Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
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 to the extent of available details, the study has been judged as reliable with restrictions.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Sample: Fine white crystalline material
Marking: FDA 71-55 (Tartaric acid)

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals and environmental conditions:
Virgin adult female albino CD-1 outbred mice were gang-housed in disposable plastic cages in temperature and humidity-controlled
quarters with free access to food and fresh tap water. They were mated with young adult males, and observation of the vaginal sperm
plug was considered Day 0 of gestation.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
10 mL/kg bw
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Beginning on Day 6 and continuing daily through Day 15 of gestation, the females were dosed with the indicated dosages by oral intubation; the controls were sham treated.
Duration of test:
10 consecutive days
Doses / concentrations
Remarks:
Doses / Concentrations:
274 mg/Kg/bw
Basis:
actual ingested
No. of animals per sex per dose:
32 mated and 22 pregnants at 274 mg/kg
Control animals:
yes, sham-exposed

Examinations

Maternal examinations:
Body weights were recorded on Days 0, 6, 11, 15, and 17 of gestation. All animals were observed daily for appearance and behavior
with particular attention to food consumption and weight, in order to rule out any abnormalities which may have occurred as a result
of anorexic effects in the pregnant female animal.
On Day 17 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantations sites,
resorptions site, and live dan dead fetus were recorded.
The body weights of the live pups were also recorded. The urogenital tract of each dam was examined in detail for anatomical
normality.
All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetus of each litter
underwent detailed visceral examinations employing the Wilson technique. The remaining two-thirds were cleared in potassium
hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no data

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
274 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: other:
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

at 274 mg/kg the results were the following:

Pregnancies:

total: 22, died before day 17°: 0, to term: 22

Live litters:

total: 21

Implant sites:

total: 243, average/dam: 11.1

Resorption:

total: 18, dams with one or more site resorbed: 8, dams with all sites resorbed: 1, partial resorptions: 36.4%, total resorptions: 4.55%

Live fetuses:

total: 222, average/dam: 10.1, sex ratio (M/F): 0.87

dead fetuses:

total: 3, dams with one or more dead: 3, dams with all dead: -, partial dead: 13.6%, all dead: -, average fetus weight: 0.91.

Skeletal findings (fetuses affected/litters affected):

Live fetuses examined (at term): 155/21

Sternebrae: incomplete oss.: 32/17, bipartite: 4/3, missing: 6/4

Ribs: More than 13: 37/16

Vertebrae: 2/2

Extremities: incomplete oss: 2/2

Miscellaneous: Hyoid missing: 26/11, Hyoid reduced: 11/9

Soft tissue abnormalities:

1 pups Gastroschisis

Applicant's summary and conclusion

Conclusions:
The administration of up to 274 mg/Kg (body weight) of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or 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 occuring spontaneously in the sham-treated controls.
Executive summary:

The administration of up to 274 mg/Kg (body weight) of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or 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 occuring spontaneously in the sham-treated controls.