FENVALERATE
CASRN: 51630-58-1
For other data, click on the Table of Contents

Human Health Effects:

Evidence for Carcinogenicity:

Evaluation: No data were available from studies in humans. There is inadequate evidence for the carcinogenicity of fenvalerate in experimental animals. Overall evaluation: Fenvalerate is not classifiable as to its carcinogenicity to humans (Group 3).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 53 324 (1991)]**PEER REVIEWED**

Human Toxicity Excerpts:

One notable form of toxicity associated with synthetic pyrethroids has been a cutaneous paresthesia observed in workers spraying esters containing alpha-cyano substituent (deltamethrin, cypermethrin, fenvalerate). The paresthesia developed several hours following exposure, being described as a stinging or burning sensation on the skin which, in some cases, progressed to a tingling and numbness, the effects lasting some 12 to 18 hours.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 594]**PEER REVIEWED**

Treatment is supportive, and most casual exposures require only decontamination. Topical vitamin E may ameliorate the parethesias that accompany contact with synthetic pyrethroids containing an alpha-cyano group (eg fenvalerate, cypermethrin, flucythrinate).
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1081]**PEER REVIEWED**

Fenvalerate can induce numbness, itching, tingling, and burning sensations in exposed workers, which develop after a latent period of approximately 30 min, peak by 8 hours, and disappear within 24 hours.
[WHO; Environmental Health Criteria 95: Fenvalerate p.19 (1990)]**PEER REVIEWED**

Among 23 workers exposed to synthetic pyrethroids, including fenvalerate, 19 experienced one or more episodes of abnormal facial sensation. Developing between 30 min and 3 hr after exposure and persisting for 30 min to 8 hr. However, there were no abnormal neurological signs, and electrophysiological studies showed normal responses in the arms and legs. The symptoms were most likely due to transient lowering of the threshold of sensory nerve fibers or sensory nerve endings following exposure of the facial skin to pyrethroids.
[WHO; Environmental Health Criteria 95: Fenvalerate p.86 (1990)]**PEER REVIEWED**

Selected individuals who had worked extensively with fenvalerate in the delta region of the Mississippi and Alabama, USA, were interviewed and examined. They had, on some occasions, noted paraesthesia associated with exposure to /fenvalerate/. The cutaneous sensation was described as a stinging or burning, which progressed to numbness in approximately one third of the exposed workers. The sensation typically began a number of hours after contact, peaked in the evening, and rarely was present the following morning. The intensity of the sensation varied according to the type and extent of exposure. Clinical signs of inflammation such as edema or vesiculation were not apparent. Erythema was present in a few individuals but this was difficult to distinguish from sunburn. Several environmental factors were found to affect the cutaneous sensation associated with fenvalerate exposure.
[WHO; Environmental Health Criteria 95: Fenvalerate p.86 (1990)]**PEER REVIEWED**

Despite early reports of negative findings, fenvalerate produced local irritant symptoms in 73% of plant nursery workers handling treated seedlings. Tingling or burning sensations were also described after accidental splashing of the facial skin with fenvalerate. A study of human volunteers who were exposed to fenvalerate applied to the ear lobe reported that paresthesia (ie, numbness combined with irritating abnormal sensation) could be experienced in severe cases. The threshold application appeared to be less than 10 ug/sq cm. All reports agree that the sensation appears after a latent period of about 30 min and persists for 0.5-24 hr, depending on severity.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.592 (1991)]**PEER REVIEWED**

Clinical manifestations of 573 cases of acute pyrethroid poisoning are reviewed. The cases occurred in 14 provinces in China and involved 325 patients exposed to deltamethrin, 196 to fenvalerte, 45 to cypermethrin, and seven to other pyrethroid compounds. Of the 573 cases, 229 were of occupational origin resulting from inappropriate handling of the chemicals such as spraying with higher concentrations than allowed, sustaining longer exposure durations than recommended, spraying against the wind, clearing stoppage of sprays by mouth and hands, spraying closer than every row of crops, or not wearing personal protective equipment. Those occupationally exposed patients experienced initial burning or itching sensations of the face within a few minutes of exposure or dizziness developing at 4 to 6 hours after exposure. Half of those occupationally exposed experienced abnoral facial sensations such as burning, itching, or tingling sensation which were exacerbated by sweating and washing with warm water. These symptoms disappeared several hours to 1 day after exposure. Systemic symptoms included dizziness, 60.6 percent; headache, 44.5 percent; nausea, 59.7 percent; anorexia, 45 percent; and fatigue, 26 percent. Vomiting occurred in 16 percent of those who were occupationally exposed. Other symptoms included chest tightness, 13.1 percent; parasthesia, 11.89 percent; palpitation, 13.1 percent; blurred vision, 7 percent; and increased sweating, 6.7 percent. Coarse muscular fasciculations developed in large muscles of extremities in the more serious cases. In those suffering from convulsions, seizures could arise up to 30 times a day for the first week. Blood tests revealed leukocytosis in 15 percent. Treatment consisted of symptomatic and supportive therapy including gastric lavage. Most recovered in 6 days.
[He F et al; Archives of Toxicology 63 (1): 54-8 (1989)]**PEER REVIEWED**

Mitotic process disturbance by fenvalerate, a pyrethroid insecticide, was investigated in human peripheral blood lymphocyte cultures by analyzing C-mitosis frequency. Cell cultures were established from whole heparinized blood from two healthy donors. After incubation for 48 hr, cells were incubated for 24 hr in 2 to 50 ug/ml fenvalerate, or without fenvalerate (control). One hundred metaphases per concn were examined for both complete and partial C-mitosis. The frequency of C-mitosis was reported as 18 and 24% for control, 17 and 38% for incubation with 2 ug/ml, 52 and 48% for 4 ug/ml, 61 and 60% for 10 ug/ml, 99 and 90% for 20 ug/ml, 74 and 97% for 40 ug/ml, 70 and 98% for 5 ug/ml, and 100% (both samples) for the positive control 0.01 ug/ml demecolcine. Fenvalerate results were highly significant (0.001) by the chi square test at all concn except 2 ug/ml. Mitotic arrest was confirmed by absence of anaphase and telophase figures. Results were in good agreement with previous long term, low dose studies in rats. C-mitosis disruption was considered a cytological indicator of normal spindle function inhibition or disruption.
[Carbonell E et al; Toxicology Letters 48 (1): 45-8 (1989)]**PEER REVIEWED**

Clinical manifestations of 573 cases of acute pyrethroid poisoning are reviewed. The cases occurred in 14 provinces in China and involved 325 patients exposed to deltamethrin, 196 to fenvalerate, 45 to cypermethrin, and seven to other pyrethroid compounds. Of the 573 cases, 229 were of occupational origin resulting from inappropriate handling of the chemicals such as spraying with higher concn than allowed, sustaining longer exposure durations than recommended, spraying against the wind, clearing stoppage of sprays by mouth and hands, spraying closer than every other row of crops, or not wearing personal protective equipment. Those occupationally exposed patients experienced initial burning or itching sensations of the face within a few minutes of exposure o dizziness developing at 4 to 6 hr after exposure. Half of those occupationally exposed experienced abnormal facial sensations such as burning, itching, or tingling sensations which were exacerbated by sweating and washing with warm water. These symptoms disappeared several hours to 1 day after exposure. Systemic symptoms included dizziness, 60.6%; headache, 44.5%; nausea, 59.7%; anorexia, 45%; and fatigue, 26%. Vomiting occurred in 16% of those who were occupationally exposed. Other symptoms included chest tightness, 13.1%; parasthesia, 11.89%; palpitation, 13.1%; blurred vision, 7%; and increased sweating, 6.7%. Coarse muscular fasciculations developed in large muscles of extremities in the more serious cases. In those suffering from convulsions, seizures could arise up to 30 times a day for the first week. Blood tests revealed leukocytosis in 15%. Treatment consisted of symptomatic and supportive therapy including gastri lavage. Most recovered in 6 days. Four cases were detailed for illustrative purposes.
[He F et al; Arch Toxicol 63 (1): 54-58 (1989)]**PEER REVIEWED**

Clastogenic effects in peripheral lymphocytes of cotton field workers who were exposed to different pesticides were studied. All the cells were grown in RPMI 1640 medium for 48 and 72 hr. The type of aberrations observed in the exposed group are gaps, breaks, dicentrics, exchanges, rings and polyploidy. The frequency of total chromosomal aberrations increased significantly in male pesticide applicators when compared to controls. A significant decrease in mitotic index was observed in the exposed group as compared to the control group. The 48 hr cultures showed high incidence of chromosomal aberrations and low mitotic index when compared to 72 hr cultures. The difference in chromosomal aberrations between 48 and 72 hr cultures was not significant. 24 out of 26 individuals showed ill health effects such as severe giddiness and nervous disorders.
[Rupa DS et al; Mutat Res 261 (3): 177-80 (1991)]**PEER REVIEWED**

The ability of the pyrethroid insecticide, fenvalerate, to induce mitotic micronuclei was investigated in cultured human lymphocytes. Human lymphocyte cultures were prepared by adding heparinized whole blood from healthy donors to chromosome medium supplemented with fetal calf serum, antibiotics, and glutamine. Cytochalasin-B, to block cytokinesis, and fenvalerate (10, 20, 40, 50 ug/ml) were added to the cultures simultaneously. At 72 hr, the cultures were centrifuged for determination of micronucleus frequency. The proportion of cytokinesis block cells was reduced in the presence of fenvalerate in a concn dependent manner. Fenvalerate induced a significant increase in the frequency of micronuclei, indicating clastogenic and/or aneugenic activity. The authors conclude that the findings complement previous data on the genotoxicity of fenvalerate in human lymphocytes.
[Surralles J et al; Toxicol Lett 54 (2/3): 151-155 (1990)]**PEER REVIEWED**

Synthetic pyrethroids are neither cutaneous sensitizers nor irritants. Although these compounds do not cause signs of inflammation (edema, erythema, vesiculation), they do produce paresthesias after contact. Typically, symptoms begin several hours after cutaneous exposure, peak in the evening, and resolve by the following day. /Synthetic pyrethroids/
**PEER REVIEWED**

Contact allergy from pyrethroids ... has not been observed. /Pyrethroids/
[Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988. 146]**PEER REVIEWED**

The allergenic properties of pyrethroids /with early pyrethrum preparations/ are marked in comparison with other pesticides. Many cases of contact dermatitis and respiratory allergy have been reported. Persons sensitive to ragweed pollen are particularly prone to such reactions. Preparations containing synthetic pyrethroids are less likely to cause allergic reactions than are the preparations made from pyrethrum powder. /Pyrethroids/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1629]**PEER REVIEWED**

There have been very few systemic poisonings of humans by pyrethroids. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.35 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Pyrethroids are not cholinesterase inhibitors. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.35 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Extraordinary absorbed doses may rarely cause incoordination, tremor, salivation, vomiting, diarrhea, and irritability to sound and touch. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.35 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Some pyrethroid (eg, deltamethrin, fenvalerate, cyhalothrin, lambda-cyhalothrin, flucythrinate, and cypermethrin) may cause a transient itching and/or burning sensation in exposed human skin. /Synthetic pyrethroids/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.13 (1990)]**PEER REVIEWED**

Mitotic process disturbance by fenvalerate, a pyrethroid insecticide, was investigated in human peripheral blood lymphocyte cultures by analyzing C-mitosis frequency. Cell cultures were established from whole heparinized blood from two healthy donors. After incubation for 48 hr, cells were incubated for 24 hr in 2 to 50 ug/ml fenvalerate, or without fenvalerte (control). One hundred metaphases per concentration were examined for both complete and partial C-mitosis. The frequency of C-mitosis was reported as 18 and 24% for control, 17 and 38% for incubation with 2 ug/ml, 99 and 90% for 20 ug/ml, 74 and 97% for 40 ug/ml, 70 and 98% for 5 ug/ml, and 100% (both samples) for the positive control 0.01 ug/ml demecolcine. Fenvalerate results were highly significant (0.001) by the chi square test at all concentrations except 2 ug/ml. Mitotic arrest was confirmed by absence of anaphase and telophase figures. Results were in good agreement with previous long term, low dose studies in rats. C-mitosis disruption was considered a cytological indicator of normal spindle function inhibition or disruption. ...
[Carbonell E et al; Toxicology Letters 48 (1): 45-8 (1989)]**PEER REVIEWED**

 

Skin, Eye and Respiratory Irritations:

Fenvalerate as technical Pydrin is mildly irritating to the skin, but the emulsifiable concentrate is corrosive.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

Eye, skin irritant.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

One notable form of toxicity associated with synthetic pyrethroids has been a cutaneous paresthesia observed in workers spraying esters containing alpha-cyano substituent (deltamethrin, cypermethrin, fenvalerate). The paresthesia developed several hours following exposure, being described as a stinging or burning sensation on the skin which, in some cases, progressed to a tingling and numbness, the effects lasting some 12 to 18 hours.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 594]**PEER REVIEWED**

Immediately irritating to the eye. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

The chief effect from exposure ... is skin rash particularly on moist areas of the skin. ... May irritate the eyes.
[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**

 

Medical Surveillance:

Initial medical screening: Employees should be screened for history of certain medical conditions ... which might place the employee at increased risk from /pyrethroid/ exposure. Chronic respiratory disease: In persons with chronic respiratory disease, especially asthma, the inhalation of /pyrethroids/ might cause exacerbation of symptoms due to its sensitizing properities. Skin disease: /Pyrethroids/ can cause dermatitis which may be allergic in nature. Persons with pre-existing skin disorders may be more susceptible to the effects of this agent. Any employee developing the above-listed conditions should be referred for further medical examination. /Pyrethrum/
[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 fenvalerate occurs through dermal contact and inhalation of dust and sprays, especially to workers applying the compound as an insecticide(1). Exposure to fenvalerate can occur during its production and application and, at much lower levels, from consumption of foods containing residues(2).
[(1) Parmeggiani L; Encyl Occup Health & Safety 3rd ed. Geneva, Switzerland: International Labour Office pp. 1616-46 (1983) (2) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

Air concns of fenvalerate at the breathing zone of workers spraying fenvalerate insecticide on cotton was 0.06-1.98 ug cu m(1); dermal exposure ranged from 4.71 to 141.61 ug/cu cm on forearms, hands, legs and feet(1). At a fenvalerate packing plant in China, workers were reported to be exposed to 12-55 ug/cu m in the air, with resulting skin contact(2).
[(1) Zhang Z et al; Brit J Industr Med 48: 82-6 (1991) (2) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

 

Body Burden:

Urine concns of fenvalerate of workers spraying fenvalerate insecticide on cotton was 0.01-1.98 ug/collection interval (3-12 hr) for a period up to 72 hr after spraying(1).
[(1) Zhang Z et al; Brit J Industr Med 48: 82-6 (1991)]**PEER REVIEWED**

 

Average Daily Intake:

Based upon results of the US FDA's 1990 Total Diet Study, estimated human exposure to fenvalerate from food is as follows(1): 6-11 month old child: 0.0101 ug/kg/day; 14-16 yr old male: 0.0061 ug/kg/day; 60-65 yr old female: 0.0092 ug/kg/day(1).
[(1) Winter CK; Rev Environ Contam Toxicol 127: 23-67 (1992)]**PEER REVIEWED**

 

Emergency Medical Treatment:

 

 

Emergency Medical Treatment:

 

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The following Overview, *** PYRETHRINS ***, 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   The mammalian toxicity of natural pyrethrins is
         generally low.  Very young children are perhaps more
         susceptible to poisoning because they may not hydrolyze
         the pyrethrum esters efficiently.  In humans, allergic
         reactions are the main toxic manifestations of
         pyrethrin exposure.
      1.  Pyrethrum and the pyrethrins produce typical type I
          motor symptoms in mammals.  Severe type I poisoning
          may include the following signs in humans:
           Severe fine tremor
           Marked reflex hyperexcitability
           Sympathetic activation
           Paresthesia (dermal exposure)
     o   DERMAL - These compounds are not primary irritants.
         The chief effect, however, from exposure is dermatitis.
         The usual lesion is a mild erythematous dermatitis with
         vesicles, papules in moist areas, and intense pruritus;
         a bulbous dermatitis may also occur.  Pyrethrins can
         cause allergic dermatitis and systemic allergic
         reactions.
     o   INHALATION is the major route of exposure, with airway
         irritation as the primary toxic effect.  Following
         inhalation, a stuffy, runny nose and scratchy throat
         are common.  Hypersensitivity reactions including
         wheezing, sneezing, shortness of breath and
         bronchospasm may be noted.
     o   OCULAR - Eye exposures may result in mild to severe
         corneal damage that generally  resolves with
         conservative care.
     o   Piperonyl butoxide and other compounds are often added
         to pyrethrin insecticides as synergists and may
         contribute to toxicity.
     o   Synthetic pyrethroids, which are related to pyrethrins,
         are covered in a separate management.
  HEENT
   0.2.4.1 ACUTE EXPOSURE
     o   A stuffy, runny nose and scratchy throat following
         inhalational exposure may be noted.
     o   Eye exposures may result in mild to severe corneal
         damage, decreased visual acuity and periorbital edema.
  CARDIOVASCULAR
   0.2.5.1 ACUTE EXPOSURE
     o   Hypotension and tachycardia, associated with
         anaphylaxis, may occur.
  RESPIRATORY
   0.2.6.1 ACUTE EXPOSURE
     o   Hypersensitivity reactions characterized by
         pneumonitis, cough, dyspnea, wheezing, chest pain, and
         bronchospasm may occur.  Rare cases of respiratory
         failure and cardiopulmonary arrest have been reported.
  NEUROLOGIC
   0.2.7.1 ACUTE EXPOSURE
     o   Paresthesias, headaches, and dizziness are common.
         Massive exposure may result in hyperexcitability and
         seizures, but this is rare.
  GASTROINTESTINAL
   0.2.8.1 ACUTE EXPOSURE
     o   Nausea, vomiting and abdominal pain commonly occur and
         develop within 10 to 60 minutes following ingestion.
  DERMATOLOGIC
   0.2.14.1 ACUTE EXPOSURE
     o   Irritant and contact dermatitis may develop.  Erythema
         which mimics sunburn has also been noted after
         prolonged repeated exposure.
  ENDOCRINE
   0.2.16.1 ACUTE EXPOSURE
     o   Type I motor symptoms following severe poisoning may
         result in sympathetic activation.
  IMMUNOLOGIC
   0.2.19.1 ACUTE EXPOSURE
     o   Sudden bronchospasm, swelling of oral and laryngeal
         mucous membranes, and anaphylactoid reactions have been
         reported after pyrethrum inhalation.  Hypersensitivity
         pneumonitis characterized by cough, shortness of
         breath, chest pain, and bronchospasm may be noted.
  GENOTOXICITY
    o   Pyrethrum is not mutagenic in bacterial reversion tests
        (Ray, 1991).                    
Laboratory:
  o   Pyrethrin plasma levels are not clinically useful or
      readily available.
  o   Monitor for allergic responses such as asthma or contact
      dermatitis.               
Treatment Overview:
  ORAL EXPOSURE
    o   There is no specific antidote for pyrethrin poisoning.
        Treatment is symptomatic and supportive and includes
        monitoring for the development of hypersensitivity
        reactions with respiratory distress.  Provide adequate
        airway management when needed.  Gastric decontamination
        is usually not required unless the pyrethrin product is
        combined with a hydrocarbon.
    o   ALLERGIC REACTION:  MILD:  antihistamines with or
        without epinephrine.   SEVERE:  oxygen, aggressive
        airway management, antihistamines, epinephrine  (ADULT:
        0.3 to 0.5 mL of a 1:1000 solution subcutaneously;
        CHILD:  0.01  mL/kg; may repeat in 20 to 30 min),
        corticosteroids, ECG monitoring, and IV fluids.
  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.
  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.
  DERMAL EXPOSURE
    o   DECONTAMINATION:  Remove contaminated clothing and wash
        exposed  area thoroughly with soap and water.  A
        physician may need to  examine the area if irritation or
        pain persists.
    o   Vitamin E topical application is highly effective in
        relieving paresthesias.                
Range of Toxicity:
  o   The minimal lethal dose of pyrethrum is not established,
      but is probably  in the range of 10 to 100 grams.
  o   Hypersensitivity reactions may be noted, especially
      following a chronic dermal or inhalation exposure.
      Patients with underlying asthma may be  predisposed to
      severe bronchospastic reactions after exposure.


[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:

Treatment is supportive, and most casual exposures require only decontamination. Topical vitamin E may ameliorate the paresthesias that accompany contact with synthetic pyrethroids containing an alpha-cyano group (e.g., fenvalerate, cypermethrin, flucythrinate). /Synthetic pyrethroids/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1081]**PEER REVIEWED**

DO NOT ADMIN OR INSTILL MILK, CREAM, OR OTHER SUBSTANCES CONTAINING VEGETABLE OR ANIMAL FATS, WHICH ENHANCE ABSORPTION OF LIPOPHILIC SUBSTANCES, SUCH AS ... PYRETHROIDS. DIAZEPAM (VALIUM (R)), 5-10 MG IN ADULT, 0.1 MG/KG IN CHILDREN, GIVEN ORALLY OR SLOWLY IV, SHOULD CONTROL NERVOUSNESS & TREMORS IN RARE CASES ... AFTER EXTRAORDINARY EXPOSURE TO ... PYRETHROIDS. /PYRETHRUM, PYRETHRINS, PYRETHROIDS, AND PIPERONYL BUTOXIDE/
[Morgan, D.P. Recognition and Management of Pesticide Poisonings. EPA 540/9-80-005. Washington, DC: U.S. Government Printing Office, Jan. 1982. 44]**PEER REVIEWED**

To minimize absorption of pyrethrins and piperonyl butoxide following ingestion, gastric lavage should be performed immediately and saline cathartics administered. Treatment of overdosage mainly involves symptomatic and supportive care. /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2126]**PEER REVIEWED**

Skin contamination should be removed by washing with soap and water. If irritant or paresthetic effects occur, treatment by a physician should be obtained. Because /vapor exposure/ of pyrethroid apparently accounts for paresthesia affecting the face, strenuous measures should be taken (ventilation, protective face mask and hood) to avoid vapor contact with the face and eyes. Vitamin E Oil preparations (dl-alpha tocopheryl acetate) are uniquely effective in preventing and stopping the paresthetic reaction. They are safe for application to the skin under field conditions. Corn oil is somewhat effective, but possible side effects with continuing use make it less suitable. Vaseline is less effective than corn oil and zinc oxide actually worsens the reaction. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.36 EPA540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Eye contamination should be treated immediately by prolonged flushing of the eye with copious amounts of clean water or saline. If irritation persists, professional ophthalmologic care should be obtained. ... Extraordinary measures should be taken to avoid eye and skin contamination with this product. Should accidental eye contamination occur, expert ophthalmologic care should be obtained after flushing the eye free of the chemical with copious amounts of clean water. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.36 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Ingestion of pyrethroid insecticide presents relatively little risk. However, if large amounts have been ingested, empty the stomach by intubation, aspiration, and lavage. Based on observations in laboratory animals, large ingestions of either allethrin, cismethrin, fenvalerate or deltamethrin would be the most likely to generate neurotoxic manifestations. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.36 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

If only small amounts of pyrethroid have been ingested, or if treatment has been delayed, oral administration of activated charcoal and cathartic probably represents optimal management. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.36 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

 

Animal Toxicity Studies:

 

 

Evidence for Carcinogenicity:

Evaluation: No data were available from studies in humans. There is inadequate evidence for the carcinogenicity of fenvalerate in experimental animals. Overall evaluation: Fenvalerate is not classifiable as to its carcinogenicity to humans (Group 3).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 53 324 (1991)]**PEER REVIEWED**

 

Non-Human Toxicity Excerpts:

Exposure to fenvalerate is likely to cause central nervous system stimulation with symptoms of nervousness, anxiety, salivation, tremors and convulsions. Nerve damage was observed in rats given high doses.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

... Low toxicity to mammals. ... 24 Month feeding/oncogenic (rat) study demonstrated that fenvalerate is not oncogenic.
[Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)]**PEER REVIEWED**

... Toxic to wildlife and extremely toxic to fish. Highly toxic to bees exposed to direct treatment on blooming crops and weeds.
[Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)]**PEER REVIEWED**

Rats fed fenvalerate at 2000 mg/kg diet for 8-10 days showed typical signs of acute intoxication. Reversible morphological changes in the sciatic nerve were observed in rats administered fenvalerate at 3000 mg/kg diet. Histopathological changes in sciatic nerves were also observed in rats and mice treated with a single oral dose of fenvalerate at lethal or sublethal levels.
[WHO; Environmental Health Criteria 95: Fenvalerate p.19 (1990)]**PEER REVIEWED**

Hens administered fenvalerate orally at 1000 mg/kg per day for 5 days did not show any clinical or morphological signs of delayed neurotoxicity.
[WHO; Environmental Health Criteria 95: Fenvalerate p.19 (1990)]**PEER REVIEWED**

When groups of ddY mice (35-47 of each sex per group) were administered fenvalerate in the diet for 78 wk at levels of 0, 100, 300, 1000, or 3000 mg/kg, mortality occurred at the highest dose level. Hyperexcitability was observed at 1000 mg/kg or more, and body weight was depressed at 3000 mg/kg over the 18 mo period and at 1000 and 3000 mg/kg over the first 3 mo. A variety of hematological parameters were affected at 3 mo, predominantly at the highest dose level, but no hematological changes were observed at the end of the study. Several biochemical changes suggestive of hepatotoxicity were observed at 3 mo and at termination of the study in the 300, 1000, and 3000 mg/kg groups. There were gross changes in several organ weights and in organ to body weight ratios, predominantly in the liver. Microscopic examination revealed changes in the liver, mesenteric lymph nodes, and kidney. Dose dependent granulomatous changes were observed in the liver and/or mesenteric lymph nodes in all treatment groups. At the 3 mo interim sacrifice multiple small necrotic foci in liver and changes in the epithelial cells of the proximal convoluted tubules were noted at the two highest dose levels. There were no indications in this study of tumorigenicity or carcinogenicity as a result of fenvalerate administration.
[WHO; Environmental Health Criteria 95: Fenvalerate p.71-2 (1990)]**PEER REVIEWED**

Fenvalerate has also been examined for its mutagenic potency with the Ames test in Salmonella typhimurium (TA1535, TA1538, TA98, and TA100), using dose levels of up to 1 mg/plate both with and without a metabolic enzyme system. Fenvalerate was non-mutagenic in these tests. It was also tested using hepatic metabolic enzyme systems prepared from various PCB-treated animals (three strains of rats, six strains of mice and the Syrian golden hamster). At dose levels of up to 1 mg/plate, fenvalerate was non-mutagenic.
[WHO; Environmental Health Criteria 95: Fenvalerate p.75 (1990)]**PEER REVIEWED**

Groups of pregnant ICR mice (32-33 per group) were orally administered fenvalerate at dose levels of 0, 5, 15, or 50 mg/kg per day on days 6 to 15 of gestation. Groups of 20 mice were sacrificed on day 18, and the fetuses were removed and examined for visceral and skeletal abnormalities. The remaining dams were allowed to deliver naturally and the young were maintained until weaning to evaluate postnatal deficits. Additionally two male and two female weanlings from each dam were maintained for 8 weeks and mated to investigate their reproductive potential. Although toxic signs were noted in the dams at the highest dose level, there was no significant mortality. Examination of the fetuses revealed no external, visceral, or skeletal abnormalities. Treatment of the dams with fenvalerate did not affect the reproductive performance of the offspring.
[WHO; Environmental Health Criteria 95: Fenvalerate p.78 (1990)]**PEER REVIEWED**

When groups of six male and six female rats were fed fenvalerate in the diet at a concentration of 2000 mg/kg for 8 to 10 days, all the animals showed typical signs of acute intoxication such as ataxia, tremors, and hyperexcitability. Histopathological examinations did not reveal any adverse effects of fenvalerate on the sciatic nerve.
[WHO; Environmental Health Criteria 95: Fenvalerate p.80 (1990)]**PEER REVIEWED**

the type II pyrethroids /including fenvalerate/ produce a complex poisoning syndrome and act on a wide range of tissues. They give sodium tail currents with relatively long time constants, which may be the reason for their ability to act on the whole range of excitable tissues. Type II poisoning in rats involves progressive development of nosing and exaggerated jaw opening similar to that seen in response to an irritant placed on the tongue, salivation which may be profuse, increasing extensor tone in the hind limbs causing a rolling gait, incoordination progressing to a very coarse tremor, choreoform movements of the limbs and tail often precipitated by sensory stimuli, generalized choreoathetosis (writhing spasms), tonic seizures, apnea, and death. At lower doses more subtle repetitive behavior is seen. In dogs, similar symptoms are seen but salivation and upper airway hypersecretion and gastrointestineal symptoms are more prominent.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.590 (1991)]**PEER REVIEWED**

Rats receiving 2000 ppm in their diet for 90 days died, but others receiving 1500 ppm for 15 mo showed typical motor symptoms but did not die. Rats showing severe motor symptoms developed axonal swelling and demyelination in the sciatic nerve. These changes appeared to be reversible.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.597 (1991)]**PEER REVIEWED**

Fenvalerate has no teratogenic or mutagenic activity.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.597 (1991)]**PEER REVIEWED**

In both rats and dogs fed 500-1000 ppm fenvalerte, granulomatous changes and giant cell infiltration were seen in the liver. These were, however, a foreign body response to deposition of crystals of the cholesterol 2-(4-chlorophenyl)-isovalerate ester in the liver. The esters are formed by microsomal carbaryl esterases and are highly specific for fenvalerate.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.597 (1991)]**PEER REVIEWED**

Field and laboratory toxicity tests were conducted on the grass shrimp, Palaemonetes pugio, to evaluate the usefulness of laboratory testing in estimating mortality from fenvalerate exposure associated with agricultural runoff. The study examined an integrated approach for assessing the impacts of fenvalerate on estuarine fauna, using 96 hr static renewal and 6 hr pulsed-dose laboratory toxicity tests and in situ toxicity tests. The laboratory toxicity tests with fenvalerate gave 96 hr LC50 values ranging from 0.007 to 0.071 ug/l and 6 hr pulsed dose LC50 values ranging from 0.100 to 0.130 ug/l. Comparisons of the results of two field toxicity tests with laboratory-derived LC50 values showed good agreement between field and laboratory toxicity data. The variation betweenfield and laboratory toxicity tests may have been due to the limitations of the water sampling regime used in characterizing the pesticide exposure during the field toxicity tests. These comparisons suggest that combination of laboratory and field toxicity testing is required to estimate the actual field mortality from fenvalerate exposure associated with agricultural runoff. Future studies should include composite water sampling and more frequent discrete sampling methods to better characterize field exposure regimes.
[Baughman DS et al; Environ Toxicol Chem 8 (5): 417-29 (1989)]**PEER REVIEWED**

Fenvalerate is a widely used pesticide, which has been shown recently to be nonmutagenic. Its carcinogenicity was studied in a long term experiment in inbred C57B1/6 mice given 0, 40 and 80 mg/kg body wt fenvalerate (99% pure) by gavage on 5 days/wk for 104 wk. Survival was decreased especially among females receiving the high dose. Exposure to fenvalerate resulted in a slight increase in the incidence of liver cell tumors over that in controls only in male mice receiving the high dose. No significant difference in the incidence of other types of tumors was observed in treated groups when compared with controls. Fenvalerate induced microgranulomas occurred concomitantly in the liver, spleen and lymph nodes of male and female mice, but their overall incidence did not increase with dose. In a separate experiment, groups of SJL/ola female mice were administered two different samples of fenvalerate (92% and 99% pure) once per week for 12 wk. In animals that received 92% pure compound, the latent period for induction of lymphomas was shortened and their incidence increased, when compared with the group receiving 99% pure fenvalerte and with controls.
[Cabral JR, Galendo D; Cancer Lett 49 (1): 13-8 (1990)]**PEER REVIEWED**

Pure, microcosm-cultured populations of benthic copepods were established from pristine or pesticide impacted Spartine marsh creeks and used as efficient bioassay groups to assess lethal and sublethal effects of sediment bound pesticide residues. Naturally weathered sediments contaminated with the synthetic pyrethroid insecticide fenvalerate were collected by traps moored in a tidal creek receiving major pesticide laced runoff from an agricultural watershed, and used as dosing material. Silty sediments with fenvalerate residues reaching 100 ppb were traped and then diluted with uncontaminated sediments to achieve an exposure range of 0, 25, 50 adn 100 ppb (i.e. no dilution). Despite a broad database showing extreme sensitivity to water solubilized fenvalerate by many marine invertebrates fishes, a 7 day exposure to sediment bound residues as high as 100 ppb caused no significant mortality for any life stages (i.e. nauplii, copepodites or adults) of the benthic harpacticoid copepods Microarthridion littorale or Paronychocamptus wilsoni, and no mortality for adults of enhydrosoma propinquum. However, sediment bound residues as low as 25 ppb significantly depressed egg production (50-100% reduction) and mean clutch sized (40-100% reduction) of fertile Microarthridion littorale and Paronychocamptus wilsoni. If sedimenting fenvalerate depresses copepod reproduction in the field, then lowered recruitment of new individuals will lead inevitably to a decline in population growth.
[Chandler GT; Mar Environ Res 29 (1): 65-76 (1990)]**PEER REVIEWED**

Effects of pyrethroids suggestive of tumor promoting acitivity were investigated. An in vivo assay was used to measure enhancement of nitrosodiethylamine induced enzyme altered foci in Sprague-Dawley rat liver due to fenvalerate. During the first week of fenvalerte adminstration, most rats demonstrated transient neurotoxic effects including hind limb incoordination and tremor. Slight decreases in body weight gains during the period of tumor promotion were noted in rats receiving 57 mg/kg per day. No lesions related to fenvalerate administration were noted in hematoxylin and eosin stained liver sections. Rats given fenvalerate at 75 mg/kg per day for 10 wk after partial hepatectomy and nitrosodiethylamine injection had significantly more gamma-glutamyl-transpeptidase positive foci per cubic centimeter of liver tissue compared to rats given only vehicle during the promotion phase. Slightly but nonsignificantly elevated foci incidence was noted in rats receiving 25 mg/kg per day of fenvalerate. Rats receiving fenvalerate only had no or only a few small gamma-glutamyl-transpeptidase positive hepatocyte foci. Total volume of gamma-glutamyl-transpeptidase foci was significantly increased in rats given either high dose fenvalerate or phenobarbital but was only marginally elevated with low dose fenvalerate. Fenvalerate, cypermethrin, deltamerthrin, permethrin, and the fenvalerate metabolite p-chlorphenylisovaleric acid were tested in-vitro for inhibition of intercellular gap junctional communication in Chinese hamster lung fibroblasts (V79 cells). At non-cytotoxic levels, only fenvalerate and p-chlorophenylisovaleric acid were active at inhibiting V79 cell metabolic cooperation. It was concluded that fenvalerate shows activities suggestive of potential tumor promotion.
[Flodstrom S et al; Arch Toxicol 61 (3): 218-23 (1988)]**PEER REVIEWED**

This review presents data on the impacts of pyrethroid insecticides on nontarget aquatic invertebrates. Toxicological information on both photolabile and photostable pyrethroids against insects and mammals has been evaluated. A detailed analysis is also provided on the contamination of aquatic habitats by pyrethroids through direct, purposeful use in pest control, and indirect routes such as spray drift, run-off and erosion processes. Based on laboratory data, some of the photostable and more effective compounds could be ranked in order of decreasing toxicity to nontarget species as: permethrin = fenvalerate < cypermethrin < deltamethrin. In field studies, depending and their use pattern in agricultural, silvicultural and public health pest control programs, nontarget aquatic insects such as Ephemeroptera, Odonata, Plecoptera, Hemiptera, Coleoptera and Trichoptera, and crustacean groups such as Cladocera, Ostracoda, Copepoda, Amphipoda, Isopoda and Decapoda, were more severely affected by exposure to pyrethroids than other invertebrates. In most of these cases, however, the population recovery of affected species to pretreatment levels was noticed within weeks to months after application. Moreover, the impact of these transient effects of pyrethroids on nontarget fauna resulted in short-term reductions in the populations of dependent fish species in aquatic ecosystems.
[Mian LS, Mulla MS; J Agric Entomol 9 (2): 73-98 (1992)]**PEER REVIEWED**

Two synthetic pyrethroids namely fenvalerate and decamethrin were evaluated for their subchronic dermal toxicity against male albino rats weighing from 120-125 g. The backs of the animals were clipped free of hair and each group received a daily dose of 40 ul fenvalerate and 5 ul decamethrin/kg for two weeks, five consecutive days per week. The animals were kept under observation for two more weeks. The results showed a significant fall in hemoglobin content and a decrease in the number of red blood cells accompanied with an increase in the level of serum bilirubin as indication of some degree of liver function failure. An increase in the circulating leukocytes was a common finding during the toxicity course. The results revealed an increase in blood urea levels and a temporary increase in blood glucose. The activity of whole blood acetylcholinesterase was also affected. No significant changes were detected after gross examination of the internal organs.
[Mohamed ZA; Egypt J Food Sci 16 (1-2): 79-86 (1988)]**PEER REVIEWED**

Certain natural toxins and environmental agents have been found to act on nerve membrane ionic channels in a highly specific manner. For example, the puffer fish poison, tetrodotoxin, blocks the sodium channel without affecting its gating mechanism. The sodium channel is also the major target site of the pyrethroid and DDT insecticides. Patch clamp single channel recording experiments with cultured neuroblastoma cells have revealed that individual sodium channels are kept open much longer in the presence of the pyrethroid tetramethrin than in control. This effect accounts for a marked prolongation of sodium current by tetramethrin observed in giant axons. The prolonged sodium current increases the depolarizing after potential which in turn generates repetitive after discharges. The symptoms of pyrethroid poisoning in animals can be explained on this basis. Only a very small fraction of sodium channels, less than 1%, needs to be modified by pyrethroids to produce the symptoms of poisoning. Fenvalerate, a cyano-containing type II pyrethroid, prolongs the sodium channel open time much more drastically than tetramethrin. This causes a persistent depolarization of the membrane, which in turn blocks conduction.
[Narahashi T; Arch Toxicol (Suppl 9): 3-13 (1986)]**PEER REVIEWED**

The transmitter activated ion channels are known to be important target sites of a variety of therapeutic and toxic agents. The gamma-aminobutyric acid activated chloride channel has been shown to be modulated by general anesthetics, alcohols, and the pyrethroid, cyclodiene and lindane insecticides. The general anesthetics halothane, enflurane and isoflurane greatly augmented the gamma-aminobutyric acid activated current before desensitization took place, and suppressed it after desensitization at clinically relevant concn equivalent to 1-2 minimum alveolar concn. The stimulating effect appears to be a mechanism of general anesthesia. It seems that general anesthetics have a specific affinity for the gamma-aminobutyric acid receptor channel complex. Ethanol also augmented the gamma-aminobutyric acid activated peak chloride current with little or no effect on the desensitized sustained current. Longer chain alcohols n-butanol, n-hexanol, n-octanol, and n-decanol also exerted the same type of effect, with the potency and efficacy increasing with lengthening of the carbon chain. The gamma-aminobutyric acid receptor channel complex has also been shown to be an important target site of certain insecticides. The type II pyrethroids deltamethrin and fenvalerate augmented the gamma-aminobutyric acid activated peak chloride current when applied concurrently with gamma-aminobutyric acid, but the effect was diminished as the pyrethroids were applied for long periods of time prior to gamma-aminobutyric acid application. The latter effect might explain the controversy in the literature regarding the pyrethroid action on the gamma-aminobutyric acid system. The type I pyrethroid allethrin suppressed the gamma-aminobutyric acid activated peak chloride current when co-applied with gamma-aminobutyric acid. Both types of pyrethroids suppressed the N-methyl-d-aspartate-induced current. Lindane and the cyclodienes dieldrin, endrin, heptachlor-epoxide, and isobenzan suppressed the gamma-aminobutyric acid activated chloride current. These effects can account for the convulsant action of lindane and the cyclodienes.
[Narahashi T; Adv Exp Med Biol 287: 61-73 (1991)]**PEER REVIEWED**

To characterize the behavioral effects of pyrethroid (fenvalerate) and organochlorine (endosulfan) insecticides, the effect of acute exposure to these agents on behavioral despair and forced locomotor activity responses in albino mice was studied. In the behavioral despair model, the time for which the animals remained immobile, and in the forced locomotor activity model, the ability of the mice to stay on a moving rod, was studied in control and treatment groups. The effect of pretreatment with drugs affecting cholinergic (physostigmine), GABAergic (thiosemicarbazide), dopaminergic and noradrenergic (alpha-methyl-p-tyrosine) and serotonergic (p-chlorophenylalanine) transmission was studied to investigate which neurotransmitters are involved in the behavioral effects of these compounds. Physostigmine and thiosemicarbazide further decreased the duration of immobility in fenvalerate-treated mice, while p-chlorophenylalanine antagonized the decrease in immobility duration caused by fenvalerate. alpha-Methyl-p-tyrosine pretreatment did not have any effect. Physostigmine, thiosemicarbazide, p-chlorophenylalanine and alpha-methyl-p-tyrosine pretreatments significantly decreased the time the animals stayed on the rota rod. Physostigmine, thiosemicarbazide and alpha-methyl-p-tyrosine significantly enhanced the effects of endosulfan on the rota rod, while in the forced swimming test, only alpha-methyl-p-tyrosine was found to potentiate the effects of endosulfan. PCPA pretreatment lter the response of endosulfan in either of the models studied.
[Chugh Y et al; Asia Pac J Pharmacol 6 (1): 31-6 (1991)]**PEER REVIEWED**

Toxicosis attributable to fenvalerate and N,N-diethyl-m-toluamide exposure was suspected in 2 cats. Clinical signs of toxicosis developed within 4 to 6 hr of dermal application of the pesticide. Clinical signs of toxicosis seen in both cats included hypersalivation, ataxia, and depression. In addition, seizures were seen in 1 cat. Both cats died. Analysis of skin, kidney/urine, liver, and brain tissues confirmed the presence of fenvalerate and N,N-diethyl-m-toluamide. The pyrethroid fenvalerate and the insect repellent N,N-diethyl-m-toluamide are used for the control of fleas and ticks on cats. Suspected fenvalerate/N,N-diethyl-m-toluamide toxicosis in cats is associated with tremors, hypersalivation, ataxia, vomiting, depression, and seizures.
[Dorman DC et al; J Am Vet Med Assoc 196 (1): 100-2 (1990)]**PEER REVIEWED**

The effect of systemic treatment of a synthetic pyrethroid insecticide, fenvalerate was examined in adult female rats at different doses ie, 5, 10, 20 mg/kg body wt by gavage for 21 consectuive days on regional brain levels of noradrenaline, dopamine, their acid metabolites: dihydroxyphenylacetic acid and homovanillic acid by HPLC-EC system. Rsults demonstrate pronounced inhibition of noradrenaline, dopamine, homovanillic acid dihydroxyphenylacetic acid levels in several brain regions which were neither dose related nor region specific.
[Husain R et al; Res Commun Chem Pathol Pharmacol 73 (1): 111-14 (1991)]**PEER REVIEWED**

An attempt was made to study the genotoxic effect of fenvalerate in the mouse in vivo test system using bone marrow chromosome aberration, micronucleus and sperm abnormality assays. For metaphase analyses three dose levels of the test chemical (100, 150, or 200 mg/kg) were given to Swiss mice, 10 to 12 weeks old. With the 200 mg/kg dose level, three routes of administration were employed, ip, oral and sc. For chronic treatment, five equal subdivisions of the highest acute dose were injected ip at intervals of 24 hr and the mice sacrificed at 130 hr after the first injection. The results indicated a variety of cytogenetic effects. A small and insignificant increase was noted in the frequency of chromosome aberrations with dose. Maximum aberrations were noted 24 hr after chemical treatment. An insignificant increase in chromosomal aberrations over control in the sc route of chemical administration may have been caused by a slo rate of chemical absorption from dermal tissue. The higher incidence of chromatid separations in most of the test cases suggests that fenvalerate has the ability to induce malsegregation. The occurrence of chromatid separations may be an important observation as it relates to aneuploidy. The frequency of micronucleated cells was greater with higher doses. The induction of chromosome and chromatid type deletions, exchanges and micronuclei in the bone marrow cells of mice indicated clastogenic as well as spindle poisoning actions.
[Pati PC, Bhunya SP; Mutation Research 222 (3): 149-54 (1989)]**PEER REVIEWED**

Fenvalerate @ 10.12 and20 mg/kg (eg, 1/20 and 1/10th LD50 respectively) had no effect on learning process, retrieval of memory and permanent memory traces /in rats/.
[Reddy BN et al; Indian J Exp Biol 29 (2): 176-7 (1991)]**PEER REVIEWED**

This investigation explored the behavioral and neurochemical toxicity of perinatal oral exposure to Ambush (Type I) and Pydrin (Type II), two pyrethroid formulations. Thirty six female rats were mated and exposed to various pyrethroid formulations by oral gavage from the first gestational day until their pups (culled to 8/litter) were 12 days old. Six mothers were exposed daily to one of the following treatments: corn oil control, corn oil+96% xylene, 1.25 mg/kg Pydrin (pesticidal ingredient fenvalerate), 0.125 mg/kg Pydrin, 4.0 mg/kg Ambush (pesticidal ingredient permethrin), or 0.4 mg/kg Ambush. Behavioral evaluations of locomotor activity, muscular coordination and passive avoidance learning were conducted on half of the pups from each litter (N = 24 pups/treatment condition). The other pups were sacrificed, brains were removed and sectioned into frontal cortex, hippocampus, caudate, and cerebellum for neurochemical assessment. The monoamines DA, DOPAC, 5-HIAA, 5-HT and HVA levels were determined and the amino acids aspartate, glutamate, glutamine, glycine, GABA, and taurine were determined for each of the brain regions. Gestational duration was shortened by exposure to the high doses of Pydrin and Ambush but only pups from the 4.0 mg/kg Ambush group were significantly lighter. No physical malformations were observed in pups from any of the treatment conditions, although the high Pydrin exposure condition resulted in a 4% death rate. Behavioral changes were seen for both locomotor activity and muscular coordination. The shape of across-session habituation of locomotion was different for the xylene and corn oil and the high dose Ambush groups. Both groups were less active on day 1 and more active on days 2 and 3 than the other pups. The high doses of Ambush and Pydrin produced slower intrasession habituation. Muscular coordination was improved slightly following low dose exposure to both pesticides and reduced following high dose exposures. Regional brain weights were normal for the cortex, cerebellum and caudate but the hippocampus was 64% heavier for pups treated with 4.0 mg/kg Ambush. Amino acid determinations indicated that the cerebellum was most affected where glutamate, glutamine, aspartate and taurine were reduced following xylene or pyrethroid exposure. The biogenic amine transmitter 5-HT was reduced in several brain regions following pyrethroid exposures. These data suggest that levels of Ambush and Pydrin as low as the LD50/10,000 can alter behavior and neurotransmitter functioning.
[Sylianco-Wu L et al; Neurotoxicol Teratol 12 :565 (1990)]**PEER REVIEWED**

The kinetic variations in the morphology of the alveolar cells in bronchoalveolar lavage fluid from male Sprague-Dawley rats exposed to fenvalerate suspension by a single intratracheal instillation were observed with a scanning electron microscope. The results showed that fenvalerate suspension did not induce lung injury at a dose of 0.19 mg/kg, caused a mild alveolitis at a dose of 0.93 mg/kg and led to the lung parenchyma injury at a dose of 4.7 and/or 23.3 mg/kg. The injury on the cellular membranes of pulmonary alveolar macrophages mainly revealed the appearances of pores in different sizes, pits in varied shapes and the uneven distribution of the cell ruffling (or cytoplasmic prominence), and even the disolution or death of lots of pulmonary alveolar macrophages. In addition, the conspicuous increases in polymorphonuclear neutrophils, monocytes, lymphocytes, type II pneumocytes, ciliated cells and RBC, and a number of cell aggregation could be seen. The above mentioned responses of the lung injury took place following 30 min of exposure, reached their peak about 4-24 hr after exposure, and returned t the normal state about 4 day later. The findings of present study provide the cellular morphological bases for the probe into the toxicity mechanisms of fenvalerate on the lung and for the formulation of the hygienic standards in the production and application of fenvalerate.
[Wang XR, Zhai WL; Zhongguo Yaolixue Yu Dulixue Zazhi 4 (2): 134-7 (1990)]**PEER REVIEWED**

These compounds /including fenvalerate and cypermethrin/ are generally very toxic to crustaceans and fish in laboratory bioassays.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 883]**PEER REVIEWED**

These compounds /including fenvalerate and cypermethrin/ are generally very toxic to crustaceans and fish in laboratory bioassays.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 883]**PEER REVIEWED**

Synthetic pyrethroids are neuropoisons acting on the axons in the peripheral and central nervous systems by interacting with sodium channels in mammals and/or insects. A single dose produces toxic signs in mammals, such as tremors, hyperexcitability, salivation, choreoathetosis, and paralysis. ... At near-lethal dose levels, synthetic pyrethroids cause transient changes in the nervous system, such as axonal swelling and/or breaks and myelin degeneration in sciatic nerves. They are not considered to cause delayed neurotoxicity of the kind induced by some organophosphorus compounds. /Synthetic prethroids/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.13 (1990)]**PEER REVIEWED**

Extreme doses /of pyrethroids/ have caused convulsions in laboratory animals. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.35 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Synthetic pyrethroids have been shown to be toxic for fish, aquatic arthropods, and honeybees in laboratory tests. But, in practical usage, no serious adverse effects have been noticed because of the low rates of application and lack of persistence in the environment. The toxicity of synthetic pyrethroids in birds and domestic animals is low. /Synthetic pyrethroids/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.13 (1990)]**PEER REVIEWED**

The Type II /poisoning/ syndrome, also known as the "CS syndrome," is produced by those esters containing the alpha-cyano substituent and elicits intense hyperactivity, incoordination, and convulsions in cockroaches, whereas rats display burrowing behavior, coarse tremors, clonic seizures, sinuous writhing (choreoathetosis), and profuse salivation without lacrimation; hence the term CS (choreoathetosis/salivation) syndrome. /Pyrethroid esters containing the alpha-cyano substituent/
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 593]**PEER REVIEWED**

The in vitro effects of pyrethroids on the mitogenic responsiveness of murine splenic lymphocytes to concanavalin A and lipopolysaccharide were determined. Allethrin was the most potent inhibitor, with effective concn in the range of 1X10-6 to 1.5X10-5 M. The results support the possibility of immune suppression by pyrethroid exposure. /Pyrethroids/
[Stelzer KJ, Gordon MA; Res Commun Chem Pathol Pharmacol 46 (1): 137-50 (1984)]**PEER REVIEWED**

Following absorption through the chitinous exoskeleton of arthropods, pyrethrins stimulate the nervous system, apparently by competitively interfering with cationic conductances in the lipid layer of nerve cells, thereby blocking nerve impulse transmissions. Paralysis and death follow. /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

Non-systemic insecticide with contact action. Causes paralysis initially, with death occurring later. Has some acaricidal activity. /Pyrethrins/
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A357/Aug 87]**PEER REVIEWED**

 

Non-Human Toxicity Values:

LD50 Rat oral 451 mg/kg
[Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987. 395]**PEER REVIEWED**

LD50 Rat percutaneous > 5000 mg/kg
[Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987. 395]**PEER REVIEWED**

LD50 Rat oral 3200 mg/kg /technical pydrin suspended in water/
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

LD50 Rat oral 1-3 g/kg /technical grade/
[Purdue University; National Pesticide Information Retrieval System, FenvalerateFact Sheet No. 145 (1987)]**PEER REVIEWED**

LD50 Rabbit dermal 1-3 g/kg /technical grade/
[Purdue University; National Pesticide Information Retrieval System, FenvalerateFact Sheet No. 145 (1987)]**PEER REVIEWED**

LC50 Rat inhalation > 101 g/cu m/4 hr
[Purdue University; National Pesticide Information Retrieval System, FenvalerateFact Sheet No. 145 (1987)]**PEER REVIEWED**

LD50 Rat oral 200 mg/kg
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V13 458 (1981)]**PEER REVIEWED**

LC50 Pimephales promelas (fathead minnow) 5.14 mg/l/96 hr (confidence limit 4.89- 5.40 mg/l), flow-through bioassay with measured concentrations, 25.5 deg C, dissolved oxygen 7.4 mg/l, hardness 45.5 mg/l calcium carbonate, alkalinity 41.6 mg/l calcium carbonate, and pH 7.3.
[Geiger D.L., Call D.J., Brooke L.T. (eds). Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales Promelas). Vol. IV. Superior Wisconsin:University of Wisconsin-Superior, 1988. 335]**PEER REVIEWED**

 

Ecotoxicity Values:

LC50 Rainbow trout 0.0036 mg/1/96 hr /Conditions of bioassay not specified/
[Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987. 395]**PEER REVIEWED**

LC50 Salmo salar (Atlantic salmon) 1 ug/l/96 hr, juvenile /Conditions of bioassay not specified/
[Murty, A.S. Toxicity of Pesticides to Fish. Volumes I, II. Boca Raton, FL: CRC Press Inc., 1986. 70]**PEER REVIEWED**

LC50 Pimephales promelas (fathead minnow) 0.42 mg/l/96 hr (confidence limit 0.39-0.46 mg/l), flow-through bioassay with measured concentrations, 24.5 deg C, dissolved oxygen 7.3 mg/l, hardness 44.8 mg/l calcium carbonate, alkalinity 40.9 mg/l calcium carbonate, and pH 7.8.
[Geiger D.L., D.J. Call, L.T. Brooke. (eds.). Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales- Promelas). Vol. V. Superior WI:University of Wisconsin-Superior, 1990. 277]**PEER REVIEWED**

EC50 Pimephales promelas (fathead minnow) 0.04 mg/l/96 hr (confidence limit 0.36-0.44 mg/l), flow-through bioassay with measured concentrations, 24.5 deg C, dissolved oxygen 7.3 mg/l, hardness 44.8 mg/l calcium carbonate, alkalinity 40.0 mg/l calcium carbonate, and pH 7.8. Effect: loss of equilibrium.
[Geiger D.L., D.J. Call, L.T. Brooke. (eds.). Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales- Promelas). Vol. V. Superior WI:University of Wisconsin-Superior, 1990. 277]**PEER REVIEWED**

LC50 Pimephales promelas (fathead minnow) 5.14 mg/l/96 hr (confidence limit 4.89-5.40 mg/l), flow-through bioassay with measured concentrations, 25.5 deg C, dissolved oxygen 7.4 mg/l, hardness 45.5 mg/l calcium carbonate, alkalinity 41.6 mg/l calcium carbonate, and pH 7.3. Effect: Loss of equilibrium.
[Geiger D.L., Call D.J., Brooke L.T. (eds). Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales Promelas). Vol. IV. Superior Wisconsin:University of Wisconsin-Superior, 1988. 335]**PEER REVIEWED**

LC50 Rainbow trout technical grade 76.0 ppb active ingredient/24 hr (static test)
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 670]**PEER REVIEWED**

LC50 Rainbow trout formulated product 21.0 ppb active ingredient/24 hr (static test)
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 670]**PEER REVIEWED**

LD50 Mallard oral 9932 mg/kg
[Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)]**PEER REVIEWED**

LC50 Bobwhite quail dietary > 10000 ppm
[Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)]**PEER REVIEWED**

LC50 Mallard dietary 5500 ppm /Conditions of bioassay not specified/
[Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)]**PEER REVIEWED**

LC50 Bluegill sunfish fish 0.42 ppb/96 hr /Conditions of bioassay not specified/
[Purdue University; National Pesticide Information Retrieval System, FenvalerateFact Sheet No. 145 (1987)]**PEER REVIEWED**

Metabolism/Pharmacokinetics:

Metabolism/Metabolites:

Fenvalerate undergoes hydroxylation to give 2'- or 4'- hydroxylated phenoxy esters and hydrolysis to give 3-phenoxybenzoic acid and its hydroxy derivatives (free and conjugates), 3-(4-chlorophenyl)-isovaleric acid and its hydroxy derivatives (free, lactones, and conjugates), thiocyanate, and CO2.
[Aizawa, H. Metabolic Maps of Pesticides. New York, NY: Academic Press, 1982. 189]**PEER REVIEWED**

The fate of fenvalerate in rats and mice has been studied using fenvalerate radiolabelled in the acid moiety or benzyl or cyano groups. The administered radioactivity, except that of the cyano-labelled compounds, is readily excreted (up to 99% in 6 days). The major metabolic reactions are ester cleavage and hydroxylation at the 4' position. Various oxidative and conjugation reactions that lead to a complex mixture of products have been shown to occur. When studies were carried out with fenvalerate radiolabelled in the cyano group, elimination of the radioactive dose was less rapid (up to 81% in 6 days). The remaining radioactivity was retained mainly in the skin, hair, and stomach as thiocyanate. A minor, but very important, metabolic pathway is the formation of a lipophilic conjugate of (2R)-2-(4-chlorophenyl)isovalerate. This congugate, which is implicated in the formation of granuloma, has been detected in the adrenals, liver mesenteric lymph nodes of rats, mice, and some other species.
[WHO; Environmental Health Criteria 95: Fenvalerate p.17 (1990)]**PEER REVIEWED**

Despite its lack of a cyclopropane ring in the acid, fenvalerate is rapidly metabolized in rats by ester cleavage and hydroxylation, as are the more traditional pyrethroids.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.597 (1991)]**PEER REVIEWED**

Studies with permethrin, cypermethrin and fenvalerate have established that rates of metabolism and elimination in rainbow trout are significantly lower than those reported for birds and mammals. Comparatively low lethal brain pyrethroid concn and nonneural aspects of pyrethroid intoxication in fish suggest that variations in toxicodynamics are also crucial in evaluating pyrethroid selectivity.
[Bradbury SP, Coats JR; Govt Reports Announcements & Index (GRA&I), Issue 01 (1990)]**PEER REVIEWED**

Using tracer technique of (14)C isotope, toxicokinetics of fenvalerate was studied in rats and mice. The results strongly suggested the existence of distinct differences between species in mammals in the metabolism of (14)C fenvalerate. The absorption and elimination of (14)C fenvalerate in the blood of mice following single intragastric administration was faster than that of the rats. The plasma and brain of animal have greater affinity for (14)C-fenvalerate. The absorption of fenvalerate was faster and the biological half-time was longer in brain. (14)C-fenvalerate and its metabolites were mainly eliminated through urine and fenvalerate can partially be stored in the skin and the hair of animal.
[Gong ZC et al; Chin J Prev Med 24 (5): 277-80 (1990)]**PEER REVIEWED**

On a single oraldose or five consecutive oral doses of (14)C-esfenvalerate or (14)C-fenvalerate labeled in the acid moiety to 13-day pregnant rats at rates of 2.5 and 10 mg/kg/day, respectively, the maternal blood and placenta generally showed higher (14)C levels as compared with the fetus and amniotic fluid. Both compounds and their metabolites did not transfer readily from the maternal blood to the fetus, the amount of (14)C transferred being less than 0.07% of the dose. There were no substantial differences in the fetal (14)C level and the transfer ratio ((14)C tissue level/(14)C maternal blood level) between both labeled preparations. Major (14)C-compounds in the fetus, maternal blood and placenta were the parent compounds, CPIA[2-(4-chlorophenyl)isovaleric acid] and CPIA-hydroxylated derivatives and there was no qualitative difference in metabolic fates between the two compounds, except that a trace amount of CPIA-cholesterol ester [cholesteryl (2R)-2-(4-chlorophenyl)isovalerate] was detected in the maternal blood and placenta only with fenvalerate. CPIA-cholesterol ester did not seem to transfer from the maternal blood to the fetus. Overall, esfenvalerate and fenvalerate seem to behave in the same manner as far as placental transfer was concerned.
[Shiba K et al; Nippon Noyaku Gakkai Shi 15 (2): 169-74 (1990)]**PEER REVIEWED**

The metabolic pathways for the breakdown of the pyrethroids vary little between mammalian species but vary somewhat with structure. ... Essentially, pyrethrum and allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid moiety and of the unsaturated side chain of the alcohol moiety with ester hydrolysis playing and important part, whereas for the other pyrethroids ester hydrolysis predominates. /Pyrethrum and pyrethroids/
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.588 (1991)]**PEER REVIEWED**

The relative resistance of mammals to the pyrethroids is almost wholly attributable to their ability to hydrolyze the pyrethroids rapidly to their inactive acid and alcohol components, since direct injection into the mammalian CNS leads to a susceptibility similar to that seen in insects. Some additional resistance of homeothermic organisms can also be attributed to the negative temperature coefficient of action of the pyrethroids, which are thus less toxic at mammalian body temperatures, but the major effect is metabolic. Metabolic disposal of the pyrethroids is very rapid, which means that toxicity is high by the intravenous route, moderate by slower oral absorption, and often unmeasureably low by dermal absorption. /Pyrethroids/
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.588 (1991)]**PEER REVIEWED**

FASTEST BREAKDOWN IS SEEN WITH PRIMARY ALCOHOL ESTERS OF TRANS-SUBSTITUTED ACIDS SINCE THEY UNDERGO RAPID HYDROLYTIC & OXIDATIVE ATTACK. FOR ALL SECONDARY ALCOHOL ESTERS & FOR PRIMARY ALCOHOL CIS-SUBSTITUTED CYCLOPROPANECARBOXYLATES, OXIDATIVE ATTACK IS PREDOMINANT. /PYRETHROIDS/
[The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 5: A Review of the Literature Published during 1976 and 1977. London: The Chemical Society, 1979. 469]**PEER REVIEWED**

Pyrethrins are reportedly inactivated in the GI tract following ingestion. In animals, pyrethrins are rapidly metabolized to water soluble, inactive compounds. /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

Synthetic pyrethroids are generally metabolized in mammals through ester hydrolysis, oxidation, and conjugation, and there is no tendency to accumulate in tissues. In the environment, synthetic pyrethroids are fairly rapidly degraded in soil and in plants. Ester hydrolysis and oxidation at various sites on the molecule are the major degradation processes. /Synthetic pyrethroids/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.13 (1990)]**PEER REVIEWED**

 

Absorption, Distribution & Excretion:

Poorly absorbed through rabbit skin.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

Elimination from body fat is slow, with a half-life of 7-10 days; elimination from brain is less slow, with a half-life of 2 days (Marei et al., 1982), presumably due to the more effective perfusion of brain and the presence of esterases in brain tissue.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.597 (1991)]**PEER REVIEWED**

Dermal penetration of pesticides. Compound: Fenvalervate; species: mouse; Application site: dermal; solvent: acetone; Penetration parameter: 9%, 2 hr; Method: patch. /From table/
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V1 p.140 (1991)]**PEER REVIEWED**

In mammals, following oral administration, fenvalerate is rapidly metabolized. Up to 96% is excreted in the feces within 6-14 days.
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A207/Aug 87]**PEER REVIEWED**

An in vivo rainbow trout (Salmo gairdneri) preparation was used to evaluate the gill uptake and toxicokinetics of (3)H fenvalerate ((R,S)-alpha-cyano-3- phenoxybenzyl (R,S)-2-(4-chlorophenyl)-3-methylbutyrate), a synthetic pyrethroid insecticide. Fish were exposed to technical grade fenvalerate (0.28 or 23 ng/l) or an emulsifiable-concentrate formulation (16 ng/l) for 36 to 48 h. No significant effects of emulsifiers or fenvalerate concentration on uptake were observed. The overall mean gill uptake efficiency was determined to be 28.6%. Following 8 hr to 48 hr depuration periods, carcass and bile contained 80 to 90 percent and 10 to 20 percent of the gill-absorbed doses, respectively. Analysis of biliary metabolites indicated that the glucuronide of 4'-HO-fenvalerate was the only significant degradation product. Results from the present study suggest that efficient gill uptake does not explain the extreme sensitivity of fish to fenvalerate. Rather, a low rate of biotransformation and excretion may play a significant role in the susceptibility of rainbow trout to the synthetic pyrethroid insecticides.
[Bradbury SP et al; Environ Toxicol Chem 5 (6): 567-76 (19860]**PEER REVIEWED**

Using tracertechnique of (14)C isotope, toxicokinetics of fenvalerate was studied in rats and mice. The results strongly suggested the existence of distinct differences between species in mammals in the metabolites of (14)C fenvalerate. The absorption and elimination of (14)C fenvalerate in the blood of mice following single intragastric administration was faster than that of the rats. The plasma and brain of animals have greater affinity for (14)C fenvalerate. The absorption of fenvalerate was faster and the biological half-time was longer in brain. (14)C Fenvalerate and its metabolites were mainly eliminated through urine and fenvalerate can partially be stored in the skin and the hair of animals.
[Gong ZC; Chung Hua Yu Fang I Hsueh Tsa Chih 24 (5): 277-80 (1990)]**PEER REVIEWED**

/PYRETHROIDS/ READILY PENETRATE INSECT CUTICLE AS SHOWN BY TOPICAL LD50 TO PERIPLANETA (COCKROACH) ... /PYRETHROIDS/
[White-Stevens, R. (ed.). Pesticides in the Environment: Volume 1, Part 1, Part 2. New York: Marcel Dekker, Inc., 1971. 75]**PEER REVIEWED**

WHEN RADIOACTIVE PYRETHROID IS ADMIN ORALLY TO MAMMALS, IT IS ABSORBED FROM INTESTINAL TRACT OF THE ANIMALS & DISTRIBUTED IN EVERY TISSUE EXAMINED. EXCRETION OF RADIOACTIVITY IN RATS ADMIN TRANS-ISOMER: DOSAGE: 500 MG/KG; INTERVAL 20 DAYS; URINE 36%; FECES 64%; TOTAL 100%. /PYRETHROIDS/
[MIYAMOTO J; ENVIRON HEALTH PERSPECT 14: 15-28 (1976)]**PEER REVIEWED**

Pyrethrins are absorbed through intact skin when applied topically. When animals were exposed to aerosols of pyrethrins with piperonyl butoxide being released into the air, little or none of the combination was systemically absorbed. /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

Although limited absorption may account for the low toxicity of some pyrethroids, rapid biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is probably the major factor responsible. Most pyrethroid metabolites are promptly excreted, at least in part, by the kidney. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.35 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

 

Biological Half-Life:

Elimination from body fat is slow, with a half-life of 7-10 days; elimination from brain is less slow, with a half-life of 2 days (Marei et al., 1982), presumably due to the more effective perfusion of brain and the presence of esterases in brain tissue.
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.597 (1991)]**PEER REVIEWED**

 

Mechanism of Action:

In intact locusts and neuromuscular preparations of locusts, fenvalerate caused (a) prolonged firing in the crural nerve without associated muscle contractions; (b) sustained muscle contractions; and (c) a block of neurally evoked muscle contractions at low concentrations (1x10-8 to 1x10-5 mol/l). However, fenvalerate did not cause repetitive firing and after-discharges with associated muscle contractions. The fenvalerate steroisomers with an (S) configuration in the alcohol moiety are more active pharmacologically and toxicologically than those with the (R) configuration or the racemate (R,S). It is also apparent that steroisomers with the (S) configuration in the acid moiety are more active than those with the (R) configuration or the racemate (R,S).
[WHO; Environmental Health Criteria 95: Fenvalerate p.84 (1990)]**PEER REVIEWED**

Phosphoinositide breakdown in guinea pig cerebral cortical synaptoneurosomes induced by the Type-I pyrethroids allethrin, resmethrin, and permethrin, and the Type-II pyrethroid deltamethrin and fenvalerate were investigated with various receptor agonists as well as sodium channel blockers and agents. Phosphoinositide breakdown was determined from inositol-phosphate formation by tritiated inositol labeled synaptoneurosomes. All five pyrethroids dose dependently induced phosphoinositide breakdown. Type II pyrethroids exhibited higher potency and deltamethrin was more efficacious than the Type I pyrethroids. Five uM tetrodotoxin, a blocker of voltage dependent sodium channels, partially inhibited deltamethrin (85 percent) and fenvalerate (60 percent) responses but not allethrin or resmethrin. Fenvalerate induced stimulation of phosphoinositide was additive with stimulation elicited by the receptor agonists carbamylcholine (1 mM) and norepinephrine (1000 uM) but less than additive with the sodium channel agents batrachotoxin, pumiliotoxin-B, and scorpion venom. Allethrin (100 uM) was less than additive with receptor agonists or sodium channel agents and actually significantly inhibited response to scorpion venom. Effects for 100 uM allethrin with either fenvalerate or deltamerthrin were not different from allethrin alone. Ten uM allethrin slightly decreased response to 10 to 100 uM deltamethrin. The local anesthetic dibucaine, a sodium channel activation inhibitor, completely blocked deltamethrin induced phosphoinositide breakdown but was much less effective in inhibiting allethrin response. It appears likely that Type I pyrethroids induce phosphoinositide breakdown through a mechanism other than sodium channel activation while Type II pyrethroids act in a manner analogous to other sodium channel agents.
[Gusovsky F et al; Brain Research 492 (1/2): 72-8 (1989)]**PEER REVIEWED**

Eight different synthetic pyrethroids were examined to determine their effects on the excitability of hippocampal granule cells in urethane anesthetized rats. A paired stimulus approach was used. All eight prolonged the depression of granule cells excitability that follows stimulation of their major synaptic input, the perforant path. The magnitude of this effect depended upon the class to which the pyrethroid belonged. Type I pyrethroids (those primarily producing tremor) prolonged the depression of granule cell excitability for shorter periods than did type II pyrethroids (those primarily producing salivation and choreoathetosis) or pyrethroids producing a mixed type of intoxication. No overlap was found between groups. To determine whether the difference observed between type I and type II pyrethroids was the result of an infelicitous selection of doses, cismethrin (type I) was tested over a dose range of 1.5-24 times the conscious rat iv LD50. Even at the highest dose, the prolongation remained well below that produced by type II pyrethroids. The effect of deltamethrin was shown to be consistent with the production or potentiation of a surmountable inhibitory response. This action of deltamethrin was antagonizable by mephenesin and lidocaine, but not by picrotoxin or halothane. The type of effect, its time course, and the anatagonism data suggest that type II pyrethroids enhance inhibition in the dentate gyrus. This action does not appear to be mediated by GABA receptors.
[Joy RM et al; Toxicol Appl Pharmacol 103 (3): 528-38 (1990)]**PEER REVIEWED**

The transmitter activated ion channels are known to be important target sites of a variety of therapeutic and toxic agents. The GABA activated chloride channel has been shown to be modulated by general anesthetics, alcohols, and the pyrethroid, cyclodiene and lindane insecticides. The general anesthetics halothane, enflurane and isoflurane greatly augmented the GABA activated current before desensitization took place, and suppressed it after desensitization at clinically relevant concn equivalent to 1-2 minimum alveolar concn. The stimulating effect appears to be a mechanism of general anesthesia. It seems that general anesthetics have a specific affinity for the GABA receptor-channel complex. Ethanol also augmented the GABA activated peak chloride current with little or no effect on the desensitized sustained current. Longer chain alcohols n-butanol, n-hexanol, n-octanol, and n-decanol also exerted the same type of effect, with the potency and efficacy increasing with lengthening of the carbon chain. The GABA receptor-channel complex has also been shown to be an important target site of certain insecticides. The type II pyrethroids deltamethrin and fenvalerate augmented the GABA activated peak chloride current when applied concurrently with GABA, but the effect was diminished as the pyrethroids were applied for long periods of time prior to GABA application. The latter effect might explain the controversy in the literature regarding the pyrethroid action on the GABA system. The type I pyrethroid allethrin suppressed the GABA activated peak chloride current when co-applied with GABA. Both types of pyrethroids suppressed the N-methyl-d-aspartate induced current. Lindane and the cyclodienes dieldrin, endrin, heptachlor epoxide, and isobenzan suppressed the GABA activated chloride current. These effects can account for the convulsant action of lindane and the cyclodienes.
[Narahashi T; Adv Exp Med Biol 287: 61-73 (1991)]**PEER REVIEWED**

The synthetic pyrethroids delay closure of the sodium channel, resulting in a sodium tail current that is characterized by a slow influx of sodium during the end of depolarization. Apparently the pyrethroid molecule holds the activation gate in the open position. Pyrethroids with an alpha-cyano group (e.g., fenvalerate) produce more prolonged sodium tail currents than do other pyrethroids (e.g., permethrin, bioresmethrin). The former group of pyrethroids causes more cutaneous sensations than the latter. /Synthetic pyrethroids/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1081]**PEER REVIEWED**

Interaction with sodium channels is not the only mechanism of action proposed for the pyrethroids. Their effects on the central nervous system have led various workers to suggest actions via antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, or actions on calcium ions. Since neurotransmitter specific pharmacological agents offer only poor or partical protection against poisoning, it is unlikely that one of these effects represents the primary mechanism of action of the pyrethroids, and most neurotransmitter release is secondary to increased sodium entry. /Pyrethroids/
[Hayes WJ, Laws ER, eds; Handbook of Pesticide Toxicology V2 p.588 (1991)]**PEER REVIEWED**

The symptoms of pyrethrin poisoning follow the typical pattern of nerve poisoning: (1) excitation, (2) convulsions, (3) paralysis, and (4) death. The effects of pyrethrins on the insect nervous system closely resemble those of DDT, but are apparently much less persistent. Regular, rhythmic, and spontaneous nerve discharges have been observed in insect and crustacean nerve-muscle preparations poisoned with pyrethrins. The primary target of pyrethrins seems to be the ganglia of the insect central nervous system although some pyrethrin-poisoning effect can be observed in isolated legs. /Pyrethrins/
[Matsumura, F. Toxicology of Insecticides. 2nd ed. New York, NY: Plenum Press, 1985. 147]**PEER REVIEWED**

Electrophysiologically, pyrethrins cause repetitive discharges and conduction block. /Pyrethrins/
[Matsumura, F. Toxicology of Insecticides. 2nd ed. New York, NY: Plenum Press, 1985. 147]**PEER REVIEWED**

The interaction of a series of pyrethroid insecticides with the sodium channels in myelinated nerve fibers of the clawed frog, Xenopus laevis, was investigated using the voltage clamp technique. Of 11 pyrethroids, 9 insecticidally active cmpd induced a slowly decaying sodium tail current on termination of a step depolarization, whereas the sodium current during depolarization was hardly affected. /Pyrethroids/
[Vijverberg HP M et al; Biochem Biophys Acta 728 (1): 73-82 (1983)]**PEER REVIEWED**

The biochemical process by which various pyrethroid insecticides alter membrane-bound ATPase activities of the squid nervous system was examined. Of the 5 ATP-hydrolyzing systems tested, only Ca(2+)-stimulated ATPase activities were clearly affected by the pyrethroids. The natural type /I/ pyrethroid, allethrin, primarily inhibits Ca-ATPase activity. /Pyrethroids/
[Clark JM, Matsumura F; Pestic Biochem Physiol 18 (2): 180-90 (1982)]**PEER REVIEWED**

Mode of action of pyrethrum & related cmpd has been studied more in insects & in other invertebrates than in mammals. This action involves ion transport through the membrane of nerve axons &, at least in invertebrates & lower vertebrates, it exhibits a negative temperature coefficient. In both of these important ways & in many details, the mode of action of pyrethrin & pyrethroids resembles that of DDT. Esterases & mixed-function oxidase system differ in their relative importance for metabolizing different synthetic pyrethroids. The same may be true of the constituents of pyrethrum, depending on strain, species, & other factors. /Pyrethrins and pyrethroids/
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 75]**PEER REVIEWED**

The interactions of natural pyrethrins and 9 pyrethroids with the nicotinic acetylcholine (ACh) receptor/channel complex of Torpedo electronic organ membranes were studied. None reduced (3)H-ACh binding to the receptor sites, but all inhibited (3)H-labeled perhydrohistrionicotoxin binding to the channel sites in presence of carbamylcholine. Allethrin inhibited binding noncompetitively, but (3)H-labeled imipramine binding competitively, suggesting that allethrin binds to the receptor's channel sites that bind imipramine. The pyrethroids were divided into 2 types according to their action: type A, which included allethrin, was more potent in inhibiting (3)H-H12-HTX binding and acted more rapidly. Type B, which included permethrin, was less potent and their potency increased slowly with time. The high affinities that several pyrethroids have for this nicotinic ACh receptor suggest that pyrethroids may have a synaptic site of action in addition to their well known effects on the axonal channels. /Pyrethrins and Pyrethroids/
[Abbassy MA et al; Pestic Biochem Physiol 19 (3): 299-308 (1983)]**PEER REVIEWED**

... Pyrethroid esters /containing the alpha-cyano substituent/ produce an even longer delay /than those lacking the substituent/ in sodium channel inactivation, leading to a persistent depolarization of the nerve membrane without repetitive discharge, a reduction in the amplitude of the action potential, and an eventual failure of axonal conduction and a blockade of impulses. /Pyrethroid esters containing the alpha-cyano substituent/
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 595]**PEER REVIEWED**

The primary target site of pyrethroid insecticides in the vertebrate nervous system is the sodium channel in the nerve membrane. Pyrethroids without an alpha-cyano group (allethrin, d-phenothrin, permethrin, and cismethrin) cause a moderate prolongation of the transient increase in sodium permeability of the nerve membrane during excitation. This results in relatively short trains of repetitive nerve impulses in sense organs, sensory (afferent) nerve fibers, and, in effect, nerve terminals. On the other hand the alpha-cyano pyrethroids cause a long lasting prolongation of the transient increase in sodium permeability of the nerve membrane during excitation. This results in long-lasting trains of repetitive impulses in sense organs and a frequency-dependent depression of the nerve impulse in nerve fibers. The difference in effects between permethrin and cypermethrin, which have identical molecular structures except for the presence of an alpha-cyano group on the phenoxybenzyl alcohol, indicates that it is this alpha-cyano group that is responsible for the long-lasting prolongation of the sodium permeability. Since the mechanisms responsible for nerve impulse generation and conduction are basically the same throughout the entire nervous system, pyrethroids may also induce repetitive activity in various parts of the brain. The difference in symptoms of poisoning by alpha-cyano pyrethroids, compared with the classical pyrethroids, is not necessarily due to an exclusive central site of action. It may be related to the long-lasting repetitive activity in sense organs and possibly in other parts of the nervous system, which, in a more advance state of poisoning, may be accompanied by a frequency-dependent depression of the nervous impulse. /Synthetic pyrethroids/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.89 (1990)]**PEER REVIEWED**

Pyrethroids also cause pronounced repetitive activity and a prolongation of the transient increase in sodium permeability of the nerve membrane in insects and other invertebrates. Available information indicates that the sodium channel in the nerve membrane is also the most important target site of pyrethroids in the invertebrate nervous system. /Synthetic pyrethroids/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.90 (1990)]**PEER REVIEWED**

In the electrophysiological experiments using giant axons of cray-fish, the Type II pyrethroids retain sodium channels in a modified continuous open state persistently, depolarize the membrane, and block the action potential without causing repetitive firing. /Pyrethroids type II/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.87 (1990)]**PEER REVIEWED**

Diazepam, which facilitates GABA reaction, delayed the onset of action of deltamethrin and fenvalertae, but not permethrin and allethrin, in both the mouse and cockroach. Possible mechanisms of the Type II pyrethroid syndrome include action at the GABA receptor complex or a closely linked class of neuroreceptor. /Pyrethroids type II/
[WHO; Environmental Health Criteria 99: Cyhalothrin p.87 (1990)]**PEER REVIEWED**

 

Interactions:

The ability of 3 mg/kg/day diazepam to alter the neurobehavioral and neurochemical consequences of perinatal exposure to Ambush and Pydrin was examined. Seventy-two pregnant female rats served as subjects. Half of the subjects were treated with diazepam and the other half were treated with the vehicle via subcutaneous osmotic pumps for 33 days starting on gestational day 1 Each group was further divided into six gavage treatment groups: corn oil, corn oil + 96% xylene, 1.25 or 0.125 mg/kg Pydrin, and 4.0 or 0.4 mg/kg Ambush. Behavioral evaluations were conducted on half the pups in each litter and the other pups were used for the neurochemical assays. Behavioral evaluations included locomotor activity, screen testing, and passive avoidance learning. Brains for neurochemical analysis were extracted and sectioned into frontal cortex, caudate, hippocampus and cerebellum. Neurochemical assays assessed levels of DA, DOPAC, 5-HIAA, 5-HT, HVA, aspartate, glutamate, glutamine, glycine, GABA, and taurine. Diazepam treatment did produce some neurotoxicity in the control pups but diazepam exposure did reverse elevations in amino acid levels in the cerebellum produced by both pyrethroids. In addition diazepam reversed the pyrethroid effects on activity and muscular coordination. These diazepam effects were not specific to Type I or Type II pyrethroids.
[Preston-Martin S, Correa P; Toxicologist 10 (1): 172 (1990)]**PEER REVIEWED**

This investigation explored the behavioral and neurochemical toxicity of perinatal oral exposure to Ambush (Type I) and Pydrin (Type II), two pyrethroid formulations. Thirty-six female rats were mated and exposed to various pyrethroid formulations by oral gavage from the first gestational day until their pups (culled to 8/litter) were 12 days old. Six mothers were exposed daily to one of the following treatments: corn oil control, corn oil+96% xylene, 1.25 mg/kg Pydrin (pesticidal ingredient fenvalerate), 0.125 mg/kg Pydrin, 4.0 mg/kg Ambush (pesticidal ingredient permethrin), or 0.4 mg/kg Ambush. Behavioral evaluations of locomotor activity, muscular coordination and passive avoidanc learning were conducted on half of the pups from each litter (N = 24 pups/treatment condition). The other pups were sacrificed, brains were removed and sectioned into frontal cortex, hippocampus, caudate, and cerebellum for neurochemical assessment. The monoamines DA, DOPAC, 5-HIAA, 5-HT and HVA levels were determined and the amino acids aspartate, glutamate, glutamine, glycine, GABA, and taurine were determined for each of the brain regions. Gestational duration was shortened by exposure to the high doses of Pydrin and Ambush but only pups from the 4.0 mg/kg Ambush group were significantly lighter. No physical malformations were observed in pups from any of the treatment conditions, although the high Pydrin exposure condition resulted in a 4% death rate. Behavioral changes were seen for both locomotor activity and muscular coordination. The shape of across-session habituation of locomotion was different for the xylene and corn oil and the high dose Ambush groups. Both groups were less active on day 1 and more active on days 2 and 3 than the other pups. The high doses of Ambush and Pydrin produced slower intrasession habituation. Muscular coordination was improved slightly following low dose exposure to both pesticides and reduced following high dose exposures. Regional brain weights were normal for the cortex, cerebellum and caudate but the hippocampus was 64% heavier for pups treated with 4.0 mg/kg Ambush. Amino acid determinations indicated that the cerebellum was most affected where glutamate, glutamine, aspartate and taurine were reduced following xylene or pyrethroid exposure. The biogenic amine transmitter 5-HT was reduced in several brain regions following pyrethroid exposures. These data suggest that levels of Ambush and Pydrin as low as the LD50/10,000 can alter behavior and neurotransmitter functioning.
[Shiba K et al; Neurotoxicol Teratol 12: 565 (1990)]**PEER REVIEWED**

Following the administration of a single or repeated doses of dimethoate, carbaryl, and fenvalerate, the activities of tryptophan-2,3-dioxygenase, indoleamine-2,3-dioxygenase, kynurenine, kynureninase, kynurenine-transaminase, and pyridoxal-phosphokinase were determined in the liver, kidney and lung of male Wistar rats. Treatment consisted of 10% of the median lethal dose of each insecticide given orally for the single dosing investigations and 5% of the median lethal dose was given orally for 5 consecutive days as repeated doses. Weight losses in both body and organ were noted only after repeated dose of dimethoate. Significant decreases in the activity of kynurenine-3-hydroxylase, kynurenine-2-oxoglutarate-transaminase, kynurenine-pyruvate-transaminase, and pyridoxal-phosphokinase were noted following repeated administration of dimethoate. Carbaryl in repeated doses caused significant decreases in the activity of apo-tryptophan-2,3-dioxygenase, kynurenine-2-oxoglutarate-transaminase, kynurenine-pyruvate-transaminase, and serine-glyoxylate-transaminase. An inhibition was noted in tryptophan-2,3-dioxygenase following external addition of insecticides at different concn to an incubation mixture. Other enzymes demonstrated no change in their activities following this treatment.
[Hassan AAM et al; J Environ Sc Health. Part B: Pesticides, Food Contaminants, and Agricultural Wastes B25 (3): 333-46 (1990)]**PEER REVIEWED**

/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ... /Pyrethroid/
[Buchel KH (ed); Chemistry of Pesticides p.19 (1983)]**PEER REVIEWED**

Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ... /enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage & similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 78]**PEER REVIEWED**

Pharmacology:

Therapeutic Uses:

MEDICATION (VET): ectoparasiticide
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**QC REVIEWED**

Pyrethrins with piperonyl butoxide are used for topical treatment of pediculosis(lice infestations). Combinations of pyrethrins with piperonyl butoxide are not effective for treatment of scabies (mite infestations). Although there are no well-controlled comparative studies, many clinicians consider 1% lindane to be pediculicide of choice. However, some clinicians recommend use of pyrethrins with piperonyl butoxide, esp in infants, young children, & pregnant or lactating women ... . If used correctly, 1-3 treatments ... are usually 100% effective ... Oil based (eg, petroleum distillate) combinations ... produce the quickest results. ... For treatment of pediculosis, enough gel, shampoo, or solution ... should be applied to cover affected hair & adjacent areas ... After 10 min, hair is ... washed thoroughly ... treatment should be repeated after 7-10 days to kill any newly hatched lice. /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

Interactions:

The ability of 3 mg/kg/day diazepam to alter the neurobehavioral and neurochemical consequences of perinatal exposure to Ambush and Pydrin was examined. Seventy-two pregnant female rats served as subjects. Half of the subjects were treated with diazepam and the other half were treated with the vehicle via subcutaneous osmotic pumps for 33 days starting on gestational day 1 Each group was further divided into six gavage treatment groups: corn oil, corn oil + 96% xylene, 1.25 or 0.125 mg/kg Pydrin, and 4.0 or 0.4 mg/kg Ambush. Behavioral evaluations were conducted on half the pups in each litter and the other pups were used for the neurochemical assays. Behavioral evaluations included locomotor activity, screen testing, and passive avoidance learning. Brains for neurochemical analysis were extracted and sectioned into frontal cortex, caudate, hippocampus and cerebellum. Neurochemical assays assessed levels of DA, DOPAC, 5-HIAA, 5-HT, HVA, aspartate, glutamate, glutamine, glycine, GABA, and taurine. Diazepam treatment did produce some neurotoxicity in the control pups but diazepam exposure did reverse elevations in amino acid levels in the cerebellum produced by both pyrethroids. In addition diazepam reversed the pyrethroid effects on activity and muscular coordination. These diazepam effects were not specific to Type I or Type II pyrethroids.
[Preston-Martin S, Correa P; Toxicologist 10 (1): 172 (1990)]**PEER REVIEWED**

This investigation explored the behavioral and neurochemical toxicity of perinatal oral exposure to Ambush (Type I) and Pydrin (Type II), two pyrethroid formulations. Thirty-six female rats were mated and exposed to various pyrethroid formulations by oral gavage from the first gestational day until their pups (culled to 8/litter) were 12 days old. Six mothers were exposed daily to one of the following treatments: corn oil control, corn oil+96% xylene, 1.25 mg/kg Pydrin (pesticidal ingredient fenvalerate), 0.125 mg/kg Pydrin, 4.0 mg/kg Ambush (pesticidal ingredient permethrin), or 0.4 mg/kg Ambush. Behavioral evaluations of locomotor activity, muscular coordination and passive avoidanc learning were conducted on half of the pups from each litter (N = 24 pups/treatment condition). The other pups were sacrificed, brains were removed and sectioned into frontal cortex, hippocampus, caudate, and cerebellum for neurochemical assessment. The monoamines DA, DOPAC, 5-HIAA, 5-HT and HVA levels were determined and the amino acids aspartate, glutamate, glutamine, glycine, GABA, and taurine were determined for each of the brain regions. Gestational duration was shortened by exposure to the high doses of Pydrin and Ambush but only pups from the 4.0 mg/kg Ambush group were significantly lighter. No physical malformations were observed in pups from any of the treatment conditions, although the high Pydrin exposure condition resulted in a 4% death rate. Behavioral changes were seen for both locomotor activity and muscular coordination. The shape of across-session habituation of locomotion was different for the xylene and corn oil and the high dose Ambush groups. Both groups were less active on day 1 and more active on days 2 and 3 than the other pups. The high doses of Ambush and Pydrin produced slower intrasession habituation. Muscular coordination was improved slightly following low dose exposure to both pesticides and reduced following high dose exposures. Regional brain weights were normal for the cortex, cerebellum and caudate but the hippocampus was 64% heavier for pups treated with 4.0 mg/kg Ambush. Amino acid determinations indicated that the cerebellum was most affected where glutamate, glutamine, aspartate and taurine were reduced following xylene or pyrethroid exposure. The biogenic amine transmitter 5-HT was reduced in several brain regions following pyrethroid exposures. These data suggest that levels of Ambush and Pydrin as low as the LD50/10,000 can alter behavior and neurotransmitter functioning.
[Shiba K et al; Neurotoxicol Teratol 12: 565 (1990)]**PEER REVIEWED**

Following the administration of a single or repeated doses of dimethoate, carbaryl, and fenvalerate, the activities of tryptophan-2,3-dioxygenase, indoleamine-2,3-dioxygenase, kynurenine, kynureninase, kynurenine-transaminase, and pyridoxal-phosphokinase were determined in the liver, kidney and lung of male Wistar rats. Treatment consisted of 10% of the median lethal dose of each insecticide given orally for the single dosing investigations and 5% of the median lethal dose was given orally for 5 consecutive days as repeated doses. Weight losses in both body and organ were noted only after repeated dose of dimethoate. Significant decreases in the activity of kynurenine-3-hydroxylase, kynurenine-2-oxoglutarate-transaminase, kynurenine-pyruvate-transaminase, and pyridoxal-phosphokinase were noted following repeated administration of dimethoate. Carbaryl in repeated doses caused significant decreases in the activity of apo-tryptophan-2,3-dioxygenase, kynurenine-2-oxoglutarate-transaminase, kynurenine-pyruvate-transaminase, and serine-glyoxylate-transaminase. An inhibition was noted in tryptophan-2,3-dioxygenase following external addition of insecticides at different concn to an incubation mixture. Other enzymes demonstrated no change in their activities following this treatment.
[Hassan AAM et al; J Environ Sc Health. Part B: Pesticides, Food Contaminants, and Agricultural Wastes B25 (3): 333-46 (1990)]**PEER REVIEWED**

/Pyrethroid/ detoxification ... important in flies, may be delayed by the addition of synergists ... organophosphates or carbamates ... to guarantee a lethal effect. ... /Pyrethroid/
[Buchel KH (ed); Chemistry of Pesticides p.19 (1983)]**PEER REVIEWED**

Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ... /enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage & similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/
[Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982. 78]**PEER REVIEWED**

Environmental Fate & Exposure:

Environmental Fate/Exposure Summary:

Fenvalerate's use as a contact insecticide in agriculture, in public health programs, in homes and gardens, and on cattle releases the compound directly to the environment in sprays, dusts, concentrates and other routes of application. Fenvalerate is a mixture of four stereo-isomer of which esfenvalerate is the most biologically active. If released to the atmosphere, fenvalerate will degrade rapidly in the vapor phase by reaction with photochemically produced hydroxyl radicals (estimated half-life of 10 hr). If released to soil or water, fenvalerate can degrade through biodegradation, photodegradation and aqueous hydrolysis. Screening studies have suggested that biodegradation is the primary route of degradation. Photodegradation may become the major degradation route on terrestrial surfaces (soil, plants, etc) or shallow waters exposed to sunlight. Aqueous hydrolysis may become important when the medium pH exceeds 8. Fenvalerate is not expected to leach in soil. In aquatic ecosystems, fenvalerate is expected to partition from the water column to sediment and suspended matter. Fenvalerate is reported to have half-lives of 1 to 18 days on soil surfaces, 15 days to 3 months within soil systems, 8 to 14 days on plants, and 4 to 15 days in natural water. Occupational exposure to fenvalerate occurs through dermal contact and inhalation of dust and sprays, especially to workers applying the compound as an insecticide. (SRC)
**PEER REVIEWED**

Probable Routes of Human Exposure:

Occupational exposure to fenvalerate occurs through dermal contact and inhalation of dust and sprays, especially to workers applying the compound as an insecticide(1). Exposure to fenvalerate can occur during its production and application and, at much lower levels, from consumption of foods containing residues(2).
[(1) Parmeggiani L; Encyl Occup Health & Safety 3rd ed. Geneva, Switzerland: International Labour Office pp. 1616-46 (1983) (2) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

Air concns of fenvalerate at the breathing zone of workers spraying fenvalerate insecticide on cotton was 0.06-1.98 ug cu m(1); dermal exposure ranged from 4.71 to 141.61 ug/cu cm on forearms, hands, legs and feet(1). At a fenvalerate packing plant in China, workers were reported to be exposed to 12-55 ug/cu m in the air, with resulting skin contact(2).
[(1) Zhang Z et al; Brit J Industr Med 48: 82-6 (1991) (2) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

Body Burden:

Urine concns of fenvalerate of workers spraying fenvalerate insecticide on cotton was 0.01-1.98 ug/collection interval (3-12 hr) for a period up to 72 hr after spraying(1).
[(1) Zhang Z et al; Brit J Industr Med 48: 82-6 (1991)]**PEER REVIEWED**

Average Daily Intake:

Based upon results of the US FDA's 1990 Total Diet Study, estimated human exposure to fenvalerate from food is as follows(1): 6-11 month old child: 0.0101 ug/kg/day; 14-16 yr old male: 0.0061 ug/kg/day; 60-65 yr old female: 0.0092 ug/kg/day(1).
[(1) Winter CK; Rev Environ Contam Toxicol 127: 23-67 (1992)]**PEER REVIEWED**

Artificial Pollution Sources:

Fenvalerate's use as a contact insecticide in agriculture, in public health programs, in homes and gardens, and on cattle(1) releases the compound directly to the environment in sprays, dusts, concentrates and other routes of application(SRC).
[(1) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

Environmental Fate:

TERRESTRIAL FATE: The primary route of fenvalerate degradation within most soil systems is probably biodegradation. The results of various screening studies conducted in both non-sterile and sterilized soils have indicated that microbial activity was the primary route of disappearance(1-3). The results of various field and laboratory tests have demonstrated that fenvalerate is essentially immobile in soil and will not leach appreciably(4-6). Fenvalerate is reported to have half-lives of 1 to 18 days on soil surfaces, 15 days to 3 months within soil systems and 8 to 14 days on plants(7). A review of available literature determined that the average soil half-life of fenvalerate is about 50 days(8). The US Dept of Agric's Pesticide Properties Database reports a fenvalerate soil half-life of 35 days(9). Enhanced degradation on soil surfaces is probably due to photodegradation via sunlight(10-11,SRC). Measured alkaline hydrolysis rates(12) suggest that hydrolysis may become an important fate process in moist soil systems where the pH is greater than 8(SRC).
[(1) Chapman RA et al; Bull Environ Contam Toxicol 26: 513-19 (1981) (2) Lee PW; J Agric Food Chem 33: 993-8 (1985) (3) Cotham WE Jr, Bidleman TF; J Agric Food Chem 37: 824-8 (1989) (4) Chapman RA et al; J Environ Sci Health B18: 685-90 (1983) (5) Agnihotri NP et al; J Entomol Res 13: 131-6 (1989) (6) Smith S, Willis GH; Environ Toxicol Chem 4: 425-34 (1985) (7) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991) (8) Neary DG; Soil Crop Sci Soc FL Proc 44: 18-24 (1985) (9) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-36 (1991) (10) Katagi T; J Agric Food Chem 39: 1351-6 (1991) (11) Holmstead RL et al; J Agric Food Chem 26: 954-9 (1978) (12) Camilleri P; J Agric Food Chem 32: 1122-4 (1984)]**PEER REVIEWED**

Soil degradation studies using 14-C labelled fenvalerate have identified the following fenvalerate metabolites(1-2): phenoxybenzoic acid, 3-(4-hydroxyphenoxy)benzoic acid, 4'-OH-fenvalerate, CONH2-fenvalerate, and 4-chloro-alpha-(1-methylethyl)benzene acetic acid(1-2); at the end of 12 months, evolved 14-CO2 accounted for 50.5% of applied radioactivity which indicated extensive metabolite degradation(1-2).
[(1) Lee PW; J Agric Food Chem 33: 993-8 (1985) (2) Lee PW et al; J Agric Food Chem 35: 384-7 (1987)]**PEER REVIEWED**

AQUATIC FATE: Fenvalerate can degrade in the aquatic environment through biodegradation photodegradation and aqueous hydrolysis. The results of various screening studies conducted in both non-sterile and sterilized water systems have indicated that microbial activity was a primary route of disappearance (half-lives of 14 to 34 days)(1-3). Photodegradation studies have demonstrated that sunlight can be an important fate process(4-5), and could even be the major fate process in shallow waters with intense sunlight(SRC). Measured alkaline hydrolysis rates(6) suggest that hydrolysis may become an important fate process in water systems where the pH is greater than 8(SRC). Based upon water-sediment sorption studies(7), fenvalerate can be expected to partition from the water column to sediment and suspended matter(SRC). Fenvalerate's estimated Henry's Law constant indicates that volatilization from water is not an important fate process(SRC). The half-life of fenvalerate in natural water has been reported to range from 4 to 15 days(8).
[(1) Schimmel SC et al; J Agric Food Chem 31: 104-13 (1983) (2) Kanazawa J; Environ Monitor Assess 9: 57-70 (1987) (3) Cotham WE Jr, Bidleman TF; J Agric Food Chem 37: 824-8 (1989) (4) Holmstead RL et al; J Agric Food Chem 26: 954-9 (1978) (5) Schimmel SC et al; J Agric Food Chem 31: 104-13 (1983) (6) Camilleri P; J Agric Food Chem 32: 1122-4 (1984) (7) Muir DCG et al; Environ Toxicol Chem 4: 51-61 (1985) (8) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

ATMOSPHERIC FATE: Based upon a reported vapor pressure of 2.8X10-7 mm Hg at 25 deg C(1), fenvalerate can exist in both the vapor and particulate-phases in the ambient atmosphere(2,SRC). It will degrade rapidly in the vapor phase by reaction with photochemically produced hydroxyl radicals with an estimated half-life of about 10 hr(3,SRC). Particulate-phase fenvalerate and aerosols released to air during spray applications of fenvalerate insecticide will be removed from air physically by dry and wet deposition(SRC).
[(1) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991) (2) Bidleman TF; Environ Sci Technol 22: 361-7 (1988) (3) Atkinson R; Environ Toxicol Chem 7: 435-42 (1988)]**PEER REVIEWED**

Environmental Biodegradation:

In a laboratory study using sediment and seawater collected from a salt marsh near Escambia County, FL, fenvalerate was observed to have a half-life of about 34 days(1); however, when the media was sterilized, fenvalerate showed no appreciable degradation after 28 days of incubation(1), thus suggesting that degradation was occurring through biotic means(SRC). In degradation tests using an activated sludge inoculum, the aerobic and anaerobic degradation rates of fenvalerate were 50-72% faster than in sterile controls(2); addition of a glucose medium to cometabolize the non-sterile flasks resulted in a 6-fold increase in the degradation rate under aerobic conditions(2). The aerobic (semi-open system, activated sludge inocula) and anaerobic (serum bottle technique) biodegradation rates of fenvalerate were determined in tests using both inoculated and non-inoculated (control) experiments(3); the biodegradation half-life was determined to be 13 days under both aerobic and anaerobic conditions(3).
[(1) Schimmel SC et al; J Agric Food Chem 31: 104-13 (1983) (2) Kanazawa J; Environ Monitor Assess 9: 57-70 (1987) (3) Kawamoto K, Urano K; Chemosphere 21: 1141-52 (1990)]**PEER REVIEWED**

In soil degradation studies using a mineral and an organic soil, 92-98% of applied fenvalerate disappeared after an 8-week incubation period(1); in sterile soil controls, only 6-17% of applied fenvalerate disappeared suggesting that the disappearance was primarily due to biotic processes(1). The results of a soil degradation study in a sandy loam soil (both natural and sterilized) indicated that the soil disappearance was predominantly by microbial activity(2). In seawater and seawater-sediment microcosm studies, the half-life of fenvalerate was determined to be 14-17 days in non-sterile systems and 33-41 days in sterile systems suggesting a presence of microbial activity(3).
[(1) Chapman RA et al; Bull Environ Contam Toxicol 26: 513-19 (1981) (2) Lee PW; J Agric Food Chem 33: 993-8 (1985) (3) Cotham WE Jr, Bidleman TF; J Agric Food Chem 37: 824-8 (1989)]**PEER REVIEWED**

Environmental Abiotic Degradation:

The rate constant for the vapor phase reaction of fenvalerate with photochemically produced hydroxyl radicals has been estimated to be 3.76X10-11 cu cm/molecule-sec at 25 deg C which corresponds to an atmospheric half-life of about 10 hours at an atmospheric concn of 5X10+5 hydroxyl radicals per cu cm(1,SRC). In a seawater solution study, fenvalerate had an 8 day half-life when exposed to sunlight, but a half-life greater than 14 days under no-sunlight conditions(2). Photodegradation of one isomer of fenvalerate (s,s-isomer) on thin films of intact soil, clay minerals and humic acid was examined by irradiation with a xenon lamp (wavelengths > 300 nm)(3); in all cases, irradiation increased the degradation rates of fenvalerate as follows (half-life in days with light -- half life in days in dark)(3): upland soil (100.0 - - 138.2), kaolinite (7.8 -- 391.2), montmorillonite (68.3 -- 553.4), humic acid (80.6 -- 150.8); the dominant photodegradation reactions were hydration of the cyano group and ether cleavage in the alcohol moiety(3).
[(1) Atkinson R; Environ Toxicol Chem 7: 435-42 (1988) (2) Schimmel SC et al; J Agric Food Chem 31: 104-13 (1983) (3) Katagi T; J Agric Food Chem 39: 1351-6 (1991)]**PEER REVIEWED**

Fenvalerate in various solutions (hexane, methanol, acetonitrile-water) degraded rapidly (16-18 min half-lives) when exposed to strong laboratory irradiation of > 290 nm(1); thin films of fenvalerate on glass exhibited an initial photodegradation half-life of 4 days when exposed to sunlight(1). The alkaline hydrolysis rate constant fenvalerate (optical isomer) in 1:1 dioxane water at 25 deg C was measured as 0.182 L/mol-sec(2) which corresponds to respective half-lives of 440 days, 44 days and 4.4 days at pHs of 7, 8 and 9(SRC); the alkaline hydrolysis rate constant in 1:1 dioxane water at 20 deg C was measured as 0.149 L/mol-sec(2).
[(1) Holmstead RL et al; J Agric Food Chem 26: 954-9 (1978) (2) Camilleri P; J Agric Food Chem 32: 1122-4 (1984)]**PEER REVIEWED**

Environmental Bioconcentration:

In a 28 day laboratory study, steady-state BCFs of 4700 and 570 were measured in eastern oysters (Crassostrea virginica) and sheepshead minnow (Cyprinodon variegatus), respectively(1). A BCF of 1100 was measured for one isomer of fenvalerate (s,s-isomer) in carp in a 24 hr renewal exposure following 7 days of exposure(1). In a 30 day aquatic ecosystem study, fenvalerate BCFs of 100 for fish, 491 for snails and 412 for algae were measured(1); relatively low residues in the organisms were attributed to metabolism, especially by the fish(1).
[(1) Schimmel SC et al; J Agric Food Chem 31: 104-13 (1983)]**PEER REVIEWED**

Soil Adsorption/Mobility:

In undisturbed soils with >2% organic matter, fenvalerate has been shown to be immobile(1); in a field study at an onion field in Ontario, Canada conducted between 1980 and 1982, most of the applied fenvalerate remained in the upper third of 15 cm soil cores(1). In 6-hr water-sediment sorption tests, 32% of added fenvalerate sorbed to a clay sediment while 84% of applied fenvalerate sorbed to a silty-clay sediment(2); 4% sorbed to sand(2); based upon measured isotherms and organic carbon content(2), the Koc values for fenvalerate in the silty-clay and clay sediments are log 4.04-4.22(2); the US Dept of Agric's Pesticide Properties Database reports a fenvalerate Koc of 3.72(6); according to a suggested classification scheme(3), these estimated Koc values suggest that fenvalerate is immobile in soil(SRC). In a field study near New Delhi, India, fenvalerate did not leach below a 7.5 cm depth(4). Under saturated flow conditions in soil column leaching studies, fenvalerate was found to be essentially immobile(5).
[(1) Chapman RA et al; J Environ Sci Health B18: 685-90 (1983) (2) Muir DCG et al; Environ Toxicol Chem 4: 51-61 (1985) (3) Swann RL et al; Res Rev 85: 23 (1983) (4) Agnihotri NP et al; J Entomol Res 13: 131-6 (1989) (5) Smith S, Willis GH; Environ Toxicol Chem 4: 425-34 (1985) (6) Wauchope RD et al; Rev Environ Contam Toxicol 123: 1-36 (1991)]**PEER REVIEWED**

Volatilization from Water/Soil:

The Henry's Law constant for fenvalerate can be estimated to be 1.19X10-7 atm-cu m/mole at 25 deg C using a structure estimation method(1,SRC). This value of Henry's Law constant indicates that fenvalerate is essentially non-volatile from water(2); therefore, volatilization from water will not be important(SRC). During a laboratory metabolism study, volatilization of fenvalerate from activated sludge, sediment or soil was less than 0.1%(3).
[(1) Meylan W, 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. 15-15 to 15-29 (1990) (3) Kanazawa J; Environ Monitor Assess 9: 57-70 (1987)]**PEER REVIEWED**

Effluent Concentrations:

Water collected from exterior washings of an airplane used for spray applications of fenvalerate insecticide contained fenvalerate concns of 0.004-0.02 mg/L(1); fenvalerate concns in rinses of the spray tanks were 53-528 mg/L in the first rinse, 3.15-25.2 mg/L in the second rinse and 0.32-1.80 mg/L in the third rinse(1).
[(1) Woodrow JE et al; Bull Environ Contam Toxicol 42: 22-9 (1989)]**PEER REVIEWED**

Food Survey Values:

According to compiled results of the US Food and Drug Administration's pesticide residue monitoring programs (including the Total Diet Study) for fiscal years 1978-1986, fenvalerate has been detected as a pesticide residue in American foods(1,2); the frequency of occurrence or concns of fenvalerate detected were not reported(SRC). During a 5-yr period from 1982-1986, the US FDA's Los Angeles District Laboratory analyzed 19,581 samples of domestic and imported food and feed commodities for pesticide residues(3); fenvalerate was detected in 25 samples at concns of 0.05-1.0 ppm(3). For fiscal years 1988 and 1989, 27065 food samples were collected and analyzed for pesticide residues by 10 state laboratories (CA, NY, FL, IN, MA, MI, NC, OR, VA and WI)(4); fenvalerate was detected in 54 samples (concns not reported)(4).
[(1) Yess NJ et al; J Assoc Off Anal Chem 74: 273-80 (1991) (2) Yess NJ et al J Assoc Off Anal Chem 74: 265-72 (1991) (3) Luke MA et al; J Assoc Off Anal Chem 71: 415-20 (1988) (4) Minyard JP, Roberts WE; J Assoc Off Anal Chem 74: 438-52 (1991)]**PEER REVIEWED**

Of a total of 946 samples analyzed in the 1984-1989 Canadian national surveillance program, 7 were found to contain fenvalerate residues, at levels of 0.02-0.096 mg/kg(1); most were in pears (6/114 samples) and one in lettuce (1/11 samples)(1). In Sweden, 163 of 165 samples of imported fruit and vegetables contained residues up to 0.2 mg/kg(1); one had a residue of 0.54 mg/kg(1).
[(1) IARC; IARC Monographs on the Evaluation of Carcinogen Risks to Humans. Lyon, France: World Health Organization 53: 309-28 (1991)]**PEER REVIEWED**

Milk Concentrations:

Two Holstein cows were treated with 0.5 g of fenvalerate per cow in three consecutive topical treatments at 14-day intervals(1); residues in whole milk were at a max 6 hr after treatment and declined to less than 0.2 ug/L over 21 days(1); only 0.03-0.06% of applied fenvalerate appeared in the milk as the intact insecticide(1).
[(1) Frank R et al; Pestic Sci 15: 600-4 (1984)]**PEER REVIEWED**

Environmental Standards & Regulations:

FIFRA Requirements:

Tolerances are established for residues of the insecticide Cyano(3-phenoxyphenyl)methyl-4-chloro-a-(1-methylethyl) benzeneacetate in or on the following raw agricultural commodities: Almond hulls; Almonds; Apples; Artichokes; Beans, dried; Beans, snap; Broccoli; Blueberries; Cabbage; Caneberries; Cantaloupes; Carrots; Cattle (fat, meat byproducts, and meat); Cauliflower; Collards; Corn, grain; Corn, fodder; Corn, forage; Corn, sweet, kernels & cobs; Cottonseed; Cucumbers; Currants; Eggplant; Elderberries; English walnuts; Filberts; Goats (fat, meat byproducts, and meat); Gooseberries; Hogs (fat, meat byproducts, and meat); Honeydew melons; Horses (fat, meat byproducts, and meat); Huckleberries; Milk; Milk, fat; Muskmelons; Peanuts; Peanut hulls; Pears; Peas; Peas, dried; Pecans; Peppers; Potatoes; Pumpkins; Radish, roots; Radish, tops; Sheep (fat, meat byproducts, and meat); Soybeans; Stone fruits; Sugarcane; Summer squash; Sunflower seed; Tomatoes; Turnip roots; Turnip tops; Watermelons; and Winter squash.
[40 CFR 180.379(a) (7/1/91)]**PEER REVIEWED**

A tolerance with regional registration is established for residues of the insecticide cyano(3-phenoxyphenyl)methyl-4-chloro-alpha-(1-methylethyl)benzeneacetate in or on the raw agricultural commodity okra.
[40 CFR 180.379(b) (7/1/91)]**PEER REVIEWED**

A food additive tolerance is established for residues of the insecticide cyano(3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl)benzeneacetate and an isomer, (S)-cyano(3- phenoxyphenyl)methyl-(S)-4-chloro-alpha-(1-methylethyl)-benzeneacetate, as follows: In or on all food items (other than those already covered by a higher tolerance as a result of use on growing crops) in food-handling establishments where food products are held, processed, or prepared.
[40 CFR 185.1300(a)(1) (7/1/91)]**PEER REVIEWED**

A food additive tolerance is established for residues of the insecticide cyano(3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl)benzeneacetate as follows: Application of cyano(3-phenoxyphenyl)methyl-4-chloro- alpha-(1-methylethyl)benzeneacetate shall be limited to space treatment with a max of 0.5 fluid oz of a 0.05% active ingredient soln per 1,000 cu ft of space, or as a contact spray applied as a coarse wet spray at a max of 1 gal of a 0.2% active ingredient soln per 1,000 sq ft of surface. Food must be removed or covered during treatment. Spray should not be applied directly to surfaces or utensils that may come into contact with food. Food-contact surfaces and equipment should be thoroughly cleaned with an effective cleaning compound and rinsed with potable water before using.
[40 CFR 185.1300(a)(2) (7/1/91)]**PEER REVIEWED**

To assure safe use of the additive, its label and labeling shall conform to that registered with the USEPA, and shall be used in accordance with such label and labeling.
[40 CFR 185.1300(a)(4) (7/1/91)]**PEER REVIEWED**

A regulation is established permitting residues of the insecticide cyano(3-phenoxyphenyl)methyl 4-chloro-alpha-(1-methylethyl) benzeneacetate in or on the following commodities: Dried apple pomace; Dried tomato pomace; Soybean hulls; Sugarcane bagasse; and Sunflower hulls.
[40 CFR 186.1300 (7/1/91)]**PEER REVIEWED**

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA, as amended in 1988, were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Fenvalerate is found on List B. Case No: 2280; Pesticide type: Insecticide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): alpha-Cyano-(3-phenoxylphenyl)methyl 4-chloro-alpha-(1-methylethyl)benzeneacetate; Data Call-in (DCI) Date(s): 07/11/91, 03/03/95, 07/20/95, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.
[USEPA/OPP; Status of Pesticides in Registration, Reregistration and Special Review p.182 (Spring, 1998) EPA 738-R-98-002]**QC REVIEWED**

Acceptable Daily Intakes:

FAO/WHO ADI: 0.02 mg/kg
[FAO/WHO; Pesticide Residues in Food - 1990. Evaluations Part 1 - Residues p.422 Plant Prod Protect Paper 103/1 (1990)]**QC REVIEWED**

OPP RfD= 0.025 mg/kg; EPA RfD= 0.025 mg/kg
[USEPA/OPP; Health Effects Div RfD/ADI Tracking Report p.49 (8/26/91)]**QC REVIEWED**

State Drinking Water Guidelines:

(AZ) ARIZONA 180 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)] **QC REVIEWED**

Allowable Tolerances:

Tolerances are established for residues of the insecticide cyano(3-phenoxyphenyl)methyl-4-chloro-a-(1-methylethyl) benzeneacetate in or on the following raw agricultural commodities: Almond hulls: 15.0 ppm; Almonds: 0.2 ppm; Apples: 2.0 ppm; Artichokes: 0.2 ppm; Beans, dried: 0.25 ppm; Beans, snap: 2.0 ppm; Broccoli: 2.0 ppm; Blueberries: 3.0 ppm; Cabbage: 10.0 ppm; Caneberries: 3.0 ppm; Cantaloupes: 1.0 ppm; Carrots: 0.5 ppm; Cattle (fat, meat byproducts, and meat): 1.5 ppm; Cauliflower: 0.5 ppm; Collards: 10.0 ppm; Corn, grain: 0.02 ppm; Corn (fodder and forage): 50.00 ppm; Corn, sweet, kernels & cobs: 0.1 ppm; Cottonseed: 0.2 ppm; Cucumbers: 0.5 ppm; Currants: 3.0 ppm; Eggplant: 1.0 ppm; Elderberries: 3.0 ppm; English walnuts: 0.2 ppm; Filberts: 0.2 ppm; Goats (fat, meat byproducts, and meat): 1.5 ppm; Gooseberries: 3.0 ppm; Hogs (fat, meat byproducts, and meat): 1.5 ppm; Honeydew melons: 1.0 ppm; Horses (fat, meat byproducts, and meat): 1.5 ppm; Huckleberries: 3.0 ppm; Milk: 0.3 ppm; Milk, fat: 7.0 ppm; Muskmelons: 1.0 ppm; Peanuts: 0.02 ppm; Peanut hulls: 0.10 ppm; Pears: 2.0 ppm; Peas: 1.0 ppm; Peas, dried: 0.25 ppm; Pecans: 0.2 ppm; Peppers: 1.0 ppm; Potatoes: 0.02 ppm; Pumpkins: 1.0 ppm; Radish, roots: 0.3 ppm; Radish, tops: 8.0 ppm; Sheep (fat, meat byproducts, and meat): 1.5 ppm; Soybeans: 0.05 ppm; Stone fruits: 10.0 ppm; Sugarcane: 2.0 ppm; Summer squash: 0.5 ppm; Sunflower seed: 1.0 ppm; Tomatoes: 1.0 ppm; Turnip roots: 0.5 ppm; Turnip tops: 20.0 ppm; Watermelons: 1.0 ppm; and Winter squash: 1.0 ppm.
[40 CFR 180.379(a) (7/1/91)]**PEER REVIEWED**

A tolerance with regional registration is established for residues of the insecticide cyano(3-phenoxyphenyl)methyl-4-chloro-alpha- (1-methylethyl)benzeneacetate in or on the following raw agricultural commodity: Okra: 0.1 ppm.
[40 CFR 180.379(b) (7/1/91)]**PEER REVIEWED**

A food additive tolerance of 0.05 ppm is established for residues of the insecticide cyano(3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl)benzeneacetate and an isomer, (S)-cyano(3- phenoxyphenyl)methyl-(S)-4-chloro-alpha-(1-methylethyl)-benzeneacetate, as follows: In or on all food items (other than those already covered by a higher tolerance as a result of use on growing crops) in food-handling establishments where food products are held, processed, or prepared.
[40 CFR 185.1300(a)(1) (7/1/91)]**PEER REVIEWED**

A food additive tolerance of 0.05 ppm is established for residues of the insecticide cyano(3-phenoxyphenyl) methyl-4-chloro-alpha-(1-methylethyl)benzeneacetate as follows: Application of cyano(3-phenoxyphenyl)methyl-4-chloro- alpha-(1-methylethyl)benzeneacetate shall be limited to space treatment with a max of 0.5 fluid oz of a 0.05% active ingredient soln per 1,000 cu ft of space, or as a contact spray applied as a coarse wet spray at a max of 1 gal of a 0.2% active ingredient soln per 1,000 sq ft of surface. Food must be removed or covered during treatment. Spray should not be applied directly to surfaces or utensils that may come into contact with food. Food-contact surfaces and equipment should be thoroughly cleaned with an effective cleaning compound and rinsed with potable water before using.
[40 CFR 185.1300(a)(2) (7/1/91)]**PEER REVIEWED**

A regulation is established permitting residues of the insecticide cyano(3-phenoxyphenyl)methyl 4-chloro-alpha-(1-methylethyl) benzeneacetate in or on the following commodities: Dried apple pomace: 20 ppm; Dried tomato pomace: 10 ppm; Soybean hulls: 1.0 ppm; Sugarcane bagasse: 20.0 ppm; and Sunflower hulls: 2.0 ppm.
[40 CFR 186.1300 (7/1/91)]**PEER REVIEWED**

Chemical/Physical Properties:

Molecular Formula:

C25-H22-Cl-N-O3
**PEER REVIEWED**

Molecular Weight:

419.92
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Color/Form:

Clear yellow viscous liquid
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Odor:

Mild chemical odor
[Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)]**PEER REVIEWED**

Corrosivity:

Non-corrosive to metals.
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A207]**PEER REVIEWED**

Density/Specific Gravity:

1.17 at 23 deg C/4 deg C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Octanol/Water Partition Coefficient:

log Kow= 4.42
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 670]**PEER REVIEWED**

Solubilities:

In water at 20 deg C, < 1 mg/l. Readily soluble in most organic solvents, in acetone, ethanol, chloroform, cyclohexanone, xylene, all > 1 kg/kg at 23 deg C.
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A207]**PEER REVIEWED**

Spectral Properties:

Index of refraction: 1.5533 at 20 deg C/D
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Vapor Pressure:

1.1X10-8 mm Hg at 25 deg C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Other Chemical/Physical Properties:

Brown viscous liquid /Technical grade, 90% min fenvalerate/
[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982. 295]**PEER REVIEWED**

Has two chiral centers giving four possible optical isomers.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Decomposes gradually between 150-300 deg C. No significant breakdown 100 hr at 75 deg C.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Decomposes on distillation
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A207/Aug 87]**PEER REVIEWED**

Chemical Safety & Handling:

Skin, Eye and Respiratory Irritations:

Fenvalerate as technical Pydrin is mildly irritating to the skin, but the emulsifiable concentrate is corrosive.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

Eye, skin irritant.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

One notable form of toxicity associated with synthetic pyrethroids has been a cutaneous paresthesia observed in workers spraying esters containing alpha-cyano substituent (deltamethrin, cypermethrin, fenvalerate). The paresthesia developed several hours following exposure, being described as a stinging or burning sensation on the skin which, in some cases, progressed to a tingling and numbness, the effects lasting some 12 to 18 hours.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 594]**PEER REVIEWED**

Immediately irritating to the eye. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

The chief effect from exposure ... is skin rash particularly on moist areas of the skin. ... May irritate the eyes.
[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**

Fire Potential:

/Pyrethrins/ ... burn with difficulty. /Pyrethrins/
[Bureau of Explosives; Emergency Handling of Haz Matl in Surface Trans p.434 (1981)]**PEER REVIEWED**

Fire Fighting Procedures:

Use carbon dioxide, foam, or dry chemical /on fires involving pyrethroids/. /Pyrethrum/
[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. 2]**PEER REVIEWED**

Fire-fighting: Self-contained breathing apparatus with a full facepiece operated in pressure-demand or other positive-pressure mode. /Pyrethrum/
[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**

Extinguish fire using agent suitable for type of surrounding fire. /Pyrethrins/
[Bureau of Explosives; Emergency Handling of Haz Matl in Surface Trans p.434 (1981)]**PEER REVIEWED**

Toxic Combustion Products:

Hydrogen cyanide may be formed during thermal decomposition.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

Hazardous Reactivities & Incompatibilities:

Incompatible with alkaline materials.
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A207/Aug 87]**PEER REVIEWED**

Incompatibility: Strong oxidizers. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

... Incompatible with lime & ordinary soaps because acids & alkalies speed up processes of hydrolysis. /Pyrethrins/
[Farm Chemicals Handbook 1986. Willoughby, Ohio: Meister Publishing Co., 1986.,p. C-198]**PEER REVIEWED**

Hazardous Decomposition:

Hydrogen cyanide may be formed during thermal decomposition.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

Protective Equipment & Clothing:

Protective gloves, goggles, or full face shield when handling.
[Farm Chemicals Handbook 1991. Willoughby, OH: Meister, 1991.,p. C139]**PEER REVIEWED**

Employees should be provided with and required to use dust- and splash-proof safety goggles where /pyrethroids/ ... may contact the eyes. /Pyrethroids/
[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 be required to use impervious clothing, gloves, and face shields (eight-inch minimum). /Pyrethroids/
[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. 2]**PEER REVIEWED**

Wear appropriate equipment to prevent: Repeated or prolonged skin contact. /Pyrethrum and pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Wear eye protection to prevent: Reasonable probability of eye contact. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Recommendations for respirator selection. Max concn for use: 50 mg/cu m: Respirator Classes: Any chemical cartridge respirator with organic vapor cartridge(s) in combination with a dust, mist, and fume filter. May require eye protection. Any supplied-air respirator. May require eye protection. Any self-contained breathing apparatus. May require eye protection. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Recommendations for respirator selection. Max concn for use: 125 mg/cu m: Respirator Classes: Any supplied-air respirator operated in a continuous flow mode. May require eye protection. Any powered, air-purifying respirator with organic vapor cartridge(s) in combination with a dust, mist, and fume filter. May require eye protection. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Recommendations for respirator selection. Max concn for use: 250 mg/cu m: Respirator Classes: Any chemical cartridge respirator with a full facepiece and organic vapor cartridge(s) in combination with a high-efficiency particulate filter. Any self-contained breathing apparatus with a full facepiece. Any supplied-air respirator with a full facepiece. Any powered, air-purifying respirator with a tight-fitting facepiece and organic vapor cartridge(s) in combination with a high-efficiency particulate filter. May require eye protection. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Recommendations for respirator selection. Max concn for use: 5,000 mg/cu m: Respirator Class: Any supplied-air respirator with a full facepiece and operated in a pressure-demand or other positive pressure mode. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Recommendations for respirator selection. Condition: Emergency or planned entry into unknown concn or IDLH conditions: Respirator Classes: Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive pressure mode. Any supplied-air respirator with a full face piece and operated in pressure-demand or other positive pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive pressure mode. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Recommendations for respirator selection. Condition: Escape from suddenly occurring respiratory hazards: Respirator Classes: Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister having a high-efficiency particulate filter. Any appropriate escape-type, self-contained breathing apparatus. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

 

Preventive Measures:

Avoid eye, skin, mouth contact.
[Farm Chemicals Handbook 1991. Willoughby, OH: Meister, 1991.,p. C139]**PEER REVIEWED**

SRP: The scientific literature supports the wearing of contact lenses in industrial environments, as part of a program to protect the eye against chemical compounds and minerals causing eye irritation. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases contact lenses should not be worn.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Skin that becomes contaminated with /pyrethrum/ should be promptly washed or showered with soap or mild detergent and water. /Pyrethrum/
[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**

Clothing contaminated with /pyrethrum/ should be placed in closed containers for storage until provision is made for the removal of /pyrethrum/ from the clothing. /Pyrethrum/
[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. 2]**PEER REVIEWED**

Respirators may be used when engineering and work practice controls are not technically feasible, when such controls are in the process of being installed, or when they fail or need to be supplemented. Respirators may also be used for operations which require entry into tanks or closed vessels, and in emergency situations. /Pyrethrum/
[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. 2]**PEER REVIEWED**

Employees who handle /pyrethrum/ ... should wash their hands thoroughly with soap or mild detergent and water before eating, smoking, or using toilet facilities. /Pyrethrum/
[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**

Avoid contact with skin. Keep out of any body of water. Do not contaminate water by cleaning of equipment or disposal of waste. Do not reuse empty container. Destroy it by perforating or crushing. /Pyrethrum/
[Farm Chemicals Handbook 1986. Willoughby, Ohio: Meister Publishing Co., 1986.,p. C-198]**PEER REVIEWED**

Contact lenses should not be worn when working with this chemical. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Workers should wash: Promptly when skin becomes contaminated. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Work clothing should be changed daily: If it is reasonably probable that the clothing may be contaminated. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

Remove clothing: Promptly if it is non-impervious clothing that becomes contaminated. /Pyrethrins/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS(NIOSH) Publication No. 90-117. Washington, DC: U.S. Government Printing Office, June 1990 190]**PEER REVIEWED**

If /pyrethrins/ are not involved in a fire: keep /pyrethrins/ out of water sources and sewers. Build dikes to contain flow as necessary. /Pyrethrins/
[Bureau of Explosives; Emergency Handling of Haz Matl in Surface Trans p.434 (1981)]**PEER REVIEWED**

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
**PEER REVIEWED**

Stability/Shelf Life:

More stable in acidic solution than in alkaline solution.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

Pyrethrins ... /are/ stable for long periods in water-based aerosols where ... emulsifiers give neutral water systems. /Pyrethrins/
[Farm Chemicals Handbook 1986. Willoughby, Ohio: Meister Publishing Co., 1986.,p. C-198]**PEER REVIEWED**

Storage Conditions:

Store in original containers away from food stuffs, animal feed.
[Farm Chemicals Handbook 1991. Willoughby, OH: Meister, 1991.,p. C139]**PEER REVIEWED**

Pyrethrins with piperonyl butoxide topical preparations should be stored in well-closed containers at a temperature less than 40 deg C, preferably between 15-30 deg C. /Pyrethrins/
[McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992). 2125]**PEER REVIEWED**

Cleanup Methods:

Spillages of pesticides at any stage of their storage or handling should be treated with great care. Liquid formulations may be reduced to solid phase by evaporation. Dry sweeping of solids is always hazardous: these should be removed by vacuum cleaning, or by dissolving them in water, or other solvent in the factory environment. /Pesticides/
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 1619]**PEER REVIEWED**

Environmental consideration - Land spill: Dig a pit, pond, lagoon, or holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, or cement powder. /Pyrethrins/
[Bureau of Explosives; Emergency Handling of Haz Matl in Surface Trans p.434 (1981)]**PEER REVIEWED**

Environmental consideration - Water spill: If /pyrethrins/ are dissolved, apply activated carbon at ten times the spilled amount in the region of 10 ppm or greater concn. Use mechanical dredges or lifts to remove immobilized masses of pollutants and precipitates. /Pyrethrins/
[Bureau of Explosives; Emergency Handling of Haz Matl in Surface Trans p.434 (1981)]**PEER REVIEWED**

Disposal Methods:

Incineration would be an effective disposal procedure where permitted. If an efficient incinerator is not available, the product should be mixed with large amounts of combustible material and contact with the smoke should be avoided. /Pyrethrin products/
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 762]**PEER REVIEWED**

The following wastewater treatment technology has been investigated for chlorinated pesticides: Concentration process: Resin adsorption. /Chlorinated pesticides/
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-195 (1982)]**PEER REVIEWED**

The following wastewater treatment technology has been investigated for chlorinated pesticides: Concentration process: Resin adsorption. /Chlorinated pesticides/
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-195 (1982)]**PEER REVIEWED**

Group I Containers: Combustible containers from organic or metallo-organic pesticides (except organic mercury, lead, cadmium, or arsenic compounds) should be disposed of in pesticide incinerators or in specified landfill sites. /Organic or metallo-organic pesticides/
[40 CFR 165.9(a) (7/1/90)]**PEER REVIEWED**

Group II Containers: Non-combustible containers from organic or metallo-organic pesticides (except organic mercury, lead, cadmium, or arsenic compounds) must first be triple-rinsed. Containers that are in good condition may be returned to the manufacturer or formulator of the pesticide product, or to a drum reconditioner for reuse with the same type of pesticide product, if such reuse is legal under Department of Transportation regulations (eg 49 CFR 173.28). Containers that are not to be reused should be punctured ... and transported to a scrap metal facility for recycling, disposal or burial in a designated landfill. /Organic or metallo-organic pesticides/
[40 CFR 165.9(b) (7/1/90)]**PEER REVIEWED**

Occupational Exposure Standards:

Manufacturing/Use Information:

Major Uses:

Highly active contact insecticide effective against a wide range of pests, including strains resistant to organochlorine, organophosphorus, and carbamate insecticides. It controls insects that attack leaves or fruits on various crops, including cotton, fruit, vegetables and vines at 25-250 g ai/ha, and is persistent under various field conditions. It is also used in public health and animal husbandry, controlling flies in cattle sheds for 60 days at 100 mg/sq m wall, and is effective against Boophilus at 200-300 mg/l.
[Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987. 395]**PEER REVIEWED**

A broad-spectrum insecticide for use on cotton and fruit.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-261]**PEER REVIEWED**

/For treatment of animals/ apply one or two tags per head as needed. Will aid in control of face flies. Will control ear ticks.
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982. 913]**PEER REVIEWED**

Uses include control of chewing, sucking, and boring insects (particularly Lepidoptera, Diptera, Orthoptera, Hemiptera, and Coleoptera) in fruit, vines, olives, hops, nuts, vegetables, cucurbits, cotton, oilseed, rape, sunflowers, lucerne, cereals, maize, sorghum, potatoes, beet, groundnuts, soya beans, tobacco, sugar cane, ornamentals, forestry, and on non-crop land. Also used for control of flying and crawling insects in public health situtations and in animal houses.
[Hartley, D. and H. Kidd (eds.). The Agrochemicals Handbook. 2nd ed. Lechworth, Herts, England: The Royal Society of Chemistry, 1987.,p. A207/AUG 87]**PEER REVIEWED**

Insecticide /Pyrethrins/
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 1267]**PEER REVIEWED**

MEDICATION (VET)
**QC REVIEWED**

MEDICATION
**QC REVIEWED**

Manufacturers:

Du Pont Co, Hq, 1007 Market St, Wilmington, DE 19898; (302) 774-1000, (800) 441-7515, Du Pont Agricultural Products; Production site: Axis, AL 36505
[SRI. 1992 Directory of Chemical Producers-United States of America. Menlo Park, CA: SRI International, 1992. 834]**PEER REVIEWED**

Methods of Manufacturing:

... prepared by esterification of 3-phenoxybenzaldehyde cyanohydrin with 2-(4-chlorophenyl)isovaleroyl chloride.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 53 313 (1991)]**PEER REVIEWED**

... condensation of 3-phenoxy-alpha-halobenzyl cyanide with the isovaleric acid in the presence of a base such as potassium carbonate.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 53 313 (1991)]**PEER REVIEWED**

General Manufacturing Information:

A synthetic pyrethroid insecticide without the usual cyclopropane ring.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 629]**PEER REVIEWED**

/Pyrethroids/ are modern synthetic insecticides similar chemically to natural pyrethrins, but modified to increase stability in the natural environment. /Pyrethroids/
[Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed. p.34 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**

Formulations/Preparations:

Emulsifiable concentrate, dust, granules, wettable powder.
[Farm Chemicals Handbook 1991. Willoughby, OH: Meister, 1991.,p. C138]**PEER REVIEWED**

Technical grade 90% min of fenvalerate.
[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982. 295]**PEER REVIEWED**

An emulsifiable concentrate, marketed as Pydrin 2.4 EC Insecticide, is comprised of 32% technical Pydrin and 68% aromatic hydrocarbon solvents and emulsifiers.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-161]**PEER REVIEWED**

Ectrin 8%
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982. 913]**PEER REVIEWED**

Laboratory Methods:

Analytic Laboratory Methods:

Fenvalerate canbe determined by GLC with a flame ionization detector (3% ov-17 glass column with temperature programming). The detection limit is 0.054 ug/ml.
[WHO; Environmental Health Criteria 95: Fenvalerate p.86 (1990)]**PEER REVIEWED**

Product analysis is by HPLC or by GLC. Residues may be determined by GLC with ECD.
[Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987. 396]**PEER REVIEWED**

Pyrethrins ... in pesticide formulations are analyzed using gas chromatography equipped with flame ionization detection. Average recovery is 98% with a precision of 0.0044-0.011. /Pyrethrins/
[Association of Official Analytical Chemists. Official Methods of Analysis. 15th ed. and Supplements. Washington, DC: Association of Analytical Chemists, 1990,p. V1 172]**PEER REVIEWED**

... Liquid chromatography method has been developed to quantitate pyrethrins in pesticide formulations. ... Detection was monitored at 240 nm. ... Percent coefficients of variation ranged from 1.39 to 9.68 with the majority less than 5.00. ... /Pyrethrins/
[Bushway RJ; J Assoc Off Anal Chem 68 (6): 1134-6 (1985)]**PEER REVIEWED**

Pyrethrins were detected in soils by gas chromatography after extraction with hexane. /Pyrethrins/
[Siltanen H et al; Ryrethrum Post 14 (3): 65-7 (1978)]**PEER REVIEWED**

Low level pyrethrin formulations are extracted with tetrahydrofuran and determined via capillary gas chromatography with electron capture detection. ... Analysis of 5 formulations gave an average standard deviation of 3.3%. /Pyrethrins/
[Stringham RW, Schutz RP; J Assoc Off Anal Chem 68 (6): 1137-9 (1985)]**PEER REVIEWED**

Special References:

Special Reports:

Clark JR et al; Toxicity of pyrethroids to Marine Invertebrates and Fish: A Literature Review and Test Results with Sediment-Sorbed Chemicals. Environ Toxicol Chem 8 (5): 393-401 (1989). Data on acute and chronic toxicity of permethrin, fenvalerate, cypermethrin, and flucythrinate to marine invertebrates and fishes are reviewed.

Miyamoto J; Environ Health Perspect 14: 15-28 (1976). Degradation, metabolism, and toxicity of synthetic pyrethroids.

Miyamoto J, et al; Pure Appl Chem 53: 1967-2022 (1981). The chemistry, metabolism, and residue analysis of synthetic pyrethroids.

Hutson DH; Progress in Drug Metabolism 3: 215-252 (1979). The metabolic fate of synthetic pyrethroid insecticides in mammals.

Gammon DW; Fundam Appl Toxicol (5) 1: 9-23 (1985). Correlations between in vitro and in vivo mechanisms of pyrethroid insecticide action.

Casida JE et al; Ann Rev Pharmacol Toxicol 23: 413-38 (1983). The mechanisms of selective action of pyrethroid insecticide are discussed.

Papadopoulou-Mourkidou E; Residue Rev 89: 179-208 (1983). A review with many references on analysis of allethrin & other pyrethroid insecticides.

Purdue University; National Pesticide Information Retrieval System, Fenvalerate Fact Sheet No. 145 (1987)

WHO; Environmental Health Criteria 95: Fenvalerate (1990)

Synonyms and Identifiers:

Related HSDB Records:

6625 [ESFENVALERATE] (isomer)

Synonyms:

S-5602
**PEER REVIEWED**

Balmark
**PEER REVIEWED**

Belmark
**PEER REVIEWED**

4-Chloro-alpha-(1-methylethyl)benzeneacetic acid cyano(3-phenoxyphenyl)methyl ester
**PEER REVIEWED**

(+)Alpha-cyano-3-phenoxybenzyl-(+)-alpha-(4-chlorophenyl)isovalerate
**PEER REVIEWED**

alpha-Cyano-3-phenoxy-benzyl alpha-(4-chlorophenyl)isovalerate
**PEER REVIEWED**

Alpha-cyano-3-phenoxybenzyl 2-(4-chlorophenyl)-3-methylbutyrate
**PEER REVIEWED**

alpha-Cyano-3-phenoxy-benzyl alpha-isopropyl-4-chlorophenylacetate
**PEER REVIEWED**

alpha-cyano-3-phenoxybenzyl isopropyl-4-chlorophenylacetate
**PEER REVIEWED**

cyano(3-Phenoxyphenyl)methyl 4-chloro-alpha-(1-methylethyl)benzeneacetate
**PEER REVIEWED**

(cyano(3-phenoxyphenyl)methyl-4-chloro-alpha-(1-methylethyl)phenylacetate)
**PEER REVIEWED**

Ectrin
**PEER REVIEWED**

EPA Shaughnessy Code: 109301
**PEER REVIEWED**

Fenkill
**PEER REVIEWED**

Phenvalerate
**PEER REVIEWED**

Pydrin
**PEER REVIEWED**

Pyridin
**PEER REVIEWED**

(RS)-alpha-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate
**PEER REVIEWED**

Sanmarton
**PEER REVIEWED**

SD-43775
**PEER REVIEWED**

Sumibac
**PEER REVIEWED**

Sumicidin
**PEER REVIEWED**

Sumifleece
**PEER REVIEWED**

Sumifly
**PEER REVIEWED**

Sumipower
**PEER REVIEWED**

Sumitick
**PEER REVIEWED**

Sumkidin
**PEER REVIEWED**

Tirade
**PEER REVIEWED**

WL43775
**PEER REVIEWED**

Formulations/Preparations:

Emulsifiable concentrate, dust, granules, wettable powder.
[Farm Chemicals Handbook 1991. Willoughby, OH: Meister, 1991.,p. C138]**PEER REVIEWED**

Technical grade 90% min of fenvalerate.
[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982. 295]**PEER REVIEWED**

An emulsifiable concentrate, marketed as Pydrin 2.4 EC Insecticide, is comprised of 32% technical Pydrin and 68% aromatic hydrocarbon solvents and emulsifiers.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-161]**PEER REVIEWED**

Ectrin 8%
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982. 913]**PEER REVIEWED**

Administrative Information:

Hazardous Substances Databank Number: 6640
Last Revision Date: 20010808
Last Review Date: Reviewed by SRP on 3/11/1993
Update History:

Field Update on 08/08/2001, 1 field added/edited/deleted.
Field Update on 05/16/2001, 1 field added/edited/deleted.
Complete Update on 09/12/2000, 1 field added/edited/deleted.
Complete Update on 06/12/2000, 1 field added/edited/deleted.
Complete Update on 03/13/2000, 1 field added/edited/deleted.
Complete Update on 02/08/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/27/1999, 1 field added/edited/deleted.
Complete Update on 06/03/1998, 1 field added/edited/deleted.
Complete Update on 11/01/1997, 1 field added/edited/deleted.
Complete Update on 05/09/1997, 1 field added/edited/deleted.
Complete Update on 04/24/1997, 2 fields added/edited/deleted.
Complete Update on 03/18/1997, 2 fields added/edited/deleted.
Complete Update on 02/28/1997, 1 field added/edited/deleted.
Complete Update on 10/20/1996, 1 field added/edited/deleted.
Complete Update on 05/14/1996, 1 field added/edited/deleted.
Complete Update on 02/01/1996, 1 field added/edited/deleted.
Complete Update on 08/21/1995, 1 field added/edited/deleted.
Complete Update on 11/28/1994, 1 field added/edited/deleted.
Complete Update on 03/01/1994, 75 fields added/edited/deleted.

Record Length: 174506