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METHOPRENE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Methoprene, a long chain hydrocarbon ester (terpenoid), is an insect growth regulator which mimics the action of insect juvenile hormones.

Specific Substances

    1) 11-Methoxy-3,7,11-trimethyl-2,4-dodecadienoic
    2) acid 1 methylethyl ester
    3) Isopropyl 11-methoxy-3,7,11-trimethyldodeca-
    4) trans-2, trans-4-dienoate
    5) Manta
    6) ENT 70460
    7) Molecular Formula: C19-H34-O3
    8) CAS 40596-69-8
    9) ALTOSID
    10) KABAT
    11) ZR 515
    1.2.1) MOLECULAR FORMULA
    1) C19-H34-O3

Available Forms Sources

    A) FORMS
    1) Trade Names and Commercial Products (Morgan, 1989; Hartley & Kidd, 1987):
    1) Altosid
    2) Apex
    3) Diacon
    4) Dianex
    5) Kabat
    6) Minex
    7) Pharorid
    8) Precor
    9) ZR-515
    2) Commercial product formulations include bait concentrate, briquets, emulsifiable concentrate, foggers, sprays, soluble concentrate, and suspension concentrate.
    B) USES
    1) Methoprene, a long chain hydrocarbon ester (terpenoid), is an insect growth regulator which mimics the action of insect juvenile hormones. It is effective against several insect species such as ants, mosquitoes, flies, beetles, lice, and moths (S Sweetman , 2001; Morgan, 1989; Hartley & Kidd, 1987).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) There has been no specific human toxicity or treatment recommended for this insect growth regulator.
    0.2.4) HEENT
    A) Eye irritation has not been a problem.
    0.2.14) DERMATOLOGIC
    A) Methoprene has not been shown to irritate skin.
    0.2.20) REPRODUCTIVE
    A) NEGATIVE for teratogenic effects in rats, hamsters, rabbits, rats, sheep, and swine.

Laboratory Monitoring

    A) BLOOD LEVELS not established in humans.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment recommendations are limited due to a lack of human experience. Only supportive care may be recommended at this time.
    B) This pesticide has a low toxicity to non-target species. Treatment should only be necessary when large amounts (greater than 5 g/kg) have been ingested. Decontamination should only be used following ingestion of large amounts.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.

Range Of Toxicity

    A) TOXIC DOSE - Not established in humans.
    B) LD50 in animals has been greater than 3 g/kg.

Clinical Effects

Summary Of Exposure

    A) There has been no specific human toxicity or treatment recommended for this insect growth regulator.

Heent

    3.4.1) SUMMARY
    A) Eye irritation has not been a problem.
    3.4.3) EYES
    A) IRRITATION - Non-irritating to eyes (Morgan, 1989).

Dermatologic

    3.14.1) SUMMARY
    A) Methoprene has not been shown to irritate skin.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Methoprene has not been shown to irritate skin (Morgan, 1989).

Reproductive

    3.20.1) SUMMARY
    A) NEGATIVE for teratogenic effects in rats, hamsters, rabbits, rats, sheep, and swine.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) NEGATIVE for teratogenic effects in rats at 1000 mg/kg (Hartley & Kidd, 1987)
    2) NEGATIVE for teratogenic effects in hamsters, rabbits, rats, sheep, and swine (Wright, 1976)

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS40596-69-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) BLOOD LEVELS not established in humans.

Methods

    A) CHROMATOGRAPHY
    1) Products have been analyzed by gas-liquid chromatography with flame ionization detection (Dunham, 1978) and by infrared spectrophotometry (Giang & Jaffe, 1980).
    2) Residues are analyzed by gas-liquid chromatography with flame ionization detection (Dunham, 1978) and by high pressure liquid chromatography (Chamberlain, 1985).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Monitoring

    A) BLOOD LEVELS not established in humans.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS/NOT RECOMMENDED -
    1) Emesis will seldom be necessary due to low toxicity and, when methoprene is in a hydrocarbon base, activated charcoal may be preferable.
    B) ACTIVATED CHARCOAL -
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) This product has a low toxicity to non-target species (Thomson, 1982). Amounts necessary to kill animals have been greater than 5 grams/kilogram. Treatment should only be necessary when large amounts have been ingested. The statements below regarding oral decontamination should only be used after ingestion of large amounts.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) No treatment is necessary for small amounts.
    2) Symptoms have not been seen in humans. Treatment recommendations are supportive.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) Has a low systemic toxicity via the dermal route and is not irritating to skin (Morgan, 1989).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) TOXIC DOSE - Not established in humans.
    B) LD50 in animals has been greater than 3 g/kg.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Toxic Dose - Not established in humans.

Maximum Tolerated Exposure

    A) ANIMAL DATA
    1) Rats receiving 5,000 milligrams/kilogram and mice receiving 2,500 milligrams/kilogram methoprene in diet for 2 years showed no adverse effects (Hartley & Kidd, 1987).

Workplace Standards

    A) ACGIH TLV Values for CAS40596-69-8 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS40596-69-8 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS40596-69-8 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS40596-69-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)RAT:
    a) 25 gm/kg (RTECS, 2001)

Pharmacology Toxicology

Toxicologic Mechanism

    A) Methoprene, a long chain hydrocarbon ester (terpenoid), is an insect growth regulator or juvenile hormone which is effective against several insect species. Methoprene, when applied to larval stages, regulates insect growth by preventing metamorphosis to viable adults (Morgan, 1989; Hartley & Kidd, 1987).

Physicochemical

Physical Characteristics

    A) Amber liquid (Budavari, 1996)

Molecular Weight

    A) 310.48 (Budavari, 1996)

Animal Toxicology

Clinical Effects

    11.1.2) BOVINE/CATTLE
    A) No clinical signs of toxicosis were noted in toxicologic evaluations of methoprene in cattle (Wright, 1976).
    11.1.3) CANINE/DOG
    A) Toxicologic evaluation of methoprene did not reveal any clinical signs of toxicosis in dogs (Wright, 1976).
    11.1.9) OVINE/SHEEP
    A) No clinical signs of toxicosis were noted in toxicologic evaluations of methoprene in sheep (Wright, 1976).
    11.1.10) PORCINE/SWINE
    A) Administration of methoprene has not produced any clinical signs of toxicosis in swine during toxicologic evaluation studies (Wright, 1976).
    11.1.12) RODENT
    A) Toxicologic evaluation of methoprene did not reveal any clinical signs of toxicosis in hamsters, guinea pigs, rabbits, and rats (Wright, 1976).

Range Of Toxicity

    11.3.1) THERAPEUTIC DOSE
    A) CAT
    1) Methoprene 0.15% applied as a fog at an average rate of 3.66 mg of methoprene/m(2) resulted in 99.1 to 100% inhibition of adult flea emergence for 280 to 287 days after application (Pers Comm, 1988).
    B) CATTLE
    1) Methoprene mixed in concentrate ration at 1 mg/kg of body weight daily for 8 days and fed to cattle was effective in providing complete control of face fly larvae that breed in manure (Garg & Donahue, 1989).
    2) Administration of mineral blocks impregnated with methoprene inhibited 87% of horn fly development. This technique was effective for control of stable flies (Garg & Donahue, 1989).
    3) Administration to cattle of a sustained-release bolus preparation containing 1% methoprene was the best delivery method for controlling horn fly infestation (Miller et al, 1977).
    C) DOG
    1) Methoprene 0.15% applied as a fog at an average rate of 3.66 mg of methoprene/m(2) resulted in 99.1 to 100% inhibition of adult flea emergence for 280 to 287 days after application (Pers Comm, 1988).
    11.3.2) MINIMAL TOXIC DOSE
    A) LACK OF INFORMATION
    1) No specific information on a minimal toxic dose was available at the time of this review.

Kinetics

    11.5.1) ABSORPTION
    A) LACK OF INFORMATION
    1) There was no specific information on absorption at the time of this review.
    11.5.3) METABOLISM
    A) CATTLE
    1) Simple acetates that are incorporate into fatty acids, lactose, and cholesterol were the observed compounds tagged in milk and blood 1 week after oral administration of radiolabeled methoprene to a cow (EPA, 1981).
    11.5.4) ELIMINATION
    A) CATTLE
    1) Up to 19.8% of an orally administered dose of methoprene was eliminated in the urine as radioactive metabolite. Unchanged methoprene was eliminated in feces (EPA, 1981).

References

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