1-benzyl-5-phenylbarbituric acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-04-15 - 2014-05-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-benzyl-5-phenylbarbituric acid

EC Number:

276-940-2

EC Name:

1-benzyl-5-phenylbarbituric acid

Cas Number:

72846-00-5

Molecular formula:

C17H14N2O3

IUPAC Name:

1-benzyl-5-phenylpyrimidine-2,4,6(1H,3H,5H)-trione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Name: 1-Benzyl-5-Phenyl-Barbituric acid
Common Name: BPBA
Batch No.: 20130303
CAS No.: 72846-00-5
Physical State: solid / powder
Colour: white
Purity: 99.0%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species/strain: WISTAR rats Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female (non-pregnant and nulliparous)
Number of animals: 3 per step
Age at the
beginning of the study: 8-12 weeks old
Body weight on the
day of administration: Step 1: animals no.: 01 – 03, 165 - 178 g
Step 2: animals no.: 04 – 06, 157 - 185 g
Step 3: animals no.: 07 – 09, 173 - 185 g
Step 4: animals no.: 10 – 12, 178 - 192 g
Housing and Feeding Conditions
- 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 (lot no. 1526)
- 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 were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 131113)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed 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:

The starting dose was selected to be 300 mg/kg body weight. No compound-related mortality was recorded for all animals of step 1. As no signs of toxicity were noted a further step at this dose level was first differed and it was decided to proceed with a next step at 2000 mg/kg body weight, for animal welfare reasons. No compound-related mortality was recorded for any animal of step 2 during the first 24h of treatment. Based on these results and according to the acute toxic class method regime, a third step was performed with animals at a dose of 2000 mg/kg body weight. Compound-related mortality was recorded for all animals of step 2 and step 3 during the fourth up to the sixth day of observation. For correct LD50 determination a fourth step was performed with animals at a dose of 300 mg/kg body weight. No compound-related mortality was recorded for all animals of step 4. Based on these results and according to the acute toxic class method regime no further testing was required.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Observation Period
The surviving animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
10.8. Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
10.9. Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
10.10. Pathology
The animals which had to be sacrificed for ethical reasons during the observation period were necropsied as soon as they were killed.
At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial; lot no.: 231073; expiry date: 31 July 2016) at a dosage of approximately 8 mL/kg bw.
All animals were subjected to gross necropsy. All gross pathological changes were recorded and in case of findings the tissues were preserved for a possible histopathological evaluation.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

Under the conditions of the present study, a single oral application of the test item 1-Benzyl-5-Phenyl-Barbituric acid to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality.

Clinical signs:

other: yes

Gross pathology:

Stomach:
gaseous distension

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 1-Benzyl-5-Phenyl-Barbituric acid to rats at a dose of 300 mg/kg body weight was associated with no signs of toxicity or mortality.
Under the conditions of the present study, a single oral application of the test item 1-Benzyl-5-Phenyl-Barbituric acid to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality.
The median lethal dose of 1-Benzyl-5-Phenyl-Barbituric acid after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 500 mg/ kg bw
In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item 1-Benzyl-5-Phenyl-Barbituric acid has obligatory labelling requirement for toxicity.
According to Annex I of Regulation (EC) 1272/2008 the test item 1-Benzyl-5-Phenyl-Barbituric acid has obligatory labelling requirement for toxicity and is classified into Category 4.
According to GHS (Globally Harmonized Classification System) the test item 1-Benzyl-5-Phenyl-Barbituric acid has obligatory labelling requirement for toxicity and is classified into Category 4.

Executive summary:

Under the conditions of the present study, a single oral application of the test item 1-Benzyl-5-Phenyl-Barbituric acid to rats at a dose of 300 mg/kg body weight was associated with no signs of toxicity or mortality.

Under the conditions of the present study, a single oral application of the test item 1-Benzyl-5-Phenyl-Barbituric acid to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality.

The median lethal dose of 1-Benzyl-5-Phenyl-Barbituric acid after a single oral administration to female rats, observed over a period of 14 days is:

LD50 cut-off (rat): 500 mg/ kg bw

In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item 1-Benzyl-5-Phenyl-Barbituric acid has obligatory labelling requirement for toxicity.

According to Annex I of Regulation (EC) 1272/2008 the test item 1-Benzyl-5-Phenyl-Barbituric acid has obligatory labelling requirement for toxicity and is classified into Category 4.

According to GHS (Globally Harmonized Classification System) the test item 1-Benzyl-5-Phenyl-Barbituric acid has obligatory labelling requirement for toxicity and is classified into Category 4.