Sodium 5-N-butylbenzotriazole

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

Study period:

11.09.1990 - 5.10.1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 5-N-butylbenzotriazole

EC Number:

404-450-2

EC Name:

Sodium 5-N-butylbenzotriazole

Cas Number:

118685-34-0

Molecular formula:

CCCCc1ccc2c(c1)nnn2[Na]

IUPAC Name:

sodium 5-butyl-1H-1,2,3-benzotriazol-1-ide

Test material form:

solid: particulate/powder

Details on test material:

Identity: cobratec 435
Batch number: HRC 20.3.89/2
Purity: 85-90%
Description: Brown solid
Storage: room temperature under ambient lighting conditions
Stability: Stability of the test compound and of the test compound in the vehicle were not determined in this test, though information from the Sponsor indicates Cobratec 435 is stable in water.

Test animals

Species:

mouse

Strain:

CD-1

Details on species / strain selection:

Specific Pathogen Free CD-1 outbred mice of Swiss origin

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent, England
- Age at study initiation: approximately 35 days old
- Weight at study initiation: Between 22 g and 24 g
- Assigned to test groups randomly: Yes
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

Negative control: 3 sampling times being 24, 48 or 72 hours after dosing.
Positive control: 3 sampling times being 24 hours after dosing.

Doses / concentrations

Remarks:

Doses / Concentrations:

Basis:
nominal in diet
All animals in all groups were dosed with the standard volume of 20 ml/kg bodyweight.)

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

bone marrow smears

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

It is concluded from the results obtained that Cobratec 435 shows no evidence of mutagenic potential or bone marrow cell toxicity when administered as a single oral dose in this in vivo test procedure.

Executive summary:

1. In this assessment of the effect of Cobratec 435 on the incídence of micronucleated polychromatic erythrocytes in mice, a dosage of 600 mg/kg bodyweight was administered as a single oral dose by intragastric gavage. (A preliminary toxicity test had indicated that the maximum tolerable dosage of Cobratec 435 was approxÍmately 600 mg/kg).

2. Negative and positive control groups were dosed in an identical manner, orally by intragastric gavage. The negative control group received the vehicle, distilled water. The positive control group was treated with mitomycin C, at 12 mg/kg bodyweight.

3. Bone marrow smears were obtained from the negative control and test compound groups at 3 sampling times; these being 24,48 or 72 hours after dosing. Bone marrow smears were obtained from the positive control group 24 hours after dosing. One smear from each animal was examined for the presence of micronuclei in 1000 polychromatic erythrocytes. The ratio of polychromatic to normochromatic erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal. A record of the incidence of micronucleated normochromatic erythrocytes was also kept.

4. At all sampling times, mice treated with Cobratec 435 did not show any significant increase in the frequency of micronucleated polychromatic erythrocytes.

5. There was no significant decrease in the ratio of polychromatic to normochromatic erythrocytes after treatment of the animals with

Cobratec 435.

6. The positive control compound, mitomycin C, produced large, highly signifícant increases in the frequency of micronucleated polychromatic erythrocytes together with decreases in the ratio of polychromatic to normochromatic erythrocytes.