Registration Dossier

Administrative data

Description of key information

MPG, propoxylated: skin irritation: slight skin irritant: not classified
MPG, propoxylated: eye irritation: slight transient irritation: not classified.
Tetrapropylene Glycol, a major component of PPG, has been tested for skin and eye irritation in rabbits. Although the tests were not conducted according to a guideline or GLPs, adequate information was available to determine the tests and resulting data are reliable. Based on the results, Tetrapropylene Glycol is considered as non-irritating to skin and slightly irritating to the eye.
Tetrapropylene Glycol Crude (also known as Tripropylene Glycol Bottoms), representative of PPG/PG Highers composition with a significant proportion of tetrapropylene glycol and tripropylene glycol, has been tested for skin and eye irritation in rabbits. Although the tests were not conducted according to a guideline or GLPs, adequate information was available to determine the tests and resulting data are reliable. Based on the results, Tetrapropylene Glycol Crude (also known as Tripropylene Glycol Bottoms) is considered as non-irritating to skin and moderately irritating to the eye, irritation which resolved by 7-d post-instillation.
Tetrapropylene Glycol was evaluated for primary irritation potential in humans. A 25% concentration was used. Negative controls of distilled water and mineral oil USP and a positive control of 0.5% sodium lauryl sulfate were also tested.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

The study on MPG, propoxylated for skin irritation performed with 6 rabbits and according to the EPA 870.2500 protocol and the propoxylated propane-1,2-diol (molecular weight 230) was considered as a slight skin irritant following 4 or 24 hour semi-occlusive exposure to rabbit skin. Eye irritation of Propane-1,2 -diol propoxylated has been tested in a protocol similar to EU Method B.5 with six rabbits. Minor and transient effects on the conjuctivae were observed 1 hr after application in all 6 animals which were all fully reversible after 24 hrs.

Tetrapropylene Glycol, a major component of PPG, has been tested for skin and eye irritation in rabbits (Dow, 1996). Although the tests were not conducted according to a guideline or GLPs, adequate information was available to determine the tests and resulting data are reliable. Topical application for 24 h to abdominal sites (clipped intact and abraded, which were occluded) and inside ear of one New Zealand White male rabbit over 3 (abraded) or 5 (intact & ear) days. No signs of irritation were noted for the intact or abraded abdominal sites over the duration of the study; the inside ear site demonstrated slight erythema on several days but was completely resolved by test day 8; body weight decreased slightly over the course of the study (~5.6%), which was judged to be not biologically significant. Based on these results, Tetrapropylene Glycol is considered not irritating to skin.Tetrapropylene Glycol was tested for eye irritation by application of test substance (0.1 ml neat material) to both eyes of a New Zealand White female rabbit. One eye was washed with water after 30 seconds of exposure; the other eye was washed with water after 1 h of exposure. Moderate discomfort (ophthaine anaesthetic was administered to both eyes) and very slight redness were noted in one eye immediately post-dosing, with very slight conjunctival inflammation present in both eyes at 1 h, 24 h, and 40 h post-dosing. The irritation resolved by 72 h post-instillation. The rabbit gained weight over the 4-day observation period.

 

Based on the results, Tetrapropylene Glycol is considered as non-irritating to skin and slightly irritating to the eye. 

 

Tetrapropylene Glycol Crude (also known as Tripropylene Glycol Bottoms) has been tested for skin and eye irritation in rabbits (Dow, 1984). Although these tests were not conducted according to a guideline or GLPs, adequate information was available to determine that these tests are considered reliable as supporting data. For skin irritation, 0.5 ml of neat test material was applied to (clipped) intact and abraded skin sites of 6 New Zealand White rabbits and covered for 24 h. The skin sites were evaluated at the time of removal of the covering, and 24 h, 48 h, and 72 h afterwards. Prolonged (24 h) contact with 0.5 ml of the undiluted test material resulted in very slight redness (average erythema score at 24 h = 0.67), but no edema. The overall primary irritation score was 0.17 out of a possible 8, therefore Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms) is considered as non-irritating to skin. For eye irritation, 0.1 ml of Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms) was instilled in the conjuntival sac of both eyes of a single New Zealand White female rabbit; one eye was washed after 1 h. Both the washed and unwashed eyes were evaluated 1 h, 24 h, 48 h, and 7 days post-instillation. Observations included slight discomfort, moderate conjunctival irritation with swelling, redness, and moderate clouding of the cornea. All clinical signs were resolved by 7-day post-instillation, thus Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms) exhibited moderate irritation to the eye that was completely resolved by 7 days.

Tetrapropylene Glcyol (25% aqueous solution), a major component of PPG/PG Highers, was evaluated for induction of primary skin irritation in 33 humans, with conduct of a single Insult Patch Test protocol. Although this study was not conducted as a guideline study, nor under GLP, a modern report describes the protocol and resulting data adequately to determine they are reliable. Under the test conditions, Tetrapropylene Glycol did not induce primary skin irritation in 33 human subjects, following a 24h occluded exposure; Tetrapropylene Glycol was considered to be less irritating than the sites treated with water.

 

Thus both Tetrapropylene Glycol and Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms) are considered as non-irritating to skin; Tetrapropylene Glycol is slightly irritating to the eye while Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms) is moderately irritating to the eye but irritation is resolved by 7 days.

Justification for classification or non-classification

The findings in the available studies with MPG, propoxylated on skin irritation and eye irritation do not warrant classification according to the EU criteria.

Based on the skin irritation results for bothTetrapropylene Glycoland Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms), classification is not warranted in accordance with Directive 67/548/EEC and EU Classification, Labelling, and Packaging of Substances and Mixtures (CLP) Regulation (EC)No. 1272/2008. Based on the eye irritation results for Tetrapropylene Glycol and Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms), instillation of neat test material was slightly (or moderately) irritating, however all clinical signs were completely resolved by 7 days post-instillation. Given the complete resolution by 72 h or 7 days, and the minimal eye effects noted, the classification of Tetrapropylene Glycol and Tetrapropylene Glycol Crude (Tripropylene Glycol Bottoms)for eye irritation is not warranted in accordance to Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No.1272/2008.

Based on the results from the primary irritation test in humans, Tetrapropylene Glcyol clasification is not warranted in accordance with Directive 67/548/EEC and EU Classificaiion, Labelling, and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.