Vinyl 4-(1,1-dimethylethyl)benzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July - Sept. 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

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:

17.12.2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

30.05.2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

EPA 712-C-02-190, December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Vinyl 4-(1,1-dimethylethyl)benzoate

EC Number:

239-510-5

EC Name:

Vinyl 4-(1,1-dimethylethyl)benzoate

Cas Number:

15484-80-7

Molecular formula:

C13H16O2

IUPAC Name:

ethenyl 4-tert-butylbenzoate

Test material form:

liquid

Details on test material:

- Name: SAT 200028
- Batch No.: 19K2505
- Physical State: liquid
- Purity: 99.0%
- Expiry Date: 30 June 2021
- Storage Conditions: at room temperature, protected from light
- Safety Precautions: The routine hygienic procedures were sufficient to assure
personnel health and safety.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

ANIMALS
- Species/strain: WISTAR rats Crl: WI(Han)
- Source: Charles River, 97633 Sulzfeld, Germany
- Sex: Female (non-pregnant and nulliparous)
- Number of animals: 5
- Age at the beginning of the study: animal no. 1: 8–9 weeks animals no. 2-5: 9–10 weeks
- Body weight on the day of administration: animal no. 1: 171 g; animal no. 2: 180 g; animal no. 3: 175 g; animal no. 4: 185 g; animal no. 5: 179 g

The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to the German Act on Animal Welfare the animals were bred for experimental purposes.

The animals were randomly selected and marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 17 to 18 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 3 hours post dosing.

HUSBANDRY
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals will be kept in groups unless health status requires individual housing. IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich Product Testing Munich GmbH
- Adequate acclimatisation period (6 days for animal no. 1 and 13 days for animals no. 2. no. 3, no. 4 and no. 5)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:

300 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Sighting Study
The starting dose for the sighting study was 300 mg/kg body weight.
No compound-related mortality was recorded for the first animal dosed.

Main Test
Another four animals were dosed with 300 mg/kg body weight and no compound-related mortality was recorded. Based on these results and according to the fixed dose method regime no further testing was required.

Observation Period
All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: Acute oral toxicity characteristics observed after a single dose administration. The most relevant clinical findings in the animals were reduced spontaneous activity, hunched posture, wasp waist, prone position, piloerection half-closed eyes, eyes closed,

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the present study, a single oral application of the test item SAT 200028 to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity but no mortality.
The determined LD50 cut-off value of SAT 200028 after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 300 mg/kg bw < LD50 < 2000 mg/kg bw

Executive summary:

Five female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. The test item was diluted with the vehicle corn oil (see 10.3) at a concentration of 0.03 g/mL and administered at a dose volume of 10 mL/kg.
All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study but showing signs of toxicity.
The most relevant clinical findings in the animals were reduced spontaneous activity, hunched posture, wasp waist, prone position, piloerection half-closed eyes, eyes closed, abnormal breathing and diarrhea. All animals recovered within up to 2 days post-dose.
Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain.
At necropsy, no treatment-related macroscopic findings were observed in any animal of the sighting or main study.
- LD50 cut-off (rat): 300 mg/kg bw < LD50 < 2000 mg/kg bw
- Species/strain: WISTAR Crl: WI(Han) rats
- Vehicle: corn oil
- Number of animals: 1 animal sighting study / 4 animals main study

 

Conclusion
Under the conditions of the present study, a single oral application of the test item SAT 200028 to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity but no mortality.
The determined LD50 cut-off value of SAT 200028 after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 300 mg/kg bw < LD50 < 2000 mg/kg bw