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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:
1978-07-10 - 1978-09-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
yes
Remarks:
Two doses tested. No positive control.
Principles of method if other than guideline:
The test material was administered orally in single doses to male albino mice (Tif: MAG f [SPF]) which were then mated to untreated females from the same strain over a period of six weeks. At the end of each week the females were replaced by new ones. Doses of 1000 and 3000 mg/kg were given. The experiment was done to evaluate any cytotoxic or mutagenic effects on the male germinal cells as expressed by the loss of pre-implantation zygotes as well as by the rate of deaths of post-implantation stages of embryonic development.
GLP compliance:
no
Type of assay:
rodent dominant lethal assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Substance type: organic
- Physical state: solid

Test animals

Species:
mouse
Strain:
other: Tif: MAG f [SPF]
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: closed SPF breeding colony
- Age at study initiation: about 2 ½ - 6 months
- Diet: Standard diet: NAFAG No. 890
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Humidity (%): 60 ± 5
- Photoperiod (hrs dark / hrs light): 14 / 10

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose) and water
- Concentration of test material in vehicle: 1000 and 3000 mg/kg in 0.2 mL vehicle /10 g bw
- Amount of vehicle (if gavage or dermal): 0.2 mL/g bw
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The compound was administered orally by intubation in single doses of 1000 and 3000 mg/kg to each 20 males. An aqueous solution of carboxymethylcellulose served as the vehicle (0.2 mL/10 g of body weight). The control group was treated with the vehicle only. The females remained untreated.
Duration of treatment / exposure:
single dose
Frequency of treatment:
once
Post exposure period:
6 w
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 each of which was placed in a cage with 2 untreated females immediately after treatment. At the end of 1 week, the females were removed and replaced by another group of 2 females.
Control animals:
yes, concurrent vehicle
Positive control(s):
none

Examinations

Tissues and cell types examined:
The first week after administration of the drug general condition and symptomatology were checked on the males.
Statistics:
To compare the totals of the number of implantations - indicating possible pre-implantation losses - Student's t test or Mann-Whitney' U-test was used. The totals of the numbers of mated and pregnant dams or embryonic deaths were compared with the aid of the x^2-test or Fisher's exact test. Whenever necessary, a test on the heterogeneity of the material was performed. Experimental data, particularly on the numbers of implantations and early embryonic deaths were compared with "spontaneous data" of a cumulative of untreated controls observed over a longer period of time (autopsy on day 18 of pregnancy).

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined
Additional information on results:
The data on mating ratio, on the numbers of implantations, and embryonic deaths are comparable for all groups.

Any other information on results incl. tables

SUMMARY OF RESULTS

Number of females mated  number of females with deciduomata only number of females pregnant number of implantations Live embryos Embryonic death
Dose group (mg/kg) Number of females total % total % total % total average SD total % total %
Mating 1 0 40 31 77.5 0 0 27 87.1 253 9.37 2.31 228 90.1 25 9.9
1000 40 38 95 1 2.6 34 89.5 322 9.47 3.13 298 92.5 24 7.5
3000 40 34 85 0 0 29 85.3 295 10.17 2.61 264 89.5 31 10.5
Mating 2 0 38 34 89.5 0 0 27 79.4 288 10.67 2.67 258 89.6 30 10.4
1000 40 37 92.5 0 0 34 91.9 326 9.59 3.08 297 91.1 29 8.9
3000 40 31 77.5 0 0 28 90.3 269 9.61 2.33 238 88.5 31 11.5
Mating 3 0 38 35 92.1 1 2.9 32 31.4 343 10.72 1.69 304 88.6 39 11.4
1000 40 39 97.5 0 0 34 87.2 341 10.03 1.96 315 92.4 26 7.6
3000 40 32 80 0 0 28 87.5 268 9.57 3.07 248 92.5 20 7.5
Mating 4 0 38 33 68.8 0 0 27 81.8 280 10.37 3.01 267 95.4 13 4.6
1000 40 37 92.5 0 0 35 94.6 354 10.11 2.26 325 91.8 29 8.2
3000 40 31 77.5 0 0 29 93.5 294 10.14 1.83 263 89.5 31 10.5
Mating 5 0 38 31 81.6 0 0 28 90.3 288 10.29 1.88 264 91.7 24 8.3
1000 40 36 90 0 0 28 77.8 292 10.43 2.56 275 94.2 17 5.8
3000 40 32 80 0 0 28 87.5 305 10.89 1.69 285 93.4 20 6.6
Mating 6 0 38 31 81.6 1 3.2 26 83.9 282 10.85 2.74 258 91.5 24 8.5
1000 40 35 87.5 0 0 31 88.6 346 11.16 2.34 315 91 31 9
3000 40 31 77.5 0 0 23 74.2 252 10.96 1.99 231 91.7 21 8.3
Cumulative control 450 4 0.9 378 84 4062 10.77 2.29 3717 91.5 345 8.5

Applicant's summary and conclusion

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