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Toxicological information

Genetic toxicity: in vivo

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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: The study was conducted according to the O.E.C.D. test guideline 474 (1981) with GLP compliance.

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)
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropyl o-tolyl ether
EC Number:
218-645-3
EC Name:
2,3-epoxypropyl o-tolyl ether
Cas Number:
2210-79-9
Molecular formula:
C10H12O2
IUPAC Name:
2-[(2-methylphenoxy)methyl]oxirane
Constituent 2
Reference substance name:
Oxirane, 2-[(2-methylphenoxy)methyl]-
IUPAC Name:
Oxirane, 2-[(2-methylphenoxy)methyl]-
Details on test material:
As per IUCLID Sections 1.1. 1.2. and 4.1.

Test animals

Species:
mouse
Strain:
other: BKW
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female albino BKW strain mice were supplied by Bantin & Kingman Ltd., Grimston, Aldborough, Hull4 U.K. At the start of the study the males weighed 24 - 30gm, and the females 22 - 28 gm, and were approximately five to eight weeks old. After a minimum acclimatisation period of five days the animals were placed on-study.

The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of a 3 - 4 hr fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.

The animal room was maintained at a temperature of 22 - 24°C and relative humidity of 42 - 67 %. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Arachis oil for the test substance and the positive control.
Details on exposure:
All animals on-study were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Duration of treatment / exposure:
As per the O.E.C.D. test guideline 474 (1981) the duration of treatment before sacrifice was, 24, 48 and 72 hr.
Frequency of treatment:
Once
Post exposure period:
None
Doses / concentrations
Remarks:
Doses / Concentrations:
2000 mg/Kg of body weight, the maximum tolerated dose.
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide in arachis oil at 50 mg/Kg of body weight.

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
Immediately following sacrifice (i.e. 24, 48 or 72 hours following dosing), one femur was dissected from each animal, aspirated with foetal calf serum and bone marrow smears prepared following centrifugation and re-suspension. The smears were air-dried, fixed in absolute methanol, and stained in May-Grunwald/Giemsa.
Evaluation criteria:
Stained bone marrow smears were examined at random using light microscopy at x 1000 magnification. The incidence of micronucleated cells per 1000 polychromatic erythrocytes PCE (blue stained immature cells) per animal was scored. In addition, the number of normochromatic erythrocytes NCE (pink stained mature cells) associated with 1000 polychromatic erythrocytes were counted; these cells were also scored for incidence of micronuclei.
Statistics:
When necessary, all data were statistically analysed using appropriate statistical methods as recommended by the UKEMS sub-committee on guidelines for mutagenicity testing, Report, part III (1989).

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
based on clinical signs.
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
There was no significant increase in the frequency of micronucleated PCE’s in any of the test material treatment groups when compared to their concurrent vehicle control groups. There was no significant change in the NCE/PCE ratio in any of the test material treatment groups when compared to their concurrent vehicle control groups. This suggests that the test substance may have not reached the target organ bone marrow.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test substance did not induce evidence of chromosome damage in the bone marrow of treated mice under the conditions of the study. The test substance did not induce evidence of cytotoxicity to the bone marrow.
Executive summary:

The test substance, 2,3-epoxypropyl o-tolyl ether was accessed for the potentical to cause chromosome damage in an O.E.C.D. test guideline no. 474 mouse micronucleus test at a single oral dose level of 2000 mg/Kg of body weight. The test substance did not induce evidence of chromosome damage in the bone marrow of treated mice under the conditions of the study. The test substance did not induce evidence of cytotoxicity to the bone marrow.