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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 January 2003 to 30 January 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

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)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Details on test material:
Identification: HSY-2701
Description: Red powder
Batch: 02J-20
Purity: 99.99 wt%
Test substance storage: At room temperature protected
Stability in vehicle: Not indicated
Expiry date: 29 June 2003

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
- Age at study initiation: Approximately 9 weeks old.
- Weight at study initiation: 182 to 209 g for females and 255 to 274 g for males. (Body weight variation 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: Group housing of 3 animals per sex cage in labelled Macrolon cages (type IV; height 18 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet (e.g. ad libitum): Free access to standard pelleted laboratory animal diet (from Altomin (code VRF 1), Lage, Germany)
- Water (e.g. ad libitum): Free access to tap-water.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 °C
- Humidity (%): 30-70 % RH
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day.

All females were nulliparous and non-pregnant

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed by the testing laboratory
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 animals per sex per dose (6 in total, 3 males and 3 females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/viability observations were performed twice daily. Bodyweights were recorded on day 1 (pre-administration), 8 and 15. Clinical signs were recorded 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:
Maximum grade 4 - grading slight (1) to very severe (4)
Maximum grade 3 - grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)
- Necropsy of survivors performed: yes, macroscopic examinations were recorded
Statistics:
The test substance substance was ranked within LD50 value ranges of 0-25, 25-200, 200-2000 or exceeding 2000 mg/kg body weight. No statistical analysis was performed (The method used was not intended to allow the calculation of a precise LD50 value).
The results were evaluated according to the EC criteria for classification and labelling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and ammendments of the Directive published in the Official Journal of the European Communities).

Results and discussion

Preliminary study:
not applicable to test methodology.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Red discolouration of the faeces was noted.
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 same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
No further observations were included.

Any other information on results incl. tables

Table 1: Clinical Signs

Test Day

1

1

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Max grade

Hours after Treatment

0

2

4

 

Females 2000 mg/kg

Animal 1

Skin/Fur

 

Red Discolouration (Faeces)

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

(1)

Animal 2

Posture

 

Hunched Posture

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

-

-

(1)

Skin/Fur

 

Red Discolouration (Faeces)

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

(1)

Animal 3

Skin/Fur

 

Red Discolouration (Faeces)

-

-

-

-

1

-

-

-

-

-

-

-

-

-

-

-

-

(1)

Males 2000 mg/kg

Animal 4

Skin/Fur/Plumage

 

Red Discolouration (Faeces)

-

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

(1)

Animal 5

Skin/Fur

 

Red Discolouration (Faeces)

-

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

(1)

Animal 6

Skin/Fur

 

Red Discolouration (Faeces)

-

-

-

1

1

-

-

-

-

-

-

-

-

-

-

-

-

(1)

 

Table 2: Bodyweights (Gram)

SEX/DOSE LEVEL

ANIMAL

DAY 1

DAY 8

DAY 15

Females 2000 mg/kg

 

1

182

219

227

2

208

242

266

3

209

255

265

Mean

200

239

253

Std. Dev.

15

18

22

N

3

3

3

Males 2000 mg/kg

 

1

256

312

334

2

274

328

357

3

255

316

347

Mean

262

319

346

Std. Dev.

11

8

12

N

3

3

3

 

Table 3: Macroscopic findings

Animal

Finding

Day of Death

Females 2000 mg/kg

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

Males 2000 mg/kg

1

No findings noted

Scheduled necropsy Day 15 after treatment

2

No findings noted

Scheduled necropsy Day 15 after treatment

3

No findings noted

Scheduled necropsy Day 15 after treatment

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of HSY-2701 in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

In a GLP compliant study, the acute toxicity of HSY-2701 was determined in accordance with OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method). 6 Wistar rats (3 male and 3 females) were dosed with 2000 mg/kg bw in corn oil. The LD50 of HSY-2701 was determined to be >2000 mg/kg bw.

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