2-Propanol, 1,1'-(tridecylimino)bis-

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: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

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

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Batch No: Batch 704/ tank 328 (ZST-Nr. 90/460)

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Tierfarm Fuellinsdorf, CH-4414 Fuellinsdorf/Basel, Switzerland
- Age at study initiation: minimum 10 weeks
- Weight at study initiation: 30 g
- Fasting period before study: 18 h
- Housing: single, Makrolon Type I, with wire mesh top (Ehret GmbH, D-7830 Emmendingen 14)
- Diet: pelleted standard diet (Altromin 1324, D-4937 Lage/Lippe)
- Water: tap water ad libitum
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Duration of treatment / exposure:

24-48-72 h

Frequency of treatment:

once

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:
212.5; 425; 850 mg/kg for 24 h; 850 mg/kg bw additionally for 48-72 h
Basis:
actual ingested

No. of animals per sex per dose:

10

Control animals:

yes

Positive control(s):

cyclophosphamide
- Route of administration: oral gavage
- Doses / concentrations: 30 mg/kg bw.

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
On the basis of pre-experiments doses below 1000 mg/kg b.w. of N-Tridecyldiisopropanolamin were estimated to be close to the maximum tolerated dose. Therefore 850 mg/kg bw were used as highest dose in the micronucleus assay.

DETAILS OF SLIDE PREPARATION:
The femora were removed, the epiphyses were cut off and the marrow was flushed out with fetal calf serum, using a 5 ml syringe. The cell suspension was centrifuged at 1,500 rpm for 10 minutes and the supernatant was discarded. A small drop of the resuspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald (Merck, D-6100 Darmstadt)/ Giemsa (Gurr, BDH limited Poole, Great Britain). Cover slips were mounted with EUKITT (Kindler, D-7800 Freiburg). At least one slide was made from each bone marrow sample.

METHOD OF ANALYSIS:
Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives. 1000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed as normochromatic erythrocytes per 1000 PCEs. The analysis was performed with coded slides.

Statistics:

Statistical significance at the five per cent level (p < 0 .05) was evaluated by means of the non-parametric Mann-Whitney test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

In a series of pre-experiments and in the main test 850 mg/kg b.w. caused toxic reactions including mortality (2/18 females in the pre-test and 2/15 females in the main test)

Vehicle controls validity:

not specified

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Test group	dose mg/kg bw.	sampling time (h)	PECs with MN (%)	PCE/NCE
Suspending agent	0	24	0.11	1000/806
Test article	212.5	24	0.12	1000/859
Test article	425	24	0.13	1000/809
Test article	850	24	0.15	1000/702
Cyclophosphamide	30	24	2.13	1000/725
Suspending agent	0	48	0.07	1000/827
Test article	850	48	0.07	1000/817
Suspending agent	0	72	0.08	1000/787
Test article	850	72	0.13	1000/763

PCE= polychromatic erythrocytes

NCE = normochromatic erythrocytes

MN = micronuclei