Bumetrizole

Genetic toxicity: in vivo

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Doses / concentrations 2

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.