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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
Adequacy of study:
key study
Study period:
20 October 1997 to 28 October 1997
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3,5 xylenol
- Physical state: Solid (red crystals)
- Analytical purity: 99.3%
- Impurities (identity and concentrations): not stated
- Lot/batch No.: 224033
- Formulation analysis confirmed that the doses prepared were acceptable
- Storage condition of test material: Room temperature

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
Single oral administration
Frequency of treatment:
Single oral administration
Post exposure period:
24 and 48 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
375, 750 and 1500 mg/kg (24 hr) and 1500 mg/kg (48 hr)
Basis:
no data
No. of animals per sex per dose:
5 animals/dose/sex
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
Polychromatic erthyrocyte (PCE) examined for the presence of micornulcuei
PCE and noromchromatic erthyrocytes (NCE) counted as a measure of toxiciy

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
Clincial signs of toxicity, with mortality
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Table 1: Male and female combined data - 24hr time point

Dose (mg/kg)

PCE

NCE

Total

%PCE

MN PCE

0

20000

7942

27944

39.7

1.5

75

20000

7225

27228

36.1

1.0

750

20000

6986

26991

34.9

0.7

1500

20000

8175

28182

40.2

1.0

CPA 20

10000

4610

14612

46.1

11.6**

VIN 0.15

10000

4721

14721

47.2

60.9**

CPA - cyclophosphamide

VIN - Vincristine

** p<0.01

Table 2: Male and female combined data - 48hr time point

Dose (mg/kg)

PCE

NCE

Total

%PCE

MN PCE

0

20000

7968

27968

39.8

0.8

1500

16000

9474

25484

59.2

0.8

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
It is concluded that 3,5 xylenol did not induce micronuclei in the polychromatic erthrocytes of the bone marrow following sampling at 24 and 48 hours post dosing of both male and female rats when tested at a dose of 1500 mg/kg (deemed a maximum tolerated dose) under the conditions of the assay described.
Executive summary:

In a bone marrow micronucleus assay using NMRI mice, a single oral gavage of 3,5-xylenol was administered to groups of male and female animals, employing a dose volume of 10 mL/kg. Doses were selected from a pilot toxicity study doses of 1500 and 1750 mg/kg/bw were administered. Mortality was observed in at 1750mg/kg and evident signs of toxicity were observed at 1500mg/kg. The MTD was therefore deemed to be 1500 mg/kg.

 

Negative control groups were treated with vehicle only (olive oil) and positive control groups were treated with the clastogen, cyclophosphamide (CPA, 20 mg/kg bw) or the aneugen, vincristine (0.15 mg/kg). Mouse bone marrow was sampled at 24 and 48 hours after dosing for the vehicle and 3,5 xylenol dosed groups. A single sampling time of 24 hours after dosing was used for both positive control groups. Slides of bone marrow cells were prepared from five animals/sex/time point for each group and scored for the occurrence of micronucleated polychromatic erythrocytes (MN PCE) and PCE/total erythrocyte ratios.

 

Deaths (1 male and 1 female) at 1500mg/kg, 48 hr sample point were observed. Clinical signs of toxicity included irregular breathing (375mg/kg). squatting posture (750mg/kg) and piloerection and squatting (1500mg/kg). There were no marked decreases in mean PCE/total erythrocyte ratio observed for any of the 3,5 xylenol treated groups compared to the vehicle control group for either time point.

 

Analysis of the mean MN PCE group data indicated that there was no statistically significant increases MN PCE frequency compared to concurrent control values for either sex. Indiviudaul animal and group mean MN PCE frequencies were consistent with both the concurrent vehicle control values and the historical control. Positive control treatment induced the appropriate response. 

 

Formulation analysis confirmed the suitability of the doses prepared.

 

It is concluded that 3,5 xylenol did not induce micronuclei in the polychromatic erthrocytes of the bone marrow following sampling at 24 and 48 hours post dosing of both male and female rats when tested at a dose of 1500 mg/kg (deemed a maximum tolerated dose) under the conditions of the assay described.