Pyrolytic sugar

Acute Toxicity: oral

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

Test material information

Constituent 1

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

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:

other: No signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period

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.