Dioctadecyl 3,3'-thiodipropionate

Developmental toxicity / teratogenicity

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:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2023

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Version / remarks:

June 2018

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dioctadecyl 3,3'-thiodipropionate

EC Number:

211-750-5

EC Name:

Dioctadecyl 3,3'-thiodipropionate

Cas Number:

693-36-7

Molecular formula:

C42H82O4S

IUPAC Name:

dioctadecyl 3,3'-thiodipropionate

Test material form:

solid: flakes

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 10-14 weeks
- Housing: Animals will be individually housed in polycarbonate cages (Makrolon type MIII, height 18 cm) containing sterilized wooden fibers as bedding material (Lignocel S 8 15, JRS J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet (e.g. ad libitum): SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany ad libitum except during designated procedures
- Water (e.g. ad libitum): Municipal tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C.
- Humidity (%): 40 to 70%.
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 17.08.2022 - 09.06.2022

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% Methylcellulose

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: at least weekly preparation, dosing formulations will be removed from the refrigerator and stirred at room temperature for at least 30 minutes before dosing and dosed within 24 hours after removal from the refrigerator. Test material dosing formulations will be kept at room temperature until dosing. If practically possible, the dosing formulations and vehicle will be continuously stirred until and during dosing. No adjustment will be made for specific gravity of the vehicle and test material. No correction will be made for the purity/composition of the test material.

VEHICLE
- Justification for use and choice of vehicle (if other than water): substance is not soluble in water. A homogeneous and stable dispersion was achieved in the chosen vehicle in trial experiments which was well tolerated by animals in dose-range finding studies.
- Concentration in vehicle: 10, 30, 100 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentration control and homogeneity analysis. Stability analyses performed previously in conjunction with the method development and validation study demonstrated that the test material is stable in the vehicle when prepared and stored under the same conditions at concentrations bracketing those used in the present study.

Details on mating procedure:

- Impregnation procedure: Untreated females will be mated at the Supplier and will be at Day 0 or 1 post-coitum on arrival at the Test Facility (Day 0 post-coitum is the day of successful mating).

Duration of treatment / exposure:

Day 6 to Day 20 post-coitum.

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

22

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: dose selection was based on the results of a preliminary test in pregnant rats and a 14-day dose range-finding study in non-pregnant rats. The highest dose selected represents the limit dose for the study design as specified in the corresponding OECD guideline. Dose spacing of 3 was chosen in accordance with the recommendations of the OECD guideline 414.
- Fasting period before blood sampling for (rat) dam thyroid hormones: no
- Time of day for (rat) dam blood sampling: day 21 post-coitum

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Mortality check at least twice daily beginning upon arrival through termination/release. Except on days of receipt and necropsy where frequency will be at least once daily. Cageside observations at least once daily immediately postdose, starting on Day 6 post coitum up to and including the day prior to necropsy.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: On Days 2, 6, 15 and 21 post coitum

BODY WEIGHT: Yes
- Time schedule for examinations: On Days 2, 6, 9, 12, 15, 18 and 21 post-coitum.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, Over Days 2-6, 6-9, 9-12, 12-15, 15-18 and 18-21 post coitum.

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: thyroid gland

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: placental morphology

Blood sampling:

- Plasma: No
- Serum: Yes
- Volume collected: 1 mL

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [half per litter]
- Head examinations: Yes: [half per litter]
- Anogenital distance of all live rodent pups: yes

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Maternal abnormalities

Abnormalities:

not specified

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified