2,2'-methyliminodiethanol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

Method according to Schmid (1975) and McGregor (1980)

GLP compliance:

not specified

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-methyliminodiethanol

EC Number:

203-312-7

EC Name:

2,2'-methyliminodiethanol

Cas Number:

105-59-9

Molecular formula:

C5H13NO2

IUPAC Name:

2-[(2-hydroxyethyl)(methyl)amino]ethan-1-ol

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6-8 weeks

Administration / exposure

Route of administration:

intraperitoneal

Duration of treatment / exposure:

single application

Frequency of treatment:

once

Post exposure period:

30, 48 and 72 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

175 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

350 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

560 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Route of administration: i.p.
- Doses / concentrations: 0.3 mg/kg
- 30 h post dosing

Examinations

Tissues and cell types examined:

peripheral blood erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
based on pretest: about 80, 50 and 25 % of the LD50

DETAILS OF SLIDE PREPARATION:
Slides of blood smears were stained with Gurr's R-66 Giemsa diluted in phosphate buffer, coded and read without knowledge of treatment group to prevent bias.

METHOD OF ANALYSIS:
The polychromatic/normochromatic erythrocyte ratio for approximately 1000 total cells for each animal was calculated to provide an estimate of cytotoxicity.

Evaluation criteria:

A positive result was concluded if at least one statistical significant increase above vehicle control was an indication of a dose-related effect.

Statistics:

Data were compared for significant differences using the Fisher's Exact Test.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

There were no significant differences in the polychromatic erythrocyte to normochromatic erythrocyte ratios at any dosage. Furthermore, no significant increases in the incidence of micronucleated polychromatic erythrocyte were observed at any sampling time. Therefore, MDEA is not considered to be inducer of micronuclei under the condition of this in vivo test.

Any other information on results incl. tables

Induction of micronucleus in peripheral erythrocytes:

Sex	Mean PCE/1000 NCE (±SD)
	Water	TEM	MDEA (mg/kg)
			175	350	560
30 h postdosing
Male	52±24	36±8	55±17	64±11	70±12
Female	35±10	36±9	41±8	48±9	41±14
48 h postdosing
Male	43±13		45±17	43±12	36±4
Female	31±6		34±18	32±12	38±4
72 h postdosing
Male	39±7		38±12	36±14	32±14
Female	32±9		31±11	39±9	24±7

Sex	Mean MN-PCE/1000 NCE (±SD)
	Water	TEM	MDEA (mg/kg)
			175	350	560
30 h postdosing
Male	5.4±3.2	42.0±8^b	4.8±2.4	6.6±2.9	4.8±3.5
Female	2.6±1.7	43±15 ^b	4.2±2.8	3.0±0.7	1.6±1.5
48 h postdosing
Male	3.8±3.1		4.2±2.8	5.0±4.4	3.0±2.0
Female	2.4±1.5		3.8±2.4	2.2±1.3	2.6±2.7
72 h postdosing
Male	5.0±2.0		2.6±2.1	7.0±5.6	2.7±1.2
Female	3.2±1.1		2.2±1.3	3.0±2.8	2.8±1.9

There were no significant differences in the polychromatic erythrocyte to normochromatic erythrocyte ratios at any dosage. Furthermore, no significant increases in the incidence of micronucleated polychromatic erythrocyte were observed at any sampling time. Therefore, MDEA is not considered to be inducer of micronuclei under the condition of this in vivo test.