Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
The potential for isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol to cause contact dermal sensitization is well understood. For the skin sensitization endpoint, a key and two supporting studies exist. The key study was performed by Perstorp AB using NesterolTM, the trade name for isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol. The two supporting studies were conducted with TexanolTM Ester-Alcohol, the Eastman trade name for isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol. The key study was performed under GLP and according to guideline. There are no epidemiological studies or well-documented episodes of allergic contact dermatitis caused by human exposure to isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol. In the key guinea pig maximization test performed by Perstop AB, 10 guinea pigs/sex were intradermally injected with the following: Freund's complete adjuvant diluted with an equal volume of water for irrigation, NesterolTM 10% (v/v) in 5% acetone in Alembicol D, and NesterolTM 10% (v/v) in a 50:50 mixture of Freund's complete adjuvant and 5% acetone in Alembicol D. Six days after intradermal injections, the animals were exposed topically to a 10% solution of sodium lauryl sulfate. The following day 0.4ml NesterolTM (neat) was topically applied and in contact with the skin for 24 hours. Two weeks after the induction period, the animals were challenged with 0.4 ml of either NesterolTM (neat) or a 50:50 solution of NesterolTM in acetone. NesterolTM remained in place for 24 hours under occlusion at which time the patches were removed. The animals were observed for dermal responses at 24, 48, and 72 hours after application of the challenge patch. Irritation, necrosis at injection sites receiving Freund's Complete Adjuvant in test and control animals, slight irritation at injection sites receiving NesterolTM 10% (v/v) in 5% acetone in Alembicol D and in control animals receiving 5 % acetone in Alembicol D alone, was observed during the induction phase. No dermal irritation or sensitization was observed after the challenge phase of the study. Under the conditions of the study, NesterolTM did not indicate a potential for dermal sensitization. The potential for isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol (TexanolTM Ester-Alcohol) to cause dermal sensitization was also determined in two supporting studies. In a study conducted under an internal Eastman Kodak Company protocol, three groups of five Hartley guinea pigs were induced and challenged, by epicutaneous exposure, with either a 1% concentration of isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol (test group), a suspension of acetone, dioxane, and guinea pig fat (negative/vehicle control), or with phenylhydrazine (positive control). Skin examinations at 24 and 48 hours after the challenge dose indicated no positive sensitization reactions in the test or negative control groups. The positive control group of animals produced a significant sensitization response. Under conditions of this study, isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol was not considered to be a dermal sensitizer. In a summary report for a study conducted according to OECD Guideline 406, ten guinea pigs were immunized with the test material using the footpad technique and challenged via dermal application. Under conditions of this study, skin examination after the challenge application indicated no positive response in any of the animals. In a non-guideline study in which guinea pigs were repeatedly exposed topically to 1% of the test material for a total of eight applications over a ten-day period, there was no increased incidence of erythema or edema when compared to the negative control group. The response in the positive control group, treated with topical application of the known skin sensitizer phenylhydrazine, was as expected. Taken together, all three studies support the conclusion that isobutyric acid, monoester with 2,2,4-trimethylpentane-1,3-diol is not sensitizing.

Justification for classification or non-classification

No evidence of a sensitization response was observed when guinea pigs were immunized with isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol by the footpad technique and challenged via dermal application or repeatedly exposed topically to the test material for a total of eight applications over a ten day period and there is no evidence that isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol is a dermal sensitizer in humans. In addition, a GLP, guideline compliant GPMT study gave no evidence that isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol is a skin sensitizer. Based on a weight-of-the evidence assessment, isobutyric acid, monoester with 2,2,4 -trimethylpentane-1,3 -diol is not classified for “Skin Sensitization” according to EU CLP.