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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
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: all criteria are fulfilled for a high quality study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 483 (Mammalian Spermatogonial Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian germ cell cytogenetic assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
TK 10622 (Araldite PT 810, TGIC, 97%)
Purity: 97%, TGIC (technical grade, batch-no. 144727)

Test animals

Species:
mouse
Strain:
other: strain B6D2F1
Sex:
male
Details on test animals and environmental conditions:
Young adult male B6D2F1 mice were housed in groups of 3 in polypropylene cages with solid floors with saft wood beddings; water and food was available ad libitum, they were kept at a 12-hour dark/light cycle with 20 air changes/hour in the animal rooms at a temperature of 18-24 °C, and a relative humidity of 46-66 %. Acclimatization was 18 days, and the age was 82 days at treatment start (weight 27-31 gm).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
0.5% carbocymethylcellulose in water
Details on exposure:
Male mice were exposed orally (gavage) to TGIC (technical grade, 97%, batch-no. 144727) in 0.5% CMC (aqueous solution) on 5 consecutive days
Duration of treatment / exposure:
immediate (seconds) for gavaging
Frequency of treatment:
once on 5 consecutive days
Post exposure period:
24 h
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 28.75, 57.5, and 115 mg/kg
Basis:
analytical conc.
No. of animals per sex per dose:
5 males
Control animals:
yes, concurrent vehicle
Positive control(s):
yes, group 0.3 mg/kg mitomycin C (single dose, intra-peritoneally

Examinations

Tissues and cell types examined:
testes were dissected and seminiferous tubules were excised and spermatogonial cells prepared for slides.
Details of tissue and slide preparation:
Standard procedure with Giemsa staining
Evaluation criteria:
as outlined in the guideline
Statistics:
none

Results and discussion

Test results
Sex:
male
Genotoxicity:
positive
Remarks:
increase in major chromosomal aberrations
Toxicity:
yes
Remarks:
change of cytotoxic ratio
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
The cytotoxic ratio changed from 2.95 (control) to 0.48 (high dose group).
No significant differences in body weight were observed during the 5-day treatment period.
A significant increase in major chromosomal aberrations (without gaps) occurred in high dose and low dose group, as well as in the mitomycin C group (positive control).
The number of gaps was also increased in the same dose groups. Although, the intermediate dose group showed fewer major aberrations, but several chromatid exchanges which were not found in the negative control group

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
It is concluded that TGIC caused a mutagenic effect in mouse spermatogonial cells upon oral exposure.
Executive summary:

1)     The cytotoxic ratio changed from 2.95 (control) to 0.48 (high dose group).

2)     No significant differences in body weight were observed during the 5-day treatment period.

3)     A significant increase in major chromosomal aberrations (without gaps) occurred in high dose and low dose group, as well as in the mitomycin C group (positive control).

4)     The number of gaps was also increased in the same dose groups. Although, the intermediate dose group showed fewer major aberrations, but several chromatid exchanges which were not found in the negative control group

It is concluded that TGIC caused a mutagenic effect in mouse spermatogonial cells upon oral exposure