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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 2021
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,6-anhydro-β-D-glucose
EC Number:
207-855-0
EC Name:
1,6-anhydro-β-D-glucose
Cas Number:
498-07-7
Molecular formula:
C6H10O5
IUPAC Name:
(1R,2S,3S,4R,5R)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol
Constituent 2
Chemical structure
Reference substance name:
Glycollaldehyde
EC Number:
205-484-9
EC Name:
Glycollaldehyde
Cas Number:
141-46-8
Molecular formula:
C2H4O2
IUPAC Name:
2-hydroxyacetaldehyde
Constituent 3
Reference substance name:
Organic acids
IUPAC Name:
Organic acids
Constituent 4
Reference substance name:
Ketones
IUPAC Name:
Ketones
Constituent 5
Reference substance name:
Phenols
IUPAC Name:
Phenols
Constituent 6
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
water
Constituent 7
Reference substance name:
Oligomers of sugars and anhydrosugars
IUPAC Name:
Oligomers of sugars and anhydrosugars
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institute of Experimental Pharmacology and Toxicology, Center of Experimental Medicine of the Slovak Academy of Sciences, Dobrá Voda, Slovak Republic
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 222g, 220g, 219g, 189g, 195g, 190g
- Fasting period before study: Animals were fasted prior to dosing (food but not water was withheld over-night)
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage, in a room equipped with central air- conditioning.
- Diet (e.g. ad libitum): A standard laboratory food KKZ-P/M (UEFT CEM SAS) was available ad libitum.
- Water (e.g. ad libitum): The animals received tap water for human consumption. Supply of drinking water was unlimited.
- Acclimation period: The animals were acclimated to the condition identical to the condition during the experiment at least 5 days prior to the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The room temperature was maintained within the range of 22±2 °C.
- Humidity (%): The relative humidity was 55±10 %.
- Photoperiod (hrs dark / hrs light): The light regime was set to a 12-hour light / 12-hour dark cycle.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Aqua Pro Injectione Bieffe
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2000 mg of the test item/4 mL
- Amount of vehicle (if gavage): 4 ml
- Justification for choice of vehicle: Ultra pure water such as API is a common vehicle for water soluble items in toxicity studies like OECD TG 423

CLASS METHOD
- Rationale for the selection of the starting dose: Available information indicated that the test item was likely to be non-toxic regarding acute toxicity therefore we chose a dose of 2000 mg of BTG Pyrolytic Sugar per kg body weight to be used as a starting dose.
Doses:
Single dose of 2000 mg/kg body weight mixed with 4ml of the vehicle.
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: The animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2 and 4 hours later. Each animal was inspected daily for the next 14 days.
- Frequency of observations and weighing: Individual weights of animals were determined shortly before the test item administration and weekly thereafter.
- Observations included: Changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behavioural patterns. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: All test animals were subjected to gross necropsy.
- Other examinations performed: External body surface and orifices, the appearance of tissues and organs in the thoracic cavity (trachea, esophagus, heart, aorta, lungs with main stem bronchi, thymus, tracheobronchial lymph node) and in the abdominal cavity (liver, spleen, adrenal glands, kidneys, ovaries, uterus including cervix, urinary bladder, small intestine, large intestine, pancreas, stomach, mesenteric lymph nodes).
Statistics:
not specified

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
other: Mortality
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
No signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period
Body weight:
The body weights of all animals increased during the study
Gross pathology:
No visible pathological findings were observed

Any other information on results incl. tables

Summary results of body weight

Sex

Dose

ID

Body Weight (g)

Body Weight Difference (g)

Initial

Week 1

Week 2

Week 1 - Initial

Week 2 - Initial

Week 2 – Week 1

Female

2000 mg/kg

1

222

238

244

16

22

6

2

220

231

235

11

15

4

3

219

231

235

12

16

4

4

189

224

227

35

38

3

5

195

227

247

32

52

20

6

190

223

230

33

40

7

Necropsy Results

Sex

Dose

ID

Result

Female

2000 mg/kg

1

no findings

2

no findings

3

no findings

4

no findings

5

no findings

6

no findings

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item when administered as a single oral dose to Wistar rats.
The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the test item is likely to be non-toxic regarding acute toxicity, therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose. The test item at this dose did not cause death in the next 48 hours and therefore another 3 females were treated at the same dose level. It did not induce signs of intoxication, change of health, nor any other adverse reactions during 14-days observation period. During necropsy it was not observed any macroscopic findings in any of the animals.

It was concluded that the LD50 of the test item is greater than 2000 mg/kg body weight after single oral administration to Wistar rats.