The irritant potential of n-propanol (nonanoic acid vehicle) in cumulative skin irritation: a validation study of two different human in vivo test models.

BACKGROUND/PURPOSE: Human in vivo cumulative irritation tests with low-grade irritants simulate real-life exposure to skin irritants. The test outcome depends not only on the substance tested but also on the design of the assay. More than one experimental irritant is usually used because chemicals have diverse mechanisms of action on the skin. We used sodium lauryl sulfate (SLS) and nonanoic acid (NON) in three different concentrations plus their vehicles, water and n-propanol, respectively, to validate our test models and to optimize test concentrations. METHODS: Healthy volunteer forearm skin was exposed in two different cumulative test models: a repeated open model (ROAT) and an exaggerated wash test model. ROAT: 10-min daily exposures for 5+4 days (no irritation on weekend) to SLS 0% (water), 0.5%, 1.0% and 2.0% on the right arm and NON 0% (n-propanol neat), 10%, 20% and 30% on the left arm. Wash test: induction of irritation by three daily washings for 6 days and maintenance of the dermatitis by two daily washings for 12 days with SLS 0%, 5%, 10% and 15% or NON 0%, 30%, 40% and 50%. Reactions were evaluated clinically and instrumentally (transepidermal water loss, colorimetry and hydration) at sequential time points. Additionally, for the wash test, subjective pain scores were obtained from the volunteers. RESULTS: In the ROAT, n-propanol exhibited irritation potential at the level of SLS 1.0% and, by visual scoring, was only found to be significantly different from the two highest concentrations of NON (20% and 30%). In the wash test, n-propanol was much less irritating than SLS, and it could only be distinguished statistically from NON (any concentration) by visual reading. For both test models, n-propanol, by instrumental measurements, was not significantly different from any NON concentration. CONCLUSION: In cumulative irritation test assays, n-propanol appears to be quite irritant itself and may thus be a significant contributor to NON irritation. Moreover, n-propanol was more irritant in the ROAT compared with the wash test.