Icaridin

229.32

229.32

423-210-8

N51GQX0837

DTXSID0034227

Colorless liquid

49.8

2

Colourless liquid

1.07 at 20 deg C

< -170 deg C

296 deg C

153.9±20.4 °C

1.478

In acetone, 7520 g/L at 20 deg C

Safe Storage of Pesticides. Always store pesticides in their original containers, complete with labels that list ingredients, directions for use, and first aid steps in case of accidental poisoning. Never store pesticides in cabinets with or near food, animal feed, or medical supplies. Do not store pesticides in places where flooding is possible or in places where they might spill or leak into wells, drains, ground water, or surface water.

4.43X10-4 mm Hg at 25 deg C

Nearly odorless

Henry's Law constant = 1.6X10-8 atm-cu m/mole at 25 °C (est)

Hydroxyl radical reaction rate constant = 5.6X10-11 cu cm/molec- sec at 25 °C (est)

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal.|Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Do cut or puncture other empty pesticide containers made of metal or plastic to prevent someone from reusing them. Wrap the empty container and put it in the trash after you have rinsed it.

USEPA; Office of Prevention, Pesticides and Toxic Substances, New Pesticide Fact Sheet for Picaridin (May 20, 2005).[Available from, as of June 24, 2016: https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-070705_01-May-05.pdf]

|Warning|H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P264, P280, P305+P351+P338, and P337+P313|Aggregated GHS information provided by 46 companies from 1 notifications to the ECHA C&L Inventory.|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

If a spill occurs, clean it up promptly. Don't wash it away. Instead, sprinkle the spill with sawdust, vermiculite, or kitty litter. Sweep it into a plastic garbage bag, and dispose of it as directed on the pesticide product label.|After Applying a Pesticide, Indoors or Outdoors. To remove pesticide residues, use a bucket to rinse tools or equipment three times, including any containers or utensils that you used when mixing the pesticide. Then pour the rinsewater into the pesticide sprayer and reuse the solution by applying it according to the pesticide product label directions. After applying any pesticide wash your hands and any other parts of your body that may have come in contact with the pesticide..To prevent tracking pesticides inside, remove or rinse your boots or shoes before entering your home. Wash any clothes that have been exposed to a lot of pesticide separately from your regular wash.

Picaridin was detected in most influent and some effluent samples collected Nov 2007, Feb, June and Sept 2008 from two waste water treatment plants in the metropolitan area of A Coruna, Spain(1).

Oral LD50 values in fasted and non-fasted male rats were 2236 mg/kg and 4743 mg/kg, respectively. Acute dermal LD50 values in rats were greater than 2000 mg/kg and 5000 mg/kg. The LC50 over a 4-hour exposure period exceeded 4364 mg/m^3 in male rats, and the NOEL was determined to be 2153 mg/m^3. While icaridin is considered to be practically non-toxic upon dermal and inhalation exposure, there have been cases of allergic contact dermatitis associated with pruritis and erythema upon dermal application. In an animal study following application of icaridin to the skin of rats at doses of 50, 100, or 200 mg/kg/day each weekday for two years, there were no signs of potential carcinogenicity. The United States Environmental Protection Agency claims that icaridin is not likely to be carcinogenic to humans. In a two-generation reproductive study on rats, administering 50, 100, or 200 mg/kg icaridin to the rats' skin weekly beginning 10 weeks before mating and continuing through to weaning of the pups. Findings from the study concluded that chronic icaridin exposure to the skin at doses as high as 200 mg/kg did not result in reproductive toxicity.|IDENTIFICATION AND USE: Picaridin is a colorless liquid. Picaridin is an insect repellent, for application to human or animal skin. In particular, it is used as mosquito repellent. HUMAN EXPOSURE AND TOXICITY: Allergic contact dermatitis has been reported in a human following routine application of picaridin and produced erythema and pruritis. It is not clear whether the solvent methyl glucose-dioleate had a causative or additive effect. However, insect repellents containing picaridin may be acceptable alternatives in patients who demonstrate sensitivity to products containing DEET. Primary symptoms across all insect repellent exposures included ocular irritation/pain, vomiting, red eye/conjunctivitis, and oral irritation. Unintentional ingestion of picaridin-containing and other insect repellents was associated only with minor toxicity. ANIMAL STUDIES: The skin of 50 rats/sex/group was treated with 0, 50, 100 or 200 mg/kg/day 5 days per week for 2 years (the two year cohort). Additionally, 20 animals/sex/group were treated with 0 or 200 mg/kg/kg and 10 animals/sex/group were treated with 50 or 100 mg/kg/day of the test material. These animals received the treatment for one year (one year cohort). There was no apparent effect of an increased mortality due to the treatment. There was no treatment-related effect upon mean body weight, food consumption, clinical signs, ophthalmology, hematology, clinical chemistry, urinalysis, absolute or relative organ weights, or histopathology. The skin of 30 rats/sex/group was treated with 0, 50, 100, or 200 mg/kg/day 5 days/week for two generations. The treatment periods included 10 weeks prior to mating, mating, 3 weeks gestation and 3 weeks of lactation. At that time, 30 F1 animals/sex/group were selected as parents and treated for an additional 10 weeks, followed by mating and 3 weeks each for gestation and lactation of the F2 generation. There were no apparent treatment-related clinical signs related to systemic toxicity or effects upon the mean body weights and food consumption of the parental animals in either generation. At the application site, hyperkeratosis and acanthosis, apparent for even some of the control animals, increased in severity in a dose-related manner. There was no effect upon the reproductive parameters or development of the offspring in either generation. Picaridin was tested in S. typhimurium TA98, TA100, TA1535 and TA1537 strains at levels ranging from 8 to 5000 ug/plate (both trials) with or without metabolic activation and incubated for 48 hours at 37 °C. There was no apparent treatment-related increase in the incidence of reverse mutation. There was no treatment-related increase in the number of micronuclei in mouse micronucleus test.

Picaridin and oxybenzone are two active ingredients found in repellent and sunscreen preparations, respectively. We performed a series of in vitro diffusion studies to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Permeation of picaridin (PCR) and oxybenzone (OBZ) across human epidermis was suppressed when both active ingredients were used concurrently; increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. The findings were different from concurrent use of repellent DEET and sunscreen oxybenzone in which a synergistic permeation enhancement was observed. Further comparative studies are therefore needed to understand permeation mechanisms and interactions between picaridin and oxybenzone.|Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances.

LD50 Rat oral 4743 mg/kg|LD50 Rat dermal >2000 mg/kg|LC50 Rat (male) inhalation >4364 mg/cu m 4hr

/OTHER TOXICITY INFORMATION/ ... Mosquitoes use their sense of smell to detect DEET, but there are currently two hypotheses regarding its mode of action: activation of ionotropic receptor IR40a vs. odorant receptor(s). Here, we demonstrate that DEET, picaridin, insect repellent 3535, and p-menthan-3,8-diol activate the odorant receptor CquiOR136 of the southern house mosquito, Culex quinquefasciatus. Electrophysiological and behavioral assays showed that CquiIR40a knockdown had no significant effect on DEET detection and repellency. By contrast, reduction of CquiOR136 transcript levels led to a significant decrease in electroantennographic responses to DEET and a complete lack of repellency. Thus, direct activation of an odorant receptor, not an ionotropic receptor, is necessary for DEET reception and repellency in Culex mosquitoes. Interestingly, methyl jasmonate, a repellent derived from the nonvolatile jasmonic acid in the signaling pathway of plant defenses, elicited robust responses in CquiOR136-CquiOrco-expressing Xenopus oocytes, thus suggesting a possible link between natural products with long insect-plant evolutionary history and synthetic repellents.|/OTHER TOXICITY INFORMATION/ Acts on certain olfactory receptor cell types to reduce the activating or attracting effect of odor sources.|/OTHER TOXICITY INFORMATION/ The interactions between insect repellents and the olfactory system have been widely studied, however relatively little is known about the effects of repellents on the gustatory system of insects. In this study, we show that the gustatory receptor neuron (GRN) located in the medial styloconic sensilla on the maxillary palps of gypsy moth larvae, and known to be sensitive to feeding deterrents, also responds to the insect repellents DEET, IR3535, and picaridin. These repellents did not elicit responses in the lateral styloconic sensilla. Moreover, behavioral studies demonstrated that each repellent deterred feeding. This is the first study to show perception of insect repellents by the gustatory system of a lepidopteran larva and suggests that detection of a range of bitter or aversive compounds may be a broadly conserved feature among insects.

There is no available information on the protein binding of icaridin.

Picaridin's production may result in its release to the environment through various waste streams; its use as an insect repellent(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that picaridin is expected to have high mobility in soil(SRC). Volatilization of picaridin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.6X10-8 atm-cu m/mole(SRC), based upon its vapor pressure, 4.43X10-4 mm Hg(3), and water solubility, 8200 mg/L(3). Picaridin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Biodegradation data in soil were not available(SRC, 2016).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a structure estimation method(2), indicates that picaridin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.6X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 4.43X10-4 mm Hg(4), and water solubility, 8200 mg/L(4). Picaridin did not undergo hydrolysis at pH 5, 7 and 9, 25 °C over 30 days(4). According to a classification scheme(5), an estimated BCF of 14(SRC), from its log Kow of 2.23(4) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2016).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), picaridin, which has a vapor pressure of 4.43X10-4 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase picaridin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7 hours(SRC), calculated from its rate constant of 5.6X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Picaridin does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of picaridin with photochemically-produced hydroxyl radicals has been estimated as 5.6X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Picaridin did not undergo hydrolysis at pH 5, 7 and 9, 25 °C over 30 days(2). Picaridin does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 14 was calculated in fish for picaridin(SRC), using a log Kow of 2.23(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of picaridin can be estimated to be 80(SRC). According to a classification scheme(2), this estimated Koc value suggests that picaridin is expected to have high mobility in soil.

The Henry's Law constant for picaridin is estimated as 1.6X10-8 atm-cu m/mole(SRC) derived from its vapor pressure, 4.43X10-4 mm Hg(1), and water solubility, 8200 mg/L(1). This Henry's Law constant indicates that picaridin is expected to be essentially nonvolatile from water and moist soil surfaces(2). Picaridin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

DRINKING WATER: Picaridin was detected at <10 ng/L in some tap water samples collected from five private homes located in different places of the city of A Coruna, Spain(1).

Occupational exposure to picaridin may occur through inhalation and dermal contact with this compound at workplaces where picaridin is produced or used. Monitoring and use data indicate that the general population may be exposed to picaridin via inhalation of mist and dermal contact with consumer products containing picaridin. (SRC)|Picaridin is listed at 5-34% in eight products used as pesticides and pet care products(1).

Icaridin is indicated for use to repel insects, such as mosquitoes, biting flies, ticks, chiggers, and fleas, via topical use or over clothing.

Icaridin is a cyclic amine and piperidine compound that is expected to stimulate the sensory hairs on the antennae of insects.

In a dermal metabolism rat study, dermal application of 20 mg/kg of radio-labeled icaridin resulted in 61-66% of the dose absorbed through the skin. Following topical application of 20 mg/kg on rats, the peak plasma concentrations were measured to be 0.5 μg/mL in male rats and 0.8-1.6 μg/mL in female rats. In a study of human volunteers, less than 6% of the applied doses were absorbed after topical application of 14.7 or 15.0 mg of technical grade icaridin and covering the application site with a protective wrap for eight hours.|Following topical administration on rats at doses of 20 mg/kg, urinary excretion was reported to be the primary route of elimination where 73-88% of the parent compound was recovered in the urine. At doses of 200 mg/kg, 33-40% of the administered dose was excreted in the urine or feces. No data were available on the composition of parent compound and metabolites in the urine of either animals or humans.|In a rat study, dermal application of icaridin at doses of either 20 mg/kg or 200 mg/kg resulted in plasma concentrations ranging from 0.5 μg/ml for males and 0.8-1.6 μg/ml for females in the 20 mg/kg test group, and 4.48 μg/ml in male rats and 1.70 μg/ml and female rats in the 200 mg/kg test group. Icaridin applied to the arms of human volunteers was not found in blood plasma.|There is no available information on the clearance of icaridin.|Picaridin and oxybenzone are two active ingredients found in repellent and sunscreen preparations, respectively. We performed a series of in vitro diffusion studies to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Permeation of picaridin (PCR) and oxybenzone (OBZ) across human epidermis was suppressed when both active ingredients were used concurrently; increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. The findings were different from concurrent use of repellent DEET and sunscreen oxybenzone in which a synergistic permeation enhancement was observed. Further comparative studies are therefore needed to understand permeation mechanisms and interactions between picaridin and oxybenzone.|Increased awareness of skin cancer and mosquito-transmitted diseases has increased use of insect repellents and sunscreens. The challenge in setting recommendations for use and reapplication, especially when used concomitantly, lies in finding the balance between applying a durable product effective in withstanding natural and physical factors such as water, sweat, temperature and abrasion, while limiting percutaneous absorption and decreasing risk of potential dermal and systemic toxicity. Inorganic sunscreens show no or little percutaneous absorption or toxic effects in comparison to organic sunscreens, which show varying levels of dermal penetration and cutaneous adverse effects. An alternative to N,N-diethyl-m-toluamide (DEET), the traditional gold standard compound in insect repellents, picaridin appears as efficacious, has lower risk of toxicity, and when used simultaneously with sunscreen may decrease percutaneous absorption of both compounds. Conversely, combined use of DEET and sunscreen results in significantly higher absorption of both compounds. It is important to increase consumer awareness of "washing in" of various compounds leading to increased risk of toxicity, as well as differences in reapplication need due to "washing off" caused by water, sweat and abrasion. Although much remains to be studied, to maximize efficacy and decrease toxicity, contemporary research tools, including dermatopharmokinetics, should aid these prospective advances.|The skin of 6 male human volunteers/group was exposed to 15.0 or 14.7 mg/person (37 uCi/person) of 14C-KBR 3023 (undiluted) or as a preparation in ethanol (15% (w/w). The subjects were exposed to the test material for 8 hours under a non-occlusive protective wrap. At the end of the treatment period, the treated area was swabbed with isopropyl alcohol and rinsed with the alcohol. The swabs and alcohol were saved for further analysis. Tape stripping in the proximity of the dosing site was performed at 1, 23 and 45 hours post-exposure. Blood samples were drawn at 0, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 and 120 hours post-application from both the ipsilateral and contralateral arms. Urine was collected prior to dosing and in the following intervals: 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, 48 to 60, 60 to 72, 72 to 84, 84 to 96, 96 to 108, 108 to 120, and 120 to 128 hours post-application. Feces were collected throughout the 128 hour collection period. Most of the applied dose was recovered in the rinsate and on the swabs, protective covering and duoderm at the end of the exposure period, 94.16% and 95.23% of the test material in ethanol and the undiluted test material, respectively. Radiolabel was recovered in the urine of the test subjects (mean values: 3.76% (range: 2.20 to 7.00%) and 1.66% (range: 0.70 to 2.29%) of the applied dose for the solution and undiluted material, respectively). Ninety three to 94% of the label was recovered in the 1st 24 hours. Recovery of radiolabelled compound from the plasma was negligible. Absorption of the radiolabelled compound through the skin was quite limited under the conditions of the study. The use of a vehicle (ethanol) seemed to enhance its absorption.|... The skin of a total of 5 rats/sex was treated daily for 2 weeks with 20 mg/kg of unlabeled KBR 3023 technical (purity: 99.1%), followed by exposure to a single dose of 20 mg/kg of the radiolabeled test material for 7 days. /In a second test/ the skin of a total of 5 rats/sex was exposed to a single dose of 200 mg/kg of the radiolabeled test material for 7 days. ... The primary route of excretion was the urine (73 to 88% of the absorbed dose). Pretreatment did not appear to affect the excretion profile. For the 200 mg/kg dermal treatment, the mean percentages of the administered dose which were recovered in the urine and feces ranged between 33 and 40% for the males and females, respectively. The radioactivity recovered in the urine represented 78 and 91% of the total for males and females, respectively.

There is limited data on the metabolism and resulting metabolites of the drug; however, it is estimated that icaridin undergoes phase I metabolic reactions involving 2-methylpropyl side chain or the piperidine ring being hydroxylated. It is also noted that the hydroxyethyl sidechain was oxidized to produce a carbonyl group. There was very little Phase 2 metabolism of the icaridin.|Analysis of the metabolites revealed that the predominant modifications of the parent compound were phase 1 reactions in which the piperidine ring or the 2-methylpropyl sidechain was hydroxylated or the hydroxyethyl sidechain was oxidized to the carbonyl moiety. Phase 2 conjugation reactions with glucuronide, linoleic or oleic acid constituted a very minor fraction of the recovered metabolites.

The first elimination half-lives of icaridin were determined in a study of five male and female rats treated with a single dose of 20 mg/kg icaridin dermally. The half-lives were 35.7 hours for male and 23.9 hours in female rats. In another study of rats treated daily for 2 weeks with 20 mg/kg of unlabeled icaridin, followed by exposure to a single dose of 20 mg/kg of the radiolabeled icaridin for 7 days, the 1st elimination half-lives were 10.9 and 9.1 hours for the males and females, respectively. The 2nd half-lives were 144 and 105 hours, respectively.|Five rats/sex were dosed iv in the femoral vein with a single dose of 20 mg/kg of the test material. The test material was prepared in physiological saline. ... The 1st , 2nd and 3rd elimination half-lives were 0.9, 5.2 and 45.5 hours for the males and 0.7, 2.8 and 73.0 hours for the females.|... The skin of a total of 5 rats/sex was exposed to a single dose of 20 mg/kg of the radiolabeled test material for 7 days. ... Only 1st elimination half-lives were determined for the low dose dermal studies. These half-lives were 35.7 ... hours for the males and 23.9 ... hours for the females.|... The skin of a total of 5 rats/sex was treated daily for 2 weeks with 20 mg/kg of unlabeled KBR 3023 technical (purity: 99.1%), followed by exposure to a single dose of 20 mg/kg of the radiolabeled test material for 7 days. ... For the high dose dermal treatments, the 1st elimination half-lives were 10.9 and 9.1 hours for the males and females, respectively. The 2nd half-lives were 144 and 105 hours, respectively.

The exact mechanism and target molecules of icaridin repelling insects are not fully understood; it is presumed that piperine interacts with the olfactory system consisting of odorant receptors (ORs) that need a common co-receptor (ORCO), and of ionotropic receptors (IR), leading to the insect's inability to recognize its host's cues. It is also suggested that icaridin may bind to odorant binding protein 1 (AgamOBP1) at different binding sites. A study demonstrated that icaridin inhibited the odorant-induced responses of AaOR2 and AaOR8 expressed in Xenopus oocytes, leading to altered olfactory inputs by olfactory sensory neurons (OSN).|DEET, 2-undecanone (2-U), IR3535 and Picaridin are widely used as insect repellents to prevent interactions between humans and many arthropods including mosquitoes. Their molecular action has only recently been studied, yielding seemingly contradictory theories including odorant-dependent inhibitory and odorant-independent excitatory activities on insect olfactory sensory neurons (OSNs) and odorant receptor proteins (ORs). Here we characterize the action of these repellents on two Aedes aegypti ORs, AaOR2 and AaOR8, individually co-expressed with the common co-receptor AaOR7 in Xenopus oocytes; these ORs are respectively activated by the odors indole (AaOR2) and (R)-(-)-1-octen3-ol (AaOR8), odorants used to locate oviposition sites and host animals. In the absence of odorants, DEET activates AaOR2 but not AaOR8, while 2-U activates AaOR8 but not AaOR2; IR3535 and Picaridin do not activate these ORs. In the presence of odors, DEET strongly inhibits AaOR8 but not AaOR2, while 2-U strongly inhibits AaOR2 but not AaOR8; IR3535 and Picaridin strongly inhibit both ORs. These data demonstrate that repellents can act as olfactory agonists or antagonists, thus modulating OR activity, bringing concordance to conflicting models.

Treat skin irritation with oral antihistamines and topical steroids.|For eye exposure, irrigate eyes with copious amounts of water or normal saline. If contact lenses are present, they should be removed.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ For the use of topical insect repellents, DEET and picaridin, human health risk assessments were conducted for various population subgroups. Acute, subchronic, and chronic dermal exposures were examined. No-observed-effect-levels (NOELs) of 200, 300, and 100 mg/kg body weight (BW) were used as endpoints for DEET for acute, subchronic, and chronic exposures, respectively. For picaridin, a NOEL of 2000 mg/kg BW/day for acute exposure and a NOEL of 200 mg/kg BW/day for subchronic and chronic exposures were used. Daily exposures to several population subgroups were estimated. Risks were characterized using the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100. Estimates of daily exposures ranged from 2 to 59 mg/kg BW/day for DEET and 2 to 22 mg/kg BW/day for picaridin. Children had the lowest MOEs. However, none of the estimated exposures exceeded NOELs for either repellent. At 40% DEET for acute exposure, children < or = 12 years had MOEs below 100. For subchronic and chronic exposures children at > or = 25% DEET and at 15% picaridin had MOEs below 100. Therefore, we found no significant toxicological risks from typical usage of these topical insect repellents.|/SIGNS AND SYMPTOMS/ Allergic contact dermatitis has been reported in a human following routine application /of picaridin/ and produced erythema and pruritis. It is not clear whether the solvent methyl glucose-dioleate had a causative or additive effect.|/CASE REPORTS/ Topical insect repellent is commonly used throughout the world. Active ingredients typically include N,N-diethyl-meta-toluamide (DEET) or picaridin. Reactions to topical repellents have ranged from contact dermatitis to urticaria. Exposure to DEET can produce contact urticaria; however, it is unknown if patients with a sensitivity to DEET can tolerate picaridin. We report the case of a 22-year-old man who presented for evaluation of contact urticaria that had developed immediately after the application of insect repellent and contact with individuals who had used DEET-containing repellents. No systemic manifestations were noted. Commercially available products containing DEET or picaridin were used for open patch testing. The patient showed immediate urticarial responses to 7% DEET and 7% DEET in ethanol, but patch tests for 5% picaridin and 5% picaridin in ethanol were negative. Based on these results, we conclude that insect repellents containing picaridin may be acceptable alternatives in patients who demonstrate sensitivity to products containing DEET.|/SURVEILLANCE/ ... The purpose of this study was to review National Poison Data System (NPDS) data regarding ingestion of insect repellents containing picaridin and compare those to insect repellents containing DEET and other insect repellents not containing DEET. NPDS was queried for single agent human insect repellent ingestions reported between 1 January 2000 and 31 May 2015 using the American Association of Poison Control Center generic categories 201048 (Insect Repellents with DEET) and 201049 (Insect Repellents without DEET). Picaridin-containing product exposures were assessed using Poisindex product ID 6744589. Insect repellents of unknown type were not included. 68,429 exposures occurred; 24% were non-DEET-containing products, of which 2% were picaridin-containing products. Among picaridin exposures, 92.9% were managed outside of a health-care facility; there were no reported cases of major effect or death, and only one case of moderate effect. Primary symptoms across all insect repellent exposures included ocular irritation/pain, vomiting, red eye/conjunctivitis, and oral irritation. Treatment primarily included dilution/irrigation/wash. Unintentional ingestion of picaridin-containing and other insect repellents was associated only with minor toxicity and was generally managed outside of a health-care facility.

1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine

Cutter Insect Repellent 7K (Spectrum, A Division of United Industries Corporation): Active ingredient: Picaridin 7.0%.|Cutter Insect Repellent 5KT (Spectrum, A Division of United Industries Corporation): Active ingredient: Picaridin 5.75%.|Cutter Insect Repellent 15KP (Spectrum, A Division of United Industries Corporation): Active ingredient: Picaridin 15.0%.|Cutter Insect Repellent 15KA (Spectrum, A Division of United Industries Corporation): Active ingredient: Picaridin 15.0%.|For more Formulations/Preparations (Complete) data for PICARIDIN (28 total), please visit the HSDB record page.