Registration Dossier

Administrative data

Description of key information

Morpholine is alkaline and is corrosive (cat. 1B) to skin and mucous membranes.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

With regard to the key- and supporting studies from Huntsman, Morpholine was considered to be highly corrosive (Huntsman 1997, Key-study) and was identified as corrosive dependent on the applied criteria (Huntsman 1986, Huntsman 1993, Huntsman 1997). The corrosive potential of Morpholine was measured by applying 0.1 g mixture (0.1, 0.5, 2, 5 and 10% Morpholine in petrolatum) to guinea-pig skin for 24 h (Wang and Suskind 1988). Observations were made 1, 24 and 48 h after removal of the test materials, and no noticeable effects were found in this supporting study.

In an in-house study classified as second key study, two rabbits were treated for 1, 5, 15 min or 20 h using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance. The animals were observed for 3 weeks and skin changes were recorded daily account. The application of the test substance for 1 min caused in 1 animal hemorrhagic areas and leathery-like necrosis at the end of the observation period. The application for 5 min caused after 24 h parchment-like necrosis in one animal and hemorrhagic areas after 24 h and leathery-like necrosis after 8 days. The application of the test substance for 15 min caused hemorrhagic areas, edema and parchment-like necrosis after 24 h which declined to leathery-like necrosis after 8 days. Leathery-like necrosis is considered as a full-thickness necrosis (BASF AG XVI). In a further study, noticed as supporting study, rabbits were treated with aqueous solutions of 2, 20, 40 and 60% Morpholine and the skin reactions were evaluated after 0.5, 24, 48 and 72 h. A 2% solution of Morpholine caused skin irritation after 72 h, whereas 40% and 60% solutions immediately caused reddening of the skin (Loden, 1985).

Eye irritation

Eye injury in rabbits was reported in several acute studies. Noticed in an in-house study classified as key study, one drop of undiluted Morpholine in rabbit eyes, repeated once after 5 min, caused oedema, opacity, staphyloma and corrosion of the eye mucous membranes within 24 h (BASF AG XVI). In a further key study it was demonstrated that 0.1 mL of undiluted Morpholine resulted in necrosis in and around the eyes (Koch1985); acting like a corrosive substance. Before these investigations, eye injury in rabbits was tested also by Smyth et al. (1954), who reported severe eye burns with 0.5 mL of a 1% solution Morpholine. With regard to other test animals, in-life clinical examinations in rats exposed to up to 0.54 g/m³ (150 ppm) Morpholine revealed increased incidences in inflammation of the cornea at week 103 of a chronic inhalation study (Huntsman 2147-102, cf. 7.5.3). Findings included keratitis, oedema, abrasion, scarring, and ulceration with or without neovascularization and corneal epithelial hyperplasia. A high incidence of retinal degeneration was observed, primarily in female animals, which was probably an age-related light-induced retinal degeneration.

 

Respiratory irritation

Studies of acute inhalation toxicity of Morpholine revealed irritation of the mucous membranes. In a key study there is indication that the test substance causes local irritation to exposed tissues including respiratory tract (BASF AG XVI/352, cf. 7.2.2). A supporting study noticed irritation of nose and eyes (mucous membranes) after exposure of rats to Morpholine for 6 hours to whole body at a nominal concentration of 5000 ppm equivalent to ca. 18.1 mg/L; 9/10 animals died after one treatment (Huntsman 2147-100, cf. 7.2.2).


Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No 1272/2008. Based on these information the test item is considered to be classified for skin and eye irritation cat. 1A and cat. 1, respectively under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

However, as the substance is already listed in Annex VI of Regulation (EC) No 1272/2008 concerning skin and eye irritation (cat. 1B, H314), the harmonized classification is used.