Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1974-05-01 to 1975-10-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test substance was evaluated in a rodent dominant lethal test using methods comparable to OECD Test Guideline 478. A repeat-dose treatment regimen (once daily for 5 days) was used; however, justification for this treatment regimen was not provided in the study report. Also, the age and weight of the test animals were not specified in the study report, and housing and feeding conditions of the animals were not reported. The source, purity and other characteristics of the test substance were not reported. A positive control was not concurrently run in the study. Observations of the animals during the experiment, including signs of toxicity, were not reported. The results did not include individual animal data for each mating (i.e., identity of each male and female mated). The mating interval, dose level for males, and the numbers of live implants and dead implants were not reported for each female; only summary results for each dose group were reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
Deviations:
yes
Remarks:
See rationale for reliability above.
Principles of method if other than guideline:
N/A
GLP compliance:
no
Remarks:
N/A
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): UDX-7577 (dodecyl dimethyl amine oxide)
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): 235.7
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): N/A
- Substance type: Active
- Physical state: N/A

Test animals

Species:
mouse
Strain:
other: C3D2F1/J
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Jackson Labs in Bar Harbor, Maine
- Age at study initiation: sexually mature
- Weight at study initiation: N/A
- Assigned to test groups randomly: yes; no data provided in the study on the randomization procedure
- Fasting period before study: N/A
- Housing: N/A
- Diet (e.g. ad libitum): N/A
- Water (e.g. ad libitum): N/A
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): N/A
- Humidity (%): N/A
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): N/A


IN-LIFE DATES: From: N/A To: N/A

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: N/A
- Concentration of test material in vehicle: N/A
- Amount of vehicle (if gavage or dermal): N/A
- Type and concentration of dispersant aid (if powder): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: N/A


DIET PREPARATION
- Rate of preparation of diet (frequency): N/A
- Mixing appropriate amounts with (Type of food): N/A
- Storage temperature of food: N/A
Duration of treatment / exposure:
The animals were administered the test substance for five consecutive days.
Frequency of treatment:
daily
Post exposure period:
N/A
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 100, and 1000 mg DDAO/kg BW
Basis:
other: No data was provided on whether the oral dose was through gavage, diet or drinking water.
No. of animals per sex per dose:
20
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle
Positive control(s):
none
- Justification for choice of positive control(s): N/A
- Route of administration: N/A
- Doses / concentrations:N/A

Examinations

Tissues and cell types examined:
Total implantations, resorptions, and dead embryos were enumerated and recorded.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: N/A


TREATMENT AND SAMPLING TIMES (in addition to information in specific fields): Immediately after the males received their final treatment, each male was caged separately with two untreated virgin female mice of the same strain for a period of seven days. This mating procedure was continued weekly for an additional six weeks, thus encompassing the entire spermatogenic cycle of the mouse.
On day 13 or 14 of pregnancy (as measured from the mid-week of presumptive mating), the females were sacrificed. Total implantations, resorptions, and dead embryos were enumerated and recorded.


DETAILS OF SLIDE PREPARATION: N/A


METHOD OF ANALYSIS: The mutagenic potential of the test substance was detected using the following criteria: 1) increase in the frequency of dead implantations, 2) reduction in average number of living embryos, 3) reduction in average number of implantations, and 4) a reduction in the frequency of fertile matings. Corpora lutea counts which are laborious to do and are inaccurate in mice, were omitted. The numbers of total implants in test animals were compared with those in concurrent controls, thus affording a simple measure of preimplantion losses.
Mutagenic indices were calculated by the following equation:
(resorptions + dead embryos)/(total implantations) x 100 = mutagenic index


OTHER: N/A
Evaluation criteria:
N/A
Statistics:
Analysis of the data was carried out by use of the Chi-Square test (p=0.05), DF=1), which directly compares values obtained in each test group to the appropriate control group. Any significant differences between a control and test group in any of the biological parameters mentioned above were interpreted as a mutagenic response.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Remarks:
N/A
Toxicity:
not specified
Remarks:
N/A
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
not applicable
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: N/A
- Solubility: N/A
- Clinical signs of toxicity in test animals: N/A
- Evidence of cytotoxicity in tissue analyzed: N/A
- Rationale for exposure: N/A
- Harvest times: N/A
- High dose with and without activation: N/A
- Other: N/A


RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels (for Cytogenetic or SCE assay): N/A
- Induction of micronuclei (for Micronucleus assay): N/A
- Ratio of PCE/NCE (for Micronucleus assay): N/A
- Appropriateness of dose levels and route: N/A
- Statistical evaluation: N/A

Any other information on results incl. tables

The pregnancy rate, as a means of measuring antifertility effects, was not significantly affected by treatment when compared with both control groups.

Total implants (including live fetuses), early fetal deaths, and late fetal deaths, were scored individually for each pregnant mouse and weekly averages were determined for each experimental group. No significant reduction in the average number of total implants per pregnancy, which presumably reflects preimplantation losses of genetically damaged zygotes, was detected in any treated group.

No mutagenic effects, as measured by an increase in the average number of fetal deaths per pregnancy, were evident. Significant or consistent differences were not found in the incidence of early deaths for control and test substance treated mice in the study.

The data indicated no dose response or treatment related mutagenic effects when expressed as the mutagenic index. When it came to group data obtained from uterine examinations all group results were comparable in every respect.

Applicant's summary and conclusion

Conclusions:
Three groups of twenty male mice (C3D2F1/J strain) were given daily oral doses of dodecyl dimethyl amine oxide in water for five consecutive days of 10, 100 or 1000 mg/kg BW to test for mutagenicity in the dominant lethal assay. The number of total implantations, resorptions and late deaths were enumerated and recorded. Under conditions of the assay the test substance did not induce a positive mutagenic response at any of the levels tested.
Executive summary:

Three groups of twenty male mice (C3D2F1/J strain) were given daily oral doses of test substance for five consecutive days of 10, 100 or 1000 mg/kg to test for mutagenicity in the dominant lethal assay.

After the last treatment each male was housed with two untreated females for one week. In order to study successive germ cell stages of the males, each male was housed with two additional females per week for a total of seven weeks. On day thirteen of gestation (measured from the mid-week of presumptive mating), the females were sacrificed and uterine examinations were made. The number of total implantations, resorptions and late deaths were enumerated and recorded. Systemic toxicity to the male rats was not noted in the report.

No significant reduction in the average number of total implants per pregnancy, which presumably reflects preimplantation losses of genetically damaged zygotes, was detected in any treated group.

No mutagenic effects, as measured by an increase in the average number of fetal deaths per pregnancy, were evident. Significant or consistent differences were not found in the incidence of early deaths for control and test substance treated mice in the study.

The data indicated no dose response or treatment related mutagenic effects when expressed as the mutagenic index. When it came to group data obtained from uterine examinations all group results were comparable in every respect.

Analysis of these data using the Chi-square test (p= 0.05, DF=1) indicated that the test substance did not induce a positive mutagenic response at any of the levels tested.