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EC number: 203-815-1
CAS number: 110-91-8
a key combined chronic/carcinogenicity study (Harbison et al., 1989),
male and female Sprague Dawley rats were exposed via inhalation to 0,
36, 181 or 543 mg/m3 Morpholine (99.2 %) for 6 hours a day, 5 days per
week for 52 (interim sacrifice) or 104 weeks (terminal sacrifice).
Findings in this study were limited to local effects of irritation
(ocular and nasal cavity effects) noted during clinical observation and
ophthalmoscopic examination, and were confirmed histopathologically.
There was no evidence of increased incidence of carcinogenesis due to
Morpholine inhalation at doses up to and including 543 mg/m3. In a
supporting carcinogenicity study (Kitano et al., 1997), Morpholine (>97
%) was administered in the diet to male Fischer rats at approximately
220 mg/kg bw for a period of 23 weeks in combination with (i) a
preceding 4-week initiation phase characterised by a treatment with 6
known carcinogens and/or (ii) sodium nitrite concurrently given in the
drinking water for 23 weeks. Morpholine alone was not tested; however,
Morpholine plus initiation treatment (without sodium nitrite treatment)
as well as Morpholine plus sodium nitrite treatment (without initiation
treatment) did not induce tumour promotion.
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
the provided information, the test item is considered not to be
classified for carcinogenicity under Regulation (EC) No.1272/2008, as
amended for the fifteenth time in Regulation (EU) 2020/1182.
key combined chronic/carcinogenicity study (Harbison et al., 1989) Morpholine
was administered by whole body inhalation exposure to Sprague-Dawley
rats at mean concentrations of 0, 36, 181 or 543 mg/m³ (6 h/day, 5
days/week) for 52 weeks (10 animals/sex/group) or for 104 weeks (60
animals/sex/group). No treatment-related changes in mortality, body
weights, organ weights, or clinical pathology parameters were observed.
Ophthalmoscopic examinations at week 103 revealed signs of eye
irritation. Histological findings were limited to ocular and anterior
nasal cavity effects, consistent with the known irritating properties of Morpholine.
At the doses tested, there was no evidence of increased incidence of
carcinogenesis due to chronic Morpholine inhalation. Since only local
effects were noted, under the conditions of this study, the NOAEC for
carcinogenicity was >543 mg/m³.
In a supporting carcinogenicity study
(Kitano et al., 1997), the effects of dietary Morpholine administration
at a dose level of 0.5 % (approx. 220 mg/kg bw) to male Fischer 344 rats
(10 or 20 animals/group) were investigated for a period of 23 weeks (i)
in combination with sodium nitrite given in the drinking water following
an initiation phase, (ii) without sodium nitrite following an initiation
phase and (iii) in combination with sodium nitrite without initiation
phase. In an additional experiment, male Fischer 344 rats (14 or 5
animals/group) received a dietary treatment with morpholine (2.0 %) for
1 hour with subsequent administration of sodium nitrite for
determination of N-nitroso compounds in the stomach and to detect DNA
adduct generation. Both experiments were run with concurrent control
groups. Morpholine alone was not tested. The initiation treatment
decreased the body weight of rats compared to non-initiated groups. The
group that was initiated and received sodium nitrite in the drinking
water and morpholine in the diet was significantly lower in body weight
than the group that was only initiated. However, the liver and kidneys
weights were increased. The combination of initiation followed by sodium
nitrite and Morpholine caused an increase in the number and area of
GST-P positive liver foci as compared to the group that was only
initiated, indicating that Morpholine plus sodium nitrite, but not Morpholine
alone, has a tumour promoting effect. Treatment with Morpholine or Morpholine
plus sodium nitrite did not clearly lead to an increased tumour
incidence. No tumours were induced by Morpholine plus sodium nitrite in
the absence of initiation. The mean N-nitrosomorpholine yield in the
group given Morpholine plus sodium nitrite was 6720 µg. No DNA adducts
related to morpholine treatment were detected immunohistochemically.
a further supporing study Shibata et al.(1987b)
0.25 % and
1 % Morpholine
oil acid salt (MOAS) (equivalent
to 0.06 and
to the drinking water of two groups of 50 male
and 50 female
B63F1 mice for a period of 96 weeks.
After a further eight weeks, the survivors were killed. The survival
rate was not affected but
the body weights of males in the higher
dose group and those of die females in both groups were significantly
reduced.The male mice treated with1 % MOAS underwent
a significant increase in hyperplasia in the forestomach epithelium (+15
die lower dose group and those of the females, there was no change in
the incidence relative to the controls. This study did not show any
carcinogenic effects of MOAS in mice at levels of up to 1.0% in the
there was no evidence of carcinogenic activity of Morpholine.
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