2-methylaminoethanol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Zeiger etal., 1987. Salmonella Mutagenicity Tests: III.Results From the Testing of 255 Chemicals. Publication
BASF AG, 2008. In vitro mammalian chromosome-aberration test. According to the GLP and OECD guideline 473.
BASF AG, 2010. Mutation at the hprt locus of L5178Y mouse lymphoma cells using the Microtitre R fluctuation technique. According to the GLP and OECD guideline 476.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Dec 2007 - 26 Jun 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 473)

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

S9-mix from Aroclor 1254 treated male Sprague-Dawley rats

Test concentrations with justification for top dose:

50, 100, 200, 400, 800 µg/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: culture medium (MEM: Minimal Essential Medium)
- Justification for choice of solvent/vehicle: good solubility in water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

MEM

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: Without metabolic activation: 500 μg/mL ethyl methanesulfonate; with metabolic activation: 0.5 μg/mL cyclophosphamide

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 4 and 18 h
- Fixation time (start of exposure up to fixation or harvest of cells): 18 h and 28 h

SPINDLE INHIBITOR (cytogenetic assays): colcemid
STAIN (for cytogenetic assays): After drying, the slides were stained with 7.5% (v/v) Giemsa/Titrisol solution pH 7.2 for 10 minutes. After being rinsed twice in purified water and clarified in xylene, the slides were mounted in Corbit-Balsam.

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 1000

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

Statistics:

A comparison of each dose group with the negative control group was carried out using Fisher's exact test for the hypothesis of equal proportions. This test was Bonferroni-Holm corrected versus the dose groups separately for each time and was performed one-sided.

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: The pH value of the stock solutions was adjusted to physilogical values prior to testing.
- Effects of osmolality: the osmolarity was not influenced by test substance treatment.

COMPARISON WITH HISTORICAL CONTROL DATA: yes

Remarks on result:

other: all strains/cell types tested

According to the results of the present in vitro cytogenetic study, the test substance Methylaminoethanol did not lead to a relevant increase in the number of structural chromosomal aberrations incl. and excl. gaps either without S9 mix or after the addition of a metabolizing system in two experiments performed independently of each other selecting different exposure times (4 and 18 hours) and sampling times (18 and 28 hours). The types and frequencies of structural chromosome aberrations were close to the range of the concurrent negative control values at both sampling times and clearly within in the range of the historical negative control data. 

 

Under the experimental conditions chosen here, the conclusion is drawn that Methylaminoethanol is not a chromosome-damaging (clastogenic) substance under in vitro conditions using V79 cells in the absence and the presence of metabolic activation.

Conclusions:

Interpretation of results:
negative with metabolic activation
negative without metabolic activation

Not chromosome-damaging

Executive summary:

A chromosome-aberration test was performed according to OECD guideline 473.

Under the experimental conditions chosen here, the conclusion is drawn that N-Methylaminoethanol is not a chromosome-damaging (clastogenic) substance under in vitro conditions using V79 cells in the absence and the presence of metabolic activation.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiated on 10 November 2009 and was completed (final report issued) on 8 April 2010. Experimental work started on 11 November 2009 and was completed on 26 January 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conducted in accordance with current testing guidelines and GLP-compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Type of assay:

mammalian cell gene mutation assay

Target gene:

Hypoxanthine-guanine phosphoribosyl transferase (hprt) locus (6-thioguanine [6TG] resistance)

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

- Type and identity of media: RPMI 1640
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes

L5178Y tk +/- (3.7.2C) mouse lymphoma cells were stored as frozen stocks in liquid nitrogen. Each batch of frozen cells was purged of tk- mutants, checked for spontaneous mutant frequency and that it was mycoplasma free. For each experiment, at least one vial was thawed rapidly, the cells diluted in RPMI 10 and incubated in a humidified atmosphere of 5% v/v CO2 in air. When the cells were growing well, subcultures were established in an appropriate number of flasks.

Metabolic activation:

with and without

Metabolic activation system:

Arocolor 1254 induced rat liver post-mitochondrial fraction (S-9)

Test concentrations with justification for top dose:

Experiment 1: 50 to 600 µg/mL in the absence of S-9 and from 100 to 750 µg/mL in the presence. 7 days after: 500 µg/mL was the highest concentration analysed to determine viability and 6TG (6-thioguanine) resistance in the absence and 600 µg/mL in the presence of S9.
Experiment 2: 50 to 600 µg/mL in the absence of S-9 and from 100 to 700 µg/mL in the presence of S-9. 7 days after: 450 µg/mL was the highest concentration analysed to determine viability and 6TG (6-thioguanine) resistance in the absence and 500 µg/mL in the presence of S9.

Range-finder: 23.47, 46.94, 93.89, 187.8, 375.6 and 751.1 µg/mL
Experiment 1: 50, 100, 200, 250, 300, 350, 400, 450, 500 and 600 µg/mL (without S-9), and 100, 200, 300, 350, 400, 450, 500, 550, 600 and 750 µg/mL (with S-9)
Experiment 2: 50, 100, 200, 300, 350, 400, 450, 500, 550 and 600 µg/mL (without S-9), and 100, 200, 300, 400, 450, 500, 550, 575, 600 and 700 µg/mL (with S-9)

Vehicle / solvent:

- Justification for choice of vehicle: Preliminary solubility data indicated that N-Methylaminoethanol (MMEA) was soluble in sterile water for injection (purified water) at concentrations up to at least 72.16 mg/mL. The solubility limit in culture medium was in excess of 7216 µg/mL, as indicated by a lack of precipitation at this concentration 3 hours after test article addition. A maximum concentration of 751.1 µg/mL was selected for the cytotoxicity range-finder experiment, in order that treatments were performed up to 10 mM. Concentrations for the Mutation Experiments were selected based on the results of this cytotoxicity range-finder experiment.
Test article solutions were prepared by formulating N-Methylaminoethanol (MMEA) under subdued light conditions in purified water (with the aid of vortex mixing, as required) immediately prior to assay to give the maximum required treatment solution concentration.

Negative solvent / vehicle controls:

yes

Remarks:

Purified water diluted 10-fold in the treatment medium

Positive controls:

yes

Remarks:

4-nitroquinoline 1 oxide (NQO), Benzo[a]pyrene (B[a]P, + S-9) (Both prepared in DMSO).

Positive control substance:

benzo(a)pyrene

Remarks:

NQO at 0.10 and 0.15 µg/mL final concentration; B[a]P at 2.00 and 3.00 µg/mL final concentration

Untreated negative controls:

yes

Remarks:

purified water

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

without S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in suspension: fluctuation protocol
DURATION
- Preincubation period: 3h
- Exposure duration:
- Expression time (cells in growth medium): 7 days
NUMBER OF CELLS EVALUATED: 20,000
DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative total growth: In the cytotoxicity Range-Finder Experiment, six concentrations were tested in the absence and presence of S 9, ranging from 23.47 to 751.1 µg/mL (equivalent to 10 mM at the highest concentration tested). The highest concentration to give >10% relative survival (RS) was 375.6 µg/mL, which gave 30% and 45% RS in the absence and presence of S 9, respectively.

OTHER EXAMINATIONS:
- Other: survival (relative cloning efficiency, viability and 6TG resistance

Metabolic activation system
Rat liver S-9 fraction from male Sprague Dawley rats induced with Aroclor 1254. Batches were stored at –80ºC prior to use. Each batch was checked by the manufacturer for sterility, protein content, ability to convert known promutagens to bacterial mutagens and cytochrome P- 450-catalysed enzyme activities.
Treatment was carried out both in the absence and presence of S-9, prepared in the following way:
Glucose-6-phosphate (G6P: 180 mg/mL), β-Nicotinamide adenine dinucleotide phosphate (NADP: 25 mg/mL), Potassium chloride (KCl: 150 mM) and rat liver S-9 were mixed in the ratio 1:1:1:2. For all cultures treated in the presence of S-9, a 1 mL aliquot of the mix was added to each cell culture (19 mL) to give a total of 20 mL. Cultures treated in the absence of S-9 received 1 mL KCl (150 mM). The final concentration of the liver homogenate in the test system was 2%.

Evaluation criteria:

For valid data, the test article was considered to induce forward mutation at the hprt locus in mouse lymphoma L5178Y cells if:
1. the mutant frequency at one or more concentrations was significantly greater than that of the negative control (p≤0.05)
2. there was a significant concentration relationship as indicated by the linear trend analysis (p≤0.05)
3. the effects described above were reproducible.
Results that only partially satisfy the assessment criteria described above were considered on a case-by-case basis.

Statistics:

Statistical significance of mutant frequencies was carried out according to the UKEMS guidelines [8] (cited in the original study report). Thus the control log mutant frequency (LMF) was compared with the LMF from each treatment concentration, and secondly the data were checked for a linear trend in mutant frequency with test article treatment. These tests require the calculation of the heterogeneity factor to obtain a modified estimate of variance.

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

see Table 2 (Experiment 2 and 3)

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The highest concentration to give >10% relative survival (RS) was 375.6 µg/mL, which gave 30% and 45% RS in the absence and presence of S-9, respectively

Vehicle controls validity:

valid

Positive controls validity:

not applicable

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: At the highest concentration tested in the cytotoxicity Range-Finder Experiment (751.1 µg/mL), a marked increase in pH (of ≥ 1 unit, compared to the concurrent vehicle controls) was observed at 751.1 µg/mL in the absence and presence of S-9. Further pH measurements were therefore made in Experiments 1 and 2.
- Effects of osmolality: At the highest concentration tested in the cytotoxicity Range-Finder Experiment (751.1 µg/mL), no marked changes in osmolality, compared to the concurrent vehicle controls, were observed.

RANGE-FINDING/SCREENING STUDIES: TOXICITY
In the cytotoxicity Range-Finder Experiment, six concentrations were tested in the absence and presence of S 9 ranging from 23.47 to 751.1 µg/mL (equivalent to 10 mM at the highest concentration tested). The highest concentration to give >10% RS was 375.6 µg/mL, which gave 30% and 45% RS in the absence and presence of S 9, respectively. The % RS values are shown in Table 1.

Accordingly, for Experiment 1 ten concentrations, ranging from 50 to 600 µg/mL in the absence of S 9 and from 100 to 750 µg/mL in the presence of S-9, were tested. Seven days after treatment, the highest concentrations tested in the absence of S-9 (600 µg/mL) and in the presence of S 9 (750 µg/mL) were considered too toxic for selection to determine viability and 6TG resistance. All other concentrations were selected. The highest concentrations analysed were 500 µg/mL in the absence of S 9 and 600 µg/mL in the presence of S 9, which gave 16% and 7% RS, respectively (see Table 8). In the presence of S-9, no concentration gave 10-20% RS (cultures treated at 550 and 600 µg/mL gave 26% and 7% RS, respectively, therefore both concentrations were analysed).
In Experiment 2 ten concentrations, ranging from 50 to 600 µg/mL in the absence of S 9 and from 100 to 700 µg/mL in the presence of S-9, were tested. Seven days after treatment, the highest three concentrations tested in the absence of S-9 (500 to 600 µg/mL) and in the presence of S 9 (575 to 700 µg/mL) were considered too toxic for selection to determine viability and 6TG resistance. In addition, the lowest concentrations tested in the absence and presence of S-9 (50 and 100 µg/mL, respectively) were not selected as there were sufficient non-toxic concentrations. All other concentrations were selected. The highest concentrations analysed were 450 µg/mL in the absence of S 9 and 500 µg/mL in the presence of S 9, which gave 8% and 17% RS, respectively (see Table 8). In the absence of S-9, no concentration gave 10 20% RS (cultures treated at 400 and 450 µg/mL gave 30% and 8% RS, respectively, therefore both concentrations were analysed).

COMPARISON WITH HISTORICAL CONTROL DATA:
The assay was considered valid if the following criteria were met:
1.the mutant frequencies in the negative (vehicle) control cultures fell within the normal range (not more than three times the historical mean value)
2.at least one concentration of each of the positive control chemicals induced a clear increase in mutant frequency (the difference between the positive and negative control mutant frequencies was greater than half the historical mean value).

ADDITIONAL INFORMATION ON CYTOTOXICITY:

Remarks on result:

other: all strains/cell types tested

The acceptance criteria were met and the study was therefore accepted as valid.

Table 2: Range-finder experiment Treatment (µg/mL) -S-9 %RS +S-9 %RS 0 100 100 23.47 82 86 46.94 81 77 93.89 88 67 187.8 66 84 375.6 30 45 751.1 0 0 %RS    Percentage Relative Survival  Table 3: Experiment 1 (3-hour treatment in the absence and presence of S-9) Treatment (µg/mL) -S-9 %RS                 MF§ Treatment (µg/mL) +S-9 %RS                 M F§ 0 50 100 200 250 300 350 400 450 500 100 105 100 80 77 72 54 44 24 16      7.38 6.76     NS 7.31     NS 7.20     NS 9.52     NS   7.62    NS    5.93    NS 7.37    NS 8.74    NS 7.15    NS 0 100 200 300 350 400 450 500 550 600   100 99 93 84 81 82 61 53 26 7        6.97 6.22      NS 8.23     NS 5.65     NS 5.94     NS 6.74     NS 5.52     NS 6.92     NS 6.25     NS 6.64     NS Linear trend                        7 Linear trend                           NS NQO 0.1 0.15   68 53   60.53 65.51 B[a]P 2 3   79 57   34.06 53.10 §                     6TG resistant mutants 10^6viable cells 7 days after treatment % RS             Percent relative survival adjusted by post treatment cell counts NS                 Not significant   Table 4: Experiment 2 (3-hour treatment in the absence and presence of S-9) Treatment (µg/mL) -S-9 %RS                               MF§ Treatment (µg/mL) +S-9 %RS                           MF§ 0 100 200 300 350 400 450 100 112 100 66 57 30 8        6.05 6.06     NS 3.90     NS 5.64     NS 6.91     NS 5.75     NS 6.13     NS   0 200 300 400 450 500 550 100 107 88 72 68 55 17        6.08 4.58      NS 5.27      NS 4.81      NS 4.45      NS 5.19      NS 6.87      NS         Linear trend                                           NS       Linear trend                                            NS NQO 0.1 0.15   84 73   29.20 23.62 B[a]P 2 3   73 19   42.89 65.55 §                     6TG resistant mutants/10^6viable cells 7 days after treatment % RS             Percent relative survival adjusted by post treatment cell counts NS                 Not significant

Conclusions:

Interpretation of results: negative
It is concluded that N-Methylaminoethanol (MMEA) did not induce mutation at the hprt locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. These conditions included treatments up to highly toxic concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S-9).

Executive summary:

N‑Methylaminoethanol (MMEA) was assayed for mutation at the hypoxanthine‑guanine phosphoribosyl transferase (hprt) locus (6-thioguanine [6TG] resistance) in mouse lymphoma cells using a fluctuation protocol. The study consisted of a cytotoxicity Range-Finding Experiment followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254 induced rat liver post‑mitochondrial fraction (S‑9). The test article was formulated in water for injection.

In the cytotoxicity Range-Finder Experiment, six concentrations were tested in the absence and presence of S‑9, ranging from 23.47 to 751.1 µg/mL (equivalent to 10 mM at the highest concentration tested). The highest concentration to give >10 % relative survival (RS) was 375.6 µg/mL, which gave 30 % and 45 % RS in the absence and presence of S‑9, respectively.

Accordingly, for Experiment 1 ten concentrations, ranging from 50 to 600 µg/mL in the absence of S‑9 and from 100 to 750 µg/mL in the presence of S-9, were tested. Seven days after treatment, the highest concentrations analysed to determine viability and 6TG resistance were 500 µg/mL in the absence of S‑9 and 600 µg/mL in the presence of S‑9, which gave 16 % and 7 % RS, respectively. In the presence of S-9, no concentration gave 10‑20 % RS (cultures treated at 550 and 600 µg/mL gave 26 % and 7 % RS, respectively, therefore both concentrations were analysed).

In Experiment 2 ten concentrations, ranging from 50 to 600 µg/mL in the absence of S‑9 and from 100 to 700 µg/mL in the presence of S-9, were tested. Seven days after treatment, the highest concentrations analysed to determine viability and 6TG resistance were 450 µg/mL in the absence of S‑9 and 500 µg/mL in the presence of S‑9, which gave 8 % and 17 % RS, respectively. In the absence of S-9, no concentration gave 10‑20 % RS (cultures treated at 400 and 450 µg/mL gave 30 % and 8 % RS, respectively, therefore both concentrations were analysed).

Negative (vehicle) and positive control treatments were included in each Mutation Experiment in the absence and presence of S-9. Mutant frequencies in negative control cultures fell within normal ranges and clear increases in mutation were induced by the positive control chemicals 4-nitroquinoline 1-oxide (without S-9) and benzo(a)pyrene (with S-9). Therefore the study was accepted as valid.

In Experiments 1 and 2, no statistically significant increases in mutant frequency were observed following treatment with N‑Methylaminoethanol (MMEA) at any concentration tested in the absence or presence of S‑9 and there were no linear trends. Although concentrations giving <10 % RS were analysed in the presence of S-9 in Experiment 1 and in the absence of S-9 in Experiment 2, there was no evidence of mutagenic activity at either concentration, therefore this did not affect data interpretation.

It is concluded that N‑Methylaminoethanol (MMEA) did not induce mutation at the hprt locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. These conditions included treatments up to highly toxic concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S‑9).

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no guideline study, well described publication

Principles of method if other than guideline:

no guideline followed, method is described below

GLP compliance:

not specified

Type of assay:

bacterial gene mutation assay

Target gene:

details see below

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium TA 97

Details on mammalian cell type (if applicable):

liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

none

Test concentrations with justification for top dose:

details are given below

Vehicle / solvent:

details are given below

Details on test system and experimental conditions:

All chemicals were tested under code using a preincubation modification of the Salmonellalmicrosome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.

Evaluation criteria:

An individual trial was judged mutagenic (+) if a dose-related increase over the corresponding solvent control was seen, and it was judged weakly mutagenic C+W) if a low-level dose response was seen. A trial was considered questionable (?) if a dose-related increase was judged insufficiently high to justify a call of " + W," if only a single dose was elevated over the control, or if a non-dose-related increase was seen. The distinctions between a weak mutagenic response and a mutagenic response, or between a weak mutagenic response and a questionable mutagenic response are highly subjective.
A chemical was judged to be mutagenic (+), or weakly mutagenic (+W), if it produced a reproducible, dose-related increase in his+ revertants over the corresponding solvent controls in replicate trials. A chemical was considered to be questionable (?) if a reproducible increase of hist revertants did not meet the criteria for either a " + " or " + W," or if only single doses produced an increase in his+ revertants in repeat trials. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or nonmutagenicity .

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 97

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

N-Methylethanolamine is stated to be nonmutagenic.

Conclusions:

Interpretation of results:
negative

N-Methylethanolamine is stated to be nonmutagenic.

Executive summary:

A bacterial gene mutation assay was performed with and without metabolic activation:

N-Methylethanolamine is stated to be nonmutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No study available

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the bacterial gene mutation assay MMEA was not mutagenic with and without metabolic activation (Zeiger, 1987).

In a chromosome-aberration test performed using V79 cells, MMEA did not lead to a relevant increase in the number of structural chromosomal aberrations in the absence and presence of metabolic activation (BASF AG, 2008). The types and frequencies of structural chromosome aberrations were close to the range of the concurrent negative control values at both sampling times and clearly within in the range of the historical negative control data. MMEA did also not induce mutation at the hprt locus of L5178Y mouse lymphoma cells up to highly toxic concentrations tested (BASF AG, 2010).

N-Methylethanolamine is stated to be nonmutagenic.

Justification for selection of genetic toxicity endpoint
No study is selected since all studies are negative

Justification for classification or non-classification

The classification is not warranted according to the criteria of EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations No 1272/2008.

Besides the substance is classified as:

GHS:

- Acute toxicity - oral: Cat 4, H302:harmful if swallowed

- Acute toxicity -dermal: Cat 4, H312:harmful in contact with skin.

-Skin Corr.1B, H314:causes severe skin burns and eye damage

- Eye Damage 1:H318:causes serious eye damage.

- STOT SE Cat.3, H335:may cause respiratory irritation, C>=5%

- Repro 2, H361 F/D: Suspected of damaging fertility or the unborn child <state specific effect if known> <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

and

- STOT RE Cat 2,H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>; Affected organs: other: the kidney, testes, epidymides, ovaries, liver, and spleen).