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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:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: June 2015; signature: September 2015
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
phenyl pent-4-enoate
EC Number:
812-668-8
Cas Number:
51231-09-5
Molecular formula:
C11H12O2
IUPAC Name:
phenyl pent-4-enoate
Test material form:
liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: Approximately 4 °C, in the dark
- Other: clear colourless

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 171-179 g (300 mg/kg including sighting test; sentinel); 179 g (2000 mg/kg sighting test; sentinel); The weight variation did not exceed ±20% of the mean weight in the definitive test (300 mg/kg bw).
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70%
- Air changes (per hr): > 15 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: To: 2015-12-16 to 2016-01-06

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The 300 mg/kg bw and 2000 mg/kg bw dose levels were treated stepwise. Singuarly and in the absence of mortality or evident toxicity a further group of 4 was tested in the appropriate dose level.
Doses:
300 mg/kg bw (initial sighting test and main study)
2000 mg/kg bw (initial sighting test)
No. of animals per sex per dose:
1 (sighting study) and 4 (main study) as applicable; total 5 per dose (in definitive test).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw (sentinel and definitive test): No mortality
2000 mg/kg bw (sentinel): Mortality.
Clinical signs:
300 mg/kg bw (sentinel and definitive test): No signs of systemic toxicity were noted.
2000 mg/kg bw (sentinel): Hunched posture on day of dosing.
Body weight:
300 mg/kg bw (sentinel and definitive test): All animals showed expected bodyweight gains over the study period.
2000 mg/kg bw (sentinel): Not applicable.
Gross pathology:
300 mg/kg bw (sentinel and definitive test): Abnormalities noted at necropsy in 1/5: Epithelial sloughing of the gastric mucosa and non glandular epithelium of the stomach. No abnormalities were noted at necropsy of 4/5.
2000 mg/kg bw (sentinel): Abnormalities noted at necropsy were dark liver, dark kidneys, gaseous stomach and epithelial sloughing of the gastric mucosa and non glandular epithelium of the stomach.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw in female Wistar rats.
Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 300 mg/kg bw in a solution in arachis oil BP and following an absence of toxicity then at 2000 mg/kg bw. Subsequently, at a further group of four fasted females was given a single oral dose of test item, at a dose level of 300 mg/kg body weight. The animal treated at a dose level of 2000 mg/kg was found dead 1 day after dosing. There were no mortality at a dose level of 300 mg/kg. Hunched posture was noted during the day of dosing in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity and all animals showed expected gains in bodyweight over the study period at a dose level of 300 mg/kg. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg, that was found dead, were dark liver, dark kidneys, gaseous stomach and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. Abnormalities noted at necropsy of one animal, treated at a dose level of 300 mg/kg, were epithelial sloughing of the gastric mucosa and non glandular epithelium of the stomach. No abnormalities were noted at necropsy of four animals treated at a dose level of 300 mg/kg. Under the conditions of this study, the oral LD50 was estimated to be in the range of 300 - 2000 mg/kg bw in the female Wistar rat. The test substance was classified as Acute Oral Toxicity: Category 4 according to Regulation (EC) 1272/2008.

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