Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2002-09-17 to 2002-10-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP; OECD guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17. December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 30. September 1996
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
444-860-9
EC Name:
-
Cas Number:
474510-57-1
Molecular formula:
C21 H24 O4
IUPAC Name:
2-hydroxy-1-(4-(4-(2-hydroxy-2-methylpropionyl) benzyl) phenyl)-2-methylpropan-1-one
Details on test material:
- Description: slightly yellow solid
- Purity: 94.1 % (Assay)
- Stability of test item dilution: Stable in PEG 300 for hours

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services; CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 9 weeks; Females: 13 weeks
- Weight at study initiation (mean): Males: 245.1 g; Females: 183.7 g
- Fasting period before study: fasted for approximately 17 hours before treatment; food was provided again approximately 3 hours after dosing.
- Housing: In groups of 3 rats/sex in Makrrolon type-4 cages
- Diet: Pelleted standard Provimi Kliba 3433 rat maintenance diet, ad libitum
- Water: Community tap water from Fullinsdorf ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Air changes : 10-15 air changes per hour
- Photoperiod: 12 hours fluorescent light/ 12 hours dark, music during the light period

IN-LIFE DATES: From: 17-Sept-2002 To: 10-Oct-2002

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
(PEG 300)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL, based on dose volume
- Amount of vehicle (if gavage): a dose volume of 10 mL/kg bw was used
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial, which was performed before the study initiation date.
- Lot/batch no. (if required): 433337/1 20602


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


Doses:
2000 mg/kg bw/d
No. of animals per sex per dose:
3 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality and viability: twice daily during days 1-15; body weights: On test days 1 (prior to administration), 8 and 15; clinical signs: daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during
days 2-15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
A slight hunched posture was observed in all females at the 2-, 3- and 5-hour examinations on day 1 and was present again in one female on days 2 and 3 and in all females from day 8 to 15. The coats of all females were slightly ruffled at the 2-, 3- and 5-hour examinations and continued in one female up to day 3. This clinical sign re-appeared in all females on day 8 and slight to moderate ruffled fur persisted until termination on day 15. In addition, all females were emaciated from day 10 to 15.
The same clinical signs were observed in the males after administration of the test item. Hunched posture and slightly ruffled fur was apparent in all males from 1 to 5 hours after treatment. Hunched posture and slight to moderate ruffled fur persisted in one male throughout the entire observation period and was present in the remaining two males from day 5 to 15. Emaciation was evident in all males from day 8 to 15.
Body weight:
With the exception of one female which showed a loss of body weight (7.8 %) during the first week after treatment, a body weight loss (19 to 26%) was observed in all animals between treatment start and the end of the observation period.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Any other information on results incl. tables

The median lethal dose of the test item after single oral administration to rats of both sexes, observed over a period of 15 days is:

LD50 (rat) > 2000 mg/kg bw/d.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information