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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:
equivalent or similar 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), adopted November 2000 and 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): UM-235
- Physical state: white powder
- Lot/batch No.: #SI-1
- 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:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany (strain: Crl:(WI) BR (outbred, SPF-Quality))
- Age at study initiation: 11 weeks
- Weight at study initiation: male (mean) 343 ± 18 g, female (mean) 212 ± 13 g (did not exceed ±20 % of the mean)
- Fasting period before study: a maximum of 20 hours, up to 3-4 hours after dosing
- Housing: group housing of 3 animals per cage in Makrolon cages (type IV) 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 (actual range)
- Humidity (%): 47 - 79 (actual range)
- 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:
VEHICLE
- Concentration in vehicle: 200 mg/mL (w/w) (calculated from dose volume of 10 mL/kg and dose of 2000 mg/kg bw)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: based on trial formulations performed at the test lab
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for viabiliy and mortality: twice daily; clinical signs: at periodic intervals at the day of dosing and once daily thereafter until Day15 (for grading of symptoms see Table 1 under "any other information on material and methods including tables"); weighing: Day 1 pre-administration and on Days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No effects were observed up to and including the highest dose level. According to OECD 423, the LD50 cut-off value is set at 5000 mg/kg bw.
Mortality:
No mortalities occurred.
Clinical signs:
Piloerection in 3/3 males and 3/3 females was seen 2 and 4 hours after dosing, in females it was still visible 1 day after dosing. Hunched posture for 3/3 females was noted 4 hours after dosing, for 1/3 females hunched posture was still seen 1 day after dosing. 3/3 male animals showed hunched posture already 2 hours after dosing. For 1/3 males this clinical sign was still detectable 2 days after dosing, whereas for the other 2 males it was reversed by one and two days after dosing. Further, 3/3 females showed uncoordinated movements 2 and 4 hours after dosing and 1/3 females showed chromodacryorrhoea 2 and 4 hours after dosing (see Table 2).
Body weight:
Slight body weight loss or reduced body weight gain was noted in the males between Days 8 and 15 (9.5%). No effects on body weight were noted in the females (see Table 3)
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 2. Table for acute oral toxicity.

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/3/3

2 h - Day2

---

0

Females

2000

0/3/3

2 h - Day3

---

0

LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used           

 

Table 3. Body weights (g)

Sex/Dose Level

Animal

Day1

Day8

Day15

Females/2000 mg/kg bw

1

236

266

277

 

2

216

245

254

 

3

212

239

247

 

Mean

221

250

259

 

Standard deviation

13

14

16

 

N

3

3

3

Males/2000 mg/kg bw

1

359

410

406

 

2

323

371

372

 

3

348

403

404

 

Mean

343

395

394

 

Standard deviation

18

21

19

 

N

3

3

3

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