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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study with acceptable restrictions (partly limited documentation, e.g. no details about the test substance)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1974
Report date:
1974
Reference Type:
publication
Title:
Study on the mutagenic effects of formamides and acetamides in the dominant lethal test
Author:
Peh J
Year:
1974
Bibliographic source:
Chromosome aberrations by industrial chemicals and vinyl chioride toxicity. Proceedings of 2nd International Symposium, Milano

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
no
GLP compliance:
no
Type of assay:
rodent dominant lethal assay

Test material

Constituent 1
Reference substance name:
monomethylformamide
IUPAC Name:
monomethylformamide
Details on test material:
no details

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male
Details on test animals or test system and environmental conditions:
Source: Wiga, Sulzfeld, Germany
Mean body weight at initiation: 31 g;
initial age: 12-14 weeks
single cages except during mating (1 male with 3 virgin females)
Housing condition:
temperature 20-24°C
rel. air humidity: 50-60%
light/dark cycle: 12/12h

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Details on exposure:
Dose: 1/5 of the LD50 in male mice
Application volume: 0.1 ml per mouse
Duration of treatment / exposure:
single application
Frequency of treatment:
single application
Post exposure period:
8 weeks for treated males
Doses / concentrations
Remarks:
Doses / Concentrations:
560 mg/kg bw
Basis:

No. of animals per sex per dose:
20 males per group
Control animals:
yes, concurrent no treatment
Positive control(s):
0.125 mg/kg bw Trenimon®

Examinations

Tissues and cell types examined:
Each treated male mice mated with 3 virgin females for 1 week; this procedure was repeated with further virgin females for 7 weeks (totally 8 matings in 8 weeks); each female was sacrificed at day 18 after initiation of mating.
Determined parameters
Number of pregnant dams (conception rate)
total number of implantations
living fetuses
dead fetuses
early resorptions
late resorptions
Mutation index: dead fetuses + early resorptions + late resoptions/total implantations
Evaluation criteria:
Statistically significant increase of mutation rate/index in the treated group.
Statistics:
Level of significance: p<=0.05

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Conception rate in females of the 1st and 2nd week was reduced; this effects was considered to be related to the toxic effects in males; conception rate not altered in week 3-8.
Mean number of implantations was not affected in the treatment group.
Slight but significant increase in mutation index in week 3 but still within the historical control range. In the positive control the mutation index was significantly increased in week 1 -3.

Effects in treated males
General condition of treated males was reduced, 6 males died the day after injection; reduced body weight in the 1st week after treatment, normal thereafter. Necropsy of dead males: intestinal atony, liver congestion; no effects in survivors.
No symptoms in positive control.

Any other information on results incl. tables

Mutations in the dominant lethal assay in mice after i.p. injection of N-methylformamide (NMF)

Specified group

Mutation index in week

1

2

3

4

5

6

7

8

Untreated control

11.5

9.8

9.4

13.0

11.2

13.2

7.7

9.2

Positive control

40.5*

46.1*

26.5*

6.9

6.1

9.2

11.3

8.8

NMF treated

13.2

8.1

15.4*

8.9

9.3

12.7

8.3

8.6

*: significant

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No germ cell mutation was detected in the mouse dominant lethal test at toxic dose levels.
Executive summary:

Comparable to Guideline study with acceptable restrictions (partly limited documentation, e.g. no details about the test substance; no vehicle control but untreated control).

In the dominant lethal assay 20 male NMRI mice received a single i.p. injection of 560 mg/kg bw. Treated males, concurrent untreated and positive controls were mated with virgin females (1 male/3 females) the week after treatment; mating for one week with further females was repeated for 7 weeks (totally 8 matings for each male). Females were sacrificed day18 after mating initiation; conception rate and mutation index (dead fetuses and all resorptions per total number of implantations) were determined. The conception rate was reduced in week 1 and 2 in the treatment group due to toxic effects (6/20 males were found dead). However, no effects were detected on the mutation index. The positive control was valid.

Conclusion: No germ cell mutation was detected in the mouse dominant lethal test at toxic dose levels.

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