(+)-tartaric acid

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:

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1.25 mg/kg bw
Basis:
actual ingested
both in acute and subacute tests

Doses / concentrations 2

Remarks:

Doses / Concentrations:
12.5 mg/kg bw
Basis:
actual ingested
both in acute and subacute tests

Doses / concentrations 3

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.