Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March-April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

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:
no

Test material

Constituent 1
Reference substance name:
Not yet assigned
IUPAC Name:
Not yet assigned
Constituent 2
Reference substance name:
Spent liquor from semi-chemical pulping containing spent inorganic process chemicals and dissolved organic substances originating from the wood raw material
IUPAC Name:
Spent liquor from semi-chemical pulping containing spent inorganic process chemicals and dissolved organic substances originating from the wood raw material
Details on test material:
Name: "SCP liquor 1".
Chemical name: Spent liquor from semi-chemical pulping.
Molecular formula: UVCB.
Batch No.: Not stated.
CAS No.: 66071-92-9
EC No.: 266-111-3.
Appearance: Brown and viscous liquid
Solubility: In water: The substance is a water solution.
pH: ~ 7.
Conditions of storage: Room temperature. Storage in the dark but may be used under light.
Stability at conditions of storage: Not available.
Expiry date: Not available.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Species, strain: Rats, Crl:CD(SD).
Supplier: Charles River Deutschland GmbH, D-97633 Sulzfeld.
Number and sex: 12 females.
Age: Between 8 and 12 weeks at the time of the administration.
Health conditions: A health inspection was performed prior to the commencement of treatment to ensure that the animals were in a good state of health.
Hygiene: Optimal hygienic conditions.
Room number: EI1-11.
Room temperature: Ranges from 19.93 to 21.13 °C (continuous control and recording).
Relative humidity: Ranges from 43.51 to 58.59 % (continuous control and recording).
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Single caging in Makrolon cages type III (37.5 cm x 21.5 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
Bedding material: Aspen wood chips, Fa. ABEDD Dominik Mayr KEG, A-8580 Köflach, autoclaved. Random samples of the bedding material are analysed for contaminants by the supplier. Changes 1 / week.
Environmental enrichment: Nibbling wood bricks (10 cm x 2 cm x 2 cm) and nesting material, both from the same material and source as the bedding material, were offered to the animals once a week.
Feed: Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany. Analysis of the feed for ingredients and contaminants is performed randomly by Ssniff.
Exception: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
Water: Tap water from an automatic watering system, ad libitum. Random samples of the water are analysed by the "AGES", A-1226 Vienna, to check, if the water fulfils the requirements for drinking water for humans.
Identification: Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation: At least 7 days.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A peroral administration was performed once in the morning by stomach intubation using a metal gavage.
Vehicle: deionised water.
Dose volume: 10 mL per kg body weight.
Justification: The test substance was sufficiently soluble in water and water shall be used preferably, according to the guidelines.
The solutions were prepared freshly before administration and were administered within 30 minutes after the preparation.
As no prior information on the toxicity of the test substance was available, a starting dose of 300 mg of the test substance per kg body weight was chosen. The further proceeding was in accordance with the guideline/directive:
• Step 1: 300 mg per kg body weight.
• Step 2: 300 mg per kg body weight.
• Step 3: 2000 mg per kg body weight.
• Step 4: 2000 mg per kg body weight.



Doses:
300 and 2000 mg/kg body weight
No. of animals per sex per dose:
3 per step (6 females per dose)
Control animals:
no
Details on study design:
Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 14 days. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
Body weights were determined
• before administration.
• 7 days p.a.
• 14 days p.a.
Body weight gain was calculated for each week of the study, i.e. between
• 0 and 7 days p.a.
• 7 and 14 days p.a.
The animals were sacrificed by inhalation of 80 % CO2 + 20 % air 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
All animals survived until the scheduled termination of the study.
Clinical signs:
All animals did not show any clinical signs during the entire observation period.
Body weight:
All but 1/6 of the high dosed animals gained weight in both weeks p.a.
Gross pathology:
No abnormal findings were made in all animals at the necropsy 14 d p.a.

Any other information on results incl. tables

Table:    Body weights and body weight gain

             Individual data, means and standard deviations SD.

Dose

Animal

Body weight (g)

Body weight gain (g)

mg/kg (Step No.)

No.

before
administr.

7 days
p.a.

14 days
p.a.

death

0-7 days
p.a.

7-14 days
p.a.

300

41

207

245

268

-

38

23

(1)

42

207

248

265

-

41

17

 

43

212

247

261

-

35

14

 

mean

208.7

246.7

264.7

-

38.0

18.0

 

SD

2.9

1.5

3.5

-

3.0

4.6

300

44

218

260

272

-

42

12

(2)

45

215

250

278

-

35

28

 

46

225

262

272

-

37

10

 

mean

219.3

257.3

274.0

-

38.0

16.7

 

SD

5.1

6.4

3.5

-

3.6

9.9

2000

51

210

238

248

-

28

10

(3)

52

194

217

220

-

23

3

 

53

207

227

246

-

20

19

 

mean

203.7

227.3

238.0

-

23.7

10.7

 

SD

8.5

10.5

15.6

-

4.0

8.0

2000

54

208

229

233

-

21

4

(4)

55

226

261

256

-

35

-5

 

56

225

252

256

-

27

4

 

mean

219.7

247.3

248.3

-

27.7

1.0

 

SD

10.1

16.5

13.3

-

7.0

5.2

Table:    Observations in life

Findings

Dose
(mg/kg), Step No.

Animal Nos.

Observation time
(p.a.)
first    last

Maximum grade of severity

no clinical signs

300, 1

41, 42, 43

0 h / 14 d

-

 

300, 2

44, 45, 46

0 h / 14 d

-

 

2000, 3

51, 52, 53

0 h / 14 d

-

 

2000, 4

54, 55, 56

0 h / 14 d

-

Table:    Necropsy findings

             Number of animals examined: 12 females.

SYSTEM
Organ, finding

Dose
(mg/kg)

Step No.

Animal Nos.

no abnormal findings

300

1

41, 42, 43

 

300

2

44, 45, 46

 

2000

3

51, 52, 53

 

2000

4

54, 55, 56

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to Commission Directive 2001/59/EC "SCP liquor 1" does not require classification for acute oral toxicity.
Executive summary:

The aim of the study was to investigate acute toxic effects of the test substance after a single peroral administration to rats.

Methods and investigations were performed in conformance with the OECD-Guideline 423, 17 December 2001 and the Council Regulation (EC) No 440/2008, Method B.1 tris.

"SCP liquor 1" was administered once orally via gavage as a solution in deionised water to female Crl:CD(SD) rats.

The dosing was performed sequentially to groups of 3 animals per step using a starting dose of 300 mg per kg body weight and 2000 mg per kg body weight as the second dose. The dose volume was 10 mL per kg body weight for all groups.

Investigations

·      Body weights: before administration, 7 and 14 days after the administration (p.a.).

·      Clinical observations: at least once per day.

·      Necropsy: The animals were sacrificed and necropsied 14 days p.a.

Results

Dose
(mg/kg)

Step No.

No. of animals

Prominent findings

exposed

affected

deceased

in life

post mortem

300

1

3

0

0

none

none

300

2

3

0

0

none

none

2000

3

3

0

0

none

none

2000

4

3

0

0

none

none

 

Presence of signs in life

no signs

Full recovery of the survivors

not applicable

Body weights

all but 1/6 of the high dosed animals gained weight in both weeks p.a.

 

 

Findings in life and post mortem indicate

no toxic effects present

 

 

LD50, oralaccording to OECD

> 5000 mg/kg body weight

Conclusion

No toxic effects of the test substance were noted by signs in life and post mortem at a dose of 2000 mg test substance per kg body weight. No mortality occurred.

As no animals died, the LD50, oralwas determined to be > 2000 mg/kg body weight.
Based on the guidance given in OECD guideline 423 (annex 2c), the LD50, oralcan be assessed to be > 5000 mg/kg body weight.

According to Commission Directive 2001/59/EC "SCP liquor 1" does not require classification for acute oral toxicity.