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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test guideline (migrated information)
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 met hodology and to the extent of available details, the study has been judged as reliable with restrictions.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Teratologic evaluation tartaric acid in hamster
Author:
Kenneth Morgareidge
Year:
1973
Bibliographic source:
Food and drug research laboratories, inc.
Reference Type:
other: secondary source
Title:
Safety Assessment for Tartaric Acid, CAS Number 82-69-4
Author:
Tobacco Documents Library
Year:
1996
Bibliographic source:
Tobacco Documents Library

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OTS 798.4700 (Reproduction and Fertility Effects)
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
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
Specific details on test material used for the study:
no data

Test animals

Species:
hamster
Strain:
not specified
Details on species / strain selection:
no data
Sex:
female
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
other: oral intubation
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Details on exposure:
5 consecutive days
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
5 consecutive days
Frequency of treatment:
no data
Details on study schedule:
no data
Doses / concentrationsopen allclose all
Dose / conc.:
2.3 other: mg/kg bw
Dose / conc.:
225 other: mg/kg bw
No. of animals per sex per dose:
25 mated and 22 pregnants
Control animals:
yes, sham-exposed
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
nidation or maternal survival
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
no data
Postmortem examinations (parental animals):
no data
Postmortem examinations (offspring):
soft or skeletal tissue defects in the offspring were recorded
Statistics:
no data
Reproductive indices:
no data
Offspring viability indices:
no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Description (incidence and severity):
no data
Dermal irritation (if dermal study):
not specified
Description (incidence and severity):
no data
Mortality:
not specified
Description (incidence):
no data
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
no data
Food efficiency:
not specified
Description (incidence and severity):
no data
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
no data
Ophthalmological findings:
not specified
Haematological findings:
not specified
Description (incidence and severity):
no data
Clinical biochemistry findings:
not specified
Description (incidence and severity):
no data
Urinalysis findings:
not specified
Description (incidence and severity):
no data
Behaviour (functional findings):
not specified
Description (incidence and severity):
no data
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Description (incidence and severity):
no data
Histopathological findings: non-neoplastic:
not specified
Description (incidence and severity):
no data
Histopathological findings: neoplastic:
not specified
Description (incidence and severity):
no data
Other effects:
not specified
Description (incidence and severity):
no data

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Description (incidence and severity):
no data
Reproductive function: sperm measures:
not examined
Description (incidence and severity):
only female were administered the substance.
Reproductive performance:
not specified
Description (incidence and severity):
no data

Effect levels (P0)

Dose descriptor:
other: highest dose tested
Effect level:
ca. 225 mg/kg bw (total dose)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No maternal toxicity is observed. No teratogenicity is observed
Remarks on result:
not determinable
Remarks:
no NOAEC identified Generation: P and F1 (migrated information)

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Description (incidence and severity):
no data
Dermal irritation (if dermal study):
not specified
Description (incidence and severity):
no data
Mortality:
not specified
Description (incidence):
no data
Body weight and weight changes:
not specified
Description (incidence and severity):
no data
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
no data
Food efficiency:
not specified
Description (incidence and severity):
no data
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
no data
Ophthalmological findings:
not specified
Description (incidence and severity):
no data
Haematological findings:
not specified
Description (incidence and severity):
no data
Clinical biochemistry findings:
not specified
Description (incidence and severity):
no data
Urinalysis findings:
not specified
Description (incidence and severity):
no data
Behaviour (functional findings):
not specified
Description (incidence and severity):
no data
Immunological findings:
not specified
Description (incidence and severity):
no data
Organ weight findings including organ / body weight ratios:
not specified
Description (incidence and severity):
no data
Gross pathological findings:
not specified
Description (incidence and severity):
no data
Neuropathological findings:
not specified
Description (incidence and severity):
no data
Histopathological findings: non-neoplastic:
not specified
Description (incidence and severity):
no data
Histopathological findings: neoplastic:
not specified
Description (incidence and severity):
no data
Other effects:
not specified
Description (incidence and severity):
no data
Details on results:
no data

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Description (incidence and severity):
no data
Reproductive function: sperm measures:
not specified
Description (incidence and severity):
no data
Reproductive performance:
not specified
Description (incidence and severity):
no data

Details on results (P1)

no data

Effect levels (P1)

Dose descriptor:
other: not specified
Based on:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Description (incidence and severity):
no data
Dermal irritation (if dermal study):
not specified
Description (incidence and severity):
no data
Mortality / viability:
not specified
Description (incidence and severity):
fetal survival were recorded but no data were reported , only qualitative data are available.
Body weight and weight changes:
not specified
Description (incidence and severity):
no data
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
no data
Food efficiency:
not specified
Description (incidence and severity):
no data
Water consumption and compound intake (if drinking water study):
not specified
Description (incidence and severity):
no data
Ophthalmological findings:
not specified
Description (incidence and severity):
no data
Haematological findings:
not specified
Description (incidence and severity):
no data
Clinical biochemistry findings:
not specified
Description (incidence and severity):
no data
Urinalysis findings:
not specified
Description (incidence and severity):
no data
Sexual maturation:
not specified
Description (incidence and severity):
no data
Organ weight findings including organ / body weight ratios:
not specified
Description (incidence and severity):
no data
Gross pathological findings:
not specified
Description (incidence and severity):
no data
Histopathological findings:
not specified
Description (incidence and severity):
no data
Other effects:
not specified
Description (incidence and severity):
soft or skeletal tissue defects in the offspring were recorded but no data were reported, only qualitative data are available.

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified
Description (incidence and severity):
no data

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified
Description (incidence and severity):
no data

Details on results (F1)

no data

Effect levels (F1)

Dose descriptor:
other: Not relevant
Generation:
other: Not relevant
Based on:
other: Not relevant
Sex:
not specified
Basis for effect level:
other: Not relevant
Remarks on result:
other: Not relevant The substance was administered to the pregnant dams only.

Results: F2 generation

General toxicity (F2)

Clinical signs:
not examined
Description (incidence and severity):
no data
Dermal irritation (if dermal study):
not examined
Description (incidence and severity):
no data
Mortality / viability:
not examined
Description (incidence and severity):
no data
Body weight and weight changes:
not examined
Description (incidence and severity):
no data
Food consumption and compound intake (if feeding study):
not examined
Description (incidence and severity):
no data
Food efficiency:
not examined
Description (incidence and severity):
no data
Water consumption and compound intake (if drinking water study):
not examined
Description (incidence and severity):
no data
Ophthalmological findings:
not examined
Description (incidence and severity):
no data
Haematological findings:
not examined
Description (incidence and severity):
no data
Clinical biochemistry findings:
not examined
Description (incidence and severity):
no data
Urinalysis findings:
not examined
Description (incidence and severity):
no data
Sexual maturation:
not examined
Description (incidence and severity):
no data
Organ weight findings including organ / body weight ratios:
not examined
Description (incidence and severity):
no data
Gross pathological findings:
not examined
Description (incidence and severity):
no data
Histopathological findings:
not examined
Description (incidence and severity):
no data
Other effects:
not examined
Description (incidence and severity):
no data

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not examined
Description (incidence and severity):
no data

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not examined
Description (incidence and severity):
no data

Details on results (F2)

no data

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

at 225 mg/kg the results were the following:

Pregnancies:

total: 22, died before day 14°: 1, to term: 21

Live litters:

total: 21

Implant sites:

total: 300, average/dam: 14.3

Resorption:

total: 4, dams with one or more site resorbed: 4, dams with all sites resorbed: -, partial resorptions:

19.1%, total resorptions: -

Live fetuses:

total: 295, average/dam: 14.1, sex ratio (M/F): 1.01

dead fetuses:

total: 1, dams with one or more dead: 1, dams with all dead: -, partial dead: 4.76%, all dead: -,

average fetus weight: 1.76

Skeletal findings (fetuses affected/litters affected):

Live fetuses examined (at term): 203/21

Sternebrae: incomplete oss.: 73/20, bipartite: 22/12, missing: 38/14

Ribs: More than 13: 33/15

Vertebrae: 6/4

Extremities: incomplete oss.: 7/5

Miscellaneous: Hyoid missing: 4/2, Hyoid reduced: 5/4

Soft tissue abnormalities:

1 pups Gastroschisis

Applicant's summary and conclusion

Conclusions:
The administration of up to 225 mg/kg bw of the test material to pregnant hamster for 5 consecutive
days had no clearly discernible effects on nidationor on maternal or fetal survival. The number of
abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number
occurring spontaneously in the sham-treated controls.
Executive summary:

A test was conducted to determine the teratogenic potential off L(+)-tartaric acid.

Pregnant hamsters orally administered doses of L(+)-tartaric acid ranging from 2.3-225 mg/kg bw for

5 days.

The animals were subjected to Cesarean section on day 14. The substance under investigation exhibited

no teratogenic activity (nidation, maternal or fetal survival, or soft or skeletal tissue defects in the

offspring) in hamsters under the given test conditions.

No clearly discernible effects on nidationor on maternal or fetal survival. The number of abnormalities

seen in either soft or skeletal tissues of the test groups did not differ from the number occurring

spontaneously in the sham-treated controls.