Fifth Edition, 1999
              J. Routt Reigart, M.D.
      Professor of Pediatrics, Medical University of South Carolina

           James R. Roberts, M.D., M.P.H.
    Assistant Professor of Pediatrics, Medical University of South Carolina
        Support for this publication was provided by:
         Certification and Worker Protection Branch
           Field and External Affairs Division
             Office of Pesticide Programs
          U.S. Environmental Protection Agency
             401 M Street SW (7506C)
              Washington, DC 20460

        For additional copies or more information:
               Tel: 703-305-7666

   The manual is available in electronic format on the Internet at:

We are grateful to the Office of Pesticide Programs, Environmental Protection Agency, for giving us the
opportunity to collaborate on this new edition. Our thanks go to Kevin Keaney, Acting Branch Chief, for
his support and vision, and for giving this publication priority attention. Particular mention should also be
made of the efforts of Jerome M. Blondell, Ph.D., M.P.H., and Ameesha Mehta, M.P.H., whose oversight
and constant assistance were invaluable in moving this project forward. Ana Maria Osorio, M.D., M.P.H.,
contributed Chapter 3, Environmental and Occupational History, to this manual.
    Experts in clinical toxicology conducted critical reviews of draft material. We are greatly appreciative
of the time and effort of the following reviewers:

                       Jeffery Lloyd Burgess, M.D., M.P.H.
                       Assistant Professor
                       Environmental Occupational Health Unit
                       University of Arizona Prevention Center

                       Matthew C. Keifer, M.D., M.P.H.
                       Assistant Professor
                       Department of Medicine/Environmental Health
                       University of Washington

                       Wayne R. Snodgrass, M.D, Ph.D.
                       Professor and Head
                       Clinical Pharmacology-Toxicology
                       Texas  Poison Center

                       Sheldon L.Wagner, M.D.
                       Professor of Clinical Toxicology
                       Oregon State University

    Many other individuals contributed their time and skill to this publication. We are very appreciative
of the tireless efforts of Patricia Clark, our administrative  assistant, who spent endless hours in text
review, securing references, communicating with reviewers, and  otherwise making the revision process
possible and easier than anticipated. Gilah Langner of Stretton Associates, Inc., provided editorial super-
vision. Will Packard and Sarah Carter of Free  Hand  Press, Inc. were responsible for the format  and
layout of the manual.

Cover photographs by Steve Delaney, EPA.

Section I: General Information
1    Introduction 	2
2    General Principles in the Management of Acute Pesticide Poisonings 	  10
3    Environmental and Occupational History	  17

Section II: Insecticides
4    Organophosphate Insecticides	34
5    N-Methyl Carbamate Insecticides	48
6    Solid Organochlorine Insecticides	55
7    Biologicals and Insecticides of Biological Origin	63
8    Other Insecticides, Acaricides, and Repellents	74

Section III: Herbicides
9    Chlorophenoxy Herbicides 	94
10   Pentachlorophenol	99
11   Nitrophenolic and Nitrocresolic Herbicides 	 104
12   Paraquat and Diquat	 108
13   Other Herbicides	 118

Section IV: Other Pesticides
14   Arsenical Pesticides 	 126
15   Fungicides 	 137
16   Fumigants	 156
17   Rodenticides	 169
18   Miscellaneous Pesticides, Solvents, and Adjuvants	 183
19   Disinfectants	 196

Section V
Index of Signs and Symptoms	210
Index of Pesticide Products	223

List of Tables

Dosage Tables
     Sorbitol	12
     Activated Charcoal	13
     Syrup of Ipecac	14
     Diazepam	14
     Lorazepam	15
     Atropine	42
     Pralidoxime  	43
     Atropine  	51
     Diazepam	58
     Atropine  Sulfate	68, 72
     Calcium Gluconate	84
     Lorazepam	  102
     Bentonite and Fuller's Earth	  113
     Morphine Sulfate	  115
     BAL (Dimercaprol) 	  130
     D -penicillamine	  131
     DMSA (Succimer)  	  131
     DMPS	131
     Cyanide Antidotes	  166
     Supplemental Sodium Nitrite and Sodium Thiosulfate 	  167
     Phytonadione	  171
     Aquamephyton*	  172
     Calcium Gluconate	  178

     Pesticides Most  Often Implicated in Symptomatic Illnesses, 1996	5
     California Occupational Illnesses Due to Pesticides, 1991-1995 	6
     Screening Questions for Occupational and Environmental Exposures	 18
     Adult Interview for Occupational and Environmental Exposures	26
     Steps in Investigating a Disease Outbreak	26
     Approximate Lower Limits of Normal Plasma and
          Red Cell Cholinesterase Activities in Humans 	39
     Toxicity of Common Herbicides	  119

          Section I

                                 CHAPTER 1
                                 This fifth edition of Recognition and Management of Pesticide Poisonings is an up-
                                 date and expansion of the 1989 fourth edition. The Office of Pesticide Pro-
                                 grams of the United States Environmental Protection Agency has sponsored
                                 the series since 1973. The purpose of the manual is to provide health profes-
                                 sionals with recently available information on the health hazards of pesticides
                                 currently in use, and current consensus recommendations for management of
                                 poisonings and injuries caused by them.
                                     Pesticide poisoning is a commonly under-diagnosed illness in America to-
                                 day.  Despite recommendations by the  Institute of Medicine and others urging
                                 the integration of environmental medicine into medical education, health care
                                 providers generally receive a very limited amount of training in occupational
                                 and environmental health, and in pesticide-related illnesses, in particular.'The
                                 updating of this manual is part of a larger initiative of the U.S. Environmental
                                 Protection Agency,  in conjunction with numerous federal agencies, associa-
                                 tions of health professionals, and related organizations to help  health care
                                 providers become better aware, educated, and trained  in the area of pesticide-
                                 related health concerns. This larger initiative, entitled Pesticides and National
                                 Strategies for Health Care Providers, was launched in April 1998.
                                     As with previous updates, this new edition incorporates new pesticide prod-
                                 ucts that are  not necessarily widely known among health professionals. The
                                 accumulated  "use experience" of formulators, applicators, and field workers
                                 provides an expanding basis for judging safety and identifying the environmen-
                                 tal and workplace hazards of old and new pesticides. Major episodes of adverse
                                 health effects reported in medical and scientific  periodicals have been  taken
                                 into account. This literature also contributes importantly to improved under-
                                 standing of toxic mechanisms. Clinical toxicology is a dynamic field of medi-
                                 cine; new treatment methods are developed regularly, and the  effectiveness of
                                 old as well as new modalities is subject to constant critical review.
                                     There is general agreement that prevention of pesticide poisoning remains a
                                 much surer path to safety and health than reliance on treatment. In addition to
                                 the inherent  toxicity of pesticides, none of the medical procedures or  drugs
                                 used in treating poisonings is risk-free.  In fact, many antidotes are toxic in their
                                 own right, and such apparently simple procedures as gastric intubation  incur
                                 substantial risk. The clinical toxicologist must often weigh the hazards of vari-
                                 ous courses of action—sometimes including no treatment at all—against the
                                 risks of various interventions, such as gastric emptying, catharsis, administration

of intravenous fluids, or administration of an antidote, if available. Clinical man-
agement decisions have to be made promptly and, as often as not, on the basis
of limited scientific and medical information. The complex circumstances of
human poisonings rarely allow precise comparisons of alternative management.
In no sense, then, are the treatment recommendations in  this  book infallible
guides to successful  outcomes.They are no more than consensus judgments of
the  best available clinical management options.
    This manual deals almost entirely with short-term  (acute) harmful effects
of pesticides. Although obviously important, the subject of chronic effects  is
too complex to deal with exhaustively in a manual designed as guidance for
emergency management. Nonetheless, appropriate treatment of serious expo-
sures to pesticides represents an important step  in avoiding chronic as well as
acute disease.
    The pesticides and commercial products mentioned in this manual do not
represent the universe of pesticide products in existence. They were selected
based on frequency  of use and exposure, severity of toxicity, and prior experi-
ence with acute poisonings. Products are discussed in this manual that have
been discontinued or whose U.S. pesticide registration has been revoked but
are judged to still be of risk due to use elsewhere or where there is a probability
of residual stocks. Agents long out of use in the U.S. and elsewhere were not
included in the manual.
    The amount of pesticide absorbed is a critical factor in making treatment
decisions, and estimation of dosage in many circumstances of pesticide expo-
sure remains difficult.The terms "small amount" and "large amount" used in
this book are obviously ambiguous, but the quality of exposure information
obtained rarely justifies more specific terminology.
    Sometimes the circumstances of exposure are a rough guide to the amount
absorbed. Exposure  to spray drift properly  diluted for field application is not
likely to convey a large  dose unless exposure  has been prolonged. Spills of
concentrated technical material onto the skin or clothing may well represent a
large dose of pesticide unless the  contamination  is promptly removed. Brief
dermal  exposure  to foliage residues of cholinesterase-inhibiting pesticides  is
not likely to  lead  to poisoning, but prolonged exposures may well do so. Sui-
cidal ingestions almost always involve "large amounts," requiring the most ag-
gressive management.  Except in children, accidental pesticide ingestions are
likely to be spat out or vomited.  Ingestions of pesticides  by children are the
most difficult to evaluate. The therapist usually must base clinical management
decisions on "worst  case" assumptions of dosage. Childhood poisonings are still
further complicated by the greater vulnerability  of the very young, not only to
pesticides themselves, but also to drugs and treatment procedures. The nature
of neurological development in children entails  an additional level of risk that
is not present in  adults. Some adult  groups such as farmwrokers  with  poor
nutrition and high exposure may also be at increased risk.
                                                                                            INTRODUCTION • 3

                                  Key Principles
                                     General methods of managing pesticide poisonings are presented in Chap-
                                  ter 2 and reflect a broad base of clinical experience. The following key points
                                  deserve emphasis. The need to protect the airway from aspiration of vomitus
                                  cannot be overstated. Death has occasionally resulted from this complication,
                                  even following ingestions of substances having relatively low toxic potential. In
                                  poisonings  by  agents that depress central nervous system function or cause
                                  convulsions, early placement of a cuffed endotracheal tube  (even when this
                                  requires  light general anesthesia) may be life saving. Maintenance of adequate
                                  pulmonary  gas exchange is another essential  element of poisoning manage-
                                  ment that deserves  constant reemphasis.
                                     Gastric  intubation, with aspiration and lavage, remains a useful method for
                                  removing poisons from the stomach shortly after they have  been swallowed,
                                  but the time after  ingestion during which lavage is likely to be beneficial  is
                                  shorter than many clinical toxicologists have  thought. Rarely are significant
                                  amounts of  swallowed toxicants recovered more than 1-2 hours after ingestion,
                                  and, in many instances,  the bulk of swallowed  material passes into the duode-
                                  num and beyond in  15-30 minutes.  In addition, the majority of controlled
                                  studies evaluating the effectiveness of gastric emptying procedures are done for
                                  ingestions of solid material (pills) rather than liquids.
                                     Full advantage  should be taken of new highly adsorbent charcoals that are
                                  effective in  binding some pesticides in the gut. Unfortunately, charcoal does
                                  not adsorb all pesticides, and its efficiency against many of them is not known.
                                  In poisonings caused  by large intakes of pesticide, hemodialysis  and
                                  hemoperfusion over adsorbents continue to be tested as methods for reducing
                                  body burdens. Against some toxicants, these procedures appear valuable. Over-
                                  all effectiveness appears  to depend not only on efficiency of clearance from the
                                  blood, but also on the mobility of toxicant already distributed to tissues before
                                  the extracorporeal blood-purification procedure is started.The volume of dis-
                                  tribution and avidity of tissue binding are important considerations in making
                                  such decisions. The critical determinant of success in using these systems may
                                  well be the speed with which they can be put into operation before tissue-
                                  damaging stores of toxicant have accumulated.
                                     There remains  a need for systematic reporting of pesticide poisonings to a
                                  central agency so that accurate statistics describing the frequency and circum-
                                  stances of poisoning can be compiled, and efforts to limit these occurrences can
                                  be properly directed. In some countries there has been an increase in the use of
                                  pesticides as instruments of suicide and  even homicide. Producers are now
                                  devoting considerable effort to modifying formulation and packaging to deter
                                  these misuses.This  work is important because  suicidal ingestions are often the
                                  most difficult pesticide poisonings to treat successfully.

Common Pesticide Poisonings
    The pesticides most often implicated in poisonings, injuries, and illnesses,
according to 1996 data from the American Association of Poison Control Centers
Toxic Exposure Surveillance System, are listed below.
    The list is based on symptomatic cases classified as minor, moderate, major,
or fatal  outcome for unintentional cases involving a single product. Numbers
of cases are reported for both children under six years of age and for adults and
older children. Suicide/homicide (intentional) cases have been excluded. Cases
listed as organophosphates (and the other categories as well) may also include
other insecticides such as carbamates and  organochlorines in a single product.

Pesticide or Pesticide Class
Pyrethrins and pyrethroids**
Pine oil disinfectants
Hypochlorite disinfectants
Insect repellents
Phenol disinfectants
Carbamate insecticides
Organochlorine insecticides
Phenoxy herbicides
Anticoagulant rodenticides
All Other Pesticides
Total all pesticides/disinfectants
* Totals include a small number of cases with
** Rough estimate: includes some veterinary
< 6 years
unknown age.
products not classified by chemical type.
American Association of Poison Control Centers, Toxic
1996 data.
    Approximately 90% of symptomatic cases involve only minor symptoms of
the type that could typically be treated at home with dilution or just observation.
However, seven of the top ten categories listed in  the table above (organo-
phosphates, py re thr ins/pyre thro ids, hypochlorite disinfectants, carbamates,
organochlorines, phenoxy herbicides, and anticoagulant rodenticides) are much
more likely to require medical attention.
    This list cannot be considered representative of all symptomatic poisonings
because it only shows cases reported to Poison Control Centers. However, it does
give a sense of the relative frequency and risk of poisoning from various agents or
classes of agents. The  relative frequency of cases generally reflects how widely a
product is used in the environment. For example, a number of disinfectants occur
in the top ten partly because they are far more commonly found in the home and
work environment than other pesticides (see also the table of occupational cases

                                  below). Denominator information on the population at risk (numbers exposed)
                                  would be needed to better understand the relative  risk of different pesticides.
                                  However, the main purpose of these tables is to give physicians a sense of what
                                  types of cases they are most likely to see in their practice.
                                      Although suicide cases make up roughly 3% of pesticide-related  calls to
                                  Poison Control Centers, they may account for nearly 10% of the cases seen in
                                  a health  care facility. The  leading types of products involved in suicidal cases
                                  include anticoagulant rodenticides (20% of total suicide attempts), pine oil dis-
                                  infectants (14%),organophosphates (ll%),pyrethrins/pyrethroids (6%),unknown
                                  rodenticides (5%), carbamate insecticides (4%), and  phenol disinfectants
PESTICIDES, 1991-1995
Rank Pesticide
1 Sodium hypochlorite
2 Quaternary ammonia
3 Chlorine
4 Glutaraldehyde
5 Chlorpyrifos
6 Sulfur
7 Glyphosate
8 Propargite
9 Metam sodium**
10 Cyanuric acid
All Other
Total all pesticides/disinfectants
* Topical includes skin, eye, and respiratory
** Train derailment led to a cluster of cases

due to metam

sodium in 1991.
Source: Louise Mehler, M.S., California Pesticide Illness Surveillance Program
Environmental Protection Agency.


                                      Poison Control  Centers are best at capturing pesticide exposures which
                                  occur in residential environments. However, occupational exposures are not as
                                  well covered.  California's Pesticide Illness Surveillance Program is generally
                                  regarded as the best in the  country. The table above presents the number  of
                                  occupationally-related cases in California reported from  1991 through 1995
                                  where a pesticide was considered a probable or definite cause of the resulting
                                  illness. Pesticide combinations, where  the primary pesticide responsible for the
                                  illness  could not be  identified, are not included in this table. Among persons
                                  who encounter pesticides in the course of their occupational activities, dermal
                                  and eye injuries, rather than systemic  poisonings, are more common. Systemic
                                  poisonings, however, are likely to be more severe.

Format of this Manual
    An effort has been made to format this book for quick reference by thor-
ough indexing and minimal references to other pages or chapters. However,
many different agents commonly require similar procedures in treating poison-
ings and it is not practical to repeat these protocols in every chapter. General
principles for management of pesticide poisoning, including skin and eye de-
contamination,  gastrointestinal decontamination, and control  of convulsions
are considered in Chapter 2, General Principles. These principles  are refer-
enced throughout.
    Changes in this reformatted edition include: tabular listings  of Commercial
Products in each chapter, the addition of a new chapter on Disinfectants (Chapter
19), and the addition of a chapter on Environmental and Occupational History
(Chapter 3), which places pesticide poisonings in the context of other environ-
mental and occupational exposures, provides questionnaires designed to elicit ex-
posure information, discusses resources available to the practitioner, and  provides a
list of governmental and non-government contacts and Web sites  for more infor-
mation. In addition, each chapter is referenced to key references in readily accessible
current literature.  Most references were selected as primary references in peer
review journals, although some review papers are also included.
    The contents of this book have been derived from many sources:  published
texts, current medical, toxicological, and pesticide product literature, and direct
communications with experts in clinical toxicology and pesticide toxicology and
environmental and occupational health specialists. A list of the major text sources
follows this introduction.

1.  Institute of Medicine. Role of the Primary Care Physician in Occupational and Environ-
   mental Medicine, Washington, DC: Institute of Medicine, 1988.
Texts and Handbooks on Pesticides,
Pesticide Toxicology, and Clinical Toxicology

Agricultural Chemicals Books I, II, III, IV
Thomson Publications, Fresno, CA, 1994-95

Agrochemicals Desk Reference: Environmental Data
John H. Montgomery
Lewis Publishers, Boca Raton, FL, 1995

The Agrochemicals Handbook, 3rd Edition
The Royal Society of Chemistry, Cambridge, England, 1994
                                                                                          INTRODUCTION • 7

                                Biological Monitoring Methods for Industrial Chemicals,
                                  2nd Edition
                                Randall C. Baselt
                                Biomedical Publications, Davis, CA, 1988

                                Casarett and Doull's Toxicology, 5th Edition
                                John Doull, Curtis D. Klaassen, and Mary O. Amdur
                                Macmillan Publishing Company, New York, NY, 1996

                                Chemicals Identified in Human Biological Media: A Data Base
                                Compiled by M.Virginia Cone, Margaret F. Baldauf, Fay M. Martin, and John
                                  T. Ensminger
                                Oak Ridge National Laboratory, 1980

                                Clinical Toxicology of Agricultural Chemicals
                                Sheldon L.Wagner, M.D.
                                Oregon State University Press, Corvallis, OR, 1981

                                Clinical Toxicology of Commercial Products, 5th Edition
                                Robert E. Gosselin, Roger P. Smith and  Harold C. Hodge, with assistance of
                                  Jeannette E. Braddock
                                Williams and Wilkins, Baltimore, MD, 1984

                                Farm Chemicals Handbook
                                Charlotte Sine, Editorial Director
                                Meister Publishing Company, Willoughby, Ohio, 1998

                                Handbook of Pesticide Toxicology
                                Wayland J. Hayes, Jr. and Edward R. Laws, Jr., Editors
                                Academic Press, San Diego, CA 1991

                                Handbook of Poisoning: Prevention, Diagnosis and Treatment,
                                  12th Edition
                                Robert H. Dreisbach and William O. Robertson
                                Appleton and Lange, East Norwalk, CT, 1987

                                Herbicide Handbook, 7th Edition
                                Weed Science Society of America, 1994

                                Medical Toxicology: Diagnosis and Treatment of Human Poisoning
                                Matthew J. Ellenhorn and Donald G. Barceloux
                                Elsevier, New York, NY, 1988

The Merck Index, llth Edition
Martha Windholz and Susan Budavari, Editors
Merck and Company, Inc., Rahway, NJ, 1989

Patty's Industrial  Hygiene and Toxicology, 4th Revised Edition
George D. Clayton and Florence E. Clayton
Wiley Interscience,  New York, NY, 1991-95

Pesticide Manual, llth Edition
CDS Tomlin
The British Crop Protection Council, Farnham, Surrey, United Kingdom, 1997

Pesticide Pro files :Toxi city, Environmental Impact, and Fate
Michael A. Kamrin  (Editor)
Lewis Publishers, Boca Raton, FL, 1997

The Pharmacological Basis of Therapeutics, 8th Edition
Louis S. Goodman and Alfred Gilman
Pergamon Press, New York, NY, 1990

Barry H.  Rumack, N.K. Sayre, and C.R. German, Editors
Micromedex, Englewood, CO,  1974-98

Poisoning: A Guide to Clinical Diagnosis and Treatment, 2nd Edition
W. F Von Oettingen
W. B. Saunders Company, Philadelphia, PA, 1958
                                                                                      INTRODUCTION • 9

                              CHAPTER 2
                              General  Principles  in
                              the Management of
                              Acute Pesticide Poisonings
                              This chapter describes basic management techniques applicable to most acute
                              pesticide poisonings. Where special considerations and treatments are required
                              for a particular pesticide, they are addressed separately in the appropriate chapter.

                              Skin Decontamination
                                 Decontamination must proceed concurrently with whatever resuscitative
                              and antidotal measures are necessary to preserve life. Shower patient with soap
                              and water, and shampoo hair to remove chemicals from skin and hair. If there
                              are any indications of weakness, ataxia, or other neurologic impairment, cloth-
                              ing should be removed and a complete bath and shampoo given while the
                              victim is recumbent. The possibility of pesticide sequestered under fingernails
                              or in skin folds should not be overlooked.
                                 Flush contaminating chemicals from eyes with  copious amounts of clean
                              water for 10-15 minutes. If eye irritation is present after decontamination, oph-
                              thalmologic consultation is appropriate.
                                 Persons attending the victim should avoid direct contact with heavily con-
                              taminated  clothing and vomitus. Contaminated clothing  should  be promptly
                              removed, bagged, and laundered before returning. Shoes and other leather items
                              cannot usually be decontaminated and should be discarded. Note that pesti-
                              cides can contaminate the inside surfaces of gloves, boots, and headgear. De-
                              contamination should especially be considered for emergency  personnel such
                              as ambulance drivers at the site of a spill or contamination. Wear rubber gloves
                              while washing pesticide from skin and hair of patient. Latex and other surgical
                              or precautionary gloves usually will not always adequately protect from pesti-
                              cide contamination, so only rubber gloves are appropriate for this purpose.

                              Airway Protection

                                 Ensure that  a clear airway exists. Suction any oral secretions  using a large
                              bore suction device if necessary. Intubate the trachea if the patient has respira-
                              tory depression or if the patient appears obtunded or otherwise neurologically

impaired. Administer oxygen as necessary to maintain adequate tissue oxygen-
ation. In severe poisonings, it may be necessary to mechanically support pul-
monary ventilation for several days.
    Note on Specific Pesticides: There are several special considerations
with regard to certain pesticides. In organophosphate and carbamate poi-
soning, adequate tissue oxygenation is essential prior to administering atropine.
As important, in paraquat and diquat poisoning, oxygen is contraindicated
early in the poisoning because of progressive oxygen toxicity to the lung tissue.
See specific chapters for more details.
Gastrointestinal Decontamination
    A joint position statement has recently been released by the American
Academy of Clinical Toxicology and the European Association of Poisons Centres
and Clinical Toxicologists on various methods of gastrointestinal decontamina-
tion. A summary  of the position statement accompanies the description of
each procedure.
1. Gastric Lavage
    If the patient presents within 60 minutes of ingestion, lavage may be con-
sidered. Insert an orogastric tube and follow with fluid, usually normal saline.
Aspirate back the fluid in an attempt to remove any toxicant. If the patient is
neurologically impaired, airway protection with a cuffed endotracheal tube is
indicated prior to gastric lavage.
    Lavage performed more than 60 minutes after ingestion has not proven to
be beneficial and runs the risk of inducing bleeding, perforation, or scarring
due to additional trauma to already traumatized tissues. It is almost always nec-
essary first  to control seizures before attempting gastric  lavage or any other
method of  GI decontamination.
    Studies of poison recovery have been performed mainly with solid mate-
rial such as pills.There are no  controlled studies of pesticide recovery by these
methods. Reported recovery  of material at 60 minutes in several studies was
8%-32%.''2 There is further evidence that lavage may propel the material  into
the small bowel,  thus increasing absorption.3
    Note on Specific Pesticides: Lavage is contraindicated in hydrocarbon
ingestion, a common vehicle in many pesticide formulations.
    Position Statement:  Gastric lavage should not be routinely used in the
management of poisons. Lavage is indicated only when a patient has ingested a
potentially  life-threatening amount of poison and the procedure  can be done
within 60 minutes of ingestion. Even then, clinical benefit has not been con-
firmed in controlled studies.4
                                                                                      GENERAL PRINCIPLES • 11

                                 2. Catharsis
                                     Sorbitol and magnesium citrate are commonly used cathartic agents. Be-
                                 cause magnesium citrate has not been studied as much, its use is not described
                                 here. Sorbitol is often included  in charcoal formulations. It will increase gut
                                 motility to improve excretion of the charcoal-poison complex. The dosage of
                                 sorbitol is 1-2 g/kg as a one-time dose. Repeat doses of cathartics may result in
                                 fluid and electrolyte imbalances, particularly in children, and are therefore not
                                 recommended. Sorbitol is formulated  in 70% and 35% solutions  and usually
                                 packaged  in 100 mL bottles. The gram dosage of sorbitol in a 100 mL bottle
                                 can be calculated by multiplying 100 (mL)  x 0.7 (for 70% solution) x 1.285 g
                                 sorbitol/mL.Therefore the dose in mL is as follows:
                                     Dosage of Sorbitol:
                                      • Adults: 70% sorbitol, 1-2 mL/kg.
                                      • Children:35% sorbitol, 1.5-2.3 mL/kg (maximum dosage: 50 g).
                                     Note on Specific Pesticides: Significant poisoning with organophos-
                                 phates, carbamates, and arsenicals generally results in a profuse diarrhea. Poi-
                                 soning with diquat and to a lesser extent paraquat results in an ileus.The use of
                                 sorbitol is not recommended in any of the above pesticide poisonings.
                                     Position Statement: The administration of a cathartic alone has no role
                                 in the management of the poisoned patient. There are no definite indications
                                 for the use of cathartics in the management of the poisoned patient. Data are
                                 conflicting with regard to use in combination with activated  charcoal, and its
                                 routine use is not endorsed. If a cathartic is used, it should  be as a single dose in
                                 order to minimize adverse effects.  There are numerous contraindications,
                                 including absent bowel sounds, abdominal trauma or surgery, or  intestinal
                                 perforation or obstruction. It is also contraindicated  in volume depletion,
                                 hypotension, electrolyte imbalance, or the ingestion of a corrosive substance.5
                                 3. Activated Charcoal Adsorption
                                     Activated charcoal is an effective absorbent for many poisonings.Volunteer
                                 studies suggest that it will reduce the amount of poison absorbed if given within
                                 60 minutes.6 There are insufficient data to support or exclude its use if time
                                 from ingestion is prolonged, although some poisons that are less soluble may be
                                 adsorbed beyond 60 minutes. Clinical trials with charcoal have been done with
                                 poisons other than pesticides. There is some  evidence  that paraquat is well
                                 adsorbed by activated charcoal.7'8 Charcoal has been anecdotally successful with
                                 other pesticides.

    Dosage of Activated Charcoal:
     •  Adults and children over 12years: 25-100 g in 300-800 mL water.
     •  Children under 12years: 25-50 g per dose.
     •  Infants and toddlers under 20 kg. I g per kg body weight.
Many activated charcoal formulations come premixed with sorbitol. Avoid giv-
ing more than one dose of sorbitol as a cathartic in infants and children due to
the risk of rapid shifts of intravascular fluid.
    Encourage the victim to swallow the adsorbent even though spontaneous vom-
iting continues. Antiemetic therapy may help control vomiting in adults or older
children. As an alternative, activated  charcoal may be administered through an
orogastric tube or diluted with water and administered slowly through a nasogastric
tube. Repeated administration of charcoal or other absorbent every 2-4 hours may
be beneficial in both children and adults, but  use of a cathartic such as sorbitol
should be avoided after the first dose. Repeated doses  of activated charcoal should
not be administered if the gut is atonic.The use of charcoal without airway protec-
tion is contraindicated in the neurologically impaired patient.
    Note on  Specific Pesticides:  The use of charcoal without airway pro-
tection should be used with caution in poisons such as organophosphates, car-
bamates, and organochlorines  if they are prepared in a hydrocarbon solution.
    Position Statement: Single-dose  activated charcoal should not be used
routinely in the management of poisoned patients. Charcoal appears to be most
effective within 60 minutes of ingestion and may be considered for use for this
time period. Although it may be considered 60 minutes after ingestion, there is
insufficient evidence to support or deny its use for this  time  period. Despite
improved binding of poisons within 60 minutes, only one study exists9 to suggest
that there  is improved clinical outcome. Activated charcoal is contraindicated in
an unprotected airway, a GI tract not anatomically intact, and when charcoal
therapy may increase the risk of aspiration of a hydrocarbon-based pesticide.6
4. Syrup of Ipecac
    Ipecac has been used as an emetic since the 1950s. In a pediatric study,
administration of ipecac resulted in vomiting  within 30 minutes in 88% of
children.10 However, in light of the recent review of the clinical effectiveness of
ipecac, it is no longer recommended for routine use in most poisonings.
Most clinical  trials  involve the use of pill  form ingestants such as aspirin,2'11
acetaminophen,12 ampicillin,1 and multiple types of tablets.13 No clinical trials
have been done with pesticides. In 1996, more than 2 million human exposures
to a poisonous substances were reported to American poison centers. Ipecac
was recommended for decontamination in only 1.8% of all exposures.14
                                                                                         GENERAL PRINCIPLES • 13

                                     Dosage of Syrup of Ipecac:
                                      • Adolescents and adults: 15-30 mL followed immediately with 240 mL
                                        of water.
                                      • Children 1-12 years: 15 mL preceded or followed by 120 to 240
                                        mL of water.
                                      • Infants 6 months to 12 months: 5-10 mL preceded or followed by 120
                                        to 240 mL of water.

                                     Dose may be repeated in all age groups if emesis does not occur within
                                     20-30  minutes.
                                     Position Statement: Ipecac syrup should not be administered routinely
                                 in poisoned  patients. If ipecac is used, it should be administered within 60
                                 minutes of the ingestion. Even then, clinical studies have demonstrated no ben-
                                 efit from its use. It should be considered only in an alert conscious patient who
                                 has ingested a potentially  toxic ingestion. Contraindications to its use  include
                                 the following: patients with diminished airway protective reflexes, the ingestion
                                 of hydrocarbons with a high aspiration potential, the ingestion of a corrosive
                                 substance, or the ingestion of a substance in which advanced life support may
                                 be necessary within the next 60 minutes.15
                                 5.  Seizures
                                     Lorazepam is increasingly being recognized as the drug of choice for status
                                 epilepticus, although there are few reports of its use with certain pesticides.
                                 One must be prepared to assist ventilation with lorazepam and any other medi-
                                 cation used to control seizures. See dosage table on next page.
                                     For organochlorine compounds, use of lorazepam has not been reported
                                 in the literature. Diazepam is often used for this, and is still used in other pesti-
                                 cide poisonings.
                                     Dosage of Diazepam:
                                      • Adults: 5-10 mg IV and repeat every 5-10 minutes to maximum of
                                        30 mg.
                                      • Children: 0.2-0.5 mg/kg IV every 5 minutes to maximum of 10 mg
                                        in children over 5 years and 5 mg in children under 5 years.

    Dosage of Lorazepam:
     • Adults:2-4 mg/dose given IV over 2-5 minutes. Repeat if necessary
       to a maximum of 8 mg in a  12 hour period.
     • Adolescents: Same as adult  dose, except maximum dose is 4 mg.
     • Children under 12years: 0.05-0.10 mg/kg IV over 2-5 minutes. Re-
       peat if necessary .05  mg/kg 10-15 minutes after first dose, with a
       maximum dose of 4 mg.

    Caution: Be prepared to assist  pulmonary ventilation mechanically if
    respiration is depressed, to intubate the trachea if laryngospasm occurs,
    and to counteract hypotensive reactions.
    Phenobarbital is an additional treatment option for seizure control. Dos-
age for  infants, children, and  adults  is 15-20 mg/kg  as  an IV  loading
dose. An additional 5 mg/kg IV may be given every  15-30 minutes to a
maximum of 30 mg/kg. The drug should be pushed no faster than 1  mg/
    For  seizure management, most patients respond well to usual management
consisting of benzodiazepines, or phenytoin and phenobarbital.
1.  Tenenbein M, Cohen S, and Sitar DS. Efficacy of ipecac-induced emesis, orogastric lavage,
   and activated charcoal for acute drug overdose. Ann EmergMed 1987;16:838- 41.
2.  Danel V, Henry IA, and Glucksman E. Activated charcoal, emesis, and gastric lavage in aspi-
   rin overdose. Br Med J 1988;296:1507.
3.  Saetta IP, March S, Gaunt ME, et al. Gastric emptying procedures in the self-poisoned pa-
   tient: Are we forcing gastric content beyond the pylorus? ]R Soc Med 1991;84:274-6.
4  American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical
   Toxicologists. Position statement: Gastric lavage. JToxicol Clin Toxicol 1997;35:711-9.
5.  American Academy of Clinical Toxicology, European Association of Poisons Centres  and
   Clinical Toxicologists. Position statement: Cathartics. JToxicol Clin Toxicol 1997;35:743-52.
6.  American Academy of Clinical Toxicology, European Association of Poisons Centres  and
   ClinicalToxicologists. Position statement: Single-dose activated charcoal. JToxicol Clin Toxicol
7.  Gaudreault P, Friedman PA, and  Lovejoy FH Ir. Efficacy of activated charcoal and magne-
   sium citrate in the treatment of oral paraquat intoxication. Ann Emerg Med 1985;14:123-5.
8.  Terada H, MiyoshiT, Imaki M, et al. Studies on in vitro  paraquat and diquat removal by
   activated carbon. JExp Med 1994;41:31-40.
9.  Merigian KS,Woodward M, Hedges IR, et al. Prospective evaluation of gastric emptying in
   the self-poisoned patient. Am J Emerg Med 1990;8:479-83.
                                                                                                GENERAL PRINCIPLES  • 15

                                         10.  Robertson W Syrup of ipecac: A slow or fast emetic? AJDC 1962;103:136-9.
                                         11.  Curtis RA, Barone J, and Giacona N. Efficacy of ipecac and activated charcoal/cathartic.
                                             Arch Intern Med 1984; 144:48-52.
                                         12.  McNamara RM, Aaron CK, Gemborys M, et al. Efficacy of charcoal cathartic versus ipecac in
                                             reducing serum acetaminophen in a simulated overdose. Ann Emerg Med 1989;18:934-8.
                                         13.  Neuvonen PJ.Vartiainen M, and Tokola O. Comparison of activated charcoal and ipecac
                                             syrup in prevention of drug absorption.  Eur J Clin Pharmacol 1983;24:557-62.
                                         14.  Litovitz  RL, Smilkstein M,  Felberg L, et al. 1996 Annual  Report  of the American
                                             Association of Poison Control CentersToxic Exposure Surveillance System. Am J Emerg Med
                                         15.  American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical
                                             Toxicologists. Position statement: Ipecac syrup. JToxicol ClinToxicol 1997;35:699-709.

Environmental  and
Occupational  History
Pesticide poisonings may go unrecognized because of the failure to take a proper
exposure history. This chapter is intended to remedy this often overlooked area
by providing basic tools for taking a complete exposure history. In some situ-
ations where exposures are complex or multiple and/or symptoms atypical, it is
important to consider consultation with clinical toxicologists or specialists in
environmental and occupational medicine. Local Poison Control Centers should
also be considered when there are questions about diagnosis and treatment.
    Although this manual deals primarily with pesticide-related diseases and
injury, the approach to identifying exposures is similar regardless of the specific
hazard involved. It is important to ascertain whether other non-pesticide ex-
posures are involved because of potential interactions between these hazards
and the pesticide of interest (e.g., pesticide intoxication and heat stress in agri-
cultural field workers) .Thus, the following section on pesticide exposures should
be seen in the context of an overall exposure assessment.
    Most pesticide-related diseases have clinical presentations that are similar
to common medical  conditions and display nonspecific symptoms and physical
signs. Knowledge of a patient's exposure to occupational and environmental
factors is important for diagnostic, therapeutic, rehabilitative and public health
purposes.Thus, it is essential to obtain an adequate history of any environmen-
tal or occupational exposure which could cause disease or exacerbate an exist-
ing medical condition.
    In addition to the appropriate patient history-taking, one must also con-
sider any other persons that may be similarly exposed  in the home, work or
community environment. Each  environmental or occupational disease identi-
fied should be considered a potential sentinel health event which may require
follow-up activities to identify the exposure source and any additional cases. By
identifying and eliminating the exposure source, one can prevent continued
exposure to the initial patient and any other individuals involved.
    Patients with these types of diseases may be seen by health  care providers
that are not familiar with these conditions. If an appropriate history is obtained
and there appears to  be a  suspect environmental or  occupational exposure, the
health care provider can obtain consultation with specialists (e.g., industrial
hygienists, toxicologists, medical specialists, etc.) in  the field of environmental
and occupational health. For the more severe sentinel health events and those
                                                                               ENVIRONMENTAL AND
                                                                               OCCUPATIONAL HISTORY   • 17

                                  that involve numerous exposed individuals, additional assistance can be ob-
                                  tained by contacting the state health department, state regulatory agency (e.g.,
                                  the agriculture department in the case of pesticide illness and injury), or other
                                  related organizations (see list at end of chapter). Furthermore, some states re-
                                  quire reporting of certain  environmental and occupational conditions (e.g.,
                                  pesticide case reporting in Arizona, California,  Florida, Oregon, Texas, and
                                      This chapter reviews the types of questions to be asked in taking an occupa-
                                  tional and environmental history (for both adult and pediatric patients), discusses
                                  legal, ethical, and public health considerations, and lists information resources.
                                  Taking an Exposure  History
                                      Given the time constraints of most health care providers, a few screening
                                  questions are likely to be  preferable to a lengthy questionnaire in identifying
                                  occupational or environmental hazards. The screening questions below could
                                  be incorporated  into an existing  general health questionnaire or  routine
                                  patient interview.
                                     SCREENING QUESTIONS FOR OCCUPATIONAL
                                     AND ENVIRONMENTAL EXPOSURES*
                                     For an adult patient:
                                     After establishing the chief complaint and history of the presenting illness:
                                          •  What kind of work do you do?
                                          •  (if unemployed) Do you think your health problems are related to your home
                                            or other location?
                                          •  (if employed) Do you think your health problems are related to your work? Are
                                            your symptoms better or worse when you are at home or at work?
                                          •  Are you now or have you previously been exposed to pesticides, solvents, or
                                            other chemicals, dusts, fumes, radiation, or loud noise?

                                     For a pediatric patient (questions asked of parent or guardian):
                                          •  Do you think the patient's health problems are related to the home, daycare,
                                            school, or other location?
                                          •  Has there been any exposure to pesticides, solvents or other chemicals, dusts,
                                            fumes,  radiation, or loud noise?
                                          •  What kind of work do the parents or other household members engage in?
                                  If the clinical presentation or initial medical history suggests a potential occu-
                                  pational or environmental exposure, a detailed exposure interview is needed.
                                  An extensive exposure history provides a more complete picture of pertinent
                                  exposure factors and can take up to an hour. The detailed interview includes
                                  questions on occupational  exposure, environmental exposure, symptoms and
                                  medical conditions, and non-occupational exposure potentially related to ill-
                                  ness or injury. Although the focus is on pesticide exposures and related health

effects, concurrent non-pesticide exposures need to be considered in the over-
all patient health assessment. Questions typical of a detailed interview are listed
on the next several pages, preceded by special concerns in addressing exposures
of children and agricultural workers. For further details on taking a history for
all types of occupational and environmental hazards, consult the ATSDR mono-
graph entitled "Taking an Exposure History"1  or a general occupational and
environmental medicine reference text.2
Special  Patient Populations

    In comparison to adults, children may be at greater risk from pesticide
exposures due to growth and developmental factors. Consideration of fetal,
infant, toddler or child characteristics is helpful in an exposure evaluation: physical
location, breathing zones, oxygen consumption, food consumption, types of
foods consumed and normal behavioral development.3 Furthermore, transpla-
cental absorption and breast milk may pose additional routes of exposure. Al-
though environmental  (and, at times, occupational)  exposure to pesticides is
the focus of this chapter, the  most significant hazard for children is uninten-
tional ingestion.4  Thus, it is very important to ask about pesticides used and
stored in the home, day care facility, school, and play  areas.

Agricultural Workers
    Data from California's mandatory pesticide poisoning reporting system would
imply an annual national estimate of 10,000-20,000 cases of farmworker poison-
ing.5 However, it is believed that these figures still represent serious underreporting
due to the  lack of medical access for many farmworkers and misdiagnosis by
some clinicians. For these high-risk patients, the exposure history should include
specific questions about the agricultural work being done. For example:
    •   Are pesticides being used at home or work?
    •   Were the fields wet when you were picking?
    •   Was any spraying going on while you were working in the fields?
    •   Do you get sick during or after working in the fields?
The use of pesticides in the residence and taking home agricultural pesticides or
contaminated work clothes  that are not properly separated from other clothes
may pose hazards for other household members as well.
Obtaining Additional Pesticide Information
    In addition to the patient history, it is often helpful to obtain further infor-
mation on suspect pesticide products.Two documents are useful starting points
                                                                                  ENVIRONMENTAL AND
                                                                                  OCCUPATIONAL HISTORY   • 19

                   (Questions marked in bold type are especially important for a pesticide exposure history)

                   (1)  Adult Patient
                   OCCUPATIONAL EXPOSURE
                        •  What is your occupation? (If unemployed, go to next section)
                        •  How long have you been doing this job?
                        •  Describe your work and what hazards you are exposed to (e.g., pesticides, solvents or other
                          chemicals, dust, fumes, metals, fibers, radiation, biologic agents, noise, heat, cold, vibration)
                        •  Under what circumstances do you use protective equipment? (e.g., work clothes, safety glasses,
                          respirator, gloves, and hearing  protection)
                        •  Do you smoke or eat at the worksite?
                        •  List previous jobs in chronological order, include full and part-time, temporary, second jobs,
                          summer jobs, and military experience. (Because this question can take a long time to answer, one
                          option is to ask the patient to fill out a form with this question on it prior to the formal history taking by
                          the clinician. Another option is to take a shorter history by asking the patient to list only the prior jobs
                          that involved the agents of interest. For example, one could ask for all current and past jobs involving
                          pesticide exposure.)
                        •  Are pesticides (e.g., bug or weed killers, flea and tick sprays, collars, powders, or shampoos)
                          used in your  home or garden or on your pet?
                        •  Do you or any household member have a hobby with exposure to any hazardous materials (e.g.,
                          pesticides,  paints, ceramics, solvents, metals, glues)?
                        •  If pesticides are used:
                          •  Is a licensed pesticide applicator involved?
                          •  Are children allowed to play in areas recently treated with pesticides?
                          •  Where are the pesticides stored?
                          •  Is food handled properly (e.g., washing of raw fruits and vegetables)?
                        •  Did you ever  live near a facility which could have contaminated the surrounding area (e.g., mine,
                          plant, smelter, dump site)?
                        •  Have you ever changed your residence because of a health problem?
                        •  Does your drinking water come from a private well, city water supply, and/or grocery store?
                        •  Do you work on your car?
                        •  Which of the following do you have in your home: air conditioner/purifier, central heating (gas or oil), gas stove,
                          electric stove, fireplace, wood stove, or humidifier?
                        •  Have you recently acquired new furniture or carpet, or remodeled your home?
                        •  Have you weatherized your home recently?
                        •  Approximately what year was your home built?
                          (If employed)
                          • Does the timing of your symptoms have any relationship to your work hours?
                          • Has anyone else at work suffered the same or similar problems?
                        •  Does the timing of yoursymptoms have any relationship to environmental activities listed above?
                        •  Has any other household member or nearby neighbor suffered similar health problems?

     • Do you use tobacco? If yes, in what forms (cigarettes, pipe, cigar, chewing tobacco)? About how many
       do you smoke or how much tobacco do you use per day? At what age did you start using tobacco? Are
       there other tobacco smokers in the home?
     • Do you drink alcohol? How much per day or week? At what age did you start?
     • What medications or drugs are you taking? (Include prescription and non-prescription uses)
     • Has anyone in the family worked with hazardous materials that they might have brought home
       (e.g., pesticides, asbestos, lead)? (If yes, inquire about household members potentially exposed.)
(2)  PedJatrJC Patient (questions asked of parent or guardian)
     • What is your occupation and that of other household members?  (If no employed individuals, goto
       next section)
     • Describe your work and what hazards you are exposed to (e.g., pesticides, solvents or other
       chemicals, dust, fumes, metals, fibers, radiation, biologic agents, noise, heat, cold, vibration)
     • Are pesticides (e.g., bug or weed killers, flea and tick sprays, collars, powders, or shampoos)
       used in your home or garden or on your pet?
     • Do you or any household member have a hobby with exposure to any hazardous materials (e.g.,
       pesticides, paints, ceramics, solvents, metals, glues)?
     • If pesticides are used:
       •  Is a licensed pesticide applicator involved?
       •  Are children allowed to play in areas recently treated with pesticides?
       •  Where are the pesticides stored?
       •  Is food handled properly (e.g., washing of raw fruits and vegetables)?
     • Has the patient ever lived near a facility which could have contaminated the surrounding area
       (e.g., mine, plant, smelter, dump site)?
     • Has the patient ever changed residence because of a health problem?
     • Does the patient's drinking water come from a private well, city water supply, and/or grocery
     • Which of the following are in the patient's home: air conditioner/purifier, central heating (gas or oil), gas stove,
       electric stove, fireplace, wood stove, or humidifier?
     • Is there recently acquired new furniture or carpet, or recent home remodeling in the patient's home?
     • Has the home been weatherized recently?
     • Approximately what year was the home built?
     • Does the timing of symptoms have any relationship to environmental activities listed above?
     • Has any  other household member or nearby neighbor suffered similar health problems?
     • Are there tobacco smokers in the home? If yes, in what forms (cigarettes, pipe, cigar, chewing tobacco)?
     • What medications or drugs is the patient taking? (Include prescription and non-prescription uses)
     • Has anyone in the family worked with hazardous materials that they might have brought home
       (e.g., pesticides, asbestos, lead)? (If yes, inquire about household members potentially exposed.)
                                                                                           ENVIRONMENTAL AND
                                                                                           OCCUPATIONAL HISTORY
•  21

                                 in the identification and evaluation of the pesticide exposure: the material safety
                                 data sheet (MSDS) and the pesticide label.

                                     •   Material Safety Data Sheet (MSDS). Under OSHA's Hazard
                                         Communications Standard (29 CFR 1910.1200), all chemical manu-
                                         facturers are required to provide an MSDS for each hazardous chemi-
                                         cal they produce or import. Employers are required to keep copies
                                         of MSDSs and make them available to the workers. The following
                                         items are contained in an MSDS:
                                         - Material identification
                                         - Ingredients and occupational exposure limits
                                         - Physical  data
                                         - Fire and explosion data
                                         - Reactivity data
                                         - Health hazard data
                                         - Spill, leak, and disposal procedures
                                         - Special protection data
                                         - Special precautions and comments.

                                         These documents tend to have very limited information on health
                                         effects and  some of the active ingredients may be omitted due  to
                                         trade secret considerations. One cannot rely solely on an MSDS  in
                                         making medical determinations.
                                     •   Pesticide label. EPA requires that all pesticide products bear labels
                                         that provide certain information.This information can help in evalu-
                                         ating pesticide health effects and necessary precautions. The items
                                         covered include the following:
                                         - Product  name
                                         - Manufacturer
                                         - EPA registration number
                                         - Active ingredients
                                         - Precautionary statements:
                                           i.  Human hazard  signal words "Danger" (most hazardous),
                                               "Warning," and "Caution" (least hazardous)
                                           ii.  Child hazard warning
                                           iii. Statement of  practical treatment  (signs and symptoms  of
                                               poisoning, first aid, antidotes, and note to physicians in the
                                               event of a poisoning)
                                           iv.  Hazards to humans and domestic animals
                                           v.  Environmental hazards
                                           vi. Physical or chemical hazards

        -  Directions for use
        -  Name and address of manufacturer
        -  Net contents
        -  EPA registration number
        -  EPA establishment number
        -  Worker Protection Standard (WPS) designation, including re-
          stricted entry interval and personal protection equipment required
          (see WPS description on page 25).
        The EPA registration number is useful when contacting EPA for infor-
        mation or when calling the National Pesticide Telecommunications
        Network hotline (see page 29). Pesticide labels may differ from one
        state to another based  on area-specific considerations. Also, different
        formulations of the same active ingredients may result in different label
        information.The pesticide label lists information only for active ingre-
        dients (not for inert components) and rarely contains information on
        chronic health effects (e.g., cancer and neurologic, reproductive, and
        respiratory diseases) .6 Although further pesticide  information is often
        needed, these documents should be considered as the first step in iden-
        tifying and understanding the health effects of a given pesticide.
          For the agricultural worker  patient, the health care provider has
        two legal bases — the EPA Worker Protection Standard and USDA
        regulations under the 1990 Farm Bill — for  obtaining from the
        employer the pesticide product name to which the patient was ex-
        posed.When requesting this information, the clinician  should keep
        the patient's name confidential whenever possible.

Assessing  the Relationship of
Work or Environment to Disease
    Because pesticides and other chemical and physical hazards are often asso-
ciated with nonspecific medical complaints, it is very important to  link the
review of systems with the timing of suspected exposure to the hazardous agent.
The Index of Signs and Symptoms in Section V provides a quick reference to
symptoms and medical conditions associated with specific pesticides. Further
details on  the  toxicology, confirmatory tests, and treatment of illnesses related
to pesticides are provided in each chapter of this manual. A general understand-
ing of pesticide classes and some  of the more common agents is helpful in
making a pesticide related disease diagnoses.
    In evaluating the association of a given pesticide exposure in the workplace
or environment and a clinical condition, key factors to consider are:
    •   Symptoms and  physical signs  appropriate for  the pesticide being
                                                                                   ENVIRONMENTAL AND
                                                                                   OCCUPATIONAL HISTORY   •  23

                                     •   Co-workers or others in the environment who are ill
                                     •   Timing of the problems
                                     •   Confirmation of physical exposure to the pesticide
                                     •   Environmental monitoring data
                                     •   Biomonitoring results
                                     •   Biological plausibility of the resulting health effect
                                     •   Ruling out non-pesticide exposures or pre-existing illnesses.

                                     A concurrent non-pesticide exposure can either have no health effect, ex-
                                 acerbate an existing pesticide health effect, or solely cause the health effect in a
                                 patient. In the more complicated exposure scenarios, assistance should be sought
                                 from specialists in occupational and environmental health (see Information Re-
                                 sources on page 27).

                                 Legal, Ethical, and Public  Health Considerations
                                     Following  are some considerations  related to  government regulation of
                                 pesticides, ethical factors, and public health concerns that health care providers
                                 should be aware of in assessing a possible pesticide exposure.

                                 Reporting Requirements
                                     When evaluating a patient with a pesticide-related medical condition, it
                                 is important to understand the state-specific reporting requirements for the
                                 workers' compensation system (if there has been an  occupational exposure)
                                 or surveillance system. Reporting a workers' compensation  case can have
                                 significant implications for the worker being evaluated. If the clinician is not
                                 familiar with this system or is uncomfortable evaluating work-related health
                                 events, it is important to seek an occupational medicine consultation or make
                                 an appropriate referral.
                                     At least six states have surveillance systems within their state health depart-
                                 ments that cover both occupational and environmental pesticide poisonings: Cali-
                                 fornia, Florida, New York, Oregon, Texas, and Washington. These surveillance
                                 systems collect case reports on pesticide-related illness and injury from clinicians
                                 and other sources; conduct selected interviews, field  investigations, and research
                                 projects; and function as a resource for pesticide information within their state. In
                                 some states, as noted earlier, pesticide case reporting is legally mandated.

                                 Regulatory Agencies
                                     Since its formation in 1970, EPA has been the lead agency for the regula-
                                 tion of pesticide use under the Federal Insecticide, Fungicide and Rodenticide
                                 Act. EPA's mandates include the registration of all  pesticides used in the United
                                 States, setting restricted entry intervals, specification and approval  of label in-

formation, and setting acceptable food and water tolerance levels. In addition,
EPA works in partnership with state and tribal agencies to implement two field
programs  — the certification and training program for pesticide  applicators
and the agricultural worker protection standard — to protect workers and
handlers from pesticide exposures. EPA sets national standards for certification
of over 1 million private  and commercial pesticide applicators.
    The authority to enforce EPA regulations is delegated  to  the states. For
example, calls concerning non-compliance with the worker protection stan-
dard can typically be made to the state agricultural department. In five states,
the department  of the environment  or other state agency  has enforcement
authority. Anonymous calls can be made if workers anticipate possible retalia-
tory action by management. It should be noted that not all state departments of
agriculture have similar regulations. In California, for instance,  employers are
required to obtain medical supervision and biological monitoring  of agricul-
tural workers who apply pesticides containing cholinesterase-inhibiting com-
pounds. This requirement is not found in the federal regulations.
    Outside  the agricultural setting, the Occupational Safety and Health
Administration (OSHA) has jurisdiction over workplace exposures. All workers
involved in pesticide manufacturing would be  covered by OSHA. OSHA sets
permissible exposure levels for selected pesticides. Approximately half the states
are covered by the federal OSHA; the rest have their own state-plan OSHA.
Individual state plans may choose to be more protective in setting their workplace
standards.  Anonymous calls can also be made to either state-plan or federal
OSHA agencies.
    For pesticide contamination in water, EPA sets enforceable  maximum
containment levels. In food and drug-related outbreaks, EPA works jointly with
the Food and Drug Administration (FDA)  and the  U.S. Department  of
Agriculture (USDA)  to monitor  and regulate pesticide residues and their
metabolites. Tolerance limits are established  for many pesticides and their
metabolites in raw agricultural commodities.
    In evaluating a patient with pesticide exposure, the clinician may need
to report a pesticide intoxication to the appropriate health and/or regulatory

Worker Protection Standard
    EPA s Worker Protection Standard (WPS)  became fully effective  in  1995.
The intent of the regulation is to eliminate or reduce pesticide exposure, mitigate
exposures that occur, and  inform  agricultural workers about the hazards  of
pesticides. The WPS applies to two types of workers in the farm, greenhouse,
nursery, and forest industries: (1) agricultural pesticide handlers  (mixer, loader,
applicator, equipment cleaner or repair person, and flagger), and (2) field workers
(cultivator or harvester).
    The WPS includes requirements that agricultural employers notify workers
about pesticide treatments in advance, offer basic pesticide safety training, provide
                                                                                   ENVIRONMENTAL AND
                                                                                   OCCUPATIONAL HISTORY   • 25

                                   personal  protective equipment for direct  work  with pesticides, and observe
                                   restricted entry interval (REI) times. (The REI is a required waiting period before
                                   workers can return to areas treated with pesticides.)  Of special interest to health
                                   care providers, the WPS also requires agricultural employers to:
                                       •   Post an emergency medical facility address and phone number in a
                                          central location.
                                       •   Arrange immediate transport from the agricultural establishment to
                                          a medical facility for a pesticide-affected worker.
                                       •   Supply the affected worker and medical personnel with product name,
                                          EPA registration number, active ingredient, label medical information,
                                          a description of how the pesticide was used, and exposure information.

                                   Ethical  Considerations
                                       Attempts to investigate an occupational pesticide exposure may call for ob-
                                   taining further information from the worksite manager or owner. Any contact
                                   with the worksite should be taken in consultation with the patient because of the
                                   potential  for retaliatory actions (such as loss of job or pay cuts). Ideally, a request
                                   for a workplace visit or more information about pesticide exposure at the work-
                                   place will occur with the patients agreement. In situations  where  the health
                                   hazard  is  substantial and many individuals might be affected, a call to a state
                                   pesticide  surveillance system (if available), agricultural health and safely center (if
                                   nearby), can provide the National Institute  for Occupational Safety and Health
                                   (NIOSH) or state agricultural agency the  assistance needed  for a disease out-
                                   break investigation.
                                       Similarly, the discovery of pesticide contamination in a  residence, school,
                                   daycare setting, food  product, or other environmental site or product can have
                                   public health, financial, and  legal consequences for  the patient and other indi-
                                   viduals (e.g., building owner, school district, food  producer). It is prudent to
                                   discuss these situations and follow-up options with the patient as well as a knowl-
                                   edgeable  environmental health specialist and appropriate state or local agencies.

                                   Public Health Considerations
                                       Health care providers are often the first to identify a sentinel health event that
                                   upon further investigation develops into  a full-blown disease outbreak. A disease
                                   outbreak  is defined as a statistically elevated  rate  of disease among a well-defined
                                   population as compared to a standard population. For example, complaints about
                                   infertility  problems among workers at a dibromochloropropane (DBCP) manufac-
                                   turing plant in California led to diagnoses of azoospermia (lack of sperm) or oli-
                                   gospermia (decreased sperm count) among a handful of otherwise healthy young
                                   men working at the plant.7 An eventual disease outbreak investigation resulted in the
                                   first published report of a male reproductive toxicant in the workplace. At the time,
                                   DBCP  was used as a nematocide; it has since been banned in the United States.
                                       Disease outbreak investigations are conducted for all kinds of exposures

and health events, not only those in the occupational and environmental area.
Usually, assistance from government or university experts is needed in the in-
vestigation, which may require access to information, expertise, and resources
beyond that  available to the average clinician. The steps involved in such an
investigation and the types of information typically gathered in the preliminary
clinical stages are outlined below.The clinician must be aware that an outbreak
investigation may be needed when a severe and widespread exposure  and dis-
ease scenario exists. For more  information on disease outbreak investigations,
consult the literature.8'9

     •  Confirm diagnosis of initial case reports (the "index" cases)
     •  Identify other unrecognized cases
     •  Establish a case definition
     •  Characterize cases by person, place, and time characteristics (e.g., age, race, ethnicity, gen-
       der, location within a company or a neighborhood, timeline of exposure and health events)
     •  Create plot of case incidence by time (an epidemic curve)
     •  Determine if a dose-response relationship exists (i.e., more severe clinical case presen-
       tation for individuals with higher exposures)
     •  Derive an attack rate and determine if statistical significance is achieved (divide num-
       ber of incident cases by number of exposed individuals and multiply by 100 to obtain
       attack rate percentage)
Information Resources

Government Agencies:

EPA Office of Pesticide Programs
Overall pesticide regulation with special programs on agricultural workers and
pesticide applicators. Specific programs include the promotion of the reduc-
tion of pesticide use, establishment of tolerance levels for food, and investiga-
tion of pesticide releases and exposure events.

Address:      EPA - Office of Pesticide Programs
             401 M Street SW (7501C)
             Washington, DC  20460
Telephone:   703-305-7090
Web site:     www.epa.gov/pesticides

EPA - Certification and Worker Protection Branch
Within the Office of Pesticide Programs, the Certification and Worker Protec-
tion Branch addresses worker-related pesticide issues and pesticide applicator
certification activities. Special emphasis is placed on the adequate training of
farm workers, pesticide applicators, and health care providers. Various training
                                                                                      ENVIRONMENTAL AND
                                                                                      OCCUPATIONAL HISTORY    • 27

                                 materials in several languages are available.
                                 Address:     EPA - OPP
                                             401  M Street SW (7506C)
                                             Washington, DC 20460
                                 Telephone:  703-305-7666
                                 Web site:    www.epa.gov/pesticides/safety

                                 Occupational Safety and Health Administration (OSHA)
                                 More than 100 million workers and 6.5 million employers are covered under
                                 the  Occupational Safety and Health Act, which covers workers in pesticide
                                 manufacturing as  well as other industries. OSHA and its state partners have
                                 approximately 2100 inspectors, plus investigators, standards writers, educators,
                                 physicians, and other staff in over 200 offices across the country. OSHA sets
                                 protective  workplace standards, enforces the standards, and offers employers
                                 and employees technical assistance and consultation programs. Note that some
                                 states have their own OSHA plan.

                                 Address:     OSHA - US DDL
                                             Room N3647
                                             Constitution Ave NW
                                             Washington, DC 20210
                                 Telephone:  202-219-8021
                                 Web site:    www.osha.gov

                                 Food and Drug Administration (FDA)
                                 Drug and food pesticide issues.
                                 Address:     FDA
                                             National Center for Toxicological Research
                                             5600 Fishers Lane
                                             Rockville, MD 20857
                                 Telephone:  301-443-3170
                                 Internet:    gopher.nctr.fda.gov

                                 USDA Extension Service
                                 USDA's Extension Service works with its university partners, the state land-
                                 grant system, to  provide  farmers and ranchers information to reduce and
                                 prevent agricultural-related work incidents. The Pesticide Applicator Training
                                 program trains applicators in the  safe  use of pesticides and coordinates
                                 pesticide-related safety training programs.
                                 Address:     USDA
                                             14th & Independence SW
                                             Washington, DC 20250
                                 Telephone:  202-720-2791
                                 Web site:    www.reeusda.gov

National Center for Environmental Health (NCEH),
Centers for Disease Control (CDC)
NCEH provides expertise in environmental pesticide case surveillance and dis-
ease outbreak investigations.

Address:     NCEH, CDC
            Mailstop F29
            4770 Buford Highway NE
            Atlanta, GA 30341
Tel:         770-488-7030
Web site:    www.cdc.gov/nceh/ncehhome.htm

National Institute for Occupational Safety and Health (NIOSH),
Centers for Disease Control (CDC)
NIOSH is the federal agency responsible for conducting research on occupational
disease and injury. NIOSH may investigate potentially hazardous working condi-
tions upon request, makes recommendations on preventing workplace disease and
injury, and provides training to occupational safely and health professionals.
Address:     NIOSH
            Humphrey Building, Room 715H
            200 Independence Ave SW
            Washington, DC 20201
Hotline:      1-800-356-4674
Web site:    www.cdc.gov/niosh/homepage.html

NIOSH Agricultural Health and Safety Centers
NIOSH has funded eight Agricultural Health and Safety Centers throughout
the country which involve clinicians and other health specialists in the area of
pesticide-related illness and  injury.The NIOSH-supported centers are:
University of California Agricultural
Health and Safety Center
Old Davis Road
University of California
Davis, CA 95616
Tel: 916-752-4050

High  Plains Intermountain Center
for Agricultural Health and Safety
Colorado State University
Fort Collins, CO 80523
Tel: 970-491-6152
Great Plains Center for Agricultural
University of Iowa
Iowa City, IA 52242
Tel: 319-335-4415

Southeast Center for Agricultural
Health and Injury Prevention
University of Kentucky
Department of Preventive Medicine
Lexington, KY 40536
Tel: 606-323-6836
                                                                                 ENVIRONMENTAL AND
                                                                                 OCCUPATIONAL HISTORY   • 29

                                 Northeast Center  for Agricultural
                                 and Occupational Health
                                 One Atwell Road
                                 Cooperstown, NY  13326
                                 Tel: 607-547-6023

                                 Southwest Center  for Agricultural
                                 Health, Injury and Education
                                 University of Texas
                                 Health Center at Tyler
                                 PO Box 2003
                                 Tyler,TX 75710
                                 Tel: 903-877-5896
                  Pacific Northwest Agricultural Safety
                  and Health Center
                  University of Washington
                  Department of Environmental Health
                  Seattle, WA 98195
                  Tel: 206-543-0916

                  Midwest Center for Agricultural
                  Research, Education and Disease and
                  Injury Prevention
                  National Farm Medicine Center
                  Marshfield,WI 54449-5790
                  Tel: 715-389-3415
                                 Non-Governmental Organizations:
                                 National Pesticide Telecommunications Network
                                 The National Pesticide Telecommunications Network  (NPTN) is based  at
                                 Oregon State University and is cooperatively sponsored by the University and
                                 EPA. NPTN serves as a source of objective, science-based pesticide informa-
                                 tion on a wide range of pesticide-related topics, such as recognition  and man-
                                 agement of pesticide poisonings, safety information, health and environmental
                                 effects, referrals for investigation of pesticide incidents and emergency treat-
                                 ment for both humans and animals, and cleanup and disposal procedures.
                                    A toll-free telephone service  provides pesticide information to callers  in
                                 the continental United States, Puerto Rico, and the Virgin Islands. Additionally,
                                 pesticide questions and comments can be sent to an e-mail address. The Web
                                 site has links to other sites and databases for further information.
                                 NPTN hotline:       1-800-858-7378
                                 Hours of operation:   9:30 am - 7:30 pm E.S.T daily except holidays
                                 Web site:            http://ace.orst.edu/info/nptn/
                                 E-mail address:       nptn@ace.orst.edu

                                 Farmworker Justice Fund
                                 The Farmworker Justice Fund can provide an appropriate referral to a network of
                                 legal services and nonprofit groups which represent farmworkers for free.
                                 E-mail address:
 Farmworker Justice Fund
1111 19th Street, NW, Suite 1000
Washington, DC 20036

American Farm Bureau Federation
The AFBF is the nation's largest general farm organization. Information on how
to contact individual state-based farm bureaus  is available on their Web site.
Web site:     www.fb.com

Association of Occupational and  Environmental Clinics (AOEC)
This association is a network of 63 clinics representing more than 250 specialists.
Address:     AOEC
             1010 Vermont Ave, NW, Suite 513
             Washington, DC 20005
Telephone:   202-347-4976
Web site:

Poison Control Centers
For a list of state and regional poison control centers, or the nearest location,
consult the NPTN Web site (http://ace.orst.edu/info/nptn).

Pesticide Information Databases:
Extension Toxicology Network  (EXTOXNET)
http://ace.ace. orst. edu/info/extoxnet
The Extension Service's Toxicology Network, EXTOXNET, provides science-
based information about pesticides to health care providers treating pesticide-
related  health concerns.  Pesticide toxicological information is developed
cooperatively by the University of California-Davis, Oregon State University,
Michigan State University, Cornell  University, and the University of Idaho.

www. epa.go v/ngispgm 3/iris
The Integrated Risk Information System - IRIS - is an electronic database, main-
tained by  EPA, on human health effects that may result from exposure to various
chemicals in the environment. IRIS is intended for those without extensive training
in toxicology, but with some knowledge of health sciences. It provides hazard iden-
tification and dose-response assessment information. Combined with specific expo-
sure information, the data in IRIS can  be used for  characterization of the public
health risks of a chemical in a particular situation that can lead to a risk management
decision designed to  protect public health. Extensive supporting documentation
available online.
                                                                                   ENVIRONMENTAL AND
                                                                                   OCCUPATIONAL HISTORY   • 31

                                      Agency for Toxic Substances  and Disease Registry
                                      ATSDR (part of the Department of Human Health and Services) publishes
                                      fact sheets and other information on pesticides and other toxic substances.

                                      California  Pesticide Databases
                                      http://www. cdpr. ca.gov/docs/database/database.htm
                                      Includes Pesticidal Chemical Ingredients Queries, links to EPA s Officeof Pesticide
                                      Programs chemical dictionary, Product/Label Database Queries (updated nightly),
                                      a current listing of California's Section 18 Emergency Exemptions, and more.

                                      1.  Frank A and Balk S. ATSDR Case Studies in Environmental Medicine #26, Taking an
                                         Exposure History. Atlanta: Agency forToxic Substances and Disease Registry, Oct. 1992.
                                      2.  LaDou J. Approach to the diagnosis  of occupational illness. In: LaDou J (ed). Occupational
                                         and Environmental Medicine, 2nd ed. Stamford, CT: Appleton and Lange, 1997.
                                      3.  Bearer C. Chapter 10: Pediatric developmental toxicology. In: Brooks SM, Gochfield M.Herzstein
                                         J, et al. Environmental Medicine. St. Louis, MO: Mosby Yearbook, 1995, pp. 115-28.
                                      4.  Jackson RJ. Chapter 31: Hazards of pesticides to children. Ibid, pp. 377-82.
                                      5.  Blondell JM. Epidemiology of pesticide poisonings in the United States, with special refer-
                                         ence to occupational cases. In: Keifer MC (ed). Human Health Effects of  Pesticides, Occu-
                                         pational Medicine: State of the Art Reviews, Philadelphia: Hanley &  Belfus, Inc., 1997.
                                      6.  Keifer MC (ed). Ibid.
                                      7.  Osorio, AM. Chapter 26: Male reproductive toxicology. In: LaDou J (ed), op. cit.
                                      8.  Brooks SM, Gochfield M, Herzstein  J, et al. Environmental Medicine. St. Louis, MO: Mosby
                                         Yearbook, 1995.
                                      9.  Steenland  K. Case Studies in Occupational Epidemiology. New York: Oxford University
                                         Press, 1993.

    Section II

                                   CHAPTER 4

•  Acts through
   phosphorylation of the
   acetylcholinesterase enzyme
   at nerve endings
•  Absorbed by inhalation,
   ingestion, and skin
•  Muscarinic, nicotinic & CNS

Signs and Symptoms:
•  Headache, hypersecretion,
   muscle  twitching, nausea,
•  Respiratory depression,
   seizures, loss of
•  Miosis is often a helpful
   diagnostic sign

•  Clear airway, improve tissue
•  Administer atropine sulfate
•  Pralidoxime may be
•  Proceed concurrently with
•  Morphine, succinylcholine,
   phenothiazines, reserpine
Organophosphate  Insecticides
Since the removal of organochlorine insecticides from use, organophosphate
insecticides have become the most widely used insecticides available today. More
than forty of them are currently registered for use and all run the risk of acute
and subacute toxicity. Organophosphates are used in agriculture, in the home,
in gardens,  and in veterinary practice. All apparently share a common mecha-
nism of cholinesterase inhibition and can cause similar symptoms. Because they
share this mechanism, exposure to the same organophosphate by multiple routes
or to multiple Organophosphates by multiple routes can lead to serious additive
toxicity. It is important to understand, however, that there is a wide range of
toxicity in  these agents and wide  variation in cutaneous absorption, making
specific identification and management quite important.
    Organophosphates poison insects and mammals primarily by phosphory-
lation of the acetylcholinesterase enzyme (AChE) at nerve endings.The result
is a loss of available AChE so that the effector organ becomes overstimulated by
the excess acetylcholine (ACh, the impulse-transmitting substance) in the nerve
ending.The enzyme is critical to normal control of nerve impulse transmission
from nerve fibers to smooth and  skeletal muscle cells, glandular cells, and
autonomic ganglia, as well as within the central nervous system (CNS). Some
critical proportion of the tissue enzyme mass must be inactivated by phospho-
rylation before symptoms and signs of poisoning become manifest.
    At sufficient dosage, loss of enzyme function allows accumulation of ACh
peripherally at cholinergic neuroeffector junctions (muscarinic effects), skeletal
nerve-muscle junctions, and autonomic  ganglia (nicotinic effects), as well as
centrally. At cholinergic  nerve junctions with smooth muscle and gland cells,
high ACh concentration causes muscle contraction and secretion, respectively.
At skeletal muscle junctions, excess ACh may be excitatory (cause muscle twitch-
ing), but may also weaken or paralyze the  cell by depolarizing the end-plate. In
the CNS, high ACh concentrations cause sensory and behavioral disturbances,
incoordination, depressed motor function, and respiratory depression. Increased
pulmonary secretions coupled with respiratory failure are the usual causes of
death from organophosphate poisoning. Recovery depends ultimately on gen-
eration of new enzyme in all critical tissues.


ace p hate
azinphos- methyl*
E-Z-Off D
VC-13 Nemacide
Pestox XIV
ethyl parathion*
Easy off-D
methyl parathion*
methyl trithion
Pestox XV
oxydemeton- methyl
G 28029

propyl thiopyro-
tetraethyl pyrophos-

+ Indicates high toxicity. Highly
toxic organophosphates have
listed oral LD50 values (rat) less
than or equal to 50 mg/kg body
weight. Most other organo-
phosphates included in this table
are considered moderately toxic,
with LD50 values in excess of 50
mg/kg and less than 500 mg/kg.

                                     Organophosphates are efficiently absorbed by inhalation, ingestion, and skin
                                  penetration. There is considerable variation in the relative absorption by these
                                  various routes. For instance, the oral LD5Q of parathion in rats is between 3-8 mg/
                                  kg, which is quite toxic,1-2 and essentially equivalent to dermal absorption with
                                  an LD5Q of 8 mg/kg.2 On the other hand, the toxicity of phosalone is much
                                  lower from the dermal route than the oral route, with rat LD5Qs of 1500  mg/kg
                                  and 120 mg/kg, respectively.2 In general, the highly toxic agents are more likely
                                  to have high-order dermal toxicity than the moderately toxic agents.

                                     Chemical Classes: To some degree, the  occurrence of poisoning depends
                                  on the rate at which the pesticide  is absorbed. Breakdown occurs  chiefly by
                                  hydrolysis in the liver; rates of hydrolysis vary widely from one compound to
                                  another. In the case of certain Organophosphates whose breakdown is relatively
                                  slow,  significant temporary storage in body fat may occur. Some Organophos-
                                  phates such as diazinon and methyl parathion have significant lipid solubility,
                                  allowing fat storage with delayed toxicity due to late release.3 Delayed toxicity
                                  may  also  occur atypically  with  other Organophosphates,  specifically
                                  dichlorofenthion and demeton-methyl.4 Many organothiophosphates  readily
                                  undergo conversion from thions (P=S) to oxons (P=O). Conversion occurs in
                                  the environment under the influence  of oxygen and  light, and in the body,
                                  chiefly by the action of liver microsomes. Oxons are  much more toxic than
                                  thions, but oxons break down more readily. Ultimately, both thions and oxons
                                  are hydrolyzed at the ester linkage, yielding alkyl phosphates and leaving groups,
                                  both  of which are of relatively low toxicity. They are either excreted or  further
                                  transformed in the body before excretion.
                                     The distinction between the different chemical classes becomes important
                                  when the physician interprets tests from reference laboratories.This can be espe-
                                  cially important when the lab analyzes for the parent compound (i.e., chlorpyrifos
                                  in its thiophosphate form) instead of the  metabolite form  (chlorpyrifos  will be
                                  completely metabolized to the oxon after the  first pass through the liver).
                                     Within one or two days of initial organophosphate binding to AChE, some
                                  phosphorylated acetylcholinesterase enzyme  can be de-phosphorylated (reac-
                                  tivated)  by the oxime  antidote pralidoxime. As time progresses, the enzyme-
                                  phosphoryl bond is strengthened by loss of one alkyl group from the phosphoryl
                                  adduct, a process called aging. Pralidoxime reactivation is therefore  no longer
                                  possible after a couple of days,5 although in some cases, improvement has still
                                  been seen with pralidoxime administration days after exposure.6

                                     OPIDN: Rarely, certain Organophosphates have caused a different kind of
                                  neurotoxicity consisting of damage to the afferent fibers of peripheral and cen-
                                  tral nerves and associated with inhibition of "neuropathy target esterase" (NTE).
                                  This  delayed syndrome has been termed organophosphate-induced delayed
                                  neuropathy (OPIDN), and is manifested chiefly by weakness or paralysis  and
                                  paresthesia of the extremities.7 OPIDN predominantly affects the legs and may

persist for weeks to years.These rare occurrences have been found shortly after
an acute and often massive exposure, but in some cases, symptoms have per-
sisted for months to years. Only a few of the many organophosphates used as
pesticides have been implicated as causes of delayed neuropathy in humans.
EPA guidelines require that organophosphate and carbamate compounds which
are candidate pesticides be tested in susceptible animal species for this neuro-
toxic property.
    Three epidemiologic studies with an exposed group and a control group
also suggest that a proportion of patients acutely poisoned from any organo-
phosphate can experience some long-term neuropsychiatric sequelae. The
findings show significantly worse performance on a battery of neurobehavioral
tests, including memory, concentration, and mood, and  compound-specific
peripheral neuropathy in some cases.These findings are subtle and may some-
times be picked up only on neuropsychologic testing rather than on a neuro-
logic exam.8"10 Follow-ups  of case series have occasionally found  some
individuals reporting  persistent headaches, blurred vision, muscle  weakness,
depression, memory and concentration  problems, irritability, and/or develop-
ment of intolerance to selected chemical odors.11"15

    Intermediate Syndrome: In addition to acute poisoning episodes and
OPIDN, an intermediate syndrome has  been described.This syndrome occurs
after resolution of the acute cholinergic crisis, generally 24-96 hours after ex-
posure. It is characterized by  acute respiratory paresis and  muscular weakness,
primarily in the facial, neck, and proximal limb muscles. In addition, it is often
accompanied by cranial nerve palsies and depressed tendon reflexes. Like OPIDN,
this syndrome lacks muscarinic symptomatology, and appears to result from a
combined pre- and post-synaptic dysfunction of neuromuscular transmission.
Symptoms do not respond well to atropine and oximes; therefore treatment is
mainly supportive.16'17 The most common compounds involved in this syn-
drome are methyl parathion, fenthion, and dimethoate, although one case with
ethyl parathion was also observed.17
    Other specific properties  of individual organophosphates  may render them
more hazardous than basic toxicity data suggest. By-products  can develop in long-
stored malathion which strongly inhibit the hepatic enzymes operative in malathion
degradation, thus enhancing its toxicity. Certain organophosphates are exception-
ally prone to storage in fat tissue, prolonging the need for antidote for several days
as stored pesticide is released back into the circulation. Animal studies have demon-
strated potentiation of effect when two or more organophosphates are absorbed
simultaneously;  enzymes critical to the degradation of one  are inhibited by the
other. Animal studies have also demonstrated a protective effect from phenobar-
bital  which induces hepatic degradation  of the  pesticide.1 Degradation of some
compounds to a trimethyl phosphate can  cause restrictive lung  disease.18
                                                                                       ORGANOPHOSPHATES • 37

                                  Signs and Symptoms of Poisoning
                                     Symptoms of acute organophosphate  poisoning develop during or after
                                  exposure, within minutes to hours, depending on the method of contact. Ex-
                                  posure by inhalation results in the  fastest appearance of toxic symptoms, fol-
                                  lowed by the gastrointestinal route and finally the dermal route. All signs and
                                  symptoms are cholinergic in nature and affect muscarinic, nicotinic, and central
                                  nervous system receptors.5The critical symptoms in management are the respi-
                                  ratory symptoms. Sufficient  muscular fasciculations  and  weakness are often
                                  observed  as to require respiratory  support; respiratory arrest can  occur sud-
                                  denly. Likewise, bronchorrhea and bronchospasm may often impede efforts at
                                  adequate  oxygenation of the patient.
                                     Bronchospasm and  bronchorrhea can occur,  producing tightness in the
                                  chest, wheezing, productive cough, and pulmonary edema. A life threatening
                                  severity of poisoning is signified by loss of consciousness, incontinence, con-
                                  vulsions, and respiratory depression. The primary cause of death is respiratory
                                  failure, and there usually is a secondary cardiovascular component. The classic
                                  cardiovascular sign is bradycardia which can progress to sinus arrest. However,
                                  this may be superseded by tachycardia and hypertension from nicotinic (sym-
                                  pathetic ganglia) stimulation.19 Toxic myocardiopathy has been a prominent
                                  feature of some severe organophosphate poisonings.
                                     Some of the most commonly  reported early symptoms include headache,
                                  nausea, dizziness, and hypersecretion, the latter of which is manifested by sweat-
                                  ing, salivation, lacrimation, and rhinorrhea. Muscle twitching, weakness, tremor,
                                  incoordination, vomiting, abdominal cramps, and diarrhea all signal worsening of
                                  the poisoned state. Miosis is often a helpful diagnostic sign and the patient may
                                  report blurred and/or dark vision. Anxiety and restlessness are prominent, as are a
                                  few reports of choreaform movements. Psychiatric symptoms including depres-
                                  sion, memory loss, and confusion have been reported.Toxic psychosis, manifested
                                  as confusion or bizarre behavior, has been misdiagnosed as alcohol intoxication.
                                     Children will often present with a slightly different clinical picture than adults.
                                  Some of the typical cholinergic signs of bradycardia, muscular fasciculations, lac-
                                  rimation, and sweating were less common. Seizures (22%-25%) and mental status
                                  changes including lethargy and coma (54%-96%)  were common.20'21 In com-
                                  parison, only 2-3% of adults present with seizures. Other common presenting
                                  signs in children include flaccid muscle weakness, miosis, and excessive salivation.
                                  In one study, 80% of cases were transferred with the wrong preliminary diagno-
                                  sis.20 In a second study, 88% of the parents initially denied any exposure history.21
                                     See the preceding Toxicology section  for information regarding the fea-
                                  tures  of the intermediate syndrome and OPIDN.

Confirmation of Poisoning
    If poisoning is probable, treat the patient immediately. Do not wait
for laboratory confirmation.
    Blood samples should be drawn to measure plasma pseudocholinesterase
and red blood cell AChE levels. Depressions of plasma pseudocholinesterase
and/or RBC acetylcholinersterase enzyme activities are generally available bio-
chemical indicators of excessive organophosphate absorption. Certain organo-
   Methods            Plasma    RBC

   pH (Michel)            0.45     0.55

   pH Stat (Nabb-Whitfield)  2.3      8.0

   BMC Reagent Set
     (Ellman-Boehringer)     1,875

   DupontACA           <8

   Garry-Routh (Micro)

   Technicon             2.0      8.0
Male 7.8
Female 5.8
   Whole units

ApH per ml per hr

|iM per ml per min

mU per ml per min

Units per ml

HM-SH per 3mL per min

|iM per ml per min
   * Because measurement technique varies among laboratories, more accurate estimates of
     minimum normal values are usually provided by individual laboratories.
phosphates may selectively inhibit either plasma pseudocholinesterase or RBC
acetylcholinesterase.22 A minimum amount of organophosphate must be ab-
sorbed to depress blood cholinesterase activities, but enzyme activities, espe-
cially plasma pseudocholinesterase, may  be lowered by dosages considerably
less than are required to cause symptomatic poisoning.The enzyme depression
is usually apparent within a few minutes or hours of significant absorption of
organophosphate. Depression of the plasma enzyme generally persists several
days to a few weeks.The RBC enzyme activity may not reach its minimum for
several days, and usually remains depressed longer, sometimes 1 -3 months, until
new enzyme replaces that  inactivated by organophosphate. The above  table
lists approximate lower limits of normal plasma and RBC cholinesterase activi-
ties of human blood, measured  by several methods. Lower levels usually in-
dicate excessive absorption  of a cholinesterase-inhibiting chemical.
                                                                                     ORGANOPHOSPHATES • 39

                                     In certain conditions, the activities of plasma and RBC cholinesterase are
                                 depressed in the absence of chemical inhibition. About 3% of individuals have
                                 a genetically determined low level of plasma pseudocholinesterase. These
                                 persons are particularly vulnerable to the action of the muscle-paralyzing drug
                                 succinylcholine  (often administered to surgical patients), but not to organo-
                                 phosphates. Patients with hepatitis, cirrhosis, malnutrition, chronic alcoholism,
                                 and dermatomyositis exhibit low plasma cholinesterase activities. A number of
                                 toxicants, notably cocaine, carbon disulfide, benzalkonium salts, organic  mer-
                                 cury compounds, ciguatoxins, and solanines may reduce plasma pseudocho-
                                 linesterase activity. Early pregnancy, birth control  pills,  and metoclopramide
                                 may also  cause some depression. The RBC acetylcholinesterase is less likely
                                 than the plasma enzyme to be affected by factors other than organophosphates.
                                 It is, however, reduced in certain rare conditions that damage the red cell mem-
                                 brane, such as hemolytic anemia.
                                     The alkyl phosphates and phenols to which organophosphates are hydro-
                                 lyzed in the body can often be detected in the urine  during pesticide absorp-
                                 tion and up to about 48 hours thereafter.These analyses are sometimes useful in
                                 identifying and quantifying the actual pesticide to which workers have  been
                                 exposed. Urinary alkyl phosphate and phenol analyses can demonstrate orga-
                                 nophosphate absorption at lower dosages than those required to depress cho-
                                 linesterase activities and at much lower dosages than those required to produce
                                 symptoms and  signs. Their presence may simply be  a result of organophos-
                                 phates in the food chain.
                                     Detection of intact organophosphates in the blood is usually not possible
                                 except during or soon after absorption of a substantial amount. In general,
                                 organophosphates do not remain  unhydrolyzed in  the blood for more than a
                                 few minutes or hours, unless the quantity absorbed is large or the hydrolyzing
                                 liver enzymes are inhibited.
                                 Caution: Persons attending the victim should avoid direct contact with heavily contami-
                                 nated clothing and vomitus. Wear rubber gloves while washing pesticide from skin and
                                 hair. Vinyl gloves provide no protection.

                                 1. Airway protection. Ensure that a clear airway exists. Intubate the patient
                                 and aspirate the secretions with  a large-bore suction  device if necessary.
                                 Administer oxygen by mechanically assisted pulmonary ventilation if respiration
                                 is  depressed. Improve tissue oxygenation as much as possible  before
                                 administering atropine,  so as to minimize the risk  of ventricular
                                 fibrillation. In severe poisonings, it may be necessary  to support pulmonary
                                 ventilation mechanically for several days.

2. Atropine sulfate. Administer atropine sulfate intravenously, or intramuscu-
larly if intravenous injection is not possible. Remember that atropine can be
administered through  an endotracheal tube if initial IV  access is  difficult to
obtain. Depending on the severity of poisoning, doses of atropine ranging from
very low to as high as  300 mg per day may be required,23 or even continuous
infusion.24-25 (See dosage on next page.)
    The objective of atropine antidotal therapy is to antagonize the effects of
excessive concentrations of acetylcholine at end-organs having muscarinic re-
ceptors. Atropine does not reactivate the cholinesterase enzyme or accelerate
disposition of organophosphate. Recrudescence of poisoning may occur if tis-
sue concentrations of organophosphate remain  high when the effect of atro-
pine wears off. Atropine is effective against muscarinic manifestations, but  it is
ineffective against nicotinic actions, specifically  muscle weakness and twitch-
ing, and respiratory depression.
    Despite these limitations, atropine is often a life-saving agent in organophos-
phate poisonings. Favorable response to a test dose of atropine (1 mg in adults,
0.01 mg/kg in children under  12 years) can help differentiate poisoning by anti-
cholinesterase agents from other conditions. However, lack of response, with no
evidence of atropinization (atropine refractoriness) is typical of more severe poi-
sonings.The adjunctive use of nebulized atropine has been reported to improve
respiratory distress, decrease bronchial secretions,  and  increase oxygenation.26

3. Glycopyrolate has been studied as an alternative to atropine and found to
have  similar outcomes  using continuous infusion. Ampules  of  7.5 mg of
glycopyrolate were added to 200 mL of saline and this infusion was titrated  to the
desired effects of dry mucous membranes and heart rate above 60 beats/mm.
During this study, atropine was used as a bolus for a heart rate less than 60 beats/
min.The other apparent advantage to this regimen was  a decreased number of
respiratory infections. This may represent an alternative when there is a concern
for respiratory infection due to excessive and difficult to control secretions, and in
the presence of altered level of consciousness where the distinction  between
atropine toxicity or relapse of organophosphate poisoning is unclear.27

4. Pralidoxime. Before administration of pralidoxime, draw a blood sample
(heparinized) for cholinesterase analysis (since pralidoxime tends to reverse the
cholinesterase depression).Administer pralidoxime (Protopam, 2-PAM) a cho-
linesterase  reactivator, in cases of severe poisoning by organophosphate  pesti-
cides in which respiratory depression, muscle weakness, and/or twitching are
severe. (See dosage table on page 43.) When administered early  (usually  less
than 48 hours after poisoning), pralidoxime relieves the  nicotinic as well  as the
muscarinic effects of poisoning. Pralidoxime works by reactivating the cho-
linesterase  and also  by slowing the "aging" process of phosphorylated cho-
linesterase to a non-reactivatable form.
    Note: Pralidoxime is of limited value and may actually be hazardous in poi-
sonings by the cholinesterase-inhibiting carbamate compounds (see Chapter 5).
                                                                                        ORGANOPHOSPHATES •  41

                                     Dosage of Atropine:
                                     In moderately severe poisoning (hypersecretion and other end-organ
                                     manifestations without central nervous system depression), the follow-
                                     ing dosage schedules have been used:
                                      • Adults and children over 12years: 2.0-4.0 mg, repeated every 15 min-
                                        utes until pulmonary secretions are controlled, which may be ac-
                                        companied by other signs of atropinization, including flushing, dry
                                        mouth,  dilated pupils, and tachycardia  (pulse of  140 per minute).
                                        Warning: In cases of ingestion of liquid concentrates of organo-
                                        phosphate pesticides, hydrocarbon aspiration may complicate these
                                        poisonings. Pulmonary edema and poor oxygenation in these cases
                                        will not respond to atropine and should be treated as a case of acute
                                        respiratory distress syndrome.
                                      • Children under 12years: 0.05-0.1 mg/kg body weight, repeated ev-
                                        ery 15 minutes until atropinization is achieved.There is a minimum
                                        dose of 0.1  mg  in children.  Maintain  atropinization  by repeated
                                        doses  based  on recurrence of symptoms for 2-12 hours or longer
                                        depending on severity of poisoning.

                                     Maintain atropinization with repeated dosing as indicated by clinical
                                     status. Crackles in the lung bases nearly  always  indicate inadequate
                                     atropinization.  Pulmonary improvement may not parallel other signs
                                     of atropinization. Continuation of, or return of, cholinergic signs indi-
                                     cates the need for more atropine. When  symptoms are  stable for as
                                     much as six hours, the dosing may be decreased.

                                     Severely poisoned individuals may exhibit remarkable tolerance to at-
                                     ropine; two or more times the dosages suggested above may be needed.
                                     The dose of atropine may be increased and the dosing  interval  de-
                                     creased as needed to control symptoms. Continuous intravenous infu-
                                     sion of atropine  may be  necessary when atropine  requirements are
                                     massive.  The  desired end-point is the reversal of muscarinic
                                     symptoms and signs with improvement in  pulmonary status
                                     and oxygenation, without an  arbitrary dose  limit. Preservative-free
                                     atropine  products should be used whenever possible.

                                     Note: Persons not poisoned or only slightly poisoned by organophos-
                                     phates may develop  signs of atropine toxicity from such large doses.
                                     Fever, muscle fibrillations, and delirium are the main signs of atropine
                                     toxicity. If these appear while the patient is fully atropinized, atropine
                                     administration  should be discontinued, at  least temporarily, while the
                                     severity of poisoning is reevaluated.

    Dosage of Pralidoxime:
     •  Adults and children over 12years: 1.0-2.0 g by intravenous infusion at a
       rate of no more than 0.2 g per minute. Slow administration of pralidoxime
       is strongly recommended and may be achieved by administering the
       total dose in 100 mL of normal saline over 30 minutes, or longer.
     •  Children under  12 years: 20-50 mg/kg body weight (depending on
       severity of poisoning) intravenously, mixed in 100 mL of normal
       saline and infused over 30  minutes.
Dosage of pralidoxime may be repeated in 1-2 hours, then at 10-12 hour inter-
vals if needed. In very severe poisonings, dosage rates may be doubled. Repeated
doses of pralidoxime are usually required. In cases that involve continuing ab-
sorption of organophosphate (as after ingestion of large amount), or continuing
transfer of highly lipophilic organophosphate from fat into blood, it may be  nec-
essary to continue administration of pralidoxime for several days beyond the 48
hour post-exposure interval usually cited as the limit of its effectiveness. Pralidoxime
may also be given as a continuous infusion of approximately 500 mg/hour based
on animal case studies and adult patient reports.28-29
    Blood pressure should be monitored  during administration because of the
occasional occurrence of hypertensive crisis. Administration should be slowed
or stopped if blood pressure  rises  to hazardous levels.  Be prepared  to assist
pulmonary ventilation mechanically if respiration is depressed during or  after
pralidoxime administration. If intravenous injection is not possible, pralidoxime
may be given by deep intramuscular injection.

5. Skin decontamination. In patients who have been poisoned by organo-
phosphate contamination of skin, clothing, hair, and/or eyes, decontamination
must proceed concurrently with whatever resuscitative and antidotal measures
are  necessary to preserve life.  Flush the chemical from the eyes with  copious
amounts of clean water. If no symptoms are evident in a patient who  remains
alert and physically stable, a prompt shower and shampoo may be appropriate,
provided the  patient is carefully observed to insure against any sudden appear-
ance of poisoning. If there are any indications of weakness, ataxia, or other
neurologic impairment, clothing should be removed and a complete bath and
shampoo given while the victim is recumbent, using copious  amounts of soap
and water. Attendants should wear rubber gloves as vinyl provides no protec-
tion against skin absorption. Surgical green soap is excellent for this purpose,
but ordinary soap is about as good. Wash the chemical from skin folds and from
under fingernails.
                                                                                       ORGANOPHOSPHATES • 43

                                      Contaminated clothing should be promptly removed, bagged, and laundered
                                  before returning. Contaminated leather shoes should be discarded. Note that the
                                  pesticide can contaminate the inside surfaces of gloves, boots, and headgear.

                                  6. Gastrointestinal decontamination. If organophosphate has been ingested
                                  in quantity probably sufficient to cause poisoning, consideration should be given
                                  to gastrointestinal decontamination, as outlined in Chapter  2, General Prin-
                                  ciples. If the patient has already vomited, which is most likely in serious expo-
                                  sures, further efforts at GI decontamination may not be indicated. In significant
                                  ingestions, diarrhea and/or vomiting are so constant  that charcoal adsorption
                                  and catharsis are not indicated.

                                  7. Observation.  Observe patient closely for at least 72 hours to ensure that
                                  symptoms (sweating, visual disturbances, vomiting, diarrhea, chest and abdomi-
                                  nal distress, and sometimes pulmonary edema) do not recur as atropinization is
                                  withdrawn. In very severe poisonings by ingested organophosphates, particu-
                                  larly the more lipophilic and slowly hydrolyzed compounds,  metabolic dispo-
                                  sition  of toxicant  may require as many as  5-14 days. In  some cases, this slow
                                  elimination may combine with profound cholinesterase inhibition to require
                                  atropinization for several days or  even weeks. As dosage is reduced, the lung
                                  bases should be checked frequently for crackles. If crackles are heard, or if there
                                  is a return of miosis, bradycardia, sweating, or  other cholinergic signs, atropin-
                                  ization must be re-established promptly.

                                  8. Furosemide may  be considered if pulmonary edema persists in the lungs
                                  even after full atropinization. It should not be used until the maximum benefit of
                                  atropine has been realized. Consult package insert for dosage and administration.

                                  9. Pulmonary ventilation. Particularly in poisonings by large ingested doses
                                  of organophosphate, monitor pulmonary ventilation carefully, even after recov-
                                  ery  from muscarinic  symptomatology, to forestall respiratory failure. In some
                                  cases, respiratory failure has developed several  days following organophosphate
                                  ingestion, and has persisted for days to weeks.

                                  10. Hydrocarbon aspiration may complicate poisonings that involve inges-
                                  tion of liquid concentrates of organophosphate pesticides. Pulmonary edema
                                  and poor oxygenation in these cases will not respond to atropine and should be
                                  treated as a case of acute respiratory distress syndrome.

                                  11. Cardiopulmonary monitoring. In severely poisoned patients, monitor
                                  cardiac status by continuous EGG recording. Some organophosphates have sig-
                                  nificant cardiac toxicity.

12. Seizure control. Rarely, in severe organophosphate poisonings, convul-
sions occur despite therapy with atropine and pralidoxime. Insure that causes
unrelated to pesticide toxicity are not responsible: head trauma, cerebral anoxia,
or mixed poisoning. Drugs useful  in controlling convulsions are  discussed in
Chapter 2. The  benzodiazepines  (diazepam or lorazepam) are the agents of
choice as initial therapy.

13. Contraindications. The following drugs are contraindicated in nearly all
organophosphate poisoning cases: morphine, succinylcholine, theophylline,
phenothiazines, and reserpine. Adrenergic amines should be given  only if there
is a specific indication, such as marked hypotension.

14. Re-exposures. Persons  who  have been clinically poisoned  by organo-
phosphate  pesticides should not be re-exposed to cholinesterase-inhibiting
chemicals until symptoms and signs have resolved completely and blood cho-
linesterase activities have returned to at least 80 percent of pre-poisoning levels.
If blood cholinesterase was not measured prior to poisoning, blood enzyme
activities should reach at least minimum  normal levels (see table on page  39)
before the patient is returned to a  pesticide-contaminated environment.

15. Do not administer atropine or pralidoxime prophylactically to workers
exposed to organophosphate pesticides. Prophylactic dosage with either atropine
or pralidoxime may mask early signs and symptoms of organophosphate poison-
ing and thus allow  the worker to  continue exposure and possibly progress to
more  severe poisoning. Atropine itself may enhance the health hazards of  the
agricultural work setting: impaired  heat loss due to reduced sweating and im-
paired  ability to operate mechanical equipment due to blurred  vision. This  can
be caused by mydriasis, one of the effects of atropine.

General Chemical  Structure
R  is usually either ethyl or methyl. The insecticides with a double bonded sulfur are
organothiophosphates, but are converted to organophosphates in the liver. Phosphonate
contains an alkyl (R-) in place of one  alkoxy group  (RO-). "X" is called the "leaving
group " and is the principal metabolite for a  specific identification.

                     RO^   4, S (or 0)
                     no'   ^ o   	
                                    [Leaving Group|
                                                                                       ORGANOPHOSPHATES • 45

                                        1.  DuBois KP. The toxicity of organophosphorous compounds to mammals. Bull World Health
                                            Organ 1971;44:233-40.
                                        2.  Pasquet J, Mazuret A, Fournel J, et al. Acute oral and percutaneous toxicity of phosalone in the
                                            rat, in comparison with azinphosmethyl and parathion. Toxicol Appl Pharmacol 1976;37:85-92.
                                        3.  Garcia-Repetto R, Martinez D, and Repetto M. Coefficient of distribution of some organo-
                                            phosphorus pesticides in rat tissue. Vet Hum Toxicol 1995;37:226-9.
                                        4.  Gallo MA and Lawryk NJ. Organic phosphorus pesticides. In: Haves WJ and Laws ER (eds),
                                            Handbook of Pesticide Toxicology, vol 2, Classes of Pesticides. San Diego,  CA: Academic
                                            Press Inc., 1991.
                                        5.  Taylor R Anticholinesterase agents. In: Gilman AG and Goodman LS (eds), The Pharmaco-
                                            logical Basis of Therapeutics. New York: Macmillan Publishing Co. Inc.; 1985, pp. 110-28.
                                        6.  De Kort WL, Kiestra SH, and Sangster B.The use of atropine and oximes in organophos-
                                            phate intoxications: A modified approach. Clin Toxicol 1988;26:199-208.
                                        7.  Jamal JA. Neurological syndromes of organophosphorus compounds. Adverse Drug React
                                            Toxicol Rev 1997;16(3): 133-70.
                                        8.  Steenland K, Jenkins B.Ames RG, et al. Chronic neurological sequelae to  organophosphate
                                            poisoning. Am J Public Health 1994;84:731-6.
                                        9.  Savage E, KeefeT, Mounce L, et al. Chronic neurological sequelae of acute  organophosphate
                                            pesticide poisoning. Arch Environ Health 1988;43:38-45.
                                        10. Rosenstock L, Keifer  M, Daniell VV et al. Chronic  central  nervous system effects of acute
                                            organophosphate pesticide intoxication. Lancet 1991;338:223-7.
                                        11. Gershon S and Shaw  FH. Psychiatric sequelae of chronic  exposure to organophosphorus
                                            insecticides. Lancet 1961; 1:1371-4.
                                        12. Metcalf DR and Holmes JH. EEG, psychological, and neurological alterations in humans
                                            with organophosphorus exposure. Ann NYAcad Sci 1969;160:357-65.
                                        13. Holmes JH and Gaon MD. Observations on acute and multiple exposure to anticholinest-
                                            erase agents. Trans Am Clin Climatol Assoc 1957; 68:86-103.
                                        14. Hirshberg A and Lerman Y Clinical problems in organophosphate insecticide poisoning:The
                                            use of a computerized information system. Fundam Appl Toxicol 1984; 4:S209-14.
                                        15. Miller CS and Mitzel HC. Chemical sensitivity attributed to pesticide exposure versus re-
                                            modeling. Arch Environ Health 1995; 50:119-29.
                                        16. DeBleeker J.Willems J,Van Den Neucker K, et al. Prolonged toxicity with intermediate
                                            syndrome  after combined parathion and methyl parathion poisoning.  Clin Toxicol
                                        17. DeBleecker J,Van Den Neucker  K,  and  Colardyn F. Intermediate syndrome in organo-
                                            phosphorous poisoning:A prospective study. Crit Care Med  1993;21:1706-11.
                                        18. Aldridge WN  and Nemery B. Toxicology of trialkylphosphorothioates with particular
                                            reference to lung toxicity. Fundam Appl Toxicol 1984; 4:5215-23.
                                        19. Bardin PG.Van Eeden SF, Moolman JA, et al.  Organophosphate and carbamate poisoning.
                                            Arch Intern Med 1994; 154:1433-41.
                                        20. Zwiener RJ and Ginsburg CM. Organophosphate and carbamate poisoning in infants and
                                            children. Pediatrics 1988;81:121-683.
                                        21. Sofer S.Tal A, and Shahak E. Carbamate and organophosphate poisoning in early childhood.
                                            PediatrEmerg Care 1989;5(4):222-5.

22.  Sullivan JB and Blose J. Organophosphate and carbamate insecticides. In: Sullivan JB and
    Krieger GR (eds), Hazardous Materials Toxicology. Baltimore, MD: Williams and Wilkins,
    1992, pp. 1015-26.
23.  Goswamy R, Chaudhuri A, and Mahashur AA. Study of respiratory failure in organophos-
    phate and carbamate poisoning. Heart Lung 1994;23:466-72.
24.  LeBlanc FN, Benson BE, and Gilg AD. A severe Organophosphate poisoning requiring the
    use of an atropine drip. Clin Toxicol 1986;24:69-76.
25.  DuToit PW, Muller FO, Van Tender WM, et al. Experience with the intensive care manage-
    ment of Organophosphate insecticide poisoning. S Afr Med J 1981;60:227-9.
26.  Shockley LW. The use of inhaled nebulized atropine for the treatment of malathion poison-
    ing. ClinToxicol 1989;27:183-92.
27.  Bardin PG and van Eeden SE Organophosphate poisoning: Grading the severity and compar-
    ing treatment between atropine and glycopyrrolate. Crit Care Med 1990; 18:956-60.
28.  Thompson DF, Thompson GD, Greenwood RB, et al. Therapeutic dosing of pralidoxime
    chloride. Drug  Intell Clin Pharm 1987;21:590-2.
29.  Tush GM and  Anstead MI. Pralidoxime continuous infusion in the treatment of Organo-
    phosphate poisoning. Ann Pharmawther 1997;31:441-4.
                                                                                                        ORGANOPHOSPHATES  • 47

                                   CHAPTER 5

•  Cause reversible
   carbamylation of AChE
•  Muscarinic, nicotinic, CNS

Signs and Symptoms:
•  Malaise, muscle weakness,
   dizziness, sweating
•  Headache, salivation,
   nausea, vomiting,
   abdominal pain, diarrhea
•  CNS depression, pulmonary
   edema in serious cases

•  Clear airway, improve tissue
•  Administer atropine sulfate
•  Proceed immediately with
N-Methyl  Carbamate
N-Methyl carbamate insecticides are widely used in homes, gardens, and agri-
culture. They share with organophosphates the capacity to inhibit cholinest-
erase enzymes and therefore share similar symptomatology during acute and
chronic exposures. Likewise, exposure can occur by several routes in the same
individual due to multiple uses, and there is likely to be additive toxicity with
simultaneous exposure to organophosphates. However, due to the  somewhat
different affinity for cholinesterases, as compared to organophosphates, these
poisonings are often somewhat easier to treat, as discussed later in this chapter.
    The N-methyl carbamate esters cause reversible carbamylation of the ace-
tylcholinesterase enzyme, allowing accumulation of acetylcholine, the
neuromediator substance, at parasympathetic neuroeffector junctions (muscar-
inic effects), at skeletal muscle myoneural junctions and autonomic ganglia (nico-
tinic effects), and in the brain (CNS effects).The carbamyl-acetylcholinesterase
combination dissociates more readily than the phosphoryl-acetylcholinesterase
complex produced by organophosphate compounds. This lability has several
important consequences: (1) it tends to limit the duration of N-methyl car-
bamate poisonings, (2) it accounts for the greater span between symptom-
producing and lethal doses than in most organophosphate compounds, and (3)
it frequently invalidates the measurement of blood cholinesterase activity as a
diagnostic index of poisoning (see below).
    N-methyl carbamates are absorbed by inhalation and ingestion and some-
what by skin penetration, although the latter tends to be the less toxic route. For
example, carbofuran has a rat oral LD50  of 5 mg/kg, compared to a rat dermal
LD5Q of 120 mg/kg, which makes the oral route approximately 24 times more
toxic when ingested.1 N-methyl carbamates are hydrolyzed enzymatically by the
liver; degradation products are excreted by the kidneys and the liver.
    At cholinergic nerve junctions with smooth muscle and gland cells, high
acetylcholine concentration causes muscle contraction and secretion, respec-
tively. At skeletal muscle junctions, excess acetylcholine may be excitatory (cause
muscle twitching), but may also weaken  or paralyze the cell by depolarizing the
end-plate. In the brain, elevated acetylcholine concentrations may cause sen-

sory and behavioral disturbances, incoordination, and depressed motor func-
tion (rarely seizures), even though the N-methyl carbamates do not penetrate
the central nervous system very efficiently. Respiratory depression combined
with pulmonary edema is the usual cause of death from poisoning by N-me-
thyl carbamate compounds.
Signs and Symptoms of Poisoning

    As with organophosphate poisoning, the signs and symptoms are based on
excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate
poisonings tend to be of shorter duration because the inhibition of nervous tissue
AchE is reversible, and carbamates are more rapidly metabolized.2 Bradycardia and
seizures are less common than in organophosphate poisonings. However, blood
cholinesterase levels may be misleading due to in vitro reactivation of a
carbamylated enzyme.3'4 A falsely "normal" level can make the  diagnosis more
difficult in the acute presentation in the absence of an exposure history.
    The primary manifestations of serious toxicity are central nervous system
depression, as manifested by coma, seizures, and hypotonicity, and  nicotinic
effects including hypertension and cardiorespiratory depression. Dyspnea, bron-
chospasm, and bronchorrhea with eventual pulmonary edema  are other  seri-
ous signs. Recent information indicates that children and adults differ in  their
clinical presentation. Children are more likely than adults to present with the
CNS symptoms above. While children can still develop the classic muscarinic
signs, the absence of them does not exclude the possibility of carbamate poi-
soning in the presence of CNS depression.5
    Malaise, muscle weakness, dizziness, and sweating are commonly reported
early symptoms. Headache, salivation, nausea, vomiting, abdominal pain, and
diarrhea are often prominent. Miosis with blurred vision, incoordination, muscle
twitching, and slurred speech are reported.
Confirmation of Poisoning

    If there are strong clinical indications of acute N-methyl carbam-
ate poisoning, and/or a history of carbamate exposure, treat the pa-
tient immediately. Do not wait for laboratory confirmation.
    Blood  for plasma pseudocholinesterase and RBC AChE should be ob-
tained. Be advised that unless a substantial amount of N-methyl carbamate has
been absorbed and a blood sample is taken within an hour or two, it is unlikely
that blood cholinesterase  activities will be found depressed. Even under the
above circumstances, a rapid test for enzyme activity must be used to detect an
effect, because enzyme reactivation occurs in vitro as well as in vivo. See the table
on  page 39 for methods of measurement of blood  cholinesterase activities, if
circumstances appear to warrant performance of the test.
Commercial Products
formetanate hydrochloride*
  Vydate L
                                                                                      (Continued on the next page)
                                                                                     N-METHYL CARBAMATES • 49

Commercial Products

+ Indicates high toxicity.
  Highly toxic N-methyl
  carbamates have listed oral
  LD50 values (rat) less than or
  equal to 50 mg/kg body
  weight. Most other
  carbamates included in this
  table are considered
  moderately toxic, with LD50
  values in excess of 50 mg/
  kg and less than 500 mg/kg.
    Absorption of some N-methyl carbamates can be confirmed by analysis of
urine for unique metabolites: alpha-naphthol from carbaryl, isopropoxyphenol
from  propoxur, carbofuran phenol from carbofuran, and aldicarb sulfone, sul-
foxide, and nitrile from aldicarb.These complex analyses, when available, can be
useful in identifying the responsible agent and following the course of carbam-
ate disposition.
    Caution: Persons attending the victim should avoid direct contact with
heavily contaminated clothing and vomitus.Wear rubber gloves while washing
pesticide from skin and hair. Vinyl gloves provide no protection.

1. Airway protection. Ensure that a  clear airway exists. Intubate the patient
and aspirate the secretions with a large-bore suction device if necessary. Ad-
minister oxygen by mechanically assisted pulmonary ventilation if respiration is
depressed. Improve tissue oxygenation  as much as possible before ad-
ministering atropine, to minimize the risk of ventricular fibrillation.
In severe  poisonings, it may be necessary to support pulmonary ventilation
mechanically for several days.

2. Atropine. Administer atropine sulfate  intravenously, or intramuscularly if
intravenous injection is not possible. Remember that atropine can be adminis-
tered through an endotracheal tube if initial IV access  is difficult to obtain.
Carbamates usually reverse with much smaller dosages of atropine than those
required to reverse  organophosphates.6 (See dosage on next page.)
    The objective of atropine antidotal therapy is to antagonize the effects of
excessive concentrations of acetylcholine at end-organs having muscarinic re-
ceptors. Atropine does not reactivate the cholinesterase enzyme or accelerate
excretion or breakdown of carbamate.  Recrudescence  of poisoning may occur
if tissue concentrations of toxicant remain high when the effect of atropine
wears off. Atropine is effective against muscarinic manifestations, but is ineffec-
tive against nicotinic actions, specifically, muscle weakness and twitching, and
respiratory depression.
    Despite these limitations, atropine  is often a life-saving agent in N-methyl
carbamate poisonings. Favorable response to a test dose of atropine (1  mg in
adults, 0.01  mg/kg in children under  12 years) given intravenously can help
differentiate poisoning by anticholinesterase agents from other conditions such
as cardiogenic pulmonary edema and hydrocarbon ingestion. However, lack of
response to the test dose, indicating no atropinization (atropine refractoriness),
is characteristic of moderately severe to severe  poisoning and indicates a need
for further atropine. If the test dose does not result in mydriasis and drying of
secretions, the patient can be considered atropine refractory.

Dosage of Atropine:

In moderately severe poisoning (hypersecretion and other end-organ
manifestations without central nervous system depression), the follow-
ing dosage schedules have proven effective:
 •  Adults and children over 12years: 2.0-4.0 mg, repeated every 15 min-
   utes until pulmonary secretions are controlled, which may be ac-
   companied by other signs of atropinization, including flushing, dry
   mouth, dilated pupils, and tachycardia (pulse of 140 per minute).
   Warning: In cases of ingestion of liquid concentrates of carbamate
   pesticides, hydrocarbon aspiration may complicate these poisonings.
   Pulmonary edema and  poor oxygenation in these cases  will not
   respond to atropine and should be treated as a case of acute respira-
   tory distress syndrome.
 •  Children under 12years: 0.05-0.1 mg/kg body weight, repeated every
   15 minutes until pulmonary secretions are controlled, which may be
   accompanied by other  signs of atropinization as above  (heart rates
   vary depending on age of child with young toddlers having a rate
   approaching 200).There is a minimum dose of 0.1 mg in children.

Maintain atropinization by repeated doses based on recurrence of symp-
toms for 2-12 hours or longer depending on severity of poisoning. Crack-
les in the lung bases nearly always indicate inadequate atropinization and
pulmonary improvement may not parallel other signs. Continuation or
return of cholinergic signs indicates the need for more atropine.

Severely poisoned individuals may exhibit remarkable tolerance to at-
ropine; two or more times the dosages suggested above may be needed.
Reversal of muscarinic manifestations, rather than a specific dosage, is
the object of atropine therapy. However, prolonged intensive intrave-
nous administration  of atropine sometimes required in organophos-
phate poisonings is rarely needed in treating carbamate poisoning.

Note: Persons not poisoned or only slightly poisoned  by N-methyl
carbamates may develop signs of atropine toxicity from such large doses.
Fever, muscle fibrillations, and delirium are the main signs of atropine
toxicity. If these signs appear while the patient is fully atropinized, atro-
pine administration should be discontinued, at least temporarily, while
the severity of poisoning is reevaluated.
                                                                                  N-METHYL CARBAMATES • 51

                                  3. Skin decontamination. In patients with contaminated skin, clothing, hair,
                                  and/or eyes, decontamination must proceed concurrently with what-
                                  ever resuscitative and antidotal measures are needed to preserve life.
                                  Flush the chemical from eyes with copious amounts of clean water. For asymp-
                                  tomatic individuals who are alert and physically able, a prompt shower and
                                  shampoo may be appropriate for thorough skin decontamination, provided the
                                  patient is carefully observed to insure against sudden appearance of poisoning.
                                  If there are any indications of weakness ataxia or other neurologic impairment,
                                  clothing should be removed and a complete bath and shampoo given while the
                                  victim is recumbent, using copious amounts of soap and  water. Attendants should
                                  wear rubber gloves  as vinyl provides no protection against skin absorption.
                                  Wash the chemical from skin folds and from under fingernails.
                                      Contaminated clothing should be promptly removed, bagged, and  laundered
                                  before returning. Contaminated leather shoes should be  discarded. Note that the
                                  pesticide can contaminate the inside surfaces of gloves, boots, and headgear.

                                  4. Gastrointestinal decontamination. If N-methyl carbamate has been ingested
                                  in a quantity probably sufficient to cause poisoning, consideration should be given
                                  to gastrointestinal decontamination as outlined in Chapter 2. If the patient has
                                  presented with a recent ingestion and is still asymptomatic, adsorption of poison
                                  with activated charcoal may be beneficial. In significant ingestions, diarrhea and/or
                                  vomiting are so constant that charcoal adsorption and catharsis are not indicated.
                                  Attention should be given to oxygen, airway management, and atropine.

                                  5. Urine sample. Save a urine sample for metabolite analysis if there is need to
                                  identify the agent responsible for the poisoning.

                                  6. Pralidoxime is probably of little value in N-methyl carbamate poisonings,
                                  because atropine alone is effective. Although not indicated in isolated carbam-
                                  ate poisoning, pralidoxime appears to be useful in cases of mixed carbamate/
                                  organophosphate poisonings, and cases of an unknown pesticide with muscar-
                                  inic symptoms on presentation.7'8 See Chapter 4,Treatment section,  p. 41.

                                  7. Observation. Observe patient closely for at least 24 hours to ensure that symp-
                                  toms (sweating, visual disturbances, vomiting, diarrhea, chest and abdominal distress,
                                  and sometimes pulmonary edema) do not recur as atropinization is withdrawn.The
                                  observation period should be longer in the case  of a mixed pesticide  ingestion,
                                  because of the prolonged and delayed symptoms associated with organophosphate
                                  poisoning. As the dosage of atropine is reduced over time, check the lung bases
                                  frequently for crackles. Atropinization must be re-established promptly, if crackles
                                  are heard, or if there is a return of miosis, sweating, or other signs of poisoning.

                                  8. Furosemide may be considered for relief of pulmonary edema if crackles
                                  persist in the lungs even after full atropinization. It should not be considered

until the maximum effect of atropine has been achieved. Consult package in-
sert for dosage and administration.

9. Pulmonary  ventilation. Particularly in poisonings by large doses of N-
methyl carbamates, monitor pulmonary ventilation carefully, even after recov-
ery from muscarinic symptomatology, to forestall respiratory failure.

10. Cardiopulmonary monitoring. In severely poisoned patients, monitor
cardiac status by continuous EGG recording.

11. Contraindications. The following drugs are probably contraindicated in
nearly all N-methyl carbamate poisoning cases: morphine, succinlycholine, theo-
phylline, phenothiazines, and  reserpine.  Adrenergic amines should be given
only if there is a specific indication, such as marked hypotension.

12. Hydrocarbon aspiration may complicate poisonings that involve inges-
tion of liquid concentrates of some carbamates that are formulated in a petro-
leum  product base. Pulmonary edema and poor oxygenation in these cases will
not respond to  atropine and should  be treated  as cases of acute respiratory
distress syndrome.

13. Do not administer atropine prophylactically to workers exposed to
N-methyl carbamate pesticides. Prophylactic dosage may mask early symptoms
and signs of carbamate poisoning and thus allow the worker to continue expo-
sure and possibly progress  to more severe poisoning. Atropine itself may en-
hance the health hazards of the agricultural work setting: impaired heat loss
due to reduced  sweating and  impaired ability to operate  mechanical equip-
ment due to blurred vision (mydriasis).

General Chemical Structure
1.  Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety
   and Health, Cincinnati, OH. (CD-ROMVersion, Micromedex, Inc. Englewood, CA 1991.)
2.  Ecobichon DJ. Toxic effect of pesticides. In: Klaassen CD (ed), Casarett & Doull's Toxicol-
   ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, p. 659.
3.  Rotenberg M and Almog S. Evaluation of the decarbamylation process of cholinesterase
   during assay of enzyme activity. Clin ChimActa 1995;240:107-16.
                                                                                      N-METHYL CARBAMATES • 53

                                         4.   Jokanovic M and Maksimovic M. Abnormal cholinesterase activity: Understanding and in-
                                             terpretation. EurJ Clin Chem Clin Biochem 1997;35:11-6.
                                         5.   Lifshitz M, Shahak E.BolotinA.et al. Carbamate poisoning in early childhood and in adults.
                                             Ota Toxto/1997:35:25-7.
                                         6.   Goswarny R et al. Study of respiratory failure in organophosphate and carbamate poisoning.
                                             Heart Lung 1994;23:466-72.
                                         7.   Lifshitz M.Totenberg M, Sofer S, et al. Carbamate poisoning and oxime treatment in chil-
                                             dren: A clinical and laboratory study. Pediatrics 1994;93:652-5.
                                         8.   Kurtz PH. Pralidoxime in the treatment of carbamate intoxication. AmJEmerg Med 1990,8:68-70.

Solid  Organochlorine  Insecticides
EPA has sharply curtailed the availability of many organochlorines, particularly
DDT, aldrin, dieldrin, heptachlor, mirex, chlordecone, and chlordane. Others,
however, remain the  active ingredients of various home and garden products
and some agricultural, structural, and environmental pest control products.
Hexachlorobenzene is a fungicide used as a seed protectant and is discussed
further in Chapter 15, Fungicides.
    Technical hexachlorocyclohexane (misnamed benzene hexachloride, BHC)
includes multiple stereoisomers; only the gamma isomer (lindane) is insecticidal.
Lindane is the active ingredient of some pest control products used in the home
and garden, on the farm, and in forestry and animal husbandry. It is also the active
agent in the medicine Kwell*, used for human ectoparasitic disease. Lindane has
been reported on numerous occasions to be associated with acute neurological
toxicity either from ingestion or in persons treated for scabies or lice.1"6
    In varying degrees, organochlorines are absorbed from the gut and also by
the lung and across the skin. The efficiency of dermal absorption is variable.
Hexachlorocyclohexane, including lindane, the cyclodienes (aldrin, dieldrin,
endrin, chlordane, heptachlor), and endosulfan are efficiently absorbed across
the skin, while dermal absorption efficiencies of DDT, dicofol, marlate, tox-
aphene, and mirex are substantially less.7 Lindane has a documented 9.3% der-
mal absorption rate,8 and is absorbed even more efficiently across abraded skin. '-9
This becomes especially  important when taking into account its use on chil-
dren with severe dermatitis associated with scabies. Fat and fat solvents enhance
gastrointestinal, and probably dermal, absorption of organochlorines. While most
of the solid organochlorines are not highly volatile, pesticide-laden aerosol or
dust particles trapped in respiratory mucous and subsequently swallowed may
lead to significant gastrointestinal absorption.
    Following exposure to some organochlorines (notably DDT), a significant
part of the absorbed dose is stored in fat tissue as the unchanged parent com-
pound. Most organochlorines are in some degree dechlorinated, oxidized, then
conjugated. The chief route  of excretion  is biliary, although nearly all orga-
nochlorines yield measurable urinary metabolites. Unfortunately, many of the
unmetabolized pesticides are efficiently reabsorbed by the intestine (enterohepatic
circulation), substantially retarding fecal excretion.

Signs and Symptoms:
•  Absorbed dose is stored in
   fat tissue
•  Sensory disturbances:
   hyperesthesia and
   paresthesia, headache,
   dizziness, nausea,
   hyperexcitable state
•  Convulsions

•  Anticonvulsants
•  Administer oxygen
•  Cardiopulmonary

•  Epinephrine, other
   adrenergic amines, atropine
•  Animal or vegetable  oils or
   fats taken orally
                                                                                  SOLID ORGANOCHLORINES • 55

Commercial Products

benzene hexachloride (BHC)*
  (multiple trade names)
  (multiple trade names)
  (multiple trade names)
  (multiple trade names)
  (multiple trade names)
  gamma BHC or HCH
  (multiple trade names)
terpene polychlorinates*

 * All U.S. registrations have
   been cancelled.

** Registered in the United
   States only for
   underground use in
   power lines for fire ants.
    Metabolic dispositions of DDT and DDE (a DDT degradation product), the
beta isomer of hexachlorocyclohexane, dieldrin, heptachlor epoxide, and mirex
tend to be slow, leading to storage in body fat. Storable lipophilic compounds are
likely to be excreted in maternal milk.6-10-11 On the other hand, rapid metabolic
dispositions of lindane, methoxychlor, dienochlor, endrin, chlorobenzilate, dicofol,
toxaphene, perthane, and endosulfan reduce the likelihood that these organochlo-
rines will be detected as  residues in body fat, blood, or milk.
    The chief acute toxic action of organochlorine pesticides is on the nervous
system, where these compounds induce a hyperexcitable state in the brain.12
This effect is manifest mainly as convulsions, sometimes limited to myoclonic
jerking, but often expressed as violent seizures. Convulsions caused by cyclodienes
may recur over periods of several days. Other less severe signs  of neurologic
toxicity such as paresthesias, tremor, ataxia, and hyperreflexia are also characteristic
of acute organochlorine poisoning. Agents such as DDT and methoxychlor
tend to cause the less severe effects, while the  cyclodienes, mirex, and lindane
are associated with the  more severe seizures and fatalities.7 Convulsions may
cause death by  interfering with pulmonary gas exchange and by generating
severe metabolic acidosis.
    High tissue concentrations of organochlorines increase myocardial irritability,
predisposing to cardiac arrhythmia.When tissue organochlorine concentrations
drop below threshold  levels, recovery from  the poisoning  occurs.
Organochlorines are not cholinesterase inhibitors.
    High tissue levels of some organochlorines (notably DDT, DDE, and cy-
clodienes) have  been shown to  induce hepatic microsomal drug-metabolizing
enzymes.13 This tends to accelerate excretion of the pesticides themselves, but
may also stimulate biotransformation of critical natural substances, such as ste-
roid hormones and therapeutic drugs, occasionally necessitating re-evaluation
of required dosages in persons intensively exposed to organochlorines. Human
absorption of organochlorine sufficient to cause enzyme induction is likely to
occur only as a  result of prolonged intensive exposure.
    Ingestion of hexachlorobenzene-treated wheat has been associated  with
human dermal toxicity diagnosed as porphyria cutanea tarda.The skin blisters,
becomes very sensitive to sunlight, and heals poorly, resulting in scarring and
contracture formation.14 Unlike other organochlorine compounds, there have
been no reported cases of convulsions caused by the fungicide hexachloro-
benzene. Lindane and chlordane have rarely been associated anecdotally with
certain hematological disorders, including aplastic anemia and  megaloblastic
    There has been considerable interest recently in the interaction of orga-
nochlorines with endocrine receptors, particularly estrogen and androgen
receptors. In vitro studies and animal experimentation have supported the view
that the function of the endocrine system may  be altered by these interac-
tions.17'18 This in turn may alter the reproductive development and success of
animals and humans. In addition, some organochlorines may inhibit lactation
and may also be developmental toxicants.10 Due to evidence of carcinogenic

potential, some organochlorines have lost registration for use in the United
States or had their uses restricted. Although these effects are important, they are
beyond the scope of this manual.
Signs and Symptoms of Poisoning
    Early manifestations of poisoning by some organochlorine pesticides, par-
ticularly DDT, are often sensory disturbances: hyperesthesia and paresthesia of
the face and extremities. Headache, dizziness, nausea, vomiting, incoordination,
tremor, and mental confusion are also reported. More severe poisoning causes
myoclonic jerking movements, then generalized tonic-clonic convulsions. Coma
and respiratory depression may follow the seizures.
    Poisoning by the cyclodienes and toxaphene is more likely to begin with
the sudden onset of convulsions, and is often not preceded by the premonitory
manifestations mentioned above. Seizures caused by cyclodienes may appear as
long as 48  hours after exposure, and then may recur periodically over several
days following the initial episode. Because lindane and  toxaphene are more
rapidly biotransformed in the body and excreted, they are less likely than diel-
drin, aldrin, and chlordane to cause delayed or recurrent seizures.
Confirmation of Poisoning

    Organochlorine pesticides and/or their metabolites can sometimes be iden-
tified in blood by gas-liquid chromatographic examination of samples taken
within a few days of significant pesticide absorption. Such tests are performed
by a limited number of government, university, and private laboratories, which
can usually be contacted through poison control centers or health departments.
Some organochlorine pesticides or their products (notably DDT, dieldrin, mirex,
heptachlor, epoxide, chlordecone)  persist in tissues and blood for  weeks or
months after absorption, but others are likely to be  excreted in a  few days,
limiting the likelihood of detection. Blood levels tend to correlate more with
acute toxicity, while levels found in adipose tissue and breast milk usually re-
flect more long-term and historic exposure.19
    Chromatographic methods make possible detection of most organochlo-
rines at concentrations much lower than those associated with symptoms of
toxicity. Therefore, a positive finding in a blood sample does not, of itself Justify
a diagnosis of acute poisoning. Lindane appears in the literature more frequently
than other compounds.The time of acquisition of the blood level in relation to
exposure time must be taken into account when interpreting blood levels. In
one study, lindane levels were measured at 10.3 ng/mL in healthy volunteers
three days after application to the skin.20
    In a study with childhood dermal absorption using children with scabies
and a non-affected control group, lindane peaked at 28 ng/mL 6 hours after
application in the affected group, and at 24 ng/mL in the control group. At 48
                                                                                   SOLID ORGANOCHLORINES • 57

                                 hours, levels were 6 ng/mL and 5 ng/mL respectively. Findings from this study
                                 also provide evidence for increased absorption across abraded skin.9 A child
                                 with severely abraded skin was treated for scabies and developed seizures.Three
                                 days after exposure, his lindane level was 54 ng/mL.1 Most reports of acute
                                 toxicity from lindane involve blood levels of 130 ng/mL or greater, with the
                                 most severe and fatal cases involving levels exceeding 500 ng/mL.2
                                     DDT, DDE, and a few other organochlorines are still found at very low
                                 levels in blood samples  from the general U.S. population, presumably due to
                                 past and/or current low-level contamination of food by these environmentally
                                 persistent pesticides.
                                     In the  absence  of corresponding elevations of blood levels, the amount of
                                 stored pesticides is not likely to be of clinical significance.  Measurements of uri-
                                 nary metabolites of some organochlorine pesticides can be useful in monitoring
                                 occupational exposures; however, the analytical methods are complex, and are
                                 not likely to detect amounts of metabolites generated by minimal exposures.
                                 1. Observation. Persons exposed to high levels of organochlorine pesticides
                                 by any route should be observed for sensory disturbances, incoordination, speech
                                 slurring, mental aberrations, and involuntary motor activity that would warn of
                                 imminent convulsions.

                                 2. Convulsions. If convulsions occur, place the victim in the left lateral decu-
                                 bitus position with the head down. Move away furniture or other solid objects
                                 that could  be a source of injury. If jaw movements are violent, place  padded
                                 tongue blades between the teeth to protect  the tongue. Whenever possible,
                                 remove dentures and other removable dental work. Aspirate oral and pharyn-
                                 geal secretion, and when possible, insert an oropharyngeal airway to maintain
                                 an open passage unobstructed by the tongue. Minimize noise and any manipu-
                                 lation of the  patient that may trigger seizure activity.
                                     Dosage of Diazepam:
                                      • Adults'. 5-10 mg IV and repeat every 5-10 minutes to maximum of 30 mg.
                                      • Children: 0.2 to 0.5 mg/kg every 5 minutes to maximum of 10 mg in
                                        children over 5 years, and maximum of 5 mg in children under 5 years.

                                     Although lorazepam is widely accepted as a treatment of choice for
                                     status epilepticus, there are no  reports of its use for organochlorine
                                     intoxication. Some cases have required aggressive seizure management
                                     including the addition of phenobarbital and the induction of pento-
                                     barbital coma.

    Seizures in patients caused by organochlorine toxicity are likely to be pro-
longed and difficult to control. Status epilepticus is common. For this reason,
patients with seizures that do not respond immediately to anticonvulsants should
be transferred as soon as possible to a trauma center and will generally require
intensive care admission  until seizures are controlled and neurologic status is
improved. Initial therapy  with benzodiazepines should be instituted.

3. Oxygen. Administer oxygen by mask. Maintain pulmonary gas exchange by
mechanically assisted ventilation whenever respiration is depressed.

4. Skin decontamination. Skin decontamination should be done thoroughly,
as outlined in Chapter 2.

5. Gastrointestinal decontamination. If organochlorine has been ingested
in a quantity sufficient to cause poisoning and the patient presents within an
hour, consideration should be given to gastric decontamination procedures, as
outlined in Chapter 2. If the patient presents more than an hour after ingestion,
activated charcoal may still be beneficial. If the victim is convulsing, it is almost
always necessary first to control seizures before attempting gastric decontami-
nation. Activated charcoal administration has been advocated in such poison-
ings, but there is little human or experimental evidence to support it.

6. Respiratory failure. Particularly  in  poisonings  by large doses of
organochlorine, monitor pulmonary  ventilation  carefully to forestall
respiratory failure. Assist pulmonary ventilation mechanically with  oxygen
whenever respiration is depressed. Since these compounds are often formulated
in a hydrocarbon vehicle, hydrocarbon aspiration may occur with ingestion of
these agents.  The hydrocarbon aspiration should be managed in accordance
with accepted medical practice as a case of acute respiratory distress syndrome
which will usually require intensive care management.

7. Cardiac monitoring. In severely poisoned patients, monitor cardiac  status
by continuous EGG recording to detect arrhythmia.

8. Contraindications. Do not give epinephrine, other adrenergic amines, or
atropine unless absolutely necessary because of the enhanced myocardial irrita-
bility induced by chlorinated  hydrocarbons, which predisposes to ventricular
fibrillation. Do not give  animal or vegetable oils or  fats by mouth. They en-
hance gastrointestinal absorption of the lipophilic organochlorines.

9. Phenobarbital. To control seizures and myoclonic movements that some-
times persist  for several  days following acute poisoning by the more slowly
excreted  organochlorines, phenobarbital given orally is likely to be effective.
                                                                                    SOLID ORGANOCHLORINES • 59

                                Dosage should be based on manifestations in the individual case and on infor-
                                mation contained in the package insert.

                                10. Cholestryamine resin accelerates the biliary-fecal excretion of the more
                                slowly eliminated organochlorine compounds.21 It is usually administered in 4
                                g doses, 4 times a day, before meals and at bedtime.The usual dose for children
                                is 240 mg/kg/24 hours, divided Q 8 hours. The dose may be mixed with a
                                pulpy fruit or liquid. It should never be given in its dry form and must always
                                be administered with water, other liquids or a pulpy fruit. Prolonged treatment
                                (several weeks or months) may be necessary.

                                11. Convalescence. During convalescence, enhance carbohydrate, protein, and
                                vitamin intake by diet or parenteral therapy.
                                General Chemical Structures
                                                                 Cl       Cl
                                                                                   Cl   Cl
             Cl  Cl
Cl  Cl       Cl  Cl

               Cl         Cl
1.   Friedman SJ. Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythro-
    derma. Arch Dermatol 1987;123:1056-8.
2.   Aks SE, Krantz A, Hryhorczuk DO, et al. Acute accidental lindane ingestion in toddlers. Ann
    EmergMed 1995;25(5):647-51.
3.   Tenenbein M. Seizures after lindane therapy. J Am Geriatr Soc 1991;39(4):394-5.
4.   Solomon BA, Haut SR, Carr EM, and  Shalita AR. Neurotoxic reaction to lindane in an HIV-
    seropositive patient: An old medication's new problem. /Fam Pract 1995;40(3):291-6.
5.   FischerTE Lindane toxicity in a 24-year-old woman. Ann EmergMed 1994;24(5):972-4.
6.   Solomon LM.Fahrner L,and West DP Gamma benzene hexachloride toxicity. Arch Dermatol
7.   Echobichon DJ.Toxic effects of pesticides. In Klaassen CD (ed), Casarett & Doull'sToxicol-
    ogy: The  Basic Science of Poisons, 5th  ed. New York: McGraw-Hill, 1996, pp. 649-55.
8.   Feldmann RJ and Maibach HI. Percutaneous penetration of some pesticides and herbicides
    in man. Toxicol andAppl Pharmacol 1974;28:126-32.
9.   Ginsburg CM, Lowry W, and Reisch JS. Absorption of lindane (gamma benzene hexachlo-
    ride) in infants and children. /Pediatr  1997;91(6):998-1000.
10. RoganWJ. Pollutants in breast milk. Arch PediatrAdolesc Med 1996;150:981-90.
11. Stevens MF, Ebell GF, and Psaila-Savona P. Organochlorine pesticides in Western Australian
    nursing mothers. MedJAust 1993;158(4):238-41.
12. Joy RM.The effects of neurotoxicants on kindling and kindled seizures. FundamApplToxicol
13. Hunter J, Maxwell JD, Stewart DA, et al. Increased hepatic microsomal enzyme activity from
    occupational exposure to certain organochlorine pesticides. Nature 1972;237:399-401.
14. Booth  NH and McDowell JR. Toxicity of hexachlorobenzene and associated residues in
    edible animal tissues. J Am Vet Med Assoc 1975;166(6):591-5.
15. RauchAE.Kowalsky SF, LesarTS.et al. Lindane (Kwell)-induced aplastic anemia. Arch Intern
    Med 1990; 150:2393-5.
16. Furie B andTrubowitz S. Insecticides and blood dyscrasias. Chlordane exposure and self-
    limited refractory megaloblastic anemia. JAMA 1976;235(16):1720-2.
17. Vonier PM, Grain DA, McLachlan JA, et al. Interaction of environmental chemicals with the
    estrogen  and progesterone receptors  from the oviduct of the American alligator. Environ
    Health Perspect 1996;104(12): 1318-22.
                                                                                                     SOLID ORGANOCHLORINES •  61

                                         18. Fry DM. Reproductive effects in birds exposed to pesticides and industrial chemicals. Environ
                                            Health Perspect 1995;103(Suppl 7):165-71.
                                         19. Frank R, Rasper J, Srnout MS, and Braun HE. Organochlorine residues in adipose tissues,
                                            blood and milk from Ontario residents, 1976-1985. Can J Public Health 1988;79:150-8.
                                         20. Hosier J.Tschan C, Hignite CE, et al. Topical application of lindane cream (Kwell) and
                                            antipyrine metabolism. /Invest Dermatol 1980;74:51-3.
                                         21. Cohn WJ, Boylan JJ, Blanke RV, et al. Treatment of chlordecone (Kepone) toxicity with
                                            cholestyramine. NewEngl JMed 1978;298(5):243-8.

Biologicals and Insecticides
of  Biological  Origin
This chapter covers several widely-used insecticidal products of natural origin, as
well as certain agents often identified as biological control agents. Of the many
living control agents, only the bacterial agent Bacillus thuringiensis will be discussed
in detail, since it is one  of the most widely used. Many other agents, such as
parasitic wasps and insects, are so host-specific that they pose little or no risk to
human health.The agents are discussed in this chapter in alphabetic order.


    This biologically-obtained insecticide is derived from the Neem  tree
(Azadirachta indica).  It is an insect growth regulator that interferes with the
molting hormone ecdysone.

    Azadirachtin causes severe dermal and gastrointestinal  irritation.  Central
nervous system stimulation and depression have been seen.This agent is prima-
rily used and manufactured in India; little use or exposures are expected in the
United States.

•   Derived from living systems
•   Bacillus thuringensis is the
   most important live agent
•   Generally of low order

Signs and Symptoms:
•   Highly variable based on
   specific agents
•   Several cause
   gastrointestinal irritation
•   Nicotine and rotenone may
   have serious CNS effects
•   Nicotine and sabadilla may
   have cardiovascular effects

•   Specific to the agent
•   Skin, eye, and Gl
   decontamination  may be
•   Nicotine, rotenone, and
   sabadilla require aggressive
1. Skin decontamination. If skin exposure occurs, the skin should be thor-
oughly washed with soap and water.

2. Gastrointestinal decontamination. Due to the severe gastrointestinal ir-
ritation, gastric emptying and catharsis are not indicated. Consideration should
be given to administration of activated charcoal as outlined in Chapter 2.
                                                                                        BIOLOGICALS • 63

Commercial Products
Bacillus thuringiensis
 Variety aizawai:
 Variety israelensis:
 Variety kurstaki:
 Variety morrisoni
 Variety tenebrionis:
gibberellicacid (GA3)
  Pro-Gibb Plus
  Black Leaf 40
  Nico Soap
(Continued on the next page)
    Several strains of Bacillus thuringiensis are pathogenic to some insects. The
bacterial organisms are cultured, then harvested in spore form for use as insec-
ticide. Production methods vary widely. Proteinaceous and nucleotide-like toxins
generated by the vegetative forms (which infect insects) are responsible for the
insecticidal effect.The spores are formulated as wettable powders, flowable con-
centrates, and granules for application to field crops and for control of mosqui-
toes and black flies.

    The varieties of Bacillus thuringiensis used commercially survive when in-
jected into mice, and at least one of the  purified insecticidal toxins is toxic to
mice. Infections of humans have been extremely rare. A single case report of
ingestion by volunteers of Bacillus thuringiensis var. galleriae resulted in fever and
gastrointestinal symptoms. However, this agent is not registered as a pesticide.
B. thuringiensis products are exempt from tolerance on raw agricultural com-
modities  in  the United States. Neither  irritative nor sensitizing effects have
been reported in workers preparing and applying commercial products.

1. Skin decontamination. Skin contamination should be removed with soap
and water. Eye contamination should be flushed from the eyes with clean water
or saline. If irritation persists, or if there is any indication of infection, treatment
by a physician should be obtained.
    A single case of corneal ulcer caused by a splash of B. thuringiensis suspen-
sion into the eye was successfully treated by subconjunctival injection of gen-
tamicin (20 mg) and cefazolin (25 mg).1

2. Gastrointestinal decontamination. If a B. thuringiensis product has been
ingested, the patient should be observed for manifestations of bacterial gastro-
enteritis: abdominal cramps, vomiting, and diarrhea. The illness is likely to be
self-limited if it occurs at all.The patient should be treated symptomatically and
fluid support provided as appropriate.

    This compound is derived from clove oil. It is used as an insect attractant.

    Eugenol is similar in its clinical effects to phenol. Although it works as an
anesthetic, in large doses it can cause burns to epithelial surfaces.2 Sloughing of
mucous membranes has occurred as an allergic reaction to a small dose applied
topically in the mouth.3 Gastric mucosal lesions have been reported in animals,
but no lesions were seen on endoscopy after clove oil ingestion.4 Large doses
may result in coma and liver dysfunction.5


    Treatment is primarily supportive as there is no antidote. If mucosal burns
are present, consider endoscopy to look for other ulcerations.
Commercial Products
  Rotenone Solution FK-11
  Agri-Mycin 17
  Paushamycin, Tech.

*Discontinued in the U.S.
GIBBERELLIC ACID  (Gibberellin, GA3)

    Gibberellic acid is not a pesticide, but it is commonly used in agricultural
production as a growth-promoting agent. It is a metabolic product of a cul-
tured fungus, formulated in tablets, granules, and liquid concentrates for appli-
cation to soil beneath growing plants and trees.

    Experimental animals tolerate large oral doses without apparent adverse
effect. No human poisonings have been reported. Sensitization has not been
reported, and irritant effects are not remarkable.

1. Skin decontamination. Wash contamination from skin with soap and
water. Flush contamination from eyes with clean water or saline. If irritation
occurs, obtain medical treatment.

2. Gastrointestinal decontamination. If gibberellic acid has been swallowed,
there is no reason to expect adverse effects.

    Nicotine is an alkaloid contained in the leaves of many species of plants,
but is usually obtained commercially from tobacco. A 14% preparation of the
free alkaloid is marketed as a greenhouse fumigant. Significant volatilization of
nicotine occurs. Commercial nicotine insecticides have long been known as
Black Leaf 40. This formulation was  discontinued in 1992. Other currently
                                                                                          BIOLOGICALS • 65

                                 available formulations include dusts formulated with naphthalene and dried
                                 blood used to repel dogs and rabbits. Be aware of Green Tobacco Syndrome
                                 from dermal absorption.Very little nicotine insecticide is currently used in the
                                 United  States, although old preparations of nicotine insecticides may  still be
                                 found on occasion.6 Today, most nicotine poisonings  are the result of ingestion
                                 of tobacco products and incorrect use of nicotine skin patches.
                                     Nicotine alkaloid is efficiently absorbed by the gut, lung, and skin. Exten-
                                 sive biotransformation occurs in the liver with 70-75% occurring as a first pass
                                 effect.7 Both the liver and kidney participate in the formation and excretion of
                                 multiple end-products, which are excreted within a few hours. Estimates of the
                                 half-life of nicotine range from about one hour in smokers to as much as two
                                 hours in non-smokers.8'9
                                     Toxic action is  complex. At low doses, autonomic ganglia are  stimulated.
                                 Higher doses result in blockade of autonomic ganglia and skeletal muscle neuro-
                                 muscular junctions, and direct effects on the central nervous system. Paralysis and
                                 vascular collapse are prominent features of acute poisoning, but death is often due
                                 to respiratory paralysis, which may  ensue promptly after the first symptoms of
                                 poisoning. Nicotine is not an inhibitor of the cholinesterase enzyme.
                                 Signs and Symptoms of Poisoning
                                     Early and prominent symptoms of poisoning include salivation, sweating,
                                 dizziness, nausea, vomiting, and diarrhea. Burning sensations in the mouth and
                                 throat, agitation, confusion, headache, and abdominal pain are reported. If dos-
                                 age has been high, vascular  collapse with hypotension, bradycardia  or  other
                                 arrythmias, dyspnea then respiratory failure, and unconsciousness may ensue
                                 promptly.6'10'11'12 In some cases, hypertension and tachycardia may precede hy-
                                 potension and bradycardia, with the latter two signs leading to shock.11'12 Sei-
                                 zures may also  occur.6'11 In one case of ingestion of a large dose of nicotine
                                 alkaloid pesticide, the patient developed asystole within two minutes. He later
                                 developed seizures and refractory hypotension.6
                                 Confirmation of Poisoning
                                     Urine content of the metabolite cotinine can be used to confirm absorp-
                                 tion of nicotine.

1. Skin decontamination. If liquid or aerosol spray has come in contact with
skin, wash the area thoroughly with soap and water. If eyes have been contami-
nated, flush them thoroughly with clean water or saline. If irritation persists,
obtain specialized medical treatment.
    If symptoms of poisoning appear during exposure to an airborne nicotine
insecticide, remove the person from the contaminated environment immediately,
wash any skin areas that may be contaminated, then transport the victim to the
nearest treatment facility. Although mild poisoning may  resolve  without treat-
ment, it is often difficult to predict the ultimate severity of poisoning at the onset.

2.  Pulmonary  ventilation. If there is  any indication of loss of respiratory
drive, maintain pulmonary ventilation by mechanical means, using supplemen-
tal oxygen if available, or mouth-to-mouth or mouth-to-nose methods if nec-
essary. Toxic effects of nicotine other than respiratory depression are usually
survivable.The importance of maintaining adequate gas  exchange is therefore

3. Gastrointestinal decontamination. If a nicotine-containing product has
been ingested recently, immediate  steps must be taken to limit gastrointestinal
absorption. If the patient is fully alert, immediate oral administration of acti-
vated charcoal as outlined in Chapter 2 is probably the best initial step in man-
agement. Repeated administration of activated charcoal at half or  more the
initial dosage every 2-4 hours may be beneficial. Since diarrhea is often a part
of this poisoning, it is usually not necessary or appropriate to administer a
cathartic. Do not administer syrup of ipecac.

4. Cardiac monitoring. Monitor cardiac status by electrocardiography and
measure blood pressure frequently. Cardiopulmonary resuscitation may
be necessary. Vascular collapse may require administration of norepinephrine
and/or dopamine. Consult package inserts for dosages and routes of adminis-
tration.  Infusions of electrolyte solutions, plasma, and/or blood may also be
required to combat shock.

5. Atropine sulfate. There is no specific antidote for nicotine poisoning. Se-
vere hypersecretion (especially salivation  and diarrhea) or bradycardia may be
treated with intravenous atropine sulfate.  See dosage on  next page.
                                                                                             BIOLOGICALS • 67

                                     Dosage of Atropine Sulfate:
                                      • Adults and children over 12years:OA-0.5 mg slowly IV, repeated every
                                        5 minutes if necessary.
                                      • Children under 12years:0.01 mg/kg body weight, slowly IV, repeated
                                        every 5 minutes if necessary.There is a minimum dose of 0.1 mg.
                                  6. Convulsions should be controlled as outlined in Chapter 2. If the patient
                                  survives for four hours, complete recovery is likely.

                                  PYRETHRUM AND PYRETHRINS

                                     Pyrethrum is the oleoresin extract of dried chrysanthemum flowers. The
                                  extract contains about 50% active insecticidal ingredients known as pyrethrins.
                                  The ketoalcoholic esters of chrysanthemic and pyrethroic acids  are known as
                                  pyrethrins, cinerins, and jasmolins. These strongly lipophilic esters rapidly pen-
                                  etrate  many insects and paralyze their nervous systems. Both crude pyrethrum
                                  extract and purified pyrethrins are contained in various commercial products,
                                  commonly dissolved in petroleum distillates. Some are packaged  in pressurized
                                  containers ("bug-bombs"), usually in combination with the synergists piperonyl
                                  butoxide and n-octyl bicycloheptene dicarboximide.The synergists retard enzy-
                                  matic  degradation of pyrethrins. Some  commercial products also  contain
                                  organophosphate or carbamate insecticides.These are included because the rapid
                                  paralytic effect of pyrethrins on insects ("quick knockdown") is not always lethal.
                                     Pyrethrum and pyrethrin products are used mainly for indoor pest  control.
                                  They are not sufficiently stable in light and heat to remain as active residues on
                                  crops.  The synthetic insecticides  known as pyrethroids (chemically similar to
                                  pyrethrins) do have the stability needed for agricultural applications. Pyrethroids
                                  are discussed separately in Chapter 8.

                                     Crude pyrethrum is a dermal and respiratory allergen, probably due mainly
                                  to non-insecticidal ingredients. Contact dermatitis and allergic respiratory re-
                                  actions (rhinitis and asthma) have occurred following exposures.13'14 Single cases
                                  exhibiting anaphylactic15 and pneumonitic manifestations16 have also been re-
                                  ported. The refined pyrethrins are probably less allergenic, but appear to retain
                                  some irritant and/or sensitizing properties.
                                     Pyrethrins are absorbed across the gut and pulmonary membrane, but only
                                  slightly across intact skin.They are very effectively hydrolyzed  to inert products
                                  by mammalian liver enzymes.This rapid degradation combined with relatively

poor bioavailability probably accounts in large part for their relatively low mam-
malian toxicity. Dogs fed  extraordinary doses exhibit tremor, ataxia, labored
breathing, and salivation. Similar neurotoxicity rarely, if ever, has been observed
in humans, even in individuals who have used pyrethrins for body lice control
(extensive contact) or pyrethrum as an anthelmintic (ingestion).
    In cases of human exposure to commercial products, the possible role of
other toxicants in the products should be kept in mind.The synergists pipero-
nyl butoxide and n-octyl bicycloheptene dicarboximide have low toxic poten-
tial in humans, but organophosphates or carbamates  included in the product
may  have significant toxicity. Pyrethrins themselves do not inhibit cholinest-
erase  enzyme.
Confirmation of Poisoning
    There are at present no practical tests for pyrethrin metabolites or pyrethrin
effects on human enzymes or tissues that can be used to confirm absorption.
1. Antihistamines are effective in controlling most allergic reactions. Severe
asthmatic reactions, particularly in predisposed persons, may require adminis-
tration of inhaled B2-agonists and/or systemic corticosteroids. Inhalation ex-
posure should be carefully avoided in the future.

2. Anaphylaxis-type reactions may  require  sub-cutaneous epinephrine,
epinepherine, and respiratory support.15

3. Contact dermatitis may require extended administration of topical corti-
costeroid preparations. This should be done under the supervision of a physi-
cian. Future contact with the allergen must be avoided.

4. Eye contamination should be  removed by flushing the eye with  large
amounts of clean water or saline. Specialized ophthalmologic care should be
obtained if irritation persists.

5. Other toxic manifestations caused  by other ingredients must be treated ac-
cording to their respective toxic actions, independent of pyrethrin-related effects.

6. Gastrointestinal decontamination. Even though most ingestions of pyre-
thrin  products  present little risk, if  a large  amount  of pyrethrin-containing
material has been ingested and  the  patient is seen within one hour, consider
gastric emptying. If the patient is seen later, or if gastric emptying is performed,
consider administration of activated  charcoal as described in Chapter 2.
                                                                                             BIOLOGICALS • 69

                                    Although this natural substance is present in a number of plants, the source
                                 of most rotenone used in the United States is the dried derris root imported
                                 from Central and South America. It is formulated as dusts, powders, and sprays
                                 (less than 5% active ingredient) for use in gardens and on food crops. Many
                                 products contain piperonyl butoxide as synergist, and other pesticides  are in-
                                 cluded in some commercial products. Rotenone degrades rapidly in the envi-
                                 ronment. Emulsions of rotenone are applied to lakes and ponds to kill fish.
                                    Although rotenone is toxic to the nervous systems of insects, fish, and birds,
                                 commercial rotenone  products have presented little hazard to humans  over
                                 many decades. Neither fatalities nor systemic poisonings have been reported in
                                 relation to ordinary use. However, there is one report of a fatality in a child
                                 who  ingested a product called Gallocide, which contains rotenone and etheral
                                 oils, including clove oil. She developed a gradual loss of consciousness over two
                                 hours and died of respiratory arrest.17
                                    Numbness of oral  mucous membranes has been reported in workers  who
                                 got dust from the powdered derris root in their mouths. Dermatitis and respira-
                                 tory tract irritation have also been reported in occupationally exposed persons.
                                    When rotenone has been injected into animals, tremors, vomiting, incoor-
                                 dination,  convulsions, and respiratory arrest have been observed.These effects
                                 have  not been reported in occupationally exposed humans.
                                 1.  Skin decontamination. Skin contamination should be removed by wash-
                                 ing with soap and water. Eye contamination should be removed by flushing the
                                 eye thoroughly with clean water or saline. Dust in the mouth should be washed
                                 out. If irritation persists, medical treatment should be obtained.

                                 2. Gastrointestinal decontamination. If a large amount of a rotenone-con-
                                 taining product has been swallowed and retained and the patient is seen within
                                 an hour of exposure, consideration should be given to gastric emptying. Whether
                                 or not gastric  emptying is performed, consider use  of activated charcoal as
                                 outlined in Chapter 2.

                                 3. Respiratory support should be used as necessary if mental status changes
                                 and/or respiratory depression occurs.

SABADILLA (Veratrum alkaloid)

    Sabadilla consists of the powdered ripe seeds of a South American lily. It is
used as dust, with lime or sulfur, or dissolved in kerosene, mainly to kill ecto-
parasites on domestic animals and humans. Insecticidal alkaloids are those of
the veratrum type. The concentration of alkaloids in commercial sabadilla is
usually less than 0.5%. Little or no sabadilla is used in the United States today,
but some is probably used in other countries. Most toxic encounters with ver-
atrum alkaloid occur from the inadvertent ingestion of the plant.18
    Sabadilla dust is very irritating to the upper respiratory tract, causing sneez-
ing, and is also irritating to the skin.Veratrin alkaloids are apparently absorbed
across the skin and gut, and probably by the lung as well. Veratrin alkaloids have a
digitalis-like action on the heart muscles (impaired conduction and arrhythmia).
    Although poisoning by medicinal veratrum preparations may have occurred
in the past, systemic poisoning by sabadilla preparations used as insecticides has
been very rare. The prominent symptoms of veratrum alkaloid poisoning are
severe nausea and vomiting, followed by hypotension and bradycardia. Other
arrythmias or A-V block may occur.18'19

1. Skin decontamination. Contaminated skin should be washed thoroughly
with soap and water. If eyes are affected, they should be flushed with copious
amounts of clean water or saline. If skin or eye irritation persists, medical treat-
ment should be obtained.

2. Gastrointestinal decontamination. If a large amount of sabadilla pesticide
product has been ingested in the past hour and retained, consider gastric empty-
ing.This may be followed by administration of charcoal. If only a small amount of
sabadilla pesticide has been ingested and retained, or if treatment is delayed, and if
the patient remains fully alert, immediate oral administration of activated char-
coal probably represents reasonable management, as outlined in Chapter 2.

3. Cardiac monitoring.  If there is a suspicion that significant amounts of
sabadilla alkaloids have been absorbed, EGG monitoring of cardiac activity for
arrhythmia and conduction  defects is appropriate. Bradycardia may be treated
with atropine.18'19 See dosage on next page.
                                                                                            BIOLOGICALS • 71

                                        Dosage of Atropine Sulfate:

                                        • Adults and children over 12years: 0.4-0.5 mg slowly IV repeated ev-
                                          ery 5 minutes if necessary.

                                        • Children under 12years:0.01 mg/kg body weight, slowly IV, repeated
                                          every 5 minutes if necessary. (There is a minimum dose of 0.1 mg).

                                        Streptomycin sulfate and nitrate are used as pesticides for the control of a
                                    variety of commercially important bacterial plant pathogens. Streptomycin is
                                    an antibiotic derived from the growth of Streptomyces griseus.
                                        This antibiotic shares a toxic profile  with the aminoglycoside antibiotics
                                   commonly used to treat human diseases. Its major modes of toxicity are neph-
                                   rotoxicity and ototoxicity. Fortunately, it is  poorly absorbed from the gastrointes-
                                   tinal tract, so systemic toxicity is unlikely  with ingestion.
                                        If a large amount of streptomycin has been ingested within one hour of the
                                   patient's receiving care, gastric emptying should be considered. Administration
                                   of activated charcoal, as outlined in Chapter 2, should be considered.
                                    1.  Samples JR and Buettner H. Corneal ulcer caused by a biological insecticide  (Bacillus
                                       thuringiensis). Am J Ophthalmol 1983;95:258.
                                    2.  Isaacs G. Permanent local anesthesia and anhydrosis after clove oil spillage. Lancet 1983; 1:882.
                                    3.  Barkin ME, Boyd JP, and Cohen S. Acute allergic reaction to eugenol. Oral Surg Oral Med Oral
                                       Pathol 1984;57:441-2.
                                    4.  Lane BW, Ellenhorn MJ, HulbertTV, et al. Clove oil ingestion in an infant. Hum Exp Toxicol
                                    5.  Hartnoll G, Moore D, and Douek D. Near fatal ingestion of oil of cloves. Arch Dis Child
                                    6.  Lavoie FW and HarrisTM. Fatal nicotine ingestion. ]Emerg Med 1991;9:133-6.
                                    7.  Svensson CK. Clinical pharmacokinetics of nicotine. Clin Pharm 1987; 12:30-40.

8.   Kyerematen MS, Damiano MD, Dvorchik BH, et al. Smoking-induced changes in nicotine
    disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin Pharmacol
    Ther 1982:32:769-80.
9.   Feyerabend C, Ings RMJ, and Russell MAH. Nicotine pharmacokinetics and its application
    to intake from smoking. BrJ Clin Pharmacol 1985;19:239-47.
10. Woolf A, Burkhart K, CaraccioT, et al. Self-poisoning among adults using multiple transdermal
    nicotine patches. JToxicol Clin Toxicol 1996;34:691-8.
11. Sanchez P, Ducasse JL, Lapeyre-Mestre M, et al. Nicotine poisoning as a cause of cardiac
    arrest? (letter). JToxicol Clin Toxicol 1996;34:475-6.
12. Malizia E, Andreucci G, Alfani  F, et al. Acute intoxication with nicotine alkaloids and can-
    nabinoids in children from ingestion of cigarettes. HumToxicol 1983;2:315-6.
13. Moretto A. Indoor spraying with the pyrethroid insecticide lambda-cyhalothrin: Effects on
    spraymen and inhabitants of sprayed houses. Bull World Health Organ 1991; 69:591-4.
14. Newton JG and Breslin ABX. Asthmatic reactions to a commonly used aerosol insect killer.
    MedJAust 1983; 1:378-80.
15. Culver  CA, Malina JJ, and Talbert RL. Probable  anaphylactoid  reaction to a pyrethrin
    pediculocide shampoo. Clin Pharm  1988;7:846-9.
16. Carlson JE and Villaveces JW Hypersensitivity pneumonitis due  to  pyrethrum. JAMA
17. DeWilde AR. A case of fatal rotenone poisoning in a child. ]Forensic Sci 1986;31 (4): 1492-8.
18. Jaffe AM, Gephardt D, and Courtemanche L. Poisoning due to ingestion of veratrum viride
    (false hellebore). JEmerg Med 1990;8:161-7.
19. Quatrehomme G, Bertrand F, Chauvet C, et al. Intoxication from veratrum album. Hum Exp
    Toxicol 1993;12:lll-5.
                                                                                                                   BIOLOGICALS • 73


•  Multiple agents, with
  widely varying toxicity
•  Careful history will usually
  reveal exposure history
•  Agents of particular
  concern due to wide use
  are pyrethroids,
  diethyltoluamide, and

Signs and Symptoms:
•  Variable and highly related
  to the specific agent
•  Boric acid causes severe
  erythematous and
  exfoliative rash (boiled
  lobster appearance)
•  Agents such as boric acid,
  diethyltoluamide, and
  pyrethroids should be
  suspected in cases of
  unusual  nervous system

•  Specific to the agents
•  Skin and Gl
•  Severe CNS symptoms may
  require intensive care
Other Insecticides,
Acaricides,  and  Repellents
This chapter discusses insecticides, acaricides, and repellents that have toxico-
logic characteristics distinct from the insecticides discussed in previous chap-
ters. Pesticides reviewed include: alkyl phthalates, benzyl benzoate, borates,
chlordimeform,  chlorobenzilate, cyhexatin,  diethyltoluamide, fluorides,
haloaromatic urea compounds, methoprene, propargite, pyrethroids, and sulfur.

    Dimethyl phthalate has been widely used as an insect repellent applied
directly to the skin. Dibutylphthalate is impregnated into fabric for the same
purpose. It is more resistant to laundering than dimethyl phthalate.

    Dimethyl phthalate is strongly irritating to the eyes and mucous membranes.
It has caused little or no irritation when applied to skin, and dermal absorption is
apparently minimal. It has not caused sensitization.Tests in rodents have indicated
low systemic toxicity, but large ingested doses  cause gastrointestinal irritation,
central nervous system depression, coma, and hypotension.
    No antidote is available. Supportive measures (hydration, oxygen if needed)
are probably adequate to manage all but the most severe poisonings.
                                  BENZYL BENZOATE

                                      Incorporated into lotions and ointments, this agent has been used for many
                                  years in veterinary and human medicine against mites and lice. Apart  from
                                  occasional cases of skin irritation, adverse effects have been few.The efficiency

of skin absorption is not known. Absorbed  benzyl benzoate is  rapidly
biotransformed to hippuric acid which is excreted in the urine.When given in
large doses to laboratory animals, benzyl benzoate causes excitement, incoordi-
nation, paralysis of the limbs, convulsions, respiratory paralysis, and death. No
human poisonings have been reported.

1. Skin decontamination. If significant irritant effect appears, medications
should be discontinued and the skin cleansed with soap and water. Eye con-
tamination should be treated by prolonged flushing with clean water or saline.

2. Gastrointestinal decontamination. If a potentially toxic amount has been
swallowed and retained and the patient is seen soon after exposure, gastrointes-
tinal decontamination should be considered as outlined in Chapter 2.

3. Seizures. If seizures occur, control may require anticonvulsant medication
as outlined in Chapter 2.

    Boric acid is formulated as tablets and powder to kill larvae in livestock
confinement areas and cockroaches, ants, and other insects in residences. Rarely,
solutions are sprayed as a nonselective herbicide.

    Boric acid powders and pellets scattered on the floors of homes do present
a hazard to children. Their frequent use for roach control increases access for
ingestion. A series of 784 patients has been described with no fatalities and
minimum toxicity. Only 12% of these patients had symptoms of toxicity, mostly
to the gastrointestinal tract.' However, there have been some recent reports of
fatal poisonings,2'3 and a great many poisonings of newborns which occurred
in the 1950s and 1960s often ended in death.4'5 Historically, many poisonings
have resulted from injudicious uses in human medicine aimed at suppressing
bacterial growth, such as compresses for burns,  powders for diaper rash, and
irrigation solutions.6'7 With the increased use of boric acid for  roach control,
suicidal or accidental ingestion is still likely to  occur.3'7
    Borax dust is moderately irritating to skin. Inhaled dust caused irritation of
the respiratory tract among workers in a borax plant. Symptoms included nasal
irritation, mucous membrane dryness, cough, shortness  of breath, and chest
Commercial Products
 dimethyl phthalate

 boric acid
 sodium polyborates
  Polybor 3
 sodium tetraborate




  Skeeter Beater
  Skeeter Cheater
  Skintastic for Kids

 sodium fluoride (wood
 protection only)
 sodium fluosilicate (sodium
 silico fluoride) (nr)
 sodium fluoaluminate

(Continued on the next page)
                                                                                        OTHER INSECTICIDES  • 75

Commercial Products




 barthrin (nr)
 biopermethrin (nr)
 bioresmethrin (nr)
 cismethrin (nr)

(Continued on the next page)
    When determining toxicity to boric acid from ingestion, it is important to
distinguish between acute and chronic exposure. Chronic  ingestion is more
likely to cause significant toxicity than acute exposure.1'2 Borates are well ab-
sorbed by the gut and by abraded or burned skin, but not by intact skin.6 The
kidney efficiently excretes them.The residence half-life in humans averages 13
hours, in a range of 4-28 hours.1
    The gastrointestinal tract, skin, vascular system, and brain are the principal
organs and tissues effected. Nausea, persistent vomiting, abdominal pain, and
diarrhea reflect a toxic  gastroenteritis.1'2'7 Lethargy and headache  may occur,
but are more infrequent.1 In severe poisonings, a beefy red skin rash, most often
affecting palms,  soles, buttocks, and scrotum, has been described.  It has  been
characterized as a "boiled lobster appearance." The intense erythema is fol-
lowed by extensive exfoliation.2'5'10 This may be difficult to distinguish  from
staphylcoccal scalded skin syndrome.10
    Headache, weakness, lethargy, restlessness, and tremors may  occur, but are
less frequent than gastrointestinal effects.1 Seven infants who  were exposed to a
mixture of borax and honey on their pacifiers developed seizures.11 Uncon-
sciousness and respiratory depression signify life-threatening brain injury. Cy-
anosis, weak pulse, hypotension, and cold clammy skin indicate shock, which is
sometimes the cause of death in borate poisoning.2'3'7
    Acute renal  failure (oliguria or  anuria) may be a consequence of shock, of
direct toxic action on renal  tubule cells, or both. It occurs in  severe borate
poisoning.2'3'5'10 Metabolic acidosis may be a consequence of the acid itself, of
seizure activity, or of metabolic derangements.2 Fever is sometimes present in
the absence of infection.
Confirmation of Poisoning

    Borate can be measured in serum by colorimetric methods, as well by
high-temperature atomic spectrometric methods. Urine borate concentrations
in non-exposed individuals are in the range of 0.004-.66 mg/dL. Normal se-
rum levels range up to 0.2  mg/dL in adults, and in children to 0.125 mg/dL.7
Levels reported in toxic incidents have varied widely, and it is felt that serum
levels are of little use in guiding therapy.'

1. Skin  decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
                                   2. Gastrointestinal decontamination. In acute poisonings, if a large amount

has been ingested and the patient is seen within one hour of exposure, gas-
trointestinal decontamination should be considered as outlined in Chapter 2. It
is important to keep in mind that vomiting and diarrhea are common, and
severe poisoning may be associated with seizures.Therefore induction of erne-
sis by syrup of ipecac is probably contraindicated in these exposures. Catharsis
is not indicated if diarrhea is present.

3. Intravenous fluids. If ingestion of borate has been massive (several grams),
or has extended over several days, administer intravenous glucose and electro-
lyte solutions to sustain urinary excretion of borate. Monitor fluid balance and
serum electrolytes (including bicarbonate  capacity)  regularly. Monitor cardiac
status by EGG. Test the urine for protein  and  cells to detect renal injury, and
monitor serum concentration of borate. Metabolic acidosis may be treated with
sodium bicarbonate. If shock develops, it may be necessary to infuse plasma or
whole blood. Administer oxygen continuously. If oliguria (less than 25-30 mL
urine formed per hour) occurs, intravenous fluids must be slowed or stopped to
avoid overloading the circulation. Such patients should usually be referred to a
center capable of providing intensive care  for critically ill patients.

4. Hemodialysis. If renal failure occurs, hemodialysis may be necessary to
sustain fluid balance and normal extracellular fluid composition. Hemodialysis
has had limited success in enhancing clearance of borates.1

5. Peritoneal dialysis has been performed in borate poisoning5-12 and is felt to
be as effective as, and safer than, exchange transfusion in removing borate. No
large study of efficacy  has been done, but it  is still used somewhat less fre-
quently than hemodialysis.1

6. Seizures  should be controlled as recommended for other agents and out-
lined Chapter 2.

    Chlordimeform is an ovicide and acaricide. Formulations are emulsifiable
concentrates and water-soluble powders.

    In a reported episode of occupational exposure to chlordimeform, several
workers developed hematuria. Hemorrhagic cystitis, probably due to chloraniline
biodegradation products, was the source of the blood in the urine. Symptoms
reported by the affected workers included gross hematuria, dysuria, urinary
frequency and urgency, penile  discharge, abdominal and back pain, a general-
Commercial Products
 fenothrin (nr)
 fenpropanate (nr)
 furethrin (nr)
 phthalthrin (nr)

(Continued on the next page)
                                                                                          OTHER INSECTICIDES •  77

Commercial Products


  many commercial products

nr = not registered or withdrawn
ized "hot" sensation, sleepiness, skin rash and desquamation, a sweet taste, and
anorexia. Symptoms persisted for 2-8 weeks after exposure was terminated.13
In a single case, methemoglobinemia was reported.14 Chlordimeform is not a
cholinesterase inhibitor. Chlordimeform has been voluntarily cancelled in the
U.S. due to concerns regarding increased bladder cancer incidence seen in
manufacturing workers.
Confirmation of Poisoning
    Although methods do exist for measurement of urinary excretion prod-
ucts, these tests are not generally available.
                                 1. Precautions. Strenuous efforts should be made to protect against inhalation
                                 and dermal contact with Chlordimeform because absorption is evidently effi-

                                 2. Skin decontamination. Wash skin with soap and water as outlined in
                                 Chapter 2. Eye contamination should be removed by prolonged flushing of the
                                 eye with copious amounts of clean water or saline. If irritation persists, special-
                                 ized  medical treatment should be obtained.

                                 3. Gastrointestinal decontamination. If Chlordimeform has been ingested
                                 no more than an hour prior to treatment, consider gastrointestinal decontami-
                                 nation as outlined in Chapter 2. Repeated doses of charcoal every 2-4 hours
                                 may  be beneficial.

                                 4. Hydration. Because catharsis may cause serious dehydration and electrolyte
                                 disturbances in young children, fluid balance and serum electrolytes should be
                                 monitored. An adequate state of hydration should be maintained by oral and/
                                 or intravenous fluids to support Chlordimeform  excretion.

                                 5. Urinary analysis. Repeated analyses of urine for protein and  red cells
                                 should be done to detect injury to the urinary tract. Disappearance of hema-
                                 turia can ordinarily be expected in 2-8 weeks. Relief from other symptoms can
                                 usually be expected earlier.
                                     Chlorobenzilate is a chlorinated hydrocarbon acaricide, usually formulated
                                 as an emulsion or wettable powder for application in orchards. Use in the
                                 United States has been discontinued.


    Chlorobenzilate is moderately irritating to the skin and eyes. Although struc-
turally similar to DDT, chlorobenzilate is much more rapidly excreted following
absorption, chiefly in the urine as the benzophenone and benzole acid deriva-
tives. Based on observation of dosed animals, extreme absorbed doses may cause
tremors, ataxia, and muscle weakness.There has been one case in humans of toxic
encephalopathy following spraying in a field for 14 days at 10 hours per day.The
patient did not wear a mask while spraying. His symptoms included muscle pain,
weakness, fever, and mental status changes progressing to a tonic-clonic seizure.
He recovered without sequelae within 6 days. Treatment included  respiratory
support and seizure control with phenobarbital and phenytoin.15
    Chlorobenzilate is not a cholinesterase inhibitor.
1. Skin decontamination.  Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.

2. Gastrointestinal decontamination. If a large amount of chlorobenzilate
was ingested within a few hours prior to treatment, consider gastrointestinal
decontamination as outlined in Chapter 2. If the absorbed dose of chlorobenzilate
was small, if treatment is  delayed, and  if  the patient is asymptomatic, oral ad-
ministration of activated charcoal and  sorbitol may be indicated. Do not give
fats or oils.

3. Seizures. Any seizures should be treated as outlined in Chapter 2.


    Tricyclohexyl tin  hydroxide is formulated as a 50% wettable powder for
control of mites on ornamentals, hops,  nut  trees, and some fruit trees. It is
moderately irritating,  particularly to the eyes. While information on the  sys-
temic toxicity of this specific tin compound  is lacking, it should probably be
assumed that cyhexatin can be absorbed to some extent across the skin, and that
substantial absorbed doses would cause nervous system injury (see organotin
compounds in Chapter 15, Fungicides).  Cyhexatin has been voluntarily can-
celled in the United States.
                                                                                      OTHER INSECTICIDES  • 79

                                 1. Skin decontamination. Wash skin with soap and water. Remove contami-
                                 nation from the eyes by prolonged flushing with clean water or saline.

                                 2. Gastrointestinal decontamination. Management of poisonings by inges-
                                 tion should proceed on the assumption that cyhexatin  is toxic, even though
                                 rodent LD5Q values are fairly high, and no human poisonings have been re-
                                 ported. Treatment should be as with other organotin compounds.
                                 DIETHYLTOLUAMIDE  (DEBT)
                                     This chemical is a widely-used liquid insect repellent, suitable for application
                                 to skin or to fabrics. It comes in  a wide range of concentrations from 5% (Off!,
                                 Skintastic for KidsR) to 100% (MuskolR). Compared to the widespread use of the
                                 product, there are relatively few cases of toxicity16 However, if used improperly,
                                 ingested, or a very high concentration is used on children, especially repeatedly
                                 over large skin surfaces, the potential for severe toxicity exists.17 DEET is formu-
                                 lated with ethyl or isopropyl alcohol.
                                     For many years, diethyltoluamide has been effective and generally well
                                 tolerated as an insect repellent applied to human skin, although tingling, mild
                                 irritation, and sometimes desquamation have followed repeated application. In
                                 some cases, DEET has caused contact dermatitis and excerbation of pre-exist-
                                 ing skin disease.18'19 It is very irritating to the eyes, but not corrosive.
                                     Serious adverse effects have occurred when used under tropical condition,
                                 when it was applied to areas of skin that were occluded during sleep (mainly
                                 the antecubital and popliteal fossae). Under these conditions, the skin became
                                 red and tender, then exhibited blistering and erosion, leaving painful weeping
                                 denuded areas that were slow to heal. Severe scarring occasionally resulted
                                 from some of these severe  reactions.20
                                     DEET is efficiently absorbed  across the skin and by the gut. Blood concen-
                                 trations of about 0.3 mg/dL have been reported  several hours after  dermal
                                 application in  the prescribed fashion.17 The amount absorbed increases as the
                                 concentration  of DEET rises. In  addition, many commercial formulations are
                                 prepared with  ethanol as a solvent, which further increases absorption.21 Toxic
                                 encephalopathic reactions have apparently occurred in rare instances following
                                 dermal application, mainly in children who were intensively treated.22'23'24The
                                 more frequent cause of systemic toxicity has been ingestion: deliberate in adults
                                 and accidental in young children.16'17

    Manifestations of toxic encephalopathy have been behavioral disorders in-
cluding headache, restlessness, irritability, ataxia, rapid loss of consciousness,
hypotension, and seizures. Some cases have shown flaccid paralysis and areflexia.
Deaths have occurred following very large doses.16-17-22 Blood levels of DEET
found in fatal systemic poisonings have ranged from 168 to 240 mg per liter.17
Interpretation of DEET toxicity in some fatal cases has been complicated by
effects of simultaneously ingested  ethanol, tranquilizers, and other drugs. One
well-documented case of anaphylactic reaction  to DEET has been reported.
One fatal  case of encephalopathy in a child heterozygous for ornithine  car-
bamoyl transferase deficiency resembled Reyes syndrome, but the postmortem
appearance of the liver was not characteristic of  the syndrome.
    Discretion should be exercised in recommending DEET for persons who have
acne, psoriasis, an atopic predisposition, or other chronic skin condition. It should
not be applied to any skin  area that  is likely to be opposed to another skin surface
for a significant period of time (antecubital and popliteal fossae, inguinal areas) ,22
    Great caution should be exercised in using DEET on children. Avoid re-
peated application day after day. Applications should  be  limited to exposed
areas of skin, using as little repellent as possible and washing off after  use. Do
not apply  to eyes  and mouth and, with young children, do not apply  to their
hands. Low concentrations (10% or below) are effective and may be preferred
in most situations. There are formulations labeled for  children  that have
concentrations  of 5  to 6.5% DEET25 If continuous  repellent protection is
necessary,  DEET should be alternated with a repellent having another active
ingredient. If headache or any kind of emotional or behavioral change occurs,
use of DEET should be discontinued immediately.
Confirmation of Poisoning
    Methods exist for measurement of DEET in blood and tissues and of me-
tabolites in urine, but these are not widely available.

1. Skin decontamination. Wash skin with soap and water as outlined  in
Chapter 2. Eye contamination should be removed by prolonged flushing  of
the eye with copious amounts of clean water or saline. If irritation persists,
specialized medical treatment should be obtained. Topical steroids and oral
antihistamines have been  used  for severe skin reactions that occasionally
follow application of DEET21

2. Gastrointestinal decontamination. If a substantial amount of DEET
has been ingested within an hour of treatment, gastrointestinal decontami-
nation should be considered as outlined in Chapter 2. Induced emesis is
                                                                                      OTHER INSECTICIDES • 81

                                  usually considered contraindicated in these poisonings due to the rapid
                                  onset of seizures.

                                  3. Seizures. Treatment is  primarily supportive, with control of seizures by
                                  anticonvulsants, as  outlined in Chapter 2. Persons surviving poisoning by in-
                                  gestion of DEET have usually recovered within 36 hours or less.16'17

                                     Sodium fluoride is a crystalline mineral once widely used in the United
                                  States for control  of larvae and crawling insects in homes, barns, warehouses,
                                  and other storage  areas. It is highly toxic to all plant and animal life. The only
                                  remaining use permitted is for wood treatement
                                     Sodium fluosilicate  (sodium silico fluoride) has been used to control ec-
                                  toparasites on livestock, as well as crawling insects in homes and work build-
                                  ings.  It is approximately as toxic as sodium fluoride. All uses in the U.S. have
                                  been cancelled.
                                     Sodium fluoaluminate (Cryolite) is a stable mineral containing fluoride. It
                                  is used as an insecticide  on some vegetables and fruits. Cryolite has very low
                                  water solubility, does not yield  fluoride ion on decomposition, and presents
                                  very  little toxic hazard to mammals, including humans.
                                     Hydrofluoric  acid is an important industrial toxicant, but is not used as a
                                  pesticide. Sulfuryl fluoride is discussed in Chapter 16, Fumigants.
                                     Sodium fluoride and fluosilicate used as insecticides present a serious haz-
                                  ard to humans because of high inherent toxicity, and the possibility that chil-
                                  dren  crawling on floors of treated dwellings will ingest the material.
                                     Absorption across the skin is probably slight, and methods of pesticide use
                                  rarely include a hazard of inhalation, but uptake of ingested fluoride by the gut
                                  is efficient and potentially lethal. Excretion is chiefly in the urine. Within the
                                  first 24 hours  of intoxication, renal clearance of fluoride from the blood is
                                  rapid. However, patients go on to continue to excrete large amounts of fluoride
                                  for several days. This is thought to be  due to a rapid binding of fluoride to a
                                  body store, probably bone. The  subsequent release  of fluoride from bone is
                                  gradual enough not to cause a  recurrence of toxicity26'27 Large loads of ab-
                                  sorbed  fluoride may potentially poison renal tubule cells, resulting in acute
                                  renal failure. Children will have  greater skeletal uptake of fluoride than adults,
                                  therefore limiting the  amount the kidney needs to handle. Despite this, chil-
                                  dren are still at great risk because of their smaller body mass compared to adults
                                  in relation to the amount ingested.27

    The toxic effects of fluoride in mammals are multiple, and all may threaten
life.The primary effects from fluoride result from an inhibition of critical intra-
cellular enzymes and the direct effect on ionized calcium in extra-cellular fluid.
Hypocalcemia commonly occurs.26'28-29-30
    Ingested fluoride is transformed in the stomach to hydrofluoric acid, which
has a corrosive effect on the epithelial lining of the gastrointestinal tract.Thirst,
abdominal pain, vomiting, and diarrhea are usual symptoms. Hemorrhage in
the gastric mucosa, ulceration, erosions, and edema are common signs.31
    Absorbed fluoride ion reduces extracellular  fluid concentrations  of
calcium and magnesium. Hypocalcemia sometimes results in tetany.30 Cardiac
arrhythmia and shock are often prominent features of severe poisoning.
Hypotension and severe arrhythmia, sometimes progressing to ventricular
fibrillation, may also occur.26-32 These probably result from combinations of
effects of fluid and electrolyte disturbances including hyperkalemia32 and direct
actions of fluoride on heart and vascular tissues. Fluoride may directly affect the
central nervous system, resulting in  headache, muscle weakness, stupor,
convulsions, and coma.26'27'28 Respiratory failure and ventricular arrythmias are
common causes of death.26-27
Confirmation of Poisoning
    A population drinking water with a concentration of 1 mg per liter will
have a plasma inorganic fluoride concentration between 0.01 and 0.03 mg per
liter28 and rarely above 0.10 mg per liter. In fatal cases of poisoning, plasma
levels of 3.5 mg per liter and higher have been recorded, although survival has
been reported in patients with levels as high as 14 mg per liter.26-28
Treatment: Fluoride Toxicosis
1. Skin decontamination.  Wash skin with soap and water as outlined  in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.

2. Gastrointestinal decontamination.  If sodium fluoride or  sodium
fluosilicate has been ingested, consider gastric decontamination as outlined in
Chapter 2.
    If the victim is obtunded  or if vomiting precludes oral administration, the
airway should be protected by endotracheal intubation, then the stomach should
be gently intubated and lavaged with several ounces of one of the liquids named
below. Activated charcoal is not likely to be of use because it does not bind the
fluoride ion well.
                                                                                      OTHER INSECTICIDES • 83

                                  3. Calcium and magnesium. If the victim is fully alert, and if vomiting does
                                  not totally prevent swallowing of a neutralizing agent, prompt oral administra-
                                  tion of milk, calcium gluconate, or magnesium citrate will precipitate
                                  fluoride ion in the gut and therefore may be life-saving.The milk provides the
                                  calcium ions that will bind to fluoride, thereby reducing absorption. Magne-
                                  sium-based antacids have also been used to neutralize the acid and facilitate the
                                  production of poorly absorbed salts.26  There  are no data on the optimum
                                  amounts to be administered.

                                  4. Blood analysis. A blood specimen should be drawn for serum electrolyte
                                  analysis for sodium, potassium, calcium, magnesium, fluoride, and bicarbon-
                                  ate capacity. Blood should also be  drawn to type and cross match for blood

                                  5. Intravenous fluids (initially 5% dextrose in 0.9% saline) should be started
                                  to combat dehydration, shock, and metabolic acidosis. Fluid balance should be
                                  monitored closely to forestall fluid overload if renal failure occurs. If metabolic
                                  acidosis is detected, sodium bicarbonate should be administered to keep the
                                  urine alkaline as this may hasten excretion.27 Intravenous fluids must be stopped
                                  if anuria or oliguria (less than 25-30 mL per hour) develops.

                                  6. Hemodialysis should be reserved for compromised renal function.26

                                  7.  Monitor cardiac status  by continuous electrocardiography. Ventricular
                                  arrhythmia may necessitate DC cardioversion.

                                  S.Tetany. If overt or latent tetany occurs, or if hypocalcemia is demonstrated,
                                  or  if it appears likely  that a significant amount  of fluoride has been absorbed,
                                  administer 10 mL of 10% calcium gluconate  intravenously, at no more than
                                  1 mL per minute.
                                     Dosage of Calcium Gluconate:
                                     Supplied as 100 mg/mL (10% solution)
                                      • Adults and children over 12years: 10 mL of 10% solution, given slowly,
                                        intravenously. Repeat as necessary.
                                      • Children under 12 years: 200-500 mg/kg/24 hr divided Q6 hr. For
                                        cardiac arrest, 100 mg/kg/dose. Repeat dosage as needed.
                                 9. Oxygen by mask should be administered for hypotension, shock, cardiac
                                 arrhythmia, or cyanosis. Shock may require administration of plasma or blood.

10. Acid Burns. Since these compounds can cause severe acid burns to the
esophagus and stomach, patients should be referred for surgical evaluation and
endoscopy. If burns are documented, treatment for acid burns should be  con-
tinued by a surgeon or gastroenterologist.
Treatment: Sodium Fluoaluminate (Cryolite)
    Cryolite is much less toxic than other fluorides. If a very large amount has
been ingested, it may be appropriate to measure serum calcium to insure that
hypocalcemia has not occurred. If so, intravenous 10% calcium gluconate would
be indicated (see 8 above). It is unlikely that treatment for fluoride toxicity
would be necessary following ingestion of sodium fluoaluminate.

    Diflubenzuron is a haloaromatic substituted urea which controls insects by
impairing chitin deposition in the larval exoskeleton. It is formulated in wet-
table powders, oil dispersible concentrate, and granules for use in agriculture
and forestry, for aerial application against gypsy moth, and in settings where fly
populations tend to be large, such as feedlots. Teflubenzuron is another
haloaromatic substituted urea insecticide with similar toxicologic properties.
    There is limited absorption of diflubenzuron across the skin and intestinal
lining of mammals, after which enzymatic hydrolysis and excretion rapidly
eliminate the pesticide from tissues. Irritant effects are not reported and sys-
temic toxicity is low. Methemoglobinemia is a theoretical risk from chloraniline
formed hydrolytically, but no  reports of this form of toxicity have been re-
ported in humans or animals from diflubenzuron exposure.Teflubenzuron also
shows low systemic toxicity.
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, obtain
specialized medical treatment. Sensitization reactions may require steroid therapy.

2. Gastrointestinal decontamination. If large amounts of propargite  have
been ingested and the patient is seen within an hour, consider gastrointestinal
decontamination. For small ingestions, consider oral administration of activated
charcoal and sorbitol.
                                                                                    OTHER INSECTICIDES • 85

                                    Methoprene is a long chain hydrocarbon ester active as an insect growth
                                regulator. It is effective against several insect species. Formulations include slow-
                                release briquets, sprays, foggers, and baits.
                                    Methoprene is neither an irritant nor a sensitizer in humans or laboratory
                                animals. Systemic toxicity in laboratory animals is very low. No human poi-
                                sonings or adverse reactions in exposed workers have been reported.
                                1. Skin decontamination.  Wash contaminated skin with soap and water.
                                Flush contamination from eyes with copious amounts of clean water or saline.
                                If irritation persists, medical attention must be obtained.

                                2. Gastrointestinal decontamination. If a very large amount of methoprene
                                has been ingested, oral administration of charcoal may be considered.
                                    Propargite is an acaricide with residual action. Formulations are wettable
                                powders and emulsifiable concentrates.
                                    Propargite exhibits very little systemic toxicity in animals. No systemic
                                poisonings have been reported in humans. However, many workers having
                                dermal contact with this acaricide, especially during the summer months, have
                                experienced skin irritation and possibly sensitization in some cases.33 Eye irri-
                                tation has also occurred. For this reason, stringent measures should be taken to
                                prevent inhalation or any skin or eye contamination by propargite.
                                Confirmation of Poisoning
                                    There is no readily available method for detecting absorption of propargite.

    Treatment of contamination and ingestions should proceed essentially as
outlined for haloaromatic substituted urea.

    These modern synthetic insecticides are similar chemically to natural pyre-
thrins, but modified to increase stability in the natural environment. They are
now widely used in  agriculture, in homes and gardens, and for treatment of
ectoparasitic disease.
    Pyrethroids are formulated as emulsifiable concentrates, wettable powders,
granules, and concentrates for ultra low volume application.They may be com-
bined with additional pesticides (sometimes highly toxic) in the technical product
or tank-mixed with other pesticides at the time of application. AASTAR (dis-
continued 1992), for instance, was a combination of flucythrinate and phorate.
Phorate is a highly toxic organophosphate. Nix and Elimite are permethrin
creams applied to control human ectoparasites.
    Certain pyrethroids exhibit striking neurotoxicity in laboratory animals when
administered by intravenous injection, and some are toxic by the oral route. How-
ever, systemic toxicity by inhalation and dermal absorption is low. Although lim-
ited  absorption may account for  the low toxicity of some pyrethroids, rapid
biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is
probably the major factor responsible for this phenomenon.34 Most pyrethroid
metabolites are promptly excreted, at least in part, by the kidney.
    The most severe, although more uncommon, toxicity is to the central ner-
vous system. Seizures have been reported in severe cases of pyrethroid intoxica-
tion. Of 573  cases  reviewed in China, there  were 51 cases with disturbed
consciousness and 34 cases with seizures. Of those, only 5 were from occupa-
tional exposure.35 Seizures are more common with exposure to the more toxic
cyano-pyrethroids, which include fenvalerate, flucythrinate, cypermethrin,
deltapermethrin, and fluvalinate.34 There are no reports in the literature of sei-
zures in humans from exposure  to permethrin.
    Apart from central nervous system toxicity, some pyrethroids do cause dis-
tressing paresthesias when liquid or volatilized materials contact human skin.
Again, these symptoms are more  common with exposure to the pyrethroids
whose structures include cyano-groups.34 Sensations are described as stinging,
burning, itching, and tingling, progressing to numbness.35<36<37  The skin of the
face  seems to  be most commonly affected, but the face, hands, forearms, and
neck are sometimes involved. Sweating, exposure to sun or heat, and applica-
                                                                                       OTHER INSECTICIDES • 87

                             tion of water enhance the disagreeable sensations. Sometimes the effect is noted
                             within minutes of exposure, but a 1-2 hour delay in appearance of symptoms is
                             more common.36'37Sensations  rarely persist more than 24 hours. Little or no
                             inflammatory reaction is apparent where the paresthesia are reported; the effect
                             is presumed to result from pyrethroid  contact with  sensory nerve endings in
                             the skin.The paresthetic reaction is not allergic in nature, although sensitization
                             and allergic responses have been reported as an independent phenomenon with
                             pyrethroid exposure. Neither race, skin type, nor disposition to allergic disease
                             affects the likelihood or severity of the reaction.
                                 Persons treated with permethrin for lice or flea infestations sometimes ex-
                             perience itching and burning at the site of application, but this is chiefly an
                             exacerbation of sensations caused by the parasites themselves, and is not typical
                             of the paresthetic reaction described above.
                                 Other signs and symptoms of toxicity include abnormal facial sensation, diz-
                             ziness, salivation, headache, fatigue, vomiting, diarrhea, and irritability to sound
                             and touch. In more severe cases, pulmonary edema and muscle fasciculations can
                             develop.35 Due  to the inclusion of unique solvent ingredients, certain formula-
                             tions  of fluvalinate are corrosive to the eyes. Pyrethroids are not cholinesterase
                             inhibitors. However, there have been some cases in which pyrethroid poisoning
                             has been misdiagnosed as organophosphate poisoning, due to some of the similar
                             presenting signs, and some patients have died from atropine toxicity35
                             1. Skin decontamination. Wash skin promptly with soap and water as out-
                             lined in Chapter 2. If irritant or paresthetic effects occur, obtain treatment by a
                             physician. Because volatilization of pyrethroids apparently accounts for pares-
                             thesia affecting the face, strenuous measures should be taken (ventilation, pro-
                             tective face mask and  hood) to avoid vapor contact with the face and eyes.
                             Vitamin E oil preparations (dL-alpha tocopheryl acetate) are uniquely effective
                             in preventing and stopping the paresthetic reaction.37'38They are safe for appli-
                             cation to the skin under field conditions. Corn oil is somewhat effective, but
                             possible side effects  with continuing use make it less suitable. Vaseline is less
                             effective than corn oil. Zinc oxide actually worsens the  reaction.

                             2. Eye contamination. Some  pyrethroid compounds can be very corrosive
                             to the eyes. Extraordinary measures should be  taken to avoid eye contamina-
                             tion. The eye should be treated immediately by prolonged flushing of the eye
                             with copious amounts of clean water or saline. If irritation persists, obtain pro-
                             fessional ophthalmologic care.

                             3. Gastrointestinal decontamination. If large amounts of pyrethroids, espe-
                             cially the  cyano-pyrethroids, have been ingested and the patient is seen soon

after exposure, consider gastrointestinal decontamination as outlined in Chap-
ter 2. Based on observations in laboratory animals34 and humans,35 large ingestions
of allethrin, cismethrin, fluvalinate, fenvalerate, or deltamethrin would be the
most likely to generate neurotoxic manifestations.
    If only small amounts of pyrethroid have been ingested, or if treatment
has been delayed, oral administration of activated charcoal and cathartic prob-
ably represents optimal management. Do not  give  cathartic if patient has
diarrhea or an ileus.

4. Other treatments.  Several drugs are effective in  relieving the pyrethroid
neurotoxic manifestations observed in deliberately poisoned laboratory animals,
but none has been tested in human poisonings. Therefore, neither efficacy nor
safety under these circumstances is known. Furthermore, moderate neurotoxic
symptoms and signs are likely to resolve spontaneously  if they do occur.

5. Seizures. Any seizures should be treated as outlined in Chapter 2.
    Elemental sulfur is an acaricide and fungicide widely used  on orchard,
ornamental, vegetable, grain, and other crops. It is prepared as dust in various
particle sizes and applied as such, or it may be formulated with various minerals
to improve flowability, or applied as an aqueous emulsion or wettable powder.
    Elemental sulfur is moderately irritating to the skin and is associated with
occupationally  related irritant dermatitis.39 Airborne dust is irritating to  the
eyes and the respiratory tract. In hot sunny environments, there may be some
oxidation of foliage-deposited sulfur to gaseous sulfur oxides, which are very
irritating to the eyes and respiratory tract.
    Ingested sulfur powder induces catharsis, and has been used medicinally
(usually with molasses) for that purpose. Some hydrogen sulfide is formed in
the large intestine and this may present a degree of toxic hazard.The character-
istic smell of rotten eggs may aid in the diagnosis. An adult has survived inges-
tion of 200 grams.40
    Ingested colloidal sulfur is efficiently absorbed by the gut and is promptly
excreted in the urine as inorganic sulfate.
                                                                                        OTHER INSECTICIDES • 89

                                     1. Skin decontamination. Wash skin with soap and water. Contamination of
                                     the eyes should be removed by prolonged flushing with clean saline or water. If
                                     eye irritation persists, obtain ophthamologic care.

                                     2. Gastrointestinal  decontamination. Unless an extraordinary amount of
                                     sulfur (several grams)  has been ingested  shortly prior to treatment, there is
                                     probably no need for gastrointestinal decontamination. Adsorbability of sulfur
                                     on activated charcoal has not been tested.
                                         The most serious consequence of sulfur ingestion is likely to be  that of
                                     catharsis, resulting in dehydration and electrolyte depletion, particularly in chil-
                                     dren. If diarrhea is severe, oral or intravenous administration of glucose and/or
                                     electrolyte solutions may be appropriate.
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                                     2.  Restuccio A, Mortensen ME, and Kelley MT. Fatal ingestion of boric acid in an adult. Am J
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                                     3.  Ishii Y, Fujizuka N.TakahashiT, et al. A fatal case of acute boric acid poisoning. Clin Toxicol
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25. Hebert AA and Carlton S. Getting bugs to bug off: A review of  insect repellents. Contemp
    Pediatr 1998; 15:85-95.
26. YolkenR.Konecny Band McCarthy B. Acute fluoride poisoning. Pediatrics 1976;58(l):90-3.
27. Heifetz  SB and Horowitz HS. Amounts of  fluoride  in self-administered dental products:
    Safety considerations for children. Pediatrics 1986;77(6):876-82.
28. Gessner BD, Beler M, Middaugh JB, and Whitford GM. Acute fluoride poisoning from a
    public water system. NewEngl JMed 1994;330(2):95-9.
29. Swanson B, Bilandrinos DT, Shevlin JM, and Willett JR. Death from accidental ingestion of
    an ammonium and sodium bifluoride glass etching compound. Vet Hum Toxicol 1993; 35 (4): 351.
30. Harchelroad B and Goetz C. Systemic fluoride intoxication with leukocytosis and pyrexia.
    Vet Hum Toxicol 1993;35(4):351.
31. Spak  CJ, Sjostedt S, Eleborg B, et al. Tissue  response of gastric mucosa after ingestion of
    fluoride. Br Med J 1989;298:1686-7.
32. Baltazar RD, Mower MM, Reider  R, et al. Acute fluoride poisoning leading to fatal hyper-
    kalemia. Chest 1980;78:660.
33. Saunders BD, Ames RG, Knaak JB, et al. Outbreak of omite-cr-induced dermatitis among
    orange pickers inTulare County, California. / Occup Med 1987;29:409-13.
34. Dorman DC and BeasleyVR. Neurotoxicology of pyrethrin and the pyrethroid insecticides.
35. He B, Wang S, Bui B, et al. Clinical manifestations and diagnosis of acute pyrethroid poison-
    ing. ArchToxicol 1989;63:54-8.
36. Tucker SB and Blannigan SA. Cutaneous effects from occupational exposure to fenvalerate.
    Arch Toxicol 1983;54:195-202.
37. Blannigan SA,Tucker SB, Key MM, et al. Synthetic pyrethroid insecticides: Adermatological
    evaluation. Br J Ind Med 1985;42:363-72.
                                                                                                           OTHER INSECTICIDES  •  91

                                         38.  Tucker SB, Flannigan SA, and Ross CE. Inhibitions of cutaneous paresthesia resulting from
                                             synthetic pyrethroid exposure. Int JDermatol 1984;10:686-9.
                                         39.  O'Malley MA. Skin reactions to pesticides. Occup Med 1997; 12:327-45.
                                         40.  Schwartz SM, Carroll HM, and Scharschmidt LA. Sublimed (inorganic) sulfur ingestion - A
                                             cause of life-threatening metabolic  acidosis with  a  high anion gap. Arch Intern Med

   Section III

                                   CHAPTER 9

Signs and Symptoms:
•  Irritating to skin and
   mucous membranes
•  Vomiting, diarrhea,
   headache, confusion,
   bizarre or aggressive
   behavior, peculiar odor on
•  Metabolic acidosis, renal
   failure, tachycardia
• Washing, Gl
• Administer IV
• Forced alkaline diuresis
Chlorophenoxy  Herbicides
Chlorophenoxy compounds are sometimes mixed into commercial fertilizers
to control growth of broadleaf weeds. Several hundred commercial products
contain Chlorophenoxy herbicides in various forms, concentrations, and com-
binations. In some cases, the same name is used for products with different
ingredients. The exact composition must therefore be determined from the
product label. Sodium, potassium, and alkylamine salts are commonly formu-
lated as aqueous solutions, while the less water-soluble esters are applied as
emulsions. Low molecular weight esters are more volatile than the acids, salts,
or long-chain esters.
    Some of the Chlorophenoxy acids, salts, and esters are moderately irritating
to skin, eyes, and respiratory and gastrointestinal linings. In a few individuals,
local depigmentation has apparently resulted from protracted dermal contact
with Chlorophenoxy compounds.
    Chlorophenoxy compounds are  well absorbed from  the gastrointestinal
tract.1 They are less well absorbed from the lung. Cutaneous absorption appears
to be minimal.2 The compounds are not significantly stored in fat. Excretion
occurs almost entirely by way of urine. Apart from some  conjugation of the
acids, there is limited  biotransformation in the body.1'2 The compounds are
highly protein bound.2 The average residence half-life of 2,4-D in humans is
between  13 and 39 hours,1'3'4'5 while that of 2,4,5-T is about 24 hours. Excre-
tion is greatly enhanced in alkaline urine,4'5'6 and with a half-life as prolonged
as 70-90 hours with acidic urine.6 Half-life is also longer with large doses and
prolonged exposure.
    Given in large doses to experimental animals, 2,4-D causes vomiting, diar-
rhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic injury
to the liver, kidneys, and central nervous system. Myotonia (stiffness and inco-
ordination of hind extremities) develops in some species and is apparently due
to CNS damage: demyelination has been observed in the dorsal columns of the
cord, and EEC changes have indicated functional disturbances in the brains of
heavily-dosed experimental animals.
    Ingestion of large amounts of Chlorophenoxy acids  has resulted in severe
metabolic acidosis in humans. Such cases have been associated with electrocar-

diographic changes, myotonia, muscle weakness, myoglobinuria, and elevated
serum creatine phosphokinase, all reflecting injury  to  striated muscle.
Chlorophenoxy acids are weak uncouplers of oxidative phosphorylation; there-
fore, extraordinary doses may produce hyperthermia from increased produc-
tion of body heat.5
    In the manufacture of some of these herbicides, other more toxic sub-
stances can be formed at excessive  temperatures. These include chlorinated
dibenzo  dioxin (CDD) and  chlorinated dibenzo  furan  (CDF). The 2,3,7,8-
tetra CDD form is extraordinarily toxic to multiple mammalian tissues; it is
formed only in the synthesis of 2,4,5-T Hexa-, hepta-, and octa-compounds
exhibit less systemic toxicity, but are the likely cause of chloracne (a chronic,
disfiguring skin condition) seen in  workers engaged in the manufacture of
2,4,5-T and certain other chlorinated  organic compounds.7 Although toxic
effects, notably chloracne, have been observed in manufacturing plant workers,
these effects have not been observed in formulators or applicators regularly
exposed to 2,4,5-T or other chlorophenoxy compounds. All uses of 2,4,5-T in
the U.S. have been cancelled.
    The medical literature contains reports of peripheral neuropathy following
what seemed to be minor dermal exposures to 2,4-D8  It is not certain that
exposures to other neurotoxicants were entirely excluded in these cases. Single
doses of 5 mg/kg body weight of 2,4-D and 2,4,5-T have been administered to
human subjects without any adverse  effects. One subject consumed 500 mg of
2,4-D per day for 3 weeks without experiencing symptoms or signs of illness.
Commercial Products

2,4-dichlorophenoxyacetic acid
 acid (2,4-DP)
 acid (2,4-DB)
2,4,5-trichlorophenoxy acetic
 acid (2,4,5-T)
mecoprop (MCPP)
2-methyl-3, 6 dichlorobenzoic
Signs and Symptoms of Poisoning
    Chlorophenoxy compounds are moderately irritating to skin and mucous
membranes. Inhalation of sprays may cause burning sensations in the nasophar-
ynx and chest, and coughing may result. Prolonged inhalation sometimes causes
dizziness. Adjuvant chemicals added to enhance foliage penetration might ac-
count for the irritant effects of some formulations.
    Manifestations of systemic toxicity of chlorophenoxy compounds are known
mainly from clinical experience with cases of deliberate suicidal ingestion of
large quantities. Most reports of fatal outcomes involve renal failure, acidosis,
electrolyte imbalance, and a resultant multiple organ failure.3'6'9 The agents most
often involved in these incidents have been 2,4-D and mecoprop. The toxic
effects of other chlorophenoxy compounds are probably similar but not identical.
    Patients will present within a few hours of ingestion with vomiting, diar-
rhea, headache, confusion, and bizarre  or aggressive behavior. Mental status
changes occur with progression to coma in severe cases.4'5'6 A peculiar odor is
often noticed on the breath. Body  temperature may be moderately  elevated,
but this is rarely  a life-threatening  feature of the poisoning. The  respiratory
drive is not depressed. Conversely, hyperventilation is sometimes evident, prob-
                  • 95

                                 ably secondary to the  metabolic acidosis that occurs. Muscle weakness and
                                 peripheral neuropathy have been reported after occupational exposure.6 Con-
                                 vulsions occur very rarely. With effective urinary excretion  of the toxicant,
                                 consciousness  usually returns in 48-96 hours.4'5-6
                                     As mentioned above, chlorophenoxy compounds cause significant meta-
                                 bolic changes.  Metabolic acidosis is manifest as a low arterial pH and bicarbon-
                                 ate content. The urine is usually acidic. Skeletal muscle injury, if it occurs, is
                                 reflected in elevated creatine phosphokinase,  and sometimes  myoglobinuria.
                                 Moderate elevations of blood urea nitrogen and serum creatinine are com-
                                 monly found  as the toxicant is excreted. Cases of renal failure are reported,
                                 often with  an  accompanying hyperkalemia or hypocalcemia that was thought
                                 to result in the cardiovascular instability that led to death.3-9Tachycardia is com-
                                 monly observed, and hypotension has also been reported.3-4-6T-wave flattening
                                 has also been observed.5 Mild leukocytosis and biochemical changes indicative
                                 of liver cell injury have been reported.
                                     Myotonia  and muscle weakness may persist for months after acute  poison-
                                 ing.5 Electromyographic and nerve conduction studies in some recovering pa-
                                 tients have  demonstrated a mild proximal neuropathy and myopathy.
                                 Confirmation of Poisoning

                                     Gas-liquid  chromatographic methods are available  for detecting
                                 chlorophenoxy compounds in blood and urine. These analyses are useful in
                                 confirming and assessing the magnitude of chlorophenoxy absorption. Poison-
                                 ing characterized by unconsciousness has shown initial blood  chlorophenoxy
                                 concentrations ranging from 80 to more than 1000 mg per liter.4 Urine samples
                                 should be collected as soon as possible after exposure because the herbicides
                                 may be almost completely excreted in 24-72 hours under normal conditions.
                                 Urine samples can also confirm overexposure. In a study of asymptomatic her-
                                 bicide applicators, their urinary excretion of chlorophenoxy compounds rarely
                                 exceeded  1-2 mg/L.10The half-life may be  much longer in cases of intoxica-
                                 tion depending on the extent of absorption  and urine pH.
                                     Analyses can be performed at special laboratories usually known to local poi-
                                 son control centers.  If the  clinical scenario indicates that excessive exposure to
                                 chlorophenoxy compounds has occurred, initiate appropriate treatment measures
                                 immediately. Do not wait for chemical confirmation of toxicant absorption.
                                 1. Precautions. Individuals with chronic skin disease or known sensitivity to
                                 these herbicides should either avoid using them or take strict precautions to
                                 avoid contact (respirator, gloves, etc.).

2. Respiratory protection. If any symptoms of illness occur during or fol-
lowing inhalation of spray, remove victim from contact with the material for at
least 2-3 days. Allow subsequent contact with chlorophenoxy compounds only
if effective respiratory protection is practiced.

3. Skin decontamination. Flush contaminating chemicals from eyes with
copious amounts of clean water for  10-15 minutes. If irritation persists, an
ophthalmologic examination should be performed.

4. Gastrointestinal decontamination. If substantial amounts of chlorophenoxy
compounds have been ingested, spontaneous emesis may occur. Gastric decon-
tamination procedures may be considered, as outlined in Chapter 2.

5. Intravenous fluids. Administer intravenous fluids to accelerate excretion of
the chlorophenoxy compound, and to limit concentration of the toxicant in
the kidney. A urine flow  of 4-6 mL/minute  is desirable. Intravenous saline/
dextrose has sufficed to rescue comatose patients who drank 2,4-D and mecoprop
several hours before hospital admission.
    Caution: Monitor urine protein and cells, BUN, serum creatinine, serum
electrolytes, and fluid  intake/output carefully  to insure  that renal function re-
mains unimpaired and that fluid overload does not occur.

6. Diuresis. Forced alkaline diuresis has been used successfully in management
of suicidal ingestions of chlorophenoxy compounds, especially when initiated
early.4'5'6 Alkalinizing the urine  by including sodium bicarbonate (44-88 mEq
per liter) in the intravenous solution accelerates excretion of 2,4-D dramati-
cally and mecoprop excretion substantially. Urine pH  should be maintained
between 7.6 and 8.8. Include potassium chloride as needed to offset increased
potassium losses: add 20-40 mEq of potassium chloride to each liter of intrave-
nous solution. It is crucial to monitor serum electrolytes  carefully, especially
potassium and calcium.
    There may possibly be some hazard to  the kidneys when urine concentra-
tions of toxicant are very high, so the integrity  of renal  function  and fluid
balance  should be monitored carefully as the chlorophenoxy compound is ex-
creted. Renal failure has occurred in patients with severe intoxication during
alkaline diuresis. In one case, the diuresis was  begun 26 hours after ingestion,6
and the  other two  were initiated a couple  days after poisoning.3'9

7. Hemodialysis is not  likely to be  of significant benefit in poisonings by
chlorophenoxy compounds. It  has been used in  four  patients who  survived
intoxication.11 However, given the highly protein-bound nature of these herbi-
cides and lack of any other evidence, hemodialysis is not recommended.2
                                                                                        HERBICIDES      •  97

                                      8. Follow-up clinical examination should include electromyographic and
                                      nerve conduction studies to detect any neuropathic changes and neuromuscu-
                                      lar junction defects.

                                      General Chemical  Structure
                                                            Cl (orCH3)
                                      1.  Kohli JD, Khanna RN, Gupta BN, et al. Absorption and excretion of 2,4-dichlorophenoxy-
                                          acetic. Xenobiotica 1974;4(2):97-100.
                                      2.  Arnold EK, Beasley MS, and Beasley VR. The pharmacokinetics of chlorinated phenoxy
                                          acid Herbicides:A literature review. Vet Hum Toxicol 1989;31(2):121-5.
                                      3.  KellerT, Skopp G,Wu M, et al. Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D).
                                          Forensic Sci Int 1994;65:13-8.
                                      4.  Friesen EG, Jones GR, andVaughan D. Clinical presentation and management of acute 2,4-
                                          D oral ingestion. Drug Saf 1990;5(2): 155-90.
                                      5.  Prescott LF, Park J,  and Darrien I.Treatment of severe 2,4-D and mecoprop intoxication
                                          with alkaline diuresis.  En journal of Clinical Pharmacology 1979;7:111-116.
                                      6.  Flanagan RJ, Meredith TJ, Ruprah M, et  al. Alkaline diuresis for acute poisoning with
                                          chlorophenoxy herbicides and ioxynil. Lancet 1990;335:454-8.
                                      7.  Poskitt LB, Duffill MB, and Rademaker M. Chloracne, palmoplantar keratoderma and local-
                                          ized scleroderma in a  weed sprayer. Clin and Exp Dermatol 1994; 19:264-7.
                                      8.  O'Reilly JE Prolonged coma and delayed peripheral  neuropathy after ingestion of
                                          phenoxyacetic acid  weedkillers. Postgrad Med Journal 1984;60:76-7.
                                      9.  Kancir CB, Anderson C, and Olesen AS. Marked hypocalcemia in a fatal poisoning with
                                          chlorinated phenoxy acid derivatives. Clin Toxicol 26(3&4):257-64.
                                      10. Kolmodin-Hedman B, Hoglund S, and Akerblom M. Studies on phenoxy acid herbicides, I,
                                          Field study: Occupational  exposure to  phenoxy acid herbicides (MCPA, dichlorprop,
                                          mecoprop,and 2,4-D) in agriculture. ArchToxicol 1983;54:257-65.
                                      11. Durakovic Z, Durakovic A, Durakovic S, et al. Poisoning with 2,4- dichlorophenoxyacetic
                                          acid treated by hemodialysis. ArchToxicol 1992;66:518-21.

Pentachlorophenol (PCP) is currently registered in the United States only as
a restricted use pesticide for use as a wood preservative. PCP has been used as
an herbicide, algacide, defoliant, wood preservative, germicide, fungicide, and
molluscicide.1 As a wood preservative, it is commonly applied as a 0.1% solu-
tion in mineral spirits, No. 2 fuel oil, or kerosene. It is used in pressure treat-
ment of lumber at  5%  concentration. Weed killers  have contained  higher
    Pentachlorophenol volatilizes from treated wood and fabric. It has a signifi-
cant phenolic odor, which becomes quite strong when the material is heated.
Excessively treated interior surfaces may be a source of exposure sufficient to
cause irritation of eyes, nose, and throat.
    Technical PCP contains lower chlorinated phenols (4-12%) plus traces of
chlorobenzodioxins, chlorobenzofurans, and chlorobenzenes. Incomplete com-
bustion of PCP-treated wood may lead to the formation of these compounds.

    PCP is readily absorbed across the skin, the lungs, and the gastrointestinal
lining. In animals, the dermal LD50 is of the same  order of magnitude as the
oral. With acute  exposure it is rapidly excreted, mainly in the urine, as un-
changed PCP and as  PCP glucuronide. In chronic exposures, the elimination
half-life has been reported to be very long, up to 20  days.2 In another study,
three volunteers took consecutive oral doses of PCP, and a half-life of 20 days
was also found.The long half-life was attributed to  the low urinary clearance
because of high protein binding.3 In the blood, a large fraction of absorbed
PCP is protein-bound. It is  widely distributed to other tissues in the body,
including kidney, heart, and adrenal glands.
    At certain concentrations, PCP is irritating to mucous membranes and
skin. Contact dermatitis is common among workers having contact with PCP.
In a study of employees involved in the manufacture of PCP, chloracne was
found in 7% of the workers, and the risk was significantly higher among em-
ployees with documented skin contact compared to employees without skin
contact.4 Urticaria has also been reported as an uncommon response in ex-
posed persons.

• Absorbed by skin, lung, Gl
• Fatalities reported,
  associated with intensive
  exposure in hot

Signs and Symptoms:
• Irritation of the nose,
  throat, and eyes
• Hyperthermia, muscle
  spasm, tremor, labored
  breathing, and chest
  tightness indicate serious

• No specific antidote
• Control fever, replace fluids,
• Decontaminate eyes, skin,
  hair, clothing
• Monitor cardiac status,
  control agitation

• Salicylates for fever control
                                                                                    PENTACHLOROPHENOL • 99

Commercial Products

The sodium salt is sodium
    The primary toxicological mechanism is increased cellular oxidative me-
tabolism resulting from the uncoupling of oxidative phosphorylation. Heat pro-
duction is increased and leads to clinical hyperthermia.This clinical state may
mimic the signs and symptoms found in hyperthyroidism. Internally, large doses
are toxic to the liver, kidneys, and nervous system.
    Based on laboratory experimentation on animals, PCP has been reported
to have fetotoxic and  embrotoxic properties and to bind to various hormone
receptors.5'6 Epidemiological evidence suggests exposed persons may be at risk
for miscarriages, reduced birth weight, and other malformations.7-8
    Albuminuria, glycosuria, aminoaciduria, and elevated BUN reflect renal
injury. Liver enlargement, anemia, and leukopenia have been reported in some
intensively exposed workers. Elevated serum alkaline phosphatase, AST, and
LDH enzymes indicate  significant insult to the liver, including both cellular
damage and some degree of biliary obstruction.
                                    Signs and Symptoms of Poisoning
                                       The most common effects of airborne PCP include local irritation of the
                                    nose, throat, and eyes, producing a stuffy nose, scratchy throat, and tearing.
                                    Dermal exposure is also common and may lead to irritation, contact dermatitis,
                                    or  more rarely,  diffuse urticaria or chloracne. Individual  cases of exfoliative
                                    dermatitis of the hands and diffuse urticaria and angioedema of the hands have
                                    been reported in intensively exposed workers. Several infant deaths occurred in
                                    a nursery where a PCP-containing diaper rinse had been used.
                                       Severe poisoning and  death have  occurred as a result of intensive PCP
                                    exposure. Acute poisoning occurs with systemic absorption which can occur
                                    by  any route of sufficient dosage. Most  occupational poisonings occur through
                                    dermal contact. Hyperthermia, muscle spasm, tremor, labored breathing, and
                                    chest tightness indicate serious poisoning. The patient may also complain of
                                    abdominal pain, and exhibit  vomiting, restlessness, and mental confusion. Ta-
                                    chycardia and increased respiratory rate are usually apparent. Other commonly
                                    reported signs and symptoms of systemic poisoning include profuse sweating,
                                    weakness, dizziness, anorexia, and intense thirst. Workers  exposed over long
                                    periods may experience weight loss.
                                       Most adult  fatalities have occurred in persons working in hot environ-
                                    ments where hyperthermia is poorly tolerated. Cases of aplastic  anemia and
                                    leukemia have been reported which were associated temporally with PCP ex-
                                    posure. Causal relationships in these cases were not established.9 Peripheral neu-
                                    ropathies have also been reported in some  cases of long-term occupational
                                    exposure; however, a causal relationship has not been supported by longitudi-
                                    nal studies.10

Confirmation of Poisoning
    If poisoning is strongly suspected on the basis of exposure, symptoms, and
signs, do not postpone treatment until diagnosis is confirmed.
    PCP can be measured in blood, urine, and adipose tissue  by gas-liquid
chromatography. Plasma levels can be much greater than urine levels (ratio of
blood to urine  is 1.0 to 2.5) so care must be taken in interpreting results.10'11
There is no clear-cut determination of what constitutes an abnormally high
level of PCP, and there is great variability  among different references. Most
information on the extent of serum levels  in relation to toxicity  is based on
individual cases or small series of patients. Reports exist of asymptomatic in-
fants with serum levels as high as 26 parts per million (ppm).11'12 However, most
reports of non-occupational exposure in the general public involve levels in the
parts per billion range.1-13"15 Food is probably the main source  of this nano-
gram-level  dosage.1 Serum levels among occupationally exposed  persons often
exceed  1 ppm.1 A report of a lethal  case describes a plasma level of 16  ppm,16
but most cases generally involve serum  levels  in the range of 100 ppm or
higher.11-17 It is  reasonable to assume that levels greater than 1 ppm are consis-
tent with an unusual exposure and that levels approaching 100 ppm are cause
for great concern.

1. Supportive treatment and hyperthermia control. There is no specific
antidote to  the poisoning; therefore treatment is supportive in nature including
oxygen, fluid replacement, and most importantly, fever control.
    Reduce elevated body temperature by physical means. Administer sponge
baths and use fans to increase evaporation.18  In fully conscious patients, admin-
ister cold, sugar-containing liquids by mouth as tolerated. Cooling blankets and
ice packs to body surfaces may also be used.
    Antipyretic therapy with salicylates is strongly contraindicated as salicy-
lates also uncouple oxidative phosphorylation. Other antipyretics are thought
to be of no use because of the peripherally mediated mechanism  of hyperther-
mia in poisoning of this nature. Neither the safety nor the effectiveness of the
other antipyretics has been tested.
    Administer oxygen continuously by mask to minimize tissue anoxia. Un-
less there are manifestations of cerebral or pulmonary edema or  of inadequate
renal function, administer intravenous fluids to  restore hydration and support
physiologic mechanisms for heat loss and  toxicant disposition. Monitor serum
electrolytes, adjusting IV infusions to stabilize electrolyte concentrations. Fol-
low urine contents of albumin and cells, and keep an accurate hourly record of
intake/output to forestall fluid overload if renal function declines.
    Caution: In the presence of cerebral edema and/or impaired  renal func-
tion, intravenous fluids must be administered very cautiously to avoid increased
                                                                                    PENTACHLOROPHENOL • 101

                                 intracranial pressure and pulmonary edema. Central monitoring of venous and
                                 pulmonary wedge pressures may be indicated. Such critically ill patients should
                                 be treated in an intensive care unit.

                                 2. Skin decontamination. Flush the chemical from eyes with copious amounts
                                 of clean water. Perform skin decontamination as described in Chapter 2.

                                 3. Cardiopulmonary  monitoring. In severe poisonings, monitor pulmo-
                                 nary status carefully to insure adequate gas exchange, and  monitor cardiac sta-
                                 tus  by EGG to detect arrhythmias. The toxicant  itself and severe electrolyte
                                 disturbances may predispose to arrhythmias and myocardial weakness.

                                 4. Neurological. To reduce production of heat in the body, control agitation and
                                 involuntary motor activity with sedation. Lorazepam or other benzodiazepines
                                 should be effective, although use of these drugs in these poisonings has not been
                                 reported. If lorazepam is chosen, administer slowly, intravenously.
                                     Dosage of Lorazepam:
                                      • Adults:  2-4 mg/dose IV given over 2-5 minutes. Repeat if necessary
                                       to a maximum of 8 mg in a 12-hour period.
                                      • Adolescents: Same as adult dose, except maximum dose is 4 mg.
                                      • Children under 12years: 0.05-0.10 mg/kg IV over 2-5 minutes. Re-
                                       peat if necessary 0.05 mg/kg 10-15 minutes after first dose, with a
                                       maximum dose of 4 mg.

                                     Caution: Be prepared to assist pulmonary ventilation mechanically if
                                     respiration is depressed, to intubate the trachea if laryngospasm occurs,
                                     and to counteract hypotensive reactions.
                                 5. Gastrointestinal decontamination. If PGP has been ingested in a quan-
                                 tity sufficient to cause poisoning and the patient presents within one hour,
                                 consider gastric decontamination as outlined in Chapter 2.

                                 6. Nutrition. During convalescence, administer a high-calorie, high-vitamin
                                 diet to restore body fat and carbohydrates. Discourage subsequent contact with
                                 the toxicant for 4-8 weeks  (depending on severity of poisoning) to allow full
                                 restoration of normal metabolic processes.

Chemical Structure
1.   Jorens PG and  Schepens PJC. Human pentachlorophenol  poisoning. Hum Exp Toxicol
2.   Kalman DA and Horstman SW Persistence of tetrachlorophenol and pentachlorophenol in
    exposed woodworkers. JToxicol ClinToxicol 1983;20:343.
3.   Uhl S, Schrnid P and Schlatter C. Pharmacokinetics of pentachlorophenol in man. Arch
    Toxicol \986;58:182-6.
4.   O'Malley MA, Carpenter AV, Sweeney MH, et al. Chloracne associated with employment in
    the production of pentachlorophenol. Am ]Ind Med 1990;17:411-21.
5.   Danzo BJ. Environmental xenobiotics may disrupt normal endocrine function by interfer-
    ing with the binding of physiological ligands to steroid receptors and binding  proteins.
    Environ Health Perspect 1997:105:294-301.
 6.  Tran DQ.KlotzDM.Ladlie BL.et al.  Inhibition of progesterone receptor activity in yeast by
    synthetic chemicals. Biochem Biophys Res Commun 1996;229:518-23.
7.   Dimich-Ward H, Hertzman C.Teschke K, et al. Reproductive effects of paternal exposure to
    chlorophenate  wood preservatives in the sawmill  industry.  Scand J Work Environ Health
8.   DeMaeyer J, Schepens PJ, Jorens PG, andVerstaete R.  Exposure to pentachlorophenol as a
    possible cause of miscarriages.  BrJ Obstet Gynaecol  1995;102:1010-1.
9.   Roberts HJ.Aplastic anemia due to pentachlorophenol.  NewEngl]Med 1981;305:1650-1.
10.  Casarett LJ, Bevenue A.Yauger WL, and Whalen SA. Observations on pentachlorophenol in
    human blood and urine. Am Ind HygAssoc J 1969;30:360-6.
11.  Clayton GD and Clayton FE (eds). Patty's Industrial Hygiene and Toxicology, vol 2B, 4th ed.
    New York: John Wiley & Sons,  1994, pp. 1605-13.
12.  Robson AM, Kissane JM, Elvick WH, et al. Pentachclorophenol poisoning in a nursery for
    newborn infants: Clinical features and treatment. /Pediatr 1969;75:309-16.
13.  Gomez-Catalan J,To-Figueras J, Planas J, et al. Pentachlorophenol and hexachlorobenzene in
    serum and urine of the population of Barcelona. Hum Toxicol  1987;6:397-400.
14.  Wylie JA, Gabica J, Benson WW,  and Yoder J. Exposure and contamination of the air and
    employees of a pentachlorophenol plant, Idaho-1972. Pest Monit J 1975;9:150-3.
15.  Wagner SL. Pentachlorophenol.  In: Clinical Toxicology of Agricultural Chemicals. Corvallis,
    OR: Oregon State University Press, 1981, pp.  131-7.
16.  Wood S, Rom WN, White GL, and Logan DC. Pentachlorophenol poisoning. / Occup Med
17.  Gray RE, Gilliland RD, Smith EE, et al. Pentachlorophenol intoxication:  Report of a fatal
    case, with comments on the clinical course and  pathologic anatomy. Arch Environ Health
18.  Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
    agement and cooling in 14 patients. Arch Intern Med 1986; 146:87-90.
                                                                                                     PENTACHLOROPHENOL •  103

                                   CHAPTER 11

•  Highly toxic herbicides
•  Affect hepatic, renal, and
   nervous systems

Signs and Symptoms:
•  Sweating, thirst, fever,
   headache, confusion,
   malaise, and restlessness
•  Hyperthermia, tachycardia,
   tachypnea in serious cases
•  Characteristic bright yellow
   staining of skin and hair
   often present with topical

•  No specific antidote
•  Replace oxygen and fluids,
   control temperature
•  Decontaminate skin, hair,

•  Antipyretic therapy with
•  Atropine
Nitrophenolic  and
Nitrocresolic Herbicides
These highly toxic chemicals have many uses in agriculture worldwide, as her-
bicides (weed-killing and defoliation), acaricides, nematocides, ovicides, and
fungicides. Relatively insoluble in water, most technical products are dissolved
in organic solvents and formulated for spray application as emulsions. There are
some wettable powder formulations. Only dinocap continues to have active
registrations in the United States.
    Nitroaromatic compounds are highly toxic to humans and animals with
LD5Qs in the range of 25 to 50 mg/kg.1 Most nitrophenols and nitrocresols are
well absorbed by the skin, gastrointestinal tract, or lung when fine droplets are
inhaled.2 Fatal poisonings have occurred as a result of dermal contamination;
more  common is a moderate irritation of the skin and mucous membranes.
    Nitrophenols and nitrocresols undergo some biotransformation in humans,
chiefly reduction (one nitro group to an amino group) and conjugation at the
phenolic site. Although nitrophenols and metabolites appear consistently in
the urine of poisoned individuals, hepatic excretion is probably the main route
of disposition. Elimination is slow with a documented half-life in humans be-
tween 5 and  14 days.1 Blood and tissue  concentrations tend to increase  pro-
gressively if an individual is substantially exposed on successive days.
    The basic mechanism of toxicity is stimulation of oxidative metabolism in
cell mitochondria, by the uncoupling of oxidative phosphorylation.This leads
to hyperthermia, tachycardia, headache, malaise, and dehydration, and in time,
depletes carbohydrate and fat stores. The major systems prone to toxicity are
the hepatic, renal, and nervous systems. The nitrophenols are more active as
uncouplers than chlorophenols such as pentachlorophenol (described in chap-
ter 10). Hyperthermia and direct toxicity on the brain cause restlessness and
headache, and in severe  cases, seizures, coma, and cerebral edema. The  higher
the ambient temperature, such as in an outdoor agricultural environment, the
more  difficult it is to dissipate the heat.1'2 Liver parenchyma and renal tubules
show  degenerative changes. Albuminuria, pyuria, hematuria, and azotemia are
signs of renal injury.

     Cataracts occur in laboratory animals given nitrophenols, and have oc-
curred in humans, both as a result of ill-advised medicinal use and as a conse-
quence of chronic, occupational exposure.3 Cataract formation is sometimes
accompanied by glaucoma.
Signs and Symptoms of Poisoning

    Most patients present within a few hours of exposure with generalized
non-specific signs and symptoms including profuse sweating, thirst, fever, head-
ache, confusion, malaise, and restlessness.The skin may appear warm and flushed
as hyperthermia develops, along with tachycardia, and tachypnea, all of which
indicate a serious degree of poisoning. Apprehension, anxiety, manic behavior,
seizures, and coma reflect cerebral injury; seizures and coma signify an immedi-
ately life-threatening intoxication. Labored breathing and cyanosis are conse-
quences of the stimulated metabolism and  tissue anoxia. Renal failure may
occur  early in cases  of severe exposure. Liver damage  is first manifested  by
jaundice, and  cell death can occur within 48 hours and is dose-dependent.4
Death may occur within 24 to 48 hours after exposure in cases of severe poi-
soning.2 In cases of survival of severe poisoning, complete resolution  of symp-
toms may be slow due to the  toxicant's long half-life.1-5
    A  characteristic bright yellow staining of skin and hair is often present with
topical exposure and can be an important diagnostic clue to the clinician.1'2'5
Yellow staining of the sclerae and urine  indicates absorption of potentially
toxic amounts. Weight loss occurs in persons continually exposed to  relatively
low doses of nitrophenols or nitrocresols.1'3
Confirmation of Poisoning

    If poisoning is probable, do not await confirmation before beginning treatment.
Save urine and blood specimens on ice at temperature below 20ฐ C in the event
confirmation is necessary later on. Unmetabolized nitrophenols and nitrocresols
can be identified spectrophotometrically, or by gas-liquid chromatography in the
serum at concentrations well below those that have been associated with acute
poisonings.The data on exposure and systemic levels of compounds in this group
are limited, and most reports specify the compound dinitro-ortho-cresol. In general,
blood levels of 10 mcg/dL or greater are usually seen when systemic toxicity is
evident.1'6 One fatal case occured with a level of 75 mcg/dL.6 Blood analysis is
useful in confirming the cause of poisoning. Monitoring of levels should be done
routinely during acute intoxication in order to establish a decay curve to determine
when therapy can be safely discontinued.
Commercial Products
  Chemsect DNOC
  Elgetol 30
  Chermox PE
  Chemox General
  Chemox General
  Chemox PE
  Chemsect DNBP
  Dinitro General Dynamyte
  Dinitro Weed Killer 5
  Elgetol 318
  Nitropone C
  Premerge 3
  Snox General
  Vertac General Weed Killer
  Vertac Selective Weed Killer
dinoseb acetate*
dinoseb methacrylate*
  Am box
                                                                                      (Continued on the next page)
                                                                                          NITROPHENOLS &
                                                                                          NITROCRESOLS   • 105

Commercial Products
  FMC 9044
  Hoe 002784
  NIA 9044
dinoterb acetate*
dinoterb salts*

* All U.S. registrations have
  been cancelled
1. Supportive treatment and hyperthermia control. There is no specific
antidote to poisoning with nitrophenolic or nitrocresolic herbicides.Treatment
is supportive in nature and includes oxygen, fluid replacement, and  tempera-
ture control.
    Reduce elevated body temperature by physical means. Administer
sponge baths and ice packs, and use a fan to promote air flow and evaporation.7
In fully conscious patients, administer cold, sugar-containing liquids by mouth
as tolerated.

2. Contraindications. Antipyretic therapy with salicylates is  strongly
contraindicated as salicylates also uncouple oxidative phosphorylation. Other
antipyretics are thought to be of no use because of the peripherally  mediated
mechanism of hyperthermia in poisoning of this nature. Neither the safety nor
the  effectiveness of other antipyretics has been tested.
    Atropine is also absolutely contraindicated! It is essential not to con
fuse the clinical signs for dinitrophenol with manifestations for cholinesterase
inhibition poisoning.2

3. Skin decontamination. If poisoning has been caused by contamination of
body surfaces, bathe and shampoo contaminated skin and hair promptly and
thoroughly with soap and water, or water alone if soap is not available. Wash the
chemical from skin folds and from under fingernails. Care should be taken to
prevent dermal contamination of hospital staff. See Chapter 2.

4. Other Treatment. Other aspects of treatment are identical to management
of pentachlorophenol poisoning, detailed in Chapter 10.
                                    General Chemical  Structure
                                                    02N{'     \)0-H   or

                                                   (ALKYL)   (ALKYL)
                                    1.  Leftwich RB, Floro IF, Neal RA, et al. Dinitrophenol poisoning: A diagnosis to consider in
                                       undiagnosed fever. South Med J 1982;75:182-5.
                                    2.  Finkel AJ. Herbicides: Dinitrophenols. In: Hamilton and Hardy's IndustrialToxicology, 4th ed.
                                       Boston: lohn Wright PSG, Inc., 1983, pp. 301-2.
                                    3.  Kurt TL, Anderson R, Petty C, et al. Dinitrophenol in weight loss:The poison center and
                                       public safety. Vet Hum Toxicol 1986;28:574-5.

4.   Palmeira CM, Moreno AJ, and Madeira VM. Thiols metabolism is altered by the herbicides
    paraquat,dinoseb,and 2.4-D:A study in isolated hepatocytes. ToxicolLett 1995;81:115-23.
5.   Smith WD. An investigation of suspected dinoseb poisoning after agricultural use of a herbi-
    cide. Practitioner 1981;225:923-6.
6.   NIOSH. Criteria document: Occupational exposure to dinitro-orthocresol. Cincinnati: NIOSH,
7.   Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
    agement and cooling in 14 patients. Arch Intern Med 1986; 146:87-90.
                                                                                                              NITROPHENOLS &
                                                                                                              NITROCRESOLS    •  107

                                     CHAPTER 12

•  Life-threatening effects on
   Gl tract, kidney, liver, heart,
   other organs
•  Pulmonary fibrosis is the
   usual cause of death in
   paraquat poisoning (but not

Signs and Symptoms:
•  Paraquat and diquat
   (ingestion): burning pain in
   the mouth, throat, chest,
   upper abdomen; pulmonary
   edema, pancreatitis, other
   renal, CNS effects
•  Paraquat (dermal): dry and
   fissured hands, horizontal
   ridging or loss of fingernails,
   ulceration and abrasion
•  Diquat: neurologic toxicity

•  Immediate Gl
   decontamination with
   Bentonite, Fuller's Earth, or
   activated charcoal
•  Maintain urinary output by
   administering IV, but
   monitor fluids in case of
   renal failure
•  Decontaminate eyes and
•  No supplemental oxygen
   unless patient develops
   severe hypoxemia
Paraquat  and  Diquat
The dipyridyl compounds paraquat and  diquat  are non-selective contact
herbicides  that are relatively  widely-used, primarily in agriculture and by
government agencies and industries for control of weeds. While paraquat is a
restricted-use  pesticide in most forms for most uses in  the United States,  its
wide usage leads to significant potential for misuse and  accidental and  inten-
tional poisonings. In the  past few decades,  paraquat has  been a popular agent
for suicide, but recent experience indicates a  decline in such intentional
poisonings. Paraquat and  diquat are highly toxic compounds and management
of poisonings  requires a great  deal of  skill and knowledge of  proper manage-
ment procedures.

    When ingested in adequate dosage (see below), paraquat has life-threaten-
ing effects on the  gastrointestinal tract, kidney, liver, heart, and other organs.
The LD5Q in humans is approximately 3-5 mg/kg, which translates into as little
as 10-15 ml of a 20% solution.1'2
    The lung is the primary target organ of paraquat, and pulmonary effects
represent the most lethal and least treatable manifestation of toxicity. However,
toxicity from inhalation is rare.The primary mechanism is through the genera-
tion of free radicals with oxidative damage to lung tissue.1'2 While acute pul-
monary edema and early lung damage may occur within a few hours  of severe
acute  exposures,3'4 the  delayed toxic damage of pulmonary fibrosis, the usual
cause  of death, most commonly occurs 7-14 days after the ingestion.5 In pa-
tients who ingested a very large amount of concentrated solution (20%), some
have died more rapidly  (within 48 hours) from circulatory failure.5
    Both types I and II pneumatocytes appear to selectively accumulate paraquat.
Biotransformation  of paraquat in these cells results in free-radical production
with resulting lipid peroxidation and cell injury.1'2'4 Hemorrhage proteinaceous
edema fluid and leukocytes infiltrate the alveolar spaces, after which there is rapid
proliferation of fibroblasts.There is a progressive decline in arterial oxygen tension
and CO2 diffusion capacity.  Such a  severe impairment of gas exchange causes
progressive proliferation of fibrous connective tissue in the  alveoli and eventual
death from asphyxia and tissue anoxia.6 One prospective study of survivors suggests

that some of the fibrous toxic damage may be reversible as evidence exists of
markedly improved pulmonary function three months after survival.7
    Local skin damage includes contact dermatitis. Prolonged contact will pro-
duce erythema, blistering, abrasion and ulceration, and fingernail changes.8-9
Although absorption across intact skin is slow, abraded or  eroded skin allows
efficient absorption.
    The gastrointestinal (GI) tract is the site of initial or phase I toxicity to the
mucosal surfaces following ingestion of the substance.This toxicity is manifested
by swelling, edema, and painful ulceration of the mouth, pharynx, esophagus,
stomach, and intestine. With higher levels, other GI toxicity includes centrizonal
hepatocellular injury which can cause elevated bilirubin, and hepatocellular en-
zymes such as AST, ALT, and LDH.
    Damage to the proximal  renal tubule is  often more reversible than the
destruction to lung tissue. However, impaired renal function may play a critical
role in determining the outcome of paraquat poisoning. Normal tubule cells
actively secrete paraquat into the urine, efficiently clearing it from the blood.
However, high  blood concentrations poison the secretory mechanism and may
destroy the cells. Diquat poisoning typically results in greater renal injury com-
pared to paraquat.
    Focal necrosis of the myocardium and skeletal muscle are the main features
of toxicity to any type of muscle tissue, and typically occur as a second phase.
Ingestion has also been reported to cause cerebral edema and brain damage.10
    Although much concern  has been expressed about the effects of smoking
paraquat-contaminated marijuana, toxic effects caused by this mechanism have
been either very rare or nonexistent. Most paraquat that contaminates marijuana
is pyrolyzed during smoking to dipyridyl, which is a product of combustion of
the leaf  material itself (including marijuana) and presents little toxic hazard.
Signs and Symptoms of Poisoning
    Initial clinical signs depend upon the route of exposure. Early symptoms
and signs of poisoning by ingestion are burning pain in the mouth, throat,
chest, and upper abdomen, due to the corrosive effect of paraquat on the mu-
cosal lining. Diarrhea, which is sometimes bloody, can also occur.  Giddiness,
headache, fever, myalgia, lethargy, and coma are other examples  of CNS and
systemic findings. Pancreatitis may  cause severe abdominal pain. Proteinuria,
hematuria, pyuria, and azotemia reflect renal injury. Oliguria/anuria indicate
acute tubular necrosis.
    Because the kidney is almost the exclusive route of paraquat elimination
from body tissues, renal failure fosters a build-up of tissue concentrations, in-
cluding those in the lung. Unfortunately, this pathogenic sequence  may occur
in the first several hours following  paraquat ingestion, generating lethal con-
centrations of paraquat in lung tissue before therapeutic measures to limit ab-
sorption and enhance disposition have taken effect. It is probably for this reason
Commercial Products
Liquid Concentrates:

In combination with other
With diquat:
  Weedol (a 2.5% soluble
  granule formulation)

With diuron:

With monolinuron:

With simazine:
Ortho Diquat
                                                                                       PARAQUAT & DIQUAT • 109

                                 that methods for enhancing paraquat disposition several hours following inges-
                                 tion have had little effect on mortality.
                                     Cough, dyspnea, and tachypnea usually appear 2-4 days following paraquat
                                 ingestion, but may be delayed as long as 14 days. Progressive cyanosis and dys-
                                 pnea reflect deteriorating gas exchange in the damaged lung. In some cases, the
                                 coughing up of frothy sputum (pulmonary edema) is the early and principal
                                 manifestation of paraquat lung injury.
                                     Clinical experience has offered a rough dose-effect scale on which to base
                                 prognosis in cases of paraquat ingestion:9
                                     •    Less than 20 rng paraquat ion per kg body weight (less than 7.5
                                         mL of 20% [w/v]  paraquat concentrate): No  symptoms or only
                                         gastrointestinal symptoms occur. Recovery is likely.

                                     •    Twenty to 40 mg paraquat ion per kg body weight (7.5-15.0 mL
                                         of 20% [w/v] paraquat concentrate): Pulmonary fibroplasia ensues.
                                         Death occurs in most cases, but may be delayed 2-3 weeks.

                                     •    More than 40 mg paraquat ion  per kg body weight (more than
                                         15.0 mL of 20% [w/v]  paraquat concentrate): Multiple organ
                                         damage  occurs as in class II, but is more rapidly progressive. Often
                                         characterized by marked ulceration of the oropharynx. Mortality is
                                         essentially 100% in 1-7 days.

                                     Dermal signs are common among agriculture workers with acute paraquat
                                 toxicity. Particularly in concentrated form, paraquat causes localized injury to
                                 tissues with which it comes into contact. Fatal poisonings are reported to
                                 have occurred as a result of protracted dermal contamination by paraquat, but
                                 this is likely to  occur  only when the skin  is abraded, eroded, or diseased,
                                 when more efficient systemic absorption can occur. With an intact dermal
                                 barrier, paraquat leaves the skin of the hands dry and fissured, can cause hori-
                                 zontal ridging of the fingernails, and may even  result in the loss of fingernails.
                                 Prolonged  contact with skin will create ulceration and abrasion, sufficient to
                                 allow systemic absorption.
                                     In addition, some agriculture workers can be exposed through prolonged
                                 inhalation  of spray droplets, and develop nosebleeds due  to local damage.
                                 However, inhalation has not resulted  in  systemic toxicity, due  to the low
                                 vapor pressure and lower  concentration of paraquat field formulations. Eye
                                 contamination with diquat concentrate or stronger solutions results in severe
                                 conjunctivitis and sometimes protracted corneal opacification.
                                     The hepatic injury  from paraquat may be severe enough to  cause jaun-
                                 dice, which signifies severe injury. However, hepatotoxicity is rarely a major
                                 determinant to clinical outcome. No other hepatic signs  or symptoms are
                                 present other than the abnormal laboratory values mentioned in the Toxicol-
                                 ogy section.


    Diquat poisoning is much less common than paraquat poisoning, so that
human reports and animal experimental data for diquat poisoning are less ex-
tensive than for paraquat. Systemically absorbed diquat is not selectively con-
centrated in lung tissue, as is paraquat, and pulmonary injury by diquat is less
prominent. In animal studies, diquat causes mild, reversible  injury to type I
pneumatocytes, but does not injure the type II cells. No progressive pulmonary
fibrosis has been noted in diquat poisoning.11"13
    However, diquat has severe toxic effects on the central nervous system that
are not typical of paraquat poisoning.12-13 While laboratory experimentation has
suggested that diquat is not directly neurotoxic, there have been relatively con-
sistent pathologic brain changes noted in reported fatal cases of diquat poison-
ing.These consist of brain stem infarction, particularly involving the pons.12 It
is not clear whether these post-mortem  changes represent direct toxicity or
secondary effects related to  the systemic  illness and therapy. (See Signs and
Symptoms section for CNS clinical effects.)
    There is  probably significant absorption of diquat across abraded or ulcer-
ated skin.
Signs and Symptoms of Poisoning
    In many human diquat poisoning cases, clinical signs of neurologic toxicity
are the most important. These include nervousness, irritability, restlessness, com-
bativeness, disorientation, nonsensical statements, inability to recognize friends
or family members, and diminished reflexes. Neurologic effects may progress to
coma, accompanied by tonic-clonic seizures, and result  in the death of the
patient.12'13 Parkinsonism has also been reported following dermal exposure to
    Except for the CNS signs listed in the preceding paragraph, early symp-
toms of poisoning by ingested diquat are similar to those from paraquat, reflect-
ing its corrosive effect on tissues. They  include burning pain in the mouth,
throat, chest, and abdomen, intense nausea and vomiting, and diarrhea. If the
dosage was small, these symptoms may be delayed 1-2 days. Blood may appear
in the vomitus and feces. Intestinal ileus, with pooling of fluid in the gut, has
characterized several human poisonings by diquat.
    The kidney is the principal excretory pathway for diquat absorbed into the
body. Renal damage is therefore an important feature of poisonings. Proteinuria,
hematuria, and pyuria may progress to renal failure and azotemia. Elevations of
serum alkaline phosphatase, AST, ALT, and LDH reflect liver  injury. Jaundice
may develop.
                                                                                     PARAQUAT & DIQUAT -111

                                     If the patient survives several hours or days, circulatory function may fail
                                 due to dehydration. Hypotension and tachycardia can occur, with shock result-
                                 ing in death. Other cardiorespiratory problems may develop, such as toxic car-
                                 diomyopathy or a secondary infection such as bronchopneumonia.
                                     Diquat is somewhat less damaging to the skin than paraquat, but irritant
                                 effects may appear following dermal contamination with the concentrate. There
                                 is probably significant absorption of diquat across abraded or ulcerated skin.
                                     The great majority of poisonings by paraquat and diquat (discussed below)
                                 have been caused by ingestion with suicidal intent in most cases, particularly in
                                 Japan11 and many developing countries. Since 1987, there has been a decline in
                                 most countries in  the total numbers of suicidal deaths attributed to paraquat
                                 and diquat. Nearly all of the few poisonings caused by occupational exposure
                                 have been survived, but the mortality rate among persons who have swallowed
                                 paraquat or diquat remains high.1'5 Avoidance of this  mortality will probably
                                 have to  rely on preventive strategies or on stopping gastrointestinal absorption
                                 very soon after the toxicant has been ingested.
                                     Even though  intestinal absorption  of dipyridyls  is relatively slow, lethal
                                 uptake by critical  organs and tissues apparently occurs within 18 hours, and
                                 possibly within 6 hours, following ingestion of toxic quantities of paraquat or
                                 diquat. Bipyridyls have large volumes of distribution. Once distribution to tis-
                                 sues  has occurred, measures to remove bipyridyls from  the blood are very inef-
                                 ficient in reducing the total body burden.
                                      Several strategies are being tested to reduce the frequency of these occur-
                                 rences. These include the addition of emetics, stenching agents, gelling sub-
                                 stances,  and bittering agents such as sodim denatonium.
                                 Confirmation of Poisoning: Paraquat and Diquat

                                     At some treatment facilities, a simple colorimetric test is used to identify
                                 paraquat and diquat in the urine, and to give a rough indication of the magni-
                                 tude of absorbed dose. To one volume of urine, add 0.5 volume of freshly
                                 prepared 1% sodium dithionite (sodium hydrosulfite)  in one normal sodium
                                 hydroxide (1.0 N NaOH). Observe color at the end of one minute. A blue
                                 color indicates the presence of paraquat in  excess of 0.5  mg  per liter. Both
                                 positive and negative controls should be run to ensure that the dithionite has
                                 not undergone oxidation in storage.
                                     When urine collected within 24 hours of paraquat ingestion is tested, the
                                 dithionite test appears to have some prognostic value: concentrations less than
                                 one milligram per liter (no color to light blue) generally predict survival, while
                                 concentrations in excess of one milligram per liter (navy  blue to dark blue)
                                 often foretell a fatal outcome.
                                     Diquat in urine  yields a green color with the dithionite  test. Although
                                 there is less  experience with this test in diquat poisonings, the association of
                                 bad prognosis with intense color is probably similar.

    Paraquat and diquat can be measured in blood and urine by spectrophoto-
metric, gas chromatographic, liquid chromatographic, and radioimmunoassay
methods. These tests are available in numerous clinical reference laboratories
and sometimes by the manufacturing company. Survival is likely if plasma con-
centrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg per liter at 4, 6, 10, 16,
and 24 hours, respectively, after ingestion.15
1. Skin and eye decontamination. Flush skin immediately with copious
amounts of water. Material splashed in the eyes must be removed by pro-
longed irrigation with clean water. Eye contamination should thereafter be
treated by an ophthalmologist. Mild skin reactions usually respond if there is no
further contact with the pesticide, but the irritation may take several weeks to
resolve. Severe injuries with inflammation, cracking, secondary infection, or
nail injury should be treated by a dermatologist.

2. Gastrointestinal decontamination. If paraquat or diquat have been in-
gested, immediate administration of adsorbent  is the one therapeutic
measure most likely to have a favorable effect. Bentonite (7.5% suspension)
and Fuller's Earth (15% suspension) are highly effective, but sometimes not
    Dosage of Bentonite and Fuller's Earth:
     • Adults and children over 12years: 100-150 g.
     • Children under 12 years: 2 gm/kg body weight.
    Caution: Hypercalcemia and fecaliths have sometimes occurred fol-
    lowing administration of Fuller's Earth.
    Activated charcoal is nearly as effective, and is widely available. See Chapter
2 for dosage of charcoal and further information on gastric decontamination.
    Lavage has not been shown to be effective and should not be performed
unless the patient is seen within an hour of ingestion. Later lavage runs the risk
of inducing bleeding, perforation, or scarring due to additional trauma to al-
ready traumatized tissues. Repeated administration of charcoal or other absor-
bent every 2-4 hours may be beneficial in both children and adults, but use of
a cathartic such as sorbitol should be avoided after the first dose. Cathartics and
repeat doses of activated charcoal should not be administered if the gut is atonic.
Check  frequently  for bowel  sounds. Ileus occurs commonly in diquat
poisoning, less often in paraquat poisoning.
                                                                                     PARAQUAT & DIQUAT • 113

                                 3. Samples. Secure a blood sample as soon as possible for paraquat analysis, and
                                 urine samples for either paraquat and/or diquat. Serial samples of urine for either
                                 agent and plasma for paraquat may be followed for prognostic information.

                                 4. Respiration. Do not administer supplemental oxygen until the pa
                                 tient develops severe hypoxemia. High concentrations of oxygen in the  lung
                                 increase the injury induced by paraquat, and possibly by diquat as well.There
                                 may be some advantage in placing the patient in a moderately hypoxic envi-
                                 ronment, i.e., 15%-16% oxygen, although the benefit of this treatment measure
                                 has not been established empirically  in human poisonings. Inhalation of nitric
                                 oxide has been suggested as a method to maintain tissue oxygenation at low
                                 inspired oxygen concentrations, but its efficacy is unproven. When the  lung
                                 injury is so far advanced that there is no expectation of recovery, oxygen  may
                                 be given to  relieve air hunger.

                                 5. Intensive care. In serious poisonings, care should be provided in an inten-
                                 sive care setting, to  allow  proper monitoring of body functions and skilled
                                 performance of necessary invasive monitoring and procedures.

                                 6. Fluids. It is essential to  maintain adequate urinary output.4 Administer in-
                                 travenous fluids: isotonic saline, Ringer's solution, or 5% glucose in water.This
                                 is highly advantageous early in poisonings as a means of correcting dehydra-
                                 tion, accelerating toxicant excretion, reducing tubular fluid concentrations  of
                                 paraquat, and correcting any metabolic acidosis. However,  fluid balance must
                                 be monitored carefully to forestall fluid overload if renal failure develops. Monitor
                                 the urine regularly for protein and cells, to warn of impending tubular necrosis.
                                 Intravenous infusions must be stopped if renal failure occurs,  and extracorpo-
                                 real hemodialysis is indicated. Hemodialysis is not effective in clearing paraquat
                                 or diquat  from the blood and tissues.

                                 7. Hemoperfusion over cellophane-coated activated charcoal may be consid-
                                 ered. The procedure has been used in many paraquat poisonings because the
                                 adsorbent does efficiently remove paraquat from the perfused blood. However,
                                 recent reviews of effectiveness have failed to show any reduction in mortality as
                                 a  result of hemoperfusion.1'4 The apparent  reason for this is the very small
                                 proportion of paraquat body burden carried in the circulating blood even when
                                 only a few hours have elapsed after ingestion. Theoretically, a  patient who can
                                 be hemoperfused within 10 hours of paraquat ingestion may derive some mar-
                                 ginal benefit, but this has not been demonstrated.
                                     If hemoperfusion is attempted, blood calcium and platelet concentrations
                                 must be monitored. Calcium and platelets must be replenished if these con-
                                 stituents are depleted by the procedure.

8. Seizure control. Convulsions and psychotic behavior sometimes encoun-
tered in diquat poisoning may be best controlled by lorazepam, given slowly
intravenously, as outlined in  Chapter 2.  Control convulsions as outlined in
Chapter 2.

9. Other  drugs. Many drugs have been  tested in animals or given in human
bipyridyl poisonings without clear evidence of benefit or harm: corticoster-
oids, superoxide dismutase, propranolol, cyclophosphamide, vitamin E, ribofla-
vin, niacin, ascorbic acid, clofibrate, desferrioxamine, acetylcysteine, and terpin
hydrate. However, recent evidence regarding the use of cyclophosphamide
and methylprednisolone may be effective in reducing the mortality associ-
ated with moderate to severe paraquat poisoning.Two studies found a reduced
mortality associated with the treatment, while one study found no difference.16
The dosages used for cyclophosphamide and methylprednisolone were 1 gram
daily for two days and 1 gram daily for three days respectively, and were given
after hemoperfusion. Each drug was administered as a two hour infusion, and
white cell counts, serum creatinine levels, chest radiography, and liver function
tests were  monitored.16

10. Pain management. Morphine sulfate is usually required to  control the
pain associated with deep mucosal erosions of the mouth, pharynx, and esophagus,
as well as  abdominal pain from pancreatitis and enteritis. Mouthwashes, cold
fluids, ice  cream, or anesthetic lozenges may also help to relieve  pain in the
mouth and throat.
    Dosage of Morphine Sulfate:
     • Adults and children over 12 years: 10-15 mg subcutaneously every 4
     • Children under 12years: 0.1-0.2 mg /kg body weight every 4 hours.
11. Transplantation. With severe pulmonary toxicity, recovery of the patient
may only be accomplished  by lung transplantation. However, the transplanted
lung is susceptible to subsequent damage due to redistribution of paraquat.17
                                                                                     PARAQUAT & DIQUAT • 115

                                       General Chemical Structures
CK— +N

—fci ^-
                                                                       N  — CH3
                                                                                                 CH2— CH2   2 Br"
                                       1.   Pond SM. Manifestations and management of paraquat poisoning. MedJAust 1990; 152:256-9.
                                       2.   Giulivi C, Lavagno CC, Lucesoli F, et al. Lung damage in paraquat poisoning and hyper-
                                           baric oxyen exposure: superoxide-mediated inhibition of phospholipase A2. Free Radic
                                           BiolMed 1995; 18:203-13.
                                       3.   Nordquist RE, Nguyen H, Poyer JL, et al. The role of free radicals  in paraquat-induced
                                           corneal lesions. Free Radic Res 1995;23:61-71.
                                       4.   Honore P, Hantson P Fauville JP et al. Paraquat poisoning: State of the art. Acta Clin Belg
                                       5.   Bismuth C, Gamier R, Dally S, et al. Prognosis  and  treatment of paraquat poisoning: A
                                           review of 28 cases. JToxicol ClinToxicol 1982; 19:461-74.
                                       6.   Harsanyi L, Nemeth A, and Lang A. Paraquat (gramoxone) poisoning in south-west Hun-
                                           gary, 1977-1984. Am JForensic Med Pathol 1987;8:131-4.
                                       7.   Lee CC, Lin JL, and Liu L. Recovery of respiratory function in survivors with paraquat
                                           intoxication (abstract). Ann EmergMed 1995;26:721-2.
                                       8.   Tungsanga K, Chusilp S, Israsena S, et al. Paraquat poisoning: Evidence of systemic toxicity
                                           after dermal exposure. Postgrad Med J  1983;59:338-9.
                                       9.   Vale JA, MeredithTJ, and Buckley BM. Paraquat poisoning: Clinical features and immediate
                                           general management. HumToxicol 1987;6:41-7.
                                       10.  Hughes JT. Brain damage due to paraquat poisoning: A fatal case with neuropathological
                                           examination of the brain. Neurotoxicology 1988;9:243-8.
                                       11.  Lam HF, Azawa J, Gupta BN, et al. A comparison of the effects of paraquat and diquat on
                                           lung compliance, lung volume, and single-breath diffusing capacity  in the  rat.  Toxicology
                                       12.  Vanholder R, Colardyn F, DeReuck J, et al. Diquat intoxication: Report of two  cases and
                                           review of the literature. Am J Med 1981;70:1267-71.
                                       13.  Olson KR. Paraquat and diquat. In: Olson KR et al. (eds), Poisoning and Drug Overdose, 2nd
                                           ed. Norwalk CT: Appelton and Lange, 1994, pp. 245-6.
                                       14.  Sechi GP, AgnettiV, Piredda M, et al. Acute and persistent Parkinsonism after use of diquat.
                                           Neurology 1992;42:261-3.
                                       15.  Proudfoot AT, Stewart MS, LevittT, et al. Paraquat poisoning: Significance of plasma-paraquat
                                           concentrations. Lancet 1979;2:330-2.

16.  Lin JL, Wei MC, and LiuYC. Pulse therapy with cyclophosphamide and methyprednislone
    in  patients with moderate  to  severe paraquat poisoning: A preliminary report. Thorax
17.  Toronto Lung Transplant Group. Sequential bilateral lung transplantation for paraquat poi-
    soning. A case report.  JThoracic Cardiovas Surg 1985;89:734-42.
                                                                                                      PARAQUAT & DIQUAT •  117

                                 CHAPTER 13
                                 Other Herbicides
                                Many herbicides are now available for use in agriculture and for lawn and
                                garden weed control. This  chapter discusses herbicides other than the
                                chlorophenoxys, nitrophenols and chlorophenols, arsenicals, and dipyridyls, which
                                are the subjects of separate chapters. Many modern herbicides kill weeds selec-
                                tively by impairing metabolic processes that are unique to plant life. For this
                                reason, their systemic toxicities in  mammals are generally low. Nonetheless,
                                some herbicides pose a significant  risk of poisoning if handled carelessly, and
                                many are irritating to eyes, skin, and mucous membranes.
                                    For several good reasons, all of the herbicides mentioned in this chapter
                                should be handled and applied only with full attention to safety measures that
                                minimize personal contact. Many formulations contain adjuvants (stabilizers,
                                penetrants, surfactants) that may have significant irritating and toxic effects. A
                                number of premixed formulations contain two or more active ingredients; the
                                companion pesticides may be more toxic than the principal herbicide. Good
                                hygienic practice should not be disregarded just because a pesticide is reported
                                to have a high LD50 in laboratory rodents.
                                    Health  professionals who may need to assess  the  consequences  of  prior
                                exposure should understand the fate of these  compounds after absorption by
                                humans.The water-soluble herbicides are not retained in body tissues for long
                                periods, as were the old lipophilic  organochlorine insecticides, such as DDT.
                                Most are excreted, mainly in the urine, within one to four days.
                                    The table on the following pages lists the more commonly used herbicides
                                not discussed elsewhere in this manual. The rat acute oral LD5Q is given as a
                                rough index of potential lethal toxicity. (If several values are reported by various
                                sources, the lowest is recorded here.) The adverse effect information is drawn
                                from  many sources, including product labels, textbooks, published case histo-
                                ries, and some unpublished reports.The listing cannot be considered inclusive,
                                either of herbicide products or of effects.


Chemical Class

Aliphatic acids



anisic acid



Carbamates and

Generic Name


acid (dalapon)











dial late

Dual, Pennant,


Lasso, Alanox
Ramrod, Bexton,
DPA, Chem
Rice, Propanex,
Riselect, Stam,
Kerb, Rapier

TCBA, Tribac,

Dyclomec, Barrier


Azac, Azar



Tillam, PEBC

Eptam, Eradicane
Bolero, Saturn

Acute Oral LD50














Known or
Adverse Effects
to eyes
and skin.
Irritating to
skin, eyes,
and respiratory

Mild irritant.
Dermal irritant
and sensitizer.
Irritating to skin,
eyes, and
respiratory tract.

irritating to eyes
irritating to skin
and respiratory
Minimal toxic,
irritant effects
Irritating to eyes
and respiratory
Some are
irritating to
eyes, skin, and
respiratory tract,
particularly in
Some may be
weak inhibitors
of cholinesterase.

                                                                          OTHER HERBICIDES • 119

                            TOXICITY OF COMMON HERBICIDES

Chemical Class


Nicotinic acid



Generic Name



Garlon, Turflon
Tarn ex
Prowl, Stomp,
Wax Up
Surflan, Dirimal
Benefin, Balan,
Balfin, Quilan



Acute Oral LD50
>1 0,000
>1 0,000
>1 0,000
>1 0,000


Known or
Adverse Effects
Skin irritants.
May generate
at high dosage.
Irritating to skin
and eyes.
Irritating to skin
and eyes.
May be
These herbicides
do not uncouple
or generate
May be mildly
irritating. These
herbicides do not
or generate

May be
Irritating to eyes
and skin. Does
not contain
Minimal toxic
and irritant
Irritating to eyes,
skin, and upper
respiratory tract.
Irritating to eyes,
skin, and upper
respiratory tract.


Chemical Class

Picolinic acid



Generic Name















Dachthal, DCPA


Tordon, Pinene

Ametrex, Evik,

Aatrex, Atranex,

Bladex, Fortrol


Sencor, Lexone,
Sencoral, Sencorex

Caparol, Gesagard,
Primatol, Prozinex
Gesatop, Princep,
Caliber 90
Primatol M
Ternit, Prebane,
Gesafram 50
Pramitol 25E

Amerol, Azolan,
Azole, Weedazol

Acute Oral LD50
>1 0,000














>1 0,000

Known or
Adverse Effects
irritating to eyes.
Free acid is highly
toxic. Irritating to
skin, eyes and
respiratory tract.
See Chapter 18.
Irritating to skin,
eyes, and
respiratory tract.
Low systemic
is unlikely
unless large
have been
are moderately
irritating to
the eyes,
skin, and

This particular
formulation of
prometon is
strongly irritating
to eyes, skin, and
respiratory tract.
Minimal systemic
toxicity. Slight
irritant effect.
                                                                          OTHER HERBICIDES • 121

                               TOXICITY OF COMMON HERBICIDES
                                                                                       Known or
Chemical Class

Generic Name





Dicuran, Tolurex
Crisuron, Dailon,
Direx, Diurex,
Karmex, Unidron,
Alon, Arelon,
IP50, Tolkan
Afalon, Linex,
Linorox, Linurex,
Lorox, Sarclex

Deftor, Dosaflo,
Purivel, Sulerex
Ares in

Acute Oral LD50
>1 1,000
>1 0,000





>1 1,000


Adverse Effects
Irritant to skin,
eyes, and
respiratory tract.
toxicity is
unlikely unless
large amounts
have been
ureas are
irritating to
eyes, skin, and

                                                           Spike, Tebusan    644

Confirmation of Poisoning
    Although there are analytical methods for residues of many of the herbi-
cides mentioned in this chapter and for some of the mammalian metabolites
generated from them, these procedures are not generally available to confirm
human absorption of the chemicals. Exposure must be determined from a re-
cent history of occupational contact or accidental or deliberate ingestion.
1. Skin decontamination. Skin contamination should be treated promptly
by washing with soap and water. Contamination of the eyes should be treated
immediately by prolonged flushing of the  eyes with large amounts  of clean
water. If dermal or ocular irritation persists, medical attention should be ob-
tained without delay. See Chapter 2.

2. Gastrointestinal decontamination. Ingestions of these herbicides are likely
to be followed by vomiting and diarrhea due to their irritant properties. Man-
agement depends on: (1) the best estimate  of the quantity ingested,  (2) time
elapsed since ingestion, and (3) the clinical status of the subject.
    Activated charcoal  is probably effective in limiting  irritant effects and
reducing absorption of most or all of these herbicides. Aluminum hydroxide
antacids may be useful in neutralizing the irritant actions of  more acidic agents.
Sorbitol should be given to induce catharsis if bowel sounds are present and if
spontaneous diarrhea has not already commenced. Dehydration and electrolyte
disturbances may be severe enough to require oral or intravenous fluids.
    There are no specific antidotes for poisoning by these herbicides. In the
case of suicidal ingestions, particularly,  the  possibility must always be kept in
mind that multiple toxic substances may have been swallowed.
    If large amounts of herbicide have been  ingested  and  the patient is seen
within an hour of the ingestion, gastrointestinal decontamination should be
considered, as outlined in Chapter 2.
    If the amount of ingested  herbicides was small, if effective emesis has al-
ready occurred, or if treatment is delayed,  administer activated charcoal and
sorbitol by mouth.

3. Intravenous fluids.  If serious dehydration and electrolyte depletion have
occurred as a result of vomiting and diarrhea, monitor blood  electrolytes and
fluid balance and administer intravenous infusions of glucose, normal saline, Ringers
solution, or Ringer's lactate to restore extracellular fluid volume  and electrolytes.
Follow this with oral nutrients as soon as fluids can be retained.
                                                                                       OTHER HERBICIDES • 123

                                  4. Supportive measures are ordinarily sufficient for successful management
                                  of excessive exposures to these herbicides (endothall is an exception—see Chap-
                                  ter 18, p. 187). If the patient's condition deteriorates in spite of good supportive
                                  care, the operation of an alternative or additional toxicant should be suspected.

      Section IV

                                   CHAPTER 14

•  Life-threatening effects
   on CNS, blood vessels,
   kidney, liver

Signs and Symptoms:
•  In acute cases, garlic odor
   of the breath and feces,
   metallic taste in mouth,
   adverse Gl symptoms
•  In chronic cases, muscle
   weakness, fatigue,
   weight loss,
   hyperpig mentation,
   hyperkeratosis, Mees

•  Gl decontamination
•  Chelation therapy
   Dimercaprol (BAL) or
   DMPS to accelerate
   arsenic excretion
Arsenical  Pesticides
Many arsenic compounds have been discontinued in the United States as a
result of government regulations. However, arsenical pesticides are still widely
available in some countries, and many homes and farms have leftover supplies
that continue to represent some residual risk.
    Arsine gas is discussed separately on page 132.
    Arsenic is a natural element that has both metal and nonmetal physical/
chemical properties. In some respects, it resembles nitrogen, phosphorus, anti-
mony, and bismuth in its chemical behavior. In nature, it exists in elemental,
trivalent (-3 or +3), and pentavalent (+5) states. It binds covalently with most
nonmetals (notably oxygen and sulfur) and with metals (for example, calcium
and lead). It forms stable trivalent and pentavalent organic compounds. In bio-
chemical behavior, it resembles phosphorus, competing with phosphorus ana-
logs for chemical binding sites.
    Toxicity of the various arsenic compounds in mammals extends  over a
wide range, determined in part by the unique biochemical actions of each
compound, but also by absorbability and efficiency of biotransformation and
disposition. Overall, arsines present the greatest toxic hazard, followed closely
by arsenites (inorganic trivalent compounds). Inorganic pentavalent compounds
(arsenates) are somewhat less toxic than arsenites, while the  organic (methy-
lated) pentavalent compounds represent the least hazard of the arsenicals that
are used as pesticides.1
    The pentavalent arsenicals are relatively water soluble and absorbable across
mucous membranes.Trivalent arsenicals, having greater lipid solubility, are more
readily absorbed across the skin.2 However, poisonings by dermal absorption of
either form have been extremely rare. Ingestion has been the usual basis of
poisoning; gut absorption efficiency depends on the physical form of the com-
pound, its solubility characteristics, the gastric pH, gastrointestinal motility, and
gut microbial transformation. Arsine exposure occurs primarily through inha-
lation, and toxic effects may also occur with other arsenicals through inhalation
of aerosols.
    Once absorbed, many arsenicals cause toxic injury to cells of the nervous
system, blood vessels, liver, kidney, and other tissues. Two biochemical mecha-

nisms of toxicity are recognized: (1) reversible combination with thiol groups
contained in tissue proteins and enzymes, and (2) substitution of arsenic anions
for phosphate in many reactions, including those critical to oxidative phosphory-
lation. Arsenic is readily metabolized in the kidney to a methylated form, which
is much less toxic and easily excreted. However, it is generally safest to manage
cases of arsenical pesticide ingestion as though all forms are highly toxic.
    The unique toxicology of arsine gas is described later in this chapter.
Signs and Symptoms of Poisoning

    Manifestations of acute poisoning are distinguishable from those of chronic
    Acute  arsenic poisoning:  Symptoms and signs usually appear within
one hour after ingestion, but may be delayed several hours. Garlic odor of the
breath and feces may help to identify the toxicant in a severely poisoned pa-
tient.There is often a metallic taste in the mouth. Adverse gastrointestinal (GI)
effects predominate, with vomiting, abdominal pain, and  rice-water or bloody
diarrhea being the most common. Other GI effects include inflammation, vesicle
formation and eventual  sloughing of the mucosa in the mouth, pharynx, and
esophagus.3 These effects result from the action of an arsenical metabolite on
blood  vessels  generally,  and  the splanchnic  vasculature in particular, causing
dilation and increased capillary permeability.
    The central nervous system is also commonly affected during acute expo-
sure. Symptoms may begin with headache, dizziness, drowsiness, and confusion.
Symptoms may progress to include muscle weakness and spasms, hypothermia,
lethargy, delirium, coma, and  convulsions.1  Renal  injury is manifest as pro-
teinuria, hematuria, glycosuria, oliguria, casts in the urine, and, in severe poi-
soning, acute  tubular necrosis. Cardiovascular  manifestations include shock,
cyanosis, and  cardiac arrhythmia,4-5 which are due  to direct toxic action and
electrolyte disturbances.  Liver damage may be manifested by elevated liver en-
zymes and jaundice. Injury to blood-forming tissues may cause anemia, leuko-
penia, and thrombocytopenia.
    Death usually occurs one to three days following onset of symptoms and is
often the result of circulatory failure, although renal failure  also may contrib-
ute.1 If the patient survives, painful paresthesias, tingling, and numbness in the
hands and feet may be experienced as a delayed sequela of acute exposure.This
sensorimotor  peripheral neuropathy, which may include muscle weakness and
spasms, typically begins  1-3 weeks after exposure.6 The muscle weakness may
be confused with  Guillain-Barre syndrome.7
    Chronic  arsenic poisoning from repeated absorption of toxic amounts
generally has an insidious onset of clinical effects and may be difficult to diag-
nose. Neurologic, dermal, and nonspecific manifestations are usually more promi-
nent than the  gastrointestinal effects that characterize acute poisoning. Muscle
Commercial Products
(Many have been discontinued)
arsenic acid
  Hi-Yield DessicantH-10
arsenic trioxide
cacodylic acid (sodium
  Phytar 560
  Rad-E-Cate 25
calcium acid methane arsonate
  Super Crab-E-Rad-Calar
  Super Dal-E-Rad
calcium arsenate
  tricalcium arsenate
calcium arsenite
  London purple
  mono-calcium arsenite
copper acetoarsenite
  Emerald green
  French green
  Mitis green
  Paris green
  Schweinfurt green
copper arsenite (acid copper
disodium methane arsonate
  Ansar 8100
  Methar 30
  Weed-E-Rad 360
lead arsenate
methane arsonic acid (MAA)
monoammonium methane
  arsonate (MAMA)
monosodium methane arsonate
  Ansar 170

(Continued on the next page)
                                                                                               ARSENICALS • 127

Commercial Products
  Arsonate Liquid
  Bueno 6
  Daconate 6
  Drexar 530
  Merge 823
  Target MSMA
sodium arsenate
  disodium arsenate
  Jones Ant Killer
sodium arsenite
  Prodalumnol Double
zinc arsenate
weakness and fatigue can occur, as can anorexia and weight loss. Hyperpig-
mentation  is a common sign, and tends to be accentuated in areas that are
already more pigmented, such as the groin and areola. Hyperkeratosis is an-
other very common sign, especially on the palms and soles.8-9 Subcutaneous
edema of the face, eyelids, and ankles, stomatitis, white striations across the nails
(Mees lines), and sometimes loss of nails or hair are other signs of chronic,
continuous exposure.1-9 On occasion, these hyperkeratotic papules have under-
gone  malignant transformation.8 Years after exposure, dermatologic findings
include squamous cell and basal cell carcinoma, often in sun-protected areas.
    Neurologic symptoms are also common with chronic exposure. Peripheral
neuropathy, manifested by paresthesia, pain, anesthesia, paresis, and ataxia, may
be a prominent feature. It may often begin with sensory symptoms in the lower
extremities and progress to muscular weakness and eventually paralysis and
muscle wasting. Although less common, encephalopathy can develop with speech
and mental disturbances very much like those seen in  thiamine deficiency
(Wernicke's syndrome).
    Other organ systems are affected with arsenic toxicity. Liver injury reflected
in hepatomegaly and jaundice may progress to cirrhosis,  portal hypertension,
and ascites.  Arsenic has direct glomerular and tubular toxicity resulting in oliguria,
proteinuria, and hematuria. Electrocardiographic abnormalities (prolongation
of the Q-T interval) and peripheral vascular disease have been reported. The
latter  includes acrocyanosis, Raynaud's phenomenon, and frank gangrene.1-10
Hematologic abnormalities include anemia, leukopenia, and thrombocytopenia.1
Late sequelae of protracted high intakes of arsenic include skin cancer as described
above and an increased risk of lung cancer.1-8
                                    Confirmation of Poisoning

                                        Measurement of 24-hour urinary excretion of arsenic (micrograms per
                                    day) is the most common way to confirm excessive absorption and is the
                                    preferred method to follow serial levels and evaluate chronic exposure.1-11
                                    Spot urine arsenic analysis expressed as a ratio with urinary creatinine is the
                                    recommended method to evaluate occupational exposures.12 Methods to de-
                                    termine blood arsenic concentration are available; however blood levels  tend
                                    to poorly correlate with exposure except in the initial acute  phase.11-13  Spe-
                                    cial metal-free acid-washed containers should be used for sample collection.
                                    Arsenic excretion above 100 meg per day should be viewed  with suspicion
                                    and the test should be repeated.
                                        Excretions above 200 meg per day reflect a toxic intake, unless seafood was
                                    ingested.11-13-14-15 Diets rich in seafood, primarily shellfish in the previous 48
                                    hours, may generate  24-hour urine excretion levels as high as 200 meg per day
                                    and sometimes more.3'14 The majority of marine arsenic that is excreted  is in
                                    the methylated form (arsenobetaine)  and is not considered acutely toxic. How-
   128  • ARSENICALS

ever, a recent study supports that some of the arsenic released from mussels may
contain higher amounts of arsenic trioxide than previously thought.14 Urinary
arsenic may be speciated into inorganic and organic fractions to help deter-
mine the source of the exposure and to help guide treatment.
    Concentrations of arsenic in blood, urine, or other biologic materials can be
measured by either wet or dry ashing, followed by colorimetric or atomic ab-
sorption spectrometric analysis.The latter method is preferred. Blood concentra-
tions in excess of about 100 meg per liter probably indicate  excessive intake or
occupational exposure, provided that seafood was not ingested before the sample
was taken.3-11'13-15 Blood samples tend to correlate with urine  samples during the
early stages of acute ingestion,11 but because  arsenic is rapidly cleared from the
blood, the 24-hour urine sample remains the preferred method for detection and
for ongoing monitoring.1'11'13 Hair has been used for evaluation of chronic expo-
sure. Levels in unexposed people are usually less than 1 mg/kg; levels in individu-
als with chronic poisoning range between 1 and 5 mg/kg.15 Hair samples should
be viewed with caution because external environmental contamination such as
air pollution may artificially elevate arsenic levels.
    Special tests for arsine toxicosis are described on page  132 under "Arsine
    The following discussion applies principally to poisonings by arsenicals in
solid or dissolved form. Treatment of poisoning by arsine gas requires special
measures described below on page 132.

1. Skin decontamination. Wash arsenical pesticide from skin and hair with
copious amounts of soap and water. Flush contaminant from eyes with clean
water. If irritation persists, specialized medical treatment should be obtained.
See Chapter 2.

2.  Gastrointestinal  decontamination. If arsenical pesticide  has been in-
gested within the first hour of treatment, consideration should be given to GI
decontamination, as outlined in Chapter 2. Because poisoning by ingested ar-
senic almost always results in profuse diarrhea, it is generally not appropriate to
administer a cathartic.

3. Intravenous fluids. Administer intravenous fluids to restore  adequate hy-
dration, support urine flow, and correct electrolyte imbalances. Monitor in-
take/output continuously to guard against fluid overload. If acute renal failure
occurs, monitor blood electrolytes regularly. Blood transfusions and oxygen by
mask may be needed to combat shock.
                                                                                             ARSENICALS • 129

                                  4. Cardiopulmonary monitoring. Monitor cardiac status by EGG to detect
                                  ventricular arrhythmias including prolonged Q-T interval and ventricular ta-
                                  chycardia, and toxic myocardiopathy (T wave inversion, long S-T interval).

                                  5. Chelation therapy. Administration of Dimercaprol (BAL) is usually indi-
                                  cated in symptomatic arsenic poisonings, although DMPS, where available, may
                                  prove to be a better antidote.The following dosage schedule has proven to be
                                  effective in accelerating arsenic excretion.
                                      Monitor urinary arsenic excretion while any chelating agent is being ad-
                                  ministered. When 24-hour excretion falls below 50 meg per day, it usually  is
                                  advisable to discontinue the chelation therapy.
                                     RECOMMENDED INTRAMUSCULAR DOSAGE OF BAL
                                     (DIMERCAPROL) IN ARSENIC POISONING
                                     1st day

                                     2nd day

                                     3rd day

                                     Each of the following
                                     days for 10 days, or
                                     until recovery
Severe Poisoning
 3.0 mg/kg q4h
 (6 injections)
 3.0 mg/kg q4h
 (6 injections)
 3.0 mg/kg q6h
 (4 injections)
 3.0 mg/kg q1 2 hr
 (2 injections)
Mild Poisoning
 2.5 mg/kg q6h
 (4 injections)
 2.5 mg/kg q6h
 (4 injections)
 2.5 mg/kg q1 2h
 (2 injections)
 2.5 mg/kg qd
 (1 injection)
                                     BAL is provided as a 100 mg/mL solution in oil. Dosages in the table are in terms of BAL
                                     itself, not of the solution. Dosages for children are consistent with the "Mild Poisoning"
                                     schedule and can be between 2.5 and 3.0 mg/kg per dose.16
                                  Caution: Disagreeable side effects often accompany the use of BAL: nausea,
                                  headache, burning and tingling sensations, sweating, pain in the back and abdo-
                                  men, tremor, restlessness, tachycardia, hypertension, and fever. Coma and con-
                                  vulsions occur at very high dosage. Sterile abscesses may form at injection sites.
                                  Acute  symptoms usually subside in 30-90 minutes. Antihistamine drugs or an
                                  oral dose of 25-50 mg ephedrine sulfate or pseudoephedrine  provide relief.
                                  These  are more effective if given a few minutes before the injection of BAL.
                                  BAL may potentially have other adverse effects. In rabbits, treatment of arsenite
                                  exposure with BAL increased brain arsenic levels.17

                                  6. Oral treatments. After the gastrointestinal tract is reasonably free of arsenic,
                                  oral administration of d-penicillamine, Succimer  (DMSA), or DMPS  should
                                  probably replace BAL therapy. However, d-penicillamine has demonstrated lim-
                                  ited effectiveness for arsenic exposure in experimental models.18

    Dosage of d-penicillamine:
     • Adults and children over 12 years: 0.5 g every 6 hours, given 30-60
      minutes before meals and at bedtime for about 5 days.
     • Children under 12years:O.I g/kg body weight, every 6 hours, given
      30-60 minutes before meals and at bedtime for about 5 days. Not to
      exceed  1.0 g per day.

    Caution:  Adverse reactions to short-term therapy are rare. However,
    persons allergic to penicillin should not receive d-penicillamine
    as they may suffer allergic reactions to it.
    Succimer (DMSA) has been shown to be an effective chelator of arsenic,
though it is not labeled for this indication.19 In Europe, DMPS has been used
successfully in treatment of arsenic poisoning. In light of the lack of effective-
ness of d-penicillamine, coupled with the low toxicity and high therapeutic
index of DMPS and DMSA, it appears that the latter two agents may be  the
preferred method for chronic toxicity or when oral chelation is acceptable.18-19
    Dosage of DMSA (Succimer):
     • Adults and Children: 10 mg/kg every 8 hours for 5 days, followed by
      10 mg/kg every 12 hours for an additional 14 days. (Maximum 500
      mg per dose). Should be given with food.

    Dosage of DMPS:
     • Adults: 100 mg every 8 hours for 3 weeks to 9 months.
7. Hemodialysis.  Extracorporeal hemodialysis, used in combination with
BAL therapy, has limited effectiveness in removing arsenic from the blood.
Hemodialysis is clearly indicated to enhance arsenic elimination and main-
tain extracellular fluid composition if acute renal failure occurs.

8. Renal function. In patients with intact renal function, alkalinization of
the urine by sodium bicarbonate to maintain urine pH >7.5 may help pro-
tect renal function  in the face of hemolysis occurring as part of the acute
                                                                                           ARSENICALS •  131

Signs and Symptoms:
•  Malaise, dizziness, nausea,
   abdominal pain
•  Hemoglobinuria and

•  Supportive
•  Exchange transfusion may
   be considered
    Arsine is not used as a pesticide. However, some poisonings by arsine
have occurred in pesticide manufacturing plants and metal refining op-
erations when arsenicals came into contact with mineral acids or strong
reducing agents.

    Arsine is a powerful hemolysin, a toxic action not exhibited by other
arsenicals. In some individuals, very little inhalation exposure is required to
cause a serious hemolytic reaction. Exposure times of 30 minutes at 25-50
parts per million are considered lethal.20 Symptoms of poisoning  usually
appear 1-24 hours after exposure: headache, malaise, weakness, dizziness,
dyspnea, nausea, abdominal pain, and vomiting. Dark red urine (hemoglo-
binuria) is often passed 4-6 hours after  exposure. Usually 1-2 days after
hemoglobinuria appears, jaundice is evident. Hemolytic anemia, sometimes
profound, usually provides  diagnostic confirmation and can cause severe
weakness. Abdominal tenderness and liver enlargement are often apparent.
Basophilic stippling of  red cells, red cell fragments, and ghosts are seen in
the blood smear. Methemoglobinemia and methemoglobinuria are evi-
dent. Elevated concentrations of arsenic are found in the urine, but these
are not nearly as high as are found in poisonings by solid arsenicals. Plasma
content of unconjugated bilirubin is elevated.
    Renal failure due to direct toxic action of arsine and to products of
hemolysis represents the chief threat to life in arsine poisoning.21
    Polyneuropathy and a mild  psycho-organic syndrome are reported to
have followed arsine intoxication after a latency of 1-6 months.

1.  Remove the victim to fresh air.
2.  Administer intravenous fluids to keep the urine as dilute as possible and to
support excretion of arsenic and products of hemolysis. Include sufficient
sodium bicarbonate to keep the urine alkaline (pH greater than  7.5).
   Caution: Monitor fluid balance carefully to avoid fluid  overload if
renal failure supervenes. Monitor plasma electrolytes to detect disturbances
(particularly hyperkalemia) as early as possible.
3.  Monitor urinary arsenic excretion to assess severity of poisoning. The
amount of arsine that must be absorbed to cause poisoning is small, and
therefore high levels of urinary arsenic excretion may not always occur,
even in the face of significant poisoning.21'22
4.  If poisoning is severe, exchange blood transfusion may be considered.
It was successful in rescuing one adult victim of arsine poisoning.
5.  Extracorporeal hemodialysis may be necessary to maintain normal extra-
cellular fluid composition and to enhance arsenic elimination if renal failure
occurs, but it is not very effective in removing arsine carried in the blood.

General Chemical  Structures
           Arsenic trioxide
               /   \
                      "White arsenic." Arsenous oxide. Has been
                      discontinued but still may be available
                      from prior registrations.
           Sodium arsenite
           Na-0-As = 0
                      Sodanit, Prodalumnol Double.  All uses
                      discontinued in the U.S.
           Calcium arsenite
             O —As=O
             Ca  (approx.)
                      Mono-calcium arsenite, London purple.
                      Flowable powder for insecticidal use on
                      fruit. All uses discontinued in the U.S.
           Copper arsenite
        (Acid copper arsenite)
        HO-Cu-O-As = O
                      Wettable powder, for use as insecticide,
                      wood preservative. All uses discontinued
                      in the U.S.
        Copper acetoarsenite
                      Insecticide. Paris green, Schweinfurt green,
                      Emerald green, French green, Mitis green.
                      No longer used in the U.S.; still used
                      outside U.S.
                                     Not a pesticide. Occasionally generated
                                     during manufacture of arsenicals.

             Arsenic acid
                \  I
                      Hi-Yield Dessicant H-10, Zotox. Water
                      solutions used as defoliants, herbicides, and
                      wood preservatives.
           Sodium arsenate
            NaO  OH
                      Disodium arsenate. Jones Ant Killer. All
                      uses discontinued, but may still be
                      encountered from old registration.
                                                                                                ARSENICALS • 133

                                              Calcium arsenate
                                              O            O
    O      O            O     O
  x  \   //               ^   x \
Ca    As — O — Ca — O — As    Ca  the U S
  \  x                        \ x
    O                          O
Tricalcium arsenate, Spra-cal,Turf-Cal.
Flowable powder formulations used
against weeds, grubs. No longer used in
                                                Lead arsenate

                                                    O  OH
                                                  x  \
                                                Pb     As = O
                                                  \  /
                                      Gypsine, Soprabel. Limited use in the
                                      U.S.; wettable powder used as insecticide
                                      outside the U.S.
                                     x \  ,
                                   In     As
                                     \ x
             Zinc arsenate
           O             00
          5-               ^  x  \
          — O — In — O —  As    In
                              \  x
                                                                          Powder once used in U.S. as insecticide
                                                                          on potatoes and tomatoes.
                                          ORGANIC (PENTAVALENT)

                                     Cacodylic acid (sodium cacodylate)   Non-selective herbicide, defoliant,
                                                                          silvicide. Bolate, Bolls-Eye, Bophy, Dilic,
                                                                                      6Q> Rad_E_Cate 25; Salvo.
                                                            (or Na)
                                            Methane arsonic acid
                                                CH3      OH
                                                    \  x
                                      MAA. Non-selective herbicide.
                                       Monosodium methane arsonate
                                                CH3      OH
                                                   \  x
MSMA. Non-selective herbicide,
defoliant, silvicide. Ansar 170, Arsonate
Liquid, Bueno 6, Daconate 6, Dal-E-Rad,
Drexar 530, Herbi-All, Merge 823,
Mesamate.Target MSMA,Trans-Vert,
Weed-E-Rad, Weed-Hoe.
                                         Disodium methane arsonate
                                                CH3      ONa
                                                    \  x
                                                   •x   \
                                                 O       ONa
                                      DSMA. Selective post-emergence
                                      herbicide, silvicide. Ansar 8100, Arrhenal,
                                      Arsinyl, Crab-E-Rad, Di-Tac, DMA,
                                      Methar 30, Sodar, Weed-E-Rad 360.
                                     Monoammonium methane arsonate  MAMA. Selective post-emergence
                                                CH3      ONH4           herbicide. No longer used in the U.S.
                                                    \  X

    Calcium acid methane arsonate     CAMA. Selective post-emergence
    r*u       /-ILJ         LJ/-I       ^u     herbicide. Calar, Super Crab-E-Rad-
    UM3       Un         HU       UM3                      ,-,,-,
        \   X                \   /         Calar, Super Dal-E-Rad.
         As                   As
       ^   \               /    ^
    O        O - Ca -  O        O
1.   Malachowski ME. An update on arsenic. Clln Lab Med 1990; 10(3):459-72.
2.   Ellenhorn, MJ. Arsenic: Metals and related compounds. In: Ellenhorn's Medical Toxicology,
    Diagnosis and Treatment of Human Poisoning, 2nd ed. Baltimore: Williams & Wilkins,
    1997, p. 1540.
3.   Campbell JP and Alvarez JA. Acute arsenic intoxication. Am Fam Physician 1989; 40(6):93-7.
4.   St. Petery J, Gross C, and Victorica BE. Ventricular fibrillation caused by arsenic poisoning.
    AJDC  1970; 120:367-71.
5.   Goldsmith S and From AHL. Arsenic-induced atypical ventricular tachycardia. New Engl J
    Med 1980; 303(19). 1096-8.
6.   Heyman A, Pfeiffer JB Jr., Willett RW, et al. Peripheral neuropathy caused by arsenical in-
    toxication. A study of 41 cases with observations on the effects of BAL (2,3-dimercapto-
    propanol). N Engl J Med 1956;254:401-9.
7.   Donofrio PD.WilbournAJ.AlbersJW, etal. Acute arsenic intoxication presenting as Guillain-
    Barre-like syndrome. Muscle Nerve 1987; 10:114-20.
8.   Maloney ME. Arsenic  in dermatology. Dermatol Surg 1996;22:301-4.
9.   Navarro B,  Sayas MJ, Atienza A, and Leon R An unhappily married man  with thick soles.
    Lancet 1996;347:1596.
10. LinTH, Huang YL, and Wang MY. Arsenic species in drinking water, hair, fingernails, and
    urine of patients with blackfoot disease. JToxicol Environ Health 1998;53A:85-93.
11. Fesmire FM, Schauben JL, and Roberge RJ. Survival following massive arsenic ingestion.
    AmJEmergMed, 1998;6(6):602-6.
12. ACGIH. 1997TLVs and BEIs.Threshold limit values for chemical substances and physical
    agents. Biological exposure indices. Cincinnati, 1997.
13. Wagner SL  and Weswig P. Arsenic in blood and urine of forest workers. Arch Environ Health
    1974; 28:77-9.
14. Buchet JP, Pauwels J, and Lauwerys R. Assessment of exposure to inorganic arsenic follow-
    ing ingestion of marine organisms by volunteers. Environ Res 1994;66:44-51.
15. Baselt RA and Cravey RH. Arsenic. In: Disposition ofToxic Drugs and Chemicals in Men,
    3rd ed. Chicago, IL: Year  Book Medical Publishers, 1990, pp. 65-9.
16. Barone MA. Drug doses; Dimercaprol. In:The Harriet Lane Handbook, 14th ed. Baltimore:
    Mosby, 1996, p. 525.
17. Hoover TD and Aposhian HV. BAL increased the arsenic-74 content of rabbit brain. Toxicol
    Appl Pharmacol 1983; 70:160-2.
                                                                                                              ARSENICALS •  135

                                         18.  Kreppel H, Reichl FX, Forth W, and Fichtl B. Lack of effectiveness of d-penicillamine in
                                             experimental arsenic poisoning.  Vet Hum Toxicol 1989;31:l-5.
                                         19.  Muckter H, Liebl B, Beichl FX, et al. Are we ready to replace dimercaprol (BAL) as an
                                             arsenic antidote? Hum Exp Toxicol 1997;16:460-5.
                                         20.  Blackwell M and Robbins A. NIOSH Current  Intelligence Bulletin #32,Arsine (arsenic
                                             hydride) poisoning in the workplace. Am Ind HygAssoc J 1979;40:A56-61.
                                         21.  Fowler BA andWeissberg JB.Arsine poisoning. New Engl JMed 1974;291:1171-4.
                                         22.  Rathus E, Stingon RG, and Putrnan JL. Arsine poisoning, country style. MedJAust 1979;!: 163-6.

Fungicides are extensively used in industry, agriculture, and the home and gar-
den for a number of purposes, including: protection of seed grain during stor-
age, shipment, and germination; protection of mature crops, berries, seedlings,
flowers, and grasses in the field, in storage, and during shipment; suppression of
mildews that attack painted surfaces; control of slime in paper pulps; and pro-
tection of carpet and fabrics in the home.
    Fungicides vary enormously in their potential for causing adverse effects in
humans. Historically, some of the most tragic  epidemics of pesticide poisoning
occurred because of mistaken consumption of seed grain treated with organic
mercury or hexachlorobenzene. However, most fungicides currently in use are
unlikely to cause frequent or severe systemic poisonings for several reasons.
First, many have low inherent toxicity in mammals and are  inefficiently ab-
sorbed. Second, many fungicides are formulated as suspensions of wettable pow-
ders or granules, from which rapid, efficient absorption is unlikely. And third,
methods  of application are such that relatively few individuals are intensively
exposed. Apart from systemic poisonings, fungicides as a class are probably re-
sponsible for a disproportionate number of irritant injuries to skin and mucous
membranes, as well as dermal sensitization.
    The following discussion covers the  recognized adverse effects of widely
used fungicides.  For fungicides that have caused systemic poisoning, recom-
mendations for management of poisonings and injuries are set forth. For fungi-
cides not known to have caused systemic poisonings in the past, only general
guidelines can be offered.
    The discussion of fungicide-related adverse effects proceeds in this order:

    •   Substituted Benzenes
    •   Thiocarbamates

    •   Ethylene Bis Dithiocarbamates
    •   Thiophthalimides

    •   Copper  Compounds
    •   Organomercury Compounds

    •   Organotin Compounds
    •   Cadmium Compounds

    •   Miscellaneous Organic  Fungicides

•  Numerous fungicides in use
   with varying levels of
•  Other than organomercury
   compounds, most
   fungicides are unlikely to be
   absorbed enough to cause
   systemic poisonings

Signs and Symptoms:
•  Variable

•  Dermal and eye
•  Gl decontamination
•  Intravenous fluids

•  Atropine. Fungicides are
   not cholinesterase
                                                                                           FUNGICIDES •  137

Commercial Products
  Terraneb SP
  Clorto Caffaro
  Daconil 2787
  Exotherm Termil
  Ceku C.B.
  No Bunt

* Discontinued in the U.S.
    Chloroneb is supplied as wettable powder for treatment of soil and seed.
This agent exhibits very low oral toxicity in mammals. It may be moderately
irritating to skin and mucous membranes. The metabolite dichloromethoxy-
phenol is excreted in the urine. No cases of systemic poisoning in humans have
been reported.
    Chlorothalonil is available as wettable powder, water dispersible granules,
and flowable powders. Chlorothalonil has caused irritation of skin and mucous
membranes of the eye and respiratory tract on contact. Cases of allergic contact
dermatitis have been reported.There is one report of immediate anaphylactoid
reaction to skin contact.' It is apparently  poorly absorbed across the skin and
the gastrointestinal lining. No cases of systemic poisoning in humans have been
    Dicloran is a broad-spectrum fungicide widely used to protect perishable
produce. It  is  formulated as wettable powder, dusts, and  flowable powders.
Dicloran is absorbed by  occupationally exposed workers, but it is promptly
eliminated, at  least partly in the urine. Biotransformation products include
dichloroaminophenol, which is an uncoupler of oxidative phosphorylation (en-
hances heat production). Extraordinary doses of dicloran given to laboratory
animals cause liver injury and corneal opacities.
    Based on laboratory animal studies and effects of similar compounds, large
doses might be expected to cause liver injury, pyrexia, corneal opacities, and
possibly methemoglobinemia. None of these have been observed in  humans
exposed to DCNA.
    Hexachlorobenzene.Principal  formulations are dusts and powders.
Hexachlorobenzene differs chemically and toxicologically from hexachlorocy-
clohexane,the gamma isomer of which (lindane) is still a widely-used insecticide.
    Although this seed protectant fungicide has only slight irritant effects and
relatively low single-dose toxicity, long-term ingestion of HCB-treated grain
by Turkish farm dwellers in the late 1950s  caused several  thousand  cases of
toxic porphyria resembling porphyria cutanea tarda.2This condition  was due
to impaired hemoglobin synthesis, leading to toxic end-products (porphyrins)
in body tissues.The disease was characterized by excretion of red-tinged (por-
phyrin-containing) urine, bullous lesions of light-exposed  skin, scarring and
atrophy of skin with overgrowth of hair, liver enlargement, loss of appetite,
arthritic disease, and wasting of skeletal  muscle mass. Although most adults
ultimately recovered after they stopped consuming the HCB-treated grain, some
infants nursed by affected mothers died.
    Hexachlorobenzene is effectively dechlorinated and oxidized in humans;
trichlorophenols are the major urinary excretion products. Disposition is suffi-
ciently prompt that occupationally exposed  workers usually show only slight

elevation of blood HCB concentrations. HCB is sometimes present in blood
specimens from "non-occupationally exposed" persons in concentrations of up
to 5 meg per liter. Residues in food are the probable cause.
    Pentachloronitrobenzene is used to dress seed and  treat soil. Formula-
tions  include  emulsifiable concentrates, wettable  powders, and granules.
Hexachlorobenzene is a minor contaminant to technical PCNB.
    High concentrations in prolonged contact with skin have caused sensitiza-
tion in some tested volunteers, but neither irritation nor sensitization has been
reported in occupationally exposed workers. One case of conjunctivitis and keratitis
occurred following eye contamination.This resolved slowly but completely.
    Systemic poisonings have not been reported. Clearance in laboratory ani-
mals is slow, probably due to  enterohepatic recirculation. Excretion is chiefly
biliary, with some conversion to pentachloroaniline, pentachlorophenol, and
other metabolites in the liver. Although a methemoglobinemic effect might be
suspected  (as from nitrobenzene), this  has not been reported in humans or
animals, nor has toxic porphyria (as from hexachlorobenzene) been reported.

Confirmation of Poisoning

    Hexachlorobenzene (HCB) can be measured in blood by gas chromatog-
raphy. Chlorophenol metabolites can be measured in the urine. Although in-
herited disease  and a number of exogenous  agents may cause porphyrins to
appear in the urine, a test for porphyrins may be useful for toxicological diag-
nosis if there has been a known exposure to HCB or if a patient exhibits signs
suggestive of porphyria cutanea tarda.
    Gas chromatography  can be  used to measure PCNB and metabolites,
chlorothalonil, and chloroneb, but the analysis is not widely available. Methods
have also been described for analysis of dicloran, but they are not widely available.

1. Skin decontamination. Dermal contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water. If irritation persists, specialized medical care  should be  obtained. See
Chapter 2.

2. Gastrointestinal decontamination. If a large amount of the fungicide has
been ingested in the last  few hours, and if copious vomiting has not already
occurred, it may be reasonable to consider GI decontamination. Activated char-
coal can be used along with the addition of the cathartic sorbitol to the char-
coal slurry. If sorbitol is given separately, it should  be  diluted with an equal
volume of water before administration. No more than  one dose of sorbitol is
recommended and it should be used with caution in children and the elderly.
See Chapter 2 for appropriate dosages.
                                                                                           FUNGICIDES • 139

Commercial Products
  Carbamate WDG
  A7 Vapam
  Busan 1020
  Metam-Fluid BASF
  Solasan 500
  Chipco Thiram 75
  Fermide 850
  Pomarsol forte
  Spotrete WP 75
  Tram eta n
  Vancide MZ-96
  Ziram F4
  Ziram Technical
  Zirex 90
    If contact with the toxicant has been minimal (for example, oral contami-
nation only, promptly flushed out of the mouth),  administration of charcoal
without a cathartic, followed by careful  observation of the patient, probably
represents optimal management.

3. Porphyria. Persons affected by porphyria should avoid sunlight, which ex-
acerbates the dermal injury by porphyrins.


Thiocarbamates are commonly formulated as dusts, wettable powders, or water
suspensions. They are used to protect seeds, seedlings, ornamentals, turf, veg-
etables, fruit, and apples. Unlike the N-methyl carbamates (Chapter  5),
thiocarbamates  have very little insecticidal potency. A few exhibit weak anti-
cholinesterase activity, but most have no significant effect on this enzyme. Overall,
they are less of a threat to human health than the insecticidal carbamates. Fun-
gicidal thiocarbamates are discussed in this section, while those used as herbi-
cides are considered in Chapter 13.


    Metam-sodium is formulated in aqueous solutions for application as a soil
biocide and fumigant to kill fungi, bacteria, weed seeds, nematodes, and insects.
All homeowner uses have been cancelled in the United States.


    Metam-sodium can be very irritating to the skin. Poisonings by ingestion
of metam-sodium have not been reported. Although animal feeding studies do
not indicate extraordinary toxicity of metam-sodium by ingestion, its decom-
position in water  yields methyl isothiocyanate, a gas that is extremely irritating
to respiratory mucous membranes, to the eyes, and to the lungs. Inhalation of
methyl isothiocyanate may cause pulmonary edema (severe respiratory distress,
coughing  of bloody, frothy sputum). For this reason, metam-sodium is consid-
ered a fumigant. It must be used in outdoor settings only, and stringent precau-
tions must be taken to avoid inhalation of evolved gas.
    Theoretically, exposure to metam-sodium may predispose the individual
to Antabuse reactions if alcohol is ingested after exposure. (See Thiram.) How-
ever, no such occurrences have been reported.

Confirmation of Poisoining
    No tests for metam-sodium or its breakdown products in body fluids are
1. Skin decontamination. Skin contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water to avoid burns and corneal injury. If dermal or eye irritation persists,
specialized medical treatment should be obtained. See Chapter 2.

2. Gastrointestinal decontamination. If a  large amount has been ingested
recently, consider gastric emptying or charcoal and cathartic. See Chapter 2 for
appropriate dosages.

3. Pulmonary edema. If pulmonary irritation or edema occur as a result of
inhaling methyl isothiocyanate, transport the victim promptly to a medical fa-
cility. Treatment for pulmonary edema should proceed as outlined in Chapter
16, Fumigants.

4. Contraindicated: Metam-sodium is not a cholinesterase inhibitor. Atro-
pine is not an antidote.
    Thiram  is a common component of latex and  possibly  responsible for
some of the allergies attributed to latex.
    Thiram dust is moderately irritating to human skin, eyes, and respiratory
mucous membranes. Contact dermatitis has occurred in occupationally ex-
posed workers. A few individuals have experienced sensitization to thiram.3
    Systemic human poisonings by thiram itself have been very few, probably
due to limited absorption in most circumstances involving human exposure.
Those which have been reported have been similar clinically to toxic reactions
to disulfiram (Antabuse), the ethyl analogue of thiram which  has been exten-
sively used in alcohol aversion therapy.3 In laboratory animals, thiram at high
dosage has effects similar to those of disulfiram (hyperactivity, ataxia, loss of
muscle tone, dyspnea, and convulsions), but thiram appears  to be about 10
times as toxic as disulfiram.
                                                                                          FUNGICIDES • 141

                                    Neither thiram nor disulfiram are cholinesterase inhibitors. Both, however,
                                inhibit the enzyme acetaldehyde dehydrogenase, which is critical to the
                                conversion of acetaldehyde to acetic acid. This is the basis for the "Antabuse
                                reaction" that occurs when ethanol is consumed by a person on regular disulfiram
                                dosage. The reaction includes symptoms of nausea, vomiting, pounding headache,
                                dizziness, faintness, mental confusion, dyspnea, chest and abdominal pain, profuse
                                sweating, and skin rash. In rare instances, Antabuse reactions may have occurred
                                in workers who drank alcohol after previously being exposed to thiram.
                                Confirmation of Poisoning
                                    Urinary xanthurenic acid excretion  has been  used to monitor workers
                                exposed to thiram.The test is not generally available.
                                Treatment: Thiram Toxicosis
                                1. Skin decontamination. Wash thiram from the skin with soap and water.
                                Flush contamination from the eyes with copious amounts of clean water. If irri-
                                tation of skin or eyes persists, specialized medical treatment should be obtained.

                                2. Gastrointestinal decontamination. If a large amount of thiram has been
                                swallowed within 60 minutes of presentation, and effective vomiting has not
                                already occurred, the stomach may be  emptied by intubation, aspiration, and
                                lavage, taking all  precautions to protect the airway from aspiration of vomitus.
                                Lavage should be followed by instillation of activated charcoal and cathartic. If
                                only a small amount of thiram has been ingested and/or treatment has been
                                delayed, oral administration of activated charcoal and cathartic probably repre-
                                sents optimal management.

                                3. Intravenous  fluids. Appropriate IV fluids should be infused, especially if
                                vomiting and diarrhea are  severe.  Serum electrolytes and glucose should be
                                monitored and replaced as needed.
                                Treatment: Acetaldehyde Toxicosis (Antabuse Reaction)
                                1. Immediate management. Oxygen inhalation, Trendelenburg position-
                                ing, and intravenous fluids are usually effective  in relieving manifestations of
                                Antabuse reactions.
                                2. Alochol avoidance. Persons who have absorbed any significant amount of
                                thiocarbamates must avoid alcoholic beverages for at least three weeks. Dispo-
                                sition of thiocarbamates is slow, and their inhibitory effects on enzymes are
                                slowly reversible.

    These are formulated as flowable and wettable powders, used widely on
fruit and nut trees, apples, vegetables, and tobacco.
    Dust from these fungicides is irritating to the skin, respiratory tract, and
eyes. Prolonged inhalation of ziram is said to have caused neural and visual
disturbances, and, in a single case of poisoning, a fatal hemolytic reaction.Theo-
retically, exposure to ziram or ferbam may predispose the individual to Antabuse
reactions if alcohol is ingested after exposure. (SeeThiram.) However, no such
occurrences have been reported.
Confirmation of Poisoning
    No tests for these fungicides or their breakdown products in body fluids
are available.
1. Skin decontamination. Skin contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water. If dermal or eye irritation persists, specialized medical treatment should
be obtained. See Chapter 2.

2. Gastrointestinal decontamination. If substantial amounts of ferbam or
ziram have been ingested  recently, consideration should be given to gastric
emptying. If dosage was small and/or several hours have elapsed since inges-
tion, oral administration of charcoal and a cathartic probably represents optimal

3. Hemolysis. If hemolysis occurs, intravenous fluids should be administered,
and induction of diuresis considered.
                                                                                         FUNGICIDES • 143

Commercial Products

  Kypman 80
  Manex 80
  Chem Bam
  Spring Bak
  Parzate C


    Maneb and zineb are formulated as wettable and flowable powders. Nabam
is provided as a soluble powder and in water solution. Mancozeb is a coordina-
tion product of zinc ion and maneb. It is formulated as a dust and as wettable
and liquid flowable powders.


    These fungicides may cause irritation of the skin, respiratory tract, and eyes.
Both maneb and zineb have apparently been responsible for some cases of chronic
skin disease in occupationally exposed workers, possibly by sensitization.
    Although marked adverse effects may follow injection of EBDC compounds
into animals, systemic toxicity by oral and dermal routes is generally low. Nabam
exhibits the greatest toxicity, probably due to its greater water  solubility and
absorbability. Maneb is moderately soluble in water, but mancozeb and zineb
are  essentially water insoluble. Absorption of the latter fungicides across skin
and mucous membranes is probably very limited. Systemic poisonings of humans
have been extremely rare. However, zineb apparently precipitated an episode of
hemolytic anemia  in one worker predisposed by reason of multiple red cell
enzyme deficiencies.4 Maneb exposure has been reported in one person who
developed acute renal failure and was treated with hemodialysis.5 Another person
developed behavioral and neurological symptoms including tonic-clonic seizures
after handling maneb. He recovered uneventfully with supportive care.6
    The EBDC compounds are not inhibitors of cholinesterase or of acetalde-
hyde dehydrogenase.They do not induce cholinergic illness or "Antabuse" re-
                                 Confirmation of Poisoining

                                    No tests for these fungicides or their breakdown products in body fluids
                                 are available.
                                    See Treatment for Substituted Benzenes, p. 139.

Commercial Products

    These agents are widely used to protect seed, field crops, and stored pro-
duce.They are formulated as dusts and wettable powders. Captafol is no longer
registered for use in the United States.

    All of these  fungicides are moderately irritating to the skin, eyes, and
respiratory tract. Dermal sensitization may occur; captafol appears to have been
responsible for several episodes of occupational contact dermatitis.7'8 No systemic
poisonings by thiophthalimides have been reported in humans, although captafol
has been reported to have exacerbated asthma after occupational exposure.9
Laboratory  animals given very large doses of captan exhibit hypothermia,
irritability, listlessness, anorexia, hyporeflexia, and oliguria, the latter with
glycosuria and hematuria.
Confirmation of Poisoning

    Captan fungicides are metabolized in the body to yield two metabolites
that can be measured in the urine.10

    See Treatment for Substituted Benzenes, p. 139.



    Insoluble compounds are formulated as wettable powders and dusts. Soluble
salts are prepared as aqueous solutions. Some organometallic compounds are
soluble in mineral oils.
    A great many commercial copper-containing fungicides are available. Some
are mixtures of copper compounds. Others include lime, other metals, and
other fungicides. Compositions of specific products can usually be provided by
manufacturers or by poison control centers.
    Copper-arsenic compounds such as Paris green may still be used in agri-
culture outside the U.S. Toxicity of these compounds is chiefly due to arsenic
content (see  Chapter 14, Arsenical Pesticides).
  Fungitrol II
Inorganic Copper Compounds
copper acetate
copper ammonium carbonate
copper carbonate, basic
copper hydroxide
copper lime dust
copper oxychloride
copper potassium sulfide
copper silicate
copper sulfate
cupric oxide
cuprous oxide
  Bordeaux Mixture

Organic Copper Compunds
copper linoleate
copper naphthenate
copper oleate
copper phenyl salicylate
copper quinolinolate
copper resinate
* Discontinued in the U.S.
                                                                                        FUNGICIDES • 145

                                     The dust and powder preparations of copper compounds are irritating to the
                                 skin, respiratory tract, and particularly to the eyes. Soluble copper salts (such as
                                 the sulfate  and acetate) are corrosive to mucous membranes and the cornea.
                                 Limited solubility and absorption probably account for the generally low sys-
                                 temic toxicity  of most compounds. The more  absorbable organic copper com-
                                 pounds exhibit the greatest systemic toxicity in laboratory animals. Irritant effects
                                 from occupational exposures to copper-containing fungicides have been  fairly
                                 frequent. Most of what is known about mammalian toxicity of copper com-
                                 pounds has come from veterinary toxicology (livestock seem uniquely vulner-
                                 able) and poisonings in humans due to deliberate ingestion of copper sulfate or to
                                 consumption of water or  food that had been contained in copper vessels.
                                     Early signs and symptoms  of copper poisoning include a metallic  taste,
                                 nausea, vomiting, and epigastric pain. In more severe poisonings, the gastrointes-
                                 tinal irritation will  worsen with hemetemesis and melanotic stools. Jaundice
                                 and hepatomegaly are common.n'12Hemolysis can occur, resulting in circula-
                                 tory collapse  and shock. Methemoglobinemia has been reported in these
                                 cases.11'13'14 Acute renal failure with oliguria can  also occur. Shock is a primary
                                 cause of death early in the course, and renal failure and hepatic failure contrib-
                                 ute to  death more than 24 hours after poisoning.15
                                     Management of poisonings by ingestion of copper-containing fungicides
                                 depends entirely on the chemical nature of the compound: the strongly ionized
                                 salts present the greatest hazard; the oxides, hydroxides, oxychloride, and
                                 oxysulfate are less likely to cause severe systemic poisoning.

                                 1. Skin decontamination. Dust and powder should be washed from the skin
                                 with soap and water. Flush the eyes free of irritating dust, powder, or solution,
                                 using clean water or saline. If eye or dermal irritation persists, specialized medi-
                                 cal treatment should be obtained. Eye irritation may be severe. See Chapter 2.

                                 2. Anti-corrosive. Give water or milk as soon as possible to dilute the toxicant
                                 and mitigate corrosive action on the mouth, esophagus, and gut.

                                 3. Gastrointestinal decontamination. Vomiting is usually spontaneous in
                                 acute copper ingestion. Further induction of emesis is contraindicated because
                                 the corrosive nature of some copper salts  can cause further damage to the
                                 esophagus. Further GI decontamination should be determined on a case-by-
                                 case basis, as outlined in Chapter 2. Gastric lavage may cause further damage.15
                                 Charcoal  has not  been widely studied in  metal poisonings as an effective

    Caution: Gastric intubation may pose a serious risk of esophageal perfo-
ration if corrosive action has been severe. In this event, it may be best to avoid
gastric intubation.

4. Intravenous fluids. If indications of systemic illness appear, administer in-
travenous fluids containing glucose and electrolytes. Monitor fluid balance, and
correct blood electrolyte concentrations as needed. If shock develops, give blood
transfusions and vasopressor amines, as required.

5. Hemolysis. Monitor plasma for evidence of hemolysis (free  hemoglobin)
and the red cells for methemoglobin. If hemolysis occurs, alkalinize the urine
to about pH 7.5 by adding sodium bicarbonate to the intravenous infusion
fluid. Also, mannitol diuresis may be considered. If methemoglobinemia is se-
vere (> 30%), or the patient is cyanotic, administer methylene blue.The dosage
for adults/child is 1-2 mg/kg/dose, given as a slow IV push over a few minutes,
every 4 hours as needed.15

6. Pain management. Severe pain may require the administration of mor-

7. Chelating agents.  The value of chelating agents in copper poisoning has
not been established.16 However, BAL appears to accelerate copper excretion
and may alleviate illness. D-penicillamine  is the treatment for Wilson's disease
due to chronic copper toxicity; however, in the  context of severe vomiting
and/or mental status changes from an acute ingestion, BAL would be a more
likely initial choice.13'15 For a recommended schedule of dosage for initial therapy
with BAL and subsequent penicillamine administration, see Chapter 14, Ar-
senical Pesticides.
Commercial Products
Methyl Mercury
methyl mercury acetate

Methoxyethyl Mercury
methoxyethyl mercury acetate
  Panogen M
methoxyethyl mercury chloride
  Emisan 6

Phenyl mercuric Acetate
  Tag HE 331
8. Hemodialysis. Although hemodialysis is indicated for patients with renal
failure, copper is not effectively removed in the dialysate.11



    These fungicides have been formulated as aqueous  solutions and dusts.
They have been used chiefly as seed protectants. Use of alkyl mercury fungicides
in the  United States has been virtually prohibited for several years. Phenyl-
mercuric acetate is no longer permitted to be used in the United States.
                                                                                        FUNGICIDES • 147

                                      The  mercurial fungicides are  among the most toxic pesticides ever
                                 developed, for both chronic and acute hazards. Epidemics of severe, often fatal,
                                 neurologic disease have occurred when indigent residents of less developed
                                 countries  consumed methyl mercury-treated grain intended for planting of
                                 crops.17'18  Poisoning has  also occurred from eating meat  from animals fed
                                 mercury-treated seed.19 Most of what is known of poisoning by organic mercurial
                                 fungicides has come from these occurrences.
                                     Organic mercury compounds are efficiently absorbed across the gut  and
                                 possibly across the skin.Volatile  organic mercury is readily taken up across the
                                 pulmonary membrane. Methyl mercury is selectively concentrated in the tissue
                                 of the nervous system, and also in red blood cells. Other alkyl mercury com-
                                 pounds are probably distributed similarly. Excretion occurs almost entirely by
                                 way of the bile into the bowel. The  residence  half-life of methyl mercury in
                                 humans is about 65 days.20 There is significant conversion of organic mercury
                                 to inorganic mercury in the red cell.
                                     Early  symptoms of poisoning are metallic taste in the mouth, numbness
                                 and tingling of the digits and face, tremor, headache, fatigue, emotional lability,
                                 and difficulty thinking. Manifestations of more severe poisoning are incoordi-
                                 nation, slurred speech, loss of position sense, hearing loss, constriction of visual
                                 fields, spasticity or rigidity of muscle  movements, and deterioration of mental
                                 capacity. Many poisonings caused by  ingestion of organic mercurials have  ter-
                                 minated fatally, and a large percentage of survivors have suffered severe perma-
                                 nent neurologic damage.17"19
                                     Phenylmercuric acetate is not as extremely toxic as the alkyl mercury com-
                                 pounds. It is not as efficiently absorbed from the gut as methyl mercury21 Phenyl-
                                 mercuric acetate had been used to prevent fungal growth in latex paint. There
                                 have been reports of acrodynia in persons exposed to mercury vapor from use of
                                 interior latex paint. Symptoms include fever, erythema and desquamation of hands
                                 and feet, muscular weakness, leg  cramps, and  personality changes.22  Phenyl-
                                 mercuric compounds have since been banned from latex paint.20
                                 Confirmation of Poisoning
                                     Mercury content of blood and tissues can be measured by atomic absorp-
                                 tion spectrometry. Blood levels of 5 mcg/dL or greater are considered elevated
                                 for acute exposure.21 Special procedures are needed for extraction and mea-
                                 surement of organic mercury compounds specifically.

Commercial Products
    Every possible precaution should be taken to avoid exposure to organic
mercury compounds. Ingestion of an organic mercury compound, even at low
dosage, is life threatening, and management is difficult.Very little can be done
to mitigate neurologic damage caused by organic mercurials.
    Persons experiencing symptoms (metallic taste in mouth) after inhalation of
volatile organic mercury compounds (methyl mercury is the most volatile) should
be removed promptly from the contaminated environment and observed closely
for indications of neurologic impairment. Following are the basic steps in man-
agement of poisoning:

1. Skin decontamination. Skin and hair contaminated by mercury-contain-
ing dust or solution should be cleansed with soap and water. Flush contamina-
tion from the eyes with clean water. If irritation persists, specialized medical
care should be obtained. See Chapter 2.

2. Gastrointestinal decontamination. Consider gastrointestinal decontami-
nation as outlined in Chapter 2.

3. Chelation is an essential part of the management of mercury poisoning. For
dosages of specific agents, see Chapter 14, Arsenical Pesticides. Succimer (DMSA)
appears to be the most effective agent available in the United States. Dimerca-
prol (BAL) is contraindicated in these poisonings due to its potential to in-
crease brain levels of mercury.20 EDTA is apparently of little value in poisonings
by organic mercury. D-penicillamine is probably useful, is available in the United
States, and  has proven effective in reducing the residence half-life of methyl
mercury in poisoned  humans.20 2,3-dimercaptopropane-l-sulfonate acid
(DMPS) and N-acetyl-D,L-penicillamine (NAP) are probably also useful but
are not currently approved for use in the United States.

4. Hemodialysis. Extracorporeal hemodialysis and hemoperfusion may be
considered, although experience to date has not been encouraging.
fentin acetate*
fentin chloride*
fentin hydroxide
  Super Tin
triphenyl tin

* Discontinued in the U.S.
    These compounds are formulated as wettable and flowable powders for use
mainly as fungicides to control blights on field crops and orchard trees. Fentin
chloride was also prepared as an emulsifiable concentrate for use as a mollusci-
cide (Aquatin  20  EC, discontinued 1995).Tributyltin salts are used as fungi-
cides and antifouling agents on ships. They are somewhat more toxic by the
oral route than triphenyltin, but toxic actions are otherwise probably similar.
                                                                                           FUNGICIDES • 149

Commercial Products

cadmium chloride*
cadmium succinate*
cadmium sulfate*
  Crag Turf Fungicide
  Miller 531

* Discontinued in the U.S.
    These agents are irritating to the eyes, respiratory tract, and skin. They are
probably absorbed to a limited extent by the skin and gastrointestinal tract. Manifes-
tations of toxicity are due principally to effects on the central nervous system:
headache, nausea, vomiting, dizziness, and sometimes convulsions and  loss of
consciousness.  Photophobia and mental disturbances occur. Epigastric  pain is
reported, even in poisoning caused by inhalation. Elevation of blood sugar, suffi-
cient to cause glycosuria, has occurred in some cases. The phenyltin fungicides
are  less toxic than  ethyltin compounds, which have caused cerebral edema,
neurologic damage, and  death  in severely  poisoned  individuals who were
exposed dermally to a medicinal compound of this type.23 No deaths and very
few poisonings have been reported as a result of occupational exposures to phenyltin
                                  1. Skin decontamination. Skin contamination should be removed by wash-
                                  ing with soap and water. Flush contaminants from the eyes with clean water or
                                  saline. If irritation persists, specialized medical treatment should be obtained.
                                  See Chapter 2.

                                  2. Gastrointestinal decontamination. If large amounts of phenyltin com-
                                  pound have been ingested in the past hour, measures may be taken to decon-
                                  taminate the gastrointestinal tract, as outlined in Chapter 2.

                                  3. Chelating agents. Neither BAL, penicillamine, nor other chelating agents
                                  have been effective in lowering tissue stores of organotin compounds in  ex-
                                  perimental animals.
                                  CADMIUM  COMPOUNDS	
                                      Cadmium salts have been used to treat fungal diseases affecting turf and the
                                  bark of orchard trees.They were formulated as solutions and emulsions. Miller
                                  531 and Crag Turf Fungicide 531 were complexes of cadmium, calcium, cop-
                                  per, chromium, and zinc oxides.They are now marketed as a generic fungicide.
                                  Kromad is a mixture of cadmium sebacate, potassium chromate, and thiram.
                                  Cad-Trete is a mixture of cadmium chloride  and thiram. All cadmium fungi-
                                  cides in the U.S. have been discontinued.

    Cadmium salts and oxides are very irritating to the respiratory and gas-
trointestinal tracts. Inhaled cadmium dust or fumes can cause respiratory toxic-
ity after a latency period of several hours, including a mild, self-limited illness
of fever, cough, malaise, headaches, and abdominal pain, similar to metal fume
fever. A more  severe form of toxicity includes chemical pneumonitis, and  is
associated with labored breathing, chest pain, and a sometimes fatal hemor-
rhagic pulmonary edema.24-25 Symptoms may persist for weeks.
    Ingested cadmium causes nausea, vomiting, diarrhea, abdominal pain, and
tenesmus. Relatively small inhaled and ingested doses produce serious symp-
toms. Protracted absorption of cadmium has led to renal damage (proteinuria
and azotemia), anemia, liver injury  (jaundice), and defective bone structure
(pathologic fractures) in chronically exposed persons. Prolonged inhalation of
cadmium dust has contributed to chronic obstructive pulmonary disease.26
Confirmation of Poisoning
     Cadmium can be measured in body fluids by appropriate extraction, fol-
lowed by flame absorption spectrometry. It is reported that blood cadmium
concentrations tend to correlate with acute exposure and urine levels tend to
reflect total body burden. Blood levels exceeding 5 mcg/dL suggest excessive
exposure.25 Urinary excretion in excess of 100 meg per day suggests an unusu-
ally high body burden.
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Flush contamination from the eyes  with copious
amounts of clean water or saline. If irritation persists, specialized medical treat-
ment should be obtained. See Chapter 2.

2.  Pulmonary edema. Respiratory irritation resulting from inhalation of
small amounts  of cadmium dust may resolve spontaneously,  requiring no
treatment. More severe reactions, including pulmonary edema and pneumonitis,
may require  aggressive measures, including positive pressure mechanical
pulmonary ventilation, monitoring of blood gases, administration of diuretics,
steroid medications, and antibiotics.25 Codeine sulfate may be needed to control
cough and chest pain.

3. Gastrointestinal decontamination. The irritant action of ingested cadmium
products on the gastrointestinal tract is so strong that spontaneous  vomiting
and diarrhea often eliminate nearly all unabsorbed cadmium from the gut. If
                                                                                           FUNGICIDES •  151

Commercial Products
  Ben I ate
  Tersan 1991
  Venture I

* Discontinued in the U.S.
retention of some cadmium in the lower GI tract is  suspected, further
gastrointestinal decontamination may be considered, as outlined in Chapter 2.

4. Intravenous  fluids may be required to overcome dehydration caused by
vomiting and diarrhea. Also, fluids limit cadmium toxicity affecting the kidneys
and liver.  However, great care must  be taken to monitor fluid balance  and
blood electrolyte concentrations, so that failing renal function does not lead to
fluid overload.

5. Chelation therapy with calcium disodium EDTA may be considered for
acute poisoning, depending on measured cadmium in blood and urine, and the
status of renal function. Its  therapeutic value in cadmium poisoning has not
been established, and use of the agent carries the risk that unduly rapid transfer
of cadmium  to the kidney may  precipitate renal failure.  Urine protein  and
blood urea nitrogen and creatinine should be carefully monitored during therapy.
The dosage should be 75 mg/kg/day in three to six divided doses for 5 days.
The total dose for the 5-day course should not exceed 500  mg/kg.27 Succimer
(DMSA) has  also been  used in this poisoning, but has not been demonstrated
to be efficacious.

6. Contraindications: Dimercaprol (BAL) is not recommended for treatment
of cadmium poisoning, chiefly because of the risk of renal injury by mobilized

7. Liver function. Monitor urine content of protein and cells regularly, and
perform liver function tests for indications of injury to these organs.


    Some modern organic fungicides are widely used. Reports of adverse ef-
fects on humans are few. Some of the  known properties  of these agents are
listed below.
    Anilazine is supplied as  wettable  and flowable powders. Used on veg-
etables, cereals, coffee, ornamentals, and turf.This product has caused skin irri-
tation in exposed workers. Acute oral and dermal toxicity in laboratory animals
is low. Human systemic poisonings have not been reported.
    Benomyl is a synthetic organic  fungistat having little or  no acute toxic
effect in mammals. No systemic poisonings  have been reported in humans.
Although the molecule contains a carbamate grouping, benomyl is not a cho-
linesterase inhibitor. It is poorly absorbed across skin; whatever is absorbed is
promptly metabolized and excreted.
    Skin injuries to exposed individuals have occurred, and dermal sensitiza-
tion has been found among agricultural workers exposed to foliage residues.

    Cycloheximide is formulated as wettable powder, sometimes combined
with other fungicides. Cycloheximide is a product of fungal culture, effective
against fungal diseases of ornamentals and grasses. It is selectively toxic to rats,
much less toxic to dogs and monkeys. No human poisonings have been reported.
Animals given  toxic  doses exhibit salivation, bloody  diarrhea,  tremors, and
excitement, leading to coma and death  due to cardiovascular collapse.
Hydrocortisone increases the rate  of survival of deliberately poisoned rats.
Atropine, epinephrine, methoxyphenamine, and hexamethonium all  relieved
the symptoms of poisoning, but did not improve survival.
    Dodine is formulated as a wettable powder. It is commonly applied to
berries, nuts, peaches, apples, pears, and to trees afflicted with leaf blight. Dodine
is a cationic surfactant with antifungal activity. It is absorbed across the skin and
is irritating to skin, eyes, and gastrointestinal tract. Acute oral and dermal toxic-
ity  in laboratory animals is moderate. Poisonings in humans have not been
reported. Based on animal studies, ingestion would probably cause nausea, vom-
iting, and diarrhea.
    Iprodione  is supplied as wettable powder and other formulations. It is
used on berries, grapes, fruit, vegetables, grasses, and ornamentals, and as a seed
dressing. Iprodione  exhibits low acute oral and dermal toxicity  in laboratory
animals. No human poisonings have been reported.
    Metalaxyl is supplied as emulsifiable and  flowable concentrates. It is used
to control soil-borne fungal diseases on fruit trees, cotton, hops, soybeans, pea-
nuts, ornamentals and grasses. Also used as seed dressing. Metalaxyl exhibits low
acute oral and  dermal toxicity in laboratory animals. No human  poisonings
have been reported.
    Etridiazole is supplied as wettable powder and granules for application to
soil as a fungicide and nitrification inhibitor.  Contact may result in irritation of
skin and eyes. Systemic  toxicity is low. Human poisonings have  not been re-
    Thiabendazole is widely used as an agricultural fungicide,  but most ex-
perience with its toxicology in humans has  come from medicinal  use against
intestinal parasites. Oral doses administered for this purpose are far greater than
those likely to be absorbed in the  course of occupational exposure.Thiabenda-
zole is rapidly metabolized and excreted in  the urine, mostly as  a conjugated
hydroxy-metabolite. Symptoms and signs that sometimes follow ingestion are:
dizziness, nausea, vomiting, diarrhea, epigastric distress, lethargy, fever, flushing,
chills, rash and  local edema, headache, tinnitus, paresthesia, and  hypotension.
Blood  enzyme  tests may indicate liver injury. Persons with liver and kidney
disease may be unusually vulnerable  to toxic effects. Adverse effects from use of
thiabendazole as a fungicide have not been reported.
    Triadimefon is supplied as wettable powder, emulsifiable concentrate, sus-
pension  concentrate,  paste, and dry flowable powder.  Used on  fruit, cereals,
vegetables, coffee, ornamentals, sugarcane, pineapple, and turf, triadimefon ex-
hibits moderate acute oral toxicity in laboratory animals, but dermal toxicity is
                                                                                             FUNGICIDES • 153

                                     low. It causes irritation if eyes are contaminated.Triadimefon is absorbed across
                                     the skin. Overexposures of humans are  said to have resulted in hyperactivity
                                     followed by sedation.
                                         Triforine  is supplied as  emulsifiable concentrate and wettable powder.
                                     Used on berries, fruit, vegetables, and ornamentals, triforine exhibits low acute
                                     oral  and dermal  toxicity  in laboratory  animals. Mammals rapidly  excrete it
                                     chiefly as a urinary metabolite. No human poisonings have been reported.
                                     Confirmation of Poisoining
                                          There are no  generally available laboratory tests for these organic fungi-
                                     cides or their metabolites in body fluids.
                                          See Treatment for Substituted Benzenes, p. 139.
                                     1.  Dannaker CJ, Maibach HI, and O'Malley M. Contact urticaria and anaphylaxis to the fun-
                                         gicide chlorothalonil. Cutis 1993;52:3120-5.
                                     2.  Peters HA, Gocrnen A, Cripps DJ, et al. Epidemiology of hexachlorobenzene-induced por-
                                         phyria in Turkey: Clinical and laboratory follow-up after 25 years. Arch Neural 1992;39:744-9.
                                     3.  Dalvi RR. Toxicology of thirarn (tetramethylthiuram disulfide): A review. Vet Hum Toxicol
                                     4.  Pinkhans J, Djaldetti M, Joshua H, et al. Sulfahemoglobinemia and acute hemolytic anemia
                                         with Heinz bodies following contact with a fungicide-zinc ethylene bisdithiocarbamate in a
                                         subject with glucose-6-phosphate dehydrogenase deficiency and hypocatalasemia. Blood
                                     5.  Koizumi A, Shiojima S, Omiya M, et al. Acute renal failure and  maneb  (manganouis
                                         ethylenebis[dithiocarbamate]) exposure. JAMA 1979;242:2583-5.
                                     6.  Israeli R, Sculsky M, andTiberin P. Acute intoxication due to exposure to maneb and zineb:
                                         A case with behavioral and central nervous system  changes. Scand J Work Environ Health
                                     7.  Peluso AM.Tardio M, Adamo F, et al. Multiple sensitization due to bis-dithiocarbamate and
                                         thiophthalimide pesticides. Contact Dermatitis 1991;25:327.
                                     8.  Vilaplana J and Romaguera C. Captan, a rare contact sensitizer in hairdressing. Contact Der-
                                         matitis 1993:29:107.
                                     9.  Royce S, Wald P, Sheppard  D, et al. Occupational asthma in a pesticides manufacturing
                                         worker. Chest 1993; 103:295-6.
                                     10. Krieger RI and Thongsinthusak T Captan metabolism in humans yields two biomarkers,
                                         tetrahydrophthalimide (THPI) and thiazolidine-2-thione-4-carboxylic acid (TTCA) in urine.
                                         Drug ChemToxicol 1993; 16:207-25.

11.  Agarwal SK.Tiwari SC, and Dash SC. Spectrum of poisoning requiring haemodialysis in a
    tertiary care hospital in India. Int JArtif Organs 1993;16:20-3.
12.  Lament DL and Duflou JALC. Copper sulfate: Not a harmless chemical. Am J Forensic Med
    Pathol 1988;9:226-7.
13.  Chugh KS, Singhal PC, and Sharma BK. Methemoglobinemia in acute copper sulfate poi-
    soning. Ann Intern Med 1975:82:226-9.
14.  Jantsch W, Kulig K, and Rumack BH. Massive copper sulfate ingestion resulting in hepato-
    toxicity. ClinToxicol 1984-85;22:585-8.
15.  POISINDEXฎ: Copper poisoning. Englewood, CO: Micromedex, 1998.
16.  Hantson P, Lievens M, and Mahieu P. Accidental ingestion of a zinc and copper sulfate
    preparation. ClinToxicol 1996;34:725-30.
17.  Bakir F, Rustam H.Tikritis S, et al. Clinical and epidemiological aspects of methylmercury
    poisoning. Postgrad Med J 1980;56:1-10.
18.  Grandjean  P,  Weihe P, and Nielsen JB. Methylmercury; Significance of intrauterine and
    postnatal exposures. Clin Chem 1994;40:1395-1400.
19.  Snyder RD. Congenital mercury poisoning. NewEngl]Med 1971;284:1014-5.
20.  ClarksonTW. Mercury— An element of mystery. New Engl J Med 1990;323:1137-8.
21.  Agency for Toxic Substances and Disease Registry. Mercury toxicity Am Fam Physician
22.  Agocs MM, Etzel RA, Parrish  RG, et al. Mercury exposure from interior latex paint. New
    Engl J Med  1990:323:1096-100.
23.  Colosio C.Tomasini M, Cairoli S, et al. Occupational triphenyltin acetate poisoning: A case
    report. Br JInd Med 1991;48:136-9.
24.  Barnhart S  and Rosenstock L. Cadmium chemical pneumonitis. Chest 1984;86:789-91.
25.  Ando Y, Shibata E.Tsuchiyama F, et al. Elevated urinary cadmium concentrations in a patient
    with acute  cadmium pneumonitis. Scand JWork Environ Health 1996;22:150-3.
26.  Hendrick DJ. Occupational and chronic obstructive pulmonary disease (COPD). Thorax
27.  Klaassen CD. Heavy metals and heavy metal antagonists. In: Gilman AG, RallTW, Niew AS,
    et al (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics,  3rd ed. New
    York: Pergamon Press, 1990, pp. 1605-6.
                                                                                                               FUNGICIDES •  155

                                    CHAPTER 16

•  Easily absorbed in lung, gut,

Signs and Symptoms:
•  Highly variable based on
•  Many are irritants
•  Carbon disulfide,
   chloroform, hydrogen
   cyanide, and naphthalene
   may have serious CNS
•  Methyl  bromide  and
   aluminum phosphide
   (phosphine gas)  cause
   pulmonary edema
•  Hydrogen cyanide causes
   severe hypoxia without
   cyanosis in early stages

•  Skin and eye
•  Oxygen and diuresis for
   pulmonary edema
•  Specific measures needed
   for various agents

•  Ipecac should not be used
   in cyanide poisoning
Fumigants have remarkable capacities for diffusion, a property essential to their
function. Some readily penetrate rubber and neoprene personal protective gear,
as well as human skin. They are rapidly absorbed across the pulmonary mem-
brane, gut, and skin. Special adsorbents are required in respirator canisters to
protect exposed workers from airborne fumigant gases. Even these may not
provide complete protection when air concentrations of fumigants are high.
    The packaging and formulation of fumigants are complex. Fumigants which
are  gases  at room temperature (methyl bromide, ethylene oxide, sulfur dioxide,
hydrogen cyanide, sulfuryl fluoride) are provided in compressed gas cylinders. Liq-
uids are marketed in cans or drums. Solids which sublime, such as naphthalene,
must be packaged so as to prevent significant contact with air before they are used.
    Mixtures of fumigants have  several advantages. Carbon tetrachloride re-
duces the explosiveness of carbon disulfide and acrylonitrile. Chloropicrin, having
a strong odor and irritant effect, is often added as a "warning agent" to other
liquid fumigants.
    Liquid halocarbons and carbon disulfide evaporate into the air while naph-
thalene sublimes. Paraformaldehyde  slowly  depolymerizes to formaldehyde.
Aluminum phosphide slowly reacts with water vapor in the air to liberate  phos-
phine, an extremely toxic gas. Metam sodium, also a fumigant, is covered under
thiocarbamates in Chapter 15, Fungicides.
               (in alphabetical order)

    Acrolein (acrylaldehyde) is an extremely irritating gas used as a fumigant
and an aquatic herbicide. The vapor causes lacrimation and upper respiratory
tract irritation, which may lead to laryngeal edema, bronchospasm, and delayed
pulmonary edema. The consequences of ingestion are essentially the same as
those that follow ingestion of formaldehyde. Contact with the skin may cause
    Acrylonitrile is biotransformed in the body to hydrogen cyanide.Toxic-
ity and mechanisms of poisoning are  essentially the same as for cyanide  (see
under hydrogen cyanide below), except that acrylonitrile is irritating to the
eyes and to the upper respiratory tract.
    Carbon disulfide vapor is only moderately irritating to upper respiratory
membranes, but it has an offensive "rotten cabbage" odor. Acute toxicity is due
   156 • FUMIGANTS

chiefly to effects on the central nervous system. Inhalation of high concentra-
tions for short periods has caused headache, dizziness, nausea, hallucinations,
delirium, progressive  paralysis, and death from respiratory failure. More pro-
longed exposure to lesser amounts has lead to blindness, deafness, paresthesia,
painful neuropathy, and  paralysis. Carbon disulfide is a potent skin irritant,
often causing severe burns. Long-term occupational exposures have been shown to
accelerate atherosclerosis, leading to ischemic myocardiopathy, polyneuropathy,
and gastrointestinal dysfunction.1 Toxic damage to the liver and kidneys may
result in severe functional deficits of these  organs. Reproductive failure has
been noted.
    Carbon tetrachloride  is less toxic than chloroform as a central nervous
system depressant, but is  much more severely hepatotoxic, particularly follow-
ing ingestion. Liver cell damage is apparently due to free radicals generated in
the process of initial dechlorination.2 Cardiac arrhythmias, progressing to
fibrillation, may follow  inhalation of high concentrations of carbon tetra-
chloride or ingestion of the liquid. Kidney injury also occurs sometimes with
minimal hepatic toxicity.The kidney injury may be manifested by acute tubular
necrosis  or by azotemia  and general renal failure. Even topical exposure has
resulted in acute renal toxicity.3
    Chloroform has an agreeable sweet odor and is only slightly irritating to
the respiratory tract.  It is well absorbed from the lungs and is also  absorbed
from the skin and  gastrointestinal tract. It is a powerful central nervous system
depressant (in fact, an anesthetic).4  Inhalation of toxic concentrations in air
leads to dizziness, loss  of sensation and motor power, and then unconsciousness.
Inhalation of large amounts causes cardiac arrhythmias, sometimes progressing
to ventricular fibrillation. Large absorbed doses damage the functional cells of
the liver and kidney. Ingestion is more likely to cause serious liver and kidney
injury than is inhalation  of the vapor.
    Chloropicrin is  severely irritating to the upper respiratory tract, eyes, and
skin. Inhalation of an irritant concentration sometimes leads to vomiting. In-
gestion could be expected to cause a corrosive gastroenteritis.
    Dibromochloropropane  is irritating  to skin, eyes, and the respiratory
tract. Eye damage has resulted from repeated  exposure to the vapors. When
absorbed, it causes headache, nausea, vomiting, ataxia, and slurred speech. Liver
and kidney damage  are prominent  features of acute poisoning.  Chronic
exposure to relatively low concentrations has led  to temporary or permanent
sterility of workers in a manufacturing plant, by causing diffuse necrosis of
seminiferous tubule  cells. Because  it  is  much less odiferous  than  ethylene
dibromide, exposure of workers to toxic concentrations of DBCP is more likely.
Its use  has been cancelled in the  U.S.
    Dichloropropene and dichloropropane are strongly irritating to the
skin, eyes, and respiratory tract. Bronchospasm may result from inhalation of
high concentrations. Liver, kidney, and cardiac toxicity are seen in animals, but
there are limited data  in humans. It appears that risk of such toxicity is relatively
low for humans except via ingestion of large quantities.
Commercial Products
  carbon tetrachloride*
    propylene dichloride
    Telone II Soil Fumigant
  ethylene dibromide*
  ethylene dichloride*
  methyl bromide
    Sobrom 98
  methylene chloride*


  hydrogen cyanide*
    hydrocyanic acid
    prussic acid
(Continued on the next page)
                                                                                               FUMIGANTS • 157

Commercial Products

    Magnacide B
    Magnacide H
  ethylene oxide

  phosphine (liberated from
  aluminum phosphide or
  magnesium phosphide)
    Ag toxin

  carbon disulfide*
  sulfur dioxide
  sulfuryl fluoride

* Discontinued in the U.S.
    Ethylene dibromide is a severe irritant to skin, eyes, and respiratory tract.
The liquid causes blistering and erosion of skin, and is corrosive to the eyes.
Once absorbed, it may cause  pulmonary edema and central nervous system
depression. Damage to testicular tissue has occurred in animals.5  Long-term
exposure may have some damaging effect on testicular tissue. Persons poisoned
by ingestion have suffered chemical gastroenteritis, liver necrosis, and renal tu-
bular damage. Death is usually due to respiratory or circulatory failure. A pow-
erful disagreeable odor is advantageous in warning occupationally  exposed
workers of the presence of this gas.
    Ethylene dichloride is moderately irritating to the eyes and respiratory
tract. Respiratory symptoms may have a delayed onset. It depresses the central
nervous system, induces cardiac arrhythmias, and damages the liver and kidney,
in much the same way as carbon tetrachloride. Symptoms and signs of poison-
ing include headache, nausea, vomiting, dizziness, diarrhea, hypotension, cy-
anosis, and unconsciousness.
    Ethylene oxide and propylene oxide are irritants to all tissues they
contact. Aqueous solutions of ethylene oxide cause blistering and erosion of the
affected skin. The area of skin may thereafter be  sensitized to the fumigant.
Inhalation of high concentrations is likely to cause pulmonary edema and car-
diac arrhythmias. Headache, nausea, vomiting, weakness, and a persistent cough
are common early manifestations of acute poisoning. Coughing of bloody, frothy
sputum is characteristic of pulmonary edema.
    Airborne formaldehyde  is irritating to the  eyes and to membranes of the
upper respiratory tract. In some individuals, it is a  potent sensitizer, causing aller-
gic  dermatitis. In addition, it has been associated with asthma-like symptoms,
though there  remains some controversy as to whether these represent true aller-
gic asthma caused by formaldehyde.6'7'8 High air concentrations may cause laryn-
geal edema, asthma, or tracheobronchitis, but apparently not pulmonary edema.
Aqueous solutions in contact with the skin cause hardening and roughness, due
to superficial coagulation of the keratin layer. Ingested formaldehyde attacks the
membrane lining of the stomach and intestine, causing necrosis and ulceration.
Absorbed formaldehyde is rapidly converted to formic acid.The latter is partly
responsible for the metabolic acidosis that is characteristic of formaldehyde poi-
soning. Circulatory collapse and renal failure may follow the devastating effects of
ingested formaldehyde on the gut, leading to death. Paraformaldehyde is a poly-
mer which slowly releases formaldehyde into the air. Toxicity is somewhat less
than that of formaldehyde, because of the slow evolution of gas.
    Hydrogen cyanide gas causes poisoning by inactivating cytochrome oxi-
dase, the final enzyme essential to  mammalian cellular respiration. The patient
will have signs of severe hypoxia, however, and in  some cases may not appear
cyanotic. This is due to the failure of hemoglobin reduction in the face of loss
of cellular respiration. This will result  in a pink or red color to the skin and
arteriolization of retinal veins. In addition to the suggestive physical findings,
   158 • FUMIGANTS

one may also find an unusually high pO2 on a venous blood gas.9 Cyanosis is a
late sign and indicates circulatory collapse.
    The  cells of the brain appear to be the most vulnerable to cyanide action.
Presenting signs are nonspecific and can be  found with many poisonings.
Unconsciousness and death may occur immediately following inhalation of a
high cyanide concentration, respiratory failure being the principal mechanism.
Metabolic acidosis is another common presenting sign. Lesser exposures cause
a constriction and numbness in the  throat, stiffness of the jaw, salivation, nausea,
vomiting, lightheadedness, and apprehension. Worsening of the poisoning
is manifest as violent tonic or clonic convulsions.  Fixed, dilated pupils,
bradycardia, and irregular gasping respiration (or apnea)  are typical of profound
poisoning. The heart often continues to beat after breathing has stopped.9'10
A bitter almond odor to the breath or vomitus may be a clue to poisoning, but
not all individuals are able to detect this odor.9
    Methyl bromide is colorless and nearly odorless, but is severely irritating
to the lower respiratory tract, sometimes inducing pulmonary edema, hemor-
rhage,  or a  confluent pneumonia. The onset of respiratory distress may be
delayed 4-12 hours after exposure. It is a central nervous system depressant, but
may also cause convulsions. Early  symptoms of acute  poisoning include
headache, dizziness, nausea, vomiting, tremor,  slurred speech, and ataxia.The
more severe cases of poisoning exhibit myoclonic and generalized tonic clonic
seizures, which are sometimes refractory to initial therapy. Residual neurologi-
cal deficits including myoclonic seizures, ataxia, muscle weakness,  tremors,
behavioral disturbances, and diminished reflexes may persist in more severely
poisoned patients.11'12 If liquid methyl bromide contacts the skin,  severe
burning,  itching, and blister formation occur. Skin necrosis may be deep and
    Methylene chloride is one of the less toxic halocarbons. It is absorbed by
inhalation and to a limited extent across the skin. Exposure to high concentra-
tions may cause central nervous  system depression,  manifested as fatigue,
weakness, and drowsiness. Some absorbed methylene chloride is degraded to
carbon monoxide in humans, yielding increased  blood concentrations of
carboxyhemoglobin. However, concentrations are rarely high enough to cause
symptoms of carbon monoxide poisoning. Ingestion has caused death from
gastrointestinal hemorrhage, severe liver damage, coma, shock, metabolic
acidosis, and renal injury. In laboratory animals, extraordinary dosage has caused
irritability, tremor, and narcosis, leading to death. When heated to that point of
decomposition, one of the  products is the highly toxic phosgene gas that has
caused a  significant acute pneumonitis.13
     Naphthalene is a solid white  hydrocarbon long used in ball, flake, or cake
form as a moth repellent. It sublimes slowly.The vapor has a sharp, pungent odor
that is irritating to the eyes  and  upper respiratory tract. Inhalation of high con-
centrations causes headache, dizziness, nausea, and vomiting. Intensive prolonged
inhalation exposure, or ingestion or dermal exposure (from contact with heavily
                                                                                            FUMIGANTS •  159

                                  treated fabric) may cause hemolysis, particularly in persons afflicted with glu-
                                  cose-6-phosphate dehydrogenase  deficiency.14 The inheritance of glucose-6-
                                  phosphate dehydrogenase (G-6-PD) deficiency is by a sex-linked gene with
                                  intermediate dominance. For this reason it is  most commonly expressed in
                                  heterozygous males. However, homozygous females, who are far less common,
                                  will have a similar expression. Heterozygous females have only a mild depres-
                                  sion of this  enzyme. This illness is most common in non-white African and
                                  African-American ethnic groups. It is also seen  in some Mediterranean ethnic
                                     It is actually the metabolites of naphthalene that are responsible for the hemoly-
                                  sis. 15 Secondary renal tubular damage may ensue from the naphthol and from the
                                  products of hemolysis. Convulsions and coma may occur, particularly in children.
                                  In infants, high levels of hemoglobin, methemoglobin, and bilirubin in the plasma
                                  may lead to encephalopathy. Kernicterus has been specifically described as a com-
                                  plication of exposure to naphthalene with severe hemolysis and resulting hyper-
                                  bilirubinemia. Some individuals exhibit dermal sensitivity to naphthalene.
                                     Paradichlorobenzene is solid at room temperature, and is now widely
                                  used as a  moth repellent, air freshener, and deodorizer in homes  and in public
                                  facilities.The vapor is only mildly irritating to the nose and eyes. Liver injury
                                  and tremor  may occur following ingestion of large  amounts. Although acci-
                                  dental ingestions, especially by children, have been fairly common, symptom-
                                  atic human poisonings have been rare. Other stereoisomers of dichlorobenzene
                                  are more toxic than the para-isomer.
                                     Phosphine  gas is extremely irritating to the  respiratory tract. It also pro-
                                  duces  severe  systemic toxicity.  It is used as a fumigant by placing  solid aluminum
                                  phosphide (phostoxin)  near produce or in other  storage spaces.  Through hy-
                                  drolysis, phosphine gas is slowly released. Most severe acute exposures have in-
                                  volved ingestion of the solid aluminum phosphide, which is rapidly converted to
                                  phosphine by acid hydrolysis in the stomach. Poisoning due to ingestion carries a
                                  high mortality rate (50 to 90%).16'17 Mechanisms of toxicity are not well under-
                                  stood. Extracellular magnesium levels have been found to be slightly elevated,
                                  suggesting a  depletion of intracellular magnesium from myocardial damage.18
                                     Poisonings had become  quite frequent during  the  late 1980s and early
                                  1990s in some parts of India.16'17 The principal manifestations of poisoning are
                                  fatigue, nausea, headache, dizziness, thirst, cough, shortness of breath, tachycar-
                                  dia, chest tightness, paresthesia, and jaundice. Cardiogenic shock is present in
                                  more  severe cases. Pulmonary edema is a common cause of  death. In other
                                  fatalities, ventricular  arrythmias, conduction disturbances, and asystole devel-
                                  oped.16'19 Odor is said to resemble that of decaying fish.
                                     Sulfur dioxide  is a highly irritant gas, so disagreeable that persons inhal-
                                  ing it  are  usually prompted to seek uncontaminated air as soon  as possible.
                                  However, laryngospasm and pulmonary edema have occurred, occasionally lead-
                                  ing to severe respiratory distress and death. It is sometimes a cause of reactive
                                  airways disease in occupationally exposed persons.

    Sulfuryl fluoride  has been used extensively for structural fumigation.
Although use experience has  generally been good, some fatalities have oc-
curred when fumigated  buildings have been prematurely reentered by unpro-
tected  individuals.20 Since this material is heavier than air, fatal hypoxia may
follow early reentry. Manifestations of poisoning have been nose, eye, and throat
irritation, weakness, nausea, vomiting, dyspnea, cough, restlessness, muscle twitch-
ing, and seizures. Renal  injury  may induce proteinuria and azotemia.
Confirmation of Poisoning

    There are no  practical tests for absorbed alkyl  oxides, aldehydes,  or
phosphine that would be helpful in diagnosis of poisoning.
    Carbon  disulfide can be measured in urine by gas chromatography, but
the test is not generally available.
    Cyanide  ion from cyanide itself or acrylonitrile can be measured  in
whole blood and urine by an ion-specific electrode or by colorimetry. Symp-
toms of toxicity may appear at blood levels above 0.10 mg per liter.10 Urine
cyanide is usually less than 0.30 mg per liter in nonsmokers, but as much as 0.80
mg per liter in smokers. Thiocyanate, the  metabolite of cyanide, can also  be
measured in blood and urine. It is elevated at blood levels exceeding 12 mg per
liter.10 Urine thiocyanate is usually less than 4  mg per liter in nonsmokers, but
may be as high as 17 mg per liter in smokers.
    Methyl bromide yields inorganic bromide in the body. Methyl bromide
itself has a short half-life and is usually not detectable after 24 hours.The bromide
anion is slowly excreted in the urine (half-life about 10 days), and is the preferred
method of serum measurement.11 The serum  from persons having no excep-
tional exposure to bromide usually contains less than 1 mg bromide ion per 100
mL.The possible contributions of medicinal bromides to elevated blood content
and urinary excretion must be considered, but if methyl bromide is the exclusive
source, serum bromide exceeding 6 mg per 100 mL probably means some ab-
sorption, and 15 mg per 100 mL is consistent with symptoms of acute poisoning.
Inorganic bromide is considerably less toxic than methyl bromide; serum  con-
centrations in excess of 150 mg per 100 mL occur commonly in persons taking
inorganic bromide medications. In some European countries, blood  bromide
concentrations are monitored routinely in workers exposed to methyl bromide.
Blood levels over 3 mg per 100 mL are considered a warning that personal pro-
tective measures must be improved. A bromide concentration over 5 mg per 100
mL requires that the worker be removed from the fumigant-contaminated envi-
ronment until blood concentrations decline to  less than 3 mg per 100 mL.
    Methylene chloride is converted to carbon monoxide in the body, gener-
ating carboxyhemoglobinemia, which can be measured by clinical laboratories.
    Naphthalene is converted mainly to alpha naphthol in the body and promptly
excreted in conjugated form in the urine. Alpha naphthol can be measured by gas
                                                                                            FUMIGANTS • 161

                                 chromatography. Many halocarbons can be measured in blood by gas chromato-
                                 graphic methods. Some can be measured in the expired air as well.
                                     Paradichlorobenzene is metabolized mainly to 2,5-dichlorophenol, which
                                 is conjugated and excreted in the urine. This product can be measured chro-
                                     A serum fluoride concentration of 0.5 mg per liter was measured in one
                                 fatality from sulfuryl  fluoride fumigation. Serum fluoride  in persons not
                                 exceptionally exposed rarely exceeds 0.1 mg per liter.
                                      Large industrial concerns sometimes monitor human absorption of
                                 halocarbons by analysis of expired air. Similar technology is available in some
                                 departments of anesthesiology These analyses are rarely needed to identify the
                                 offending toxicant, because this is known from the exposure history. In managing
                                 difficult cases of poisoning, however, it may be helpful to monitor breath concen-
                                 trations of toxic gas to evaluate disposition of the fumigant. Testing of the urine
                                 for  protein and red cells is needed to detect renal injury. Free hemoglobin in
                                 urine most likely reflects hemolysis, as from naphthalene. Elevations of alkaline
                                 phosphatase, lactate dehydrogenase (LDH), serum GGT, ALT, AST, and certain
                                 other enzymes are sensitive indices of insult to liver cells. More severe damage
                                 increases plasma concentrations  of bilirubin. The chest x-ray may be used to
                                 confirm the occurrence of pulmonary edema. Electromyography may be useful
                                 in evaluating peripheral nerve injury. Sperm counts may be appropriate for workers
                                 exposed to dibromochloropropane and ethylene dibromide.
                                     Some occupational health  agencies now urge periodic neurologic and
                                 neuropsychologic testing of workers heavily exposed to fumigants and solvents
                                 to detect injury to the nervous system as early as possible.This would be  par-
                                 ticularly desirable in  the  case of exposures to such agents as methyl bromide
                                 and carbon disulfide which have well-documented chronic neurotoxic effects.
                                 1. Skin decontamination. Flush contaminating fumigants from the skin and
                                 eyes with copious amounts of water or saline for at least  15  minutes. Some
                                 fumigants are corrosive to  the cornea and may cause blindness. Specialized
                                 medical treatment should be obtained promptly following decontamination.
                                 Skin contamination may cause blistering and deep chemical burns. Absorption
                                 of some fumigants across the skin may be sufficient to cause systemic poisoning
                                 in the absence of fumigant inhalation. For all these reasons, decontamination of
                                 eyes and skin must be immediate and thorough. See  Chapter 2.

                                 2. Physical placement. Remove victims of fumigant inhalation to fresh air
                                 immediately. Even though initial symptoms and signs are mild, keep the victim
                                 quiet, in a semi-reclining position. Minimum physical activity limits the likeli-
                                 hood of pulmonary edema.

3. Respiration. If victim is not breathing, clear the airway of secretions and
resuscitate with positive pressure oxygen apparatus. If this is not available, use
chest compression to sustain respiration. If victim is pulseless, employ cardiac

4. Pulmonary edema. If pulmonary edema is evident, there are several mea-
sures available to sustain life. Medical judgment must be relied upon, however,
in the management of each  case. The following procedures  are  generally
    •   Put the victim in a sitting  position with a backrest.

    •   Use  intermittent and/or continuous  positive pressure  oxygen to
        relieve hypoxemia. (Do not give oxygen at greater concentrations
        or longer periods than necessary, because it may exaggerate the fu-
        migant injury to lung tissue. Monitor arterial  pO2.)
    •   Slowly administer furosemide, 40 mg, intravenously (0.5-1 mg/kg
        in children up to 20 mg), to reduce venous load by inducing diure-
        sis. Consult package insert for additional directions and  warnings.

Some patients may benefit from careful administration  of anxiolytic  drugs.
Whenever possible, such patients should be managed  by  intensivists in an in-
tensive care  center. Limit victim's physical activity for at least 4  weeks. Severe
physical weakness usually indicates persistent pulmonary injury.  Serial pulmo-
nary function testing may be useful in assessing recovery.

5. Shock. Combat shock by placing victim in the Trendelenburg position and
administering plasma, whole blood, and/or electrolyte and  glucose solutions
intravenously, with great care, to avoid pulmonary edema. Central venous pres-
sure should be monitored continuously. Vasopressor amines must be given with
great caution, because of the irritability of the  myocardium.

6. Control  convulsions. Seizures are most likely to occur in  poisonings by
methyl bromide, hydrogen cyanide, acrylonitrile, phosphine, and carbon disul-
fide. See Chapter 2 for seizure  management. In some cases of methyl bromide,
seizures have been refractory to benzodiazepines and  diphenylhydantoin, and
the authors resorted to anesthesia using thiopental.11

7. Gastrointestinal  decontamination. If a fumigant liquid or  solid has been
ingested less than an hour prior to treatment,  consider gastric emptying, fol-
lowed by activated charcoal, as suggested in Chapter 2.

8. Fluid balance should be monitored, and urine sediment should be checked
regularly for indications of tubular injury. Measure serum alkaline phosphatase,
LDH, ALT, AST, and bilirubin to assess liver injury.
                                                                                            FUMIGANTS •  163

                                 9. Extracorporeal hemodialysis may be needed to regulate extracellular
                                 fluid composition if renal failure supervenes. It is probably not very effective in
                                 removing lipophilic fumigant compounds from blood, but it is, of course, effec-
                                 tive in controlling extracellular fluid composition if renal failure occurs.

                                 10. Specific fumigants. Certain specific measures are recommended in poi-
                                 sonings by particular fumigants (carbon disulfide, carbon tetrachloride, naph-
                                 thalene, phosphine gas, and hydrogen cyanide and acrylonitrile):

                                     •   Carbon Disulfide: Mild poisonings by carbon disulfide inhalation
                                         may be managed best by no more than careful observation, even
                                         though sensory hallucinations, delirium, and behavioral aberrations
                                         can be alarming. Severe poisonings may require specific measures. If
                                         manic behavior threatens the safety of the victim, diazepam (5-10
                                         mg in adults, 0.2-0.4 mg/kg in children), administered slowly, intra-
                                         venously, may be helpful as a tranquilizer. Give as much as is neces-
                                         sary to achieve sedation. Do not give catecholamine-releasing agents
                                         such as reserpine and amphetamines.

                                     •   Carbon Tetrachloride: For carbon tetrachloride poisoning, sev-
                                         eral treatment measures have been suggested to limit the severity of
                                         hepatic necrosis. Hyperbaric oxygen has been used with some suc-
                                         cess.2 Oral administration of N-acetyl cysteine (MucomystR) may
                                         be worthwhile as a means of reducing free radical injury.21 Dilute
                                         the proprietary 20% product 1:4 in a carbonated beverage, and give
                                         about 140 mg/kg body weight of the diluted solution as a loading
                                         dose.Then give 70 mg/kg every 4 hours after the loading dose for a
                                         total of 17 doses. (This dosage schedule is used for acetaminophen
                                         poisonings.) Administration via duodenal tube may be necessary in
                                         a few patients who cannot tolerate Mucomyst.22 Intravenous ad-
                                         ministration of N-acetyl cysteine may be used; more information is
                                         available through poison control centers.

                                     •   Naphthalene: Naphthalene toxicosis  caused  by vapor inhalation
                                         can usually be  managed simply by removing the individual to fresh
                                         air. Skin contamination  should  be removed promptly  by  washing
                                         with soap and water. Eye contamination should be removed by flush-
                                         ing with copious amounts of clean water. Eye  irritation may be
                                         severe, and if it persists, should receive ophthalmalogic attention.
                                            Examine the plasma for evidence of hemolysis: a reddish-brown
                                         tinge, especially in the blood smear for "ghosts" and Heinz bodies. If
                                         present, monitor red blood cell count and hematocrit  for anemia,
                                         urine for protein and cells. Measure direct-and  indirect-reacting bi-

lirubin in the plasma. Monitor fluid balance and blood electrolytes.
If possible, monitor urinary excretion of naphthol to assess severity
of poisoning and clinical progress.
   If hemolysis is clinically significant, administer intravenous fluids
to accelerate urinary excretion of the naphthol metabolite and pro-
tect the kidney from products of hemolysis. Use Ringer's lactate or
sodium bicarbonate to keep urine  pH above 7.5. Consider the use
of mannitol or furosemide to promote diuresis. If urine flow de-
clines, intravenous infusions must be stopped to prevent fluid over-
load and hemodialysis should be considered.15 If anemia is severe,
blood transfusions may be needed.

Phosphine Gas: Recent experience  in India suggests that therapy
with magnesium sulfate may  decrease the likelihood of a fatal out-
come.16'19'23 The  mechanism is unclear, but may possibly be due to
the membrane stabilization properties of magnesium in protecting
the heart from fatal arrythmias. In one series of 90 patients, magne-
sium sulfate  was found to decrease the  mortality from 90% to 52%.16
Two controlled  studies have  been done, one  of which showed a
reduction in mortality from 52% to 22%.23 The other study found
no effect on mortality.24 The dosage for magnesium sulfate is: 3
grams during the first 3 hours as a continous infusion, followed by 6
grams per 24 hours for the next 3 to 5 days.16

Hydrogen  Cyanide and Acrylonitrile: Poisonings by hydrogen
cyanide and acrylonitrile gases or liquids are treated essentially the
same as poisoning by cyanide salts. Because cyanide is so promptly
absorbed following ingestion, treatment should commence  with
prompt administration of oxygen and antidotes. Gastrointestinal
decontamination should be considered if the patient presents within
a short interval after ingestion, and only after the above life-saving
treatment has commenced. Ipecac  should be  avoided due to the
potential for rapid onset of loss of consciousness.

The three antidotes — amyl nitrite, sodium nitrite, and sodium thio-
sulfate — are available as a kit called the Lilly Cyanide Antidote Kit,
available from Eli Lilly and Company,  Indianapolis, IN.The dosages
vary between adults and children and  are outlined below.
                                                                                     FUMIGANTS • 165

                                     Dosage of Cyanide Antidotes

                                      • Administer oxygen continuously. Hyperbaric oxygen has been evalu-
                                        ated as effective in this condition.25 If respiration fails, maintain pul-
                                        monary ventilation mechanically.
                                      • Administer amyl nitrite ampules by inhalation for 15-30 seconds
                                        of every minute, while a fresh solution of 3% sodium nitrite is being
                                        prepared. This solution is ready prepared in commercial cyanide
                                        antidote kits.
                                      • As soon as solution is available, inject intravenously 10 mL of 3%
                                        sodium nitrite solution over a 5-minute interval, keeping the needle
                                        in place.

                                     Caution: Monitor pulse and blood pressure during administration of amyl
                                     nitrite and sodium nitrite. If systolic blood pressure falls below 80 mm Hg,
                                     slow or stop nitrite administration until blood pressure recovers.
                                      • Follow sodium nitrite injection with an infusion of 50 mL of 25%
                                        aqueous solution of sodium thiosulfate administered over a 10-
                                        minute period. Initial adult dose should not exceed 12.5 g.
                                      • If symptoms persist or recur, treatment by sodium nitrite and so-
                                        dium thiosulfate should be repeated at half the dosages listed above.
                                      • Measure hemoglobin and methemoglobin in blood. If more than
                                        50% of total hemoglobin has been converted  to methemoglobin,
                                        blood transfusion or exchange transfusion should be considered, be-
                                        cause conversion back to normal hemoglobin proceeds slowly.

                                      • Give amyl nitrite,  oxygen, and mechanical respiratory support as
                                        recommended for  adults. The  following dosages of antidotes have
                                        been recommended for children.26
                                      • Children over 25 kg body  weight should receive adult dosages of
                                        sodium nitrite and sodium  thiosulfate.
                                      • Children less than 25 kg body weight should first have two 3-4 mL
                                        samples of blood drawn and then, through the same needle, receive
                                        0.15-0.33 mL/kg up to 10 mL of the 3% solution of sodium nitrite
                                        injected over a 5-minute interval. Following sodium nitrite, admin-
                                        ister an infusion of 1.65 mL/kg of 25% sodium thiosulfate at a rate
                                        of 3-5  mL per minute.
                                                                                           ... continued

       At this point, determine the hemoglobin content of the  pretreat-
       ment blood sample. If symptoms and signs of poisoning persist or
       return, give supplemental infusions of sodium nitrite and sodium
       thiosulfate based on hemoglobin level, as presented in the table.These
       recommended  quantities are calculated to avoid life-threatening
       methemoglobinemia  in anemic children. They are aimed at con-
       verting approximately 40% of circulating hemoglobin to methemo-
       globin. If possible, monitor blood methemoglobin concentrations as
       treatment proceeds.

Volume of 3%
Sodium Nitrite

25% Sodium
Although various cobalt salts, chelates, and organic combinations have shown
some promise as antidotes to cyanide, they are not generally available in the
United States. None has been shown to surpass the nitrite-thiosulfate regimen
in effectiveness.
1.  Wilcosky TC and Tyroler HA. Mortality from heart disease among workers exposed to
   solvents. / Occup Med 1983;25:879-85.
2.  Truss C and Killenberg R Treatment of carbon tetrachloride poisoning with hyperbaric
   oxygen. Gastroenterology 1982;82:767-9.
   Perez AJ, Courel M, Sobrado J, et al. Acute renal failure after topical application of carbon
   tetrachloride. Lancet 1987;l:515-6.
4.  Dykes MH. Halogenated hydrocarbon ingestion. Intern Anesthesiol Clin 1970;8:357-68.
   Amir D. The spermicidal effect of ethylene dibromide in bulls and rams. Mol Reprod Dev
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                                        6.  Smedley J. Is formaldehyde an important cause of allergic respiratory disease?  Clin Exp
                                            Allergy 1996;26:247-9.
                                        7.  Krzyzanowski M, Quackenboss JJ, and Lebowitz MD. Chronic respiratory effects of indoor
                                            formaldehyde exposure. Environ Res 1990;52:117-25.
                                        8.  Harving H, Korsgaard J, Pedersen OF, et al. Pulmonary function and bronchial reactivity in
                                            asthmatics during low-level formaldehyde exposure. Lung 1990;168:15-21.
                                        9.  Johnson RP and Mellors JW Arteriolization of venous blood gases: A clue to the diagnosis of
                                            cyanide poisoning. JEmerg Med 1988;6:401-4.
                                        10. Yen D.TsaiJ.Wang LM.et al.The clinical experience of acute cyanide poisoning. Am J Emerg
                                            Med 1995:13:524-8.
                                        11. Hustinx WNM, van de Laar  RTH, van Huffelen A, et al. Systemic effects of inhalational
                                            methyl bromide poisoning: A study of nine cases occupationally exposed due to inadvertent
                                            spread during fumigation. BrJIndMed 1993;50:155-9.
                                        12. Deschamps FJ andTurpin JC. Methyl bromide intoxication during grain store fumigation.
                                            OccupatMed 1996;48:89-90.
                                        13. Snyder  RW, Mishel HS, and  Christensen GC. Pulmonary toxicity following exposure to
                                            methylene chloride and its combustion product, phosgene. Chest 1992;101:860-1.
                                        14. Shannon K and Buchanan GR. Severe hemolytic anemia in black children with glucose-6-
                                            phosphate dehydrogenase deficiency. Pediatrics 1982;70:364-9.
                                        15. Gosselin RE, Smith HC, and Hodge HC  (eds). Naphthalene. In: Clinical Toxicology of
                                            Commercial Products, 5th ed. Baltimore:Williams &Wilkins, 1984, pp. III-307-ll.
                                        16. Katira R, Elhence GP, Mehrotra ML, et al. A study of aluminum phosphide poisoning with
                                            special reference to electrocardiographic changes. JAssoc Physicians India 1990;38:471-3.
                                        17. Singh S, Singh D, Wig N, et al. Aluminum phosphide ingestion: A clinico-pathologic study.
                                            ClinToxicol 1996;34:703-6.
                                        18. Singh RB, Singh  RG, and Singh U. Hypermagnesemia following aluminum phosphide
                                            poisoning. Int J Clin PharmacolTherToxicol 1991;29:82-5.
                                        19. Gupta S and Ahlawat SK.Aluminum phosphide poisoning:A review. ClinToxicol 1995;33:19-24.
                                        20. Scheuerman EH. Suicide by exposure to sulfuryl fluoride. J Forensic Sci 1986;31:1154-8.
                                        21. Ruprah  M, MantTGK, and Flanagan RJ. Acute carbon tetrachloride poisoning in 19 pa-
                                            tients: Implications for diagnosis and treatment. Lancet 1985;l:1027-9.
                                        22. Anker AL and  Smilkenstein MJ. Acetaminophen: Concepts and controversies. Emerg Med
                                            Clin North Am  1994;12:335-49.
                                        23. Chugh SN, Kumar P Sharma A, et al. Magnesium status and parenteral magnesium sulphate
                                            therapy in acute aluminum phosphide intoxication. Magnesium Res 1994;7:289-94.
                                        24. Siwach  SB, Singh P, Ahlawat  S, et al. Serum and tissue magnesium content  in patients of
                                            aluminum phosphide poisoning and critical evaluation of high dose magnesium sulphate
                                            therapy in reducing mortality. /Assoc Physicians India 1994;42:107-10.
                                        25. Myers RAM  and Schnitzer BM. Hyperbaric oxygen use: Update  1984.  Postgrad Med
                                        26. Mofenson HC, Greensher J, Horowitz R, and Berlin CM.Treatment of cyanide poisoning.
                                            Pediatrics 1970:46:793-6.

A wide variety of materials are used as rodenticides.They pose particular risks for
accidental poisonings for several reasons. First, as agents specifically designed to
kill mammals, often their toxicity is  very similar for the target rodents and for
humans. (Warfarin and other anticoagulant rodenticides were initially developed
to  overcome this problem by creating compounds that were highly toxic to ro-
dents, particularly after repeated exposures, but much less toxic to humans.) Sec-
ond, since rodents usually share environments with humans and other mammals,
the risk of accidental exposure is an integral part of the placement of baits for the
rodents. Finally, as rodents have developed resistance to existing rodenticides, there
is a continuous need to develop new and potentially more toxic rodenticides. As
rodents have become resistant to warfarin baits, for example, the development of
"superwarfarins" has increased the risk to humans.1-2 It is important to be familiar
with use patterns and development of more toxic compounds and to make every
effort to identify the actual agent used in order to institute the most appropriate
management for these poisonings.


    Warfarin and related compounds (coumarins and indandiones) are the most
commonly ingested rodenticides in the United States, with 13,345 exposures
reported in 1996.3 Gastrointestinal absorption of these toxicants is efficient.
Warfarin can be absorbed across  the skin, but this has occurred only under
extraordinary circumstances.
    Coumarins and indandiones  depress the hepatic synthesis of vitamin K
dependent blood-clotting factors  (II (prothrombin),VII, IX, and X).The anti-
prothrombin effect is best known, and is the basis for detection and assessment
of clinical poisoning.The agents also increase permeability of capillaries through-
out the body, predisposing the animal to widespread internal hemorrhage.This
generally occurs in the rodent after several days of warfarin ingestion due to the
long half-lives of the vitamin K dependent clotting factors,1-2 although lethal
hemorrhage may follow smaller doses of the modern, more toxic compounds.1
    The lengthened prothrombin time (PT) from a toxic dose of coumarins or
indandiones may be evident within 24 hours, but usually reaches a maximum

•  Newer "superwarfarins"
   are widely available and
   toxic at much lower doses
   than conventional warfarin

Signs and Symptoms:
•  Variable depending on
•  Warfarin compounds cause
•  Pulmonary edema results
   from phosphine gas (from
   zinc phosphide)
•  Cardiovascular, Gl, and CNS
   effects predominate with
•  Seizures are primary
   manifestation of strychnine
   and fluoroacetamide

•  Specific to agent
•  Vitamin K1 (phytonadione)
   for warfarin-related
•  Control seizures
•  Proceed with
   concurrently with life-saving

•  Neither Vitamins K3 nor K4
   may be used as a substitute
   for Vitamin K1
•  Chelating agents are not
   effective in thallium
                                                                                           RODENTICIDES •  169

Commercial Products
  Ratak Plus

*Discontinued in the U.S.
in 36-72 hours.li4'5 Lengthened PT occurs in response to doses much lower
than that necessary to cause hemorrhage. There is concern that the more toxic
modern compounds, such as brodifacoum and difenacoum, may cause serious
poisoning of nontarget mammals, including  humans, at much lower dosage.
Brodifacoum, one of the superwarfarins, is much more toxic, with a dose as low
as 1 mg in an adult or 0.014 mg/kg in a child sufficient to produce toxicity.1
    Symptomatic poisoning, with prolonged symptoms due to the long half-
lives of superwarfarins, has been reported even with single exposures; however,
these are usually intentional and  are large single dosages.2 Because of their
toxicity in relation to warfarin, patients may require higher dosages of vitamin
K and will require longer monitoring of their PT. One patient required vita-
min K for several months following discharge.6 Another patient was released
from  the hospital with  significant clinical improvement and only slightly el-
evated coagulation studies after brodifacoum ingestion.Two and a half weeks
later, he presented in a comatose state and was found to have massive intracra-
nial hemorrhage.7
    Clinical effects of these agents usually begin several days after ingestion, due
to the long half-life of the factors. Primary manifestations include  nosebleeds,
bleeding gums, hematuria, melena, and extensive ecchymoses.1'2'6'7-8 Patients may
also have symptoms of anemia, including fatigue and dyspnea on exertion.8 If the
poisoning is severe, the patient may progress to shock and death.
    Unlike the coumarin compounds, some indandiones cause symptoms and
signs  of neurologic and cardiopulmonary injury  in laboratory rats leading to
death before hemorrhage occurs. These actions may account for  the greater
toxicity of indandiones in  rodents. Neither neurologic nor cardiopulmonary
manifestations have been reported in human poisonings.

Confirmation of Poisoning

    Coumarin or indandione poisoning results in an increase in prothrombin
time, the result of reduced plasma prothrombin concentration. This is a reliable
test for absorption of physiologically significant doses. Detectable reduction in
prothrombin occurs within 24-48 hours of ingestion and persists for 1 -3 weeks.li4'5
The manufacturers can often measure blood levels of the more toxic coumarins.8

1. Determine quantity ingested. If it is certain that the patient ingested no
more than a mouthful or two of warfarin- or indandione-treated bait, or a
single swallow or less of bait treated with the more toxic brodifacoum or
bromadiolone compounds, medical treatment is probably unnecessary.

2. Vitamin Kr A patient presenting within 24 hours after ingestion will likely
have a normal PT. However, in a study of 110 children who were poisoned by
superwarfarins, primarily brodifacoum, a child's PT was significantly more likely
to be prolonged at 48 hours after having a normal PT at 24 hours.5Therefore, for
suicidal ingestions with large amounts taken, if there is uncertainty about the
amount of bait ingested or the general health of the patient, phytonadione (vita-
min Kj) given orally protects against the anticoagulant  effect of these rodenti-
cides, with essentially no risk to the patient. In accidental ingestions with healthy
children involving only a taste or single swallow, no medical treatment is re-
quired, but children should be observed for bleeding and bruising. If a larger
amount may have been ingested, PT should  be monitored at 24 and 48 hours,
with phytonadione therapy initiated for elevated PT or clinical signs of bleeding.
    Caution: Phytonadione, specifically, is required. Neither vitamin K3 (me-
nadione, HykinoneR) nor vitamin K4 (menadiol)  is an antidote for these anti-
    Dosage of Phytonadione (oral):
     •  Adults and children over 12years: 15-25 mg.
     •  Children under 12years: 5-10 mg.

    Alternatively, a colloidal preparation of phytonadione, AquamephytonR,
    may be given intramuscularly. For adults and children over 12 years,
    give 5-10 mg; for children under 12, give 1-5 mg.
       Ensure that patients (especially children) are carefully observed for
    at least 4-5 days after ingestion.The indandiones and some of the more
    recently introduced coumarins  may have other toxic effects.
3. Gastrointestinal decontamination. If large  amounts  of anticoagulant
have been ingested  within several hours prior to treatment, consider gastric
decontamination procedures as outlined Chapter 2.

4. Determine  prothrombin time. If anticoagulant has been ingested any
time in the preceding 15 days, determination of the PT provides a basis for
judging the severity of poisoning. Patients who ingest large amounts, particu-
larly of the superwarfarin compounds, will likely have a very prolonged period
of decreased prothrombin activity. Patients may need to be treated for as long as
3 or 4 months.6-7
    If the prothrombin time is significantly lengthened, give AquamephytonR
intramuscularly.  See  next page for dosage.
                                                                                           RODENTICIDES • 171

                                     Dosage of AquamephytonR (intramuscular):
                                     • Adults and children over 12years: 5-10 mg.
                                     • Children under 12years: 1-5 mg.

                                     Decide dose within these ranges according to the degree of prothrom-
                                     bin time lengthening and, in children, the age and weight of the child.
                                     Substantially higher doses of phytonadione (50 to 125 mg) have been
                                     required in some poisonings with brodifacoum when bleeding and PT
                                     elevation persisted despite therapy.6'7'9
                                        Repeat prothrombin time in 24 hours. If it has not decreased from
                                     the original value, repeat AquamephytonR dosage.
                                 5. Bleeding. If victim is bleeding as a result of anticoagulant poisoning, ad-
                                 minister AquamephytonR intravenously: up to 10 mg in adults and children
                                 over 12 years, and up to 5 mg in children under 12 years. Initial dosage should
                                 be decided chiefly on the basis of the severity of bleeding. Subsequent dosages
                                 may need  to be  adjusted based on response, especially in the case of the
                                 superwarfarins.6'7'9 Repeat intravenous AquamephytonR in 24 hours if bleeding
                                 continues. Inject at rates not exceeding 5% of the total dose per minute. Intra-
                                 venous infusion of the AquamephytonR diluted in saline or glucose solution is
                                 recommended. Bleeding is usually controlled in 3-6 hours.
                                     Caution: Adverse reactions, some fatal, have occurred  from intravenous
                                 phytonadione injections, even when recommended dosage limits and injection
                                 rates were observed. For this reason, the intravenous route should be used only
                                 in cases of severe poisoning. Flushing, dizziness, hypotension, dyspnea, and cy-
                                 anosis have characterized adverse reactions.
                                     Antidotal therapy in cases of severe bleeding should be supplemented with
                                 transfusion of fresh blood or plasma. Use of fresh blood or plasma represents the
                                 most rapidly effective method of stopping hemorrhage due to these anticoagu-
                                 lants, but the effect may not endure.Therefore, the transfusions should be given
                                 along with phytonadione therapy.
                                     Determine  PT and hemoglobin concentrations every 6-12 hours to assess
                                 effectiveness of antihemorrhagic measures. When normal blood coagulation is
                                 restored, it may  be advisable to drain large hematomata.
                                     Ferrous sulfate therapy may be appropriate in the recuperative  period to
                                 rebuild lost erythrocyte mass.

                                                                                     Commercial Products

    Thallium sulfate  is well absorbed from the gut and across the skin. It
exhibits a very large volume of distribution (tissue uptake) and is distributed
chiefly to the kidney and liver, both of which participate in thallium excretion.
Most blood-borne thallium is in the red cells. Elimination half-life from blood
in the adult human is about 1.9 days. Most authors report the LD5Q in humans
to be between 10 and 15 mg/kg.10
    Unlike other inorganic rodenticides like yellow phosphorus and zinc phos-
phide, thallium poisoning tends to have a more  insidious onset with a wide
variety of toxic manifestations. Alopecia is a fairly consistent feature of thallium
poisoning that is often helpful diagnostically; however, it occurs two weeks or
more after poisoning and is not helpful early in the presentation.10-11 In addi-
tion to hair loss, the gastrointestinal system, central nervous system, cardiovas-
cular system, renal system, and skin are prominently affected by toxic intakes.
    Early symptoms include abdominal pain, nausea, vomiting, bloody diar-
rhea, stomatitis, and salivation. Ileus may appear later on. Elevated liver enzymes
may occur, indicating tissue damage. Other patients experience signs of central
nervous system toxicity including headache, lethargy, muscle weakness,
paresthesias, tremor, ptosis, and ataxia.These usually occur several days to more
than a week after  exposure.10'12 Extremely painful paraesthesias, either  in the
presence or absence of gastrointestinal signs, may be the primary presenting
complaint.11'13 Myoclonic movements,  convulsions, delirium, and coma  reflect
more severe neurologic involvement. Fever is a bad prognostic indication of
brain damage.
    Cardiovascular effects include early hypotension, due at least in part to a
toxic myocardiopathy.Ventricular arrythmias may occur. Hypertension occurs
later and is probably a result of vasoconstriction.The urine may show protein
and red cells. Patients may also develop alveolar edema and hyaline membrane
formation in the lungs,  consistent with a diagnosis of Acute Respiratory Dis-
tress Syndrome.14 Death from thallium  poisoning may be caused by respiratory
paralysis or cardiovascular collapse. Absorption of nonlethal doses of thallium
has caused protracted painful neuropathies and paresis, optic  nerve atrophy,
persistent ataxia, dementia, seizures, and coma.11
    Yellow phosphorus (also known as white phosphorus) is a corrosive agent
and  damages all tissues  it comes in contact with, including skin and the gut
lining. Initial symptoms  usually reflect mucosal injury and occur a few minutes
to 24 hours following ingestion. The first symptoms include severe vomiting
and burning pain in the  throat, chest, and abdomen.The emesis may be bloody
(either red, brown, or black)15 and on occasion may have a garlic smell.16'17 In
some cases, central nervous system signs such as lethargy, restlessness, and irrita-
thallium sulfate
yellow phosphorus
zinc phosphide

Yellow phosphorus is not sold
in the United States. Zinc
phosphide is still registered in
the United States, and can be
found in U.S. retail stores.
Thallium sulfate is no longer
registered for pesticidal use,
but is used by government
agencies only.
                                                                                            RODENTICIDES •  173

                                 bility are the earliest symptoms, followed by symptoms of gastrointestinal in-
                                 jury. Shock and cardiopulmonary arrest leading to death may occur early in
                                 severe ingestions.17
                                     If the patient survives, a relatively symptom-free period of a few hours or
                                 days may occur, although this is not always the case.15The third stage of toxicity
                                 then ensues with systemic signs indicating severe injury to the liver, myocar-
                                 dium, and brain. This is due to phosphine gas (PH3) formed in and absorbed
                                 from the gut. Nausea and vomiting recur. Hemorrhage occurs at various sites
                                 reflecting a depression of clotting factor synthesis in the damaged liver. Also,
                                 thrombocytopenia may contribute. Hepatomegaly and jaundice appear. Hypo-
                                 volemic shock and toxic myocarditis may develop. Brain injury is manifested by
                                 convulsions, delirium, and coma. Anuric renal failure commonly develops due
                                 to  shock and to the toxic effects of phosphorus products  and  accumulating
                                 bilirubin on renal tubules.The mortality rate of phosphorus poisonings may be
                                 as high as 50 percent.15
                                     Zinc phosphide is much less corrosive to skin and mucous membranes
                                 than yellow phosphorus, but inhalation of dust may induce pulmonary edema.
                                 The emetic effect of zinc released in the gut may provide a measure of protection;
                                 however, phosphine will be produced in the gut and absorbed along with the
                                 zinc. Nausea and vomiting, excitement, chills, chest tightness, dyspnea, and cough
                                 may progress to pulmonary edema. Patients face many of the same systemic tox-
                                 icities  as  encountered with yellow phosphorus, including hepatic failure with
                                 jaundice and hemorrhage,  delirium, convulsions, and coma (from toxic encepha-
                                 lopathy), tetany from hypocalcemia, and anuria from renal tubular damage.Ven-
                                 tricular arrythmias from cardiomyopathy and shock also occur and are another
                                 common cause of death.16'18 Inhalation of phosphine gas from  improper use of
                                 phosphide rodenticides has resulted in pulmonary edema, myocardial injury, and
                                 multisystem involvement.19 For more information about the effects of phosphine
                                 gas poisoning, see the section  on phosphine in Chapter 16, Fumigants.
                                 Confirmation of Poisoning
                                     Phosphorus and phosphides sometimes impart a foul rotten fish odor
                                 to vomitus, feces, and sometimes the breath. Luminescence of vomitus or feces
                                 is an occasional feature of phosphorus ingestion. Hyperphosphatemia and hy-
                                 pocalcemia occur in some cases, but are not consistent findings.
                                     Thallium can be measured in the serum, urine, and hair. Hair analysis is
                                 likely to be useful only in establishing protracted prior absorption. Serum con-
                                 centration does not exceed 30 meg per liter in non-exposed persons.The most
                                 reliable method for diagnosis is considered a 24-hour urine excretion. The
                                 normal value is less than 10 meg/liter per 24 hours.10-13

Treatment: Thallium Sulfate
1. Gastrointestinal decontamination. If thallium sulfate was swallowed less
than an hour prior to treatment, consider gastrointestinal decontamination as
outlined in Chapter 2. Multiple doses of activated charcoal may be helpful in
increasing thallium elimination.13

2. Electrolyte and glucose solutions should be given by intravenous infu-
sion to support urinary excretion of thallium by diuresis. Monitor fluid balance
carefully to insure that fluid overload does not occur. If shock develops, give
whole blood, plasma, or plasma expanders. Pressor amines must be used very
carefully in light of myocardial injury. Monitor EGG for arrhythmias.

3. Convulsions. Control seizures and myoclonic jerking as outlined in Chap-
ter 2.

4. Combined hemodialysis and hemoperfusion has proven moderately
effective in reducing the body burden of thallium in victims of severe poison-
ing. In one case, peritoneal dialysis was not effective.

5. Chelation therapy. Several methods for chelating and/or accelerating dis-
position of thallium have been tested and found  either relatively ineffective or
hazardous. Chelating agents are not recommended in thallium poisoning. Po-
tassium chloride  has been recommended. However it has been  reported to
increase toxicity to the brain,11'14 and  has not shown to increase elimination in
6. Potassium ferric  ferrocyanide (Prussian  Blue) orally enhances fecal
excretion of thallium by exchange of potassium for thallium in the gut. It is not
available or approved for use in humans in the United States. Reports of its use
in humans are anecdotal and do not strongly support its use.
Treatment: Yellow Phosphorus and Zinc Phosphide
1. Skin decontamination. Brush or scrape non-adherent phosphorus from
the  skin. Wash skin burns with copious amounts of water. Make sure all par-
ticles of phosphorus have been removed. If burned area is infected, cover with
an antimicrobial creme. See Chapter 2.

2. Supportive management. Poisonings by ingested yellow phosphorus or
zinc phosphide are extremely difficult to manage. Treatment is basically sup-
portive and symptomatic. Control of airway and convulsions must be  estab-
lished prior to considering gastrointestinal decontamination as described in
Chapter 2.
                                                                                        RODENTICIDES • 175

                                    Caution: Highly toxic phosphine gas may evolve from emesis, lavage fluid,
                                 and feces of victims of these poisons.The patient's room should be well venti-
                                 lated. Persons attending the patient must wear gloves to avoid contact with the

                                 3. Lavage with 1:5000 potassium permanganate solution has been used in the
                                 management of ingested phosphorus compounds in the past; however, there is
                                 not sufficient evidence for its efficacy and we do not recommend it.

                                 4. Catharsis is probably not indicated, but there may be some benefit in ad-
                                 ministering mineral oil. Dosage is 100 mL for adults  and children over 12 years,
                                 and 1.5 mL/kg body weight in children under 12 years. Do not give vegetable
                                 oils or fats.

                                 5. Transfusions. Combat shock and acidosis with transfusions of whole blood
                                 and appropriate intravenous fluids. Monitor fluid balance and central venous
                                 pressure to avoid fluid overload. Monitor blood electrolytes, glucose, and pH to
                                 guide  choice of intravenous solutions. Administer  100% oxygen by mask or
                                 nasal tube.

                                 6. Oxygen. Combat pulmonary edema with intermittent or continuous posi-
                                 tive pressure  oxygen.

                                 7. Renal protection. Monitor urine albumin, glucose, and sediment to detect
                                 early  renal injury. Extracorporeal hemodialysis will be required if acute renal
                                 failure occurs, but it does not enhance excretion of phosphorus. Monitor EGG
                                 to detect myocardial impairment.

                                 8. Liver damage. Monitor serum alkaline phosphatase, LDH, ALT, AST,  pro-
                                 thrombin time, and bilirubin  to evaluate liver damage. Administer
                                 AquamephytonR (vitamin Kj)  if prothrombin level  declines.

                                 9. Pain management. Morphine sulphate may be necessary to control pain.
                                 Adult dose: 2-15 mg IM/IV/SC Q 2-6 hours prn. Child's dose: 0.1-0.2  mg/
                                 kg/dose Q 2-4 hours.

                                 10. Phosphine gas.  For specific therapy due to phosphine gas, refer to the
                                 treatment of phosphine poisoning in Chapter 16, Fumigants.

Commercial Products
    Crimidine is a synthetic chlorinated pyrimidine compound that, in adequate
dosage, causes violent convulsions similar to those produced by strychnine.
    Sodium fluoroacetate and fluoroacetamide are readily absorbed by
the gut, but only to a limited extent across skin.The toxic mechanism is distinct
from that of fluoride salts.Three molecules of fluoroacetate or fluoroacetamide
are combined in the liver to form a molecule of fluorocitrate, which  poisons
critical enzymes of the tricarboxylic acid  (Krebs) cycle, blocking  cellular
respiration. The heart, brain, and kidneys are the organs most prominently a
ffected.The effect on the heart is to cause arrhythmias, progressing to ventri-
cular fibrillation, which is a common cause of death. Metabolic acidosis, shock,
electrolyte imbalance, and  respiratory distress are all  poor prognostic signs.
Neurotoxicity is expressed as  violent tonic-clonic convulsions, spasms, and
rigor, sometimes not occurring for hours after ingestion.21
    Strychnine is a natural toxin (nux vomica) which causes violent convul-
sions by direct excitatory action on the cells of the central nervous  system,
chiefly the spinal cord. Death is caused by convulsive interference with  pulmo-
nary function, by depression of respiratory center activity, or both. Strychnine
is detoxified in the liver. Residence half-life is about 10 hours in humans. On-
set of symptoms is usually within 15-20 minutes of ingestion. Lethal  dose in
adults is reported to be between 50 and 100 mg, although as little as 15  mg can
kill a child.22
  Compound 1081
sodium fluoroacetate
  Compound 1080

* Discontinued in the U.S.

Only specially trained
personnel are allowed to use
strychnine. Crimidine and
sodium fluoroacetate are no
longer registered for use as
Confirmation of Poisoning
    There are no generally available tests to confirm poisoning by the convul-
sant rodenticides.
Treatment: Sodium Fluoroacetate and Fluoroacetamide
    Poisonings by these compounds have occurred almost entirely as a result of
accidental and suicidal ingestions.  If the  poison  was  ingested shortly before
treatment and convulsions have not yet occurred, the first step in treatment is
to remove the toxicant from the gut. If the victim is already convulsing, how-
ever, it is necessary first to control the seizures before gastric lavage and cathar-
sis are undertaken.

1. Control seizures as outlined  in Chapter 2. Seizure  activity from these
compounds may be so severe that doses necessary for seizure control may para-
lyze respiration.  For  this reason, it is best to intubate  the trachea as early as
                                                                                         RODENTICIDES • 177

                                 possible in the course of seizure control, and support pulmonary ventilation
                                 mechanically.This has the added advantage of protecting the airway from aspi-
                                 ration of regurgitated gastric contents.

                                 2. Gastrointestinal decontamination. If the patient is seen within an hour
                                 of exposure and is not convulsing, consider gastrointestinal decontamination as
                                 outlined in Chapter 2.

                                 3. Administer intravenous fluids cautiously to support  excretion of ab-
                                 sorbed toxicant. It is especially important to avoid fluid  overload in the pres-
                                 ence of a weak and irritable myocardium.

                                 4. Monitor electocardiogram for arrhythmias and, if detected, treat with an
                                 appropriate antiarrhythmic drug. Facilities for electroshock cardioversion should
                                 be  at hand. Some victims of fluoroacetate poisoning have been rescued after
                                 repeated cardioversions.

                                 5. Calcium gluconate (10% solution) given slowly intravenously should be
                                 given to relieve hypocalcemia. Care must be taken to avoid extravasation.
                                     Dosage of Calcium Gluconate:
                                     Supplied as 100 mg/mL (10% solution)
                                     • Adults and children over 12years: 10 mL of 10% solution, given slowly,
                                       intravenously. Repeat as necessary.
                                     • Children under 12 years: 200-500 mg/kg/24 hr divided Q6 hr. For
                                       cardiac arrest, 100 mg/kg/dose. Repeat dosage as needed.
                                 6. Other therapies. Antidotal efficacy of glycerol monacetate and ethanol,
                                 observed in animals, has not been substantiated in humans.These therapies are
                                 not recommended in humans.
                                 Treatment: Strychnine or Crimidine
                                     Strychnine and crimidine cause violent convulsions shortly following in-
                                 gestion of toxic doses. Both poisons are probably well adsorbed onto charcoal.
                                 If the patient is seen fully conscious and not convulsing a few moments after
                                 the  ingestion, great benefit may derive from the immediate ingestion of acti-
                                 vated charcoal. If the patient is already obtunded or convulsing, the involuntary
                                 motor activity must be controlled before steps are taken to empty the gut and
                                 limit toxicant absorption.

1. Control seizures as outlined in Chapter 2.

2. Gastrointestinal decontamination. Consider gastrointestinal decontami-
nation if patient is seen within an hour of ingestion.

3. Administer intravenous  fluids to support excretion of absorbed toxi-
cants. Inclusion of sodium bicarbonate  in the infusion fluid counteracts meta-
bolic  acidosis generated by convulsions. Effectiveness of hemodialysis and
hemoperfusion has not been tested.


    Red squill is a little-used rodenticide, consisting of the inner portions of a
small  cabbage plant grown in eastern Mediterranean countries. Its toxic prop-
erties have been  known since ancient  times and are probably due to cardiac
glycosides. For several reasons, mammals other than rodents are unlikely to be
poisoned: (1) red squill is intensely nauseant, so that animals which vomit (ro-
dents do not) are unlikely to retain the poison; (2) the glycoside is not effi-
ciently absorbed  from the gut; and (3) absorbed glycoside is rapidly excreted.
Injection of the  glycosides leads to  effects typical of digitalis: alterations in
cardiac impulse conduction and arrhythmias.
    Cholecalciferol is the activated form of vitamin D (vitamin Dj). Its toxic
effect is probably a combination  of actions on liver, kidney, and possibly the
myocardium, the last two toxicities being the result of hypercalcemia. Early symp-
toms and signs of vitamin D-induced hypercalcemia in humans are fatigue, weak-
ness, headache, and nausea. Polyuria, polydipsia, proteinuria, and azotemia result
from acute renal tubular injury by hypercalcemia.This is commonly the cause of
death. Prolonged  hypercalcemia results ultimately in nephrolithiasis and nephro-
calcinosis. Azotemia occurs as renal tubular damage progresses.

Confirmation  of Poisoning

    Cholecalciferol intoxication is indicated by an elevated concentration of
calcium (chiefly  the unbound fraction) in the serum. There are no generally
available tests for the other rodenticides or their biotransformation products.
Commercial Products
red squill*

* Discontinued in the U.S.
                                                                                        RODENTICIDES • 179

                                 Treatment: Red Squill
                                     Red squill is unlikely to cause poisoning unless ingested at substantial dos-
                                 age. The problem is usually self-correcting due to its intense emetic effect. If,
                                 for some reason, the squill is retained, syrup of ipecac, followed by 1 -2 glasses of
                                 water, should be administered to initiate vomiting. Monitor cardiac status elec-
                                 Treatment: Cholecalciferol
                                     Cholecalciferol at high dosage may cause severe poisoning and death.
                                 Human poisonings from its use as a rodenticide have not been reported, but
                                 vitamin D overdosage has occurred under clinical circumstances. Treatment is
                                 directed at limiting gastrointestinal absorption, accelerating excretion, and
                                 counteracting the hypercalcemic effect.

                                 1. Gastrointestinal decontamination. If Cholecalciferol has been ingested
                                 within an hour prior to treatment, consider gastric decontamination, as out-
                                 lined in Chapter 2. Repeated administration of charcoal at half or  more the
                                 initial dosage every 2-4 hours may be  beneficial.

                                 2. Administer intravenous fluids (normal saline or 5% glucose) at  moderate
                                 rates to support excretory mechanisms and excretion. Monitor fluid balance to
                                 avoid overload, and measure serum electrolytes periodically. Measure total and
                                 ionized calcium  levels in the blood 24 hours after Cholecalciferol ingestion to
                                 determine severity of toxic effect. Monitor urine for protein, and red and white
                                 cells to assess renal injury.

                                 3. Furosemide  (Lasix), 20-40 mg intravenously, or  40-120 mg daily by mouth
                                 may be given to promote diuresis. Dosage for children under 12 is approximately
                                 0.5-1.0 mg/kg body weight intravenously, 1.0-2.0 mg/kg body weight orally.
                                 Monitor serum potassium  after dosage; give potassium chloride if hypokalemia
                                 occurs. Consult package insert for additional directions and warnings.

                                 4. Predinisone and similar glucocorticoids reduce elevated blood calcium
                                 levels in certain diseases. Although they have not been tested in Cholecalciferol
                                 overdosage, it is possible that they would be beneficial. Dosage is approximately
                                 1 mg per kilogram per day, to a maximum of 20 mg per day.

                                 5. Calcitonin (salmon calcitonin, CalcimarR)  is a logical antidote for  Cholecal-
                                 ciferol actions, but has only very limited use  in human poisoning.23 In other
                                 conditions, the usual dosage is 4 International Units per kg body weight every
                                 12 hours, by  intramuscular or subcutaneous injection, continued  for  2-5 days.

The dose may be doubled if calcium-lowering effect is not sufficient. Calcium
gluconate for intravenous injection should be immediately available if indica-
tions of hypocalcemia (carpopedal spasm, cardiac arrhythmias) appear. Consult
package insert for additional directions and warnings.

6. Cholestryamine appears effective in the treatment of vitamin D toxicity in
animals.24 It has seen very limited use in humans.25-26
1.   Mack RB. Not all rats have four legs: Superwarfarin poisoning. N C Med] 1994;55:554-6.
2.   Katona B and Wason S. Superwarfarin poisoning. /Emerg Med 1989;7:627-31.
3.   LitovitzTL,SrnilksteinM,FelbergL,et al. 1996 Annual Report of the American Association of
    Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 1997;15:447-
4.   Burucoa C, Mura P, Robert R, et al. Chlorophacinone intoxication. ClinToxicol 1989;27:79-89.
5.   Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: A pro-
    spective study. Pediatrics 1989;84:490-4.
6.   Lipton RA and Klass EM. Human  ingestion of a 'superwarfarin' rodenticide resulting in a
    prolonged anticoagulant effect. JAMA 1984;252:3004-5.
7.   Helmuth RA, McCloskey DW, Doedens DJ, et al. Fatal ingestion of a brodifacoum-contain-
    ing rodenticide. Lab Med 1989;20:25-7.
8.   NorcrossWA, GaniatsTG, Ralph LP, et al. Accidental poisoning by warfarin-contaminated
    herbal tea. West J Med 1993;159:80-2.
9.   Kruse JA and Carlson RW Fatal rodenticide poisoning with brodifacoum. Ann Emerg Med
10.  Mayfield SR, Morgan DP, and  Roberts RJ. Acute thallium poisoning in a 3-year old child.
    Clin Pediatr (Phila) 1983;23:461-2.
11.  Bank WJ, Pleasure DE, Suzuki K, et al.Thallium poisoning. Arch Neurol 1972;26:456-64.
12.  Fred HL and Accad ME Abdominal pain, leg weakness, and alopecia in a teenage boy. Hosp
    Pract  1997:32:69-70.
13.  MeggsWJ, Hoffman RS, Shih RD, et al.Thallium poisoning from maliciously contaminated
    food. JToxicol Clin Toxicol 1994;32:723-30.
14.  Roby DS, Fein AM, Bennett RH, et al. Cardiopulmonary effects of acute thallium poison-
    ing. Chest 1984;85:236-40.
15.  McMarron MM and Gaddis GR Acute yellow phosphorus poisoning from pesticide pastes.
    ClinToxicol 1981;18:693-711.
16.  Dipalma JR.  Human toxicity from rat poison. Am Fam Physician 1981 ;24:186-9.
17.  Simon FA and Pickering LK. Acute yellow phosphorus poisoning: Smoking stool syndrome.
    JAMA 1976:235:1343-4.
18.  Patial RK, Bansal SK, Kashyap S, et al. Hypoglycaemia following zinc phosphide poisoning.
    JAssoc Physicians India 1990:38:306-7.
19.  Schoonbroodt D, Guffens P, Jousten P, et al. Acute phosphine  poisoning? A case report and
    review. Acta Clin Belg 1992;47:280-4.
                                                                                                          RODENTICIDES • 181

                                        20. Koshy KM and Lovejoy FH.Thallium ingestion with survival: Ineffectiveness of peritoneal
                                            dialysis and potassium chloride diuresis. Clin Toxicol 1981;18:521-5.
                                        21. Chi CH, Chen KW, Chan SH, et al. Clinical presentation and prognostic factors in sodium
                                            monofluoroacetate intoxication. ClinToxicol 1996;34:707-12.
                                        22. Benomran FA and Henry JD. Homicide by strychnine poisoning. Med Sci Law 1996;36:271-3.
                                        23. Buckle RM, GamlenTR, and Pullen IM.Vitamin D intoxication treated with procine calci-
                                            tonin. BrMedJ 1972;3:205-7.
                                        24. Queener SF and Bell NH. Treatment of experimental vitamin D3 intoxication in the rat
                                            with cholestyramine. Clin Res 1976;24:583A.
                                        25. Jibani M and Hodges NH. Prolonged hypercalcaemia after industrial exposure to vitamin D.
                                            Br MedJ 1985;290:748-9.
                                        26. Thomson RB and Johnson JK. Another family with acute vitamin D intoxication: Another
                                            cause of familial hypercalcaemia. Postgrad Med] 1986;62:1025-8.

Miscellaneous Pesticides,
Solvents,  and  Adjuvants
There are a variety of pesticides that do not fall into the broad categories
described in other chapters in this manual. Many of them are widely used and
are therefore associated with a high probability of human exposure. Some have
significant toxicity as well as a likelihood of human  exposure, and are of real
concern. Many of the solvents and adjuvants used in  the formulation of pesti-
cides also present a high likelihood of human exposure. Such exposures can
result in significant toxic effects  that in many cases exceed the toxicity of the
active pesticide ingredient(s). Furthermore, it is sometimes more difficult to
obtain information about the solvents and adjuvants, complicating the issues of
diagnosis and management.

    4-Aminopyridine is a highly toxic white powder used as a bird repellent. It
works by making one or two birds acutely ill, thus warning off the remaining
birds by cries of distress. It is toxic to all vertebrates.1 It is usually added to grain
baits in 0.5%-3.0% concentration, but 25% and 50% concentrates in powdered
sugar are available. Recent human exposure has come from its use as  an inves-
tigational drug in the treatment of multiple sclerosis.2'3 It is rapidly absorbed by
the gut, less effectively across skin.The chief mechanism of toxicity is enhance-
ment of cholinergic transmission in the nervous system through the release of
acetylcholine both centrally and peripherally. Due to enhanced transmission at
neuromuscular junctions, severe muscle spasms may be a prominent manifesta-
tion of toxicity.2 4-Aminopyridine is rapidly metabolized and excreted.
    No human poisonings have occurred as a result of ordinary use, but the
effects of ingestion of about 60 mg each by  two  adults have been reported.
Both experienced immediate  abdominal discomfort,  nausea and vomiting,
weakness, dizziness, and profuse  diaphoresis,  and one went on to develop a
tonic-clonic seizure and required ventilatory support. Acidosis was present in
both cases.1 Dizziness, giddiness, and  gait disturbances are common, and sei-
zures may be severe, although recovery with supportive therapy and ventilatory
support has been the usual outcome.1'2-3

•   Physicians may need to
   actively seek information
   from producers regarding
   exact makeup of "inert

Signs and Symptoms:
•   Highly variable based on
•   Many are irritants and
•   Creosote (phenolic
   compounds) give a smoky
   color to urine
•   Methemoglobinemia may
   occur with sodium
   chlorate and creosote
•   Sodium chlorate also
   causes renal injury,
   arrhythmia, shock, and
•   Pneumonitis occurs with
   hydrocarbon aspiration

•   Skin, eye, and Gl
•   Supportive care and
   seizure control
•   Methylene blue for
                                                                                    MISCELLANEOUS • 183

Commercial Products
calcium cyanamide*
  Endothall Turf Herbicide
  Herbicide 273
sodium chlorate

piperonyl butoxide

anticaking agents
granular formations
petroleum distillants
stickers and spreaders

*Discontinued in the U.S.
1. Skin decontamination. If skin or eye contamination has occurred, thor-
ough washing of the skin or eyes is indicated. See Chapter 2.

2. Gastrointestinal decontamination. If the patient is seen within an hour
of ingestion of a significant quantity of this compound, gastrointestinal decon-
tamination should be considered, as outlined in Chapter 2. If treatment is de-
layed, immediate oral administration  of charcoal and sorbitol may represent
reasonable management.

3. Seizures may require anticonvulsant medication. See Chapter 2 for dosages.

4. Muscular spasms. Neuromuscular blockade with drugs such as d-
tubocuarine, metocurine and pancuronium bromide have been used sucessfully
to relieve the muscular spasms that occur with this agent. Such therapy must be
provided in an intensive care setting.1

5. Dehydration should be treated with intravenous fluids if oral fluids cannot
be retained.

    This synthetic compound is marketed as granules containing 44% calcium
cyanamide, yielding 19.5% nitrogen. It is incorporated into soil to serve  as
fertilizer, fungicide, and herbicide. In contact with water, hydrogen cyanamide
is released. Acidic conditions accelerate this reaction. Hydrogen cyanamide is a
solid with considerable vapor pressure. It has toxic properties totally different
from those of cyanide, and it  does not degrade to cyanide.

    Calcium cyanamide  is only moderately irritating to skin, but hydrogen
cyanamide is severely irritating and caustic to skin and the inhaled gas is strongly
irritating to mucous membranes.4 Dermal and mucosal lesions in the mouth,
tongue, and upper esophagus have occurred after exposure. No systemic symp-
toms from dermal exposure  have been reported.5 Systemic poisonings have
followed inhalation of hydrogen cyanamide and ingestion of the salt. Manifes-
tations of poisoning  include flushing, headache, vertigo, dyspnea, tachycardia,
and hypotension, sometimes  progressing to shock.4 Because cyanamide is an
inhibitor of acetaldehyde dehydrogenase, ingestion of alcohol exaggerates the
symptoms. (A citrated form of cyanamide has been used in place of Antabuse in
alcohol aversion therapy.)

1. Skin decontamination.  Skin contamination with either the calcium salt
or the free form should be removed by washing with soap and water. Flush eyes
with copious amounts of clean water. If skin or eye irritation persists, medical
attention should be obtained  promptly. See Chapter 2.

2. Gastrointestinal decontamination. If large doses have been ingested within
an hour of exposure, gastrointestinal decontamination should be considered. If
dosage was small or treatment is delayed, oral administration of activated charcoal
and sorbitol probably represents reasonable management. See Chapter 2 for doses.

3. Hypotension or Antabuse-type reactions should be  treated by placing
the patient in the Trendelenburg position, giving intravenous fluids, including
plasma or blood, if needed, and, if necessary, vasopressor drugs parenterally.

4. Atropine  is not antidotal.

    Creosote is obtained by distillation of the tar formed by heating wood or
coal in the absence of oxygen. It is purified by extraction into oils. Creosote
from wood consists mainly of guaiacol (methoxy phenol) and cresol (methyl
phenol).  Coal-derived creosote contains, in addition, some phenol, pyridine,
and pyridinol. Creosote is extensively used as a wood preservative, usually by
high-pressure impregnation of lumber. It has also been used as an animal dip
and disinfectant. Much of human exposure is  in the form of various phenol
    Creosote is irritating to skin, eyes, and mucous membranes. Workers in
contact with technical creosote or with treated timbers sometimes develop
skin irritation, vesicular or papular eruptions,  dermal pigmentation,  and
occasionally gangrene and skin cancer.6 Photosensitization has been reported.
Eye contamination has resulted in conjunctivitis and keratitis, sometimes resulting
in corneal scarring.The constituents of creosote are efficiently absorbed across
the skin,  but systemic poisonings following dermal absorption have occurred
very rarely. Absorption of ingested creosote from the gut occurs promptly, and
there may be significant absorption of vapor by the lung. Conjugates of absorbed
phenolic constituents are excreted mainly in the urine. Acute toxic effects are
similar to those of lysol, but the  corrosive nature of creosote is somewhat less
because  of greater dilution of phenol  in  the creosote.7 Irritation of the
gastrointestinal tract, toxic  encephalopathy,  and renal tubular  injury are the
principal effects. A chronic toxicosis from continuing gastrointestinal absorption
(creosote used medicinally) has  been described, consisting of gastroenteritis
and visual disturbances.
                                                                                         MISCELLANEOUS • 185

                                     Manifestations of acute systemic poisoning are salivation, vomiting, dyspnea,
                                 headache, dizziness, loss of pupillary reflexes, cyanosis, hypothermia, convulsions,
                                 and coma. Death is due to multi-organ system failure as patients develop shock,
                                 acidosis, respiratory depression, and anuric renal failure.
                                 Confirmation of Poisoning
                                     The presence of phenolic oxidation products imparts a dark, smoky color
                                 to the urine.7 If there is suspicion of poisoning, addition of a few drops of ferric
                                 chloride solution to the urine yields a violet or blue color, indicating the pres-
                                 ence of phenolic compounds.
                                 1. Skin decontamination. Stringent measures should be taken to avoid con-
                                 tamination of skin or eyes and inhalation of vapor. Skin contamination should
                                 be promptly washed off with soap and water.  Remove eye contamination by
                                 washing with copious amounts of water, then obtain specialized medical atten-
                                 tion promptly because corneal injury may be severe. See Chapter 2.

                                 2. Gastrointestinal decontamination. If a significant amount of creosote has
                                 been ingested and the patient is alert and able to swallow, immediately administer
                                 a slurry of activated charcoal by mouth. Further efforts to limit absorption will
                                 depend on whether there has been corrosive injury to the esophagus. If pharyn-
                                 geal redness and swelling are evident, neither induced emesis nor gastric lavage is
                                 advisable due to potential re-exposure of the esophagus to the creosote, or perfo-
                                 ration of the esophagus from a gastric tube. For further information on  gastric
                                 decontamination, including charcoal dosing, see Chapter 2.

                                 3. Maintain pulmonary ventilation mechanically with oxygen, if necessary.

                                 4. Blood and urine samples. Draw a blood  sample to test for methemoglo-
                                 binemia, to measure BUN and blood electrolytes, and to check for signs of liver
                                 injury  (bilirubin, GGT, LDH, ALT, AST, and  alkaline phosphatase). Examine
                                 the urine for protein and cells, and for "smoky" phenolic excretion products.

                                 5. Intravenous fluids. Give fluids intravenously to correct dehydration and
                                 electrolyte disturbances. Include glucose to protect the liver and bicarbonate to
                                 relieve  metabolic acidosis, as necessary. Monitor fluid balance carefully to signal
                                 discontinuation of intravenous fluids if renal failure occurs. Plasma or blood
                                 transfusion may be needed to overcome shock.

                                 6. Monitor ECG  to detect arrhythmias and/or conduction defects that may
                                 appear  as manifestations of a toxic myocardiopathy.

7. Convulsions. Anticonvulsants may be needed to control seizures as out-
lined in Chapter 2.

8. Hemodialysis is not effective in accelerating disposition of phenol (or,
presumably, creosote), but hemoperfusion over charcoal probably is effective.8
This should be considered in severe creosote poisonings.

9. Methemoglobinemia is rarely severe, but intravenous administration of 1%
methylene blue may be considered if 25-30% of hemoglobin is converted. Dose
is 0.1 mL of 1% solution per kg body weight, given over no less than 10 minutes.
Nausea, dizziness, and a transient increase in blood pressure may occur.
    As the free acid or as sodium, potassium, or amine salts, endothall is used as
a contact herbicide, defoliant, aquatic herbicide, and algacide. It is formulated in
aqueous solutions and granules at various strengths.
    Endothall is irritating to the skin, eyes, and mucous membranes. It is well
absorbed across abraded skin and from the gastrointestinal tract. Recognized
systemic toxic mechanisms in mammals are: corrosive effects on the gastrointes-
tinal tract (particularly from high concentrations of the free acid);  cardiomy-
opathy and vascular injury leading to shock; and central nervous system injury,
causing convulsions and respiratory depression. A single case has been reported
of lethal poisoning in a previously  healthy 21-year-old man who died after
ingestion of 7-8 grams of endothall. In this patient, hemorrhage and edema
were noted in the gastrointestinal tract and lungs.9 There are no standards for
levels, and they are not considered useful in management.
1. Skin decontamination. Wash endothall from the skin with soap and water.
Flush contamination from the eyes with copious amounts of clean water. Ob-
tain medical attention if irritation of skin or eyes persists. See Chapter 2.

2. Gastrointestinal decontamination. If a large quantity has been ingested, the
patient is seen within an hour of exposure, and is fully alert and not convulsing,
gastrointestinal decontamination  should be considered as outlined in Chapter 2.
Lavage is usually contraindicated  due to the corrosive nature of this agent.
                                                                                         MISCELLANEOUS • 187

                                 3.  Intubation. If there are  indications of corrosive effects in the  pharynx,
                                 gastric intubation should not be attempted because of the risk of esophageal
                                 perforation.Treatment procedures appropriate for ingestions of corrosives (strong
                                 acids and alkalis) may be necessary. Referral should be made to a surgeon or
                                 gastroenterologist for consideration of endoscopy.

                                 4. Oxygen should be given  by mask. If respiratory drive is weak, pulmonary
                                 ventilation may have to be supported mechanically.

                                 5. Monitor blood pressure closely. Infusions of plasma, blood, other volume
                                 expanders, and pressors may be needed to combat shock.

                                 6. Administer intravenous fluids to correct dehydration, stabilize electro-
                                 lytes, provide sugar, and support mechanisms for toxicant disposition. Give va-
                                 soactive amines very carefully in light of possible myocardiopathy.

                                 7. Convulsions. Seizures may require administration of diazepam and/or other

                                 8. Hemodialysis.  It is not known whether hemodialysis or hemoperfusion
                                 would be effective in removing endothall from the blood.This option should
                                 be considered if the patient's  condition deteriorates despite supportive care.

                                     Metaldehyde is a four-unit cyclic polymer of acetaldehyde which has long
                                 been used to kill slugs and snails, which are attracted to it without the use of
                                 bait. Occasional poisonings of animals and  children have resulted from inges-
                                 tion of pellets intended as molluscicide, but tablets designed as a combustible
                                 fuel ("meta-fuel") have also been responsible for human poisonings.10 Another
                                 form of exposure is "snow storm tablets," which the user places at the end of a
                                 lighted cigarette to create  snow. Toxicity  occurs through inhalation  of
                                 metaldehyde fumes."The biochemical mechanism of poisoning is not known.
                                 Both acetaldehyde and metaldehyde produced similar effects in dogs; however,
                                 acetaldehyde was not  detected  in the plasma or urine  of the metaldehyde-
                                 poisoned dogs.12
                                     Ingestion of a toxic dose is often followed shortly by nausea and vomiting.
                                 The other primary  features of toxicity are pyrexia, generalized seizures, and
                                 mental status changes,  sometimes leading to coma.10'13 Other signs and symp-
                                 toms that may occur include hypersalivation, facial flushing, dizziness, tachyp-
                                 nea, and  acidosis.10'11  Pneumonitis has followed inhalational exposure  to

metaldehyde.11 While most cases are dramatic with significant seizures and coma,
fatal events are infrequent.10-13 Poisoned animals show tremors, ataxia, hyperes-
thesia, salivation, ataxia, and seizures.12 Autopsy findings in fatal human poison-
ings indicate severe damage to liver cells and renal tubular epithelium.
Confirmation of Poisoning
    Metaldehyde can be measured in the blood and urine, although there are
very few reports of levels among poisoned humans. One patient who had se-
vere tonic clonic seizures and was comatose had a metaldehyde level in the
serum  of 125  mg/L with a half-life of 27  hours. This patient did not have
detectable acetaldehyde in the serum.13
1. Gastrointestinal decontamination. If ingestion occurred within an hour
of treatment, consider gastrointestinal decontamination as outlined in Chapter 2.
Activated charcoal may well be useful against metaldehyde.

2. Convulsions. If seizures occur, sedative anticonvulsants must be adminis-
tered. See Chapter 2 for dosage.

3. Supportive treatment. Appropriate supportive treatment including intra-
venous fluids containing saline and glucose should be given. Sodium bicarbon-
ate may be considered in the event of severe metabolic acidosis. Fluid balance
and electrolytes must be monitored carefully to avoid fluid overload if renal
failure supervenes.

4. Renal  failure. There is no specific antidote for metaldehyde poisoning.
Hemodialysis is probably not effective in removing metaldehyde, but must be
instituted if renal failure occurs. The effectiveness of hemoperfusion has not
been tested.

5. Liver function tests and urine sediment examination should be done to
assess liver and kidney injury in poisoned patients.
    Sodium chlorate is used in agriculture as a defoliant, nonselective contact
herbicide, and semipermanent soil sterilant. Because of its explosive nature, it
must be formulated with water-soluble fire retardant material, such as sodium
metaborate, soda ash, magnesium chloride, or urea. It is usually applied in water
                                                                                        MISCELLANEOUS •  189

                                     Sodium chlorate is irritating to skin, eyes, and mucous membranes of the
                                 upper respiratory tract.14 Dermal absorption is slight. Even though gastrointes-
                                 tinal absorption  is also inefficient, severe  (sometimes fatal) poisoning follows
                                 ingestion of a toxic dose, estimated at about 20 grams in the adult human.
                                 Excretion is chiefly in the urine. The principal mechanisms of toxicity are
                                 hemolysis, methemoglobin formation, cardiac arrhythmia (partly secondary to
                                 hyperkalemia), and renal tubular injury.14'15
                                     The irritant action on the gut causes nausea, vomiting, and abdominal pain.
                                 Once absorbed, hemoglobin is rapidly oxidized to methemoglobin, and intravas-
                                 cular hemolysis occurs.14 Cyanosis is prominent if methemoglobinemia is severe
                                 and may be the only presenting sign.15 Acute tubular necrosis and hemoglobin-
                                 uria may result from the hemolysis or direct toxic injury. Plasma and urine are
                                 dark brown  from the  presence of free hemoglobin and methemoglobin.14'15'16
                                 Release of potassium from red cell destruction results in  hyperkalemia which
                                 may be severe enough to cause life-threatening arrythmias.16 The liver and spleen
                                 are often enlarged due to  uptake of hemolyzed erythrocytes.15 Hypoxemia may
                                 lead to convulsions. Death may be the result of shock, tissue hypoxia, renal failure,
                                 hyperkalemia, or disseminated intravascular coagulation (DIG).14'15'16
                                 Confirmation of Poisoning
                                     There are no widely available tests specifically for chlorate. Dark brown
                                 staining of the plasma and urine indicates the action of a strong oxidizing agent
                                 on hemoglobin. See Chapter 2.
                                 1. Skin decontamination. Skin contamination should be removed immedi-
                                 ately by washing with soap and water. Medical  attention should be sought if
                                 irritation persists. Flush contamination from eyes with copious amounts of clean
                                 water, then obtain specialized medical attention  promptly, because irritant ac-
                                 tion may be severe. See Chapter 2.

                                 2. Gastrointestinal decontamination. If sodium chlorate has been ingested
                                 within an hour prior to treatment, consider gastrointestinal decontamination as
                                 outlined in Chapter 2.

                                 3. Oxygen. If respiration is depressed, ventilatory support may be necessary.

                                 4. Sodium thiosulfate has been recommended as an antidote against absorbed
                                 sodium chlorate.Thiosulfate is thought to inactivate the chlorate ion to form the

less toxic chloride ion. It can be given orally or as an IV infusion over 60-90
minutes.The dose is 2-5 g dissolved in 200 mL of 5% sodium bicarbonate.14

5. Monitor blood pressure, fluid balance, blood electrolytes, BUN, methemo-
globin, and bilirubin, as well as urine protein, cells and free hemoglobin con-
tent, and  EGG. Widening of the QRS complex and prolongation of the  PR
interval indicate hyperkalemic cardiac toxicity.

6. Milk may be helpful in relieving the pain of gastric irritation.

7. Administer intravenous fluids to sustain chlorate excretion.  Maintain
urine pH in the alkaline range by adding sodium bicarbonate to the infusion
fluid. Monitor urine production closely, so that intravenous fluids can be slowed
or discontinued if renal failure occurs. Blood  transfusion  may be needed  if
hemolysis and methemoglobinemia are severe. Exchange transfusion has been
recommended to enhance clearance and treat DIG.16

8. Hemodialysis may be life-saving in severe poisoning. It is effective in re-
moving chlorate from the  blood,  provides a  means to control hyperkalemia,
and makes possible the control of  extracellular fluid volume and  composition
while renal function remains impaired.

9. Methemoglobinemia. Administration of methylene blue to reverse meth-
emoglobinemia may be  considered if  as much as 25-30% of hemoglobin  is
converted. Give intravenously 0.1 mL/kg body weight of a  1% solution over a
period of at least 10 minutes. An increase in blood pressure, nausea, and dizzi-
ness may  occur, but these effects are usually transient. As the use of this agent in
chlorate poisoning has not proven beneficial  in the past, it  is still advisable to
proceed to exchange transfusion as stated in #7.
    Synergists are chemical agents included in pesticide products to enhance
the killing power of the active ingredients.The widely-used insecticide syner-
gist, piperonyl butoxide, acts by inhibiting the enzymatic degradation of pyre-
thrins, rotenone, N-methyl carbamates, and possibly some other insecticides.
There is limited dermal absorption on contact. Inherent toxicity in mammals is
low. Large absorbed doses may theoretically enhance the toxic  hazard of the
rapidly metabolized insecticides used today, although inhibition of human drug-
metabolizing enzymes by these agents has not actually been demonstrated.Their
presence in pesticide products to which humans are exposed does not change
                                                                                        MISCELLANEOUS •  191

                                 the basic approach to management of poisoning, except that some possibility of
                                 enhanced toxicity of the active insecticidal ingredients should be kept in mind.
                                 SOLVENTS AND ADJUVANTS

                                     Liquid materials in which pesticides are dissolved and the solids on which
                                 they are adsorbed (sometimes called carriers or vehicles) are selected by pro-
                                 ducers to achieve stability of the active ingredient, convenience in handling
                                 and application, and maximum killing power following application. Often, the
                                 particular solvents and adjuvants selected by pesticide manufacturers are re-
                                 sponsible for giving their commercial products a competitive edge. For this
                                 reason, their inclusion in marketed products is usually proprietary information,
                                 not available to the general public except in emergencies. If a poisoning emer-
                                 gency exists, pesticide companies will usually cooperate in supplying physicians
                                 with information needed to provide treatment. Some companies will put the
                                 inert  ingredients on the Material Safety Data  Sheet (MSDS). The  physician
                                 should seek this information to assist in evaluating all possible exposures. A
                                 direct request to the producer is the quickest way to secure this information.
                                 Physicians may  also contact EPA directly for this information (tel: 703-305-
                                 7090) if needed for proper management of a case.
                                     Petroleum  distillates  are the most commonly used  solvents  for lipo-
                                 philic pesticides. Most insecticides are lipophilic.The distillates are mixtures of
                                 aliphatic and aromatic hydrocarbons and have low boiling points.
                                     Sometimes  specific hydrocarbons, such as toluene  or xylene  (strongly
                                 odiferous), are added  to stabilize the solution of insecticide or make it more
                                 emulsifiable. Hydrocarbon-dissolved pesticides  are usually diluted for applica-
                                 tion by adding measured amounts of water to  form emulsions. Some chlori-
                                 nated hydrocarbons may be  present in particular technical mixtures. A strong
                                 odor lingering after application of a structural pest control spray is often due to
                                 the solvent rather than the active ingredient.
                                     Less lipophilic active  ingredients are sometimes  dissolved  in mixtures of
                                 alcohols, glycols, ethers, or various chlorinated solvents. It is possible that these
                                 enhance the  dermal absorbability of some pesticides. Some solvents, such as
                                 methanol and isopropanol, may represent a significant toxic hazard if swallowed
                                 in sufficient dosage.
                                     Granular formulations utilize various clay materials which adsorb pesti-
                                 cide, retain it in more or less  stable form until application, then desorb the
                                 material slowly into treated soil. There is  some significant desorption  when
                                 granules are in contact with human skin and very substantial desorption into
                                 gastrointestinal secretions if granules are swallowed. The clay materials them-
                                 selves are not a toxic hazard.
                                     Dusts are infrequently  used today. Various  forms of talc (silicatecarbonate
                                 particles)  have  been used in the past to adsorb  pesticides for application to

foliage. Particle sizes are such that these dusts are usually trapped in the upper
respiratory mucous when inhaled.When the mucous is swallowed, the particles
desorb pesticide into gastrointestinal secretions. Dust formulations may, there-
fore, release enough of some pesticides to cause systemic poisonings.
    Stickers and spreaders (film extenders) are organic substances added to
formulations to disperse  pesticide over treated foliage  surfaces and enhance
adhesion.The availability and persistence of residue on the leaf surfaces is thereby
increased. Substances used include proteinaceous materials (milk products, wheat
flour, blood albumin, gelatin), oils, gums, resins, clays, polyoxyethylene glycols,
terpenes, and other viscid organics. Some also include sulfated alcohols, fatty
acid esters,  and alkyl and petroleum  sulfonates. For persons exposed in the
course of formulation or application of pesticides, these adjuvants probably add
little or no toxic hazard to that inherent in the active pesticidal  ingredients.
    Emulsifiers serve to stabilize water-oil emulsions formed  when water is
added to technical hydrocarbon concentrates. Chemically, they resemble deter-
gents (one part of the molecule lipophilic, the other hydrophilic). Long-chain
alkyl  sulfonate  ethers  of polyethylene glycol and polyoxyethylene  oleate are
exemplary emulsifiers. They have low inherent mammalian toxicity, and  their
presence probably has little effect on the overall toxicity of formulated products
which include them.
    Penetrants facilitate the transfer  of herbicide from foliage surface to the
interior tissues. Some are lipids while others are detergent (surfactant) in na-
ture. Substances used include heavy petroleum oils  and  distillates, polyol fatty
acid esters, polyethoxylated fatty acid esters, aryl alkyl polyoxyethylene glycols,
alkyl  amine acetate, alkyl aryl sulfonates, polyhydric alcohols, and alkyl phos-
phates. Some of these are eye and skin irritants, and may account for the  irritant
effects of particular herbicide formulations  whose  active  ingredients  do not
have this property.
    Safeners are substances added to mixtures of fertilizers with pesticides (com-
monly herbicides) to limit the formation of undesirable reaction products. Some
substances used are alcohol sulfates, sodium alkyl butane diamate, polyesters of
sodium thiobutane dioate, and benzene acetonitrile derivatives. Some are mod-
erately irritating to the skin and eyes. Systemic toxicities are generally low.
    Anticaking agents are added to granular and dust formulations to facili-
tate application by preventing cakes and clumps. Among several products used
are the sodium salt of mono- and  di-methyl  naphthalene sulfonate, and diato-
maceous earth. Diatomaceous earth  has little adverse effect  except a  drying
action on the skin. Methyl naphthalenes are said to be skin irritants and  photo-
sensitizers; whether their derivatives have this effect is not known.
                                                                                            MISCELLANEOUS • 193

                                       Petroleum distillates are mineral hydrocarbons which undergo limited ab-
                                   sorption across the gut. In general, clinical toxicologists do not recommend in-
                                   duced emesis or gastric lavage in treating ingestions of these materials, because of
                                   the serious risk of hydrocarbon pneumonitis if even tiny amounts of the liquid
                                   are aspirated into the lung. However, this injunction against emptying the stom-
                                   ach may be set aside when the petroleum distillate is a vehicle for toxic pesticides
                                   in significant concentration. In such cases, if the patient is seen within one hour
                                   of exposure, gastrointestinal decontamination should be considered.
                                       Rapid respiration, cyanosis, tachycardia, and low-grade  fever are the usual
                                   indications of frank hydrocarbon pneumonitis. Patients with presumed hydrocar-
                                   bon pneumonitis, who are  symptomatic, should usually be hospitalized, prefer-
                                   ably in an intensive  care setting. If the patient has pulmonary symptoms, a chest
                                   x-ray should be taken to detect or confirm signs of pneumonitis. In addition, the
                                   urine should be examined for protein, sugar, acetone, casts, and cells, and an EGG
                                   should be  examined for arrhythmias and conduction defects. Mechanically as-
                                   sisted pulmonary ventilation with 100% oxygen may be required. Hydrocarbon
                                   pneumonitis is sometimes fatal, and survivors may require several weeks for full
                                   recovery. In milder cases, clinical improvement usually occurs within several days,
                                   although radiographic findings will remain abnormal for longer periods.17
                                       The presence of chlorinated solvents in some formulations may add sig-
                                   nificantly to the toxic hazard,  particularly if the product is ingested. Certain
                                   adjuvants are irritants to skin, eyes, and mucous membranes, and may account
                                   for the irritant properties of some products whose active ingredients  do not
                                   have this effect. With these exceptions, however, the presence of adjuvants in
                                   most finished pesticide products probably does not enhance  or reduce systemic
                                   mammalian toxicity to any great  extent.
                                   1.   Spyker DA, Lynch C, Shabanowitz J, et al. Poisoning with 4-aminopyridine: Report of three
                                       cases. ClinToxicol 1980;16:487-97.
                                   2.   PickettTA and Enns R. Atypical presentation of 4-aminopyridine overdose. Ann Emerg Med
                                   3.   Stork CM and Hoffman RS. Characterization of 4-aminopyridine in overdose. Clin Toxicol
                                   4.   Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
                                       NJ: Noyes Publications, 1991, pp. 316-7.
                                   5.   Torrelo A, Soria C, Rocamora A, et al. Lichen planus-like eruption with esophageal involve-
                                       ment as a result of cyanamide. JAmAcad Dermatol 1990;23:1168-9.
                                   6.   Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
                                       NJ: Noyes Publications, 1991, pp. 450-3.
                                   7.   Bowman CE, Muhleman MF, and Walters E.  A fatal case of creosote poisoning. Postgrad Med

8.   Christiansen RG and Klaman JS. Successful treatment of phenol poisoning with charcoal
    hemoperfusion. Vet Hum Toxicol 1996;38:27-8.
9.   Allender WJ. Suicidal poisoning by endothall. ]Anal Toxicol 1983;7:79-82.
10. LongstrethWT and Pierson DJ. Metaldehyde poisoning from slug bait ingestion. West j Med
11. Jay MS, Kearns GL, StoneV, et al.Toxic pneumonitis in an adolescent following exposure to
    snow storm tablets. J' Adolesc Health 1988;9:431-3.
12. Booze TF and Oehme FW An investigation of metaldehyde and acetaldehyde toxicities in
    dogs. Fundam ApplToxicol 1986;6:440-6.
13. Moody JP and Inglis FG. Persistence of metaldehyde  during acute molluscicide poisoning.
    Hum Exp Toxicol 1992;ll:361-2.
14. Helliwell M and Nunn J. Mortality in sodium chlorate poisoning. Br MedJ 1979; 1:1119.
15. Steffen C and Seitz R. Severe chlorate poisoning: Report of a case. Arch Toxicol 1981;48:281-8.
16. Smith EA and Oehme FW A review of selected herbicides and their toxicities. Vet Hum
    Toxicol \991:33:596-608.
17. Anas N, Namasonthi V, and Ginsburg CM. Criteria for hospitalizing children who have
    ingested products containing hydrocarbons. JAMA 1981;246:840-3.
                                                                                                             MISCELLANEOUS • 195

                                    CHAPTER 19

•  Compounds are registered
   for medical or medicinal use
   rather than as pesticides
•  Several are among the most
   frequently reported human
   poisonings in the U.S.
•  Iodine is well absorbed
   through abraded or burned
A wide variety of disinfectant agents are used to destroy microorganisms and
they differ greatly in their toxic effects. Most disinfectants can conveniently be
grouped into a few categories, some of which are also represented in other
classes of pesticides. Many of these materials are not registered as pesticides, but
are  registered for medical or medicinal use. This chapter reviews a few of the
more common or more severely toxic  disinfectants.
Signs and Symptoms:
•  Highly variable based on
•  Many are irritants and
•  Iodine causes neurological
   symptoms, shock, renal
   failure, and hyperkalemia
•  Pine oil can cause aspiration

   Follow general principles of
   decontamination and
   supportive care

•  Gastric emptying and
   procedures are
   contraindicated in
   poisonings due to corrosive
   agents and pine oil
    Alcohols have a long history of use as disinfectants. Often disinfectants are
mixtures, usually  of ethanol and isopropyl alcohol (isopropanol). The alcohol
most commonly used in households as a disinfectant is isopropyl alcohol, com-
monly marketed  as a  70% solution. It is a clear, colorless liquid with an odor
similar to ethanol.
Toxicology of Isopropyl Alcohol
    Isopropyl alcohol is well and rapidly absorbed from the gastrointestinal tract.
It is also well absorbed by skin and by inhalation. It is considered to be more toxic
to the central nervous system than ethanol, with similar effects. Both ingestion
and inhalation  at high  concentrations can result in the rapid onset of CNS
depression with subsequent coma  and death. Apnea commonly accompanies
this CNS depression.1'2  Similar neurological toxicity has been reported with
excessive topical exposure to the  umbilicus of a neonate.3 Irritation of the
gastrointestinal tract results in gastritis and severe vomiting. Isopropyl alcohol may
also produce mild hepatic injury with acute exposures. Acute tubular necrosis has
been reported with this agent,1 but the renal toxicity is not as great as with
methanol poisonings. Ketosis without metabolic acidosis but  prominent hypogly-
cemia is common.2'3 This ketosis is the result  of direct  metabolism  of this
compound to acetone.1'3 Monitoring of isopropyl levels is useful, when available.
In addition,  blood levels of acetone and glucose should  be determined to aid
in management.

Confirmation of Poisoning
Commercial Products
    Isopropyl alcohol can be measured in the blood and urine. Serum acetone
can also be measured. Blood isopropyl alcohol levels of 128-200 mg/dL have
been associated with death.
Treatment: Isopropyl Alcohol

1. Gastrointestinal decontamination. Since the onset of coma is often rapid
with this poisoning, induced emesis is contraindicated,  though spontaneous
vomiting often occurs. If the patient has ingested a large amount, has not vom-
ited, and is seen within one hour of exposure, consideration should be given to
gastric emptying by lavage as outlined in Chapter 2.
    Isopropyl alcohol is well adsorbed to charcoal, so activated charcoal should
probably be administered, as outlined in Chapter 2.

2. Supportive care for hypotension and respiratory depression is critical to
survival and  should be administered whenever possible in  an intensive care

3.  If hypoglycemia occurs, glucose administration is  indicated in order to
maintain normoglycemia.

4. Hemodialysis has been reported to be  beneficial in patients with severe
poisoning unresponsive to standard supportive therapy.1'4

    The two aldehydes most commonly used as disinfectants are formaldehyde
and glutaraldehyde. Formaldehyde is discussed in Chapter 17, Fumigants. Glu-
taraldehyde is very similar to formaldehyde in its toxicity and treatment, al-
though it is probably slightly less toxic. Glutaraldehyde is commonly prepared
as an aqueous solution at a 2% concentration, and is slightly alkaline in this
solution. It has been reported to cause respiratory irritation, resulting in rhini-
tis5-6 and occupational asthma.6'7-8 It has also resulted rarely  in palpitations and
tachycardia in human subjects. At high dosage, given orally,  it results in gas-
trointestinal irritation with diarrhea, which may be hemorrhagic. Due to the
irritant effects of glutaraldehyde, the wearing of personal protective equipment
is required for the protection of skin (29 CFR 1910.132),  and eyes (29 CFR
1910.133). OSHA standards require  the use of appropriate respirators by em-
ployees that may  be exposed to glutaraldehyde during routine or emergency
work procedures  (29 CFR 1910.134).
  Isopropyl alcohol


  benzalkonium chloride
  cetylpyridium chloride


  calcium hypochlorite
  sodium hypochlorite


  phenylmercuric acetate
  phenylmercuric nitrate


                                                                                           DISINFECTANTS • 197

                                Treatment: Glutaraldehyde
                                1. Gastrointestinal decontamination. If a large amount has been ingested
                                and retained, and the patient is seen within one hour of exposure, consider
                                gastric emptying as described in Chapter 2. Administration of activated char-
                                coal should be considered, as described in Chapter 2.

                                2. Oxygen. If patient has been in an area with strong odor of glutaraldehyde
                                due to vaporization, remove to fresh air area and administer oxygen as needed.

                                3. Skin  decontamination. If skin irritation is noted, vigorous skin decon-
                                tamination is indicated. However, systemic toxicity from skin exposure appears
                                 CATIONIC  DETERGENTS

                                    Several cationic detergents are used as disinfectants. All share the capacity,
                                 in sufficient concentration, to behave as caustic agents, capable of causing rather
                                 severe, caustic burns. It appears that concentrations greater than approximately
                                 7.5% are necessary to produce significant caustic injuries. However, experience
                                 with  human  exposures to these compounds is very limited. The three agents
                                 most commonly used as detergent disinfectants are benzalkonium chloride,
                                 cetrimide, and cetylpyridium chloride.
                                    Though  there are no cetrimide preparations available in the U.S., several
                                 are available in European Union countries. Concentrated solutions are usually
                                 only  available in industrial settings, such as production of consumer products,
                                 or for use in hospitals  for disinfectant purposes.Therefore, acute poisonings are
                                    In low-concentration solutions, these agents have been reported to cause
                                eye discomfort as well as skin rashes and irritation. In stronger concentrations,
                                they can cause severe corneal and skin burns. Likewise, strong concentrations
                                will result in  caustic burns to lips, oral mucosa, esophagus, and  stomach.9-10
                                Vomiting, diarrhea, and abdominal pain have been reported.11 Necrosis of the
                                gut, with peritonitis, has also been reported.12 In severe exposures, there are also
                                reports of CNS depression, liver injury, and pulmonary edema.9-11
                                1. Skin decontamination. If a high-concentration solution has been applied
                                to skin, aggressive skin contamination and treatment of burns is appropriate. If

a high concentration solution is in contact with the eyes, profuse washing of
the eyes is indicated followed by a careful exam of the corneas. If burns have
occurred, appropriate ophthalmologic care should be provided.

2. Gastrointestinal decontamination. Gastric emptying and other methods
of gastrointestinal decontamination are contraindicated in these poisonings.
Some experts recommend  cautious dilution with small amounts of milk or
water.9'13 Acidic solutions such as juices should never be offered for dilution.

3. Endoscopy. If a highly concentrated solution was ingested or oral burns are
noted, the patient needs urgent endoscopy for grading of the caustic injury.The
endoscopy should be performed within 24 hours to minimize the risk of per-
foration from the procedure.12 A competent surgeon or gastroenterologist should
provide subsequent care.

4. Other agents. Although corticosteroids are commonly used to treat these
burns, their use remains controversial. Use of other agents, such as H2 antago-
nists and sulcralfate, has been reported but remains controversial at this time.

5. CNS, pulmonary and other systemic effects should be treated symptom-
atically, consistent with sound medical practice.

    Chlorhexidine is a cationic biguanide, available in concentrations up to 4%
as a topical agent used as a skin cleanser and mouthwash. Skin preparations of
0.5%-4% are marketed under the trade names HibiclensR and HibistatR. It is
also marketed as a mouthwash in a 0.12% solution under the trade name PeridexR.
There is very little human experience with poisonings, as these concentrations
do not appear to be significantly toxic.
    Chlorhexidine is poorly absorbed from skin or the gastrointestinal tract.
Therefore most effects noted have been primarily local. If a low concentration
solution is ingested or applied to the skin, mild local irritation  can be seen.
Contact dermatitis, urticaria, and anaphylaxis have followed repeated skin ex-
posures to this agent.14'15 Corneal injuries have been described in several cases
after inadvertent exposure of the eyes to the 4% concentration.These injuries
have resulted in permanent corneal  scarring.16  Esophageal burns have been
reported in a single case after ingestion of a large quantity of a 20% solution of
this agent.17 Ulcerative colitis has been described after an enema of the  4%
                                                                                         DISINFECTANTS • 199

                                 solution mixed with tap water (10 mL in 2 liters water).18 Liver toxicity can
                                 occur with large exposures.17

                                 1. Gastrointestinal decontamination. If ingestion of a large quantity has
                                 occurred within an hour and the patient has not vomited, gastrointestinal de-
                                 contamination  as described in Chapter 2  should be considered. If a highly
                                 concentrated solution has been ingested, manage as a caustic ingestion as de-
                                 scribed in the cationic detergents, without gastrointestinal decontamination.

                                 2. Liver injury panel should be performed with large ingestions.

                                 3. Eye decontamination. If eye exposure has occurred, the eyes should be
                                 vigorously irrigated and a careful ophthalmologic exam should be performed
                                 for corneal injury. If an injury has occurred, an ophthalmologic consultation
                                 should be obtained.

                                    Hypochlorites  are implicated in a large proportion of the disinfectant
                                 poisonings reported to poison control centers in the United States. Most are
                                 solutions of sodium or calcium hypochlorite solutions. Chloramine, a disin-
                                 fectant used by many municipal water supplies, is an infrequent cause of acute
                                 poisonings. Sodium and calcium hypochlorite solutions are of relatively low
                                 toxicity.They are mildly corrosive to the eyes,19 and mucous membrane burns
                                 have been reported.20 Significant poisonings are very infrequent with these
                                 agents in solution.21
                                    When hypochlorite solutions are mixed with acids or ammonia solutions,
                                 chlorine or chloramine gas is produced, resulting  in an irritant with pulmonary
                                 toxicity. Many brief exposures have led to transient symptoms requiring lim-
                                 ited emergency department management.22  However, in cases of prolonged
                                 exposure or exposure to high concentrations, there is the potential for severe
                                 toxic pneumonitis.23 While severe injury may be the  exception to the rule,
                                 great efforts should  be made to discourage mixing of these materials with acid
                                 or ammonia.
                                 1.  Gastric decontamination. After oral exposures, gastric emptying is not
                                 indicated. If a granular material is ingested, and the patient has symptomatic
                                 mucosal burns, referral to a surgeon or gastroenterologist for consideration of
                                 endoscopy and management may be appropriate.

2. Dilution with water or milk not to exceed approximately 15 mL/kg in a
child or 120-240 mL in an adult is probably appropriate if vomiting has not
occurred. Administration of acids is contraindicated, due to the risk or increas-
ing generation of chlorine gas.

3. Eye decontamination. If eyes were exposed, they should  be  irrigated
profusely with water or saline. If corneal burns are detected, referral to an
ophthalmologist is appropriate.

4. Skin decontamination. Skin exposure should also be managed by copi-
ous water dilutions. See Chapter 2.

5. Fresh air. If exposure to vapors or chlorine or chloramine gas has occurred,
patient should immediately be moved to fresh air. If symptoms occur or persist,
oxygenation should be assessed and oxygen should be administered as needed. If
persistent symptoms  occur,  a  chest film should be obtained and hospital care
considered. Intensive  care may need to be provided in severe inhalations.
    The most common iodine-containing disinfectant is povidone-iodine
(proviodine), in 7.5-10% solutions. Povidone-iodine is described as an iodophor,
which is a complex of iodine and polyvinylpyrrolidone, a solubilizing agent. It
is intended to liberate free iodine in solution for its effect. Although reported
concentrations of iodine in these solutions  is only 80-120  ugm/dL, the total
available iodine is approximately 10% of the  povidone-iodine.Therefore a 10%
solution will have in the range of 1% total available iodine.
Toxicology of Povidone-iodine
    This compound is very poorly absorbed from the gastrointestinal tract, due
to the rapid conversion of free iodine to iodide in the stomach. Although
highly concentrated iodine solutions or iodine salts are corrosive to the gas-
trointestinal tract,24 solutions of povidone-iodine have little caustic potential.
Likewise, the compound is poorly absorbed from intact skin. All symptomatic
poisonings reported have  occurred either after repeated exposure to burned
skin, or following irrigation of wounds, joints, or serosal surfaces such as the
mediastinum.25"28 The one exception was an infant who received an enema of
povidone-iodine in a polyethylene glycol solution, followed by whole bowel
irrigation  with polyethylene glycol mixed with povidone-iodine. This child
died with  severe hyperglycemia and very high iodine levels.24
    In povidone-iodine exposures by these routes, the primary symptoms ini-
tially appear to be neurological, with headache, dizziness, delirium, hallucina-
                                                                                         DISINFECTANTS •  201

                                tions, and seizures.26 Hypotension, arrythmias, cyanosis, metabolic acidosis, shock,
                                and acute renal failure occur in severe cases.25<27<28 Hepatic injury, manifested by
                                elevated serum transaminase levels, has also been reported with very high level
                                exposures.27 Hyperkalemia has occurred, and the serum chloride may be falsely
                                elevated due to the presence of a second halide.25
                                Treatment: Povidone-lodine
                                1. Skin decontamination. Remove skin contamination by vigorous washing
                                with soap and water. See Chapter 2.

                                2. Gastrointestinal decontamination. If the patient is seen soon after a very
                                large  ingestion, and vomiting has not occurred, consider gastrointestinal de-
                                contamination, as outlined in Chapter 2. Consider single dose charcoal.

                                3. Iodine clearance is apparently enhanced by procedures that enhance chlo-
                                ride excretion. Therefore, osmotic or choluretic diuresis is probably indicated
                                in these poisonings, if symptomatic.

                                4. Seizures. Treat seizures with anticonvulsants, as outlined in Chapter 2.

                                5. Monitor thyroid function following recovery to confirm euthyroid state.


                                    A wide variety of organic mercurials have been used as disinfectants and as
                                preservatives. Nearly all uses have been banned in the United States. The tox-
                                icity and treatment of exposure to these compounds is  described in detail in
                                Chapter 15, Fungicides, under  organomercury compounds and will  not be
                                repeated here.


                                    Several phenols are  used as  disinfectants. Cresol and thymol are alkyl de-
                                rivatives of phenol, while hexachlorophene and triclosan are chlorinated phenols.
                                Common commercial preparations are LysolR, a 50% solution of mixed cresols
                                in soap, and hexachlorophene, marketed under several trade names in soap bars
                                and some cosmetics. Cresols and hexachlorophene are discussed individually as
                                examples of these  compounds that are familiar and for which there are some
                                human data.

Toxicology of Cresols
    Cresols, in common with phenol and other phenolic compounds, are highly
corrosive to all surfaces.With ingestion of concentrated forms they cause severe
corrosive injury to the mouth and upper gastrointestinal tract. Likewise, severe
eye and skin caustic injuries can occur with cresol exposure.29 Symptoms usu-
ally include nausea, vomiting, and diarrhea. Hypotension, myocardial failure,
pulmonary edema, and neurological changes may also occur.30 Liver and renal
toxicity, methemoglobinemia, and hemolysis have all been reported.30-31 After
long-term, repeated exposure, contact dermatitis may complicate these expo-
sures. These compounds are well absorbed from the gastrointestinal tract and
are also significantly absorbed from the skin and by inhalation.
Treatment: Cresols
1. Gastrointestinal decontamination. Due to the corrosive nature of these
compounds, gastrointestinal decontamination should not be attempted. Con-
sideration of dilution with milk or water is appropriate if vomiting has not

2. Endoscopy. If a corrosive injury has occurred with burns to the mouth, or
if there is a clear history of gastrointestinal exposure, endoscopy should be
considered and a gastroenterologist or surgeon should be consulted for diagno-
sis and management.

3. Skin decontamination.  If skin or eye contamination has occurred, copi-
ous irrigation should be performed. This should be followed by a careful eye
examination for  corneal burns. If corneal burns  are noted, ophthalmologic
consultation should be obtained.

4. Respiratory and circulatory support should be provided in accordance
with sound medical management. If severe systemic symptoms persist, the pa-
tient should be treated in an intensive care unit, if  possible.
Toxicology of Hexachlorophene
    Hexachlorophene is well absorbed orally and dermally. Dermal exposures
have led to severe toxicity and death in neonates, due to application to dam-
aged skin, or repeated or high-concentration skin exposures.32 Hexachlorophene
should never be used as a disinfectant on open wounds or abraded or inflamed
skin surfaces. In  distinction to  other  phenolic compounds, this agent is not
significantly caustic and exposure does not result in the severe caustic injuries
seen with other phenolic chemicals.
                                                                                       DISINFECTANTS • 203

                                     Hexachlorophene is a potent neurotoxicant. It  causes brain edema and
                                 spongy degeneration of white matter.33 This neurotoxicity can be seen after
                                 acute or chronic exposures, either by skin absorption or ingestion.The nervous
                                 system symptoms are complex. Lethargy is an early manifestation, followed by
                                 muscular weakness, muscular fasciculation, irritability, cerebral edema, and pa-
                                 ralysis, leading to coma and death. Seizures  commonly occur in more severe
                                 cases.32-34 Blindness and optic atrophy have been reported following exposure
                                 to hexachlorophene.35
                                     In addition to the neurological effects, common early symptoms of poison-
                                 ing are vomiting, diarrhea, and anorexia.34 These findings have been accompa-
                                 nied in animals by significant hepatotoxicity36 With skin exposure, an erythema-
                                 tous desquamative rash is  often noted at the site of exposure.34 With chronic
                                 exposure, contact dermatitis may be noted. In severe poisonings, cardiovascular
                                 symptoms, including hypotension and bradycardia, have been noted.37 In a single
                                 case, repeated exposure to this compound led to asthma in a pediatric nurse.38
                                 Treatment: Hexachlorophene
                                 1. Gastrointestinal decontamination. Since this agent is not generally caustic,
                                 consideration should be given to aggressive gastrointestinal decontamination. If
                                 the patient has ingested a significant amount and is seen within one hour of
                                 exposure, gastric emptying is likely to be useful, as described in Chapter 2.
                                     Since hexachlorophene is thought to have an enterohepatic recirculation, it
                                 is possible that repeated dosing of activated charcoal, as outlined in Chapter 2,
                                 will enhance clearance of this compound. However, hexachlorophene does not
                                 bind well to charcoal and there are no clinical trials of this therapy for this agent.

                                 2. Other therapies. Though this compound is quite toxic systemically and
                                 enhanced clearance methods would appear beneficial, there is no evidence to
                                 support the efficacy of hemodialysis, peritoneal dialysis, hemoperfusion, or ex-
                                 change transfusion.37

                                 3. Skin decontamination. If exposure has occurred through the skin, aggres-
                                 sive washing of skin with soap or detergent and water is probably beneficial, to
                                 remove any residues still on the skin. Since hexachlorophene  is not soluble in
                                 water, water washing alone will provide no significant benefit. See Chapter 2.

                                 4. Neurological  support and  control of seizures is critical to survival and
                                 should be performed, when possible, in an intensive care setting. Seizure con-
                                 trol should be in accordance with recommendations in Chapter 2.

                                 5. Cardiovascular and respiratory support are also very important to sue
                                 cess in treating severe poisonings with this agent and should be provided in an
                                 intensive care unit in accordance with accepted medical practice.


    Pine oil detergent and disinfectant solutions are among the most common
poisonings reported to poison control centers in the U.S. A relatively high
number of these are reported as serious or fatal. Pine oil is found in a variety of
household and commercial cleaners and disinfectants. It is a mixture of mono-
terpenes derived from the distillation of wood from various pine species, with
approximately 57% being alpha-pinene.39 Its most common side effects in smaller
dosage are irritation of mucous membranes, gastrointestinal irritation, mild res-
piratory and CNS depression, and renal toxicity Larger ingestions can result in
severe respiratory distress, cardiovascular collapse, and severe CNS effects. Re-
nal failure and myoglobinuria have also been reported in severe poisonings.40
Since even  small ingestions can result  in severe  aspiration pneumonia, all
ingestions should be considered potentially hazardous.
    While many of the reported effects of poisoning with this agent are related
to direct irritant effect on mucous membranes, gastrointestinal tract, and lung
(by aspiration), some reports suggest significant absorption from oral and rectal
exposures. Other reports suggest a lesser rate of absorption.39  While alpha-
terpineol can be measured in blood, there are no data relating levels to degree
of toxicity.  Consequently, this measure  is not considered useful in guiding
diagnosis and management.
1.  Gastrointestinal decontamination. Since there is a high risk of aspira-
tion pneumonia, induced emesis is usually considered contraindicated in these
poisonings. However, spontaneous emesis may occur due to direct irritation of
the gastric mucosa.
    If the patient is seen within an hour of ingestion and a large amount has
been ingested, gastric emptying by intubation and lavage may be considered, as
described in Chapter 2. However, some studies have suggested greater rates of
complications with lavage than with  ipecac-induced emesis.40
    There is no evidence that activated charcoal is helpful in these poisonings.
Likewise, though a variety of enhanced elimination methods have been pro-
posed and tried, there is no evidence to support their efficacy.

2.  Eye decontamination.  If eye exposure has occurred, copious irrigation
of the eyes is appropriate.

3.  Pulmonary symptoms.  The patient should be observed for at least six
hours with any significant ingestion in order to observe the onset of any symp-
toms, particularly pulmonary symptoms.  If any pulmonary symptoms  are ob-
served, the patient should have  a chest film and measurement of oxygenation,
                                                                                          DISINFECTANTS • 205

                                       and hospitalization is appropriate. With severe pulmonary symptoms, transfer
                                       to an intensive care unit is usually appropriate. With severe aspiration, manage-
                                       ment should be handled as in any severe aspiration pneumonia, in accordance
                                       with accepted medical practice. Other severe systemic effects should be treated
                                       in accordance with accepted medical practice.

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31. ChanTK.Mak LW, and Ng RR Methemoglobinemia.heme bodies, and acute massive  intra-
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                                                                                                             DISINFECTANTS  • 207

                                 Index of Signs  and  Symptoms
                                Presented in this chapter are lists of pesticides reported to have caused particu-
                                lar symptoms and signs, or combinations thereof, in poisoned individuals.The
                                lists may help direct the attention of health professionals to possible toxic causes
                                of the various disease manifestations, prompting inquiry into likelihood of ex-
                                posure to the listed chemicals. If certain agents appear suspect, inquiry can then
                                be made into the presence of additional manifestations typical of poisoning by
                                those substances.
                                    The limitations of this approach to diagnosis must be understood. First, all
                                manifestations of illness  have  multiple causes, pesticidal and  nonpesticidal.
                                Second, there are no specific symptoms or signs that  are invariably present in
                                poisonings by particular pesticides.Third, many poisonings are characterized by
                                unexpected manifestations.
                                    Finally, neither route of exposure nor dosage of pesticide is taken into
                                account in this listing. For example, effects of high-dose ingestion are not
                                distinguished from effects of relatively low-dose  dermal absorption, nor are
                                topical effects distinguished from systemic dermal manifestations. The lists of
                                pesticides can only be regarded as clues to prompt further inquiry by the inter-
                                viewing professional.
                                    The term manifestation means either symptom or sign.The  word "poison-
                                ing" is used loosely in these headings to include topical as well as systemic effects.
                                Pesticides which are relatively consistent in causing particular manifestations are
                                listed in the middle column, headed "Characteristic of These Agents." Pesticides
                                that have caused various conditions with less consistency, or are  less prominent
                                features of poisoning, are listed in the right-hand column, headed "Occurs
                                withThese Agents." Obviously, the distinction is not clear-cut.
                                    Some symptoms (malaise, fatigue, dizziness) occur  so commonly  in poi-
                                soned individuals that they have little or no value in differential diagnosis, and
                                are therefore  not included in these tables.

Rotten egg odor
(fever, pyrexia)
Hot sensations
Alcohol intolerance
Sweet taste
in the mouth
Metallic taste in the
Salty, soapy taste
In the mouth

Chlorophenoxy compounds
Inorganic arsenicals
Sodium fluoride
Carbamate insecticides
Calcium cyanamide
Inorganic arsenicals
Organic mercury
Sodium fluoride


Inorganic arsenicals
Chlorophenoxy compounds
Cadmium dusts


Halocarbon fumigants
Inorganic arsenicals

                                                                   SIGNS AND SYMPTOMS -211


Blistering, or
Erosion (without

Contact dermatitis


Dermal sensitization

Beefy red palms, soles

Copper, organotin, cadmium
Metam sodium
Sodium chlorate
Sodium hypochlorite
Quaternary ammonia
Cationic detergents
Ethylene oxide
Aero le in
Methyl bromide
Ethylene dibromide
Aliphatic acids
Ethylene oxide

Liquid fumigants
Chlorophenoxy compounds
Herbicides with
irritant properties
Petroleum distillate

Thiram plus alcohol




Skin (continued)



Yellow stain
Keratoses, brown


Excessive hair growth
Loss of hair
Loss of fingernails

Brittle nails, white striations

Sweating, diaphoresis

Sodium fluoride
Sodium chlorate
Cadmium dusts
Sodium fluoroacetate
Inorganic arsenicals

Carbon tetrachloride
Sodium chlorate


Carbamate insecticides

Carbamate insecticides
Agents that cause shock,
myocardiopathy, severe
arrhythmias or convulsions

Inorganic arsenicals
Copper compounds

Inorganic arsenicals
Inorganic arsenicals
Inorganic arsenicals
Copper compounds

                                                                                     SIGNS AND SYMPTOMS -213

(irritation of mucous
membranes, tearing)
Yellow schlerae
Constricted visual fields
Optic atrophy
Dilated pupils
Unreactive pupils
Copper compounds
Organotin compounds
Cadmium compounds
Metam sodium
Aero le in
Sulfur dioxide
Ethylene oxide
Methyl bromide
Carbamate insecticides
Aero le in
Carbamate insecticides

Organic mercury

Carbamate insecticides
Chlorophenoxy compounds
Aliphatic acids
Agents that cause jaundice
(see above under Skin)

Organotin compounds

Nicotine (early)


Nervous  System
 (chiefly facial,
Nicotine (late)
Paresthesia of extremities
                            Inorganic arsenicals
                            Organic mercury
                            Sodium fluoroacetate
                            Carbon disulfide
                             Pyrethroids (transitory)
                            Carbamate insecticides
                            Inorganic arsenicals
                            Organic mercury
                            Cadmium compounds
                            Organotin compounds
                            Copper compounds
                            Halocarbon fumigants
Behavioral - mood
(confusion, excitement,
  mania, disorientation,
  emotional lability)
Organic mercury
Inorganic arsenicals
Organotin compounds
Sodium fluoroacetate
Carbon disulfide
Methyl bromide
Carbamate insecticides
Sodium fluoride
Depression, stupor, coma,
 respiratory failure, often
 without convulsions
Carbamate insecticides
Sodium fluoride
Inorganic arsenicals
Sulfuryl fluoride
Halocarbon fumigants
Chlorophenoxy compounds
Alkyl phthalates
                                                                                                 SIGNS AND SYMPTOMS -215

                           Nervous System (continued)

(clonic-tonic) sometimes
leading to coma

Muscle twitching

Tetany, carpopedal spasms


(including ataxia)

Paresis, muscle weakness

Hearing loss
Sodium fluoroacetate
Carbon disulfide
Sodium chlorate
Carbamate insecticides
Sulfuryl fluoride

Organic mercury
Carbamate insecticides
Halocarbon fumigants
Carbamate insecticides
Carbon disulfide
Inorganic arsenicals
Carbamate insecticides
Organic mercury
Inorganic arsenicals
Organotin compounds
Sulfuryl fluoride
Methyl bromide
Chlorophenoxy compounds
Carbamate insecticides

Organic mercury
Chlorophenoxy compounds

Chlorophenoxy compounds


Organic mercury

Organic mercury


Nervous System (continued)
Hypotension shock
Sodium fluoride
Sodium chlorate
Copper compounds
Inorganic arsenicals
Nicotine (late)
Alkyl phthalate
Thallium (early)
Nicotine (early)
Cardiovascular System
Cardiac arrhythmias
Sodium fluoroacetate
Halocarbon fumigants
Sodium fluoride
Ethylene oxide
Sodium chlorate
Veratrum alkaloid (sabadilla)
Inorganic arsenicals
Bradycardia (sometimes to
Carbamate insecticides
                                                                                          SIGNS AND SYMPTOMS -217

                          Respiratory System

Upper respiratory tract
irritation, rhinitis, scratchy
throat, cough

Runny nose

Pulmonary edema
(many chemicals come
packaged in a
hydrocarbon vehicle, well
known to cause
pulmonary edema)

Pulmonary consolidation


Aero le in
Ethylene dibromide
Sulfur dioxide
Sulfuryl fluoride
Cadmium dusts
Inorganic arsenicals
Carbamate insecticides

Methyl bromide
Ethylene oxide
Ethylene dibromide
Aero le in
Sulfur dioxide
Cationic detergents
Methyl isothiocyanate
Cadmium dusts
Methyl bromide
Carbamate insecticides
Cadmium dusts
Sulfuryl fluoride
Methyl bromide
Sulfur dioxide
Dry formulation of copper, tin,
zinc compounds
Dusts of thiocarbamate and
other organic pesticides
Chlorophenoxy compounds
Aliphatic acides

Dry formulation of copper, tin,
zinc compounds
Dusts of thiocarbamate and
other organic pesticides
Chlorophenoxy compounds
Aliphatic acides
Carbamate insecticides




Gastrointestinal Tract and Liver
Nausea, vomiting,
 commonly followed by
Carbamate insecticides
Cadmium compounds
Organotin compounds
Copper compounds
Sodium chlorate
Chlorophenoxy compounds
Carbon disulfide
Halocarbon fumigants
Red quill
Methyl  bromide
Veratrum alkaloid
B. thuringiensis
Ethylene dichloride
Ethylene oxide
Many pesticides have some
 irritant property
Diarrhea (first)
B. thuringiensis
Cationic detergents
Chlorophenoxy compounds
Diarrhea (bloody)
                                                                                             SIGNS AND SYMPTOMS -219

                                 Gastrointestinal Tract and  Liver (continued)

Abdominal pain



Carbamate insecticides
Inorganic arsenicals
Cadmium compounds
Copper compounds
Organotin compounds
Inorganic arsenicals
Copper compounds
Carbamate insecticides
Sodium fluoride
Cadmium compounds

Chlorophenoxy compounds
Aliphatic acids
Sodium chlorate
Fumigants (ingested)



Copper compounds
Sodium chlorate
Carbon tetrachloride
Inorganic arsenicals
                                 Jaundice -
                                 see section on Skin


Sometimes leading
to oliguria
Acute renal failure with
azote mia

Dysuria, hematuria, pyuria

Wine-red urine
Smoky urine

Inorganic arsenicals
Copper compounds
Sodium fluoride
Sodium chlorate
Sulfuryl fluoride
Ethylene dibromide
Sodium chlorate


Cadmium compounds
Chlorophenoxy compounds
Organotin compounds


Organotin compounds

Reproductive System
Low sperm count
                                                                      SIGNS AND SYMPTOMS • 221

Elevated LDH
alkaline phosphatase,
ALT, AST enzymes
Depressed RBC
Acetylcholinesterase and
Sodium chlorate
Sodium chlorate
Sodium chlorate

Sodium chlorate
Inorganic arsenicals
Inorganic arsenicals
Carbon tetrachloride
Copper compounds
Carbon tetrachloride
Sodium fluoride

Organotin compounds

Inorganic arsenicals
Sodium chlorate
Chlorophenoxy compounds
Carbamate insecticides

Index of Pesticide Products
1,2-dichloropropane	157
1,2-epoxyethane	158
1,3-dichloropropene	157
2-benzyl-4-chlorophenol	197
2-methyl-3, 6 dichlorobenzoic acid. 95
2,3,6-TBA	119
2,4-D	94-95,97-98
2,4-DB	95
2,4-dichlorophenoxyacetic acid . 95, 98
2,4-dichlorophenoxybutyric acid.... 95
2,4-dichlorophenoxypropionic acid  95
2,4-DP	95
2,4,5-T	94-95
2,4,5-trichlorophenoxy acetic acid.. 95
4-Aminopyridine 	 183-184, 194
4-tert-amylphenol	197
1080	177
1081	177
A7Vapam	140
Aaterra	152
Aatrex	121
Abate	 35
Abathion	 35
Abol	 49
Acaraben	 75
acaricides	74, 104
Acarstin	 75
Accelerate 	184
Accotab	120
Accothion	 35
acephate	 35
acetamides	119
Acrex	105
Acricid	105
acrolein	 156, 158
acrylonitrile	 156-157, 161, 163-165
Actellic	 35
Activol	 64
Actor 	109
Afalon	122
Aficida 	 49
Afugan	 35
Agree	 64
Agri-Mycin 17	 65
Agritox 	 35
Agrosan	147
Agrothion	 35
Agtoxin	158
Akar	 75
alachlor	119
Alanox	119
alcohols	192-193, 196-197
aldehydes	 158, 161, 197
aldicarb 	49, 50
aldrin  	 55-57
Align	 64
alkyl phthalates	 74-75
allethrin  	76, 89
Allisan	138
Alon	122
Alphos 	158
Altosid 	 76
Amaze	 35
Ambox	105
Ambush 	 77
Amerol	121
Ametrex	121
ametryn	121
Amex	120
aminocarb	 49
4-Aminopyridine 	 183-184, 194
aminotriazole 	121
Amiral	152
amitrole	121
Ammo 	 76
anilazine	152
anilides	119
Ansar  170	 127,134
AnsarSlOO	 127,134
Anthio 	 35
anticaking agents	 184, 193
Anticarie	138
anticoagulant rodenticides	5,6
Antimilace	184
Apache	 35
Apachlor	 35
Apex	 76
Aphox	 49
Apl-Luster	152
aprocarb	 50
Aquabac	 64
Aquacide	109
Aquathol	 121, 184
Aquinite	157
Arbotect	152
Arelon	122
Aresin 	122
Aretit  	105
Arrhenal	 127,134
Arsenal	120
                                                                                     INDEX OF PESTICIDES • 223

                                   arsenic acid	 127, 133
                                   arsenic trioxide	127, 129, 133
                                   arsenical pesticides .. 126, 145, 147, 149
                                   arsinegas	126-127, 129,132
                                   Arsinyl 	 127,134
                                   Arsonate Liquid	 128, 134
                                   Aspon 	 35
                                   Aspor	144
                                   asulam	119
                                   Asulox	119
                                   Asuntol	 35
                                   Atranex	121
                                   atrazine 	121
                                   Aules	140
                                   Auton 	 75
                                   Avicol 	138
                                   Avitrol	184
                                   Azac	119
                                   Azadirachtin	63-64
                                   Azar	119
                                   Azatin	 64
                                   azinphos-methyl	 35
                                   Azodrin	 35
                                   Azofene	 35
                                   Azolan 	121
                                   Azole 	121
                                   Aztec 	 35

                                   Bacillus thuringiensis 	 64, 72
                                   Bactimos	 64
                                   Bactospeine	 64
                                   Bactur	 64
                                   Balan	120
                                   Balfin	120
                                   Banvel	95,119
                                   Barricade 	 76
                                   Barrier 	119
                                   barthrin	 76
                                   Basagran	119
                                   Basalin	120
                                   Basanite	105
                                   Bash	 35
                                   Batasan	149
                                   Baygon	 50
                                   Bayleton	152
                                   Bayrusil	 35
                                   Baytex	 35
                                   Baythion 	 35
                                   Baythroid	 76
                                   Belmark	 77
                                   bendiocarb  	 49
                                   Benefin	120
                                   Benex 	152
                                   benfluralin	120
Benlate	152
benomyl	152
bensulide	 35
bentazone	119
benzalkonium chloride	 197-198
Benzamide	119
benzene hexachloride	 56
Benzilan	 75
Benzofuroline	 77
Benzothiadiazinone dioxide	119
Benzyl benzoate	 75
2-benzyl-4-chlorophenol	197
Berelex	 64
Betadine	197
Betasan	 35
Bexton	119
Bidrin	 35
Bilevon 	197
binapacryl 	105
bioallethrin	 76
Biologicals	 63
biopermethrin	 76
bioresmethrin	 76
Birlane 	 35
Black Leaf 40 	 64-65
Bladafum	 35
Bladex	121
Bo-Ana	 35
Bolate 	 127,134
Bolero	119
Bolls-Eye	 127,134
Bollwhip	 64
Bolstar	 35
bomyl	 35
Bophy	 127,134
borates 	 74-77
Borax	75-76,90
Bordeaux Mixture	145
boric acid	74-76, 90
Brace	 35
Bravo 	138
Brestan	149
Brodan	 35
brodifacoum	 170-172, 181
bromacil	122
bromadiolone	170
Bromofume	157
Bromone	170
bromophos	 35
bromophos-ethyl	 35
Broot 	 50
Bueno6	 128,134
bufencarb	 49
Busanl020 	140
butralin 	120

butylate	119
Bux	 49
cacodylic acid	 127, 134
Cad-Trete 	150
Caddy	150
Cadminate 	150
cadmium chloride	150
cadmium compounds	 137, 150
cadmium succinate	150
cadmium sulfate 	150
cadusafos	 35
Caid	170
Calar	 127,135
calcium acid methane arsonate. 127, 135
calcium arsenate	 127, 134
calcium arsenite	 127, 133
calcium cyanamide 	184
calcium hypochlorite	 197, 200
Caldon	105
Caliber 90	121
CAMA	127,135
Caparol	121
Captaf	145
captafol 	145
captan 	 145, 154
Captanex	145
CarbamateWDG  	140
carbamates	 5,12-13,49-50,
Carbamult	 50
Carbanilates	120
carbaryl	 49-50
carbofuran	48-50
carbon disulfide	40,156-158,
carbon tetrachloride	157-158, 164,
carbophenothion	 35
Carpene	152
Carzol	 49
Casoron 	119
Castrix	177
cationic detergents	 197-198, 200
CCN52	 76
Cekiuron	122
CekuC.B	138
Cekugib	 64
Cekumeta	184
Cekuquat	109
Celathion	 35
Celfume	157
Celmide	157
Ceresan	147
cetrimide	 197-198, 206
cetylpyridium chloride	  197-198
Chem Bam 	144
Chem-Fish	 64
Chemox General	105
ChemoxPE  	105
Chemsect DNBP	105
Chemsect DNOC	105
Chermox PE	105
ChipcoThiram75	140
chlordane	55-57, 61
chlordecone  	55-57, 62
chlordimeform	 74-75, 77-78
chlorethoxyfos	 35
chlorfenvinphos	 35
chlorhexidine	 197-199, 206
chlorimuron	122
chlormephos	 35
Chloro-IPC  	120
chlorobenzilate .... 56, 74-75, 78-79, 91
chloroform	  156-157
chloroneb	  138-139
chlorophacinone	  170, 181
Chlorophen	100
chlorophenoxy herbicides	94, 98
chloropicrin	  156-157
chlorothalonil	 138-139, 154
chlorotoluron	122
chlorphoxim 	 35
chlorpropham 	120
chlorpyrifos	6, 35-36
chlorthaldimethyl	121
chlorthiophos	 35
cholecalciferol 	  179-180
Chrysron	 77
Ciodrin	 35
cismethrin	76, 89
Classic	122
cloethocarb 	 49
clomazone	120
Clorto Caffaro	138
Clortosip	138
Clortran	138
Co-Ral	 35
Co-Rax	170
Cobex	120
Comite  	 76
Command	120
Compound 1080	177
Compound 1081	177
Contrac	170
Contraven	 35
convulsants	177
copper acetate 	145
copper acetoarsenite	  127, 133
                                                                                          INDEX OF PESTICIDES • 225

                                  copper ammonium carbonate	145
                                  copper arsenite
                                      (acid copper arsenite)	127
                                  copper carbonate, basic	145
                                  copper compounds	 137, 145-146
                                  copper hydroxide 	145
                                  copper lime dust	145
                                  copper linoleate	145
                                  copper oxychloride  	145
                                  copper potassium sulfide	145
                                  copper silicate	145
                                  copper sulfate	 145-146, 155
                                  Cotoran 	122
                                  cottonex	122
                                  coumachlor	170
                                  coumafene 	170
                                  coumaphos	 35
                                  coumarins	 169-171
                                  coumatetralyl	170
                                  Counter	 35
                                  Cov-R-Tox	170
                                  Crab-E-Rad	 127,134
                                  CragTurf Fungicide 	150
                                  creosote	 183-187, 194
                                  cresol	105,185,197, 202-203, 207
                                  crimidine 	 177-178
                                  Crisazina	121
                                  Crisfolatan	145
                                  Crisfuran	 49
                                  Crisquat	109
                                  Crisuron	122
                                  Crotothane	105
                                  crotoxyphos	 35
                                  crufomate	 35
                                  Cryolite	 75,82,85
                                  Cuman	140
                                  cupric oxide	145
                                  cuprous oxide	145
                                  Curacron	 35
                                  Curamil	 35
                                  Curaterr	 49
                                  Curitan	152
                                  cyanamide	 184, 194
                                  cyanazine 	121
                                  cyanofenphos 	 35
                                  cyanophos	 35
                                  Cyanox 	 35
                                  Cybolt	 77
                                  cycloate	119
                                  cycloheximide	 152-153
                                  Cyflee	 35
                                  cyfluthrin	 76
                                  Cygon	 35
                                  cyhexatin 	 74-75,79-80
                                  Cylan	 35
cythioate 	 35
Cythion 	 35
Cytrolane	 35
2,4-D	94-95,97-98
D-D92	157
D-trans	 76
Dachthal 	121
Daconate 6	 128, 134
Daconil2787 	138
Dailon	122
Dal-E-Rad	 128,134
Dalapon	119
Danitol	 77
Dapacryl 	106
Dart	 76
Dasanit	 35
2,4-DB	95
DBCP	26,157
DCNA	138
DCPA	121
DDT	55-58,79,118
De-Fol-Ate	184
De-Green	 35
Decis	 77
DEET	80-82,91
DEF	35
DeFend	 35
Defol	184
Deftor	122
Delnav 	 35
DeltaDust	 77
DeltaGard 	 77
deltamethrin	77, 89
Deltex	 77
demeton	 35
demeton-S-methyl	 35
Demon  	 77
Denarin	152
Dermaadex 	197
Des-i-cate 	184
Design	 64
desmetryn	121
Dessin	105
Detamide	 75

Dethdiet	179
Dextrone	109
Dexuron 	109
Di-allate	119
Di-Tac	127,134
Diacon	 76
dialifor 	 35
diallate 	119
Dianex	 76
Diaract	 76
diatomaceous earth	193
diazinon	35-36
Dibrom	 35
dibromochloropropane	26, 157, 162
dibromoethane	157
dibutylphthalate	 74-75
dicamba	95, 119
Dicarbam	 49
dichlobenil	119
dichloroethane 	157
dichlorofenthion	35-36
2,4-dichlorophenoxyacetic acid .. 95,98
2,4-dichlorophenoxybutyric acid	 95
2,4-dichlorophenoxypropionic acid . 95
1,2-dichloropropane	157
1,3-dichloropropene	157
dichloropropionic acid	119
dichlorprop	95, 98
dichlorvos 	 35
dicloran	 138-139
dicofol	 55-56
dicrotophos	 35
Dicuran	122
dieldrin	 55-57
Dieldrite 	 56
dienochlor	 56
diethyltoluamide	 74-75, 80, 91
difenacoum	170
diflubenzuron	76, 85
Difolatan	145
Dilie	 127,134
Dimecron	 35
dimefos	 35
dimephenthoate 	 35
dimetan	 49
Dimethan	 49
dimethoate	35, 37
dimethrin	 77
dimethyl phthalate	74, 75
Dimilin	 76
dinitramine	120
Dinitro	 105,107
Dinitro General Dynamyte	105
Dinitro Weed Killer 5	105
Dinitro-3  	105
dinitrocresol 	105
dinitrophenol 	 105-106
dinobuton	105
dinocap	 104-105
Dinofen 	105
dinopenton 	105
dinoprop 	105
dinosam 	105
dinoseb 	 105, 107
dinoseb acetate	105
dinoseb methacrylate	105
dinosulfon	106
dinoterb acetate	106
dinoterb salts	106
dinoterbon	106
dioxacarb	 49
dioxathion	 35
Dipel	 64
diphacin	170
diphacinone 	170
Dipher 	144
Dipterex	 35
diquat	 11-12,15,108-116
Direx 	122
Dirimal 	120
disinfectants	 5-7, 196-199
disodium arsenate	 128, 133
disodium methane arsonate ... 127, 134
disulfoton	 35
Disyston	 35
ditalimfos 	 35
Dithane	144
Dithione 	 35
Ditrac	170
Diurex 	122
Diuron	122
diuron	 109,122
DMA	127,134
DMP 	 75
DNAP	105
DNBP	105
DNC	105
DNOC	105
dodine	152
Dojyopicrin	157
Dolochlor 	157
Dosaflo	122
Dotan	 35
2,4-DP	95
DPA	119
DPX 1410	49
Dragnet	 77
Drawinol	105
Draza 	 49
DrexarSSO	 128,134
                                                                                           INDEX OF PESTICIDES • 227

                                  Drop-Leaf	184
                                  DSE	144
                                  DSMA	127,134
                                  Dual	119
                                  Duraphos	 35
                                  Duratox	 35
                                  Dursban	 35
                                  dusts	18,66,70,90,138,
                                  Dycarb	 49
                                  Dyclomec 	119
                                  Dyfonate	 35
                                  Dylox	 35
                                  Dyrene	152

                                  E601	35
                                  E-48	35
                                  E-D-Bee	157
                                  E-Z-OffD	35
                                  E605	35
                                  Earthcide	138
                                  Easyoff-D	 35
                                  EBDC compounds	144
                                  Ebufos	 35
                                  EDB	157
                                  EDC	157
                                  edifenphos	 35
                                  Ekamet	 35
                                  Ekatin	 35
                                  Eksmin	 77
                                  Elecron 	 49
                                  Elimite	 77
                                  ElgetolSO	105
                                  Elgetol318	105
                                  Emerald  green	 127, 133
                                  Emisan 6 	147
                                  emulsifiers	 184, 193
                                  Endosan	106
                                  endosulfan	55, 56
                                  endothall..  121,124,184,187-188,195
                                  Endothall Turf Herbicide	184
                                  endothion 	 35
                                  endrin	 55-56
                                  Entex	 35
                                  EPBP	35
                                  EPN	35
                                  1,2-epoxyethane	158
                                  EPTC	119
                                  Eradicane	119
                                  Esgram	109
                                  ethalfluralin	120
                                  Ethanox  	 35
                                  Ethazol	152
                                  ethion	 35
ethoprop 	 35
ethyl parathion	35, 37
ethylene dibromide .... 157-158, 162, 167
ethylene dichloride	 157-158
ethylene oxide	 156, 158
ETO	158
etridiazole	 152-153
etrimfos	 35
Etrofolan	 49
Eugenol 	64-65, 72
Evik	121
Exofene	197
ExothermTermil	138
Fac	 35
Fall	184
Famarin	170
Famfos	 35
Famid	 49
famphur	 35
Far-go	119
fenamiphos	 35
Fenchlorphos 	 35
fenitrothion	 35
Fenkill	 77
fenophosphon 	 35
fenothrin	 77
fenoxycarb 	 49
fenpropanate	 77
Fenpropar	 76
fenpropathrin	 77
fensulfothion	 35
fenthion	35, 37
fentin acetate	149
fentin chloride	149
fentin hydroxide	149
fenvalerate	 77, 87, 89, 91
ferbam	 140, 143
Ferberk 	140
FermideSSO	140
Fernasan	140
Fernos	 49
Ficam	 49
Flectron	 77
fluchloralin	120
flucythrinate	77, 87
Fluent	 77
flumeturon	122
fluorides	 74,82,85
fluoroacetamide	 169, 177
fluvalinate	77,87-89
FMC9044	106
Folbex	 75
Folcord 	 77

Folex	  35
Folosan	138
Folpan	145
folpet 	145
Foltaf	145
fonofos	  35
formaldehyde	 156, 158, 168, 197
formetanate hydrochloride 	  49
formothion 	  35
Fortress 	  35
Fortrol	121
fosamine	120
fosthietan 	  35
French green	 127, 133
Frunax-DS	170
Fumex 	158
fumigants 	82, 141, 156, 162,
Fumitoxin	158
fungicides	55,79,104,137,
Funginex	152
Fungitrol II 	145
Furadan	  49
furethrin	  77
Futura	  64
G 28029	35
GA3	64-65
Gallotox	147
gamma BHC or HCH 	 56
Gamophen	197
Gardona	 35
Gardoprim	121
Garlon	120
Gebutox	105
Gesafram 50	121
Gesagard 	121
Gesapax	121
Gesatop	121
gibberellic Acid 	 64-65
Gibberellin	64-65
Gibrel	 64
glutaraldehyde	6, 197-198
Glycophene	152
Glyfonox	120
Glyphosate	 6
glyphosate	120
Gnatrol	 64
Go-Go-San	120
Goldquat	109
Gramocil	109
Gramonol 	109
Gramoxone	109
gramoxone	116
Gramuron	109
granular formulations 	192
Granurex	122
Grocel	 64
Gusathion 	 35
Guthion	 35
Gypsine	 127,134

Haipen	145
Halizan	184
haloaromatic substituted ureas	 85
halocarbon fumigants 	156-157,
Hanane 	 35
Havoc 	170
HCB	 138-139
HCH	56
Hel-Fire	105
Helothion 	 35
heptachlor	 55-57
heptenophos	 35
Herald	 77
Herbi-All	 128,134
Herbicide 273 	184
Herbodox	120
hexachlor	 56
hexachloran	 56
hexachlorobenzene	55-56, 61, 103,
hexachlorophene	197, 202-204, 207
Hexadrin	 56
Hexaferb	140
Hexathane	144
Hexathir	140
Hexazir	140
Hi-Yield Dessicant H-10	 127, 133
Hibiclens	 197, 206
Hibistat	197
hiometon	 35
Hoe 002784	106
hosalone	 35
Hostaquick	 35
Hostathion	 35
hydrocyanic acid	157
hydrogen cyanide .... 156-158, 163-165
Hydrothol	184
hypochlorites 	 197,200
Hyvar	122

IBP	35
imazapyr	120
Imidan 	 35
                                                                                         INDEX OF PESTICIDES • 229

                                  indandiones	 169-171
                                  inorganic copper compounds	145
                                  Iodines	197
                                  iodofenphos 	 35
                                  loprep	197
                                  IP50	122
                                  iprodione 	 152-153
                                  isazofos	 35
                                  isofenphos	 35
                                  isolan 	 49
                                  Isopestox	 35
                                  isoprocarb 	 49
                                  isopropanol 	 184, 192, 196
                                  isopropyl alcohol	80, 196-197, 206
                                  isoproturon	122
                                  isoxathion	 35
                                  isoxazolidinone	120
                                  Jones Ant Killer	 128,133

                                  Rabat 	 76
                                  Rack	127,134
                                  Kafil	 77
                                  KafilSuper	 77
                                  Karathane	105
                                  Karbation	140
                                  Karmex	122
                                  Karphos 	 35
                                  Kayafume	157
                                  Kelthane	 56
                                  Kepone	56, 62
                                  Kerb	119
                                  Kiloseb	105
                                  Kitazin	 35
                                  Klerat	170
                                  Knockmate 	140
                                  Koban	152
                                  Kobu	138
                                  Kobutol	138
                                  Kopfume	157
                                  Korlan	 35
                                  Krenite	120
                                  Kromad	150
                                  Kryocide	 75
                                  Kusatol	184
                                  Kwell	55-56,61-62
                                  Kypfarin	170
                                  KypmanSO 	144
                                  Kypzin	144
                                  Lance ...
Lannate	 49
Lanox	 49
Larvacide	157
Larvin	 50
Lasso	119
Lead arsenate	134
lead arsenate	127
Leafex	184
lenacil 	122
leptophos 	 35
Lescosan	 35
Lexone	121
lindane	55-58, 61-62, 138
Linex  	122
Linorox	122
Linurex	122
linuron	122
Liphadione	170
Liqua-Tox	170
London purple	 127, 133
Lorox	122
Lorsban	 35
Lysol	185,197,207

M-Diphar 	144
MAA	 127,134
Magnacide B	158
Magnacide H  	158
Maki	170
malathion	 35, 37, 47
MAMA	127,134
mancozeb	144
Mancozin	144
maneb	 144, 154
Maneba	144
Manex 	144
ManexSO	144
manzeb 	144
Manzin 	144
Maposol	140
Marlate	 55-56
Matacil	 49
Mattch	 64
MCPA	95,98
MeBr	157
mecoprop	95, 97-98
Melprex 	152
MEMA	147
MEMC	147
Meothrin 	 77
mephosfolan	 35
Mercuram	140

mercurials 	148-149, 197, 202
mercurobutol 	197
mercurochrome	197
Merge 823 	 128,134
Merpafol	145
Merpan	145
merphos	 35
Mertect	152
merthiolate	197
Mesamate	 128, 134
Mesurol	 49
Metadelphene 	 75
metalaxyl	 152-153
metaldehyde	184, 188-189, 195
metalkamate	 49
Metam-Fluid BASF	140
metam-sodium	 140-141
Metaran 	 75
Metason	184
Metasystox-R	 35
Metasystox-S	 35
Metasystoxl	 35
Meth-O-Gas	157
methabenzthiazuron	122
methamidophos	 35
methane arsonic acid	 127, 134
methanol	 184, 192, 196
MetharSO	 127,134
methidathion	 35
methomyl	 49
methoprene	 74, 76, 86
methoxychlor	 56
methoxyethyl mercury acetate 	147
methoxyethyl mercury chloride	147
methoxyethyl mercury compounds ..147
methyl bromide	 156-157, 159,
2-methyl-3, 6 dichlorobenzoic acid ... 95
methyl mercury acetate 	147
methyl mercury compounds	147
methyl naphthalenes	193
methyl parathion	35-37, 46
methyl trithion	 35
methylene chloride.  157, 159, 161, 168
metobromuron	122
metolachlor	119
metoxuron 	122
metribuzin 	121
mevinphos	 35
mexacarbate 	 49
Mezene	140
MGK	75
Micromite	 76
Microzul 	170
Mightikill	 76
Miller 531 	150
Milo-Pro	121
Minex	 76
mipafox	 35
Miral	 35
mirex	 55-57
Mitis green	 127, 133
Mocap 	 35
Monitor	 35
mono-calcium arsenite	 127, 133
monoammonium methane
     arsonate	 127, 134
monocrotophos	 35
monolinuron	 109, 122
monosodium methane
     arsonate	 127, 134
monuron	122
Morrocid 	106
MSMA	 127,134
Multamat	 49
Muritan 	179
Muskol	 75
Mycodifol	145

N-2790	35
n-methyl carbamates	 48-51,
nabam	144
naled	 35
Namekil	184
naphthalene	66, 156-157, 159-162,
naphthenate	145
naramycin 	152
Neburex	122
neburon 	122
Neemazad	 64
Neemazal	 64
Neemix	 64
Neguvon	 35
Nem-A-Tak	 35
Nemacur	 35
Nemafume	157
Nemanax	157
Nemaset	157
Nemasol	140
Nemispor	144
Neopynamin	 78
Nephis	157
Nexagan	 35
Nexion  	 35
NIA9044 	106
Nico Soap	 64
                                                                                         INDEX OF PESTICIDES •  231

                                   nicotine	 63-67, 72-73
                                   Niomil	 49
                                   Nitrador	105
                                   nitrocresolic herbicides	 104-105
                                   nitrolime	184
                                   nitromersol	197
                                   nitrophenolic herbicides  . 104-105, 118
                                   Nitropone  C 	105
                                   Nix	 77
                                   No Bunt 	138
                                   Nomersam	140
                                   Nomolt	 76
                                   Novodor	 64
                                   Noxfire 	 64
                                   Noxfish	 64
                                   NRDC 149 	 77
                                   Nudrin	 49
                                   Nusyn-Foxfish	 64
                                   Nuvanol-N	 35
                                   oleate	 145, 193
                                   Omite	76,91
                                   OMPA	35
                                   organic copper compounds	146
                                   organochlorines	 5, 13, 55-59
                                   organomercury compounds	 137,
                                   organophosphates .... 5-6, 12-13, 34-37,
                                   organotin compounds	79, 80, 137,
                                   Ornamite	 76
                                   Orthene	 35
                                   Ortho Diquat	109
                                   Orthocide	145
                                   oryzalin	120
                                   Oust	122
                                   Outflank 	 77
                                   Oxadiazolinone	120
                                   oxadiazon	120
                                   oxamyl	 49
                                   oxirane	158
                                   Oxotin	 75
                                   oxydemeton-methyl	 35
                                   oxydeprofos	 35
                                   Panogen	147
                                   Panogen M	147
Pansoil 	152
Para-col	109
paradichlorobenzene	157, 160, 162
paraformaldehyde	 156, 158
paraquat	 11-12,15,107-117
Parathion	35, 46
Par is green 	127,133,145
Parzate 	144
ParzateC  	144
Pathclear 	109
Pattonex	122
Paushamycin.Tech	 65
Payoff	 77
PCNB	 138-139
PCP	99,100-102
PEBC	119
pebulate 	119
Penchlorol	100
pendimethalin	120
penetrants	 118, 184, 193
Pennant	119
Penncap-M 	 35
Penncozeb	144
Pennstyl 	 75
Penta	100
Pentac	 56
pentachloronitrobenzene	 138-139
pentachlorophenol	99, 103-104,
Pentacon	100
Pentagen	138
Penwar	100
Peridex	197
Permasect	 77
permethrin	77, 87-88
Perthrine	 77
PestoxXIV	 35
PestoxXV	 35
petroleum distillates	68, 192, 194
Phaltan	145
Pharmadine	197
Pharorid	 76
phencapton	 35
phenol(s)	5-6, 40, 50, 65, 99,185,
Phenostat-A	149
Phenthoate	 35
phenthoate	 35
Phentinoacetate	149
phenyl salicylate 	145
phenylmercuric acetate	197
phenylmercuric nitrate 	197
phenylphenol 	197
Phisohex	197
Phorate  	 87

phorate	35, 87
phosalone	35-36, 46
Phosdrin 	 35
phosfolan	 35
phosmet	 35
phosphamidon	 35
phosphine 	 156, 158, 160-161,
phostebupirim	 35
Phostoxin	158
phostoxin	160
Phosvel 	 35
Phosvin	173
phoxim 	 35
phthalthrin	 77
Phytar560	 127,134
Pic-Clor	157
picloram	121
pindone	170
pine oil	5-6,196-197, 205, 207
Pinene	121
pinene	205
piperonyl butoxide	 68-70, 184, 191
pirimicarb 	 49
pirimiphos-ethyl	 35
pirimiphos-methyl	 35
Pirimor	 49
pival	170
pivaldione 	170
pivalyn	170
Plantomycin	 65
Plictran 	 75
PMAA	147
Poast	120
PolyborS 	 75
Polyram-Ultra	140
Polytrin	 77
Pomarsol forte	140
Pounce	 77
povidone-iodine	197, 201-202, 207
Pramex	 77
Pramitol25E	121
Prebane	121
Precor	 76
Preeglone	109
Preglone	109
Premerge 3	105
Prenfish	 64
Primatol	121
PrimatolM 	121
Primicid	 35
Primin 	 49
Princep 	121
Pro-Gibb	 64
Pro-Gibb Plus	 64
Proban 	 35
Prodalumnol Double	 128, 133
Prodan 	 75
profenofos	 35
profluralin 	120
Prokil	 75
Prolate	 35
Prolex	119
promecarb	 50
prometon	121
Prometrex	121
prometryn	121
pronamide	119
propachlor	119
Propanex	119
propanil	119
propargite	6, 74, 85-86
propazine 	121
propetamphos	 35
propionate	147
propoxur	 50
propyl thiopyrophosphate	 35
propylene dichloride 	157
prothoate	 35
Prowl	120
Proxol	 35
Prozinex	121
prussic acid	157
Purivel 	122
Pynamin	 76
Pynosect	 77
pyrazophos	 35
pyrethrins	 5-6, 68-69, 87, 191
pyrethroids	5-6, 68, 74, 76, 87-88
pyrethrum	68-69, 73
pyridaphenthion	 35
Quickfos	158
Quilan 	120
quinalphos	 35
quinolinolate	 145, 147
Quintox	179
quintozene	138

Rabon	 35
Racumin	170
Rad-E-Cate 25	 127,134
Ramik	170
Rampage	179
Rampart	 35
Ramrod 	119
Ramucide	170
Rapid	49, 194
                                                                                          INDEX OF PESTICIDES • 233

                                   Rapier	119
                                   Ratak	170
                                   RatakPlus	170
                                   Ratomet	170
                                   Raviac	170
                                   RAX	170
                                   red squill 	179
                                   Reglone	109
                                   Regulex	 64
                                   repellents	 5, 74, 91
                                   resinate	145
                                   resmethrin	 77
                                   Revenge	119
                                   Ridall-Zinc	173
                                   Ridomil	152
                                   Ripcord 	 77
                                   Riselect	119
                                   Ro-Neet	119
                                   rodenticides	5-6, 169, 171,
                                   Rodine  	179
                                   Rody 	 77
                                   ronnel 	 35
                                   Ronstar	120
                                   Rotacide	 65
                                   rotenone 	64, 70
                                   Rotenone Solution FK-11 	 65
                                   Roundup	120
                                   Rovral	152
                                   Rozol	170
                                   Ruelene	 35
                                   Rugby	 35
                                   S-Seven	 35
                                   sabadilla	 63, 65, 71
                                   safeners 	 184,193
                                   Safrotin 	 35
                                   Safsan	 75
                                   SAGA	78
                                   Salvo	127,134
                                   Sanifume	158
                                   Sanspor 	145
                                   Saprol	152
                                   Sarclex 	122
                                   Saturn	119
                                   schradan	 35
                                   Schweinfurt green	 127, 133
                                   Selinon	105
                                   Semeron	121
                                   Sencor	121
                                   Sencoral	121
                                   Sencorex	121
                                   sethoxydim	120
                                   Setrete	147
Sevin	 49
Shaphos	158
Shimmer-ex	147
siduron	122
simazine	 109, 121
Sinbar 	122
Sinituho	100
Sinox 	105
Siperin	 77
Skeetal 	 64
Skeeter Beater	 75
Skeeter Cheater	 75
Skintastic for Kids 	 75
Snox General 	105
Sobrom98 	157
Sodanit	 128,133
Sodar 	 127,134
sodium arsenate	 128, 133
sodium arsenite  	 128, 133
sodium cacodylate	 127, 134
sodium chlorate	183-184,
sodium fluoaluminate	 75, 82, 85
sodium fluoride	75, 82-83
sodium fluoroacetate 	177
sodium fluosilicate	75, 82-83
sodium hypochlorite 	6, 197, 206
sodium polyborates	 75
sodium silico fluoride	75, 82
sodium tetraborate decahydrate	 75
Sok-Bt	 64
SolasanSOO 	140
solvents and adjuvants	 183, 192
Sometam	140
Sonalan	120
Soprabel	 127, 134
Sopranebe	144
Spike	122
SpotreteWP75	140
Spotrete-F	140
Spra-cal	 127,134
Spring Bak	144
Sprout-Nip 	120
Stam	119
Stampede 	119
stickers and spreaders	 184, 193
Stomp	120
streptomycin	65, 72
Strobane	 56
strychnine	169, 177-178, 182
Subdue	152
Subitex	105
substituted benzenes	 137-138,
Sulerex	122

sulfemeturon-methyl	122
sulfotep 	 35
sulfur	6,71,74,78,89,90,92
sulfur dioxide 	 156, 158, 160
sulfuryl fluoride	 82, 156, 158,
sulprofos	 35
Sumicidin	 77
Sumithion	 35
Super Crab-E-Rad-Calar	 127, 135
Super Dal-E-Rad	 127, 135
Super Tin	149
Supracide	 35
Surecide	 35
Surflan 	120
Surgi-Cen	197
Surofene	197
Suspend	 77
Sutan	119
Suzu	149
Suzu-H	149
Swat	 35
synergists	 68-69, 184, 191
Sypren-Fish	 65
systox	 35
2,4,5-T	94-95
Tag HL 331	147
Talan	105
Talcord	 77
Talon 	170
Tamex	120
Target MSMA	 128, 134
Tattoo	 49
2,3,6-TBA	119
TCA	119
TCBA	119
Tebusan	122
tebuthiuron	122
Tecto	152
teflubenzuron	76, 85
Teknar	 64
Telone II Soil Fumigant	157
temephos 	 35
Temik  	 49
terabacil  	122
terbucarb	119
terbufos	 35
terbuthylazine	121
Terbutrex 	121
Ternit	121
terpene polychlorinates 	 56
Terraklene	109
Terraneb SP 	138
Terrazole	152
Tersan 1991	152
4-tert-amylphenol	197
tertutryn 	121
tetrachlorvinphos 	 35
tetraethyl pyrophosphate	 35
tetramethrin	 78
Tetrapom 	140
Texosan	197
thallium sulfate	 173, 175
thiabendazole	 152-153
Thibenzole	152
Thimer  	140
thimerosol	197
Thimet	 35
thiobencarb	119
thiocarbamate insecticides	137, 140,
thiocarbamate herbicides	119
thiodicarb	 50
Thioknock	140
Thiophal	145
thiophos	 35
thiophthalimides	 137, 145
Thiotepp	 35
Thiotex	140
thiram	140-143,150,154
Thiramad	140
Thirasan	140
Thiuramin	140
Thuricide	 64
thymol	 197,202
Tiguvon	 35
Tillam	119
Tinmate	149
Tirampa	140
TMTD	140
Tolban	120
Tolkan	122
toluene	 184,192
Tolurex  	122
Tomcat	170
Topitox	170
Torak 	 35
Tordon	121
Torus	 49
Tota-col 	109
Tox-Hid	170
toxaphene 	 55-57
TPTA	149
Tralex	 78
tralomethrin	 78
Trametan	140
Trans-Vert	 128,134
                                                                                         INDEX OF PESTICIDES • 235

                                   Treflan	120
                                   Tri-PCNB 	138
                                   triadimefon	 152-154
                                   triallate	119
                                   triazines	121
                                   Triazole	121
                                   triazophos 	 35
                                   Tribac 	119
                                   Tribactur	 64
                                   Tribunil	122
                                   tricalcium arsenate	 127, 134
                                   Tricarbamix	140
                                   trichlorfon	 35
                                   trichloroacetic acid	119
                                   trichlorobenzoic acid	119
                                   trichloromethane	157
                                   trichloronate  	 35
                                   2,4,5-trichlorophenoxy acetic acid ... 95
                                   triclopyr	120
                                   triclosan	 197,202
                                   trifluralin	120
                                   Trifocide	105
                                   Triforine	154
                                   triforine 	 152, 154
                                   Trifungol	140
                                   Trimangol	144
                                   Trimaton	140
                                   trimethacarb	 50
                                   triphenyl tin	149
                                   Tripomol	140
                                   Triscabol 	140
                                   Trithion	 35
                                   Tritoftorol	144
                                   Triumph 	 35
                                   Truban	152
                                   Tuads 	140
                                   Tubotin	149
                                   Tuffcide	138
                                   Tupersan 	122
                                   Turcam	 49
                                   Turf-Cal	 127,134
                                   Turflon	120
                                   Turplex	 64

                                   Ultracide	 35
                                   Unicrop DNBP	105
                                   Unidron	122
                                   Unisan 	147
                                   uracils	122
                                   Ustadd 	 77

                                   Vancide MZ-96	140
                                   Vapam	140
Venturol	152
Venzar	122
veratrum alkaloid	 71
Vernam	119
vernolate	119
Vertac	105
Vertac  General Weed Killer	105
Vertac  Selective Weed Killer 	105
Vigilante 	 76
Vikane 	158
Volid	170
Vondcaptan	145
Vonduron	122
VPM	140
Vydate L	 49

warfarin 	 169-170, 181
Wax Up 	120
Weed-E-Rad	 128, 134
Weed-E-Rad 360	 127,134
Weed-Hoe	 128,134
Weedazol  	121
Weedol	109

XenTari 	 64
xylene	 184,192
yellow phosphorus	 173-175, 181

Zebtox	144
Zectran	 49
Ziman-Dithane	144
zinc arsenate	 128, 134
zinc phosphide	169, 173-175, 181
Zinc-Tox	173
Zincmate  	140
zineb	 144, 154
ziram	 140,143
ZiramF4	140
Ziram Technical	140
Zirberk 	140
Zirex90	140
Ziride 	140
Zitox	140
Zolone	 35
zoocoumarin	170
Zotox	127,133