Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-08-05 to 2010-08-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed in accordance with OECD principles of GLP with no deviations. Furthermore, the study fulfilled the validity criteria described in the OECD guideline.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2011

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
Principles of method if other than guideline:
NA
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
PC2414
IUPAC Name:
PC2414
Details on test material:
- Name of test material (as cited in study report): PC2414
- Lot/batch No.: Y5UB376
- Expiration date of the lot/batch: 2013-03-01

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: female wistar (RccHam:WIST) strain rats
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 172-201 g
- Fasting period before study: overnight prior to dosing
- Housing: groups of up to five by sex in suspended polypropylene cages furnished with softwood woodflakes and fitted with stainless steel mesh lids
- Diet (e.g. ad libitum): tap water ad libitum. Water routinely analysed for contimants.
- Water (e.g. ad libitum): certified rat and mouse diet from accredited supplier ad libitum. Diet routinely analysed for contimants.
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours of continous artificial light in each twenty-four hour period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Remarks:
PC2414 did not dissolve in distilled water or arachis oil. DMSO was therfore chosen as vehicle.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): a dose volume of 10 ml/kg was used
- Justification for choice of vehicle: PC2414 was not soluble in water or arachis oil, DMSO was therefore used

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000 mg/kg bw was as the starting dose based on available toxicological information
Doses:
2000 mg/kg bw (sighting and main study)
No. of animals per sex per dose:
Sighting study: 1 (2000 mg/kg bw)
Main study: 4 (2000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations peformed twice daily during working days and once daily during weekends. Bodyweights
were recorded on Day 0 (prior to docing), Day 7 and 14 or at death.
- Necropsy of survivors performed: yes, gross necropsy was performed
- Other examinations performed: Clinical observations was performed half an hour and 1,2 and 4 hours after dosing, then at leats once daily for 14 days
Statistics:
NA

Results and discussion

Preliminary study:
No toxicity was observed in a sighting test with one animal using a dose level of 2000 mg/kg bw. Based on this result, a limit tests was performed using an additional group of four animals treated at a dose level of 2000 mg/kg bw.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
There were no signs of systemic toxicity
Body weight:
All animals showed expected gains in bodyweight
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
NA

Any other information on results incl. tables

NA

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of PC2414 was estimated to be greater than 2000 mg/kg bw. In accordance with the Globally Harmonised Classification System PC2414 is not classified.
Executive summary:

The acute oral toxicity of PC2414 was assessed in rats using the fixed dose method as described in OECD guideline 420 and EC guideline B1. Following a sighting test at a dose level of 2000 mg/kg bw, an additional four fasted female rats were given a single oral dose of PC2414, as a solution in DMSO, at a dose level of 2000 mg/kg bw. There were no deaths, no signs of systemic toxicity, no effect on body weight gain and no abnormalities at necropsy in this limit study.

The acute oral median lethal dose (LD50) of PC2414 was estimated to be greater than 2000 mg/kg bw. In accordance with the Globally Harmonised Classification System PC2414 is not classified.