Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1978-07-10, 1978-09-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on a positive control are available. Only two dose levels were tested (OECD478: normally three).

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4,4-Dioctyldiphenylamine
- Substance type: organic
- Physical state: beige powder

Test animals

Species:
mouse
Strain:
CD-1
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:
5 consecutive days
Frequency of treatment:
5 times
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.2 g/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
0.67 g/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
2.0 g/kg
Basis:
actual ingested
No. of animals per sex per dose:
10
Control animals:
yes
Positive control(s):
none

Examinations

Tissues and cell types examined:
The number of dead and living implants and total implementation sites were recorded standardized.
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 χ2-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:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The data on mating ratio, on the numbers of implantations, and embryonic deaths are comparable for all groups.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
There was no evidence of postimplementation loss under test conditions. The substance is therefore considered negative in this test.