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Description of key information

In accordance with column 2 of REACH Annex VII, a sensitisation study does not need to be conducted because the substance is classified for skin corrosivity. Given as supplementary information, no skin sensitization was seen in an animal study with guinea pigs tested with a 2% solution of Morpholine.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion (Category 1, 1A, 1B or 1C)
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
A modification of Buehler's method was employed in this study.
GLP compliance:
not specified
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Lab.
- Age at study initiation: 5 - 6 weeks
- Weight at study initiation: 350 - 450 g
- Housing: individual cages
- Diet: pellet diet

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 1 [70 ± 2° F]
- Humidity: 45 %
- Air changes: 10 changes/hour
- Photoperiod: 12 hours dark/12 hours light
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
No. of animals per dose:
10 animals
Details on study design:
RANGE FINDING TEST: yes

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6
- Exposure period: 24 h
- Test groups: Morpholine in petrolatum
- Control group: Pure white petrolatum only
- Site: shaved nape
- Frequency of applications: ca. every 2nd day
- Duration: 0 - 14 d
- Concentrations: 5% (amount noted to produce minimal-intensity erythema)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: (15)
- Exposure period: 24 h
- Test groups: Morpholine in petrolatum
- Control group: Pure white petrolatum only
- Site: left flank
- Concentrations: 0.1, 0.5, 2 %
- Evaluation: 1, 24, 48 h and 7 days after removal
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1% Morpholine
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 % Morpholine
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2% Morpholine
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1% Morpholine
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5% Morpholine
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
2% Morpholine
No. with + reactions:
0
Total no. in group:
10

The sensitizing potential of Morpholine was tested on 10 guinea pigs by Buehler's method. Morpholine (2 %in Vaseline) proved not to be skin sensitizing. Thus, the Morpholine ring alone was incapable of inducing sensitization. A positive reaction in animals sensitized to 4,4-'dithiodimorpholine was attributed by the authors to irritation in hypersensitive animals.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Since morpholine is alkaline and is corrosive to skin and mucous membranes, a sensitisation study does not need to be conducted in accordance with column 2 of REACH Annex VII.

However, the sensitizing potential of morpholine was tested on 10 guinea pigs by Buehler's method (Wang & Suskind, 1988). Morpholine (2 % in vaseline) proved not to be skin sensitizing. In an in vitro experiment it was investigated whether or not morpholine, being a haptene, reacts with amino acids, thereby unfolding a sensitizing action. No reaction occurred with either lysine, cysteine or glycine (Wang & Tabor, 1988).


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There are no human data available indicating a respiratory sensitisation potential.

Justification for classification or non-classification

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

Morpholine is classified for skin corrosivity. Thus, in accordance with column 2 of REACH Annex VII, a sensitisation study does not need to be conducted. There are data available indicating no dermal sensitisation potential of Morpholine. Based on this information, the test item is considered not to be classified for skin sensitisation under Regulation (EC) No.1272/2008, as amended for the fifteenth time in Regulation (EU) 2020/1182.