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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1972
Report date:
1972

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
no necropsy of dams, no statistics and no historical control data, no uterine weight, no purity or physical/chemical properties reported, acclimatization, temperature and humidity not reported, concentrations and stability not verified
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Didodecyl 3,3'-thiodipropionate
EC Number:
204-614-1
EC Name:
Didodecyl 3,3'-thiodipropionate
Cas Number:
123-28-4
Molecular formula:
C30H58O4S
IUPAC Name:
didodecyl 3,3'-sulfanediyldipropanoate
Details on test material:
Fine white powdered material

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data, virgin
- Weight at study initiation: average 217 g
- Fasting period before study: no data
- Housing: individually housed in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, but no further details given
- Humidity (%): controlled, but no further details given
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
1ml/kg bw
Analytical verification of doses or concentrations:
no
Details on mating procedure:
Females were mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation.
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.
Frequency of treatment:
daily
Duration of test:
During pregnancy until cesarian on day 20.
Doses / concentrationsopen allclose all
Dose / conc.:
16 mg/kg bw/day (actual dose received)
Dose / conc.:
74 mg/kg bw/day (actual dose received)
Dose / conc.:
350 mg/kg bw/day (actual dose received)
Dose / conc.:
1 600 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
20 or 21, depending on the group
Control animals:
yes, concurrent vehicle
Details on study design:
250.0 mg/kg of aspirin was used as a postive control.
Attention was called to the fact that this is the seventeenth of a series of reports performed for the US FDA. Eventually, a total of at least 42 compounds were planned to be tested in 21 pairs; each pair being run concurrently against one sham-treated control and one positive control group. Because
of the inherent variability of biological data of the type dealt with. Here, the accumulation and pooling of sequential sets of control values would greatly enhance the statistical value of the findings and I the ultimate reliability of the test results.

Examinations

Maternal examinations:
Body weights were recorded on Days 0,6,11,15, and 20 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.
Ovaries and uterine content:
On Day 20 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantation site abd resorption sites were recorded. The urogenital tract of each dam was examined in detail for anatomical normality. The number of live and dead fetuses were recorded.
Fetal examinations:
The body weights of the live pups were recorded.
All fetuses were examined grossly for the presence of extemal congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations employing 10x magnification. The remaining two-thirds were cleared in potassiiam hydroxide (KOH), stained with alizarin red dye and examined for skeletal defects.

Statistics:
not performed
Historical control data:
Not available at the time of reporting.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
No maternal toxic effects reported.
The method part states that clinical signs were assessed, but no separate section is given in the results part. No mortalitiy occured and the body weight development was not affected. Necropsy was not performed.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 600 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: no effects reported

Results (fetuses)

Details on embryotoxic / teratogenic effects:
no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Treatment with aspirin at 250 mg/kg bw resulted in an increased number of resorptions, dead fetuses, missing, bipartitie or incompletely ossified sternebrae, incompletely ossified vertebrae and incompletely closed skulls.

Applicant's summary and conclusion

Conclusions:
The substance is not teratogenic in rats.
Executive summary:

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rats 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 occurring spontanously in the sham-treated controls.