Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 Jul - 08 Aug 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - 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 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
adopted June 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF) Nov. 2000
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): AF-654
- Physical state: white powder
- Lot/batch No.: #CE-201
- Expiration date of the lot/batch: 01 Jan 2005
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:(WI) BR (outbred, SPF-Quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: female (mean) 230 ± 32 g; male (mean) 358 ± 19 g
- Fasting period before study: over night
- Housing: 3 animals per sex per cage in labelled Makrolon type IV cages containing purified sawdust as bedding material
- Diet: standard pelleted laboratory animal diet (Altromin, code VRF 1), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.1 - 24.5
- Humidity (%): 47 - 79
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
The dose level of 2000 mg/kg bw was reached by administration of two times 1000 mg/kg bw (10 mL/kg bw) within 24 hours. The first on t=0 and the second on approx. t=1 hour.

VEHICLE
- Amount of vehicle (if gavage): Two administrations of formulation of the test substance at 10 mL/kg bw
- Justification for choice of vehicle: vehicle was selected based on trial formulations performed at the testing laboratory
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1st step: 3 females
2nd step: 3 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality was observed twice daily. Animals were observed at periodic intervals on the day of dosing and once daily thereafter for clinical signs. Weighing was done prior to dosing (day 1) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: According to OECD Guideline 423, Annex 2d, a cut-off value of 5000 mg/kg bw was derived based on a limit test with 2000 mg/kg bw, since no mortality occurred in any step.
Mortality:
No mortality occurred.
Clinical signs:
Clinical signs were noted in all animals between days 1 and 3 and included lethargy, hunched posture, uncoordinated movements and piloerection in all animals. In addition, ptosis were noted in all males on day 1.
Body weight:
Body weight gain was normal during the study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 1. Table for acute oral toxicity

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/3/3

Day1 – Day2

---

0

Females

2000

0/3/3

Day1 – Day3

---

0

LD50 > 2000 mg/kg bw

 Day 1 refers to the day of test substance administration.                                                                                    

* first number = number of dead animals                                 

  second number = number of animals with 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:
DSD: not classified
CLP: not classified