TOXICOLOGICAL PROFILE FOR 

PYRETHRINS AND PYRETHROIDS
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

September 2003 
PYRETHRINS AND PYRETHROIDS 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. 
PYRETHRINS AND PYRETHROIDS iii 

UPDATE STATEMENT
 

A Toxicological Profile for pyrethrins and pyrethroids, Draft for Public Comment was released in 

September, 2001. This edition supersedes any previously released draft or final profile. 

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

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

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch 

1600 Clifton Road NE, 

Mailstop E-29 

Atlanta, Georgia 30333 



 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 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: 1-888-42-ATSDR or (404) 498-0110 Fax: (404) 498-0093 

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

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

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

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

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

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

Toxicity; and numerous chemical-specific case studies. 
 

 

PYRETHRINS AND PYRETHROIDS 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, 55 West Seegers Road, Arlington Heights, IL 

60005 • Phone: 847-818-1800 • FAX: 847-818-9266. 
PYRETHRINS AND PYRETHROIDS ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

G. Daniel Todd, Ph.D. 

ATSDR, Division of Toxicology, Atlanta, GA 

David Wohlers, Ph.D. 

Mario Citra, Ph.D. 

Syracuse Research Corporation, North Syracuse, NY 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

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

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

end points. 

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

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

profile, and makes recommendations for derivation of MRLs. 

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

consistency across profiles and adherence to instructions in the Guidance. 

PYRETHRINS AND PYRETHROIDS xi 

PEER REVIEW
 

A peer review panel was assembled for pyrethrins and pyrethroids. The panel consisted of the following 

members: 

1. Sam Kacew, Ph.D., Professor of Pharmacology, Department of Cellular & Molecular Medicine, 

University of Ottawa, Ottawa, Ontario, Canada; 

2. Harihara Mehendale, Ph.D., DABT, Professor and Kitty DeGree Endowed Chair in Toxicology, 

School of Pharmacy, The University of Louisiana at Monroe, Monroe, Louisiana; and 

3. Stephen B. Tucker, M.D., Clinical Professor of Dermatology, The University of Texas-Houston 

Medical School, The Woodlands, Texas. 

These experts collectively have knowledge of pyrethrins and pyrethroids physical and chemical 

properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

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

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

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

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

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

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

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

PYRETHRINS AND PYRETHROIDS xiii 

CONTENTS 

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

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

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

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

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

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

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

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

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

1.1 WHAT ARE PYRETHRINS AND PYRETHROIDS?...............................................................1 

1.2 WHAT HAPPENS TO PYRETHRINS AND PYRETHROIDS WHEN THEY ENTER 

 THE ENVIRONMENT? .............................................................................................................3
 

1.3 HOW MIGHT I BE EXPOSED TO PYRETHRINS AND PYRETHROIDS? ..........................4 

1.4 HOW CAN PYRETHRINS AND PYRETHROIDS ENTER AND LEAVE MY BODY? ....... 4 

1.5 HOW CAN PYRETHRINS AND PYRETHROIDS AFFECT MY HEALTH?.........................5 

1.6 HOW CAN PYRETHRINS AND PYRETHROIDS AFFECT CHILDREN?............................6 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO PYRETHRINS 

 AND PYRETHROIDS? ..............................................................................................................7 

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

TO PYRETHRINS AND PYRETHROIDS? ..............................................................................8 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

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

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

2. RELEVANCE TO PUBLIC HEALTH .................................................................................................13 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PYRETHRINS AND 

PYRETHROIDS IN THE UNITED STATES ..........................................................................13 

2.2 SUMMARY OF HEALTH EFFECTS......................................................................................16 

2.3 MINIMAL RISK LEVELS (MRLs) .........................................................................................18 

3. HEALTH EFFECTS..............................................................................................................................23 

3.1 INTRODUCTION.....................................................................................................................23 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................23 

3.2.1 Inhalation Exposure ..........................................................................................................26 

3.2.1.1 Death ............................................................................................................................26 

3.2.1.2 Systemic Effects...........................................................................................................27 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................29 

3.2.1.4 Neurological Effects.....................................................................................................29 

3.2.1.5 Reproductive Effects....................................................................................................31 
PYRETHRINS AND PYRETHROIDS xiv 

3.2.1.6 Developmental Effects .................................................................................................31 

3.2.1.7 Cancer...........................................................................................................................31 

3.2.2 Oral Exposure ...................................................................................................................31 

3.2.2.1 Death ............................................................................................................................31 

3.2.2.2 Systemic Effects...........................................................................................................35 

3.2.2.3 Immunological and Lymphoreticular Effects...............................................................57 

3.2.2.4 Neurological Effects.....................................................................................................58 

3.2.2.5 Reproductive Effects....................................................................................................61 

3.2.2.6 Developmental Effects .................................................................................................62 

3.2.2.7 Cancer...........................................................................................................................65 

3.2.3 Dermal Exposure ..............................................................................................................66 

3.2.3.1 Death ............................................................................................................................66 

3.2.3.2 Systemic Effects...........................................................................................................67 

3.2.3.3 Immunological and Lymphoreticular Effects...............................................................68 

3.2.3.4 Neurological Effects.....................................................................................................68 

3.2.3.5 Reproductive Effects....................................................................................................70 

3.2.3.6 Developmental Effects .................................................................................................70 

3.2.3.7 Cancer...........................................................................................................................70 

3.3 GENOTOXICITY .....................................................................................................................71 

3.4 TOXICOKINETICS..................................................................................................................77 

3.4.1 Absorption ........................................................................................................................84 

3.4.1.1 Inhalation Exposure......................................................................................................84 

3.4.1.2 Oral Exposure...............................................................................................................84 

3.4.1.3 Dermal Exposure ..........................................................................................................86 

3.4.2 Distribution .......................................................................................................................87 

3.4.2.1 Inhalation Exposure......................................................................................................87 

3.4.2.2 Oral Exposure...............................................................................................................88 

3.4.2.3 Dermal Exposure ..........................................................................................................90 

3.4.2.4 Other Routes of Exposure ............................................................................................90 

3.4.3 Metabolism .......................................................................................................................91 

3.4.3.1 Inhalation Exposure......................................................................................................94 

3.4.3.2 Oral Exposure...............................................................................................................94 

3.4.3.3 Dermal Exposure .......................................................................................................... 95 

3.4.4 Elimination and Excretion ................................................................................................95 

3.4.4.1 Inhalation Exposure......................................................................................................95 

3.4.4.2 Oral Exposure...............................................................................................................96 

3.4.4.3 Dermal Exposure ..........................................................................................................98 

3.4.4.4 Other Routes of Exposure ............................................................................................99 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models.........99 

3.5 MECHANISMS OF ACTION ................................................................................................102 

3.5.1 Pharmacokinetic Mechanisms ........................................................................................102 

3.5.2 Mechanisms of Toxicity .................................................................................................103 

3.5.3 Animal-to-Human Extrapolations...................................................................................106 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ........................106 

3.7 CHILDREN’S SUSCEPTIBILITY.........................................................................................108 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ..................................................................112 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Pyrethrins and Pyrethroids........113 

3.8.2 Biomarkers Used to Characterize Effects Caused by Pyrethrins and Pyrethroids..........113 

3.9 INTERACTIONS WITH OTHER CHEMICALS ..................................................................114 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE.............................................115 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................116 
PYRETHRINS AND PYRETHROIDS xv 

3.11.1 Reducing Peak Absorption Following Exposure ............................................................116 

3.11.2 Reducing Body Burden...................................................................................................117 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .........................................117 

3.12 ADEQUACY OF THE DATABASE......................................................................................118 

3.12.1 Existing Information on Health Effects of Pyrethrins and Pyrethroids ..........................118 

3.12.2 Identification of Data Needs ...........................................................................................120 

3.12.3 Ongoing Studies..............................................................................................................129 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................131 

4.1 CHEMICAL IDENTITY......................................................................................................... 131 

4.2 PHYSICAL AND CHEMICAL PROPERTIES......................................................................141 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................153 

5.1 PRODUCTION .......................................................................................................................153 

5.2 IMPORT/EXPORT .................................................................................................................159 

5.3 USE..........................................................................................................................................159 

5.4 DISPOSAL..............................................................................................................................159 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................165 

6.1 OVERVIEW............................................................................................................................165 

6.2 RELEASES TO THE ENVIRONMENT................................................................................170 

6.2.1 Air...................................................................................................................................170 

6.2.2 Water...............................................................................................................................174 

6.2.3 Soil..................................................................................................................................174 

6.3 ENVIRONMENTAL FATE....................................................................................................175 

6.3.1 Transport and Partitioning ..............................................................................................175 

6.3.2 Transformation and Degradation ....................................................................................179 

6.3.2.1 Air.............................................................................................................................179 

6.3.2.2 Water ........................................................................................................................181 

6.3.2.3 Sediment and Soil.....................................................................................................183 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT...............................185 

6.4.1 Air...................................................................................................................................185 

6.4.2 Water...............................................................................................................................186 

6.4.3 Sediment and Soil ...........................................................................................................187 

6.4.4 Other Environmental Media ...........................................................................................188 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .....................................194 

6.6 EXPOSURES OF CHILDREN...............................................................................................197 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...........................................198 

6.8 ADEQUACY OF THE DATABASE......................................................................................199 

6.8.1 Identification of Data Needs ...........................................................................................200 

6.8.2 Ongoing Studies..............................................................................................................203 

7. ANALYTICAL METHODS ...............................................................................................................205 

7.1 BIOLOGICAL MATERIALS.................................................................................................205 

7.2 ENVIRONMENTAL SAMPLES............................................................................................206 

7.3 ADEQUACY OF THE DATABASE......................................................................................209 

7.3.1 Identification of Data Needs ...........................................................................................215 

7.3.2 Ongoing Studies..............................................................................................................216 

8. REGULATIONS AND ADVISORIES ...............................................................................................217 
PYRETHRINS AND PYRETHROIDS xvi 

9. REFERENCES ....................................................................................................................................227 

10. GLOSSARY ......................................................................................................................................281 

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

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

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS.................................................C-1 
PYRETHRINS AND PYRETHROIDS xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Pyrethroids - Inhalation............................................................... 33 

3-2. Levels of Significant Exposure to Pyrethroids - Oral........................................................................ 51 

3-3. Metabolic Diagram for Deltamethrin, Permethrin, and Cypermethrin...............................................93 

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

Hypothetical Chemical Substance .....................................................................................................101 

3-5. Existing Information on Health Effects of Pyrethrins and Pyrethroids............................................119 

4-1. Four Possible Isomers of Type I Pyrethroids....................................................................................140 

4-2. Illustration of the S Conformer about the Alpha Carbon for the Type II Pyrethroid Cyhalothrin ...152 

6-1. Frequency of NPL Sites with Pyrethrins Contamination..................................................................166
 

6-2. Frequency of NPL Sites with Pyrethroid Contamination .................................................................167 
PYRETHRINS AND PYRETHROIDS xviii 
PYRETHRINS AND PYRETHROIDS xix 

LIST OF TABLES
 

2-1. Pyrethrins and Pyrethroids Discussed in the Profile...........................................................................14 

3-1. Levels of Significant Exposure to Pyrethrins and Pyrethroids - Inhalation....................................... 32 

3-2. Levels of Significant Exposure to Pyrethrins and Pyrethroids - Oral................................................ 36 

3-3. Genotoxicity of Pyrethrins In Vitro ....................................................................................................72 

3-4. Genotoxicity of Type I Pyrethroids In Vivo........................................................................................73 

3-5. Genotoxicity of Type II Pyrethroids In Vivo ......................................................................................74 

3-6. Genotoxicity of Type I Pyrethroids In Vitro.......................................................................................78 

3-7. Genotoxicity of Type II Pyrethroids In Vitro .....................................................................................80 

4-1. Chemical Identity of the Pyrethrins..................................................................................................132 

4-2. Chemical Identity of Selected Pyrethroids.......................................................................................134 

4-3. Stereoisomers of Selected Pyrethroids .............................................................................................142 

4-4. Physical and Chemical Properties of Pyrethrins...............................................................................144 

4-5. Physical and Chemical Properties of Selected Pyrethroids..............................................................146
 

5-1. U.S. Producers of Pyrethrins and Pyrethroids..................................................................................154 

5-2. Facilities that Produce, Process, or Use Pyrethroids .......................................................................155 

5-3. Acid and Alcohol Feedstocks in the Pyrethroids Synthesis .............................................................156 

5-4. Uses of Pyrethroids...........................................................................................................................160 

6-1. Trends of National Pyrethroid Use ...................................................................................................171 

6-2. Releases to the Environment from Facilities that Produce, Process, or Use Pyrethroids.................172 

6-3. Levels of Pyrethroids Detected in Foods..........................................................................................189 

6-4. Average Daily Intake (AVDI, ng/kg/day) of Permethrin in Eight Population Groups.....................195 

7-1. Analytical Methods for Determining Pyrethrins and Pyrethroids in Biological Materials...............207 

7-2. Analytical Methods for Determining Pyrethrins and Pyrethroids in Environmental Samples.........210 
PYRETHRINS AND PYRETHROIDS xx 

8-1. Regulations and Guidelines Applicable to Pyrethrins and Pyrethroids............................................218 

8-2. Tolerances for Residues Applicable to Pyrethrins and Pyrethroids (ppm).......................................222 
 

PYRETHRINS AND PYRETHROIDS 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about pyrethrins and pyrethroids and the effects of 

exposure. 

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

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

long-term federal cleanup activities. Pyrethrins and pyrethroids have been found in at least 5 and 

2 of the 1,636 current or former NPL sites, respectively. However, the total number of NPL sites 

evaluated for these substances is not known. As more sites are evaluated, the sites at which 

pyrethrins and pyrethroids are found may increase. This information is important because 

exposure to these substances may harm you and because these sites may be sources of exposure. 

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

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

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

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

If you are exposed to pyrethrins and pyrethroids, many factors determine whether you'll be 

harmed. These factors include the dose (how much), the duration (how long), and how you 

come in contact with them. You must also consider the other chemicals you're exposed to and 

your age, sex, diet, family traits, lifestyle, and state of health. 

1.1 WHAT ARE PYRETHRINS AND PYRETHROIDS? 

Pyrethrum is a naturally occurring mixture of chemicals found in certain chrysanthemum 

flowers. Pyrethrum was first recognized as having insecticidal properties around 1800 in Asia 

and was used to kill ticks and various insects such as fleas and mosquitos. Six individual 

chemicals have active insecticidal properties in the pyrethrum extract, and these compounds are 

called pyrethrins. Pyrethrum looks like a tan-colored dust as ground flowers or a syrupy liquid 
PYRETHRINS AND PYRETHROIDS 2 

1. PUBLIC HEALTH STATEMENT 

as the crude extract. Pyrethrins are only slightly soluble in water, but they dissolve in organic 

solvents like alcohol, chlorinated hydrocarbons, and kerosene. Pyrethrins are often used in 

household insecticides and products to control insects on pets or livestock. Pyrethrins break 

down quickly in the environment, especially when exposed to natural sunlight. 

Pyrethroids are manufactured chemicals that are very similar in structure to the pyrethrins, but 

are often more toxic to insects, as well as to mammals, and last longer in the environment than 

pyrethrins. More than 1,000 synthetic pyrethroids have been developed, but less than a dozen of 

them are currently used in the United States. Pyrethrins and pyrethroids are often combined 

commercially with other chemicals called synergists, which enhance the insecticidal activity of 

the pyrethrins and pyrethroids. The synergists prevent some enzymes from breaking down the 

pyrethrins and pyrethroids, thus increasing their toxicity. 

Most commercial pyrethroids are not one single molecule; rather, they are several molecules 

with the same chemical formula that have their atoms joined together in the same sequence, but 

have a different arrangement of the atoms in space. Such compounds are called stereoisomers. 

If the stereoisomers are not mirror images of one another, they are called diastereomers and have 

different physical properties like boiling point, melting point, and solubility. If they are 

nonsuperimposable mirror images of each other, they are called enantiomers and properties like 

boiling point, melting point, and solubility are identical. However, both diastereomers and 

enantiomers can have different insecticidal properties and different toxicities. Some pyrethroids 

are composed of as many as eight different stereoisomers. 

Technical-grade (concentrated) pyrethrins and pyrethroids are usually mixed with carriers or 

solvents to produce a commercial-grade formulated product. The formulated product contains 

many inert ingredients that can increase the toxicity of the product when compared to the 

technical-grade material. By law, the active ingredient must be identified by name on the 

pesticide label and its percentage must be provided. Nonactive ingredients (sometimes called 

inert ingredients) do not need to be identified by name on a pesticide label, only the percentage 

of nonactive ingredients must be specified, so it is often difficult to determine what other 

chemicals are included in the final formulated product. 
PYRETHRINS AND PYRETHROIDS 3 

1. PUBLIC HEALTH STATEMENT 

1.2 WHAT HAPPENS TO PYRETHRINS AND PYRETHROIDS WHEN THEY 

ENTER THE ENVIRONMENT? 

Pyrethrins and pyrethroids are primarily released to air because of their use as insecticides. 

Sometimes they are sprayed on crops from planes and helicopters or sprayed from the ground by 

trucks, tractors, or hand-held applicators. They are also used to control flying insects like 

mosquitos and flies on livestock and pets. These compounds are also in aerosol bombs and 

sprays that can be used indoors. Pyrethrins can be released naturally from chrysanthemum 

flowers, but these releases are small compared with the amounts used as commercial 

insecticides. Manufacturing facilities that produce these compounds can also release them to the 

environment during the production process. 

In air, all six of the pyrethrins and many of the pyrethroids are broken down or degraded rapidly 

by sunlight or other compounds found in the atmosphere. Often, they last only 1 or 2 days 

before being degraded. Rain and snow help remove the pyrethroids from air that are not rapidly 

degraded. Since many of these compounds are extremely toxic to fish, they are usually not 

sprayed directly onto water, but they can enter lakes, ponds, rivers, and streams from rainfall or 

runoff from agricultural fields. These compounds bind strongly to dirt and usually are not very 

mobile in soil. Pyrethrins and pyrethroids are not easily taken up by the roots of plants and 

vegetation because they are strongly bound to the soil; however, they are often sprayed directly 

onto crops and plants so they may be found on leaves, fruits, and vegetables. Because these 

compounds adsorb so strongly to soil, pyrethrins and pyrethroids usually do not leach into 

groundwater, do not contaminate drinking water supplies, and volatilize from soil surfaces 

slowly. These compounds are eventually degraded by the microorganisms in soil and water. 

They can also be degraded by sunlight at the surfaces of water, soil, or plants. However, some of 

the more recently developed pyrethroids can persist in the environment for a few months before 

they are degraded. 

For more information about the fate and movement of pyrethrins and pyrethroids in the 

environment, see Chapter 6. 
PYRETHRINS AND PYRETHROIDS 4 

1. PUBLIC HEALTH STATEMENT 

1.3 HOW MIGHT I BE EXPOSED TO PYRETHRINS AND PYRETHROIDS? 

You can be exposed to pyrethrins and pyrethroids in several ways. Eating foods that are 

contaminated with these compounds is the most likely way. You can also breathe in air that 

contains these compounds. This is especially possible soon after the insecticide has been 

sprayed. After spraying, these compounds can also come in contact with your skin and you can 

be exposed by dermal contact. These compounds are contained in many household insecticides, 

pet sprays, and shampoos. Some pyrethroids are also used as lice treatments that are applied 

directly to the head and as mosquito repellents that can be applied to your clothes. A common 

treatment for scabies is the application of a pyrethroid to the affected skin surface excluding the 

scalp. The use of these products can lead to exposure. 

The average daily intake of permethrin (the most frequently used pyrethroid in the United States) 

for a 70 kilogram adult male is estimated as about 3.2 micrograms per day (1 microgram equals 

1/1,000,000 of a gram). This value is about 1,000 times less than the acceptable daily intake 

(ADI) of permethrin derived by the United Nations’ Food and Agriculture Organization (FAO) 

and the World Health Organization (WHO). 

1.4 HOW CAN PYRETHRINS AND PYRETHROIDS ENTER AND LEAVE MY 

BODY? 

Pyrethrins and pyrethroids usually enter the body when people eat foods contaminated by these 

chemicals. They may also enter your body by breathing air that contains these compounds or 

through dermal exposure when you use commercially available insecticides that contain 

pyrethrins and pyrethroids. These chemicals are absorbed by the body when you eat 

contaminated foods and breathe contaminated air, but they are not as easily absorbed through the 

skin when you touch contaminated soil, vegetation, or insecticides containing these compounds. 

Some insect repellents that are applied to the skin contain pyrethrins or pyrethroids in addition to 

another chemical called DEET, which may allow the pyrethrins or pyrethroids to enter your body 
PYRETHRINS AND PYRETHROIDS 5 

1. PUBLIC HEALTH STATEMENT 

more easily. Pyrethrins and pyrethroids can enter your body if you swallow drinking water 

contaminated with these compounds, but since pyrethrins and pyrethroids are rarely found in 

drinking water, this will be a minor exposure route. Accidental exposures to pyrethrins or 

pyrethroids may also occur if these pesticides are improperly used. 

Pyrethrins and pyrethroids that enter the body leave quickly, mainly in the urine, but also in feces 

and breath. These compounds are also quickly broken down by the body into other chemicals 

called metabolites. The concentration of these chemicals in the urine increases as the amount of 

the exposure goes up. If exposure levels are very high or if exposure occurs over a long time, 

then pyrethrins and pyrethroids can build up in fatty tissue and remain in the body for a little 

longer. Certain types of pyrethroids can also be retained for longer periods of time in the skin 

and hair. 

Chapter 3 contains more information on how pyrethrins and pyrethroids enter and leave the 

human body. 

1.5 HOW CAN PYRETHRINS AND PYRETHROIDS AFFECT MY HEALTH? 

Pyrethrins and pyrethroids interfere with the way that the nerves and brain function. If you get a 

large amount of pyrethrins or pyrethroids on your skin, you may get feelings of numbness, 

itching, burning, stinging, tingling, or warmth that could last for a few hours. You are not likely 

to be exposed to amounts of pyrethrins or pyrethroids by breathing air, eating food, or touching 

anything that would cause enough pyrethrins or pyrethroids to enter your body and cause other 

problems. But if very large amounts of these chemicals were to enter your body, you might 

experience dizziness, headache, and nausea that might last for several hours. Larger amounts 

might cause muscle twitching, reduced energy, and changes in awareness. Even larger amounts 

could cause convulsions and loss of consciousness that could last for several days. Allergic 

reactions have been seen in a few individuals who used products that contain pyrethrins or 

pyrethroids. There is no evidence that pyrethrins or pyrethroids cause birth defects in humans or 

affect the ability of humans to produce children. There is evidence from animal studies that 
PYRETHRINS AND PYRETHROIDS 6 

1. PUBLIC HEALTH STATEMENT 

pyrethrins and pyrethroids might be capable of causing cancer in people, but the evidence comes 

from animals that ate very large amounts of pyrethrins or pyrethroids for a lifetime. 

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

who have been harmed, scientists use many tests. 

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

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

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

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

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

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

with strict animal care guidelines. 

Animal studies show effects of pyrethrins and pyrethroids similar to those seen in people 

exposed to very high amounts of these chemicals. In addition, exposure to pyrethrins or 

pyrethroids might affect the ability of some animals to reproduce and may also cause cancer. 

1.6 HOW CAN PYRETHRINS AND PYRETHROIDS AFFECT CHILDREN? 

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

to maturity at 18 years of age in humans. 

Children exposed to large amounts of pyrethrins or pyrethroids would be expected to be affected 

in the same manner as adults. If children were to get a large amount of pyrethrins or pyrethroids 

on their skin, they might get feelings of numbness, itching, burning, tingling, or warmth that 

could last for a few hours. If very large amounts of these chemicals were to enter a child’s body, 

the child might experience dizziness, headache, and nausea that might last for several hours. 

Even larger amounts could cause muscle twitches, tremors, convulsions, and loss of 

consciousness that could last up to several days. 
PYRETHRINS AND PYRETHROIDS 7 

1. PUBLIC HEALTH STATEMENT 

Pyrethroids might be able to penetrate the skin of infants and young children more easily than the 

skin of adults. Infants and young children are more easily dehydrated than adults through 

exercise, flue, colds, and the conditions that contribute to fluid loss. Therefore, pyrethroids that 

penetrate the skin may become more concentrated in internal tissues of the young. 

There is no evidence in humans that pyrethrins or pyrethroids cause birth defects. Some young 

animals showed signs of possible damage to the body’s defense system that fights infection after 

their mothers were exposed to pyrethroids while their babies were developing in the womb. 

There is some indication that the developing brain of some very young animals could be affected 

by pyrethroids. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO PYRETHRINS 

 AND PYRETHROIDS? 

If your doctor finds that you have been exposed to significant amounts of pyrethrins or 

pyrethroids, ask whether your children might also be exposed. Your doctor might need to ask 

your state health department to investigate. 

Pyrethrins and pyrethroids are effective insecticides that are often used in household sprays, 

aerosol bombs, insect repellents, pet shampoos, and lice treatments. Using products containing 

these compounds will expose you to these chemicals. If you decide to use these products, 

carefully follow the instructions on how to apply them properly and how long to wait before reentering the treated area. Do not apply more than the recommended amount. Pesticides and 

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

poisoning. Always store pesticides in their original labeled containers; never store pesticides in 

containers that young children would find attractive, such as old soda bottles. If you feel sick 

after a pesticide has been used in your home, call the local poison control center or see a doctor. 

Keep your poison control center’s number next to the phone. If a close neighbor or someone 

living nearby is applying pyrethrins or pyrethroids, you may want to remain indoors with your 

children and pets in order to avoid being accidentally exposed to these chemicals. Certain 

pyrethroids, such as permethrin, phenothrin, and resmethrin, are sprayed to control mosquitos 
PYRETHRINS AND PYRETHROIDS 8 

1. PUBLIC HEALTH STATEMENT 

during the spring and summer. Remaining indoors and closing your windows while your 

neighborhood is being sprayed will lessen your exposure. 

Since these compounds frequently are used on crops, they are often detected in fruits and 

vegetables. Make sure you wash fruits and vegetables thoroughly before eating them. Trim the 

fat from meat and poultry because pesticides often concentrate in fat. These compounds are 

often detected in soils, especially in agricultural areas. Some children eat a lot of dirt. You 

should discourage your children from eating dirt. Make sure they wash their hands frequently 

and before eating. Discourage your children from putting their hands in their mouths or any 

other hand-to-mouth activity. 

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

EXPOSED TO PYRETHRINS AND PYRETHROIDS? 

Methods exist that can detect pyrethrins and pyrethroids in blood and urine. Because these 

compounds are broken down in the body quickly, there are also ways to measure the metabolites 

of these chemicals in human blood and urine. These methods are not available in a doctor’s 

office because special equipment is required. However, a sample taken in a doctor’s office can 

be shipped to a special medical laboratory, if necessary. These laboratories are usually located at 

research universities or affiliated with government agencies such as the Centers for Disease 

Control and Prevention (CDC). Your doctor may need to contact the county health department 

for a list of laboratories that can perform these tests. Because pyrethrins and pyrethroids break 

down in the body rapidly, these methods are useful only if exposure has occurred within the last 

few days. At this time, these methods can tell only if you have been exposed to pyrethrins or 

pyrethroids and cannot tell if you will have any adverse health effects. Methods also exist that 

can measure the concentration of pyrethrins and pyrethroids in air, water, soil, and foods. 

For pesticide emergencies, the National Pesticide Information Center (NPIC) (formerly called 

the National Pesticide Telecommunications Network [NPTN]) located at Oregon State 

University, is also available. The NPIC (telephone number: 1-800-858-7378 for the general 
PYRETHRINS AND PYRETHROIDS 9 

1. PUBLIC HEALTH STATEMENT 

public and 1-800-858-7377 for medical profession/government agencies) provides information 

about pesticides to anyone in the United States. 

Chapter 7 contains more information regarding the measurement of pyrethrins and pyrethroids in 

humans and environmental samples. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

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

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

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

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

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

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

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

Occupational Safety and Health (NIOSH). 

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

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

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

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

studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

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

provides it. Some regulations and recommendations for pyrethrins and pyrethroids include the 

following: 

The WHO has recommended that the level of permethrin in drinking water not exceed 

20 micrograms per liter (μg/L). OSHA regulates the level of pyrethrins in workplace air. The 
PYRETHRINS AND PYRETHROIDS 10 

1. PUBLIC HEALTH STATEMENT 

occupational exposure limits for an 8-hour workday, 40-hour workweek are 5 mg per cubic 

meter (mg/m3). The EPA has recommended daily oral exposure limits for 10 different 

pyrethroids. These limits range from 0.005 to 0.05 mg/kg/day. 

In September of 1997, the EPA issued a request to pesticide formulators to voluntarily change 

the term “inert ingredients” to “other ingredients” on pesticide labels because the general public 

often believed that inert ingredients meant harmless ingredients. Since federal law does not 

define inert ingredients on the basis of toxicity or hazard to humans, it should not be assumed 

that all inert ingredients are nontoxic. The EPA publishes a list of all inert ingredients used in 

currently registered pesticides, but it does not specify which ingredients are contained in any 

specific formulated product. 

For more information on regulations and guidelines, 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 resulting 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 ToxProfiles CD-ROM by calling the information and 

technical assistance toll-free number at 1-888-42ATSDR (1-888-422-8737), by email at 

atsdric@cdc.gov, or by writing at: 
 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 11 

1. PUBLIC HEALTH STATEMENT 

Agency for Toxic Substances and Disease Registry 

Division of Toxicology 

1600 Clifton Road NE 

Mailstop E-29 

Atlanta, GA 30333 

Fax: 1-404-498-0093 

For-profit organizations may request a copy of final 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/ 

PYRETHRINS AND PYRETHROIDS 13 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO PYRETHRINS AND 

PYRETHROIDS IN THE UNITED STATES 

Pyrethrum is the natural extract that occurs in the flowers of Chrysanthemum cinerariaefolium and 

Chrysanthemum cineum. Pyrethrum has long been recognized as possessing insecticidal properties; over 

the years, first the chemical extracts of pyrethrum, and then more recently, the specific synthetic chemical 

analogs have been produced. The six active insecticidal compounds of pyrethrum are called pyrethrins. 

The six individual pyrethrins are pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I, and jasmolin II. 

The pyrethroids are synthetic analogs and derivatives of the original pyrethrins and represent a diverse 

group of over 1,000 powerful insecticides. Although they are based on the chemical structure and 

biological activity of the pyrethrins, the development of synthetic pyrethroids has involved extensive 

chemical modifications that make these compounds more toxic and less degradable in the environment. 

A list of the pyrethrins and some of the more common pyrethroids is presented in Table 2-1. While many 

pyrethroids have been developed, only about a dozen or so are frequently used in the United States. The 

individual pyrethroids are typically grouped into two general classes, called Type I and Type II, based on 

a combination of toxicological and physical properties, which is further described in Chapters 3 and 4. 

Also, the individual pyrethroid substances, due to a complex chemical structure, are often composed of 

two, four, or eight isomers, and their commercially manufactured products routinely contain a mixture of 

these various isomers. Thus, the production of individual pyrethroids with slightly varying isomeric 

ratios can often be the reason for the differences in the reported toxicities of the same compound. See 

Chapter 4 for the structures and explanation of the isomerism, as well as more information on the 

chemical and physical properties of the pyrethrins and pyrethroids. 

Both groups, the pyrethrins and the pyrethroids, are very important insecticides because of their rapid 

paralysis of flying insects, relatively low mammalian toxicity, and rapid rate of degradation in the 

environment. They are typically used as insecticides for both home and commercial use. Also, the 

pyrethrins and pyrethroids are often formulated with compounds such as piperonyl butoxide, piperonyl 

sulfoxide, and sesamex, which act as synergists to increase the effectiveness of the insecticide. Currently, 

the products containing small amounts of pyrethroids for uses around the home are still classified as 

general use pesticides; however, emulsified or granular concentrate formulations that are applied to fields 

were classified as restricted use pesticides by EPA in 1995. Formulated commercial pyrethroid products 
 

 

 

PYRETHRINS AND PYRETHROIDS 14 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. Pyrethrins and Pyrethroids Discussed in the Profilea 

Pyrethrins Type I pyrethroids Type II pyrethroid 

Constituents of Derivatives of pyrethrins that Derivatives of pyrethrins that include a 

natural pyrethrum do not include a cyano group cyano group and may elicit sinuous 

extract and may elicit tremors writhing (choreoathetosis) and salivation 

Pyrethrin I Allethrin Cyfluthrin 

Pyrethrin II Bifenthrin Cyhalothrin 

Cinerin I Permethrin Cypermethrin 

Cinerin II Phenothrin(Bio) Deltamethrin 

Jasmolin I Resmethrin Fenvalerate 

Jasmolin II Tefluthrin Fenpropathrin 

Tetramethrin	 Flucythrinate 

Flumethrin 

Fluvalinate 

Tralomethrin 

a

Type I and Type II pyrethroids are described in more detail in Section 3.5.2, Mechanisms of Toxicity. 
PYRETHRINS AND PYRETHROIDS 15 

2. RELEVANCE TO PUBLIC HEALTH 

(like most pesticides), also contain a high percentage of other (sometimes referred to as “inert”) 

ingredients, many of which may be potentially toxic. Federal law only requires that the percentage of 

“inert” ingredients be defined and does not require the actual chemicals that make up the “inert” 

ingredients to be identified on a pesticide label. 

Pyrethrins and pyrethroids are released to the environment due to their use as insecticides. They can be 

applied to crops from aerial and ground-based sprayers or applied indoors from commercially available 

sprays or aerosol bombs. These compounds are readily degraded in the atmosphere by natural sunlight 

and usually do not persist for more than several days to a few weeks. Certain pyrethroids such as 

permethrin and cyhalothrin, where the isobutenyl group attached to the cyclopropane moiety has been 

altered, are slightly more stable to sunlight than other pyrethroids. Air concentrations are usually in the 

μg/m3

 range (both indoors and outdoors) after spraying, but diminish over time as these compounds are 

degraded or removed by wet and dry deposition. In soils, pyrethrins and pyrethroids are not very mobile 

and usually do not leach into groundwater, unless a large spill has occurred. These compounds are 

biodegraded in soil and water and can also undergo hydrolysis under alkaline conditions. Since these 

compounds adsorb strongly to soils, they are not taken up substantially by the roots of vascular plants. 

These compounds bioconcentrate in aquatic organisms and are extremely toxic to fish. 

The general population is primarily exposed to pyrethrins and pyrethroids from the ingestion of foods, 

particularly vegetables and fruits. Exposure due to inhalation of ambient air is also possible after these 

compounds have been used. Pyrethrins and pyrethroids are also employed in a variety of pet shampoos, 

lice treatments, household insecticide sprays, and aerosol bombs that can be used in or around the home, 

and the use of these products can lead to both dermal and inhalation exposure. Occupational exposure to 

agricultural workers who apply these compounds onto crops can be substantial, with dermal exposure 

considered the most important pathway (see Section 6.5). 

The average daily intake (AVDI) of permethrin for eight different age/sex groups has been estimated 

from market basket surveys conducted by the Food and Drug Administration (FDA). Based upon market 

basket surveys conducted from 1986 to 1991, the AVDI of permethrin ranges from about 36 to 

71 ng/kg/day (see Table 6-4). Since permethrin is the most frequently used pyrethroid in the United 

States, the data from these surveys may represent a reasonable first approximation for the average total 

intake of all the pyrethroids. 
 

PYRETHRINS AND PYRETHROIDS 16 

2. RELEVANCE TO PUBLIC HEALTH 

2.2 SUMMARY OF HEALTH EFFECTS 

Pyrethrins and pyrethroids are used extensively as effective insecticides, but pose relatively little hazard 

to mammals (including humans) by natural routes of exposure at levels likely to be encountered in the 

environment or resulting from the normal use of pyrethrin- or pyrethroid-containing substances. Signs 

and symptoms of acute toxicity vary according to the type of pyrethroid to which one may be exposed. 

However, almost all systemic effects are related to the action of pyrethrins and pyrethroids on the nervous 

system. These chemicals exert their profound effect by prolonging the open phase of the sodium channel 

gates when a nerve cell is excited. In rodents, effects such as tremors are induced if the open state is 

prolonged for brief periods; effects such as sinuous writhing (choreoathetosis) and salivation occur if the 

open state is prolonged for longer periods. Neurological signs typically result from acute toxicity. Lowlevel chronic exposures to pyrethrins and pyrethroids usually do not cause neurological signs in 

mammals, largely due to rapid metabolism and elimination. However, direct skin contact may cause 

temporary paresthesia (abnormal cutaneous sensations such as tingling, burning, stinging, numbness, and 

itching) that is limited to the area of contact. Available animal data do not indicate that pyrethrins or 

pyrethroids significantly affect end points other than the nervous system, although changes in liver weight 

and metabolism of chemicals have sometimes been used as an index of adverse effect levels for 

pyrethroids. Results of a few recent animal studies suggest that neurodevelopmental, reproductive, and 

immunological effects may result following exposure to some pyrethroids at levels below those that 

induce overt signs of neurotoxicity. Available data indicate that pyrethrins may be a carcinogenic 

concern to humans. No human data are available regarding the potential for pyrethroids to cross the 

placental barrier and enter a developing fetus. Limited animal data indicate that transfer of pyrethroids 

across the placenta to the fetus may occur. Although pyrethroids have not been identified in human breast 

milk, very low levels of pyrethroids (<1% of an orally administered dose) are excreted into milk of 

lactating animals. 

Neurological Effects. Pyrethrins and pyrethroids act principally on the sodium channels of nerve 

cells in exerting their toxic effects. Two different types of pyrethroids are recognized, based on 

differences in basic structure (the presence or absence of a cyano group in the alpha position) and the 

symptoms of poisoning in laboratory rodents. Type I pyrethroids do not include a cyano group; their 

effects typically include rapid onset of aggressive behavior and increased sensitivity to external stimuli, 

followed by fine tremor, prostration with coarse whole body tremor, elevated body temperature, coma, 

and death. The term T-syndrome (from tremor) has been applied to Type I responses. Clinical signs of 

neurotoxicity in animals exposed to pyrethrins are similar to those of Type I pyrethroids. Type II 
 

 

PYRETHRINS AND PYRETHROIDS 17 

2. RELEVANCE TO PUBLIC HEALTH 

pyrethroids include a cyano group; their effects are usually characterized by pawing and burrowing 

behavior, followed by profuse salivation, increased startle response, abnormal hindlimb movements, and 

coarse whole body tremors that progress to sinuous writhing (choreoathetosis). Clonic seizures may be 

observed prior to death. Body temperature usually is not increased, but may decrease. The term 

CS-syndrome (from choreoathetosis and salivation) has been applied to Type II responses. In general, the 

distinction between Type I and Type II pyrethroids is clear. However, two of the cyano-pyrethroids, 

fenpropathrin and cyphenothrin, have been shown to trigger responses intermediate to those of T- and 

CS-syndrome, characterized by both tremors and salivation. These neurological responses to pyrethroid 

poisoning are typically of acute duration. There is no evidence to indicate that long-term, low-level 

exposure of adults to pyrethroids might result in more severe neurological effects. 

Whereas distinctive signs of these neurotoxic symptoms (T- and CS-syndrome) occur in humans 

diagnosed with mild to severe pyrethroid poisoning, levels high enough to trigger these symptoms are not 

likely to occur under most exposure scenarios. Pyrethroids (particularly Type II pyrethroids containing 

the cyano group) frequently induce paresthesia among individuals occupationally exposed via unprotected 

areas of the skin. This effect is often observed at exposure levels far below those in which other clinical 

signs of neurotoxicity might be expected to occur. Pyrethroid-induced parasthesia typically peaks within 

3–6 hours following dermal exposure and resolves within 12–24 hours. Some animal studies indicate that 

exposure to pyrethroids may result in other less overt signs of neurotoxicity, such as changes in startle 

and avoidance responses, altered levels of spontaneous motor activity, and changes in operant conditioned 

responses, which may occur at levels below those eliciting typical T- or CS-syndrome. 

Cancer. Increased incidences of thyroid follicular cell tumors were reported in male and female rats 

administered pyrethrins (57.57% pyrethrum extract) in the diet for 2 years. The female rats also exhibited 

increased incidences of hepatocellular adenomas and combined adenomas and/or carcinomas. In a review 

of this rat carcinogenicity study, the Cancer Assessment Review Committee for pyrethrins attributed the 

increased incidences of thyroid and liver tumors to pyrethrum treatment and classified pyrethrins as 

“likely to be a human carcinogen by the oral route.” 

Developmental Effects. Standard developmental studies have not elucidated typical signs of 

developmental toxicity in animals exposed to pyrethrins or pyrethroids. 

Eriksson and coworkers reported alterations in brain muscarinic receptor density and increased 

spontaneous activity in mice that had received oral (gavage) doses of pyrethroids during critical stages of 
 

PYRETHRINS AND PYRETHROIDS 18 

2. RELEVANCE TO PUBLIC HEALTH 

neonatal neurological development; however, limitations in study design and lack of success in 

duplicating the results render the studies of questionable value for the purpose of risk assessment. In 

utero exposure of rats resulted in cellular changes indicative of compromised immunological function. 

Reproductive Effects. Standard reproductive toxicity studies, including some that were performed 

for three successive generations, did not indicate that pyrethrins or pyrethroids might be of particular 

concern to reproductive success. However, a few recent studies have indicated that relatively low-level, 

intermediate-duration oral exposure of adult male laboratory animals to some Type II pyrethroids may 

result in damage to reproductive organs, abnormal sperm characteristics, reduced plasma testosterone 

levels, and reduced fertility. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Inhalation MRLs 

No inhalation MRLs were derived for pyrethrins or pyrethroids for inhalation exposure since adequate 

data were not available for this route of exposure. 

Oral MRLs 

No oral MRLs were derived for pyrethrins since adequate data were not available. Oral MRLs were 

derived for selected pyrethroids, based on cleared reviews (Data Evaluation Records, DERs) of studies 

submitted to EPA by the pesticide industry and a study published in the open literature (McDaniel and 

Moser 1993. The DERs were used because the associated primary studies were not available to ATSDR 

for independent assessment. The MRLs were developed for specific technical-grade pyrethroids and may 

not be applied to a different composition of that pyrethroid or for a different pyrethroid. For example, the 

intermediate-duration oral MRL of 0.2 mg/kg/day that was derived for permethrin accounts for oral 

exposure to technical-grade permethrin (95.3% purity; isomeric ratio 50/50 cis/trans; corn oil vehicle). 

Isomeric ratio, administration vehicle, purity of the compound, and formulation of a pyrethroidcontaining pesticide must all be taken into account when assessing the risk of exposure. 
PYRETHRINS AND PYRETHROIDS 19 

2. RELEVANCE TO PUBLIC HEALTH 

Acute-duration Oral MRLs 

•	 An MRL of 0.3 mg/kg/day has been derived for acute-duration oral exposure (14 days or less) 

to permethrin (95% purity; 50/50 cis/trans). 

This MRL is based on a no-observed-adverse-effect level (NOAEL) of 25 mg/kg for neurological 

impairment in rats (McDaniel and Moser 1993). An uncertainty factor of 100 was used (10 for animal to 

human extrapolation and 10 to account for intrahuman variation). Groups of Long-Evans rats 

(8/sex/dose) were administered permethrin (95% purity; 50/50 cis/trans; in corn oil vehicle) in single 

gavage doses of 0, 25, 75, or 150 mg/kg. Selected rats from each dose group were subjected to functional 

observational battery (FOB) and motor activity assessment at 2 and 4 hours following dosing. A lowestobserved-adverse-effect level (LOAEL) of 75 mg/kg was identified for neurological impairment that 

included increased excitability and aggressiveness, abnormal motor movement, and decreased grip 

strength and motor activity. 

•	 An MRL of 0.02 mg/kg/day has been derived for acute-duration oral exposure (14 days or less) 

to cypermethrin (97% purity; 50/50 cis/trans). 

This MRL is based on a lowest-observed-adverse-effect level (LOAEL) of 20 mg/kg for neurological 

impairment in rats (McDaniel and Moser 1993). An uncertainty factor of 1,000 was used (10 for lack of a 

NOAEL, 10 for animal to human extrapolation, and 10 to account for intrahuman variation). Groups of 

Long-Evans rats (8/sex/dose) were administered cypermethrin (97% purity; 50/50 cis/trans; in corn oil 

vehicle) in single gavage doses of 0, 20, 60, or 120 mg/kg. Selected rats from each dose group were 

subjected to functional observational battery (FOB) and motor activity assessment at 2 and 4 hours 

following dosing. LOAEL of 20 mg/kg was identified for neurological impairment that statistically 

significantly altered gait and decreased motor activity. A NOAEL was not established. 

•	 An MRL of 0.01 mg/kg/day has been derived for acute-duration oral exposure (14 days or less) 

to cyhalothrin. 

This MRL is based on a NOAEL of 1 mg/kg/day for gastrointestinal effects (diarrhea) in dogs (EPA 

1981). An uncertainty factor of 100 was used (10 for animal to human extrapolation and 10 to account 

for intrahuman variation). Groups of 4–5-month-old male and female beagle dogs (6/sex/dose) were 

administered cyhalothrin (in corn oil vehicle) in gelatin capsules at doses of 0, 1.0, 2.5, or 10.0 mg/kg/day 

for 26 weeks. The dosing volume was 0.1 mL/kg body weight. A dose-related increase in diarrhea was 

observed as early as the first week of treatment, and persisted throughout the study (7, 26, and 39% 
PYRETHRINS AND PYRETHROIDS 20 

2. RELEVANCE TO PUBLIC HEALTH 

greater incidences of diarrhea in low-, mid-, and high-dose dogs, respectively, relative to controls). The 

7% increased incidence of diarrhea at the 1.0 mg/kg/day dose level may not be a clear indication of an 

adverse treatment-related effect. However, the 26% increased incidence of diarrhea at 2.5 mg/kg/day is 

considered to represent a definitive adverse effect. Thus, the 2.5 mg/kg/day dose level is considered a 

LOAEL for gastrointestinal effects. A detailed description of the test substance was not provided in the 

study. The acute-duration oral MRL is based on the assumption that the test substance consisted of 

technical-grade cyhalothrin with a purity of approximately 90%. 

Intermediate-duration Oral MRLs 

•	 An MRL of 0.2 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to permethrin (technical grade, approximately 95% assumed purity; 50/50 cis/trans). 

This MRL is based on a NOAEL of 15.5 mg/kg/day for neurological impairment in rats (EPA 1994b). 

An uncertainty factor of 100 was used (10 for animal to human extrapolation and 10 to account for 

intrahuman variation). Groups of Sprague-Dawley rats (10/sex/dose) were administered permethrin 

(technical grade; 50/50 cis/trans) in the diet for 13 weeks at concentrations of 0, 250, 1,500, or 2,500 ppm 

(respective time-weighted average doses of 0, 15.5, 91.5, or 150.4 mg/kg/day for males and 0, 18.7, 

111.4, or 189.7 mg/kg/day for females). Hindlimb splay was observed as early as days 38 and 18 in some 

1,500-ppm males and females, respectively. Other signs of neurotoxicity in the 1,500-ppm rats first 

appeared between treatment days 35 and 68. Signs of neurotoxicity appeared earlier and were more 

prevalent in rats of the 2,500-ppm treatment group. There were no signs of neurotoxicity in rats of the 

250-ppm treatment group. This study identified a LOAEL of 1,500 ppm (91.5 and 111.4 mg/kg/day in 

males and females, respectively) for neurotoxicity. 

•	 An MRL of 0.01 mg/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to cyhalothrin. 

This MRL is based on a NOAEL of 1 mg/kg/day for gastrointestinal effects (diarrhea) in dogs (EPA 

1981). An uncertainty factor of 100 was used (10 for animal to human extrapolation and 10 to account 

for intrahuman variation). Groups of 4–5-month-old male and female beagle dogs (6/sex/dose) were 

administered cyhalothrin (in corn oil vehicle) in gelatin capsules at doses of 0, 1.0, 2.5, or 10.0 mg/kg/day 

for 26 weeks. The dosing volume was 0.1 mL/kg body weight. A dose-related increase in diarrhea was 

observed throughout the study (7, 26, and 39% greater incidences of diarrhea in low-, mid-, and high-dose 

dogs, respectively, relative to controls). The 7% increased incidence of diarrhea at the 1.0 mg/kg/day 

dose level may not be a clear indication of an adverse treatment-related effect. However, the 26% 
PYRETHRINS AND PYRETHROIDS 21 

2. RELEVANCE TO PUBLIC HEALTH 

increased incidence of diarrhea at 2.5 mg/kg/day is considered to represent a definitive adverse effect. 

Thus, the 2.5 mg/kg/day dose level is considered a LOAEL for gastrointestinal effects. A detailed 

description of the test substance was not provided in the study. The intermediate-duration oral MRL is 

based on the assumption that the test substance consisted of technical-grade cyhalothrin with a purity of 

approximately 90%. 

Chronic-duration Oral MRLs 

No clinical signs of neurotoxicity were observed in rats administered permethrin (93.9% purity; 

40/60 cis/trans ratio) in the diet for two years at concentrations up to 1,000 ppm (Ishmael and Litchfield 

1994). This study was not used as the basis of a chronic-duration oral MRL because the concentrations of 

permethrin in the diet were not adjusted for decreased food consumption as the rats aged. However, 

during the second year of treatment, when the rats consumed considerably less food per kilogram of body 

weight, the permethrin doses were approximately 40 mg/kg/day for male and female rats. Thus, a 

NOAEL of at least 40 mg/kg/day was identified in this study. For this reason, the intermediate-duration 

oral MRL of 0.2 mg/kg/day that was based on a NOAEL of 15.5 mg/kg/day should be protective for 

chronic-duration oral exposure to permethrin with a purity approaching 95% and approximately equal 

amounts of cis and trans isomers. 

An average daily intake (AVDI) of 36–71 ng/kg/day has been estimated for permethrin (see Table 6-4), 

the most frequently used pyrethroid in the United States (see Table 6-1). The acute- and intermediateduration oral MRLs of 0.2 mg/kg/day should be protective of acute- and intermediate-duration oral 

exposure to permethrin, with the exception of accidental or intentional ingestion of permethrin in amounts 

several orders of magnitude greater than those experienced during the normal consumption of food or 

drinking water containing permethrin residues. 

PYRETHRINS AND PYRETHROIDS 23 

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 pyrethrins and 

pyrethroids. 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. 

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 
PYRETHRINS AND PYRETHROIDS 24 

3. HEALTH EFFECTS 

"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. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of pyrethrins and 

pyrethroids are indicated in Table 3-2 and Figure 3-2. 

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

made for pyrethrins and pyrethroids. An MRL is defined as an estimate of daily human exposure to a 

substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a 

specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the 

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

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

effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and 

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

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

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

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

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

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

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

significant human exposure improve, these MRLs will be revised. 
 

PYRETHRINS AND PYRETHROIDS 25 

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. 

Pyrethrum, the natural extract of the flowers of Chrysanthemum cinerariaefolium and Chrysanthemum 

cocineum, contains six active insecticidal compounds called pyrethrins. Pyrethroids are synthetic analogs 

and derivatives of pyrethrins and represent a diverse group of over 1,000 powerful insecticides (MuellerBeilschmidt 1990). Although they are based on the chemical structure and biological activity of the 

pyrethrins, the development of synthetic pyrethroids has involved extensive chemical modifications that 

make these compounds more toxic and less degradable in the environment. The pyrethrins and some of 

the more common pyrethroids are listed in Table 2-1. Pyrethrins and pyrethroids pose relatively little 

hazard to mammals (including humans) by common routes of exposure at levels likely to be encountered 

in the environment or resulting from the normal use of pyrethrin- or pyrethroid-containing substances. 

Two different types of pyrethroids are recognized, based on differences in basic structure (the presence or 

absence of a cyano group) and the symptoms of poisoning in laboratory rodents (Coats 1990; Verschoyle 

and Aldridge 1980). In general, Type I pyrethroids do not include a cyano group, and clinical signs of 

Type I pyrethroid-induced toxicity include whole body tremors. Type II pyrethroids include a cyano 

group and are characterized by their elicitation of salivation and sinuous writhing (choreoathetosis). 

Toxicity among the various pyrethroids varies greatly, as is evidenced by the wide range in LD50 values 

(concentrations or doses that result in 50% mortality in exposed laboratory animals). These differences 

are dependent on a number of factors including specific pyrethroid, ratios of stereo and optical isomers 

within a given pyrethroid formulation, and vehicle. Acute oral LD50 values are generally lower in Type II 

than Type I pyrethroids, indicating a greater degree of toxicity for Type II pyrethroids. In the case of 

tetramethrin, like all other Type I pyrethroids, isomers of the 1R conformation are considerably more 

toxic than those of the 1S conformation. The 1S isomer can also inhibit toxicity by competitive inhibition 

at a number of stereospecific pyrethroid binding sites, thus preventing binding of the more toxic 1R 

isomer (Narahashi 1986). Furthermore, it has been observed that the cis isomers possess greater 

mammalian toxicity than the trans isomers. For Type II pyrethroids, the S conformation at the alpha 

carbon adjacent to the cyano group is considerably more toxic than the R conformation. Consult 

Chapter 4 for additional information regarding the structural properties of Type I and Type II pyrethroids. 

Neurological signs are typically the result of acute toxicity and do not appear to be significantly amplified 

following repeated low-level exposures. This may be a result of rapid metabolism and elimination of 
 

PYRETHRINS AND PYRETHROIDS 26 

3. HEALTH EFFECTS 

pyrethrins and pyrethroids by mammals. Available animal data indicate that the nervous system is the 

primary target of pyrethrin- or pyrethroid-induced toxicity. However, changes in liver weight and liver 

metabolism of chemicals have sometimes been used as an index of adverse effect levels for pyrethroids. 

In addition, a few recent studies indicate the potential for adverse neurodevelopmental, reproductive, and 

immunological effects at exposure levels below those expected to result in overt signs of neurotoxicity. 

Available data indicate that pyrethrins may be a carcinogenic concern to humans. 

Based on the wide range of differences in levels of animal toxicity to pyrethrins and various pyrethroids, 

factors related to chemical properties and exposure scenarios of a given pyrethroid must be taken into 

account when assessing health risk. Human exposure to pesticides such as pyrethrins and pyrethroids 

often involves simultaneous exposure to other chemicals, which may range from impurities in a technical 

grade of a particular pyrethrin- or pyrethroid-containing product to dispersal agents, wetting agents, 

solubility agents, and additional pesticides in a given end-formulated product. 

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

Two case reports were located in which death was associated with allergic reactions to dog shampoo 

products containing pyrethrins (Wax and Hoffman 1994). An 11-year-old girl, who had been diagnosed 

with asthma at 6 years of age, was asymptomatic when she began to wash her dog with a shampoo 

containing 0.2% pyrethrin. Within 10 minutes, the subject suffered a severe acute asthmatic attack and 

died <3 hours later, despite medical treatment (Wagner 2000). This girl had experienced a mild increase 

in asthmatic symptoms when she had used the same shampoo 2 years earlier. A 37-year-old female, who 

had a 10-year history of mild asthma that did not require chronic medication, developed severe shortness 

of breath 5 minutes after beginning to wash her dog with a shampoo containing 0.06% pyrethrin (Wax 

and Hoffman 1994). The subject quickly went into cardiopulmonary arrest and died a short time later, 

despite efforts to revive her. Postmortem examination revealed pulmonary findings consistent with 

reactive airway responses. The relative contributions of inhalation and dermal exposure routes were not 

addressed in these reports. No other reports were located regarding death in humans following inhalation 

exposure to pyrethrins or pyrethroids. 

Information regarding death in animals following inhalation exposure to pyrethrins or pyrethroids is 

mainly derived from studies designed to assess lethal toxicity in animals following airborne exposure to 
 

 

PYRETHRINS AND PYRETHROIDS 27 

3. HEALTH EFFECTS 

pyrethrins or pyrethroids for durations of 2–4 hours. In rats exposed to pyrethrum extract, an estimated 

airborne concentration in which death could be expected in 50% of the exposed animals (LC50) was 

3,400 mg/m3

 (Schoenig 1995). Most synthetic pyrethroids are more toxic than natural pyrethrins (the 

active neurotoxic components of pyrethrum extract). Results from studies of rats exposed to synthetic 

pyrethroids indicate LC50 values ranging from approximately 23 to 1,000 mg/m3

 (Curry and Bennett 

1985; Flucke and Thyssen 1980; Hext 1987; Kavlock et al. 1979; Pauluhn and Thyssen 1982). No 

specific patterns could be discerned regarding the relatively wide range of LC50 values among the various 

pyrethroids for which inhalation data were available. One series of studies assessed acute inhalation 

lethality of several Type I pyrethroids (Miyamoto 1976). In most cases, lethality was not observed 

following exposure to airborne pyrethroid concentrations ranging from 685 to 2,500 mg/m3

. In some 

cases, higher concentrations could not be attained. The only report of death was in rats and mice exposed 

to a mixture of (+)-allethronyl (+)-trans allethrin for 3 hours. LC50 values were 1,600 and 2,720 mg/m3 

for rats and mice, respectively, but minimum concentrations in which death was noted were not presented 

in the report. Miyamoto (1976) also assessed the toxicity of several Type I pyrethroids in rats and mice 

repeatedly exposed (2–4 hours/day, 5 days/week for 4 weeks) to atmospheres containing pyrethroid 

concentrations ranging from 6.1 to 210 mg/m3

. Although clinical signs of toxicity were noted at 

concentrations of 61.3 mg/m3

 (allethrin) and 200 mg/m3 (furamethrin), no exposure-related deaths 

occurred during the study period. 

3.2.1.2 Systemic Effects 

No reports were located in which cardiovascular, gastrointestinal, musculoskeletal, renal, endocrine, 

dermal, or ocular effects were associated with inhalation exposure of humans or animals to pyrethrins or 

pyrethroids. Systemic effects related to occupational exposure are generally associated with dermal 

exposure to pyrethrins or pyrethroids, and are therefore presented in Section 3.2.3.2. 

Respiratory Effects. Limited information was available regarding respiratory effects in humans 

following inhalation exposure to pyrethrins or pyrethroids. Hypersensitivity pneumonitis, characterized 

by pleuritic chest pain, nonproductive cough, and shortness of breath, was diagnosed in a 24-year-old 

woman following repeated indoor use of a pyrethrum-based insecticide (Carlson and Villaveces 1977). A 

pulmonary challenge test to the insecticide resulted in an itchy and runny nose within 2 minutes following 

initiation of exposure, but no cough or shortness of breath. Subsequent skin tests resulted in immediate 

skin reactions and allergic pulmonary responses to pyrethrum, but not to other ingredients in the 
 

 

PYRETHRINS AND PYRETHROIDS 28 

3. HEALTH EFFECTS 

insecticide. Signs of respiratory irritation, such as shortness of breath, cough, and congestion, were 

reported among five office workers, commencing upon entry into a building that had been treated for 

termites 2 days previously with a cypermethrin formulation that contained xylene-based aromatic 

petroleum solvents, trimethylbenzene, and paraffinic oils (Lessenger 1992). Symptoms worsened after 

the air-conditioning system was activated in an attempt to clear the air. It was determined that a portion 

of the insecticide had been injected into ventilation ducts. The possible influence of inert ingredients was 

not evaluated. Among 12 workers who sprayed lambda-cyhalothrin indoors, daily interviews following 

spraying on each of 6 consecutive days revealed 11 complaints of nasal irritation and 6 complaints of 

throat irritation (Moretto 1991). Coughing, dyspnea, increased nasal secretions, and sneezing were 

reported by plant nursery workers who used pyrethroids for treating conifer seedlings (Kolmodin-Hedman 

et al. 1982). Sniffles and sneezes were noted in subjects exposed to deltamethrin and fenvalerate while 

packaging the insecticides (He et al. 1988). 

Signs of respiratory irritation were reported in laboratory animals acutely exposed to aerosols of 

pyrethroids at lethal or near-lethal airborne concentrations (Curry and Bennett 1985; Flucke and Thyssen 

1980; Hext 1987; Pauluhn and Thyssen 1982). Intermediate-duration (90-day) repeated exposures of rats 

to mean analytical pyrethrin concentrations $30 mg/m3

 resulted in clinical and microscopic evidence of 

respiratory irritation; a no-effect level was 11 mg/m3

 (Schoenig 1995). More detailed information 

regarding respiratory effects was not available in the report. 

Hematological Effects. In studies available for review, no information was located regarding 

hematological effects in humans following inhalation exposure to pyrethrins or pyrethroids. Available 

information regarding adverse hematological effects in animals is limited to a single account in which 

anemia was indicated in rats repeatedly exposed to pyrethrins at mean analytical airborne concentrations 

$30 mg/m3

 for 90 days (Schoenig 1995). More detailed information regarding hematological effects was 

not available in the report. 

Hepatic Effects. In studies available for review, no information was located regarding hepatic effects 

in humans following inhalation exposure to pyrethrins or pyrethroids. Available information regarding 

hepatic effects in animals is limited to a single account in which increased liver weights were reported in 

rats repeatedly exposed to pyrethrins at a mean analytical airborne concentration of 356 mg/m3

 for 

90 days (Schoenig 1995). 
 

PYRETHRINS AND PYRETHROIDS 29 

3. HEALTH EFFECTS 

Body Weight Effects. No information was located regarding body weight effects in humans 

following inhalation exposure to pyrethrins or pyrethroids. Available information regarding body weight 

effects in animals is limited. Decreased body weight gains were reported in rats repeatedly exposed to 

pyrethrins at mean analytical airborne concentrations $100 mg/m3

 for 90 days (Schoenig 1995). 

3.2.1.3 Immunological and Lymphoreticular Effects 

Hypersensitivity pneumonitis, characterized by pleuritic chest pain, nonproductive cough, and shortness 

of breath, was diagnosed in a 24-year-old woman who was hospitalized for 2 weeks following repeated 

indoor use of a pyrethrum-based insecticide (Carlson and Villaveces 1977). In this patient, levels of 

antibodies IgG, IgM, and IgE were all elevated. Symptomatic treatment was employed, and a week after 

discharge, a pulmonary challenge test to the insecticide resulted in an itchy and runny nose within 

2 minutes following initiation of exposure, but no cough or shortness of breath. Subsequent skin tests 

resulted in immediate skin reactions and allergic pulmonary response to pyrethrum, but not to other 

ingredients in the insecticide. In a review of literature pertaining to pyrethrum (Moore 1975), it was 

noted that many individuals who were sensitive to ragweed were also sensitive to pyrethrum, but that the 

sensitization effect arose mainly from a volatile oil contained in the pyrethrum extract, not from the 

pyrethrins. On the other hand, pyrethrins were implicated in two cases of severe asthmatic reactions to 

exposure to dog shampoo products containing pyrethrins (Wagner 2000; Wax and Hoffman 1994). A 

45-year-old female animal keeper, who was suspected to be suffering from pesticide intoxication, 

indicated that she had been exposed to pyrethroid insecticides over a period of 13 years (Mitsche et al. 

2000). Upon skin (scratch) testing, dose-dependent allergic responses (wheals and flares) were elicited 

from the Type I pyrethroids, S-bioallethrin and permethrin. 

No animal studies were located in which inhalation exposure to pyrethrins or pyrethroids could be 

associated with immunological or lymphoreticular effects. 

3.2.1.4 Neurological Effects 

Shortness of breath, nausea, headache, and irritability were experienced by five office workers upon 

entering their work area 2 days after it had been sprayed with cypermethrin in an effort to eliminate 

termites (Lessenger 1992). The symptoms were exacerbated when the air-conditioning system was 
PYRETHRINS AND PYRETHROIDS 30 

3. HEALTH EFFECTS 

activated to ventilate the area, but levels of cypermethrin in the air were not measured. Signs of 

neurotoxicity have been associated with acute occupational (inhalation and dermal) exposure to various 

pyrethroids during outdoor or indoor spraying (Chen et al. 1991; He et al. 1991; Moretto 1991; Shujie et 

al. 1988; Zhang et al. 1991). In a cross-sectional survey on the prevalence of acute pyrethroid poisoning 

of cotton workers conducted in China in 1987 and 1988 (Chen et al. 1991), approximately 27% (696 of 

2,588) of the workers who sprayed pure pyrethroids reported having experienced symptoms such as 

abnormal facial sensations (paresthesia), dizziness, headache, nausea, loss of appetite, blurred vision, and 

tightness of the chest. Eight of these workers were diagnosed with mild acute pyrethroid poisoning, 

characterized in part by listlessness and muscular fasciculations. He et al. (1991) reported increased 

peripheral nerve excitability in cotton workers following 3 days of exposure to deltamethrin during 

spraying. Nerve excitability was assessed by presenting two sequential electrical stimuli of equal 

intensity and duration to the median nerve area of the wrist and recording the median nerve activity at the 

lateral side of the elbow. Following deltamethrin exposure, median nerve conduction measurements 

revealed a significant increase in the supernormal period, defined as a period after recovery of normal 

excitability (from a given action potential) during which an action potential induced by a second stimulus 

is higher in amplitude than the first action potential. In some of these studies, air concentrations of 

pyrethroids in the breathing zone of the sprayers were measured and ranged from approximately 0.005 to 

2.0 μg/m3

. However, one study reported air concentrations as high as 24 μg/m3 (Shujie et al. 1988). 

Among sprayers, dermal contact was considered to be the major source of exposure, although some of the 

sprayers also reported symptoms of nasal and laryngeal irritation (Moretto 1991). Facial paresthesia, 

dizziness, fatigue, miliary red facial papules, and sniffles and sneezes were noted in subjects exposed to 

deltamethrin and fenvalerate while packaging the insecticides (He et al. 1988). Air sampling indicated 

pyrethroid levels in the range of 0.005–0.055 mg/m3

, but dermal contact was also evident, and may have 

been the basis for increased signs of toxicity during summer months. 

In studies of acute lethality associated with inhalation exposure to pyrethrins or pyrethroids, neurological 

effects were observed at or near lethal exposure levels. However, most studies do not include doseresponse data for exposure levels much lower than those resulting in death. Tremors were observed in 

rats acutely exposed to pyrethrins at mean analytical airborne concentrations $2,100 mg/m3

, but not at a 

concentration of 690 mg/m3

 (Schoenig 1995). Acute exposure of rats to aerosols of a 13% formulation of 

cyhalothrin, at analytical concentrations ranging from 3.6 to 68 mg/m3

, resulted in dose-related increasing 

severity of neurological signs, ranging from temporary lethargy, abnormal posture, and salivation at the 

lowest concentration, to convulsions and death within 15 minutes postexposure at the highest 

concentration (Curry and Bennett 1985). Disturbed posture and abnormal motor activity were observed 
PYRETHRINS AND PYRETHROIDS 31 

3. HEALTH EFFECTS 

in rats exposed to aerosols of cyfluthrin for 4 hours at an analytical concentration of 17 mg/m3, the lowest 

level presented. A concentration of 735 mg/m3

, which was lethal to many of the rats, caused severe 

behavioral disturbances in surviving rats that continued for 3 days postexposure (Pauluhn and Thyssen 

1982). A group of female rats exhibited no signs of toxicity in response to acute exposure to cyfluthrin at 

an analytical concentration of 44 mg/m3 (Flucke and Thyssen 1980). Both male and female rats, similarly 

exposed to a concentration of 57 mg cyfluthrin/m3

, showed signs of restlessness and altered gait. Labored 

breathing, hyperactivity, and tremors were reported in rats repeatedly exposed (6 hours/day, 5 days/week 

for 90 days) to pyrethrins at a mean airborne concentration of 356 mg/m3

 (Schoenig 1995). Repeated 

6-hour inhalation exposures to atmospheres containing cyfluthrin concentrations of 10.5 mg/m3

 or higher 

resulted in dose-related unspecified clinical signs of behavioral disorders (Flucke and Thyssen 1980; 

Thyssen 1980). Occasional salivation was observed in rats repeatedly exposed to atmospheres of 

cypermethrin at a concentration of 50 mg/m3

; a concentration of 250 mg/m3 resulted in additional signs of 

neurotoxicity that included decreased activity, lacrymation, head and paw flicking, and tip toe gait (EPA 

1996). 

The highest NOAEL values and all LOAEL values from each reliable study for neurological effects in 

each species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

No reports were located regarding the following health effects in humans or animals following inhalation 

exposure to pyrethrins or pyrethroids: 

3.2.1.5 Reproductive Effects 

3.2.1.6 Developmental Effects 

3.2.1.7 Cancer 

3.2.2 Oral Exposure 

3.2.2.1 Death 

Among 573 cases of acute pyrethroid poisoning reported in China between 1983 and 1988, 344 cases 

with accidental poisoning were considered to have been largely due to ingestion of pyrethroids (He et al. 

1989). Four deaths were reported; two of these were related to occupational exposure. Peter et al. (1996) 
Table 3-1 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Inhalation 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/m3) (mg/m3) (mg/m3) Chemical Form 

ACUTE EXPOSURE 

Death 

1 Rat 1x Schoenig 1995 3400 (LC50) (CD) 4 hr Pyrethrum extract 

Neurological 

2 Rat 1x Schoenig 1995 2100 (tremors) 4 hr (CD) Pyrethrum extract 

690 

INTERMEDIATE EXPOSURE 

Systemic 

3 Rat 21 d EPA 1996 

Hemato 250 6 hr/d, 5 d/wk (Wistar) Cypermethrin 1:1 cis:trans 

(nose-only) 

Bd Wt 250 

Neurological 

4 Rat 21 d EPA 1996 

10 50 (salivation) 6 hr/d, 5 d/wk (Wistar) Cypermethrin 1:1 cis:trans 

(nose-only) 

a The number corresponds to entries in Figure 3-1.
 

Bd Wt = body weight; d = day(s); Hemato = hematological; hr = hour(s); LC50 = lethal concentration, 50% kill; x = time(s); wk = week(s)
 
10000 

Death Neurological Hematological Body Weight Neurological 

Figure 3-1. Levels of Significant Exposure to Pyrethrins and Pyrethroids - inhalation 

Acute (≤14 days) Intermediate (15-364 days) 

mg/m3 

1r 

2r 

1000 

2r 

3r 3r 

100 

4r 

10 4r 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog m-Mouse j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat h-Rabbit e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig a-Sheep s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow g-Guinea Pig 
 

PYRETHRINS AND PYRETHROIDS 34 

reported the death of a 30-year-old male approximately 2 days after he had consumed about 30 mL of 

deltamethrin. In another case, an adult male rapidly developed convulsions, became comatose, and died 

shortly after having accidentally ingested an unknown amount of 10% cypermethrin (Poulos et al. 1982). 

No other information was located regarding death in humans following oral exposure to pyrethrins or 

pyrethroids. 

Animal studies associate mortality with relatively high oral exposure to pyrethrins and pyrethroids. Acute 

oral LD50 values for total pyrethrins from undiluted pyrethrum extract were 2,370 and 1,030 mg/kg in 

male and female rats, respectively (Schoenig 1995). Acute oral LD50 values for pyrethroids in rats range 

from approximately 18 to >5,000 mg/kg (Casida et al. 1983; Metcalf 1995; Valentine 1990). The wide 

range in LD50 values is dependent on a number of factors including specific pyrethroid, ratios of stereo 

and optical isomers within a given pyrethroid formulation, and vehicle. For example, an acute oral LD50 

value of 3,801 mg/kg was reported for rats receiving a gavage dose of permethrin (45/55 cis/trans) neat, 

whereas the LD50 value was 584 mg/kg when the dose was administered in corn oil vehicle (DOD 1977). 

Acute oral LD50 values are generally lower in Type II than Type I pyrethroids, indicating a greater degree 

of toxicity for Type II pyrethroids. Pyrethroid-induced mortality appears to be influenced by ambient 

temperature. Acute oral LD50 values for cismethrin in female rats increased from 157 mg/kg at 4EC to 

197 mg/kg at 20EC and >1,000 mg/kg at 30EC (White et al. 1976). In a 4-week oral study, mortality was 

observed in rats after 3–5 days of daily oral administration of cyfluthrin at a dose level of 80 mg/kg/day 

(Flucke and Schilde 1980). In mice, repeated administration of fenvalerate, at a dose level of 

80 mg/kg/day, also resulted in mortality that was considered to be compound related (Cabral and Galendo 

1990). In 90-day oral studies, compound-related death was noted in rats and mice given diets containing 

pyrethrins at concentrations $10,000 ppm (800 and 1,900 mg/kg/day for rats and mice, respectively) 

(Schoenig 1995). Compound-related mortality was also reported in pregnant rats and rabbits repeatedly 

administered oral doses of pyrethrins (in 0.5% methyl cellulose) $150 and 600 mg/kg/day, respectively 

(Schoenig 1995). Three of four dogs died during an 8-week oral study in which pyrethrins were 

administered in the diet at a concentration of 6,000 ppm (approximate dose of 100 mg/kg/day) (Schoenig 

1995). One of six dogs, administered 1,000 ppm of fenvalerate in the diet (approximate dose of 

80 mg/kg/day), was euthanized in extremis during week 24 after exhibiting signs of extreme neurotoxicity 

(Parker et al. 1984b). One of six dogs, given daily oral doses of cyhalothrin at 3.5 mg/kg, was killed 

during week 46 of a 52-week oral dosing study, due to persistent pyrethroid-induced convulsions (Hext et 

al. 1986). Mortality was also observed during a 90-day oral exposure to permethrin in the diets of rats 

(DOD 1977). All 10 male and female rats in the projected 850 mg/kg/day exposure groups died during 

the study; actual doses were 505 and 870 mg/kg/day in males and females, respectively. Mortality was 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 35 

3. HEALTH EFFECTS 

not significantly increased in rats or mice administered permethrin in the diet at concentrations resulting 

in estimated daily doses of up to 104 mg/kg/day for 2 years in rats or 350 mg/kg/day for 98 weeks in mice 

(Ishmael and Litchfield 1988). 

Selected oral LD50 values for some pyrethroids are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

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

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

No reports were located regarding respiratory, cardiovascular, musculoskeletal, dermal, or ocular effects 

following oral exposure of humans or animals to pyrethrins or pyrethroids. 

Gastrointestinal Effects. Information regarding gastrointestinal effects following oral exposure is 

mainly limited to clinical signs following exposure to pyrethroids. Symptoms such as epigastric pain, 

nausea, vomiting, and diarrhea have been reported in human subjects who consumed relatively large 

quantities of pyrethroids (Gotoh et al. 1998; He et al. 1989). Diarrhea was reported in dogs ingesting 

pyrethroids in the diet at dose levels as low as 1–6 mg/kg/day for treatment periods ranging from 

13 weeks to 1 year (EPA 1981; IRIS 2003a, 2003b, 2003c). Gastritis and mucosal erosion and ulceration 

were observed in male mice fed esfenvalerate in the diet for 90 days at a concentration resulting in a mean 

dose of 106 mg/kg/day (EPA 1991a). 

Hematological Effects. Information regarding hematological effects following oral exposure is 

limited. Leukocytosis was observed in 15% of 235 human cases of pyrethroid poisoning in which blood 

tests were performed (He et al. 1989). In most animal studies that examined hematological end points, no 

significant alterations were observed. However, Shakoori et al. (1992a) reported significantly decreased 

red blood cell count, hemoglobin content, and mean corpuscular hemoglobin, as well as increased white 

blood cell count in rabbits following daily oral administration of fenvalerate at a dose level of 10 mg/kg 

for 7 days. Schoenig (1995) reported evidence of anemia in surviving dogs that were fed pyrethrins in the 

diet for 8 weeks at a concentration resulting in a dose level of approximately 100 mg/kg/day. Decreases 

in red blood cell counts, hemoglobin, and hematocrit were observed in male and female mice fed 

esfenvalerate in the diet for 90 days at a concentration resulting in mean doses of 106 and 113 mg/kg/day, 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

ACUTE EXPOSURE 

Death 

1 Rat once DOD 1977 

413 F (LD50) (NS) (GO) Permethrin (45/55 cis/trans) 

2 Rat once DOD 1977 

3801 F (LD50) (Sprague­ (G) Permethrin (45/55 cis/trans) Dawley)
 

3 Rat once DOD 1977 

383 M (LD50) (Sprague­ (GO) Permethrin (45/55 cis/trans) Dawley)
 

4 Rat once DOD 1977 

4892 M (LD50) (Long­ (G) Permethrin (45/55 cis/trans) Evans) b
 

2712 F (LD50) 

5 Rat once DOD 1977 

584 M (LD50) (Sprague- (GO) Permethrin (45/55 cis/trans) Dawley)
 

6 Rat 14 d b DOD 1977 

699 M (death in 6/6) (Sprague- (F) Permethrin (45/55 cis/trans) Dawley)
 769 F (death in 5/6) 

7 Rat 14 d DOD 1977 

515 F (death in 3/6 in first 5 days) (Long- (F) Permethrin (45/55 cis/trans) Evans)
 

8 Rat once Schoenig 1995 2370 M (LD50) (CD) 4 hr Pyrethrum extract b 

(NS) 1030 F (LD50) 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

LOAEL 

NOAEL Less Serious

(mg/kg/day) (mg/kg/day) 

Serious 

System (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Reference 

Chemical Form 

9 

10 

Systemic 

(LongEvans) 

Rat 

(SpragueDawley) 

Rat 

(F) 

14 d 

(F) 

14 d 

Hepatic 

Hepatic 186 

b 

M 

210 F 

218 (increased liver-to-body weight 

ratio) 

F 

379 (increased liver-to-body weight 

ratio) 

M 

369 

b 

(increased liver-to-body weight 

ratio) 

F 

DOD 1977 

Permethrin (45/55 cis/trans) 

DOD 1977 

Permethrin (45/55 cis/trans) 

11 

(SpragueDawley) 

Rat 

(GO) 

Gd 6-15 

1x/d Bd Wt 40 F 80 (suppressed maternal body 

weight gain, 33% lower than 

controls) 

F 

EPA 1994a 

Resmethrin 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Neurological 

12 Rat 14 d b DOD 1977 

186 M 379 M (muscle tremors) (Sprague­ (F) Permethrin (45/55 cis/trans) Dawley) b
 

210 F 369 F (muscle tremors) 

13 Rat 14 d b b DOD 1977 

185 M (muscle tremors) (Long- (F) 

92 M 

Permethrin (45/55 cis/trans) Evans)
 114 F 218 F (muscle tremors) 

14 Rat Gd 6-15 EPA 1988c 

(CD) 1x/d 75 F 

Pyrethrum extract 

(G) 

15 Rat Gd 6-15 EPA 1988c 

37.5 F 75 F (transient tremors 2/5 dams) (CD) 1x/d Pyrethrum extract 

(G) 

16 Rat Gd 7-16 EPA 1991b 

150 (Wistar) 1X/d Permethrin (40/60 cis/trans) 

(GO) 

17 Rat Gd 7-16 EPA 1991b 

50 F 150 F (tremors, head flicking, (Wistar) 1X/d

piloerection) Permethrin (40/60 cis/trans) 

(GO) 

18 Rat once EPA 1992b 

5 20 (tremors, salivation, ataxia) (Sprague- (GO) Esfenvalerate
 Dawley)
 

19 Rat Gd 6-15 EPA 1994a 

(Sprague­ 1x/d 80 F 

Resmethrin 

Dawley) (GO) 
a 

Key to Species 

figure (Strain) 

20 

(LongEvans) 

Rat 

21 

(LongEvans) 

Rat 

22 

(CD) 

Rat 

23 

(New 

Zealand) 

Rabbit 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

once 

(GO) 

once 

(GO) 

once 

(NS) 

Gd 7-19 

1x/d 

(G) 

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

LOAEL 

NOAEL Less Serious Serious 

System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

25 c 

20 

d 

(altered gait, decreased 

activity) 

75 (abnormal motor movements, 

decreased grip strength) 

710 M 

320 

b 

F 

25 F 100 (salivation, head arching, 

labored breathing in 1/16 does) 

F 

Reference 

Chemical Form 

McDaniel and Moser 1993
 

Permethrin 50:50 cis:trans
 

McDaniel and Moser 1993
 

Cypermethrin 50:50 cis:trans 

Schoenig 1995
 

Pyrethrum extract
 

EPA 1988c
 

Pyrethrum extract
 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Neurological 

24 Rabbit Gd 7-19 EPA 1988c 

150 F 300 F (tremors in 1/5 does, 11% (New 1x/d 

weight loss) Pyrethrum extract Zealand) (G)
 

Developmental 

25 Rat Gd 6-15 EPA 1988c 

75 (CD) 1x/d Pyrethrum extract 

(G) 

26 Rat Gd 6-15 EPA 1988c 

150 (CD) 1x/d Pyrethrum extract 

(G) 

27 Rat Gd 7-16 EPA 1991b 

150 (Wistar) 1X/d Permethrin (40/60 cis/trans) 

(GO) 

28 Rat Gd 6-15 EPA 1994a 

40 80 (slightly increased incidences (Beagle) 1x/d 

of skeletal variations, delayed Resmethrin

(GO) ossification) 

29 Rabbit Gd 7-19 EPA 1988c 

150 (New 1x/d Pyrethrum extract Zealand) (G)
 

INTERMEDIATE EXPOSURE 

Death 

30 Rat 90 d b DOD 1977 

505 M (death in 10/10) (Sprague­ (F) Permethrin (45/55 cis/trans) Dawley)
 870 F (death in 10/10) 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

LOAEL 

NOAEL Less Serious

(mg/kg/day) (mg/kg/day) 

Serious 

System (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Reference 

Chemical Form 

31 

Systemic 

(SpragueDawley) 

Rat 

(F) 

90 d 

Hepatic 73.6 

b 

M 

76.3 F 

243.5 

b 

(increased liver-to-body weight 

ratio) 

M 

250.7 (increased liver-to-body weight 

ratio) 

F 

DOD 1977 

Permethrin (45/55 cis/trans) 

32 

33 

(Wistar) 

Rat 

(Wistar) 

Rat 

(F) 

28 d 

(F) 

90 d 

Bd Wt 

Ocular 

Bd Wt 

1 F 

21.2 M 

5.4 M 21.2 (depressed body weight, 

10-16%) 

M 

EPA 1985a 

Cyhalothrin 

EPA 1985b 

Cyhalothrin 

34 

(CD) 

Rat 

(GO) 

Gd 6-15 

1x/d Bd Wt 15 F 

EPA 1986a 

Cyhalothrin 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

LOAEL 

NOAEL Less Serious

(mg/kg/day) (mg/kg/day) 

Serious 

System (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Reference 

Chemical Form 

35 

Systemic 

(Wistar) 

Rat continuous 

Bd Wt 9.2 

b 

M 

10.3 F 

EPA 1986b 

Cyhalothrin 

36 

(SpragueDawley) 

Rat 

(F) 

13 wk 

Bd Wt 150.35 

b 

M 

189.66 F 

EPA 1994b 

Permethrin 50:50 cis:trans 

37 

38 

(B6C3F1) 

Mouse 

(Beagle) 

Dog 

(F) 

90 d 

(C) 

26 wk 

1x/d 

Gastro 

Hemato 

Dermal 

Bd Wt 

Gastro 

Ocular 

30.5 

b 

M 

113 F 

30.5 

b 

M 

36.8 F 

30.5 

b 

M 

36.8 F 

30.5 

b 

M 

36.8 F 

1 

e 

10 

106 (mucosal erosion and 

ulceration, gastritis) 

M 

106 

b 

(decreased RBCs, hemoglobin, 

hematocrit) 

M 

113 (decreased RBCs, hemoglobin, 

hematocrit) 

F 

106 

b 

(dermatitis, hyperkeratosis, 

ulceration) 

M 

113 (dermatitis, hyperkeratosis, 

ulceration) 

F 

106 

b 

(50% suppressed body weight 

gain) 

M 

113 (35% suppressed body weight 

gain) 

F 

2.5 (diarrhea) 

EPA 1991a 

Esfenvalerate 

EPA 1981 

Cyhalothrin 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Bd Wt 10 

Neurological 

39 Rat >120 d EPA 1992c 

27 (hypersensitivity to sound) continuous (CD) Cypermethrin 

(F) 

40	 Rat 2 gen EPA 1994a 

(CD) continuous 70.8 

Resmethrin 

(F) 

41	 Rat 13 wk f b EPA 1994b 

15.49 M	 91.51 M (tremors, staggered gait, (Sprague- (F) hindlimb splay) Permethrin 50:50 cis:trans
 Dawley)
 18.66 F 

111.37 F (tremors, staggered gait, 

hindlimb splay) 

42	 Mouse 90 d b b EPA 1991a 

30.5 M	 106 M (tremors, staggered gait, (B6C3F1) (F) hindlimb splay) Esfenvalerate 

36.8 F 

113 F (multiple signs including 

tremors, convulsions, abnormal 

gait) 

43	 Dog 26 wk EPA 1981 

2.5	 10 (muscle tremors, (Beagle) 1x/d

incoordination) Cyhalothrin 

(C) 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Reproductive 

44 Rat 65 d Abd El-Aziz et al. 1994 

1 M (50% reduction in successful (albino) 1x/d 

impregnation) Deltamethrin 

(GW) 

45 Rat continuous b EPA 1986b 

9.2 M (Wistar) Cyhalothrin 

10.3 F 

46 Rat continuous EPA 1992c 

(CD) (F) 

45 

Cypermethrin 

47 Rat 2 gen EPA 1994a 

70.8 continuous (CD) Resmethrin 

(F) 

Developmental 

48 Rat Gd 6-15 EPA 1986a 

15 (CD) 1x/d Cyhalothrin 

(GO) 

49 Rat 2 gen EPA 1994a 

34.8 70.8 (decreased pup survival) continuous (CD) Resmethrin 

(F) 

50 Rat Gd 4-21 Malaviya et al. 1993 10 (increased levels of dopamine (Wistar) Ld 1-21

and muscarinic receptors in Fenvalerate 1x/day
 striatal membrane) (GO) 

51 Rat Gd 4-21 Malaviya et al. 1993 15 (increased levels of dopamine (Wistar) Ld 1-21

and muscarinic receptors in Cypermethrin 1x/day striatal membrane) (GO) 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

LOAEL 

NOAEL Less Serious

(mg/kg/day) (mg/kg/day) 

Serious 

System (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Reference 

Chemical Form 

52 

53 

(Wistar) 

Rat 

(Wistar) 

Rat 

(GO) 

Gd 4-21 

1x/day 

(GO) 

Gd 4-21 

1x/day 

15 

10 

(increased levels of muscarinic 

receptors in striatal membrane) 

(decreased levels of dopamine 

receptors in striatal membrane) 

Malaviya et al. 1993 

Cypermethrin 

Malaviya et al. 1993 

Fenvalerate 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(mg/kg/day)

LOAEL 

Reference 

Chemical Form 

Less Serious

(mg/kg/day) 

Serious 

(mg/kg/day) 

54 

55 

56 

57 

CHRONIC EXPOSURE 

Systemic 

Rat 2 yr

(Alpk/AP) (F) 

Rat 2 yr 

(CD) (F) 

Mouse 2 yr 

(CD-1) (F) 

Mouse 18 mo 

(CD-1) (F) 

Hemato 

Ocular 

Bd Wt 

Hemato 

Hepatic 

Ocular 

Bd Wt 

Hepatic 

b 

21.5 M 

23.1 F 

b 

21.5 M 

23.1 F 

21.5 M 

b 

4.6 F 

b 

130 M 

173 F 

b 

130 M 

173 F 

b 

130 M 

173 F 

51 F 

b 

13.8 M 

16.6 F 

23.1 F (decreased body weight, 

12.5%) 

b 

346 M (hepatic effects including 

increased liver weight, 

discoloration, vacuolar fatty 

changes) 

EPA 1985c 

Cyhalothrin 

EPA 1994c 

Pyrethrum extract 

EPA 1985d 

Cyhalothrin 

EPA 1994c 

Pyrethrum extract 

413 F	 (liver effects including 

increased liver weight, 

discoloration) 
a 

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

LOAEL 

NOAEL Less Serious

(mg/kg/day) (mg/kg/day) 

Serious 

System (mg/kg/day)

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Reference 

Chemical Form 

Bd Wt 686 

b 

M 

834 F 

58 

(CD-1) 

Mouse 

(F) 

85 wk 

Cardio 

Gastro 

Hepatic 

Renal 

Bd Wt 

137.9 

b 

M 

165.8 F 

137.9 

b 

M 

165.8 F 

137.9 

b 

M 

165.8 F 

137.9 

b 

M 

165.8 F 

137.9 

b 

M 

165.8 F 

EPA 1994d 

Resmethrin 
a 

Key to Species 

figure (Strain) 

59 

Neurological 

(CD) 

Rat 

60 

(Wistar) 

Rat 

61 

(SpragueDawley) 

Rat 

62 

(CD-1) 

Mouse 

63 

(CD-1) 

Mouse 

64 

(CD-1) 

Mouse 

65 

(Swiss) 

Mouse 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

2 yr 

(F) 

2 yr 

(F) 

104 wk 

(F) 

2 yr 

(F) 

18 mo 

(F) 

85 wk 

(F) 

2 yr 

(F) 

Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

LOAEL 

NOAEL Less Serious Serious 

System (mg/kg/day) (mg/kg/day) (mg/kg/day) 

b 

130 M 

173 F 

b b 

37.5 M 187.2 M (slight whole body tremors 

during first 2 weeks) 

40.2 F	 200.1 F (slight whole body tremors 

during first 2 weeks) 

b 

17 M 70 M (abnormal gait, muscular 

incoordination) 

20 F 

57.6 M 

b 

51 F 

b 

686 M 

834 F 

b 

137.9 M 

165.8 F 

b 

295.1 M 

348.1 F 

Reference 

Chemical Form 

EPA 1994c
 

Pyrethrum extract
 

Ishmael and Litchfield 1988
 

Permethrin (40/60 cis/trans)
 

Parker et al. 1984a
 

Fenvalerate
 

EPA 1985d 

Cyhalothrin 

EPA 1994c
 

Pyrethrum extract
 

EPA 1994d 

Resmethrin 

Ishmael and Litchfield 1988
 

Permethrin (40/60 cis/trans)
 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

66 Dog 1 yr EPA 1983 

100 1000 (tremors, incoordinated gait, (Beagle) (C) convulsions, excessive Permethrin (40/60 cis/trans) 

salivation) 

67 Dog 1 yr EPA 1987 

(Beagle) (F) 

5 

Esfenvalerate 

68 Dog 52 wk Hext et al. 1986 

0.5 3.5 (muscle tremors, ataxia) (Beagle) 1x/d Cyhalothrin 

(GO) 

69 Dog 52 wk IRIS 2003a 

5 15 (tremors, gait abnormalities, (Beagle) incoordination, disorientation, Cypermethrin 

hypersensitivity to sound) 
Table 3-2 Levels of Significant Exposure to Pyrethrins And Pyrethroids - Oral (continued) 

Exposure/ LOAEL

a Duration/ 

Key to Species Frequency NOAEL Less Serious Serious Reference 

figure (Strain) (Specific Route) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form 

Cancer 

70 Rat 2 yr b EPA 1994c 

42.9 M (CEL: thyroid follicular cell (CD) (F) adenomas) Pyrethrum extract
 

173 F (thyroid and liver tumors) 

a The number corresponds to entries in Figure 3-2. 

b Differences in levels of health effects and cancer effects between males and females are not indicated in Figure 3-2. Where such differences exist, only the levels of effects 

for the most sensitive gender are presented. 

c Used to derive an acute-duration oral minimal risk level (MRL) of 0.3 mg/kg/day for permethrin (95% purity; 50/50 cis/trans). The MRL was derived by dividing the NOAEL of 25 

mg/kg/day by an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for intrahuman variation). 

d Used to derive an acute-duration oral minimal risk level (MRL) of 0.02 mg/kg/day for cypermethrin (97% purity, 50/50 cis/trans, in corn oil vehicle). The MRL was derived by 

dividing the LOAEL of 20 mg/kg/day by an uncertainty factor of 1000 (10 for the use of a LOAEL, 10 for animal to human extrapolation and 10 for intrahuman variation). 

e Used to derive both an acute- and intermediate-duration oral minimal risk level (MRL) of 0.01 mg/kg/day for cyhalothrin. The MRL was derived by dividing the NOAEL of 1 

mg/kg/day by an uncertainty factor of 100 (10 for animal to human extrapolation and 10 for intrahuman variation). 

f Used to derive an intermediate-duration oral minimal risk level (MRL) of 0.2 mg/kg/day for permethrin. The MRL was derived by dividing the NOAEL of 15.5 mg/kg/day by an 

uncertainty factor of 100 (10 for animal to human extrapolation and 10 for intrahuman variation). 

B = both; Bd Wt = body weight; (C) = capsule; cardio = cardiovascular; d = day(s); (F) = feed; F = female; (G) = gavage; gastro = gastrointestinal; gen = generation; Gd = 

gestation day; (GO) = gavage in oil; (GW) = gavage in water; hemato = hematological; hr = hour(s); Ld = lactation day; LD50 = lethal dose, 50% kill; LOAEL = 

lowest-observed-adverse-effect level; M = male; mg/kg/day = milligram per kilogram per day; mo = month(s); NOAEL = no-observed-adverse-effect level; (NS) = not specified; 

ppd = post-parturition day; wk = week(s); x = time; yr = year(s) 
10000 

Death 

Figure 3-2. Levels of Significant Exposure to Pyrethrins and Pyrethroids - Oral 

Acute (≤14 days) 

Systemic

Gastrointestinal Hepatic Body Weight Neurological 

4r 

8r6r

1000 

5r 7r 1r 3r 10r 12r 22r 24h 

9r 10r 12r 13r 16r 17r 24h 

100 13r 23h 11r 19r 

17r 

14r 15r 20r 

11r 

20r 

15r 

23h 18r 21r 

10 

18r 

1 38d 

Permethrin 

0.1 

Cyhalothrin Cypermethrin 0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

mg/kg/day 

2r 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
1000 

Death Gastrointestinal Hematological Hepatic Dermal Ocular Body Weight Neurological Reproductive Developme

Figure 3-2. Levels of Significant Exposure to Pyrethrins and Pyrethroids - Oral (Continue

Intermediate (15-364 days) 

Systemic 

mg/kg/day 

30r 

31r 

36r 

100 37m 37m 37m 37m 42m 41r 

31r 40r 47r 49r 

46r 

49r 37m 37m 37m 37m 42m 39r 

33r 33r 

34r 41r 48r 51r 

10 38d 38d 43d 50r 

35r 45r 

33r 

38d 43d 

1 38d 32r 44r 

Permethrin 

0.1 

Cyhalothrin 0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
10000 

Cardiovascular Gastrointestinal Hematological Hepatic Renal Ocular Body Weight Neurological Cancer * 

Figure 3-2. Levels of Significant Exposure to Pyrethrins and Pyrethroids - Oral (Continued) 

Chronic (≥365 days) 

mg/kg/day 

1000 66d 

57m 63m 

57m 65m 

60r 

58m 58m 55r 58m 55r 58m 55r 58m 64m 59r 

100 66d 

61r 

56m 62m 70r 60r 

54r 54r 54r

61r 69d 57m

10

67d 69d 54r 68d 

1 

68d 

*Doses represent the lowest dose tested per study that produced a tumorigenic response and do not imply the existence of a threshold for the cancer endpoint. 

0.1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

 NOAEL - Animals NOAEL - Humans 

p-Pig h-Rabbit s-Hamster q-Cow a-Sheep g-Guinea Pig 
 

 

 

PYRETHRINS AND PYRETHROIDS 54 

3. HEALTH EFFECTS 

respectively (EPA 1991a). In a 6-month feeding study in dogs, decreased red blood cell counts and 

decreased hematocrit and hemoglobin were observed at a dietary concentration of fenpropathrin that 

resulted in a dose level of approximately 20 mg/kg/day (Parker et al. 1984b). Hematology and blood 

chemistry data from rats and mice, administered permethrin in the diet at concentrations resulting in 

estimated doses of up to 104 mg/kg/day for 2 years (rats) or 350 mg/kg/day for 98 weeks (mice), did not 

indicate significant treatment-related hematological effects (Ishmael and Litchfield 1988). Hematological 

effects were not seen in male or female rats fed cyhalothrin or pyrethrum extract in the diet for 2 years at 

concentrations resulting in cyhalothrin doses of 21.5 and 23.1 mg/kg/day (males and females, 

respectively) or total pyrethrin doses of 130 and 173 mg/kg/day (males and females, respectively) (EPA 

1985c, 1994c). 

In a number of oral animal studies that were performed for the pesticide industry and evaluated by the 

EPA, statistically significant hematological effects were attributed to adaptive responses rather than 

pyrethroid-induced hematotoxicity per se. However, treatment-related anemia was reported in mice 

treated for 90 days with esfenvalerate in the food, which resulted in doses of approximately 106– 

113 mg/kg/day (EPA 1991a). 

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

to pyrethrins or pyrethroids. Some animal studies indicated increased liver weights, congestion, 

hepatocellular hypertrophy, and other microscopic signs of liver changes in laboratory animals during 

intermediate- and chronic-duration oral exposure to pyrethrins or pyrethroids, particularly at dose levels 

also resulting in clinical signs of neurotoxicity (Hext et al. 1986; IRIS 2003d, 2003e; Ishmael and 

Litchfield 1988; Parker et al. 1984a, 1984b; Schoenig 1995). Increased liver enzyme activity has also 

been observed in some animal studies (EPA 1985a, 1985b, 1994c; Schoenig 1995). These hepatic effects 

may reflect, at least in part, an adaptive response similar to that seen following exposure to many other 

xenobiotics (Ishmael and Litchfield 1988; Okuno et al. 1986a). Increased liver weight and liver 

discoloration were noted in mice fed pyrethrum extract in the diet for 18 months at concentrations 

resulting in doses of total pyrethrins of approximately 346 and 413 mg/kg/day in males and females, 

respectively. The male mice also exhibited vacuolar fatty liver changes (EPA 1994c). 

Renal Effects. No studies were located regarding renal effects in humans following oral exposure to 

pyrethrins or pyrethroids. Available information regarding renal effects in animals is limited to a report 

of decreased kidney weights and tubular degeneration in rats consuming pyrethrins (from pyrethrum 

extract) in the diet at concentrations resulting in dose levels $320 mg/kg/day for 90 days (Schoenig 
 

 

 

PYRETHRINS AND PYRETHROIDS 55 

3. HEALTH EFFECTS 

1995), and a report of a small decrease in kidney weight in male rats receiving permethrin in the diet at 

concentrations resulting in estimated daily doses of 19.4–91.5 mg/kg for 2 years (Ishmael and Litchfield 

1988). However, the magnitude and statistical significance of these renal changes were not presented in 

these reports. In a 2-year feeding study reported by Sumitomo Chemical America, Inc., and summarized 

in IRIS (2003c), increased absolute and relative kidney weights were observed in male (but not female) 

rats fed fenpropathrin (in corn oil) at a dietary concentration of 600 ppm (calculated daily doses of 

22.8 and 23.98 mg/kg for males and females, respectively). 

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

exposure to pyrethrins or pyrethroids. Limited data were available regarding endocrine effects in animals 

following oral exposure to pyrethroids. Serum levels of the thyroid hormones T3 and T4 were 

significantly decreased in mice administered fenvalerate at a dose level of 120 mg/kg/day for 15 days 

(Maiti and Kar 1998). Akhtar et al. (1996) reported similar effects in rats administered bifenthrin or 

lambda-cyhalothrin at daily oral dose levels of 0.5 mg/rat (approximately 0.75 mg/kg/day) and 0.2 mg/rat 

(approximately 2 mg/kg/day), respectively, for 21 days. Lambda-cyhalothrin treated rats also exhibited a 

significantly decreased serum T3/T4 ratio, relative to controls. In addition, both bifenthrin and lambdacyhalothrin treatment resulted in significantly increased serum TSH levels, compared with control rats. 

The studies of Maiti and Kar (1998) and Akhtar et al. (1996) did not include dose-response information, 

nor were thyroid tissues examined. However, these studies indicate that pyrethroids may exert a direct or 

indirect influence on the thyroid. Pyrethroid-induced decreased plasma testosterone may also serve as an 

indication of potential for pyrethroid-mediated endocrine effects. Significantly reduced plasma 

testosterone levels were noted as early as day 14 in groups of male rats administered deltamethrin in oral 

doses of 1 or 2 mg/kg for 65 days, and remained lower than controls throughout 21 days of posttreatment 

observation (Abd El-Aziz et al. 1994). El-Khalek et al. (1999) observed significant decreases in plasma 

testosterone levels in rats administered cypermethrin in oral doses of 3.8 or 7.7 mg/kg/day for 65 days, 

also demonstrating that this effect lasted throughout 30 days of posttreatment observation. In a 2-year 

feeding study reported by Sumitomo Chemical America, Inc., and summarized in IRIS (2003c), absolute 

and relative pituitary weights were nearly doubled in male rats fed fenpropathrin (in corn oil) at a dietary 

concentration of 600 ppm (calculated daily dose of 22.8 mg/kg). Female rats of the 600 ppm group 

(calculated daily dose of 23.98 mg/kg) exhibited decreased absolute and relative ovary weights. 

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

oral exposure to pyrethrins or pyrethroids. Reduced body weights or body weight gains were reported in 

some studies of laboratory animals administered pyrethrins (from pyrethrum extract) for intermediate or 
PYRETHRINS AND PYRETHROIDS 56 

3. HEALTH EFFECTS 

chronic durations. For instance, decreased body weight gain and food consumption were observed in rats 

administered 3,000–20,000 ppm (total pyrethrins; approximately 320–1,600 mg/kg/day) in the diet for 

90 days. Decreased body weight and food consumption were noted in dogs administered total pyrethrins 

at 6,000 ppm (approximately 100 mg/kg/day) in the diet for 8 weeks. Decreased body weight was also 

reported in rats administered total pyrethrins at 3,000 ppm (approximately 250 mg/kg/day) in the diet for 

104 weeks. Weight loss was observed in rabbit does administered 600 mg total pyrethrins/kg/day on 

gestation days 7–19. In a 2-generation reproductive toxicity study involving dietary exposure, decreased 

body weights and food consumption were observed in F1 parental rats that had been exposed to pyrethrins 

during fetal and neonatal development, as well as premating, mating, and gestation. The reports of 

Schoenig (1995) did not include more detailed descriptions of body weight effects at dose levels that also 

resulted in clinical signs of neurotoxicity (Ishmael and Litchfield 1988; Parker et al. 1984a; Schoenig 

1995). 

The EPA (IRIS 2003c) reviewed a report by Sumitomo Chemical America, Inc. in which slightly reduced 

weight gain was noted in dogs administered fenpropathrin in the diet at dose levels $500 ppm 

(12.5 mg/kg/day) for 3 months. Ishmael and Litchfield (1988) reported initial decreases in body weight 

gain in rats and mice administered permethrin at 2,500 ppm in the diet for 2 years (rats) or a lifetime 

(mice), in the absence of apparent changes in food consumption. Estimated daily doses of permethrin 

were 91.5 and 103.8 mg/kg/day for male and female rats, respectively, and 295.1 and 348.1 mg/kg/day for 

male and female mice, respectively, based on body weight and food consumption values presented. The 

decreased body weight gain was seen only during the first 6 weeks of treatment in rats and sporadically 

during the first 52 weeks of treatment in mice. Parker et al. (1984a) observed significant decreases in 

mean body weight gain among rats fed fenvalerate at 1,000 ppm in the diet (approximate doses of 70 and 

80 mg/kg/day for males and females, respectively) from week 16 (males) and week 44 (females) through 

week 104. No treatment-related changes in food consumption were observed, and no treatment-related 

significant changes in body weight were seen in groups receiving #250 ppm of fenvalerate in the diet, 

relative to controls. Suppressed body weight gain was seen in male and female mice ingesting daily doses 

of esfenvalerate of 106 and 113 mg/kg, respectively, for 90 days (EPA 1991a). Female rats, administered 

cyhalothrin in the diet at a concentration resulting in a dose level of 23.1 mg/kg/day for 2 years, exhibited 

body weights that were 12.5% lower than controls (EPA 1985c). 
PYRETHRINS AND PYRETHROIDS 57 

3. HEALTH EFFECTS 

3.2.2.3 Immunological and Lymphoreticular Effects 

No reports were located in which immunological or lymphoreticular effects in humans could be 

specifically associated with oral exposure to pyrethrins or pyrethroids. See Section 3.2.1.3 for 

information regarding immunological effects in humans following exposures to pyrethrins or pyrethroids 

that were likely mixed (inhalation, dermal, and possibly oral). 

Information on immunotoxicity of selected pyrethroids is available from oral studies in rats, mice, and 

rabbits repeatedly administered pyrethroids at doses low enough that clinical signs of neurotoxicity were 

not observed (Blaylock et al. 1995; Demian 1998; Demian and El-Sayed 1993; Dési et al. 1986; 

Lukowicz-Ratajczak and Krechniak 1992). Dési et al. (1986) conducted a series of studies in rats and 

rabbits. In rats, a single oral dose of cypermethrin at 125 mg/kg resulted in statistically significant 

changes, which included suppression of the humoral immune response, decreases in rosette-forming 

lymphocytes and ratio of lymphocytes to leukocytes, and decreased relative spleen weight. Although 

doses of cypermethrin at 6.25, 12.5, or 25 mg/kg/day for 6 or 12 weeks did not result in significant 

changes in relative spleen weight, a significantly reduced humoral immune response was observed at the 

25 mg/kg/day dose level, and both the 12.5 and 25 mg/kg/day levels resulted in significant decreases in 

rosette-forming lymphocytes. Dose-dependent significant suppression of the humoral immune response 

in rabbits was observed by the end of week 1 of a study in which cypermethrin was administered orally to 

rabbits 5 days/week for 6 weeks at levels of 75, 150, or 300 mg/kg/day. 

Lukowicz-Ratajczak and Krechniak (1992) administered deltamethrin to female mice in oral doses of 

6 mg/kg/day for 84 days or 15 mg/kg/day for 14 days. Treatment at both dose levels resulted in 

significant immunosuppression of the humoral immune response and a significant decrease in enzyme 

activity in lymphocytes isolated from the lymph nodes and spleen. These effects occurred earlier in the 

treatment period in high-dose mice. Other signs of immunotoxicity included decreased numbers of 

splenic plaque-forming cells, decreased percentages of rosette-forming lymphocytes in lymph nodes and 

spleen, depressed cell-mediated immune response that was expressed as decreased swelling of the foot 

pad in response to deltramethrin exposure of mice previously immunized with sheep red blood cells, and 

decreased interleukin-1 activity. 

Demian and coworkers (Demian 1998; Demian and El-Sayed 1993) demonstrated dose-related 

deltamethrin-induced suppression of the humoral immune response, decreased numbers of splenic plaqueforming cells and rosette-forming lymphocytes, decreased total serum protein (as well as alpha-1-, 
PYRETHRINS AND PYRETHROIDS 58 

3. HEALTH EFFECTS 

alpha-2-, and gamma-globulins), and increased serum albumin content in male mice. Doses used by 

Demian and coworkers were described as being 0.1 and 0.2 of the oral LD50 value, but this value was not 

identified in the reports. 

Blaylock et al. (1995) assessed the immunotoxic potential of permethrin by examining immune responses 

of splenocytes from female mice that had been administered permethrin at 0–0.4 mg/kg/day (0–1% of the 

oral LD50 value) for 10 days. At the highest dose tested (0.4 mg/kg/day), significantly reduced mixed 

lymphocyte responses, T-lymphocyte cytotoxic activity, and natural killer cell activity were observed in 

the absence of significant treatment-related changes in spleen weights. The toxicological significance of 

these findings is uncertain because the mice were not assessed for compromised immune function. 

Severe leukopenia was observed in male rats orally administered cypermethrin at 40 mg/kg/day for 

90 days (Varshneya et al. 1992). A delayed type skin hypersensitivity test, performed on day 61 

(following intradermal injection of tuberculin on day 60), revealed 24 and 27% decreases in reactivity in 

the 20 and 40 mg/kg/day dose groups, respectively. Examination of organ weights revealed a significant 

decrease in relative spleen weight within the high-dose group. However, no definite treatment-induced 

effect was noticed in the humoral immune response. Madsen et al. (1996) reported increased numbers of 

antibody forming cells in the spleen and enhanced natural killer cell activity in rats administered 

deltamethrin at oral dose levels of 5 or 10 mg/kg/day for 28 days. See Section 3.2.2.6 for information 

regarding immunological effects in rats exposed via their mothers during gestation. 

The highest NOAEL values and all LOAEL values from each reliable study for immunological and 

lymphoreticular effects in each species and duration category are recorded in Table 3-2 and plotted in 

Figure 3-2. 

3.2.2.4 Neurological Effects 

In cases of accidental or intentional ingestion of relatively large quantities of solutions containing 

pyrethroids, neurotoxic signs such as headache, muscular fasciculations, convulsions, and coma have 

been reported (Gotoh et al. 1998; He et al. 1989; Peter et al. 1996). 

Numerous investigators have reported signs of neurotoxicity in laboratory animals administered lethal and 

sublethal oral doses of pyrethrins and pyrethroids. Two different types of pyrethroids are recognized, 
 

 

PYRETHRINS AND PYRETHROIDS 59 

3. HEALTH EFFECTS 

based on symptoms of poisoning and chemical structure (Coats 1990; Verschoyle and Aldridge 1980). 

Chapter 4 contains information regarding chemical properties of Type I and Type II pyrethroids. Type I 

pyrethroids induce neurological signs that include aggressive behavior and increased sensitivity to 

external stimuli, fine tremor, prostration with coarse whole body tremor, elevated body temperature, and 

coma. Pyrethrins induce neurological effects similar to those induced by Type I pyrethroids (Mbaria et al. 

1993; Schoenig 1995). Effects induced by Type II pyrethroids include pawing and burrowing behavior, 

profuse salivation, increased startle response, abnormal hindlimb movements, and coarse whole body 

tremor that progresses to sinuous writhing (choreoathetosis). The presence of a cyano group within 

Type II pyrethroids also distinguishes this group from Type I pyrethroids. However, fenpropathrin and 

cyphenothrin, which are considered to be Type II pyrethroids by the presence of a cyano group, induce 

intermediate neurological responses characterized by both tremors (typical of Type I pyrethroids) and 

salivation (typical of Type II pyrethroids) (Miyamoto et al. 1995; Wright et al. 1988). 

Acute oral dosing with Type I or Type II pyrethroids results in typical clinical signs of neurotoxicity 

within minutes to hours, with symptoms subsiding within several hours to a few days (EPA 1992b; 

Eriksson and Nordberg 1990; Hudson et al. 1986; Parker et al. 1983, 1984a, 1984b, 1985; Ray and 

Cremer 1979; Southwood 1984). Refer to Section 3.5.2 for a detailed discussion of mechanisms of 

toxicity associated with exposure to Type I and Type II pyrethroids. Several investigators reported 

typical signs of Type I or Type II pyrethroid poisoning in laboratory animals during repeated oral 

administration of pyrethrins or pyrethroids (from 2 days to 2 years), but there were few indications that 

repeated or continuous exposure might result in cumulative neurological effects (Cabral and Galendo 

1990; DOD 1977; EPA 1983, 1988c, 1991a, 1991b, 1994b; Flucke and Schilde 1980; Hext et al. 1986; 

IRIS 2003a, 2003b, 2003c; Ishmael and Litchfield 1988; Mohan et al. 1998; Parker et al. 1984a, 1984b; 

Schoenig 1995). For example, Ishmael and Litchfield (1988) administered permethrin in the diet of rats 

and mice for 2 years and a lifetime (up to 98 weeks), respectively. Male and female rats were 

administered permethrin at concentrations that resulted in daily doses of 19.4, 37.5, and 91.5 mg/kg/day 

and 19.1, 40.2, and 103.8 mg/kg/day, respectively. Estimated doses to male and female mice were 28.7, 

124.2, and 295.1 mg/kg/day and 42.8, 135.8, and 348.1 mg/kg/day, respectively. During the first 2 weeks 

of treatment, high-dose male and female rats exhibited slight whole body tremors, hypersensitivity to 

noise and other disturbances, and piloerection. These findings were not seen at lower dose levels. None 

of the groups of mice exhibited clinical signs of treatment-related neurotoxicity. Histological and 

ultrastructural examination of sciatic nerves at interim (52 weeks in rats, 26 and 52 weeks in mice) and 

terminal kills revealed no signs of permethrin-induced abnormalities. In a cancer bioassay, Cabral and 

Galendo (1990) administered fenvalerate (in arachis oil vehicle) to mice via gavage at 0, 40, or 
PYRETHRINS AND PYRETHROIDS 60 

3. HEALTH EFFECTS 

80 mg/kg/day for 2 years. Reported noncancer effects were limited, but included observation of 

choreoathetosis and salivation in high-dose female mice. Parker et al. (1984a) fed fenvalerate to rats at 

dietary concentrations ranging from 1 to 1,000 ppm (0.07–70 mg/kg/day in males and 0.08–80 mg/kg/day 

in females) for 2 years. Five of 50 high-dose male rats exhibited clinical signs of neurotoxicity (abnormal 

gait, ataxia, muscular incoordination) during weeks 3 and 4. There was no report of clinical signs of 

neurotoxicity in other treatment groups. 

Crofton et al. (1995) demonstrated the significance of vehicle in the expression of neurological effects in 

rats given single oral doses of deltamethrin. The lowest doses at which at least 50% of the exposed 

animals exhibited decreased motor activity (ED50) ranged from 5.1 mg/kg for deltamethrin in corn oil to 

>1,000 mg/kg for deltamethrin in methyl cellulose. 

Some investigators have assessed other aspects of neurotoxicity in animals administered oral doses of 

pyrethroids, often at doses much lower than those resulting in typical clinical signs. For example, Crofton 

and Reiter (1988) observed significant decreases in motor activity of rats following administration of a 

Type I pyrethroid (permethrin) at 200 mg/kg and Type II pyrethroids (cyfluthrin at 12.5 mg/kg, 

fenvalerate at 30 mg/kg, flucythrinate at 2.5 mg/kg, cypermethrin at 30 mg/kg, fluvalinate at 15 mg/kg, 

and a pyrethroid identified as RU26607 at 3 mg/kg). Crofton and Reiter (1988) also found that some of 

the pyrethroids tested affected the acoustic startle response by altering the amplitude or latency. In 

another rat study, a Type I pyrethroid (NAK 1901) enhanced the acoustic startle response amplitude in a 

dose-dependent manner, whereas a Type II pyrethroid (cypermethrin) had no effect on amplitude or 

latency, even at a dose level that elicited clinical signs (Hijzen et al. 1988). Hypersensitivity to sound was 

noted in some rats administered cypermethrin in the diet at a concentration resulting in daily intakes of 

27 mg/kg for 83 days (EPA 1992c). Reduced locomotion and rearing frequency were observed in rats 

administered fenvalerate at single oral doses of 10 mg/kg (Spinosa et al. 1999). No treatment-related 

effects were seen in passive avoidance. Husain et al. (1991) observed pronounced treatment-related 

changes in brain levels of the neurotransmitters noradrenaline and dopamine, as well as their acid 

metabolites, following oral administration of fenvalerate at doses of 5–20 mg/kg/day for 21 days. The 

changes did not appear to be either dose-related or region specific, although the brain regions most 

affected appeared to be those that contribute most significantly to motor function and aggression. 

Significant increases were noted in grouped total activity and individual nonambulatory (but not 

ambulatory) activity of male mice observed for 4 hours following single oral administration of permethrin 

at 50 mg/kg or fenvalerate at 30 mg/kg (Mitchell et al. 1988). These effects were observed in the absence 

of typical clinical signs of pyrethroid-induced neurotoxicity. In another set of behavioral paradigms in 
PYRETHRINS AND PYRETHROIDS 61 

3. HEALTH EFFECTS 

mice, fenvalerate, administered in single oral doses of 15–45 mg/kg (as little as 1/24 of the LD50 value), 

resulted in significantly increased startle response latency and decreased ambulation and rearing in open 

field (Mandhane and Chopde 1997). Dose-related increased immobility in tail-suspension test and 

attenuated haloperidol-induced catalepsy were also observed. Axonal damage was observed in peripheral 

nerves of laboratory animals that had been administered pyrethroids in oral doses sufficient to induce 

clinical signs of neurotoxicity; the damage resolved upon cessation of treatment (Calore et al. 2000; 

Parker et al. 1985; Rose and Dewar 1983). Although the typical primary Type I and Type II clinical 

responses to pyrethroid poisoning can be explained by the action of Type I and Type II pyrethroids on 

sodium channels, the basis for these other pyrethroid-associated neurological changes is not presently 

known (see Section 3.5.2 for a discussion of mechanisms of toxicity). 

The highest NOAEL values and all LOAEL values from each reliable study for neurological effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.5 Reproductive Effects 

No reports were located regarding reproductive effects in humans following oral exposure to pyrethrins or 

pyrethroids. 

No signs of exposure-related adverse effects on reproductive parameters, including male or female 

fertility indices, litter size, and numbers of viable and stillborn pups, were observed in a 2-generation 

reproductive study of rats administered pyrethrins (from pyrethrum extract) in the diet at concentrations 

up to 3,000 ppm (resulting in an average daily dose of approximately 240 mg/kg) (Schoenig 1995). No 

signs of reproductive toxicity were observed in a 3-generation reproductive toxicity study of 

fenpropathrin administered in the diet at concentrations up to 250 ppm (resulting in an average daily dose 

of approximately 25 mg/kg) (Hend et al. 1979). In another 3-generation reproductive toxicity study, rats 

were administered cyfluthrin in the diet at concentrations of 50, 150, or 450 ppm (resulting in average 

daily doses of 4, 11–14, or 35–40 mg/kg/day, respectively, in males and 5.5, 14–16, or 46–50 mg/kg/day, 

respectively, in females) (Loeser and Eiben 1983). Treatment-related reduced viability, decreased 

lactation, and decreased birth weight or weight gain were observed in some generations at concentrations 

$150 ppm. 
 

PYRETHRINS AND PYRETHROIDS 62 

3. HEALTH EFFECTS 

Some investigators have reported adverse effects in male reprodutive organs following intermediateduration oral exposure to pyrethroids at dose levels below those eliciting clinical signs of neurotoxicity. 

Abd El-Aziz et al. (1994) reported that male rats, administered deltamethrin in oral doses as low as 

1 mg/kg/day (the lowest level tested) for 65 days, exhibited significantly lower weights of testicles, 

seminal vesicles, and prostate gland than vehicle controls. Sperm analysis of treated rats revealed 

significantly reduced sperm cell concentration, live cell percentage, and motility index, and a significantly 

higher percentage of total sperm abnormalities, relative to controls. Plasma testosterone levels were 

significantly reduced as early as 14 days following the beginning of treatment, remaining significantly 

lower 21 days after treatment ceased. Male fertility was tested at the end of treatment and 60 days 

posttreatment. At both time points, the percentage of successful matings to untreated female rats was 

50% that of controls. 

Similarly, oral administration of cypermethrin to male rats at 3.8 and 7.7 mg/kg/day (El-Khalek et al. 

1999) and fenvalerate at 20 or 100 mg/kg/day (Hassan et al. 1993) for 65 days resulted in reduced male 

reproductive organ weights and significantly altered sperm characteristics. Hassan et al. (1993) also 

found reduced percentages of pregnancies in untreated female rats that were mated with fenvaleratetreated males, while El-Khalek et al. (1999) observed significant decreases in plasma testosterone levels 

in cypermethrin-treated rats. 

The highest NOAEL values and all LOAEL values from each reliable study for reproductive effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No reports were located regarding developmental effects in humans following oral exposure to pyrethrins 

or pyrethroids. 

Standard tests for developmental effects in animals following oral exposure to pyrethrins or pyrethroids 

provide little indication that pyrethrins or pyrethroids might pose a significant developmental toxicity 

concern. However, more focused testing has revealed some persistent neurotoxic effects in animals 

exposed in utero and or via lactation. 
 

PYRETHRINS AND PYRETHROIDS 63 

3. HEALTH EFFECTS 

Oral administration of pyrethrins (from pyrethrum extract) to female rats on gestation days 6–15 at doses 

in the range of 5–600 mg (total pyrethrins)/kg/day did not cause apparent developmental effects, even at 

doses in which maternal toxicity was observed (Schoenig 1995). However, high postimplantation loss 

was noted when pregnant rabbits were administered total pyrethrins at 600 mg/kg/day on gestation 

days 7–19 (Schoenig 1995). This dose level resulted in serious maternal toxicity (tremors, convulsions, 

and death). The World Health Organization (WHO 2001) reviewed the database for various pyrethroids 

and published a number of Environmental Health Criteria documents in which animal developmental 

toxicity studies (mostly unpublished or proprietary information from chemical organizations) provided 

little indication that pyrethroids might pose a developmental toxicity concern. The EPA evaluated a 

number of studies that included developmental toxicity end points, which are briefly summarized in 

documents in which reference doses (RfDs) were derived for selected Type I and Type II pyrethroids 

(IRIS 2003f). Cleared reviews (Data Evaluation Records) of some of the original studies, submitted to 

EPA as confidential business information, are available to the public. Most of the studies do not indicate 

that pyrethroids are of biologically significant developmental toxicity concern. However, decreased pup 

survival was noted in rats following parental exposure to resmethrin in the diet at a concentration 

resulting in a dose level of 70.8 mg/kg/day prior to mating and throughout gestation and lactation (EPA 

1994a). Gavage administration of resmethrin (80 mg/kg/day) to other rats during gestation days 

6–15 resulted in slightly increased incidences of skeletal variations and delayed ossification (EPA 1994a). 

No serious signs of fetotoxicity or teratogenicity were observed in fetuses of rats administered 

deltamethrin at doses of 1, 2.5, or 5 mg/kg/day during gestation days 6 through 15, although the highest 

dose level resulted in the death of 4/20 treated dams (Bhaumik and Gupta 1990). Oral administration of 

cypermethrin to pregnant rats at 2, 4, or 8 mg/kg/day on gestation days 6–15 resulted in neither maternal 

toxicity nor significant incidences of fetotoxicity or teratogenicity (Gupta 1990). Abdel-Khalik et al. 

(1993) reported significant dose-dependent postimplantation loss and retarded growth in fetuses of rat 

dams administered deltamethrin at oral dose levels of 1, 2.5, or 5 mg/kg/day on gestation days 6–15. 

However, since treatment-related significantly increased placental weight was noted at all dose levels, the 

investigators considered the developmental effects to have resulted, at least in part, from compromised 

placental tissues in treated dams. Kavlock et al. (1979) found no significant treatment-related signs of 

fetotoxicity or teratogenicity in fetuses of rat or mouse dams administered deltamethrin during major 

stages of organogenesis at dose levels up to and including those eliciting overt signs of maternal toxicity 

(up to 12 and 5 mg/kg/day in rat and mouse dams, respectively). In addition, deltamethrin administration 

to rat dams from gestation day 7 through lactation day 15, at daily oral doses of 2.5 or 5.0 mg/kg, resulted 

in no sign of adverse effects in 6-week-old female offspring that were subjected to open field 
PYRETHRINS AND PYRETHROIDS 64 

3. HEALTH EFFECTS 

measurements of activity and exploration, although a dose-related depression in growth was observed 

during the period of lactation. 

Eriksson and coworkers (Ahlbom et al. 1994; Eriksson and Fredriksson 1991; Eriksson and Nordberg 

1990; Talts et al. 1998a) reported altered locomotory behavior and changes in muscarinic acetylcholine 

(MACh) receptor density in the cerebral cortex of adult mice that had been exposed to bioallethrin or 

deltamethrin at oral gavage dose levels in the range of 0.21 to 0.7 mg/kg/day during neonatal stages of 

development (post partum days 6–10). No significant differences were observed in locomotion of 

17-day-old mice, relative to controls. However, when examined at 4 months of age, both bioallethrinand deltamethrin-treated mice exhibited significantly increased spontaneous locomotor behavior 

(Eriksson and Fredriksson 1991). In contrast to the findings in the 0.21–0.7 mg/kg dose groups, mice 

administered 42 mg bioallethrin/kg daily exhibited significant decreases in locomotion and total activity 

counts and no significant differences in densities of MACh receptor density. Underlying mechanisms 

responsible for the differences observed in low-dose groups (0.21–0.7 mg/kg) and mice in the 42 mg/kg 

dose group, a level approaching that which would be expected to result in overt clinical signs of 

neurotoxicity, could not be explained. Other investigators (Ray et al. 2002; Tsuji et al. 2002) were unable 

to duplicate the results of Eriksson and coworkers. 

Malaviya et al. (1993) observed significant increases in the levels of dopamine and muscarinic receptors 

of striatal membrane in rat pups that had been exposed to fenvalerate or cypermethrin in utero. In this 

study, pregnant dams were administered 10 mg fenvalerate/kg or 15 mg cypermethrin/kg on gestation 

days 5 through 21. These effects were more pronounced in pups that continued to be exposed via their 

mothers throughout 3 weeks of postpartum lactation. Other significant treatment-related effects in the 

brain included increased acetylcholinesterase activity and decreased activities of monoamine oxidase and 

Na+

- and K+-ATPase from gestational exposure to fenvalerate, decreases in monoamine oxidase and 

acetylcholinesterase during lactation in fenvalerate-exposed pups, and decreases in acetylcholinesterase 

and Na+

- and K+-ATPase during lactation in cypermethrin-exposed pups. The toxicological relevance of 

increased brain acetylcholinesterase activity is uncertain because cholinesterase levels are naturally highly 

variable. 

Moniz et al. (1990) demonstrated pyrethroid-induced disruption of avoidance learning (significantly 

decreased latency in avoidance to the dark area of a maze) in 97- and 104-day-old adult rats that had 

nursed from mothers exposed to cyhalothrin in the drinking water throughout the entire period of lactation 
PYRETHRINS AND PYRETHROIDS 65 

3. HEALTH EFFECTS 

at a level resulting in an estimated maternal cyhalothrin dose of 27 mg/kg/day. During the exposure 

period, no indication of neurotoxicity was seen in motor activity of dams or nursing pups. 

Santoni and coworkers reported treatment-related increases in natural killer (NK) cell and antibodydependent cytotoxic activity, impaired thymocyte function, and increased and decreased numbers of 

T cells in peripheral blood and spleen, respectively, in rats after their mothers had been orally 

administered cypermethrin during gestation at 50 mg/kg/day, a dose schedule that did not result in clinical 

signs of maternal toxicity (Santoni et al. 1997, 1998, 1999). In one phase of these studies, marked and 

long-lasting increases were noted in plasma adrenaline and noradrenaline concentrations of offspring 

(from treated dams) that were tested up to 90 days postpartum (Santoni et al. 1999). The toxicological 

significance of these results is uncertain. 

The highest NOAEL values and all LOAEL values from each reliable study for developmental effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.7 Cancer 

No reports were located regarding cancer in humans following oral exposure to pyrethrins or pyrethroids. 

Results of cancer bioassays in laboratory animals are mixed. Pyrethrum extract was not oncogenic in 

mice following dietary administration at total pyrethrin concentrations of up to 5,000 ppm (approximately 

850 mg/kg/day) for 18 months (EPA 1994c; Schoenig 1995). However, increased incidences of thyroid 

follicular cell tumors were reported in male rats administered pyrethrum extract in the diet at total 

pyrethrin concentrations of 1,000 ppm (approximately 42.9 mg/kg/day) and in both male and female rats 

receiving approximately 173 mg/kg/day (EPA 1994c; Schoenig 1995). The 3,000-ppm (173 mg/kg/day) 

group of female rats also exhibited increased incidences of hepatocellular adenomas and combined 

adenomas and/or carcinomas. In a review of this rat carcinogenicity study, the Cancer Assessment 

Review Committee for pyrethrins (EPA 1999) attributed the increased incidences of thyroid and liver 

tumors to pyrethrum treatment and classified pyrethrins as “likely to be a human carcinogen by the oral 

route.” 

Cancer bioassays of selected synthetic pyrethroids have also produced mixed results. Ishmael and 

Litchfield (1988) administered permethrin (40/60 cis/trans) in the diet to rats at concentrations of 500, 
 

 

PYRETHRINS AND PYRETHROIDS 66 

3. HEALTH EFFECTS 

1,000, or 2,500 ppm for 2 years and to mice at concentrations of 250, 1,000, or 2,500 ppm for a lifetime. 

The estimated daily doses in high-dose rats were 91.5 and 103.8 mg/kg/day for males and females, 

respectively, based on body weight and food consumption values presented. Estimated doses to the highdose mice were 295.1 and 348.1 mg/kg/day for males and females, respectively. There was no evidence 

for a carcinogenic effect in treated rats. The high-dose male (but not female) mice exhibited statistically 

significant elevated incidences of benign lung tumors (17/70 high-dose males versus 11/70 in controls). 

Cancer bioassays that employed a 25/75 (cis/trans) mixture of permethrin isomers at dietary 

concentrations resulting in permethrin doses of up to 250 mg/kg/day in both rats and mice revealed no 

evidence of carcinogenicity in rats and statistically significantly elevated incidences of benign lung 

tumors in female, but not male, mice (15/74 high-dose females versus 3/96 in controls). 

The World Health Organization (WHO 2001) reviewed the database for various pyrethroids and 

published a number of Environmental Health Criteria documents in which animal cancer bioassays 

(mostly proprietary information from chemical organizations) provided little indication that pyrethroids 

should be considered carcinogens. No indications of a carcinogenic effect were observed in other cancer 

bioassays of fenvalerate-treated rats (Parker et al. 1984a) and mice (Cabral and Galendo 1990; Parker et 

al. 1983). 

The Cancer Effect Levels are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

Two case reports were located in which death was associated with allergic reactions to dog shampoo 

products containing pyrethrins (Wagner 2000; Wax and Hoffman 1994). The relative contributions of 

inhalation and dermal exposure routes were not addressed. No other reports were located regarding death 

in humans following dermal exposure to pyrethrins or pyrethroids. 

Several studies designed to assess the lethality of pyrethrins and pyrethroids could not establish dermal 

LD50 values (exposure level resulting in death of 50% of the dosed animals), even when administered the 

highest concentrations possible for given pyrethrin- or pyrethroid-containing substances (see Kavlock et 

al. 1979; Litchfield 1985; Schoenig 1995). However, El-Elaimy (1986) observed 100% mortality within 

4 days among male rats exposed by daily dermal applications of cyfluthrin that resulted in daily doses of 
 

 

PYRETHRINS AND PYRETHROIDS 67 

3. HEALTH EFFECTS 

1,845 or 2,460 mg cyfluthrin/kg/day. Rats receiving daily doses of 615 or 1,250 mg/kg/day survived a 

7-day treatment period. Death was noted in 2/10 male mice within 48 hours following dermal application 

of 1,800 mg fenvalerate/kg (Mitchell et al. 1988). Acute dermal LD50 values for laboratory animals, 

listed by a secondary source (Metcalf 1995) for several pyrethroids, were considered to be >5,000 mg/kg, 

but dermal LD50 values for tefluthrin, cyhalothrin, and cyfluthrin were in the range of 148–696 mg/kg. 

However, primary sources for these values were not listed and could not be verified. Deaths in domestic 

cats have been associated with erroneous exposure to concentrated (45–65%) permethrin products 

designed to be used as flea treatment for dogs (Meyer 1999). The increased sensitivity of the cat to 

concentrated permethrin may be the result of less efficient hepatic glucuronidation (Whittem 1995), a 

second step in the metabolism of pyrethroids in mammalian systems. No other information was located 

regarding death in animals following dermal exposure to pyrethrins or pyrethroids. 

3.2.3.2 Systemic Effects 

No reliable reports were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, endocrine, or body weight effects in humans or animals following dermal 

exposure to pyrethrins or pyrethroids. 

Dermal Effects. Slight skin irritation was observed in workers in plants producing pyrethrum extract 

to be used as insecticide powders in an early study by McCord et al. (1921). Paresthesia (an abnormal 

cutaneous sensation sometimes described as tingling, burning, stinging, numbness, and/or itching) has 

been reported in individuals occupationally exposed to pyrethroids that contact the skin; however, 

paresthesia is generally considered to be a neurological effect, not a dermal effect (see Section 3.2.3.4). 

Reports were not located in which dermal exposure to pyrethrins or pyrethroids could be associated with 

other dermal effects in humans. 

Animal studies indicate that dermal exposure to pyrethrins or pyrethroids may result in slight dermal 

irritation, but they do not elicit strongly positive responses in standard dermal sensitization tests (see, for 

example, DOD 1977; Litchfield 1985; Schoenig 1995). 

Ocular Effects. No reliable reports were located regarding ocular effects in humans following dermal 

exposure to pyrethrins or pyrethroids. Some workers reported irritation of the eyes after dipping conifer 

seedlings into solutions containing fenvalerate or permethrin (Kolmodin-Hedman et al. 1982); however, 

control groups were not included in the survey. 
 

PYRETHRINS AND PYRETHROIDS 68 

3. HEALTH EFFECTS 

Animal studies indicate that pyrethrins and pyrethroids may cause mild ocular irritation upon contact with 

the eye (see, for example, DOD 1977; Litchfield 1985; Schoenig 1995). 

3.2.3.3 Immunological and Lymphoreticular Effects 

A single case report was located in which a 47-year-old farmer developed a hypersensitive response that 

included a widespread dermal rash after dipping sheep in a solution, the active component of which was 

flumethrin (Box and Lee 1996). The relative contributions of dermal and inhalation exposure were not 

indicated in the report. See Section 3.2.1.3 for information regarding immunological effects in humans 

following exposures to pyrethrins or pyrethroids that were likely mixed (inhalation, dermal, and possibly 

oral). 

No reports were located regarding immunological effects in animals following dermal exposure to 

pyrethrins or pyrethroids. 

3.2.3.4 Neurological Effects 

Paresthesia (an abnormal cutaneous sensation sometimes described as tingling, burning, stinging, 

numbness, and itching) has been widely reported among individuals occupationally exposed to 

pyrethroids (Flannigan and Tucker 1985; Flannigan et al. 1985b; Knox et al. 1984; LeQuesne and 

Maxwell 1980; Tucker and Flannigan 1983; see also Vijverberg and van den Bercken 1990 for a 

summary of available information on occupationally-induced paresthesia). This effect is considered to be 

the result of a direct effect on intracutaneous nerve endings following dermal exposure to pyrethroids 

(LeQuesne and Maxwell 1980; Wilks 2000). In a double-blind study of volunteers exposed to fenvalerate 

via application to the earlobe (0.081 mg/cm2

), the onset of cutaneous sensations occurred at 1 hour 

postapplication, peaked at 3–6 hours, and lasted approximately 24 hours (Knox et al. 1984). Sensations 

included numbness, itching, burning, tingling, and warmth. A similar time-course for paresthesia was 

noted among agricultural workers exposed during or shortly following the spraying of fenvalerate on field 

crops (Tucker and Flannigan 1983). Type I (permethrin) and Type II (cypermethrin, fenvalerate, and 

flucythrinate) pyrethroids have been shown to induce differing severity in paresthesia responses in 

volunteers exposed on separate days to each pyrethroid in doses of 0.13 mg/cm2

 (Flannigan and Tucker 

1985). The mildest responses were elicited by permethrin. Both cypermethrin and fenvalerate induced 
PYRETHRINS AND PYRETHROIDS 69 

3. HEALTH EFFECTS 

significantly more severe responses than those of permethrin. Responses to cypermethrin were 

significantly more severe than those induced by the other three pyrethroids (see Section 3.5.2 for a 

discussion of mechanisms responsible for differences in toxicity among various pyrethroids). 

Signs of mild acute pyrethroid poisoning include dizziness, headache, and nausea, in addition to 

paresthesia. These signs have been associated with acute occupational (inhalation and dermal) exposure 

to various pyrethroids during outdoor or indoor spraying (Chen et al. 1991; Moretto 1991; Shujie et al. 

1988; Zhang et al. 1991). Based on measurements of pyrethroids deposited on gauze pads during 

spraying, estimates of dermal deposits on exposed skin ranged from 0.013 to 0.347 μg/cm2

 (Chen et al. 

1991) and from <0.01 to 141.61 μg/cm2

 (Zhang et al. 1991). Although dermal exposure was considered 

to be the major source of exposure, inhalation exposure was also likely. Facial paresthesia, dizziness, 

fatigue, miliary red facial papules, and sniffles and sneezes were noted in subjects exposed to 

deltamethrin and fenvalerate while packaging the insecticides (He et al. 1988). Both inhalation and 

dermal exposures were likely, although increased toxicity during summer months was indication that 

dermal exposure may have been increased when greater areas of skin were exposed due to warmer 

weather. He et al. (1991) reported increased peripheral nerve excitability in individuals following 3 days 

of exposure to deltamethrin during spraying, in the absence of other clinical signs of acute pyrethroid 

poisoning. Higher levels of exposure to pyrethroids result in additional clinical signs such as listlessness, 

muscular fasciculations, and mild disturbance of consciousness, indicative of moderate acute pyrethroid 

poisoning (Chen et al. 1991; He et al. 1989). Even higher exposure levels may result in convulsive 

attacks and coma (severe acute pyrethroid poisoning), effects that may last for several weeks (He et al. 

1989). 

Limited information was available regarding neurological effects in animals following dermal exposure to 

pyrethrins or pyrethroids. El-Elaimy (1986) observed signs of pyrethroid poisoning (chewing, licking, 

and salivation) in groups of rats receiving daily dermal applications of cyfluthrin for up to 7 days. In this 

study, dose levels were 0, 615, 1,250, 1,845, and 2,460 mg cyfluthrin/kg/day. Pawing, whole body 

tremors, and choreoathetosis were noted at the two highest dose levels, which were also lethal. The 

description of the findings did not indicate whether clinical signs of neurotoxicity were seen at all dose 

levels. Significant increases were noted in grouped total activity and individual nonambulatory (but not 

ambulatory) activity of male mice observed for 4 hours following single dermal applications of 300 mg 

permethrin/kg or $600 mg fenvalerate/kg (Mitchell et al. 1988). These effects were observed in the 

absence of typical clinical signs of pyrethroid-induced neurotoxicity. Guinea pigs responded to dermal 

applications of permethrin or fenvalerate by licking, rubbing, scratching, or biting the area of application 
PYRETHRINS AND PYRETHROIDS 70 

3. HEALTH EFFECTS 

(Cagen et al. 1984). These behavioral responses were indicative of paresthesia (considered to result from 

a direct action of pyrethroids on sensory nerve endings), since these responses were elicited in the 

absence of visible signs of dermal irritation. 

3.2.3.5 Reproductive Effects 

No reports were located regarding reproductive effects in humans or animals following dermal exposure 

to pyrethrins or pyrethroids. 

3.2.3.6 Developmental Effects 

No reports were located regarding developmental effects in humans following dermal exposure to 

pyrethrins or pyrethroids. 

Available information regarding developmental effects in animals is limited to a single study in which 

1 mL of a 0.018% solution of cyhalothrin was applied daily to the skin of pregnant rats throughout 

gestation (Gomes et al. 1991a). Assuming a mature dam body weight of 0.32 kg (EPA 1988a), the initial 

dermal dose to the dams was approximately 56 mg/kg/day. A control group was similarly treated with 

vehicle only. Relative to controls, treated pups exhibited delays in development of fur, ear and eye 

opening, and testes descent into the scrotum. At weaning and 90 days of age, the frequency of 

spontaneous locomotion and active avoidance responses did not differ significantly among treated and 

control groups of offspring. However, when tested as adults for motivational responses, the total number 

of head-dips in a hole-board test (an index of motivational state) was decreased in offspring of treated 

dams, relative to control offspring. 

3.2.3.7 Cancer 

No reports were located regarding cancer in humans or animals following dermal exposure to pyrethrins 

or pyrethroids. 
PYRETHRINS AND PYRETHROIDS 71 

3. HEALTH EFFECTS 

3.3 GENOTOXICITY 

Limited information regarding the genotoxicity of natural pyrethrins was located in the studies available 

for review. As shown in Table 3-3, natural pyrethrins, tested in the standard Ames test in various 

Salmonella strains and in Escherichia coli with or without metabolic activation gave negative results 

(Moriya et al. 1983). 

Much more information has been generated regarding the genotoxic properties of both Type I and Type II 

pyrethroids. For example, administration of the Type I pyrethroids cismethrin (31 or 40 mg/kg) or 

bioresmethrin (1,000 mg/kg) to female Sprague-Dawley rats by gavage significantly increased the 

percentage of micronuclei in bone marrow (Hoellinger et al. 1987). In male and female CD-1 mice, 

intraperitoneal administration of a single dose of permethrin at up to 275 mg/kg failed to increase the 

percentage of micronuclei in bone marrow (Chruścielska and Kalhorn 1999). In a 28-day study in male 

Wistar rats, daily administration of permethrin (12.6, 50.3, or 125.7 mg/kg) by gavage significantly 

increased the number of chromosome aberrations in a dose-related manner (Institóris et al. 1999b). A 

commercial formulation of permethrin fed to the larva of Drosophila was mutagenic in the sex-linked 

recessive lethal mutation assay in Drosophila, affecting the DNA of both spermatogonia and 

spermatocytes (Kale et al. 1995). In contrast, in a study by Gupta et al. (1990), treating adult males 

resulted in no significant differences in frequencies of spontaneous mutations. The genotoxicity of Type I 

pyrethroids in vivo is summarized in Table 3-4. 

Several Type II pyrethroids have been tested for genotoxicity in mammalian systems (mostly to rats and 

mice) following oral, parenteral, or dermal administration of the compounds (Table 3-5). Tests conducted 

with cypermethrin showed that doses $30 mg/kg administered intraperitoneally significantly increased 

the incidence of chromosomal aberrations and micronuclei in bone marrow and the percent of sperm with 

head abnormalities (Bhunya and Pati 1988). A dose of 50 mg/kg by gavage, but not dermally, also 

induced chromosomal aberrations in bone marrow (Bhunya and Pati 1988). Of the three assays used by 

these investigators, the sperm abnormality test was found to be the most sensitive and the micronucleus 

test was determined to be the least sensitive. Chromosomal aberrations in mouse bone marrow and spleen 

cells have also been observed in other studies with higher doses of cypermethrin (Amer et al. 1993). 

Increased incidences of sister chromatid exchanges were also reported by Amer et al. (1993) in mouse 

bone marrow after an intraperitoneal dose of 180 mg cypermethrin/kg and by Chauhan et al. (1997) after 

a gavage dose of 32 mg cypermethrin/kg, but not 21.1 mg cypermethrin/kg. Experiments conducted with 

cypermethrin-dosed rats showed increased chromosomal aberrations in bone marrow after administration 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 72 

3. HEALTH EFFECTS 

Table 3-3. Genotoxicity of Pyrethrins In Vitro 

With Without 

Species (test system) Chemical End point activation activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium Pyrethrins Gene mutation – – Moriya et al. 1983
 

(TA100, TA98, TA1535, 

TA1537, TA1538)
 

Escherichia coli (WP2 hcr) Pyrethrins Gene mutation – – Moriya et al. 1983
 

– = negative result 
 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 73 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Type I Pyrethroids In Vivo 

Species 

(test system) Chemical End point Results Reference 

Eukaryotic organisms: 

Drosophila Permethrin Sex linked + Kale et al. 1995 

recessive lethal 

Drosophila Permethrin Sex linked – Gupta et al. 1990 

recessive lethal 

Mammalian cells: 

Rat bone marrow Bioresmethrin Micronuclei + Hoellinger et al. 1987 

Rat bone marrow Cismethrin Micronuclei + Hoellinger et al. 1987 

Rat bone marrow Permethrin Chromosomal + Institóris et al. 1999b
 

aberrations
 

Rat bone marrow Permethrin Micronuclei + Hoellinger et al. 1987
 

Mouse bone marrow Permethrin Micronuclei – ChruÑcielska and Kalhorn 1999 

– = negative result; + = positive result 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 74 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Type II Pyrethroids In Vivo 

Species (test system) Chemical End point Results Reference 

Eukaryotic organisms: 

Drosophila Cypermethrin Sex-linked recessive lethal ± Batiste-Alentorn et al. 

1986 

Drosophila Cypermethrin Sex-chromosome loss – Batiste-Alentorn et al. 

1986 

Drosophila Cypermethrin Non-disjunction – Batiste-Alentorn et al. 

1986 

Drosophila Supercyper- Sex-linked recessive lethal – Miadoková et al. 1992 

methrin 

Drosophila Supercyper- Sex-chromosome loss, – Miadoková et al. 1992 

methrin non-disjunction, frequency 

of deletion 

Mammalian systems: 

Rat bone marrow Cypermethrin Chromosomal aberrations + Institóris et al. 1999b 

Rat bone marrow Cypermethrin Chromosomal aberrations – Nehéz et al. 2000 

Mouse bone marrow Cypermethrin Chromosomal aberrations +, – Bhunya and Pati 1988 

Mouse bone marrow Cypermethrin Chromosomal aberrations + Amer et al. 1993 

Mouse spleen cells Cypermethrin Chromosomal aberrations + Amer et al. 1993 

Mouse bone marrow Cypermethrin Sister chromatid exchange + Chauhan et al. 1997 

Mouse bone marrow Cypermethrin Sister chromatid exchange + Amer et al. 1993 

Rat bone marrow Cypermethrin Micronuclei – Hoellinger et al. 1987 

Mouse bone marrow Cypermethrin Micronuclei + Bhunya and Pati 1988 

Mouse sperm Cypermethrin Cellular abnormalities + Bhunya and Pati 1988 

Rat bone marrow Deltamethrin Chromosomal aberrations + Agarwal et al. 1994 

Mouse bone marrow Deltamethrin Chromosomal aberrations + Bhunya and Pati 1990 

Mouse bone marrow Deltamethrin Chromosomal aberrations – Poláková and Vargová 

1983 

Mouse bone marrow Deltamethrin Sister chromatid exchange + Chauhan et al. 1997 

Rat bone marrow Deltamethrin Micronuclei + Agarwal et al. 1994 

Rat bone marrow Deltamethrin Micronuclei – Hoellinger et al. 1987 

Mouse bone marrow Deltamethrin Micronuclei + Bhunya and Pati 1990 

Mouse bone marrow Deltamethrin Micronuclei + Gandhi et al. 1995 

Rat testes Deltamethrin DNA fragmentation + El-Gohary et al. 1999 

Mouse sperm Deltamethrin Cellular abnormalities + Bhunya and Pati 1990 

Mouse Deltamethrin Dominant lethal mutations – Shukla and Taneja 

2000 
 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 75 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Type II Pyrethroids In Vivo 

Species (test system) Chemical End point Results Reference 

Rat bone marrow Fenpropathrin Micronuclei + Oraby 1997 

(Meothrin) 

Mouse bone marrow Fenpropathrin Micronuclei – Ryu et al. 1996 

Rat bone marrow Fenvalerate Chromosomal aberrations + Chatterjee et al. 1982 

Mouse bone marrow Fenvalerate Chromosomal aberrations + Ghosh et al. 1992 

Mouse bone marrow Fenvalerate Chromosomal aberrations + Pati and Bhunya 1989 

Mouse sperm Fenvalerate Cellular abnormalities + Pati and Bhunya 1989 

Mouse bone marrow Flumethrin Chromosomal aberrations +, – Nakano et al. 1996 

Mouse bone marrow Flumethrin Micronuclei +, – Nakano et al. 1996 

– = negative result; + = positive result; ± = weak positive result; +, – = both positive and negative results; 

DNA = deoxyribonucleic acid 
 

 

PYRETHRINS AND PYRETHROIDS 76 

3. HEALTH EFFECTS 

at 22.2 mg/kg/day for 28 days, but not at 11.1 mg/kg/day (Institóris et al. 1999b). However, Nehéz et al. 

(2000), also in a 4-week gavage study, did not find increases in chromosomal aberrations in bone marrow 

from rats treated with up to 22 mg cypermethrin/kg/day. No significantly increased incidences of 

micronuclei were observed in rat bone marrow following acute treatment by gavage with 15 mg 

cypermethrin/kg (Hoellinger et al. 1987). 

Studies of deltamethrin-dosed mice showed increased chromosomal aberrations and micronuclei in bone 

marrow cells as well as sperm abnormalities following acute intraperitoneal treatment with $10 mg/kg 

(Bhunya and Pati 1990). Increased sister chromatid exchanges were detected after a single 20 mg/kg 

dose, but not after doses of 13.2 mg/kg or lower (Chauhan et al. 1997). No statistically significant 

increase in dominant lethal mutation rate was seen in mice treated orally with 0.36, 0.72, or 1.08 mg 

deltamethrin/kg (Shukla and Taneja 2000). In rats, acute intraperitoneal administration of deltamethrin at 

$5.6 mg/kg induced micronuclei in bone marrow cells (Agarwal et al. 1994), but gavage administration of 

up to 20 mg/kg did not (Hoellinger et al. 1987). This is consistent with other experiments conducted by 

Agarwal et al. (1994) in which intraperitoneal and subcutaneous administration of deltamethrin 

($11.2 mg/kg) proved to be more efficient routes for inducing chromosomal aberrations than gavage. 

Deltamethrin also was shown to induce DNA fragmentation in sections of rat testes following 

intraperitoneal administration of 1 mg/kg/day (only level tested) for 21 days (El-Gohary et al. 1999). 

In mice dosed intraperitoneally, fenvalerate induced chromosomal aberrations in bone marrow cells at 

$32.5 mg/kg (Ghosh et al. 1992; Pati and Bhunya 1989), micronuclei at 150 mg/kg, and sperm 

abnormalities at 100 mg/kg (Pati and Bhunya 1989). Fenvalerate also induced chromosomal aberrations 

in rat bone marrow cells following gavage dosing at $50 mg/kg/day for 21 days (Chatterjee et al. 1982). 

Studies conducted with flumethrin in mice showed induction of chromosomal aberrations in bone marrow 

cells after a single dermal application of 5,325 mg/kg to a shaved area or a single intraperitoneal injection 

of 2,083 mg/kg, but not after repeated intraperitoneal injections of 128 mg/kg (Nakano et al. 1996). In 

contrast, micronuclei frequency was not significantly affected after a single dermal dose of 5,325 mg/kg, 

but was increased after repeated intraperitoneal doses of 128 mg/kg (Nakano et al. 1996). Additional 

studies found no significant change in chromosomal aberrations in mouse bone marrow following a single 

gavage administration of deltamethrin by gavage at up to 6.8 mg/kg (Poláková and Vargová 1983) or of 

micronuclei after an intraperitoneal dose of up to 105 mg fenpropathrin/kg (Ryu et al. 1996). However, 

14 daily doses of fenpropathrin by gavage at $0.074 mg/kg/day increased the frequency of micronuclei in 

rat bone marrow (Oraby 1997); a dose of 0.0074 mg/kg/day was without significant effect. 
PYRETHRINS AND PYRETHROIDS 77 

3. HEALTH EFFECTS 

A limited number of studies of Type II pyrethroids in Drosophila show mostly nonmutagenic results 

under the experimental conditions of the tests. Batiste-Alentorn et al. (1986) showed a significant 

increase in the frequency of sex-linked recessive lethal mutations after adult ingestion or larval feeding of 

cypermethrin. However, there were no significant increases in the frequency of sex-chromosome loss or 

nondisjunction. Similar negative results were reported by Miadoková et al. (1992). 

Many in vitro studies have also been conducted on both Type I and Type II pyrethroids (Tables 3-6 and 

3-7). Many papers investigated gene mutations in various Salmonella strains both with and without 

metabolic activation and, for the most part, the results did not indicate a mutagenic response. In yeast, 

results were inconsistent, although there was some evidence of mutations of mitochondrial DNA, 

particularly when commercial formulations were tested, but not when only the active ingredient was 

tested (Chruścielska et al. 1999). 

In vitro experiments in mammalian cells show a greater percentage of mutagenic effects than the bacteria 

and yeast studies (Tables 3-6 and 3-7). Investigations of human, pig, and cattle lymphocytes, Chinese and 

Syrian hamster cells, and mouse spleen cells were positive for several genetic end points. Chromosomal 

aberrations, sister chromatid exchange, increased micronuclei, DNA damage, C-mitosis induction, and 

other damage were all observed. However, as with the bacteria studies, no consistent pattern was seen 

that could relate genotoxicity to the presence or absence of metabolic activation of the pyrethroids by 

liver cells or enzymes. 

3.4 TOXICOKINETICS 

Pyrethroids have been classified into two major categories, Type I or Type II, based on distinct 

toxicological mechanisms (see Section 3.5.2 for details regarding the classification of pyrethroids). 

Although synthetic pyrethroids are all derivatives of the natural pyrethrins, they exhibit a wide structural 

diversity and some differences in their toxicokinetics. The differences are most apparent in the 

metabolism of individual pyrethroid compounds (see Section 3.4.3). Thus, while generalizations are 

made in the profile regarding the toxicokinetics of the major pyrethroid classes and the basis for these 

generalizations is provided, the reader is cautioned about applying these generalizations too strictly to 

specific pyrethroid compounds, even within a class. Relevant literature regarding the toxicokinetics of 

specific pyrethroid compounds is cited where appropriate to this review, and the reader is encouraged to 

pursue such literature if information is needed regarding specific pyrethroid compounds. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 78 

3. HEALTH EFFECTS 

Table 3-6. Genotoxicity of Type I Pyrethroids In Vitro 

With Without 

Species (test system) Chemical End point activation activation Reference 

Prokaryotic organisms: 

Escherichia coli	 Allethrin Gene mutation –a Moriya et al. 1983 

(WP2 her)
 

Salmonella typhimurium Allethrin Gene mutation –b Hour et al. 1998
 

(TA98, JK1)
 

S. typhimurium Allethrin Gene mutation +b Hour et al. 1998
 

(JK3, JK947)
 

S. typhimurium Allethrin Gene mutation –a Moriya et al. 1983
 

(TA98, TA1535, TA1537, 

TA1538)
 

S. typhimurium (TA100)	 Allethrin Gene mutation + + Moriya et al. 1983 

S. typhimurium Allethrin Gene mutation + – Herrera and 

(TA97, TA100, TA104) Laborda 1988
 

S. typhimurium Allethrin Gene mutation – – Herrera and 

(TA98, TA1535, TA1538, Laborda 1988
 

TA1537)
 

S. typhimurium Bioresmethrin Gene mutation – – Pluijmen et al. 1984 

(TA98, TA100) 

S. typhimurium Cismethrin Gene mutation – – Pluijmen et al. 1984 

(TA98, T100) 

E. coli (WP2 her)	 Permethrin Gene mutation –a Moriya et al. 1983 

S. typhimurium Permethrin Gene mutation – – Pluijmen et al. 1984
 

(TA98, TA100)
 

S. typhimurium Permethrin Gene mutation –a Moriya et al. 1983
 

(TA98, TA100, TA1535, 

TA1537, TA1538)
 

S. typhimurium Permethrin Gene mutation – Bartsch et al. 1980
 

(TA98, TA100)
 

S. typhimurium Permethrin Gene mutation – – Herrera and 

(TA97, TA98, TA100, Laborda 1988
 

TA104, TA1535, TA1537, 

TA1538)
 

S. typhimurium Resmethrin Gene mutation – – Pluijmen et al. 1984 

(TA98, TA100) 

S. typhimurium Resmethrin Gene mutation – – Herrera and 

(TA97, TA98, TA100, Laborda 1988
 

TA104, TA1535, TA1537, 

TA1538)
 

Eukaryotic organisms: 

Yeast (Strain A and HB)	 Ambush Mitochondrial + ChruÑcielska et al. 

25EC mutation 1999 

(Permethrin) 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 79 

3. HEALTH EFFECTS 

Table 3-6. Genotoxicity of Type I Pyrethroids In Vitro 

With Without 

Species (test system) Chemical End point activation activation Reference 

Yeast (Strain A and HB) Permethrin Mitochondrial – ChruÑcielska et al. 

mutation 1999 

Mammalian cells: 

Chinese hamster ovary Bioresmethrin Gene mutation	 – Pluijmen et al. 1984 

cells 

Chinese hamster ovary Cismethrin Gene mutation – Pluijmen et al. 1984 

cells 

Chinese hamster ovary Permethrin Chromosomal + Barrueco et al. 

cells aberrations 1994
 

Human lymphocytes Permethrin Chromosomal – + Barrueco et al. 

aberrations 1992
 

Human lymphocytes Permethrin Chromosomal + Barrueco et al. 

aberrations 1994
 

Human lymphocytes Permethrin	 Sister ± ± Barrueco et al. 

chromatid 1992
 

exchange
 

Human lymphocytes Permethrin Micronuclei + Barrueco et al. 

1992
 

Human lymphocytes Permethrin Micronuclei – Surrallés et al. 

1995
 

Human whole blood Permethrin Micronuclei – Surrallés et al. 

1995 

Chinese hamster ovary Permethrin Gene mutation – Pluijmen et al. 1984 

cells 

Chinese hamster ovary Resmethrin Gene mutation – Pluijmen et al. 1984 

cells 

a

Not clear whether tests were performed with or without activation. 

b

Tests assumed to be performed without activation because use of activation was not discussed in the study.
 

– = negative result; + = positive result; ± = weak positive result 
 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 80 

3. HEALTH EFFECTS 

Table 3-7. Genotoxicity of Type II Pyrethroids In Vitro 

Species With Without 

(test system) Chemical End point activation activation Reference 

Prokaryotic organisms: 

Salmonella 

typhimurium
 

(TA98, 100) 

S. typhimurium 

(TA98) 

S. typhimurium 

(TA100) 

S. typhimurium 

(TA98, TA100) 

S. typhimurium 

(TA98, TA100, 

TA1535, TA1537) 

S. typhimurium 

(TA98, TA100) 

S. typhimurium 

(TA97, TA98, TA100, 

TA1535, TA1538) 

Eukaryotic organisms: 

Yeast 

(Strains A and HB)
 

Yeast 

(Strains A and HB)
 

Yeast 

(Strains A and HB)
 

Yeast 

(Strains A and HB)
 

Yeast 

(Strains A and HB)
 

Yeast Strain D7
 

Yeast Strain D7
 

Yeast Strain D7
 

Yeast Strain D7
 

Yeast Strain D7
 

Cypermethrin 

Deltamethrin 

Deltamethrin 

Deltamethrin 

Fenpropathrin 

Fenvalerate 

Supercypermethrin 

Cypermethrin 

Fastac 10EC 

(10% alphacypermethrin) 

Deltamethrin 

Decis 2.5EC 

(2.5% deltamethrin) 

Karate 025EC 

(25 g/L lambdacyhalothrin) 

Supercypermethrin 

Supercypermethrin 

Supercypermethrin 

Supercypermethrin 

Supercypermethrin 

Gene mutation – 

Gene mutation – 

Gene mutation – 

Gene mutation – 

Gene mutation – 

Gene mutation – 

Gene mutation – 

Mitochondrial 

mutation 

Mitochondrial 

mutation 

Mitochondrial 

mutation 

Mitochondrial 

mutation 

Mitochondrial 

mutation 

Mitotic crossover 

Conversion at 

the tryptophan 

locus 

Conversion at 

the tryptophan 

locus 

Gene reversion 

mutations 

Point mutations 

at isoleucine 

locus 

– 

+ 

– 

– 

– 

– 

– 

± 

– 

+ 

+ 

± or – 

± or – 

+ 

+ 

+ 

Pluijmen et al. 1984 

Bartsch et al. 1980 

Bartsch et al. 1980 

Pluijmen et al. 1984 

Ryu et al. 1996 

Pluijmen et al. 1984 

Miadoková et al. 

1991 

ChruÑcielska et al. 

1999 

ChruÑcielska et al. 

1999 

ChruÑcielska et al. 

1999 

ChruÑcielska et al. 

1999 

ChruÑcielska et al. 

1999 

Vl...ková 1991 

Vl...ková 1991 

Miadoková et al. 

1992 

Vl...ková 1991 

Miadoková et al. 

1992 
 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 81 

3. HEALTH EFFECTS 

Table 3-7. Genotoxicity of Type II Pyrethroids In Vitro 

Species With Without 

(test system) Chemical End point activation activation Reference 

Mammalian systems: 

Human lymphocytes Cypermethrin	 Sister – Puig et al. 1989
 

chromatid 

exchange
 

Human lymphocytes Cypermethrin	 Micronuclei ± Surrallés et al. 1995 

Human whole blood Cypermethrin	 Micronuclei ± Surrallés et al. 1995 

Mouse spleen cells Cypermethrin	 Chromosomal + Amer et al. 1993 

aberrations 

Mouse spleen cells Cypermethrin	 Sister + Amer et al. 1993 

chromatid 

exchange 

Chinese hamster Cypermethrin Gene mutation – Pluijmen et al. 1984 

ovary cells 

Human lymphocytes Deltamethrin	 Sister ± Dolara et al. 1992 

chromatid 

exchange 

Human lymphocytes Deltamethrin	 Sister – – Villarini et al. 1998 

chromatid 

exchange 

Human lymphocytes Deltamethrin	 Micronuclei ± Surrallés et al. 1995 

Human lymphocytes Deltamethrin	 Micronuclei – – Villarini et al. 1998 

Human lymphocytes Deltamethrin	 DNA damage + ± Villarini et al. 1998 

Human whole blood Deltamethrin	 Micronuclei ± Surrallés et al. 1995 

Chinese hamster Deltamethrin	 Gene mutation – Pluijmen et al. 1984 

ovary cells
 

Chinese hamster Fenpropathrin Chromosomal – – Ryu et al. 1996
 

lung fibroblasts aberrations
 

Human lymphocytes Fenpropathrin	 Micronuclei ± Surrallés et al. 1995 

Human whole blood Fenpropathrin	 Micronuclei ± Surrallés et al. 1995 

Human lymphocytes Fenvalerate	 Chromosomal + Puig et al. 1989 

aberrations 

Chinese hamster Fenvalerate Chromosomal + – Caballo et al. 1992 

ovary cells aberrations 

Chinese hamster Fenvalerate Sister + + Caballo et al. 1992 

ovary cells chromatid 

exchange 

Human lymphocytes Fenvalerate Micronuclei – Surrallés et al. 1995 
 

 

 

PYRETHRINS AND PYRETHROIDS 82 

3. HEALTH EFFECTS 

Table 3-7. Genotoxicity of Type II Pyrethroids In Vitro 

Species With Without 

(test system) Chemical End point activation activation Reference 

Human whole blood Fenvalerate	 Micronuclei – Surrallés et al. 1995 

Human lymphocytes Fenvalerate	 C–mitosis + Carbonell et al. 

induction	 1989 

Chinese hamster Fenvalerate	 Gene mutation – Pluijmen et al. 1984 

ovary cells 

Pig lymphocytes Supermethrin	 Chromosomal + Dianovský and 

aberrations Šiviková 1997 

Cattle lymphocytes Supermethrin	 Chromosomal + Dianovský and 

aberrations Šiviková 1997 

Pig lymphocytes Supermethrin	 Sister – Dianovský and 

chromatid Šiviková 1997 

exchange 

Cattle lymphocytes Supermethrin	 Sister ± Dianovský and 

chromatid Šiviková 1997 

exchange 

Syrian hamster Supercyper- Morphological + SlameÁová et al. 

embryo cells methrin	 transformation 1992 

BHK21 (baby Supercyper- Anchorage + + SlameÁová et al. 

hamster kidney cells) methrin	 independent 1992 

growth 

– = negative result; + = positive result; ± = weak positive result; DNA = deoxyribonucleic acid 
PYRETHRINS AND PYRETHROIDS 83 

3. HEALTH EFFECTS 

Results of studies of volunteers and laboratory animals indicate that Type I and Type II pyrethroid 

compounds are absorbed from the gastrointestinal tract following oral exposure. Absorption is 

incomplete, with minimum estimates for absorption between 40 and 60% of an orally or intragastrically 

administered dose. However, first-pass metabolism may contribute significantly to under-estimation of 

the absorption of pyrethroids. Pyrethroids are rapidly absorbed in humans following inhalation exposure, 

but no estimates are available regarding how much of an inhaled dose is absorbed. Only small amounts 

(<2% of the applied dose) of pyrethroids are absorbed following dermal exposure, and the rate of 

absorption from this route is much slower than by the oral or inhaled routes. Pyrethroids may be stored in 

skin and then slowly released into the systemic circulation. Distribution of pyrethroids has not been well 

studied in humans; most of the available information is based on the results of studies in animals. 

Following absorption, pyrethroids are widely and rapidly distributed to most tissues, particularly to 

tissues with a high lipid content, and are concentrated in central and peripheral nervous tissues. Although 

there is little information on the metabolism of pyrethroids in humans, metabolism of pyrethroids has 

been extensively studied in animal models. The major metabolic pathways for pyrethroids are hydrolysis 

of the central ester bond, oxidative attacks at several sites, and conjugation reactions, to produce a 

complex array of primary and secondary water-soluble metabolites that undergo urinary excretion. 

Information on the specific enzymes involved in the metabolism of pyrethroid compounds is limited, but 

it appears to involve nonspecific microsomal carboxyesterases and microsomal mixed function oxidases, 

which are located in nearly all tissue types, with particularly high activities in the liver. Since microsomal 

enzymes play an important role in the metabolism of pyrethroids, it is expected that many tissue types are 

potentially capable of rapidly metabolizing these compounds. Elimination and excretion of pyrethroids in 

humans have not been extensively studied. Elimination appears to follow first-order kinetics, with 

elimination half-times in humans ranging from 6.4 to 16.5 hours, depending upon the specific pyrethroid 

and the exposure route studied. For most pyrethroids, elimination is nearly complete within 5 days of 

exposure, although certain isomers can persist in the body for a longer period of time. Pyrethroids have 

been shown to undergo urinary and fecal excretion in humans, but other routes of excretion, such as 

exhalation of volatile products, have not been studied. In animals, Type I and Type II pyrethroids 

undergo urinary, fecal, and biliary excretion, with urinary and fecal excretion as the primary routes; small 

quantities are also excreted in milk. Pyrethroids do not appear to be excreted as parent compounds via 

expired air of animals. 
 

PYRETHRINS AND PYRETHROIDS 84 

3. HEALTH EFFECTS 

3.4.1 Absorption 

Pyrethrins and pyrethroids are used to control insects in agricultural, commercial, and houshold 

environments. Since aerial application is the typical method by which pyrethrin- and pyrethroidcontaining substances are dispersed, the use of such substances may result in combinations of inhalation, 

oral, and dermal exposure. 

3.4.1.1 Inhalation Exposure 

Several studies demonstrate absorption of Type I and Type II pyrethroids following occupational 

exposure through identification of pyrethroid metabolites in urine (Aprea et al. 1997; Chester et al. 1987, 

1992; Kühn et al. 1999; Leng et al. 1996, 1997b). In some cases, plasma levels of pyrethroids were below 

the limits of detection (5 μg/L) (Leng et al. 1997a, 1997b). Absorption of cyfluthrin in workers was 

confirmed by measurement of plasma cyfluthrin levels, although estimates of total exposure levels of 

cyfluthrin in these workers were not available (Leng and Lewalter 1999). It appears that pyrethroids are 

rapidly absorbed following inhalation, based on the appearance of urinary metabolites within 30 minutes 

of exposure (Leng et al. 1997a). In this study, an increase in the amount of urinary metabolites correlated 

with increasing exposure levels, indicating that absorption by the inhalation route is not capacity-limited, 

at least over the range of exposures studied (10–160 mg/m3

). However, occupational exposure of humans 

to pyrethroids may include inhalation, oral, and/or dermal routes. Studies providing estimates for total 

absorption of pyrethroids following inhalation or occupational exposure were not identified. 

No information was located regarding absorption of pyrethroids following inhalation exposure in animals. 

3.4.1.2 Oral Exposure 

Available information regarding oral exposure of humans indicates that both Type I and Type II 

pyrethroids are absorbed from the gastrointestinal tract. A 59-year-old male attempted suicide by 

drinking approximately 600 mL of 20% permethrin emulsion (143 grams) (Gotoh et al. 1998). The 

emulsion contained a mix of cis and trans isomers (43.5% cis and 56.5% trans). Maximal plasma 

concentrations of permethrin occurred 3–4 hours after ingestion. Both isomers were detected in plasma, 

indicating that both cis and trans isomers of permethrin are absorbed following oral administration. It is 

not possible to determine the fraction of the administered dose that was absorbed in this patient. Oral 
PYRETHRINS AND PYRETHROIDS 85 

3. HEALTH EFFECTS 

exposure of a single volunteer demonstrated absorption of cyfluthrin by measurement of cyfluthrin 

metabolites in the urine, with an estimated minimum oral absorption of 40%, based on recovery of urinary 

cyfluthrin metabolites (Leng et al. 1997b). Similar results were observed in male volunteers exposed to 

cypermethrin, with absorption estimates ranging from 36 to 63% of the administered dose (Eadsforth and 

Baldwin 1983; Eadsforth et al. 1988; Woollen et al. 1992). Estimates of absorption following oral 

exposure to pyrethroids may be low, however, since they are based on the appearance of metabolites in 

the urine and do not consider other routes of excretion, such as biliary excretion. 

Observations in humans are supported by the results of animal studies. In several mammalian species, 

absorption of Type I pyrethroids following oral administration has been demonstrated by the presence of 

pyrethroid compounds in plasma, urine, and milk (Anadón et al. 1991b; Elliott et al. 1976; Gaughan et al. 

1977, 1978; Hunt and Gilbert 1977; Ohsawa and Casida 1980; Tomigahara et al. 1994a, 1994b; Ueda et 

al. 1975a, 1975b). Following oral administration of a single dose of permethrin to rats, peak plasma 

levels of permethrin occurred 3–4 hours after ingestion, with an estimated total absorption of 

approximately 60% of the administered dose (Anadón et al. 1991b). In cows administered resmethrin 

orally, 43% of the administered dose was excreted in the urine as resmethrin metabolites, indicating a 

minimum absorption of 43% of the administered dose (Ridlen et al. 1984). Absorption of several Type II 

pyrethroids following oral administration has been demonstrated by the presence of pyrethroid 

compounds in plasma, urine, and milk (Anadón et al. 1996; Quistad and Selim 1983; Quistad et al. 1982, 

1983). In Rhesus monkeys exposed to oral doses of 14C-fluvalinate, peak plasma levels were observed 2– 

3 hours after administration, with 37% of the administered dose eliminated in the urine as metabolites 

(Quistad and Selim 1983). Khan et al. (1986, 1990) demonstrated that 14C-labeled deltamethrin was 

absorbed by rats following the ingestion of plant material containing bound residues of the pyrethroid. 

Differences in the rate and extent of absorption in young versus older rats were demonstrated in one study 

of rats administered 14C-fluvalinate by gavage (Quistad et al. 1983). In younger rats (7 weeks old), peak 

plasma levels of 14C occurred at 7 hours, compared to 14 hours in older rats. However, lower plasma 

14C levels were observed in younger compared to older rats; thus, it is not clear whether fractional 

absorption was lower or higher in the younger rats. No information was located that could serve as a 

basis for predicting the effects of age on absorption of pyrethroids from the human gastrointestinal tract. 

No information was located regarding possible sex-related differences in absorption of ingested 

pyrethroids in humans or animals. 
PYRETHRINS AND PYRETHROIDS 86 

3. HEALTH EFFECTS 

3.4.1.3 Dermal Exposure 

Limited information is available regarding absorption of Type I or Type II pyrethroids following dermal 

exposure in humans. Following dermal application of permethrin to patients for treatment of scabies, the 

estimated absorption of permethrin was 0.5% of the applied dose, based upon the urinary excretion of 

permethrin metabolites (van der Rhee et al. 1989). Urinary excretion of metabolites persisted for 7– 

10 days following a single dermal application, suggesting that pyrethroids may be stored in skin and 

slowly released into the systemic circulation. A study using an in vitro preparation of human skin 

indicated that only a small fraction (approximately 0.7%) of a topically applied dose of permethrin fully 

penetrated the skin after a single 48-hour exposure, with small amounts of permethrin identified in the 

epidermal and dermal layers (Franz et al. 1996). Two studies evaluated the absorption of cypermethrin 

following dermal application of a single dose to volunteers (Eadsforth et al. 1988; Woollen et al. 1992). 

Based upon the recovery of urinary metabolites of cypermethrin, it was estimated that 0.3–1.8% of the 

applied dose was absorbed. Peak urinary excretion of metabolites was observed between 14 and 36 hours 

after application. This is in contrast to observations following oral exposure of cypermethrin in humans 

in which the urinary excretion rate of metabolites was highest during the first 24 hours after dosing 

(Woollen et al. 1992). 

Limited animal data are available regarding absorption of Type I or Type II pyrethroids following dermal 

exposure. Results of one study in rats are consistent with findings in humans; approximately 0.7% of a 

dermal application of fluvalinate was absorbed (Quistad et al. 1983). A single study indicates that 

fenvalerate is absorbed more quickly following dermal exposure to goats compared with other 

mammalian species, with peak plasma concentrations reached 2 hours after dosing (Mandal et al. 1996). 

The total percutaneous absorption of fenvalerate was not determined in that study. Percutaneous 

absorption of permethrin was demonstrated in guinea pigs in vivo following a single dermal application 

(Franz et al. 1996). In this study, absorption was found to be 20-fold greater than that measured in a 

preparation of human skin. The percutaneous absorption of permethrin in rats, as measured by recovery 

of 14C in urine and feces, was estimated to be 46% of the applied dose (Shah et al. 1987). This finding is 

not consistent with lower estimates from other studies in humans and animals and may be attributed to 

lack of restraint of the animals, allowing for oral exposure from licking of the application site. However, 

insufficient information is provided in the report to confirm this possibility. In this same study, there was 

no difference in the absorption of young (33 days) versus adult rats exposed to a single dermal application 

of permethrin. 
PYRETHRINS AND PYRETHROIDS 87 

3. HEALTH EFFECTS 

No additional information was located regarding sex- or age-related differences in absorption of 

pyrethroids following dermal exposure in humans or animals. There is no obvious structural basis for 

predicting substantial differences in the percutaneous absorption of Type I and Type II compounds in 

humans. 

3.4.2 Distribution 

No information is available regarding the distribution of Type I and Type II pyrethroid compounds or 

pyrethroid metabolites in humans, except for information regarding the distribution of pyrethroids and 

pyrethroid metabolites into excretory compartments. Given the lipophilic nature of pyrethroids, it is 

expected that, in humans, they are widely distributed and undergo rapid distribution to tissues with a high 

lipid content, including fat and central and peripheral nervous tissues. Based upon observations of central 

and peripheral nervous system toxicity in humans exposed to pyrethroid compounds, it is apparent that 

distribution of pyrethroids to these tissues occurs (Aldridge 1990; Casida et al. 1983; Vijverberg and van 

den Bercken 1990). Since pyrethroid metabolites are less lipid soluble than the parent compounds, it is 

expected that distribution of metabolites to central and peripheral nervous tissues would be decreased 

compared to that of the parent compounds. Studies in several mammalian species confirm that 

pyrethroids are widely and rapidly distributed to many tissues, including liver and kidney, and are 

concentrated in central and peripheral nervous tissues. In pregnant and lactating animals, pyrethroids are 

distributed into milk. Although animal studies of placental transfer of pyrethroids indicate that 

pyrethroids do not cross the placenta in substantial amounts or accumulate in the fetus (Kaneko et al. 

1984b; Quistad et al. 1982; Shiba et al. 1990), other animal studies indicate that in utero exposure to 

pyrethroids may result in persistent effects on neurotransmitters (Malaviya et al. 1993; Santoni et al. 

1999) and on the immune system (Santoni et al. 1997, 1998, 1999). Interpretation of results obtained 

from many of the distribution studies in animals is limited by the study design; the distribution of 

pyrethroids was typically evaluated in tissues collected from animals after most of the chemical had been 

excreted from the body (1–8 days after treatment with the last dose). 

3.4.2.1 Inhalation Exposure 

No information was located regarding the distribution of pyrethroids in humans or animals following 

inhalation exposure. 
PYRETHRINS AND PYRETHROIDS 88 

3. HEALTH EFFECTS 

3.4.2.2 Oral Exposure 

Limited information is available on the distribution of Type I or Type II pyrethroids in humans following 

oral exposure, and most of the available information describes the distribution of pyrethroids and 

pyrethroid metabolites into excretory compartments (reviewed in Section 3.4.3.2). Based on the results of 

a study in which plasma permethrin concentrations were measured in an adult male who ingested 

permethrin in a suicide attempt, permethrin appears to follow a two-compartment model, with distribution 

half-times for the trans and cis compounds of 5.08 and 4.82 hours, respectively (Gotoh at el. 1998). One 

study that investigated the elimination of 14C-deltamethrin in volunteers following oral administration 

showed that small amounts of deltamethrin or its metabolites were distributed to saliva (Stockis et al. 

1985). In this same study, evaluation of the distribution of 14C in plasma indicated that approximately 

25% of the plasma 14C was associated with red blood cells. 

In rats, permethrin was rapidly distributed to nervous tissues after administration of a single oral dose, 

with a distribution half-time of 4.85 hours (Anadón et al. 1991b). Plasma levels of permethrin exhibited a 

bi-phasic decline, which can be represented by a two-compartment model with a rapid distribution phase. 

Based on a large apparent volume of distribution, it appears that permethrin is distributed in both 

extracellular and intracellular fluids, indicating that pyrethroids can easily cross cell membranes. 

Permethrin concentrations in nervous tissue were higher than those measured in plasma, indicating that 

permethrin is concentrated in nerve tissue relative to plasma. Concentrations in nerve tissue were highest 

in the sciatic nerve, followed by (in decreasing order) hypothalamus, frontal cortex, hippocampus, 

caudate putamen, cerebellum, and medulla oblongata. Peak concentrations were observed to occur within 

4 hours of dosing in both nerve tissue and plasma. Permethrin was also distributed to the liver, with peak 

concentrations observed within 4 hours of dosing. Concentrations of permethrin metabolites (m-phenoxybenzyl alcohol and m-phenoxybenzoic acid) in nerve tissues were lower than those observed for the 

parent compound. Although it is not possible to determine if the permethrin metabolites entered the nerve 

tissue from blood or if permethrin was metabolized to its metabolites in nerve tissue, distribution of the 

more lipid soluble parent compounds into nerve tissue is considered more likely (Anadón et al. 1991a, 

1991b). 14C-Permethrin or its metabolites are also rapidly distributed to the kidney following oral 

administration to rats, with levels of 14C in the kidney peaking approximately 4 hours after dosing 

(Miyamoto et al. 1968). Studies in lactating cows indicate that very low levels of Type I pyrethroids 

(e.g., <0.5% of the administered dose) are distributed into milk (Gaughan et al. 1978; Ridlen et al. 1984). 

Following oral exposure, permethrin or its metabolites have also been detected in fat of cows and rats up 

to12 days after dosing (Gaughan et al. 1977, 1978). 
 

PYRETHRINS AND PYRETHROIDS 89 

3. HEALTH EFFECTS 

Fluvalinate was widely distributed in rats following oral exposure to 14C-fluvalinate, based on detection of 

small amounts of 14C in nearly all tissue types (Ruzo et al. 1978). However, interpretation of these results 

must be made with caution, since tissue levels of 14C were measured in animals that had been sacrificed 

8 days after oral dosing and nearly all of the 14C had been eliminated from the body by that time. In rats, 

deltamethrin was rapidly distributed to nerve tissues after administration of a single oral dose, with a 

distribution half-time of 2.1 hours (Anadón et al. 1996). Plasma levels of deltamethrin exhibited a biphasic decline, which can be represented by a two-compartment model with a rapid distribution phase. 

Deltamethrin concentrations in nerve tissue were higher than those measured in plasma, indicating that 

deltamethrin is concentrated in nervous tissue relative to plasma. Concentrations in nerve tissue were 

highest in the hypothalamus, followed by (in decreasing order) hippocampus, cerebellum, frontal cortex, 

caudate putamen, and medulla oblongata, with peak concentrations occurring between 4 and 6 hours after 

oral administration. Similar distribution was observed for the 4-OH-metabolite of deltamethrin but, in 

general, the concentrations of metabolite measured in each tissue were less than those measured for the 

parent compound. It is not possible to determine if the metabolite entered the nervous tissue from blood 

or if deltamethrin was metabolized to the 4-OH-metabolite by nervous tissue. However, distribution of 

the more lipid soluble parent compounds into nerve tissue is considered more likely due to the lower lipid 

solubility of the metabolites (Anadón et al. 1996). Deltamethrin and its 4-OH metabolite were also 

detected in vas deferens and anococcygeus muscle at concentrations that were greater than plasma but 

less than those observed in nervous tissue (Anadón et al. 1996). Residual amounts of pyrethroids have 

been measured in fat several days after oral exposure to lambs and cows (Quistad et al. 1982; Wszolek et 

al. 1981a, 1981b). Studies in lactating cows indicate that Type II pyrethroids are rapidly distributed into 

milk after exposure to a single oral dose, but that only small amounts of the total dose are distributed to 

milk (0.4–0.9% of the administered dose) (Quistad et al. 1982; Wszolek et al. 1980). Pyrethroids do not 

appear to cross the placenta in substantial amounts or accumulate in the fetus of animals, as evidenced by 

the results of dosing of pregnant rats and a single cow. Measurements of radioactivity in fetuses of rats 

administered radiolabeled pyrethroids indicated that <0.004% of the administered dose of the Type I 

pyrethroid, tetramethrin, was recovered in the fetus (Kaneko et al. 1984b). Recovered activity from 

radiolabeled fenvalerate (a Type II pyrethroid) was <0.07% (Shiba et al. 1990). Eight days after a 

pregnant cow was given a single dose of 14C-fluvalinate, only trace amounts of 14C were detected in the 

fetus (Quistad et al. 1982). 

The results of Anadón and coworkers (Anadón et al. 1991b, 1996) indicate that the Type II pyrethroid, 

fluvalinate, may be more rapidly distributed than permethrin, a Type I pyrethroid, following dermal 
 

PYRETHRINS AND PYRETHROIDS 90 

3. HEALTH EFFECTS 

exposure in rats. These apparent differences in distribution of permethrin and fluvalinate could be the 

result of chemical or toxicokinetic differences in these pyrethroids or Type I and Type II pyrethroids in 

general, although no data are presently available to confirm or refute this possibility. 

No information was located regarding distribution within tissues of pyrethroid compounds following oral 

exposure of humans or animals. No information was located regarding sex- or age-related differences in 

distribution of Type I and Type II pyrethroids following oral exposure of humans or animals. 

3.4.2.3 Dermal Exposure 

No information is available regarding distribution of Type I or Type II pyrethroids in humans following 

dermal exposure, and available data from animal studies are limited. In guinea pigs exposed to dermally 

applied permethrin, the concentration of permethrin measured in brain tissue 24 hours after dosing was 

7-fold higher than that of plasma (Franz et al. 1996). Residual tissue concentrations of fenvalerate, but 

not of its metabolites, were determined 4 days after administration of a single dermal dose to goats 

(Mandal et al. 1996). The highest concentration was observed in the adrenal gland, followed by (in 

decreasing order) biceps muscle, omental fat, liver, kidney, lung, and cerebrum. Interpretation of these 

data is hindered because at the time of fenvalerate tissue content measurement, the majority of the dose 

had been eliminated (only small amounts of fenvalerate remained in plasma at 3 days after dosing). No 

additional studies were located concerning distribution of Type I or Type II pyrethroids, and no 

information was available regarding age- or sex-related differences in distribution. 

3.4.2.4 Other Routes of Exposure 

No information was located regarding distribution of pyrethroids in humans following exposure by other 

routes. 

Following intravenous administration in rats, Type I and Type II pyrethroids are rapidly and widely 

distributed to tissues and are concentrated in nervous tissue (Anadón et al. 1991b, 1996; Gray and Rickard 

1982; Gray et al. 1980a; Silver and Dauterman 1989a). Plasma levels of parent compound exhibit a biphasic decline and fit a two-compartment model with rapid distribution phase (Anadón et al. 1991b, 

1996). Distribution to the central nervous system is very rapid, with concentrations reaching peak levels 
PYRETHRINS AND PYRETHROIDS 91 

3. HEALTH EFFECTS 

within 5 minutes of administration (Gray et al. 1980a). Following intraperitoneal injection of rats with 

Type I pyrethroids, pyrethroids are rapidly distributed to the liver and are found to be associated with 

several subcellular fractions, including microsomes, indicating that pyrethroids are rapidly distributed to a 

detoxifying organ (Graillot and Hoellinger 1982). Results of these studies provide supportive evidence 

for the expectedly rapid and wide distribution of pyrethroids after absorption in humans. 

No information was located regarding sex- or age-related differences in distribution of pyrethroids 

following parenteral exposure. 

3.4.3 Metabolism 

Extensive study of the metabolic pathways involved in the biotransformation of pyrethroids in humans 

has not been undertaken. Information on the metabolism of Type I and Type II pyrethroid compounds in 

humans is based upon identification of pyrethroid metabolites in urine and blood obtained in a small 

number of studies conducted under controlled conditions or following occupational exposures. In 

contrast, the metabolism of Type I and Type II pyrethroid compounds has been extensively studied in 

several mammalian animal models. Since the metabolites that have been identified in humans have also 

been identified in other mammalian species, it is unlikely that there are significant qualitative differences 

between humans and other mammals in the major metabolic pathways for pyrethroids, although some 

species differences do undoubtedly exist (Anadón et al. 1991b; Eadsforth and Baldwin 1983; Eadsforth et 

al. 1988; Elliott et al. 1976; Gaughan et al. 1977; Leng et al. 1997a, 1997b; Woollen et al. 1992). The 

following summary of pyrethroid metabolism is based on the results of extensive investigations of the 

metabolism of pyrethroids in mammalian models. It is presumed that these metabolic pathways pertain to 

human metabolism of pyrethroid compounds, although there may be important quantitative differences 

between species. 

All synthetic pyrethroid compounds appear to be degraded by similar metabolic processes in mammals. 

Upon administration of pyrethroids to mammals, biotransformation takes place through hydrolysis of the 

central ester bond, oxidative attacks at several sites, and conjugation reactions to produce a complex array 

of primary and secondary water-soluble metabolites that undergo urinary and biliary excretion (Casida et 

al. 1983; Gray and Soderlund 1985; Leng et al. 1999a). It is widely accepted that metabolism results in 

the formation of compounds that have little or no demonstrable toxicity, although the formation of 

reactive or toxic intermediates cannot be ruled out, and it appears that cleavage of the ester bond results in 

substantial detoxification (Gray and Soderlund 1985; Hutson 1979). For halogenated pyrethroids (such as 
PYRETHRINS AND PYRETHROIDS 92 

3. HEALTH EFFECTS 

cyfluthrin, cypermethrin, and permethrin), rapid hydrolytic cleavage of the ester bond is followed by 

oxidation to yield carboxylic acid derivatives and phenoxybenzoic acid derivatives (Leng et al. 1997a, 

1997b). These metabolites are, in general, excreted as alcohols, phenols, carboxylic acids, and their 

glycine, sulfate, glucuronide, or glucoside conjugates (Aprea et al. 1997; Casida et al. 1983). Metabolic 

pathways for permethrin, cypermethrin, and deltamethrin are shown in Figure 3-3. However, depending 

upon the type of pyrethroid compound, either oxidation or hydrolysis may predominate (Miyamoto 1976). 

The presence of the alpha-cyano group of the Type II pyrethroid compounds has been shown to decrease 

the rate of hydrolytic cleavage of the ester bond (Casida et al. 1983). Many of the trans enantiomers of 

pyrethroid compounds are metabolized mainly through hydrolytic cleavage of the ester linkage, with 

subsequent oxidation and/or conjugation of the component alcohol and acid moieties, whereas certain cis 

enantiomers are more resistant to hydrolytic attack and are degraded via oxidation at various sites of the 

molecule (Miyamoto 1976; Shono et al. 1979). For pyrethroids containing an alpha-cyanophenoxybenzyl 

substituent (Type II pyrethroids), cleavage of the ester bond results in the release of cyanide, which is 

rapidly converted mainly to thiocyanate (Casida et al. 1983; Gray and Soderlund 1985; Ohkawa et al. 

1979). It does not appear that there is significant additional metabolic fragmentation of the acid and 

alcohol moieties, since metabolism studies with 14C-labeled pyrethroid compounds yield little or no 

detectable 14CO2 (Ohkawa et al. 1979; Ruzo et al. 1978). 

Information on the specific enzymes involved in the metabolism of pyrethroid compounds is limited. 

Metabolism appears to involve nonspecific microsomal carboxyesterases and microsomal mixed function 

oxidases, which are located in nearly all tissue types (Casida et al. 1983; Miyamoto 1976; Shono et al. 

1979). Since microsomal enzymes play an important role in the metabolism of pyrethroids, it is expected 

that many tissue types are potentially capable of rapidly metabolizing these compounds, with a 

particularly important role for the liver. Pyrethroids are metabolized in blood in vitro (Gray and Rickard 

1982). Metabolism of pyrethroids may also occur in the brain (Anadón et al. 1996; Ghiasuddin and 

Soderlund 1984), which may contribute to the detoxification of some pyrethroids in mammals 

(Ghiasuddin and Soderlund 1984). 

Information on the effects of induction or inhibition of microsomal enzymes by other chemicals or drugs 

on the rate of metabolism of pyrethroid compounds in humans or animals was not identified. 

No information was located regarding sex- or age-related differences in metabolism of pyrethroids 

following exposure in humans or animals. 
O 

C 

H 

C COO

H 

C 

H 

C 

H 

3CH CH3

CN

R1 

R2 R3 1 

C 

H 

C 

H 

C 

H 

3CH CH3

COOH 

R1 

R2 3 

O 

HOOC 

2 

O 

HOOC 

OH 

4 

taurine conjugate 

glycine conjugate 

glutamic acid conjugate 

glucuronide 

{

deltamethrin R1 = R2 = Br R3 = CN 

permethrin R1 = R2 = Cl R3 = H 

cypermethrin R1 = R2 = Cl R3 = CN 

1 

2 { 3-phenoxybenzoic acid (3-PBA) 

4 { 3-(4-hydroxy)-phenoxybenzoic acid (4-OHPBA) 

3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane carboxylic acid (DCVA) 

3-(2,2-dibromovinyl)-2,2-dimethy-cyclopropane carboxylic acid (DBVA) 3{

Figure 3-3. Metabolic Diagram for Deltamethrin, Permethrin, and Cypermethrin 

PYRETHRINS AND PYRETHROIDS 93 

3. HEALTH EFFECTS 
 

PYRETHRINS AND PYRETHROIDS 94 

3. HEALTH EFFECTS 

3.4.3.1 Inhalation Exposure 

The results of a single study of cyfluthrin in humans demonstrate that, when administered by the 

inhalation route, pyrethroids are rapidly metabolized, with metabolites appearing in the urine by 

30 minutes after exposure (Leng et al. 1997a). 

No studies were located regarding metabolism of pyrethroids following inhalation exposure to animals. 

3.4.3.2 Oral Exposure 

Given the important role of hepatic microsomal enzymes in the biotransformation of xenobiotics, accurate 

estimates of absorption following oral administration of pyrethroid compounds must take into account 

first-pass metabolism. Studies in humans indicate that the absorption of orally administered pyrethroids 

is incomplete; however, these studies do not provide evidence for first pass metabolism (Eadsforth and 

Baldwin 1983; Eadsforth et al. 1988; Woollen et al. 1992). Results of a study in isolated perfused rat 

liver are supportive for an important role for first-pass metabolism of pyrethroid compounds (Silver and 

Dauterman 1989b). In this study, the hepatic extraction ratios for both cis and trans isomers of 

tetramethrin were approximately 0.9, and both the cis and trans isomers were rapidly metabolized by the 

liver. If the high in vitro extraction is indicative of in vivo, then first-pass extraction from the hepatic 

portal circulation and metabolism would be likely. Incomplete absorption of pyrethroids following oral 

exposure may also result from metabolism within the gastrointestinal tract or binding to poorly absorbed 

components of the ingesta. Results of studies in rats indicate that pyrethroid metabolites are produced 

within the gastrointestinal tract (Tomigahara et al. 1994b). Metabolites from permethrin were recovered 

in the feces following oral administration to rats, suggesting the possibility of metabolism in the 

gastrointestinal tract or fecal elimination of metabolites formed after absorption (Gaughan et al. 1977). 

Although no information is available regarding sex-related differences in metabolism following oral 

administration of pyrethroids in humans, no differences in metabolism were observed in male and female 

rats orally exposed to pyrethroids (Quistad et al. 1983). 
PYRETHRINS AND PYRETHROIDS 95 

3. HEALTH EFFECTS 

3.4.3.3 Dermal Exposure 

Little information is available regarding metabolism of pyrethroid compounds following dermal exposure. 

Following dermal application of permethrin to patients for treatment of scabies, permethrin metabolites 

were recovered from urine (van der Rhee et al. 1989). Results of a single study in volunteers comparing 

urinary metabolite profiles following oral and dermal exposure to cis- and trans-cypermethrin isomers 

demonstrated a difference in the urinary metabolite profiles following exposure by each route (Woollen et 

al. 1992). Following oral exposure, urine contained a higher proportion of trans-metabolites compared to 

that obtained following dermal exposure. These results could indicate differences in absorption or 

metabolism between these two routes of exposure. 

No information was located regarding sex- or age-related differences in metabolism following dermal 

administration of pyrethroids to humans or animals. 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

The results of a single study examining urinary metabolites in humans following inhalation exposure to 

cyfluthrin indicate that elimination follows first-order kinetics, with 93% of the urinary elimination 

complete within 24 hours of exposure (Leng et al. 1997a). Elimination half-times for the cyfluthrin 

metabolites cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA), 4-fluoro3-phenoxybenzoic acid (FPBA), and their isomers ranged from 5.3 to 6.9 hours. These elimination halftimes remained constant over a range of exposure levels, providing supportive evidence that pyrethroids 

exhibit first-order elimination kinetics. The amounts of cyfluthrin metabolites excreted in urine correlated 

with increasing exposure levels, demonstrating that urinary levels of pyrethroid metabolites may be a 

useful indicator of exposure level. 

Several studies of occupational exposure of humans to pyrethroids were located; however, the exposures 

may have been by the inhalation, oral, or dermal routes, or a combination of these routes. Following 

occupational exposure to Type I and Type II pyrethroid compounds, excretion of pyrethroid metabolites 

in the urine occurs and is nearly complete within 4 days of exposure (Aprea et al. 1997; Chester et al. 
PYRETHRINS AND PYRETHROIDS 96 

3. HEALTH EFFECTS 

1987; Kühn et al. 1999). Based on elimination of cyfluthrin from plasma, the elimination half-time is 

estimated to be between 0.5 and 2 hours (Leng and Lewalter 1999). Based on elimination of metabolites 

into the urine, the elimination half-times are 5 hours for cyfluthrin and 8 hours for cypermethrin (Kühn et 

al. 1999). No information was provided in these studies regarding the amount of pyrethroid eliminated by 

nonurinary routes. 

No information was located regarding sex- or age-related differences, or other factors, that might affect 

the elimination and excretion of pyrethroids following inhalation exposure of humans or animals. 

3.4.4.2 Oral Exposure 

Limited information is available regarding the elimination and excretion of Type I and Type II pyrethroid 

compounds following oral exposure in humans. The elimination half-time of cis-permethrin in plasma 

following ingestion of a mix of cis and trans isomers of permethrin in a suicide attempt was 

approximately 67 hours (Gotoh et al. 1998). Trans-permethrin was eliminated from the blood more 

quickly than the cis isomer and was undetectable in blood after 25 hours. However, an estimate of the 

plasma elimination half-time for the trans isomer was not reported. This patient was noted to have a 

history of chronic renal dysfunction, but no specific details were reported. Therefore, it is not possible to 

determine how this patient’s renal status may have affected the elimination of permethrin from the 

plasma. In humans exposed to single oral doses of Type II pyrethroids, the elimination half-time based 

on the appearance of metabolites in the urine has been estimated to be between 6 and 13 hours (Leng et 

al. 1997b; Woollen et al. 1992). Approximately 35–50% of the administered dose was excreted in the 

urine as metabolites during the first 5 days after dosing, with peak urinary excretion rates observed during 

the first 24 hours after dosing (Eadsforth and Baldwin 1983; Eadsforth et al. 1988; Leng et al. 1997b; 

Woollen et al. 1992). It is not possible to determine the percentage of the administered dose that was 

eliminated in the urine in these studies since only the urinary pyrethroid metabolites, and not total urinary 

pyrethroids (parent compound plus metabolites), were measured. Fecal elimination following oral dosing 

of Type II pyrethroids in humans has been confirmed based on the results of one study in humans, but 

neither the fraction of the administered dose excreted in feces nor the identity of the compounds excreted 

in feces were determined (Stockis et al. 1985). 

Results of animal studies indicate that Type I and Type II pyrethroids are almost completely eliminated 

from the body within 4–12 days following oral exposure, with the majority of the dose eliminated within 

the first 12–48 hours (Anadón et al. 1996; Elliott et al. 1976; Gaughan et al. 1977; Hunt and Gilbert 1977; 
 

 

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Lee et al. 1985; Quistad and Selim 1983; Quistad et al. 1982; Ridlen et al. 1984; Ruzo et al. 1978; Staiger 

and Quistad 1984; Wszolek et al. 1980). Type I and Type II pyrethroids exhibit first-order elimination 

kinetics. An estimate for the elimination half-time of permethrin in rats is approximately 8 hours 

(Anadón et al. 1991b). In oral studies, the plasma elimination half-time for fluvalinate in Rhesus 

monkeys was 2–3 hours, whereas, in rats, the elimination half-time of deltamethrin was 38.5 hours, 

although the time from administration to peak levels of the pyrethroids in both studies was similar 

(approximately 2–3 hours) (Anadón et al. 1996; Quistad and Selim 1983). It is not known if the 

differences in the elimination half-times observed in these studies are related to species differences, 

differences in dose, or differences in the elimination kinetics of the specific pyrethroid compounds. 

In monkeys, cows, and rats, a large portion of the orally administered dose (43–56%) is excreted in the 

urine (Quistad and Selim 1983; Quistad et al. 1982; Ridlen et al. 1984; Staiger and Quistad 1984), 

primarily as metabolites. In rats subject to oral exposure, almost all of the pyrethroids recovered in the 

urine are metabolites, with urine containing very little of the unchanged compound (Ueda et al. 1975b). 

In monkeys, cows, and rats, approximately 45–60% of the orally administered dose is excreted in the 

feces as a mix of parent compound and metabolites (Miyamoto et al. 1968; Quistad and Selim 1983; 

Quistad et al. 1982; Ridlen et al. 1984; Staiger and Quistad 1984; Ueda et al. 1975b). The urinary 

excretion route appears to be more important for trans-permethrin metabolites, while the fecal excretion 

route appears to be more important for cis-permethrin metabolites (Elliott et al. 1976; Hunt and Gilbert 

1977). 

Studies performed using cows, rats, and monkeys indicate that pyrethroids undergo biliary excretion, 

although estimates for the amount of biliary excretion were not available in these studies (Quistad and 

Selim 1983; Quistad et al. 1982, 1983). Based on the results of a study in isolated perfused rat liver, it 

appears that tetramethrin may undergo extensive biliary excretion (Silver and Dauterman 1989b). Studies 

in lactating cows and goats indicate that only very low levels of Type I pyrethroids are excreted (<1% of 

the administered dose) in milk (Gaughan et al. 1978; Hunt and Gilbert 1977; Quistad et al. 1982; Ridlen 

et al. 1984; Wszolek et al. 1980). In one study, one pregnant cow was administered a single oral dose of 

14C-fluvalinate and tissues were examined for radioactivity 8 days after dosing (Quistad et al. 1982). 

Analysis of the 14C content of the fetus indicates minimal transfer of fluvalinate or its metabolites to the 

fetus (approximately 1x10-5% of the administered dose). It does not appear that pyrethroids are excreted 

in significant amounts via expired air (Gaughan et al. 1977; Ohkawa et al. 1979; Ruzo et al. 1978; Ueda et 

al. 1975b). 
PYRETHRINS AND PYRETHROIDS 98 

3. HEALTH EFFECTS 

Apart from the finding that pyrethroids may be excreted in milk, no additional information was located 

regarding sex-related differences, and no information was located regarding age-related differences, 

which might affect the elimination and excretion of pyrethroids following oral exposure of humans or 

animals. 

3.4.4.3 Dermal Exposure 

Limited information is available regarding elimination and excretion of pyrethroids following dermal 

exposure in humans. Results of two studies in humans exposed to single dermal doses of cypermethrin 

indicate that a small fraction (0.1–1.2%) of the administered dose is excreted in the urine as metabolites 

(Eadsforth et al. 1988; Woollen et al. 1992). Peak urinary excretion rates were observed between 12 and 

36 hours after dosing (Woollen et al. 1992). Following dermal application of a single permethrin dose to 

patients for treatment of scabies, permethrin metabolites were excreted in urine, with urinary excretion 

persisting for 7 days after exposure (van der Rhee et al. 1989). 

In rats exposed to single dermal doses of permethrin, >90% of the absorbed dose was excreted in urine 

and feces, with a urine-to-fecal ratio of approximately 4:1 (Shah et al. 1987). While results of this study 

may provide evidence for fecal excretion following exposure by a nonoral route, it is possible that oral 

exposure occurred through licking of the application site if the animals were not properly restrained. In 

this study, no differences were noted in urinary excretion between young and adult rats. No other studies 

were located in which age-related differences in elimination and excretion of pyrethroids or their 

metabolites were assessed following dermal exposure. Following dermal exposure of rats to 

14C-fluvalinate, 0.7 and 0.8% of the administered radioactivity was excreted in the urine and feces, 

respectively (Quistad et al. 1983). In this study, one group of animals was not restrained and the animals 

were able to lick the application site, which may have resulted in oral exposure and higher urinary and 

fecal excretion of 14C. 

No information was located regarding sex-related differences, or other factors, that might affect the 

elimination and excretion of pyrethroids following dermal exposure in humans or animals. 
PYRETHRINS AND PYRETHROIDS 99 

3. HEALTH EFFECTS 

3.4.4.4 Other Routes of Exposure 

No information was located regarding the elimination and excretion of Type I or Type II pyrethroids in 

humans following parenteral exposure. In rats administered a mix of cis- and trans-tetramethrin 

intravenously, the elimination half-time for the cis isomer was less (72 minutes) than that observed for the 

trans isomer (125 minutes) (Silver and Dauterman 1989a). Following intravenous administration to the 

rats, tetramethrin metabolites were recovered from both urine and, to a lesser extent, feces, providing 

evidence for biliary excretion. No unmetabolized tetramethrin was recovered in the urine. Only a small 

amount of the parent cis isomer was identified in the feces. Fecal excretion appears to be the major 

excretory pathway for the cis isomer, whereas urinary excretion appears to be the major excretory route 

for the trans isomer. Thus, biliary elimination appears to be more important for the cis isomer than for the 

trans isomer. In rats administered deltamethrin and its metabolite (4-OH-deltamethrin) intravenously, 

elimination half-times were 33 and 25 hours, respectively. In another phase of this study involving 

gavage administration, similar elimination rates were observed (Anadón et al. 1996). 

No information was located regarding age- or sex-related differences that might affect the excretion and 

elimination of pyrethroids following parenteral exposure in humans or animals. 

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 et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 
PYRETHRINS AND PYRETHROIDS 100 

3. HEALTH EFFECTS 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) is 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-4 shows a conceptualized representation of a PBPK model. 

No PBPK models for exposure to pyrethroid compounds were identified. Thorough study of the 

toxicokinetic profiles of Type I and Type II pyrethroids in humans or experimental animals has not been 

undertaken. Empirical models for exposure to Type I (permethrin) and Type II (deltamethrin) pyrethroids 

have been developed based upon the results of two studies in rats (Anadón et al. 1991b, 1996). The 
 

PYRETHRINS AND PYRETHROIDS 101 

3. HEALTH EFFECTS 

Figure 3-4. Conceptual Representation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance 

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by 

inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 102 

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empirical models developed from these toxicokinetic studies yielded similar results for both compounds, 

indicating that the biodisposition of Type I and Type II compounds is similar. Pyrethroids are rapidly 

absorbed following oral exposure. Following oral and intravenous exposure, permethrin and deltamethrin 

plasma kinetics are described by a two-compartment model with a relatively rapid distribution phase, 

followed by a slower elimination phase. Following intravenous administration, the distribution and 

elimination half-times were 0.46 and 8.67 hours for permethrin, respectively, and 1.39 and 33.0 hours for 

deltamethrin, respectively. Under these experimental conditions, permethrin was eliminated more rapidly 

than deltamethrin. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

Absorption. No information was located regarding the mechanism of absorption of pyrethroids from 

the gastrointestinal tract. Since pyrethroids are lipophilic compounds, it is presumed that they cross 

intestinal cells and pass into the circulation by diffusion across lipid membranes. No information was 

identified on the location of absorption of pyrethroids within the gastrointestinal tract. However, it is 

presumed that most of the absorption takes place in the intestines due to the large exposed surface area. 

Although no information was located regarding the mechanism of absorption through the skin or across 

alveolar membranes, it is presumed that pyrethroids cross these barriers by diffusion across lipid 

membranes. 

Distribution. No information was located regarding the transport of pyrethroid compounds in blood. 

Pyrethroids are distributed to nearly all tissues and are concentrated in tissues with high lipid contents, 

such as fat and nerve tissue (Anadón et al. 1991b, 1996). It is likely that the pattern of concentration in 

lipid-rich tissues is due to the high lipid solubility of pyrethroid compounds. Since metabolism of 

pyrethroids results in products that are more water-soluble than the parent compounds, it is likely that the 

metabolites are less able to cross the blood-brain barrier, unless there are facilitated mechanisms for 

transport of pyrethroid metabolites that have not yet been characterized. 

Metabolism. Upon administration of pyrethroids to mammals, biotransformation takes place through 

hydrolysis of the central ester bond, oxidative attacks at several sites, and conjugation reactions to 

produce a complex array of primary and secondary water-soluble metabolites that undergo urinary 

excretion (Casida et al. 1983; Gray and Soderlund 1985; Leng et al. 1999a, 1999b). It is well accepted 
 

 

PYRETHRINS AND PYRETHROIDS 103 

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that these metabolites have little or no demonstrable toxicity, although the formation of reactive or toxic 

intermediates cannot be ruled out, and it appears that cleavage of the ester bond results in detoxification 

(Gray and Soderlund 1985). For halogenated pyrethroids (such as cyfluthrin, cypermethrin, and 

permethrin), rapid hydrolytic cleavage of the ester bond is followed by oxidation to yield carboxylic acid 

derivatives and phenoxybenzoic acid derivatives (Leng et al. 1997a, 1997b). These metabolites are then 

generally metabolized further and form conjugated products with compounds such as glycine, sulfate, and 

glucuronic acid (Aprea et al. 1997; Casida et al. 1983). Information on the specific enzymes involved in 

metabolism of pyrethroid compounds is limited. Metabolism appears to involve nonspecific microsomal 

carboxyesterases and microsomal mixed function oxidases, which are located in nearly all tissue types. 

Excretion. No information was located regarding the specific mechanisms of excretion of pyrethroid 

compounds. However, metabolism of pyrethroids results in products that are water soluble and, therefore, 

are more readily eliminated from the body by renal and biliary excretion. No information is available 

regarding the mechanisms of excretion of pyrethroids and pyrethroid metabolites by the kidney, but it is 

expected that pyrethroids and their metabolites are eliminated, at least in part, by glomerular filtration 

since their molecular size is not restrictive for passage though the glomerular membrane. However, there 

is no information on the extent to which these compounds bind to plasma proteins, which might restrict 

their glomerular filtration. No information was located regarding mechanisms of excretion for the biliary 

or salivary routes of elimination. No information was located regarding mechanisms involved in the 

passage of pyrethroids into milk, although excretion into milk most likely occurs via lipid diffusion across 

membranes with retention in milk fat. 

3.5.2 Mechanisms of Toxicity 

The primary site of action for pyrethrins and pyrethroids is the sodium channel of nerve cells, as is also 

the case for DDT and its analogs (for reviews, see Cassida et al. 1983; Coats 1990; Narahashi 1985; 

Sattelle and Yamamoto 1988; Soderlund 1995; Soderlund et al. 2002; Valentine 1990; Vijverberg and van 

den Bercken 1990). Using a variety of methods, including voltage clamp and patch clamp techniques, it 

has been shown that pyrethrins and pyrethroids slow the closing of sodium channel gates following an 

initial influx of sodium during the depolarizing phase of an action potential, which results in a prolonged 

sodium tail current (Narahashi 1986; Vijverberg and Van den Bercken 1982). Two different types of 

pyrethroids are recognized, based on differences in basic structure (the presence or absence of a cyano 

group in the alpha position), and the symptoms of poisoning (Coats 1990; Verschoyle and Aldridge 

1980). Type I pyrethroids do not include a cyano group; their effects in rodents typically include rapid 
PYRETHRINS AND PYRETHROIDS 104 

3. HEALTH EFFECTS 

onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, 

prostration with coarse whole body tremor, elevated body temperature, coma, and death. The term 

T-syndrome (from tremor) has been applied to Type I responses. Type II pyrethroids include a cyano 

group; their effects in rodents are usually characterized by pawing and burrowing behavior, followed by 

profuse salivation, increased startle response, abnormal hindlimb movements, and coarse whole body 

tremor that progresses to sinuous writhing (choreoathetosis). Clonic seizures may be observed prior to 

death. Body temperature is not increased, but may decrease. The term CS-syndrome (from 

choreoathetosis and salivation) has been applied to Type II responses. Two of the cyano-pyrethroids, 

fenpropathrin and cyphenothrin, have been shown to trigger responses intermediate to those of 

T-syndrome and CS-syndrome, characterized by both tremors and salivation (Miyamoto et al. 1995; 

Wright et al. 1988). Mechanisms underlying this intermediate response type have not been elucidated. 

Occupational exposure to pyrethroids (particularly Type II pyrethroids containing the cyano group) 

frequently leads to paresthesia (abnormal cutaneous sensations such as tingling, burning, numbness, and 

itching). This response is considered to be the result of the direct action of pyrethroids on sensory nerve 

endings (LeQuesne and Maxwell 1980; Wilks 2000), causing repetitive firing in these fibers (Vijverberg 

and van den Bercken 1990). 

Marked differences exist in the duration of action on the sodium channel gate, particularly between 

Type I and Type II pyrethroids. These differences may account for the differences observed in toxic 

effects elicited in laboratory animals. Measurements of sodium tail currents in frog nerve fibers treated 

with Type I pyrethroids measure approximately 6–150 milliseconds in duration, whereas those generated 

from Type II pyrethroids last much longer (290 milliseconds to as long as several seconds) (Narahashi 

1986; Vijverberg et al. 1986). The shorter-duration sodium tail current generated by Type I pyrethroids 

results in an elevated after potential that may cause repetitive discharges. The longer-duration sodium tail 

current generated by Type II pyrethroids may result in summation of after potentials, which can cause 

gradual depolarization of the nerve and frequency-dependent suppression of action potentials. For both 

Type I and Type II pyrethroids, the magnitude of effect on sodium influx is strongly dependent on 

temperature, increasing markedly with cooling (Narahashi 1971, 1976; Vijverberg et al. 1983). The 

action of pyrethroids on as little as 0.6% of the sodium channel gates results in repetitive after-discharges 

that could lead to neurotoxic symptoms in animals (Narahashi 1996; Song and Narahashi 1996). 

Pyrethroids appear to bind to the membrane lipid phase in the immediate vicinity of the sodium channel, 

thus modifying the channel kinetics. Results of radioligand binding assays indicate that the actions of 

DDT and pyrethroids on the sodium channel are site-specific, functionally distinct from, but allosterically 
 

 

 

PYRETHRINS AND PYRETHROIDS 105 

3. HEALTH EFFECTS 

coupled to, sites 2, 3, and 5 of the 5 known neurotoxin-binding domains of the sodium channel (Lombet 

et al. 1988). Pyrethroids do not appear to influence sodium channel properties such as cation selectivity 

and cation binding (Yamamoto et al. 1986). 

Stereochemistry dictates the degree of toxicity that will be expressed by a given pyrethroid formulation or 

mixture. In the case of tetramethrin, like all other Type I pyrethroids, the 1R conformation is 

considerably more toxic than the 1S conformation. The 1S isomer can also inhibit toxicity by competitive 

inhibition at a number of stereospecific pyrethroid binding sites, thus preventing binding of the more 

toxic 1R isomer (Narahashi 1986). Furthermore, it has been observed that the cis isomers possess greater 

mammalian toxicity than the trans isomers. For these reasons, recent formulations of tetramethrin 

(d-tetramethrin) contain predominantly the 1R cis and 1R trans isomers in a ratio of 20:80 (Tomlin 1997). 

Type II pyrethroids have been shown to inhibit specific binding at or near the picrotoxin site of GABAA 

receptors in mouse brain (Crofton et al. 1987; Lawrence and Casida 1983), specifically inhibiting GABAdependent chloride flux (Bloomquist et al. 1986). However, taken together, the results of a number of 

studies that investigated the actions of pyrethrins and pyrethroids on ligand-gated ion channels indicate a 

limited role for the GABAA receptor in pyrethroid-induced neurotoxicity (Bloomquist 1993). 

Recently, Forshaw et al. (2000) demonstrated that voltage-gated chloride channels may play a role in 

Type II, but not Type I, pyrethroid poisoning. Their patch test experiments showed that ivermectin and 

pentobarbitone significantly increased open chloride channel probability in mouse neuroblastoma cells. 

When rats were pretreated with ivermectin or pentobarbitone and subsequently administered the Type II 

pyrethroid deltamethrin, comparatively reduced severity of neurotoxic effects was observed. This was an 

indication that these chemicals effectively antagonized Type II pyrethroid poisoning. Changes in 

neurotoxic effects were not observed when the Type I pyrethroid, cismethrin, was used. 

Other pyrethroid-induced effects include altered concentrations of catecholamines, blood glucose, and 

lactate, and marked changes in cerebral blood flow. However, these effects may be secondary effects 

arising from neural dysfunction resulting from the action of pyrethroids on the sodium and chloride 

channels. 
 

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3.5.3 Animal-to-Human Extrapolations 

Limited information is available regarding the specific mechanisms involved in the toxicokinetics of 

pyrethroids in either humans or animals. Therefore, it is difficult to assess how the toxicokinetic data 

obtained from studies in laboratory animals may differ from that obtained in humans. It is presumed that 

the toxicokinetic mechanisms involved are generally similar in all mammalian species, although 

quantitative interspecies differences most certainly exist. Absorption and distribution of pyrethroids 

appear to be largely determined by the lipid-soluble nature of these compounds. Therefore, it is expected 

that the absorption and distribution of pyrethroids in humans will be similar to that observed in other 

mammalian species. In both humans and animals, pyrethroids appear to be metabolized by nonspecific 

microsomal carboxyesterases and microsomal mixed function oxidases, which are located in nearly all 

tissue types and are common to all mammalian species. Since the metabolites that have been identified in 

humans have also been identified in other mammalian species, it is unlikely that there are significant 

qualitative differences between humans and most animal species for the major metabolic pathways for 

pyrethroids (Anadón et al. 1991b; Eadsforth and Baldwin 1983; Eadsforth et al. 1988; Elliott et al. 1976; 

Gaughan et al. 1977; Leng et al. 1997b; Woollen et al. 1992). The cat appears to be an exception, 

exhibiting increased sensitivity to the toxic actions of pyrethroids. This increased sensitivity may be the 

result of less efficient hepatic glucuronidation in the cat (Whittem 1995), a second step in the metabolism 

of pyrethroids in mammalian systems. Pyrethroids and their metabolites are excreted primarily in the 

urine and feces, and it is likely that mechanisms involved are the same in all mammalian species. If 

interspecies differences exist in sodium channel kinetics, such differences could increase the uncertainty 

related to interspecies extrapolation. 

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 Colborn and Clement (1992), was also used in 1996 when Congress mandated the 

Environmental Protection Agency (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), which in 1998 completed its deliberations and made 
 

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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). 

The potential for pyrethroids to act as endocrine disruptors has been investigated in a limited number of 

studies in vitro (Eil and Nisula 1990; Garey and Wolff 1998; Go et al. 1999). Using Ishikawa Var-I 

human endometrial cancer cell line and the T47D human breast cancer cell line, cell lines that produce 

phosphatase as an indicator of hormonal activity, Garey and Wolff (1998) demonstrated that fenvalerate 

and phenothrin induced significant estrogenicity at concentrations of 10 μM. Similar tests performed 

using d-trans-allethrin and permethrin did not result in apparent estrogenicity. None of the four 

pyrethroids showed significant estrogen antagonist activity or acted as progestins, but fenvalerate and 

d-trans-allethrin significantly antagonized the action of progesterone in T47D cells. Go et al. (1999) 

found that micromolar concentrations of phenothrin or fenvalerate induced pS2 expression in the MCF-7 

human breast cell carcinoma cell line by 5-fold, indicating that these pyrethroids may induce estrogenic 

activity. The fact that phenothrin-induced pS2 expression was suppressed by antiestrogen co-treatment is 

a further indication that phenothrin may affect endocrine function. Other pyrethroids (fenvalerate, 

permethrin, and cypermethrin) were also found to induce pS2 expression (Chen et al. 2002). Several 

pyrethroids have been shown to interact with androgen binding sites in dispersed intact human genital 

skin fibroblasts, with varying degrees of potency, but at levels comparable to those resulting in the same 

order of binding observed using cimetidine, a known inhibitor of androgen receptor binding (Eil and 
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Nisula 1990). Pyrethrins and bioallethrin were found to displace [3H]testosterone from sex hormone 

binding globulin in human plasma, at inhibitory levels up to 50% (Eil and Nisula 1990). 

Data regarding potential for pyrethrins and pyrethroids to act as endocrine disruptors in vivo include 

findings of reduced reproductive organ weights, significantly altered sperm characteristics, and reduced 

plasma testosterone levels in male rats administered oral doses of pyrethroids for up to 65 days (Abd 

El-Aziz et al. 1994; Abd El-Khalek et al. 1999; Hassan et al. 1993). However, there was no evidence of 

androgenicity or estrogenicity following repeated oral gavage exposure of castrated male rats (5-day 

Hershberger assay) and ovariectomized female rats (3-day uterotrophic assay) to esfenvalerate, 

fenvalerate, or permethrin at doses high enough to elicit classical clinical signs of neurotoxicity 

(Kunimatsu et al. 2002). 

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. 

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 
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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). 

Differences between children and adults regarding the toxicokinetics of pyrethroid compounds have not 

been investigated in humans, and there is insufficient information from studies conducted in immature 

laboratory animals to allow for prediction of particular sensitivities in children. However, based on what 

is known about the toxicokinetics of pyrethroid compounds, some general areas of concern for exposure 

of children to pyrethroids can be identified. 

Limited information is available regarding the ability of pyrethroid compounds to cross the placenta and 

be distributed to the fetus. Measurements of radioactivity in fetuses of rats administered radiolabeled 

pyrethroids indicated that <0.004% of the administered dose of the Type I pyrethroid, tetramethrin, was 

recovered in the fetus (Kaneko et al. 1984b). Recovered activity from radiolabeled fenvalerate (a Type II 
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pyrethroid) was <0.07% (Shiba et al. 1990). Eight days after a pregnant cow was given a single dose of 

14C-fluvalinate, only trace amounts (approximately 1x10-5% of the administered dose) of 14C were 

detected in the fetus (Quistad et al. 1982). However, given the fact that exposure of rat fetuses to 

pyrethroids via their mothers resulted in persistent alterations in brain neurotransmitter numbers 

(Malaviya et al. 1993), it would appear that concentrations that reached the fetal brain were sufficient to 

cause a consistent effect. 

Pyrethroids are eliminated from the body primarily by metabolism and subsequent excretion of 

metabolites via the urine and feces. Hepatic metabolism of pyrethroids is of critical importance for the 

detoxification and, ultimately, the excretion of these compounds. Although biotransformation reactions 

are catalyzed largely by microsomal enzymes, and enzymatic activity is involved in conjugation 

reactions, the specific enzymes involved in pyrethroid metabolism have not been identified. The ability 

of children to detoxify pyrethroid compounds through metabolic pathways may be different from that of 

adults (Komori et al. 1990; Leeder and Kearns 1997; NRC 1993; Vieira et al. 1996). Using lethality as an 

indicator of toxicity in a study designed to assess age-related susceptibility to pyrethroids, Sheets et al. 

(1994) found that adult rats were approximately 16 and 7 times less sensitive to orally administered 

deltamethrin than 11- and 21-day-old rats, respectively. Cantalamessa (1993) administered acute oral 

doses of permethrin or cypermethrin to 8-, 16-, and 21-day-old rats, as well as adult rats. For both 

permethrin and cypermethrin, acute oral LD50 values increased with increasing age, indicating greater 

sensitivity in younger rats. No significant changes in LD50 values were seen in young rats pretreated with 

either tri-o-tolyl phosphate (TOTP, an esterase inhibitor) or piperonyl butoxide (PB, a monooxygenase 

inhibitor). However, TOTP pretreatment in adult rats resulted in a significant increase in pyrethroidinduced lethality. Increased lethality in adult rats pretreated with PB did not reach the level of statistical 

significance. These results suggest the possibility that increased susceptibility of young animals to 

pyrethroid poisoning may be related to less efficient enzyme production than in adult animals. If children 

have a decreased metabolic capacity compared to adults, altered distribution and excretion of pyrethroids 

could result. However, age-related differences in responses of animals to near-lethal doses of pyrethroids 

do not provide a firm basis for human risk assessment. 

Since pyrethroid metabolites are water-soluble compounds, it is likely that their ability to cross the bloodbrain barrier is limited. In children, a decrease in the production of these polar metabolites could result in 

an increased distribution of unmetabolized pyrethroids to the central nervous system. There also could be 

an increase in the distribution of pyrethroids to the central nervous system due to immature development 

of the blood-brain barrier. Very little unmetabolized pyrethroid is excreted in the urine, most likely 
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because pyrethroid compounds are very lipid soluble and, if filtered by the glomerulus, are likely to 

undergo extensive renal reabsorption via lipid diffusion. If the metabolism of pyrethroids is decreased in 

children, a decrease in the renal excretion of pyrethroids may occur. Since specific details on the 

mechanisms of the renal handling of pyrethroids are not known, it is unclear how immature renal 

functions may affect the excretion of pyrethroids and pyrethroid metabolites in newborns and young 

children. 

Exposure to pyrethroids through ingestion of breast milk in nursing infants has not been investigated in 

humans. However, only very low levels of pyrethroids (<1% of the orally administered dose) are 

excreted into milk of lactating cows and goats, which would suggest that exposures in human by this 

route may be similarly low (Gaughan et al. 1978; Hunt and Gilbert 1977; Quistad et al.1982; Ridlen et al. 

1984; Wszolek et al. 1980). The relatively low transfers of lipophilic pyrethroids to milk presumably 

reflects competing pathways of elimination, including relatively rapid and extensive metabolism to more 

water-soluble metabolites and excretion in urine and feces. 

Pyrethroids do not appear to impair gross morphological development in animals. Some investigators 

have suggested that repeated oral exposure of neonatal mice to selected pyrethroids may result in altered 

locomotor behavior and changes in brain neurotransmitter receptor densities as adults (Ahlbom et al. 

1994; Eriksson and Fredriksson 1991; Talts et al. 1998a). However, limitations in study design and the 

inability to duplicate the results (Ray et al. 2002) render the findings of Eriksson and coworkers of 

questionable toxicological significance. 

Children may be more likely to be exposed to pyrethroids than adults. Behavioral patterns of children can 

result in higher rates of ingestion of soil and dust, which may contain pyrethroid compounds following 

spraying. Examples of activities that tend to promote soil and dust ingestion preferentially in children 

include playing and crawling on the ground and floor, hand-to-mouth activity, mouthing of objects, and 

indiscriminate eating of food items on the ground or floor. Pyrethroids are also used in shampoos and 

creams for treatment of patients with lice and scabies. Hand-to-mouth behavior may increase the risk of 

exposure in children under these conditions of use. 
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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 or substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to pyrethrins and pyrethroids 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 pyrethrins and pyrethroids 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 
 

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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 Pyrethrins and Pyrethroids 

Measurement of urinary metabolites of pyrethroids may serve as biomarkers of exposure. In several 

studies in humans exposed to pyrethroids occupationally, the presence of pyrethroid metabolites in urine 

has been used to confirm exposure (Aprea et al. 1997; Kühn et al. 1999; Leng et al. 1996, 1997a, 1997b). 

Chemically, synthetic pyrethroids are esters of chrysanthemic acid and specific alcohols, such as 

3-phenoxybenzyl alcohol. Hydrolytic cleavage of the ester bond in vivo yields chrysanthemic acid 

derivatives and 3-phenoxybenzoic (3-PBA) (Aprea et al. 1997; Kühn et al. 1999; Leng et al. 1997a, 

1997b). The specific pyrethroid metabolites found in urine vary depending upon the parent compound, 

which may have some modifications to the chrysanthemic acid moiety (Kühn et al. 1999). Results of a 

single study in humans following inhalation exposure to cyfluthrin indicate that the amounts of cyfluthrin 

metabolites excreted in urine correlate with increasing exposure levels (Leng et al. 1997a). Thus, urinary 

levels of pyrethroid metabolites may be a useful indicator of exposure level; however, at this time, there is 

insufficient information to allow for correlation of the amount of metabolites measured in the urine to the 

body burden of pyrethroids or to the level of exposure to pyrethroids. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Pyrethrins and Pyrethroids 

Paresthesia (an abnormal cutaneous sensation sometimes described as tingling, burning, stinging, 

numbness, and itching) has been widely reported among individuals occupationally exposed to 

pyrethroids (see Vijverberg and van den Bercken 1990 for a summary of available information on 

occupationally-induced paresthesia). Other symptoms associated with occupational exposure to 

pyrethroids include dizziness, headache, nausea, loss of appetite, blurred vision, and tightness of the 

chest. Mild acute pyrethroid poisoning is characterized in part by listlessness and muscular 

fasciculations. Increased peripheral nerve excitability was measured in cotton workers following 3 days 

of exposure to deltamethrin during spraying. Whereas paresthesia may be a biomarker of effect for 

humans occupationally exposed to pyrethroids, other reported symptoms are not specifically indicative of 

pyrethrin or pyrethroid poisoning. 
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3.9 INTERACTIONS WITH OTHER CHEMICALS 

Pyrethroids are eliminated through biotransformation reactions that are catalyzed by microsomal 

enzymes, although the specific enzymes involved have not been identified. Results from studies of 

laboratory animals show that inhibition of hydrolytic reactions and of oxidative metabolism increases the 

toxicity of pyrethroids, while induction of microsomal oxidases decreases the toxicity of pyrethroids 

(Hutson 1979). Therefore, it appears that chemicals or drugs capable of inducing or inhibiting the 

enzymes involved in pyrethroid biotransformation reactions can alter the metabolism of pyrethroids. 

Since the metabolites of pyrethroids are more water soluble than the parent compounds, they are less 

likely to cross the blood-brain barrier and are more easily excreted by the kidney and liver than the parent 

compounds. Thus, alterations in the metabolism of pyrethroids through inhibition or induction of 

microsomal enzymes could alter the distribution and excretion of pyrethroids. For example, piperonyl 

butoxide, a common insecticide synergist, inhibits microsomal enzymes and potentiates the toxic effects 

of pyrethrins and pyrethroids to mammals. 

Limited evidence exists to suggest that some Gulf War veterans with chronic, nonspecific symptoms may 

be experiencing neurological dysfunction due to low-level exposures to mixtures of anti-cholinesterase 

agents, insect repellents, and pyrethroids that might have additive or synergistic effects (Haley and Kurt 

1997; Haley et al. 1997a, 1997b). To test this hypothesis, McCain et al. (1997) administered rats oral 

doses of a short-acting anti-cholinesterase agent (pyridostigmine bromide), an insect repellent (DEET), 

and permethrin, alone or in combination, and found that combined exposure resulted in a higher degree of 

lethality than that which would be expected from additive lethal values obtained for each chemical 

separately. Abu-Qare and Abou-Donia (2001a) demonstrated that co-administration of DEET and 

permethrin to the skin of rats resulted in significantly increased release of brain mitochondrial 

cytochrome c, whereas no significant effect was seen following applications of either chemical alone. 

The effects of combined exposure may be the result of synergistic effects that are expressed following 

absorption since results of an in situ assay of mouse skin revealed that DEET appeared to inhibit the 

dermal absorption of permethrin (Baynes et al. 1997). Synergistic effects could potentially occur in 

workers who spray a variety of pesticides, although no data were available to indicate such effects. 

Another indication of an adverse toxic interaction between pyrethroids and other chemicals is the finding 

of significantly increased chromosomal aberrations in bone marrow cells of rats orally administered 

repeated doses of cypermethrin and lead, in combination (Nehéz et al. 2000). This effect was significant 
 

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when compared with both control animals and those administered cypermethrin or lead separately, and 

appeared to be greater than an additive effect. 

See Section 3.11.3 for information regarding chemicals used to reduce the toxic effects of pyrethrins and 

pyrethroids. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to pyrethrins or pyrethroids than 

will most persons exposed to the same level of pyrethrins or pyrethroids 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 pyrethrins or 

pyrethroids, or compromised function of organs affected by pyrethrins or pyrethroids. Populations who 

are at greater risk due to their unusually high exposure to pyrethrins or pyrethroids are discussed in 

Section 6.7, Populations With Potentially High Exposures. 

Pyrethroids are eliminated from the body primarily by metabolism and subsequent excretion of 

metabolites into the urine. Individuals with impaired liver function that results in decreased ability to 

metabolize pyrethrins or pyrethroids are likely to have increased susceptibility to the toxic effects of 

pyrethrins or pyrethroids. Since urine and bile are the major excretory routes for pyrethrin and pyrethroid 

metabolites, kidney and/or liver disease are likely to delay elimination of metabolites from the body. 

However, no studies were located in which metabolites of pyrethrins or pyrethroids were shown to exert 

toxic effects in humans or animals. Young animals may be more susceptible during stages when enzymes 

responsible for metabolizing absorbed pyrethroids are not fully developed (Cantalamessa 1993) or during 

critical stages of neonatal brain development (Ahlbom et al. 1994; Eriksson and Fredriksson 1991; Talts 

et al. 1998a). A predisposition for asthma may contribute to pyrethrin- or pyrethroid-induced respiratory 

effects. Allergic reactions have been observed in a few individuals following exposure to products that 

contain pyrethrins or pyrethroids. However, such responses may be due, at least in part, to “inert 

ingredients” in such products. 
 

 

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3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to pyrethrins or pyrethroids. 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 

pyrethrins. 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 pyrethrins: 

Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Medical toxicology: Diagnosis and treatment of 

human poisoning. 2nd edition. Baltimore: Williams & Wilkins, 1626–1627. 

Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. 1998. Goldfrank’s toxicologic emergencies. 6th 

edition. Stamford: Appleton & Lange, 1455–1456. 

Haddad LM, Shannon MW, Winchester JF, eds. 1998. Clinical management of poisoning and drug 

overdose. 3rd edition. Philadelphia: W.B. Saunders, 482–483. 

3.11.1 Reducing Peak Absorption Following Exposure 

Inhalation Exposure. There is little information regarding the degree of absorption following 

inhalation exposure to pyrethrins or pyrethroids, although it is presumed that absorption will occur via 

diffusion across lipid membranes. However, there is no known effective way to reduce absorption 

following inhalation exposure to pyrethrins or pyrethroids. 

Oral Exposure. Pyrethrins and pyrethroids are rapidly absorbed following oral exposure and it is 

presumed that absorption occurs across the intestinal mucosa via diffusion. There is, however, very little 

information available regarding the rate or extent of absorption following oral administration in humans. 

Use of lavage and activated charcoal would likely result in reduced absorption following oral exposure, 

and charcoal may aid in removing compounds undergoing enterohepatic recirculation. It is also presumed 

that some absorption could occur in the mouth and stomach and, therefore, mouth rinsing may modestly 

contribute to decreasing absorption following oral exposure. 
 

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Dermal Exposure. Pyrethrins and pyrethroids are not well absorbed following dermal exposure, but 

limited absorption through the skin does occur. Washing of the skin with soap and water would reduce 

dermal absorption. If the eyes are affected, proper rinsing procedures should be followed. 

No information was located regarding the effectiveness of various methods intended to reduce peak 

absorption of pyrethrins or pyrethroids following exposure. 

3.11.2 Reducing Body Burden 

No information was located regarding the effectiveness of various methods intended to reduce pyrethrin 

or pyrethroid body burden following absorption. 

Pyrethrins and pyrethroids are substantially detoxified through biotransformation reactions catalyzed by 

microsomal enzymes, although the specific enzymes involved have not been identified. It is anticipated 

that the body burden would be reduced more quickly if these enzymes are induced; however, until the 

specific enzymes involved are identified, it is not possible to specify protocols to reduce the body burden 

of pyrethrins or pyrethroids through induction of microsomal enzymes. Metabolites of pyrethrins and 

pyrethroids are excreted in urine and bile, but no specific information is available regarding the renal or 

hepatic handling of these metabolites. Increased fluid consumption, which increases the rate of urine 

production and excretion, may help to decrease the body burden of pyrethroid metabolites since they are 

water soluble and excreted in the urine. Activated charcoal might aid in removing pyrethrins or 

pyrethroids undergoing enterohepatic circulation. However, since pyrethrins and pyrethroids are rapidly 

metabolized by mammalian detoxification systems, such methods for reducing body burden might not 

effectively shorten the time during which pyrethrins and pyrethroids exert their toxic effects. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

No information was located regarding effective methods for interfering with the mechanism of action for 

pyrethrin- or pyrethroid-induced toxic effects. Anticonvulsant drugs have varying degrees of therapeutic 

efficacy in various animal species treated with a variety of pyrethroids, and may not be regarded as 

specific antidotes for pyrethroid poisoning in general (Vijverberg and van den Bercken 1990). Muscle 

relaxants such as mephenesin and methocarbamol may be more effective counters to pyrethroid 

poisoning, but appear to be more effective against Type II than Type I pyrethroids (Bradbury et al. 1981; 
 

 

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Hiromori et al. 1986). Atropine appears to be effective in reducing pyrethroid-induced effects such as 

salivation and choreoathetosis in animals (Ray and Cremer 1979). Agents such as ivermectin and 

pentobarbitone, which act as agonists at chloride channels, have been shown to reduce salivation and 

choreoathetosis, respectively, in animals (Forshaw and Ray 1997). Dermal applications of Vitamin E and 

local anesthetic creams have effectively reduced symptoms of paresthesia following dermal exposure to 

pyrethroids (Flannigan et al. 1985b; Malley et al. 1985; Tucker et al. 1984). 

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 pyrethrins and pyrethroids 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 pyrethrins and pyrethroids. 

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 Pyrethrins and Pyrethroids 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

pyrethrins and pyrethroids are summarized in Figure 3-5. The purpose of this figure is to illustrate the 

existing information concerning the health effects of pyrethrins and pyrethroids. Each dot in the figure 

indicates that one or more studies provide information associated with that particular effect. The dot does 

not necessarily imply anything about the quality of the study or studies, nor should missing information in 

this figure be interpreted as a “data need”. A data need, as defined in ATSDR’s Decision Guide for 

Identifying Substance-Specific Data Needs Related to Toxicological Profiles (Agency for Toxic 

Substances and Disease Registry 1989), is substance-specific information necessary to conduct 
 

PYRETHRINS AND PYRETHROIDS 119 

3. HEALTH EFFECTS 

Figure 3-5. Existing Information on Health Effects of

Pyrethrins and Pyrethroids 
 

PYRETHRINS AND PYRETHROIDS 120 

3. HEALTH EFFECTS 

comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any 

substance-specific information missing from the scientific literature. 

Available data regarding health effects in humans exposed to pyrethrins or pyrethroids largely concern 

occupational exposure during crop applications in which exposure was considered to have occurred 

primarily via dermal contact, although inhalation exposure could not be ruled out. Therefore, Figure 3-5 

indicates that information exists for both inhalation and dermal exposure routes. A number of human 

cases involved intentional ingestion of pyrethroids. Both inhalation and dermal exposures were likely in 

the few reported cases of reactive airway responses. Some occupational exposures were considered to 

have been of intermediate or chronic duration due to repeated exposures ranging from weeks to years. 

However, observed health effects following repeated exposure to pyrethrins or pyrethroids were similar to 

those that characterize acute pyrethroid poisoning. 

The database for health effects following oral exposure to pyrethrins or pyrethroids in experimental 

animals is substantial. However, as can be seen in Figure 3-5, information regarding health effects 

following inhalation or dermal exposure is more limited. The nervous system appears to be the 

predominant target of pyrethrin- and pyrethroid-induced toxicity. Genotoxicity data on pyrethrins and 

pyrethroids are available from studies in vivo and in vitro; results of genotoxicity tests are predominantly 

negative. Pyrethrum extract (containing 57.7% pyrethrins) may induce cancer in laboratory animals as 

evidenced by increased incidences of liver and thyroid tumors in rats exposed orally for a lifetime. Based 

on currently available animal cancer bioassays, synthetic pyrethroids do not appear to pose a particular 

carcinogenicity concern. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Reports in which inhalation could be considered to be a significant route 

of exposure to pyrethrins or pyrethroids are mainly available from studies of workers involved in the 

manufacture or use of the chemicals (Chen et al. 1991; Flannigan and Tucker 1985; Flannigan et al. 

1985b; He et al. 1988, 1989, 1991; Knox et al. 1984; Kolmodin-Hedman et al. 1982; LeQuesne and 

Maxwell 1980; Moretto 1991; Shujie et al. 1988; Tucker and Flannigan 1983; Zhang et al. 1991). 

Limitations associated with these reports include lack of quantitative exposure data, lack of data on 

duration of exposure, and the possibility of multiple routes of exposure (i.e., dermal as well as inhalation). 

Dermal exposure was considered to have been the principal exposure route among individuals involved 
 

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with spraying pyrethroids. A limited report in which inhalation exposure was considered to be the 

primary exposure route did not include exposure levels (Lessenger 1992). Limited animal inhalation 

toxicity data are available for pyrethrins and pyrethroids (Curry and Bennett 1985; Flucke and Thyssen 

1980; Hext 1987; Kavlock et al. 1979; Miyamoto 1976; Pauluhn and Thyssen 1982; Schoenig 1995), but 

these studies mainly concerned lethality or used exposure levels at which serious neurological effects 

were elicited. Due to the limited nature of the human and animal data, an acute inhalation MRL could not 

be derived. Additional peer-reviewed animal studies designed to examine the effects of acute inhalation 

exposure to pyrethrins and pyrethroids would strengthen the database of currently available information. 

The nervous system is the major target of pyrethrin- and pyrethroid-induced toxicity. Numerous reports 

describe clinical signs of neurotoxicity in humans (Gotoh et al. 1998; He et al. 1989; Peter et al. 1996) 

and laboratory animals (Eriksson and Nordberg 1990; Hudson et al. 1986; Parker et al. 1983, 1984a, 

1984b, 1985; Ray and Cremer 1979; Southwood 1984) following acute oral exposure to relatively high 

doses of pyrethrins or pyrethroids. One research group (Eriksson and coworkers) has reported 

neurological effects in adult mice that had been administered acute oral doses of pyrethroids during 

critical stages of neonatal brain growth (postpartum days 10–16) at exposure levels much lower than 

those eliciting the classical clinical signs of neurotoxicity (Ahlbom et al. 1994; Eriksson and Fredriksson 

1991; Eriksson and Nordberg 1990; Talts et al. 1998a). Another group of investigators (Ray et al. 2002) 

duplicated the study design of Eriksson and coworkers, but did not observe a toxicologically significant 

neurological effect. Additional studies designed to assess developmental neurotoxic effects at relatively 

low levels of oral exposure to pyrethrins and pyrethroids could serve to support or refute the findings of 

Eriksson and coworkers. 

Paresthesia (an abnormal cutaneous sensation sometimes described as tingling, burning, stinging, 

numbness, and itching) has been widely reported by individuals occupationally exposed to pyrethroids 

(Flannigan and Tucker 1985; Flannigan et al. 1985b; Knox et al. 1984; LeQuesne and Maxwell 1980; 

Tucker and Flannigan 1983). Higher levels of exposure to various pyrethroids have resulted in mild acute 

pyrethroid poisoning that included dizziness, headache, and nausea (Chen et al. 1991; Moretto 1991; 

Shujie et al. 1988; Zhang et al. 1991). However, human studies typically involved the potential for 

multiple exposure routes and exposure levels were not quantified. Limited available peer-reviewed 

animal data indicate neurotoxicity following acute dermal exposure to pyrethroids (El-Elaimy 1986; 

Meyer 1999; Mitchell et al. 1988). Analysis of results of acute dermal toxicity testing by the pesticide 

industry might preclude the need for additional animal studies. 
 

 

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Acute-duration inhalation MRLs were not derived for pyrethrins or pyrethroids due to the limited 

available information concerning health effects following inhalation exposure to pyrethrins or 

pyrethroids. Acute-duration oral MRLs were derived for permethrin, cypermethrin, and cyhalothrin. As 

information becomes available for additional pyrethroids, acute-duration oral MRLs can be derived for 

them as well. 

Intermediate-Duration Exposure. Available reports of toxicoses in humans occupationally 

exposed to pyrethrins or pyrethroids include multiple exposure routes (dermal, inhalation, and possibly 

oral) and lack quantitative exposure data. Oral data and limited inhalation data were available for 

laboratory animals repeatedly exposed to pyrethrins or pyrethroids (Cabral and Galendo 1990; DOD 

1977; Flucke and Schilde 1980; Hext et al. 1986; IRIS 2003a, 2003b, 2003c; Ishmael and Litchfield 1988; 

Miyamoto 1976; Mohan et al. 1998; Parker et al. 1984a, 1984b; Schoenig 1995), but there were few 

indications that repeated or continuous exposure result in cumulative neurological effects in animals 

exposed as adults. Intermediate-duration inhalation MRLs were not derived for pyrethrins or pyrethroids 

due to the limited available information concerning health effects following inhalation exposure to 

pyrethrins or pyrethroids. Intermediate-duration oral MRLs were derived for permethrin and cyhalothrin. 

As information becomes available for additional pyrethroids, intermediate-duration oral MRLs can be 

derived for them as well. 

Chronic-Duration Exposure and Cancer. Available reports of toxicity in humans occupationally 

exposed to pyrethrins or pyrethroids include multiple exposure routes (dermal, inhalation, and possibly 

oral) and lack quantitative exposure data. Oral data were available for laboratory animals chronically 

exposed to pyrethrins or pyrethroids (Cabral and Galendo 1990; Hext et al. 1986; IRIS 2003a, 2003b, 

2003c; Ishmael and Litchfield 1988; Parker et al. 1984a; Schoenig 1995), but there were no indications 

that repeated or continuous exposure might result in cumulative neurological effects. Chronic-duration 

inhalation MRLs were not derived for pyrethrins or pyrethroids due to the limited available information 

concerning health effects following inhalation exposure to pyrethrins or pyrethroids. Chronic-duration 

oral MRLs were not derived for pyrethrins or pyrethroids, due to inadequate data. 

Available cancer bioassays of animals administered pyrethrins or selected pyrethroids orally provide 

equivocal evidence of a carcinogenic effect (Cabral and Galendo 1990; EPA 1994c; Ishmael and 

Litchfield 1988; Miyamoto 1976; Parker et al. 1983, 1984a; Schoenig 1995). Additional information 

from the pesticide industry should be reviewed in the process of assessing the need for additional studies. 
 

 

 

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Genotoxicity. No information was located regarding the genotoxicity of pyrethrins or pyrethroids in 

humans. Limited information indicated that pyrethrins were not mutagenic in bacterial test systems in 

vitro (see Table 3-3). Type I and Type II pyrethroids generally tested negative for mutagenicity in 

prokaryotic test systems, but some positive results were obtained for mutation in yeast cells exposed to 

selected Type I and Type II pyrethroids (see Tables 3-6 and 3-7). Tests in mammalian systems, both in 

vivo and in vitro, indicated that Type I and Type II pyrethroids had the potential to induce chromosomal 

damage (see Tables 3-6 and 3-7). 

Reproductive Toxicity. No information was located regarding pyrethrin- or pyrethroid-induced 

reproductive toxicity in humans. Reproductive toxicity was not observed in rats administered oral doses 

of pyrethrins in the diet at concentrations resulting in average daily doses of 240 mg/kg for 2 generations 

(Schoenig 1995). One 3-generation study found no evidence for reproductive toxicity from fenpropathrin 

at an oral dose level of 25 mg/kg/day (Hend et al. 1979). However, Abd El-Aziz et al. (1994) reported 

significantly reduced fertility in male rats following intermediate-duration oral exposure to deltamethrin 

at a dose level of 1 mg/kg/day. Additional reproductive toxicity studies could be designed to support or 

refute these results. 

Developmental Toxicity. No information was located regarding pyrethrin- or pyrethroid-induced 

developmental toxicity in humans. Most available developmental toxicity studies in animals do not 

indicate that pyrethrins or pyrethroids might be considered to be developmental toxicity hazards. The 

World Health Organization (WHO 2001), and EPA (IRIS 2003f) reviewed a number of unpublished or 

proprietary developmental toxicity studies performed for various chemical organizations. The summaries 

of WHO (2001) and EPA (IRIS 2003f) indicate that classical developmental effects are not elicited 

following exposure to pyrethroids. 

Recent studies by Eriksson and coworkers suggest that exposure to pyrethroids during neonatal stages of 

development when the brain is rapidly growing, may result in adverse neurological effects (changes in 

MACh receptor density in the cerebral cortex and increased spontaneous locomotor behavior) that are not 

apparent until adulthood (Ahlbom et al. 1994; Eriksson and Fredriksson 1991; Eriksson and Nordberg 

1990; Talts et al. 1998a). However, limitations in study design and lack of success in duplicating the 

results (Ray et al. 2002; Tsuji et al. 2002) render the studies of Eriksson and coworkers of questionable 

value for the purpose of risk assessment. Additional studies should be designed to support or refute the 

findings of Eriksson and coworkers. 
 

 

 

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Immunotoxicity. A few cases of hypersensitive responses in humans exposed to pyrethrins and 

pyrethroids have been documented in available literature (Box and Lee 1996; Carlson and Villaveces 

1977; Wagner 2000; Wax and Hoffman 1994). Available information regarding immunotoxicity in 

animals was limited to oral studies in which administration of selected pyrethroids resulted in 

immunotoxic effects such as suppression of the humoral immune response, alterations in lymphocytes, 

leukopenia, altered natural killer cell activity, and decreased spleen weight (Blaylock et al. 1995; Demian 

1998; Demian and El-Sayed 1993; Dési et al. 1986; Lukowicz-Ratajczak and Krechniak 1992; Varshneya 

et al. 1992). No adequate studies are available in humans to assess the immunotoxic potential of 

pyrethrins or pyrethroids. Studies measuring specific immunologic parameters in occupationally exposed 

populations might provide useful information. However, inherent variation among human subjects would 

necessitate very large sample sizes. Animal studies designed to investigate the mechanism for pyrethroidinduced immunotoxicity might help to identify special populations at risk for such effects. 

Neurotoxicity. Abundant human data show that exposure to large amounts of pyrethroids, either by 

accidental or intentional ingestion or by dermal and inhalation exposure during unprotected handling or 

spraying of pyrethroids, may result in clinical signs of neurotoxicity (Chen et al. 1991; Flannigan and 

Tucker 1985; Flannigan et al. 1985b; Gotoh et al. 1998; He et al. 1989, 1991; Knox et al. 1984; LeQuesne 

and Maxwell 1980; Moretto 1991; Peter et al. 1996; Shujie et al. 1988; Tucker and Flannigan 1983; 

Zhang et al. 1991). Exposure of laboratory rodents to selected Type I and Type II pyrethroids has been 

shown to trigger typical signs of Type I (aggressive behavior and increased sensitivity to external stimuli, 

fine tremor, prostration with coarse whole body tremor, elevated body temperature, and coma) and 

Type II (pawing and burrowing behavior, profuse salivation, increased startle response, abnormal 

hindlimb movements, and choreoathetosis) pyrethroid poisoning. Although the majority of animal 

studies reporting neurotoxic effects employed oral exposure (EPA 1988c, 1991a, 1991b, 1992b, 1992c, 

1994b; Eriksson and Nordberg 1990; Hudson et al. 1986; McDaniel and Moser 1993; Parker et al. 1983, 

1984a, 1984b, 1985; Ray and Cremer 1979; Southwood 1984), these effects were also elicited following 

inhalation and dermal exposure (Curry and Bennett 1985; El-Elaimy 1986; Pauluhn and Thyssen 1982; 

Schoenig 1995). Several investigators reported typical signs of Type I or Type II pyrethroid poisoning in 

laboratory rodents during repeated oral administration of pyrethrins or pyrethroids (from 2 days to 

2 years), but there were few indications that repeated or continuous exposure might result in cumulative 

neurological effects (Cabral and Galendo 1990; DOD 1977; Flucke and Schilde 1980; Hext et al. 1986; 

IRIS 2003a, 2003b, 2003c; Ishmael and Litchfield 1988; Mohan et al. 1998; Parker et al. 1984a, 1984b; 

Schoenig 1995). Some investigators have reported signs of neurotoxicity such as altered locomotor 
 

 

 

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activity, altered acoustic startle response, decreased active avoidance response, and changes in brain 

neurotransmitter concentrations at pyrethroid exposure levels below those eliciting clinical signs of 

Type I or Type II pyrethroid poisoning (Crofton and Reiter 1988; Hijzen et al. 1988; Husain et al. 1991; 

Mandhane and Chopde 1997; Mitchell et al. 1988; Moniz et al. 1994; Spinosa et al. 1999). Additional 

studies of the neurotoxicity of pyrethrins and pyrethroids should assess sensory function in humans and 

sensitivity of unique populations such as farm workers, children of farm workers, the elderly, and 

veterans of the Gulf War. 

Epidemiological and Human Dosimetry Studies. Available information regarding the health 

effects of pyrethrins and pyrethroids in humans mainly concerns reports of neurological effects following 

accidental or intentional ingestion or during unprotected handling or spraying (Chen et al. 1991; 

Flannigan and Tucker 1985; Flannigan et al. 1985b; Gotoh et al. 1998; He et al. 1989, 1991; Knox et al. 

1984; LeQuesne and Maxwell 1980; Moretto 1991; Peter et al. 1996; Shujie et al. 1988; Tucker and 

Flannigan 1983; Zhang et al. 1991). Occupational exposure to pyrethrins and pyrethroids may be 

confounded by differences in specific formulations and by concurrent exposures to other pesticides. 

Pesticide applicators, farm workers, individuals involved in production of pyrethrins or pyrethroids, and 

individuals exposed in recently sprayed homes or offices might serve as a focus for well-designed 

epidemiological studies for further assessment of neurological effects of pyrethrins and pyrethroids, as 

well as assessment of other potential adverse effects, such as immunotoxicity. Studies of dosimetry 

would be useful in future epidemiological studies. 

Biomarkers of Exposure and Effect. 

Exposure. Measurement of urinary metabolites of pyrethroids can serve as useful markers of exposure 

(Aprea et al. 1997; Kühn et al. 1999; Leng et al. 1996, 1997a, 1997b). However, there is insufficient 

information from studies in humans or animals to allow for correlation of the amounts of metabolites 

measured in the urine to the body burden of pyrethroids or to the level of exposure to pyrethroids. 

Additional information regarding the relationship of urinary pyrethroid metabolite levels to pyrethroid 

body burden and to exposure levels could improve the ability to monitor worker’s exposure to 

pyrethroids. Also, residues of pyrethrins and pyrethroids and their metabolites should be determined in 

blood of humans (antemortem) and in blood, digestive tract contents, liver, kidney, and brain of animals 

and accidently exposed or suicide victims (postmortem). Without detailed knowledge regarding the 

appearance and disappearance of parent compounds and metabolites over the course of a toxicosis, 

confirmed diagnoses will remain elusive to impossible. 
 

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Effect. Biomarkers of effect for pyrethrins and pyrethriods include typical neurotoxic signs of acute 

pyrethroid poisoning (Coats 1990; Verschoyle and Aldridge 1980). Although these clinical signs are 

distinctive, they are not totally unique to pyrethrin or pyrethroid poisoning. 

Absorption, Distribution, Metabolism, and Excretion. The absorption, distribution, 

metabolism, and excretion of pyrethrins or pyrethroids following exposure by any route are not well 

characterized in humans. While many studies have investigated these processes for pyrethroids in various 

laboratory animals, in general, toxicokinetics of these compounds are not well defined. No PBPK models 

of pyrethrins or pyrethroids have been reported. Information to support the development of a PBPK 

model for pyrethrins or pyrethroids has not been systematically compiled and is currently insufficient to 

support such models (e.g., mechanisms and kinetic constants and variables of metabolism, tissue partition 

coefficients). Such models would be useful for predicting body burdens and, if combined with doseresponse models, for predicting health effects of pyrethrins and pyrethroids associated with known or 

projected exposures. 

Absorption. Although results of studies in humans and laboratory animals demonstrate that pyrethroids 

are absorbed following exposure by the inhaled, oral, and dermal routes, further studies would be helpful 

for quantifying the absorption and time-course of absorption by each exposure route. It has been 

proposed that pyrethroids are stored in the skin following dermal exposure and are slowly released into 

the systemic circulation (Eadsforth et al. 1988; Woollen et al. 1992). Given the importance of the dermal 

route in occupational exposure to pyrethroids, additional information regarding the time-course of 

absorption following dermal exposure would be helpful. Little information is available concerning roles 

such factors as diet, age, sex, or other chemicals and drugs might play in the absorption of pyrethroids by 

any route in humans and animals. Further studies are needed to examine these factors and define 

potential differences in absorption over a range of pyrethrins and pyrethroids. 

Distribution. The distribution of pyrethrins and pyrethroids in humans and animals has not been well 

studied. From the results of studies in laboratory animals, it is concluded that pyrethroids are rapidly and 

widely distributed and are concentrated in central and peripheral nerve tissues (Anadón et al. 1991a, 

1991b, 1996; Gray and Rickard 1982; Gray et al. 1980). Additional investigations on distribution would 

provide a further understanding of the extent of distribution of pyrethroids to nervous system tissues (a 

principal target of pyrethroid toxicity) and to define the time-course for distribution and tissue retention, 

particularly in tissues that are targets for toxicity. Extremely limited information is available regarding 
 

 

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3. HEALTH EFFECTS 

distribution of pyrethroids to the fetus and into breast milk. Additional studies are needed to assess the 

potential risks of exposure in utero and via breast milk. Additional studies also may be warranted to 

identify factors that may alter distribution of pyrethroids and to define potential differences in distribution 

with respect to age and sex. 

Metabolism. The metabolism of pyrethrins and pyrethroids in humans has not been well defined. 

Although the metabolism of pyrethroids has been extensively studied in laboratory animals, the specific 

enzymes responsible for the biotransformation of pyrethroids have not been identified. Further research 

identifying these enzymes would allow the evaluation of many potential factors, such as age, sex, and 

other chemicals and drugs, that could alter the metabolism of pyrethroids. This is of particular 

importance since metabolism of pyrethroids is generally accepted as the primary detoxifying mechanism 

in mammals (Gray and Soderlund 1985; Hutson 1979). 

Elimination and Excretion. The elimination and excretion of pyrethrins and pyrethroids in humans have 

not been well defined and information is limited to studies investigating the elimination of pyrethroids 

from the plasma and excretion of pyrethroids into the urine. Additional information on nonurinary 

excretory routes and information to quantify excretion by each route in humans would be helpful for 

predicting routes and elimination kinetics in humans. Based on the limited information available in 

humans, it is not possible to predict precisely how long pyrethroids will remain in the body following 

exposure by various routes. Further study on the elimination kinetics of a range of pyrethroids by each 

route of exposure would be helpful for developing predictive models in humans. There is little 

information available regarding the mechanisms of excretion in either humans or animals. Further study 

on these mechanisms would allow assessment of the many potential factors, such as age, sex, and other 

chemicals and drugs, that could alter the elimination and excretion of pyrethroids. 

Comparative Toxicokinetics. Insufficient information is available regarding comparative 

toxicokinetics of pyrethrins or pyrethroids in humans and laboratory animals. Further investigations on 

potential differences in humans and animals may help to determine appropriate species and strains of 

animals to use in predicting the toxicokinetics of pyrethroids in humans. Evaluation of mechanisms, 

character, and extent of human variability in the disposition of pyrethroids is also warranted. 

Methods for Reducing Toxic Effects. Other than general guidelines of washing the skin with soap 

and water following dermal exposure and use of gastric lavage and activated charcoal following oral 

exposure, little additional information is available regarding methods for reducing absorption of 
 

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3. HEALTH EFFECTS 

pyrethroids. Additional studies on factors that could affect the absorption and metabolism of pyrethroids, 

such as diet and concomitant exposure to other chemicals and drugs, would be helpful in understanding 

the impact of these factors on risks from occupational exposures. 

Children’s Susceptibility. Neurotoxic effects have been well characterized in humans exposed to 

pyrethrins and pyrethroids. Information mainly derives from individuals occupationally exposed during 

spraying. No reports on exposed children were found, but it is reasonable to assume that children would 

exhibit signs and symptoms similar to those in adults under similar exposure conditions. No information 

was located regarding developmental toxicity in humans exposed to pyrethrins or pyrethroids. Studies in 

animals have suggested that neonatal exposure to pyrethroids may result in neurological effects first 

observed in adulthood (Ahlbom et al. 1994; Eriksson and Fredriksson 1991; Eriksson and Nordberg 1990; 

Talts et al. 1998a). These results could not be confirmed by independent investigators (Ray et al. 2002). 

No human data were located regarding age-related differences in the pharmacokinetics of pyrethrins or 

pyrethroids. Limited animal data suggest that young animals may be more susceptible to pyrethroid 

poisoning, possibly due to less efficient production of enzymes responsible for detoxification 

(Cantalamessa 1993). 

Extremely limited data suggest that pyrethroids may be minimally transferred across the placenta to the 

fetus (Quistad et al. 1982). Very low levels of pyrethroids have been measured in the milk of lactating 

cows and goats (Gaughan et al. 1978; Hunt and Gilbert 1977; Quistad et al.1982; Ridlen et al. 1984; 

Wszolek et al. 1980). 

No data were located regarding pediatric-specific methods to reduce peak absorption of pyrethrins or 

pyrethroids following exposure, to reduce body burdens, or to interfere with mechanisms of action. 

Based on available information, it is reasonable to assume that methods recommended for treating adults 

will also be applicable to children. 

Child health data needs relating to exposure are discussed in 6.8.1 Identification of Data Needs: 

Exposures of Children. 
PYRETHRINS AND PYRETHROIDS 129 

3. HEALTH EFFECTS 

3.12.3 Ongoing Studies 

The Federal Research In Progress database (FEDRIP 2003) lists an ongoing study in which Dr. B. 

Wilson, from the University of California, Davis, California has proposed the development of biomarkers 

of exposure and effect for organophosphorus and pyrethroid insecticidal sprays. Two studies were 

located in the Computer Retrieval of Information in Scientific Projects database (CRISP 2003). Dr. S. 

Holladay, from Virginia Polytechnic Institute and State University, Blacksburg, Virginia, is investigating 

the immunotoxicity of permethrin. Dr. D. Soderlund, from Cornell University, Ithaca, New York, is 

investigating specific mechanisms of action of pyrethroids in vertebrate systems. Dr. T. Narahashi, from 

Northwestern University, Chicago, Illinois, is investigating differential actions of Type II pyrethroids on 

sodium channels. 

 

PYRETHRINS AND PYRETHROIDS 131 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

The naturally-occurring pyrethrins, extracted from chrysanthemum flowers, are esters of chrysanthemic 

acid (Pyrethrin I, Cinerin I, and Jasmolin I) and esters of pyrethric acid (Pyrethrin II, Cinerin II, and 

Jasmolin II). In the United States, the pyrethrum extract is standardized as 45–55% w/w total pyrethrins. 

The typical proportion of Pyrethrins I to II is 0.2:2.8, while the ratio of pyrethrins:cinerins:jasmolins 

is 71:21:7 (Tomlin 1997). Information regarding the chemical identity of the pyrethrins is presented in 

Table 4-1. 

Pyrethroids are synthetic esters derived from the naturally-occurring pyrethrins. One exception to the 

axiom that all pyrethroids are esters of carboxylic acids is noteworthy. There is a group of oxime ethers 

that exhibits insecticidal activity similar in nature to the pyrethrins and pyrethroid esters (Davies 1985). 

Little data exist regarding these compounds, and no commercial products have been produced. 

Commercially available pyrethroids include allethrin, bifenthrin, bioresmethrin, cyfluthrin, cyhalothrin, 

cypermethrin, deltamethrin, esfenvalerate (fenvalerate), flucythrinate, flumethrin, fluvalinate, 

fenpropathrin, permethrin, phenothrin, resmethrin, tefluthrin, tetramethrin, and tralomethrin. Information 

regarding the chemical identity of pyrethroids is shown in Table 4-2. 

With the exception of deltamethrin, pyrethroids are a complex mixture of isomers rather than one single 

pure compound. For pyrethroids possessing the cyclopropane moiety, isomerism about the cyclopropane 

ring greatly influences the toxicity of these insecticides. The presence of two chiral centers in the ring 

results in two pairs of diastereomers. The diastereomers and their nonsuperimposable mirror images 

(enantiomers) are illustrated in Figure 4-1. In this figure, the C-1 position of the ring is assigned to the 

carbon atom bonded to the ester moiety. It is also customary to designate the stereochemistry at the C-3 

position as simply cis or trans relative to the ester group bonded to C-1 rather than assigning its absolute 

configuration. The 1R conformations about the cyclopropane ring are considerably more toxic than the 

1S isomers. Both the cis and trans isomers show insecticidal activity, but have differing mammalian 

toxicities, with the cis isomers being more potent (Ray 1991). Pyrethroids that contain a cyano 

substituent at the alcohol moiety (Type II pyrethroids) demonstrate differing toxicity based upon the 

optical isomerism of the alpha carbon. It has been demonstrated that the S conformation about the alpha 

carbon is considerably more toxic towards insects when compared to the R conformation (Dorman and 
O 

O 

O 

O O 

O 

O 

O 

O 

 

 

PYRETHRINS AND PYRETHROIDS 132 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of the Pyrethrins 

Characteristic Pyrethrin I Cinerin I Jasmolin I 

Synonym(s)b 

Ratio of isomers 

Registered trade name(s) 

Chemical formula 

Chemical structure 

(Z)-(S)-2-methyl-4-oxo3-(penta-2,4­

dienyl)cyclo pent-2­

enyl (1R)-trans-2,2­

dimethyl-3-(2-methyl 

prop-1-enyl)cyclopropanecarboxylate 

Pure isomer 

Alfadex, Evergreen, 

ExciteR, Milon, Pycon, 

Pyrocide, Pyronyl 

C21H28O3 

(Z)-(S)-3-(but-2-enyl)­

2-methyl-4­

oxocyclopent-2-enyl 

(1R)-trans-2,2-di 

methyl-3-(2-methyl 

prop-1-enyl)cyclopropanecarboxylate 

Pure isomer 

Alfadex, Evergreen, 

ExciteR, Milon, Pycon, 

Pyrocide, Pyronyl 

C20H28O3 

(Z)-(S)-2-methyl-4-oxo3-(pent-2­

enyl)cyclopent-2-enyl 

(1R)-trans-2,2-dimethyl-3-(2­

methylprop-1-enyl)­

cyclopropanecarboxylate 

Pure isomer 

Alfadex, Evergreen, 

ExciteR, Milon, Pycon, 

Pyrocide, Pyronyl 

C21H30O3 

Identification numbers:

 CAS registry 121-21-1 25402-06-6 4466-14-2

 NIOSH RTECSc GZ1725000 GZ1540000 No data 

EPA hazardous wasted No data No data No data

 OHM/TADS No data No data No data

 DOT/UN/NA/IMCO shipping No data No data 6302 

HSDBd 6302 6837 No data

 NCI No data No data No data 
O O 

O 

O O 

O 

O 

O O 

O O O 

O 

O O 

 

 

PYRETHRINS AND PYRETHROIDS 133 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of the Pyrethrins 

Characteristic Pyrethrin II Cinerin II Jasmolin II 

Synonym(s)b 

Ratio of isomers 

Registered trade name(s) 

Chemical formula 

Chemical structure 

(Z)-(S)-2-methyl-4­

oxo-3-(penta-2,4­

dienyl)cyclo pent-2­

enyl (E)-(1R)-trans-3­

(2-methoxy carbon 

ylprop-1-enyl)-2,2­

dimethylcyclopropanecarboxylate 

Pure isomer 

Alfadex, Evergreen, 

ExciteR, Milon, Pycon, 

Pyrocide, Pyronyl 

C22H28O5 

(Z)-(S)-3-(but-2-enyl)-2­

methyl-4-oxocyclopent-2­

enyl (E)-(1R)-trans-3-(2­

methoxycarbonylprop-1­

enyl)-2,2-dimethyl 

cyclopropanecarboxylate 

Pure isomer 

Alfadex, Evergreen, 

ExciteR, Milon, Pycon, 

Pyrocide, Pyronyl 

C21H28O5 

(Z)-(S)-2-methyl-4-oxo3-(pent-2­

enyl)cyclopent-2-enyl 

(E)-(1R)-trans-3-(2­

methoxycarbonylprop-1­

enyl)-2,2-dimethylcyclopropanecarboxylate 

Pure isomer 

Alfadex, Evergreen, 

ExciteR, Milon, Pycon, 

Pyrocide, Pyronyl 

C22H30O3 

Identification numbers:

 CAS registry 121-29-9 121-20-0 1172-63-0

 NIOSH RTECSc GZ0700000 No data No data 

EPA hazardous wasted No data No data No data

 OHM/TADS No data No data No data

 DOT/UN/NA/IMCO shipping No data No data No data

 HSDBd 6303 6838 No data

 NCI No data No data No data 

a

All information obtained from Tomlin, 1997 except where noted. 

b

Chemical names used are those currently indexed by the Chemical Abstracts Service. c

NIOSH 1987 

d

HSDB 2001 

e

 WHO 2001 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; HSDB = Hazardous 

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 
 

O 

Cl O O O F 

F O O 

O 

O 

F 

 

PYRETHRINS AND PYRETHROIDS 134 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Chemical Identity of Selected Pyrethroidsa 

Characteristic	 Allethrin Bifenthrin Bioresmethrin 

Synonym(s)b	 2-methyl-4-oxo-3-(2- (2-methyl[1,1'-biphenyl]- (1R-trans)-[5­

propenyl)-2-cyclopenten- 3-yl)methyl 3-(2-chloro- phenylmethyl)-3­

1-yl 2,2-dimethyl-3-(2- 3,3,3-trifluoro-1- furanyl]mehtyl 2,2­

methyl-1- propenyl)-2,2- dimethyl-3-(2-methyl-1­

propenyl)cycloprane- dimethylcyclopropane- propenyl)cyclopropanecarboxylate carboxylate carboxylate 

Ratio of isomers $95% (1R)-isomers $97% cis-isomer $90% (1R)-trans-isomer 

$75% trans-isomers 

Registered trade name(s) Pyresin, Pynamin Forte, Talstar Isathrine 

Exthrin 

Chemical formula C19H26O3 C23H22ClF3O2 C22H26O3 

Chemical structure 

Identification numbers:

 CAS registry 584-79-2 82657-04-3 28434-01-7

 NIOSH RTECSc GZ1925000 GZ1227800 GZ1227800 

EPA hazardous waste No data No data No data

 OHM/TADS No data No data No data

 DOT/UN/NA/IMCO shipping NA2902, NA2588, No data No data

UN2588, UN2902, 

UN2903, UN3201, 

IMO3.2, IMO6.1 

HSDBd 1511 6568 6568 

NCI No data No data No data
 
F
 

Cl
 

O 

Cl O 

O CN 

O O 

F O CN
 Cl
 

F F 

Cl 

O 

Cl O 

O CN 

 

 

PYRETHRINS AND PYRETHROIDS 135 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Chemical Identity of Selected Pyrethroidsa 

Characteristic Cyfluthrin Cyhalothrin Cypermethrin 

Synonym(s)b 

Ratio of isomers 

Registered trade name(s) 

Chemical formula 

Chemical structure 

Identification numbers:

 CAS registry 

 NIOSH RTECSc 

EPA hazardous waste 

 OHM/TADS 

 DOT/UN/NA/IMCO shipping 

HSDBd

 NCI 

Cyano(4-fluoro-3-phenoxyphenyl)methyl 3-(2,2­

dichloroethenyl)-2,2­

dimethylcyclopropanecarboxylate 

Unstated 

stereochemistry 

Baythroid, Baygon 

aerosol, Solfacb 

C22H18Cl2FNO3 

68359-37-5 

GZ1253000 

No data 

No data 

No data 

6599 

No data 

[1",3"(Z)]-(±)-Cyano-(3­

phenoxyphenyl)methyl 

3-(2-chloro-3,3,3­

trifluoro-1-propenyl)2,2­

dimethylcyclopropanecarboxylate 

$95% cis-isomers 

Cyhalon, Grenade 

C23H19ClF3NO3 

68085-85-8 

GZ122770 

No data 

No data 

No data 

6791 

No data 

Cyano(3-phenoxyphenyl 

)methyl 3-(2,2-dichloro 

ethenyl)-2,2-dimethylcyclopropanecarboxylate 

Unstated 

stereochemistry 

Arrivo, Cymbush, 

Cymperator, Cynoff, 

Ripcord, Basathrin, 

Demar, Grand, Starcypb 

C22H19Br2NO3 

52315-07-8

GZ1250000 

No data

No data

No data

6600

No data 
 

 

Br 

O O Br 

O CN 

Cl 

O O 

O CN 

O 

O 

O CN 

 

PYRETHRINS AND PYRETHROIDS 136 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Chemical Identity of Selected Pyrethroidsa 

Characteristic Deltamethrin 

Synonym(s)b 

Ratio of isomers 

Registered trade name(s) 

Chemical formula 

Chemical structure 

Identification numbers:

 CAS registry 

 NIOSH RTECSc 

EPA hazardous waste 

 OHM/TADS 

 DOT/UN/NA/IMCO shipping 

HSDBd 

NCI 

[1R-[1"(S*),3"]]-Cyano 

(3-phenoxyphenyl)methyl 3-(2,2­

dibromo ethenyl)-2,2­

dimethylcyclopropanecarboxylate, 

decamethrin 

$98% single isomer 

Butox, Decis, K-Othrin, 

Kordon, Sadethrinb 

C22H19Br2NO3 

52918-63-5 

GZ1233000, 

GZ1232000 

No data 

No data 

No data 

6604 

No data 

Esfenvalerate

{S-R*,R*]-Cyano(3­

phenoxyphenyl)methyl 

4-chloro-2-(1-methylethyl)benzeneacetate, 

fenvalerate 

$75% (S,S)-isomers 

Sumi-alfa, Sumi-alpha, 

Asana (esfenvalerate), 

Pydrin, Ectrin,Sumicidin, 

Arfen, Dufen, Fenval 

(fenvalerate)b 

C25H22ClNO3 

66230-04-4, 51630-58-1 

(fenvalerate) 

CY1576367, 

CY1576350 

CY1576350 

No data 

No data 

6625, 6640 

No data 

Fenpropathrin 

Cyano(3-phenoxyphenyl)methyl 2,2,3,3­

tetramethylcyclopropanecarboxylate(racemate) 

fenpropanate 

(unspecified) 

Unstated 

stereochemistry 

Danitol, Herald, 

Meothrin, Rody, Digitalb 

C22H23NO3 

64257-84-7 (racemic), 

39515-41-8 

(stereochemistry)

GZ2090500, 

GZ2090000
 

No data

No data

No data

6636 

No data
 
F O
 

H F O O 

O CN 

Cl 

F 

O 

Cl O 

O CN 

Cl 

N O O F H 

O CN 

F F 

 

 

 

PYRETHRINS AND PYRETHROIDS 137 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Chemical Identity of Selected Pyrethroidsa 

Characteristic Flucythrinate 

Synonym(s) b 

Ratio of isomers 

Registered trade name(s) 

Chemical formula 

Chemical structure 

Identification numbers:

 CAS registry 

 NIOSH RTECSc 

EPA hazardous waste 

 OHM/TADS 

 DOT/UN/NA/IMCO shipping 

HSDBd 

NCI 

Cyano(3-phenoxyphenyl)methyl 4­

(difluoromethoxy)-"-(1­

methylethyl)benzeneacetate 

No data 

Cybolt, Cythrin, Pay-off, 

Fluent 

C26H23F2NO4 

70124-77-5 

CY1578620 

No data 

No data 

No data 

6647 

No data 

Flumethrin 

"-Cyano-4-fluoro-3­

phenoxybenzyl 3-(ß,4­

dichlorostyryl)-2,2­

dimethylcyclopropanecarboxylate 

Unstated 

stereochemistry 

Bayticol, Bayvarol 

C28H22Cl2FNO3 

69770-45-2 

No data 

No data 

No data 

No data 

No data 

No data 

Fluvalinate 

Cyano(3-phenoxyphenyl)methyl N-N-[2­

chloro-4-(trifluoromethyphenyl)-DLvalinate, D-valinate 

Tau-fluvalinate is a 1:1 

mixture of (R)-a-cyano, 

2-(R) and (S)-a- cyano, 

2-(R) diasteriomers 

Klartan, Mavrik 

C26H22ClF3N2O3 

69409-94-5, 

102851-06-9 (taufluvalinate)

YV9397100 

No data

No data

No data

6659 

No data 
 

 

O 

O 

O O O O O O O Cl Cl 

 

PYRETHRINS AND PYRETHROIDS 138 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Chemical Identity of Selected Pyrethroidsa 

Characteristic	 Permethrin Phenothrin Resmethrin 

Synonym(s)b	 (3- (3- [5-Phenylmethyl)-3­

Phenoxyphenyl)methyl3- Phenoxyphenyl)methyl- furanyl]mehtyl 2,2­

(2,2-dichloroehenyl)-2,2- 2,2-dimethyl-3-(2- dimethyl-3-(2-methyl-1­

dimethylcyclopropane- methyl-1-propenyl)- propenyl)cyclopropanecarboxylate cyclopropanecarboxylate carboxylate 

Ratio of isomers	 (1R, trans):(1R,cis):(1S, Mixed isomers 20–30% (1RS)-cistrans):(1S, cis)=3:2:3:2e	 isomers 

80–70% (1(RS)-transisomers) 

Registered trade name(s)	 Ambush, Assithrin, Sumithrin Synthrin, Chrysron 

Cliper, Coopex, Corsair, 

Dragnet, Dragon, Kafil, 

Eksmin, Perkill, Pounce 

Chemical formula	 C21H20Cl2O3 C23H26O3 C22H26O3 

Chemical structure 

Identification numbers:

 CAS registry 52645-53-1 26002-80-2 10453-86-8

 NIOSH RTECSc GZ1255000 GZ1975000 GZ1310000 

EPA hazardous wasted No data No data No data

 OHM/TADS No data No data No data

 DOT/UN/NA/IMCO shipping No data No data No data

 HSDBd 6740 3922 6790

 NCI No data No data No data 
F O F C H 3 

O Br O F O N O

F O F O C N C l 	 O O Br Br F	 B r F 

 

 

PYRETHRINS AND PYRETHROIDS 139 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Chemical Identity of Selected Pyrethroidsa 

Characteristic	 Tefluthrin Tetramethrin Tralomethrin 

Synonym(s) b	 [1",3"(Z)]-(±)-(2,3,5,6- (1,3,4,5,6,7-Hexahydro- Cyano(3-phenoxyphenyl)­

Tetrafluoro-4- 1,3-dioxo-2H-isoindol-2- methyl 2,2-dimethyl-3­

methylphenyl)methyl 3- yl)methyl 2,2-dimethyl-3- (1,2,2,2-tetrabromoethyl)­

(2-chloro-3,3,3-trifluoro- (2-methyl-1-propenyl)- cyclopropanecarboxylate 

1propenyl)-2,2-dimethyl- cyclopropanecarboxylate 

cyclopropanecarboxylate 

Ratio of isomers Mixture of isomers (1R, trans):(1R,cis):(1S, Unstated stereochemistry 

trans):(1S, cis)=4:1:4:1e 

Registered trade name(s) Force, Fireban Neo-Pynamin, Duracide Saga, Scout, Tralox, 

Tracker, Tralate 

Chemical formula C17H14ClF7O2 C19H25NO4 C22H19Br4NO3 

Chemical structure	 

Identification numbers:

 CAS registry 79538-32-2 7696-12-0 66841-25-6

 NIOSH RTECSc GZ1227850 GX1730000 GZ2009500 

EPA hazardous waste No data No data No data

 OHM/TADS No data No data No data

 DOT/UN/NA/IMCO shipping No data No data No data

 HSDBd No data 6738 6604

 NCI No data No data No data 

a

All information obtained from Tomlin, 1997 except where noted. 

b

Chemical names used are those currently indexed by the Chemical Abstracts Service. c

NIOSH 1987 

d

HSDB 2001 

e

 WHO 2001 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; HSDB = Hazardous 

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 
O 

H H 

O R' R 

R O R' 

H O H 

1S cis configuration 1R cis configuration 

O 

O R' R H H 

H R O R' H 

O 

1S trans configuration 1R trans configuration 

PYRETHRINS AND PYRETHROIDS 140 

4. CHEMICAL AND PHYSICAL INFORMATION 

Figure 4-1. Four Possible Isomers of Type I Pyrethroids 
PYRETHRINS AND PYRETHROIDS 141 

4. CHEMICAL AND PHYSICAL INFORMATION 

Beasley 1991). Figure 4-2 illustrates the S conformation of the type II pyrethroid cyhalothrin about the 

alpha carbon. Pyrethroids such as cyfluthrin, cypermethrin, and cyhalothrin possess three chiral centers, 

and thus consist of eight possible isomers. The production of pyrethroids with differing isomeric ratios is 

one reason for the wide variation in reported toxicities of these compounds. For example, cypermethrin is 

formulated as four different insecticides (alpha-, beta-, theta- and zeta-cypermethrin) depending upon the 

ratio of the different isomers; and each of these products has different toxicologic properties. The 

complex compositions of several important pyrethroids are illustrated in Table 4-3. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of the pyrethrins and selected pyrethroids are 

located in Tables 4-4 and 4-5, respectively. Generally, pyrethrins and pyrethroids have low vapor 

pressures, low Henry’s law constants, and large octanol/water coefficients (Kow), and are not very soluble 

in water. Aside from their interaction with polarized light, enantiomers possess identical physical 

properties (e.g., boiling point, melting point, solubility, etc.). Diastereomers have different physical 

properties however, and changes in the geometrical isomeric composition can lead to different values in 

the properties reported for the pyrethroids listed in Table 4-5. 
 

PYRETHRINS AND PYRETHROIDS 142 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-3. Stereoisomers of Selected Pyrethroidsa 

Pyrethroid Different products Isomer composition 

Cypermethrin alpha-cypermethrin Racemic mixture comprised of: 

(S)-alpha-cyano-3-phenoxybenzyl-(1R)-cis-3-(2,2­

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

and (R)-alpha-cyano-3-phenoxybenzyl-(1S)-cis-3-(2,2­

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

beta-cypermethrin Mixture comprised of two enantiomeric pairs in a 2:3 

ratio: 

(S)-alpha-cyano-3-phenoxybenzyl-(1R)-cis-3-(2,2­

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

and (R)-alpha-cyano-3-phenoxybenzyl-(1S)-cis-3-(2,2­

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

with (S)-alpha-cyano-3-phenoxybenzyl-(1R)-trans-3­

(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate and (R)-alpha-cyano-3-phenoxybenzyl­

(1S)-trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

theta-cypermethrin Racemic mixture comprised of: 

(S)-alpha-cyano-3-phenoxybenzyl-(1R)-trans-3-(2,2­

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

and (R)-alpha-cyano-3-phenoxybenzyl-(1S)-trans-3­

(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

zeta-cypermethrin Mixture of the stereoisomers: 

(S)-alpha-cyano-3­

phenoxybenzyl(1RS,3RS;1RS,3SR)-3-(2,2­

dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate 

where the ratio of the (S); (1RS,3RS) isomeric pair to 

the (S);(1RS,3SR) isomeric pair lies in the range of 

45-55 to 55-45. 
PYRETHRINS AND PYRETHROIDS 143 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-3. Stereoisomers of Selected Pyrethroidsa 

Pyrethroid Different products Isomer composition 

Cyfluthrin cyfluthrin Comprised of a mixture of the 4 diastereomeric pairs 

of enantiomers: 

I = (R)-alpha-cyano-4-fluoro-3-phenoxybenzyl-(1R)­

cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate + (S)-alpha, (1S)-cis 

II = (S)-alpha-cyano-4-fluoro-3-phenoxybenzyl-(1R)­

cis -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate + (R)-alpha, (1S)-cis 

III = (R)-alpha-cyano-4-fluoro-3-phenoxybenzyl-(1R)­

trans -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate + (S)-alpha, (1S)-trans 

IV = (S)-alpha-cyano-4-fluoro-3-phenoxybenzyl-(1R)­

trans -3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate + (R)-alpha, (1S)-trans 

The technical grade product consists of 23-26% I, 16­

19% II, 33-36% III and 22-25% IV. 

beta-cyfluthrin Mixture of II and IV in a 1:2 ratio. 

Cyhalothrin cyhalothrin (RS)-alpha-cyano-3-phenoxybenzyl (Z) (1RS)-cis-3­

(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate 

lambda-cyhalothrin Racemic mixture comprised of: 

(S)-alpha-cyano-3-phenoxybenzyl (Z) (1R)-cis-3-(2­

chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate and (R)-alpha-cyano-3­

phenoxybenzyl (Z) (1S)-cis-3-(2-chloro-3,3,3­

trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate 

a

All information obtained from Tomlin 1997. 
 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 144 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-4. Physical and Chemical Properties of Pyrethrinsa 

Property Pyrethrin I Cinerin I Jasmolin I 

Molecular weight 328.5 316.4 330.5 

Color No data No data No data 

Physical state Viscous liquidb No data No data 

Melting point, EC No data No data No data 

Boiling point, EC 146–150 at 0.0005 mm 

Hg, 170 at 0.1 mm Hgc 

136–138 at 0.008 mm 

Hgd 

No data 

Density, g/cm3

 at 25 EC 1.51 (18 °C) No data No data 

Odor No data No data No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water, mg/L 0.2 Insoluble 0.03i 

Organic solvent(s) Soluble Soluble No data 

Partition coefficients: 

Log Kow 5.9 5.93i 6.42i 

Vapor pressure, mm 2.03x10-5 1.1x10-6i 4.8x10-7i 

Hg at 25 EC 

Henry’s Law constant, 

atm-m3

/mol at 25 EC 

7.7x10-7i 9.6x10-7i 1.3x10-6i 

Autoignition No data No data No data 

temperature 

Flashpoint, EC No data No data No data 

(Pensky-Martens 

closed cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

Air (25 EC1)e 1 mg/m3

=0.074 ppm 1 mg/m3=0.077 ppm 1 mg/m3=0.074 ppm 

Explosive limits No data No data No data 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 145 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-4. Physical and Chemical Properties of Pyrethrinsa 

Property Pyrethrin II Cinerin II Jasmolin II 

Molecular weight 372.5 360.4 357.7 

Color No data No data No data 

Physical state Viscous liquidb Viscous oil b No data 

Melting point, EC No data No data No data 

Boiling point, EC 192–193 at 0.007 mm Hg, 182–184 at 0.001 mm No data 

200 at 0.1 mm Hgc Hg 

Density, g/cm3

 at 25 EC No data No data No data 

Odor No data No data No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water, mg/L 9.0 Insoluble 0.09i 

Organic solvent(s) Soluble Soluble No data 

Partition coefficients: 

Log Kow 4.3 4.98i 5.47i 

Vapor pressure, mm Hg 3.98x10-7 4.6x10-7i 1.9x10-7i 

at 25 EC 

Henry’s Law constant, 7.4x10-10i 9.2x10-10i 1.2x10-9i 

atm-m3/mol at 25 EC 

Autoignition No data No data No data 

temperature 

Flashpoint, EC (Pensky- No data No data No data 

Martens closed cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

Air (25 EC1)e 1 mg/m3

=0.066 ppm 1 mg/m3=0.068 ppm 1 mg/m3=0.065 ppm 

Explosive limits No data No data No data 

a

All information obtained from HSDB 2001 except where noted 

b

Technical grade 

c

Tomlin 1997 

d

Budavari 1996 

g

USDA 2001a 

e

These air conversion factors were calculated by using the average molecular weight and ideal gas law. f

Milne 1995 

h

Howard and Meylan 1997 

i

Estimated value from EPIWIN (Syracuse Research Corporation) 
 

PYRETHRINS AND PYRETHROIDS 146 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-5. Physical and Chemical Properties of Selected Pyrethroids a 

Property Allethrin Bifenthrin Bioresmethrinb 

Molecular weight 302.4 422.9 338.4 

Color Pale yellowb,c Light brownc Yellow to brownc 

Physical state Viscous liquid Viscous oil Viscous liquidc 

Melting point, EC ~4 68–70 71.5-83d 

Boiling point, EC 281.5 No data Dec. >180 

Density, g/cm3

 at 25 EC 1.01 (25 EC) 1.212 (25 EC) 1.050 (20 EC) 

Odor No data No data No data 

Odor threshold: 

 Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water, mg/L 4.6 (25 EC) 0.1 <0.3 (25 EC) 

 Organic solvent(s) Soluble Soluble Soluble 

Partition coefficients: 

Log Kow 4.8 6e >4.7 

Vapor pressure, mm Hg at 25 EC 1.2x10-6 (21 EC) 1.8x10-4d 1.4x10-8 

Henry’s Law constant, atm- 6.1x10-7i <1.0x10-3d 1.3x10-7f 

m3

/mol at 25 EC 

Autoignition temperature No data No data No data 

Flashpoint, EC (Pensky-Martens 87b 165b 92b 

 closed cup) 

Flammability limits No data No data No data 

Conversion factors

 Air (25 EC1)g 1 mg/m3

=0.081 ppm 1 mg/m3=0.058 ppm 1 mg/m3=0.072 ppm 

Explosive limits No data No data No data 
PYRETHRINS AND PYRETHROIDS 147 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-5. Physical and Chemical Properties of Selected Pyrethroidsa 

Property Cyfluthrin Cyhalothrin Cypermethrin 

Molecular weightc 453.3 449.9 416.3 

Color Yellowish brownc Yellow-brownc Yellow brownb,c 

Physical state Oil (A) Viscous liquidc Viscous semi-solidb,c 

Melting point, EC 60 (A) 49.2g 80.5 

Boiling point, EC No data 187–190 No data 

Density, g/cm3

 at 25 EC No data 1.25 1.25 

Odor Aromatic Mild Odorless 

Odor threshold: 

 Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water, mg/L 0.002 (20 EC)g 0.003 (20 EC) 0.004 (20 EC) 

 Organic solvent(s) Soluble Soluble Soluble 

Partition coefficients: 

 Log Kow 5.94 6.9 6.6 

Vapor pressure, mm Hg at 25 EC 2.03x10-9d 1.5x10-9 (20 EC)d 3.07x10-9 (20 EC) 

Henry’s Law constant, atm- 9.5x10-7h 1.8x10-7d 4.2x10-7d 

m3

/mol at 25 EC 

Autoignition temperature No data No data No data 

Flashpoint, EC (Pensky-Martens 107b >100b No data 

 closed cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

 Air (25 EC1)e 1 mg/m3

=0.054 ppm 1 mg/m3=0.054 ppm 1 mg/m3=0.059 ppm 

Explosive limits No data No data No data 
PYRETHRINS AND PYRETHROIDS 148 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-5. Physical and Chemical Properties of Selected Pyrethroidsa 

Property Deltamethrin Esfenvalerate Fenpropathrin 

Molecular weightc 505.2 419.9 349.4 

Color Colorless Colorless Yellow brownc 

Physical state Crystals Crystals Solidc 

Melting point, EC 101–102 59–60.2 45–50 

Boiling point, EC No data 151–167 No data 

Density, g/cm3

 at 25 EC 0.55b 1.175 1.15 (25 EC) 

Odor Odorless No data No data 

Odor threshold: 

 Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water, mg/L <0.002 0.0002 (25 EC) 0.014 (25 EC)d 

 Organic solvent(s) Soluble Soluble Soluble 

Partition coefficients: 

 Log Kow 6.1 

Vapor pressure, mm Hg at 25 EC 1.5x10-8 

4.0 

1.5x10-9 

6.0 (20 EC) 

5.5x10-6 (20 EC) 

Henry’s Law constant, atmm3

/mol at 25 EC 

1.2x10-4 4.1x10-7d 1.8x10-4g 

Autoignition temperature No data No data No data 

Flashpoint, EC (Pensky-Martens No data 256b No data 

 closed cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

 Air (25 EC1)g 1 mg/m3

=0.048 ppm 1 mg/m3=0.058 ppm 1 mg/m3=0.070 ppm 

Explosive limits No data No data No data 
 

PYRETHRINS AND PYRETHROIDS 149 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-5. Physical and Chemical Properties of Selected Pyrethroidsa 

Property Flucythrinate Flumethrinb Fluvalinate 

Molecular weightc 451.5 510.4 502.9 

Color Dark amberb,c Yellowishc Yellow-amberc 

Physical state Viscous liquidc Viscous oilc Viscous liquidc 

Melting point, EC No data No data No data 

Boiling point, EC 108 at 0.35 mm Hg >250 >450 

164 at 0.07 mm Hgb 

Density, g/cm3 at 25 EC 1.189 (22 EC) No data 1.29 

Odor No data No data No data 

Odor threshold: 

 Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water, mg/L 0.5 (21 EC) 9.7x10-5f 0.002 

 Organic solvent(s) Soluble No data Soluble 

Partition coefficients: 

 Log Kow 4.7d 7.65i 4.26g 

Vapor pressure, mm Hg at 25 EC 8.5x10-9d 3.9x10-9f 5.7x10-7d 

Henry’s Law constant, atm- 8.47x10-8d 4.2x10-8f 3.05x10-5d 

m3

/mol at 25 EC 

Autoignition temperature No data No data No data 

Flashpoint, EC (Pensky-Martens No data No data 90c 

 closed cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

 Air (25 EC1)e 1 mg/m3

=0.054 ppm 1 mg/m3=0.048 ppm 1 mg/m3=0.049 ppm 

Explosive limits No data No data No data 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 150 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-5. Physical and Chemical Properties of Selected Pyrethroidsa 

Property Permethrin Phenothrin Resmethrin 

Molecular weightc 391.3 350.5 338.4 

Color Colorless to yellowc Colorless Colorless 

Physical state Crystals to viscous 

liquidc 

Liquid Crystals 

Melting point, EC 34–35 No data 56.5 

Boiling point, EC 220 at 0.05 mm Hgf >290 Dec. at >180 EC 

Density, g/cm3

 at 25 EC 1.19–1.27 (20 EC) 1.061 0.96-0.97 (20 EC) 

Odor No data No data Chrysanthemate 

Odor threshold: 

 Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water, mg/L 0.006 (20 EC) 2.0 (30 EC) 0.037 (25 EC)b 

 Organic solvent(s) Soluble Soluble Soluble 

Partition coefficients: 

 Log Kow 

Vapor pressure, mm Hg 

6.5 

2.2x10-8 

7.54f 

1.4x10-7b 

5.43 

1.13x10-8i 

at 25 EC 

Henry’s Law constant, 

atm-m3

/mol at 25 EC 

1.9x10-6d 1.4x10-6f <8.9x107d 

Autoignition No data No data No data 

temperature 

Flashpoint, EC (Pensky­ >100b 107b 129b 

Martens closed cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

 Air (25 EC1)e 1 mg/m3

=0.062 ppm 1 mg/m3=0.070 ppm 1 mg/m3=0.072 ppm 

Explosive limits No data No data No data 
PYRETHRINS AND PYRETHROIDS 151 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-5. Physical and Chemical Properties of Selected Pyrethroidsa 

Property Tefluthrinb Tetramethrin Tralomethrin 

Molecular weight 418.7 331.4 665.0 

Color Colorless Colorless Yellow orange 

Physical state Solid Crystals Resinoid 

Melting point, EC 44.6 65–80 138–148 

Boiling point, EC 153 at 1 mm Hg 180–190 No data 

Density, g/cm3

 at 25 EC 1.48 1.1 (20 EC) 1.70 (20 EC) 

Odor No data No data No data 

Odor threshold: 

 Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water, mg/L 0.002 (20 EC) 1.83b 0.08 

 Organic solvent(s) Soluble Soluble Soluble 

Partition coefficients: 

 Log Kow 

Vapor pressure, mm Hg 

6.5 

6.0x10-5 

4.6c 

7.1x10-6b 

7.6f 

3.6x10-11 

 at 25 EC 

Henry’s Law constant, 

atm-m3

/mol at 25 EC 

4.6x10-4f 8.3x10-9f 3.9x10-15d 

Autoignition No data No data No data 

temperature 

Flashpoint, EC (Pensky­ 124 No data No data 

Martens open cup) 

Flammability limits, EC No data No data No data 

Conversion factors 

 Air (25 EC1)g 1 mg/m3

=0.058 ppm 1 mg/m3=0.074 ppm 1 mg/m3=0.074 ppm 

Explosive limits No data No data No data 

a

All information obtained from HSDB 2001 except where noted 

b

Tomlin 1997 

c

Technical grade 

d

USDA 2001a 

e

Milne 1995 

f

Estimated value from EPIWIN (Syracuse Research Corporation) g

These air conversion factors were calculated by using the average molecular weight and ideal gas law h

Budavari 1996 

i

Howard and Meylan 1997 
H 

O 

O 

F CN O 

Cl 

F 

F 

PYRETHRINS AND PYRETHROIDS 152 

4. CHEMICAL AND PHYSICAL INFORMATION 

Figure 4-2. Illustration of the S Conformer about the Alpha Carbon 

for the Type II Pyrethroid Cyhalothrin 
PYRETHRINS AND PYRETHROIDS 153 

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

5.1 PRODUCTION 

Information regarding the manufacturers of various pyrethrins and pyrethroids in the United States is 

given in Table 5-1 (SRI 2000). Table 5-2 lists the number of facilities in each state that produce, process, 

or import pyrethrins and pyrethroids for commercial use. The intended use and the range of maximum 

amounts of these substances that are stored on site are also included. The data listed in these tables are 

derived from the Toxics Release Inventory (TRI99 2001). Only certain types of facilities were required 

to report, and this is not an exhaustive list. The only pyrethroids that are on the list are allethrin, 

bifenthrin, cyfluthrin, cyhalothrin, fenpropathrin, fluvalinate, permethrin, phenothrin, resmethrin, and 

tetramethrin (TRI99 2001). Furthermore, data have only been reported for bifenthrin, cyfluthrin, 

permethrin, resmethrin, and tetramethrin. No data regarding the production volumes are available. 

Naturally-occurring pyrethrins are produced by certain species of chrysanthemum plants (Chrysanthemum 

cinerariaefolium and Chrysanthemum cineum). Either the flowers are dried and powdered or the oils 

within the flowers are extracted with solvents such as petroleum ether, acetone, or acetic acid (Metcalf 

1995). Synthetic pyrethroids are manufactured by the esterification of an appropriate acid with an 

appropriate alcohol (Table 5-3). 

Technical-grade (concentrated) pyrethroids are usually formulated for use in commercial products. The 

formulated product may contain up to 99% inert (“secret”) ingredients that improve storing, application 

handling, or effectiveness. The EPA publishes a complete list of all inert ingredients found in pesticide 

products registered in the United States, and categorizes them along the following four classes: (1) inert 

ingredients of toxicological concern; (2) potentially toxic inert ingredients; (3) inert ingredients of 

unknown toxicity; and (4) inerts of minimal concern (EPA 2003). Even though the EPA publishes a list 

of all inert ingredients used in currently registered pesticides, it does not specify which ingredients are 

contained in any specific formulated product, and federal law does not require the pesticide label to 

identity the inert ingredients unless they are categorized as class one inert ingredients. A common 

formulation used in pyrethrin and pyrethroid products is an emulsifiable concentrate (EC). The primary 

inert ingredients in a pesticide product formulated as an EC are an emulsifier and a petroleum solvent, 

such as kerosene. Other popular formulations are aerosol dispenser (AE), wettable powder (WP), 

dustable powder (DP), and water dispersible granules (WG) (Tomlin 1997). 
PYRETHRINS AND PYRETHROIDS 154 

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

Table 5-1. U.S. Producers of Pyrethrins and Pyrethroids 

Pyrethroid Producer Production site 

Bifenthrin FMC Corporation Baltimore, Maryland 

Cyfluthrin Bayer Corporation Kansas City, Missouri; Shawnee, Kansas 

Cypermethrin Astra Zeneca Cold Creek, Alabama 

FMC Corporation Baltimore, Maryland 

Esfenvalerate Du Pont Axis, Alabama 

Fluvalinate BASF Corporation Beaumont, Texas 

Permethrin Astra Zeneca Cold Creek, Alabama 

FMC Corporation Baltimore, Maryland 

Pyrethrins (Pyrethrum) McLaughlin Gormley King Chaska, Minnesota 

SureCo Incorporated Fort Valley, Georgia 

Source: SRI 2000 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 155 

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

Table 5-2. Facilities that Produce, Process, or Use Pyrethroids 

Number of Minimum amount Maximum amount 

Statea facilities on site in poundsb on site in poundsb Activities and usesc 

Bifenthrin 

FL 1 100,000 999,999 8 

IL 1 10,000 99,999 8 

TX 1 10,000 99,999 2, 3, 8 

Cyfluthrin 

MO 1 100,000 999,999 8 

TX 1 10,000 99,999 8 

Permethrin 

AL 1 100,000 999,999 1, 4 

AR 1 10,000 99,999 8 

FL 1 1,000,000 9,999,999 8 

GA 1 100,000 999,999 8 

IL 1 10,000 99,999 8 

LA 1 1,000 9,999 8 

MD 1 1,000,000 9,999,999 1, 4 

NJ 1 1,000 9,999 8 

TN 1 10,000 99,999 8 

TX 2 10,000 99,999 2, 3, 8, 10 

WI 1 10,000 99,999 8 

Resmethrin 

TX 1 10,000 99,999 8 

Tetramethrin 

WI 1 10,000 99,999 8 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 10. Repackaging 

2. Import 7. Reactant 11. Chemical Processing Aid 

3. Onsite use/processing 8. Formulation Component 12. Manufacturing Aid 

4. Sale/Distribution 9. Article Component 13. Ancillary/Other Uses 

5. Byproduct 

Source: TRI99 2001 
5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. Acid and Alcohol Feedstocks in the Pyrethroids Synthesis 

Pyrethroid Acid Alcohol 

Allethrin O O 

O 

O 

Bifenthrin F O F 

O F 

O 

Cl 

Bioresmethrin O O 

O
 

O 

Cyfluthrin O CN O O Cl O H 

Cl F 

Cyhalothrin F O 

H 

CN

O O 

F O F 

Cl 

Cypermethrin O 

H 

CN O O Cl O 

Cl 

Deltamethrin O CN O 

H 

O Br O 

Br 

PYRETHRINS AND PYRETHROIDS 156 
5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. Acid and Alcohol Feedstocks in the Pyrethroids Synthesis 

Esfenvalerate H O CN O 

H 

Cl O

O 

Fenproparthrin O CN O O 

O H 

Flucythrinate H O O CN

O 

O H

F O

F 

Flumethrin Cl 

Fluvalinate CF3

Cl 

O 

O H 

F 

O 

O CN

O 

O 

N 

H O O 

H 

CN 

Permethrin O O 

O 

Cl O 

Cl 

PYRETHRINS AND PYRETHROIDS 157 
5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. Acid and Alcohol Feedstocks in the Pyrethroids Synthesis 

Phenothrin O O 

O 

O 

Resmethrin O 

O O O 

Tefluthrin O F 

Cl NC 

O F 

CF3 O 

F F 

Tralomethrin Br O CN O O 

Br3C O H 

Tetramethrin O 

O N 

O 

Source: HSDB 2001 

PYRETHRINS AND PYRETHROIDS 158 
 

PYRETHRINS AND PYRETHROIDS 159 

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

5.2 IMPORT/EXPORT 

No data regarding the import or export volumes of pyrethrins and pyrethroids are available. 

5.3 USE 

Naturally-occurring pyrethrins were first used around 1800 in the Transcaucasus region of Asia to control 

human lice, mosquitoes, cockroaches, beetles, and flies. Pyrethroids are broad-spectrum insecticides, 

effective against a wide range of flying, crawling, chewing, and sucking insects of the orders Coleoptera, 

Diptera, Hemiptera (Homoptera and Heteroptera), Hymenoptera, Lepidoptera, Orthoptera, and 

Thysanoptera. They are used as household insecticides, as grain protectants, and to control pests on 

edible products just prior to harvest (Metcalf 1989). They are used in a variety of locations including 

residential, public, and commercial buildings, animal houses, warehouses, fields, and green houses. They 

are also extensively used in the field of veterinary medicine (Davies 1985). 

All concentrated formulations of pyrethroids were classified as restricted use pesticides by the EPA in 

1995 (EPA 2000a). This classification restricts a pesticide to be used only by a certified applicator, or 

under the direct supervision of a certified applicator. Detailed information regarding the amounts applied 

and use of individual pyrethroids is provided in Table 5-4. The data shown in Table 5-4 were developed 

from state-wide estimates of pesticide use rates on cropland and do not include pesticide applications to 

noncropland areas (i.e., home use, greenhouse use, etc.). 

5.4 DISPOSAL 

All pyrethrins and pyrethroids as well as piperonyl butoxide are listed as toxic substances under 

Section 313 of the Emergency Planning and Community Right to Know Act (EPCRA) under Title III of 

the Superfund Amendments and Reauthorization Act (SARA) (EPA 1995). Disposal of wastes 

containing these compounds is controlled by a number of federal regulations (see Chapter 8). According 

to the TRI, in 1999, an estimated 1,239 pounds of permethrin were transferred off-site, presumably for 

disposal (TRI99 2001). No other pyrethroids or pyrethrins were reported as having off-site transfers in 

1999 (TRI99 2001). 
 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 160 

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

Table 5-4. Uses of Pyrethroids 

Pyrethroid Amounta Insectsb,c,d Cropsb,c,d Other locations 

(pounds) and applicationsb,c 

Allethrin NA Flies, mosquitoes, 

ants 

N/A Residential, public 

health, animal 

Bifenthrin 

Bioresmethrin 

114,377 

NA 

Beetles, weevils, 

houseflies, 

mosquitoes, lice, 

bedbugs, aphids, 

moths, cockroaches, 

locusts 

Houseflies, 

mosquitoes, 

cockroaches 

Alfalfa hay, beans, 

cantaloupes, cereals, corn, 

cotton, field and grass seed, 

hops, melons, oilseed rape, 

potatoes, peas, raspberries, 

watermelons, squash 

NA 

houses, topical 

application in pet 

sprays and 

shampoos 

NA 

Household, public 

health, animal 

houses 

Cyfluthrin 

Cyhalothrin 

151,422 

NA 

Aphids, cabbage 

stem flea beetle, 

cockroaches house 

flies, mosquitoes, 

rape winter stem 

weevil 

Bedbugs, beetles, 

houseflies, ked, lice, 

Alfalfa, cereals, cotton, citrus, 

deciduous fruit, ground nuts, 

maize, oilseed rape, pears, 

potatoes, rice, sugar beet, 

sugarcane, tobacco, 

vegetables 

N/A 

Green houses 

Public health, animal 

houses, inert 

mosquitoes, moths, 

weevils 

surfaces 

Cypermethrin 215,066 Cockroaches, flies, 

mosquitoes, moths 

Cotton, lettuce, onions, pears, 

peaches, pecans, sugar beets 

Residential and 

commercial 

buildings, animal 

houses 

Deltamethrin NA Aphids, beetles, bollworm, bud-worm, 

caterpillars, cicadas, 

codling moths, tortrix 

moths, weevils, 

Alfalfa, beet, cereals, coffee, 

cotton, figs, fruits, hops, maize, 

oilseed rape, olives, oil palms, 

potatoes, rice, soybeans, 

sunflowers, tea, tobacco, 

Forests, households, 

animal houses, 

stored products 

whitefly, winter 

moths 

vegetables 

Esfenvalerate 215,919 Beetles, moths Cabbage, corn, cotton, fruit 

trees, grains, groundnuts, 

maize, pecan, potatoes, 

sorghum, soybeans, sugar 

cane, sunflowers, sweet corn, 

Ornamentals, noncrop land 

tomatoes, vegetables, wheats 
 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 161 

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

Table 5-4. Uses of Pyrethroids 

Pyrethroid Amounta Insectsb,c,d Cropsb,c,d Other locations 

(pounds) and applicationsb,c 

Fenproparthrin 146,707 

Flucythrinate NA 

Flumethrin NA 

Fenvalerate 61,582 

Fluvalinate NA 

Permethrin 1,055,097 

Phenotrhin NA 

Resmethrin NA 

Aphids, armyworms, 

bollworms, budworms, cabbage 

looper, cabbageworms, cutworms, 

diamondback moth, 

fruit moths, leafminers, leafrollers, 

leaf-worms, 

lepidopterous larvae, 

mites, mosquito, 

psyllas, stem-borers, 

ticks, tortrixies, 

tuber-worms, 

whiteflies 

Boll-worms, leafworms, sucking 

insects, whiteflies, 

beetles 

Lice, ticks, psoroptic, 

chorioptic and 

sarcoptic munge 

Beetles, 

cockroaches, flies, 

locusts, mosquitos, 

moths 

Aphids, leafhoppers, moths, 

spider mites, thrips, 

white-flies 

Ants, beetle, bollworm, bud-worm, 

fleas, flies, lice, 

moths, mosquitos, 

termites, weevils 

Ants, bedbugs, 

cockroaches, fleas, 

houseflies, lice, 

mosquitoes, ticks 

Flying and crawling 

insects, mosquitoes 

houseflies, german 

cockroaches 

Cotton, citrus, fruits, pome, Glasshouse, 

tomatoes, vegetables, vines ornamental trees 

Cotton, vines, strawberries, NA
 

citrus fruit, bananas, 

pineapples, olives, coffee, 

cocoa, hops, vegetables, 

soybeans, cereals, maize,
 

alfalfa, sugarbeet, sunflowers, 

tobacco
 

NA NA
 

Alfalfa hay, apples, beet, Ornamentals,
 

cereals, cotton, corn, forestry, non-crop 

cucurbita, fruit, green beans, land
 

groundnuts, hops, maize, nuts, 

oilseed rape, olives, potatoes, 

sorghum, soybeans, squash, 

sugarcane, sunflower, 

vegetables, vines, tobacco 

Apples, cereals, cotton, pears, Outdoor and indoor 

peaches, tobacco, vegetables, ornamentals, turf
 

vines 

Alfalfa hay, corn, cotton, Home gardens, 

grains, lettuce, onion, green houses, pet 

peaches, potatoes, sweet sprays, and 

corn, tomatoes, wheat shampoos
 

NA	 Public buildings, 

stored grain, pet 

sprays, and 

shampoos 

NA	 Homes, 

greenhouses, indoor 

landscapes, 

mushroom houses, 

industrial sites 
 

 

PYRETHRINS AND PYRETHROIDS 162 

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

Table 5-4. Uses of Pyrethroids 

Pyrethroid Amounta 

(pounds) 

Insectsb,c,d Cropsb,c,d Other locations 

and applicationsb,c 

Tefluthrin 423,973 Beetles, houseflies, 

mosquitoes moths, 

weevils 

Corn, maize, sugar beet, 

sweet corn 

NA 

Tetramethrin NA Flies, cockroaches, NA Public health, home 

Tralomethrin 53,331 

mosquitoes, wasps 

Aphids, beetles, 

cockroaches, moths, 

weevils 

Cereals, coffee, cotton, fruit, 

maize, oilseed rape, rice, 

soybeans, tobacco, vegetables 

and garden use 

Wood protection, 

homes, public 

health, stored grain, 

animal houses 

a

USGS 2001 

b

HSDB 2001 

c

Metcalf 1995 

d

Tomlin 1997 

N/A = not available 
PYRETHRINS AND PYRETHROIDS 163 

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

The EPA Office of Pesticide Programs has detailed labels for the use, storage, and disposal of all 

pesticides, including registered products containing pyrethrins and pyrethroids. All pesticide products are 

required to bear instructions for the storage and disposal of the pesticides and the pesticide containers. 

Storage and disposal instructions cover the appropriate storage of the pesticide product; disposal of any 

unused pesticide product or any rinse liquids resulting from cleaning of pesticide application equipment; 

and the disposal of the pesticide container. State and local regulations may be stricter than the federal 

requirements listed on the label. 

 

PYRETHRINS AND PYRETHROIDS 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Pyrethrins and pyrethroids have been identified in at least 5 and 2 of the 1,636 hazardous waste sites, 

respectively, that have been proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 

2003). However, the number of sites evaluated for pyrethrins and pyrethroids is not known. The 

frequency of these sites can be seen in Figure 6-1 and 6-2, respectively. All of these sites are located 

within the United States. 

Pyrethrum is the natural extract derived from the flowers of Chrysanthemum cinerariaefolium and 

Chrysanthemum cineum (Metcalf 1995). Pyrethrum has long been recognized as possessing insecticidal 

properties, and the manufacture of flea and louse powders employing this extract began in Asia around 

1800. The six active insecticidal compounds of pyrethrum are called pyrethrins. The individual 

pyrethrins are pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I, and jasmolin II. These compounds 

are esters of two carboxylic acids (chrysanthemic acid and pyrethric acid) and three cyclopentenolones 

(pyrethrolone, cinerolone, and jasmolone). See Chapter 4 for the structures as well as the chemical and 

physical properties of these compounds. Synthetic pyrethroids are a diverse class of over 1,000 powerful 

insecticides that are structurally similar to the pyrethrins (Mueller-Beilschmidt 1990). Although they are 

based on the chemical structure and biological activity of the pyrethrins, the development of synthetic 

pyrethroids has involved extensive chemical modifications that make these compounds more toxic and 

less degradable in the environment. Products containing small amounts of pyrethroids for uses around the 

home are still classified as general use pesticides; however, emulsified or granular concentrate 

formulations that are applied to fields were classified as restricted use pesticides by the EPA in 

1995 (EPA 2000a). The restricted use classification restricts a pesticide to be used only by a certified 

applicator, or under the direct supervision of a certified applicator. Although many pyrethroids have been 

developed, less than a dozen are used with any frequency in the United States, with permethrin being the 

most commonly employed pyrethroid. 

Pyrethrins and pyrethroids are released to the environment primarily as a result of their use as 

insecticides. These compounds are very important insecticides because of their rapid paralysis of flying 

insects, relatively low mammalian toxicity, and rapid rate of degradation in the environment. Often, 
PYRETHRINS AND PYRETHROIDS 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Pyrethrins Contamination 

1 

Frequency of

NPL Sites 

Derived fr om HazDat 2003 
PYRETHRINS AND PYRETHROIDS 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-2. Frequency of NPL Sites with Pyrethroid Contamination 

1 

Frequency of

NPL Sites 

Derived from HazDat 2003 
 

 

PYRETHRINS AND PYRETHROIDS 168 

6. POTENTIAL FOR HUMAN EXPOSURE 

pyrethrins and pyrethroids are formulated with compounds such as piperonyl butoxide, piperonyl 

sulfoxide, and sesamex, which act as synergists to increase the effectiveness of the insecticide. 

Pyrethrins are rapidly detoxified by enzymes of insects, and often, the paralyzed insect may survive and 

recover neurological function before mortality. The synergists are relatively nontoxic by themselves, but 

prevent the insect from detoxifying the active insecticide, thus increasing their effectiveness. At 

sufficient levels, the synergists may also increase the toxicity of pyrethrins and some pyrethroids in 

mammals. Pyrethrins are largely used indoors against flying insects in sprays, pet shampoos, and aerosol 

bombs, which contain about 0.04–0.25% of active ingredient and about 5–10 times this amount of 

piperonyl butoxide or other synergists to attenuate detoxification (Metcalf 1989). They also can be 

employed in multi-purpose insecticides for use on livestock, grains, fruits, and vegetables. Since the 

pyrethrins are not very stable when exposed to sunlight, their outdoor use on crops has diminished as 

relatively light-stable pyrethroids have been developed. The different pyrethroids are used in many ways 

to control a wide variety of insects on crops, pets, and livestock. The toxicity of the pyrethroids is 

influenced by the isomeric properties of the compound. For pyrethroids possessing the cyclopropane 

moiety, the trans isomers tend to be rapidly eliminated by mammals and possess less toxicity than the cis 

isomers. For example, the oral LD50 (rats) of 1R cis resmethrin is about 168 mg/kg, but the value for the 

1R trans isomer is >8,000 mg/kg (Dorman and Beasley 1991). Pyrethroids that contain the alpha-S-cyano 

phenoxybenzyl alcohol moiety demonstrate considerably greater toxicity when compared to the R 

configuration (Dorman and Beasley 1991). The enhanced insecticidal activity of esfenvalerate over 

fenvalerate is one example of this (Tomlin 1997). Esfenvalerate has become the preferred compound in 

the United States because it requires lower application rates than fenvalerate and is thus a more powerful 

insecticide. Esfenvalerate contains a much higher percentage of the alpha-S-cyano phenoxybenzyl 

alcohol isomer than fenvalerate. For most of the pyrethroids discussed, the approximate isomeric ratios 

of the technical-grade products have been reported by Tomlin (1997). 

Technical-grade (concentrated) pyrethrins and pyrethroids are usually formulated (mixed with carriers 

and solvents) for use in commercial products, and the toxicity of the formulated commercial product is 

not necessarily identical to the toxicity of the pure material. Inert ingredients and contaminants in 

pyrethroid formulations often contain suspected carcinogens or chemicals that depress the central nervous 

system (Mueller-Beilschmidt 1990). The EPA publishes a complete list of all inert ingredients found in 

pesticide products registered in the United States, and categorizes them along the following four classes: 

(1) inert ingredients of toxicological concern; (2) potentially toxic inert ingredients; (3) inert ingredients 

of unknown toxicity; and (4) inerts of minimal concern (EPA 2003). Under federal law, inert ingredients 
PYRETHRINS AND PYRETHROIDS 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

are not required to be disclosed on pesticides labels unless they contain a class one inert ingredient. Even 

though the EPA publishes a list of all inert ingredients used in currently registered pesticides, it does not 

specify the identity or quantity of inert ingredients that are used in a specific formulation. 

The most important route of exposure to pyrethrins and pyrethroids for the general population is through 

the ingestion of foods, especially vegetables and fruits that have been sprayed with these insecticides. 

Farmers, pesticide applicators, and persons using these insecticides on a regular basis may also receive 

additional exposure through inhalation and dermal contact. Many of these compounds are employed in 

household products such as pet shampoos, household sprays, mosquito repellents, and lice treatments, and 

the general population can be exposed to these compounds through these uses. 

The natural pyrethrins and many pyrethroids are rapidly degraded in the environment via photolysis, 

hydrolysis, and biodegradation. The environmental persistence times of many of these compounds are in 

the range of 1–2 days. The least persistent pyrethroids are allethrin, phenothrin, resmethrin, and 

tetramethrin. Structural modifications have made certain pyrethroids such as permethrin, cypermethrin, 

cyfluthrin, cyhalothrin, deltamethrin, fenvalerate, tefluthrin, and tralomethrin more persistent. For this 

reason, these compounds are utilized more often outdoors on crops than the relatively light-unstable 

pyrethroids and pyrethrins. Pyrethrins and pyrethroids are extremely toxic to fish and environmentally 

beneficial insects such as bees. In field situations, the hazard to bees is often lessened because bees are 

repelled by pyrethroids, which reduces their contact with plant surfaces that have recently been sprayed 

and decreases the chance of receiving a lethal dose. The natural pyrethrins and several pyrethroids are 

relatively nontoxic to mammals, but some pyrethroids such as deltamethrin, flucythrinate, cyhalothrin, 

permethrin, and tefluthrin have demonstrated considerable toxicity (Metcalf 1995). For example, flea 

applications containing a high concentration of permethrin made for use on dogs have often been 

associated with the accidental poisoning of cats when improperly used. 

In soils, these compounds adsorb strongly and do not leach appreciably into groundwater. These 

compounds are not considerably taken up by the roots of vascular plants; however, they are deposited 

upon the leafy region of vegetation following spraying. In general, most of these compounds have 

relatively low vapor pressures and Henry’s law constants, and as a result, volatilization from soil and 

water surfaces occurs slowly. Volatilization from foliage and household surfaces such as glass windows 

or floors occurs more rapidly since these compounds do not adhere to these surfaces as strongly in 

comparison to soils. 
PYRETHRINS AND PYRETHROIDS 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2 RELEASES TO THE ENVIRONMENT 

Pyrethrum is found naturally in the environment as a constituent of Chrysanthemum cinerariaefolium and 

Chrysanthemum cineum (Metcalf 1995). However, the majority of releases of pyrethrins and pyrethroids 

are due to their use as insecticides. The estimated amounts of bifenthrin, cyfluthrin, cyhalothrin, 

cypermethrin, deltamethrin, esfenvalerate, fenpropathrin, fenvalerate, permethrin, tefluthrin, and 

tralomethrin applied to crops in the United States in 1992 and 1997 are summarized in Table 6-1 

(Gianessi and Silvers 2000). No data were identified for any other pyrethroid or any of the pyrethrins. 

Similar findings have been reported by the United States Geological Survey (USGS) 1992 Census of 

Agriculture (USGS 2001) (See Table 5-4). 

6.2.1 Air 

Releases to the air represent the most important emission pathway of pyrethrins and pyrethroids. Most 

applications of these insecticides involve aerial or ground spraying of crops or other vegetation, as well as 

the use of aerosol bombs and sprays indoors. 

Manufacturing facilities may also release pyrethrins and pyrethroids during their production. A list of 

chemicals has been compiled for which releases are required to be reported to the EPA for the SARA 

Section 313 Toxics Release Inventory (TRI) (EPA 1995). The only pyrethroids that are on the list are 

allethrin, bifenthrin, cyfluthrin, cyhalothrin, fenpropathrin, fluvalinate, permethrin, phenothrin, 

resmethrin, and tetramethrin (TRI99 2001). Furthermore, data have only been reported for bifenthrin, 

cyfluthrin, permethrin, resmethrin, and tetramethrin. According to the TRI (Table 6-2), an estimated total 

of 546 pounds of bifenthrin, 16 pounds of cyfluthrin, 2,593 pounds of permethrin, 22 pounds of 

resmethrin, and 10,080 pounds of tetramethrin were discharged to air from manufacturing and processing 

facilities in the United States in 1999 (TRI99 2001). The TRI data should be used with caution since only 

certain types of facilities are required to report. This is not an exhaustive list. 

Pyrethrins or pyrethroids were not detected in air at the 1,636 NPL hazardous waste sites (HazDat 2003). 
PYRETHRINS AND PYRETHROIDS 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Trends of National Pyrethroid Use 

Amounts applied Amounts applied 

Pyrethroid (pounds) 1992 (pounds) 1997 Percent change 

Bifenthrin 116,716 110,246 -5 

Cyfluthrin 124,360 177,782 +43 

lambda Cyhalothrin 205,329 321,284 +57 

Cypermethrin 228,082 187,991 -18 

Deltamethrin 0 27,045 

Esfenvalerate 331,522 228,885 -31 

Fenpropathrin 66,368 31,839 -49 

Fenvalerate 66,281 0 -100 

Permethrin 1,068,598 1,066,056 -1 

Tefluthrin 238,429 576,865 +142 

Tralomethrin 60,105 23,767 -60 

Source: Gianessi and Silvers 2000 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 172 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or 

Use Pyrethroids
 

Reported amounts released in pounds per yeara 

Total onTotal on- Total off- and 

Stateb 

Number of 

facilities Airc Water 

Underground 

injection Land 

site 

released 

site 

releasee 

off-site 

release 

Bifenthrin 

FL 1 36 0 No data No data 36 No data 36 

IL 1 10 No data No data No data 10 No data 10 

MD 1 No data No data No data No data No data No data No data 

NY 1 No data No data No data No data No data No data No data 

TX 1 500 No data No data No data 500 No data 500 

Total 5 546 0 0 0 546 0 546 

Cyfluthrin 

MD 1 No data No data No data No data No data No data No data 

MO 1 11 72 No data No data 83 No data 83 

NJ 1 No data No data No data No data No data No data No data 

TX 2 5 No data No data No data 5 No data 5 

Total 5 16 72 0 0 88 0 88 

Permethrin 

AL 1 497 0 No data No data 497 4 501 

AR 2 500 No data No data No data 500 1,235 1,735 

AZ 1 No data No data No data No data No data No data No data 

FL 1 193 0 No data No data 193 No data 193 

GA 2 1 No data No data No data 1 No data 1 

IL 2 10 No data No data No data 10 No data 10 

LA 2 10 No data No data 31,000 31,010 No data 31,010 

MD 1 10 0 No data No data 10 No data 10 

MN 1 No data No data No data No data No data No data No data 

MO 2 No data No data No data No data No data No data No data 

NJ 1 No data No data No data No data No data No data No data 

TN 1 751 No data No data No data 751 No data 751 

TX 4 621 No data No data No data 621 No data 621 

WI 1 0 No data No data No data 0 No data 0 
 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 173 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or 

Use Pyrethroids
 

Reported amounts released in pounds per yeara 

Total onTotal on- Total off- and 

Stateb 

Number of 

facilities Airc Water 

Underground 

injection Land 

site 

released 

site 

releasee 

off-site 

release 

Total 22 2,593 0 0 31,000 33,593 1,239 34,832 

Resmethrin 

GA 1 No data No data No data No data No data No data No data 

MO 1 No data No data No data No data No data No data No data 

TX 1 22 No data No data No data 22 No data 22 

Total 3 22 0 0 0 22 0 22 

Tetramethrin 

IN 1 10,080 No data No data No data 10,080 No data 10,080 

MN 1 No data No data No data No data No data No data No data 

MO 1 No data No data No data No data No data No data No data 

WI 1 0 No data No data No data 0 No data 0 

Total 4 10,080 0 0 0 10,080 0 10,080 

Grand 39 13,257 72 0 31,000 44,329 1,239 45,568 

Total 

a

Data in TRI are maximum amounts released by each facility.

b

Post office state abbreviations are used. 

c

The sum of fugitive and stack releases are included in releases to air by a given facility.

d

The sum of all releases of the chemical to air, land, water, and underground injection wells. 

e

Total amount of chemical transferred off-site, including to publicly owned treatment works (POTW). 

Source: TRI99 2001 
PYRETHRINS AND PYRETHROIDS 174 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.2 Water 

Direct releases to water are expected to be low for pyrethrins and pyrethroids because these compounds 

are primarily applied aerially or from ground-based sprayers directly to crops and vegetation. Spray drift 

following the application of these compounds, however, may contaminate nearby waters. Pyrethroids 

such as resmethrin, phenothrin, and permethrin, which are often used in mosquito control, are prohibited 

from being applied to open water or within 100 feet of lakes, rivers, and streams due to their high toxicity 

to fish (EPA 2000b). 

Runoff water from fields or waste water from manufacturing facilities may contain pyrethrins and 

pyrethroids. For example, pyrethrin I and II were detected in runoff water following the application of a 

multi-purpose insecticide containing pyrethrins to a field in Franklin County, Kentucky (Antonious et al. 

1997). Leachate collected near a pesticide manufacturing plant in Barcelona, Spain contained 

cypermethrin at concentrations exceeding 5–10 ppm (Rivera et al. 1985). Fenvalerate was detected in 

runoff water from an agricultural region in the Nicolet River Basin of Quebec, Canada at an average 

concentration of 0.05 μg/L in June of 1989 (Caux et al. 1996). 

According to the TRI, an estimated total of 72 pounds of cyfluthrin (Table 6-2) was discharged to water 

from manufacturing and processing facilities in the United States in 1999 (TRI99 2001). The data listed 

in the TRI should be used with caution since only certain types of facilities are required to report. This is 

not an exhaustive list. 

Pyrethrins or pyrethroids were not detected in groundwater or surface water at the 1,636 NPL hazardous 

waste sites (HazDat 2003). 

6.2.3 Soil 

Releases of pyrethrins and pyrethroids to soils typically result from deposition following aerial or boom 

spraying of crops or vegetation. Improper disposal also may account for some sources in soil. 

According to the TRI, 31,000 pounds of permethrin were discharged to land from manufacturing and 

processing facilities in the United States in 1999 (TRI99 2001). The data listed in the TRI should be used 

with caution since only certain types of facilities are required to report. This is not an exhaustive list. 
 

 

PYRETHRINS AND PYRETHROIDS 175 

6. POTENTIAL FOR HUMAN EXPOSURE 

Pyrethrins were detected in soil collected at two of the NPL hazardous waste sites where it was detected 

in some environmental media (HazDat 2003). Pyrethroids were not detected in soil at the 1,636 NPL 

hazardous waste sites. 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Spray drift following the application of any pesticide is an important source of environmental 

contamination and is responsible for much of the aerial transport of these compounds. Spray drift is 

simply the movement of the applied insecticide outside the intended target area by mass transport or 

diffusion. The characteristics of spray drift are influenced largely by meteorologic conditions and the 

method of application. Wind velocity is the dominant environmental factor that affects spray drift. 

Droplet size, height of flight, aircraft speed, and boom length are the dominant spraying and equipment 

factors that affect spray drift. Application parameters can be optimized, but they are different for 

different insecticides (e.g., some insecticides are more effective with large droplets and/or high spray 

rates and others are more effective with small droplets and/or low spray rates). In an aerial deposition 

study of deltamethrin involving spray application from an airplane, peak deposition to the ground was 

0.5–1.2 ng/cm2

 (Johnstone et al. 1987). A site 4 km away from the spray zone received ground 

depositions as high as 0.2 ng/cm2

, although most areas outside the spray zone received insignificant 

deposition. During application of insecticides to an apple orchard in Massachusetts approximately 1 acre 

in size, fenvalerate was detected downwind of the spray zone (75 feet away) at a maximum concentration 

of 1.28 μg/m3

 (Clark et al. 1991). Within 2 hours, the level had been reduced to 0.03 μg/m3. 

Based on the vapor pressure of the pyrethrins and pyrethroids (Tables 4-4 and 4-5, respectively), these 

compounds are expected to exist in both vapor and particulate phases in the ambient atmosphere. Vapor 

phase pyrethrins and pyrethroids are rapidly degraded in the atmosphere by direct photolysis and reaction 

with oxidants found in air such as photochemically-produced hydroxyl radicals, ozone, and nitrate 

radicals. Particulate phase compounds are slower to degrade, however, and can travel long distances 

before being removed from the air by wet and dry deposition. The concentrations of 13 different 

pesticides in the atmosphere and rainfall were studied in an area of eastern France in 1992 (Millet et al. 

1997). Fenpropathrin was detected in the vapor phase at concentrations ranging from 0.03 to 2.7 ng/mL 

and in the particulate-phase at concentrations of 0.03–4 ng/mL (Millet et al. 1997). 
PYRETHRINS AND PYRETHROIDS 176 

6. POTENTIAL FOR HUMAN EXPOSURE 

Pyrethrins and pyrethroids are strongly adsorbed to soil surfaces and are not considered very mobile. A 

wide range of Koc values has been reported by different authors, but most of these values indicate a high 

degree of adsorption and little leaching potential. The Koc values for the pyrethrins were estimated to 

range from 700 (cinerin II) to 27,200 (pyrethrin I) (Crosby 1995). Adsorption data are available for 

several pyrethroids from the U.S. Department of Agriculture Pesticide Database (USDA 2001a). The Koc 

values for permethrin range from 10,471 to 86,000. The Koc values in silt loam, sandy loam, sediment, 

and sand were 19,340, 20,865, 44,070, and 60,870, respectively. The Koc values of cypermethrin in 

loamy sand (pH 5.4, 2.1% organic matter), sandy loam (pH 6.5, 3.4% organic matter), silt loam (pH 5.6, 

2.0% organic matter), loamy sand (pH 4.7, 15.6% organic matter), and loam (pH 7.1, 5.2% organic 

matter) were 160,000; 84,000; 22,000; 34,000; and 5,800, respectively (USDA 2001a). The Koc values 

were 3,700 to 64,125, 1,000 to 12,000, and 5,000 to 340,000 for cyfluthrin, fenvalerate, and 

fenpropathrin, respectively. The movement of deltamethrin, cypermethrin, permethrin, and their 

degradation products were studied in clay and loamy sands (Kaufman et al. 1981). Deltamethrin, 

permethrin (both cis and trans isomers) and cypermethrin (both cis and trans isomers), were considered 

immobile in all soils tested. The degradation products studied, cis, trans 3-(2,3-dichloroethenyl)­

2,2-dimethylcyclopropanecarboxylate; 3-phenoxybenzyl alcohol; and 3-phenoxybenzoic acid showed 

some level of mobility. 

Volatilization from water and soil is expected to occur slowly for many of the pyrethroids since these 

compounds generally have low vapor pressures and Henry’s law constants (Table 4-5). When released to 

water, partitioning to suspended solids and sediment occurs rapidly. These compounds adsorb strongly to 

suspended solids and sediment in the water column, and this process significantly attenuates 

volatilization. Laboratory studies indicated that >95% of an initially applied amount of permethrin was 

adsorbed onto lake sediment and only 7–9% of the adsorbed complex could be desorbed from the 

sediment following four successive rinses with distilled water (Sharom and Solomon 1981). Compounds 

with relatively large Henry’s law constants, such as deltamethrin, volatilize more readily from water 

surfaces than other pyrethroids. Muir et al. (1985) determined that after deltamethrin was applied to 

ponds, approximately 6% volatilized over the course of a 2-day incubation period. However, the major 

partitioning process was adsorption to suspended solids and sediment. Maguire et al. (1989) observed 

that deltamethrin applied to a pond in Canada was rapidly dissipated by photolysis, hydrolysis, and 

volatilization. Laboratory studies using sterilized pond water showed that volatilization losses increased 

if the deltamethrin was sprayed directly onto the surface of the water rather than injecting the solution 

into the subsurface water. Volatilization losses from foliage may be considerably greater than 
 

 

PYRETHRINS AND PYRETHROIDS 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

volatilization from soils because pyrethrins and pyrethroids do not adsorb as strongly to the leafy 

component of vegetation as to soils (Boehncke et al. 1990). Laboratory and field tests were conducted to 

evaluate volatilization losses of deltamethrin sprayed on plant and soil surfaces (Boehncke et al. 1990). 

Under the summer time conditions of the field tests, mean evaporative losses from lettuce, kohlrabi, green 

beans, and summer wheat ranged from 12 to 71% over a 24-hour period, while evaporative losses from 

soil were approximately 24% in 24 hours. Since pyrethrin I, cinerin I, and jasmolin I have larger Henry’s 

law constants than the corresponding esters (pyrethrin II, cinerin II, and jasmolin II), they are expected to 

volatilize from moist soils and water more rapidly. The estimated volatilization half-lives of pyrethrin I, 

cinerin I, and jasmolin I from soil range from 1.8 to 2.7 days, while the half-life values for pyrethrin II, 

cinerin II, and jasmolin II range from 36.8 to 97 days (Crosby 1995). Pyrethrins and pyrethroids are often 

used indoors in sprays or aerosol bombs, and the volatilization rates from glass or floor surfaces may be 

significantly faster than from soils since these compounds are not likely to adsorb as strongly to these 

surfaces. 

Pyrethrins and pyrethroids can bioconcentrate in aquatic organisms and are extremely toxic to fish. The 

bioconcentration factor (BCF) of permethrin, fenvalerate, deltamethrin, and cypermethrin in rainbow trout 

(Oncorhynchus mykiss) and sheepshead minnow (Cyprinodon variegatus) were approximately 450–600, 

180–600, 100–1,200 and 120–400, respectively (Haitzer et al. 1998). The BCF values varied 

considerably as the amount of dissolved organic matter in the water column was changed (Haitzer et al. 

1998). The steady-state BCF values of fenvalerate and permethrin in eastern oysters (Crassostrea 

virginica) were measured as 4,700 and 1,900, respectively, over a 28-day incubation period (Schimmel et 

al. 1983). In pesticide-free water, the contaminated oysters depurated permethrin and fenvalerate to 

nondetectable levels in 1 week. Insect BCF values after 6 hours of exposure to sublethal permethrin 

concentrations were 18, 30, 7, 4, and 24 for black fly, caddisfly, damsefly, water scavenger, and mayfly, 

respectively (Tang and Siegfried 1996). Using a static test system and a 3-day incubation period, the 

BCF value for cypermethrin in golden ide fish (Leuciscus idus melanotus) was measured as 420 (Freitag 

et al. 1985). In a series of field tests designed to simulate the environmental fate of tralomethrin and 

deltamethrin due to spray drift and field runoff, fathead minnows were exposed to different levels of these 

pyrethroids (Erstfeld 1999). Over the course of a 7-day incubation period, the minnows were analyzed 

and BCF values of 219 and 315 were calculated for days 4 and 7, respectively, for the tralomethrin spray 

drift pond microcosms. The BCF values were 185 and 143 for days 4 and 7, respectively, for the 

tralomethrin runoff water microcosms. The BCF values were 260 and 185 for days 4 and 7, respectively, 

for the deltamethrin spray drift pond microcosms and the BCF values were 169 and 166 for days 4 and 7, 

respectively, for the deltamethrin runoff water microcosms. 
PYRETHRINS AND PYRETHROIDS 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

Little data exist regarding the uptake and transport of pyrethrins and pyrethroids by plant material. Since 

many of these compounds are rapidly degraded in the environment, this transport mechanism may not be 

an important environmental fate process other than the initial settling of these compounds on the canopy 

following deposition. The aerial surface of a plant, including foliage, is covered by a cuticle, which 

serves as a barrier to water loss and to prevent penetration of applied chemicals or environmental 

pollutants (Paterson et al. 1990). Once deposited on the surface, a chemical may be degraded, bind to the 

cuticle, or diffuse into the plant through the stomata. Parihar and Gupta (1998) demonstrated that 

fenvalerate applied to the surface of pigeon pea (Cajanus cajan) in India under field conditions was 

rapidly degraded and did not accumulate significantly in the plants. The fenvalerate residues were below 

detection limits at 15 and 20 days postapplication for two different application rates. These compounds 

can also be taken up from the soil by the roots of the plant. Since pyrethrins and pyrethroids adsorb 

strongly to soils, their uptake from roots and transport within plants is expected to be limited. Lettuce, 

beets, and wheat planted in soil 30, 120, and 365 days after treatment of [14C]-fenvalerate were shown to 

accumulate very little 14C when harvested at maturity (Lee 1985). Furthermore, it was demonstrated that 

very little downward movement of the radiolabeled fenvalerate occurred in the soils and that little, if any, 

fenvalerate or its degradation products are taken up by the roots of these plants. Chemicals may enter 

aquatic plants in solution directly from the water. Erstfeld (1999) demonstrated that aquatic plants 

accumulate deltamethrin and tralomethrin from the water column, in a series of pond and runoff water 

microcosms. Following application of tralomethrin, the BCF values in macrophytes were 18,200 and 

8,290 in pond and water runoff microcosms, respectively, at 7 days postapplication (Erstfeld 1999). This 

observation is consistent with the data of Muir et al. (1985) that observed deltamethrin residues in aquatic 

plants at concentrations ranging from 253 to 1,021 ng/g 24 hours after application of 1.8–2.5 μg/L 

deltamethrin solution to a pond. Similarly, permethrin applied to the surface of a fast-flowing stream was 

taken up by aquatic plants (Sundaram 1991). Following application of 1.658 g of permethrin to the 

stream surface, permethrin concentrations in aquatic plants located 280 m from the application site ranged 

from 6.78 ng/g (420 minutes postapplication) to 17.6 ng/g (60 minutes postapplication). It was concluded 

that the permethrin was largely absorbed in foliar waxes in the water arum and was slowly desorbed and 

lost by hydrolytic or microbial degradation. 
PYRETHRINS AND PYRETHROIDS 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2 Transformation and Degradation 

Many studies use first-order kinetics to model the dissipation of pesticides in the environment because a 

half-life for the chemical can be defined. The half-life represents the calculated time for loss of the first 

50% of the substance. However, in many cases, the time required for the loss of the remaining substance 

may be substantially longer, and the rate of disappearance may decline further as time progresses. This is 

often the case for the disappearance of pesticides in soils. For simplicity, the term half-life in this 

document is used to indicate the estimated time for the initial disappearance of 50% of the compound and 

does not necessarily imply that first-order kinetics were observed throughout the experiment unless 

otherwise noted. 

6.3.2.1 Air 

Pyrethrins and pyrethroids in the ambient atmosphere are degraded rapidly through reaction with 

atmospheric oxidants or by direct photolysis. Based upon rate constants for the reaction with hydroxyl 

radicals and ozone molecules derived from a structure estimation method (Meylan and Howard 1993), the 

atmospheric half-lives of the pyrethrins are on the order of several minutes to a few hours (HSDB 2001). 

These compounds are also rapidly degraded by direct photolysis. Chen and Casida (1969) observed that 

thin films of pyrethrin I applied to glass plates underwent 90% photodecomposition within 0.2 hours, 

while a dark control underwent very little loss. 

Pyrethroids where the isobutenyl group attached to the cyclopropane moiety has been altered are more 

stable to sunlight than the early pyrethroids like allethrin or resmethrin. For this reason, pyrethroids such 

as permethrin, deltamethrin, cyhalothrin, cyfluthrin, and cypermethrin are more frequently applied 

outdoors to crops in comparison to the rapidly degraded pyrethroids like resmethrin and allethrin. When 

exposed to daylight as a thin film indoors near a window, phenothrin decomposed with a half-life of about 

6 days, whereas about 60% of applied permethrin remained undecomposed after 20 days (WHO 1990c). 

Thus, the replacement of the isobutenyl group with the dichlorovinyl substituent significantly enhanced 

the photostability of permethrin in comparison to phenothrin (WHO 1990c). The photodegradation halflife of permethrin on thin films exposed to light at 295–305 nm was in the range of 5–7 days, while the 

half-lives for deltamethrin and cis cypermethrin were 6 and 7.5 days, respectively (Chen et al. 1984). 

Cypermethrin exposed to ultraviolet (UV) light >290 nm, underwent 30.2% photomineralization over a 
 

 

PYRETHRINS AND PYRETHROIDS 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

17-hour irradiation period (Freitag et al. 1985). The photodegradation half-life of tetramethrin on glass 

films exposed to a sunlamp was approximately 1 hour, with nearly 100% photodecomposition observed 

after 15 hours of illumination (Chen and Casida 1969). Allethrin applied to glass films was degraded 

approximately 90% in 8 hours when irradiated with UV light, but some of the loss was attributed to 

volatilization (Chen and Casida 1969). Aqueous suspensions of allethrin underwent approximately 

11.1% photodecomposition after only 15 minutes of exposure to sunlight (Ivie and Casida 1971b). It was 

also observed that the addition of chloroplasts to the suspensions photosensitized the photolysis and 

increased degradation rates in sunlight, suggesting that photodegradation on crops is a very rapid process. 

The photolysis half-life of resmethrin films on glass plates ranged from about 20 to 90 minutes when 

exposed to forenoon and midday sunlight conditions (Samsonov and Makarov 1996). The fastest rates 

were observed during midday sunlight and in the presence of the sensitizer methylene blue. Resmethrin 

also underwent direct photolysis when aerosols were irradiated with sunlight. Photodecomposition 

products of resmethrin included chrysanthemic acid, phenylacetic acid, benzyl alcohol, benzaldehyde, 

benzoic acid, and various chrysanthemates (Ueda et al. 1974). Cyhalothrin was reported as being stable 

to light, with <10% photodecomposition after 20 months while stored under sunlight conditions (Tomlin 

1997). However, on soil surfaces and in aqueous solutions at pH 5, cyhalothrin was degraded upon 

exposure to sunlight with a reported half-life of about 30 days (WHO 1990a). 

Compounds, such as nitroanilines, that absorb light in the environmental UV spectrum have been shown 

to photostabilize pyrethrins and pyrethroids (Dureja et al. 1984). Following irradiation at 360 nm for 

18 hours, the percent recoveries of pyrethrins, allethrin, kadethrin, resmethrin, tetramethrin, phenothrin, 

and fenpropathrin on silica gel plates were 1, 2, 0, 7, 2, 29, and 28%, respectively (Dureja et al. 1984). 

Following the addition of the herbicide trifluralin, the amounts recovered after irradiation were: 

pyrethrins, 54%; allethrin, 78%; kadethrin, 47%; resmethrin, 85%; tetramethrin, 77%; phenothrin, 66%; 

and fenpropathrin, 83% (Dureja et al. 1984). Pyrethroids with halogenated acid moieties were also 

protected from photodecomposition due to the addition of trifluralin. Following irradiation at 360 nm for 

32 hours on silica gel plates, the percent recoveries of permethrin, cypermethrin, deltamethrin, and 

fenvalerate were 32, 19, 25, and 23%, respectively. With the addition of trifluralin, the percent recoveries 

increased to 65% for permethrin, 83% for cypermethrin, 57% for deltamethrin, and 90% for fenvalerate 

(Dureja et al. 1984). Deltamethrin-impregnated cotton strips were degraded upon irradiation with UV 

light at differing rates, depending upon the color of the fabric and whether or not a UV absorber was 

added to the impregnating solution (Hussain and Perschke 1991). When white cotton fabric treated with 

deltamethrin alone was irradiated for 24 hours, nearly 100% photodegradation was observed. However, 

deltamethrin applied to blue and black fabric was degraded approximately 44.9 and 37.5%, respectively, 
 

PYRETHRINS AND PYRETHROIDS 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

over a 24-hour irradiation period (Hussain and Perschke 1991). Addition of the UV absorber 

2,4-dihydroxybenzophenone also decreased the amount of degradation following exposure to UV light. 

6.3.2.2 Water 

Since pyrethrins and pyrethroids undergo photolysis in the atmosphere, they are also degraded by this 

mechanism in sunlit surface waters. Photosensitizing agents found in natural waters such as fulvic and 

humic acids increase the rate of photolysis. The photolysis half-life of permethrin in seawater exposed to 

outdoor light was determined to be 14 days and the half-life of fenvalerate was measured as 8 days 

(Schimmel et al. 1983). Little change in concentration was observed when each pyrethroid was incubated 

in dark constant temperature controls. Photolysis half-lives of 27.1 and 19.6 hours were determined for 

respective cis and trans isomers of permethrin, respectively, in 800 mL of pond water exposed to sunlight 

(Rawn et al. 1982). The photodegradation half-life of cypermethrin in a distilled water solution ranged 

from 2.6 to 3.6 days and the half-lives in river and seawater were in the range of 0.6–1.0 days when 

exposed to sunlight (Takahashi et al. 1985a). The cis isomers underwent photodegradation at greater 

rates than the trans isomers. The photodegradation half-life of deltamethrin in distilled water was 

1–2 days, while the half-life in river water was longer, yet still <5 days when solutions were exposed to 

sunlight (Maguire 1990). The photolysis half-lives of fenpropathrin in distilled water, distilled water with 

humic acid, river water, and seawater were 13.5, 6, 2.7, and 1.6 weeks, respectively, when exposed to 

sunlight (Takahashi et al. 1985c). 

These compounds also undergo hydrolysis in the environment at varying rates depending upon pH and 

temperature. Generally, hydrolysis is only an important environmental fate process under alkaline 

conditions and at temperatures of 20 EC or greater. The hydrolysis half-life of cyfluthrin is about 

231 days at pH 7, but about 2 days at pH 8 (USDA 2001a). At pH 5 and pH 7, permethrin is stable 

towards abiotic hydrolysis, but at pH 9, the abiotic hydrolysis half-life is about 50 days (USDA 2001a). 

The aqueous hydrolysis half-lives of cypermethrin in sterile water-ethanol (99:1) phosphate buffers at 

25 EC were determined to be 99, 69, 63, and 50 weeks at pH values of 4.5, 6, 7, and 8, respectively 

(Chapman and Cole 1982). The half-lives of an 8 ppb solution of fluvalinate at 25 EC were 48, 22.5, and 

1.13 days at pH 5, 7, and 9, respectively (Tomlin 1997). The hydrolysis of fenpropathrin in buffer 

solution was studied under various pH and temperature conditions (Takahashi et al. 1985b). At 25 EC, 

the hydrolysis half-lives of fenpropathrin were approximately 2.2 years and 8 days at pH 7 and 9, 
PYRETHRINS AND PYRETHROIDS 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

respectively (Takahashi et al. 1985b). At 40 EC, the half-lives were about 80 days and 19 hours at pH 7 

and 9, respectively (Takahashi et al. 1985b). 

Pyrethroids are readily degraded by environmental microorganisms. The half-life of permethrin in a 

sediment/seawater solution was <2.5 days, but under sterile conditions, there was no significant change in 

the permethrin concentration over a 4-week incubation period, suggesting that biodegradation was 

responsible for the loss under nonsterile conditions (Schimmel et al. 1983). The half-life of fenvalerate in 

the sediment/seawater solution was 27–42 days under nonsterile conditions and little loss was noted under 

sterilized conditions (Schimmel et al. 1983). Pond and runoff water microcosms were constructed to 

simulate the fate and persistence of tralomethrin and deltamethrin under field conditions following spray 

drift over a 7-day study period (Erstfeld 1999). The degradation profiles of tralomethrin in water showed 

rapid conversion to deltamethrin with a calculated half-life of about 6.8 hours. The resulting deltamethrin 

was further degraded to decamethrinic acid with a half-life of about 81 hours. In sediment, tralomethrin 

was rapidly converted to deltamethrin. Two experiments were conducted to evaluate the persistence of 

fenvalerate in seawater and seawater/sediment microcosms under different conditions (Cotham and 

Bidleman 1989). The half-lives of fenvalerate in unsterilized seawater at pH 8 and 8.05 were 17 and 

14 days, respectively. The half-lives of fenvalerate in heat sterilized seawater at pH 8 and 8.05 were 

41 and 33 days, respectively (Cotham and Bidleman 1989). Bioresmethrin, cypermethrin, deltamethrin, 

permethrin, fenvalerate, and Nuerelle DX 50 (50 grams cypermethrin and 500 grams chlorpyriphos 

mixture) were degraded at different rates in a model ecosystem consisting of polluted river water and 

sediment under aerobic conditions (Lutnicka et al. 1999). The temperature of the ecosystem was 

15–19 EC and the pH was 7.7. The ranges of half-lives in the model ecosystem were: bioresmethrin, 

1.2–4.6 days; cypermethrin, 4.7–30.8 days; deltamethrin, 0.5–0.8 days; permethrin, 1.1–3.6 days; 

fenvalerate, 3.5–4.4 days; and cypermethrin in the Nuerelle DX 50 mixture, 11.6–30.4 days (Lutnicka et 

al. 1999). It was also noted that the degradation rates of the pyrethroids followed first-order kinetics, and 

that only fenvalerate and cypermethrin residues remained at detectable levels 56 days postapplication. 

No data exist regarding the degradation of pyrethrins in water. Based upon degradation studies of 

structurally similar esters and the degradation rates of the pyrethroids, it has been concluded that 

pyrethrins should degrade rapidly in water (Crosby 1995). 
 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2.3 Sediment and Soil 

Laboratory and field studies suggest that pyrethroids are degraded faster in soils than many of the longlasting organochlorine, organophosphorus, and carbamate pesticides. Fenvalerate and deltamethrin 

appear to be the most persistent compounds in commercial use, especially in soils containing a high clay 

content or a large percentage of organic matter. 

Chapman et al. (1981) studied the persistence of permethrin, cypermethrin, deltamethrin, fenpropathrin, 

and fenvalerate in sterile and nonsterile soils in order to assess the importance of biodegradation versus 

abiotic transformation mechanisms. After initial application of 1 ppm of each pyrethroid in a mineral 

soil, the percentages of pesticide recovered after an 8-week incubation period were: fenpropathrin, 2%; 

permethrin, 6%; cypermethrin, 4%; fenvalerate, 12%; and deltamethrin, 52%. Over 90% of each 

pyrethroid was recovered from heat sterilized soils, suggesting that biodegradation plays a crucial role in 

the disappearance of these compounds. Similar results were obtained in a richly organic soil, although the 

amounts degraded were lower over the 8-week incubation period. In the organic soil, the percent 

recoveries after 8 weeks were as follows: fenpropathrin, 8%; permethrin, 16%; cypermethrin, 16%; 

fenvalerate, 58%; and deltamethrin, 74%. The USDA Pesticide Database lists half-lives in the range of 

88–287 days for fenvalerate, 56–63 days for cyfluthrin, 4–40 days for permethrin, and 6–60 days for 

cypermethrin in aerobic soils (USDA 2001a). In a biodegradation study using deltamethrin as the sole 

carbon source and pure bacterial isolates from soil as inoculum, 35.7–44.4% of the initially applied 

deltamethrin metabolized in 1 week and 59.7–72.5% was degraded in 2 weeks (Khan et al. 1988). In the 

absence of bacterial isolates, only 3–10% of the deltamethrin was degraded. Deltamethrin was applied to 

a sandy loam from Alberta, Canada at an initial fortification level of 17.5 g/ha (42.5 ppb) and studied 

under indoor laboratory conditions and field conditions over a 52-week incubation period (Hill 1983). 

The half-life of deltamethrin under the field conditions was 6.8 weeks, and approximately 5–7% of the 

applied deltamethrin remained after 52 weeks. The half-life of the deltamethrin in the indoor experiments 

was 4.8 weeks and the differences in persistence between the field and laboratory experiments were 

attributed to climate effects. In both cases, the degradation was exponential and the decay could be 

reasonably fit to first-order kinetic equations (Hill 1983). It was noted that in the field experiments, the 

rate of degradation was slowed during the winter months. The anaerobic degradation of cyfluthrin in 

heavy clay soils was studied under laboratory conditions for a period of 140 days at different moisture 

levels and organic matter content (Smith et al. 1995). The percentages of cyfluthrin recovered in an 

unamended soil after 31, 73, 115, and 140 days were 50.8, 27.9, 14.8, and 15%, respectively. The 

percentages of cyfluthrin recovered in a soil amended with organic matter from cotton plant residue were 
 

 

 

PYRETHRINS AND PYRETHROIDS 184 

6. POTENTIAL FOR HUMAN EXPOSURE 

35.2, 20.9, 14.4, and 9.4%, respectively, over the same incubation periods. The disappearance of 

cyfluthrin was not significantly affected by the moisture content of the soils (Smith et al. 1995). The halflives of fluvalinate and flucythrinate in agricultural soil were 6.8–8.0 days and 9.4–11.9 days, 

respectively, depending upon the application rate (Agnihotri and Jain 1987). It was observed that the rate 

of disappearance followed first-order kinetics, and that after 40 days, neither insecticide remained at 

detectable levels in the soil (Agnihotri and Jain 1987). The half-lives of fenvalerate in a tidal marsh 

sediment ecosystem, with sediment obtained from the Chesapeake Bay, were calculated as 6.3 days 

(0.2 ppm initial concentration) and 8.8 days (1 ppm initial concentration) (Caplan et al. 1984). It was not 

possible to determine the exact mechanism of degradation (hydrolysis, biodegradation, or photolysis) 

since no dark or sterile controls were run; however, biodegradation and hydrolysis were the most likely 

routes since the fenvalerate was initially incorporated into the sediment, shielding it from substantial 

sunlight. The half-life of fenvalerate in a sediment/seawater (obtained from Charleston, South Carolina) 

system at pH 7.3–7.7 was 12 days (Cotham and Bidleman 1989). The half-life of fenvalerate applied to 

sandy loam and silty clay loam soils at an initial concentration of 5 ppm was approximately 75–80 days 

under indoor laboratory conditions (Lee 1985). The half-life under outdoor conditions was approximately 

60 days (Lee 1985). 

Since light is attenuated as a function of depth from the soil surface, photolysis of pyrethrins and 

pyrethroids is only an important environmental fate process at the surface of the soil. The photodegradation of cypermethrin was studied by exposing various soil surface applications to sunlight for 

7–10 days (Takahashi et al. 1985a). The half-lives on soil surfaces exposed to sunlight ranged from 0.6 to 

1.9 days, while half-lives on non-illuminated soils were >7 days. The photodegradation products 

resulting from exposure of cypermethrin to sunlight included various carbanoyl and hydroxy derivatives, 

a variety of benzoic acid derivatives, several lactone derivatives, and several aliphatic carboxylic acid 

derivatives (Takahashi et al. 1985a). The photodegradation of esfenvalerate on thin films of soil, clay, 

and humic material was studied (Katagi 1991). Half-lives ranged from about 8 to 100 days with reaction 

at the cyano group and ether cleavage in the alcohol moiety responsible for the photodegradation on the 

surfaces tested. The shortest photolysis half-lives were observed when esfenvalerate was incorporated 

into the clay thin films. The half-life of fenpropathrin on the surface of a sterilized sandy loam was 

3–4 days following irradiation with natural sunlight (Dureja 1990). After 15 days, it was observed that 

only about 12% of the original amount remained (Dureja 1990). 

A mid-summer field study in Alberta, Canada was performed to determine the persistence of deltamethrin 

on crops and litter in order to establish a minimum time interval between treatment of pastures and 
 

PYRETHRINS AND PYRETHROIDS 185 

6. POTENTIAL FOR HUMAN EXPOSURE 

grazing by cattle (Hill and Johnson 1987). The average half-life of deltamethrin applied to two pastures 

to control grasshoppers was 5.8 days on the forage and 17 days on the litter (Hill and Johnson 1987). The 

authors attributed the rapid initial loss of deltamethrin to surface processes including volatilization and 

photolysis, but the remainder of the loss occurred by degradation through metabolic and chemical 

processes. The longer half-life of deltamethrin on the litter reflects a lower initial loss of the chemical 

through surface processes (volatilization and photolysis) due to the litter being more sheltered. 

No data exist regarding the degradation rates of pyrethrins in soil. Based upon hydrolysis and 

biodegradation studies of structurally similar esters and the relatively rapid degradation rates of the 

pyrethroids, it has been concluded that pyrethrins should degrade rapidly in soil (Crosby 1995). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Pyrethrins and pyrethroids have been detected at low levels in ambient air, indoor air samples, surface 

water, groundwater, and drinking water. These compounds have also been detected in soils, sediment, 

various foods, and animals. Quantitative concentration information is presented in the following sections. 

6.4.1 Air 

Pyrethrins and pyrethroids are used in both indoor and outdoor settings to control insects; therefore, these 

compounds are frequently detected in the air of homes and buildings after their use. During a study of 

pesticide use in Florida, permethrin was qualitatively identified in the porch or patio of two out of eight 

homes in Jacksonville, during August of 1985 (Lewis et al. 1988). During a study of pesticide occurrence 

in indoor air of New Jersey households, permethrin was detected at concentrations of 2,550 ng/g (cis) and 

3,850 ng/g (trans) in household dust immediately following its application as an aerosol flea treatment 

(Roinestad et al. 1993). The concentrations decreased to 550 ng/g (cis) and 675 ng/g (trans) 8 weeks 

postapplication. Permethrin, resmethrin, and cypermethrin were detected in the ambient air of 

commercial pest control buildings in North Carolina at concentration ranges of 0.03–2.34, 0.31–14.10, 

and 0.02–11.66 μg/m3

, respectively (Wright et al. 1996). The concentrations of cypermethrin detected in 

the air of vacant dormitory rooms following its application for cockroach control were 18.2, 8.5, 3.0, 7.1, 

4.4, 0.6, and 0.3 μg/m3

 at 0, 7, 28, 42, 56, 70, and 84 days postapplication, respectively (Wright et al. 

1993). The concentration in untreated rooms adjacent to the sprayed rooms ranged from 0.1 μg/m3 

(84 days postapplication) to 6.4 μg/m3

 (immediately following application). The indoor air concentration 
 

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6. POTENTIAL FOR HUMAN EXPOSURE 

of allethrin in a public community college cafeteria after bi-monthly applications ranged from 0.2 ng/m3 

(13 days after application) to 48 ng/m3

 (0.1 days after application) (Eitzer 1991). The maximum airborne 

residue of fenpropathrin in greenhouse air after application was 0.28 μg/m3

 (Siebers and Mattusch 1996). 

The mean and maximum concentrations of vapor-phase fenpropathrin in air collected at Colmar, France 

between 1991 and 1993 were 0.5 and 2.7 ng/mL, respectively (Millet et al. 1997), while the mean and 

maximum concentrations of particulate-phase fenpropathrin in air were 0.6 and 4 ng/mL, respectively 

(Millet et al. 1997). The concentrations of permethrin and cypermethrin in airborne particulate matter in 

areas of Saudi Arabia with heavy insecticide use were 1.84–30.70 and 0.28–3.61 μg/m3

, respectively 

(Badawy 1998). 

6.4.2 Water 

Permethrin was detected in 24 of 12,253 ambient surface water samples in the United States at an average 

concentration of 0.0137 μg/L (EPA 2000c). Permethrin was detected 6 hours postapplication at 

concentrations of 0.017 and 0.018 μg/L in 2 of 6 samples from a slow-moving creek approximately 

60 meters from a potato field where permethrin was applied via aerial spraying (Frank et al. 1991). 

Concentrations as high as 0.28 μg/L were observed 10 minutes postapplication, but decreased rapidly. In 

1996, the average permethrin concentration in surface waters from agricultural areas in Thailand was 

2.81 μg/L (Thapinta and Hudak 2000). The deposition of cypermethrin on the surface of three streams 

adjacent to vineyards in France that were sprayed (via mistblowers) with cypermethrin were in the range 

of 0.04–0.45 mg/m2

 and cypermethrin concentrations in subsurface water of the streams were in the range 

of 0.4–1.7 μg/L soon after spraying, but decreased to <0.1 μg/L within a period of about 5 hours 

(Crossland et al. 1982). 

Since pyrethrins and pyrethroids adsorb strongly to soils, they are not often detected at elevated 

concentrations in groundwater and drinking water. In an EPA compilation of monitoring studies of 

pesticides in groundwater from 1971 to 1991, fenvalerate was detected in 5 out of 345 wells at 

concentrations of 0.01–0.28 μg/L and permethrin was detected in 4 out of 1,097 wells at concentrations of 

0.01–1.25 μg/L (EPA 1992). Cypermethrin was not detected in 311 wells sampled, tralomethrin was not 

detected in 188 wells sampled, and pyrethrins were not detected in 144 wells sampled (EPA 1992). As 

part of the National Drinking Water Contaminant Occurrence Database, permethrin was detected in 3 of 

73 ambient spring water samples at an average concentration of 0.0133 μg/L and in 3 of 5,728 ambient 
 

PYRETHRINS AND PYRETHROIDS 187 

6. POTENTIAL FOR HUMAN EXPOSURE 

groundwater samples at an average concentration of 0.011 μg/L (EPA 2000c). Permethrin was not 

detected in 94 wells analyzed in a 1992 USGS study of pesticides in near-surface aquifers in the Midwest 

(Kolpin et al. 1995). In the 1993–1995 USGS survey of pesticides in shallow groundwater throughout the 

United States, permethrin was detected in 2 out of 1,034 sites at a maximum concentration of 0.007 μg/L 

(Kolpin et al. 1998). 

6.4.3 Sediment and Soil 

Pyrethrins and pyrethroids are detected in agricultural soils or sediment from lakes, rivers, and streams 

that may have been contaminated from spray drift or runoff water. Following the application of a multipurpose insecticide containing pyrethrins on a field in Franklin County Kentucky, the concentrations of 

pyrethrin I and II decreased in the soil as a function of time. After 1 hour, 1, 4, 8, 12, 18, 24, and 30 days, 

the concentrations of pyrethrin I were 9, 5.1, 3.9, 2.1, 0.9, 1.3, 0.3, and 0.8 μg/kg, respectively (Antonious 

et al. 1997). The concentrations of pyrethrin II over the same time frame were 900, 140, 103, 23, 1, 1, 1, 

and 1 μg/kg. The average concentration of permethrin in soils collected from 48 agrochemical facilities 

located throughout the state of Illinois was 190 μg/kg, with a range of concentrations from 11 to 

4.22x105

 μg/kg (Krapac et al. 1995). During 1996–1997, concentrations of permethrin in soil samples 

from cultivated areas in Thailand ranged from 62.41 to 1,178.40 μg/kg (Thapinta and Hudak 2000). 

Fenvalerate was detected in soil samples of two fields near the Nicolet River Basin in Quebec, Canada at 

concentrations of 20 and 8 μg/kg (0–5 cm depth) and 2 and 5 μg/kg (25–30 cm depth) (Caux et al. 1996). 

Permethrin was detected in the soil of two potato farms in Canada at concentrations ranging from 110 to 

380 μg/kg at 6 hours after application via aerial spraying (Frank et al. 1991). The concentrations 

decreased to 6–220 μg/kg at 6 days postapplication and 8–15 μg/kg at 30 days postapplication (Frank et 

al. 1991). 

Permethrin was detected in three of six sediment samples at concentrations of 18.1–21.1 μg/kg from a 

creek approximately 60 meters from a potato field where permethrin was applied via aerial spraying 

(Frank et al. 1991). At 30 days postapplication, permethrin was detected in only one of six samples at a 

concentration of 10 μg/kg (Frank et al. 1991). Sediment samples from an industrialized area of the 

Meltham Catchment in England contained permethrin at concentrations of 0.26–309.5 μg/kg and 

cyfluthrin at concentrations of 0.086–5.8 μg/kg (Yasin et al. 1996). Deltamethrin was detected in 

sediment samples of the Vemmenhog Catchment in Sweden at an average concentration of 20 μg/kg 

(Kreuger et al. 1999). 
PYRETHRINS AND PYRETHROIDS 188 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.4 Other Environmental Media 

According to the 1999 Food and Drug Administration (FDA) Pesticide Monitoring Program, permethrin 

was identified in 54 out of 1,040 food composites analyzed (FDA 2001). No range of levels was 

reported. Fenvalerate and fluvalinate were also qualitatively identified in food products, but no 

percentage of occurrence or concentrations were listed. Permethrin was also identified in 10 out of 

78 baby foods at concentrations of 0.6–60 μg/kg and fenvalerate was identified in 1 out of 78 baby foods 

at a concentration of 5 μg/kg (FDA 2001). Resmethrin has been identified, but not quantified, in corn, 

cornmeal, flour, and wheat (Simonaitis and Cail 1975). An FDA analysis of 320 food groups conducted 

from 1991 to 1999 determined that pyrethroids were present at varying levels in several foods. The 

results of this study pertaining to pyrethroids are summarized in Table 6-3 (FDA 2000c). 

Cypermethrin was detected in the milk from cows wearing ear tags impregnated with cypermethrin to 

control horn flies and other insects (Braun et al. 1985). Over a 21-day period, 60 milk samples were 

obtained from 10 cows. Only 11 out of 60 butterfat samples contained cypermethrin above the detection 

limit of 4 μg/kg. The range of concentrations in the butterfat of these 11 samples was 4.0–9.6 μg/kg 

(Braun et al. 1985). Flumethrin, deltamethrin, cypermethrin, and cyhalothrin were detected in the milk of 

10 dairy cows after single dermal applications at recommended doses (Bissacot and Vassilieff 1997a). 

The highest mean concentration for flumethrin was observed 28 days postapplication, while the highest 

mean concentrations for cypermethrin and cyhalothrin were observed 1 day postapplication. The highest 

mean concentration of deltamethrin in the milk was observed 7 days postapplication. 

Fenvalerate residues were detected in a variety of nontarget vertebrate and invertebrate species after 

application onto a cotton field to control bollworm and tobacco budworm (Bennet et al. 1983). Terrestrial 

invertebrates contained the lowest levels, while the highest residue concentrations were found in fish and 

insects. Fenvalerate levels in ppm were as follows: house mouse, 0.01; dickcissel, 0.02; ribbon snake, 

0.12; toad, 0.02; golden shiner, 0.47; mosquitofish, 0.32; snail, 0.53; and ground beetle, 0.55 (Bennett et 

al. 1983). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 189 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Levels of Pyrethroids Detected in Foods 

Mean Minimum Maximum 

Pyrethroid Food item n (ppm) (ppm) (ppm) 

Bifenthrin Raw strawberries 3 0.0487 0.0040 0.084 

Cyfluthrin Green peppers 1 0.002 0.002 0.002 

Cyfluthrin Raw raddish 1 0.013 0.013 0.013 

Cyfluthrin Beef chow mein 1 0.004 0.004 0.004 

lambda cyhalothrin Tomato sauce 1 0.003 0.003 0.003 

lambda cyhalothrin Green peppers 1 0.01 0.01 0.01 

lambda cyhalothrin Stuffed peppers 1 0.002 0.002 0.002 

Cypermethrin Broccoli 1 0.0013 0.0013 0.0013 

Cypermethrin Collards 7 0.442 0.052 1.247 

Cypermethrin Iceberg lettuce 2 0.0185 0.013 0.024 

Esfenvalerate Collards 4 0.0535 0.021 0.099 

Esfenvalerate Raw tomatoes 5 0.0146 0.005 0.02 

Esfenvalerate Green peppers 4 0.015 0.009 0.024 

Esfenvalerate Catsup 1 0.002 0.002 0.002 

Esfenvalerate Strained peaches/junior 2 0.0065 0.005 0.008 

Esfenvalerate Fruit dessert/junior 2 0.0025 0.002 0.003 

Esfenvalerate Raw apricot 1 0.06 0.06 0.06 

Esfenvalerate Mushrooms 1 0.019 0.019 0.019 

Esfenvalerate Stuffed peppers 3 0.005 0.003 0.007 

Fenvalerate Raw apricot 2 0.03 0.024 0.036 

Fenvalerate Strained peaches/junior 1 0.011 0.011 0.011 

Fenvalerate Red grapes 1 0.006 0.006 0.006 

Fenvalerate Raw cherries 1 0.11 0.11 0.11 

Fenvalerate Collards 12 0.1188 0.015 0.373 

Fenvalerate Raw tomatoes 4 0.0418 0.004 0.134 

Fenvalerate Green beans 2 0.017 0.015 0.019 

Fenvalerate Okra 1 0.032 0.032 0.032 

Fenvalerate Stuffed peppers 1 0.004 0.004 0.004 

Fenvalerate Tacos 1 0.002 0.002 0.002 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 190 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Levels of Pyrethroids Detected in Foods 

Mean Minimum Maximum 

Pyrethroid Food item n (ppm) (ppm) (ppm) 

Permethrin (cis) Baked ham 1 0.001 0.001 0.001 

Permethrin (trans) Baked ham 1 0.001 0.001 0.001 

Permethrin (cis) Fried eggs 1 0.001 0.001 0.001 

Permethrin (trans) Fried eggs 1 0.0006 0.0006 0.0006 

Permethrin (cis) Dry roasted peanuts 1 0.006 0.006 0.006 

Permethrin (trans) Dry roasted peanuts 1 0.009 0.009 0.009 

Permethrin (cis) Popcorn 1 0.007 0.007 0.007 

Permethrin (trans) Popcorn 1 0.007 0.007 0.007 

Permethrin (cis) Rye bread 2 0.0099 0.0008 0.019 

Permethrin (trans) Rye bread 2 0.0109 0.0007 0.021 

Permethrin (cis) Raw peaches 3 0.0107 0.006 0.018 

Permethrin (trans) Raw peaches 3 0.014 0.006 0.027 

Permethrin (cis) Raw cantaloupe 2 0.045 0.004 0.005 

Permethrin (cis) Raw cherries 1 0.022 0.022 0.022 

Permethrin (trans) Raw cherries 1 0.022 0.022 0.022 

Permethrin (cis) Dried prunes 1 0.002 0.002 0.002 

Permethrin (trans) Dried prunes 1 0.002 0.002 0.002 

Permethrin (cis) Spinach 22 0.6283 0.003 2.31 

Permethrin (trans) Spinach 22 0.6803 0.002 2.74 

Permethrin (cis) Collards 22 0.3331 0.002 1.33 

Permethrin (trans) Collards 22 0.285 0.002 0.853 

Permethrin (cis) Iceberg lettuce 5 0.0104 0.0009 0.036 

Permethrin (trans) Iceberg lettuce 5 0.009 0.0009 0.034 

Permethrin (cis) Canned sauerkraut 1 0.0004 0.0004 0.0004 

Permethrin (trans) Canned sauerkraut 1 0.0005 0.0005 0.0005 

Permethrin (cis) Broccoli 10 0.0047 0.001 0.014 

Permethrin (trans) Broccoli 10 0.0037 0.0007 0.009 

Permethrin (cis) Raw celery 22 0.0113 0.001 0.031 

Permethrin (trans) Raw celery 22 0.0093 0.001 0.023 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 191 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Levels of Pyrethroids Detected in Foods 

Mean Minimum Maximum 

Pyrethroid Food item n (ppm) (ppm) (ppm) 

Permethrin (cis) Asparagus 2 0.0862 0.0003 0.172 

Permethrin (trans) Asparagus 2 0.1087 0.0003 0.217 

Permethrin (cis) Cauliflower 1 0.004 0.004 0.004 

Permethrin (trans) Cauliflower 1 0.002 0.002 0.002 

Permethrin (cis) Raw tomato 16 0.0072 0.0006 0.015 

Permethrin (trans) Raw tomato 16 0.0072 0.0005 0.015 

Permethrin (cis) Green beans 1 0.005 0.005 0.005 

Permethrin (trans) Green beans 1 0.003 0.003 0.003 

Permethrin (cis) Green pepper 11 0.0332 0.005 0.081 

Permethrin (trans) Green pepper 11 0.0411 0.006 0.079 

Permethrin (cis) Raw raddish 1 0.001 0.001 0.001 

Permethrin (trans) Raw raddish 1 0.0005 0.0005 0.0005 

Permethrin (cis) Meatloaf 1 0.0006 0.0005 0.0006 

Permethrin (trans) Meatloaf 1 0.0006 0.0005 0.0006 

Permethrin (cis) Butter 1 0.002 0.002 0.002 

Permethrin (trans) Butter 1 0.003 0.003 0.003 

Permethrin (cis) Half & Half cream 1 0.0003 0.0003 0.0003 

Permethrin (trans) Half & Half cream 1 0.0005 0.0005 0.0005 

Permethrin (cis) Catsup 1 0.0009 0.0009 0.0009 

Permethrin (trans) Catsup 1 0.0007 0.0007 0.0007 

Permethrin (cis) Pumpkin pie 7 0.0024 0.0006 0.006 

Permethrin (trans) Pumpkin pie 7 0.0031 0.001 0.008 

Permethrin (cis) Chicken 1 0.001 0.001 0.001 

Permethrin (trans) Chicken 1 0.0008 0.0008 0.0008 

Permethrin (cis) Vegetables and chicken 1 0.001 0.001 0.001 

Permethrin (trans) Vegetables and chicken 1 0.001 0.001 0.001 

Permethrin (cis) Strained green 2 0.0035 0.002 0.005 

beans/junior 

Permethrin (trans) Strained green 2 0.0035 0.002 0.005 

beans/junior 

Permethrin (cis) Creamed spinach/junior 8 0.0372 0.0006 0.138 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 192 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Levels of Pyrethroids Detected in Foods 

Mean Minimum Maximum 

Pyrethroid Food item n (ppm) (ppm) (ppm) 

Permethrin (trans) Creamed spinach/junior 8 0.0338 0.0004 0.12 

Permethrin (cis) Strained peaches/junior 14 0.0185 0.0006 0.078 

Permethrin (trans) Strained peaches/junior 14 0.022 0.0007 0.099 

Permethrin (cis) Strained pears/junior 3 0.0013 0.0008 0.002 

Permethrin (trans) Strained pears/junior 3 0.0009 0.0008 0.001 

Permethrin (cis) Fruit dessert/junior 17 0.0045 0.0009 0.013 

Permethrin (trans) Fruit dessert/junior 17 0.0057 0.0006 0.019 

Permethrin (cis) Veal cutlet 1 0.002 0.002 0.002 

Permethrin (trans) Veal cutlet 1 0.002 0.002 0.002 

Permethrin (cis) Wheat bread 1 0.0009 0.0009 0.0009 

Permethrin (trans) Wheat bread 1 0.0009 0.0009 0.0009 

Permethrin (cis) Canned peaches 1 0.0004 0.0004 0.0004 

Permethrin (trans) Canned peaches 1 0.0005 0.0005 0.0005 

Permethrin (cis) Canned tomatoes 3 0.0015 0.0004 0.002 

Permethrin (trans) Canned tomatoes 3 0.0016 0.0007 0.002 

Permethrin (cis) Brussel sprouts 12 0.0154 0.0004 0.127 

Permethrin (trans) Brussel sprouts 12 0.0124 0.0003 0.1 

Permethrin (cis) Mushrooms 6 0.0285 0.0003 0.159 

Permethrin (trans) Mushrooms 6 0.0221 0.0002 0.125 

Permethrin (cis) Turnips 1 0.001 0.001 0.001 

Permethrin (trans) Turnips 1 0.001 0.001 0.001 

Permethrin (cis) Okra 1 0.002 0.002 0.002 

Permethrin (trans) Okra 1 0.002 0.002 0.002 

Permethrin (cis) Beef stroganoff 1 0.018 0.018 0.018 

Permethrin (trans) Beef stroganoff 1 0.01 0.01 0.01 

Permethrin (cis) Stuffed peppers 9 0.0138 0.0005 0.074 

Permethrin (trans) Stuffed peppers 9 0.0171 0.0007 0.093 

Permethrin (cis) Tuna casserole 6 0.0014 0.0008 0.002 

Permethrin (trans) Tuna caracole 6 0.0012 0.0005 0.003 
 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 

6. POTENTIAL FOR HUMAN EXPOSURE 

193 

Table 6-3. Levels of Pyrethroids Detected in Foods 

Pyrethroid Food item n 

Mean 

(ppm) 

Minimum 

(ppm) 

Maximum 

(ppm) 

Permethrin (cis) Quarter pound 1 0.005 0.005 0.005 

cheeseburger 

Permethrin (trans) Quarter pound 1 0.001 0.001 0.001 

cheeseburger 

Permethrin (cis) Tacos 3 0.0015 0.0004 0.003 

Permethrin (trans) Tacos 3 0.0018 0.0005 0.004 

Permethrin (cis) Pizza 2 0.0006 0.0004 0.0007 

Permethrin (trans) Pizza 2 0.0006 0.0003 0.0008 

Permethrin (cis) Beef chow mein 6 0.0016 0.0006 0.003 

Permethrin (trans) Beef chow mein 6 0.001 0.0006 0.002 

Permethrin (cis) Split peas with 1 0.0008 0.0008 0.0008 

vegetables and ham 

Permethrin (trans) Split peas with 1 0.0009 0.0009 0.0009 

vegetables and ham 

Permethrin (cis) Strained squash/junior 2 0.0009 0.0008 0.0009 

Permethrin (trans) Strained squash/junior 2 0.0009 0.0008 0.0009 

n = number of detections 

Source: FDA 2000c 
PYRETHRINS AND PYRETHROIDS 194 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The general population is exposed to pyrethrins and pyrethroids primarily from food sources, especially 

fruits and vegetables. The average daily intake (AVDI) of permethrin per unit of body weight (ng/kgbody weight-per day) in eight population groups was estimated using the FDA's monitoring program for 

chemical contaminants in the U.S. food supply. The data were obtained from the FDA Total Diet Studies 

conducted in 1982–1984 (Gunderson 1988), 1984–1986 (Gunderson 1995a), and 1986–1991 (Gunderson 

1995b) and are summarized in Table 6-4. These data can be compared to the United Nations’ Food and 

Agriculture Organization (FAO) and the World Health Organization (WHO) acceptable daily intake 

(ADI) value for technical-grade permethrin of 50,000 ng/kg-body weight per day (Gunderson 1995b). 

The ADI of a chemical is defined as the maximum daily intake, which, during a lifetime, appears to be 

without appreciable risk. These values can be used to derive a rough estimate for the AVDI for all 

pyrethrins and pyrethroids because permethrin is the pyrethroid found most often in foods (see Table 6-3). 

Many household products used to control insects, such as aerosol bombs, spray insecticides, and pet 

shampoos, contain pyrethrins and pyrethroids, and therefore, dermal and inhalation exposures are 

possible. Because of the low mobility of these compounds in soil surfaces, pyrethrins and pyrethroids are 

rarely detected at elevated levels in drinking water or groundwater, with the exception of shallow wells 

near agricultural areas. 

Occupational exposure to pyrethrins and pyrethroids will occur by inhalation and dermal contact with 

these compounds at workplaces where they are produced or used. The National Institute of Occupational 

Safety and Health (NIOSH) has conducted National Occupational Exposure Surveys (NOES) for 

pyrethrum and selected pyrethroids (NIOSH 1989). The NOES data do not include farm workers who are 

likely to be exposed to these compounds. Therefore, the estimated occupational exposures reported are 

likely to be greatly underestimated. Furthermore, these surveys were conducted prior to the development 

of many of the more recent pyrethroids and no current surveys exist. NIOSH (NOES 1981–1983) has 

statistically estimated that 11,296 total workers (1,537 of these are females) are exposed to pyrethrum in 

the United States (NIOSH 1989). Similarly, NIOSH has statistically estimated that 9,244 workers 

(1,758 of these are female) are potentially exposed to tetramethrin in the United States, and 

27,596 workers (3,998 of these are female) are potentially exposed to resmethrin in the United States 

(NIOSH 1989). The NOES database does not contain information on the frequency, level, or duration of 
 

 

 

PYRETHRINS AND PYRETHROIDS 195 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Average Daily Intake (AVDI, ng/kg/day) of Permethrin in Eight 

Population Groups 

Infants Toddlers 14–16­ 14–16­ 25–30­ 25–30­ 60–65­ 60–65­

Date (6–11 (2 years) year-old year-old year-old year-old year-old year-old 

months) females males females males females males 

1982– 1.2 5.6 3.3 3.0 5.0 4.1 6.5 5.4 

1984a 

1984– 89 25 10.7 14.9 15.1 13.7 24.2 22.4 

1986b 

1986– 46.5 70.7 35.7 41.5 56.5 46.0 58.6 59.2 

1991c 

a

Gunderson 1988 

b

Gunderson 1995a 

c

Gunderson 1995b 
 

 

PYRETHRINS AND PYRETHROIDS 196 

6. POTENTIAL FOR HUMAN EXPOSURE 

the exposure of workers to any of the chemicals listed therein. They are surveys that only provide 

estimates of workers potentially exposed to the chemicals. 

The concentration of 3-phenoxybenzoic acid (3-PBA), a urinary metabolite of permethrin, was measured 

in the urine of an agricultural worker in Japan exposed to this pyrethroid during its application to cabbage 

plants (Asakawa et al. 1996). The concentration of 3-PBA was 2.9 ng/mL (6 hours postapplication), 

5.1 ng/mL (the morning after application), and 1.4 ng/mL (3 days postapplication) (Asakawa et al. 1996). 

Even though the worker was covered by protective clothing, it was determined that permethrin permeated 

the worker’s clothing and led to significant dermal exposure, particularly on the arms and legs (Asakawa 

et al. 1996). In a study of 50 Chinese workers applying deltamethrin and fenvalerate onto cotton fields, it 

was determined that dermal exposure represented the main route of exposure for the workers. Inhalation 

exposure rates were determined to be on the order of μg/hour, while dermal exposure was on the order of 

mg/hour (Zhang et al. 1991). Dermal exposure to deltamethrin for a pilot applying the insecticide on 

crops while flying an ultra-light aircraft was estimated as 10.8 μg/hour (Yoshida et al. 1990). A groundbased flagman on duty during the aerial spraying received an estimated dermal exposure of 25.4 μg/hour 

and dermal exposure to workers manually spraying deltamethrin was 2,800–65,400 μg/hour (Yoshida et 

al. 1990). The 1,000-fold exposure difference between hand-held applicators and aerial applicators was 

due, in part, to work practices of the workers. Dermal exposures on different regions of the bodies of 

6 pesticide applicators who sprayed cypermethrin in tea plantations in China were measured (Wan 1990). 

Exposures (in μg/100 cm2

) were as follows: face: 0.06–0.72; chest: 0.11–2.06; abdomen: 0.09–2.68; 

thigh: 0.41–17.3; and ankle: 0.15–32.6. Total dermal exposures based upon spray amounts were 

186–1,140 mg/kg for nonhand areas and 46.1 mg/kg for hands only (Wan 1990). Dermal exposure to 

permethrin was shown to be far greater than inhalation exposure for two applicators involved in the 

spraying of this pyrethroid onto tomatoes in greenhouses (Adamis et al. 1985). The estimated respiratory 

exposure rate for these workers was 0.004 mg/hour and the dermal exposure rate was 3.8 mg/hour 

(Adamis et al. 1985). However, based upon the findings of animal studies, the absorption of pyrethroids 

is likely to be higher via oral and inhalation pathways when compared to dermal absorption (Eadsforth et 

al. 1988; van der Rhee et al. 1989; Woollen et al. 1992). Estimates of pyrethroid absorption in humans 

following dermal application range from about 0.3 to 1.8% of the administered dose (see Section 3.4). 
PYRETHRINS AND PYRETHROIDS 197 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 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). 

Children are exposed to pyrethrins and pyrethroids by similar routes that affect adults. Ingestion of foods 

is the most important exposure pathway for children. The AVDI of permethrin has been reported as 

46.5 ng/kg-body weight/day for 6–11-month-old infants and 70.7 ng/kg-body weight/day for 2-year-old 

toddlers (Gunderson 1995b). No measurements have been made of these compounds in amniotic fluid, 

meconium, cord blood, neonatal blood, or any other tissues that may indicate prenatal exposure. No data 

have been reported on the levels of pyrethrins or pyrethroids in breast milk. 

The tendency of young children to ingest soil, either intentionally through pica or unintentionally through 

hand-to-mouth activity, is well documented. These behavioral traits can result in ingestion of pyrethrins 

and pyrethroids present in soil and dust. Since these compounds are adsorbed strongly to soils, they may 

not be in a highly bioavailable form. Young children often play on the ground or on carpets and this will 

increase the likelihood of dermal exposure and inhalation of contaminated particles from soil, household 

dust and treated surfaces. The transfer of allethrin residues from a carpeted floor to human subjects 

wearing dosimeter clothing was studied (Ross et al. 1990). For gloves, socks, shirts, and tights of 

subjects performing standardized aerobic exercises, the transfer coefficient ranged from 2.8 to 34.3 μg 

allethrin/cm2

 clothing for a period of up to 12.5 hours after applying allethrin (via foggers) to the carpet. 

The transfer rates decreased with time after application (Ross et al. 1990). Pyrethrins and pyrethroids are 

also frequently used in products such as pet shampoos or sprays, and since children often spend a great 

deal of time playing with pets, this can increase childhood exposure. Pyrethrins and certain pyrethroids 

have been employed in head lice treatment products, which are often used on children. Very little data 
PYRETHRINS AND PYRETHROIDS 198 

6. POTENTIAL FOR HUMAN EXPOSURE 

were located regarding the concentrations of pyrethroids in milk and dairy samples. No pyrethroids were 

detected in any milk or dairy samples from the FDA Market Basket Surveys compiled from the 1991 to 

1999 data (FDA 2000c). However, cypermethrin was detected in the milk from cows wearing ear tags 

impregnated with cypermethrin to control certain insects (Braun et al. 1985). Flumethrin, deltamethrin, 

cypermethrin, and cyhalothrin were detected in the milk of cows after single dermal applications 

(Bissacot and Vassilieff 1997a). Children may be exposed to pyrethrins and pyrethroids from the 

clothing of parents who work as pesticide applicators. Asakawa et al. (1996) documented that permethrin 

adhered to a worker’s clothing and different parts of the body following the application of this insecticide 

onto a cabbage field. Similar findings were obtained for cotton sprayers using deltamethrin and 

fenvalerate (Zhang et al. 1991). Washing the affected clothing does not necessarily assure that all of the 

pyrethroids will be removed from the contaminated garments. Fabrics that simulated the clothing worn 

by workers applying cypermethrin insecticides were found to contain 1.7–2.3 μg/cm2

 before laundering; 

after laundering, levels of 0.3–1.1 ng/cm2

 remained in the fabric (Laughlin et al. 1991). A study was 

conducted to determine the ability of laundry practices used by farm families to remove pesticides from 

clothing (Rigakis et al. 1987). After one wash, 2–18% of initial deltamethrin remained on fabrics, and 

after two washes, 1–10% of initial deltamethrin remained on fabrics (Rigakis et al. 1987). Pretreating the 

fabric with a prewash spot removal product especially formulated to assist in the removal of oily stains 

resulted in the lowest recoveries. Cotton strips were coated with deltamethrin and then rinsed in 

deionized water for 1 hour (Hussain and Perschke 1991). After four rinses, only 37.7% of the initial 

deltamethrin was removed from the cotton. Impregnating the cotton with various paraffin wax and oils 

(corn, linseed, silicone) before coating with deltamethrin resulted in even lower percentages removed 

when washed (9.9–29.2% removal). 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Aside from agricultural workers or insect control applicators, populations with potentially high exposures 

to pyrethrins or pyrethroids are small. Workers involved in the manufacturing and production of these 

insecticides are likely to be exposed to higher levels than the general population. Veterinarian 

professionals or pet groomers who frequently apply pyrethrin- and pyrethroid-containing shampoos or 

flea applications to animals may also be exposed to high levels of these compounds through dermal 

routes. Persons residing near farms or orchards may be subject to spray drift following application of 

these insecticides onto crops. Humans who use shampoos or sprays that contain pyrethrins or pyrethroids 

for their pets are likely to be exposed to higher levels of these compounds than persons without pets. 
 

 

PYRETHRINS AND PYRETHROIDS 199 

6. POTENTIAL FOR HUMAN EXPOSURE 

Home gardeners who use pyrethroids and pyrethrins for insect control either in the garden or within the 

household itself may be exposed to high levels. Diet is also a key factor in relative human exposure level 

to pyrethrins and pyrethroids. As shown in Table 6-3, these compounds are frequently detected at varying 

levels in fruits and vegetables. 

Permethrin is part of the United States Department Of Defense (DOD) Insect Repellent System and was 

issued in the Persian Gulf War to military personnel as a ready to use insect repellent for clothing 

application. It is also labeled for use on battle dress clothing and bed netting (Cecchine et al. 2000). 

Phenothrin was also used for spraying on bed netting and inside of aircrafts to prevent transport of insects. 

Due to an absence of sampling data and information about pesticide application rates, individual 

exposures were reconstructed by means of interviews with service personnel. The DOD reported that 

approximately 44 and 28% of all service personal in the Gulf used permethrin and phenothrin sprays, 

respectively, and that the guidelines for their recommended use were not always strictly adhered to (DOD 

2001). This may have led to excessive exposures to these insecticides by some members of the military 

serving in the Persian Gulf. 

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 pyrethrins and pyrethroids are 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 pyrethrins and pyrethroids. 

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. 
 

 

 

PYRETHRINS AND PYRETHROIDS 200 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. As illustrated in Tables 4-4 and 4-5, the relevant physical and 

chemical properties of pyrethrins and the pyrethroids that are used in the United States are not entirely 

known. There are several pyrethroids that have been developed, and adequate data may not be available 

for all of them (Mueller-Beilschmidt 1990). Furthermore, inert ingredients used in formulated pesticide 

products are usually not disclosed. This makes a thorough evaluation of the final commercial product 

challenging. Complete disclosure of all the ingredients used in a formulated product would aid in the 

evaluation of both physical and toxicological properties of the pesticide. 

Production, Import/Export, Use, Release, and Disposal. Knowledge of a chemical's 

production volume is important because it may correlate with environmental contamination and human 

exposure. If a chemical's production volume is high, then there is an increased probability of general 

population exposure via consumer products and environmental sources, such as air, drinking water, and 

food. 

The TRI99 (2001), which became available in 2001, has been used in this profile. The only pyrethroids 

that are on the list are allethrin, bifenthrin, cyfluthrin, cyhalothrin, fenpropathrin, fluvalinate, permethrin, 

phenothrin, resmethrin, and tetramethrin (TRI99 2001). Furthermore, data have only been reported for 

bifenthrin, cyfluthrin, permethrin, resmethrin, and tetramethrin. More detailed site- and medium-specific 

(e.g., air, water, or soil) release data for more pyrethroids are necessary. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit chemical release and off-site transfer information to the EPA. TRI, which contains this 

information for 1999, became available in 2001. This database will be updated yearly and should provide 

a list of industrial production facilities and emissions. 

Environmental Fate. Information is available to permit assessment of the environmental fate and 

transport of the pyrethrins and pyrethroids in air (Chen and Casida 1969; Chen et al. 1984; HSDB 2001; 

Samsonov and Makarov 1996; Ueda et al. 1974), water (Maguire 1990; Rawn et al. 1982; Schimmel et al. 

1983; USDA 2001a), and soil (Chapman et al. 1981; Hill 1983; Khan et al. 1988; Smith et al. 1995; 

USDA 2001a). Most of these compounds are rapidly degraded in the air by photolysis or through the 

reaction with oxidants such as hydroxyl radicals, ozone, or nitrate radicals found in the atmosphere. 

Many of the recently developed pyrethroids such as cyhalothrin are more stable towards sunlight than the 

early light sensitive pyrethroids like allethrin and resmethrin. Volatilization from water surfaces may be 
 

 

 

PYRETHRINS AND PYRETHROIDS 201 

6. POTENTIAL FOR HUMAN EXPOSURE 

an important fate process for pyrethrins and pyrethroids with relatively large Henry’s law constants, but 

adsorption to suspended solids and sediments will attenuate this process. Photolysis in sunlit surface 

waters has been demonstrated for several pyrethroids (Maguire 1990; Rawn et al. 1982; Schimmel et al. 

1983). Hydrolysis is also an important environmental fate process in water or moist soil under alkaline 

conditions (Chapman and Cole 1982; USDA 2001a). Biodegradation occurs in water, soil, and sediment 

at varying rates (Cotham and Bidleman 1989; Hill 1983; Schimmel et al. 1983; Smith et al. 1995; USDA 

2001a). Photolysis and volatilization of these compounds can occur on soil and plant surfaces (Hill and 

Johnson 1987; Takahashi et al. 1985a). These compounds are not expected to leach extensively since 

they have very little mobility in soils (USDA 2001a). 

While it can be reasonably concluded that pyrethrins will biodegrade in the environment based upon their 

chemical structure, there are no specific biodegradation studies of the six pyrethrins. Furthermore, there 

are several synthetic pyrethroids for which experimental data regarding their biodegradation, 

bioconcentration, photolysis, adsorption, and hydrolysis are not available. Studies on these pyrethroids 

are warranted. 

Bioavailability from Environmental Media. The bioavailability of pyrethrins and pyrethroids 

from contaminated air, water, soil, or plant material in the environment has not been adequately studied. 

14C-labeled deltamethrin was used to treat wheat grains that were ultimately fed to rats (Khan et al. 1990). 

The 14C residues were excreted in the urine and feces of the rats and trace amounts were also present in 

the lungs and kidneys, which suggests that the bound deltamethrin residues in the wheat were bioavailable 

(Khan et al. 1990). A similar experiment was performed using deltamethrin 14C labeled at either the 

methyl or benzylic position applied to bean plants (Khan et al. 1986). Four days after feeding rats the 

contaminated material, 60% (methyl 14C labeled) and 53% (benzylic 14C labeled) of the dose was excreted 

in the feces, while 31% (methyl 14C labeled) and 20% (benzylic 14C labeled) of the dose was excreted in 

the urine. No radioactivity was detected in the liver, kidney, brain, or lung tissue of the sacrificed rats. 

Workers applying pyrethroids in the field have a much greater dermal exposure rate when compared to 

inhalation exposure (Adamis et al. 1985; Wan 1990; Yoshida et al. 1990; Zhang et al. 1991), but the 

percentage of pyrethroid absorbed dermally is less than oral and inhalation absorption (Eadsforth et al. 

1988; van der Rhee et al. 1989; Woollen et al. 1992). Since these compounds adsorb strongly to soils, 

bioavailability from soil may be limited, but absorption and bioavailability studies of these compounds 

from soils are lacking. Studies are needed on the bioavailability of these compounds from actual 

environmental media and on differences in bioavailability for the various pyrethrins and pyrethroids. 
 

 

 

 

PYRETHRINS AND PYRETHROIDS 202 

6. POTENTIAL FOR HUMAN EXPOSURE 

Food Chain Bioaccumulation. Bioconcentration occurs in aquatic organisms (Freitag et al. 1985; 

Haitzer et al. 1998; Schimmel et al. 1983). There is no evidence to indicate that bioaccumulation occurs 

in aquatic or terrestrial species, but studies are needed to determine if pyrethrins and pyrethroids 

bioaccumulate up the food chain. 

Exposure Levels in Environmental Media. Atmospheric concentrations of pyrethrins or 

pyrethroids are usually on the order of μg/m3

 immediately after their application (Eitzer 1991; Siebers and 

Mattusch 1996), but the levels decrease with time because these compounds undergo rapid degradation in 

the atmosphere. These compounds are infrequently detected in groundwater and drinking water in the 

United States because of their strong adsorption to soils and relatively rapid rate of degradation. 

Pyrethrins and pyrethroids are found in soils following their application, but their levels decrease with 

time. The average concentration of permethrin in soils collected from 48 agrochemical facilities located 

throughout the state of Illinois was 190 μg/kg (Krapac et al. 1995). More data regarding the levels of 

pyrethrins and pyrethroids in water and soil surfaces are needed in order to produce better estimates of the 

potential for human exposure to these compounds. Foods, especially fruits and vegetables, have been 

shown to contain pyrethroids at varying levels (Table 6-3). Continued monitoring data of these 

compounds in foods are necessary since ingestion of food sources is the most likely route of widespread 

human exposure. 

Exposure Levels in Humans. The general population is exposed to pyrethrins and pyrethroids 

primarily through the ingestion of food sources. The AVDI of permethrin, the most frequently used 

pyrethroid in the United States, has been estimated for eight different population groups (Gunderson 

1988, 1995a, 1995b). Additional data regarding the AVDI for other pyrethroids and pyrethrins would be 

useful in assessing total exposure for the U.S. population. The use of household insecticides containing 

these compounds can also lead to dermal and inhalation exposure. Workers employed in the agricultural 

industry, veterinary industry, or pet grooming business may be occupationally exposed to high levels of 

these compounds. Dermal exposure has been shown to be greater than inhalation exposure for applicators 

involved in the spraying of pyrethroids (Adamis et al. 1985; Wan 1990), but dermal absorption appears to 

be lower than the amount absorbed from the other routes. While body burden studies were located for 

persons occupationally exposed (Asakawa et al. 1996; Wan 1990), body burden studies are needed for the 

general population of the United States. 
 

 

 

PYRETHRINS AND PYRETHROIDS 203 

6. POTENTIAL FOR HUMAN EXPOSURE 

Exposures of Children. Estimates regarding the AVDI of permethrin for children are available 

(Gunderson 1988, 1995a, 1995b). Additional data regarding the AVDI for other pyrethroids and 

pyrethrins would be useful to assess childhood exposure more thoroughly. Body burden studies of 

children are also necessary. Since children may be exposed to these compounds from pica, bioavailability 

studies from soils would be useful for a wide array of pyrethrins and pyrethroids. 

Child health data needs relating to susceptibility are discussed in 3.12.2 Identification of Data Needs: 

Children’s Susceptibility. 

Exposure Registries. No exposure registries for pyrethrins and pyrethroids were located. These 

substances are not currently among the compounds for which a subregistry has been established in the 

National Exposure Registry. The substances will be considered in the future when chemical selection is 

made for subregistries to be established. The information amassed in the National Exposure Registry 

facilitates epidemiological research needed to assess adverse health outcomes that may be related to 

exposure to pyrethrins and pyrethroids. 

The development of a registry of exposures would provide a useful reference tool for monitoring 

exposure levels and frequencies over time. Such a registry would allow an assessment of the variations in 

exposure levels from various sources. Also it could be used to assess the effect of geographical, seasonal, 

or regulatory actions on the level of exposure from a certain source. These assessments, in turn, would 

provide a better understanding of the needs for research or data acquisition based on the current exposure 

levels. 

6.8.2 Ongoing Studies 

The Federal Research Programs In Progress (FEDRIP 2001), Current Research Information System 

(CRIS/USDA 2001), and Computer Retrieval of Information on Scientific Projects (CRISP 2001) 

databases indicate that several projects are ongoing that may fill some existing data gaps. Symbiotech 

Inc., located in Wallingford, Connecticut, is investigating a topical preparation of permethrin intended for 

use on humans as an insect repellent (FEDRIP 2001). Researchers at the University of Arkansas (Dr. 

Meisch and Dr. Bernhardt) are investigating the efficacy and environmental effects of various pyrethroids 

for mosquito control in riceland systems (CRIS/USDA 2001). Dr. Epstein from the University of 
PYRETHRINS AND PYRETHROIDS 204 

6. POTENTIAL FOR HUMAN EXPOSURE 

California Davis, is developing software based on the California Department of Pesticide Regulation's 

Pesticide Use Reports to document trends in fungicide and insecticide use on grapes and almonds, 

respectively (CRIS/USDA 2001). Dr. Hammock from the University of California Davis is attempting to 

develop and validate single compound, as well as class selective immunoassays for urinary metabolites of 

hazardous compounds (including pyrethroids) for use as biomarkers of internal exposure to these 

compounds (CRISP 2001). 
 

PYRETHRINS AND PYRETHROIDS 205 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring pyrethrins and pyrethroids, its metabolites, and other biomarkers of 

exposure and effect to pyrethrins and pyrethroids. 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 

Exposure to pyrethrins and pyrethroids is most commonly evaluated by the analysis of urine and blood 

using gas chromatography (GC) combined with electron capture detection (ECD), flame ionization 

detection (FID), or mass spectrometry (MS) and high performance liquid chromatography (HPLC) 

coupled with ultraviolet (UV) detector. Recovery is generally high, and sensitivity is in the parts per 

billion (ppb) range. 

A simple and rapid method for the isolation of synthetic pyrethroids using a solid phase extraction 

method is described by Junting and Chichang (1991). A similar method that employs HPLC for analysis 

was used to quantify pyrethrins in plasma by Wintersteiger et al. (1994). This method eliminates timeconsuming repeated extractions with organic solvents and centrifugations without losing the efficiency of 

recovery. 

Pyrethrins and pyrethroids are extensively metabolized by the cleavage of the ester linkage, oxidation, 

and conjugation. Metabolites formed are less lipophilic, and are rapidly and easily excreted in the urine. 

Exposure to pyrethrins and pyrethroids can be monitored by the detection of these excreted metabolites. 

Pyrethroids such as cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, fenvalerate, phenothrin, and 

permethrin can be metabolized resulting in the formation of halosubstituted chrysanthemic and 
PYRETHRINS AND PYRETHROIDS 206 

7. ANALYTICAL METHODS 

3-phenoxybenzoic acids (Angrer and Ritter 1997; Yao et al. 1992). The rapid metabolism of the 

pyrethroids makes it useful to monitor for pyrethroid metabolites in the urine of exposed individuals 

rather than monitoring the actual concentration of the pyrethroid itself in blood (Leng et al. 1999a). Also, 

it has been demonstrated that storing frozen urine samples for up to a year results in no further 

degradation of the metabolites (Leng et al. 1999a). In contrast, pyrethroids stored in plasma are 

susceptible to continued degradation (Leng et al. 1999a). 

Methods for analyzing pyrethrins and pyrethroids as well as the metabolites in biological samples are 

shown in Table 7-1. 

7.2 ENVIRONMENTAL SAMPLES 

Concerns about contamination of environmental media, plants, and animals with pyrethrins have led to 

the need for more rapid, sensitive, and selective methods of analysis. As with biological samples, the 

most common methods of analysis are GC combined with ECD, FID, or flame photometric detection 

(FPD) and HPLC coupled with UV detector. Thermal conductivity detectors, thermionic detectors, and 

nitrogen phosphorus detectors have also been used in conjunction with GC. 

Pyrethrins and pyrethroids are nonpolar compounds and nonsystemic in plants; thus, the extraction 

procedures in environmental samples are simpler than those used for organophosphate and carbamate 

insecticides. Generally, the samples are homogenized with a nonpolar solvent, such as hexane or 

benzene, or a binary solvent mixture, such as hexane-acetone, hexane-isopropanol, or light petroleumdiethyl ether. The pyrethrins and pyrethroids, along with a wide variety of other lipophilic substances are 

co-extracted during this procedure. The resulting solution is dried with anhydrous sodium sulfate. If 

there are too many co-extracted compounds, separation by liquid-liquid partition or column 

chromatography is performed. Samples with a low water content, such as tea, tobacco, and straw, are 

usually extracted with a binary solvent mixture, as are moist vegetables and fruits. Soil samples are first 

ground and filtered to remove large particles and stones, and then are extracted with acetone-hexane, 

methanol, acetone, or acetonitrile. Pyrethrins and pyrethroids are extracted from water samples with 

hexane, methylene chloride, or acetonitrile with subsequent drying with anhydrous sodium sulfate. 
 

 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 207 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Pyrethrins and Pyrethroids 

in Biological Materials 

Sample 

Sample Analytical detection Percent 

matrix	 Analyte Preparation method method limit recovery Reference 

Blood, Deltamethrin, 

milk	 cyhalothrin 

cypermethrin, 

flumethrin 

Plasma	 Pyrethrins 

Plasma	 Cyfluthrin, 

cypermethrin, 

permethrin 

Plasma,	 Fenopropathrin, 

urine	 permethrin, 

cypermethrin, 

fenvalerate, 

deltamethrin 

Urine	 Cis- and trans3-(2,2-dichlorovinyl)­

2,2-dimethylcycloprane-1­

carboxylic acid; 

3-phenoxybenzoic acid; fluorophenoxybenzoic 

acid 

Acidify with 1 N HCl; LC/UV 1.0 μg/kg 78–91 Bissacot and 

extract twice with Vassilieff 

CH3CN and filter; 1997a, 1997b 

extract filtrate with 

hexane and discard 

the hexane phase; 

remove CH3CN under 

a stream of N2 and 

heat to dryness; 

cleanup on a silica gel 

column; dissolve in 

CH3CN and filter 

through a 0.45 μm 

pore cellulose filter 

Dilute centrifuged RPHPLC/UV 0.167 mg/L 70–72 Wintersteiger 

plasma with water; et al. 1994 

cleanup on a solid 

phase extraction 

column; elute with 

methanol 

Precipitation of GC/ECD 5 μg/L No data Leng et al. 

proteins followed by 1999a 

liquid-liquid extraction 

Mix samples with 70% GC/FID 2 mg/L 81–93 Junting and 

methanol; pour on to 90–102 Chuichang 

Sep-Pak C18 columns 1991 

pretreated with 

chloroform, methanol, 

methanol/water, and 

water; wash with 

water; elute with 

chloroform; evaporate 

to dryness under 

stream of N2; 

redissolve in ethanol 

Liquid-liquid GC/MS 0.5 μg/L No data Leng et al. 

extraction followed by 1999b 

methylation of the free 

acid metabolites 
 

 

 

PYRETHRINS AND PYRETHROIDS 208 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Pyrethrins and Pyrethroids 

in Biological Materials 

Sample 

matrix Analyte Preparation method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery Reference 

Urine Cis- and trans3-(2,2-dichlorovinyl)­

2,2-dimethylcycloprane1-carboxylic 

acid; cis-3­

(2,2-dibromovinyl)­

2,2-dimethylcycloprane-1-carboxylic acid; 

3-phenoxybenzoic acid; 

Acidify with AcOH; 

add concentrated 

H2SO4; heat at 90 °C 

for 1 hour; cleanup on 

C18 column; elute with 

methanol into a vial 

containing concentrated H2SO4; 

complete derivatization on water bath 

for 1 hour; extract with 

hexane 

GC/MS 0.3–0.5 μg/L 90–98 Angerer and 

Ritter 1997 

4-fluoro3-phenoxy-benzoic acid 

Urine Dibromovinyldimethylcyclopropane carboxylic acid, 

3-phenoxybenzyl-hydroxyethyl acetate, 

3-phenoxybenzoic acid 

Adjust pH of sample 

to 6.5; extract with 

hexane; evaporate to 

dryness; redissolve in 

methanol 

RPHPLC/UV No data 95 Yao et al. 

1992 

Urine Deltamethrin, 

fenvalerate 

Extract with hexane; 

concentrate and 

GC/ECD 0.2 μg/L 92–95.3 Yi-Qun et al. 

1994 

cleanup on Florisil 

column; elute with 

benzene; dry on 

anhydrous Na2SO4 

AcOH = acetic acid; CH3CN = acetonitrile; ECD = electron capture detector; FID = flame ionization detector; GC = gas 

chromatography; HCl = hydrochloric acid; H2SO4 = sulfuric acid; LC = liquid chromatography; MS = mass 

spectrometry; N2 = nitrogen; Na2SO4 = sodium sulfate; RPHPLC = reverse phase high performance liquid 

chromatography; UV = ultra-violet detection 
 

 

PYRETHRINS AND PYRETHROIDS 209 

7. ANALYTICAL METHODS 

In the analysis of pyrethrins, the total residues of the six active compounds are often analyzed for, but in 

the analysis of pyrethroids, the individual compounds are usually quantified (Chen and Wang 1996). An 

extensive review of the chromatographic methods employed for the determination of pyrethrins and 

pyrethroids in foods, crops, and environmental media has been published (Chen and Wang 1996). Many 

pyrethroids such as bifenthrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, fenvalerate, and 

permethrin possess one or more halogenated atoms which are sensitive to ECD. Often, derivitization is 

used to create a sensitive group for pyrethroids that do not possess halogenated atoms (allethrin, 

resmethrin, phenothrin, and tetramethrin, for example), or to improve the sensitivity and peak tailing 

situations in some halogenated pyrethroids (Chen and Wang 1996). Consequently, GC/ECD is the most 

popular analytical approach for analyzing pyrethroids in environmental samples. 

A detection limit of 0.1 μg/m3

 and a mean recovery of 100.15% has been reported for the analysis of 

cypermethrin in air using GC/ECD (Pomorska 1999), while permethrin and resmethrin had detection 

limits in the ng/m3

 and very good recoveries with a GC/MS method (Roinestad et al. 1993). This is 

comparable to methods used for the determination of other pyrethroids in air using GC (EMMI 1997). 

The analysis of pyrethrins and pyrethroids in water is also accomplished through the use of GC and 

HPLC. Detection limits in the ppb (μg/L) range have been achieved (EMMI 1997). A method for the 

analysis of selected pyrethroids in soils has been described by Alawi et al. (1990) that utilizes GC 

equipped with a nitrogen phosphorus detector (NPD). 

Methods for analyzing pyrethrins in environmental samples are shown in Table 7-2. 

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 pyrethrins and pyrethroids are 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 pyrethrins. 

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 
 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 210 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Pyrethrins and Pyrethroids in 

Environmental Samples
 

Sample Analyte Preparation Analytical Sample Percent Reference 

matrix method method detection recovery 

limit 

Air Allethrin, Air samples GC/ECD; 0.1–50 μg/m3 No data ASTM 

fenvalerate, collected on a GC/NPD; D4861 

pyrethrin I, sorbent cartridge; GC/FPD; EMMI 1997 

resmethrin extract with 5% HPLC/UV 

diethyl ether in 

hexane 

Air Cypermethrin Air samples GC/ECD 0.1 μg/m3 100.15 Pomorska 

collected on a (mean 1999 

sorbent cartridge; recovery) 

extract with acetone 

Air Resmethrin, Air samples GC/MS 1 ng/m3 109.5–110.9 Roinestad 

permethrin collected on filter 

paper or Tenax 

(permethrin); 

10 ng/m3 

(permethrin); 

84.6 

et al. 1993 

tubes; extract with (resmethrin) (resmethrin) 

acetone 

Air (dust) Resmethrin, Dust samples are GC/MS 50 ng/g 94.8–124.4 Roinestad 

permethrin homogenized in a (permethrin); (permethrin); et al. 1993 

blender or food 100 ng/g 82.6 

processor; extract (resmethrin) (resmethrin) 

with acetone 

Air Pyrethrums Air samples HPLC/UV 0.020 mg/m3 No data NIOSH 

collected with 5008 EMMI 

sampling pump 1997 

equipped with filter; 

extract with CH3CN 

Fats, oils, Allethrin, Dissolve fat in GC/ECD No data No data FDA 211.1; 

milk, cheese, bifenthrin, petroleum ether; FDA 231.1 

fish deltamethrin, extract with CH3CN; EMMI 1997 

esfenvalerate, dilute with water; 

fenvalerate, clean up on Florisil 

permethrin, column; extract with 

tetramethrin, petroleum 

tralomethrin ether/ethyl ether 

Fatty and Allethrin, Dissolve fat in GLC/ECD No data No data FDA 252 

non fatty bifenthrin, petroleum ether; EMMI 1997 

foods cyfluthrin, extract with CH3CN; 

deltamethrin, dilute with water; 

esfenvalerate, cleanup on Florisil 

fenpropathrin, column; elute with a 

fenvalerate, series of eluants— 

fluvalinate, methylene chloride, 

permethrin, hexane, and CH3CN 

tetramethrin, 

tralomethrin 
 

 

PYRETHRINS AND PYRETHROIDS 211 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Pyrethrins and Pyrethroids in 

Environmental Samples
 

Sample Analyte Preparation Analytical Sample Percent Reference 

matrix method method detection recovery 

limit 

Non-fatty Allethrin, Extract with CH3CN 

foods	 bifenthrin, or CH3CN/water 

cyfluthrin, mixture; dilute with 

deltamethrin, water; extract with 

esfenvalerate, petroleum ether; 

fenpropathrin, cleanup on Florisil 

fenvalerate, column; elute with 

fluvalinate, petroleum 

permethrin, ether/ethyl ether 

tetramethrin, 

tralomethrin 

Non-fatty Bifenthrin, Blend with acetone 

food	 cyfluthrin, and filter; extract 

deltamethrin, with petroleum ether 

esfenvalerate, and methylene 

fenvalerate, chloride; concenflucythrinate, trate to remove 

fluvalinate, methylene chloride 

permethrin 

Non-fatty Deltamethrin, Blend with acetone 

food fenpropathrin, and filter; extract 

tralomethrin with methylene 

chloride; cleanup on 

a column containing 

charcoal, MgO, and 

Celite 545; elute 

with CH3CNbenzene 

Fruits, Bifenthrin, Homogenize in 

vegetables, cyhalothrin, CH3CN and filter; 

grains cypermethrin, extract with hexane; 

deltamethrin, wash with 4% NaCl; 

fenpropathrin, dry over anhydrous 

fenvalerate, Na2SO4; evaporate 

fluvalinate, to dryness; redispermethrin solve in hexane; 

extract with CH3CN; 

evaporate to 

dryness; redissolve 

in hexane; cleanup 

on Florisil column; 

elute with a mixture 

of petroleum ether 

and ethyl ether. 

GC/FPD No data No data	 FDA 232.1 

EMMI 1997 

GC/ECD; No data No data FDA 232.4 

GC/FPD EMMI 1997 

GC/FPD; No data No data FDA 232.3 

GC/TSD EMMI 1997 

GC/ECD No data >70	 Pang et al. 

1997 
 

 

 

PYRETHRINS AND PYRETHROIDS 212 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Pyrethrins and Pyrethroids in 

Environmental Samples
 

Sample Analyte Preparation Analytical Sample Percent Reference 

matrix method method detection recovery 

limit 

Groundwater, 

drinking 

water 

Waste water, 

municipal 

and 

industrial 

Waste water, 

industrial 

Soil 

Pet 

shampoo 

Permethrin 

Allethrin, 

cyfluthrin, 

fenvalerate, 

phenothrin, 

pyrethrins I, 

pyrethrins II, 

resmethrin, 

tetramethrin 

Resmethrin 

Cypermethrin, 

permethrin, 

cyfluthrin, 

fluvalinate, 

deltamethrin 

Pyrethrins I, 

pyrethrins II, 

tetramethrin 

Extract with GC/ECD 0.5 μg/L No data EMSLC 508 

methylene chloride; EMMI 1997 

dry over anhydrous 

Na2SO4; concentrate; add methyl 

tert-butyl ether 

Saturate sample HPLC/UV 2 μg/L No data EAD 1660 

with NaCl; extract EMMI 1997 

with CH3CN; 

concentrate extract 

Extract with GC/FID 36 μg/L No data EMSLC 616 

methylene chloride; EMMI 1997 

dry over anhydrous 

Na2SO4; 

concentrate 

Extract with acetone GC/NPD 0.004–0.012 114 Alawi et al. 

saturated with mg/kg 1990 

sodium chloride; dry 

with Na2SO4 

Dilute with water HPLC/UV No data No data EPA-B 

and add Celite 545; GC/FID EMMI 1997 

add to a Celite 

column; elute with 

petroleum ether; 

filter through 0.5 μm 

filter 
 

 

 

 

 

PYRETHRINS AND PYRETHROIDS 213 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Pyrethrins and Pyrethroids in 

Environmental Samples
 

Sample Analyte Preparation Analytical Sample Percent Reference 

matrix method method detection recovery 

limit 

Pesticide Pyrethrins I, Extract with Titration No data No data AOAC 

formulation pyrethrins II petroleum ether; 936.05 

filter; evaporate the EMMI 1997 

filtrate to <1 mL; 

add 0.5 N alcoholic 

NaOH and reflux 

gently; concentrate; 

add Filter-Cel and 

10% BaCl2 filter; 

neutralize with 

H2SO4 using 

phenolphthalein; 

extract with 

petroleum ether; 

extract with 0.1 N 

NaOH; add Deniges 

reagent and let 

stand in darkness; 

add alcohol and 

precipitate HgCl 

with NaCl solution; 

filter; add dilute HCl; 

add chloroform and 

ICl solution 

Pesticide Permethrin Dissolve in methyl GC/FID No data No data AOAC 

formulation isobutyl ketone 986.03 

EMMI 1997 

Pesticide Deltamethrin Dissolve (and HPLC/UV No data No data AOAC 

formulation sonicate) in 991.03 

isooctane-1,4­ EMMI 1997 

dioxane; filter 

Pesticide Allethrin Add ethylenedia- Titration No data No data AOAC 

formulation mine; swirl; let 953.05 

stand; wash with EMMI 1997 

pyridine; add 

thymophthalein 

indicator; titrate with 

0.1 N NaOMe 

Pesticide Pyrethrums Dilute with acetone; GC/FID No data No data AOAC 

formulation add dicyclohexyl 982.02 

phthalate (internal EMMI 1997 

standard) 
 

 

PYRETHRINS AND PYRETHROIDS 214 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Pyrethrins and Pyrethroids in 

Environmental Samples
 

Sample 

matrix 

Analyte Preparation 

method 

Analytical 

method 

Sample 

detection 

limit 

Percent 

recovery 

Reference 

Pesticide 

formulation 

Pyrethrins I, 

pyrethrins II 

Add sample to a 

column packed, 

bottom to top, with 

anhydrous Na2SO4, 

Florisil, and 

GC/FID No data No data EPA-B 

EMMI 1997 

anhydrous Na2SO4; 

wash with hexane; 

elute with acetone; 

evaporate to 

dryness; dissolve 

residue in carbon 

Aerosol 

formulation 

Resmethrin 

disulfide; dry over 

anhydrous Na2SO4 

Cool can in freezer 

overnight; punch 

holes in can to 

GC/TCD No data No data PMD-Res 

EMMI 1997 

relieve pressure; 

open can and warm 

to room temperature; remove 

remaining volatiles 

by placing in a 

water bath; dissolve 

residue in benzene 

Aerosol 

formulation 

Resmethrin Cool can in freezer 

overnight; punch 

holes in can to 

RPHPLC/ 

UV 

No data No data PMD-Res 

EPA-B 

EMMI 1997 

relieve pressure; 

open can and warm 

to room temperature; remove 

remaining volatiles 

by placing in a 

water bath; dissolve 

residue in methanol 

BaCl = barium chloride; CH3CN = acetonitrile; ECD = electron capture detector; FID = flame ionization detector; 

FPD = flame photometric detector; GC = gas chromatography; HCl = hydrochloric acid; HgCl = mercuric chloride; 

HPLC = high performance liquid chromatography; H2SO4 = sulfuric acid; ICl =iodine monochloride; MgO = magnesium 

oxide; NaCl = sodium chloride; NaOH = sodium hydroxide; NaOMe = sodium methoxide; Na2SO4 = sodium sulfate; 

NPD = nitrogen phosphorus detector; RPHPLC = reverse phase high performance liquid chromatography; 

TCD = thermal conductivity detector; TSD = thermionic detector; UV = ultra-violet detection
 
 

 

PYRETHRINS AND PYRETHROIDS 215 

7. ANALYTICAL METHODS 

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. Methods for detecting and quantifying pyrethrins and pyrethroids in blood (Bissacot and 

Vassilief 1997a, 1997b), plasma (Junting and Chuichang 1991; Wintersteiger et al. 1994), and urine 

(Junting and Chuichang 1991; Yi-Qun et al. 1994) are available. Chromatographic techniques, such as 

GC and HPLC, were used to isolate pyrethrins and their degradation products. ECD, FID, UV, and MS 

were coupled with the separation techniques to detect these compounds. Sensitivity was high (blood: 

1 μg/kg; plasma: 2–0.17 μg/kg; urine: 0.2–0.5 μg/L). These methods can accurately detect pyrethrins at 

background concentrations in blood, plasma, and urine. Methods are available to characterize the 

metabolites of selected pyrethroids in urine (Angrer and Ritter 1997; Leng et al. 1999a; Yi-Qun et al. 

1994). The sensitivity is high and the recovery is good. The existing methods for detecting the pyrethrins 

in biological samples seem to be adequate. 

Effect. Other than the clinical signs of Type I and Type II pyrethroid poisoning discussed in 

Section 3.8.2, there are no known biomarkers of effect for pyrethrins and pyrethroids. It is important to 

note that while these effects are characteristic signs of pyrethroid poisoning, they are not exclusive to 

pyrethroid poisoning. In humans, pyrethroids are rapidly metabolized by esterase, mainly in the liver, and 

it may be possible to correlate carboxyesterase activity with pyrethroid induced adverse effects (Leng et 

al. 1999b). However, human plasma contains very little carboxyesterases and the liver is not accessible 

for routine measurements. As a parameter of carboxyesterase activity for Type II pyrethroids, the 

production of cyanic acid in human lymphocytes was measured (Leng et al. 1999b). Initial findings 

indicate that the determination of carboxyesterase activity in lymphocytes may potentially be used as a 

marker for individual susceptibility. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods are available to measure pyrethrins in air (EMMI 1997; Pomorska 1999), foods 

(EMMI 1997), water (EMMI 1997), waste water (EMMI 1997), soil (Alawi et al. 1990), and in 

formulations (methods by American Society for Testing Materials [ASTM], NIOSH, Food and Drug 
PYRETHRINS AND PYRETHROIDS 216 

7. ANALYTICAL METHODS 

Administration [FDA], EPA, Environmental Measurements Laboratory Center [EMLC], Engineering and 

Analysis Division [EAD], and AOAC). Sensitivity and recovery are not mentioned for several of the 

methods. 

7.3.2 Ongoing Studies 

Z. Elrassi, of Oklahoma State University, is conducting research on the development of high performance 

capillary electrophoresis (HPCE) and capillary electrochromatography (CEC) methods for the rapid, 

sensitive, and efficient separation of pesticides and their metabolites (CRIS 2001). B.W. Blair, of the 

Canadian Food Inspection Agency, Food Inspection Directorate, Lab Services Division, is developing a 

rapid, simple, and inexpensive immunological assay technology for low molecular weight contaminants 

of significance in food safety testing, as a tool for monitoring contaminants in foods and other 

environmental media (CRIS 2001). 

In a study sponsored by the National Institute of Environmental Health Sciences at University of 

California, Davis, research is being performed to develop and validate single compounds, as well as a 

class selective immunoassay for urinary metabolites of hazardous compounds such as pyrethroids for use 

as biomarkers of internal exposure to theses compounds (CRISP 2001). 
PYRETHRINS AND PYRETHOIDS 217 

8. REGULATIONS AND ADVISORIES 

Available information on international, national, and state regulations and standards of pyrethrins and 

pyrethroids is presented in Table 8-1. Information concerning tolerances for residues of pyrethrins and 

selected pyrethroids is presented in Table 8-2. 

ATSDR has not derived acute-, intermediate-, or chronic-duration inhalation MRLs for pyrethrins or 

pyrethroids because adequate data were not available for this route of exposure. 

ATSDR derived an acute-duration oral MRL of 0.3 mg/kg/day for permethrin, based on a NOAEL of 

25 mg/kg/day for neurological impairment in rats. An uncertainty factor of 100 was used (10 for animal 

to human extrapolation and 10 to account for intrahuman variation) to derive the MRL. 

ATSDR derived an acute-duration oral MRL of 0.02 mg/kg/day for cypermethrin (97% purity; 

50/50 cis/trans), based on a LOAEL of 20 mg/kg for neurological impairment in rats (McDaniel and 

Moser 1993). An uncertainty factor of 1,000 was used (10 for lack of a NOAEL, 10 for animal to human 

extrapolation, and 10 to account for intrahuman variation) to derive the MRL. 

ATSDR derived an acute-duration oral MRL of 0.01 mg/kg/day for cyhalothrin, based on a NOAEL of 

1 mg/kg/day for gastrointestinal effects in dogs. An uncertainty factor of 100 was used (10 for animal to 

human extrapolation and 10 to account for intrahuman variation) to derive the MRL. 

ATSDR derived an intermediate-duration oral MRL of 0.2 mg/kg/day for permethrin, based on a NOAEL 

of 15.5 mg/kg/day for neurological impairment in rats. An uncertainty factor of 100 was used (10 for 

animal to human extrapolation and 10 to account for intrahuman variation) to derive the MRL. 

ATSDR derived an intermediate-duration oral MRL of 0.01 mg/kg/day for cyhalothrin, based on a 

NOAEL of 1 mg/kg/day for gastrointestinal effects in dogs. An uncertainty factor of 100 was used 

(10 for animal to human extrapolation and 10 to account for intrahuman variation) to derive the MRL. 
 

 

 

 

PYRETHRINS AND PYRETHOIDS 218 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pyrethrins and Pyrethroids 

Agency Description Information References 

INTERNATIONAL 

Guidelines: 

 IARC Carcinogenic classification

 Deltamethrin

 Fenvalerate 

Permethrin 

WHO Drinking water guideline 

Permethrin 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV-TWACpyrethrum 

NIOSH REL (TWA)Cpyrethrum 

IDLHCpyrethrum 

OSHA PEL (8-hour TWA)Cpyrethrum 

General industry (total dust) 

PEL (8-hour TWA)Cpyrethrum 

Construction industry (total

 dust) 

PEL (8-hour TWA)Cpyrethrum 

Shipyard industry (total 

dust) 

b. Water 

EPA Water pollution; determination 

of reportable quantityCpyrethrin 

Water pollution; designation of 

hazardous 

substanceCpyrethrin 

NPDES; toxic pollutants and 

hazardous substances required 

to be identified by existing 

dischargers if expected to be 

presentCpyrethrins 

c. Food 

FDA Pyrethrins in combination with 

piperonyl butoxide may be 

safely used for insect control on 

bags intended for use in 

contact with dried food 

Group 3a 

20 μg/L 

5 mg/m3

5 mg/m3 

5,000 mg/m3 

5 mg/m3 

5 mg/m3 

5 mg/m3 

1 pound 

IARC 2001 

WHO 2001 

 ACGIH 2000

NIOSH 2001

OSHA 2001a 

29CFR1910.1000 

Table Z-1 

OSHA 2001c 

29CFR1926.55 

Appendix A 

OSHA 2001b 

29CFR1915.1000 

Table Z 

EPA 2001c 

40CFR117.3 

 EPA 2001a 

40CFR116.4 

 EPA 2001d 

40CFR122 

Appendix D 

 FDA 2000a 

21CFR178.3720 
 

 

 

 

PYRETHRINS AND PYRETHOIDS 219 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pyrethrins and Pyrethroids 

Agency Description Information References 

NATIONAL (cont.) 

USDA Labeling of treated seed with 

pyrethrinsC”don=t use for food, 

feed, or oil purposes” 

Oat 

Sorghum 

d. Other 

 ACGIH Carcinogenicity classification 

Cpyrethrum 

DOT SuperfundCreportable quantity 

 Pyrethrins 

EPA RfD (mg/kg/day) 

Type I Pyrethroids

 Biphenthrin 

 Permethrin

 Resmethrin 

Type II Pyrethroids 

 Baythroid/Cyfluthrin 

 Cyhalothrin/Karate 

 Cypermethrin

 Danitol/Fenpropathrin

 Fluvalinate 

 Pydrin/Fenvalerate 

 Tralomethrin 

SuperfundCreportable quantity 

Pyrethrins 

Toxic chemical release 

reporting; Community Right-toKnowCeffective date 

 Fenvalerate 

Permethrin 

FDA New animal drugCfor use in the 

treatment of ear mites in dogs 

and cats 

STATE 

Regulations and 

Guidelines: 

a. Air 

Alaska Air contaminant standard 

(TWA)Cpyrethrum 

California Airborne contaminant 

Cpyrethrum 

 Connecticut HAPCpyrethrum 

 Hawaii Air contaminantCpyrethrum

 PEL 

STEL 

USDA 2001b 

7CFR201.31a(d) 

1 ppm 

3 ppm 

A4b

 ACGIH 2000

DOT 2001 

1 pound 49CFR172.101 

Appendix A 

IRIS 2003e 

1.5x10-2 

5.0x10-2 

3.0x10-2 

2.5x10-2 

5.0x10-3 

1.0x10-2 

2.5x10-2 

1.0x10-2 

2.5x10-2 

7.5x10-3 

EPA 2001b 

1 pound 40CFR302.4 

EPA 2001e 

40CFR372.65 

01/01/95 

01/01/95 

0.05% pyrethrins FDA 2000b 

21CFR524.2140 

5 mg/m3

 BNA 2001 

 BNA 2001 

 BNA 2001 

BNA 2001 

5 mg/m3 

10 mg/m3 
 

 

PYRETHRINS AND PYRETHOIDS 220 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pyrethrins and Pyrethroids 

Agency Description Information References 

STATE (cont.)

 Idaho Toxic air pollutantsCpyrethrum 

OEL 

EL 

AAC 

5 mg/m3 

3.33x10-1 pounds/hour 

0.25 mg/m3 

BNA 2001 

Kentucky Air qualityCpyrethrum 

TAL 20.0 mg/m3 

BNA 2001 

 Averaging time 

 Significant levels 

8 hours 

1.276x10-3 pounds/hour 

 Michigan Air contaminantCmaximum BNA 2001 

allowable concentrations 

 Pyrethrum 5 mg/m3 

Air contaminant (PEL-TWA) 

 Pyrethrum 5 mg/m3 

BNA 2001 

Montana Occupational air contaminant 5 mg/m3

 BNA 2001 

(TLV) for pyrethrum 

 New Hampshire Toxic air pollutantsCpyrethrum 5 mg/m3

 BNA 2001 

 New Mexico Toxic air pollutantsCpyrethrum 

OEL 

 Emissions 

5.05 mg/m3 

3.33x10-1 pounds/hour 

BNA 2001 

New York Air contaminant (TLV) 

 Pyrethrum 5 mg/m3 

BNA 2001 

Oregon Air contaminant (TLV) 

 Pyrethrum 5 mg/m3 

BNA 2001 

 South Carolina Toxic air emissionsCpyrethrum 

 Maximum allowable 50 μg/m3 

BNA 2001 

 concentration 

Washington Toxic air pollutants (ASIL 1.7 μg/m3

 BNA 2001 

24-hour average) for pyrethrum 

 Wisconsin Emission limitsCpyrethrum 

<25 feet emission point 4.176x10-1 pounds/hour 

BNA 2001 

>25 feet emission point 1.7520 pounds/hour 

b. Water 

Arizona Drinking water guideline HSDB 2001 

 Fenvalerate 180 μg/L 

Florida Drinking water guideline HSDB 2001 

Permethrin 350 μg/L 

 Cypermethrin 700 μg/L 

c. Food No data 

d. Other 

California Pesticide registrationCactive BNA 2001 

ingredients 

Fluvalinate 

Permethrin 

 Pyrethrins

 Resmethrin 
 

PYRETHRINS AND PYRETHOIDS 221 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Pyrethrins and Pyrethroids 

Agency Description Information References 

STATE (cont.)

 Hazardous substance BNA 2001 

 Pyrethrins

 Pyrethrum 

Florida Toxic substances in the BNA 2001 

workplaceCpyrethrum 

Georgia Regulated substances and soil 

concentrations that trigger 

notification 

 BNA 2001 

 Pyrethrin I 

 Pyrethrin II 

Pyrethrins and Pyrethroids

 Pyrethrum 

 Pyrethrum I 

Massachusetts Containers adequately labeled 

pursuant to federal law 

Cpyrethrum 

 BNA 2001 

Oil and hazardous material BNA 2001 

 Pyrethrin 1 

 Pyrethrin 2 

 Pyrethrins

 Pyrethroids 

 Pyrethrum 

 Minnesota Hazardous substance BNA 2001 

Cpyrethrum 

New Jersey Hazardous substance 

Permethrin 

 BNA 2001 

 Phenothrin 

 Pyrethrin I 

 Pyrethrin II 

 Pyrethrum 

 Resmethrin 

 Tetramethrin

a

Group 3: not classifiable as to its carcinogenicity to humans

b

A4: not classifiable as a human carcinogen 

AAC = acceptable ambient concentrations; ACGIH = American Conference of Governmental Industrial Hygienists; 

ASIL = acceptable source impact levels; CFR = Code of Federal Regulations; DOT = Department of 

Transportation; EL = emissions levels; EPA = Environmental Protection Agency; FDA = Food and Drug 

Administration; HAP = hazardous air pollutant; HSDB = Hazardous Substances Data Bank; IARC = International 

Agency for Research on Cancer; IDLH = immediately dangerous to life and health; NIOSH = National Institute of 

Occupational Safety and Health; NPDES = National Pollutant Discharge Elimination System; OEL = occupational 

exposure limit; OSHA = Occupational Safety and Health Administration; PEL = permissible exposure limit; 

REL = recommended exposure limit; RfD = oral reference dose; STEL = short-term exposure limit; 

TAL = threshold ambient limits; TLV = threshold limit value; TWA = time-weighted average; USDA = United States 

Department of Agriculture; WHO = World Health Organization 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHOIDS 222 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Tolerances for Residues Applicable to Pyrethrins and Pyrethroids (ppm) 

Type I Type II Pyrethroids 

Pyrethroids 

Per- Cyper- Delta- Fenprop- Fenval- Fluvali- TraloPyrethrin Allethrin methrin methrin methrin athrin erate nate methrin 

 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 

180.128 180.113 180.378 180.418 180.435 180.466 180.379 180.427 180.422 

Alfalfa, fresh C C 25.0 C C C C C C

Alfalfa, hay C C 55.0 C C C C C C

Almond hulls C C 0.05 C C C 15.0 C C

Almonds 1.0 C 20.0 C C C 0.2 C C

Apples 1.0 4.0 0.05 C C C 2.0 C C

Artichokes C C 10.0 C C C 0.2 C C

Asparagus C C 1.0 C C C C C C

Avocados C C 1.0 C C C C C C

Barley 3.0 2.0 C C C C C C C

Beans 1.0 C C C C C C C C

Beans, dried C C C C C C 0.25 C C

Beans, snap C C C C C C 2.0 C C

Birdseed 3.0 C C C C C C C C

mixtures 

Blackberries 1.0 4.0 C C C C C C C

Blueberries 1.0 4.0 C C C C 3.0 C C

Boysen­ 1.0 4.0 C C C C C C C

berries 

Brassica, C C C 2.0 C 3.0 C C C

head and 

stem 

Brassica, C C C 14.0 C C C C C

leafy 

Broccoli C C 1.0 C C C 2.0 C 0.5 

Brussels C C 1.0 C C C C C C

sprouts 

Buckwheat 3.0 C C C C C C C C

Cabbage C C 6.0 C C C 10.0 C C

Cranberries C C C C C C 3.0 C C

Cantaloupes C C C C C C 1.0 C C

Carrots C C C C C C 0.5 C C

Cattle, fat 0.1 C 3.0 0.05 C 1.0 1.5 0.01 C

Cattle, meat 0.1 C 0.25 0.05 C 0.1 1.5 0.01 C

Cattle, meat 0.1 C 2.0 0.05 C 0.1 1.5 0.01 C

byproducts 

Cauliflower C C 1.0 C C C 0.5 C C

Celery C C 5.0 C C C C C C

Cherries 1.0 4.0 3.0 C C C C C C

Citrus, dried C C C C C 4.0 C C C
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHOIDS 223 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Tolerances for Residues Applicable to Pyrethrins and Pyrethroids (ppm) 

Type I 

Pyrethroids 

Type II Pyrethroids 

Pyrethrin Allethrin 

Permethrin Cypermethrin Deltamethrin Fenpropathrin Fenvalerate Fluvalinate Tralomethrin 

 40CFR 

180.128 

40CFR 

180.113 

40CFR 

180.378 

40CFR 

180.418 

40CFR 

180.435 

40CFR 

180.466 

40CFR 

180.379 

40CFR 

180.427 

40CFR 

180.422 

pulp 

Citrus, oil C C C C C 75.0 C C C

Cocoa beans 1.0 C C C C C C C C

Coffee C C C C C C C 0.01 C

Collards C C 20.0 C C C 10.0 C C

Copra 1.0 C C C C C C C C

Corn, fodder C C 60.0 C C C 50.0 C C

Corn, forage C C 60.0 C C C 50.0 C C

Corn, grain C 2.0 0.05 C C C 0.02 C C

Corn, 

including 

popcorn 

3.0 C C C C C C C C

Corn, sweet, 

kernels and 

cobs 

C C 0.1 C C C 0.1 C C

Cottonseed 1.0 C 0.5 0.5 0.04 1.0 0.2 0.1 0.02 

Cottonseed, 

hulls 

C C C C C C C 0.3 C

Cottonseed 

oil 

C C C C 0.2 3.0 C 1.0 0.2 

Crabapples 1.0 4.0 C C C C C C C

Cucumbers C C C C C C 0.5 C C

Currants 1.0 4.0 C C C C 3.0 C C

Dewberries 1.0 4.0 C C C C C C C

Eggplant C C 1.0 C C C 1.0 C C

Eggs 0.1 C 1.0 C C 0.05 C 0.01 C

Elderberries C C C C C C 3.0 C C

English 

walnuts 

C C C C C C 0.2 C C

Figs 1.0 4.0 C C C C C C C

Filberts C C 0.05 C C C 0.2 C C

Flaxseed 1.0 C C C C C C C C

Fruits, citrus, 

crop 

group 10 

C C C C C 2.0 C C C

Fruits, pome, 

crop 

group 11 

C C C C C 5.0 C C C

Garlic C C 0.1 C C C C C C

Goats, fat 0.1 C 3.0 0.05 C 1.0 1.5 0.01 C
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHOIDS 224 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Tolerances for Residues Applicable to Pyrethrins and Pyrethroids (ppm) 

Type I 

Pyrethroids 

Type II Pyrethroids 

Pyrethrin Allethrin 

Permethrin Cypermethrin Deltamethrin Fenpropathrin Fenvalerate Fluvalinate Tralomethrin 

 40CFR 

180.128 

40CFR 

180.113 

40CFR 

180.378 

40CFR 

180.418 

40CFR 

180.435 

40CFR 

180.466 

40CFR 

180.379 

40CFR 

180.427 

40CFR 

180.422 

Goats, meat 0.1 C 0.25 0.05 C 0.1 1.5 0.01 C

Goats, meat 

byproducts 

0.1 C 2.0 0.05 C 0.1 1.5 0.01 C

Gooseberries 1.0 4.0 C C C C 3.0 C C

Grain, 

sorghum 

1.0 2.0 C C C C C C C

Grapes C 4.0 C C C 5.0 C C C

Grasses, 

range 

C C 15.0 C C C C C C

Guavas C 4.0 C C C C C C C

Hogs, fat 0.1 C 3.0 0.05 C 1.0 1.5 0.01 C

Hogs, meat 0.1 C 0.25 0.05 C 0.1 1.5 0.01 C

Hogs, meat 

byproducts 

0.1 C 3.0 0.05 C 0.1 1.5 0.01 C

Honey C C C C C C C 0.05 C

Honeydew 

melons 

C C C C C C 1.5 C C

Horseradish C C 1.0 C C C C C C

Horses, fat 0.1 C 3.0 0.05 C 1.0 1.5 0.01 C

Horses, meat 0.1 C 0.25 0.05 C 0.1 1.5 0.01 C

Horses, meat 

byproducts 

0.1 C 2.0 0.05 C 0.1 1.5 0.01 C

Huckleberries 

C 4.0 C C C C 3.0 C C

Kiwifruit C C 2.0 C C C C C C

Leafy 

vegetables, 

except 

Brassica 

C C 20.0 C C C C C C

Lettuce, 

head 

C C 20.0 10.0 C C C C 1.0 

Lettuce, leaf C C C C C C C C 3.0 

Loganberries 1.0 4.0 C C C C C C C

Mangoes 1.0 4.0 C C C C C C C

Milk C C C 0.05 C C 0.3 0.01 C

Milk, fat 0.5 C 6.25 C C 2.0 7.0 C C

Milo C 2.0 C C C C C C C

Mushrooms C C 6.0 C C C C C C

Muskmelons 1.0 4.0 C C C C 1.0 C C
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHOIDS 225 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Tolerances for Residues Applicable to Pyrethrins and Pyrethroids (ppm) 

Type I Type II Pyrethroids 

Pyrethroids 

Per- Cyper- Delta- Fenprop- Fenval- Fluvali- TraloPyrethrin Allethrin methrin methrin methrin athrin erate nate methrin 

 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 40CFR 

180.128 180.113 180.378 180.418 180.435 180.466 180.379 180.427 180.422 

Oats 1.0 2.0 C C C C C C C

Okra C C C C C C 0.1 C C

Onion, bulb C C 0.1 0.10 C C C C C

Onions, C C C 6.0 C C C C C

green 

Oranges 1.0 4.0 C C C C C C C

Papayas C C 1.0 C C C C C C

Peaches 1.0 4.0 5.0 C C C C C C

Peanut, hay C C C C C 20.0 C C C

Peanut, C C C C C 0.01 C C C

nutmeat 

Peanuts C C C C C C 0.02 C C

Peanuts, 1.0 C C C C C C C C

with shell 

removed 

Pears 1.0 4.0 3.0 C C C 2.0 C C

Peas 1.0 C C C C C 1.0 C C

Peas, dried C C C C C C 0.25 C C

Pecans C C C 0.05 C C 0.2 C C

Peppers C C C C C C 1.0 C C

Peppers, bell C C 1.0 C C C C C C

Pineapples 1.0 4.0 C C C C C C C

Pistachios C C 0.1 C C C C C C

Plums 1.0 4.0 C C C C C C C

Potatoes 0.05 C 0.05 C C C 0.02 C C

Poultry, fat 0.2 C 0.15 C C 0.05 C 0.01 C

Poultry, meat 0.2 C 0.05 C C 0.05 C 0.01 C

Poultry, meat 0.2 C 0.25 C C 0.05 C 0.01 C

byproducts 

Pumpkins C C C C C C 1.0 C C

Radish, roots C C C C C C 0.3 C C

Radish, tops C C C C C C 8.0 C C

Raisins C C C C C 10.0 C C C

Raspberries 1.0 4.0 C C C C C C C

Rice 3.0 C C C C C C C C

Rye 3.0 2.0 C C C C C C C

Sheep, fat 0.1 C 3.0 0.05 C 1.0 .5 0.01 C

Sheep, meat 0.1 C 0.25 0.05 C 0.1 1.5 0.01 C
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PYRETHRINS AND PYRETHOIDS 226 

8. REGULATIONS AND ADVISORIES 

Table 8-2. Tolerances for Residues Applicable to Pyrethrins and Pyrethroids (ppm) 

Type I 

Pyrethroids 

Type II Pyrethroids 

Pyrethrin Allethrin 

Permethrin Cypermethrin Deltamethrin Fenpropathrin Fenvalerate Fluvalinate Tralomethrin 

 40CFR 

180.128 

40CFR 

180.113 

40CFR 

180.378 

40CFR 

180.418 

40CFR 

180.435 

40CFR 

180.466 

40CFR 

180.379 

40CFR 

180.427 

40CFR 

180.422 

Sheep, meat 

byproducts 

0.1 C 2.0 0.05 C 0.1 1.5 0.01 C

Soybeans C C C C C C 0.05 C 0.05 

Soybean 

hulls 

C C 0.05 C C C 1.0 C C

Spinach C C 20.0 C C C C C C

Squash/cucu 

mber 

subgroup 

C C C C C 0.5 C C C

Stone fruits C C C C C C 10.0 C C

Strawberry C C C C C 2.0 C C C

Sugarcane C C C C C C 2.0 C C

Summer 

squash 

C C C C C C 0.5 C C

Sunflower 

seed 

C C C C C C 1.0 C 0.05 

Sweet 

potatoes 

0.05 C C C C C C C C

Tomatoes 1.0 4.0 2.0 C 0.2 0.6 1.0 C C

Tomato 

(product) 

concentrated 

C C C C 0.1 C C C C

Turnip 

greens 

C C 20.0 C C C C C C

Turnip roots C C 1.0 C C C 0.5 C C

Turnip tops C C C C C C 20.0 C C

Vegetables, 

curcurbit 

C C 3.0 C C 0.5 C C C

Walnuts 1.0 C 0.05 C C C C C C

Watercress C C 5.0 C C C C C C

Watermelons C C C C C C 1.0 C C

Wheat 3.0 2.0 C C C C C C C

Winter 

squash 

C C C C C C 1.0 C C

Source: EPA 2001f 
 

_______________________ 

PYRETHRINS AND PYRETHROIDS 227 

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PYRETHRINS AND PYRETHROIDS 281 

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 a sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—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 which examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research but are not actual research studies. 

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. 
PYRETHRINS AND PYRETHROIDS 282 

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 which examines the 

relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

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. 
PYRETHRINS AND PYRETHROIDS 283 

10. GLOSSARY 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air which has been 

reported to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLO)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical which has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a minimal risk 

level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

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. 
PYRETHRINS AND PYRETHROIDS 284 

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) which represents the best estimate of relative risk (risk as a ratio of the 

incidence among subjects exposed to a particular risk factor divided by the incidence among subjects who 

were not exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk 

of disease in the exposed group compared to the unexposed. 

Organophosphate or Organophosphorus Compound—A phosphorus containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The science of quantitatively predicting the fate (disposition) of an exogenous 

substance in an organism. Utilizing computational techniques, it provides the means of studying the 

absorption, distribution, metabolism and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments 

which, in general, do not represent real, identifiable anatomic regions of the body whereby the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 
PYRETHRINS AND PYRETHROIDS 285 

10. GLOSSARY 

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 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates and, possibly membrane permeabilities. The models also utilize biochemical information 

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called 

biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentrations for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-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. 
 

PYRETHRINS AND PYRETHROIDS 286 

10. GLOSSARY 

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. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic, that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 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. 

Toxicokinetics—The study of the absorption, distribution and elimination of toxic compounds in the 

living organism. 
PYRETHRINS AND PYRETHROIDS 287 

10. GLOSSARY 

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 one can be used; 

however a reduced UF of three may be used on a case-by-case basis, three being the approximate 

logarithmic average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
PYRETHRINS AND PYRETHROIDS 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. 
PYRETHRINS AND PYRETHROIDS A-2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels 

that have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agency wide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road NE, Mailstop E-29, Atlanta, Georgia 30333. 
 

 

 

 

 

PYRETHRINS AND PYRETHROIDS A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Permethrin 

CAS Number: 52645-53-1 

Date: August 25, 2003 

Profile Status: Third Draft Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 20 

Species: Rat 

Minimal Risk Level: 0.3 [X] mg/kg/day [ ] ppm 

Reference: McDaniel KL, Moser VC. 1993. Utility of a neurobehavioral screening battery for 

differentiating the effects of two pyrethroids, permethrin and cypermethrin. Neurotoxicol Teratol 15:71­

83. 

Experimental design and effects noted: The acute-duration oral MRL is based on the results of a study in 

which the critical effect was neurological impairment in rats. Groups of Long-Evans rats (8/sex/dose) 

were administered permethrin (95% purity; 50/50 cis/trans; in corn oil vehicle) in single gavage doses of 

0, 25, 75, or 150 mg/kg. Selected rats from each dose group were subjected to FOB and motor activity 

assessment at 2 and 4 hours following dosing. A LOAEL of 75 mg/kg was identified for neurological 

impairment that included increased excitability and aggressiveness, abnormal motor movement, and 

decreased grip strength and motor activity. The NOAEL was 25 mg/kg. 

Dose and end point used for MRL derivation: 25 mg/kg; multiple neurological effects. 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No 

Agency Contact (Chemical Manager): G. Daniel Todd, Ph.D. 
 

 

 

PYRETHRINS AND PYRETHROIDS A-4 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Cypermethrin 

CAS Number: 52315-07-8 

Date: August 25, 2003 

Profile Status: Third Draft Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 21 

Species: Rat 

Minimal Risk Level: 0.02 [X] mg/kg/day [ ] ppm 

Reference: McDaniel KL, Moser VC. 1993. Utility of a neurobehavioral screening battery for 

differentiating the effects of two pyrethroids, permethrin and cypermethrin. Neurotoxicol Teratol 15:71­

83. 

Experimental design and effects noted: The acute-duration oral MRL is based on the results of a study in 

which the critical effect was neurological impairment in rats. Groups of Long-Evans rats (8/sex/dose) 

were administered cypermethrin (97% purity; 50/50 cis/trans; in corn oil vehicle) in single gavage doses 

of 0, 20, 60, or 120 mg/kg. Selected rats from each dose group were subjected to FOB and motor activity 

assessment at 2 and 4 hours following dosing. A LOAEL of 20 mg/kg was identified for neurological 

impairment that included statistically significantly altered gait and decreased motor activity. A NOAEL 

was not established. 

Dose and end point used for MRL derivation: 20 mg/kg; neurological effects. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No 

Agency Contact (Chemical Manager): G. Daniel Todd, Ph.D. 
 

 

 

 

 

PYRETHRINS AND PYRETHROIDS A-5 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Cyhalothrin 

CAS Number: 68085-85-8 

Date: August 25, 2003 

Profile Status: Third Draft Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [X] Acute [ ] Intermediate [ ] Chronic 

Graph Key: 38 

Species: Dog 

Minimal Risk Level: 0.01 [X] mg/kg/day [ ] ppm 

Reference: EPA. 1981. Data evaluation record: Chronic toxicity (dog). Tox review 005100 (excerpt). 

Experimental design and effects noted: The acute-duration oral MRL is based on the results of a study in 

which the critical effect was increased fluid feces (diarrhea) in dogs. Groups of 4–5-month-old male and 

female beagle dogs (6/sex/dose) were administered cyhalothrin (in corn oil vehicle) in gelatin capsules at 

doses of 0, 1.0, 2.5, or 10.0 mg/kg/day for 26 weeks. The dosing volume was 0.1 mL/kg body weight. A 

dose-related increase in diarrhea was observed throughout the study, including the first week of treatment 

(7, 26, and 39% greater incidences of diarrhea in low-, mid-, and high-dose dogs, respectively, relative to 

controls). The 7% increased incidence of diarrhea at the 1.0 mg/kg/day dose level may not be clear 

indication of an adverse treatment-related effect. However, the 26% increased incidence of diarrhea at 

2.5 mg/kg/day is considered to represent a definitive adverse effect. Thus, 1.0 mg/kg/day is interpreted as 

a NOAEL and 2.5 mg/kg/day is considered a LOAEL for gastrointestinal effects. A detailed description 

of the test substance was not provided in the study. The acute-duration oral MRL is based on the 

assumption that the test substance consisted of technical-grade cyhalothrin with a purity of approximately 

90%. 

Dose and end point used for MRL derivation: 1.0 mg/kg/day; gastrointestinal effects (diarrhea). 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No 

Agency Contact (Chemical Manager): G. Daniel Todd, Ph.D. 
 

 

 

 

 

PYRETHRINS AND PYRETHROIDS A-6 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Permethrin 

CAS Number: 52645-53-1 

Date: August 25, 2003 

Profile Status: Third Draft Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 41 

Species: Rat 

Minimal Risk Level: 0.2 [X] mg/kg/day [ ] ppm 

Reference: EPA. 1994b. Memorandum: Permethrin: Review of series 81-8ss and 82-7ss acute and 

subchronic neurotoxicity screen studies and a literature publication on the neurotoxicity and commentary 

on a special positive control study with acrylamide. U.S. Environmental Protection Agency. Office of 

Pesticides and Toxic Substances. 

Experimental design and effects noted: The intermediate-duration oral MRL is based on the results of a 

study in which the critical effect was neurological impairment (tremors, impaired gait, hindlimb splay) in 

rats. Groups of Sprague-Dawley rats (10/sex/dose) were administered permethrin (technical grade; 50/50 

cis/trans) in the diet for 13 weeks at concentrations of 0, 250, 1,500, or 2,500 ppm (time-weighted average 

doses of 0, 15.5, 91.5, or 150.4 mg/kg/day for males and 0, 18.7, 111.4, or 189.7 mg/kg/day for females). 

Hindlimb splay was observed as early as days 38 and 18 in some 1,500-ppm males and females, 

respectively. Other signs of neurotoxicity in the 1,500-ppm rats first appeared between treatment days 35 

and 68. Signs of neurotoxicity appeared earlier and were more prevalent in rats of the 2,500-ppm 

treatment group. There were no signs of neurotoxicity in rats of the 250-ppm treatment group. This study 

identified a LOAEL of 1,500 ppm (91.5 and 111.4 mg/kg/day in males and females, respectively) for 

neurotoxicity and a NOAEL of 250 ppm (15.5 and 18.7 for males and females, respectively). 

Dose and end point used for MRL derivation: 15.5 mg/kg/day; neurological effects (tremors, impaired 

gait, hindlimb splay). 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Yes, conversion was 

performed by the study authors. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No 

Agency Contact (Chemical Manager): G. Daniel Todd, Ph.D. 
 

 

 

 

 

PYRETHRINS AND PYRETHROIDS A-7 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Cyhalothrin 

CAS Number: 68085-85-8 

Date: August 25, 2003 

Profile Status: Third Draft Post Public 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 38 

Species: Dog 

Minimal Risk Level: 0.01 [X] mg/kg/day [ ] ppm 

Reference: EPA. 1981. Data evaluation record: Chronic toxicity (dog). Tox review 005100 (excerpt). 

Experimental design and effects noted: The intermediate-duration oral MRL is based on the results of a 

study in which the critical effect was increased fluid feces (diarrhea) in dogs. Groups of 4–5-month-old 

male and female beagle dogs (6/sex/dose) were administered cyhalothrin (in corn oil vehicle) in gelatin 

capsules at doses of 0, 1.0, 2.5, or 10.0 mg/kg/day for 26 weeks. The dosing volume was 0.1 mL/kg body 

weight. A dose-related increase in diarrhea was observed throughout the study (7, 26, and 39% greater 

incidences of diarrhea in low-, mid-, and high-dose dogs, respectively, relative to controls). The 7% 

increased incidence of diarrhea at the 1.0 mg/kg/day dose level may not be clear indication of an adverse 

treatment-related effect. However, the 26% increased incidence of diarrhea at 2.5 mg/kg/day is 

considered to represent a definitive adverse effect. Thus, 1.0 mg/kg/day is interpreted as a NOAEL and 

2.5 mg/kg/day is considered a LOAEL for gastrointestinal effects. A detailed description of the test 

substance was not provided in the study. The intermediate-duration oral MRL is based on the assumption 

that the test substance consisted of technical-grade cyhalothrin with a purity of approximately 90%. 

Dose and end point used for MRL derivation: 1.0 mg/kg/day; gastrointestinal effects (diarrhea). 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: NA 

Was a conversion used from intermittent to continuous exposure? No 

Agency Contact (Chemical Manager): G. Daniel Todd, Ph.D. 
 

PYRETHRINS AND PYRETHROIDS 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 they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are 

presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered 

in this chapter. If data are located in the scientific literature, a table of genotoxicity information is 

included. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 
 

PYRETHRINS AND PYRETHROIDS B-2 

APPENDIX B 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These 

MRLs are not meant to support regulatory action; but to acquaint health professionals with exposure 

levels at which adverse health effects are not expected to occur in humans. 

They should help physicians and public health officials determine the safety of a community living near a 

chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"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 the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

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 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 LSE Tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) are used to summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed at 

increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer end points, and EPA's estimated range associated with an 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 No-Observed-Adverse-Effect Levels 

(NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 
PYRETHRINS AND PYRETHROIDS B-3 

APPENDIX B 

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. 

LEGEND 

See LSE Table 3-1 

(1) Route of Exposure One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. When 

sufficient data exists, three LSE tables and two LSE figures are presented in the document. The 

three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and 

dermal (LSE Table 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 2 "18r" data points in 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 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to 1,1,2,2-tetrachloroethane via 

inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the 

dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e., 

Nitschke et al. 1981. 

(7) System This column further defines the systemic effects. These systems include: respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, 1 systemic effect (respiratory) was 

investigated. 
PYRETHRINS AND PYRETHROIDS B-4 

APPENDIX B 

(8) NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which 

no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 

3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation 

MRL of 0.005 ppm (see footnote "b"). 

(9) LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study 

that caused a harmful health effect. LOAELs have been classified into "Less Serious" and 

"Serious" effects. These distinctions help readers identify the levels of exposure at which adverse 

health effects first appear and the gradation of effects with increasing dose. A brief description of 

the specific 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 Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of 

carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious 

effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report 

doses not causing measurable cancer increases. 

(12) Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in 

the footnotes. Footnote "b" indicates the NOAEL of 3 ppm in key number 18 was used to derive 

an MRL of 0.005 ppm. 

LEGEND 

See Figure 3-1 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures 

help the reader quickly compare health effects according to exposure concentrations for particular 

exposure periods. 

(13) Exposure Period The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the intermediate and chronic exposure periods are illustrated. 

(14) Health Effect These are the categories of health effects for which reliable quantitative data exists. 

The same health effects appear in the LSE table. 

(15)	 Levels of Exposure concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in 

mg/kg/day. 

(16) NOAEL In this example, 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 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The 

diamond symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 

corresponds to the entry in the LSE table. 
PYRETHRINS AND PYRETHROIDS 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 2 →

Exposure frequency/ 

Species duration 

Key to figurea 

5 6

INTERMEDIATE EXPOSURE 

System 

7 

NOAEL (ppm) 8 

Serious (ppm) 

LOAEL (effect) 

Less serious (ppm) 

9 

3 → Systemic ↓ ↓ ↓ ↓ ↓ 

3 10 (hyperplasia) b Resp 13 wk 5 d/wk 

6 hr/d 

18 Rat

4 →

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple organs) 

5 d/wk 7 hr/d 

39 Rat 89-104 wk 10 (CEL, lung tumors, nasal 

5 d/wk tumors) 

6 hr/d 

40 Mouse 79-103 wk 10 (CEL, lung tumors, 

5 d/wk hemangiosarcomas) 6 hr/d 

→

a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

12 

PYRETHRINS AND PYRETHROIDS C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACOEM American College of Occupational and Environmental Medicine 

ACGIH American Conference of Governmental Industrial Hygienists 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AOEC Association of Occupational and Environmental Clinics 

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 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AVDI average daily intake 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

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 

d day 

DCCA cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid 

Derm dermal 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 
 

PYRETHRINS AND PYRETHROIDS C-2 

APPENDIX C 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

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 

FPBA 4-fluoro-3-phenoxybenzoic acid 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

ft foot 

g gram 

GC gas chromatography 

gd gestational day 

gen generation 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

hr hour 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

in inch 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LCLo lethal concentration, low 

LC50 lethal concentration, 50% kill 

LDLo lethal dose, low 

LD50 lethal dose, 50% kill 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LT50 lethal time, 50% kill 

LOAEL lowest-observed-adverse-effect level 
 

PYRETHRINS AND PYRETHROIDS C-3 

APPENDIX C 

LSE Levels of Significant Exposure 

m meter 

MA trans,trans-muconic acid 

MACh muscarinic acetylcholine 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MFO mixed function oxidase 

mg milligram 

min minute 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mo month 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

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 

NHANES National Health and Nutrition Examination Survey 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 
PYRETHRINS AND PYRETHROIDS C-4 

APPENDIX C 

OPP Office of Pesticide Programs, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OPPT Office of Pollution Prevention and Toxics, 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 

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 

RTECS Registry of Toxic Effects of Chemical Substances 

RQ reportable quantity 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

sec second 

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 
PYRETHRINS AND PYRETHROIDS C-5 

U.S. 

USDA 

USGS 

VOC 

WBC 

wk 

WHO 

yr

> $

= 

< #

% αβγδ

μm

μg q1

* 

– 

+ 

(+) 

(–) 

APPENDIX C 

United States 

United States Department of Agriculture 

United States Geological Survey 

volatile organic compound 

white blood cell 

week 

World Health Organization 

 year 

greater than 

greater than or equal to 

equal to 

less than 

less than or equal to 

percent 

alpha 

beta 

 gamma 

delta 

 micrometer 

microgram 

cancer slope factor 

negative 

positive 

weakly positive result 

weakly negative result