5-(4-hydroxyphenyl)imidazolidine-2,4-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end on 18-JUN-2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed according to OECD guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-(4-hydroxyphenyl)imidazolidine-2,4-dione

EC Number:

219-340-8

EC Name:

5-(4-hydroxyphenyl)imidazolidine-2,4-dione

Cas Number:

2420-17-9

Molecular formula:

C9H8N2O3

IUPAC Name:

5-(4-hydroxyphenyl)imidazolidine-2,4-dione

Details on test material:

- Name of test material (as cited in study report): P-Hydroxy-phenylhydantoin
- Substance type: monoconstituent substance
- Physical state: solid
- Stability under test conditions: unknown in water
- Storage condition of test material: at room temperature, light protected

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V. (The Netherlands)
- Age at study initiation: 11 weeks
- Weight at study initiation: 186.9 g - 195.8 g
- Fasting period before study: fasted for approximately 17 to 18 hours (access to water was permitted)
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, ad libitum
- Water: Community tap water from Füllinsdorf ad libitum
- Acclimation period: ( days under laboratory conditions, after health examination

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: between 30-70%,
- Air changes: 10-15 air changes per hour
- Photoperiod: automatically controlled light cycle of 12 hours light and 12 hours dark and music played during the daytime light period

IN-LIFE DATES: from 13-Apr-2010 to 06-May-2010

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/w) in purified water
- Justification for choice of vehicle: the vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.

MAXIMUM DOSE VOLUME APPLIED: the dosing volume was 10 mL/kg body weight

CLASS METHOD
- Rationale for the selection of the starting dose: data not available

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Viability / Mortality: Daily during acclimatization. Once before treatment and within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on test day 1 (in common with the clinical signs). Twice daily during days 2 - 15.
> Clinical Signs: Daily during acclimatization and treatment. Additionally, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1.
> Body Weights: On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

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 observed

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were recorded throughout the entire observation period, except for three animals, which were noted with slightly ruffled fur from the first 30 minutes to 2 hours after administration.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (female rat): greater than 2000 mg/kg body weight

Executive summary:

Two groups, each consisting of three female RccHan:WIST (SPF) rats, were treated with PHydroxy- phenylhydantoin by single oral gavage administration at a dosage of 2000 mg/kg body weight (OECD 423, GLP). The test item was formulated in purified water at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs immediately before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded immediately before treatment, within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No intercurrent deaths occurred during the course of the study. No clinical signs were recorded throughout the entire observation period, except for three animals, which were noted with slightly ruffled fur from the first 30 minutes to 2 hours after administration. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

The median lethal dose of P-Hydroxy-phenylhydantoin after single oral administration to female rats, observed over a period of 14 days, is: LD50 (female rat): greater than 2000 mg/kg body weight

Based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, P-Hydroxy-phenylhydantoin is not classified with respect to the acute oral toxicity in the rat.