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DFP: Diisopropyl fluorophosphate. TOXNET Hazardous Substances Data Base.


From TOXNET

see for Updates: http://www.toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

DIISOPROPYL FLUOROPHOSPHATE
CASRN: 55-91-4
For other data, click on the Table of Contents

Human Health Effects:

Human Toxicity Excerpts:

... A 12-month-old boy, who had received one drop of 0.1% DFP in each eye daily for 2 months, experienced two brief apneic spells, with probable seizure activity for 1 or 2 minutes each time ... miotic, unreactive pupils, profuse nasal discharge & possible motor weakness /noted/. Eight hr after admin, he had a typical grand mal convulsion lasting 2 to 3 minutes. ... The cholinesterase activity of serum collected 60 hr after the last eye drop was below the range of normal & 44% of the average normal.
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 332]**PEER REVIEWED**

TREATMENT OF GLAUCOMA WITH POTENT, LONG-ACTING ANTICHOLINESTERASE AGENTS (INCLUDING ... ISOFLUROPHATE) FOR 6 MONTHS OR LONGER CARRIES HIGH RISK OF THE DEVELOPMENT OF A SPECIFIC TYPE OF CATARACT, WHICH BEGINS AS ANTERIOR SUBCAPSULAR VACUOLES. ALTHOUGH FORMATION OF SPONTANEOUS CATARACTS IS QUITE COMMON WITHIN COMPARABLE AGE GROUPS, THE INCIDENCE OF LENTICULAR OPACITIES UNDER SUCH CIRCUMSTANCES CAN BE AS HIGH AS 50%; THE HAZARD IS APPARENTLY INCREASED IN PROPORTION TO THE STRENGTH OF SOLUTION, FREQUENCY OF INSTILLATION, DURATION OF THERAPY, & AGE OF THE PATIENT. THE UNDERLYING MECHANISM REMAINS ELUSIVE ... MISCELLANEOUS OCULAR SIDE EFFECTS THAT MAY OCCUR FOLLOWING LOCAL INSTILLATION OF ANTICHOLINESTERASE AGENTS ARE HEADACHE, BROW PAIN, BLURRED VISION, PHACODINESIS, PERICORNEAL INJECTION, CONGESTIVE IRITIS, VARIOUS ALLERGIC REACTIONS, &, RARELY, RETINAL DETACHMENT.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 124]**PEER REVIEWED**

... DFP ... has the property of inducing a ... delayed neurotoxicity. ... The clinical picture is that of a severe polyneuritis that begins several days after exposure to a sufficient single or cumulative amt of the toxic cmpd. It is manifested initially by mild sensory disturbances, ataxia, weakness, and ready weakness of the legs, accompanied by reduced tendon reflexes & ... muscle twitching, fasciculation, & tenderness to palpation. In severe cases, the weakness may progress eventually to complete flaccid paralysis that, over the course of weeks or months, is often succeeded by a spastic paralysis with a concomitant exaggeration of reflexes. During these phases, the muscles show marked wasting. Recovery may require 2 or more yr.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 122]**PEER REVIEWED**

Do not inhale vapors. Avoid contact with skin. Even traces of the vapor cause myosis. Highly toxic; cholinesterase inhibitor.
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 744]**PEER REVIEWED**

This compound is a cholinesterase inhibitor, a neurotoxin, and has reproductive effects.
[Lunn, G., E.B. Sansone. Destruction of Hazardous Chemicals in the Laboratory. New York, NY: John Wiley & Sons, Inc. 1994. 149]**PEER REVIEWED**

The onset of the clinical manifestation of organophosphate poisoning usually occurs within 12 /hours/ of exposure.
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995. 979]**PEER REVIEWED**


Drug Warnings:

... Should be used cautiously in patients with bronchial asthma, bradycardia, or hypotension. An increase in blood pressure may occur occasionally due to a nicotinic effect on sympathetic ganglia.
[American Medical Association, AMA Department of Drugs. AMA Drug Evaluations. 5th ed. Chicago: American Medical Association, 1983. 449]**PEER REVIEWED**

Because of their cataractogenic properties & other toxicity, /diisopropyl fluorophosphate/ should be reserved for patients refractory to short-acting miotics, epinephrine, beta-blocking drugs, & possibly, carbonic anhydrase inhibitors. /Long-acting miotics, including floropryl/
[American Medical Association, AMA Department of Drugs. AMA Drug Evaluations. 5th ed. Chicago: American Medical Association, 1983. 447]**PEER REVIEWED**


Medical Surveillance:

The assessment of exposure to the organophosphate pesticides, bromophos and dicrotophos, can be accomplished through measurement of these compounds in the blood. However, since organophosphate pesticides are rapidly cleared from the blood, it is difficult to be able to detect the pesticides in blood unless very large quantities have been absorbed. This test may be useful for identification of the compound in cases of severe exposure, although documented tests for measurement of specific organophosphate pesticides in blood are very limited. Blood Reference Ranges: Normal - None detected; Exposed - Not detected; Toxic - Not established. Serum or Plasma Reference Ranges: Normal - Not established; Exposed - Not established; Toxic - Not established. Urine: The assessment of organophosphate pesticide exposure can be accomplished through measurement of the following alkyl phosphate metabolites: dimethylphosphate, diethylphosphate, dimethylthiophosphate, diethylthiophosphate, dimethyldithiophosphate, and diethyldithiophosphate. ... The one limitation to measurement of urinary alkyl metabolites is that this test is only useful for assessing recent exposure, due to the short half-life of organophosphate pesticides. Urine Reference Ranges: Normal - Note established; Exposed - Not established; Toxic - Not established. /Organophosphate Pesticides/
[Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, washington, D.C. 1997. 1857]**PEER REVIEWED**

Initial Medical Examination: A complete history and physical examination: The purpose is to detect pre-existing conditions that might place the exposed employee at increased risk, and to establish a baseline for future health monitoring. ... Examination of the respiratory system, nervous system, cardiovascular system, eyes, and attention to the cholinesterase levels in the blood should be stressed. The skin should be examined for evidence of chronic disorders. ... The cholinesterase activity in the serum and erythrocytes should be determined by using medically acceptable biochemical tests prior to any new period of exposure. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 1]**PEER REVIEWED**


Populations at Special Risk:

Persons with a history of reduced pulmonary function, convulsive disorders, or recent exposure to anticholinesterase agents would be expected to be at an increased risk. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 1]**PEER REVIEWED**

Probable Routes of Human Exposure:

Occupational exposure to diisopropyl fluorophosphate may occur through dermal contact with this compound at workplaces where diisopropyl fluorophosphate is produced or used. (SRC)
**PEER REVIEWED**


Emergency Medical Treatment:

Emergency Medical Treatment:

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The following Overview, *** DIISOPROPYL FLUOROPHOSPHATE ***, is relevant for this HSDB record chemical.

Life Support:
  o   This overview assumes that basic life support measures
      have been instituted.                           
Clinical Effects:
  SUMMARY OF EXPOSURE
   0.2.1.1 ACUTE EXPOSURE
     o   Diisopropyl fluorophosphate (DFP) is an organophosphate
         compound used as an insecticide, a substrate for the
         production of organophosphate military "nerve" gases
         and formerly as a topical miotic medication in
         ophthalmology.  The following are symptoms of
         organophosphates in general, due to the
         anticholinesterase activity of this class of compounds.
         All of these effects may not be documented for DFP, but
         could potentially occur in individual cases.
      1.  DFP forms HYDROGEN FLUORIDE is the presence of
          moisture (Refer to the HYDROFLUORIC ACID MEDITEXT(R)
          Medical Management for more information).
      2.  DFP has been used as an experimental agent in
          neuroscience because of its ability to inhibit
          cholinesterase and cause delayed peripheral
          neuropathy.  It has been also used as a miotic agent
          in the treatment of glaucoma.  Although DFP has caused
          experimental distal anoxopathy, no cases of peripheral
          neuropathy have been reported in patients treated with
          this agent for glaucoma.
      3.  Cataracts may occur following treatment of 6 or more
          months duration with DIFP.
      4.  Two workers with occupational inhalation and dermal
          DFP exposure developed dim vision, difficulty in
          focusing vision, excessive lacrimation, small pupils,
          pain behind the eyes, nausea, vomiting, and diarrhea.
     o   MUSCARINIC (PARASYMPATHETIC) EFFECTS may include
         bradycardia, bronchospasm, bronchorrhea, salivation,
         lacrimation, diaphoresis, vomiting, diarrhea, and
         miosis.  NICOTINIC (SYMPATHETIC AND MOTOR) EFFECTS may
         include tachycardia, hypertension, fasciculations,
         muscle cramps, weakness, and RESPIRATORY PARALYSIS.
         CENTRAL EFFECTS may include CNS depression, agitation,
         confusion, delirium, coma, and seizures.
     o   Children may have different predominant signs and
         symptoms than adults:  CNS depression, stupor,
         flaccidity, dyspnea, and coma are the most common signs
         in children.
  VITAL SIGNS
   0.2.3.1 ACUTE EXPOSURE
     o   Fever, bradycardia, hypotension, tachycardia, and
         hypertension may occur.
     o   A self-limited decrease in body temperature was noted
         in rats administered DFP.
  HEENT
   0.2.4.1 ACUTE EXPOSURE
     o   Miosis, lacrimation, and blurred vision are common;
         mydriasis may occur in severe poisonings.  Opsoclonus
         has been reported in one case.  Excessive salivation
         commonly occurs.
   0.2.4.2 CHRONIC EXPOSURE
     o   Decreased visual acuity and persistent photophobia may
         be seen.
     o   DFP has been used as a miotic agent for the treatment
         of glaucoma.  Rarely, angle-closure glaucoma has been
         provoked by treatment with such agents.
      1.  Patients treated with anticholinesterase medications
          (such as DFP) for glaucoma have rarely had retinal
          detachment.
  CARDIOVASCULAR
   0.2.5.1 ACUTE EXPOSURE
     o   Bradycardia, hypotension, and chest pain may occur.
         Tachycardia and hypertension may also be noted.
         Arrhythmias and conduction defects may occur in severe
         poisonings.  Myocarditis may develop.
  RESPIRATORY
   0.2.6.1 ACUTE EXPOSURE
     o   Dyspnea, rales, bronchorrhea, bronchospasm, or
         tachypnea may be noted.  Noncardiogenic pulmonary edema
         may occur in severe cases.  Chemical pneumonitis may be
         seen, especially following pulmonary aspiration of
         hydrocarbon-based diluents.
     o   Bronchospasm may occur in previously sensitized
         asthmatics or as a muscarinic pharmacological effect.
     o   Acute respiratory insufficiency is the main cause of
         death in acute poisonings.
  NEUROLOGIC
   0.2.7.1 ACUTE EXPOSURE
     o   Headache, dizziness, muscle spasms, and profound
         weakness are common.  Alterations of level of
         consciousness, anxiety, paralysis, seizures, and coma
         may occur.  Seizures may be more common in exposed
         children.
      1.  Seizures, apneic spells, miosis, profuse nasal
          discharge, and muscle weakness were noted in a
          12-month-old boy treated with DFP eye drops daily for
          2 months; serum cholinesterase level 60 hours after
          the last drop was instilled was 44% of normal.
     o   Peripheral neuropathy of the mixed sensory-motor type
         may be delayed in onset by 6 to 21 days following
         exposure to some organophosphates.  Recovery may be
         slow or incomplete.
     o   Dyskinesias may develop.  Abnormal neuropsychiatric
         tests and EEGs may persist for months following acute
         exposure.
   0.2.7.2 CHRONIC EXPOSURE
     o   DIFP has been used as an experimental agent in
         neuroscience because of its ability to inhibit
         cholinesterase and cause delayed peripheral neuropathy.
         Delayed peripheral neuropathy has been especially
         demonstrated in the standard hen assay.
     o   DIFP has been used as a miotic agent for treatment of
         glaucoma, but no cases of peripheral neuropathy have
         been reported in patients so treated.
  GASTROINTESTINAL
   0.2.8.1 ACUTE EXPOSURE
     o   Vomiting, hypersalivation, diarrhea, fecal
         incontinence, and abdominal pain may occur.
     o   Intussusception has been reported in a single pediatric
         organophosphate poisoning case.
  GENITOURINARY
   0.2.10.1 ACUTE EXPOSURE
     o   Increased urinary frequency and urinary incontinence
         have occurred.
     o   Immune-complex nephropathy with proteinuria and/or
         amorphous crystalluria may occur.
     o   Reversible renal tubular dysfunction unrelated to
         cholinesterase inhibition has been demonstrated in
         rats.
  ACID-BASE
   0.2.11.1 ACUTE EXPOSURE
     o   Metabolic acidosis has occurred in several severe
         poisonings.
  HEMATOLOGIC
   0.2.13.1 ACUTE EXPOSURE
     o   Alteration in prothrombin time and/or tendency to
         bleeding may occur.  Clinically significant bleeding or
         hypercoagulability are rare.
     o   The hallmark of organophosphate poisoning is inhibition
         of plasma pseudocholinesterase and erythrocyte
         acetylcholinesterase.
  DERMATOLOGIC
   0.2.14.1 ACUTE EXPOSURE
     o   Sweating is a consistent, but not universal, sign.
   0.2.14.2 CHRONIC EXPOSURE
     o   Dermal sensitization may occur.
  MUSCULOSKELETAL
   0.2.15.1 ACUTE EXPOSURE
     o   Muscle weakness, fatigability, and fasciculations are
         common findings, and may be delayed in onset by several
         days.  Muscle paralysis may occur.
  ENDOCRINE
   0.2.16.1 ACUTE EXPOSURE
     o   Hyperglycemia and glycosuria without ketosis may be
         present.
  METABOLISM
   0.2.17.1 ACUTE EXPOSURE
     o   Hyperglycemia and glycosuria without ketosis may occur
         in severe poisoning.
  PSYCHIATRIC
   0.2.18.1 ACUTE EXPOSURE
     o   Decreased vigilance, defects in expressive language and
         cognitive function, impaired memory, depression,
         anxiety, irritability, and psychosis have been
         reported, more commonly in persons having other
         clinical signs of organophosphate poisoning or
         pre-existing psychological conditions.
     o   Abnormal neuropsychiatric tests and EEGs may persist
         for months after acute exposure.  During chronic
         therapy with DFP for glaucoma, aggravation of
         pre-existing psychiatric symptoms and development of
         new psychiatric symptoms in normal individuals may
         occur, and can persist for up to several months after
         the medication is withdrawn.
  IMMUNOLOGIC
   0.2.19.2 CHRONIC EXPOSURE
     o   Chronic skin exposure to some organophosphates may lead
         to dermal sensitization.
  REPRODUCTIVE HAZARDS
    o   In rodents, stillbirths, metabolic, and behavioral
        effects have been observed.  DFP was not teratogenic in
        rats.
    o   No information about possible male reproductive effects
        was found in available references at the time of this
        review.
  CARCINOGENICITY
   0.2.21.3 ANIMAL OVERVIEW
     o   At the time of this review, no studies were found on
         the possible carcinogenic effects of diisopropyl
         fluorophosphate in humans.
     o   Sixteen of 100 rats administered DIFP at a dose of 0.5
         mg/kg every 72 hours for 730 days developed chromophobe
         adenomas of the pituitary gland, a tumor with a rare
         spontaneous incidence.
  GENOTOXICITY
    o   Cytogenetic studies of organophosphate-exposed workers
        have suggested possible increases in frequencies of
        chromosome aberrations, but the evidence is not
        compelling.                    
Laboratory:
  o   Determine plasma and red blood cell cholinesterase
      activities.  While there may be poor correlation between
      cholinesterase values and clinical effects, depression in
      excess of 50% activity is generally associated with severe
      symptoms.  Correlation between cholinesterase levels and
      clinical effects in milder poisonings may be poor.
  o   If respiratory tract irritation, excessive bronchial
      secretions, or bronchospasm occur following exposure,
      monitor arterial blood gases.
  o   If respiratory tract irritation, excessive bronchial
      secretions, or bronchospasm occur following exposure,
      monitor chest x-ray.                      
Treatment Overview:
  ORAL EXPOSURE
    o   EMESIS -
     1.  Because of potential seizures and coma, inducing emesis
         is CONTRAINDICATED.
    o   GASTRIC LAVAGE -
     1.  GASTRIC LAVAGE:  Consider after ingestion of a
         potentially life-threatening amount of poison if it can
         be performed soon after ingestion (generally within 1
         hour).  Protect airway by placement in Trendelenburg
         and left lateral decubitus position or by endotracheal
         intubation.  Control any seizures first.
      a.  CONTRAINDICATIONS:  Loss of airway protective reflexes
          or decreased level of consciousness in unintubated
          patients; following ingestion of corrosives;
          hydrocarbons (high aspiration potential); patients at
          risk of hemorrhage or gastrointestinal perforation;
          and trivial or non-toxic ingestion.
    o   ACTIVATED CHARCOAL/CATHARTIC -
     1.  ACTIVATED CHARCOAL/CATHARTIC:  Administer charcoal
         slurry, aqueous or mixed with saline cathartic or
         sorbitol.  The FDA suggests 240 mL of diluent/30 g of
         charcoal.  Usual charcoal dose is 25 to 100 grams in
         adults and adolescents, 25 to 50 grams in children (1
         to 12 years old), and 1 gram/kilogram in infants less
         than 1 year old.
      a.  Routine use of cathartics is NOT recommended.  If
          used, administer only ONE dose of cathartic.
          Administer one dose of a cathartic, mixed with
          charcoal or given separately.  See "Treatment:
          Prevention of Absorption" in the main document.
    o   SUCTION ORAL SECRETIONS - until atropinization.
    o   ATROPINE THERAPY - If symptomatic from
        anticholinesterase poisoning, administer IV atropine
        until atropinization is achieved (See details in main
        Treatment Section).  ADULT - 2 to 5 mg every 10 to 15
        minutes; CHILD - 0.05 mg/kg every 10 to 15 minutes.
        Atropinization may be required for hours to days
        depending on severity.
    o   PRALIDOXIME (PROTOPAM, 2-PAM) - Severe
        anticholinesterase poisoning, characterized by profound
        weakness and respiratory depression, should also be
        treated with 2-PAM.  ADULT - 1 to 2 g IV at 0.5 g per
        min; CHILD - 25 to 50 mg/kg over 5 to 30 minutes; may
        repeat in one hour and every 6 to 12 hours if muscle
        weakness is not relieved or if patient is comatose.
        CONTINUOUS INFUSION - (Controversial) - ADULT - 500
        mg/hr.  Pralidoxime may need to be administered over
        several days.
    o   SEIZURES:  Administer a benzodiazepine IV; DIAZEPAM
        (ADULT:  5 to 10 mg,  repeat every 10 to 15 min as
        needed.  CHILD:  0.2 to 0.5 mg/kg, repeat every  5 min
        as needed) or LORAZEPAM (ADULT:  4 to 8 mg; CHILD:  0.05
        to 0.1 mg/kg).
     1.  Consider phenobarbital if seizures recur after diazepam
         30 mg (adults)  or 10 mg (children > 5 years).
     2.  Monitor for hypotension, dysrhythmias, respiratory
         depression, and need  for endotracheal intubation.
         Evaluate for hypoglycemia, electrolyte disturbances,
         hypoxia.
    o   PULMONARY EDEMA (NONCARDIOGENIC):  Maintain ventilation
        and oxygenation and evaluate with frequent arterial
        blood gas or pulse oximetry monitoring.  Early use of
        PEEP and mechanical ventilation may be needed.
    o   HYPOTENSION:  Infuse 10 to 20 mL/kg isotonic fluid,
        place in Trendelenburg position.  If hypotension
        persists, administer dopamine (5 to 20 mcg/kg/min) or
        norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to
        desired response.
    o   CONTRAINDICATIONS - Succinylcholine and other
        cholinergic agents are contraindicated.
  INHALATION EXPOSURE
    o   INHALATION:  Move patient to fresh air.  Monitor for
        respiratory distress.  If cough or difficulty breathing
        develops, evaluate for respiratory tract irritation,
        bronchitis, or pneumonitis.  Administer oxygen and
        assist ventilation as required.  Treat bronchospasm with
        beta2  agonist and corticosteroid aerosols.
    o   If respiratory tract irritation or respiratory
        depression is evident, monitor arterial blood gases,
        chest x-ray, and pulmonary function tests.
    o   Carefully observe patients with inhalation exposure for
        the development of any systemic signs or symptoms and
        administer symptomatic treatment as necessary.
    o   Suction oral secretions until atropinization.
    o   ATROPINE THERAPY - If symptomatic from
        anticholinesterase poisoning, administer IV atropine
        until atropinization is achieved (See details in main
        Treatment Section).  ADULT - 2 to 5 mg every 10 to 15
        minutes; CHILD - 0.05 mg/kg every 10 to 15 minutes.
        Atropinization may be required for hours to days
        depending on severity.
    o   PRALIDOXIME (PROTOPAM, 2-PAM) - Severe
        anticholinesterase poisoning, characterized by profound
        weakness and respiratory depression, should also be
        treated with 2-PAM.  ADULT - 1 to 2 g IV at 0.5 g per
        min; CHILD - 25 to 50 mg/kg over 5 to 30 minutes; may
        repeat in one hour and every 6 to 12 hours if muscle
        weakness is not relieved or if patient is comatose.
        CONTINUOUS INFUSION - (Controversial) - ADULT - 500
        mg/hr.  Pralidoxime may need to be administered over
        several days.
    o   SEIZURES:  Administer a benzodiazepine IV; DIAZEPAM
        (ADULT:  5 to 10 mg,  repeat every 10 to 15 min as
        needed.  CHILD:  0.2 to 0.5 mg/kg, repeat every  5 min
        as needed) or LORAZEPAM (ADULT:  4 to 8 mg; CHILD:  0.05
        to 0.1 mg/kg).
     1.  Consider phenobarbital if seizures recur after diazepam
         30 mg (adults)  or 10 mg (children > 5 years).
     2.  Monitor for hypotension, dysrhythmias, respiratory
         depression, and need  for endotracheal intubation.
         Evaluate for hypoglycemia, electrolyte disturbances,
         hypoxia.
    o   PULMONARY EDEMA (NONCARDIOGENIC):  Maintain ventilation
        and oxygenation and evaluate with frequent arterial
        blood gas or pulse oximetry monitoring.  Early use of
        PEEP and mechanical ventilation may be needed.
    o   HYPOTENSION:  Infuse 10 to 20 mL/kg isotonic fluid,
        place in Trendelenburg position.  If hypotension
        persists, administer dopamine (5 to 20 mcg/kg/min) or
        norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to
        desired response.
    o   CONTRAINDICATIONS - Succinylcholine and other
        cholinergic agents are contraindicated.
  EYE EXPOSURE
    o   DECONTAMINATION:  Irrigate exposed eyes with copious
        amounts of tepid water for at least 15 minutes.  If
        irritation, pain, swelling, lacrimation, or photophobia
        persist, the patient should be seen in a health care
        facility.
    o   If respiratory tract irritation or respiratory
        depression is evident, monitor arterial blood gases,
        chest x-ray, and pulmonary function tests.
    o   Carefully observe patients with inhalation exposure for
        the development of any systemic signs or symptoms and
        administer symptomatic treatment as necessary.
    o   SUCTION ORAL SECRETIONS - until atropinization.
    o   ATROPINE THERAPY - If symptomatic from
        anticholinesterase poisoning, administer IV atropine
        until atropinization is achieved (See details in main
        Treatment Section).  ADULT - 2 to 5 mg every 10 to 15
        minutes; CHILD - 0.05 mg/kg every 10 to 15 minutes.
        Atropinization may be required for hours to days
        depending on severity.
    o   PRALIDOXIME (PROTOPAM, 2-PAM) - Severe
        anticholinesterase poisoning, characterized by profound
        weakness and respiratory depression, should also be
        treated with 2-PAM.  ADULT - 1 to 2 g IV at 0.5 g per
        min; CHILD - 25 to 50 mg/kg over 5 to 30 minutes; may
        repeat in one hour and every 6 to 12 hours if muscle
        weakness is not relieved or if patient is comatose.
        CONTINUOUS INFUSION - (Controversial) - ADULT - 500
        mg/hr.  Pralidoxime may need to be administered over
        several days.
    o   SEIZURES:  Administer a benzodiazepine IV; DIAZEPAM
        (ADULT:  5 to 10 mg,  repeat every 10 to 15 min as
        needed.  CHILD:  0.2 to 0.5 mg/kg, repeat every  5 min
        as needed) or LORAZEPAM (ADULT:  4 to 8 mg; CHILD:  0.05
        to 0.1 mg/kg).
     1.  Consider phenobarbital if seizures recur after diazepam
         30 mg (adults)  or 10 mg (children > 5 years).
     2.  Monitor for hypotension, dysrhythmias, respiratory
         depression, and need  for endotracheal intubation.
         Evaluate for hypoglycemia, electrolyte disturbances,
         hypoxia.
    o   PULMONARY EDEMA (NONCARDIOGENIC):  Maintain ventilation
        and oxygenation and evaluate with frequent arterial
        blood gas or pulse oximetry monitoring.  Early use of
        PEEP and mechanical ventilation may be needed.
    o   HYPOTENSION:  Infuse 10 to 20 mL/kg isotonic fluid,
        place in Trendelenburg position.  If hypotension
        persists, administer dopamine (5 to 20 mcg/kg/min) or
        norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to
        desired response.
    o   CONTRAINDICATIONS - Succinylcholine and other
        cholinergic agents are contraindicated.
  DERMAL EXPOSURE
    o   DECONTAMINATION:  Remove contaminated clothing and
        jewelry.  Wash  the skin, including hair and nails,
        vigorously; do repeated soap washings.  Discard
        contaminated clothing.
    o   If respiratory tract irritation or respiratory
        depression is evident, monitor arterial blood gases,
        chest x-ray, and pulmonary function tests.
    o   Carefully observe patients with inhalation exposure for
        the development of any systemic signs or symptoms and
        administer symptomatic treatment as necessary.
    o   Suction oral secretions until atropinization.
    o   ATROPINE THERAPY - If symptomatic from
        anticholinesterase poisoning, administer IV atropine
        until atropinization is achieved (See details in main
        Treatment Section).  ADULT - 2 to 5 mg every 10 to 15
        minutes; CHILD - 0.05 mg/kg every 10 to 15 minutes.
        Atropinization may be required for hours to days
        depending on severity.
    o   PRALIDOXIME (PROTOPAM, 2-PAM) - Severe
        anticholinesterase poisoning, characterized by profound
        weakness and respiratory depression, should also be
        treated with 2-PAM.  ADULT - 1 to 2 g IV at 0.5 g per
        min; CHILD - 25 to 50 mg/kg over 5 to 30 minutes; may
        repeat in one hour and every 6 to 12 hours if muscle
        weakness is not relieved or if patient is comatose.
        CONTINUOUS INFUSION - (Controversial) - ADULT - 500
        mg/hr.  Pralidoxime may need to be administered over
        several days.
    o   SEIZURES:  Administer a benzodiazepine IV; DIAZEPAM
        (ADULT:  5 to 10 mg,  repeat every 10 to 15 min as
        needed.  CHILD:  0.2 to 0.5 mg/kg, repeat every  5 min
        as needed) or LORAZEPAM (ADULT:  4 to 8 mg; CHILD:  0.05
        to 0.1 mg/kg).
     1.  Consider phenobarbital if seizures recur after diazepam
         30 mg (adults)  or 10 mg (children > 5 years).
     2.  Monitor for hypotension, dysrhythmias, respiratory
         depression, and need  for endotracheal intubation.
         Evaluate for hypoglycemia, electrolyte disturbances,
         hypoxia.
    o   PULMONARY EDEMA (NONCARDIOGENIC):  Maintain ventilation
        and oxygenation and evaluate with frequent arterial
        blood gas or pulse oximetry monitoring.  Early use of
        PEEP and mechanical ventilation may be needed.
    o   HYPOTENSION:  Infuse 10 to 20 mL/kg isotonic fluid,
        place in Trendelenburg position.  If hypotension
        persists, administer dopamine (5 to 20 mcg/kg/min) or
        norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to
        desired response.
    o   CONTRAINDICATIONS - Succinylcholine and other
        cholinergic agents are contraindicated.
Range of Toxicity:
  o   Acute toxicity is variable and depends strongly upon the
      kinetics of absorption and whether or not metabolic
      activation is required.  Sudden absorption of a less toxic
      compound may have a more severe effect.
  o   Seizures, apneic spells, miosis, profuse nasal discharge,
      and possible muscle weakness were noted in a 12-month-old
      boy treated with one drop of 0.1% DIFP eye drops in each
      eye daily for 2 months; a serum cholinesterase level 60
      hours after the last drop was instilled was 44% of normal.
  o   A single intraarterial injection of 2 mg/kg of DIFP caused
      a delayed peripheral neuropathy in the injected limb in
      cats.  Muscle fasciculations without other typical signs
      of cholinergic poisoning were seen in monkeys administered
      as little as 0.03 mg/kg twice weekly.  In dogs, similar
      findings occurred at dosages of 0.05 mg/kg twice weekly;
      in rats, a dose of 0.5 mg/kg twice weekly produced similar
      results.
  o   Reversible renal tubular dysfunction unrelated to
      cholinesterase inhibition was seen in rats administered a
      single dose of 2 to 4 mg/kg of DIFP.

[Rumack BH: POISINDEX(R) Information System. Micromedex, Inc., Englewood, CO, 2001; CCIS Volume 110, edition exp November, 2001. Hall AH & Rumack BH (Eds):TOMES(R) Information System. Micromedex, Inc., Englewood, CO, 2001; CCIS Volume 110, edition exp November, 2001.] **PEER REVIEWED**

Antidote and Emergency Treatment:

... Since thermoregulatory disturbance may itself contribute to the morbidity and mortality in individuals exposed to cholinesterase inhibitors, and since this may be independent of the effect of the toxin on cholinesterase activity, treatment should be instituted to correct hypothermia as well as to combat cholinergic stimulation directly.
[Lomax P et al; Acetycholinesterase Inhibitors and Thermoregulation: Homeostasis Therm Stress Int Symp Pharmacol Thermoregulation 6th 108-12 (1986)]**PEER REVIEWED**

... Hexamethonium, trimethaphan, and mecamylamine are ganglionic blockers which can reduce acetylcholine (ACh) release presynaptically. All these agents are capable of protecting mice from diisopropyl fluorophosphate (DFP) intoxication by prolonging the latent period of death or by completely preventing death. Combinations of these agents with 2-pyridine aldoxime methochloride (2-PAM) (50 mg/kg) improved prophylactic action even further even further. These results indicate that reduction of ACh release presynaptically plus neutralization of organophosphates with 2-PAM could be an effective way to reduce mortality in patients exposed to organophosphorus poisons.
[Chiou GC et al; Fundam Appl Toxicol 6 (1): 35-43 (1986)]**PEER REVIEWED**

... Mice were injected with several drugs which have in common the ability to block sodium-channels. Drugs tested were ketamine, phenobarbital, lidocaine, morphine, prednisolone, and lithium. All mice were injected with DFP (7.6 mg/kg) plus atropine; the treatment groups were simultaneously injected with the test drug, while controls received an equal volume of physiological saline. All the test drugs, at one or more doses, revealed protection, not only in terms of prolonging symptom onset but also in terms of mortality. The reduction in mortality was quantitatively similar for each drug. Although the various drugs could have protected by many different, coincidental mechanisms, a more parsimonious explanation is that the effect could have been due to one property which all had in common; namely, sodium-channel blockade.
[Klemm WR; Toxicol Lett 25 (3): 307-12 (1985)]**PEER REVIEWED**

Maintaining adequate respiratory function should be the first treatment measure taken. In cases of ingestion, activated charcoal is indicated. Atropine is the drug of first choice ...
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995. 979]**PEER REVIEWED**

... /Authors/ showed that the carbamate anticholinesterase physostigmine could protect cat cholinesterase against inactivation by DFP in vivo ... .
[Marrs, T.C., Maynard, R.L., Sidell, F.R.; Chemical Warfare Agents. Toxicology and Treatment. John Wiley & Sons, New York, NY. (1996). 109]**PEER REVIEWED**


Animal Toxicity Studies:

Non-Human Toxicity Excerpts:

... IN ANIMALS POISONED WITH DFP, PLASMA CHOLINESTERASE ACTIVITY RETURNS TO NORMAL WITHIN SEVERAL DAYS TO A FEW WK, BECAUSE IT IS RELATIVELY RAPIDLY REPLACED BY NEW ENZYME SYNTHESIZED IN THE LIVER. THE ACETYLCHOLINESTERASE ACTIVITY OF ERYTHROCYTES, HOWEVER, REMAINS DEPRESSED FOR DURATION OF RED CELL'S LIFE.
[Doull, J., C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: Macmillan Co., Inc., 1986. 537]**PEER REVIEWED**

IN SEVERE POISONING, MOTOR FIBERS ARE INVOLVED, & THERE IS PARALYSIS & EXTENSIVE DAMAGE TO RHOMBENCEPHALON & SPINAL CORD WITH DEGENERATION OF SPINOCEREBELLAR TRACTS, CEREBELLAR PONTINE NUCLEI, & VENTRAL LUMBAR, THORACIC, & CERVICAL TRACTS.
[Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975. 159]**PEER REVIEWED**

DIISOPROPYL FLUOROPHOSPHATE ADMIN IM TO WISTAR RATS, 0.5 MG/KG EVERY 72 HR FOR 730 DAYS, PRODUCED 16/100 PITUITARY TUMORS (CHROMOPHOBE ADENOMA). SPONTANEOUS INCIDENCE "RARE". /FROM TABLE/
[Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976. 170]**PEER REVIEWED**

THE ACUTE AND DELAYED BEHAVIORAL EFFECTS OF DFP WERE STUDIED IN WHITE-LEGHORN HENS TRAINED TO KEY-PECK UNDER A MULTIPLE FIXED-RATIO, FIXED-INTERVAL (MULT FR F1) SCHEDULE OF FOOD PRESENTATION. ACUTE EFFECTS CONSISTED OF DOSE-RELATED RESPONSE-RATE DECREASES WHICH WERE SIMILAR FOR BOTH FR AND FI SCHEDULE COMPONENTS. FOLLOWING A RETURN TO CONTROL RESPONDING FOR NO LESS THAN 7 DAYS, DELAYED EFFECTS OCCURRED. BEHAVIORAL EFFECTS PRECEDED NEUROTOXIC EFFECTS. THESE LATTER EFFECTS FIRST APPEARED AS ATAXIA AND PROGRESSED TO LEG PARALYSIS AND SOMETIMES DEATH. DELAYED EFFECTS FOLLOWED BOTH ACUTE (0.5-1.0 MG/KG) DOSES AS WELL AS DOSES (0.125-0.25 MG/KG) HAVING NO OR LITTLE ACUTE BEHAVIORAL EFFECTS.
[FORD RD, ROSENBLUM I; FED PROC FED AM SOC EXP BIOL 38 (3, PT 1): 845 (1979)]**PEER REVIEWED**

THE FINE STRUCTURE OF THE CAT SOLEUS NEUROMUSCULAR JUNCTION WAS STUDIED FOLLOWING A SINGLE INTRAARTERIAL INJECTION OF DFP. DFP INDUCED SEPARATE SUBACUTE & DELAYED MORPHOLOGIC CHANGES IN SOLEUS NONMYELINATED MOTOR NERVE TERMINALS. THREE DAYS AFTER DFP ADMIN MOTOR NERVE TERMINALS WERE REDUCED IN NUMBER. ONE WEEK FOLLOWING SOME INITIAL REGENERATION, SOLEUS MOTOR NERVE TERMINALS UNDERWENT A DELAYED TRANSIENT DEGENERATION, FOLLOWED BY REINNERVATION OF DAMAGED ENDPLATES 6-8 WK FOLLOWING DFP.
[GLAZER EJ ET AL; J NEUROCYTOL 7 (6): 741-58 (1978)]**PEER REVIEWED**

Dosages as low as 0.05 mg/kg twice/wk in dogs, 0.03 mg/kg twice/wk in monkeys, & 0.50 mg/kg twice/wk in rats led to muscular fasciculations soon after individual doses, but to no other typical signs of poisoning. Three of four monkeys developed bronchopneumonia, which investigators ... associated with excessive secretions. Cardiospasm often associated with dilatation of esophagus was seen in three dogs receiving dosages of 0.1, 0.3, & 0.5 mg/kg twice/wk, & this led to malnutrition at the higher dosages. Partial urinary incontinence was observed in the dogs on the two higher dosage levels. Both cardiospasm & urinary incontinence were considered related to inhibition of cholinesterase. Finally, hind leg paralysis developed during or before the 10th wk of dosing in dogs receiving 0.3 & 0.5 mg/kg twice/wk.
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 332]**PEER REVIEWED**

/Rats admin ip/ ... 1 to 4 mg/kg on days 8, 9, or 12 /of pregnancy/ ... no /fetal/ defects /found/, but perinatal mortality was increased & weight gain postnatally was reduced. Treatment on days 7, 8, 9, & 10 did not increase the resorption rate.
[Shepard, T. H. Catalog of Teratogenic Agents. 3rd ed. Baltimore, MD.: Johns Hopkins University Press, 1980. 103]**PEER REVIEWED**

Muscarinic receptors were down-regulated in Wistar rats after repeated exposure to DFP. The density of receptors was decr to 60-85% of the controls. Redn was observed in cortex, caudate-putamen, lateral septum, hippocampal formation, superior colliculus, and pons. The density of muscarinic receptors was unchanged in thalamic and hypothalamic nuclei, periaqueductal grey, cerebellum, inferior colliculus & reticular formation of the brain stem.
[Churchill L et al; Topographical distribution of Down-Regulated Muscarinic Receptors in Rat Brains After Repeated Exposure to Diisopropyl Phosphorofluoridate: Neuroscience 11 (2): 463-72 (1984)]**PEER REVIEWED**

The effect of chronic admin of DFP on the levels & forms of plasma cholinesterase were studied in male Wistar albino rats. The enzymatic activity was evaluated for butyrylcholinesterase (BuChE) & for acetylcholinesterase (AChE). At 1.5 and 24 hr after the treatments, BuChE was considerably more depressed than AChE. Moreover, the recovery of BuChE proceeded more slowly, its activity being restored only 7 days after the last treatment, while the recovery of AChE was completed 72 hr after the end of the treatments.
[Traina ME, Serpietri LA; Changes in the Levels and Forms of Rat Plasma Cholinesterases During Chronic Diisopropyl phosphorofluoridate Intoxication: Biochem Pharmacol 33 (4): 645-53 (1984)]**PEER REVIEWED**

The effect of a single dose of DFP (1.1 mg/kg sc) admin to rats during pregnancy was evaluated by measuring postpartum maternal & newborn brain-soluble and total acetylcholinesterases (AChE) & their molecular forms @ intervals of 1, 2, 3, 4 & 10 days between treatment & sacrifice. Subsequently, the effects of DFP were studied in 18-day-pregnant rats, fetuses & placentae @ 90 min & 24 hr after treatment. The inhibition of postpartum maternal enzymatic activity did not differ from that previously found in adult males, while inhibition was considerably less pronounced in newborns at all time intervals, with a nearly complete recovery already at 48 hr after treatment. An even faster recovery of brain enzyme was observed in 18-day fetuses from DFP-treated mothers (24-hr interval between treatment & sacrifice). In this expt, a comparable inhibition was observed at 90 min after treatment in the adult & the developing brain, excluding a major influence of disposition factors in the differential recovery phenomena.
[Bisso GM et al; Development Factors Affecting Brain Acetylcholinesterase Inhibition and Recovery in DFP-Treated Rats: Dev Neurosci 5 (5-6): 508-19 (1982)]**PEER REVIEWED**

DFP in doses of 1-4 mg/kg was tested on renal function in rats. A single dose (2, 3, or 4 mg/kg) caused an incr flow of urine of low osmolality over 6 hr after the admin of the drug with essentially a return to control status by 24 hr after either of the lower doses. The incr urine flow assoc with decr inulin clearance (4 mg/kg) and renal blood flow (3 or 4 mg/kg) suggests a direct effect of DFP on renal tubular function. These effects do not appear to be related to inhibition of cholinesterase.
[Berndt WO et al; Effects of Diisopropyl fluorophosphate (DFP) on Renal Function in the Rat. Toxicology 31 (3-4): 223-35 (1984)]**PEER REVIEWED**

The effects of acute admin of DFP (1.1 mg, sc) on sol brain acetylcholinesterase (AChE) were studied in male rats sacrificed at time intervals ranging from 3 hr to 25 days after admin. Three main molecular forms of AChE were separated. In the brain of untreated animals, the slow-, medium-, and fast-migrating forms accounted, respectively, for 64, 18, and 18% of the sol AChE activity. At 3 hr after treatment with DFP, the relative contribution of slow-migrating forms to the residual enzymic activity was decr, while that of medium-forms was incr. These changes became gradually more pronounced and reached their max at 4 days, when AChE had recovered to approx 50% of control level. Subsequently, the distribution of the molecular forms showed a progressive return toward the control pattern. The partial recovery in the initial period after max enzyme depression was mainly due to an incr of medium-migrating forms. Thus, these may be precursors of the biosynthesis of slow-migrating forms and/or there may be functional specialization of different forms.
[Michalek H et al; Molecular Forms of Rat Brain Acetylcholinesterase in DFP Intoxication and Subsequent Recovery. Neurobehav Toxicol Teratol 3 (3): 303-12 (1981)]**PEER REVIEWED**

The effects were studied of DFP, paraoxon, and parathion on the activity of ATPase of rat heart myofibers and mitochondria. The organophosphates had an inhibitory effect on ATPases. The inhibition was correlated with the duration of poisoning, the dose of the poison, and the type of the organophosphate. DFP had the highest inhibitory effects. Ca-dependent ATPase was more sensitive than the Na-K-dependent ATPase.
[Dierkes-Tizek U et al; Effect of Organophosphates on Rat Heart ATPases. Arzneim-Forsch 34 (6): 671-8 (1984)]**PEER REVIEWED**

A single injection of DFP (2 mg/kg) into a cat femoral artery produced a delayed neuropathy in the injected leg. Clinical neurotoxic signs in the DFP-treated leg were most prominent at 21-28 days after DFP admin: a high-step gait with some tip-toe walking. During that time, the capacity of the cat soleus alpha-motor nerve terminals to generate a stimulus-evoked repetitive discharge, known as SBR, was greatly attenuated. At that time, the ultrastructure of the motor nerve terminals demonstrated prominent alterations that correlated well with the motor nerve terminal SBR deficit. These alterations incl the presence of extensive whorls in nerve terminals and axoplasms, the retraction and disruption of nerve terminals from the synaptic cleft, and a widening of secondary junctional folds. From the sampled population, the incidence of normal terminals in soleus muscles of the DFP-treated leg was only 2%.
[Drakontides AB, Baker T; An Electrophysiologic and Ultrastructural Study of the Phenylmethanesulfonyl fluoride Protection Against a Delayed Organophosphorus Neuropathy. Toxicol Appl Pharmacol 70 (3): 411-22 (1983)]**PEER REVIEWED**

A number of organophosphates produced delayed neurotoxicity in man which may be modeled ... in several animal species ... /such as/ the adult hen Gallus domesticus. The development of delayed neurotoxicity was studied in adult white Leghorn hens after a single, oral dose (1.0 mg/kg) of diisopropylfluorophosphate and after the administration of repeated low-level oral doses (125 mug/kg, 5 days/wk; 1.0-5.0 mg/kg, total dose) of DFP. The relationship of dosage, time, and frequency of administration of subneurotoxic doses of DFP under conditions of a multiple-dose procedure was examined. The comparative activities of hen brain and sciatic nerve neurotoxic esterase (NTE) were studied. The percentage inhibition of NTE paralleled the incr in the degree of severity of the acute pharmacological response. The chronic dosing regimen resulted in a small, yet definite, inhibitory effect of DFP on brain NTE and cholinesterase activities. A maximum level of brain NTE inhibition occurred followed by a decrease and eventual leveling off of the inhibitory effect. The comparative NTE studies demonstrate that substrate hydrolysis by hen sciatic nerve preparations was considerably less when compared with hen brain extracts using equivalent tissue weights. The percentage of NTE of the total paraoxon-resistant activity was lower in sciatic nerve preparations compared with brain preparations. The effects of DFP on the NTE activities from brain and sciatic nerve preparations were definitely inhibitory, and quantitative differences exist between NTE content and activity in peripheral and central nervous systems.
[Olajos EJ et al; Ecotoxicol and Environ Safety 2 (3-4): 383-399 (1978)]**PEER REVIEWED**

The effects following oral and intramuscular injection of diisopropyl fluorophosphate (DFP) were studied in chickens and pigeons responding under a multiple fixed-ratio, fixed-interval schedule of food presentation. The effects for both routes for DFP were also studied in chickens responding on a multiple fixed-ratio, time-out schedule of food presentation. The effects of intramuscular DFP were studied in a rhesus monkey responding under a chain fixed-ratio, fixed-ratio schedule of sucrose presentation. The effects of DFP generally depressed fixed-ratio, fixed-interval, and time-out responding with no mean response rate increases. Doses producing behavioral effects also produced acute cholinergic effects in the chicken and the rhesus monkey but not in the pigeon. The potency and duration of DFP effects depended on the species and route of administration. The monkey was the most sensitive animal with the lowest active intramuscular dose (0.1 mg/kg) disrupting for 5 days. A higher dose (0.125 mg/kg) disrupted responding for 8 days. Intramuscular DFP disrupted responding in the chicken in a dose-related manner and with 0.25 mg/kg being the lowest active dose. Higher doses (0.5 and 0.75 mg/kg) disrupted responding for 2 days after administration. Oral DFP was much less potent than the intramuscular route in chickens and pigeons, with a marginally active dose being 1 mg/kg. Effects following oral administration lasted < 1 day. Potency was the same in the pigeon by both the oral and intramuscular routes.
[Ford RD, Rosenblum I; Ecotoxicol and Environ Safety 3 (4): 428-38 (1979)]**PEER REVIEWED**

In an attempt to learn more about the proteolytic enzymes responsible for protein turnover in cells, the effects of various protease inhibitors on protein catabolism in Escherichia coli were examined. Diisopropyl fluorophosphate, phenylmethane sulfonyl fluoride, and toluenesulfonyl fluoride were found to decrease protein breakdown in E coli, starved for a carbon source. These compounds partially inhibited protein breakdown at doses which did not inhibit growth on minimal medium. Protein breakdown in starving cells could also be inhibited reversibly by the aromatic diamidines, dibromopropamidine, and pentamidine, which are potent trypsin inhibitors. The effects of pentamidine and p-toluenesulfonyl fluoride did not require concomitant protein synthesis. Other data presented suggest that there may exist at least two proteolytic systems in E coli; one operating in all cells, which can degrade abnormal proteins, and one found in starving cells which is sensitive to sulfonyl fluorides and aromatic diamidines.
[Prouty WF et al; J Biol Chem 247 (10): 3341-52 (1972)]**PEER REVIEWED**

The effects of DFP on the release of endogenous dopamine from rat brain striatum in vitro were compared with those of the cholinergic muscarinic agonist oxotremorine, the cholinergic nicotinic agonist nicotine, the cholinergic antagonists mecamylamine and atropine, and the cholinesterase inhibitor physostigmine to elucidate the mechanisms involved in the neurotoxicity of DFP and possibly other organophosphates. DFP (1x10(-3) M) inhibited both spontaneous release and K+-stimulated dopamine release, the effect on the latter being greater than that of the former. At 10(-5) and 10(-4) M the inhibitory effects of physostigmine and oxotremorine on the K+-stimulated dopamine release were similar to DFP. Also, the apparent stimulatory effects of DFP at 10(-5) and 10(-4) M on spontaneous dopamine release were similar to those of physostigmine and oxotremorine. However, the inhibitory effects of 10(-3) M DFP on spontaneous and induced dopamine release was not observed. Apparently moderate concentrations of DFP affect dopamine release via an effect of increased acetylcholine on muscarinic receptors on dopaminergic neurons, whereas high DFP concentrations might directly attack protein sites involved in neurotransmitter release.
[Kant GJ et al; Biochem Pharmacol 33 (11): 1823-5 (1984)]**PEER REVIEWED**

... The results show that DFP ... initially increases rat sciatic nerve conduction and reduces refractoriness. Continued exposure had a diminished effect with nerve excitability eventually returning to control. During recovery, the nerve membrane responsiveness to potassium-induced depolarization significantly changed in a manner which would indicate either decreased Na, K-ATPase activity, or decreased potassium ion transmembrane flux. The data suggest that compensatory changes occcur in rat nerve in response to organophosphorus exposure, and further, that these compensatory changes involve alteration in membrane ion fluxes.
[Anderson RJ, Dunham CB; Arch Toxicol 58 (2): 97-101 (1985)]**PEER REVIEWED**

Thirty-five pregnant Wistar rats (Charles River Italia) were (DFP) injected sc with 0 or 1.1 mg/kg diisopropylfluorophosphate in arachis oil on day 6 of pregnancy, and with subsequent doses of 0.7 mg/kg each (25% LD50) on alternate days up to day 20 of pregnancy. DFP treatment was toxic to dams and caused weight reduction but not mortality. Pups of 4 DFP-treated litters were stillborn or died shortly after delivery, and 8 additional litters were lost within 48 hr after birth. The levels of brain cholinesterase (ChE) in DFP-exposed newborns did not differ from those of controls. In another experiment, 15 DFP-treated pregnant rats and 15 controls were killed either 90 min, 24 hr, or 48 hr after the last injection. Total ChE in maternal brain was consistently depressed without recovery from 90 min to 48 hr, while in fetuses an almost complete recovery occurred at 48 hr. Maximal number of 3 H quinuclinidyl benzylate binding sites was significantly decreased in maternal brain and in 21-day fetal brain.
[Michalek H et al; Fund Appl Toxicol 5:S204-S212 (1985)]**PEER REVIEWED**

... DFP was tested as an unconditioned stimulus in the conditioned taste aversion (CTA) test /rats/. DFP caused a dose-dependent conditioned taste aversion in rats which did not induce any other signs of toxicity. ... The conditioned taste aversion test appears to be a sensitive indicator of neurobehavioral effects of mild exposure to organophosphates. ...
[Roney PL et al; Pharmacol Biochem Behav 24 (3): 737-42 (1986)]**PEER REVIEWED**

The LD50 and ED50 for inhibition of acetylcholinesterase in whole mouse brain were determined after intravenous administration of diisopropyl fluorophosphate over a 10 sec period at a volume of 0.1 ml/10 g body weight. The LD50 was 3.4 mg/kg. Recovery of acetylcholinesterase activity in whole mouse brain after subLD50 doses was slow and did not reach control values by 14 days after intravenous administration. Acetylcholinesterase activity was inhibited in a dose dependent manner in whole mouse brain as well as in six brain regions (cortex, hippocampus, striatum, midbrain, medulla/pons, and cerebellum). None of these brain areas were particularly sensitive to acetylcholinesterase inhibition by the organophosphate compound. The EC50 was 0.649 mg/kg or 19% of th LD50.
[Tripathi HL, Dewey WL; J Toxicol Environ Health 26 (4): 437-46 (1989)]**PEER REVIEWED**

The luminal and mucosal de-esterification of the prodrug ester cefpodoxime proxetil and effects of esterase inhibitors such as physostigmine (eserine), isoflurophate (diisopropylfluorophosphate), edetic acid (EDTA), dithiothreitol, and mercuric chloride and drug ester competitors such as enalapril, bacampicillin, and aspirin (acetylsalicylic acid) on the hydrolysis of the prodrug were studied in vitro in New Zealand rabbit intestine, and the intestinal absorption of the prodrug was studied in vitro in white New Zealand rabbit jejunum. In rabbit intestine, enzymatic hydrolysis of the prodrug was observed in both luminal washing and mucosal homogenate. In rabbit jejunum, extensive hydrolysis of the prodrug occurred in the mucosal compartment and the accumulation of cefpodoxime in the serosal compartment was very slow. Physostigmine and isoflurophate were potent inhibitors of prodrug hydrolysis in both luminal washing and mucosal homogenate. Edetic acid was a moderate inhibitor, and dithiothreitol showed no inhibition. The luminal and mucosal activities were equally sensitive to mercuric chloride and aspirin inhibition, but slight differences were observed concerning the 50% inhibitory concentrations of bacampicillin and enalapril. The results showed that luminal choline esterases participated in the hydrolysis of cefpodoxime proxetil.
[Crauste-Manciet S et al; Int J Pharm 149 (Apr 28): 241-9 (1997)]**PEER REVIEWED**

Involvement of dorsal and ventral root activity for the depressant action of diisopropylfluorophosphate (DFP) on synaptic transmission was examined using in vitro spinal cord/root preparations. Superfusion of DFP produced a dose-dependent depression of monosynaptic reflex (MSR) and maximal depression of about 80% occurred at 1000 uM. The concentration to produce 50% of the maximal inhibition was about 100 microM of diisopropylfluorophosphate. The diisopropylfluorophosphate (100 uM)-induced depression of monosynaptic reflex was reversed by atropine (0.5 uM) but not by mecamylamine (0.5 uM). Contrary to the action on monosynaptic reflex, diisopropylfluorophosphate potentiated the ventral root potential and 1st peak of dorsal root potential. The maximal potentiation was about 25% of control in both the root potentials at 100 uM of diisopropylfluorophosphate. However, the second peak of dorsal root potential was slightly depressed (10-20% of control) by diisopropylfluorophosphate (1-1000 uM). Further, the cords treated with diisopropylfluorophosphate (100 uM) showed significant decrease in the cholinesterase (ChE) activity (27% of control). Results suggest that the diisopropylfluorophosphate-induced depression was mediated at least by two different mechanisms, one through the inhibition of ChE activity and the other through the activation axonal activity having inhibitory inputs to the segmental synaptic transmission. These inputs mediate their action through muscarinic receptors.
[Deshpande SB, DasGupta S ; Toxicol Lett 90 (2-3): 177-82 (1997)]**PEER REVIEWED**

The contribution of carboxylesterase (CarbE) to toxicity and tolerance to the organophosphorus anticholinesterases (OP-antiChE) paraoxon (diethyl p-nitrophenyl phosphate) and DFP (diisopropylphosphorofluoridate) was investigated in rats. Daily injections (20 days) of paraoxon (0.33 umol/kg) or diisopropylfluorophosphate (2.72 umol/kg) reduced AChE activity in brain to 29 or 16% and in diaphragm to 58 or 54%, respectively. The animals tolerated an accumulated 6-fold LD50 dose and survived an LD90 dose of carbachol, indicating tolerance to this cholinergic agonist. A single dose of paraoxon or diisopropylfluorophosphate significantly reduced carboxylesterase activity of plasma, lung and liver. After paraoxon, rapid recovery was seen of plasma and liver carboxylesterase while recovery after diisopropylfluorophosphate was much slower. Daily pretreatment with the carboxylesterase inhibitors CBDP (2-[o-cresyl]-4H-1,2,3-benzodioxa- phosphorin-2-oxide) (7.22 micromol/kg, s.c.) or iso-OMPA (tetraisopropylpyrophosphoramide) (8.76 umol/kg, i.p.), followed by paraoxon (0.33 micromol/kg, s.c.) 30 min later, prevented the development of tolerance to paraoxon and potentiated its toxicity. Rats died on day four of the combined treatment. The carboxylesterase inhibitors neither potentiated the diisopropylfluorophosphate toxicity, nor prevented tolerance development to diisopropylfluorophosphate. We conclude that rat plasma CarbE provides a significant protection against paraoxon toxicity because its rapid reactivation can reduce the toxicity of repeated paraoxon applications and thus contribute to tolerance development. This same mechanism does not apply to diisopropylfluorophosphate toxicity, as inhibition of carboxylesterase of plasma, liver and lung neither potentiated its toxicity, nor prevented tolerance development. These findings confirm previous observations that CarbE detoxification is of greater importance for highly toxic OP-antiChEs such as nerve agents and paraoxon than for less toxic ones such as diisopropylfluorophosphate.
[Dettbarn WD et al; Chem Biol Interact 119-20 445-54 (1999)]**PEER REVIEWED**

Rats were repeatedly administered with a low dose of diisopropylfluorosphosphate (DFP; 0.2 mg/kg/day, SC, for 9 or 21 days), an irreversible cholinesterase (ChE) inhibitor. Control rats received a daily injection of oil vehicle. Neurochemical changes occurring in the pontomesencephalic tegmentum (PMT), a brain stem region critically involved in behavioral state control, were evaluated at various times of treatment and after diisopropylfluorosphosphate withdrawal. First, enzyme assay revealed a profile of cholinesterase inhibition 6 days (74-82% inhibition). The inhibition was less pronounced in the locus coeruleus (49%). Third,(3H)QNB autoradiography showed that muscarinic receptor density was unchanged in any of the pontomesencephalic tegmentum areas selected. These results are discussed regarding the question of regional variation in susceptibility to anti-cholinesterase agents. To what extent behavioral state alterations occur concomitantly with cholinesterase activity changes is assessed in the companion article.
[Deurveilhr S et al; Pharmacology Biochemistry and Behavior 64 (1): 95-103 (1999)]**PEER REVIEWED**

Rats were repeatedly administered with low doses of diisopropylfluorophosphate (DFP; 0.2 mg/kg/day, SC), an irreversible cholinesterase (ChE) inhibitor. Control rats received a daily injection of oil vehicle or of saline. Recordings of the sleep-wake states were obtained in the 6 hr following 1, 3, 6, 9, 13, 17, and 21 injections, as well as 2, 4, and 19 days after 9-day treatment. Diisopropylfluorophosphate administration increased waking at the expense of slow-wave sleep (SWS), but not of paradoxical sleep (PS); as a . In contrast, after diisopropylfluorophosphate withdrawal, behavioral states returned to control values more rapidly (in 2-4 days) than did cholinesterase activity. These results are discussed regarding the promoting role of cholinergic neurotransmission in brain-activated states.
[Deurveilher S et al; Pharmacology Biochemistry and Behavior 64 (1): 105-114 (1999)]**PEER REVIEWED**

Humans acutely exposed to anticholinesterase (anti-ChE) pesticides often become febrile, whereas rats and other rodents become markedly hypothermic. The rat may nonetheless be a useful model for anti-cholinesterase toxicity because recent work using radiotelemetry demonstrated an elevation in core temperature of unrestrained rats for several days following acute exposure to the anti-cholinesterase, diisopropyl fluorophosphate (DFP). To discern the mechanisms of diisopropyl fluorophosphate-induced hypothermia and hyperthermia, various pharmacological agents were administered acutely or chronically to rats injected with 1.5 mg/kg diisopropyl fluorophosphate (SC). Core temperature, heart rate, and motor activity were monitored continuously via radiotelemetry. Methylscopolamine, a peripheral muscarinic antagonist, attenuated the diisopropyl fluorophosphate-induced hypothermia by 1.0 degree C and reversed the diisopropyl fluorophosphate-induced bradycardia. Chronic scopolamine, a central and peripheral muscarinic antagonist, delivered via a subcutaneously implanted minipump (9.5 mg/kg/day) blocked diisopropyl fluorophosphate-induced hypothermia and hyperthermia. Propranolol (10 mg/kg; SC), a general beta blocker, augmented the bradycardic effects of diisopropyl fluorophosphate but had no effect on body temperature. Sodium salicylate (200 and 300 mg/kg; IP), an antipyretic that inhibits prostaglandin synthesis, administered during the period of diisopropyl fluorophosphate-induced hyperthermia produced a transient recovery in body temperature. Overall, diisopropyl fluorophosphate-induced hypothermia and hyperthermia in the rat appear to be mediated via cholinergic activation in the CNS because both are blocked by scopolamine. The decrease in core temperature following sodium salicylate suggests that prostaglandin release is involved in the manifestation of diisopropyl fluorophosphate-induced hyperthermia. The elevation in core temperature after diisopropyl fluorophosphate appears to involve neurochemical pathways similar to that of fever.
[Gordon CJ; Pharmacol Biochem Behav 55 (2): 185-94 (1999)]**PEER REVIEWED**

This study compared the neurotoxic effects of triphenyl phosphite (TPP) in the rat with those seen after exposure to diisopropylphosphorofluoridate (DFP), a compound known to produce organophosphorus-induced delayed neurotoxicity (OPIDN). Animals received either three subcutaneous injections of triphenyl phosphite (1184 mg/kg body wt each dose) administered at 3-day intervals or a single subcutaneous injection of diisopropylphosphorofluoridate (4 mg/kg body wt). Triphenyl phosphite-induced clinical signs were initially observed 2 to 18 days after the last injection and included ataxia, flaccid paresis, stereotyped alternating side-to-side movements, and circling behavior. Axonal and terminal degeneration were present in the cerebellum, vestibular nuclear complex, cochlear nuclei, and superior and inferior colliculi. The subthalamic nucleus, substantia nigra, septal region, hypothalamus, thalamus, hippocampus, and cerebral cortex also contained degenerating axons and terminals. Degeneration was particularly evident in the sensorimotor cerebral cortex, mediodorsal, ventromedial, and medial geniculate thalamic nuclei and in the magnocellular preoptic and medial mammillary nuclei of the hypothalamus. Very light degeneration was present in the gracile fasciculus and nucleus. In contrast, rats injected with diisopropylphosphorofluoridate showed moderate degeneration in the gracile fasciculus and nucleus but did not display degeneration in any other brain region. Injections of diisopropylphosphorofluoridate did not produce delayed onset clinical signs. The results indicate that in the rat, different central nervous system cell groups are affected by these two organophosphorus compounds and that triphenyl phosphite affects nuclei and tracts at all levels of the neuraxis, including those associated with higher-order processing and cognitive functions. In addition, the distinct degeneration patterns produced by these two compounds support the view that triphenyl phosphite-induced neurotoxicity should not be considered as a type of organophosphorus-induced delayed neurotoxicity, but rather as a separate category of organophosphorus-induced neurotoxicity.
[Lehning EJ et al; Fundam Appl Toxicol 29 (1): 110-8 (1996)]**PEER REVIEWED**

... Daily dosing of DFP /to rats/ in a concn (0.5 mg/kg, sc) that as a single dose did not cause symptoms, produced onset of fasciculations on the third day associated with a reduced number of muscle fiber lesions. Further administration of DFP (14 days) caused disappearance of fasciculations and loss of sensitivity to necrotizing actions in all muscles tested (diaphragm, soleus, and extensor digitorum longus). Activity of all molecular forms of AChE was reduced to 20-24% of control when symtoms of cholinergic hyperactivity appeared. Continuous injections of DFP (0.5 mg/kg/day, sc) up to 14 days did not cause greater inhibition of AChE activity. Instead, recovery of enzyme activity, especially of the 4S and 10S forms, was seen. During this period choline acetyltransferase activity (ChAT) was increased in muscle (intramuscular nerves) while post-synaptic nicotinic acetylcholine receptor (nAChR) density (Bmax) was decreased to 44% without a change in the affinity constant (KD). It is concluded that neuromuscular adaptation to DFP is caused by recovery of AChE activity due to de novo synthesis and reduction in the number of nAChR.
[Gupta RC et al; Toxicol Appl Pharmacol 84 (3): 541-50 (1986)]**PEER REVIEWED**


Non-Human Toxicity Values:

LD50 Rat oral 5 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 1992]**PEER REVIEWED**


TSCA Test Submissions:

The inhibition of nonspecific esterase activity, and/or inhibition of aromatic amino acid esterase activity, and/or potential effects on specific cellular functions (phagocytosis, immunoglobulin G synthesis, and inflammatory and immune mediator release) were evaluated with organic chemicals added to human peripheral blood monocytes. Diisopropyl phosphorofluoridate at a concentration of 1.5 mM inhibited monocyte alpha-naphthyl acetate esterase activity by 65% (assay method not reported).
[General Electric Co; The Effects of Organophosphates on Monocyte Nonspecific EsteraseActivity and Peripheral Blood Monocyte Functions; 12/09/85; EPA Document no. 40-852546; Fiche No. OTS0518445] **UNREVIEWED**


Metabolism/Pharmacokinetics:

Metabolism/Metabolites:

HEN EGG-WHITE LYSOZYME WAS ALLOWED TO REACT WITH AN EXCESS OF DFP @ 25 DEG C & AT PH VALUES RANGING FROM 9.5 TO 11.0. ANALYSIS INDICATED THAT ALKYLPHOSPHORYLATION OF TYROSYL HYDROXYL GROUPS HAD OCCURRED & ... SOME OTHER AMINO ACID RESIDUES HAD ALSO BEEN PHOSPHORYLATED. SIMILAR RESULTS ... OBTAINED WITH STEM BROMELAIN, TAKA-AMYLASE A, & PAPAIN.
[Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. GovernmentPrinting Office, l974. 152]**PEER REVIEWED**

... DIISOPROPYL FLUOROPHOSPHONATE, UNDERGOES DEFLUORINATION IN BOTH MAMMALS & BACTERIA.
[Parke, D. V. The Biochemistry of Foreign Compounds. Oxford: Pergamon Press, 1968. 126]**PEER REVIEWED**

DFP is rapidly metabolized to diisopropylphosphate & is excreted, mainly in the urine. Less than 1% is eliminated by bile & lung within the first 2 hr.
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 332]**PEER REVIEWED**

WHEN SMALL AMOUNTS (0.1 MG/KG) OF DFP WERE ADMIN TO GUINEA PIGS, DFP WAS ... CONVERTED IN PART TO DIISOPROPYL PHOSPHATE (DP) ... DFP WAS DEGRADED BY PSEUDOMONAS MELOPHTHORA BUT NO METABOLITES WERE IDENTIFIED. BLUEGILL (LEPOMIS MACROCHIRUS RAFINESQUE) & CHANNEL CATFISH (ICTALURUS PUNCTALUS WALBAUM) CONVERTED DFP TO DIISOPROPYL PHOSPHATE.
[Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969. 142]**PEER REVIEWED**

An enzyme in Escherichia coli hydrolyzes isofluorophate. A superficially similar but distinctly different enzyme is found in squid nerve. The results of this study suggest that while several tissues of the squid contain only this second kind of DFP hydrolyzing enzyme, termed squid type DFPase, many other sources incl E coli contain a mixt of squid type DFPase (the name not strictly indicative of source) and the other DFP hydrolyzing enzyme, now termed Mazur type DFPase.
[Hoskin FC et al; Two Enzymes for the Detoxication of Organophosphorus Compounds--Sources, Similarities, and Significance: Fundam Appl Toxicol 4 (2, Pt 2): S165-72 (1984)]**PEER REVIEWED**


Absorption, Distribution & Excretion:

WHEN SMALL AMOUNTS (0.1 MG/KG) OF DFP WERE ADMIN TO GUINEA PIGS, DFP WAS PREFERENTIALLY BOUND BY SERUM & BY THE LUNGS. ADMIN OF LARGE AMOUNTS (3-6 MG/KG) PRODUCED UNIFORM BODY DISTRIBUTION & ACCUMULATION IN KIDNEYS & LIVER. DFP WAS CONVERTED IN PART TO DIISOPROPYL PHOSPHATE (DP). BOTH DFP & DP WERE EXCRETED MAINLY IN THE URINE. SOME APPEARED IN BILE.
[Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969. 142]**PEER REVIEWED**

TRANSPLACENTAL PASSAGE OF MORE POLAR INSECTICIDES, DFP ... HAS BEEN INFERRED FROM FETAL CHOLINESTERASE INHIBITION.
[The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 633]**PEER REVIEWED**

... Its high lipid solubility, low molecular weight, and volatility facilitate inhalation and transdermal absorption. DFP also readily penetrates the central nervous system.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996. 167]**PEER REVIEWED**

The effects of skin metabolism on percutaneous penetration of drugs with high lipophilicity were studied in vitro using rat skin pretreated with and without an esterase inhibitor, isoflurophate (diisopropylphosphofluoridate; DFP). Without diisopropylphosphofluoridate, about 96% of the total penetrated amount appeared as metabolized p-hydroxybenzoic acid in the receptor fluid after application of butylparaben, whereas about 30% penetrated as intact form after application of propylparaben. On the other hand, metabolized p-hydroxybenzoic acid was not detected in the receptor fluid under pretreatment with DFP. DFP significantly decreased the total amount that penetrated after application of butylparaben, but it did not significantly affect that of propylparaben. It was concluded that skin metabolism directly affected the total amount that penetrated in the case of highly lipophilic drugs, and that the higher the metabolic rate to hydrophilic drugs, the greater the amount that penetrated the skin.
[Bando H et al; J Pharm Sci 86 (Jun): 759-761 (1997)]**PEER REVIEWED**


Biological Half-Life:

Following iv injection of tritium-labeled DFP, the concn in arterial serum declined in two exponential phases with t1/2 of about 7 & 200 minutes, respectively, reflecting, first, fast accumulation of the compound & its metabolites in the tissue &, second, elimination.
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 332]**PEER REVIEWED**


Mechanism of Action:

Passive avoidance retention and cortical (3)H-quinuclidinyl benzilate (QNB) binding were exam in rats that were chronically treated with isofluorophate. Retention of a passive avoidance response was significantly lower when compared to vehicle-treated controls. Passive avoidance retention decr from 93% in control animals to 68% in DFP-treated rats. QNB binding studies revealed the density of muscarinic receptors in cortical homogenates was significantly reduced from 0.95 +/- 0.04 pmol/mg protein in controls to 0.72 +/- 0.04 pmol/mg protein in DFP-treated rats. Based on data that DFP causes a redn in cholinergic receptors, this study supports the hypothesis that central cholinergic receptors are assoc with mechanisms involved in memory storage.
[Gardner R et al; A Possible Mechanism for Diisopropylfluorophosphate-Induced Memory Loss in Rats. Pharmacol Biochem Behav 21 (1): 43-6 (1984)]**PEER REVIEWED**

The organophosphorus inhibitors, such as DFP, serve as true hemisubstrates, since the resultant conjugate with the active center serine phosphorylated or phosphonylated is extremely stable. ... If the alkyl groups in the phosphorylated enzyme are ethyl or methyl, a significant degree of spontaneous regeneration of active enzyme requires several hours. Secondary (as in DFP) or tertiary alkyl groups enhance the stability of the phosphorylated enzyme, & significant regeneration of active enzyme is not observed. Hence, the return of acetylcholinesterase activity depends on synthesis of new enzyme.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996. 163]**PEER REVIEWED**

The characteristic pharmacological effects of the anticholinesterase agents are due primarily to the prevention of hydrolysis of acetylcholine by acetylcholinesterase at sites of cholinergic transmission. The transmitter thus accumulates, & the action of acetylcholine that is liberated by cholinergic impulses that leak from the nerve ending is enhanced. With most of the organophosphorus agents, such as DFP, virtually all the acute effects of moderate doses are attributable to this action. For example, the characteristic miosis that follows local application of DFP to the eye is not observed after chronic postganglionic denervation of the eye because there is no effective source of endogenous acetylcholine.
[Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996. 165]**PEER REVIEWED**

Rats were treated with DFP using 1 or 2 mg/kg acutely, or with 1 mg/kg daily for 4, 14 or 28 days. Tremors, chewing movements and hind-limb abduction induced by DFP incr in a steeply dose-dependent manner. Tremor occurred in a complex spectrum of slow to intense fast types. Except for chewing, tolerance developed for these parameters, but at different rates. After acute treatment striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels were altered and the DOPAC/DA ratios were consistently incr within about the first 2 hr, suggesting an incr turnover of DA. It is suggested that the changes in DA metab arose secondarily to an elevation of brain acetylcholine following cholinesterase inhibition. A prolonged change in the levels or turnover of DA could be responsible for incr of postsynaptic DA receptor density previously found, which might then partly mediate the behavioral tolerance to DFP.
[Fernando JC et al; Effect on Striatal Dopamine Metabolism and Differential Motor Behavioral Tolerance Following Chronic Cholinesterase Inhibition with diisopropylfluorophosphate; Pharmacol Biochem Behav 20 (6): 951-7 (1984)]**PEER REVIEWED**

DFP (1X10-3 M) inhibited both spontaneous release and K+-stimulated dopamine release from rat brain striatum in vitro, the effect on the latter being greater than that on the former. At 1X10-5 and 1X10-4 M the inhibitory effects of physostigmine and oxotremorine on K+-stimulated dopamine release were similar to those of DFP. Also, the apparent stimulatory effects of DFP at 1X10-5 and 1X10-4 M on spontaneous dopamine release were similar to those of physostigmine and oxotremorine. However, the inhibitory effect of 1X10-3 M DFP on spontaneous and induced dopamine release was not observed following physostigmine or oxotremorine. Apparently, moderate DFP concn affect dopamine release via an effect of incr acetylcholine on muscarinic receptors of dopaminergic neurons, whereas high DFP concn might directly attack protein sites involved in neurotransmitter release.
[Kant GJ et al; Effects of Diisopropylfluorophosphate (DFP) and Other Cholinergic Agents on Release of Endogenous Dopamine from Rat Brain Striatum In Vitro: Biochem Pharmacol 33 (11): 1823-5 (1984)]**PEER REVIEWED**

The effects of DFP on neuromuscular transmission were explored using intracellular recording techniques in a vascular perfused rat phrenic nerve-hemidiaphragm prepn. The presence of DFP (4X10-5 M) in the perfusion medium yielded greater than 97% inhibition of acetylcholinesterase activity and resulted in a slight incr in amplitude as well as a prolongation of the decay phase of spontaneous miniature endplate potentials and evoked endplate potentials. Quantal content of evoked acetylcholine release was unaltered by DFP. Therefore, DFP appears to be an appropriate acetylcholinesterase inhibitor for studies involving the release of endogenous acetylcholine from phrenic nerve-hemidiaphragm.
[Bierkamper GG; Electrophysiological Effects of Diisopropyl fluorophosphate on Neuromuscular Transmission: Eur J Pharmacol 73 (4): 343-8 (1981)]**PEER REVIEWED**

/A study concerned/ with the feasibility of a general approach of chemical modification of an enzyme for decreasing the reactivity with organophosphorus inhibitors relative to activity towards substrate, and potential prophylaxis, has been demonstrated. Chemical modification of chymotrypsin decreases its reactivity to organophosphorus compounds. The ratios of rates of inhibition of native to modified chymotrypsin are 3:2 for sarin, 2:1 for diisopropyl fluorophosphate, 6.7:1 for soman, and 7.1:1 for cyclohexylmethylphosphonofluoridate. The bulkier the organophosphorus compound, generally the more potent its inhibition of native chymotrypsin, the slower its relative rate of inhibition of modified chymotrypsin. Inhibited native chymotrypsin could be reactivated by pralidoxime chloride more rapidly than could inhibited modified chymotrypsin. The ratios of half-times of reactivation when comparing native to modified enzymes were 2:1 for sarin and 7.8:1 for soman inhibitions. Native chymotrypsin inhibited by soman can be reactivated twice as fast as when inhibited by sarin, whereas the reverse occurs with modified ehymotrypsin.
[Ellin RI, Thompson AR; Decreased Reactivity of Organophosphorus Inhibitors Towards a Modified Chymotrypsin 16pp (1970) Edgewood Arsenal Report No. EA-TR-4414]**PEER REVIEWED**

Perfusion of the hemidiaphragm with 10 or 100 mu M of DFP reduced choline efflux by 39% and 69%, respectively. DFP administration to rats (6 mg/kg) also lowered the in vitro release of choline by 33%. The rate of ACh release from hemidiaphragm preparations perfused with DFP was lower than the rate of release from the preparations perfused with physostigmine, an acetylcholinesterase inhibitor which had no effect on choline efflux. The addition of choline (10-30 muM) to the perfusion medium restored the rate of ACh release from DFP-treated hemidiaphragms but did not further elevate ACh release from physostigmine-treated preparations. Thus, DFP inhibits choline efflux from the isolated hemidiaphragm and apparently by limiting the availability of choline for ACh synthesis, DFP reduces the rate of ACh release.
[Millington WR et al; Eur J Pharmacol 115 (1): 37-44 (1985)]**PEER REVIEWED**

Diisopropyl fluorophosphate ... is widely used as an enzyme inhibitor.
[Lunn, G., E.B. Sansone. Destruction of Hazardous Chemicals in the Laboratory. New York, NY: John Wiley & Sons, Inc. 1994. 149]**PEER REVIEWED**

Organophosphate insecticides such as ... DFP are potent cholinesterase enzyme inhibitors that act by interfering with the metabolism of acetylcholine, resulting in the accumulation of acetylcholine at neuroreceptor transmission sites.
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995. 979]**PEER REVIEWED**


Interactions:

IN SOME CASES ANOTHER PARASYMPATHOMIMETIC AGENT SUCH AS CARBACHOL ... MAY ENHANCE THE EFFECT OF ISOFLUROPHATE. HOWEVER, ACTION OF ISOFLUROPHATE IS INHIBITED BY PRIOR INSTILLATION OF PHYSOSTIGMINE.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 52:20]**PEER REVIEWED**

Phenyl methyl sulfonyl fluoride (PMSF) was able to protect hens from delayed neurotoxicity when given 4 hr before 1.7 mg/kg sc DFP. However, PMSF was ineffective at preventing paralysis when given later than 4 hr before DFP admin. These results support the notion that PMSF acts at the same site as the organophosphorus esters.
[Carrington CD, Abou-Donia MB; The Time Course of Protection from Delayed Neurotoxicity Induced by Tri-o-cresyl phosphate and O,O-diisopropyl phosphorofluoridate by Phenyl Methyl Sulfonyl Fluoride in chickens; Toxicol Lett 18 (3): 251-6 (1983)]**PEER REVIEWED**

Using the hot-plate test in mice di-isopropylfluorophosphate potentiates the antinociceptive activity of alfentanil but has no effect on the activity of morphine or fentanyl.
[Kitchen I, Green PG; Differential Effects of Di-isopropylfluorophosphate Poisoning and its Treatment on Opioid Antinociception in the Mouse: Life Sci 33 (Suppl 1): 669-72 (1983)]**PEER REVIEWED**

Skin penetration of the alkyl phophates, diisopropyl fluorophosphate (DFP) and N,N-dimethylamino-o-ethylcyanophosphate (Tabun), was investigated, in vitro and in vivo, in guinea pigs and rats. As a basis for the development of skin barrier creams (formulations), a series of polyethylene glycols was chosen. For some formulations a short-time inhibition of Tabun-penetration in vitro was found, which could not be verified in vivo. In vivo all formulations gave an enhancement of penetration. Mixed with Tabum (10:1) polyethylene glycol 400 strongly diminished the penetration of the former substance.
[Schreiber G, Herring H; Fraunhofer-Gesellschaft Zur Forderung der Angewandten Forschung, Grafschaft Inst fuer Aerobiologie 38pp (1973) Report No. BMVG-FBWT-73-30]**PEER REVIEWED**

Exptl Therapy: The delayed organophosphorus neuropathy caused by diisopropyl fluorophosphate (DFP) can be prevented by pretreatment with phenylmethanesulfonyl fluoride (PMSF). A single injection of DFP (2 mg/kg) into a cat femoral artery produced a delayed neuropathy in the injected leg. Cats which received PMSF (30 mg/kg, ip) 4 hr before DPF administration did not develop any neurotoxic signs.
[Drakontides AB, Baker T; Toxicol Appl Pharmacol 70 (3): 411-22 (1983)]**PEER REVIEWED**

... Diazepam,with atropine and obidoxime, substantially raised the LD50 of diisopropyl phosphorofluoridate (DFP) in rats.
[Marrs, T.C., Maynard, R.L., Sidell, F.R.; Chemical Warfare Agents. Toxicology and Treatment. John Wiley & Sons, New York, NY. (1996). 107]**PEER REVIEWED**

DFP injected into the femoral artery of cats causes a localized organophosphorus-induced delayed neuropathy (OPIDN). Gait disturbances develop in the treated leg 14 days after DFP exposure and reaches a maximum at 21 to 28 days after DFP. In vivo high-frequency conditioning of soleus motor nerve endings evokes stimulus-bound repetitive neural discharges (SBR) and an obligatory potentiation of the muscle contractile response (PTP). In this OPIDN model, SBR and PTP are maximally suppressed at 21 to 28 days after DFP. A high-dose regimen of methylprednisolone started 30 to 40 minutes after DFP exposure and lasting for 20 days prevented the development of OPIDN. In the methylprednisolone-DFP treated cats, SBR and PTP functions were not suppressed and not different from those in untreated normal cats.
[Baker T, Stanec A; Toxicol Appl Pharmacol 79 (2): 348-52 (1985)]**PEER REVIEWED**


Pharmacology:

Therapeutic Uses:

Cholinesterase Inhibitors; Miotics; Parasympathomimetics; Protease Inhibitors
[National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)]**PEER REVIEWED**

OCCASIONALLY BY PHYSICIANS (OPHTHALMOLOGISTS) FOR TREATMENT OF GLAUCOMA.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-299]**PEER REVIEWED**

IT IS USED TOPICALLY IN TREATMENT OF PRIMARY OPEN-ANGLE GLAUCOMA, BUT ONLY WHEN SHORT-ACTING MIOTICS HAVE FAILED. ... ALSO USED IN TREATMENT OF APHAKIC GLAUCOMA & ACCOMMODATIVE ESOTROPIA. WITHIN A DAY INTRAOCULAR TENSION DROPS, & ... MAY REMAIN DEPRESSED FOR A ... WK. MIOSIS LASTS 2 TO 4 WK.
[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980. 840]**PEER REVIEWED**

IRREVERSIBLE ANTICHOLINESTERASE ... ISOFLUROPHATE ... /IS/ ONLY OF HISTORICAL INTEREST IN TREATMENT OF MYASTHENIA GRAVIS ... UNSATISFACTORY BECAUSE OF ... TOXICITY.
[American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977. 1018]**PEER REVIEWED**

MEDICATION (VET): ... /IS/ COMMONLY USED ... /LOCALLY TO CONSTRICT THE PUPIL FOR TREATMENT OF GLAUCOMA/ IN DOGS. EFFECTS ... ARE RELATIVELY LONG LASTING & DOSAGE MUST BE CAREFULLY CONTROLLED.
[Jones, L.M., et al. Veterinary Pharmacology & Therapeutics. 4th ed. Ames: Iowa State University Press, 1977. 155]**PEER REVIEWED**

Of the organophosphorus agents, DFP has the longest duration of action & is extremely potent when applied locally; solutions in peanut or sesame oil require instillation from once daily to once weekly, & may control intraocular pressure in severe cases that are resistant to other drugs. The oily vehicle is unpleasant to most patients. Consequently, DFP has largely been replaced by echothiophate.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 124]**PEER REVIEWED**

MEDICATION: CHOLINERGIC (OPHTHALMIC)
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 744]**PEER REVIEWED**

Medication: An organophosphate anticholinesterase ... used topically in the treatment of primary open-angle glaucoma, but only when short acting miotics have failed. It is also used in the treatment of aphkic glaucoma and accomodative estropia.
[GENNARO. REMINGTON'S PHARM SCI 17TH ED 1985 p.899]**PEER REVIEWED**

MEDICATION (VET): HAS BEEN USED AS A MIOTIC
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 744]**PEER REVIEWED**

This compound is used to treat glaucoma.
[Lunn, G., E.B. Sansone. Destruction of Hazardous Chemicals in the Laboratory. New York, NY: John Wiley & Sons, Inc. 1994. 149]**PEER REVIEWED**


Drug Warnings:

... Should be used cautiously in patients with bronchial asthma, bradycardia, or hypotension. An increase in blood pressure may occur occasionally due to a nicotinic effect on sympathetic ganglia.
[American Medical Association, AMA Department of Drugs. AMA Drug Evaluations. 5th ed. Chicago: American Medical Association, 1983. 449]**PEER REVIEWED**

Because of their cataractogenic properties & other toxicity, /diisopropyl fluorophosphate/ should be reserved for patients refractory to short-acting miotics, epinephrine, beta-blocking drugs, & possibly, carbonic anhydrase inhibitors. /Long-acting miotics, including floropryl/
[American Medical Association, AMA Department of Drugs. AMA Drug Evaluations. 5th ed. Chicago: American Medical Association, 1983. 447]**PEER REVIEWED**


Interactions:

IN SOME CASES ANOTHER PARASYMPATHOMIMETIC AGENT SUCH AS CARBACHOL ... MAY ENHANCE THE EFFECT OF ISOFLUROPHATE. HOWEVER, ACTION OF ISOFLUROPHATE IS INHIBITED BY PRIOR INSTILLATION OF PHYSOSTIGMINE.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 52:20]**PEER REVIEWED**

Phenyl methyl sulfonyl fluoride (PMSF) was able to protect hens from delayed neurotoxicity when given 4 hr before 1.7 mg/kg sc DFP. However, PMSF was ineffective at preventing paralysis when given later than 4 hr before DFP admin. These results support the notion that PMSF acts at the same site as the organophosphorus esters.
[Carrington CD, Abou-Donia MB; The Time Course of Protection from Delayed Neurotoxicity Induced by Tri-o-cresyl phosphate and O,O-diisopropyl phosphorofluoridate by Phenyl Methyl Sulfonyl Fluoride in chickens; Toxicol Lett 18 (3): 251-6 (1983)]**PEER REVIEWED**

Using the hot-plate test in mice di-isopropylfluorophosphate potentiates the antinociceptive activity of alfentanil but has no effect on the activity of morphine or fentanyl.
[Kitchen I, Green PG; Differential Effects of Di-isopropylfluorophosphate Poisoning and its Treatment on Opioid Antinociception in the Mouse: Life Sci 33 (Suppl 1): 669-72 (1983)]**PEER REVIEWED**

Skin penetration of the alkyl phophates, diisopropyl fluorophosphate (DFP) and N,N-dimethylamino-o-ethylcyanophosphate (Tabun), was investigated, in vitro and in vivo, in guinea pigs and rats. As a basis for the development of skin barrier creams (formulations), a series of polyethylene glycols was chosen. For some formulations a short-time inhibition of Tabun-penetration in vitro was found, which could not be verified in vivo. In vivo all formulations gave an enhancement of penetration. Mixed with Tabum (10:1) polyethylene glycol 400 strongly diminished the penetration of the former substance.
[Schreiber G, Herring H; Fraunhofer-Gesellschaft Zur Forderung der Angewandten Forschung, Grafschaft Inst fuer Aerobiologie 38pp (1973) Report No. BMVG-FBWT-73-30]**PEER REVIEWED**

Exptl Therapy: The delayed organophosphorus neuropathy caused by diisopropyl fluorophosphate (DFP) can be prevented by pretreatment with phenylmethanesulfonyl fluoride (PMSF). A single injection of DFP (2 mg/kg) into a cat femoral artery produced a delayed neuropathy in the injected leg. Cats which received PMSF (30 mg/kg, ip) 4 hr before DPF administration did not develop any neurotoxic signs.
[Drakontides AB, Baker T; Toxicol Appl Pharmacol 70 (3): 411-22 (1983)]**PEER REVIEWED**

... Diazepam,with atropine and obidoxime, substantially raised the LD50 of diisopropyl phosphorofluoridate (DFP) in rats.
[Marrs, T.C., Maynard, R.L., Sidell, F.R.; Chemical Warfare Agents. Toxicology and Treatment. John Wiley & Sons, New York, NY. (1996). 107]**PEER REVIEWED**

DFP injected into the femoral artery of cats causes a localized organophosphorus-induced delayed neuropathy (OPIDN). Gait disturbances develop in the treated leg 14 days after DFP exposure and reaches a maximum at 21 to 28 days after DFP. In vivo high-frequency conditioning of soleus motor nerve endings evokes stimulus-bound repetitive neural discharges (SBR) and an obligatory potentiation of the muscle contractile response (PTP). In this OPIDN model, SBR and PTP are maximally suppressed at 21 to 28 days after DFP. A high-dose regimen of methylprednisolone started 30 to 40 minutes after DFP exposure and lasting for 20 days prevented the development of OPIDN. In the methylprednisolone-DFP treated cats, SBR and PTP functions were not suppressed and not different from those in untreated normal cats.
[Baker T, Stanec A; Toxicol Appl Pharmacol 79 (2): 348-52 (1985)]**PEER REVIEWED**


Environmental Fate & Exposure:

Environmental Fate/Exposure Summary:

Diisopropyl fluorophosphate's production and use as a cholinergic and miotic may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 0.54 mm Hg at 25 deg C indicates diisopropyl fluorophosphate will exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase diisopropyl fluorophosphate will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 5 hrs. If released to soil, diisopropyl fluorophosphate is expected to have very high mobility based upon an estimated Koc of 31. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole. Diisopropyl fluorophosphate will not volatilize from dry soil surfaces based upon its vapor pressure. If released into water, diisopropyl fluorophosphate is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 250 hrs and 120 days, respectively. An estimated BCF of 1 suggests the potential for bioconcentration in aquatic organisms is low. Diisopropyl fluorophosphate does undergo hydrolysis to HF and diisopropyl phosphate; half-lives range from 16.7 hrs to 2.2 days at temperatures of 37 to 25 deg C and 72 hrs to several days at temperatures of 15 to 30 deg C. Occupational exposure to diisopropyl fluorophosphate may occur through dermal contact with this compound at workplaces where diisopropyl fluorophosphate is produced or used. (SRC)
**PEER REVIEWED**


Probable Routes of Human Exposure:

Occupational exposure to diisopropyl fluorophosphate may occur through dermal contact with this compound at workplaces where diisopropyl fluorophosphate is produced or used. (SRC)
**PEER REVIEWED**


Artificial Pollution Sources:

Diisopropyl fluorophosphate's production and use as a cholinergic and miotic (in veterinary medicine)(1) may result in its release to the environment through various waste streams(SRC).
[(1) Budavari S, ed; The Merck Index. 12th ed. Whitehouse Station, NJ: Merck and Co. p. 883 (1996)]**PEER REVIEWED**


Environmental Fate:

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 31(SRC), determined from a structure estimation method(2), indicates that diisopropyl fluorophosphate is expected to have very high mobility in soil(SRC). Volatilization of diisopropyl fluorophosphate from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Diisopropyl fluorophosphate does undergo hydrolysis to HF and diisopropyl phosphate; half-lives range from 16.7 hrs-2.2 days at temperatures of 37-25 deg C(5,6) and 72 hrs-several days at temperatures of 15-30 deg C(7,8). Diisopropyl fluorophosphate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.54 mm Hg(SRC), determined from a fragment constant method(4).
[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (3) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (4) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985) (5) Ramachandran BV; Indian J Biochem Biophys 8: 112-113 (1971) (6) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc p. 7-19 (1982) (7) O'Brien RD; Toxic Phosphorus Esters. NY, NY: Academic Press pp. 29-52 (1960) (8) Saunders BC, Todd A; Some Aspects of the Chem and Tox Action of Organic Cpds Containing Phosphorus and Fluorine. Cambridge, England: Cambridge Univ Press pp. 46-9 (1957)]**PEER REVIEWED**

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 31(SRC), determined from an estimation method(2), indicates that diisopropyl fluorophosphate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 3.2X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 250 hr and 120 days, respectively(SRC). Diisopropyl fluorophosphate does undergo hydrolysis to HF and diisopropyl phosphate; half-lives range from 16.7 hrs-2.2 days at temperatures of 37-25 deg C(8,9) and 72 hrs-several days at temperatures of 15-30 deg C(10,11). According to a classification scheme(5), an estimated BCF of 1(SRC), from an estimated log Kow of 1.13(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low.
[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990) (4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (5) Franke C et al; Chemosphere 29: 1501-14 (1994) (6) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995) (7) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999) (8) Ramachandran BV; Indian J Biochem Biophys 8: 112-113 (1971) (9) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: American Chemical Society p. 7-19 (1982) (10) O'Brien RD; Toxic Phosphorus Esters. NY, NY: Academic Press, pp. 29-52 (1960) (11) Saunders BC, Todd A; Some Aspects of the Chem and Tox Action of Organic Cpds Containing Phosphorus and Fluorine. Cambridge, England: Cambridge Univ Press pp. 46-9 (1957)]**PEER REVIEWED**

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diisopropyl fluorophosphate, which has a vapor pressure of 0.54 mm Hg at 25 deg C(2), is expected to exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase diisopropyl fluorophosphate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 5 hrs(SRC), calculated from its rate constant of 8.0X10-11 cu cm/molecule-sec at 25 deg C(3) determined using a structure estimation method(3).
[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985) (3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)]**PEER REVIEWED**

Environmental Biodegradation:

Microbial cell-free extracts were found to contain lysase enzymes capable of hydrolyzing diisopropyl fluorophosphate(1). This indicates that intact microorganisms in the environment may also be capable of biodegrading diisopropyl fluorophosphate. One study reported that Pseudomonas melophthora could degrade diisopropyl fluorophosphate in the presence of yeast extract, mannitol, and acetone(2). Diisopropyl fluorophosphate was found to be rapidly degraded (no quantitative rate was given) in ruminal fluid(3), which contains anaerobic microorganisms.
[(1) Mounter LA, Tuck KD; J Biol Chem 221: 537 (1956) (2) Boush GM, Matsumura F; J Econom Entomology 60: 918-920 (1967) (3) Mounter LA et al; J Biol Chem 215: 691 (1955)]**PEER REVIEWED**


Environmental Abiotic Degradation:

The rate constant for the vapor-phase reaction of diisopropyl fluorophosphate with photochemically-produced hydroxyl radicals has been estimated as 8.0X10-11 cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Diisopropyl fluorophosphate does undergo hydrolysis. Diisopropyl fluorophosphate in a 0.03 m bicarbonate buffer with a pH of 7.4 at a temperature of 37 deg C had a half-life of 16.7 hours(2). Extrapolation of these data to 25 deg C(3) gives a half-life of approximately 2.2 days. Other researchers report a half-life of several days at 30 deg C and pH 7.6 and that in dilute solutions (pH not indicated) hydrolysis goes to completion in 72 hr at 15 deg C(4,5). A kinetic study of the hydrolysis of diisopropyl fluorophosphate in neutral and acid aqueous solutions found the reaction to be autocatalytic and catalyzed by hydrogen ions for an initial rate of 0.6%/hr that was independent of the initial concentration of diisopropyl fluorophosphate and produced diisopropyl phosphate and HF(5). Cupric ions are extremely effective at catalyzing the hydrolysis of diisopropyl fluorophosphate although other ions are less effective or without effect(4). This suggests that some soils may catalyze hydrolysis but experimental data are lacking.
[(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993) (2) Ramachandran BV; Indian J Biochem Biophys 8: 112-113 (1971) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc p. 7-19 (1982) (4) O'Brien RD; Toxic Phosphorus Esters. NY, NY: Academic Press pp. 29-52 (1960) (5) Saunders BC, Todd A; Some Aspects of the Chem and Tox Action of Organic Cpds Containing Phosphorus and Fluorine. Cambridge, England: Cambridge Univ Press, pp. 46-9 (1957)]**PEER REVIEWED**


Environmental Bioconcentration:

An estimated BCF of 1 was calculated for diisopropyl fluorophosphate(SRC), using an estimated log Kow of 1.13(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low.
[(1) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995) (2) Meylan WM et al; Environ Toxicol Chem 18: 664-72 (1999) (3) Franke C et al; Chemosphere 29: 1501-14 (1994)]**PEER REVIEWED**


Soil Adsorption/Mobility:

Using a structure estimation method based on molecular connectivity indices(1), the Koc for diisopropyl fluorophosphate can be estimated to be 31(SRC). According to a classification scheme(2), this estimated Koc value suggests that diisopropyl fluorophosphate is expected to have very high mobility in soil.
[(1) Meylan WM et al; Environ Sci Technol 26: 1560-67 (1992) (2) Swann RL et al; Res Rev 85: 17-28 (1983)]**PEER REVIEWED**


Volatilization from Water/Soil:

The Henry's Law constant for diisopropyl fluorophosphate is estimated as 3.2X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that diisopropyl fluorophosphate is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 250 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 120 days(SRC). Diisopropyl fluorophosphate's Henry's Law constant(1) indicates that volatilization from moist soil surfaces may occur(SRC). Diisopropyl fluorophosphate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.54 mm Hg(SRC), determined from a fragment constant method(3).
[(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (3) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)]**PEER REVIEWED**


Environmental Standards & Regulations:

CERCLA Reportable Quantities:

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).
[40 CFR 302.4 (7/1/99)]**PEER REVIEWED**

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Isofluorphate is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100 lbs.
[40 CFR 355 (7/1/99)]**PEER REVIEWED**


RCRA Requirements:

P043; As stipulated in 40 CFR 261.33, when diisopropyl fluorophosphate, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).
[40 CFR 261.33 (7/1/99)]**PEER REVIEWED**


Chemical/Physical Properties:

Molecular Formula:

C6-H14-F-O3-P
**PEER REVIEWED**


Molecular Weight:

184.15
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 83]**PEER REVIEWED**


Color/Form:

Liquid
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

CLEAR, COLORLESS OR FAINTLY YELLOW LIQUID
[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980. 840]**PEER REVIEWED**

Oily liquid
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997. 390]**PEER REVIEWED**


Odor:

Very weak fruity odor
[Aleksandrov VN; Toxic Agents. Washington, DC: Joint Publication Research Service. NTIS JPRS 48748. p. 53 (1969)]**PEER REVIEWED**


Boiling Point:

62 deg C @ 9 mm Hg; 46 deg C @ 5 mm Hg; 183 deg C @ 760 mm Hg (by extrapolation)
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996.,p. 8Y83]**PEER REVIEWED**


Melting Point:

-82 deg C
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**


Density/Specific Gravity:

1.055
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**


Solubilities:

Solubility in water @ 25 deg C: 1.54% wt/wt; sol in vegetable oils; not very sol in mineral oils
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

Sol in ether
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999. 262]**PEER REVIEWED**

SOL IN ALCOHOL
[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980. 840]**PEER REVIEWED**

Soluble in organic solvents, fuel and lubricants.
[Aleksandrov VN; Toxic Agents. Washington, DC: Joint Publication Research Service. NTIS JPRS 48748. p. 53 (1969)]**PEER REVIEWED**


Spectral Properties:

Index of refraction: 1.3830 @ 25 deg C/D
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

MAX ABSORPTION (ALCOHOL): 243 NM (LOG E = 0.28); 255 NM (LOG E = 0.33); 261 NM (LOG E = 0.30)
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979.,p. C-309]**PEER REVIEWED**

UV: 2-79 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 641]**PEER REVIEWED**


Vapor Density:

6.4 (Air= 1)
[Aleksandrov VN; Toxic Agents. Washington, DC: Joint Publication Research Service. NTIS JPRS 48748. p. 53 (1969)]**PEER REVIEWED**


Vapor Pressure:

0.579 mm Hg @ 20 deg C
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**


Other Chemical/Physical Properties:

Forms hydrogen fluoride in presence of moisture; decomp in water @ pH about 2.5
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

DFP yields phosphate as a result of decomposition with sulfuric acid.
[NIH/EPA; OHM/TADS (1986)]**PEER REVIEWED**

Oil/water partition coefficient: log= 0.93
[Hansch, C., A. Leo. Substituent Constants for Correlation Analysis in Chemistry and Biology. New York, NY: John Wiley and Sons, 1979. 210]**PEER REVIEWED**

Carbon tetrachloride/water partition coefficient: 1.57-1.58
[Hansch, C., A. Leo. Substituent Constants for Correlation Analysis in Chemistry and Biology. New York, NY: John Wiley and Sons, 1979. 210]**PEER REVIEWED**

The anhydride compd or oil solns are stable in glass containers at room temp.
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**


Chemical Safety & Handling:

DOT Emergency Guidelines:

Health: Toxic; may be fatal if inhaled, ingested or absorbed through skin. Inhalation or contact with some of these materials will irritate or burn skin and eyes. Fire will produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control or dilution water may cause pollution. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Fire or explosion: Highly flammable: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion and poison hazard indoors, outdoors or in sewers. Some may polymerize (P) explosively when heated or involved in a fire. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Public safety: Call Emergency Response Telephone Number. ... Isolate spill or leak area immediately for at least 100 to 200 meters (330 to 660 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate closed spaces before entering. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing which is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing is recommended for fire situations only; it is not effective in spill situations. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire, isolate for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Fire: CAUTION: All these products have a very low flash point. Use of water spray when fighting fire may be inefficient. Small fires: Dry chemical, CO2, water spray or alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. Move containers from fire area if you can do it without risk. Dike fire control water for later disposal; do not scatter the material. Do not use straight streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from the ends of tanks. For massive fire use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Spill or leak: Fully encapsulating, vapor protective clothing should be worn for spills and leaks with no fire. ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). All equipment used when handling the product must be grounded. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. A vapor suppressing foam may be used to reduce vapors. Small spills: Absorb with earth, sand or other non-combustible material and transfer to containers for later disposal. Use clean non-sparking tools to collect absorbed material. Large spills: Dike far ahead of liquid spill for later disposal. Water spray may reduce vapor; but may not prevent ignition in closed spaces. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

First aid: Move victim to fresh air. Call emergency medical care. Apply artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; induce artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. Wash skin with soap and water. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved, and take precautions to protect themselves. /Organophosphorus pesticide, liquid, flammable, poisonous; Organophosphorus pesticide, liquid, flammable, toxic; Organophosphorus pesticide, liquid, poisonous, flammable; Organophosphorus pesticide, liquid, toxic, flammable/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-131]**PEER REVIEWED**

Health: Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

Fire or explosion: Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

Public safety: CALL Emergency Response Telephone Number. ... Isolate spill or leak area immediately for at least 25 to 50 meters (80 to 160 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing which is specifically recommended by the manufacturer. Structural firefighters' protective clothing is recommended for fire situations ONLY; it is not effective in spill situations. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

Fire: Small fires: Dry chemical, CO2 or water spray. Large fires: Water spray, fog or regular foam. Move containers from fire area if you can do it without risk. Dike fire control water for later disposal; do not scatter the material. Do not use straight streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from the ends of tanks. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

Spill or leak: Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent spreading . Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**

First aid: Move victim to fresh air. Call emergency medical care. Apply artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; induce artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved, and take precautions to protect themselves. /Organophosphorus pesticide, liquid, poisonous; Organophosphorus pesticide, liquid, toxic; Organophosphorus pesticide, solid, poisonous; Organophosphorus pesticide, solid, toxic/
[U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996).,p. G-152]**PEER REVIEWED**


Fire Fighting Procedures:

Fire Fighting: Self-contained breathing apparatus with a full facepiece operated in pressure-demand or other positive pressure mode. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 5]**PEER REVIEWED**


Hazardous Decomposition:

When heated to decomposition it emits toxic fumes of /Fluoride and Phosporous Oxide/
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 1993]**PEER REVIEWED**

Forms hydrogen fluoride in presence of moisture; decomp in water @ pH about 2.5
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

DFP yields phosphate as a result of decomposition with sulfuric acid.
[NIH/EPA; OHM/TADS (1986)]**PEER REVIEWED**


Protective Equipment & Clothing:

... WHEN HANDLING ISOFLUROPHATE IN OPEN CONTAINERS, PROTECT THE EYES, NOSE, & MOUTH WITH A SUITABLE MASK, & AVOID CONTACT WITH SKIN.
[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980. 840]**PEER REVIEWED**

Data suggest break-through times of approximately an hour or more for protective clothing made of butyl or nitrile rubber. /Organo-phosphorous compounds/
[ACGIH; Guidelines Select of Chem Protect Clothing Volume #1 Field Guide p.79 (1983)]**PEER REVIEWED**

Respiratory protection is as follows: particulate or vapor concentration: 1 mg/cu m or less: Any chemical cartridge respirator with an organic vapor cartridge and dust, fume, and mist filter, including pesticide respirators which meet the requirements of this class, or any supplied-air respirator, or any self-contained breathing apparatus. 5 mg/cu m or less: A chemical cartridge respirator with a full facepiece, organic vapor cartridge, and dust, fume, and mist filter, including pesticide respirators which meet the requirements of this class, or a gas mask with a chin-style or a front- or back-mounted organic vapor canister and dust, fume, and mist filter, including pesticide respirators which meet the requirements of this class, or any supplied-air respirator with a full facepiece, helmet, or hood, or any self-contained breathing apparatus with a full facepiece. 20 mg/cu m or less: A powered air-purifying respirator with an organic vapor cartridge and high efficiency particulate filter, including pesticide respirators which meet the requirements of this class or a type C supplied-air respirator operated in pressure-demand or other positive pressure or continuous-flow mode. Greater than 20 mg/cu m or entry and escape from unknown concentrations: Self-contained breathing apparatus with a full facepiece operated in pressure-demand or other positive pressure mode, or a combination respirator which includes a type C supplied-air respirator with a full facepiece operated in pressure-demand or other positive pressure or continuous-flow mode and an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive pressure mode. Escape: Any gas mask providing protection against organic vapors and particulates or any escape self-contained breathing apparatus. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 5]**PEER REVIEWED**


Preventive Measures:

Clothing which has had any possibility of being contaminated ... should be placed into closed containers for storage until it can be discarded or provisions are made for ... removal from the clothing. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**

Provide an emergency eyewash station. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**

Non-impervious clothing which becomes contaminated ... should be removed immediately and not reworn until ... /provisions are made for/ removal /from/ the clothing. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**

Skin that becomes contaminated ... should be immediately washed ... with soap or mild detergent and water. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**

Eating and smoking should not be permitted in areas where /material/ is handled, stored, or processed. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**

Where there is any possibility of exposure of an employee's body ... facilities for quick drenching of the body should be provided within the immediate work area for emergency use. /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**

Employees should be provided with and required to use impervious clothing, gloves, face shields. ... (eight inch minimum). /Parathion/
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 3]**PEER REVIEWED**


Stability/Shelf Life:

ANHYDROUS CMPD OR OIL SOLUTIONS ARE STABLE IN GLASS CONTAINERS AT ROOM TEMPERATURES.
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 744]**PEER REVIEWED**


Storage Conditions:

... MUST BE STORED IN ITS SEALED ORIGINAL CONTAINERS, IN WELL-AIRED, FRESH & DRY STOREHOUSES OR IN SHADED & POSSIBLY WELL-AIRED PLACES. IT IS RECOMMENDED THAT THE PRODUCT'S TEMP ... NOT EXCEED 25-30 DEG C, & KEEP ... AWAY FROM SOURCES OF HEAT, FREE FLAMES OR SPARK-GENERATING EQUIPMENT. CONTAINERS MUST BE STACKED IN SUCH A WAY AS TO PERMIT FREE CIRCULATION OF AIR ... AT BOTTOM & INSIDE OF PILES. STORAGE AREAS MUST BE LOCATED AT SUITABLE DISTANCE FROM INHABITED BUILDINGS, ANIMAL SHELTERS, & FOOD STORES; MOREOVER, THEY MUST BE INACCESSIBLE TO UNAUTHORIZED PERSONS, CHILDREN, & DOMESTIC ANIMALS. /DIMETHOATE/
[Farm Chemicals Handbook 1984. Willoughby, Ohio: Meister Publishing Co., 1984.,p. C-79]**PEER REVIEWED**


Cleanup Methods:

Decontamination may be achieved by using soap washings followed by alcohol-soap washings with tincture of green soap.
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995. 979]**PEER REVIEWED**


Disposal Methods:

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P043, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.
[40 CFR 240-280, 300-306, 702-799 (7/1/96)]**PEER REVIEWED**

Potential for fluidized bed incineration with a temperature of 840-1800 deg C with residence times for liquids and gases: seconds; solids: longer.
[USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-9 (1981) EPA 68-03-3025]**PEER REVIEWED**

Potential candidate for rotary kiln incineration with a temperature of 1,500-2,900 deg C with residence times for liquids and gases: seconds; solids: hours. /Data from table/
[USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-9 (1981) EPA 68-03-3025]**PEER REVIEWED**

Potential candidate for liquid injection with a temperature of 1,200-2,900 deg C with a residence time of 0.1-2 seconds. /Data from table/
[USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-9 (1981) EPA 68-03-3025]**PEER REVIEWED**


Occupational Exposure Standards:

Manufacturing/Use Information:

Major Uses:

For Diisopropyl Fluorophosphate (USEPA/OPP PC Code: 356100) there are 0 labels match. /SRP: Not registered for current use in the U.S./
[U.S. Environmental Protection Agency/Office of Pesticide Program's Chemical Ingredients Database on Diisopropyl Fluorophosphate (55-91-4). Available from the Database Query page at http://www.cdpr.ca.gov/docs/epa/epamenu.htm as of June 14, 2000.]**PEER REVIEWED**

Therap cat: Cholinergic (ophthalmic)
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

Therap Cat (Vet): Has been used as a miotic
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

Insecticide (former use)
[Hawley, G.G. The Condensed Chemical Dictionary. 10th ed. New York: Van Nostrand Reinhold Co., 1981. 360]**PEER REVIEWED**

Relatively mild poison
[Canadian Security Intelligence Service; Chemical and Biological Terrorism: The Threat According to the Open Literature. Author: Ron Purver, Strategic Analyst, CSIS. Chemical Terrorism. Available from http://www.csis-scrs.gc.ca/eng/miscdocs/chemtere.html as of Sept 19, 2000.]**PEER REVIEWED**


Methods of Manufacturing:

Prepared by the action of phosphorus trichloride on isopropanol, chlorinating the resulting intermediate, and converting diisopropyl chlorophosphate by means of sodium fluoride: Hardy, Kosolapoff, US patent 2,409,039 (1946); see also Edgewood Arsenal, Chemical Warfare Service Tdmr 832 (April 1944); British patent 601,210 (1948).
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**


General Manufacturing Information:

Rarely used nowadays & not in agriculture.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-299]**PEER REVIEWED**


Formulations/Preparations:

DIFLUPYL
**PEER REVIEWED**

DYFLOS
**PEER REVIEWED**

Dyphlos
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 332]**PEER REVIEWED**

FLOROPRYL
**PEER REVIEWED**

FLUOROPRYL
[U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safety Health. Registry ofToxic Effects of Chemical Substances (RTECS). National Library of Medicine's current MEDLARS file.,p. 85/8412]**PEER REVIEWED**

FLUOSTIGMINE
**PEER REVIEWED**

Fluropryl
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

Isofluorophate
**PEER REVIEWED**

NEOGLAUCIT
**PEER REVIEWED**

PF-3
**PEER REVIEWED**

T-1703
**PEER REVIEWED**

TL 466
**PEER REVIEWED**

Isoflurophate ophthalmic ointment (Fluropryl) contains 0.025% isoflurophate ... in an anhydrous vehicle.
[GOODMAN. PHARM BASIS THERAP 7TH ED 1985 p.122]**PEER REVIEWED**


Laboratory Methods:

Clinical Laboratory Methods:

/SRP:/ Serum cholinesterase determinations should be conducted.
**PEER REVIEWED**


Analytic Laboratory Methods:

AOAC Method 970.52. Multiresidue method for organophosphorus pesticides. Residues are measured by glc and identified by combinations of gas, thin layer, or paper chromatography.
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990 274]**PEER REVIEWED**

A thin-film colorimetric technique for detecting and measuring vapors of diisopropyl fluorophosphate. ... The basic concept of using a minature spectrometer to monitor the color of the film with non-volatile colormetric reagents is corroborated.
[Nichols LD; Thin-Film Colorimetry for Miniature Chemical-Agent Detection Systems School of Aerospace Medicine, Brooks Airforce Base Report No. SAM-TR-83-43 19pp (1983)]**PEER REVIEWED**


Special References:

Special Reports:

Abou-Donia MB; Toxicokinetics and Metabolism of Delayed Neurotoxic Organophosphorus Esters: Neurotoxicology (Park Forest Il) 4 (1): 113-29 (1983). This is a review of the toxicokinetics and metabolism of delayed neurotoxic organophosphorus esters incl isofluorophate.


Synonyms and Identifiers:

Related HSDB Records:

197 [PARATHION] (Analog)

Synonyms:

DFP
**PEER REVIEWED**

DIFLUROPHATE
**PEER REVIEWED**

DIISOPROPOXYPHOSPHORYL FLUORIDE
**PEER REVIEWED**

Diisopropylfluorophosphate
**PEER REVIEWED**

O,O-DIISOPROPYL FLUOROPHOSPHATE
**PEER REVIEWED**

DIISOPROPYL FLUOROPHOSPHONATE
**PEER REVIEWED**

DIISOPROPYLFLUOROPHOSPHORIC ACID ESTER
**PEER REVIEWED**

DIISOPROPYL PHOSPHOFLUORIDATE
**PEER REVIEWED**

Diisopropylphosphorofluoridate
**PEER REVIEWED**

O,O'-DIISOPROPYL PHOSPHORYL FLUORIDE
**PEER REVIEWED**

FLUOPHOSPHORIC ACID, DIISOPROPYL ESTER
**PEER REVIEWED**

FLUORODIISOPROPYL PHOSPHATE
**PEER REVIEWED**

Fluorophosphoric acid, diisopropyl ester
**PEER REVIEWED**

Isoflurophosphate
**PEER REVIEWED**

ISOPROPYL FLUOPHOSPHATE
**PEER REVIEWED**

ISOPROPYL PHOSPHOROFLUORIDATE
**PEER REVIEWED**

PHOSPHOROFLUORIDIC ACID, BIS(1-METHYLETHYL) ESTER
**PEER REVIEWED**

PHOSPHOROFLUORIDIC ACID, DIISOPROPYL ESTER
**PEER REVIEWED**


Formulations/Preparations:

DIFLUPYL
**PEER REVIEWED**

DYFLOS
**PEER REVIEWED**

Dyphlos
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 332]**PEER REVIEWED**

FLOROPRYL
**PEER REVIEWED**

FLUOROPRYL
[U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safety Health. Registry ofToxic Effects of Chemical Substances (RTECS). National Library of Medicine's current MEDLARS file.,p. 85/8412]**PEER REVIEWED**

FLUOSTIGMINE
**PEER REVIEWED**

Fluropryl
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996. 883]**PEER REVIEWED**

Isofluorophate
**PEER REVIEWED**

NEOGLAUCIT
**PEER REVIEWED**

PF-3
**PEER REVIEWED**

T-1703
**PEER REVIEWED**

TL 466
**PEER REVIEWED**

Isoflurophate ophthalmic ointment (Fluropryl) contains 0.025% isoflurophate ... in an anhydrous vehicle.
[GOODMAN. PHARM BASIS THERAP 7TH ED 1985 p.122]**PEER REVIEWED**


EPA Hazardous Waste Number:

P043; Diisopropyl fluorophosphate. An acute hazardous waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate.


RTECS Number:

NIOSH/TE5075000