TOXICITY Oral LD50 values in fasted and non-fasted male rats were 2236 mg/kg and 4743 mg/kg, respectively [L4595]. Acute dermal LD50 values in rats were greater than 2000 mg/kg and 5000 mg/kg [L4595]. 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 [L4595]. While icaridin is considered to be practically non-toxic upon dermal and inhalation exposure [L4595], there have been cases of allergic contact dermatitis associated with pruritis and erythema upon dermal application [L6103]. ; ; 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 [L4595]. The United States Environmental Protection Agency claims that icaridin is not likely to be carcinogenic to humans [L6103]. 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 [L4595].

HALF-LIFE 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 [L6103]. 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 [L6103]. The 2nd half-lives were 144 and 105 hours, respectively [L6103].

ABSORPTION 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 [L4595]. 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 [L4595]. 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 [L4595].

METABOLISM 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 [L4595]. 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 [L4595].

ROE 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 [L4595]. At doses of 200 mg/kg, 33-40% of the administered dose was excreted in the urine or feces [L4595]. No data were available on the composition of parent compound and metabolites in the urine of either animals or humans [L4595].

INDICATION Icaridin is indicated for use to repel insects, such as mosquitoes, biting flies, ticks, chiggers, and fleas, via topical use or over clothing [L4617].