Human Cumulative Irritation Tests of Common Preservatives Used in Personal Care Products: A Retrospective Analysis of Over 45 000 Subjects.

The cumulative irritation test (CIT) is an accepted method used to evaluate the skin irritation potential and safety of individual ingredients and formulas of leave-on skin care and cosmetic compounds. Here, we report the results of CITs collected by JOHNSON & JOHNSON Consumer Companies, Inc. (Skillman, NJ), part of an extensive tiered program to evaluate product safety. In the CIT, test formulations were applied to the skin of adults (18-70 years) with no known skin disease or allergies, 3 times per week for 2 weeks using semi-occlusive clinical patches. Preservatives were 1 of up to 16 components of test formulas, and included ethylenediaminetetraacetic acid, diazolidinyl urea, 1,3-Bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione, parabens, isothiazolinone, phenoxyethanol, sorbates, or benzoates. Skin sites were scored after each patch removal using a 5-point scale, with 0 = no visible reaction and 4 = erythema, marked edema, or substantial vesiculation. Scores were reported as percentage of maximal irritation score. Data were analyzed from 1363 CIT studies (over 45 000 subjects). There were no significant differences in percentage of maximal scores between formulas grouped by preservative types (p > .1). Median score across the entire dataset was 0.44, with most formulas showing none or mild irritation. Although seasonal variations were observed, no correlation was noted between score and preservative concentration. In conclusion, in a large, normal subject dataset, preservatives at typical in-use concentrations did not appear to contribute to skin irritation.