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INSECT REPELLENTS - OTHER FORMULATIONS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) This management covers insect repellents that do not contain DEET or picaridin, which are covered in separate managements. These formulations of insect repellents can contain 2-ethyl-1,3-hexanediol, N,N-diethyl phenylacetamide (DEPA), dimethyl phthalate, indalone and their vehicles.
    B) For information regarding DEET-containing products, refer to the DIETHYLTOLUAMIDE-DEET management.

Specific Substances

    A) ETHYL HEXANEDIOL
    1) ETHOHEXADIOL
    2) ETHYL HEXYLENE GLYCOL
    3) OCTYLENE GLYCOL
    4) 1,3-HEXANEDIOL, 2-ETHYL-
    5) 2-ETHYL-1,3-HEXANEDIOL
    6) 2-ETHYLHEXANE-1,3-DIOL
    7) 2-ETHYLHEXANEDIOL-1,3
    8) 2-ETHYL-3-PROPYL-1,3-PROPANEDIOL
    9) 3-HYDROXYMETHYL-n-HEPTAN-4-OL
    10) CAS 94-96-2
    DIMETHYL PHTHALATE
    1) 1,2-BENZENE DICARBOXYLIC ACID DIMETHYL ESTER
    2) DIMETHYL 1,2-BENZENE DICARBOXYLATE
    3) DMP (DIMETHYL PHTHALATE)
    4) METHYL PHTHALATE
    5) PHTHALIC ACID DIMETHYL ESTER
    6) CAS 131-11-3
    OTHER COMPOUNDS
    1) DMF (INSECT REPELLANT)
    2) DI-N-PROPYL ISOCINCHOMERONATE
    3) INDALONE
    4) N,N-DIETHYLPHENYLACETAMIDE
    5) N-OCTYL BICYCLOHEPTENE DICARBOXIMIDE
    6) PHTHALSAEUREDIMETHYL ESTER (German)
    7) 2,3,4,5-BIS (2-BUTYLENE)TETRAHYDRO-2-FURALDEHYDE

    1.2.1) MOLECULAR FORMULA
    1) Dimethyl phthalateC10-H10-O4
    2) 2-Ethyl-1,3-HexanediolC8-H18-O2
    3) IndaloneC12-H18-04
    4) N,N-diethylphenylaceatmideC12-H17-N-O

Available Forms Sources

    A) USES
    1) 2-Ethyl-1,3-Hexanediol
    a) 2-Ethyl-1,3-hexanediol (EHD) has been used as an insect repellent as well as a reactive component in urethane coatings, a solvent and blending agent for printing inks, latex paints, and resins, and a chelating agent for boric acid (VanMiller et al, 1995)
    2) PHTHALATES
    a) In general, phthalates are used in many consumer products including building materials, household furnishings, cosmetics, clothing, cleaning materials, and insecticides. Low molecular weight phthalates such as diethyl phthalate (DEP), dimethyl phthalate (DMP), and dibutyl phthalate (DBP) are most often used as solvents and in adhesives, waxes, inks, cosmetics, insecticides and pharmaceuticals (Schettler, 2006).
    3) N,N-Diethyl Phenylacetamide (DEPA)
    a) DEPA has been shown to actively repel Aedes aegypti (L.) and has been shown to have broad spectrum repellency against mosquitoes, black flies, biting flies, cockroaches and land leeches. In one study, DEPA had similar repellency as DEET at 0.2 and 0.5 mg/cm(2) against black flies and mosquitoes (Kalyanasundaram & Mathew, 2006; Vijayaraghavan et al, 1991). It is a long-acting and inexpensive insect repellent (Vijayaraghavan et al, 1991).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: This management covers insect repellents that do not contain DEET (refer to DIETHYLTOLUAMIDE-DEET management) or picaridin (refer to PICARIDIN management). These formulations of insect repellents can contain 2-ethyl-1,3-hexanediol, N,N-diethyl phenylacetamide (DEPA), dimethyl phthalate, indalone and their vehicles. 2-Ethyl-1,3-hexanediol (EHD) has been used as an insect repellent as well as a reactive component in urethane coatings, a solvent and blending agent for printing inks, latex paints, and resins, and a chelating agent for boric acid. N,N-Diethyl Phenylacetamide (DEPA) is a long-acting insect repellent. In general, phthalates are used in many consumer products including building materials, household furnishings, cosmetics, clothing, cleaning materials, and insecticides. Low molecular weight phthalates such as diethyl phthalate (DEP), dimethyl phthalate (DMP), and dibutyl phthalate (DBP) are most often used as solvents and in adhesives, waxes, inks, cosmetics, insecticides and pharmaceuticals.
    B) EPIDEMIOLOGY: Exposures are uncommon. Severe toxicity is very rare.
    C) WITH POISONING/EXPOSURE
    1) Human data is very limited.
    2) ETHYL HEXANEDIOL is only slightly absorbed across the skin. It is only moderately irritating following direct contact to the eyes or mucous membrane, but not to the skin. However, it is moderately toxic on ingestion causing CNS depression. In animal studies, repeated dermal application of undiluted 2-ethyl-1,3-hexanediol produced statistically significant increases in alkaline phosphatase activity.
    3) INDALONE may cause slight skin irritation. In animal studies, kidney and liver damage occurred following protracted application to the skin of animals.
    4) DIMETHYL PHTHALATE: Based on animal studies, dermal absorption of phthalates is generally slow. Ingestion of dimethyl phthalate may produce gastric irritation, burning sensations of the lips, tongue and mouth, and CNS depression. Coma has been reported in one individual following inadvertent oral exposure.
    5) N-OCTYL BICYCLOHEPTENE DICARBOXIMIDE is not irritating to skin; extreme doses cause CNS stimulation, then depression.
    6) 2,3,4,5-BIS (2-BUTYLENE)TETRAHYDRO-2-FURALDEHYDE and DI-N-PROPYL ISOCINCHOMERONATE have low systemic toxic potential in mammals, and are not significantly irritating.
    7) N,N-DIETHYLPHENYLACETAMIDE (DEPA): In animal studies, ingestion of DEPA resulted in metabolic acidosis and hepatotoxicity. Tremors and seizures developed following inhalation or oral exposure to large doses of DEPA.
    8) VEHICLES: Ethyl and isopropyl alcohols and freon used as vehicles may contribute significantly to toxicity of some formulations.
    0.2.20) REPRODUCTIVE
    A) No embryo or fetal toxicity has been observed in rats exposed to dimethylphthalate. However, perinatal exposure to di(2-ethylhexyl) phthalate (DEHP), benzyl butyl phthalate (BBP) and diisononyl phthalate (DINP) produced alterations in sexual differentiation in male rats.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor mental status in symptomatic patients. Consider CT and lumbar puncture in patients with evidence of CNS depression to rule out other causes.
    C) Monitor liver enzymes and renal function tests in symptomatic patients.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Symptomatic and supportive care is the mainstay for treatment.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive care. Serious toxicity is not expected. Monitor patients with ingestion for potential esophageal and gastrointestinal irritation. Observe carefully for the development of bleeding or abdominal pain. Mucous membrane irritation has been reported with ingestion of dimethyl phthalate. If signs of esophageal irritation are present (pain, drooling, dysphagia), endoscopy should be considered within 24 hours of ingestion to determine the extent of injury. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
    C) NATIONAL PESTICIDE TELECOMMUNICATIONS NETWORK
    1) The National Pesticide Information Center (NPIC) is a cooperative effort of Oregon State University and the US EPA. NPIC provides consultation to poison centers and other health care professionals for the management of pesticide poisoning. Calls regarding emergency cases requiring immediate medical response will be transferred to the Oregon Poison Center.
    a) NPIC contact information: phone: 1-800-858-7378. email: npic@ace.orst.edu Hours: 8 AM to 12 PM Pacific time Monday through Friday, excluding holidays.
    D) DECONTAMINATION
    1) PREHOSPITAL: Remove clothing and wash exposed areas with soap and water. If ocular exposure develops, irrigate thoroughly. Following an inhalational exposure, move patient to fresh air. Although these agents have low order of toxicity, CNS depression may occur following significant oral ingestions of repellents containing ethyl hexanediol or dimethyl phthalate or its vehicles which may contain ethyl or isopropyl alcohol. Emesis is not recommended, although spontaneous vomiting may occur due to other ingredients in the formulation. Serious toxicity is not expected, prehospital GI decontamination is generally NOT necessary.
    2) HOSPITAL: There is no role for activated charcoal or lavage. If prehospital decontamination has not occurred, wash exposed skin and irrigate exposed eyes thoroughly.
    E) AIRWAY MANAGEMENT
    1) Airway management is very unlikely to be necessary. Ensure adequate ventilation and perform endotracheal intubation early in patients with significant CNS depression or persistent seizures.
    F) ANTIDOTE
    1) None.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate ingestion, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    H) PITFALLS
    1) Pitfalls include not evaluating for other coingestants, such as solvents and surfactants that are included with the repellents.
    I) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause seizures or CNS depression.
    0.4.3) INHALATION EXPOSURE
    A) 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 an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: 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, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Wash affected areas twice with copious amounts of soap and water. Alcohol-detergent solutions such as "green soap" are most efficient for this purpose. A physician may need to examine the exposed area if irritation or pain persist after the area is washed.

Range Of Toxicity

    A) TOXICITY: A minimum lethal dose and maximum tolerated human exposure dose have not been established. N,N-DIETHYLPHENYLACETAMIDE (DEPA): Tremors and seizures developed following inhalation or oral exposure to large doses of DEPA. DIMETHYL PHTHALATE: Based on limited data, ingestion of large doses may cause CNS depression; in one case an immediate burning sensation of the lips, tongue and mouth occurred followed by deep coma 2 hours later.

Clinical Effects

Summary Of Exposure

    A) USES: This management covers insect repellents that do not contain DEET (refer to DIETHYLTOLUAMIDE-DEET management) or picaridin (refer to PICARIDIN management). These formulations of insect repellents can contain 2-ethyl-1,3-hexanediol, N,N-diethyl phenylacetamide (DEPA), dimethyl phthalate, indalone and their vehicles. 2-Ethyl-1,3-hexanediol (EHD) has been used as an insect repellent as well as a reactive component in urethane coatings, a solvent and blending agent for printing inks, latex paints, and resins, and a chelating agent for boric acid. N,N-Diethyl Phenylacetamide (DEPA) is a long-acting insect repellent. In general, phthalates are used in many consumer products including building materials, household furnishings, cosmetics, clothing, cleaning materials, and insecticides. Low molecular weight phthalates such as diethyl phthalate (DEP), dimethyl phthalate (DMP), and dibutyl phthalate (DBP) are most often used as solvents and in adhesives, waxes, inks, cosmetics, insecticides and pharmaceuticals.
    B) EPIDEMIOLOGY: Exposures are uncommon. Severe toxicity is very rare.
    C) WITH POISONING/EXPOSURE
    1) Human data is very limited.
    2) ETHYL HEXANEDIOL is only slightly absorbed across the skin. It is only moderately irritating following direct contact to the eyes or mucous membrane, but not to the skin. However, it is moderately toxic on ingestion causing CNS depression. In animal studies, repeated dermal application of undiluted 2-ethyl-1,3-hexanediol produced statistically significant increases in alkaline phosphatase activity.
    3) INDALONE may cause slight skin irritation. In animal studies, kidney and liver damage occurred following protracted application to the skin of animals.
    4) DIMETHYL PHTHALATE: Based on animal studies, dermal absorption of phthalates is generally slow. Ingestion of dimethyl phthalate may produce gastric irritation, burning sensations of the lips, tongue and mouth, and CNS depression. Coma has been reported in one individual following inadvertent oral exposure.
    5) N-OCTYL BICYCLOHEPTENE DICARBOXIMIDE is not irritating to skin; extreme doses cause CNS stimulation, then depression.
    6) 2,3,4,5-BIS (2-BUTYLENE)TETRAHYDRO-2-FURALDEHYDE and DI-N-PROPYL ISOCINCHOMERONATE have low systemic toxic potential in mammals, and are not significantly irritating.
    7) N,N-DIETHYLPHENYLACETAMIDE (DEPA): In animal studies, ingestion of DEPA resulted in metabolic acidosis and hepatotoxicity. Tremors and seizures developed following inhalation or oral exposure to large doses of DEPA.
    8) VEHICLES: Ethyl and isopropyl alcohols and freon used as vehicles may contribute significantly to toxicity of some formulations.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) 2-ETHYL-1,3-HEXANEDIOL Is moderately irritating to the eyes (HSDB, 2006).
    3.4.6) THROAT
    A) DIMETHYL PHTHALATE: BURNING SENSATION: Ingestion of dimethyl phthalate may cause burning sensations of the lips, tongue and mouth (HSDB, 2006).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) NEUROLOGICAL FINDING
    1) WITH POISONING/EXPOSURE
    a) CNS DEPRESSION
    1) 2-ETHYL-1,3-HEXANEDIOL: Ingestion of 2-ethyl-1,3-hexanediol can cause CNS depression in humans (HSDB, 2006).
    2) DIMETHYLPHTHALATE: Based on limited data, ingestion may cause CNS depression; coma has been reported in one individual following inadvertent oral exposure (HSDB, 2006).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) N,N-DIETHYLPHENYLACETAMIDE
    a) In rats given massive concentrations of DEPA, tremors and seizures developed following inhalation or oral exposure (Vijayaraghavan et al, 1991). In an acute toxicity study in rodents and rabbits, oral toxicity resulted in hyperactivity, excessive salivation, and nasal discharge (Rao et al, 1993).
    2) N-OCTYL BICYCLOHEPTENE DICARBOXIMIDE
    a) Extreme doses cause CNS stimulation, then depression (HSDB, 2006).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH POISONING/EXPOSURE
    a) DIMETHYLPHTHALATE
    1) Inadvertent ingestion of dimethylphthalate may produce gastric irritation (HSDB, 2006).

Hepatic

    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC FUNCTION ABNORMAL
    a) INDALONE
    1) Indalone caused liver damage following protracted application to the skin of animals (HSDB, 2006).
    b) DEPA
    1) RATS: Dermal application of N,N-diethylphenylacetamide (DEPA) of 500 and 1000 mg/kg/day reduced body weight gain and caused reductions in serum alanine amino transferase, aspartate amino transferase and cholinesterase activities in rats (Rao et al, 1989).
    2) RATS: In rats, 4 hours of inhalational exposure to 1.306 mg/L of DEPA caused increased liver weight and increases in glutamate pyruvate transaminase and alkaline phosphatase activity, as well as serum cholesterol (Vijayaraghavan et al, 1991).
    2) INCREASED ALKALINE PHOSPHATASE
    a) 2-ETHYL-1,3-HEXANEDIOL
    1) In a 9-day acute study and a subchronic study with Fischer 344 rats, repeated dermal application of undiluted 2-ethyl-1,3-hexanediol produced statistically significant increases in alkaline phosphatase activity in females in the 9-day high-dose group (114 +/- 8SD Units (U)/L compared with a control value of 104 +/- 8 U/L). It was not associated with liver function abnormalities. No laboratory alterations were observed in 9-day males or in either males or females in the subchronic group (VanMiller et al, 1995).

Genitourinary

    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) KIDNEY DAMAGE
    a) INDALONE: Indalone caused kidney damage following protracted application to the skin of animals (HSDB, 2006).

Acid-Base

    3.11.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) METABOLIC ACIDOSIS
    a) N,N-DIETHYLPHENYLACETAMIDE
    1) In an acute toxicity study in rodents and rabbits, oral toxicity resulted in metabolic acidosis (Rao et al, 1993).

Hematologic

    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) 2-ETHYL-1,3-HEXANEDIOL
    a) LACK OF EFFECT: In a 9-day acute study and a subchronic study with Fischer 344 rats, repeated undiluted dermal application of 2-ethyl-1,3-hexanediol did not produce any hematologic effects (VanMiller et al, 1995).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERYTHEMA
    1) WITH POISONING/EXPOSURE
    a) 2-ETHYL-1,3-HEXANEDIOL: A human volunteer experiment demonstrated that 7 of 30 subjects developed some degree of erythema with a single application of 2-ethyl-1,3-hexanediol. With repeated applications and occlusion, 25 of 27 subjects developed some degree of erythema (Ballantyne et al, 1987).
    B) DERMATOLOGICAL FINDING
    1) WITH POISONING/EXPOSURE
    a) LACK OF EFFECT
    1) N,N-DIETHYL PHENYLACETAMIDE (DEPA): In a comparison study, no skin irritancy was reported in humans with DEPA use (Kalyanasundaram & Mathew, 2006).
    2) 2-ETHYL-1,3-HEXANEDIOL: In a study of 223 volunteers, patch testing for sensitization with undiluted 2-ethyl-1,3-hexanediol produced no serious episodes of sensitization. Three subjects developed mild skin reddening (HSDB, 2006).
    3) N-OCTYL BICYCLOHEPTENE DICARBOXIMIDE is not irritating to skin (HSDB, 2006).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ERYTHEMA
    a) 2-ETHYL-1,3-HEXANEDIOL causes erythema and dermal edema in rabbits (Ballantyne et al, 1987).
    2) SKIN IRRITATION
    a) INDALONE may cause slight skin irritation (HSDB, 2006).
    3) LACK OF EFFECT
    a) 2-ETHYL-1,3-HEXANEDIOL
    1) ANIMAL DATA: In a 9 day acute study and a subchronic study with Fischer 344 rats, repeated undiluted dermal application of 2-ethyl-1,3-hexanediol did not produce any local skin irritation or organ-specific toxicity (VanMiller et al, 1995).
    b) DI-N-PROPYL ISOCINCHOMERONATE
    1) Di-N-propyl isocinchomeronate has low systemic toxic potential in mammals, and is not significantly irritating (HSDB, 2006).
    c) PHTHALATES
    1) LACK OF EFFECT: Based on studies using rodent skin, absorption of phthalates is generally slow (Schettler, 2006).
    d) 2,3,4,5-BIS (2-BUTYLENE)TETRAHYDRO-2-FURALDEHYDE
    1) 2,3,4,5-bis (2-butylene)tetrahydro-2-furaldehyde has low systemic toxic potential in mammals, and is not significantly irritating (HSDB, 2006).

Reproductive

    3.20.1) SUMMARY
    A) No embryo or fetal toxicity has been observed in rats exposed to dimethylphthalate. However, perinatal exposure to di(2-ethylhexyl) phthalate (DEHP), benzyl butyl phthalate (BBP) and diisononyl phthalate (DINP) produced alterations in sexual differentiation in male rats.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) In a rat study, no teratogenic or embryotoxic effects were reported after dermal application on shaved skin of dimethyl phthalate at doses of 0.5, 1 and 2 mL/day for 2 hours daily for 21 days (Hansen & Meyer, 1989).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) DIMETHYLPHTHALATE
    a) In a study of 49 CD-1 mice given 3,500 mg/kg/day of dimethylphthalate by gavage feeds on days 6 to 13 of gestation, no toxic effects were noted in the treated mother or their offspring (HSDB, 2006).
    b) In another study with Sprague Dawley rats, no embryo or fetal toxicity was observed based on criteria measuring viability, growth or development (Field et al, 1993).

Carcinogenicity

    3.21.4) ANIMAL STUDIES
    A) DIMETHYL PHTHALATE
    1) Dimethyl phthalate is not classifiable as a human carcinogen based on no human data and inadequate animal data (HSDB, 2006).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor mental status in symptomatic patients. Consider CT and lumbar puncture in patients with evidence of CNS depression to rule out other causes.
    C) Monitor liver enzymes and renal function tests in symptomatic patients.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Victims poisoned by ingestion or chronic dermal exposure should be monitored for liver and kidney injury.
    4.1.4) OTHER
    A) OTHER
    1) OTHER
    a) Consider CT and lumbar puncture in patients with evidence of CNS depression to rule out other causes.

Methods

    A) The molecular mass of N-octyl bicycloheptene dicarboximide was determined by liquid chromatography-electrospray tandem mass spectrometry (LC-ES-MS-MS), along with two-dimensional nuclear magnetic resonance (NMR) spectroscopic technique to establish the structural features (Wang et al, 1999).

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 with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate ingestion, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor mental status in symptomatic patients. Consider CT and lumbar puncture in patients with evidence of CNS depression to rule out other causes.
    C) Monitor liver enzymes and renal function tests in symptomatic patients.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Although these agents have low order of toxicity, CNS depression may occur following significant oral ingestions of repellents containing ethyl hexanediol or dimethyl phthalate or its vehicles which may contain ethyl or isopropyl alcohol. Emesis is not recommended, although spontaneous vomiting may occur due to other ingredients in the formulation.
    2) Serious toxicity is not expected, prehospital GI decontamination is generally NOT necessary.
    3) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    4) 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).
    5) 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 an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    6.5.2) PREVENTION OF ABSORPTION
    A) Although these agents have low order of toxicity, CNS depression may occur following significant oral ingestions of repellents containing ethyl hexanediol or dimethyl phthalate or its vehicles which may contain ethyl or isopropyl alcohol. Emesis is not recommended, although spontaneous vomiting may occur due to other ingredients in the formulation. Serious toxicity is not expected, prehospital GI decontamination is generally NOT necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Symptomatic and supportive care is the mainstay for treatment.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive care. Serious toxicity is not expected. Monitor patients with ingestion for potential esophageal and gastrointestinal irritation. Observe carefully for the development of bleeding or abdominal pain. Mucous membrane irritation has been reported with ingestion of dimethyl phthalate. If signs of esophageal irritation are present (pain, drooling, dysphagia), endoscopy should be considered within 24 hours of ingestion to determine the extent of injury. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor mental status in symptomatic patients. Consider CT and lumbar puncture in patients with evidence of CNS depression to rule out other causes.
    3) Monitor liver enzymes and renal function tests in symptomatic patients.
    C) IRRITATION SYMPTOM
    1) Monitor patients with ingestion for potential esophageal and gastrointestinal irritation. Observe carefully for the development of bleeding or abdominal pain.
    a) Mucous membrane irritation has been reported with ingestion of dimethyl phthalate (HSDB, 2006)
    2) If signs of esophageal irritation are present (pain, drooling, dysphagia), endoscopy should be considered within 24 hours of ingestion to determine the extent of injury.
    D) EDUCATION
    1) The National Pesticide Information Center (NPIC) is a cooperative effort of Oregon State University and the US EPA. NPIC provides consultation to poison centers and other health care professionals for the management of pesticide poisoning. Calls regarding emergency cases requiring immediate medical response will be transferred to the Oregon Poison Center.
    a) NPIC contact information: phone: 1-800-858-7378. email: npic@ace.orst.edu Hours: 8 AM to 12 PM Pacific time Monday through Friday, excluding holidays.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

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).

Range Of Toxicity

Summary

    A) TOXICITY: A minimum lethal dose and maximum tolerated human exposure dose have not been established. N,N-DIETHYLPHENYLACETAMIDE (DEPA): Tremors and seizures developed following inhalation or oral exposure to large doses of DEPA. DIMETHYL PHTHALATE: Based on limited data, ingestion of large doses may cause CNS depression; in one case an immediate burning sensation of the lips, tongue and mouth occurred followed by deep coma 2 hours later.

Maximum Tolerated Exposure

    A) DIMETHYL PHTHALATE: Based on limited data, ingestion of large doses may cause CNS depression; in one case an immediate burning sensation of the lips, tongue and mouth occurred followed by deep coma 2 hours later (HSDB, 2006).
    B) N,N-DIETHYLPHENYLACETAMIDE (DEPA): Tremors and seizures developed following inhalation or oral exposure to large doses of DEPA (Vijayaraghavan et al, 1991).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) 2-ETHYL-1,3-HEXANEDIOL
    1) LD50- (ORAL)MOUSE:
    a) 1900 mg/kg (RTECS, 2006)
    2) LD50- (ORAL)RAT:
    a) 1400 mg/kg (RTECS, 2006)
    B) DIMETHYL PHTHALATE
    1) LD50- (ORAL)MOUSE:
    a) 7.2 g/kg (HSDB, 2006)
    2) LD50- (ORAL)RAT:
    a) 2.4 g/kg (HSDB, 2006)
    C) INDALONE
    1) LD50- (ORAL)MOUSE:
    a) 11600 mcL/kg (RTECS, 2006)
    2) LD50- (ORAL)RAT:
    a) 7400 mcL/kg (RTECS, 2006)
    D) N,N-DIETHYLPHENYLACETAMIDE (DEPA)
    1) LD50- (ORAL)MOUSE:
    a) 900 mg/kg (RTECS, 2006)
    2) LD50- (SKIN)MOUSE:
    a) 1600 mg/kg (RTECS, 2006)
    3) LD50- (ORAL)RAT:
    a) 825 mg/kg (RTECS, 2006)

Physicochemical

Molecular Weight

    1) Dimethyl phthalate194.20
    2) 2-Ethyl-1,3-Hexanediol146.26
    3) Indalone226.30
    4) N,N-diethylphenylaceatmide191.30

References

General Bibliography

    1) Ballantyne B, Reed ML, & Napoli D: The cutaneous irritant and sensitizing potential of 2-ethyl-1,3-hexanediol (abstract). Vet Hum Toxicol 1987; 29:475.
    2) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    3) Field EA, Price CJ, Sleet RB, et al: Developmental toxicity evaluation of diethyl and dimethyl phthalate in rats. Teratology 1993; 48(1):33-44.
    4) Gray LE, Ostby J, Furr J, et al: Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci 2000; 58(2):350-365.
    5) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2006; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    6) Hansen E & Meyer O: No embryotoxic or teratogenic effect of dimethyl phthalate in rats after epicutaneous application. Pharmacol Toxicol 1989; 64(2):237-238.
    7) Kalyanasundaram M & Mathew N: N,N-diethyl phenylacetamide (DEPA): A safe and effective repellent for personal protection against hematophagous arthropods. J Med Entomol 2006; 43(3):518-525.
    8) Liu K, Lehmann KP, Sar M, et al: Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biol Reprod 2005; 73(1):180-192.
    9) Meshram GP & Rao KM: N,N-diethylphenylacetamide, an insect repellent: absence of mutagenic response in the in vitro Ames test and in vivo mouse micronucleus test. Food Chem Toxicol 1988; 26(9):791-796.
    10) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    11) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    12) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    13) RTECS: Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 2006; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    14) Rao SS, Kaveeshwar U, & Purkayastha SS: Acute oral toxicity of insect repellent N,N-diethylphenylacetamide in mice, rats and rabbits and protective effect of sodium pentobarbital. Indian J Exp Biol 1993; 31(9):755-760.
    15) Rao SS, Swamy RV, & Ramachandran PK: Toxicity and metabolism of a new insect repellent N,N-diethylphenylacetamide in mice, rats and guinea pigs on cutaneous application. Toxicology 1989a; 58:81-89.
    16) Rao SS, Vijayaraghavan R, & Suryanarayana MV: Gas chromatographic identification of urinary metabolites of insect repellent N,N-diethylphenylacetamide on inhalation exposure in rats. J Chromatography 1989; 493:210-216.
    17) Schettler T: Human exposure to phthalates via consumer products. Int J Androl 2006; 29(1):134-139.
    18) VanMiller JP, Losco PE, Neptun DA, et al: Repeated exposure toxicity of 2-ethyl-1,3-hexanediol by cutaneous applications to the rat for 9 and 90 days. Vet Hum Toxicol 1995; 37(1):33-36.
    19) Vijayaraghavan R, Rao SS, Suryanarayana MV, et al: Acute and subacute inhalation toxicity studies of a new broad spectrum insect repellent, N,N-diethylphenylacetamide. Toxicology 1991; 67(1):85-96.
    20) Wang IH, Subramanian V, Moorman R, et al: Chiral high-performance liquid chromatography of N-octyl bicycloheptene dicarboximide and confirmatory studies using liquid chromatography-tandem mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy. J Chromatogr A 1999; 864(2):271-281.