(3-acetyloxy-2,2-dimethylpropyl) acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(acetyloxy)-2,2-dimethylpropyl acetate

EC Number:

826-122-1

Cas Number:

13431-57-7

Molecular formula:

C9 H16 O4

IUPAC Name:

3-(acetyloxy)-2,2-dimethylpropyl acetate

Test material form:

liquid

Specific details on test material used for the study:

The test item was homogeneous by visual inspection.
Storage conditions: Room temperature
Batch No.: VFH-2016-08

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: mean weight test group 1: 189.3g ; mean weight test group 2: 173.3g, mean weight test group 3: 194.7g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cages, type III
- Diet: VRF1(P); SDS Special Diets Services, Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: structure activity considerations

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred.

Mortality:

none

Clinical signs:

other: Clinical signs in the first 2000 mg/kg test group revealed in all animals an impaired general state and piloerection from hour 2 until hour 3 or 4 after administration, while dyspnea was noted at hour 2 and persisted in two animals until hour 3. In the se

Gross pathology:

There were no adverse findings observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (oral, rat) > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 300 mg/kg bw of the test item (undiluted or preparations in corn oil Ph. Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (300 mg/kg bw in 3 females and 2000 mg/kg bw in 6 females). The following test substance-related clinical observations were recorded, clinical signs occurred within the first 3 days after administration:

2000 mg/kg (first test group):

No mortality occurred

Impaired general state in all animals

Piloerection in all animals

Dyspnea in all animals

2000 mg/kg (second test group):

No mortality occurred

Impaired general state in all animals

Piloerection in all animals

Dyspnea in all animals

Cowering position in all animals

300 mg/kg (single test group):

No mortality occurred

Impaired general state in all animals

Piloerection in all animals

Dyspnea in all animals

Cowering position in all animals

The body weights of the animals increased within the normal range throughout the study period with 3 exceptions. The body weight of one animal of the second 2000 mg/kg bw. test group and two animals of the single 300 mg/kg bw. test group increased normally during the first observation week but stagnated during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (9 females). The LD50 was greater than 2000 mg/kg bw.