4,5-dihydroxy-1,3-dimethylimidazolidin-2-one

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:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

21.09.-14.10.1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study (GLP)

Remarks:

Read-across

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4,5-dihydroxy-1,3-bis(hydroxymethyl)imidazolidin-2-one

EC Number:

217-451-6

EC Name:

4,5-dihydroxy-1,3-bis(hydroxymethyl)imidazolidin-2-one

Cas Number:

1854-26-8

Molecular formula:

C5H10N2O5

IUPAC Name:

4,5-dihydroxy-1,3-bis(hydroxymethyl)imidazolidin-2-one

Details on test material:

- Name of the test substance used in the study report: Dimethyloldihydroxyethylenhamstoff (BASF-Handelsprodukt : "Fixapret CP konz .")
- CAS number (as cited in study report): 1854-26-8
- Physical state: liquid
- Analytical purity: 73%
- Lot/batch No.: 682
- Storage condition of test material: at 5°C >= 21 d

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa. Mollegaard, Germany
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 20-27g
- Assigned to test groups randomly: no
- Housing: Macrolon Typ 3
- Diet (e.g. ad libitum): Altromin Nr . N 1326, ad libitum
- Water (e.g. ad libitum): drinking water
- Acclimation period: 4 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 55+-10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
3 days before application.
0.1 ml solution was applicated to 10 g body weight.

Frequency of treatment:

single application

Post exposure period:

24 h (additionally 48 h in the 2000 mg/kg treatment)

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw/day (nominal)

Remarks:

As 73 % solution in water

Doses / concentrations 2

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Remarks:

As 73 % solution in water

Doses / concentrations 3

Dose / conc.:

2 000 mg/kg bw/day (nominal)

Remarks:

As 73 % solution in water

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Route of administration: oral
- Doses / concentrations: 20/80 mg/kg b.w. (24 hrs post exposure period)

Examinations

Tissues and cell types examined:

bone marrow of the femora; 2000 polychromatic erythrocytes per animal were studied for the presence of micronucleus.

Evaluation criteria:

Micronucleus
- are round, oval or crescent-shaped
- have a precise contour
Application of high doses of clastogenic substances can cause the appearence of several almond- or ring-shaped micronuclei.
- are uniformly coloured
- have a diameter of approximately 1/20 to 1/5 of an erythrocyt
- Es ist meistens nur ein Mikrokem vorhanden .
- Nach Behandlung mit hohen Dosen von Substanzen, die Chromosomenbrüche erzeugen, können
bei einigen Erythrozyten auch mehrere Mikrokeme auftreten, die auch mandelförmig oder ringförmig
sein können

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Substance	Dose (mg/kg)	Sex	post exposure period (h)	PCE with micronuclei	total number of PCE	Ratio PCE/NCE
vehicle	solvent	male	24	0.30	6.0	0.97
		female	24	0.34	6.8	0.96
test substance	500	male	24	0.31	6.2	0.99
		female	24	0.27	5.4	0.98
test substance	1000	male	24	0.36	7.2	1.02*
		female	24	0.32	6.4	1.00
test substance	2000	male	24	0.24	4.8	0.95
		female	24	0.26	5.2	0.97
test substance	2000	male	48	0.37	7.4	0.99
		female	48	0.33	6.6	0.99
positive ctrl	80	male	24	2.01	40.2	0.69
		female	24	1.90	38.2	0.69
positive ctrl	20	male	24	0.86	17.4	0.76
		female	24	0.82	16.4	0.86
	PCE = polychromatic erythrocyts (2000 were scored for micronuclei)
	NCE = normochromatic erythrocyts
	The NCE/PCE ratio (as an indicator of cytotoxicity) is based on the scoring of 1000 erythrocyts
	* = significantly different from the control, but within historical control data (0.6 to 1.2)