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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented report equivalent or similar to OECD guidelines

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)
GLP compliance:
not specified
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): tartaric acid
- Physical state: fine granular
- Lot/batch No.: 71382

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 10-13 weeks
- Weight at study initiation: 280-350 g
- Assigned to test groups randomly: yes
- Fasting period before study:
- Housing: 1 to 5 per cage, sanitary cages and bedding were used, and changed two times per week, at which time water containers were cleaned, sanitized and filled. Once a week, cages were repositioned on racks; racks were repositioned within rooms monthly.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4-11 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: physiol. saline
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food): a commercial 4 % fat diet
- Storage temperature of food: periodic tests to verify the absence of coliforms, salmonella and pseudomones sp. were performed.
Duration of treatment / exposure:
acute: one application
subacute: 5 days
Frequency of treatment:
acute: one application
subacute: one dose a day for five days
Post exposure period:
8 weeks in acute test
7 weeks in subacute test
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1.25 mg/kg bw
Basis:
actual ingested
both in acute and subacute tests
Remarks:
Doses / Concentrations:
12.5 mg/kg bw
Basis:
actual ingested
both in acute and subacute tests
Remarks:
Doses / Concentrations:
125 mg/kg bw
Basis:
actual ingested
both in acute and subacute tests
No. of animals per sex per dose:
10 male rats were assigned to each of 5 group in acute and subacute. Following treatment, the males were sequentially mated to 2 females per week for 8 weeks (7 in subacute study).
Control animals:
yes, concurrent vehicle
Positive control(s):
triethylenemelamine
- Route of administration: intraperitoneally
- Doses / concentrations: 0.3 mg/kg bw

Examinations

Tissues and cell types examined:
Corpora lutea, early fetal deaths, late fetal deaths and total implantations per uterine born
Statistics:
a. the fertility index
The number of pregnant females/number of mated females with the chi-square was used to compare each treatment to the control. Arbitrage’s trend was used for linear proportions to test whether the fertility index was linearly related to arithmetic or log dose.
b. totle number of implantations
the t-test was used to determine significant differences between average number of implantations per pregnant female for each treatment compared to the control. Regression techniques were used to determine whether the average number of implantations per female was related to the arithmetic or log dose.
c. total number of corpora lutea
the t-test was used to determine significant differences between average number of corpora lutea per pregnant female for each treatment compared to the control.
d. preimplantation losses
preimplantation loses were computed for each female by subtracting the number of implantations from the number of corpora lutea, Freeman-Tukey transformation was used on the preomplantation losses for each female and then the t-test was used to compare each treatment to control. Regression technique was used to determine whether the average number of preimplantation losses per female was related to the arithmetic or log dose.

Results and discussion

Any other information on results incl. tables

a. acute study

In general, significant differences between the negative control and experimental groups were shown in a few instances at vrious weeks throughout the parameter. Of note is the significant increase in average resorptions shown for the low dose group at week 8.

b. subacute study

Significant difference between the negative control and experiment groups were shown in a few instances. However, no strong indications of change were seen.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): ambiguous
no obviously results proved this substance is a potential mutagen
Executive summary:

The Dominant Lethal Test is an accurate and sensitive measure of the amount and type of fetal wastage which may occur following administration of a potential mutagen. In this test acute and subacute administration were carried out in rats, and the results can not be concluded that FDA 71 -55 is a potential mutagen.