Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin Irritation

The potential for 2,2,4,4-tetramethyl-1,3-cyclobutanediol to induce skin irritation is well understood with the key study consisting of an OECD guideline 404 study that followed GLP assurances. In that study five-tenths of a milliliter of the test substance was moistened with mineral oil and applied to the skin of three healthy rabbits for 4 hours. Following exposure, dermal irritation was evaluated by the method of Draize. Within one hour of patch removal, all three treated sites exhibited well-defined erythema and very slight edema. The overall incidence and severity of irritation decreased with time and all animals were free of dermal irritation by 72 hours. Similarly the results of two older supporting studies conducted in 1960 and 1964 that followed non-standard methods also concluded the material to be slightly irritating. The methods used in these latter two studies were even much more harsh with one study involving a 24-hour exposure under an occluded cuff and the other consisting of “10 drops” of an acetone slurry applied daily for 10 days.

 

Eye Irritation

 

The potential for 2,2,4,4-tetramethyl-1,3-cyclobutanediol to induce eye irritation is well understood with the key study consisting of an OECD guideline 405 study that followed GLP assurances considered to be the key study. In that study, the rinsed eye showed no corneal opacity or iritis at any time. Conjunctivitis was observed at one and 24 hours but absent by 48. In the unrinsed eye within 24 hours after test substance instillation, all three treated eyes exhibited corneal opacity, iritis, and conjunctivitis. The overall incidence and severity of irritation decreased gradually and all animals were free of ocular irritation by 72 hours. Under the conditions of this study, 2,2,4,4-tetramethyl-1,3-cyclobutanediol was classified as mildly and minimally irritating to the unrinsed and rinsed eye, respectively. 


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The material does not meet the requirements for classification as a skin irritant as all animals were free of dermal irritation by 72 hours and the Primary Dermal Irritation Index was only 1.6. Similarly, as shown below, the scores from the key ocular irritation study do not meet the criteria for labeling as an eye irritant.

Scores from Unrinsed Eyes

 

Rabbit No.: 16142 (Male)

Rabbit No.: 16143 (Male)

Rabbit No.: 16144 (Male)

 

Hours

Hours

Hours

 

1

24

48

72

1

24

48

72

1

24

48

72

Corneal Opacity

0

1

1

0

0

1

0

0

1

1

0

0

 

 

 

 

 

 

 

 

 

 

 

 

 

Iris

1

1

0

0

1

1

0

0

1

1

0

0

 

 

 

 

 

 

 

 

 

 

 

 

 

Conjunctiva

 

 

 

 

 

 

 

 

 

 

 

 

Redness

3

2

2

0

3

2

1

0

3

2

1

0

Chemosis

1

0

0

0

1

0

0

0

2

1

0

0

Category 2:

Skin Irritant

(1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the

onset of skin reactions; or

(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

Irritating to eyes (Category 2) if, when applied to the eye of an animal, a substance produces:

– at least in 2 of 3 tested animals, a positive response of:

– corneal opacity ≥ 1 and/or

– iritis ≥ 1, and/or

– conjunctival redness ≥ 2 and/or

– conjunctival oedema (chemosis) ≥ 2

– calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days