2,2'-iminodiethanol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study which meets scientific principles

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1992

Reference 2

Reference Type:

publication

Title:

Micronucleated erythrocyte frequency in peripheral blood of B6C3F1 mice from short-term, prechronic and chronic studies of the NTP carcinogenesis bioassay program

Author:

Witt KL, et al.

Year:

2000

Bibliographic source:

Environmental Molecular Mutagenesis, 36, 163-194

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:

Micronucleus assay on peripheral blood lymphocytes

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-iminodiethanol

EC Number:

203-868-0

EC Name:

2,2'-iminodiethanol

Cas Number:

111-42-2

Molecular formula:

C4H11NO2

IUPAC Name:

2,2'-iminodiethanol

Details on test material:

- Name of test material (as cited in study report): Diethanolamine
- Physical state: liquid, colorless to pale yellowish
- Analytical purity: >99% (GC)
- Storage condition of test material: room temperature, protected from light
- Source: Kodak Laboratory and Specialty Chemicals (Rochester, NY, USA)

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Taconic Farms, Germantown, NY,  USA
- Age at study initiation: about 5-6 weeks
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 12-13 day

Administration / exposure

Route of administration:

dermal

Vehicle:

- Vehicle(s)/solvent(s) used: ethanol

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily on working days (5 days/week)

Post exposure period:

none

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
37.5, 75, 150, 300, and 600 mg/ml
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
80, 160, 320, 630, 1250 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

10 males and 10 females

Control animals:

yes, concurrent vehicle

Positive control(s):

urethane
- Route of administration: drinking water
- Doses / concentrations: 0.2%

Examinations

Details of tissue and slide preparation:

Smears were prepared from peripheral blood samples obtained by cardiac puncture of dosed and control animals at the termination of the 13-week  
study. Smears were immediately prepared and fixed in absolute methanol.  The methanol-fixed slides were stained with Hoechst 33258/pyronin Y  
(MacGregor et al., 1983) and coded. Slides were scanned to determine the  frequency of micronuclei in 10,000 normochromatic erythrocytes (NCEs) 
in  up to 10 male and 10 female mice per dose group.

Statistics:

Log transformation of NCE data, testing for normality by the Shapiro-Wilk  test, and testing for heterogeneity of variance by Cochran's test. The frequency of micronucleated cells among NCEs was analyzed by analysis  of variance with the SAS GLM procedure. The NCE data for each dosed group  were compared with the concurrent solvent control group by Student's  t-test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

local and systemic signs of toxicity down to the lowest dose level tested

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

The test substance did not induce micronuclei in peripheral blood erythrocytes of mice exposed dermally to concentrations of up to 1250 mg/kg bw for 13 weeks.
The sensitivity of the test system was verified since the positive control substance showed the expected positive reactions.

Any other information on results incl. tables

Results summary:

The test substance did not induce micronuclei in peripheral blood erythrocytes of mice exposed dermally to concentrations of up to 1250 mg/kg bw for 13 weeks.

The sensitivity of the test system was verified since the positive control substance showed the expected positive reactions.

Detailed results:

Peripheral Blood

Study ID	Result		Route
	Male	Female
A08796	Negative	Negative	Skin Paint

A08796 - 1

Start Date	Sample Collection Time	Sex	Cell	Dosing Regimen	Trend Test P-Value
01/02/1990	24 Hours	Male	NCE	SKIN x 65, 90 Days	1.000
		Dose (mg/kg)	No. of Animals Scored	Mean MN-NCE/1000 NCE ± SEM	Pairwise P
Vehicle Control:	Ethanol	0	10	1.36 ± 0.15
Test Chemical:	Diethanolamine	80	10	1.38 ± 0.17	0.465
		160	9	1.44 ± 0.13	0.370
		320	9	1.09 ± 0.13	0.901
		630	10	1.06 ± 0.16	0.933
		1250	8	0.81 ± 0.10	0.997
Positive Control:	Urethane	0.2	3	18.62 ± 2.43	0.0001

A08796 - 2

Start Date	Sample Collection Time	Sex	Cell	Dosing Regimen	Trend Test P-Value
01/03/1990	24 Hours	Female	NCE	SKIN x 65, 90 Days	0.847
		Dose (mg/kg)	No. of Animals Scored	Mean MN-NCE/1000 NCE ± SEM	Pairwise P
Vehicle Control:	Ethanol	0	10	0.82 ± 0.11
Test Chemical:	Diethanolamine	80	10	0.79 ± 0.08	0.600
		160	10	0.81 ± 0.07	0.554
		320	10	0.73 ± 0.06	0.766
		630	10	0.71 ± 0.12	0.822
		1250	5	0.71 ± 0.14	0.776