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PICARIDIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Picaridin is a piperidine derivative used as an insect repellent intended for human use.

Specific Substances

    1) 1-(1-Methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine
    2) 1-Methylpropyl 2-(2-hydroxyethyl)-1-piperidinecarboxylate
    3) KBR 3023
    4) Bayrepel
    5) Icaridin
    6) Pikaridin
    7) Propidine
    8) Hepidanin
    9) Autan repel
    1.2.1) MOLECULAR FORMULA
    1) C12-H23-N-O3 (US Environmental Protection Agency, 2005)

Available Forms Sources

    A) FORMS
    1) Picaridin is available as an aerosol, pump spray, liquid, cream, towelette wipes, balsam or stick. Formulations containing 10% active ingredient provide 3 to 5 hours protection; formulations containing 20% active ingredient protect for up to 10 hours; formulations less than 10% are used for short-term protection(US Environmental Protection Agency, 2005; Saltigo GmbH, 2005).
    B) USES
    1) Picaridin is used as an insect repellent (US Environmental Protection Agency, 2005).

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: Picaridin is used as an insect repellent. It is available as an aerosol, pump spray, liquid, cream, towelette wipes, balsam or stick. Formulations containing 10% active ingredient provide 3 to 5 hours protection; formulations containing 20% active ingredient protect for up to 10 hours; formulations less than 10% are used for short-term protection.
    B) PHARMACOLOGY: Picaridin is a piperidine derivative insect repellent. It works similarly to DEET by blocking the olfactory stimuli on human skin, decreasing the insect's ability to locate the human.
    C) EPIDEMIOLOGY: Exposure is common. There have been no reports of serious toxicity with the use of picaridin.
    D) WITH THERAPEUTIC USE
    1) Human data is very limited. Picaridin has low acute oral, dermal, and inhalational toxicity. Contact dermatitis, including persistent itching and erythematous-edematous dermatitis, has been reported.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no human studies on the use of picaridin during pregnancy and lactation were found.
    B) Animal studies have found no effect on fertility, pregnancy, and lactation with picaridin exposure.
    0.2.21) CARCINOGENICITY
    A) The U.S. Environmental Protection Agency has determined that picaridin is unlikely to be a human carcinogen by the dermal route.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of exposure.
    B) No specific laboratory tests are necessary unless otherwise clinically indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) Treatment is symptomatic and supportive. Minimal toxicity is expected.
    B) DECONTAMINATION
    1) GI decontamination is generally not necessary. Remove contaminated clothing and wash exposed area thoroughly with soap and water. Irrigate the eyes with water after ocular exposure.
    C) AIRWAY MANAGEMENT
    1) Should not be required in these cases.
    D) ANTIDOTE
    1) None.
    E) 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: Admission is almost never necessary unless aspiration has occurred.
    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.
    F) PITFALLS
    1) Missing an ingestion of another chemical or other possible etiologies for a patient’s symptoms.
    G) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause dermatitis.
    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) 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).

Range Of Toxicity

    A) TOXICITY: A minimum toxic dose has not been established. Minimal toxicity is expected. THERAPEUTIC USE: The manufacturer recommends application of picaridin repellent (7%) every 3 to 4 hours but not more than 3 times a day.

Clinical Effects

Summary Of Exposure

    A) USES: Picaridin is used as an insect repellent. It is available as an aerosol, pump spray, liquid, cream, towelette wipes, balsam or stick. Formulations containing 10% active ingredient provide 3 to 5 hours protection; formulations containing 20% active ingredient protect for up to 10 hours; formulations less than 10% are used for short-term protection.
    B) PHARMACOLOGY: Picaridin is a piperidine derivative insect repellent. It works similarly to DEET by blocking the olfactory stimuli on human skin, decreasing the insect's ability to locate the human.
    C) EPIDEMIOLOGY: Exposure is common. There have been no reports of serious toxicity with the use of picaridin.
    D) WITH THERAPEUTIC USE
    1) Human data is very limited. Picaridin has low acute oral, dermal, and inhalational toxicity. Contact dermatitis, including persistent itching and erythematous-edematous dermatitis, has been reported.

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 39-year old man experienced persistent itching and erythematous-edematous dermatitis one day after application of picaridin. His skin became red and itchy only a few hours after the application. Patch tests were conducted and strong reactions were observed for the active ingredient picaridin as well as for an excipient, methyl glucose diolate. The dermatitis was treated with antihistamines and topical and systemic corticosteroids. The symptoms resolved in approximately 10 days with transient pigmentary lesions (Corazza et al, 2005).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no human studies on the use of picaridin during pregnancy and lactation were found.
    B) Animal studies have found no effect on fertility, pregnancy, and lactation with picaridin exposure.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF EFFECT
    1) ANIMAL STUDY - Adult rats were dermally administered either 0, 50, 100, or 200 mg picaridin/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Other than dermal findings, no compound-related necropsy findings were seen in either adults or pups. Picaridin, administered at dose levels as high as 200 mg/kg body weight did not demonstrate any toxicity (Astroff et al, 1999).
    2) ANIMAL STUDY - A similar study was conducted with Sprague-Dawley rats and Himalayan rabbits to determine potential developmental toxicity. No developmental toxicity was observed (Astroff et al, 2000).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) ANIMAL STUDIES
    1) ANIMAL STUDY - Adult rats were dermally administered either 0, 50, 100, or 200 mg picaridin/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Other than dermal findings, no compound-related necropsy findings were seen in either adults or pups. Picaridin, administered at dose levels as high as 200 mg/kg body weight did not demonstrate any toxicity (Astroff et al, 1999).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) LACK OF EFFECT
    a) ANIMAL STUDY - Adult rats were dermally administered either 0, 50, 100, or 200 mg picaridin/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Other than dermal findings, no compound-related necropsy findings were seen in either adults or pups. Picaridin, administered at dose levels as high as 200 mg/kg body weight did not demonstrate any effect on fertility (Astroff et al, 1999).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS119515-38-7 (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
    3.21.2) SUMMARY/HUMAN
    A) The U.S. Environmental Protection Agency has determined that picaridin is unlikely to be a human carcinogen by the dermal route.
    3.21.3) HUMAN STUDIES
    A) EPA STATEMENT
    1) The U.S. Environmental Protection Agency has determined that picaridin is unlikely to be a human carcinogen by the dermal route (US Environmental Protection Agency, 2005). This assessment is based on animal data. No human studies have been conducted at the time of this review.
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) RAT - Potential carcinogenicity from chronic use of dermal picaridin was studied over a 2-year period using Sprague-Dawley rats. Dermally applied dosages of 0, 50, 100 or 200 mg picaridin/kg body wt/day was used to represent subchronic, chronic, and lifetime exposure. All in-life parameters, which included body weight, food consumption, clinical observations, survival, ophthalmology, clinical chemistry, hematology, and urinalysis, were unaffected by exposure to picaridin. Postmortem analyses of organ weights and gross pathology, were also unchanged. The rat showed no evidence of a chemically induced neoplasia (Wahle et al, 1999).
    2) MOUSE - Potential carcinogenicity from chronic use of dermal picaridin was studied over an 18- month period using mice. Dermally applied dosages of 0, 50, 100 or 200 mg picaridin/kg body wt/day was used to represent subchronic, chronic, and lifetime exposure. All in-life parameters, which included body weight, food consumption, clinical observations, survival, and hematology were unaffected by exposure to picaridin. Postmortem analyses of organ weights and gross pathology, and histopathology were also unchanged. There was no evidence of a chemically induced neoplasia (Wahle et al, 1999a).

Genotoxicity

    A) Picaridin has not been shown to cause genetic or chromosomal aberrations in vitro.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of exposure.
    B) No specific laboratory tests are necessary unless otherwise clinically indicated.

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) Admission is almost never necessary unless aspiration has occurred.
    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 exposure.
    B) No specific laboratory tests are necessary unless otherwise clinically indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Minimal toxicity is expected. GI decontamination is generally not necessary.
    B) SKIN EXPOSURE
    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).
    C) EYE EXPOSURE
    1) 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).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Minimal toxicity is expected. GI decontamination is generally not necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF TOXICITY
    a) Treatment is symptomatic and supportive. Minimal toxicity is expected.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of exposure.
    2) No specific laboratory tests are necessary unless otherwise clinically indicated.

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 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).
    6.9.2) TREATMENT
    A) SKIN IRRITATION
    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).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) TOXICITY: A minimum toxic dose has not been established. Minimal toxicity is expected. THERAPEUTIC USE: The manufacturer recommends application of picaridin repellent (7%) every 3 to 4 hours but not more than 3 times a day.

Therapeutic Dose

    7.2.1) ADULT
    A) The manufacturer recommends application of picaridin repellent (7%) every three to four hours but not more than three times a day (Prod Info CUTTER(R) ADVANCED(TM) topical spray, 2005).
    7.2.2) PEDIATRIC
    A) The manufacturer recommends that an adult apply picaridin repellent on the child every three to four hours but not more than three times a day. The repellent should not be applied to the hands of children (Prod Info CUTTER(R) ADVANCED(TM) topical spray, 2005).

Workplace Standards

    A) ACGIH TLV Values for CAS119515-38-7 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS119515-38-7 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS119515-38-7 :
    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 CAS119515-38-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)RAT:
    1) 4743 mg/kg in males(US Environmental Protection Agency, 2005)
    B) LD50- (ORAL)RAT:
    1) 2236 mg/kg in males (US Environmental Protection Agency, 2005)
    C) LD50- (SKIN)RAT:
    1) Greater than 2000 mg/kg (Limit Test) (US Environmental Protection Agency, 2005)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Picaridin is a piperidine derivative insect repellent. It works similarly to DEET by blocking the olfactory stimuli on human skin, decreasing the insect's ability to locate the human (Corazza et al, 2005).

Physicochemical

Physical Characteristics

    A) Picaridin is a colorless, nearly odorless liquid that is miscible in ethanol and 2-propanol and insoluble in water (US Environmental Protection Agency, 2005).

Molecular Weight

    A) 229.36 g/mole (US Environmental Protection Agency, 2005)

References

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