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EC number: 203-815-1
CAS number: 110-91-8
Morpholine is alkaline and is corrosive to skin and mucous membranes.
animal1/animal2 (50 µL):
Mean values over 24 h, 48 h and 72 h:
Animal1: Opacity: 1.3; Chemosis: 0;
Erythema: 1.3; Iritis: 0
Animal2: Opacity: 1; Chemosis: 0; Erythema:
2; Iritis: 0
The application of 50 µL test substance
caused initially chemosis and moderate opacity and erythema. The corneal
opacity and erythema effects were not reversible within the 8 day
observation period. One animal developed ingrowing vessels at the end of
the observation period.
animal1/animal2 (100 µL):
Animal1: Opacity: 2; Chemosis: 2; Erythema:
2; Iritis: 1.3
Animal2: Opacity: 2; Chemosis: 2; Erythema:
2; Iritis: 1.3
The applicaton of 100 µL test substance
caused moderate to severe corneal opacity, erythema and chemosis. After
48 hours iritis and after 6 days staphyloma was noted. The effects were
not reversible within the 8 day observation period Severe corneal
opacity and iritis are considered to be irreversible effects to
The original BASF grading was
converted into the numerical grading according to the OECD Draize system.
In a primary dermal irritation study (Huntsman, 1997), 0.5 mL of Morpholine was applied to one site on the clipped dorsal trunk of 6 New Zealand White rabbits (3 males and 3 females) for an exposure period of 3 minutes. Observations for responses were recorded immediately after unwrap and at 55 minutes. Grading of irritation was performed according to the method of Draize. Following an exposure period of 3 minutes, severe erythema, severe oedema and necrosis were observed. Therefore, Morpholine was considered to be a severe irritant and was considered as corrosive according to DOT classification (Packaging group 1). This study is classified as key study. It satisfies the requirements of OECD test guideline 404.
In a further key skin irritation/corrosion study (BASF AG, 1967), 2 Vienna White rabbits were treated with Morpholine (99.2 %) for 1, 5, 15 min or 20 hours using occlusive conditions. An application site of 2.5 cm² was covered with the liquid test substance. The animals were observed for 3 weeks and skin changes were recorded daily. The application of the test substance for 1 min caused in 1 animal haemorrhagic areas and leathery-like necrosis at the end of the observation period. The application for 5 min caused after 24 hours parchment-like necrosis in 1 animal and haemorrhagic area after 24 hours and leathery-like necrosis after 8 days. The application of the test substance for 15 min caused haemorrhagic areas, oedema and parchment-like necrosis after 24 hours which declined to leathery-like necrosis after 8 days. Leathery-like necrosis was considered as a full-thickness necrosis. This study is classified as acceptable. It generally satisfies the guideline requirements for OECD 404.
In a supporting skin irritation/corrosion study (Loden et al., 1985), 3 albino rabbits were treated with aqueous solutions of 2, 20, 40 or 60 % Morpholine. The skin reactions to treatment were evaluated after 0.5, 24, 48 and 72 hours. A 2% solution of Morpholine caused skin irritation after 72 hours, whereas 40 and 60% solutions immediately caused reddening of the skin. This study is classified as acceptable. It satisfies the guideline requirement of OECD test guideline 404.
In a comparative study (Wang & Suskind, 1988), the irritant 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 hours. Observations were made 1, 24 and 48 hours after removal of the test material, and no noticeable effects were found. This study is classified as acceptable guideline study.
In a supporting primary dermal irritation study (Huntsman, 1993), 0.5 mL Morpholine was applied to the shaved skin of 6 male New Zealand White rabbits for exposure durations of 3 min, 60 min, 4 hours and 24 hours using a semiocclusive dressing. Following patch removal, the animals were observed for a period of 14 days. The scoring of reactions was performed according to Draize. The primary dermal irritation index was assessed. Severe erythema, severe oedema and necrosis were noted under the conditions of this study. Based on these results, Morpholine was considered as corrosive. This study is classified as acceptable. It satisfies the requirements for OECD test guideline 404.
In a primary dermal irritation study (Huntsman, 1993) using a semiocclusive dressing, 0.5 mL Morpholine was applied to the shaved skin of one male and one female New Zealand White rabbit for exposure duration of 4 hours. In this supporting study results were reported at 4 h and 48 h after exposure. Morpholine was considered to be corrosive. This study is classified as acceptable.
In a primary eye irritation study (Koch et al., 1985), 100 µL of undiluted Morpholine (99 %) was instilled into the conjunctival sac of the left eye of 3 rabbits. The eyes were washed out after 24 hours. Further exposure times were 4 and 30 seconds, respectively (3 rabbits/exposure time). Animals were observed for 21 days. Irritation was scored according to OECD guideline 405. All three expositions gave rise to eye irritation. All animals showed necrosis in and around the eyes. After an exposure time of 24 hours burns (corrosion) were observed. Two of the animals also gave rise to corrosion both inside and around the eyes at 30 seconds of exposure. After the observation period eye injuries were still observed in one animal. The authors classified Morpholine as irritant substance; however, corrosive effects in several animals were observed. Thus, Morpholine can be regarded as a corrosive substance. This study is classified acceptable. It satisfies the requirement of OECD test guideline 405.
In this acute eye irritation/corrosion study (BASF AG, 1967), the eyes of 2 Vienna White rabbits were exposed by application of 50 µL undiluted Morpholine (99.2 %) into the conjunctival sac. In a second attempt, 2 animals were treated with an additional 50 µL of the test substance 5 min after the first application. The animals were observed after 10 min, 1 and 3 hours on the day of treatment and up to 8 days afterwards. The eyes were not washed out after 24 hours. Overall, the treatment caused oedema, opacity, staphyloma and corrosion of the eye mucous membranes within 24 hours. Morpholine was graded as corrosive under the conditions of this study. This study is classified as acceptable. It satisfies the requirements of OECD test guideline 405.
In a supporting eye irritation study by Smyth et al. (1954), in which eyes of 7 New Zealand White rabbits were treated with 0.5 mL Morpholine. Based on the outcomes of this study Morpholine was considered as irritating to the rabbit eye. This study is classified an acceptable supporting study.
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.
Supportingly, the eye irritating property of DIPA/110-97-4 was also found using other laboratory methods: in vitro Short Time Exposure test by Takahashi et al., 2011 (Toxicology in vitro 25; p.1425-1334), Hansen solubility parameter to predict results of the RhCE method by Ito et al., 2021 (Toxicology in vitro 70, 105039).
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 further 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).
Labeling, and Packaging Regulation (EC) No 1272/2008
available experimental test data are reliable and suitable for the
purpose of classification under Regulation (EC) No 1272/2008. Based on
this information, the test item is considered to be classified for skin
and eye irritation Cat. 1A (H314) and Cat. 1 (H318), respectively under
Regulation (EC) No. 1272/2008, as amended for the fifteenth time in
Regulation (EU) 2020/1182.
substance is already listed in Annex VI of Regulation (EC) No 1272/2008
concerning skin and eye irritation (Cat. 1B, H314).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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