Tetramethylcyclotetrasiloxane substituted dipropylether bisphenol A

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27-April-2021 to 26-May-2021 (experimental dates)

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (Tetramethylcyclotetrasiloxane propylether) prop-1-enylether bisphenol A and Di(tetramethylcyclotetrasiloxane propylether) bisphenol A

Cas Number:

203874-34-4

Molecular formula:

(OSiHxCH3)4-CH2-CH2 -CH2- O-C6H4-C(CH3)2-C6H4-0-CH2-CH2-CH2-(SiHxCH3O)4

IUPAC Name:

Reaction mass of (Tetramethylcyclotetrasiloxane propylether) prop-1-enylether bisphenol A and Di(tetramethylcyclotetrasiloxane propylether) bisphenol A

Test material form:

liquid

Details on test material:

Appearance: Pale yellow liquid

Specific details on test material used for the study:

Appearance: pale yellow liquid
Storage Conditions: stored at 15-25°C

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 137 to 184 g
- Fasting period before study: yes (from the evening of the day prior to dosing (Day 1) until approximately 3 hours after dosing)
- Housing: in groups of up to five
- Acclimation period: 8 to 15 days
No contaminants were present in bedding, water or feed at levels which might have interfered with achieving the objective of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 40 to 70
- Air changes (per hr): minimum of 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19 April 2021 To: 26 May 2021

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Doses were administered orally, by gavage, using plastic syringes and rubber or metal catheters. Each rat was dosed once on Day 1, by passing the tip of a catheter along the oesophagus and instilling the test article into the gastric lumen.
Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the specific gravity for the neat material (1.178 g/mL).

Doses:

Main study: 2000 mg/kg bw; Preliminary test: 300 mg/kg bw and 2370 mg/kg bw

No. of animals per sex per dose:

Main study: 4 females; Preliminary test: 1 female/group

Control animals:

no

Details on study design:

The dose volume of the treated group in the preliminary test was incorrectly calculated, resulting in the animal receiving >2000 mg/kg bw.
Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes postdose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
Rats were killed on Day 15. Each animal was given isoflurane anaesthesia. Once a suitable deep plane of anaesthesia had been established, the animal was exsanguinated by the severing of major blood vessels. After exsanguination a full macroscopic necropsy was performed and all lesions were recorded.
The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.

Results and discussion

Preliminary study:

Since there were no deaths in the preliminary study, a further four fasted females were given a single
oral dose of test article at a dose level of 2000 mg/kg body weight.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

All rats gained weight during the first and second weeks of the observation period.

Gross pathology:

No abnormalities were noted at necropsy except for pale kidneys in one animal
treated at 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute oral (fixed dose) test, performed according to OECD/EC guidelines and GLP principles, the acute oral LD50 of the test item was found to be >2000 mg/kg bw.

Executive summary:

An acute oral (fixed dose) test was performed according to OECD/EC guidelines and GLP principles.

In the preliminary study fasted female rats were given the test article as a single dose by oral gavage at dose levels of 300 and 2370 mg/kg bw. Since there were no deaths in the preliminary study, a further four fasted females were given a single oral dose of test article at a dose level of 2000 mg/kg bw. The test article was administered intact by gavage at a dose volume of  1.7 mL/kg bw during the main test. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths during the study. Piloerection and a hunched posture were noted in one animal treated at 300 mg/kg bw. These clinical signs developed from 1 hour after dosing and lasted up to 4 hours after dosing. No clinical signs were seen in the animals treated at 2000 mg/kg bw. All rats gained weight during the first and second weeks of the observation period. No abnormalities were noted at necropsy except for pale kidneys in one animal treated at 2000 mg/kg bw.

In conclusion, the acute oral LD50 was found to be >2000 mg/kg bw.