2-Decyltetradecyl 3-[3-(2-decyltetradecoxy)-3-oxopropyl]sulfanylpropanoate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

read-across based on grouping of substances (category approach)

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

Justification for type of information:

Thiobis Propanoic Acid Derivatives
The category covers thiiodipropionates that are symmetrically esterified by two linear aliphatic groups ranging in size from C10 to C24
The justification for the category is based on the expectation that the close structural similarity should result in properties that are either similar or follow a pattern that correlates with changes in the molecular weights of the compounds. The category members are high-molecular weight dithiopropionate esters that differ only in the chain length of the dialkyl ester functions and are expected to follow a regular pattern for all endpoints.
Based on the structures and molecularweights of the category members, as well as available data on category members, The predictive methods and extrapolation and interpolation of data within the category are acceptable. Data provided by other sources also demonstrate that these compounds generally have mammalian toxicities that are similar (e.g., acute oral LD 50, acute irritation thresholds, and genotoxicities) or follow a pattern that parallels changes in molecular weight (e.g., repeated-dose NOAEL).

The category is adequately supported based on chemical structure and available data.

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)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

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:

- Name of test material (as cited in study report): IRGANOX PS 800
- Physical state: solid
- Stability under test conditions: stable

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 (fresh): 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:

VEHICLE
- Amount of vehicle (if gavage): 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.

Frequency of treatment:

daily

Duration of test:

During pregnancy until day 20

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

16 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

74 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

350 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

1 600 mg/kg bw/day (nominal)

No. of animals per sex per dose:

20-21, depending on the dose group

Control animals:

yes, sham-exposed

Details on study design:

250 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 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 behaviour 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 and 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 foetuses were examined grossly for the presence of extemal congenital abnormalities. One-third of the foetuses 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 the report.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Details on results:

Maternal toxic effects:no effects

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

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects
Details on maternal toxic effects:
The method part states that clinical signs were assessed, but no further details were given in the results part.
No mortalitiy occured and the body weight development was not affected.

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:

Remarks on result:

not determinable due to absence of adverse toxic effects

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 600 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other:

Remarks on result:

not determinable due to absence of adverse toxic effects

Fetal abnormalities

Key result

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The administration of up to 1600 mg/kg (body weight) of the test
material to pregnant rats for 20 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 spontaneously in
the sham-treated controls

Executive summary:

The administration of up to 1600 mg/kg (body weight) of the test
material to pregnant rats for 20 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 spontaneously in
the sham-treated controls