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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
yes
Remarks:
(only two dose levels were applied)
GLP compliance:
no
Type of assay:
rodent dominant lethal assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Bumetrizole
EC Number:
223-445-4
EC Name:
Bumetrizole
Cas Number:
3896-11-5
Molecular formula:
C17 H18 Cl N3 O
IUPAC Name:
2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol
Test material form:
solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK10048
- Lot/batch No.: EN 26580(1/75)

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.0
- Humidity (%): 50 ± 5
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
- Amount of vehicle: 0.2 mL/10 g bw
Duration of treatment / exposure:
Single dose application
Frequency of treatment:
Single dose
Post exposure period:
Males: 6 weeks
Females (not exposed): day 0 of gestation (vaginal plug); sacrificed on day 14 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Dose / conc.:
3 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
20 males
40 females
Control animals:
yes, concurrent vehicle
Positive control(s):
No positive controls were used in this particular study. However, the same laboratory that conducted this study also conducted studies on positive control substances at the same facility using the same strain of mice. The results of these tests have been published (see, for example, Fritz H et al (1973) Agents and Actions, 3, 35). This study clearly demonstrates that dominal lethal effects can be chemically induced in NMRI mice.

Examinations

Tissues and cell types examined:
Number of live embryos and embryonic resorptions/deaths
Statistics:
Total number of implantations - the t-test or Mann-Whitney's U-test
Total numbers of mated and pregnant dams or embryonic deaths - x squared test or Fisher's exact test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not specified

Any other information on results incl. tables

No evidence of dominant lethal effect was observed in the progeny of male mice treated with the test substance.

Table 1: Dominant lethal assay results

Dose Group

(mg/kg)

No. females mated*

No. of pregnant females

No. of implantations

Live embryos

Embryonic deaths

Total

%

Total

%

Total

Mean

SD

Total

%

Total

%

Mating Period I

0

38

95.0

36

94.7

408

11.33

3.80

365

89.5

43

10.5

1000

39

97.5

34

87.2

391

11.50

4.32

370

94.6

21

5.4

3000

33

82.5

21

63.6

230

10.95

3.90

213

92.6

17

7.4

Mating Period II

0

37

92.5

34

91.9

399

11.74

4.19

373

93.5

26

6.5

1000

40

100

36

90.0

481

13.36

2.32

455

94.6

26

5.4

3000

38

95.0

30

78.9

383

12.77

3.18

352

91.9

31

8.1

Mating Period III

0

40

100

34

85.0

413

12.15

3.11

388

94.0

25

6.0

1000

39

97.5

33

84.6

434

13.15

1.73

414

95.4

20

4.6

3000

40

100

32

80.0

373

11.66

2.62

358

96.0

15

4.0

Mating Period IV

0

38

95.0

30

78.9

388

12.93

1.53

357

92.0

31

8.0

1000

37

94.9

34

91.9

455

13.38

1.39

433

95.2

22

4.8

3000

35

87.5

30

85.7

384

12.80

1.67

354

92.2

30

7.8

Mating Period V

0

36

90.0

33

91.7

390

11.82

2.56

371

95.1

19

4.9

1000

38

95.0

34

89.5

442

13.00

1.74

415

93.9

27

6.1

3000

34

85.0

31

91.2

388

12.52

1.52

358

92.3

30

7.7

Mating Period VI

0

36

90.0

29

80.6

364

12.55

2.89

344

94.5

20

5.5

1000

36

90.0

32

88.9

400

12.50

1.97

371

92.8

29

7.2

3000

39

97.5

31

79.5

363

11.71

2.75

333

91.7

30

8.3

Cumulative control

328

-

281

85.7

3242

11.54

2.58

2998

92.5

244

7.5

* 40 females/group

Applicant's summary and conclusion

Conclusions:
In conclusion, in the present study the test substance did not induce chromosome aberrations and thus, is considered to be non-clastogenic.