Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 31, 2014
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
-Details on animals
Number of animals: 6 animals, 3 animals/group
Sex: Female, nulliparous and non-pregnant.
Age of animals at dosing: Young healthy adult rats, 8-9 weeks old
Body weight at treatment: 213 – 222 g
Acclimatization period: at least 5 days

- Diet: Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany (Batch no.: 186 0298, expiry date: May 2014) ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study
- Water: Animals received tap water from the municipal supply, as for human consumption from a 500 ml bottle, ad libitum. Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). The quality control results are retained in the archives at CiToxLAB Hungary Ltd.
- IN-LIFE DATES: Experimental Starting Date 13 May 2014
Experimental Completion Date 28 May 2014
Reception of Animals 08 May 2014
Treatment 13 May 2014 (females no. 6723, 6724, 6725), 14 May 2014 (females no. 6726, 6727, 6728)
Observation 13 – 27 May 2014 (females no. 6723, 6724, 6725), 14 – 28 May 2014 (females no. 6726, 6727, 6728)
Necropsy 27 May 2014 (females no. 6723, 6724, 6725), 28 May 2014 (females no. 6726, 6727, 6728)

- Husbandry
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Housing: 3 animals / cage
Cage type: Type II polypropylene/polycarbonate
Bedding: Lignocel Bedding for Laboratory Animals was available to animals during the study.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 19.7 – 24.0 °C
Relative humidity: 38 – 90%
Ventilation: 15 – 20 air exchanges/hour
Enrichment: Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
The temperature and relative humidity were recorded twice daily during the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A single oral gavage administration was followed by a fourteen-day observation period. On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.
Doses:
The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle, in the Central Dispensary Unit of CiToxLAB Hungary Ltd. on the day of administration. The formulation container was stirred continuously up to finishing the treatment.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Statistics:
no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 did not cause mortality at a dose level of 2000 mg/kg bw.
Clinical signs:
Treatment with Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 at the dose level of 2000 mg/kg bw did not cause any systemic clinical signs after the treatment until the end of the observation period.
Body weight:
Body weight gains of Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 treated animals during the study showed no indication of a test item-related effect.
Gross pathology:
No macroscopic changes were observed on Day 14.

Any other information on results incl. tables

CLINICAL OBSERVATIONS

Cage N°

Animal number

observations

Observation days

frequency

0

1

2

3

4

5

6

7-14

30’

1h

2h

3h

4h

6h

1

6723

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

6724

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

6725

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

2

6726

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

6727

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

6728

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

20/20

+ = present

h = hour (s)

' = minute

Frequency of observation = number of occurence of observation / total number of observations

BODY WEIGHT DATA

 

Cage N°

 

Animal number

Body weight (g) days

Body weight (g) days

-1

0

7

14

-1-0

0-7

7-14

-1-14

1

6723

236

216

263

281

-20

47

18

45

6724

232

217

252

264

-15

35

12

32

6725

235

222

249

270

-13

27

21

35

2

6726

239

217

251

262

-22

34

11

23

6727

232

213

255

271

-19

42

16

39

6728

236

217

261

273

-19

44

12

37

Mean

235.0

217.0

255.2

270.2

-18.0

38.2

15.0

35.2

Standard deviation

2.7

2.9

5.7

6.8

3.3

7.5

4.0

7.4

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 was found to be above 2000 mg/kg bw in female CRL:(WI) rats.
According to the Globally Harmonized System of Classification and Labelling of Chemicals and to CLP-Regulation (EC) No. 1272/2008, Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 is ranked respectively as "Category 5" or "Unclassified" for acute oral exposure.
Executive summary:

The single-dose oral toxicity of Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris) in CRL:(WI) rats. Two groups of three female CRL:(WI) rats were treated with the test item at a dose level of 2000 mg/kg bw (Group 1 and Group 2). A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test item was administered formulated in distilled water at a concentration of 200 mg/mL at a dosing volume of 10 mL/kg bw. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris. Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on Days -1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination. Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 did not cause mortality at a dose level of 2000 mg/kg bw. Treatment with Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 at the dose level of 2000 mg/kg bw did not cause any systemic clinical signs after the treatment until the end of the observation period. Body weight gains of Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 treated animals during the study showed no indication of a test item-related effect. No macroscopic changes were observed at necropsy on Day 14. Under the conditions of this study, the acute oral LD50 value of the test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 was found to be above 2000 mg/kg bw in female CRL:(WI) rats.