagonism to cholinergic development of the fetus (Spyker and Avery 1977). 

Results of subcutaneous injection studies indicate that critical periods of neurological development may 

be particularly sensitive to diazinon toxicity. Slotkin and coworkers (Jameson et al. 2007; Slotkin et al. 

2006a, 2006b, 2007) reported evidence of diazinon-induced neurodevelopmental effects in the forebrain 

and brainstem of neonatal rats at dose levels near or below those eliciting significant cholinesterase 

inhibition, the most commonly-observed indicator of diazinon toxicity. In these studies, newborn rats 

were subcutaneously injected with diazinon on postnatal days 1–4 at doses ranging from 0.5 to 

2 mg/kg/day. 

The neurotoxicity of diazinon is dependent on its bioactivation via a cytochrome P-450 mediated 

desulfuration to the oxon form (Buratti et al. 2003). Age-related differences in production and regulation 

of enzymes involved in metabolism could conceivably result in age-related differences in susceptibility to 

diazinon toxicity. Age-related differences in regulation of selected P-450 isozymes have been 

demonstrated (Leeder and Kearns 1997). Age-related differences in relative amounts of plasma ChE, 
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RBC AChE, and neural AChE could potentially play roles in susceptibility to diazinon toxicity. Because 

plasma ChE binds diazinon, lesser amounts of plasma ChE would result in greater amounts of diazinon 

and its oxon available to interact with RBC and neural AChE, which could result in increased 

susceptibility to diazinon neurotoxicity. The same reasoning is plausible for RBC AChE concentrations. 

Decreased levels of RBC AChE could result in increased sensitivity to diazinon and its oxon via increased 

binding of neural AChE. Garcia-Lopez and Monteoliva (1988) demonstrated that RBC AChE activity in 

humans increases with age, starting at birth and exceeding 60 years of age. 

In an in vitro assay designed to test the efficacy of rat liver and plasma to detoxify diazinon and its active 

metabolite, diazoxon, Padilla et al. (2004) demonstrated that liver and plasma from young rats possessed 

much less detoxification capability than adult tissues. Padilla et al. (2004) further demonstrated that oral 

administration of 75 mg diazinon/kg to 17-day-old rats resulted in 75% brain AChE inhibition, whereas 

the same dose to adult rats resulted in only 38% brain AChE inhibition. These results indicate that young 

rats may be more susceptible to the neurotoxic effects of diazinon and that age-related susceptibility may 

be at least partially associated with age-related differences in metabolic processes involved in 

detoxification. 

3.8 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 1989). The 

preferred biomarkers of exposure are generally the substance itself, 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 
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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 diazinon are discussed in Section 3.8.1. 

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 diazinon are discussed in Section 3.8.2. 

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 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Diazinon 

Diazinon is rapidly absorbed from the gastrointestinal tract and widely distributed throughout the body in 

both humans (Poklis et al. 1980) and animals (Janes et al. 1973; Mücke et al. 1970). Detection of 

diazinon in the blood and urine of occupationally-exposed workers may serve as a useful biomarker of 

very recent exposure to diazinon (Lu et al. 2006). No human or animal studies have reported the presence 

of unchanged diazinon in the urine following exposure. Traces of unchanged diazinon have been detected 

in animal feces following exposure (Mücke et al. 1970). Diazinon undergoes biotransformation to a 

variety of polar metabolites which have been detected in the urine and feces of animals. Urinary and 

fecal excretion of IMHP, DEP, and DETP have been reported following exposure of animals to diazinon 

(Iverson et al. 1975; Machin et al. 1975; Mount 1984; Mücke et al. 1970; Seiber et al. 1993; Yang et al. 

1971). Both DEP and DETP have been detected in the urine of exposed insecticide applicators (Maizlish 

et al. 1987) and volunteers administered diazinon orally or dermally (Garfitt et al. 2002). Analysis of 

blood samples for the presence of these metabolites represents a potential means of assessing exposure; 

however, only IMHP is specific for diazinon. Analysis of urine samples for metabolic products provides 
DIAZINON 116 

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a noninvasive method for detecting exposure. As diazinon is rapidly metabolized and excreted from the 

body, urinary and fecal metabolite analysis is useful only in the evaluation of recent exposures. There are 

no reports of quantitative associations between metabolite levels and exposure to diazinon in humans. 

Therefore, these biomarkers are only indicative of exposure and are not useful for dosimetric analysis. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Diazinon 

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity 

(see Section 3.5 for discussion). Two pools of cholinesterases are present in human blood; RBC AChE 

and ChE. RBC AChE is identical to AChE present in neural tissue (the target of diazinon action) while 

plasma ChE has no known physiological function. Inhibition of both forms of cholinesterase has been 

associated with exposure to diazinon in humans (Coye et al. 1987; Soliman et al. 1982) and animals 

(Barnes 1988; Davies and Holub 1980a; EPA 1996, 2000a; Kirchner et al. 1991; Makhteshim-Agan 1989; 

Rudzki et al. 1991; Trutter 1991). Inhibition of plasma, RBC, or whole blood ChE may be used as a 

marker of exposure to diazinon. However, cholinesterase inhibition is a common action of 

anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In 

addition, a wide variation in normal cholinesterase values exists in the general population, and there are 

no studies which report a quantitative association between cholinesterase activity levels and exposure to 

diazinon in humans. Thus, cholinesterase inhibition is not a specific biomarker of effect for diazinon 

exposure, but is indicative only of effect, and not useful for dosimetric analysis. 

It should be noted that plasma ChE activity has been reported to be a more sensitive marker for diazinon 

exposure than RBC AChE activity (Endo et al. 1988; Hayes et al. 1980). In light of this, it has been 

suggested that in the absence of baseline values for cholinesterase activity, sequential postexposure 

cholinesterase analyses be used to confirm a diagnosis of organophosphate poisoning (Coye et al. 1987). 

In combination with analysis of reductions in the level of cholinesterase activity, the manifestations of 

severe diazinon poisoning, clinically characterized by a collection of cholinergic signs and symptoms 

(which may include dizziness, fatigue, tachycardia or bradycardia, miosis, and vomiting) (Bichile et al. 

1983; Dagli et al. 1981; Hata et al. 1986; Kabrawala et al. 1965; Klemmer et al. 1978; Reichert et al. 

1977; Wadia et al. 1974; Wedin et al. 1984) are useful biomarkers of effect for identifying poisoned 

victims of diazinon. These manifestations are also not specific to diazinon but to anticholinesterase 

compounds (such as organophosphates and carbamates) in general. 
DIAZINON 117 

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3.9 INTERACTIONS WITH OTHER CHEMICALS 

Diazinon is one of many pesticides (organophosphates and carbamates) designed to act as AChE 

inhibitors. Significant occupational exposure to diazinon often occurs in workers who are exposed to 

other similarly-acting compounds. Neurotoxic effects in such individuals are the result of the cumulative 

dose and relative potency of each individual compound. 

Although no studies were located that specifically assessed dermal absorption of diazinon in the presence 

of other chemicals, it is generally understood that a variety of solvents influence the rate and extent of 

absorption of organophosphate pesticides following dermal exposure. 

A variety of chemicals may interfere with the toxicity of diazinon indirectly by influencing its metabolism 

through their actions on drug metabolizing enzymes. The duration and intensity of action of diazinon are 

largely determined by the speed at which it is metabolized in the body by the oxidative and hydrolytic 

liver enzymes. More than 200 drugs, insecticides, carcinogens, and other chemicals are known to induce 

the activity of liver microsomal drug-metabolizing enzymes. The characteristic biological actions of 

these chemicals are highly varied. Although there is no relationship between their actions or structures 

and their ability to induce enzymes, most of the inducers are lipid soluble at physiological pH. These 

inducers of the MFO system include the following classes of drugs: hypnotic and sedatives (barbiturates, 

ethanol); anesthetic gases (methoxyflurane, halothane); central nervous system stimulators 

(amphetamine); anticonvulsants (diphenylhydantoin); tranquilizers (meprobamate); antipsychotics 

(triflupromazine); hypoglycemic agents (carbutamide); anti-inflammatory agents (phenylbutazone); 

muscle relaxants (orphenadrine); analgesics (aspirin, morphine); antihistaminics (diphenhydramine); 

alkaloids (nicotine); insecticides (chlordane, DDT, BHC, aldrin, dieldrin, heptachlor epoxide, pyrethrins); 

steroid hormones (testosterone, progesterone, cortisone); and carcinogenic polycyclic aromatic 

hydrocarbons (3-methyl cholanthrene, 3,4-benzpyrene) (Klaassen et al. 1986; Williams and Burson 

1985). 

Thus, exposure to any of these enzyme inducers concurrent with or after exposure to diazinon may result 

in accelerated bioactivation to the more potent anticholinesterase diazoxon. The extent of toxicity 

mediated by this phenomenon is dependent on how fast diazoxon is hydrolyzed to less toxic metabolites, 

a process that is also accelerated by enzyme induction. Similarly, concurrent exposure to diazinon and 

MFO enzyme-inhibiting substances (e.g., carbon monoxide; ethylisocyanide; SKF 525A, halogenated 

alkanes, such as CCl4; alkenes, such as vinyl chloride; and allelic and acetylenic derivatives) may increase 
DIAZINON 118 

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the toxicity of diazinon by decreasing the rate of the hydrolytic dealkylation and hydrolysis of both parent 

diazinon and activated diazinon (diazoxon) (Williams and Burson 1985). The balance between activation 

and detoxification determines the biological significance of these chemical interactions with diazinon. 

Cimetidine, a histamine H2 receptor agonist used to treat peptic ulcers and other gastric acid-related 

disorders, has been shown to potentiate the toxicity of diazinon. In a series of studies, Wu et al. (1996b, 

1996c) demonstrated enhanced cholinergic signs, as well as increased brain AChE and carboxylesterase 

inhibition in diazinon-treated rats that had been pretreated with cimetidine. Significant decreases in total 

body clearance of diazinon and marked increases in the area under the plasma concentration-time curves 

following cimetidine treatment were also noted. In vitro assays demonstrated that cimetidine significantly 

decreased the hepatic metabolism of diazinon. 

Diazinon exposure may interfere with the short-acting muscle relaxant, succinylcholine, used 

concurrently with anesthetics. The action of succinylcholine is terminated by means of its hydrolysis by 

plasma ChE (Klaassen et al. 1986). Since plasma ChE is strongly inhibited by diazinon (Davies and 

Holub 1980b; Klemmer et al. 1978), it is possible that concurrent exposure to diazinon may result in the 

prolongation of the action of succinylcholine leading to prolonged muscular paralysis. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to diazinon than will most persons 

exposed to the same level of diazinon 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 diazinon, or compromised function of organs 

affected by diazinon. Populations who are at greater risk due to their unusually high exposure to diazinon 

are discussed in Section 6.7, Populations with Potentially High Exposures. 

The magnitude of diazinon toxicity, like the toxicity of any xenobiotic, is affected by the rate of its 

metabolic biotransformation to both more and less toxic substances (Klaassen et al. 1986). The newborn 

of several animal species, including humans, have a reduced ability to metabolize xenobiotics. Available 

animal data indicate that developing animals may be particularly sensitive to diazinon neurotoxicity 

(Spyker and Avery 1977). However, the effect of decreased metabolism on diazinon-induced 

neurotoxicity has not been demonstrated. 
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Studies on experimental animals showed that starvation depressed liver microsomal enzyme (P-450) 

activity due to actual loss of the enzyme protein (Boyd and Carsky 1969). Thus, dietary protein 

deficiency could potentially alter diazinon toxicity by diminishing its metabolism in the liver. Hereditary 

factors may also contribute to population sensitivity to diazinon. Atypical plasma ChE with low activity 

is present in a small percentage of the human population. This altered enzyme is the result of a hereditary 

factor with 0.04% occurrence in the population. Since plasma ChE is strongly inhibited by diazinon 

(Davies and Holub 1980b; Klemmer et al. 1978), it is expected that individuals who have atypical ChE 

(or low plasma ChE activity) will be unusually sensitive to the muscle relaxant succinylcholine (Klaassen 

et al. 1986) and may suffer prolonged muscle paralysis if administered succinylcholine while exposed to 

diazinon. Congenital low plasma ChE activity may also increase subpopulation sensitivity to diazinon 

exposure. This is because, after exposure, plasma ChE acts as a depot for diazinon due to its strong 

affinity for the substance (Davies and Holub 1980b; Klemmer et al. 1978), thus decreasing the availability 

of the diazinon dose to the target (neuromuscular tissue) of diazinon toxicity in the population with 

normal plasma ChE levels. In individuals with congenital low plasma ChE activity, less diazinon is 

bound in the blood and more unbound diazinon is in circulation to reach the target of diazinon toxicity 

(neuromuscular tissue). Ueyama et al. (2007) demonstrated significantly increased ChE and RBC and 

brain AChE inhibition in streptozotocin-induced diabetic rats compared to normal rats, an indication that 

diabetics may be more susceptible to OP-induced neurotoxicity. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to diazinon. 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 diazinon. 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 diazinon: 

Clark RF. 2002. Insecticides: Organic phosphorus compounds and carbamates. In: Goldfrank LR, 

Flomenbaum NE, Lewin NA, et al. eds. Goldfrank's toxicologic emergencies. 7th ed. New York, NY: 

Mc-Graw-Hill Medical Publishing Division, 1346-1360. 

Carlton FB, Simpson WM, Haddad LM. 1998. The organophosphates and other insecticides. In: 

Haddad LM, Shannon MW, Winchester JF, eds. Clinical management of poisoning and drug overdose. 

3rd ed. Philadelphia, PA: WB Saunders Company, 836-845. 
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Osmundson M. 1998. Insecticides and pesticides. In: Viccellio P, Bania T, Brent J, et al., eds. 

Emergency toxicology. 2nd ed. Philadelphia, PA: Lippincott-Raven Publishers, 401-413. 

3.11.1 Reducing Peak Absorption Following Exposure 

The following information was extracted from the texts listed above; specific chapters were written by 

Clark (2002), Carlton et al. (1998), and Osmundson (1998), respectively. Following dermal 

contamination with organophosphates, most texts recommend washing the skin with copious amounts of 

soap and water, which may be followed by a second washing with ethyl alcohol to remove the 

contaminant from the skin. However, it should be noted that ethyl alcohol may also enhance the dermal 

absorption of some chemicals as evidenced by its function as an enhancer in some transdermal patches. 

Contaminated clothing, including leather garments, should be destroyed. After oral ingestion, activated 

charcoal is recommended for many organophosphates, although Carlton et al. (1998) note that it may lack 

efficiency with some organophosphates. Osmundson (1998) points out that Ipecac should not be used for 

organophosphate poisoning. Cathartics may be unnecessary as intestinal motility is greatly increased. 

Gastric lavage may be performed with care to prevent aspiration, as organic solvent vehicles may 

precipitate pneumonitis. Treatment of inhaled organophosphates is mostly supportive as respiratory 

distress is a common effect of poisoning; intubation may be necessary to facilitate control of secretions. 

3.11.2 Reducing Body Burden 

Diazinon is rapidly metabolized, with an estimated mammalian biological half-life of 12–15 hours 

(Iverson et al. 1975; Mücke et al. 1970). Consequently, efforts at reducing body burdens of poisoned 

persons may not be critical to the outcome. Dialysis and hemoperfusion are not indicated in 

organophosphate poisonings because of the extensive tissue distribution of the absorbed doses (Mücke et 

al. 1970; Poklis et al. 1980). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The following information has been extracted from the texts listed above. Administration of atropine and 

pralidoxime (2-PAM) seems to be a universally accepted treatment for organophosphate poisoning. It 

should be mentioned, however, that glycopyrrolate, a quaternary ammonium compound, has also been 

used instead of atropine (Bardin and Van Eeden 1990). Unlike atropine, glycopyrrolate does not cross the 

blood-brain barrier and, therefore, has fewer central nervous system effects. Atropine is a competitive 

antagonist at muscarinic receptor sites and since it crosses the blood-brain barrier, it also treats the central 

nervous system effects. Atropine is particularly helpful in drying excessive secretions especially from the 
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tracheobronchial tree. Atropine does not antagonize nicotinic effects; therefore, 2-PAM is needed for 

treatment of muscle weakness and respiratory depression. Most texts recommend an initial dose of 1– 

2 mg for an adult and 0.05 mg/kg for children, preferably by the intravenous route. This may be repeated 

every 15–30 minutes until signs of atropinization occur. 2-PAM is a quaternary amine oxime that can 

reverse the phosphorylation of AChE and thereby restore activity. It may also prevent continued toxicity 

by detoxifying the organophosphate molecule and has an anticholinergic effect (Carlton et al. 1998). 

2-PAM and other oximes function by nucleophilic attack on the phosphorylated enzyme; the oximephosphonate is then split off, leaving the regenerated enzyme. 2-PAM should be administered as soon as 

the diagnosis is made. The initial dose is normally 1–2 g for adults and 25–50 mg/kg for children 

administered intravenously over 30–60 minutes. The dose can be repeated in 1 hour and then every 8– 

12 hours until clinical signs have diminished and the patient does not require atropine. Some patients 

may require higher doses or multiple doses, as enzyme regeneration depends on plasma levels of the 

organophosphate. A 2-PAM serum level of 4 μg/L is suggested as the minimum therapeutic threshold. 

2-PAM is considered a very safe drug with few side effects. 

3.12 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 diazinon 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 diazinon. 

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. 

3.12.1 Existing Information on Health Effects of Diazinon 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

diazinon are summarized in Figure 3-5. The purpose of this figure is to illustrate the existing information 

concerning the health effects of diazinon. Each dot in the figure indicates that one or more studies 
DIAZINON 122 

3. HEALTH EFFECTS 

Figure 3-5. Existing Information on Health Effects of Diazinon 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Human 

Inhalation 

Oral 

Dermal 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Animal 

Inhalation 

Oral 

Dermal 

Existing Studies 
DIAZINON 123 

3. HEALTH EFFECTS 

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 (Agency for Toxic Substances and Disease Registry 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. 

Most of the literature reviewed concerning the health effects of diazinon in humans described case reports 

of individuals or groups of individuals exposed either occupationally or in the home following intentional 

poisoning attempts or otherwise accidental misuse of diazinon or diazinon-containing solutions. The 

predominant route of occupational exposure is believed to be dermal while that for accidental or 

intentional exposure in the home is oral, although some inhalation exposures were reported. Thus, 

Figure 3-5 reflects that information exists for all three routes of exposure. However, all of these reports 

are limited because of the possibility of concurrent or sequential exposure to other potentially toxic 

substances present in the environment (workplace or home), such as other insecticides, or present as 

components of diazinon-containing formulations. In all cases, accurate information regarding levels and 

duration of exposure were not presented in these reports. Further, the health effects of human acute 

exposure to diazinon are much more fully characterized than those associated with intermediate and 

chronic exposures. 

Information regarding the health effects of diazinon following ingestion in laboratory animals is 

substantial, but less information is available on the effects of inhalation and dermal exposures (see 

Figure 3-5). Furthermore, the health effects of acute- and intermediate-duration exposures to diazinon are 

more fully characterized than those associated with chronic-duration exposures. The available 

information indicates that diazinon is a toxic substance to all species of experimental animals, deriving its 

toxicity from AChE inhibition. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Information is available on the effects of acute-duration exposures in 

humans and experimental animals (rats and mice). The available human data consist primarily of studies 

of cholinergic (neurological) reactions resulting from AChE inhibition. Effects noted include respiratory, 

cardiovascular, hematological, kidney, liver, gastrointestinal tract, endocrine, neurological, and 
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immunologic/lymphoreticular system toxicity (Balani et al. 1968; Bichile et al. 1983; Dagli et al. 1981; 

DePalma et al. 1970; Hata et al. 1986; Kabrawala et al. 1965; Klemmer et al. 1978; Lee 1989; Limaye 

1966; Lisi et al. 1987; Matsushita and Aoyama 1981; Poklis et al. 1980; Shankar 1967; Wadia et al. 1974; 

Wecker et al. 1985; Wedin et al. 1984; Weizman and Sofer 1992). The type of information available in 

animals includes LD50 values (Boyd and Carsky 1969; Enan et al. 1982; Gaines 1960, 1969; Harris et al. 

1969) and cholinergic (neurological) reactions resulting from AChE inhibition. Effects noted include 

respiratory, gastrointestinal, hematological, liver, kidney, immunologic/lymphoreticular, and neurological 

toxicity (Boyd and Carsky 1969; Enan et al. 1982; Lox 1983; Mihara et al. 1981). Thus, while the acute 

effects of diazinon inhalation and oral exposure in humans are well-characterized and stem principally 

from AChE inhibition, the diazinon exposure levels at which these effects begin to occur are usually not 

known. Available animal studies provide adequate insight into the AChE inhibiting action of diazinon in 

acute oral exposures. Results of one study (Davies and Holub 1980a) serve as the basis for deriving an 

acute-duration oral MRL for diazinon. Available acute-duration inhalation data in animals are restricted 

to a single report of nasal discharge, polyuria, decreased activity, and salivation in a group of five rats 

exposed to a diazinon aerosol at a concentration of 2,330 mg/m3

. This study was not suitable for MRL 

derivation because it included a single exposure level at which serious effects were observed and no 

supporting data were available. Quantitative acute-duration inhalation toxicity data for humans and 

laboratory animals are needed to assist in the derivation of an acute-duration inhalation MRL for the 

protection of populations, especially those surrounding hazardous waste sites or establishments where 

wastes containing diazinon are released into the air or water, and those that are occupationally exposed to 

high levels of diazinon for brief periods. 

Intermediate-Duration Exposure. Information is available on the effects of intermediate-duration 

exposures in humans and experimental animals (rats, dogs, pigs). The type of information available 

includes studies of cardiovascular, gastrointestinal, hematological, hepatic, musculoskeletal, renal, body 

weight, immunologic/lymphoreticular, and neurological effects (Alluwaimi and Hussein 2007; Anthony 

et al. 1986; Davies and Holub 1980a, 1980b; Earl et al. 1971; Enan et al. 1982; Kalender et al. 2005, 

2006; Lox and Davis 1983; Ogutcu et al. 2006). Data from these studies sufficiently demonstrate the 

cholinergic effects of diazinon. The adverse effects reported in humans and laboratory animals following 

exposure via inhalation, oral, or dermal routes are predominately cholinergic responses deriving from 

inhibition of AChE. An intermediate-duration inhalation MRL was derived for diazinon based on RBC 

AChE inhibition in rats (Hartman 1990). An intermediate-duration oral MRL was derived based on RBC 

AChE inhibition in orally-exposed rats (Davies and Holub 1980a). Further information on the dermal 

toxicity and toxicokinetics for all routes in both humans and laboratory animals would be helpful for use 
DIAZINON 125 

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in additional assessment of intermediate-duration exposure, especially for persons near hazardous waste 

sites or establishments where wastes containing diazinon are released, or near agricultural establishments 

where diazinon is used regularly. 

Chronic-Duration Exposure and Cancer. No adequate epidemiological studies are available 

regarding the potential carcinogenicity or systemic toxicity of diazinon resulting from chronic exposure in 

humans. Two adequate studies have been conducted with rats and mice orally exposed to diazinon (NCI 

1979). While not designed as a cancer bioassay, in a study where rats (groups of 20–30) were orally 

exposed to diazinon for 98 weeks, histopathology of some 30–40 different tissues showed no treatmentrelated increase in neoplasms (Kirchner et al. 1991). This rat study included sufficient information 

regarding AChE inhibition to justify the derivation of a chronic-duration oral MRL for diazinon. A 

52-week oral toxicity study in dogs is available as well (Rudzki et al. 1991). No chronic inhalation MRL 

was calculated for diazinon because no studies for this route are available. Toxicity and toxicokinetic 

data from well-conducted inhalation studies in both humans and laboratory animals would be helpful in 

developing a chronic-duration inhalation MRL for the protection of populations, especially those 

surrounding hazardous waste sites or establishments where wastes containing diazinon are released into 

the air or water, and those occupationally exposed to diazinon for long periods of time. 

Epidemiological studies available on diazinon are inadequate for assessing the carcinogenic potential of 

this chemical substance. The results from these studies are confounded by either concurrent or sequential 

(or both) exposures to other potentially toxic substances, mainly other insecticides (Cantor et al. 1992; 

Davis et al. 1993; Morris et al. 1986), although cancers in several tissue types (unspecified type of 

childhood brain cancer, non-Hodgkin's lymphoma, multiple myeloma) were identified in these chronic 

human exposure studies(presumed to involve multiple concurrent routes of exposure). In adequate cancer 

oral bioassays conducted in rats and mice, the NCI (1979) concluded that diazinon is not carcinogenic in 

these species under the conditions of the bioassays. Chronic inhalation and dermal bioassays would be 

helpful to determine whether long-term inhalation or dermal exposures in populations, especially those 

surrounding hazardous waste sites or establishments where wastes containing diazinon are released into 

the air or water, and those occupationally exposed to diazinon for long periods of time, are at risk of 

developing cancers. 

Genotoxicity. Chronic occupational exposure to multiple insecticides, including diazinon, has been 

associated with an increased incidence of chromosomal aberration and increased sister chromatid 

exchange in peripheral blood lymphocytes of these individuals (de Ferrari et al. 1991; Kiraly et al. 1979; 
DIAZINON 126 

3. HEALTH EFFECTS 

See et al. 1990). The results from these studies are confounded by either concurrent or sequential (or 

both) exposures to other unknown toxic substances, mainly other insecticides, that may be genotoxic. 

Significantly increased sister chromatid exchanges were noted in peripheral blood lymphocytes from a 

group of volunteers following exposure to diazinon in a sheep-dip formulation (Hatjian et al. 2000). 

However, the specific role of diazinon in the observed effect could not be determined because the sheepdip formulation contained other ingredients as well. 

Limited information is available regarding the genotoxicity of diazinon in nonhuman species in vivo. 

Diazinon did not induce sister chromatid exchanges in the bone marrow of mice administered 100 mg/kg 

diazinon by gavage (EPA 1990). Diazinon induced mutations in a wing SMART of Drosophila 

melanogaster (Çakir and Sarikaya 2005). 

The results of in vitro tests in a variety of test systems (predominantly microbial assays) are equivocal. 

Diazinon was positive for gene mutations in one test using the S. typhimurium mutagenicity or reverse 

mutation assay with metabolic activation (Wong et al. 1989) and in the mouse lymphoma cell forward 

mutation assay without metabolic activation (McGregor et al. 1988). The compound was also positive for 

chromosomal aberrations in Chinese hamster cells with metabolic activation (Matsuoka et al. 1979). In 

contrast, evaluations for genetic mutation activity in the S. typhimurium mutagenicity or reverse mutation 

assay (Marshall et al. 1976) and in the rec-assay utilizing strains of B. subtilis (Shirasu et al. 1976) 

without metabolic activation, and in tests for sister chromatid exchange in Chinese hamster cells, both 

with and without metabolic activation (Chen et al. 1982), and for chromosomal aberrations in human 

peripheral blood lymphocytes (Lopez et al. 1986), were all negative. A full battery of in vivo tests in 

animals and additional in vitro tests in microbial systems for all genetic end points is necessary for the 

determination of the genetic toxicity potential of diazinon. 

Reproductive Toxicity. No information was located on the reproductive effects of diazinon exposure 

in humans. Limited data are available regarding diazinon-induced reproductive effects in animals. 

Increased litter size was reported in one study of diazinon-treated rats (Green 1970), although a second rat 

study reported significant reduction in litter size at oral maternal diazinon doses of 0.18 and 9 mg/kg/day 

(Spyker and Avery 1977). Diazinon-induced adverse effects on reproductive tissue weights, sperm 

quality, and fertility were noted in orally-exposed male rats (Abd El-Aziz et al. 1994). Testicular atrophy 

and arrested spermatogenesis were noted in dogs administered diazinon orally at doses ≥10 mg/kg/day for 

up to 8 months (Earl et al. 1971). No adverse effects on reproduction were observed in four generations 

of rats following oral administration of diazinon to female rats from each generation for 60 days prior to 
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weaning (Green 1970). No gross or histological evidence of treatment-related damage to reproductive 

tissues was observed in rats receiving diazinon in the diet for 13 weeks (Singh 1988)or 98 weeks 

(Kirchner et al. 1991), or in dogs exposed for 13 weeks (Barnes 1988). A well-designed 

multigenerational reproductive toxicity rat or mouse study is needed to more adequately assess the 

potential for diazinon to cause reproductive toxicity in humans. 

Developmental Toxicity. Information regarding the developmental effects in humans from exposure 

to diazinon was not located. Four of the located studies in laboratory animals did not find any significant 

developmental effects in the rats, mice, hamsters, and rabbits tested (Barnett et al. 1980; Green 1970; 

Robens 1969; Spyker and Avery 1977). In two of these studies, marked reduction in rat pup birth weight 

and continued significant retardation in growth rate (Green 1970), or significantly elevated mortality in 

rat pups at weaning (Barnett et al. 1980) were reported. It has been suggested that the effects reported for 

pups derive from diazinon impairment of placental transport of nutrients or maternal regulation of fetal 

growth, or directly via antagonism to cholinergic development of the fetus (Spyker and Avery 1977). 

Collectively, the results of available studies for diazinon indicate that the compound is not of particular 

developmental toxicity concern at exposure levels lower than those resulting in maternal neurotoxicity, 

although additional neurodevelopmental toxicity studies could be designed to more critically test the 

neurodevelopmental toxicity potential. 

Immunotoxicity. Autopsy reports in which the victims were exposed to high acute doses of diazinon 

described damage to lymphoreticular organs (spleen, thymus) (Limaye 1966; Poklis et al. 1980). One 

human study reported allergic interaction between the fungicide benomyl and diazinon from prolonged 

dermal contact with diazinon (Matsushita and Aoyama 1981). Several oral animal studies also reported 

damage to immune structures in rats and dogs. Rats exhibited reduced spleen weight, splenic red pulp 

contraction, reduced thymus weight, and thymic atrophy ranging from minor to near total loss of 

thymocytes following acute exposure to moderate doses of diazinon (Boyd and Carsky 1969). Doserelated splenic degeneration after 232 days of diazinon exposure was also reported in 1/3 diazinon-treated 

dogs (Earl et al. 1971). The splenic atrophy reported in this study may be a result of the generalized 

emaciated condition of the dog due to diarrhea, emesis, and anorexia. Exposure of guinea pigs in a 

dermal sensitization study resulted in allergic interaction between the fungicide benomyl and diazinon 

(Matsushita and Aoyama 1981). Dermal application of diazinon induced delayed contact hypersensitivity 

at both 24 and 48 hours after challenge in the guinea pig maximization test (Matsushita et al. 1985). Oral 

administration of diazinon to mice resulted in increased levels of interleukin-10 in selected splenic 

lymphocyte subpopulations and decreased levels of interferon-γ in B cells (Alluwaimi and Hussein 2007). 
DIAZINON 128 

3. HEALTH EFFECTS 

These results indicate a diazinon-induced effect on cytokines involved in the regulation of cellular and 

humoral responses. No gross or histological evidence of treatment-related damage to the spleen or 

thymus was observed in rats receiving diazinon from feed for 13 weeks (Singh 1988) or 98 weeks 

(Kirchner et al. 1991), or dogs receiving diazinon in the diet for 13 weeks (Barnes 1988) or 52 weeks 

(Rudzki et al. 1991). Based on equivocal results from available animal studies, additional human and 

animal data would be helpful in defining the immunologic/lymphoreticular injury potential of diazinon in 

humans. 

Neurotoxicity. Available evidence shows that diazinon exposure in humans results in the inhibition of 

neural AChE (Coye et al. 1987; Davies and Holub 1980a, 1980b; Enan et al. 1982; Harris et al. 1969; 

Rajendra et al. 1986; Takahashi et al. 1991; Wecker et al. 1985). Severe inhibition of this enzyme results 

in accumulation of acetylcholine at its sites of action and excessive or interminable stimulation of both 

sympathetic and parasympathetic cholinergic receptors leading to muscarinic and nicotinic effects. 

Clinical signs of diazinon-induced neurotoxicity include muscular fasciculations, weakness, and paralysis; 

mydriasis; tachycardia; hypertension; miosis; excessive glandular secretions (salivation, lacrimation, 

rhinitis); nausea; urinary incontinence; vomiting; abdominal pain; diarrhea; bronchoconstriction or 

bronchospasm; increased bronchosecretion; vasodilation; bradycardia; hypotension; respiratory 

depression; anxiety; insomnia; headache; restlessness; tension; mental confusion; loss of concentration; 

apathy; drowsiness; ataxia; tremor; convulsion; and coma (Adlakha et al. 1988; Bichile et al. 1983; Coye 

et al. 1987; Kabrawala et al. 1965; Klaassen et al. 1986; Klemmer et al. 1978; Maizlish et al. 1987; 

Rayner et al. 1972; Shankar 1967, 1978; Williams and Burson 1985). These neurological effects have 

also been reported in diazinon-treated rats (Boyd and Carsky 1969; Earl et al. 1971). The current 

information from human and laboratory animal studies provides sufficient demonstration that the nervous 

system is the primary target of diazinon poisoning. The database of animal information for acute-, 

intermediate-, and chronic-duration oral exposure to diazinon is sufficiently characterized to allow the 

derivation of acute-, intermediate-, and chronic-duration oral MRLs. Health effects following 

intermediate-duration inhalation exposure to diazinon have been sufficiently characterized to allow the 

derivation of an intermediate-duration inhalation MRL. However data are lacking for acute- and chronicduration inhalation exposure. Additional animal studies to assess inhalation exposure for acute- and 

chronic-duration exposure to diazinon should be designed to allow for the derivation of inhalation MRLs 

for these exposure durations as well. Information regarding health effects following dermal exposure are 

limited (EPA 1990; Lee 1989), but indicate that dermal exposure to relatively high doses of diazinon 

would result in neurological effects similar to those elicited from oral or inhalation exposure. 
DIAZINON 129 

3. HEALTH EFFECTS 

Epidemiological and Human Dosimetry Studies. Information on the health effects of diazinon 

in humans is derived from case reports of accidental or intentional exposure to diazinon, epidemiological 

studies, and controlled exposure studies (Adlakha et al. 1988; Alavanja et al. 2004; Beane Freeman et al. 

2005; Bichile et al. 1983; Cantor et al. 1992; Dagli et al. 1981; Dahlgren et al. 2004; Davis et al. 1993; 

EPA 2000a, 2001; Hata et al. 1986; Kabrawala et al. 1965; Klemmer et al. 1978; Maizlish et al. 1987; 

Morris et al. 1986; Rayner et al. 1972; Reichert et al. 1977; Richter et al. 1992; Schenker et al. 1992; 

Shankar 1967, 1978; Soliman et al. 1982; Wadia et al. 1974; Wedin et al. 1984). The most likely 

identifiable subpopulations exposed to diazinon are pesticide applicators, farm workers, and individuals 

involved in the production of diazinon, since diazinon is no longer registered for use in residential 

pesticides in the United States (EPA 2004b). Well-designed epidemiological studies of exposed workers 

are needed. The nervous system is a known target of acute exposure, but little is known regarding 

possible long-term effects of acute exposure to high levels of diazinon or longer-term exposure at 

relatively low exposure levels. Additional epidemiological studies should assess the potential effects of 

such exposure scenarios. 

Biomarkers of Exposure and Effect. 

Exposure. Diazinon is rapidly absorbed from the gastrointestinal tract and widely distributed throughout 

the body in both humans (Poklis et al. 1980) and animals (Janes et al. 1973; Mücke et al. 1970). Potential 

biomarkers of exposure to diazinon include parent compound and metabolites of diazinon such as IMHP, 

DEP, and DETP. However neither parent compound nor metabolites of diazinon have been demonstrated 

to represent quantitative indicators of diazinon exposure levels. No human or animal studies have 

reported the presence of unchanged diazinon in the urine following exposure, although traces of 

unchanged diazinon have been detected in animal feces following exposure (Mücke et al. 1970). Urinary 

and fecal excretion of IMHP, DEP, and DETP have been reported following oral exposure of animals to 

diazinon (Iverson et al. 1975; Machin et al. 1975; Mount 1984; Mücke et al. 1970; Seiber et al. 1993; 

Yang et al. 1971). Both DEP and DETP have been detected in the urine of exposed insecticide 

applicators (Maizlish et al. 1987) and volunteers administered diazinon orally or dermally (Garfitt et al. 

2002). Although analysis of urine samples for the presence of these metabolites represents a potential 

means of assessing recent human exposure to diazinon, DEP and DETP can originate from exposure to 

other organophosphorus compounds and, therefore, are not specific for diazinon exposure. Further 

studies designed to refine the identification of metabolites specific to diazinon and provide dosimetric 

data will be useful in the search for a more dependable biomarker of diazinon exposure. 
DIAZINON 130 

3. HEALTH EFFECTS 

The development of recent analytical techniques allows for the simultaneous detection of numerous 

biomolecules, thus facilitating complete description of the genome for a particular organism (genomics). 

These techniques can be applied to analysis of multiple gene transcripts (transcriptomics), proteins 

(proteomics), and metabolites (metabolomics). The application of these techniques to conventional 

toxicology is known as toxicogenomics. Although toxicogenomic data are not presently available for 

diazinon, such data could eventually lead to a more complete understanding of pharmacokinetic pathways 

involved in diazinon toxicity and might possibly elucidate particular biomarkers of exposure. 

Effect. The major action resulting from human exposure to diazinon is the inhibition of AChE (Coye et 

al. 1987; Davies and Holub 1980a, 1980b; Enan et al. 1982; Harris et al. 1969; Rajendra et al. 1986; 

Takahashi et al. 1991; Wecker et al. 1985). Two pools of cholinesterases are present in human blood: 

RBC AChE and plasma ChE. RBC AChE is identical to AChE present in neuromuscular tissue (the 

target of diazinon action). Inhibition of both forms of cholinesterase has been associated with exposure to 

diazinon in humans (Coye et al. 1987; Soliman et al. 1982) and animals. While plasma ChE has no 

known physiological function, available data indicate that plasma ChE activity is a more sensitive marker 

for diazinon exposure than RBC AChE activity (Endo et al. 1988; Hayes et al. 1980). Therefore, future 

studies that provide qualitative and dosimetric information regarding diazinon exposure and plasma ChE 

inhibition may provide a useful biomarker of effect for diazinon (or other anticholinesterase compounds) 

exposure. Currently, no effect specific to diazinon exposure has been identified by any study. Future 

studies designed to provide such information would be useful in identifying exposure to diazinon. 

Absorption, Distribution, Metabolism, and Excretion. No studies were located regarding 

distribution and metabolism of diazinon after inhalation or dermal exposure in humans or animals, or 

regarding the excretion of diazinon after dermal exposure in animals. Diazinon was detected in several 

tissues from a woman who had ingested a lethal amount of a diazinon formulation, indicating rapid 

gastrointestinal tract absorption (Poklis et al. 1980). Rapid and extensive absorption was noted following 

the ingestion of a 0.011 mg/kg dose of diazinon by a group of five volunteers (Garfitt et al. 2002). 

Results of animal studies confirm the rapid absorption of diazinon following oral administration 

(Abdelsalam and Ford 1986; Iverson et al. 1975; Janes et al. 1973; Machin et al. 1971, 1974; Mücke et al. 

1970; Wu et al. 1996a). Dermal absorption of diazinon has also been demonstrated in humans (Garfitt et 

al. 2002; Wester et al. 1993). Animal studies confirm the observation of rapid, widespread distribution of 

absorbed diazinon (Abdelsalam and Ford 1986; Janes et al. 1973; Machin et al. 1971, 1974; Mücke et al. 

1970). Both human and animal data demonstrate rapid metabolism of diazinon and its oxon to DEP, 

DETP, and IMHP, which are predominantly excreted in the urine (Garfitt et al. 2002; Klemmer et al. 
DIAZINON 131 

3. HEALTH EFFECTS 

1978; Mücke et al. 1970; Poklis et al. 1980; Wester et al. 1993; Wu et al. 1996a). Additional studies 

designed to quantify the toxicokinetics of diazinon following inhalation, oral, and dermal exposure in 

humans and animals would be useful. Dermal exposure studies could be designed to assess the extent of 

diazinon degradation on the skin prior to absorption and the relative dermal penetrability of diazinon 

breakdown products. 

Comparative Toxicokinetics. A PBPK/PD model has been developed to predict both 

pharmacokinetic disposition of diazinon and metabolites and pharmacodynamic effect (esterase activity 

inhibition) for diazoxon in target tissues of rats and humans for multiple routes of exposure (Poet et al. 

2004). The model structure is identical for both rats and humans, with species-specific parameter values 

used for physiological volumes and flow rates and model-optimized values used for oral absorption. The 

model was evaluated for simulating oral, intravenous, and intraperitoneal doses in rats ranging from 15 to 

100 mg/kg. For humans, it was evaluated for a single oral dose level of 11 μg/kg and a dermal dose of 

4 mg/kg. In humans, the model predicts urine levels of diazinon metabolites from oral and dermal 

exposures that are very similar to observations; however, the ability of the model to accurately simulate 

levels of diazinon and diazoxon and levels of esterase inhibition in human target tissues is uncertain due 

to the lack of human data to validate these endpoints. Therefore, the model was not used for MRL 

derivation. Additional human data regarding blood and RBC diazinon and diazoxon levels would serve 

to reduce uncertainty of the human model predictions. Comparative human and rat pharmacokinetic 

studies of diazinon could also provide valuable species-specific pharmacokinetic data and reduce 

uncertainty of PBPK model predictions. 

Methods for Reducing Toxic Effects. Procedures used to limit absorption and to interfere with the 

mechanism of action of organophosphates, including diazinon, following acute exposure have been 

adequately described (Carlton et al. 1998; Clark 2002; Osmundson 1998). However, methods for 

reducing toxicity following long-term, low-level exposure are lacking, and would be needed if potential 

health effects from long-term, low-level exposure to diazinon are identified. 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 

It is not known whether children are more susceptible than adults to diazinon toxicity. A single human 

study reported neurophysiological and neuropsychological deficits and delayed bone growth in young 
DIAZINON 132 

3. HEALTH EFFECTS 

children exposed at home to a formulation of diazinon that was misused to control an infestation of fleas 

(Dahlgren et al. 2004). These results provide suggestive evidence that children may be particularly 

susceptible to diazinon toxicity during critical periods of neural and skeletal development. Results of one 

animal study indicated that fetal exposure to low levels of diazinon may result in functional deficits that 

can only be detected by systemic behavioral evaluation (Spyker and Avery 1977). Results of 

subcutaneous injection studies indicate that critical periods of neurological development may be 

particularly sensitive to diazinon toxicity (Jameson et al. 2007; Slotkin et al. 2006a, 2006b, 2007). Young 

rats appear to be more susceptible than adult rats to diazinon-induced brain AChE inhibition, which may 

be at least partially due to decreased detoxification capability in the young rats (Padilla et al. 2004). 

Additional animal studies should be designed to support initial findings of age-related differences in 

susceptibility to diazinon toxicity. 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

Three ongoing studies pertaining to diazinon were located in a search of the Federal Research in Progress 

database (FEDRIP 2006). 

Dr. L. Costa of Fred Hutchinson Cancer Research Center, Seattle, Washington is investigating 

relationships between PON1 polymorphism and diazinon and diazoxon metabolism using a 

physiologically-based kinetic model. 

Dr. J. Seifert of the University of Hawaii, Honolulu, Hawaii is searching for changes in rat liver proteins 

that may be linked to diazinon-induced alterations in blood glucose concentrations and the metabolism of 

l-tryptophan at intraperitoneally-injected doses of diazinon that are clearly neurotoxic. 

Dr. B. Wilson of the University of California, Davis, California is using organophosphates, including 

diazinon, to develop biomarkers of exposure and to study the molecular and cellular mechanisms of 

toxicity as part of a more wide-ranging project. 
DIAZINON 133 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information regarding the chemical identity of diazinon is located in Table 4-1. 

Diazinon is manufactured in the United States and formulated as granules, a wettable powder, an 

emulsifiable solution, a dust, a seed dressing, or a mixed formulation with other insecticides. 

Manufacture of diazinon for indoor use products in the United States was discontinued as of 

March 1, 2001, and manufacture of non-agricultural outdoor use products was discontinued as of 

June 30, 2003 (HSDB 2008; WHO 1998). 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of diazinon is located in Table 4-2. 
DIAZINON 134 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Diazinon 

Characteristic Information Reference 

Chemical name O,O-Diethyl O-(2-isopropyl-6-methyl4-pyrimidinyl) phosphorothioate HSDB 2008 

Synonyms(s) O,O-Diethyl-O-(2-isopropyl-4-methyl6-pyrimidinyl) phosphorothioate; O,Odiethyl-O-6-methyl-2-isopropyl-4-pyrimidinyl] 

phosphorothioate; others 

HSDB 2008 

Registered trade name(s) Diazinon; Alfa-tox; Basudin; Diazol; 

Gardentox; Knox-Out; Spectracide; others 

HSDB 2008 

Chemical formula C12H21N2O3PS HSDB 2008 

Chemical structure Kappers et al. 2001 

CH3CH2 O CH(CH3)

2 

CH3CH2 O 

N 

O N

P 

S 

CH3 

Identification numbers: 

CAS registry 333-41-5 HSDB 2008 

NIOSH RTECS TF 3325000 NIOSH 2006 

EPA hazardous waste No data 

 OHM/TADS No data 

 DOT/UN/NA/IMCO shipping UN 2783 Organophosphorouspesticides; HSDB 2008 

UN 2784 Organophosphorouspesticides; 

UN 3017 Organophosphorouspesticides; 

UN 3018 Organophosphorouspesticides; 

IM06.1 Organophosphorouspesticides; solid; 

IMO3.0 Organophosphorouspesticides; 

liquid 

HSDB 303 HSDB 2008 

NCI CO 8673 HSDB 2008 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/Intergovernmental Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substances 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 
DIAZINON 135 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Diazinon 

Property Information Reference 

Molecular weight 304.35 HSDB 2008 

Color Colorless HSDB 2008 

Physical state Liquid HSDB 2008 

Melting point No data HSDB 2008 

Boiling point 83–84 °C at 2x10-3 mm Hg; decomposes at O’Neil et al. 2001 

>120 °C 

Density: 

at 20 °C/4 °C 1.116–1.118 g/mL HSDB 2008 

Odor Faint ester-like HSDB 2008 

Odor threshold: 

 Water No data 

Air No data HSDB 2006 

Taste threshold No data 

Solubility: 

Water at 20 °C 0.004% (40 mg/L) HSDB 2008 

 Organic solvent(s) Miscible with petroleum ether, alcohols, HSDB 2008 

ether, cyclohexane, benzene and similar 

hydrocarbons 

Partition coefficients: 

 Log Kow 3.81 HSDB 2008 

 Log Koc 1.602–2.635, HSDB 2008 

average for three soils, 2.281 

Vapor pressure 

at 20 °C 9.01x10-5 mm Hg HSDB 2008 

at 40 °Cb

 1.1x10-3 mm Hg O’Neil et al. 2001 

Henry's law constant 1.17x10-7 atm-m3

/mol 

Autoignition temperature No data HSDB 2008 

Flashpoint 82.2 oC NIOSH 2006 

Flammability limits Practically nonflammable HSDB 2008 

Explosive limits No data HSDB 2008 

HSDB = Hazardous Substances Data Bank; NIOSH = National Institute for Occupational Safety and Health; 
DIAZINON 136 

4. CHEMICAL AND PHYSICAL INFORMATION 

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DIAZINON 137 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Diazinon is the Ciba-Geigy Corporation trademark name for the active ingredient O,O-diethylO-(2-isopropyl-6-methyl-4-pyrimidinyl) phosphorothioate. This organophosphorus insecticide is 

produced commercially by reacting 2-isopropyl-4-hydroxy-6-methylpyrimidine and O,O-diethyl 

phosphorochloridothioate (HSDB 2008). It is also produced by condensation of isobutyramidine with 

acetoacetate to yield the intermediate, 2-isopropyl-4-methylpyrimidine, which is transformed to diazinon 

by treatment with diethylthiophosphate acid (Müller et al. 2005). Ciba-Geigy Corporation produced this 

chemical in McIntosh, Alabama until 1994 (SRI 1994, 1995). Currently, diazinon is produced by Drexel 

Chemical Company in Cordele, Georgia (SRI 2005). 

In 1990, 4.67 million kg of diazinon were produced in the United States (Larkin and Tjeerdema 2000). 

No more recent production estimates for diazinon are available. 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). As of June 30, 2001, 

manufacturing of indoor use products containing diazinon was discontinued. Manufacture of nonagricultural outdoor use products containing diazinon was discontinued as of June 30, 2003 (EPA 2004b). 

Production amounts of diazinon would be expected to decrease due to the discontinuation of all 

residential products containing this chemical. 

Beginning on January 1, 1995, diazinon was listed as one of the newly added chemicals that 

manufacturing and processing facilities would be required to report under Title III of the Superfund 

Amendments and Reauthorization Act of 1986 (SARA) (Larkin and Tjeerdema 2000). Table 5-1 lists the 

production year, number of facilities, the state where each facility is located, and the range (in pounds) for 

each domestic manufacturer that reported the production or formulation of diazinon in 2005 (TRI05 

2007). Manufacturers are required to report Toxics Release Inventory (TRI) data to satisfy EPA 

requirements. The TRI data should be used with caution since only certain types of facilities are required 

to report (EPA 2005). This is not an exhaustive list. 
DIAZINON 138 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Facilities that Produce, Process, or Use Diazinon 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AL 6 100,000 9,999,999 1, 3, 4, 7, 9 

AR 3 1,000 99,999 9, 12 

CA 2 10,000 99,999 7 

CO 2 10,000 999,999 7 

FL 1 100,000 999,999 7 

GA 7 1,000 9,999,999 2, 3, 4, 7, 9 

IA 1 100,000 999,999 7 

IL 1 1,000 9,999 12 

KS 3 1,000 99,999 7, 8 

LA 3 1,000 999,999 12 

MO 5 1,000 9,999,999 7, 9 

NE 1 10,000 99,999 12 

NY 1 1,000 9,999 7 

OH 7 100 9,999,999 7, 8, 12 

TN 2 1,000 99,999 7, 12 

TX 7 1,000 999,999 7, 9, 12 

UT 1 10,000 99,999 12 

WI 2 1,000 99,999 7 

WY 1 10,000 99,999 7 

a

Post office state abbreviations used b

Amounts on site reported by facilities in each state c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

Source: TRI05 2007 (Data are from 2005) 
DIAZINON 139 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.2 IMPORT/EXPORT 

Official government statistics on imports and exports for chemicals such as diazinon are summarized 

under broad generic categories such as “pesticides” or “organophosphates.” In 1982, estimated diazinon 

imports to the United States were 6.41x104 kg (141,000 pounds) (HSDB 2008). No recent estimates are 

available on the volume of diazinon imported into the United States. Data on past and/or current import 

volumes are not adequate to assess trends in import volumes of this pesticide. 

The U.S. EPA has no mandate to collect comprehensive data on pesticide exports, and does not have 

permission from the Department of Commerce to access the information in export declarations (Smith 

2001). In a report by the Foundation for the Advancement of Science and Education, the authors report 

that no government agency maintains current records concerning what specific pesticides are exported by 

the United States. Between 1992 and 1994, 1.1 billion pounds of pesticides were exported with their 

exact chemical name omitted from the shipping records. Of the 25% of all pesticide exports that could be 

identified to a specific chemical, these authors identified export volumes of diazinon for 1992, 1993, and 

1994 of 4.7 million, 5.0 million, and 3.4 million pounds, respectively. The remaining 75% of all exported 

pesticides could not be identified to a specific chemical (FASE 1996). According to U.S. Customs 

records, the United States exported an estimated 5.8 million pounds of diazinon from 1997 to 2000 

(Smith 2001). 

5.3 USE 

Diazinon is an organophosphate pesticide that was first registered for use in the United States in 1956 

(EPA 2004b). It was first developed as an insecticide, acaricide, and nematicide for use on a variety of 

pests for control of soil insects and pests of fruit, vegetables, and forage and field crops (EPA 2004b). 

Diazinon is used on ranges, pastures, grasslands, and ornamentals. It is used on grubs and nematodes in 

turf, in seed treatment, and in fly control (Meister et al. 2006). It is also used against flies in greenhouses 

and mushroom houses. Other uses include applications as a topically applied pesticide agent (e.g., 

aerosols, sprays, dips, ear tags) on non-lactating livestock to control biting insects or skin parasites (EPA 

2004b; Wester et al. 1993; Worthing and Walker 1983). 

With the steady elimination of older organochlorine pesticides from the market, diazinon has replaced 

many of the organochlorine pesticides such as chlordane. In addition to applications in agriculture, 

diazinon has been heavily used in urban areas (Banks et al. 2005). It had been used extensively in home 

and garden applications, in formulations designed to prevent such pests as crickets or cockroaches from 
DIAZINON 140 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

infesting homes or offices, and in pet collars (EPA 2004b). Residential application methods included 

aerosol cans, spray equipment, and granular spreaders. Due to the emerging health and ecological risks 

posed by diazinon, manufacturers agreed to phase out and cancel all residential products. As a result, 

after December 31, 2004, no diazinon products with residential uses would be registered or sold (EPA 

2004b). It was also formerly used on golf courses and large sod farms for control of grubs and nematodes 

in turf, but these uses were suspended in the 1980s, first in the United States and then in Canada, after 

deaths occurred in migratory waterfowl (Frank et al. 1991a; Kendall et al. 1993). More cancellations and 

restrictions to be implemented in the future include: cancellation of all granular registrations (with some 

exceptions), deletion of aerial application for all uses (with some exceptions), deletion of foliar 

application on all vegetable crops, application rate reduction for ornamentals and lettuce, establishment of 

crop specific reentry intervals (REIs), cancellation of all seed treatment uses, engineering controls for all 

uses, reduction of the number of applications per growing season, and cancellation of use on some crops 

(EPA 2004b). Various types of diazinon formulations are produced including dusts, emulsifiable 

concentrates, granules, impregnated materials, microencapsulated forms, liquid, pressurized sprays, 

soluble concentrates, flowable concentrates, ready-to-use solutions, seed dressings, and wettable powders 

(EPA 2004b). 

From 1987 through 1997, total annual domestic usage of diazinon was over 13 million pounds. However, 

most of this (about 70%) was allocated to outdoor residential uses (EPA 2004b). Since residential uses of 

diazinon have been discontinued, the total annual usage would be expected to be significantly lower. In 

the EPA Interim reregistration eligibility decision for diazinon (EPA 2004b), it was estimated that 

approximately 4 million pounds of active ingredient diazinon are used annually on agricultural sites. 

According to data from the Department of Pesticide Regulation’s Pesticide Use Reports, the reported 

amount of diazinon used for both agricultural and reportable non-agricultural applications in California 

each year from 2000 to 2004 was 1,057,845; 1,001,294; 690,590; 523,786; and 492,050 pounds, 

respectively (California Environmental Protection Agency 2006). 

5.4 DISPOSAL 

Diazinon is currently considered a toxic chemical under Section 313 of the Emergency Planning and 

Community Right-To-Know Act (EPA 1995a, 1995b). Disposal of wastes containing diazinon is 

controlled by a number of federal regulations (see Chapter 8). 
DIAZINON 141 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

For ultimate disposal, large amounts of diazinon residuals should be incinerated in a unit with effluent gas 

scrubbing, while physical, chemical, and biological treatments may be appropriate for disposal of smaller 

quantities of diazinon. Two types of physical treatment systems, which have been tested and employed 

for pesticide wastes, are lined evaporation/degradation beds and granular activated sorption systems. 

Chemical treatment methods for pesticide waste degradation include photolysis, hydrolysis, and 

oxidation. Diazinon hydrolysis using sodium perborate and copper (+2) catalyst have been used (Felost 

et al. 2003). 

Composting has been used for the disposal of diazinon-contaminated soils and organic solids. Diazinon 

was reported to undergo nearly complete degradation during composting of dairy manure. Complete 

degradation was also observed to occur within 4 weeks after application to turf and 6 weeks during 

composting of grass clippings (Felost et al. 2003). 

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 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 (26 FR 6712 "Standards for 

Pesticide Containers and Containment") (EPA 1994a). 

No information was found on the past and present volumes of diazinon or diazinon-contaminated wastes 

disposed of by each disposal method. 
DIAZINON 142 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

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DIAZINON 143 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Diazinon has been identified in at least 25 of the 1,699 hazardous waste sites that have been proposed for 

inclusion on the EPA National Priorities List (NPL) (HazDat 2008). However, the number of sites 

evaluated for diazinon is not known. The frequency of these sites can be seen in Figure 6-1. Of these 

sites, all are located within the United States. 

Diazinon is released to the environment solely by human activities. Major atmospheric emissions result 

from volatilization of the chemical from soil resulting from its extensive use as an insecticide or from 

drift during pesticide application. Diazinon is released to surface waters directly by point source 

discharges, from drift during pesticide applications, and by runoff from agricultural and urban areas (EPA 

1995a, 1995b). 

Diazinon is found in all environmental compartments, but shows no pronounced tendency to partition to a 

particular environmental medium. Given adequate time, diazinon will be degraded by abiotic and biotic 

processes so that the parent compound is not persistent. Degradation products of diazinon include 

diazoxon, a toxic degradate, and 2-isopropyl-6-methyl-4-hydroxypyimidine (IMHP or oxypyrimidine), a 

persistent, less toxic degradate (EPA 2004b). Oxypyrimidine is the main soil and water degradate of 

diazinon (EPA 2004b). Diazinon has been detected in the atmosphere and trace amounts of its oxidation 

product (diazoxon) have also been detected. The diazoxon to diazinon ratio ranged from 0.056 to 7.1, but 

was generally <0.4 (Glotfelty et al. 1990a). In a study of diazinon use in the Central Valley of California, 

Seiber et al. (1993) reported that during daylight hours, the oxon to thion ratio in the atmosphere averaged 

0.52, while at night, the ratio was 0.10. Diazinon can be converted to diazoxon in the atmosphere via 

ultraviolet (UV) radiation (Seiber et al. 1993). The estimated half-life for the vapor phase reaction of 

diazinon with hydroxyl radicals is approximately 4 hours (Meylan and Howard 1993). Diazinon can be 

transported moderate distances in the air from its original point of use (Zabik and Seiber 1993). 

Diazinon released to surface waters or soil is subject to volatilization, photolysis, hydrolysis, and 

biodegradation. Biodegradation, primarily under aerobic conditions, is a major fate process for diazinon 

associated with water and soil. Diazinon can be biodegraded under anaerobic conditions as well. 

Hydrolysis is an important mechanism for degradation, particularly at low pH in water and soil. Diazinon 

has a relatively short half-life in water, ranging from 70 hours to 12 weeks depending on pH, temperature, 
DIAZINON 144 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Diazinon Contamination 
DIAZINON 145 

6. POTENTIAL FOR HUMAN EXPOSURE 

and sunlight as well as the presence of microorganisms (Chapman and Cole 1982; EPA 1976; Ferrando et 

al. 1992; Frank et al. 1991b; Scheunert et al. 1993; Schoen and Winterlin 1987; Sharom et al. 1980b). 

The half-life of diazinon in soil is influenced by the pH conditions in the soil and the soil type. The halflife values at pH 4, 7, and 10 were 66, 209, and 153 days, respectively, in sandy loam; 49, 124, and 

90 days, respectively, in clay loam; and 14, 45, and 64 days, respectively, in sandy loam amended with 

peat (Schoen and Winterlin 1987). Diazinon is moderately mobile in some soils, particularly those with 

an organic matter content <3%, and can leach from soil into groundwater. If released to water, this 

pesticide does not bioaccumulate (bioconcentration factors [BCFs] values generally <100) in aquatic 

organisms. 

In the United States, monitoring efforts under many national programs have not analyzed for this 

chemical. Diazinon has been identified in air samples from both rural and urban areas and in indoor air in 

both domestic and commercial buildings. It has also been detected in surface water, effluents from 

publicly owned treatment works (POTWs), and groundwater. It has been detected in soil and sediment in 

areas where it is extensively used in agriculture. Current information is lacking on the total amount of 

diazinon released to the environment and on the amount of diazinon that partitions into each 

environmental compartment. 

The best-documented concern over diazinon relates to acute exposures of humans during or immediately 

following pesticide applications. This concern is warranted, since diazinon has been widely used, with 

many applications in urban areas (homes and gardens) that may have increased the possibilities of human 

exposure. In order to mitigate the exposure and risk to the general population, especially children, the 

EPA has phased out all residential uses of diazinon as of December 2004 (EPA 2004b). Diazinon and its 

major metabolite, diazoxon, have significant acute toxicity to humans. General population exposure to 

diazinon may occur through ingestion of contaminated food or drinking water and inhalation. Ingestion 

of foods contaminated with small residues of diazinon is the most likely route of exposure for the general 

population not living in areas where diazinon is extensively used. The general population may also be 

exposed to diazinon through inhalation of contaminated ambient (outdoor) air. 

Populations living within or very near areas of heavy agricultural diazinon use would have an increased 

risk of exposure to relatively larger amounts of diazinon through dermal contact with contaminated 

plants, soils, surface waters, or artificial surfaces such as playground equipment and pavements; by 

inhalation of the mist formed from the applied insecticide; or by ingestion of water or food-borne 

residues. Those likely to receive the highest levels of exposure are those who are involved in the 
DIAZINON 146 

6. POTENTIAL FOR HUMAN EXPOSURE 

production, formulation, handling, and application of diazinon, farm workers who enter treated fields 

prior to the passage of the appropriate restricted entry intervals, and workers involved in the disposal of 

diazinon or diazinon-containing wastes. Dermal contact appears to be the major route of exposure for 

workers. Inhalation of diazinon in occupational settings depends on its volatility, the type of formulation 

used, and the application technique employed. 

6.2 RELEASES TO THE ENVIRONMENT 

Diazinon has been released to the environment mainly as a result of its extensive use as an insecticide for 

household lawn and garden pest control, indoor residential crack and crevice treatments and pest collars, 

and agricultural pest control. In order to reduce exposure to children and others, a December 2000 

agreement began a phase out of residential uses of diazinon, which was completed in December 2004. 

Future releases of diazinon will mainly be a result of agricultural use by aerial and ground spraying and 

spreading. For 1987 through 1997, total annual domestic usage of diazinon was over 13 million pounds. 

Approximately 4 million pounds of active ingredient diazinon are used annually on agricultural sites 

(EPA 2004b). There are no known natural sources of the compound. Diazinon has been identified in at 

least 25 of the 1,699 hazardous waste sites on the NPL (HazDat 2008). 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005). This is not an exhaustive list. Manufacturing and processing 

facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI 

chemical in a calendar year (EPA 2005). 
DIAZINON 147 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.1 Air 

Estimated releases of 358 pounds (~0.16 metric tons) of diazinon to the atmosphere from 21 domestic 

manufacturing and processing facilities in 2005, accounted for about 1.5% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI05 2007). These releases are 

summarized in Table 6-1. 

Diazinon is released into the atmosphere solely by human activities associated with its production and use 

as an insecticide. These releases include releases to ambient air from production and from agricultural 

applications. Releases have also resulted from domestic lawn and garden applications, and releases to 

indoor air from pest-control treatment of domestic and commercial buildings. It appears that diazinon 

that has been applied to a field can undergo volatilization to the atmosphere (Glotfelty et al. 1990a; 

Schomburg et al. 1991; Seiber et al. 1993; Zabik and Seiber 1993). Glotfelty et al. (1990b) estimated that 

up to 24% of the diazinon applied to dormant peach orchards may be released through long-term 

volatilization losses even though volatilization quickly declines to low levels. Before residential use was 

cancelled in 2004 (EPA 2004b), home and garden application once accounted for over 40% of total 

diazinon usage; it is not possible to estimate volatilization from these applications. 

Diazinon was detected in air at 1 of the 1,699 current or former NPL sites where diazinon has been 

identified in some environmental medium (HazDat 2008). 

6.2.2 Water 

Estimated releases of 10,287 pounds (~4.67 metric tons) of diazinon to surface water and to publicly 

owned treatment works (POTWs) from 21 domestic manufacturing and processing facilities in 2005, 

accounted for about 43% of the estimated total environmental releases from facilities required to report to 

the TRI (TRI05 2007). These releases are summarized in Table 6-1. 

Diazinon is released into water directly from point source discharges, from drift during pesticide 

applications, and from nonpoint-source runoff from agricultural and urban areas. The use of permit 

compliance bioassay testing has helped identify point source discharges with acutely toxic effluents, and 

follow-up chemical analyses have pinpointed the identity of specific toxicants (Amato et al. 1992). Such 

work has led to the identification of diazinon as a cause of toxicity in POTW discharges (Amato et al. 

1992; Burkhard and Jenson 1993). This is not surprising given the former widespread use of diazinon in 
DIAZINON 148 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or 

Use Diazinona

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej

 Off-sitek 

On- and 

off-site 

AR 2 0 No data 0 0 0 0 0 0 

AZ 1 0 No data 0 0 0 0 0 0 

CA 1 0 No data 0 0 0 0 0 0 

GA 2 9 5 0 0 0 14 0 14 

KS 1 10 No data 0 0 0 10 0 10 

LA 1 0 0 0 0 0 0 0 0 

MO 1 0 No data 0 0 0 0 0 0 

NE 1 0 No data 0 0 0 0 0 0 

OH 2 250 0 0 0 0 250 0 250 

TX 3 11 5,841 0 0 17 5,852 17 5,869 

WY 1 250 No data 0 250 3 500 3 503 

Total 16 530 5,846 0 250 20 6,626 20 6,646 

a

The TRI data should be used with caution since only certain types of facilities are required to reportNo data This is 

not an exhaustive list. Data are rounded to nearest whole number. b

Data in TRI are maximum amounts released by each facility. c

Post office state abbreviations are used. d

Number of reporting facilities. e

The sum of fugitive and point source releases are included in releases to air by a given facility. f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal 

and metal compounds). 

g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills. i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for 

disposal, unknown. 

j

The sum of all releases of the chemical to air, land, water, and underground injection wells. k

Total amount of chemical transferred off-site, including to POTWs. 

RF = reporting facilities; UI = underground injection 

Source: TRI05 2007 (Data are from 2005) 
DIAZINON 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

urban areas to control indoor pests and lawn and garden pests. It is easy for diazinon and its residues to 

reach the sewer collection systems for many POTWs. 

In addition to loadings passing through sewage treatment systems, diazinon can reach surface waters 

directly from point source discharges (Braun and Frank 1980), from nonpoint-source inputs introduced 

from agricultural (Braun and Frank 1980; Kendall et al. 1993; Maguire and Tkacz 1993; Szeto et al. 1990; 

USGS 1993; Wan et al. 1994), or from suburban runoff (Frank et al. 1991b). It is impossible to obtain 

estimates of these loadings to surface waters. Water concentrations and transport of diazinon through the 

Sacramento-San Joaquin Delta and the adjacent portions of San Francisco Bay were studied in 1993 by 

the U.S. Geological Survey (USGS 1993). Diazinon was applied as a dormant spray in the Central Valley 

of California during 2 weeks of dry weather in January 1993. Pulses of elevated diazinon concentrations 

were detected in the Sacramento and San Joaquin Rivers after a series of rainstorms in early February 

1993. All concentrations of diazinon measured in river and bay water samples exceeded 9 ng/L. 

Contaminated water samples collected from the San Joaquin River produced 100% mortality in bioassay 

tests conducted with Ceriodaphnia dubia for 12 consecutive days from February 8 to 19. The mortality of 

this sensitive indicator species was attributed to agricultural runoff of diazinon associated with the 

February rain events (USGS 1993). Banks et al. (2005) collected 1,243 surface water samples at 

70 monitoring stations from rural and urban streams in Denton, Texas during the years of 2001–2004 and 

monitored for diazinon before and after the EPA ban on its residential uses. The total number of samples 

having diazinon concentrations above the lower limits of detection significantly decreased between 2001 

and 2004, with the average diazinon concentration falling from 2.58 to 0.85 μg/L. These results indicate 

that the phasing out of residential uses of diazinon has led to a significant decrease in surface water 

occurrences (Banks et al. 2005). 

Since diazinon is moderately mobile in soils under certain conditions, it has the potential to migrate 

through the soil and into groundwater. Detections have been made in some groundwater wells in the 

United States (Cohen 1986; EPA 1989). In areas with heavy applications of diazinon combined with 

irrigation or water-level adjustment techniques, diazinon detections in groundwater also have been 

documented (Cohen 1986; Frank et al. 1987, 1990b). It has not been possible to obtain quantifiable 

estimates of these diazinon loadings to groundwater. 

Diazinon has been detected in surface water at 5 of the 1,699 current or former NPL sites and in 

groundwater at 8 of the 1,699 current or former NPL sites where diazinon has been identified in some 

environmental medium (HazDat 2008). 
DIAZINON 150 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.3 Soil 

Estimated releases of 13,123 pounds (~5.95 metric tons) of diazinon to soils from 21 domestic 

manufacturing and processing facilities in 2005, accounted for about 55% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI05 2007). No additional 

environmental releases via underground injection were reported (TRI05 2007). These releases are 

summarized in Table 6-1. 

Diazinon is released into soils primarily from its registered use on various agricultural crops and its 

former use in home garden and lawn applications. Soils are the target for the vast majority of diazinon 

applications both as a nematocide and as an insecticide agent. In agricultural areas, diazinon may also be 

transferred to aquatic sediments (Domagalski and Kuivila 1993; Szeto et al. 1990; Wan et al. 1994). 

Since diazinon undergoes various activation and degradation reactions in the course of time ranging from 

hours to months, these loadings to soils and sediments are a temporary phenomena. 

Diazinon has been detected in soil at 9 of the 1,699 current or former NPL sites and in sediment at 4 of 

the 1,699 current or former NPL sites where diazinon has been identified in some environmental medium 

(HazDat 2008). 

6.3 ENVIRONMENTAL FATE 

Diazinon can move into various environmental compartments, but there does not appear to be a major 

reservoir or sink for this chemical in any specific environmental compartment primarily because of its 

relatively rapid degradation in each environmental medium. 

6.3.1 Transport and Partitioning 

Based on its vapor pressure (see Table 4-2), if diazinon is released to the atmosphere, it will be expected 

to exist both in the vapor phase and particulate phase (Eisenreich et al. 1981). Glotfelty et al. (1990a) 

reported that during stagnant inversion fog events in the Central Valley of California, 56 and 19% of the 

diazinon in the air-phase was associated with vapor and aerosol particles, respectively, and only 24% of 

the diazinon was dissolved in the water phase. Schomburg et al. (1991) reported slightly different 

distributions for fog events resulting from advected oceanic fog. In this study, 26 and 10% of the 

diazinon in the air-phase was associated with vapor and aerosol particles, respectively; 62% of the 
DIAZINON 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

diazinon was dissolved in the water phase. Zabik and Seiber (1993) studied the atmospheric transport of 

diazinon from California's Central Valley to the Sierra Nevada Mountains. These samples collected 

during January through February 1991 represented the simultaneous collection of both vapor and 

particulate phases. Concentrations of diazinon and diazoxon were 13–10,000 and 4–3,000 pg/m3

, 

respectively, for samples collected at the 114 m elevation and 1.4–12 and 1.8–13 pg/m3

, respectively, at 

the 533 m elevation. The pesticide concentrations in air samples decreased with distance and elevation 

moving east from the Central Valley into the higher elevations of the Sierra Nevada Mountains. At times, 

air concentrations at the 114 m elevation were 1,000 times greater than concentrations detected at 533 m 

elevation. Concentrations at the 1,920 m elevation were typically below the limit of quantification. Wet 

deposition samples collected at the 114 m elevation contained up to 6,100 pg/mL diazinon and 

2,300 pg/mL diazoxon. 

Limited data based on atmospheric sampling and laboratory studies (Glotfelty et al. 1990a, 1990b) 

suggest a much greater potential for diazinon transport into the atmosphere after application to soils and 

vegetation. While the activation process (diazinon to diazoxon conversion) in the air would tend to 

transform diazinon fairly rapidly, the possibility of atmospheric transport means that this pesticide can 

move some distance from agricultural to nonagricultural areas (Glotfelty et al. 1990a, 1990b; Schomburg 

et al. 1991; Seiber et al. 1993; Zabik and Seiber 1993). 

Diazinon 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. While volatilization of 

diazinon may not be expected to be significant based upon the Henry's law constant (see Table 4-2), it can 

be an important transport process. Sanders and Seiber (1983) reported that 17% of the diazinon added to 

a model pond volatilized in 24 hours. Diazinon released to water also may be adsorbed moderately by 

soils and sediments based on its organic carbon partition coefficient (Koc) values measured in soil 

(Sharom et al. 1980a). Because this pesticide is only moderately adsorbed by some soils, leaching into 

groundwater can occur. 

Diazinon does not significantly bioaccumulate in aquatic organisms. A comparison of BCF values 

obtained for various freshwater and saltwater fish and invertebrate species is presented in Table 6-2. The 

BCF values generally range from 4 to 337, but there are only a few cases where the measured BCF value 

for diazinon exceeds 100. In those experiments where testing was continued for several days after 

exposure to the diazinon had ended, tissue residues generally decreased rapidly within 1–5 days (El Arab 

et al. 1990; Sancho et al. 1993; Tsuda et al. 1989, 1990, 1995). Despite the fairly low BCF values, some 
DIAZINON 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Bioconcentration Data for Diazinon 

Species common name/ Exposure Duration 

Scientific name type (days) BCFa

 Reference 

Freshwater

 Shrimp/Paratya compressa F 3 4 Seguchi and Asaka 1981 

compressa 

 Oriental weatherfish/Misgurnus F 14 28 Seguchi and Asaka 1981 

anguilli candatus 

 Common carp/Cyprinus carpio F 3 130 Seguchi and Asaka 1981 

Perch/Sarotherodon galilaeus S 3 39 El Arab et al. 1990 

 Rainbow trout/Oncorhynchus F 3 92 Seguchi and Asaka 1981 

mykiss 

 Brook trout/Salvelinus fontinalis F 210 25 EPA 1977 

Guppy/Poecilia reticulata R 2 39 Keizer et al. 1991 

 Zebra fish/Brachydanio rerio R 2 300 Keizer et al. 1991 

 Willow Shiner/Gnathopogon F 7 248 Tsuda et al. 1989 

caerulescens 

Killifish/Oryzias latipes F 3 20 Tsuda et al. 1995 

Killifish/O. latipes F 7 94 Tsuda et al. 1997 

 Fathead minnow/Pimephales F 2B304 337b Veith and Kosian 1983 

promelas 

Goldfish/Carassius aurapus F 7 49 Tsuda et al. 1997 

 White cloud mountain F 7 36 Tsuda et al. 1997 

fish/Tanichthys albonubes 

Saltwater 

 Sheepshead minnow/Cyprinodon F 108 147 Goodman et al. 1979 

variegatus 

a

BCF listed is the highest BCF value reported in the cited reference. b

Calculated quantitative structure-activity relationship (QSAR) value as reported in ASTER. 

BCF = bioconcentration factor; F = flow-through exposure system; S = static system; R = renewal system 
DIAZINON 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

researchers still recommend caution in consuming some aquatic species (EPA 1993c; Keizer et al. 1991). 

This is in large measure because the mechanisms that fish and invertebrates use to metabolize diazinon 

are poorly understood and seem to vary widely from species to species. In addition, diazinon and its 

metabolites have not been widely monitored in aquatic species. Since some of the metabolites of 

diazinon are themselves 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 diazinon (Keizer et al. 1991). This is partially 

the basis for the EPA recommendation to states to consider routine monitoring for diazinon in edible fish 

and shellfish species as part of their state toxics monitoring programs particularly in those watersheds 

where extensive use of diazinon is identified (EPA 1993c). 

Diazinon released in soil from its registered uses partitions to the atmosphere through volatilization, to 

surface water via runoff, and to groundwater as a result of leaching. According to Kenaga (1980), 

chemical compounds with a Koc of <100 are considered moderately to highly mobile; diazinon with a Koc 

value of 40–432 (mean of 191), therefore, would be considered moderately mobile. Additional 

parameters influencing the leaching potential of this chemical include the soil type (e.g., clay versus 

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. (1980a) found that 26, 22, 11, 11, and 7% of the diazinon 

leached from sand (after five successive 200 mL rinses), respectively. A total of 95% of the diazinon 

added to the sand leached after 10 successive 200 mL rinses. In organic soil, however, only 3, 4, 11, 9, 

and 7% of the diazinon leached from soil (after five successive 200 mL rinses), respectively. Only 50% 

of diazinon added to the organic soil leached after 10 successive 200 mL rinses. While diazinon can 

show sorption in soils with high organic content (>3%), in most other soil types, diazinon has properties 

suggesting a moderate potential for leaching into groundwater (Arienzo et al. 1994; Sharom et al. 1980a). 

Arienzo et al. (1994) tested the adsorption and mobility of diazinon in 25 soils with different 

physicochemical properties. Diazinon was found to be slightly mobile in 80% of the soils tested (those 

with organic matter content <3%), and immobile in 20% of the soils tested (those with organic matter 

content >3%). The compound leached primarily from light soils with low organic matter content. 

Levanon et al. (1994) assessed the impact of plow tillage on microbial activity and the fate of diazinon 

and other pesticides in the top 5 cm soil layer. A higher leaching rate for diazinon was detected in plow 

tillage soils than in no-tillage soils after incubation for 21 days. The no-tillage soils were characterized by 

a higher organic matter content and higher microbial populations and activity than the plow tillage soils. 

Arienzo et al. (1993) conducted a study of adsorption and mobility of diazinon in soils from aqueous 

media and mixtures of methanol-water and hexane-water. Adsorption of diazinon by soils from aqueous 
DIAZINON 154 

6. POTENTIAL FOR HUMAN EXPOSURE 

systems was related to organic matter content (i.e., the higher the organic content, the greater the 

adsorption). In methanol-water and hexane-water systems, the adsorption of diazinon by soils decreased. 

This situation may arise at hazardous waste disposal sites where pesticide waste residues and cosolvents 

may be encountered together. The presence of these organic solvents will increase the mobility 

(leachability) of diazinon in the soil and increase the potential for groundwater contamination. Diazinon 

has been detected in groundwater in the United States (Cohen 1986; EPA 1989; HazDat 2008), and in the 

Great Lakes region of Ontario, Canada (Frank et al. 1987, 1990b). 

6.3.2 Transformation and Degradation 

Diazinon is subject to a variety of abiotic and biotic degradation processes in all environmental 

compartments. 

6.3.2.1 Air 

Diazinon, once released to the atmosphere, may be subject to direct photolysis since it absorbs light in the 

spectra above 290 nm (Gore et al. 1971). Glotfelty et al. (1990a), Schomburg et al. (1991), Seiber et al. 

(1993), and Zabik and Seiber (1993), all reported the presence of diazinon and its activated product 

(diazoxon) in atmospheric samples. Glotfelty et al. (1990a) believe that diazoxon is formed by 

atmospheric oxidation especially during the daylight hours. Schomburg et al. (1991) reported that 

diazinon undergoes transformation to diazoxon during atmospheric transport from agricultural to nonagricultural areas. Seiber et al. (1993) reported mean concentrations of diazinon of 76.8 ng/m3

 and of 

diazoxon of 10.8 ng/m3

 in air samples collected near fruit and nut orchards in Parlier, California. The 

half-life (first-order kinetics) for the vapor phase reaction of diazinon with hydroxyl radicals in the 

atmosphere is estimated to be 4 hours, assuming an atmosphere containing 5x105

 hydroxyl radicals/m3 at 

25 ΕC (Meylan and Howard 1993). 

6.3.2.2 Water 

Diazinon 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. In a laboratory study, Chapman and Cole (1982) reported that pH alone influenced the halflife of diazinon maintained in sterile water-ethanol (99:1) phosphate buffer solutions at 25 ΕC. 

Degradation of diazinon was most rapid under acidic conditions with half-life values in weeks (days 

shown in parentheses) (first-order kinetics) of 0.45 (3.15), 2.0 (14), 7.8 (54.6), 10.0 (70), and 7.7 (53.9) at 
DIAZINON 155 

6. POTENTIAL FOR HUMAN EXPOSURE 

pH values of 4.5, 5.0, 6.0, 7.0, and 8.0, respectively. Garcia-Repetto et al. (1994) also studied the 

influence of pH on the degradation of diazinon in water-ethanol (9:1) solutions maintained between 

15 and 31 ΕC. These authors reported estimated half-life values (first-order kinetics) for diazinon of 1.31, 

8.57, and 8.19 days at pH values of 2, 7.5, and 8.7, respectively. The higher temperatures and lower pH 

conditions of this study may account for the more rapid degradation rates. Frank et al. (1991b) followed 

the degradation of diazinon in natural surface/groundwater samples at pH 8.2 that were either stored in 

the laboratory at 4 ΕC in the dark or at 21 ΕC under ambient indoor fluorescent light conditions for 

125 days. Under the two temperature and light regimes the half-life values (first-order kinetics) of 

diazinon were 14 days (light at 21 ΕC) and 45 days (dark at 4 ΕC). Degradation was more affected by 

temperature, suggesting that hydrolysis was the primary mode of degradation (Frank et al. 1991b). 

EPA (1976) reported that diazinon absorbs sunlight less than some of its organophosphate relatives, but 

that diazinon undergoes direct photolysis in water. The estimated half-life (first-order kinetics) for 

photolysis in aqueous solutions maintained in glass cells and irradiated with a mercury vapor lamp 

(>290 nm) was 1,000 hours (42 days). Frank et al. (1991b) investigated the degradation of diazinon in 

surface water and groundwater samples, but found little difference in the rate of diazinon degradation in 

light and dark conditions. The half-life (first-order kinetics) of diazinon of 88 days (light) and 99 days 

(dark) suggests that photolysis was not a major factor in degradation. 

Scheunert et al. (1993) studied the effects of photodegradation (via exposure to sunlight) on diazinon 

dissolved in distilled water, in a humic acid aqueous solution, and in natural water samples from the Isar 

and Rhine Rivers and Lake Ammersee in Germany with comparable samples maintained in the dark at 

25 ΕC. In the dark, river water had a higher diazinon degradation capacity than distilled water. The 

degradation capacity of natural water samples was further enhanced by exposure to sunlight. The highest 

degradation capacity was observed for the Rhine River water which also had the highest oxygen and 

hydroxyl ion concentration and the highest pH value (8.1) of the natural waters tested. 

Mansour et al. (1997) studied the photodegradation of diazinon under UV irradiation in a water/soil 

suspension and found that diazinon was converted, among other products, to the isomeric isodiazinon. 

Photodegradation was increased in the presence of titanium dioxide, hydrogen peroxide or ozone, or by 

using natural-river or lake water. 

Sharom et al. (1980b) studied the degradation of diazinon under laboratory conditions using both distilled 

water and natural water samples. Degradation was more rapid in natural water (pH 7.7) (12 weeks) than 
DIAZINON 156 

6. POTENTIAL FOR HUMAN EXPOSURE 

in sterilized natural water, sterilized distilled water, or distilled water (>16 weeks), suggesting that 

biodegradation of diazinon was occurring. Ferrando et al. (1992) conducted a laboratory microcosm 

study using both natural surface water and tap water. These experiments were conducted in aerated 

aquaria, maintained at 22 ΕC with a 12-hour light:dark period. The pH of the natural water was 9.0 and 

that of the tap water was 7.5. The half-life values (first-order kinetics) of 71 and 79 hours for the natural 

and tap water samples, respectively, both indicate rapid degradation. Under these experimental 

microcosm conditions, hydrolysis, photolysis, and biodegradation may all be operative in the natural 

water system. Wide discrepancies in the rates of diazinon degradation in water reported in the literature 

appear to be influenced by both abiotic and biotic factors. 

Bondarenko et al. (2004) investigated the persistence of diazinon in natural waters from different 

locations within the Upper Newport Bay-San Diego Creek watershed located in central Orange County, 

California. First-order half-lives for diazinon were 6.3–14.0 and 25.0–28.3 days in natural water at 

21 and 10 °C, respectively, and 51.1–54.9 days in sterilized water at 21 °C. The first-order half-lives for 

diazinon in seawater were 41.0 and 124.0 days at 21 and 10 °C, respectively. The results of the study 

suggest that under similar pH conditions, the persistence of diazinon may be prolonged in seawater. 

Sterilization greatly increased persistence of diazinon in freshwater, indicating that degradation in 

freshwater was largely attributed to microbial activity. Diazinon was found to be degraded primarily by 

abiotic processes in seawater, and the lack of microbial degradation likely contributed to its prolonged 

persistence in the seawater. Degradation in freshwater also showed temperature dependence, with 

significantly faster dissipation of diazinon at 21 °C when compared to 10 °C (Bondarenko et al. 2004). 

Although diazinon has been detected in groundwater samples in both the United States and Canada 

(Cohen 1986; EPA 1989; Frank et al. 1987, 1990b; HazDat 2008), no studies were identified concerning 

diazinon transformation and degradation processes within aquifers. Based on theoretical considerations, 

abiotic hydrolysis mechanisms would be expected to degrade diazinon within a few months (Chapman 

and Cole 1982; Cowart et al. 1971). 

6.3.2.3 Sediment and Soil 

Once released to soils and sediments, diazinon can be degraded by hydrolysis, photolysis, and 

biodegradation by several genera of microorganisms. Microbial degradation appears to be the major 

pathway for the degradation of diazinon in soils; however, under anaerobic conditions, abiotic hydrolysis 
DIAZINON 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

appears to be the most probable mechanism responsible for degradation of the compound under acidic 

soil conditions (Larkin and Tjeerdema 2000). 

The influence of soil pH on the persistence of diazinon was studied by Chapman and Cole (1982). 

Diazinon degradation was found to be more rapid in organic soils with pH values of 6.1 and 5.2 than in 

mineral soils with pH values of 6.8 and 8.0, and was slightly more rapid in the more acidic organic soil. 

Schoen and Winterlin (1987) conducted an extensive study of the effects of various soil factors and 

organic amendments on degradation of diazinon. The factors affecting the rate of diazinon degradation in 

soil were pH, soil type, organic amendments, soil moisture, and pesticide concentration. Soil pH was a 

major factor affecting degradation. At a soil concentration of 100 ppm diazinon and 50% water 

saturation, estimated half-life values (first-order kinetics) at pH 4, 7, and 10 were 66, 209, and 153 days, 

respectively, in sandy loam; 49, 124, and 90 days, respectively, in clay loam; and 14, 45, and 64 days, 

respectively, in sandy loam amended with peat. Loss of diazinon occurred in the order of sandy loam 

with peat > clay loam > sandy loam. Addition of acidic peat to the soil lowered the pH and could have 

been responsible for increased hydrolysis. Degradation of diazinon in soil was most favorable when the 

pesticide was present at low concentrations in moist soil, amended with peat or acidified to a pH of 4, and 

least favorable at high diazinon concentrations in neutral or basic mineral soil (Schoen and Winterlin 

1987). It has been observed that dissipation of diazinon from soil slows significantly as concentration 

increases above a certain level, possibly due to microbial toxicity which inhibits degradation (Felost et al. 

2003). Prolonged persistence of diazinon in soil increases the potential for runoff and leaching. 

In six types of soils, Somasundaram et al. (1991) reported that diazinon was hydrolyzed to 2-isopropyl6-methyl-4-hydroxypyrimidine (IMHP) and that the degradation product was significantly more mobile in 

these soils than its parent compound diazinon. In an earlier study, Somasundaram et al. (1989) found that 

prior applications of IMHP did not enhance degradation of diazinon. 

In a study of degradation of diazinon in three submerged tropical soils, only 2–6% of the originally 

applied diazinon remained 50–70 days post-application (Sethunathan and MacRae 1969). Degradation of 

diazinon was more rapid in nonsterilized soils, indicating microbial participation in two of the three soil 

types. In the third type (an acid clay soil), diazinon degradation was more rapid in the sterilized samples 

at pH 4.7, apparently because of the compound's instability under acid conditions. Streptomyces sp. 

isolated from the submerged soils could degrade the diazinon. In a field study of a treated cranberry bog 

by Szeto et al. (1990), disappearance of diazinon from irrigation ditch sediment (pH 4.4) and from 

sediment in an adjacent reservoir (pH 5.0) was equally rapid. These authors found that <1% of diazinon 
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6. POTENTIAL FOR HUMAN EXPOSURE 

remained 38 and 22 days post-application in the irrigation ditch and reservoir sediments, respectively. In 

nonsterilized soil, diazinon degradation was faster at 100% water saturation than at 50% water saturation. 

These results suggest that microbial activity under anaerobic conditions plays an important role in 

diazinon degradation (Schoen and Winterlin 1987). 

Photolysis of diazinon on soil surfaces was studied by Burkhard and Guth (1979). The effectiveness of 

photolysis in 24 hours was only slightly greater on moist soil surfaces (51%) than it was on dry soil 

surfaces (44%) at 45 ΕC. The major photolytic product identified for diazinon was 2-isopropyl-6-methyl4-hydroxypyrimidine. This same reaction product was found for acid hydrolysis and photolysis in 

aqueous solutions or on soil. 

Photochemical reactions in soil are significant only at the surface. When the surface soil is moist, 

photolysis may occur both with the portion dissolved in water and with the portion adsorbed to the soil. 

Mansour et al. (1997) studied the photochemical reaction of diazinon in water/soil suspensions in order to 

include the possible catalytic effects of adsorption. Under UV irradiation in a water/soil suspension, 

diazinon was converted to, among other products, the isomeric isodiazinon. Photodegradation was 

increased in the presence of titanium dioxide, hydrogen peroxide, or ozone, or by using natural river 

water or lake water. 

Gunner and Zuckerman (1968) reported synergistic microbial degradation of diazinon by two 

microorganisms, Arthrobacter sp. and Streptomyces sp. When Arthrobacter sp. and Streptomyces sp. 

were incubated separately on growth media where diazinon was the primary carbon source, neither was 

able to convert the pyrimidinyl carbon to carbon dioxide. When incubated together, only 6% of the 

parent diazinon remained, and 94% was converted to two unidentified metabolites. Two microorganisms 

isolated from flood soils also were found to hydrolyze diazinon (Adhya et al. 1981). Diazinon was 

rapidly hydrolyzed within 24 hours by both Flavobacterium sp. and Pseudomonas sp. A hydrolysis 

product of diazinon, IMHP, was metabolized more rapidly by the Flavobacterium sp. than the 

Pseudomonas sp. More recently, oxypyrimidine was reported to be the major soil degradation product of 

diazinon and is considered to be more persistent than diazinon (Larkin and Tjeerdema 2000). Barik and 

Munnecke (1982) reported that an enzyme (parathion hydrolase) obtained from Pseudomonas sp. cultures 

could hydrolyze diazinon in soils. More than 98% of 10,000 ppm of diazinon in soil can be degraded 

within 24 hours if sufficient buffer and enzyme are added to the contaminated soil. The authors report 

that it is technically feasible to use parathion hydrolase to clean up diazinon spills in the environment. 
DIAZINON 159 

6. POTENTIAL FOR HUMAN EXPOSURE 

Levanon et al. (1994) studied the effects of plow tillage on microbial activity and the degradation of 

diazinon in the 0–5 cm soil layer. In no-tillage soils, higher microbial populations and activity were 

associated with higher mineralization rates of diazinon (45% mineralization after 76 days). Enhanced 

transformation rates played a role in minimizing leaching from no-tillage soils. Synergistic effects 

between fungi and bacteria in the degradation of diazinon were also observed. The authors noted that 

almost no mineralization of the compound occurred when either fungi or bacteria were selectively 

inhibited, demonstrating synergism between the two microbial communities. A higher proportion of 

diazinon leached from the plow tillage soils than from the no-tillage soils. Microbial population and 

activity measured as biomass, bacterial counts, hyphal length of fungi, and carbon dioxide evolution were 

all higher in samples of no-tillage soils. 

6.3.2.4 Other Media 

Michel et al. (1997) studied the fate of diazinon during the composting of leaves and grass. The yard 

trimmings were amended with 14C labeled diazinon and composted for 54 days. During composting, 

11% of the 14C-diazinon was mineralized to carbon dioxide. A water extract of the finished compost 

contained 36% of the added 14C and analysis of this extract indicated that the 14C was in the form of 

2-isopropyl-IMHP, a hydrolysis product of diazinon. The remaining fraction of 14C was unidentifiable or 

associated with a high molecular weight extract fraction. The results show that during the composting, a 

relatively small amount of diazinon is mineralized to carbon dioxide, while a majority is hydrolyzed to 

potentially leachable but less toxic IMHP, high molecular weight residues, and unextractable residues that 

are presumed to have low bioavailability. 

Diazinon has been detected at a variety of waste water treatment plants. Zhang and Pehkonen (1999) 

investigated the oxidation of diazinon by aqueous chlorine and reported that the half-life is only several 

minutes at typical chlorine concentrations found in waste water treatment plants. The oxidation product 

of diazinon was reported to be diazoxon. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to diazinon depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

diazinon in unpolluted atmospheres and in pristine surface waters are often so low as to be near the limits 

of current analytical methods. In reviewing data on diazinon levels monitored or estimated in the 

environment, it should also be noted that the amount of chemical identified analytically is not necessarily 
DIAZINON 160 

6. POTENTIAL FOR HUMAN EXPOSURE 

equivalent to the amount that is bioavailable. The analytical methods available for monitoring diazinon in 

a variety of environmental media are detailed in Chapter 7. 

Most information on diazinon concentrations in various environmental media derived from large scale 

monitoring networks dates from before the mid-1980s and no longer reflects current conditions. There is 

a noticeable lack of national monitoring studies that would allow meaningful estimation of current 

diazinon concentrations associated with various environmental media. Reliable evaluation of the 

potential for human exposure to diazinon depends in part on the reliability of supporting analytical data 

from environmental samples and biological specimens. 

6.4.1 Air 

Diazinon concentrations in the atmosphere were monitored in several national studies during the 1970s 

and 1980s and more recently in several regional studies. Diazinon has been measured in outdoor air 

samples in both rural and urban environments, near production facilities, and in indoor air (associated 

with its use for pest control in domestic and commercial buildings). 

In a study of pesticide residues in ambient air sampled in 14–16 states during 1970, 1971, and 1972, 

diazinon was detected in 50% of the 2,479 samples analyzed, with a mean concentration of 2.5 ng/m3

 and 

a maximum concentration of 62.2 ng/m3

 (Kutz et al. 1976). Carey and Kutz (1985) reported that ambient 

air concentrations of diazinon collected from February through September 1980 in Perkin, Illinois, ranged 

from 1.3 to 10 ng/m3

. 

In a study of pesticide levels in ambient suburban air, diazinon was detected in 80, 80, and 40% of 

samples collected in three cities (Miami, Florida; Jackson, Mississippi; and Fort Collins, Colorado), 

respectively. The maximum diazinon concentration detected in each city was 3.9, 2.0, and 2.2 ng/m3

 for 

Miami, Florida; Jackson, Mississippi; and Fort Collins, Colorado, respectively (Kutz et al. 1976). During 

1973–1974, diazinon concentrations in air were measured in urban Miami, Florida, and in the adjacent 

Everglades National Park. Urban diazinon levels ranged from not detectable to 3.3 ng/m3

 (1.5 ng/m3 

mean); corresponding levels in Everglades National Park ranged from not detectable to 1.9 ng/m3 

(0.6 ng/m3 mean) (Lewis and Lee 1976). Nationwide, diazinon was detected in 48% of 123 urban air 

samples collected in 10 U.S. cities during 1980. The maximum diazinon concentration reported was 

23 ng/m3

 (mean 2.1 ng/m3) (Carey and Kutz 1985). 
DIAZINON 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

Most recently, non-occupational exposure to diazinon among residents of two U.S. cities (Jacksonville, 

Florida, and Springfield, Massachusetts) was studied over three seasons: summer 1986, spring 1987, and 

winter 1988 (Whitmore et al. 1994). The study focused primarily on inhalation exposures with primary 

environmental monitoring consisting of 24-hour indoor and outdoor air. For the Jacksonville, Florida, 

population, the estimated mean diazinon concentrations were 85.7–420.7 ng/m3

 in indoor air and 1.1– 

13.8 ng/m3

 in outdoor air. For the Springfield, Massachusetts, population, mean exposures were much 

less. The estimated diazinon concentrations were 2.5–48.4 ng/m3

 in indoor air and 8.2–9.2 ng/m3 in 

outdoor air. 

Ambient diazinon concentrations were measured under foggy atmospheric conditions in and around the 

Central Valley of California (Parlier, California), which is a prime agricultural area dominated by fruit, 

nut, and citrus orchards (Glotfelty et al. 1990a; Seiber et al. 1993; Zabik and Seiber 1993). In fog, 

diazinon concentration was 1.6 ng/m3

 and diazoxon (the oxon transformation product) concentration was 

0.82 ng/m3

. In a similar study, Schomburg et al. (1991) analyzed air and fog near Monterey, California, 

to determine whether the uptake of diazinon in advected oceanic fog was different from uptake in fog 

collected under stagnant inversion conditions in the Central Valley of California. Fog water 

concentrations of diazinon ranged from 0.15 to 4.8 μg/L in coastal areas; higher concentrations ranging 

from 0.31 to 18 μg/L were found in the Central Valley area. Diazinon and diazoxon favored the aqueous 

phase in foggy atmosphere, with 62.4 and 87.8%, respectively, reported in the aqueous phase. Zabik and 

Seiber (1993) studied the atmospheric transport of diazinon from California's Central Valley to the Sierra 

Nevada Mountains. Air samples collected from January through February 1991 represented the 

simultaneous collection of both vapor and particulate phases. Concentrations of diazinon and its oxon 

were 13–10,000 pg/m3

 (0.013–10 ng/m3) and 4–3,000 pg/m3 (0.004–3 ng/m3), respectively, for samples 

collected at the 114 m elevation and 1.4–12 pg/m3 (0.0014–0.012 ng/m3

) and 1.8–13 pg/m3 (0.0018– 

0.013 ng/m3

), respectively, at the 533 m elevation. The pesticide concentrations in air samples decreased 

with distance and elevation moving east from the Central Valley into the higher elevations of the Sierra 

Nevada Mountains. At times, air concentrations of diazinon at the 114 m elevation were 1,000 times 

greater than concentrations detected at 533 m elevation. Concentrations at the 1,920 m elevation were 

typically below the limit of quantification. Wet deposition samples (rain and snow) collected at the 

114 m elevation contained up to 6,100 pg/mL diazinon and 2,300 pg/mL diazoxon. Diazinon was 

detected in 100% of air samples collected from over the Mississippi River from New Orleans, Louisiana, 

to St. Paul, Minnesota, during the first 10 days of June 1994 at a mean concentration of 0.08 ng/m3 

(Majewski et al. 1998). The maximum concentration detected, 0.36 ng/m3

, was detected near a major 

metropolitan area. 
DIAZINON 162 

6. POTENTIAL FOR HUMAN EXPOSURE 

Diazinon residues in ambient air sampled within 800 m of two pesticide formulation plants in Arkansas 

(from 1970 to 1972) and within 275 m of a pesticide formulation plant in Tennessee (in 1971) were 0.3– 

18.0 ng/m3

 (mean 2.2 ng/m3) and 0.5–27.9 ng/m3 (mean 7.3 ng/m3), respectively (Lewis and Lee 1976). 

In addition to its presence in the ambient atmosphere, diazinon also has been monitored in both outdoor 

and indoor air associated with its use in a variety of domestic, commercial, and occupational exposure 

situations. Exposure to diazinon from its use in lawn and home garden applications was evaluated by 

Davis et al. (1983). Diazinon was mixed with water and sprayed using compressed air sprayers or hoseend sprayers, and potential respiratory and dermal exposures were estimated from residues collected from 

respirator filters, body pads, and hand rinsings. These authors reported mean respiratory exposures of 1.9, 

2.9, and 7.4 μg/hour associated with use of compressed air sprayers on lawns, compressed air sprayers on 

shrubs, and hose-end sprayers on lawns, respectively. The amount of diazinon collected in the respiratory 

pads was negligible compared to the amount collected on dermal pads. Total dermal exposures were 

5,700, 7,500, and 29,000 μg/hour, respectively, for the three sprayer types; however, dermal exposure of 

the hands alone accounted for ≥85% of the total dermal exposure for each sprayer type. 

Diazinon air concentrations related to vapors released from pest control strips were measured by Jackson 

and Lewis (1981). Diazinon levels in indoor air increased from 0.32 μg/m3

 at 6 hours after application of 

the pest strips to 1.34 μg/m3

 on day 15, and then declined to 1.21 μg/m3 on day 30. Air sampling in a 

retail garden store where pesticide containers with diazinon were displayed showed an average diazinon 

concentration of 3.4 μg/m3

 (Wachs et al. 1983). 

Currie et al. (1990) evaluated the concentrations of diazinon in indoor air and on working surfaces for a 

period of 10 days after application in commercial offices. The highest concentrations of diazinon 

(163 and 158 μg/m3

) were measured 4 hours post-application in two empty offices, while the 

concentration in the furnished office was 27 μg/m3

. One day post-application, levels were 125 and 

70 μg/m3

 in the two empty offices, and 27 μg/m3 in the furnished office. Air concentrations of diazinon 

continued to decline and on day 6 post-application were approximately 35 μg/m3

 in the empty offices and 

8 μg/m3

 in the furnished office. Airborne levels of diazinon were distinctly lower in the furnished office, 

and this was attributed to obstruction of the applicator's spraying path by office furniture so that a lower 

amount of diazinon was applied. Diazinon deposition on aluminum plates was measured as an indicator 

of surface contamination, measurements ranged from 0.4–15 ng/cm2

. No overall decrease in surface 

contamination occurred over time. Plates suspended 1.5–2.1 m above the floor generally exhibited higher 
DIAZINON 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

diazinon levels 24 hours post-treatment than at 1–2 hours post-treatment. The authors believe that this 

was a result of evaporation of diazinon from the carpeted floor augmented by air turbulence. Diazinon 

contamination measured by surface wipes on furniture and foil on carpet ranged from 13 to 38 ng/cm2

. 

Diazinon levels in indoor air were monitored in an animal facility treated monthly with a 1% aqueous 

diazinon formulation (Williams et al. 1987). Indoor air sampling was conducted in two areas frequented 

regularly by facility personnel, the lounge and cage-washing areas. The lounge areas were enclosed 

rooms while the cage-washing areas were open-ended and were in effect part of the corridor system of the 

facility. Air samples were collected using adsorbent sampling tubes (Supelco-20 P) for 4 hours at 

1.8 L/minute just prior to spraying on days 0, 28, and 56, approximately 16–20 hours post treatment, and 

at various intervals thereafter. Diazinon levels increased immediately after spraying, but decreased 

rapidly to 2–3 μg/m3

 in <1 day and continued to decrease to <0.05 μg/m3 until the next spraying. During 

many months of diazinon application there was little buildup in background diazinon air levels 

(<0.5 μg/m3

). 

Lenhart and Kawamoto (1994) reported air concentrations of up to 297 μg/m3

 in greenhouse air after 

spray applications of an emulsifiable concentrate of diazinon, under the trade name Clean Crop AG500, 

and concentrations up to 3,030 μg/m3

 in greenhouse air after a 4-hour cold fogging application of the 

same formulation. 

Palmgren and Lee (1984) collected samples of grain dust (dust accumulated in the dust collection systems 

of grain elevators) from six grain elevators located in the New Orleans, Louisiana, area to evaluate 

potential occupational exposures of grain elevator personnel. Diazinon concentrations in grain dust were 

<0.01 μg/g for all 31 samples collected. 

6.4.2 Water 

Carey and Kutz (1985) reported that the maximum diazinon residue collected in a national surface water 

monitoring program conducted from 1976 to 1980 was 2.38 μg/L and that diazinon was detected in only 

1.2% of the samples collected. Pereira and Hostettler (1993) conducted a study of the Mississippi River 

and its tributaries during 1991 and 1992. These authors reported that diazinon was detected in water 

samples from the Illinois River at concentrations of 20 ng/L and from several sites on the mainstem of the 

lower Mississippi River at concentrations ranging from 4 to 10 ng/L. During 1991, Domagalski and 

Kuivila (1993) monitored diazinon concentrations in water and suspended sediment collected at various 
DIAZINON 164 

6. POTENTIAL FOR HUMAN EXPOSURE 

sites in San Francisco Bay during low river discharge and after spring rain events. Diazinon was detected 

in water only after the spring rains and most (98%) of the diazinon was in the dissolved phase. 

Concentrations dissolved in the water column ranged from 4.6 to 14.6 ng/L. The authors suggest that 

diazinon may be close to equilibrium with respect to sorption or desorption on suspended sediment 

particles. 

In the Great Lakes region, diazinon was detected in surface waters in several river basins in southern 

Ontario, Canada. Braun and Frank (1980) monitored surface water concentrations of 8 organochlorine 

and 12 organophosphate pesticides in 11 agricultural watersheds in southern Ontario. All watersheds 

drained into the Great Lakes. Diazinon residues as a result of field use were detected in only one water 

shed, but the chemical was repeatedly detected in 34% of samples (1975–1976) and 74% of samples 

(1976–1977) collected from one creek. The source of the diazinon was traced to its indoor use to control 

flies in a series of mushroom houses that discharged via a drainage tile system directly to the creek. The 

maximum residues of diazinon in the stream were 140 μg/L (5.75 μg/L mean) and 26 μg/L (1.02 μg/L 

mean) in 1975–1976 and 1976–1977, respectively. Frank and Logan (1988) measured pesticide and 

industrial chemical residues at the mouth of the Grand, Saugeen, and Thames Rivers in southern Ontario, 

Canada, from 1981 through 1985. River water samples collected at the mouths of the three rivers (that 

drain into the Great Lakes) were analyzed for 20 herbicides, 3 fungicides, and 25 insecticides including 

diazinon. One water sample collected during May through August 1982 contained a mean diazinon 

concentration of 0.21 μg/L. Maguire and Tkacz (1993) monitored concentration of pesticides in surface 

water near the mouths of the Yamaska River in Quebec, Canada, and five of its tributaries during 1986 

and 1987. Diazinon was detected at the mouth of the Yamaska River at concentrations ranging from 

2.1 to 11.9 ng/L, at the mouth of the Saint-Nazaraire River at concentrations ranging from 3.1 to 

26.7 ng/L, and at the mouth of the Salvail River at concentrations ranging from 1.1 to 4.9 ng/L. Frank et 

al. (1990a) conducted a survey of 211 rural ponds in southern Ontario and measured concentrations of 

29 herbicides, fungicides, and insecticides including diazinon. Two ponds were found to be contaminated 

with diazinon, and residues in pond water ranged from 0.6 to 1.7 μg/L (1.2 μg/L mean). The source of the 

diazinon in these two cases was attributed to accidental pesticide spills during agricultural application. In 

the U.S. Geological Survey’s National Water-Quality Assessment Program 1999–2000, surface water 

samples from the Yakima River Basin, Washington were collected at 34 sites and analyzed for the 

occurrence of pesticides (USGS 2002a). Diazinon was detected in 16 of 98 surface water samples at 

concentrations ranging from <0.002 to 0.169 μg/L. Banks et al. (2005) collected 1,243 surface water 

samples at 70 monitoring stations from rural and urban streams in Denton, Texas during the years of 

2001–2004 and monitored for diazinon before and after the EPA ban on its residential uses. The total 
DIAZINON 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

number of samples having diazinon concentrations above the lower limits of detection significantly 

decreased from 2001 to 2004. The maximum and average concentrations, respectively, of diazinon 

detected each year were 2.58 and 0.32 μg/L in 2001, 1.67 and 0.10 μg/L in 2002, 1.91 and 0.06 μg/L in 

2003, and 0.85 and 0.04 μg/L in 2004. These results indicate that the phasing out of residential uses of 

diazinon has led to a significant decrease in surface water occurrences. 

Diazinon concentrations in water have also been monitored in the United States and in several Canadian 

studies associated with the use of the compound in agricultural applications. Kendall et al. (1993) 

monitored diazinon residues in ponds and creeks adjacent to a golf course in coastal Washington where 

two turf applications of diazinon were made at a rate of 2.2 kg active ingredient per hectare. A maximum 

diazinon residue of 17 μg/L was measured in the study area ponds and creeks. Wan et al. (1994) 

monitored concentrations of diazinon and six other organophosphate pesticides in farm ditches of the 

lower Fraser River Valley of British Columbia, Canada, from July to December 1991. These authors 

reported that diazinon was consistently found in ditch water (81% of samples) at 7 locations with a mean 

concentration of 0.07 μg/L (range of 0.01–0.34 μg/L). The percentage of positive detections for diazinon 

in water samples was 81%. The presence of diazinon in ditch water was correlated with consistent 

detection of diazinon residues in soils from nearby fields. Szeto et al. (1990) monitored the persistence of 

diazinon in coastal cranberry bogs and adjacent surface waters in British Columbia, Canada. Bogs were 

treated with two applications of diazinon 5G (granules) at a rate of 6 kg active ingredient per hectare 

approximately 2 weeks apart. One day after the first and second applications, maximum concentrations 

of diazinon in water in an irrigation ditch were 338 and 456 μg/L, respectively. Maximum concentrations 

in an adjacent reservoir were 78.5 and 58.1 μg/L for the first and second treatments, respectively. Water 

samples collected immediately outside the diked bog area contained a maximum of 29.1 μg/L diazinon, 

but concentrations were usually <10 μg/L. Tributary water 100 m downstream from the cranberry bog 

site contained a maximum diazinon residue of 2.8 μg/L. Li et al. (2002) monitored diazinon levels in 

water samples collected in June, August, and October 2000 from 13 agricultural water ditches in British 

Columbia, Canada near fields where diazinon was applied. Diazinon was found to range from not 

detected (<4 ng/L) to 259 ng/L, indicating that after application, high concentrations can reach local 

waterways. High diazinon concentrations, such as the 259 ng/L detection, may be of ecological relevance 

given that concentrations of 350 ng/L have been associated with toxic effects in aquatic organisms. 

Between March 1993 and May 1994, Gruber and Munn (1998) measured median and maximum diazinon 

concentrations of <0.002 and 0.018 μg/L, respectively, in Crab Creek Lateral, in which most of the flow 

is excess irrigation water, located in the Central Columbia Plateau in central Washington state. EPA’s 

Water Resources Assessment for diazinon provided estimated environmental concentrations of diazinon 
DIAZINON 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

in surface water as a result of the highest label application rate on seven crop types calculated using the 

Pesticide Root Zone Model version 3.1 (PRZM) and Exposure Analysis Modeling System 

Version 2.97.5 (EXAMS) (EPA 1999). The peak and yearly average estimated environmental 

concentrations of diazinon ranged from 8.89 to 429 μg/L and from 1.61 to 58.7 μg/L, respectively. 

Suzuki et al. (2003) monitored pesticide residues in rainwater from July 1999 to July 2000 at five 

sampling sites in Utsunomiya, eastern Japan. The annual deposited amount as an average value among 

the sampling sites for diazinon was 38.3 μg/m2

. In the 82 rainwater samples collected over the year, the 

maximum and mean concentrations of diazinon detected were 0.324 and 0.079 μg/L, respectively. 

Recently, acute toxicity of sewage treatment plant effluents to aquatic bioassay testing organisms in the 

United States has been tied to diazinon (Amato et al. 1992; Burkhard and Jenson 1993). Given the 

considerable use of diazinon in urban areas, diazinon in sewage treatment effluents is not unexpected. 

Urban nonpoint source inputs from diazinon-impregnated yard wastes, runoff from treated lawn and 

garden areas, or illegal dumping may require increased pollution prevention efforts through the National 

Pollution Discharge Elimination System (NPDES) program in many larger cities (Amato et al. 1992; 

Burkhard and Jenson 1993). A maximum diazinon residue of 1.7 μg/L in POTW effluents was associated 

with the toxic fraction in effluent bioassay tests with Ceriodaphnia dubia (Burkhard and Jenson 1993). 

Amato et al. (1992) suggest that the significance of detecting diazinon at acutely toxic concentrations in 

municipal waste water may indicate a more widespread problem. 

Schiff and Sutula (2004) detected diazinon in 93% of 128 storm-water runoff samples from eight different 

land uses over five storm events in urban southern California watersheds. The mixed agricultural land 

use had the highest flow-weighted mean diazinon concentration of 4,076.0 ng/L, followed by commercial 

and nursery agricultural land use with mean diazinon concentrations of 324.0 and 148.0 ng/L, 

respectively. High and low-density residential land use had mean concentrations of 99.2 and 67.6 ng/L, 

respectively, industrial land use had 89.6 ng/L, recreational land use had 63.2 ng/L, and the open space 

site had the lowest concentration of diazinon of <20 ng/L. Diazinon was detected in 100% of the samples 

collected at the mass emission sites Ballona Creek and Santa Monica Canyon, located in Santa Monica 

Bay, with flow-weighted mean concentrations of 242.9 and 452.3 ng/L, respectively. 

In a groundwater contamination study of 28 of California's 58 counties that evaluated over 50 pesticides 

(from both point and nonpoint sources), diazinon was detected in 12 samples (Cohen 1986). Diazinon is 

included as an analyte of interest in the EPA Pesticides in Ground Water Database (EPA 1989) and was 
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6. POTENTIAL FOR HUMAN EXPOSURE 

detected at two sites. A detection in California was related to point source contamination (residue level 

was unspecified), and a detection of 478 μg/L (maximum) and 162 μg/L (mean) in Mississippi was in an 

area where appreciable agricultural use of pesticides occurs. In the Great Lakes region, diazinon was 

found in a survey of rural wells in southern Ontario, Canada, monitored between 1979 and 1984 (Frank et 

al. 1987) and in farm wells monitored between 1986 and 1987 (Frank et al. 1990b). However, no 

concentrations of diazinon in groundwater were provided by these authors. In the U.S. Geological 

Survey’s National Water-Quality Assessment Program 1992–1996, 2,485 groundwater sites were 

sampled in 20 of the nation’s major hydrologic basins were analyzed for 90 pesticide compounds (Kolpin 

et al. 2000). Diazinon was detected at a frequency of 1.30% at 2,459 sites with a maximum detected 

concentration of 0.16 μg/L. 

Only limited data on the concentration of diazinon in drinking water are available since drinking water 

facilities are not required to monitor for diazinon (EPA 1999). EPA’s Water Resources Assessment for 

diazinon provided a drinking water assessment and set the upper bound on the drinking water exposure 

estimate through modeling with surface and groundwater data (EPA 1999). The estimated diazinon acute 

exposures in drinking water were 2.3–22, 3.0–22, and 0.90 μg/L based on agricultural and nonagricultural use surface water and groundwater, respectively. The estimated diazinon chronic exposures 

in drinking water were 0.19–5.8, 0.46–5.8, and 0.90 μg/L based on agricultural and non-agricultural use 

surface water and groundwater, respectively. Eitzer and Chevalier (1999) detected diazinon in 5 of 

53 residential drinking wells at an average concentration of 0.02 μg/L in a single town in south-central 

Connecticut which relies on groundwater for its potable water source. In the EPA’s National Survey of 

Pesticides in Drinking Water, no diazinon was detected (limit of detection of 1.10 μg/L) in 1,349 wells 

(783 rural domestic wells and 566 community water system wells) randomly selected and sampled once 

for diazinon in 38 states (EPA 1999). In February 2005, the EPA’s Office of Water added diazinon to the 

Drinking Water Contaminant Candidate List (EPA 2006j). EPA uses this list of unregulated 

contaminants to prioritize research and data collection efforts to help determine whether the specific 

contaminant should be regulated. 

6.4.3 Sediment and Soil 

Diazinon has not been the focus of many national soil or sediment monitoring programs in the United 

State, but has been monitored in regional studies associated with agricultural applications in both the 

United States and Canada. In a national surface water quality monitoring study (1976–1980), diazinon 

was detected in 0.5% of the sediment samples analyzed, with a maximum residue of 7.1 μg/L (Carey and 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Kutz 1985). Domagalski and Kuivila (1993) reported concentrations of diazinon in suspended sediments 

from various sites from San Francisco Bay ranging from not detected to 2.8 ng/g. 

Soil contamination of diazinon ranging from 95.5 mg/m2

 (2 hours post-application) to 35.6 mg/m2 

(342 hours post-application) resulted from spray applications of 4.5 kg diazinon (50 WP formulation) per 

hectare to a dormant peach orchard in the Central Valley of California (Glotfelty et al. 1990b). Diazinon 

concentrations in sediments of a cranberry bog treated with two applications of diazinon (Diazinon 5G at 

6 kg active ingredient per hectare) were measured by Szeto et al. (1990). These authors reported that the 

highest diazinon residues were 21 μg/g (wet weight) in sediments of irrigation ditches collected 4 days 

post-application. The maximum sediment concentration measured in an adjacent reservoir was 2 μg/g. 

Four days post-application, the maximum sediment concentration was 80 μg/kg in a waterway outside the 

diked bog and only 10 μg/kg in a tributary 100 meters downstream from the bog. Wan et al. (1994) 

monitored ditch water, soils, and sediments from July to December 1991 in an agricultural area in the 

lower Fraser River Valley of British Columbia, Canada. Diazinon concentrations in ditch sediment were 

detected at three sites; the mean concentrations were 8, 2, and 38 μg/kg at the Vancouver, Cloverdale, and 

Sumas Prairie sites, respectively. Diazinon was also detected in topsoil (<5 cm deep) at five sites; the 

mean concentrations were 268 μg/kg (range of 2–3,307 μg/kg), 5 μg/kg (range of 1–9 μg/kg), 769 μg/kg 

(range of 13–2,862 μg/kg), 13 μg/kg (range of 4–30 μg/kg), and 39 μg/kg (range of 1–236 μg/kg) at the 

Westham Island, Ladner, Burnaby, Cloverdale, and Sumas Prairie sites, respectively. The concentrations 

at all these stations declined from July to December. Diazinon concentrations ranging from 0.5 to 

5.4 ng/g dry weight were measured in sediments collected from the Salton Sea, an agricultural drainage 

reservoir in California, in 2000 and 2001 (Sapozhnikova et al. 2004). Sediment concentrations were 64% 

higher in 2001 than in 2000. 

Sediment samples collected from six sites in the Petaluma River, Sonoma Creek, and Napa River, which 

feed into the San Pablo Bay, California contained diazinon concentrations ranging from 8.45 to 

13.10 μg/kg (Baum et al. 2001). 

6.4.4 Other Environmental Media 

Braun and Frank (1980) reported diazinon residues in three fish species collected from a creek in southern 

Ontario, Canada, contaminated from a point source discharge. Tissue residues for the three edible fish 

species were 18 μg/g in the brown bullhead (Ictalurus nebulosus), 17 μg/g in the black crappie (Pomoxis 

nigromaculatus), and 92 μg/g in the gizzard shad (Dorosoma cepedianum). The maximum diazinon 
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6. POTENTIAL FOR HUMAN EXPOSURE 

concentrations measured in the contaminated creek water for 1975–1976 and 1976–1977 were 140 μg/L 

(5.75 μg/L mean) and 26 μg/L (1.02 μg/L mean), respectively. Sapozhnikova et al. (2004) reported 

diazinon residues in tilapia (Tilapia mossambique) and orange mouth Corvina (Cynoscion xanthulu) 

collected from the Salton Sea, an agricultural drainage reservoir in California, in May 2001. In the 

corvina, diazinon was found in the muscle, liver, gonads, and gills at mean concentrations of 5.4, 17.2, 

6.2, and 3.6 ng/g wet weight, respectively. In the tilapia, diazinon was found in the muscle, liver, gonads, 

and gills at mean concentrations of 4.4, 8.8, 5.2, and 2.4 ng/g wet weight, respectively. 

Concentrations of diazinon in ready-to-eat foods were monitored for 10 years from 1982 to 1991 through 

the FDA's Revised Market Basket Survey (KAN-DO 1995). Diazinon was detected in 894 samples of 

144 different foods at a mean concentration of 0.0019 μg/g. In the EPA’s Revised Organophosphate 

Pesticides Cumulative Risk Assessment, a summary of residue monitoring data on organophosphate 

pesticides in food for the years 1994–2000 was reported (EPA 2002). The detection of diazinon in these 

various foods and its concentration are presented in Table 6-3. The report also included a summary of 

FDA Total Diet Study analyses on organophosphate pesticides on meats for the years 1991–1999. The 

mean concentrations of diazinon residues found in meats (in mg/kg) were 0.0009 in beef steak, loin, pancooked, 0.0008 in pork chop, pan-cooked, 0.009 in lamb chop, pan-cooked, and 0.002 in lamb chop, pancooked (sample 2). Residues of diazinon in levels of 0.005–0.586 mg/L have been reported in milk (Salas 

et al. 2003). 

The frequency of occurrence of diazinon detections in the FDA Total Diet Study was 9% in 1989 (FDA 

1990), 6% in 1990 (FDA 1991), 4% in 1991 (FDA 1992), 5% from 1991 to 1993 (FDA 1994), 5% in 

1994 (FDA 1995), 3% in 1995 (FDA 1996), 2.4% in 1996 (FDA 1998), and 2% in 2003 (FDA 2005b). 

Diazinon intakes in μg/kg body weight/day, estimated for the total diet analyses were 0.0031, 0.0034, and 

0.0017 in 1989 (FDA 1990); 0.0026, 0.0022, and 0.0017 in 1990 (FDA 1991); and 0.0049, 0.0022, and 

0.0022 in 1991 (FDA 1992) for 6–11-month-old infants, 14–16-year-old-males, and 60–65-year-oldfemales, respectively. 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

While no quantitative information is available on the percentage of diazinon released to each 

environmental compartment, diazinon can be emitted to any or all environmental media (air, surface 

water, groundwater, and soil) depending on the source of the release, formulation used, and prevailing 

environmental conditions. In order to mitigate the exposure and risk to the general population, especially 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Diazinon Residues in Various Foods from 1994 to 2000 

Average Maximum 

Number Number of concentration concentration 

Food item analyzed detections (ppm)a (ppm) 

Apple juice 1,554 0 0 0 

Apples 2,472 19 1.2x10-4 0.12 

Apples (single serving) 377 1 1.9x10-5 0.007 

Bananas 1,126 0 0 0 

Broccoli 634 0 0 0 

Cantaloupe 1,640 6 4.7x10-5 0.024 

Carrots 2,071 79 6.8x10-4 0.086 

Celery 176 8 4.32x10-4 0.027 

Cherries 275 2 5.8x10-5 0.013 

Corn syrup 454 0 0 0 

Cucumbers 1,467 8 1.51x10-4 0.083 

Grape juice 1,378 0 0 0 

Grapes 2,625 38 3.04x10-4 0.15 

Green beans (canned) 854 0 0 0 

Green beans (fresh) 1,898 5 6.18x10-4 1.1 

Green beans (frozen) 743 11 1.24x10-4 0.019 

Lettuce 1,616 47 3.82x10-4 0.16 

Milk 1,366 0 0 0 

Nectarines 345 0 0 0 

Orange juice 1,392 0 0 0 

Oranges 2,636 0 0 0 

Peaches (canned) 754 0 0 0 

Peaches (fresh) 1,623 97 9.57x10-4 0.16 

Peaches (single 534 29 0.0012 0.23 

serving) 

Peanut butter 716 0 0 0 

Pears (canned) 737 2 4.9x10-5 0.018 

Pears (fresh) 1,779 39 3.56x10-4 0.094 

Pears (single serving) 696 6 2.28x10-4 0.084 

Pineapples 364 0 0 0 

Potatoes 1,770 1 2x10-6 0.003 

Poultry (adipose tissue) 476 2 1.71x10-4 0.04542 

Poultry (liver) 479 1 2.4x10-5 0.011676 

Poultry (muscle) 145 1 1.34x10-4 0.01944 

Soybean grain 748 8 5.1x10-5 0.01 

Spinach (canned) 863 0 0 0 

Spinach (fresh) 1,638 40 9.9x10-4 0.39 

Spinach (frozen) 715 8 1.17x10-4 0.024 
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6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Diazinon Residues in Various Foods from 1994 to 2000 

Average Maximum 

Number Number of concentration concentration 

Food item analyzed detections (ppm)a (ppm) 

Strawberries (fresh) 1,768 16 1.26x10-4 0.049 

Strawberries (frozen) 155 0 0 0 

Sweet bell peppers 1,468 20 1.51x10-4 0.061 

Sweet corn (canned) 652 0 0 0 

Sweet corn (fresh) 19 0 0 0 

Sweet corn (frozen) 635 0 0 0 

Sweet peas (canned) 746 0 0 0 

Sweet peas (fresh) 9 0 0 0 

Sweet peas (frozen) 703 10 1.82x10-4 0.049 

Sweet potatoes 1,559 3 8x10-6 0.007 

Tomatoes (canned) 737 1 7x10-6 0.005 

Tomatoes (fresh) 1,962 12 9.1x10-5 0.09 

Wheat 1563 24 2.39x10-4 0.028 

Winter squash (fresh) 1,216 3 2.1x10-5 0.015 

Winter squash (frozen) 470 1 1.5x10-5 0.007 

a

Nondetects were counted as zero in calculating the average. 

Source: EPA 2002 
DIAZINON 172 

6. POTENTIAL FOR HUMAN EXPOSURE 

children, the EPA has phased out all residential uses of diazinon as of December 2004 (EPA 2004b). 

General population exposure to diazinon may occur through three routes: dermal contact, inhalation, and 

ingestion of contaminated food or drinking water. Past major routes of exposure to diazinon for the 

general population were through dermal contact directly with the chemical during domestic application 

for control of home and garden pests; through dermal contact with diazinon-treated plant materials such 

as grass clippings; or through dermal contact with treated surfaces (e.g., furniture) in domestic or office 

buildings. For children particularly, potential sources of exposure were related to the indoor application 

of diazinon on furniture, rugs, and flooring and from translocation from pets. The general population may 

also be exposed to diazinon through inhalation of contaminated ambient (outdoor) air particularly in 

agricultural areas where diazinon is extensively used or in urban areas where it is applied to lawns and 

gardens. Since many commercial buildings and residential buildings were sprayed with diazinon or used 

pest control strips that vaporize diazinon, there has been the possibility of exposure from inhalation of 

vapors in these diazinon-treated indoor air spaces. The oral route of exposure may include ingestion of 

foods contaminated with small residues of diazinon or consumption of contaminated drinking water. 

Davis et al. (1983) reported that dermal exposure (rate of contact with skin) to diazinon from spray 

applications of the compound for home and garden applications ranged from 5,700 to 29,000 μg/hour 

depending on the type of sprayer used. The mean respiratory exposures ranging from 1.9 to 7.4 μg/hour, 

were negligible compared to the dermal exposures. In addition, these authors reported that dermal 

exposure of the hands, which accounted for 85% or more of the total dermal exposure, could be easily 

reduced by the use of protective gloves. 

Pesticides may be transported into homes by translocation of vapors and by track-in from outdoors on 

shoes, clothing, and animal fur. Factors such as the activities of children and pets might serve as an 

important vehicle for transport of diazinon into homes. Morgan et al. (2001) conducted a 15-day study in 

1999 to investigate the potential for a family with an indoor/outdoor pet dog to transport diazinon into a 

home and the potential exposure to the residents following lawn application. Entryway deposits on the 

doormats had diazinon residue levels as high as 135.0 μg/g 3 days after application. Airborne levels in 

the living room of the home were at least 50 times above background levels at 0, 3, 9, and 15 days after 

application, with the highest concentration being 0.18 μg/m3

 the day of application. The living room 

carpet contained diazinon residues six times greater than background levels at concentrations of 4.28, 

3.59, and 3.56 μg/g at 3, 9, and 15 days post-application. The dog had diazinon residues on its paws as 

high as 2.27 μg the day of application and 1.39 μg 3 days post-application, and also had residues as high 

as 0.47 μg/g on its fur. The data show that diazinon residues were being physically tracked in by the pet 
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6. POTENTIAL FOR HUMAN EXPOSURE 

and humans and also redistributed into the indoor air. A gradient of diazinon residues was found from the 

soil to the entryway and into the living room of the home. Also, the dog is shown to be a good vehicle for 

the uptake, transfer, and translocation into the home and is likely to expose the occupants through direct 

contact, such as petting and playing (Morgan et al. 2001). 

A study conducted by Lewis et al. (2001) also demonstrated the importance of translocation of pesticides 

from areas of application to surfaces accessible for human contact and the potential exposure through 

inhalation, dermal contact, and ingestion. Potential indoor air inhalation exposures to diazinon after 

indoor application were estimated to be as high as 0.5 μg/kg/day. Multimedia sampling at a subset of 

homes in Arizona participating in EPA’s National Human Exposure Assessment Survey was conducted in 

order to assess residential environmental exposure to pesticides (Gordon et al. 1999). Diazinon was 

found in 53% of the house dust samples at <0.02–50.5 μg/m2

; indoor air, 63%, <0.002–20.5 μg/m3; hand 

wipes, 32%, <0.01–18.4 μg; and foundation soil (2.5 cm depth), 37%, <0.007–7 μg/g. 

Non-occupational exposure to diazinon for residents of two U.S. cities (Jacksonville, Florida, and 

Springfield, Massachusetts) was studied over three seasons: summer 1986, spring 1987, and winter 1988 

(Whitmore et al. 1994). The study focused primarily on inhalation exposures with primary environmental 

monitoring consisting of 24-hour indoor air, personal air, and outdoor air. For the population of 

Jacksonville, Florida, the mean diazinon concentration ranges were 85.7–420.7 ng/m3

 for indoor air, 1.1– 

13.8 ng/m3

 for outdoor air, and 89.0–321.6 ng/m3 for personal air. For the population in Springfield, 

Massachusetts, mean exposures were much less. The diazinon concentrations were 2.5–48.4 ng/m3

 for 

indoor air, 8.2–9.2 ng/m3

 for outdoor air, and 1.4–10.1 ng/m3 for personal air. The mean air exposure for 

diazinon in Jacksonville, Florida, was 1,380 ng/day, and dietary exposures were 590–1,140 ng/day. The 

mean air exposure estimated for Springfield, Massachusetts, was almost 10 times lower (158 ng/day), 

while the dietary exposure (586 ng/day) was equal to the low end of the range for the population of 

Jacksonville, Florida. In Jacksonville, Florida, characterized as a high pesticide use area, inhalation 

exposure exceeded dietary exposure; in Springfield, Massachusetts, characterized as a low pesticide use 

area, the dietary exposure to diazinon exceeded the inhalation exposure. 

Workers employed in industries that manufacture, formulate, package, or apply diazinon and workers 

involved in the disposal of diazinon or diazinon-containing wastes have the potential to be exposed to the 

highest concentrations of diazinon. In occupational settings, dermal exposure and subsequent absorption 

through intact skin is the most important route of exposure, and inhalation exposure is generally less 

important (Jeyaratnam and Maroni 1994). Inhalation of diazinon depends on its volatility, the type of 
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6. POTENTIAL FOR HUMAN EXPOSURE 

formulation used, and the application technique employed. Occupational ingestion may occur as a result 

of poor work practices and/or lack of personal hygiene. 

NIOSH recommends that the occupational exposure level not exceed 0.1 mg/m3

 for a 10-hour TWA 

workday (NIOSH 2006a). In addition, the American Conference of Governmental Industrial Hygienists 

has recommended a time-weighted average threshold limit value (TWA-TLV) of 0.01 mg/m3

 with a skin 

notation for occupational exposure to diazinon (RTECS 2006). 

Except for professional pesticide applicators or farm workers, the exposure risks from diazinon appear 

relatively minor as long as label instructions are followed and safeguards are taken to avoid extensive 

dermal contact. Even studies of dermal exposure typical of shearers handling sheep that have been 

dipped in diazinon showed dermal absorption rates of <4% (Wester et al. 1993). Contamination was 

generally highest on the face, hands, and arms, while inhalation was a minor route of exposure as levels 

of diazinon were less than a third of the TWA occupational exposure limit (Nutley et al. 1995). Studies 

of dermal exposure for workers in grain elevators failed to detect diazinon in grain dust above the 

0.01 μg/g detection limit, although much higher levels have been reported from Australia (Palmgren and 

Lee 1984). 

The use of a 2-day lag period from the time of diazinon application to the use of office or domestic indoor 

space appears adequate to eliminate exposure risks from vapors and residues that might be incurred from 

either inhalation or dermal absorption. Air sampling of a room treated with 36 pest control strips 

measured a maximum diazinon air concentration of 1.34 μg/m3

 15 days post-application (Jackson and 

Lewis 1981). Similarly, Williams et al. (1987) found that air sampling in two animal facility areas used 

by facility personnel and treated monthly with a 1% aqueous diazinon solution measured 2–3 μg/m3 

<24 hours post-application. Currie et al. (1990) also measured diazinon air concentrations in empty and 

furnished offices treated with a 1% aqueous solution. Four hours post-application, diazinon air 

concentrations were 163 and 158 μg/m3

 in two empty offices and 28 μg/m3 in the furnished office. One 

day post-application, diazinon levels in the offices ranged from 125 μg/m3

 (empty office) to 27 μg/m3 

(furnished office), but by 2 days post-application, the highest diazinon air concentration measured was 

53 μg/m3

. Air sampling levels of diazinon 2 days post-treatment in these three indoor exposure contexts 

were well below the NIOSH 8-hour TWA permissible exposure level (PEL) of 100 μg/m3

. 

Residual air concentrations of diazinon in a commercial greenhouse were studied by Lenhart and 

Kawamoto (1994). These authors monitored diazinon air concentrations applied as a spray and by cold 
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6. POTENTIAL FOR HUMAN EXPOSURE 

fogging. The 40-minute spray application was made to a portion of the greenhouse with only passive 

ventilation (adjustable window vents). During application, circulating fans were turned off and all roof 

vents were closed. After the spray application, 1.4 L of the diazinon emulsifiable concentrate formulation 

in 18 L of water was added to each of two cold fogging machines set for a 4-hour cold fogging 

application. Air samples were collected during the work shift prior to pesticide application, hourly during 

the application, and for 4 consecutive days after the pesticide application. Full shift area air samples were 

collected. During the post-application period, air circulating fans were continuously operated and the roof 

vents were open occasionally. The 8-hour TWA for the spray application ranged from not detected to 

25 μg/m3

. The 8-hour TWA diazinon concentrations were 6.0–52 μg/m3 (Saturday), 3–30 μg/m3 

(Sunday), 2.4–17 μg/m3

 (Monday), and not detected–12 μg/m3 (Tuesday). During the cold fogging 

application, diazinon concentrations on Friday were 730–3,030 μg/m3

. Residual 8-hour TWA 

concentrations for this application were 70–250 μg/m3

 (Saturday), 27–67 μg/m3 (Sunday), 20–59 μg/m3 

(Monday), and 19–40 μg/m3

 (Tuesday). Two of the 4 samples collected on Saturday exceeded the 

NIOSH TWA permissible exposure level of 100 μg/m3

 for occupational exposures to diazinon. Results of 

this study indicate that greenhouse workers can be at risk of inhalation exposure to residual diazinon 

concentrations. The authors believe that all diazinon applications should be conducted on Friday 

evenings after the greenhouse workers have left so that much of the residual pesticide can settle over the 

weekend. 

Wright et al. (1996) conducted a study to determine the levels of insecticide residues in the ambient air of 

insecticide storage and office rooms in commercial pest control buildings. Diazinon was detected in the 

air of office rooms at levels of <0.01 to 0.36 and <0.01–0.13 μg/m3

 measured in summer and winter, 

respectively. In the air of the storage rooms, diazinon was detected at levels of <0.01–0.48 and <0.01– 

0.36 μg/m3

, respectively. The mean diazinon quantity detected in the ambient air of all company rooms 

in 38 air samples was 0.08 μg/m3

. 

Finally, air sampling at a retail garden store conducted to determine exposures for retail employees 

showed levels of diazinon averaging only 3.4 μg/m3

, well below the NIOSH TWA exposure level of 

100 μg/m3

 (Wachs et al. 1983). However, these authors point out that the air concentrations they reported 

may vary greatly among retail stores depending on the amounts and types of diazinon formulation sold, 

air temperature, condition of the packaging material (e.g., torn packaging, loose lids), prior spills, and 

types of floor coverings. 
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6. POTENTIAL FOR HUMAN EXPOSURE 

The National Occupational Exposure Survey (NOES) conducted by NIOSH from 1981 to 1983 estimated 

that 39,342 workers (including 3,216 women) employed at 3,168 facilities were potentially exposed to 

diazinon in the United States (NIOSH 2006b). The NOES database does not contain information on the 

frequency, concentration, or duration of exposure; the survey provides only estimates of workers 

potentially exposed to chemicals in the workplace. 

6.6 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 Section 3.7, Children’s Susceptibility. 

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). 

In areas where diazinon is sprayed for agricultural use, children within the general population are likely to 

be exposed to diazinon in the same ways as adults, including through contact with sprayed plants, soil, or 

other surfaces; breathing contaminated air; eating contaminated foods; or drinking contaminated water. 

Diazinon residues bound to soil or dust particles in carpets or on bare floors may present an exposure 

route for infants and toddlers through dermal contact or ingestion. Translocation from household pets 

exposed to diazinon may also present an exposure route through dermal contact or ingestion. 

Several studies suggest that house dust is an important route of toxicant exposures to young children. In a 

study of pesticide exposure to children in the home in rural areas in California, samples of house dust 

were analyzed from a day care center and 10 homes, 5 of which were also the home of at least one farm 

worker (currently working in the field) and 8 of which reported home pesticide use (Bradman et al. 1997). 

Excluding nondetects, concentrations of diazinon ranged from 0.7 to 169 mg/kg in four farm-worker 

homes and from 0.2 to 2.5 mg/kg in three nonfarm worker homes. Diazinon was detected at 0.10 mg/kg 

in the daycare center. For children in two of the homes with the highest levels of diazinon, ingestion 
DIAZINON 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

exposures leading to risks for cholinesterase inhibition exceeded the EPA Office of Pesticide Program’s 

chronic oral RfD of 9x10-5 mg/kg/day. The home with the highest level (169 mg/kg) also exceeded the 

EPA subchronic RfD of 9x10-4 mg/kg/day. Diazinon residues of 220, 125, and 52 ng were detected on 

the hands of 3 of the 11 toddlers; all 3 toddlers resided in a different farm worker home (Bradman et al. 

1997). For the child with the highest diazinon level on the hands, exposures leading to risks of 

cholinesterase inhibition due to diazinon ingestion from hand residues also exceeded the chronic RfD 

(Bradman et al. 1997). 

The Minnesota Children’s Pesticide Exposure Study (MNCPES) monitored house dust levels from 

carpets and other surfaces and hand rinses for 102 children, ages 3–13, over a 1-week sampling period 

(Lioy et al. 2000). Diazinon was detected in approximately 10% of carpet and surface samples collected. 

A different collection method yielded eight samples with detectable quantities (detection limit of 

0.076 ng/cm2

 surface) out of 194 samples collected. It was only detected in 6 of 94 hand rinse samples 

collected. Seventy-five percent of the children had played on the floor and 67% had played outside 

between hand rinse samples, increasing their exposure to diazinon present on carpets and other surfaces. 

Inhalation exposure to semivolatile pesticides in indoor air can be substantial and may be a primary route 

of exposure after residential use among homes using insecticides. However, an aggregate-exposure study 

of pesticides, including diazinon, among 102 children in Minnesota concluded that ingestion was by far 

the dominant route of exposure when compared to inhalation (Clayton et al. 2003). EPA regulatory 

action to phase out residential and some agricultural use of diazinon has been successful at reducing 

indoor air exposure in residential homes (EPA 2004b; Whyatt et al. 2004). 

Children may be exposed to diazinon and its residues in the foods that they eat. In the FDA Total Diet 

Study for infants and toddlers conducted between 1980 and 1982, the average concentration and the 

calculated average daily intake of diazinon in different food groups were determined (Gartrell et al. 

1986). In the infant diet, the average concentrations (mg/kg) and average daily intakes (μg/day) of 

diazinon by food group were 0.0002 and 0.0148 in meat, fish, and poultry, 0.0051 and 0.245 in grain and 

cereal products, and 0.0001 and 0.0016 in oils and fats, respectively. In the toddler diet the average 

concentrations (mg/kg) and average daily intakes (μg/day) of diazinon by food group were 0.0002 and 

0.0230 in meat, fish, and poultry, 0.0034 and 0.387 in grain and cereal products, 0.0004 and 0.0268 in 

vegetables, 0.0001 and 0.0157 in fruit and fruit juices, 0.0007 and 0.0114 in oils and fats, and 0.0003 and 

0.0073 in sugar and adjuncts, respectively. Data on the weight-adjusted intake of diazinon by infants and 

toddlers were determined based on the results of the FDA Total Diet Studies for fiscal years 1978– 
DIAZINON 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

1981/1982 (Gartrell et al. 1986). The reported weight-adjusted intakes of diazinon ranged from 0.002 to 

0.032 μg/kg body weight/day for infants and 0.004–0.034 μg/kg body weight/day for toddlers for the 

study years. 

Quantitative estimates of the exposure of infants and children to pesticides have been reported in the 

results of FDA Total Diet Studies conducted in the 1980s using the amounts of pesticide residues in foods 

thought to be in the diets of infants or children. Estimates of the mean intake of diazinon per unit body 

weight were made for the 6–11-month-old age group, 2-year-old age group, and the 14–16-year-old 

female and 14–16-year-old male age groups. For the period June 1984–April 1986, the estimates were 

0.0020 μg/kg/day for the 6–11-month-old group, 0.0047 μg/kg/day for the 2-year-old group, 

0.0018 μg/kg/day for the 14–16-year-old female group, and 0.0025 μg/kg/day for the 14–16-year-old 

male group (Gunderson 1995a). For the period July 1986–April 1991, the mean daily intake estimates 

were 0.0061 μg/kg/day for the 6–11-month-old group, 0.0106 μg/kg/day for the 2-year-old group, 

0.0037 μg/kg/day for the 14–16-year-old female group, and 0.0052 μg/kg/day for the 14–16-year-old 

male group (Gunderson 1995b). Diazinon residues were not detected in any of the samples of infant 

formula (milk-based without iron, canned, ready-to-serve) analyzed in the study (Gunderson 1995b). 

In the FDA regulatory monitoring of domestic foods that may be eaten by infants/children conducted 

from 1985 to 1991, the maximum residue concentrations of diazinon detected were 0.46 mg/kg in apples, 

0.17 mg/L in whole milk, 0.26 mg/kg in oranges, 0.06 mg/kg in pears, and trace amounts in bananas 

(Yess et al. 1993). In imported foods, the maximum residue concentrations of diazinon were 0.06 mg/L 

in apple juice, 0.08 mg/kg in apples, 0.11 mg/kg in pears, and trace amounts in bananas. In the FDA 

Total Diet Study of infant foods conducted over the period 1985–1991, diazinon was detected at a 

maximum residue concentration of 0.0004 mg/kg in infant mixed cereal, dry, prepared with whole milk, 

0.0004 mg/kg in beef, high meat, and vegetables, 0.0006 mg/kg in vegetables with bacon/ham, and 

0.0009 mg/kg in vegetables with beef (Yess et al. 1993). The maximum diazinon residue concentrations 

detected in adult foods eaten by infants/children reported in this study were 0.002 mg/kg in apples, red, 

with peel, raw, 0.004 mg/kg in peanut butter, creamy, and 0.005 mg/kg in pears, raw. 

Based on a calculated acute population adjusted dose (aPAD), at which no adverse health effects would 

be expected using the safety factor prescribed in the Food Quality Protection Act (FQPA), the population 

subgroup with the highest acute dietary exposure (at 63% of the aPAD) and the highest chronic dietary 

exposure (at 22% of the cPAD) is children aged 1–6 (EPA 2004b). However, values of <100% of the 
DIAZINON 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

aPAD or cPAD are considered to be not of concern (EPA 2004b). The reported aPAD and cPAD values 

were 0.0025 mg/kg/day (2.5 μg/kg/day) and 0.0002 mg/kg/day (0.2 μg/kg/day), respectively. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Other than individuals who are occupationally exposed to diazinon (during its production, formulation, 

packaging, distribution, use, or disposal), populations exposed to higher than background concentrations 

of diazinon in ambient air include those living near chemical manufacturing or processing sites, 

individuals living on farms or in the vicinity of agricultural areas where diazinon is extensively used, and 

individuals living near hazardous waste sites. Individuals living near these sites may also be exposed to 

potentially higher concentrations of diazinon or its metabolites in their drinking water if they obtain tap 

water from wells located near these sources. Children may receive higher diazinon doses from dermal 

exposures if they play on freshly treated lawns or soil. In addition, children may receive potentially 

higher oral doses from ingestion of diazinon-treated soils from their hands while playing in contaminated 

areas. In order to mitigate the exposure and risk to the general population, especially children, the EPA 

has phased out all residential uses of diazinon as of December 2004 (EPA 2004b). 

6.8 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 diazinon is available. Where adequate information is not 

available, ATSDR, in conjunction with 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 diazinon. 

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. 
DIAZINON 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. While the principal properties of diazinon are well 

characterized, (Howard 1991; HSDB 2008; NIOSH 2005; O'Neil et al. 2001) there are data gaps for 

melting point, odor and taste thresholds, autoignition temperature, and explosive limits for the compound. 

However, these properties are sufficient 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 as, or 

more toxic than, diazinon. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2005, became available in May of 2007. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Diazinon is commercially produced in the United States and abroad. Production in the United States was 

estimated to be 2.63 million kg in 1982 (HSDB 2008) and 4.67 million kg in 1990 (Larkin and Tjeerdema 

2000). Recent production volume data were not located. As of June 30, 2001, manufacturing of indoor 

use products containing diazinon was discontinued. Manufacture of non-agricultural outdoor use 

products containing diazinon was discontinued as of June 30, 2003 (EPA 2004b). Production amounts of 

diazinon should decrease due to the discontinuation of all residential products containing this chemical. 

Limited data were found on import volumes; an estimated 6.41x104 kg diazinon was imported into the 

United States in 1982 (HSDB 2008). The United States exported an estimated 5.8 million pounds of 

diazinon from 1997 to 2000 (Smith 2001). 

Diazinon is used in agriculture as an insecticide on a variety of crops. It was formerly used extensively in 

home and garden applications, such as in pest strips and on turf. Due to the emerging health and 

ecological risks posed by diazinon, manufacturers agreed to phase out and cancel all residential products. 

As a result, after December 31, 2004, no diazinon products with residential uses would be registered or 

sold (EPA 2004b). For 1987 through 1997, total annual domestic usage of diazinon was over 13 million 

pounds. However, most of this (about 70%) was allocated to outdoor residential uses (EPA 2004b). 

Since residential uses of diazinon have been discontinued, the total annual usage should be significantly 

lower. Approximately 4 million pounds of active ingredient diazinon are used annually on agricultural 

sites (EPA 2004b). 
DIAZINON 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

For ultimate disposal, large amounts of diazinon residuals should be incinerated in a unit with effluent gas 

scrubbing, while physical, chemical, and biological treatments may be appropriate for disposal of smaller 

quantities of diazinon. Composting has also been used for the disposal of diazinon-contaminated soils 

and organic solids (Felost et al. 2003). 

Environmental Fate. Diazinon is moderately mobile in some soil types (Arienzo et al. 1994; Kenaga 

1980; Sharom et al. 1980a). Information on the mobility of diazinon and on a major degradation product 

2-isopropyl-6-methyl-4-hydroxypyrimidine in various soil types is available (Arienzo et al. 1994; 

Levanon et al. 1994; Sharom et al. 1980a; Somasundaram et al. 1991). In the atmosphere, diazinon is 

subject to degradation due to photolysis (Gore et al. 1971) and reactions with hydroxyl radicals (Glotfelty 

et al. 1990a; Meylan and Howard 1993; Schomburg et al. 1991; Seiber et al. 1993). In water, diazinon is 

subject to hydrolysis, photolysis and biodegradation. The rate of degradation of diazinon in water and 

soil is strongly influenced by pH (Chapman and Cole 1982; Ferrando et al. 1992; Frank et al. 1991b; 

Garcia-Repetto et al. 1994; Sharom et al. 1980b). Diazinon undergoes only slight photolysis in water, 

with reported half-life estimates ranging from 42 to 88 days (EPA 1976; Frank et al. 1991b). Diazinon 

can be degraded at the soil surface by photolysis (Burkhard and Guth 1979), and in soils and sediment by 

hydrolysis (Chapman and Cole 1982; Levanon et al. 1994; Schoen and Winterlin 1987; Sethunathan and 

MacRae 1969; Somasundaram et al. 1989, 1991) and by biodegradation by microorganisms (Adhya et al. 

1981; Barik and Munnecke 1982; Gunner and Zuckerman 1968). Additional information on the 

mechanism by which diazinon is converted to diazoxon in the atmosphere would be useful; additional 

information on the persistence and mobility of the major degradation products of diazinon would also be 

useful in evaluating the environmental fate of diazinon and its degradation products. 

Bioavailability from Environmental Media. Diazinon can be absorbed following inhalation, 

dermal, or oral exposures. Absorption through the skin is of major concern for exposures of farmers, 

farm workers, commercial applicators, or homeowners related to the use of diazinon as an insecticide or 

nematocide (Davis et al. 1983). Absorption via inhalation is a major concern particularly with respect to 

indoor exposures to diazinon within 2 days post-application of the compound as a pest control agent in 

commercial buildings and homes (Currie et al. 1990; Jackson and Lewis 1981; Lenhart and Kawamoto 

1994; Williams et al. 1987). Additional information on the concentrations of diazinon in indoor air and in 

groundwater from domestic wells, particularly from environments near hazardous waste sites, is needed 

to determine the bioavailability of diazinon in these media. 
DIAZINON 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

Food Chain Bioaccumulation. Diazinon has an estimated low bioconcentration potential (BCF=77) 

(Kenaga 1980) in aquatic organisms, which is generally confirmed by measured BCF values obtained 

from laboratory studies with fish and other aquatic invertebrates (El Arab et al. 1990; Keizer et al. 1991; 

Sancho et al. 1993; Tsuda et al. 1989, 1995). Further information on measured BCF values for additional 

edible fish and shellfish would be helpful, as would information on tissue residues of diazinon and its 

major degradation products in edible species. No information was found on studies associated with plant 

uptake, but diazinon is rarely detected above EPA tolerance limits (Hundley et al. 1988). 

Bioaccumulation in aquatic food chains does not appear to be important, and no further information on 

biomagnification is required. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of diazinon in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

diazinon in the environment can be used in combination with the known body burden of diazinon to 

assess the potential risk of adverse health effects in populations living in the vicinity of hazardous waste 

sites. 

Diazinon is distributed in all environmental media and has been detected in ambient air (Carey and Kutz 

1985; Glotfelty et al. 1990a; Kutz et al. 1976; Lewis and Lee 1976; Schomburg et al. 1991; Seiber et al. 

1993; Zabik and Seiber 1993), in indoor air (Currie et al. 1990; Jackson and Lewis 1981; Lenhart and 

Kawamoto 1994; Palmgren and Lee 1984; Wachs et al. 1983; Williams et al. 1987), surface water (Braun 

and Frank 1980; Carey and Kutz 1985; Domagalski and Kuivila 1993; Frank and Logan 1988; Frank et 

al. 1990a; Kendall et al. 1993; Maguire and Tkacz 1993; Pereira and Hostettler 1993; Szeto et al. 1990; 

Wan et al. 1994), groundwater (Cohen 1986; EPA 1989), sediment (Carey and Kutz 1985; Domagalski 

and Kuivila 1993; Szeto et al. 1990), and some fish (Braun and Frank 1980). The levels of diazinon in 

air, surface water, groundwater, and soil have been well documented. Additional information on tissue 

residues of diazinon and 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 diazinon in contaminated media at hazardous waste sites are 

needed so that the information obtained on levels of diazinon in the environment can be used in 

combination with the known body burden of diazinon to assess the potential risk of adverse health effects 

in populations living in the vicinity of hazardous waste sites. 
DIAZINON 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

Exposure Levels in Humans. Data regarding levels of diazinon in humans from environmental 

exposures (the general population, populations living near hazardous waste sites, or occupationally 

exposed groups) are not available. It is arguable that these levels are not knowable because of the rapid 

metabolism and clearance of diazinon after it enters the body (Iverson et al. 1975; Machin et al. 1975; 

Mount 1984; Műcke et al. 1970). Additional studies which associate levels of diazinon in the 

environment and levels of diazinon metabolites in body tissues would be helpful. This information is 

necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. The exposure of children to diazinon through food ingestion has been 

estimated fairly extensively for various age groups, including infants, toddlers, and teenagers (Gunderson 

1995a, 1995b; Yess et al. 1993). Weight-adjusted intakes for these age groups have also been calculated 

(Gartrell et al. 1986). Studies have also been conducted to assess the extent of exposure of children to 

diazinon through dermal contact, inhalation, and ingestion of environmental residues (Bradman et al. 

1997; Clayton et al. 2003). Data on the body burden measurements of diazinon are needed to determine 

exposures to children living in both agricultural and non-agricultural areas. In order to assess exposures 

to nursing infants, studies of breast milk contamination would be useful. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for diazinon were located. This substance is not 

currently one of the compounds for which a sub-registry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for 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. 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2006) database provides additional information obtainable 

from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1. 

Researchers at the Agricultural Research Service are conducting a study funded by the U.S. Department 

of Agriculture (USDA) to develop watershed management systems that increase productivity and improve 
DIAZINON 184 

6. POTENTIAL FOR HUMAN EXPOSURE 

water quality and ecology in the Mississippi Delta. Best Management Practice studies will be coupled 

with research regarding the response of aquatic organisms to potential agricultural contaminants in order 

to improve development of Total Maximum Daily Loads. 

Researchers at the University of California are conducting a study funded by the USDA to develop a 

pesticide transport model to characterize the vulnerability of surface and subsurface environments to 

pesticide contamination. The study will quantify the migration of pesticides through soils, aquifiers, and 

surface streams by taking into account physical, chemical, and biological processes and evaluate the 

potential threat of pesticides and their breakdown products to surface and subsurface systems. The model 

will then be applied to basins in the Sacramento-San Joaquin River and comprehensive management 

schemes will be identified. 

Scientists at the University of California are conducting research funded by the USDA to assess the fate 

of hazardous chemicals in aquatic environments and their toxicity to resident organisms. The goals of the 

study are to characterize the dissipation and transformation processes in aquatic systems for pesticides, 

including diazinon, of current importance and to characterize the sublethal actions of pesticides in aquatic 

organisms. 

Researchers at Michigan State University are conducting a study funded by the USDA to mitigate crop 

and turf damage caused by the Japanese beetle and the European chafer in Michigan, and ultimately in the 

north central United States, through host plant resistance and introduction of natural enemies. One of the 

objectives of the study is to find an alternative to diazinon for fall and spring control of the European 

chafer. 
DIAZINON 185 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring diazinon, its metabolites, and other biomarkers of exposure and effect to 

diazinon. 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. 

7.1 BIOLOGICAL MATERIALS 

Diazinon is widely used for agricultural purposes, which may result in human exposure during 

application, and residues on or in foods can result in exposure of humans by ingestion. Although all 

indoor and outdoor residential use has been phased out and cancelled, additional exposure potentials exist 

as a result of home gardening activities and pet pest control. Consequently, methods for the 

determination of diazinon in biological samples can be used to verify that exposure and absorption has 

occurred. Since diazinon is rapidly metabolized, determination of the parent compound can only provide 

evidence of very recent exposures (see Chapter 3). Methods have been reported for metabolites, and 

these are briefly discussed below and under Biomarkers of Exposure. Table 7-1 lists the applicable 

analytical methods for determining diazinon and its metabolites in biological fluids and tissues. 

The principal method used for the detection of diazinon or its metabolites in biological samples is gas 

chromatography (GC) using a flame photometric detector (FPD), a mass spectroscopy detector (MS), an 

electron capture detector (ECD), or a flame ionization detector (FID). The preparation of samples usually 

involves variations of solid-phase extraction (SPE), and/or liquid/liquid extraction with organic solvents. 

Garcia-Repetto et al. (2001) reported a method for diazinon identification and quantification in human 

blood using SPE, GC-nitrogen phosphorus detection (NPD) analysis followed by GC-MS confirmation. 

The average recovery of diazinon in blood is 87.92%, which is in the acceptable range established by the 

EPA. The limit of detection (LOD) and the limit of quantitation (LOQ) reported in the study are 1.97 and 

6.58 μg/L, respectively. This method has improved a previous method that involved liquid-liquid 
DIAZINON 186 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Diazinon and Transformation 

Products in Biological Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Human blood Addition of 1 mg/L azobenzene, GC/MS 0.01 μg/g Absolute Musshoff et 

0.2 g ammonium sulfate and 2 mL recovery al. 2002 

0.1 M sulfuric acid to a 0.5 mL compared to 

sample of blood. Mixture is sealed a methanolic 

and heated in a vial. Samples are solution: 

collected by HS-SPME. 2.9% 

Human fatty Tissue pulverization and extraction GC/NPD No data No data Kirkbride 

tissue (from with acetone. Concentration and 1987 

greater purification by sweep co-distillation 

omentum) and Florisil/anhydrous sodium 

sulfate column chromatography. 

Elution with 20% ether in hexane 

followed by hexane. Addition of 

internal standard. 

Human Maceration of 0.5 g sample in GC/ECD; No data No data Poklis et al. 

adipose, bile, tissue grinder with acetonitrile. GC/FID 1980 

blood, brain, Addition of aqueous sodium sulfate 

stomach and partitioning into hexane. 

contents, Concentration and clean up using 

kidney, and Florisil column. 

liver 

Human urine Dilution of urine with acetonitrile, GC/FPD DEP: DEP: Reid and 

(DEP, DETP) azeotropic distillation for water 0.072 ppm; 96 (4.7% Watts 1981 

removal, evaporation of solvent, DETP: RSD); 

redissolution in acetone and 0.041 ppm DETP: 

derivatization using penta­ 99 (2.4% 

fluorobenzyl bromide. RSD) at 

0.8 ppm 

Human urine Solid phase extraction with or GC/MSD 0.01 ng 101.3% for Yokley et al. 

(2-isopropyl­ without liquid/liquid partitioning. SPE alone; 2000 

6-methyl­ 100.8% for 

4-pyrimidinol) partitioning 

and SPE 

Human urine Hydrolysis with ∃-glucuronidase, HPLC­ 0.2 ng/mL 116% low Olsson et al. 

(2-isopropyl­ solid phase extraction, liquid/liquid MS/MS urine dose; 93% 2003 

6-methyl­ extraction, and evaporation. high dose 

4-pyrimidinol) 

Bovine liver, Extraction of homogenized sample GC/FPD 0.01– Rumen Holstege et 

rumen content with methanol-dichloromethane 0.05 μg/g content: al. 1991 

(partially (10–90, v/v) followed by gel using 5 g 95 (3% 

digested grain permeation chromatography and sample RSD) at 

and vegetation silica gel solid phase extraction 0.1 μg/g; 

mixture) clean-up. liver: 88 (5% 

RSD) at 

0.05 μg/g 
DIAZINON 187 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Diazinon and Transformation 

Products in Biological Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Animal fat Sweep codistillation, Florisil clean GC/FPD No data 90 (6% Brown et al. 

up-elution with methylene chloride- RSD) at 1987 

light petroleum-acetonitrite 0.4 mg/L 

(50:48.5:1.5). 

a

Diazinon is the target analytes unless otherwise specified. 

DEP = O,O-Diethyl phosphate; DETP = O,O-Diethyl phosphorothionate; ECD = electron capture detector; FID = flame 

ionization detector; FPD = flame photometric detector; GC = gas chromatography; HPLC = high-performance liquid 

chromatography, HS = head space, MS = mass spectrometry; MS/MS = tandem mass spectrometry, MSD = mass 

selective detection; NPD = nitrogen phosphorus detector, RSD = relative standard deviation; SPE = solid-phase 

extraction; SPME = solid-phase microextraction 
DIAZINON 188 

7. ANALYTICAL METHODS 

extraction with n-hexane and benzene resulting in more complex chromatograms. Not only is the method 

more precise, it also eliminates hazardous waste emissions and exposure of technicians to toxic solvents. 

A method for the determination of diazinon in human serum has been published by researchers at the 

Centers for Disease Control and Prevention (Liu et al. 1994) in which 2-dimensional chromatography was 

used to determine 15 pesticides in 4 minutes. Supercritical fluid extraction (SFE) was used to recover 

pesticides into methylene chloride and this extract was analyzed using two 2-meter columns connected by 

an on-column thermal desorption modulator. Sensitivity for diazinon was reported to be 1.8 pg oncolumn; no details about overall recoveries were provided (Liu et al. 1994). 

Yokley et al. (2000) developed a method for valid, precise, and accurate determination of the metabolite, 

6-methyl-2-(1-methylethyl)-4(1H)-pyrimidinone (G-27550), of diazinon in urine. The sample can be 

prepared by SPE with an LOQ of 1.0 μg/L, or by SPE in conjunction with liquid/liquid partitioning (LOQ 

of 0.50 μg/L). Average recoveries of G-27550 for each sample preparation method are 101.3 and 

100.8%, respectively. The final analysis was done by GC/mass selective detection (MSD). The LOD for 

G-27550 was 0.01 ng. The report states that this is an accurate Good Laboratory Practice (GLP)-

validated method that may be used as a biomonitoring tool to determine potential diazinon exposure in 

humans (Yokley et al. 2000). 

A method for the rapid quantification of diazinon metabolite 2-isopropyl-6-methyl-pyrimidin-4-ol in 

human urine using liquid chromatography/electrospry ionization-tandem mass spectrometry has been 

published (Olsson et al. 2003). 

Diazinon was determined in bovine liver and rumen content by GC/FPD by Holstege et al. (1991) using a 

method with an LOD reported to be 0.01–0.05 μg/g using a 5-g sample. Recoveries were reported to be 

95% from rumen content and 88% from liver. Brown et al. (1987) used GC/FPD and sweep codistillation 

to determine diazinon in animal fat. The recovery was stated to be 90% (6% relative standard deviation 

[RSD]) at 0.4 ppm; no LOD information was given (Holstege et al. 1991). 

7.2 ENVIRONMENTAL SAMPLES 

Table 7-2 lists the methods used for determining diazinon and some of its degradation products in 

environmental samples. The principal separation and detection methods of diazinon and degradation 

products in environmental samples include GC or high performance liquid-chromatography (HPLC), in 
DIAZINON 189 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Air, gloves 

(surrogate 

Preconcentration from air 

sample using PUF. Soxhlet 

Capillary 

GC/MS (can 

55 ng/m3 

(5.5 m3 

73% 

(14% RSD) 

Hsu et al. 

1988 

for dermal extraction of PUF or gloves use multiple sample) 

exposure) with 5% ethyl ether/hexane. ion detection) 

Addition of deuterated internal 

standards and concentration 

using K-D and nitrogen 

blowdown. 

Air Preconcentration using Capillary No data 90% at Williams et al. 

(diazinon, 

diazoxon) 

ORBO-42 pesticide adsorbent 

tubes (Supelco). Extraction 

GC/NPD 0.1% and 

1 μg/m3 

1987 

with acetone, evaporation just (diazinon) 

to dryness and redissolution in 

100 μL acetone containing 

internal standard. 

Air Preconcentration of pesticide 

onto OVS-2 tube (13 mm 

GC/FPD 

(NIOSH 

0.0004 mg/m3 

(400 ng/m3) 

94% (2.7% 

RSD at 

NIOSH 1994 

quartz filter, XAD-2, 270 

mg/140 mg. Elution with 90% 

Method 5600) for 120 L 

sample. 

2.4 μg 

(0.01 μg/m3 

, 

toluene/10% acetone. 240 L 

sample) 

Air Air is drawn through a glass GC/FPD 3.0 μg/m3

 91.2% OSHA 1986 

tube with a glass fiber filter and 

XAD-2 adsorbent. The 

samples are desorbed with 

toluene. 

Drinking Preconcentration onto 5 μm RP-HPLC/UV 0.03– 91% (±10% Driss et al. 

water C18-silica or 7 μm polystyrene­ (254 mn) 0.06 μg/L RSD) at 1993 

divinyl benzene co-polymer (ppb) sample 

with subsequent backflush onto volumes up 

analytical HPLC column. to 300 mL 

Ground- Extraction with methylene GC/NPD 0.13 μg/L 94% EPA 1995b 

water and chloride. Drying and (18% RSD) 

finished concentration of extract then 

drinking resolution in MTBE. 

water 

Drinking Preconcentration of 2.5 mL GC/NPD Tap water: >95% (<4% Kwakman et 

water, river water onto C18 extraction disks, 20 pg/mL; RSD at al. 1992 

water rinsing with additional 1 mL and river water: 200 ppt) 

purging disk with gas to remove 20–50 pg/mL 

residual water. Elution with 

ethyl acetate directly onto GC 

pre-column with solvent 

venting. 
DIAZINON 190 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Pond water Micro liquid-liquid extraction of 

1.5 mL water with 1.5 mL 

methyl t-butyl ether; 500 μL of 

extract slowly introduced into 

GC pre-column with solvent 

venting. 

Surface Adsorption of pesticides from 

water 2 L of water onto XAD-2 and 

XAD-7 resins. Elution with 

methylene chloride, water 

removal and use of K-D to 

reduce volume. 

Raw water SPE then elution under vacuum 

and finished with ethyl acetate and 

drinking dichloromethane. The extract 

water is dried and concentrated. 

Finished LSE followed by extraction with 

drinking ethyl acetate and methylene 

water, chloride then evaporation of 

source solvent. 

water, or 

drinking 

water in any 

treatment 

stage 

Filtered Filtration of field samples using 

waste water glass-filter fibers and SPE. 

and natural- Elution of dry SPE cartridges 

water with dichloromethane and 

samples diethyl ether (4:1) followed by 

gentle evaporation of extract. 

Water Filtration using glass-fiber filters 

followed by SPE. Elution of dry 

SPE columns with ethyl acetate 

then evaporation. 

Water Filtration of 1 L of water 

followed by extraction 3 times 

with 100 mL methylene chloride 

after addition of 20 g sodium 

sulfate. Concentration using 

K-D and solvent exchange to 

benzene. Concentrations done 

under nitrogen. Fractionation 

by HPLC. 

cap. GC/FPD 0.02 μg/L 102% (5% van der Hoff et 

RSD) at al. 1993 

0.50 μg/L 

level 

GC/chemical 0.0005 μg/L 103.8% Mattern et al. 

ionization ion (14% CV) at 1991 

trap MS 1 ppb level 

GC/MS 0.015 μg/L 101% EPA 2000b 

(3% RSD) 

GC/MS 0.11 μg/L 83% EPA 1995a 

(9% RSD) 

GC/MS 0.07 μg/L 93% USGS 2002b 

(4% RSD) 

GC/FPD 0.01 μg/L 88% USGS 2002c 

(16% RSD) 

GC/FPD 0.025 μg/L 92% Seiber et al. 

(P-mode) (2% RSD) 1990 
DIAZINON 191 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Water SPME of filtered water sample; 

thermal desorption of diazinon 

from SPME fiber. 

Water Extraction of analytes from 

water using SPE; elution with 

ethyl acetate (108 μL) directly 

onto retention gap with solvent 

venting. 

Industrial Extraction of 1 L of sample with 

and 60 mL methylene chloride 

municipal 3 times. Water removal from 

waste water extract and solvent exchange 

to hexane during K-D 

concentration. 

Waste water Extraction of 1 L of water with 

15% methylene chloride in 

hexane using a separatory 

funnel. Concentration using 

K-D. Cleanup (if needed) by 

Florisil fractionation or 

acetonitrile partition. 

Water Direct injection or liquid/liquid 

extraction and concentration. 

GC/AED 1 μg/L with No data Eisert et al. 

carbon line (precision 1994 

(193 nm); 8–12 

3 μg/L with relative 

S line standard 

(181 nm) deviation) 

GC/AED 1 ng/L 105% Hankemeier et 

(100 mL (4% RSD) al. 1995 

sample) with at 5 μg/L 

P channel 

GC/FPD or 0.6 μg/L 67% EPA 1993a 

thermionic (6% RSD) 

detection 

(P-mode); 

GC/MS for 

qualitative 

identifications 

recommended. 

(Method 1657) 

GC/FPD 0.012 μg/L 94% EPA 1993b 

(P-mode) or (5.2% RSD) 

GC/thermionic 

detection. 

GC/MS for 

qualitative 

compound 

identification 

recommended. 

(Method 614) 

HPLC/UV 0.5 mg/L No data Mallet et al. 

(direct 1990 

injection); 

0.5 μg/L 

(liquid/liquid 

extraction) 

GC/FPD 1.24 ppb 71% USGS 2002d 

(7% RSD) 

Bed 

sediment 

(lake and 

stream), 

aqueous 

suspended 

sediment 

and soil 

Extraction with Soxhlet 

apparatus of minimum 25-g 

equivalent dry-weight samples 

using 350 mL dichloromethane 

and 25 mL methanol (93:7). 

Concentration and filtration of 

extract. Elution with dichloromethane through chromatographic column. Concentration 

and resolution in ethyl acetate. 
DIAZINON 192 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Soil Extraction of soil with 

(diazinon, hexane:acetone (1:1), 

diazoxon, centrifugation, separation of 

2-isopropyl- hexane from acetone/water 

4-methyl- layer. Extraction of acetone/ 

6-hydroxy- water phase with chloropyrimidine) form:diethyl ether (1:1), solvent 

exchanged to methanol. 

Hexane layer contained 

diazinon, chloroform/diethyl 

ether fraction contained 

2-isopropyl-4-methyl-6­

hydroxy-pyrimidine. 

Soil Sequential Soxhlet using 

(diazinon, acetone then methanol. 

2-isopropyl4-methyl6-hydroxypyrimidine) 

Water, soil Water: Addition of deuterated 

standards to 1 L water and 

extraction 3 times with 200 mL 

methylene chloride. Water 

removal with anhydrous sodium 

sulfate then concentration 

using K-D and nitrogen 

blowdown. Soil: Addition of 10 

mL water and deuterated 

standards to 50 g of soil 

followed by equilibration for 1 

hour. Sonication 3 times with 

acetone/hexane. Phase 

separation followed by water 

removal using sodium sulfate, 

concentration using K-D, and 

nitrogen blow-down. Spiking 

with phenanthrene-d10 before 

analysis. 

Cucumber, Chopping of produce and 

lettuce, extraction with acetone/ 

grapes methylene chloride/petroleum 

ether (1:1:1). Evaporation to 

dryness and redissolution in 

acetone and concentration. 

TLC No data No data Sethunathan 

and Yoshida 

1969 

GC, TLC, No data No data Burkhard and 

GC/MS Guth 1979 

GC/MS (SIM) 100–200 ppt Water: Lopez-Avila et 

for water, 2– 89.4% al. 1985 

4 ppb for soil (4.4% RSD) 

at 1 ppb 

Soil: 103% 

(15% RSD) 

at 20 ppb 

SFC/NPD No data No data Zegers et al. 

1994a 
DIAZINON 193 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Green 

beans, 

lettuce, 

carrot, bell 

pepper 

Kale, 

endive, 

carrots, 

lettuce, 

apples, 

potatoes, 

strawberries 

Numerous 

non-fatty 

crops 

Homogenization of produce 

with acetonitrile. Addition of 

NaCl to affect phase 

separation, removal of 

acetonitrile, water removal 

volume reduction, addition of 

deuterated internal standards. 

Extraction of crops with ethyl 

acetate and granular sodium 

sulfate, filtration, concentration 

with K-D. Sweep co-distillation 

cleanup for GC. 

Extraction with acetonitrile and 

partition into petroleum ether. 

Concentration using K-D and 

purification using Florisil 

column chromatography. 

Soybeans Grinding of 25 g samples and 

and rice extraction with 150 mL of 

2:1 acetone: methanol; filtration 

and reduction of volume to 

100 mL. Addition of water, 

NaCl followed by extraction 

with methylene chloride (2x); 

solvent evaporation and 

redissolution in methylene 

chloride:cyclohexane (1:1) and 

fractionation on Bio-Bead S-X3. 

Evaporation under N2 stream 

and redissolution in 2 mL 

hexane. 

Sweet Extraction with methylene 

cherries for chloride and cleaning with 

baby food quaternary aminesilane-silicadichloromethane. 

GC/MS 50 ppb 88% Liao et al. 

(17% RSD) 1991 

GC thermionic No data for No data AOAC 1990a 

detector GC 

GC/KCl Polarographic 80% AOAC 1990a, 

thermionic method: 1990b, 1990c 

detector; 0.2 ppm 

identifications based on 1 g 

by combin­ crop in 1 mL 

ations of gas, cell 

thin layer, and 

paper chromatography; 

polarographic 

confirmatory 

method 

GC/NPD or Rice: Rice: Hong et al. 

GC/MS (SIM) 0.01 ppm 83.4% 1993 

soybeans: (1.5% RSD) 

0.05 ppm at 1 ppm 

soybeans: 

62.7% 

(8.6% RSD) 

at 1 ppm 

GC/electron 30 ppt ≥70% at Bicchi et al. 

capture 0.01 ppm 1997 

detection/ FPD 

and GC/NPD/ 

FPD 
DIAZINON 194 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

Sample Analytical detection Percent 

matrixa Preparation method method limit recovery Reference 

Strawberries Spike samples were sliced and 

and cherries homogenized. 

Various Homogenization of sample 

fruits and (adding water if needed) and 

vegetables adsorption on activated Florisil 

to produce a free-flowing 

powder. Elution with ethyl 

acetate or methylene chloride. 

Various Homogenization of sample and 

produce extraction with acetonitrile, 

filtration, addition of salt and 

solvent evaporation. 

Redissolution of residue in 

acetone for analysis. 

Various Blending of sample with 

prepared acetone, filtration and transfer 

foods to Hydromatrix column. Elution 

with methylene chloride and 

concentration. 

Pasta, eggs Blending of samples with 

acetone and extraction with 

dichloromethane and acetone, 

water removal and volume 

reduction. Cleanup using 

carbon-celite (pasta) or C18 

SPE (eggs). 

Cow’s milk Extraction of milk 3 times with 

70% acetonitrile in water, 

filtration, removal of fat by zinc 

acetate addition, and 

partitioning with methylene 

chloride. Reduction of volume 

after drying. 

Cow’s milk Homogenization of milk, 

acetonitrile and ethanol 

followed by equilibration with a 

mixture of light petroleumacetonitrile-ethanol and 

separation of the upper phase 

and elution through a solid 

matrix cartridge. Concentration 

and drying of the eluates to a 

residue that is dissolved. 

HS-SPME 8.4 ppb in 75–88% Lambropoulou 

strawberries; and Albanis 

10.2 ppb in 2003 

cherries 

GC/NPD 4 ppb 91–103% at Kadenczki et 

0.05 mg/kg al. 1992 

GC/FPD or 100 ppb 96% Hsu et al. 

alkali FID (17% RSD) 1991 

GC/FPD No data 91% at Hopper 1988 

100 ppb 

GC/FPD ~1 ppb Pasta: 80% Leoni et al. 

at 30 ppb; 1992 

eggs: 93% 

at 13 ppb 

GC/FPD 10 ppb 89% Toyoda et al. 

(P-mode) (3.8% RSD) 1990 

at 100 ppb 

GC/FPD No data 84% at Di Muccio et 

(0.003 MDL) 0.42 μg/mL al. 1996 
DIAZINON 195 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Diazinon and Transformation 

Products in Environmental Samples 

Sample 

matrixa Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Lanolin Dissolution in hexane and 

extraction with acetonitrile. 

Addition of 5% NaCl in water to 

acetonitrile and back-extraction 

with hexane. Washing of 

hexane extract with water, 

volume reduction and 

fractionation using Florisil. 

GC/FPD 

(526 nm); 

GC/AED; 

GC/MS 

GC/FPD 

0.03 ppm; 

GC/AED 

0.6 ppm 

(phosphorus 

monitor); 

0.3 ppm 

(sulfur 

monitor); 

GC/MS 

0.6 ppm 

90% 

(6.4% RSD) 

at 1 ppm; 

95% 

(5.6% RSD) 

at 2 ppm 

Miyahara et al. 

1992 

a

Unless otherwise stated, diazinon was determined. 

AED = atomic emission detection; FPD = flame photometric detector; FPD = flame photometric detector; GC = gas 

chromatography; HPLC = high performance liquid chromatography; HS = head space, KCl = potassium chloride; 

K-D = Kuderna-Danish; LSE = liquid-solid extraction, MDL = method detection limit; MS = mass spectrometry; 

MTBE = methyl tert-butyl ether; NaCl = sodium chloride; NPD = nitrogen phosphorus detector; PUF = polyurethane 

foam; RSD = relative standard deviation; SFC = supercritical fluid chromatography; SIM = selected ion monitoring; 

SPE = solid phase extraction; SPME = solid-phase microextraction, TLC = thin layer chromatography; 

UV = ultraviolet absorbance detection 
DIAZINON 196 

7. ANALYTICAL METHODS 

conjunction with a MS detector, an NPD, or an FPD. Sample preparation methods vary depending on the 

sample matrix (EPA 1995a, 1995b; Mallet et al. 1990; OSHA 1986). The method of Williams et al. 

(1987) is applicable to both diazinon and diazoxon. The NIOSH method (NIOSH 1994) has been fully 

validated for use in occupational settings where regulatory exposure limits are of concern. 

Many methods were reported for the determination of diazinon in water. Sample preparation methods 

include either some form of liquid/liquid extraction or the use of SPE, usually C18-silica, for isolation of 

diazinon residues. Mallet et al. (1990) reported a method for environmental water based on HPLC/ultra 

violet (UV) absorbance detection with either direct injection of the water or of an aliquot of an extract. 

The LODs were as low as 0.5 μg/L with the extraction approach. Mattern et al. (1991) reported a LOD 

for diazinon in surface water of 0.0005 ppb using GC in conjunction with chemical ionization ion trap 

MS. Lopez-Avila et al. (1985) reported an isotope dilution GC/MS selected ion monitoring (SIM) 

method that is applicable to water or soil after solvent extraction. Recoveries were stated to be 89% at 

1 ppb in water and 103% at 20 ppb in soil. An LOD of 0.025 μg/kg was reported for diazinon in water 

with a recovery of 92% (2% RSD) by Seiber et al. (1990). SPE provides an easy method to isolate 

residues and can greatly reduce the amounts of solvent used in sample preparation. Driss et al. (1993) 

preconcentrated diazinon from drinking water onto C18-silica or polystyrene-divinylbenzene co-polymer 

with a subsequent backflush onto an HPLC column (UV detection). LODs as low as 30 μg/L were 

reported. Kwakman et al. (1992) preconcentrated diazinon from drinking and river water onto C18-SPE 

disks and eluted the adsorbed compounds directly into a GC pre-column. Detection was by NPD and 

excellent LODs (20 pg/L) and recoveries (>95% with <4% RSD at 200 pg/L) were reported. Although 

most of the SPE methods boasted good recoveries and LODs, one reference noted that the pesticide can 

associate with dissolved organic matter (primarily humic materials) resulting in poor retention by the SPE 

material (Johnson et al. 1991). This can reduce method recoveries. 

Diazinon can be measured in air after pre-concentration from air onto some adsorbent material with 

subsequent extraction. A method for diazinon in air has been reported that is based on the use of 

polyurethane foam (PUF) to adsorb the pesticide from the air as the air is pulled through the PUF (Hsu et 

al. 1988). The PUF is then Soxhlet-extracted and the extract volume reduced prior to capillary GC/MS 

analysis. An LOD of 55 ng/m3

 (5.5 m3 sample) and recovery of 73% were reported. Another study was 

described in which the diazinon levels in indoor air were monitored following periodic application of the 

pesticide for insect control (Williams et al. 1987). In this method, air is pulled through a commercially 

available adsorbent tube to concentrate diazinon. The tube is then extracted with acetone prior to 

GC/NPD analysis. No data were provided for the LOD, but recoveries in excess of 90% were reported at 
DIAZINON 197 

7. ANALYTICAL METHODS 

the 0.1 and 1 μg/m3 levels. This paper also indicated that diazinon can be converted to diazoxon by ozone 

and NOx in the air during the sampling process. 

SFE is also used in sample preparation methods. Supercritical trifluoromethane has been shown to extract 

diazinon from glass beads with a recovery of 86% (Hillmann and Bächmann 1995). Organophosphorus 

pesticides have also been recovered from Tenax-GC, an adsorbent used to collect diazinon during air 

sampling, and analyzed directly by GC (Raymer and Velez 1991). Supercritical fluid chromatography 

(SFC) has also been used for the determination of diazinon in water where 75 μL were injected (Zegers et 

al. 1994b). Using thermionic detection, the LOD was about 1 μg/L (1 ppb) with a reproducibility of 

better than 7% at the 5–15 μg/L level. The same authors also published an SFC-based method for 

cucumber, lettuce, and grapes (Zegers et al. 1994a) but did not specify the LOD and recovery. 

Three standardized methods were found in the Official Methods of Analysis of the Association of Official 

Analytical Chemists (AOAC 1990a, 1990b, 1990c). The first of these methods is based on the extraction 

of crops (kale, endive, carrots, lettuce, apples, potatoes, and strawberries) with ethyl acetate and isolation 

of the residue followed by a sweep codistillation cleanup prior to GC/thermionic detection (Method 

968.24). In the second method (Method 970.52), the sample is extracted with acetonitrile, and the residue 

is partitioned into petroleum ether followed by Florisil clean-up and GC/potassium chloride (KCl) 

thermionic detection. Chemical identifications are based on combinations of gas, thin-layer, and paper 

chromatography. The recovery for diazinon in this method is stated to be greater than 80%; no data on 

limits of detection were given. The third method utilizes the same extraction and clean-up techniques as 

the second and then GC/FPD for detection (Method 970.53). 

Several methods employ the homogenization of the plant material with aqueous acetonitrile (Hsu et al. 

1991; Liao et al. 1991) or other polar organic solvents such as acetone/methanol mixtures (Hong et al. 

1993). Phase separation is brought about with the addition of a salt. The acetonitrile approach is 

preferred by the California Department of Food and Agriculture because of the higher recoveries possible 

(see Table 7-2) (Lee et al. 1991). The advantage of acetonitrile is found in its ability to more readily 

solvate residues and in the ease with which the phase separation can be accomplished through the addition 

of salt (Lee et al. 1991). Reported LODs for diazinon were typically 10–50 ppb. One of the methods 

eliminated any clean-up steps after the initial extraction (Hsu et al. 1991) to provide a method with a 

faster turnaround time with some loss in sensitivity (LOD approximately 100 ppb) relative to the purified 

samples. 
DIAZINON 198 

7. ANALYTICAL METHODS 

Methods found for the determination of diazinon in animal products also used homogenization with a 

polar organic solvent as the first step in residue recovery. Toyoda et al. (1990) isolated diazinon from 

cow’s milk via partition into methylene chloride after extraction of the milk with 70% acetonitrile in 

water. Based on GC/FPD, an LOD of 10 ppb and a recovery of 89% (3.8% RSD) at 100 ppb were 

reported. Diazinon residues in eggs were studied (Leoni et al. 1992) after blending the eggs with acetone 

and partitioning into dichloromethane and acetone followed by C18-silica SPE. Based on GC/FPD 

analysis, an LOD of 1 ppb and a recovery of 93% at 13 ppb were reported. 

7.3 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 diazinon is available. Where adequate information is not 

available, ATSDR, in conjunction with 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 diazinon. 

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. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. 

Exposure. Section 3.8.1 reported on biomarkers used to identify or quantify exposure to diazinon. Some 

methods for the detection of the parent compound in biological samples were described above. The 

parent chemical is quickly metabolized so the determination of metabolites can also serve as biomarkers 

of exposure. The use of liquid chromatography (LC) coupled to hybrid quadruple time-of-flight (QTOF) 

MS has recently been reported for the elucidation and confirmation of diazinon metabolites in biological 

samples (Ibanez et al. 2006). The most specific biomarkers will be those metabolites related to 

2-isopropyl-6-methyl-4-pyrimidine (IMHP). Methods for the detection of this compound in human urine 

have been reported (Olsson et al. 2003; Yokley et al. 2000). Also a method for IMHP and its oxidized 
DIAZINON 199 

7. ANALYTICAL METHODS 

metabolite, 2-(1'-hydroxy-1'-methyl)-ethyl-6-methyl-4-hydroxypyrimidine, in dog urine has been 

described by Lawrence and Iverson (1975) with reported sensitivities in the sub-ppm range. Other 

metabolites most commonly detected are diethylphosphate (DEP) and diethylthiophosphate (DETP), 

although these compounds are not specific for diazinon as they also arise from other diethylphosphates 

and phosphorothioates (Drevenkar et al. 1993; Kudzin et al. 1991; Mount 1984; Reid and Watts 1981; 

Vasilic et al. 1993). Further studies designed to refine the identification of metabolites specific to 

diazinon and provide dosimetric data will be useful in the search for a more dependable biomarker of 

diazinon exposure. 

Effect. Biomarkers of effect include plasma cholinesterase (ChE) and erythrocyte (RBC) and brain 

acetylcholinesterase (AChE), enzymes inhibited by insecticidal organophosphorus compounds (see 

Chapter 3). Rapid, simple, and specific methods should be sought to make assays readily available to the 

clinician. Currently, no effect specific to diazinon exposure has been identified by any study. Future 

studies designed to provide such information would be useful in identifying exposure to diazinon. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Human exposure to diazinon occurs via inhalation of ambient air; ingestion of contaminated 

food and water; and dermal uptake through occupational and non-occupational contact with contaminated 

soils, surface water, and commercial preparations. Methods have been reported for the measurement of 

diazinon in various foods, soils, sludges, sediment, solid wastes, waste water, drinking water, and air. 

The methods of Hsu et al. (1988) (LOD of 55 ng/m3

) Burright (OSHA 1986) (LOD 3.0 μg/m3) are 

adequate for the determination of diazinon in air. If a 70-kg individual is assumed, method LODs of 

0.007 mg/L (7 ppb) and 0.007 mg/kg (7 ppb) in water and foods, respectively, are required for the method 

to be adequate at the oral intermediate MRL. All of the methods for detection of diazinon in water shown 

in Table 7-2 are adequate. With regard to foods, the methods of Kadenczki et al. (1992) and Leoni et al. 

(1992) for detection of diazinon are adequate. Methods for other non-fatty crops would need to be 

validated or developed if routine use were desired. Di Muccio et al. (1996) describe a quick and simple 

method for the determination of diazinon in cow’s milk; however, no data were provided given on LODs. 

Additional methods for detection of diazinon in fatty foods are needed to permit the evaluation of the 

residues in those fatty media. 

There are also methods for the analysis of diazinon degradation products in air, water, and soil. Ibanez et 

al. (2006) have reported a method for the elucidation and confirmation of degradation products in 

environmental samples. Williams et al. (1987) published a method for diazinon and its oxon (diazoxon) 
DIAZINON 200 

7. ANALYTICAL METHODS 

in air. Other methods have been reported for diazinon, its oxon, and hydrolysis products in water (Suffet 

et al. 1967), soils and water (Lichtenstein et al. 1968), and soil (Burkhard and Guth 1979). The 

hydrolysis product IMHP was studied along with diazoxon in submerged soil (Sethunathan and Yoshida 

1969). Suffet et al. (1967) demonstrated the ability of GC to separate diazinon, diazoxon, and IMHP. 

However, no validated methods for the determination of diazoxon or IMHP were found. Thus, additional 

methods are needed for the quantitative analysis of diazinon transformation products in environmental 

matrices. It will also be important to establish MRLs for the transformation products to put the analytical 

requirements into perspective. 

7.3.2 Ongoing Studies 

The following information was found as a result of a search of the Federal Research in Progress database 

(FEDRIP 2006). 

Researchers at the University of Puerto Rico, Clemson University, and the University of Tennessee are 

collaborating in a Multi-State Regional project funded by the U.S. Department of Agriculture to develop 

environmentally friendly procedures and methods for water sampling of crop management chemicals, 

including diazinon, which can be used in field situations. Procedures for solid-phase field extraction 

techniques of water, and stability during storage and shipment of the field water samples to analytical 

laboratories for testing is being investigated. The study began on October 1, 2003 and is projected to end 

September 30, 2008. Recent results are to be published in the Journal of Agriculture and Food Science. 
DIAZINON 201 

8. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding diazinon in air, water, and other 

media are summarized in Table 8-1. 

ATSDR has derived an intermediate-duration inhalation MRL of 0.01 mg/m3

 for diazinon based on a 

NOAEL of 1.57 mg/m3

 for inhibition of erythrocyte acetylcholinesterase (RBC AChE) in rabbits 

(Hartman 1990). The NOAEL of 1.57 mg/m3

 was adjusted from intermittent exposure (4 hours/day, 

5 days/week) to a continuous exposure scenario (duration-adjusted NOAEL = 0.28 mg/m3

). A 

NOAELHEC (human equivalent concentration) of 0.44 mg diazinon/m3

 was derived from the durationadjusted NOAEL using EPA (1994b) methodology (see Appendix A for details). The NOAELHEC of 

0.44 mg/m3 was divided by an uncertainty factor of 30 (3 for extrapolation from animals to humans using 

dosimetric adjustment and 10 for human variability). 

ATSDR has derived an acute-duration oral MRL of 0.006 mg/kg/day for diazinon based on a NOAEL of 

0.6 mg/kg/day and a LOAEL of 1.2 mg/kg/day for >20% RBC AChE inhibition in rats (Davies and Holub 

1980a). The NOAEL of 0.6 mg/kg/day was divided by an uncertainty factor of 100 (10 for extrapolation 

from animals to humans and 10 for human variability). 

ATSDR has derived an intermediate-duration oral MRL of 0.002 mg/kg/day for diazinon based on the 

results of benchmark dose (BMD) analysis of RBC AChE inhibition in female rats exposed to diazinon in 

the diet (Davies and Holub 1980a). The resulting BMDL20 of 0.2238 mg/kg/day was divided by an 

uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability). 

See Appendix A for details regarding BMD analysis. 

ATSDR has derived a chronic-duration oral MRL of 0.0007 mg/kg/day for diazinon based on a NOAEL 

of 0.065 mg/kg/day and a LOAEL of 5.5 mg/kg/day for >20% RBC AChE inhibition in male and female 

rats (Kirchner et al. 1991). The NOAEL of 0.065 mg/kg/day was divided by an uncertainty factor of 

100 (10 for extrapolation from animals to humans and 10 for human variability). 

EPA (IRIS 2008) does not list an oral reference dose (RfD) or an inhalation reference concentration (RfC) 

for diazinon. 
DIAZINON 202 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Diazinon 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC 

WHO 

Carcinogenicity classification 

Air quality guidelines 

Drinking water quality guidelines 

No data 

No data 

Excluded from guideline 

value derivationa 

IARC 2007 

WHO 2000 

WHO 2004 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH 

EPA 

TLV (8-hour TWA)b,c

AEGL 

 0.01 mg/m3

No data 

 ACGIH 2007 

EPA 2006a 

Hazardous air pollutant No data EPA 2006c 

42 USC 7412 

NIOSH REL (10-hour TWA)d

 IDLH 

 0.1 mg/m3

No data 

NIOSH 2005 

OSHA PEL (8-hour TWA) for general industry No data OSHA 2005 

29 CFR 1910.1000 

b. Water 

EPA Designated as hazardous substances 

in accordance with 

Yes EPA 2006b 

40 CFR 116.4 

Section 311(b)(2)(A) of the Clean 

Water Act 

Drinking water standards and health 

advisories 

EPA 2006k 

1-day health advisory for a 10-kg 

child 

0.02 mg/L 

10-day health advisory for a 10-kg 

child 

0.02 mg/L 

DWEL 

Lifetime 

National primary drinking water 

standards; monitoring requirements for 

unregulated contaminants 

Minimum reporting level 

Reportable quantities of hazardous 

substances designated pursuant to 

Section 311 of the Clean Water Act 

0.007 mg/L 

0.001 mg/L 

0.5 μg/L 

1 pound 

EPA 2006d 

40 CFR 141.40 

EPA 2006f 

40 CFR 117.3 

Water quality criteria for non-priority 

pollutants 

Freshwater 

EPA 2006e 

CMC and CCC 

Saltwater 

0.17 μg/L 
DIAZINON 203 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Diazinon 

Agency Description Information Reference 

CMC and CCC 0.82 μg/L 

NATIONAL (cont.) 

DOT Marine pollutant Yes DOT 2005 

49 CFR 172.101, 

Appendix B 

c. Food 

FDA Bottled drinking water No data FDA 2005a 

EPA Tolerances for residues (see Range: 0.1–40 ppm EPA 2006i 

40 CFR 180.153 for a complete listing 40 CFR 180.153 

of tolerances for residues on raw 

agricultural commodities) 

USDA Domestic quarantine notices; Fire ants and contain- USDA 2006 

authorized insecticide erized nonbearing blue- 7 CFR 301.81-10 

berries and fruit and nut 

plants 

d. Other 

 ACGIH Carcinogenicity classification A4e ACGIH 2007

Biological exposure indices (for acetylcholinesterase inhibiting pesticides) 

Cholinesterase activity in red blood 70% of individual’s 

cells (sampling time is discretionary) baseline 

EPA Carcinogenicity classification Group Ef

 EPA 2006k 

RfC No data IRIS 2008 

RfD No data 

Superfund, emergency planning, and 

community right-to-know 

Designated CERCLA hazardous Yes EPA 2006g 

substance 40 CFR 302.4 

Reportable quantity 1 pound 

Effective date of toxic chemical 01/01/95 EPA 2006h 

release reporting 40 CFR 372.65 
DIAZINON 204 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Diazinon 

Agency Description Information Reference 

NATIONAL (cont.)

NTP Carcinogenicity classification No data NTP 2004 

a

Excluded from guideline value derivation because it is unlikely to occur in drinking water. b

Inhalable fraction and vapor c

Skin notation: refers to the potential significant contribution to the overall exposure by the cutaneous route, including 

mucous membranes and the eyes, either by contact with vapors, liquids, or solids. d

Skin designation: indicates the potential for dermal absorption; skin exposure should be prevented as necessary 

through the use of good work practices, gloves, coveralls, goggles, and other appropriate equipment. e

A4: not classifiable as a human carcinogen f

Group E: evidence of noncarcinogenicity for humans 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Level; 

CCC = Criterion Continuous Concentration; CERCLA = Comprehensive Environmental Response, Compensation, 

and Liability Act; CFR = Code of Federal Regulations; CMC = Criteria Maximum Concentration; DOT = Department of 

Transportation; DWEL = drinking water equivalent level; EPA = Environmental Protection Agency; FDA = Food and 

Drug Administration; FR = Federal Register; IARC = International Agency for Research on Cancer; 

IDLH = immediately dangerous to life or health; IRIS = Integrated Risk Information System; NIOSH = National 

Institute for Occupational Safety and Health; NTP = National Toxicology Program; OSHA = Occupational Safety and 

Health Administration; PEL = permissible exposure limit; REL = recommended exposure limit; RfC = inhalation 

reference concentration; RfD = oral reference dose; TLV = threshold limit values; TWA = time-weighted average; 

USC = United States Code; USDA = United States Department of Agriculture; WHO = World Health Organization 
DIAZINON 205 

8. REGULATIONS AND ADVISORIES 

The International Agency for Research on Cancer (IARC) and the National Toxicology Program (NTP) 

have not classified diazinon for human carcinogenicity (IARC 2007; NTP 2004). The 2006 edition of the 

EPA Drinking Water Standards and Health Advisories includes a Group E (evidence of 

noncarcinogenicity for humans) designation for diazinon (EPA 2006k). The American Conference of 

Governmental Industrial Hygienists (ACGIH) has assigned diazinon to carcinogenicity category A4 (not 

classifiable as a human carcinogen) (ACGIH 2007). 

OSHA has not required employers of workers who are occupationally exposed to diazinon to institute 

engineering controls and work practices to reduce and maintain employee exposure at or below 

permissible exposure limits (PELs) (OSHA 2005). The American Conference of Governmental Industrial 

Hygienists (ACGIH) has recommended an 8-hour Threshold Limit Value-Time-Weighted Average (TLVTWA) of 0.01 mg/m3

 for diazinon (ACGIH 2007). NIOSH has recommended a 10-hour (TWA) 

Recommended Exposure Limit (REL) of 0.1 mg/m3

 for diazinon (NIOSH 2005). 

EPA regulates diazinon under the Clean Water Act (CWA) and the Clean Air Act (CAA) and has 

designated it as a hazardous substance and a hazardous air pollutant (HAP) (EPA 2006b, 2006c). 

Diazinon is on the list of chemicals appearing in “Toxic Chemicals Subject to Section 313 of the 

Emergency Planning and Community Right-to-Know Act of 1986" (EPA 2006h). Diazinon has been 

assigned a reportable quantity (RQ) limit of 1 pound (EPA 2006g). The RQ represents the amount of a 

designated hazardous substance which, when released to the environment, must be reported to the 

appropriate authority. 

EPA recommends a criterion continuous concentration (CCC) and a criteria maximum concentration 

(CMC) of 0.17 μg/L for fresh water and 0.82 μg/L for salt water (EPA 2006e). The CCC is an estimate of 

the highest concentration of diazinon in freshwater/saltwater to which aquatic organisms can be exposed 

indefinitely without resulting in an unacceptable effect; the CMC is the highest concentration in 

freshwater/saltwater to which aquatic organisms can be exposed for a brief period without resulting in an 

unacceptable effect. 

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), tolerances for residues on raw 

agricultural commodities for diazinon range from 0.1 to 40 ppm (EPA 2006i); see 40 CFR 180.153 for a 

complete listing of tolerances for residues and the corresponding raw agricultural commodities. 
DIAZINON 206 

8. REGULATIONS AND ADVISORIES 

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_______________________ 

DIAZINON 207 

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DIAZINON 237 

10. 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 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)—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—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—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 that 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. 

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. 
DIAZINON 238 

10. GLOSSARY 

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 of people that 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. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 
DIAZINON 239 

10. GLOSSARY 

Immunological Effects—Functional changes in the immune response. 

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. 

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 that 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 that 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. 

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. 
DIAZINON 240 

10. GLOSSARY 

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 (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that 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 OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

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—The dynamic behavior of a material in the body, used to predict 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—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, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that 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—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 
DIAZINON 241 

10. GLOSSARY 

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) concentration 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-adverse-effect 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 

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 causal 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. 
DIAZINON 242 

10. GLOSSARY 

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 group. 

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 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value-Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

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 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 

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 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
DIAZINON 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. 

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 
DIAZINON A-2 

APPENDIX A 

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 100-fold 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 and Environmental Medicine, 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 and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-32, Atlanta, Georgia 30333. 
DIAZINON A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Diazinon 

CAS Numbers: 333-41-5 

Date: June 2008 

Profile Status: Final Draft Post-Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 5 

Species: Rat 

Minimal Risk Level: 0.01 [ ] mg/kg/day [X] mg/m3 

Reference: Hartman HR. 1990. 21-Day repeated exposure inhalation toxicity in the rat. EPA guidelines 

no. 82-4. Laboratory study number 891205. Ciba-Geigy Corporation. Submitted to the U.S. 

Environmental Protection Agency. MRID41557402. 

Experimental design: Four groups of albino rats (10/sex) were exposed (nose only) to aerosols of 

diazinon (in ethanol) at concentrations of 0, 0.05, 0.46, 1.57, or 11.6 mg/m3

 for 6 hours/day, 5 days/week 

for 3 weeks. Particle size analysis was performed to ensure that the test aerosols were in the respirable 

range for the rat. Two control groups were used, one exposed to humidified filtered air only and the other 

to the carrier vehicle ethanol. The test substance was the liquid MG-8 formulation (88% diazinon). 

Exposure levels were monitored by gas chromatography. Clinical examinations included ophthalmology, 

body weight, food consumption, hematology, and blood chemistry (including plasma ChE and RBC 

AChE activity). At necropsy, organ weights and brain AChE activity were assessed and histopathological 

examinations were performed on nasal tissues and lungs from all groups and on the spleen, heart, liver, 

kidney, adrenal gland, and any tissue with gross lesions from the control and 11.6 mg/m3

 groups. 

Effect noted in study and corresponding doses: No deaths or changes in body weights or food 

consumption were observed. Piloerection was noted in most animals, particularly during the first week of 

exposure, the incidence gradually declining during weeks 2 and 3 of exposure. This sign was neither 

exposure- nor dose-related and no clinical signs of organophosphate toxicity were observed. No 

exposure-related ophthalmoscopic or histopathological lesions were found. There were no statistically 

significant exposure-related effects on hematological parameters, although minimally lower values for 

erythrocyte count, hemoglobin, and packed red cell volume were observed in female rats of the highest 

exposure level. A significantly higher lung-to-body weight ratio was observed in female rats of the 

0.46 and 1.57 mg/m3

 exposure levels, but not at the highest exposure level. The toxicological 

significance of this effect is uncertain because no histopathological evidence of exposure-related lung 

lesions was found. As shown in Table A-1, significant reductions in plasma ChE (marker for exposure) 

were seen in males at exposure levels ≥1.57 mg/m3

 and females at exposure levels ≥0.46 mg/m3. 

Organophosphate-induced plasma ChE inhibition is typically observed at exposure levels lower than 

those inducing measurable RBC or brain AChE inhibition. Plasma ChE inhibition is used as an indicator 

of exposure, but does not serve as a reliable indicator of a neurotoxic effect. Therefore, plasma ChE 

inhibition was not considered relevant to the selection of the critical effect for diazinon. However, 

inhibition of RBC AChE and brain AChE represents a relevant neurological effect. In the principal study 

(Hartman 1990), significant reductions in RBC AChE activity (surrogate marker for neural AChE 

activity) were seen in male rats at 11.6 mg/m3

 and in female rats at 1.57 and 11.6 mg/m3 (Table A-1). 

Treatment-related 20–59% RBC or brain AChE inhibition is considered to represent a less serious adverse 

effect in the absence of more clear indicators of neurotoxicity (Chou and Williams-Johnson 1998). The 

10% RBC AChE inhibition observed in the 1.57 mg/m3

 group of female rats is below the level of 

inhibition considered to represent an adverse effect. Therefore, the 1.57 mg/m3

 exposure level is a 
DIAZINON A-4 

APPENDIX A 

NOAEL and the highest exposure level (11.6 mg/m3) is the lowest-observed-adverse-effect level 

(LOAEL) for 36 and 39% RBC AChE inhibition in the male and female rats, respectively. There was no 

significant difference between brain AChE activity in any of the exposure groups of male rats and that of 

vehicle controls. All diazinon-exposed groups of female rats exhibited significantly decreased brain 

AChE activity, relative to vehicle controls. The report of significantly increased brain AChE inhibition in 

the female rats of all exposure levels is indicative of an inherent problem with the brain data set, perhaps 

related to tissue collection or quantitative analysis of enzymatic activity in the brain tissue of the female 

rats. Furthermore, results of repeated oral dosing (Singh 1988) indicate that the male and female rats are 

comparably sensitive to diazinon-induced effects on both RBC and brain AChE activity. Therefore, the 

report (Hartman 1990) of significant brain AChE inhibition in the female rats exposed to diazinon by 

inhalation at levels much lower than the LOAEL of 11.6 mg/m3

 for RBC AChE inhibition is questionable 

and a clear LOAEL for brain AChE inhibition cannot be determined. 

Table A-1. Relative Change (Percent of Control Values) in Cholinesterase 

Activities in Male and Female Rats Following Exposure to Aerosols of 

Diazinon for 90 Days

Plasma ChE RBC AChE Brain AChE 

Male rats

 0.05 mg/m3 +9%a +2% -1% 

 0.46 mg/m3

 -5% -5% +1% 

 1.57 mg/m3

 -14%b -6% -4%

 11.6 mg/m3

 -19%b -36%a -3% 

Female rats

 0.05 mg/m3

 -3% -1% -24%a

 0.46 mg/m3

 -20%b +6% -17%b

 1.57 mg/m3

 -27%a -10%b -20%b

 11.6 mg/m3

 -43%a -39%a -37%a 

a

statistically significantly different from control (p≤0.01) b

statistically significantly different from control (p≤0.05) 

AChE = acetylcholinesterase; ChE = cholinesterase; RBC = red blood cell 

Source: Hartman 1990

Dose and end point used for MRL derivation: A NOAEL of 1.57 mg/m3

; the LOAEL was 11.6 mg/m3 for 

36–39% RBC AChE inhibition in male and female rats of the principal study 

[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) 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Not applicable. 
DIAZINON A-5 

APPENDIX A 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

The NOAEL of 1.57 mg/m3

 was adjusted for intermittent exposure as follows: 

NOAELADJ = 1.57 mg diazinon/m3

 x 6 hours/24 hours x 5 days/7 days = 0.28 mg diazinon/m3 

A regional deposited dose ratio (RDDRER) of 1.558 for extrarespiratory effects was used to extrapolate 

from rats to humans. The RDDRER was calculated using EPA’s software (Version 2.3) (EPA 1994b) for 

calculating RDDRs and the parameters listed in Table A-2. 

Table A-2. Parametersa Used to Calculate the Regional Deposited Dose Ratio 

(RDDRER) for Diazinon-induced Extrarespiratory Effects Using EPA’s 

Software (Version 2.3) 

Biological parametersb Rat Human 

Surface area

 Extrathoracic 15 cm2 200 cm2

 Tracheobronchial 22.5 cm2

 3,200 cm2

 Pulmonary 0.34 m2

 54 m2 

Minute ventilation 147.24 mL 13.8 L 

Body weight 196 g 70 kg 

a

Mass Median Aerodynamic Diameter (MMAD) = 0.85 μm from lower limit of 0.8 μm and upper limit of 0.9 μm for the 

1.57 mg/m3

 exposure group of female rats reported by Hartman (1990); Geometric Standard Deviation 

(GSD) = 1.3 μm from lower limit of 1.2 μm and upper limit of 1.4 μm reported by Hartman (1990). b

Parameters are default values for rats and humans from the EPA software, except for the rat body weight which 

was the mean body weight for the 1.57 mg/m3

 exposure group of female rats. 

Source: Hartman 1990 

The human equivalent concentration was calculated using Equation 4-5 (EPA 1994b) as follows: 

NOAELHEC = NOAELADJ x RDDRER = 0.28 mg diazinon/m3

 x 1.558 = 0.44 mg diazinon/m3 

The NOAELHEC of 0.44 mg/m3

 was divided by an uncertainty factor of 30 (3 for extrapolation from 

animals to humans using dosimetric adjustment and 10 for human variability), resulting in an 

intermediate-duration inhalation MRL of 0.01 mg/m3

. 

Was a conversion used from intermittent to continuous exposure? Yes. 

Other additional studies or pertinent information that lend support to this MRL: This is the only available 

well-conducted, intermediate-duration inhalation study for diazinon. In an acute-duration study in which 

rats were exposed to 2,300 mg/m3

 diazinon for 4 hours (Holbert 1989), mild signs of organophosphate 

toxicity were noted (nasal discharge, salivation). 

Agency Contacts (Chemical Managers): G. Daniel Todd, Ph.D.; Carolyn Harper, Ph.D.; 

Paula Burgess, M.D. 
DIAZINON A-6 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Diazinon 

CAS Numbers: 333-41-5 

Date: June 2008 

Profile Status: Final Draft Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 23 

Species: Rat 

Minimal Risk Level: 0.006 [X] mg/kg/day [ ] mg/m3 

Reference: Davies DB, Holub BJ. 1980a. Toxicological evaluation of dietary diazinon in the rat. Arch 

Environ Contam Toxicol 9(6):637-650. 

Experimental design: Groups of female Wistar rats (50/group) were exposed to diazinon (99.2% purity) 

in the diet at concentrations of 0, 5, 10, or 15 ppm for 92 days. Interim assessments of neurological end 

points included treatment day 12 assessment, which represents acute-duration oral exposure. Blood 

samples were collected on treatment days 3, 8, and 12 from 10 rats/group for assessment of plasma ChE 

and RBC AChE activity. Other groups of similarly-treated rats were sacrificed (n=6) for assessment of 

brain AChE activity. All rats were assessed daily for clinical signs of neurotoxicity and body weights and 

food intake were monitored throughout the treatment period. The study authors reported starting mean 

body weight (0.139 kg), mean body weight gain (0.00163 kg/day), and mean food consumption 

(0.0178 kg/day) for all rats, and indicated that they did not significantly differ among treatment groups. 

Using the average body weight gain for 12 days (0.00163 kg/day x 12 days=0.02 kg), the average body 

weight for the 12-day period was equal to the starting body weight (0.139 kg) plus one-half the body 

weight gain during the 12-day period (0.5x0.02 kg)=0.149 kg. The diazinon dose equals the product of 

the diazinon concentration in food times the mean daily food consumption divided by the average body 

weight. Calculated in this manner, the doses to the 5-, 10-, and 15-ppm exposure groups were 0.6, 1.2, 

and 1.8 mg/kg/day, respectively. 

Effect noted in study and corresponding doses: No clinical signs of toxicity were observed in any of the 

treated groups. Compared to controls, significant plasma ChE inhibition was observed in all diazinontreated groups at all timepoints (including treatment days 3, 8, and 12). At treatment day 12, treatmentrelated effects included 43, 70, and 73% plasma ChE inhibition and 5, 22, and 33% RBC AChE inhibition 

in the 0.6, 1.2, and 1.8 mg/kg/day dose groups, respectively. There was no significant effect on brain 

AChE activity. Plasma ChE inhibition is used as an indicator of exposure, but does not serve as a reliable 

indicator of a neurotoxic effect. Therefore, plasma ChE inhibition was not considered relevant to the 

selection of the critical effect for diazinon. However, inhibition of RBC AChE and brain AChE 

represents a relevant neurological effect. Treatment-related 20–59% RBC or brain AChE inhibition is 

considered to represent a less serious adverse effect in the absence of more clear indicators of 

neurotoxicity. The principal study (Davies and Holub 1980a) identified a NOAEL of 0.6 mg/kg/day and 

a LOAEL of 1.2 mg/kg/day for 22% RBC AChE inhibition at interim day 12 assessment of female rats 

administered diazinon in the diet for 92 days. 

Dose and end point used for MRL derivation: A NOAEL of 0.6 mg/kg/day; the LOAEL was 

1.2 mg/kg/day for 22% RBC AChE inhibition 

[X] NOAEL [ ] LOAEL 
DIAZINON A-7 

APPENDIX A 

Uncertainty Factors used in MRL derivation: 

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)

[ ] 1 [ ] 3 [X] 10 (for extrapolation from animals to humans) 

[ ] 1 [ ] 3 [X] 10 (for human variability) 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Doses were 

calculated from reported mean values for initial body weight, food consumption, and body weight gain 

for the first 12 days of treatment. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: In an unpublished study 

(EPA 1996), male and female rats were administered diazinon in the diet for 28 days and assessed for 

cholinesterase inhibition at weeks 1, 2, and 4. A dose of 2.4 mg/kg/day resulted in 38–59% RBC AChE 

inhibition in both males and females, which was observed as early as week 1 and peaked at week 2. The 

next lower dose (0.02 mg/kg/day) represented a NOAEL. The principal study for deriving the acuteduration oral MRL for diazinon (Davies and Holub 1980a) was performed using only female rats. 

However, Davies and Holub (1980a) noted that dietary studies in their laboratory had demonstrated that 

female rats were more sensitive than male rats to diazinon induced plasma ChE and RBC and brain AChE 

inhibition. In light of this finding, the selection of RBC AChE inhibition in the female rats as the critical 

effect from the principal study that assessed the critical effect only in female rats (Davies and Holub 

1980a) is appropriate. 

Agency Contacts (Chemical Managers): G. Daniel Todd, Ph.D.; Carolyn Harper, Ph.D.; 

Paula Burgess, M.D. 
DIAZINON A-8 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical name: Diazinon 

CAS number(s): 333-41-5 

Date: June 2008 

Profile Status: Final Draft Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Key to figure: 63 

Species: Rat 

Minimal Risk Level: 0.002 [X] mg/kg/day [ ] ppm [ ] mg/m3 

Reference: Davies DB, Holub BJ. 1980a. Toxicological evaluation of dietary diazinon in the rat. Arch 

Environ Contam Toxicol 9(6):637-650. 

Note: Available intermediate-duration oral (dietary) toxicity studies of diazinon include 10 studies in rats 

and 2 studies in dogs (see Table A-4, page A-14, for a summary of NOAELs and LOAELs for RBC and 

brain AChE inhibition identified in these studies). Although dose spacing is variable, and in some studies 

may be in excess of 100-fold for levels at or below identified LOAELs for AChE inhibition, these studies 

collectively indicate that the threshold for less serious AChE inhibition occurs in rats and dogs at repeated 

oral dose levels between 0.2 and 2 mg/kg/day. The report of Davies and Holub (1980a) includes results 

from separate 35-, 42-, and 92-day studies. 

Experimental design: In the principal study, groups of female Wistar rats (16/group) were exposed to 

diazinon (99.2% purity) in the diet at concentrations of 0, 1, 2, 3, or 4 ppm for 42 days (Davies and Holub 

1980a). Blood samples were collected periodically from 10 rats/group for assessment of plasma ChE and 

RBC AChE activity. Six rats per group were sacrificed on day 35 for assessment of brain AChE activity. 

All rats were assessed daily for clinical signs of neurotoxicity and body weights and food intake were 

monitored throughout the treatment period. The study authors stated that female rats were used in the 

study because they were noted to be more sensitive than male rats to the neurotoxic effects of diazinon. 

The study authors reported starting mean body weight (0.149 kg), mean body weight gain 

(0.00259 kg/day), and mean food consumption (0.0178 kg/day) for all rats, and indicated that they did not 

significantly differ among treatment groups. Using the average body weight gain for 42 days 

(0.00259 kg/day x 42 days=0.11 kg), the average body weight for the 42-day period was equal to the 

starting body weight (0.149 kg) plus one-half the body weight gain during the 42-day period 

(0.5x0.11 kg)=0.2 kg. The diazinon dose equals the product of the diazinon concentration in food times 

the mean daily food consumption divided by the average body weight. Calculated in this manner, the 

doses to the 1-, 2-, 3-, and 4-ppm exposure groups were 0.09, 0.18, 0.27, and 0.36 mg/kg/day. 

Effects noted in study and corresponding doses: No clinical signs of toxicity were observed in any of the 

treated groups (Davies and Holub 1980a). Significant plasma ChE inhibition was observed at most 

timepoints in all diazinon-treated groups, relative to controls. The magnitude of inhibition in all treatment 

groups increased with time and appeared to peak around day 35, remaining near the peak level for the 

remaining 7 treatment days. Maximum plasma ChE inhibition in the 1, 2, 3, and 4 ppm treatment groups 

was approximately 35, 50, 55, and >60%, respectively. Plasma ChE inhibition is used as an indicator of 

exposure, but does not serve as a reliable indicator of a neurotoxic effect. Therefore, plasma ChE 

inhibition was not considered relevant to the selection of the critical effect for diazinon. Through 

treatment day 35, there was no significant treatment-related effect on RBC AChE activity in any of the 

treatment groups. However, on treatment day 42, significant RBC AChE inhibition was observed at 
DIAZINON A-9 

APPENDIX A 

treatment levels of 2, 3, and 4 ppm (magnitude 9, 20, and 22%, respectively). There were no indications 

of treatment-related significant brain AChE inhibition at any timepoint during the 42 days of treatment. 

The results of RBC AChE activity in the female rats of the principal study (Davies and Holub 1980a) are 

presented in Table A-3. Inhibition of RBC AChE and brain AChE represents a relevant neurological 

effect. Treatment-related 20–59% RBC or brain AChE inhibition is considered to represent a less serious 

adverse effect in the absence of more clear indicators of neurotoxicity. The principal study (Davies and 

Holub 1980a) identified a NOAEL of 0.18 mg/kg/day and a LOAEL of 0.27 mg/kg/day for 20% RBC 

AChE inhibition in female rats administered diazinon in the diet for 42 days. 

Table A-3. RBC AChE Data From Female Rats Exposed to Diazinon in the Diet 

for 42 Days 

Dose group Number of RBC AChE activity (μmole/mL Percent RBC AChE 

(mg/kg/day) rats packed cells/minute) inhibition 

0 10 0.74±0.05a 

0.09 10 0.68±0.07 8 

0.18 10 0.67±0.06 9 

0.27 10 0.59±0.04 20 

0.36 10 0.58±0.02 22 

a

Mean±standard error 

AChE = acetylcholinesterase; RBC = red blood cell 

Source: Davies and Holub 1980a 

The linear model in the EPA Benchmark Dose Software (Version 1.3.2) was fit to the female rat data for 

RBC AChE activity shown in Table A-3. A benchmark response (BMR) of 20% below the control mean 

RBC AChE activity was selected because treatment-related 20–59% RBC or brain AChE inhibition is 

considered to represent a less serious adverse effect in the absence of more clear indicators of 

neurotoxicity (Chou and Williams-Johnson 1998). Although the linear model provided adequate fit to the 

data from Table A-3, as indicated by acceptable p values for tests for (1) differences in response and/or 

variances among dose levels, (2) homogeneous or non-homogeneous variance, and (3) model mean fit, a 

non-homogeneous variance model run was suggested. Adequate fit was also provided by the linear model 

using non-homogeneous variance, which resulted in a BMD20 of 0.3267 mg/kg/day and a BMDL20 of 

0.2238 mg/kg/day. Because the simplest model, the linear model, provided adequate fit to the RBC 

AChE data from the 42-day rat study of Davies and Holub (1980a), the application of more complex 

continuous variable models was not considered necessary. The BMDL20 of 0.2238 mg/kg/day served as 

the point of departure for deriving an intermediate-duration oral MRL for diazinon. 

Figure A-1 is a plot of predicted and observed levels of RBC AChE activity in the female dogs of the 

principal study (Davies and Holub 1980a) generated from the linear model using non-homogeneous 

variance. 
DIAZINON A-10 

APPENDIX A 

Figure A-1. Predicted and Observed Levels of RBC AChE Activity in Female Dogs 

Orally Exposed to Diazinon for 42 Days* 

Linear Model with 0.95 Confidence Level 

Mean Response 

0.85 

0.8 

0.75 

0.7 

0.65 

0.6 

0.55 

0.5 

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 

BMDL BMD 

Linear 

dose 

09:44 08/08 2006 

*BMD and BMDL (in mg/kg/day) are associated with a benchmark response of 20% reduction in RBC AChE activity 

from the control value 

The linear model form and parameters output from benchmark dose analysis of RBC AChE activity in the 

female rats of the principal study (Davies and Holub 1980a) follows: 

The form of the response function is: 

Y[dose] = beta_0 + beta_1*dose + beta_2*dose^2 + ... 

Dependent variable = MEAN 

Independent variable = dose 

Signs of the polynomial coefficients are not restricted 

The variance is to be modeled as Var(i) = alpha*mean(i)^rho 

Total number of dose groups = 5 

Total number of records with missing values = 0 

Maximum number of iterations = 250 

Relative Function Convergence has been set to: 1e-008 
DIAZINON A-11 

APPENDIX A 

Parameter Convergence has been set to: 1e-008 

Default Initial Parameter Values 

alpha = 0.02612 

rho = 0 

beta_0 = 0.734 

beta_1 = -0.455556 

Parameter Estimates 95.0% Wald ConfidenceInterval 

Variable Estimate Std. Err. Lower Conf. Limit 

alpha 0.729698 0.927763 -1.08868 

rho 8.31 2.91288 2.60086 

beta_0 0.73306 0.0466142 0.641698 

beta_1 -0.448823 0.162678 -0.767667 

Asymptotic Correlation Matrix of Parameter Estimates 

alpha rho beta_0 beta_1 

alpha 1 0.99 -0.049 0.064 

rho 0.99 1 -0.053 0.068 

beta_0 -0.049 -0.053 1 -0.93 

beta_1 0.064 0.068 -0.93 1 

Table of Data and Estimated Values of Interest 

Upper Conf. Limit 

2.54808 

14.0191 

0.824422 

-0.129979 

Chi^2 Res. 

0.0934 

-0.216 

0.387 

-0.623 

0.322 

Dose N Obs Mean Obs Std Dev Est Mean Est Std Dev 

0 10 0.74 0.16 0.733 0.235 

0.09 10 0.68 0.22 0.693 0.186 

0.18 10 0.67 0.19 0.652 0.145 

0.27 10 0.59 0.13 0.612 0.111 

0.36 10 0.58 0.06 0.571 0.0835 

Model Descriptions for likelihoods calculated 

Model A1: Yij = Mu(i) + e(ij) 

Var{e(ij)} = Sigma^2 

Model A2: Yij = Mu(i) + e(ij) 

Var{e(ij)} = Sigma(i)^2 

Model A3: Yij = Mu(i) + e(ij) 
DIAZINON A-12 

APPENDIX A 

Var{e(ij)} = alpha*(Mu(i))^rho 

Model R: Yi = Mu + e(i) 

Var{e(i)} = Sigma^2 

Likelihoods of Interest 

Model Log(likelihood) DF AIC 

A1 68.760362 6 -125.520725 

A2 76.244732 10 -132.489465 

A3 74.537476 7 -135.074952 

fitted 72.450460 4 -136.900920 

R 64.715236 2 -125.430471 

Explanation of Tests 

Test 1: Does response and/or variances differ among Dose levels? (A2 vs. R) 

Test 2: Are Variances Homogeneous? (A1 vs A2) 

Test 3: Are variances adequately modeled? (A2 vs. A3) 

Test 4: Does the Model for the Mean Fit? (A3 vs. fitted) 

Tests of Interest 

Test -2*log(Likelihood Ratio) Test df p-value 

Test 1 23.059 8 0.003289 

Test 2 14.9687 4 0.004766 

Test 3 3.41451 3 0.332 

Test 4 4.17403 3 0.2433 

The p-value for Test 1 is less than .05. There appears to be a difference between 

response and/or variances among the dose levels. It seems appropriate to model the 

data 

The p-value for Test 2 is less than .05. A non-homogeneous variance model appears to 

be appropriate 

The p-value for Test 3 is greater than .05. The modeled variance appears to be 

appropriate here 

The p-value for Test 4 is greater than .05. The model chosen seems to adequately 

describe the data 
DIAZINON A-13 

APPENDIX A 

Benchmark Dose Computation 

Specified effect = 0.2 

Risk Type = Relative risk 

Confidence level = 0.95 

BMD = 0.326659 

BMDL = 0.2238 

The BMDL20 of 0.2238 mg/kg/day was divided by a total uncertainty factor (UF) of 100 (10 for 

extrapolation from animals to humans and 10 for human variability) as follows: 

Intermediate-duration oral MRL = BMDL20 ÷ UF = 0.2238 mg/kg/day ÷ 100 = 0.002 mg/kg/day 

Dose end point used for MRL derivation: BMDL20 of 0.2238 mg/kg/day for RBC AChE activity 

[ ] NOAEL [ ] LOAEL [X] Benchmark 

Uncertainty factors used in MRL derivation: 

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)

[ ] 1 [ ] 3 [X] 10 (for extrapolation from animals to humans) 

[ ] 1 [ ] 3 [X] 10 (for human variability) 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Doses were 

calculated from reported mean values for initial body weight, food consumption, and body weight gain 

for the 42-day treatment period. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: The selection of the 

BMD20 of 0.3267 mg/kg/day and its lower 95% confidence limit (BMDL20) of 0.2238 mg/kg/day from the 

female rats of the principal study (Davies and Holub 1980a) as a point of departure for deriving an 

intermediate-duration oral MRL for diazinon is supported by the results of several studies (see 

Table A-4). These studies collectively indicate that the threshold for less serious AChE inhibition occurs 

in rats and dogs at repeated oral dose levels between 0.2 and 2 mg/kg/day. The derived intermediateduration oral MRL of 0.002 mg/kg/day is supported by the free-standing NOAEL of 0.03 mg/kg/day 

identified in four male volunteers administered diazinon in gelatin capsules at a dose level of 

0.03 mg/kg/day for 28–31 days. 
DIAZINON A-14 

APPENDIX A 

Table A-4. NOAELs and LOAELs for RBC and Brain AChE Inhibition Following 

Intermediate-duration Dietary Exposure to Diazinon 

Study type NOAEL LOAEL (mg/kg/day) 

estimated doses (mg/kg/day) (mg/kg/day) AChE inhibition Reference 

28-Day rat study 0.02 (M, F) 2.4; M, F: 38–59% RBC EPA 1996 

M, F: 0, 0.02, 2.4, 23, 213 

30-Day rat study ND 2.86; 58% RBC Davies and 

F: 0, 2.86 Holub 1980b 

35-Day rat study 0.2 ND Davies and 

F: 0, 0.009, 0.05, 0.09, 0.2 Holub 1980a 

42-Day rat study 0.2 0.3; 20% RBC Davies and 

F: 0, 0.09, 0.18, 0.27, 0.36 Holub 1980a 

6-Week rat study 0.2 (M, F) 2.0; M, F: 46–61% RBC EPA 2000a 

0, 0.02, 0.05, 0.2, 2, 9.5, 28 

6-Week rat study EPA 2000a 

M: 0, 0.02, 0.04, 0.17, 1.68, 8.6, 0.17 (M) 1.68; M: 29–35% RBC 

25.8 

F: 0, 0.02, 0.05, 0.19, 1.82, 9.27, 29 0.19 (F) 1.82; F: 16–35% RBC 

6-Week rat study 0.2 (M, F) 8.4; M: 21% RBC Singh 1988 

M: 0, 0.04, 0.2, 8.4, 165 

F: 0, 0.05, 0.2, 9.4, 198 9.4; F: 21% RBC and 24% brain 

90-Day rat study Singh 1988 

M: 0, 0.03, 0.3, 15, 168 0.3 (M) 15; M: 27% RBC 

F: 0, 0.04, 0.4, 19, 212 0.4 (F) 19; F: 41% RBC 

90-Day rat study 0.018 (M, F) 1.8; M, F: 37–75% RBC EPA 1996 

0, 0.018, 1.8, 18, 180 

92-Day rat study 0.4 0.7; 40% RBC Davies and 

F: 0, 0.4, 0.7, 1 Holub 1980a 

4-Week dog study Barnes 1988 

M: 0, 0.02, 0.073, 0.8, 14.68 0.8 (M) 14.68; M: 25% RBC; 31% brain 

F: 0, 0.023, 0.082, 0.75, 15.99 0.75 (F) 5.6; F: 31% RBC; 30% brain 

13-Week dog study 0.02 (M, F) Barnes 1988 

M: 0, 0.0034, 0.02, 5.9, 10.9 5.9; M: 26% RBC; 31% brain 

F: 0, 0.0037, 0.02, 5.6, 11.6 5.6; F: 31% RBC ; 30% brain 

AChE = acetylcholinesterase; F = female; LOAEL = lowest-observed-adverse-effect level; M = male; ND = not 

determined; NOAEL = no-observed-adverse-effect level; RBC = red blood cell 

Agency Contacts (Chemical Managers): G. Daniel Todd, Ph.D.; Carolyn Harper, Ph.D.; 

Paula Burgess, M.D. 
DIAZINON A-15 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Diazinon 

CAS Numbers: 333-41-5 

Date: June 2008 

Profile Status: Final Draft Post-Public Comment 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 91 

Species: Rat 

Minimal Risk Level: 0.0007 [X] mg/kg/day [ ] mg/m3 

Reference: Kirchner FR, McCormick GC, Arthur AT. 1991. One/two year oral toxicity study in rats. 

Ciba-Geigy Corporation. Submitted to the U.S. Environmental Protection Agency. MRID41942002. 

Experimental design: (human study details or strain, number of animals per exposure/control group, sex, 

dose administration details): Diazinon MG-8 (purity 87.7%) was dissolved in acetone vehicle and added 

to the diet of male and female Sprague-Dawley rats at concentrations of 0, 0.1, 1.5, 125, or 250 ppm for 

up to 98 weeks. The study included both untreated and vehicle control groups. According to the study 

report, the corresponding doses were 0, 0.004, 0.06, 5, and 10 mg/kg/day for males and 0, 0.005, 0.07, 6, 

and 12 mg/kg/day for females). Averaged among male and female rats, the corresponding doses were 0, 

0.0045, 0.065, 5.5, and 11 mg/kg/day. Twenty rats/sex/group were treated for the full 98 weeks. Ten 

rats/sex/group were treated for 52 weeks and sacrificed for interim assessment. Additional groups of 

10 rats/sex were assigned to the untreated control, vehicle control, and 250 ppm groups and assessed for 

recovery 45 days following 52 weeks of treatment. Animals were observed daily for clinical signs of 

toxicity. Food consumption, water intake, and body weights were monitored. Ophthalmoscopic 

examinations were performed during weeks 2, 51, and 97 or 98. Blood was collected at several 

timepoints between days 88 and 684. Ten animals/sex/group from the 98-week treatment groups received 

clinical chemistry evaluation at treatment days 88, 181, 356, 390, 552, and 684. Urinalysis was 

performed on all surviving rats of the 98-week treatment groups at treatment days 81, 189, 350, 545, and 

679. All rats were subjected to comprehensive gross and microscopic pathologic examination at death or 

sacrifice. 

Effect noted in study and corresponding doses: There were no apparent treatment-related effects on 

survival, food or water consumption, body weights, or hematological or urinalysis parameters examined. 

Due to mortality in all groups including controls the study was terminated at 97 weeks. Ophthalmoscopic 

and gross and microscopic examinations did not reveal evidence of dose-related effects. The major 

findings of this study were those of dose-related decreased plasma ChE and RBC and brain AChE activity 

in both male and female rats. Significantly decreased plasma ChE activity (28–51% lower than controls) 

was noted in 0.065 mg/kg/day male rats at treatment days 88 and 684, but not at treatment days 181, 356, 

or 552 and in 0.065 mg/kg/day female rats (approximately 50% lower than controls) at most timepoints. 

High-dose male and female rats consistently exhibited significantly decreased plasma ChE activity, 

ranging from 80 to 97% lower than controls. In 0.065 mg/kg/day groups, RBC and brain AChE activity 

was not significantly decreased at any timepoint. The 5.5 mg/kg/day groups exhibited significantly 

decreased RBC AChE activity at all timepoints, ranging in magnitude from 15 to 28% and from 22 to 

25% in males and females, respectively. At the 5.5 and 11 mg/kg/day levels, the magnitude of the effect 

did not appear to increase with either duration of treatment or increased dose. Following 52 weeks of 

treatment and 45 days of recovery, RBC AChE activity had returned to control levels in high-dose male 

rats and to within 7% of control levels in high-dose female rats. Brain AChE activity was significantly 

decreased in 5.5 and 11 mg/kg/day male and female rats. In 5.5 and 11 mg/kg/day males, the magnitude 
DIAZINON A-16 

APPENDIX A 

of the effect was effect was 24 and 42%, respectively, after 684 days of treatment, but not significantly 

different from controls at 370 days. In 5.5 and 11 mg/kg/day female rats, the effect was noted at both 

370- and 684-day timepoints; the magnitude of the effect was >24% at 5.5 mg/kg/day and >40% at 

11 mg/kg/day. This study identified a NOAEL of 0.065 mg/kg/day (1.5 ppm of diazinon in the diet) and 

a LOAEL of 5.5 mg/kg/day (125 ppm of diazinon in the diet) for 22–28% decreased RBC AChE activity 

in male and female rats administered diazinon in the diet for up to 97 weeks, which is considered the 

critical effect. The effect was observed as early as day 88 of treatment and did not appear to increase in 

magnitude with duration of treatment. 

Dose and end point used for MRL derivation: A NOAEL of 0.065 mg/kg/day; the LOAEL was 

5.5 mg/kg/day for 22–28% decreased RBC AChE activity 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)

[ ] 1 [ ] 3 [X] 10 (for extrapolation from animals to humans) 

[ ] 1 [ ] 3 [X] 10 (for human variability) 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Estimated doses 

were included in the original study. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: Groups of 5-month-old 

male and female Beagle dogs (4/sex/group) were administered diazinon MG-8 (87.7% purity) in the diet 

for 52 weeks at concentrations of 0, 0.1, 0.5, 150, or 300 ppm (Rudzki et al. 1991). The highest dose 

level was reduced to 225 ppm after 14 weeks due to the lack of body weight gain at the 300 ppm level. 

According to the study authors, the corresponding diazinon doses (adjusted for purity) were 0, 0.0032, 

0.015, 4.7, and 7.7 mg/kg/day for the males and 0, 0.0037, 0.02, 4.5, and 9.1 mg/kg/day for the females. 

Averaged among male and female dogs, the corresponding doses were 0, 0.0034, 0.017, 4.6, and 

7.9 mg/kg/day. Animals were observed daily for clinical signs of toxicity. Food consumption and body 

weights were monitored throughout the study. Physical, auditory, and ophthalmoscopic examinations 

were periodically performed. Blood and urine were collected 4 weeks prior to dosing and during 

treatment weeks 13, 26, 39, and 52 for hematological and clinical chemistry assessment and urinalysis. 

At death or scheduled sacrifice, organ weights were recorded and all animals were subjected to 

histological examination of all major organs and tissues. One high-dose male was sacrificed on test day 2 

and one female in the 0.5 ppm group was found dead on test day 12. Both deaths were attributed to 

gastrointestinal infections and the animals were replaced. Clinical signs of toxicity were limited to a 

single high-dose male that exhibited signs of dehydration and emaciation. Although food consumption in 

all treatment groups of male and female dogs was lower than that of controls at most timepoints during 

the 52 weeks of treatment, there was no clear pattern of dose-related decreased food consumption. The 

4.6 mg/kg/day dose level may represent a LOAEL for body weight gain in the males, but a clear effect 

level for body weight gain was not identified in females. Plasma ChE inhibition generally exceeded 20% 

in all dose groups of males and females, with the exception of the 0.0034 mg/kg/day groups. Significant 

RBC AChE inhibition (magnitude ranging from approximately 21 to 35%) was noted in treated males and 

females of the two highest exposure groups (4.6 and 7.9 mg/kg/day), but not at lower exposure levels. 
DIAZINON A-17 

APPENDIX A 

Significant brain AChE inhibition was noted at 4.6 and 7.9 mg/kg/day in females (magnitude 25.5 and 

34.7%, respectively). High-dose males exhibited 24.8% brain AChE inhibition (not statistically 

significant). Although serum amylase activity was generally increased in diazinon-treated male and 

female dogs at most timepoints, the only statistically significant increase occurred in 4.6 mg/kg/day males 

only at week 52. There were no other treatment-related effects on clinical chemistry parameters 

examined. Ophthalmoscopic examinations, hematology, and urinalysis did not reveal evidence of 

treatment-related effects. There were no apparent treatment-related effects on organ weights and 

extensive gross and microscopic examinations were unremarkable. This study identified a NOAEL of 

0.5 ppm (0.017 mg/kg/day) and a LOAEL of 150 ppm (4.6 mg/kg/day) for RBC AChE inhibition of 20% 

or more in both male and female dogs. 

Agency Contacts (Chemical Managers): G. Daniel Todd, Ph.D.; Carolyn Harper, Ph.D.; 

Paula Burgess, M.D. 
DIAZINON A-18 

APPENDIX A 

This page is intentionally blank. 
DIAZINON 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 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-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 chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and 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 chapter. 

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 Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived 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. 
DIAZINON B-2 

APPENDIX B 

MRLs 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, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "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 that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point 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 end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect 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 levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures 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, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound 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 NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 
DIAZINON B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(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. Typically 

when sufficient data exist, 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 Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(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 two "18r" data points in sample Figure 3-1). 

(5) Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "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 

regimens 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 “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 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, one systemic effect (respiratory) was 

investigated. 

(8) NOAEL. A 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"). 
DIAZINON B-4 

APPENDIX B 

(9) LOAEL. A 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 end point 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 9 of the profile. 

(11) CEL. A 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 that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

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 acute and intermediate 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, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. 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 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
DIAZINON B-5 

APPENDIX B 

(18) Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound 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 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

Key to figurea 

Exposure frequency/ 

Species duration System 

NOAEL (ppm) 

LOAEL (effect) 

Less serious (ppm) 

Serious (ppm) 

Re

2 → INTERMEDIATE EXPOSURE 3 4 

5 6 7 8 9 10

→ Systemic ↓ ↓ ↓ ↓ ↓ ↓→

13 wk 5 d/wk 6 hr/d 

18 RatCHRONIC EXPOSURE 

Resp 3b 10 (hyperplasia) 

Nit

Cancer 

↓

38 39 40 

Rat Rat Mouse 

18 mo 5 d/wk 7 hr/d 89–104 wk 5 d/wk 6 hr/d 79–103 wk 5 d/wk 6 hr/d 

20 10 10 

(CEL, multiple organs) (CEL, lung tumors, nasal tumors) (CEL, lung tumors, hemangiosarcomas) 

WNTNT

11 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

DIAZINON B-8 

APPENDIX B 

This page is intentionally blank. 
DIAZINON C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

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 

BMD benchmark dose 

BMR benchmark response 

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 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

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/Intergovernmental Maritime Dangerous Goods Code 
DIAZINON C-2 

APPENDIX C 

DWEL drinking water exposure level 

ECD electron capture detection 

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 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

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 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 
DIAZINON C-3 

APPENDIX C 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

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 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

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 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

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 
DIAZINON C-4 

APPENDIX C 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized 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 carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
DIAZINON C-5 

APPENDIX C 

> greater than ≥ greater than or equal to 

= equal to 

< less than ≤ less than or equal to 

% percent α alpha β beta γ gamma δ delta μm micrometer μg microgram

* 

q1 cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 
DIAZINON C-6 

APPENDIX C 

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DIAZINON D-1 

APPENDIX D. INDEX 

2-isopropyl-4-methyl-6-hydroxypyrimidine (see IMHP) .........................................................................100

absorbed dose.................................................................................................................................... 115, 120 

acetylcholine ............................................................................................................. 10, 31, 38, 81, 108, 128 

acetylcholinesterase (see AChE)......................................................... 5, 10, 15, 20, 25, 29, 31, 38, 201, 203

AChE (see acetylcholinesterase)...................... 10, 11, 12, 13, 14, 15, 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 

29, 31, 32, 38, 39, 41, 71, 81, 83, 84, 92, 95, 104, 106, 

108, 114, 116, 117, 121, 123, 124, 125, 128, 130, 199 

adipose tissue ...................................................................................................................................... 99, 170 

adrenal gland......................................................................................................................................... 14, 37 

adrenals .......................................................................................................................................................78 

adsorbed .................................................................................................................................... 151, 158, 196 

adsorption.................................................................................................................................. 153, 158, 194 

aerobic.......................................................................................................................................................143 

alanine aminotransferase.............................................................................................................................76 

ambient air ................................................................................................ 147, 160, 162, 175, 179, 182, 199 

anaerobic................................................................................................................................... 143, 156, 158 

anemia.........................................................................................................................................................75 

aspartate aminotransferase (see AST).........................................................................................................76 

AST (see aspartate aminotransferase).........................................................................................................77 

atropine ............................................................................................................................. 31, 39, 41, 81, 120 

benchmark dose (see BMD)......................................................................................................................201 

bioavailability ................................................................................................................................... 159, 181 

bioconcentration factor ..................................................................................................................... 145, 152 

biodegradation....................................................................................................................... 9, 143, 156, 181 

biomarker .................................................................................. 114, 115, 116, 129, 130, 132, 185, 198, 199 

BMD (see benchmark dose)............................................................................ 14, 19, 21, 22, 24, 26, 28, 201 

BMD analysis........................................................................................................ 19, 21, 22, 24, 26, 28, 201 

body weight effects....................................................................................................... 32, 37, 71, 79, 92, 93 

brain acetylcholinesterase (see brain AChE) ............................................................................................199 

brain AChE (see brain acetylcholinesterase) ............................................. 11, 12, 14, 15, 18, 19, 21, 22, 24, 

27, 28, 84, 114, 118, 119, 132 

breast milk................................................................................................................................... 10, 176, 183 

butyrylcholinesterase ............................................................................................................................ 11, 81 

cancer .............................................................................................................. 3, 12, 40, 88, 94, 95, 112, 125 

carcinogen......................................................................................................................................... 204, 205 

carcinogenic .................................................................................................................... 12, 30, 89, 117, 125

carcinogenicity...................................................................................................................... 12, 40, 125, 205 

carcinomas ..................................................................................................................................................89 

cardiovascular ..................................................................................................... 29, 32, 71, 72, 92, 123, 124

Cardiovascular Effects .................................................................................................................... 32, 72, 92 

central nervous system............................................................................ 10, 31, 38, 107, 108, 109, 117, 120 

ChE (see cholinesterase) .......................................................... 11, 12, 14, 15, 18, 21, 24, 27, 38, 81, 82, 84, 

104, 106, 114, 116, 118, 119, 130, 199 

cholinergic ........................................................... 10, 29, 31, 39, 41, 71, 73, 78, 82, 86, 87, 92, 94, 95, 100, 

107, 108, 109, 113, 116, 118, 123, 124, 127, 128 

cholinesterase (see ChE) ............................................... 5, 11, 12, 15, 18, 39, 81, 84, 95, 113, 116, 130, 177 

cholinesterase inhibition ................................................................................... 12, 18, 84, 95, 113, 116, 177

chromosomal aberrations .................................................................................................................... 96, 126 

clearance ........................................................................................................................................... 118, 183 
DIAZINON D-2 

APPENDIX D 

continuous variable ............................................................................................................................... 26, 28 

death.................................................................................. 10, 11, 16, 27, 30, 31, 41, 42, 73, 80, 86, 89, 108 

delayed neurotoxicity..................................................................................................................................39 

deoxyribonucleic acid (see DNA)......................................................................................................... 97, 98 

DEP (see diethylphosphate)........................................ 38, 100, 101, 102, 103, 115, 129, 130, 186, 187, 199 

dermal effects.................................................................................................................................. 32, 71, 93 

DETP (see diethylthiophosphate) ..................................... 100, 101, 102, 103, 115, 129, 130, 186, 187, 199 

diethylphosphate (see DEP)................................................................................................................ 38, 199 

diethylthiophosphate (see DETP) ............................................................................................. 100, 137, 199 

DNA (see deoxyribonucleic acid)................................................................................................. 97, 98, 115 

elimination half-time.................................................................................................................................100 

endocrine................................................................................................................. 32, 71, 92, 110, 111, 123 

endocrine effects ............................................................................................................................. 37, 78, 93 

erythema......................................................................................................................................................93 

estrogenic ..................................................................................................................................................111 

fasciculations................................................................................................................... 11, 81, 82, 108, 128 

fetus........................................................................................................................... 4, 86, 87, 111, 113, 127 

gastrointestinal effects .......................................................................................................................... 72, 92 

general population......................................................................... 9, 114, 116, 145, 169, 172, 176, 179, 183 

genotoxic............................................................................................................................................. 30, 126 

genotoxicity................................................................................................................................... 12, 96, 126 

groundwater .................................................. 9, 145, 149, 151, 153, 154, 155, 156, 166, 167, 169, 181, 182 

half-life...................................................................... 102, 114, 120, 143, 145, 154, 155, 156, 157, 159, 181 

hematological effects ...................................................................................................................... 32, 74, 92 

hepatic effects ........................................................................................................................... 37, 74, 76, 92 

human equivalent concentration ......................................................................................................... 16, 201 

hydrolysis.............................................................. 9, 100, 118, 141, 143, 154, 156, 157, 158, 159, 181, 200 

hydroxyl radical ........................................................................................................................ 143, 154, 181 

IMHP (see 2 isopropyl-4 methyl-6 hydroxypyrimidine) ......................... 100, 101, 104, 106, 115, 129, 130, 

143, 157, 158, 159, 198, 200 

immunological .......................................................................................................................... 12, 30, 37, 81 

Kow ............................................................................................................................................................135 

LD50............................................................................................................................................... 42, 89, 124 

lymphoreticular..................................................................................................................... 37, 81, 124, 127 

mass spectroscopy.....................................................................................................................................185 

metabolic effects .........................................................................................................................................80 

micronuclei .................................................................................................................................................96 

milk ............................................................................................................... 4, 102, 169, 178, 194, 198, 199 

muscarinic ............................................................................................................... 10, 31, 38, 108, 120, 128 

muscarinic receptor...................................................................................................................................120 

musculoskeletal effects...............................................................................................................................32 

neonatal............................................................................................................................................... 95, 113 

neoplastic ....................................................................................................................................................88 

neurobehavioral.........................................................................................................................................110 

neurodevelopmental.............................................................................................................. 85, 95, 113, 127 

neuromuscular................................................................................................. 10, 31, 87, 108, 113, 119, 130 

neurophysiological............................................................................................................................ 113, 131 

neurotransmitter ........................................................................................................................................108 

nicotinic .......................................................................................................................... 10, 31, 38, 121, 128 

nicotinic receptor ........................................................................................................................................38 

non-Hodgkin’s lymphoma .............................................................................................................. 12, 88, 95 
DIAZINON D-3 

APPENDIX D 

nuclear.........................................................................................................................................................77 

ocular effects......................................................................................................................................... 78, 92 

organophosphate ................................................................ 10, 13, 14, 38, 39, 71, 81, 93, 94, 108, 116, 117, 

119, 120, 131, 132, 139, 155, 164, 165, 169 

pharmacodynamic ............................................................................................................. 103, 104, 106, 131 

pharmacokinetic................................................................................ 103, 104, 105, 106, 109, 112, 130, 131 

photolysis .................................................................................................. 141, 143, 154, 155, 156, 158, 181 

plasma ChE (see plasma cholinesterase) ................................. 11, 12, 14, 15, 18, 19, 21, 24, 27, 38, 39, 81, 

82, 84, 94, 106, 113, 116, 118, 119, 130 

plasma cholinesterase (see plasma ChE) ........................................................................................ 5, 38, 199 

RBC (see red blood cell)...................... 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 38, 

39, 75, 81, 82, 83, 84, 106, 114, 116, 119, 124, 130, 131, 199, 201 

RBC AChE ............................................................ 11, 12, 13, 15, 16, 18, 19, 21, 22, 23, 24, 25, 26, 27, 28, 

38, 39, 81, 82, 83, 84, 106, 114, 116, 124, 130, 201 

red blood cell (see RBC)................................................................................. 5, 11, 15, 20, 25, 75, 107, 203 

renal effects........................................................................................................................................... 37, 77 

retention ............................................................................................................................................ 191, 196 

salivation........................................................................................................... 11, 13, 39, 87, 108, 124, 128

spermatozoa ........................................................................................................................................ 85, 111 

thyroid.........................................................................................................................................................78 

toxicokinetic......................................................................................................................... 29, 124, 125,131 

tremors ............................................................................................................................................ 10, 82, 83 

vapor phase ............................................................................................................................... 143, 150, 154 

vapor pressure ...........................................................................................................................................150 

volatility ................................................................................................................................ 10, 31, 146, 173 

volatilization ..................................................................................................................... 143, 147, 151, 153