Dipotassium tartrate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

other: Data sharing dispute

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been assessed for the use in a category approach. According to the methodology and the extent of available details, the study has been jugded as reliable with restrictions.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

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

Guideline:

OECD Guideline 478 (Rodent Dominant Lethal Test)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

rodent dominant lethal assay

Test material

Test material information

Constituent 1

Reference substance name:

(+)-tartaric acid

EC Number:

201-766-0

EC Name:

(+)-tartaric acid

Cas Number:

87-69-4

Molecular formula:

C4H6O6

IUPAC Name:

(2R,3R)-2,3-dihydroxybutanedioic acid

Test material form:

not specified

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 280-350 g
- Assigned to test groubs randomly: yes
- 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 repositoned on racks; racks were repositioned within rooms monthly.
- Diet (e.g. ad libitum): ad libitum (4% fat diet)
- 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

Duration of treatment / exposure:

acute: single oral dose
subacute: five consecutive daily oral doses

Frequency of treatment:

acute: single oral dose
subacute: five consecutive daily oral doses

Post exposure period:

8 weeks in acute test
7 weeks in subacute test

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1.25 mg/kg bw/day (nominal)

Remarks:

Basis: actual ingested both in acute and subacute tests

Doses / concentrations 2

Dose / conc.:

12.5 mg/kg bw/day (nominal)

Remarks:

Basis: actual ingested both in acute and subacute tests

Doses / concentrations 3

Dose / conc.:

125 mg/kg bw/day (nominal)

Remarks:

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 virgin females per week for 8 weeks (7 in subacute study).

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Dose: 0.3 mg/kg bw

Examinations

Tissues and cell types examined:

Corpora lutea, early fetal deaths, late fetal 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. Arbitrages'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

Test results

Sex:

male/female

Genotoxicity:

ambiguous

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative. Comparing all data by rodent dominant lethal asseys, no dose- response or time-trend patterns were observed; thus, tartaric acid did induce dominant lethal mutations.