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

Abstract

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.

Skin irritation potential of cosmetic preservatives: An exposure‐relevant study

“…In the ROAT, subjects exhibited noticeable erythema on the application area after applying imidazolidinyl urea and DMDM hydantoin with mean total ISs of 0.33 and 0.13, respectively, while phenoxyethanol and the parabens resulted in no adverse response (Table 2). This observation was consistent with a previous cumulative irritation test (CIT), which suggested that the median CIT score of the tested preservatives, comprising EDTA, DMDM hydantoin, parabens, isothiazolinone, phenoxyethanol, sorbates, and benzoates, was 0.47%, with most tests showing none or mild irritation under typical in‐use conditions 27 . Although the preservatives displayed no severe reaction, such as papules or vesicles, the weak erythema response indicated a skin irritancy potential that might lead to consumer dissatisfaction.…”

“…Along with this finding, a study comparing skin irritation of several cosmetic preservatives by a 24-hr patch test illustrated that methylparaben and phenoxyethanol shared a similar mean IS that was lower than that of propylparaben. 26 In the ROAT, subjects exhibited noticeable erythema on the application area after applying imidazolidinyl urea and DMDM hydantoin with mean total ISs of 0.33 and 0.13, respectively, while phenoxyethanol and the parabens resulted in no adverse response ( 27 Although the preservatives displayed no severe reaction, such as papules or vesicles, the weak erythema response indicated a skin irritancy potential that might lead to consumer dissatisfaction.…”

Optimization of Polysorbate 80 and Sorbitan Monooleate 80 aas Emulsifiers in Foundation Makeup Containing Ethyl Cinnamate

“…The results of this test indicate that the foundation cream containing ethyl cinnamate does not cause erythema and edema in 10 probands (with each of probandus score is 0), so it could be concluded that the foundation cream preparation containing ethyl cinnamate does not cause irritation to humans and is safe to use. (Nigam, 2019;Walters et al, 2015).…”

“…The criteria of the panelists were female ages 20-30 years, physically and mentally healthy, and had no history of allergic disease (Noviandini, 2014). The test site was evaluated using the following scales: 0 = no erythema; 0.5 = minimal erythema; 1 = erythema (within patch margins); 2 = erythema (fiery color) within patch margins; 3 = erythema (fiery color) or slight vesiculation (beyond patch margins), or both; 4 = erythema (fiery color), marked edema, substantial vesiculation (far beyond patch margins) (Walters et al, 2015).…”

Amended Safety Assessment of Parabens as Used in Cosmetics

“…In 1 retrospective analysis, 1,363 cumulative irritation test studies in more than 45,000 subjects, who use-tested 151 different parabencontaining formulations (along with other ingredients), did not demonstrate parabens to be irritating in typical in-use conditions and irritation scores did not correlate with preservative concentrations. 123 Allergic contact dermatitis caused by paraben mixture was analyzed on the basis of data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2009 and 2012 from 12 European countries (Table 16). 124 Of the 52,586 tests during the study period, parabens yielded less than 1% positive reactions.…”