Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16th August 2005 to 1st September 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviation from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF guidelines (2000) including the most recent partial revisions
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: EA-3098
Description: White powder
Batch: P-32681
Purity: Not indicated by sponsor, treated as 100% pure
Storage: Room temperature in the dark
Stability under storage conditions: Stable
Expiry date: 06 June 2009

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Silzfeld, Germany.
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: 169 - 205 g. Body weight did not exceed +/- 20% of the sex mean.
- Fasting period before study: Food was withheld overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration of the test substance.
- Housing: 3 animals per cage in labelled Macrolon cages (MIV type: height 18 cm), containing sterilised sawdust as bedding material and paper as cage enrichment
- Diet: ad libitum access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany).
- Water: ad libitum access to tap water
- Acclimation period: at least five days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0°C +/-3.0°C (actual range: 20.5 - 22.5°C
- Humidity (%): actal range: 41-85%
- Air changes (per hr): approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN-LIFE DATES: From: Day 1 - day of dosing To: Day 15 - terminal sacrifice

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
Propylene glycol was used as the vehicle and was selected based on trial formulations performed and on test substance data supplied by the sponsor.


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.



Doses:
2000 mg/kg
No. of animals per sex per dose:
2 groups of 3 females, total of 6 (at 2000 mg/kg)
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females.
The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were made for mortality/viability twice daily. Bodyweights were recorded on Day 1 (pre-administration), Day 8 and Day 15.

- Necropsy of survivors performed: yes - at the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

- Other examinations performed:
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture, uncoordinated movements and piloerection
were noted in the animals on days 1 and 2.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Effects on organs:
No abnormalities were found at macroscopic post mortem
examination of the animals.
Other findings:
None

Any other information on results incl. tables

The oral LD50 value of EA-3098 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline on the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of EA-3098 in Wistar rats was established to exceed 2000 mg/kg dody weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with EA-3098 in the rat (Acute Toxic Class Method) was carried out based on the guidelines described in:

-OECD 423 (2001) "Acute Toxicity-Oral, Acute Toxic Class Method",

-EC Council Directive 67/548/EEC, Annex V, B.1 tris (2004) "Acute Oral Toxicity",

-EPA OPPTS 870.1100 (2002), "Acute Oral Toxicity - Acute Toxic Class Method"

-JMAFF guidelines (2000) including the most recent partial revisions.

EA-3098 was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture, uncoordinated movements and piloerection were noted in animals on Days 1 and 2.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic ppost mortem examination of the animals.

The oral LD50 value of EA-3098 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results EA-3098 does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the Globally Harmonised System of Classification and Labelling of Chemicals (GHS).