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Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

Skin Irritation

In a key study, the test material (E2932.01; 2,2,4 -trimethyl-1,3 -pentanediol) was applied to intact or abraided skin of 3 New Zealand White rabbits. No local changes were oberved in 5 of 6 rabbits throughout the study. In only one rabbit, in the intact skin group showed very slight erythema (score 1) at the 24 hour reading, which fully resolved by the 48 hour reading. No other local changes were observed in this rabbit at other times during the study. The calculated primary irritation index was 0.05. These data indicate that the test article is non-irritating to rabbit skin.

In addition, supporting dermal toxicity studies were available for review. In these studies, animals were administered the neat material or a 25-40% solution of the test material in an ethanol, 3A alcohol, or acetone:corn oil vehicle to clipped (and in one case abraded) skin under occluded contact for 24 hours. The conditions of exposure in these studies were significantly more stringent, i.e., 24 hours versus the 4-hour exposures used in current skin irritation animal testing. When up to 1 g/kg bw of the neat test material was applied to depilated and abraded skin under occlusive contact for 24 hours, signs of irritation were limited to slight to moderate edema and erythema (grade 2) immediately after removal of the bandage and cuff. Slight (grade 1) erythema and flaky eschars were observed at the 1 week observation with very slight signs of erythema and desquamation present at study termination. Signs of irritation in the two studies in which a 40% solution of the test material was administered in ethanol or 3A alcohol were similar to the irritation expected from application of ethanol or 3A alcohol alone.  When up to 20 mL/kg bw of a 25% solution of the test material in a 90:10 acetone:corn oil vehicle was applied to guinea pig skin under occluded contact, signs of irritation were limited to very slight edema and erythema. Based on the results of these studies, 2,2,4-trimethyl-1,3-pentanediol was not corrosive and not considered to be a primary skin irritant.

 

Eye Irritation

In a key study, the test material, 2,2,4 -trimethyl-1,3 -pentanediol, was instilled in one eye of 9 rabbits; in 6 rabbits (group 1), the test material was not disturbed following treatment, while in 3 rabbits (group 2), the treated eye was rinsed with tap water approximately 4 seconds after instillation. For rabbits in Group 1, Corneal opacity developed in one animal. Transient iritis was seen in one animal. A diffuse crimson red colorization was seen in two animals ans was accompanied in one by considerable swelling with partial eversion of the eyelids. Mild conjuctival reactions were observed in two animals. Two animals did not show any observable response to treatment throughout the observation period. The maximum average score (MAS) and median recovery time were calculated to be 7 and 2.5 days, respectively. For rabbits in Group 2, no corneal damage or iridial inflammation was seen in ay of the animals. Transient mild conjuctival reactions were observed in two animals. One animal did not show any observable response to treatment throughout the observation period. The MAS was calculated to be 2. For both groups, the highest MAS was observed at 24 hours after treatment, and all findings were fully reversible during the observation period. From these data, TMPD is considered to be a slight irritant.

Additional supporting data for the potential for 2,2,4-trimethyl-1,3-pentanediol to cause eye burns/irritation comes from a study conducted by methods that predate Good Laboratory Practices and regulatory guidelines but conducted according to acceptable scientific methodology in effect at the time of the study. In the study, one drop of a 40% solution of the test material in ethanol was instilled into the conjunctival sac of one eye of one rabbit. The animal was observed for signs of irritation at 1-, 24-, 48-hours and 14 days after test substance administration. Based on an absence of corrosivity or significant skin irritation in 24-hour dermal toxicity studies in guinea pigs and complete reversibility of irritant effects in the eye irritation study, the test material is not considered to be corrosive to the rabbit eye. Signs of irritation were noted immediately after instillation and at the 1-, 24- and 48-hour examinations. However, based on an absence of data for the vehicle alone and the absence of observations at 72-hours and 7 days following dose administration, it is not possible to determine the exact eye classification for 2,2,4-trimethyl-1,3-pentanediol. Based on the results of this study, 2,2,4-trimethyl-1,3-pentanediol is not corrosive but may be an ocular irritant.

 

Respiratory Tract Irritation

 

The potential for 2,2,4-trimethyl-1,3-pentanediol to cause respiratory tract irritation was evaluated based on the results of an acute LC50 study in which rats were exposed to 4.5 mg/mL of the test material for six hours. Based on the type and duration of clinical signs observed during and following exposure, 2,2,4-trimethyl-1,3-pentanediol is not considered to be a respiratory tract irritant.

 

 

Justification for classification or non-classification

Based on an absence of corrosivity and limited irritant effects observed when the neat test material or the test material in 25- 40% ethanol, 3A alcohol, or acetone:corn oil was applied under occluded contact to guinea pig skin for 24 hours, 2,2,4-trimethyl-1,3-pentanediol is not considered to be a primary skin irritant. 2,2,4-Trimethyl-1,3-pentanediol is not classified for Skin Irritation/Corrosion according to Annex I of Directive 67/548/EEC. Based on limited signs of irritation in the dermal toxicity studies, 2,2,4-trimethyl-1,3-pentanediol is not classified for Skin Irritation/ Corrosion according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

 

In other studies, reversible irritation was observed when either neat test material, or a 40% solution of the test material in ethanol, was instilled into the conjunctival sac of New Zealand white rabbits. 2,2,4-Trimethyl-1,3-pentanediol is not currently classified for Serious Eye Damage/ Eye Irritation according to Annex I of Directive 67/548/EEC.  Based upon numerical scores following exposure to the test material, 2,2,4-trimethyl-1,3-pentanediol is not classified for Serious Eye Damage/ Eye Irritation (Category 2) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or Category 2 or 2B for Serious Eye Damage/ Eye Irritation according to UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

 

2,2,4-Trimethyl-1,3-pentanediol is not classified for Respiratory Tract Irritation according to Annex I of Directive 67/548/EEC.  Based on the limited number of clinical signs observed in an LC50 study in which rats were exposed to 4.5 mg/mL of the test material for 6 hours, 2,2,4-trimethyl-1,3-pentanediol is not classified for Specific Target Organ Toxicity – Single Exposure Category 3 for respiratory tract irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).