1-(5-propyl-1,3-benzodioxol-2-yl)-1-ethanone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 December 2013 to 03 January 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 423 without deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on 20-22 November 2012 / signed on 24 April 2014)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-(5-propyl-2H-1,3-benzodioxol-2-yl)ethan-1-one

EC Number:

700-902-0

Cas Number:

1370699-98-1

Molecular formula:

C12H14O3

IUPAC Name:

1-(5-propyl-2H-1,3-benzodioxol-2-yl)ethan-1-one

Test material form:

liquid

Details on test material:

- Physical state: Colourless liquid
- Water solubility: 2.16 g/L
- Vapour pressure: 0.33 Pa (at 20°C) and 0.59 Pa (at 25°C)
- Partition coefficient: 2.69 (HPLC, 2013)
- Storage Conditions: 6 ± 2 °C, protected from light, under nitrogen in the original container
- Stability under test conditions: Not specified, assumed to be stable

Specific details on test material used for the study:

- Purity test date: 30 October 2013
- Storage Conditions: 4 °C in the dark under nitrogen

Test animals

Species:

rat

Strain:

other: Crl:CD (SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: ca. 8-10 weeks
- Weight at study initiation: 222-252 g
- Fasting period before study: Animals were fasted overnight prior to and approximately four hours after dosing.
- Housing: Animals were housed in groups of three rats of the same sex in solid bottomed polycarbonate cages with a stainless steel mesh lid.
- Diet: Rat and Mouse No. 1 Maintenance Diet, ad libitum
- Water: Potable water taken from the public supply, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 40-70 %
- Animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 12 December 2013 to 03 January 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
- The test substance was formulated at a concentration of 200 mg/mL in the vehicle and administered at a volume of 10 mL/kg bw. The test substance formulation was prepared on the day of dosing.

CLASS METHOD
- Rationale for the selection of the starting dose: Dose level for the study was chosen in compliance with the study guidelines. Based on information (QSAR prediction, structural alert and toxicological information for the potential surrogates) provided by the Sponsor the initial dose was 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality: Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). All animals were observed for 14 days after dosing.
- Frequency of weighing: The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly body weight changes and group mean body weights were calculated.
- Necropsy of survivors performed: Yes; all animals were humanely killed on Day 15 by carbon dioxide asphyxiation and subjected to gross necropsy.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

There were no deaths during the study.

Clinical signs:

other: Clinical signs of reaction to treatment comprised of under activity and irregular breathing seen in all females dosed at 2000 mg/kg bw, flat posture, partially closed eye lids, reduced body tone, piloerection, unsteady gait, splayed hind limbs, fast breat

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the test conditions, the substance is::
- not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw.
- classified as 'category 5' according to the GHS based on significant clinical signs observed at 2000 mg/kg bw.

Executive summary:

An acute oral toxicity study was performed according to OECD Guideline 423 and in compliance with GLP.

One group of three fasted female Crl:CD (SD) rats received a single oral gavage dose of the test substance, formulated in corn oil, at a dose level of 2000 mg/kg bw. As results at this dose level indicated the acute lethal oral dose of the test substance to be greater than 2000 mg/kg bw, in compliance with the study guidelines, a further group of three fasted females was similarly dosed at 2000 mg/kg bw to complete the study. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

There were no deaths during the study. Clinical signs of reaction to treatment comprised of under activity and irregular breathing, flat posture, partially closed eye lids, reduced body tone, piloerection, unsteady gait, splayed hind limbs, fast breathing, reduced body temperature and Hunched posture. Clinical signs were first noted from approximately 15 minutes after dosing. Recovery of animals, as judged by external appearance and behaviour, was complete by Days 2 or 3. All animals were considered to have achieved satisfactory body weight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Oral LD50 (female) > 2000 mg/kg bw.

Under the test conditions, the substance is::

- not classified according to the Annex VI of the Regulation EC No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw.

- classified as 'category 5' according to the GHS based on significant clinical signs observed at 2000 mg/kg bw.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.