Registration Dossier

Administrative data

Description of key information

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). 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.
An acute dermal toxicity study was performed with test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 in CRL:(WI) rats, in compliance with OECD Guideline No.: 402.A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period. The acute dermal median lethal dose (LD50) of the test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 was found to be greater than 2000 mg/kg body weight in male and female CRL:(WI) rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

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

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 31, 2014
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
-Details on animals
Number of animals: 5 animals/sex
Sex: Male and female, female rat were nulliparous and non-pregnant.
Age of animals at dosing: Young healthy adult rats
Body weight at treatment: 220 – 251 g
Acclimatization period: at least 6 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: 14 May 2014
Experimental Completion date: 28 May 2014
Reception of Animals 08 May 2014
Treatment 14 May 2014 (Males no.: 6937, 6938, 6939, 6940, 6941), (Females no.: 6942, 6943, 6944, 6945, 6946)
Observation 14 – 28 May 2014, (Males no.: 6937, 6938, 6939, 6940, 6941) (Females no.: 6942, 6943, 6944, 6945, 6946)
Necropsy 28 May 2014 (Males no.: 6937, 6938, 6939, 6940, 6941) (Females no.: 6942, 6943, 6944, 6945, 6946)

- Husbandry
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Housing: Individual caging
Cage type: Type II polypropylene/polycarbonate
Bedding: Lignocel Bedding for Laboratory Animals and Cotton Rolls (Supplement to Ani Pet Bedding) were available to animals during the study.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 21.4 – 25.0 °C
Relative humidity: 35 – 62 %
Ventilation: 15 – 20 air exchanges/hour
Enrichment:Rodents were housed 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.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test item was administered as a single dose without using any vehicle. The test item was placed onto a gauze pad.
The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24-hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.
At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.
Duration of exposure:
24h
Doses:
The test item was not expected to be lethal at 2000 mg/kg bw. A limit test was therefore performed.
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
A single administration was performed by the dermal route and was followed by a fourteen-day observation period.
5 males (cages 1-5) and 5 females (cages 6-10) received 2000 mg/kg bw of test subtance.
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the 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.
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.
Macroscopic examination was performed on all animals. All animals were anaesthetised with Euthasol® 40 % (details in 3.1.3.) and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.
The method used was not intended to allow the calculation of a precise LD50 value.
The test item was ranked into categories of Globally Harmonized Classification System (GHS (rev 5.) 2013).
Statistics:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
No clinical signs were observed after the treatment with the test item during the 14 day observation period.
Body weight:
There were no effects on bodyweight in any animal during the study.
Gross pathology:
No macroscopic findings were observed.
Other findings:
No dermal signs were observed after treatment with the test item during the 14 day observation period.

CLINICAL OBSERVATIONS

SEX: MALE

Cage No.

Animal No.

observations

Observation days

 

 

 

 

 

 

 

 

 

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

6937

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

6938

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

6939

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

6940

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

6941

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

 

SEX: FEMALE

Cage No.

Animal No.

observations

Observation days

 

 

 

 

 

 

 

 

 

Frequency

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1h

5h

1

6942

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

2

6943

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

3

6944

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

4

6945

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

5

6946

Symptom free

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

16/16

 

Treatment day = Day 0

+ = present

h = hour (s)

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

BODY WEIGHT DATA

SEX: MALE

Cage No.

Animal No.

Body weight (g) Days

Body weight gain (g) Days

0

7

14

0-7

7-14

0-14

1

6937

233

283

333

50

50

100

2

6938

231

293

331

62

38

100

3

6939

228

270

315

42

45

87

4

6940

220

267

318

47

51

98

5

6941

238

292

332

54

40

94

Mean

230.0

281.0

325.8

51.0

44.8

95.8

Standard deviation

6.7

12.1

8.6

7.5

5.8

5.5

 

SEX: FEMALE

Cage No.

Animal No.

Body weight (g) Days

Body weight gain (g) Days

0

7

14

0-7

7-14

0-14

1

6942

246

249

268

3

19

22

2

6943

242

253

254

11

1

12

3

6944

234

246

250

12

4

16

4

6945

251

252

264

1

12

13

5

6946

231

240

252

9

12

21

Mean

240.8

248.0

257.6

7.2

9.6

16.8

Standard deviation

8.3

5.2

7.9

4.9

7.2

4.5

 

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 was found to be greater than 2000 mg/kg body weight in male and 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 dermal exposure.
Executive summary:

An acute dermal toxicity study was performed with test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 in CRL:(WI) rats, in compliance with OECD Guideline No.: 402.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14-day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

Test item did not cause mortality at dose level of 2000 mg/kg bw. No clinical signs were observed after the treatment with the test item during the 14-day observation period. No dermal signs were observed after treatment with the test item during the 14-day observation period. There were no effects on bodyweight in any animal during the study. No macroscopic findings were observed.

The acute dermal median lethal dose (LD50) of the test item Carbohydrates and Sugars, hexitols, anhydro - LAB 4623 was found to be greater than 2000 mg/kg body weight in male and female CRL:(WI) rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
key study validity 1

Justification for selection of acute toxicity – dermal endpoint
key study validity 1

Justification for classification or non-classification

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 and for acute dermal exposure.