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EC number: 203-815-1
CAS number: 110-91-8
LD50/LC50 values derived from the key-studies were: LD50 (oral, rat)
1900 mg/kg bw, LD50
(dermal, rabbit) 500 mg/kg bw, LC50 (rat) 8000 mg/m3.
The test substance caused dose dependent
toxicity after a single ingestion and local irritations to exposed
The inhalation of a highly saturated
vapor-air-mixture caused mortality after 3 h of exposure. There was
indication that the test substance caused local irritation to exposed
tissues including respiratory tract.
acute oral toxicity of Morpholine in the rat was examined in several
toxicity studies. In general, oral administration of Morpholine to rats
resulted in LD50 values within the range of 1000 to 2000 mg/kg bw (BASF
AG, 1969; Shea, 1939; Smyth et al., 1954; Börzsönyi et al., 1981;
Huntsman, 1981). Gastrointestinal and nasal haemorrhage were reported as
clinical findings following oral Morpholine administration. When
Morpholine was administered to 7 male rats at a neutral pH, no deaths
occurred at 1000 mg/kg bw (Börzsönyi et al., 1981). In a supporting
study on guinea-pigs (Shea, 1939) a lower LD50 of 900 mg/kg bw was
Huntsman study (1981) indicating LD50=1680 mg/kg bw ) is a key study
here. The BASF study from 1967, where a LD50 of ca.1900 mg/kg bw was
derived, has been identified as a second key study. These studies
represent the most reliable studies. A reliable source of test material
was used and the test was done according to a well described BASF method
which was in compliance with the principles of OECD Guideline 401. The
same holds true for the Huntsman study.
the first key acute oral toxicity study (Huntsman, 1981), male Sprague
Dawley rats were given a single dose (oral gavage) of Morpholine at 250,
500, 1000, 2000, or 4000 mg/kg bw. Animals were then observed for 3
days. The oral LD50 was estimated as 1680 mg/kg bw. In the second key
study an acute oral toxicity study according to an internal BASF method
was performed (BASF AG, 1967). Sprague Dawley rats were given a single
oral dose of Morpholine diluted in water at 1600, 2000, 2500 or 3200
mg/kg bw. Animals were then observed for mortality and for clinical
symptoms of toxicity for 14 days. All animals were subjected to
necropsy. The oral LD50 was estimated as 1900 mg/kg bw.
an acute dermal toxicity study (Smyth et al., 1954), male rabbits were
exposed to Morpholine. The test material was applied in a single dose to
the clipped skin of the trunk beneath an impervious plastic film. After
24 hour exposure the film was removed, and mortality was considered
complete after 14 additional days. Death occurred within the observation
period. Limits of ±1.96 standard deviation using the method of Thompson
were 0.31 – 0.81 mL/kg bw. The LD50 determined in this study was 0.5
mL/kg bw. Due to the given specific density of Morpholine (1.0 g/cm3) a
LD50 of 500 mg/kg bw was derived. This study is classified as
acceptable. It satisfies the guideline requirement for an acute dermal
study according OECD 402 in principle
a supporting publication by Shea (1939), the dermal toxicity and skin
absorption of Morpholine was assessed in 7 rabbits. Undiluted,
unneutralized Morpholine was applied in a single dose of 900 mg/kg bw to
the clipped skin of the midsection of 7 rabbits. The mortality incidence
was 2/7. The 2 premature decedents had blackened necrotic skin and
inflamed oedematous derma at the site of application, and severe burns
of the underlying organs. The 5 surviving rabbits had severe burns at
the site of treatment. This study is classified as acceptable supporting
the assessment of the acute inhalation potential of the test substance a
weight of evidence approach was applied.
an acute inhalation toxicity study according to an internal BASF method
(BASF AG, 1967), male and female rats were exposed to Morpholine (99.4
%) vapour for a period of 1, 3 or 5.5 hours and observed for 7 days. All
animals were subjected to necropsy. Exposure to Morpholine at vapour
saturation concentrations resulted in 100 % lethality after 5.5 hours.
Morpholine had irritating and corrosive properties. This acute
inhalation toxicity study is classified as acceptable. It satisfies the
guideline requirement for an acute oral study according to OECD 403 in
an acute inhalation study (ILO, 1972), 6 rats were exposed to
approximately 24 mg/L. Morpholine for a period of 4 hours and then
observed for 14 days. No mortality was observed. Signs of irritation and
stained hair, but normal weight gain were noted during the 14 day
observation period. No gross lesions were found at necropsy. This acute
inhalation toxicity study is classified as acceptable supporting study.
an acute inhalation toxicity study (Huntsman, 1981) young adult rats
(5/sex) were whole body exposed to Morpholine for 6 hours at a nominal
concentration of 5000 ppm (equivalent to approx. 18.1 mg/L). Blood
around the nose and mouth, spasms and tremors, irritation of nose and
eyes were observed during the study. 9/10 animals died on day 1 of the
study (only one exposure was conducted). The last animal in this group
was sacrificed in moribund condition on day 3 of the study. This study
is classified as acceptable supporting study.
an inhalation study with rats, LC50 values of 7.8 and 8.2 mg/L were
obtained for female and male rats (Lam and Steen, 1978). In the same
publication an inhalation study with mice was reported. Here, LC50
values of 5.2 and 6.9 mg/L air were obtained for female and male mice.
to Morpholine at vapour saturation concentrations resulted in 100%
lethality after 5.5 h (BASF AG, 1967). Irritating and corrosive
properties were noted. In studies using lower Morpholine concentrations,
Lam & Van Stee (1978) obtained LC50 values of 8.2 and 7.8 mg/L for male
and female rats, respectively (exposure period was not specified; Fed.
Proc., 37: 679, abstract no. 2459: A re-evaluation of the toxicity of
morpholine). Other authors reported no deaths at a three times higher
dose level (24 mg/L) after an exposure period of 4 hours (ILO, 1972).
9/10 rats died after a single exposure to 18.1 mg/L for 6 hours
(Huntsman, 1981). With regard to other species, reported LC50 values for
mice are consistently in the range of ca. 5 - 7 mg/L (Lam and Van Stee,
1978). Based on these findings and using a conservative approach (here:
reflecting the results of Lam & Van Stee, 1978), a LC50 value of ca. 8.0
mg/L for rat is derived.
Labeling, and Packaging Regulation (EC) No 1272/2008
available data for acute toxicity are reliable and suitable for
classification purposes under Regulation (EC) No 1272/2008. Based on
this data, the substance is considered to be classified for acute oral
toxicity Cat. 4 (H302), acute inhalation toxicity Cat.3 (H331) and for
acute dermal toxicity Cat.3 (H311) under Regulation (EC) No 1272/2008, as
amended for the fifteenth time in Regulation (EU) 2020/1182.
substance is listed in Annex VI of Regulation (EC) No 1272/2008
concerning acute oral toxicity (Cat. 4, H302), acute inhalation toxicity
(Cat.4, H332) and acute dermal toxicity (Cat.4, H312).
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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