January/February 2012 • Volume 10 • Issue 1 - SKINmed Journal

January/February 2012
by nontoxic mechanisms. The EPA has established a special
committee to determine the most appropriate classification
based on established criteria. 7
Biopesticides are usually less toxic than conventional pesticides.
They generally affect only the target pest and closely
related organisms compared with broad-spectrum conventional
pesticides that may affect other organisms including birds and
mammals. 7 IR3535 received this classification because it is functionally
identical to naturally occurring b-alanine. It is a substituted
B amino acid that contains 98% 3-(N-acetyl-N-butyl)
aminopropionic acid, ethyl ester as an active ingredient and 2%
inert ingredients. The end groups are not likely to contribute
to toxicity and it acts to control the target pest via a nontoxic
mode of action. 7 In various studies, IR3535 has been shown to
be as effective as DEET. As with Picaridin the formulation, level
of repellent, and species of insect may be a factor with respect
to repellent efficacy. 1 IR3535 is also reported to be more cosmetically
elegant than DEET when evaluated in various human
Table I. Comparative Toxicology Data for IR3535, 7,8 Picaridin, 9 and DEET 10
SKINmed. 2012;10:36–39
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COSMETIC SCIENCE
studies. As of publication in 2007, the authors of Insect Repellents:
Principles, Methods, and Uses claim there were no reported
adverse reactions to IR3535. 1 IR3535 is registered for use as an
insect repellent against mosquitoes, deer ticks, body lice, and
biting flies. The formulated products are applied directly to skin.
The low toxicity data for IR3535 implies that there is reasonable
certainty of no harm for the general population, as well as subgroups
including infants and children. 7
REVIEW OF TOXICITY DATA FOR DEET,
PICARIDIN, AND IR3535
Tables I and II review toxicological data obtained from various
sources. Regarding safety classification, the World Health
Organization (WHO) classification for IR3535 is hazard class
U, indicating that the compound is unlikely to present acute
hazard in normal use. 8 The WHO classified Picaridin as class III,
indicating a slight hazard. 9,11 DEET was also designated as class
III by the WHO. 12,13
TEST IR3535 PICARIDIN DEET REPORTED DOSE
Acute toxicity oral rat (lethal dose, 50%) >5000 2236 2170 mg/kg body weight
Acute dermal toxicity rabbit or rat (lethal dose, 50%) >3000 >2000 4280 mg/kg body weight
Acute inhalation (lethal dose, 50%) >5.1 >4.3 NA mg/L
Eye irritation in rabbit Irritating to eye Moderate irritant Irritating
Skin sensitization in guinea pig No No No
Dermal sensitization human (NOEL) No No No mg/kg/d
Subchronic dermal rat (NOEL) 3000 200 300 mg/kg/d
Developmental rat (oral) 1000 400 250 mg/kg/d
Ames test (Salmonella typhimurium) Nonmutagenic Nonmutagenic Nonmutagenic
Micronucleus assay Nonmutagenic Nonmutagenic Nonmutagenic
Abbreviations: DEET, N, N-diethyl-m-toluamide; NA, not applicable; NOEL, no observed effect level. Higher scores indicate lower potential
for toxicity.
Table II. Information From Various EPA Fact Sheets5,7,9 EPA FACT SHEET CLASS IR3535 PICARIDIN DEET
Acute inhalation toxicity IV IV IV
Primary dermal irritation IV IV III
Acute oral IV III III
Acute dermal III III III
Primary eye II III III
Abbreviations: DEET, N, N-diethyl-m-toluamide; EPA, Environmental Protection Agency. Category I, very highly or highly toxic; category
II, moderately toxic; category III, slightly toxic; category IV, practically nontoxic.
Alternatives to DEET