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.