Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 Mar - 22 Apr 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Y-15866
- Physical state: colourless liquid
- Analytical purity: 72%
- Lot/batch No.: 3710-10
- Expiration date of the lot/batch: 2013-07-16
- Stability under test conditions: stability unknown in PEG 300 (vehicle)
- Storage condition of test material: at room temperature (20 ± 5 °C) and light-protected
- Other: stability under storage conditions: yes

Test animals

Species:
rat
Strain:
other: RccHan: WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., NM Horst, The Netherlands
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 175.7-189.4 g
- Fasting period before study: animals were fasted prior to test substance administration for approximately 16 to 18 h. Food was provided again approximately 3 h after dosing.
- Housing: animals were housed in groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH & Co KG, Rosenberg, Germany).
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 83/09 (Provimi Kliba AG, Kaiseraugst, Switzerland), ad libitum
- Water: community tap water from Füllinsdorf, Switzerland, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 06 Apr 2010 (group 1) or 08 Apr 2010 (group 2) To: 20 Apr 2010 (group 1) 22 Apr 2010 (group 2)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: polyethylene glycol 300 (PEG 300)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% (w/w)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: in a preliminary solubility test, the test substance was well dissolved in PEG 300.
- Lot/batch no.: S60502-099

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 in group 1 and group 2, respectively
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs and mortality once before treatment, within the first 30 min and at approximately 1, 2, 3 and 5 h after treatment on Day 1. During the observation period, animals were observed twice daily for mortality and once daily for clinical signs. Body weights were recorded on Day 1 (prior to administration) and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: experimental result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD 423
Mortality:
No mortality occurred during the study period.
Clinical signs:
Slightly ruffled fur was observed in all 6 animals 2 h after test substance administration. The ruffled fur persisted with the same severity in 2 animals of group 2 at the 3 h reading. All 6 animals of groups 1 and 2 were free of clinical signs from the 5 h reading to the end of the study (on Day 15).
Body weight:
No effect on body weight was noted.
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:
CLP: not classified
DSD: not classified
Executive summary:

The acute oral toxicity of Y-15866 was investigated in a GLP-conform study according to the acute toxic class method (OECD guideline 423). Two groups, each consisting of 3 female RccHan:WIST rats, were treated with Y-15866 diluted in PEG 300 as vehicle by single oral gavage administration at a limit dose of 2000 mg/kg bw. The animals were observed for clinical signs and mortality once before treatment, within the first 30 min and at approximately 1, 2, 3 and 5 h after treatment on Day 1. During the observation period of 14 days, animals were inspected twice daily for mortality and once daily for clinical signs. Body weights were recorded on Day 1 (prior to administration) and on Days 8 and 15. All animals were necropsied and examined macroscopically. No mortality occurred during the study period. Slightly ruffled fur was observed in all 6 animals 2 h after test substance administration. The ruffled fur persisted with the same severity in 2 animals at the 3 h reading. All 6 animals of groups 1 and 2 were free of clinical signs from the 5 h reading to the end of the study (on Day 15). The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. Based on these experimental results, the LD50 of Y-15866 was greater than 2000 mg/kg bw. According to the criteria of OECD guideline 423, the LD50 cut-off of Y-15866 may be considered to be greater than 5000 mg/kg bw.