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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Bacterial reverse mutation assay (Ames test)

An Ames test with S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 or E. coli WP2 uvr A with and without metabolic activation was evaluated in an OECD SIDS report (Key study, K2). Following test concentrations were applied: 0, 313, 625, 1250, 2500 and 5000 µg/plate (3 plates/dose; 2 replicates), the vehicle was distilled water. Solvent control and positive controls were run and judged valid. Toxicity (growth inhibition) was not observed in any strain, with or without S9 mix. No increase of revertants was observed at with or without S9 mix.

Mammalian chromosome aberration test:

A chromosome aberration test was performed with N-ethylmorpholine (NEM) with the mammalian cell line CHL/IU (Chinese hamster lung) with and without metabolic activation (key study, K2). Following doses were tested in duplicate: 0, 150, 300, 600 and 1200 µg/m for 6 hours (with and without S9) or 24 hours (without S9). With the 6 hr short-term treatment, chromosomal aberrations or polyploidy were not induced, with or without S9 mix. Moreover, chromosomal aberrations or polyploidy were not induced after the 24 hr continuous treatment without S9 mix. Cytotoxicity was not observed for 6 hr short-term treatment, with or without S9 mix, however it was observed at 1200 ug/mL for 24 hr continuous treatment without S9 mix. There were no problems observed in the control groups.

Mammalian cell gene mutation assay (TK locus in L5178Y):

Mutagenicity of N-Ethyl morpholine was studied in TK locus in L5178Y mouse lymphoma cells with and without metabolic activation. The following test concentrations, water being the vehicle, were used: Without metabolic activation: 78, 2500, 3000, 4000 and 5000 nL/mL; With metabolic activation: 78, 156, 1250, 2000 and 2500 nL/mL (in triplicate). Solvent control, negative control and positive controls were run and judged valid. The test material did not induce significant changes in the mutant frequency at the TK locus in L5178Y mouse lymphoma cells. Cytotoxicity was observed in concentrations > 1250 nL/mL (with activation) and > 5000 nL/mL (without activation). The study was rated Key K2.

Mammalian cell gene mutation assay (L5178Y TK+/-):

In addition to the cell transformation assay with BALB/3T3, Conaway CC, Myhr BC, Rundell JO, Brusick DJ (1982) also performed a cell gene mutation assay with L5178. Five dose levels (doses were selected for assays which insured a 50-90% reduction in growth at the highest concentration) were tested. Solvent control and positive controls were run and judged valid. No cytoxicity was observed. Based on mutant frequency N-methyl morpholine was clearly not mutagenic in the L5178Y TK+/- mouse lymphoma assay. This result from an analogue substance is in support to the earlier result in a study by Mhyr B, 1980. Therefore the study was rated a supporting study.

Mammalian cell transformation assay (BALB/3T3):

Conaway CC, Myhr BC, Rundell JO, Brusick DJ (1982) tested mutagenicity of N-Ethyl morpholine with BALB/3T3 mouse fibroblasts with metabolic activation. Five doses which resulted in 50-100% cell survival were tested. Solvent control, and positive controls were run and were valid, however no negative control was used. No numeric result is available. The study concluded that the result was negative, i.e. the substance is not mutagenic. The study was rated K2 and supporting.


Justification for selection of genetic toxicity endpoint
Well-documented study, equivalent to an OECD guideline, study with mammalian cells, supported by reliable bacterial reverse mutation test and chromosome aberration tests.

Short description of key information:
Genetic toxicity in vitro:
Three reliable key in vitro genetic toxicity studies with NEM are available.
N-Ethyl morpholine has been assessed in a bacterial reverse mutation test (Ames, according to OECD guideline 471) and is considered not mutagenic.
In a chromosome aberration test performed according to OECD guideline 473 , N-ethylmorpholine is considered not clastogenicwith or without metabolic activation.
In a mammalian cell gene mutation assay with L5178Y TK+/- mouse lymphoma following no specific guideline N-methyl morpholine was clearly not mutagenic with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data and according to the criteria of the CLP Regulation (EC) 1272/2008, NEM should not be classified for mutagenicity.