Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 - 21 Jul 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

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)
Version / remarks:
adopted Dec 2001
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: Japanese Ministry of Agriculture, Forestry and Fisheries, 12 Nousan, Notification No. 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
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:
- Name of test material (as cited in study report): PM-5927
- Physical state: off-white powder
- Lot/batch No.: 04-3
- Expiration date of the lot/batch: 01 Mar 2006
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar Crl:WI
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 172 ± 8 (mean ± SD, group 1) and 185 ± 2 (mean ± SD, group 2)
- Fasting period before study: animals were fasted 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 ; height 18 cm) containing sterilised sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI B.V., Someren, the Netherlands) and paper as cage-enrichment (Enviro-dri, BMI, Helmond, the Netherlands)
- Diet: standard pelleted laboratory animal diet (Altromin, code VRF 1, Lag, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 - 22.4 (actual range)
- Humidity (%): 46 - 81 (actual range)
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: the vehicle was selected based on trial formulations performed at the test laboratory and on test substance data supplied by the sponsor

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

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 (1.036).
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females (group 1)
3 females (group 2)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and morbidity twice daily; the occurrence of clinical signs was recorded at periodic intervals on Day 1, and once daily thereafter until Day 15; body weight was recorded on Day 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
Statistics:
Means and standard deviation was calculated for the body weights.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
6/6 animals had a hunched posture from 0-2 hours after dosing until Day 2. Uncoordinated movements were noted in 6/6 rats 2 hours after dosing, persisting until 4 hours after dosing in 4/6 animals.
Body weight:
No effect on body weight was noted.
Gross pathology:
No substance-related findings were noted during the necropsy and macroscopic examination.

Any other information on results incl. tables

Table 1: Mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Females

2000

0/6/6

Day 1-2 

-

0

Overall LD50 > 2000 mg/kg bw

* first number = number of dead animals                            

 second number = number of animals with systemic clinical signs             

 third number = number of animals used                           

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified