Methyl α-D-mannopyranoside

Endpoint summary

Description of key information

The test item has no acute toxic potential under the conditions of the present study, and the LD₅₀ value is higher than 2000 mg/kg body weight after single oral administration in female rats (reference 7.2.1-1).

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:

2021-03-09 to 2021-04-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

yes

Remarks:

Please refer to "Principles of method if other than guideline".

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

yes

Remarks:

Please refer to "Principles of method if other than guideline".

Principles of method if other than guideline:

The relative humidity varied from 27.6 – 52.3 %. Therefore, the relative humidity was transiently outside the guideline range of 30 - 70 %. This minor transient deviation did not influence the integrity or outcome of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River GmbH, Sulzfeld, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 9 weeks
- Weight at study initiation: 169 g (range from 162 to 179 g)
- Fasting period before study:
- Housing: During the acclimation phase, the three rats per treatment group were group-housed in type IV Makrolon® cages with a shelter on softwood bedding material (ABEDD LTE E-001, ABEDD LAB&VET Service GmbH, Austria). Play tunnels (Ref. 14153, Plexx BV, Netherlands) were placed in the cages as additional enrichment. After treatment, the rats were single housed in type III Makrolon® cages with a shelter and a play tunnel on softwood bedding material overnight. Because no clinical symptoms were seen, and the body weight development was inconspicuous one day after treatment the rats were group-housed again in type IV Makrolon® cages until the end of the observation period. The bedding was changed once a week.
- Diet: ad libitum, maintenance diet (V1534, ssniff Spezialdiäten GmbH, Germany)
- Water: ad libitum, drinking water from the community water supply. Diet was withheld from about 17 to 20 hours before start of treatment until 4 hours after administration.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.4 – 23.2
- Humidity (%): 27.6 – 52.3
- Air changes (per hr): not specified, but fully air-conditioned room
- Photoperiod (hrs dark / hrs light): not specified

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

0.25 % aqueous hydroxypropyl methylcellulose (Methocel® K4M Premium solution, 2.5 g/L distilled water)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Justification for choice of vehicle: A well-tolerated and established standard vehicle was used.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test item preparation was made directly before administration. Appropriate amounts of the test item were suspended in the vehicle using a spatula, a mini shaker (Vortex Genie 2®, Scientific Industries Inc, New York, USA), Ultra-Turrax device (Ultra-Turrax T25, IKA®-Werke GmbH & Co. KG, Staufen, Germany) and a magnetic stirrer. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

CLASS METHOD
- Rationale for the selection of the starting dose: Due to the chemical properties of the test item, mortality was not expected at the highest starting dose of 2000 mg/kg. Therefore, the treatment was started with 2000 mg/kg in three female rats and continued with further three females at 2000 mg/kg.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6; two groups with 3 females each

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15.
- Necropsy of survivors performed: yes
- Clinical signs including body weight were recorded.
- Other examinations performed: no

Statistics:

No statistical analysis was performed.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was seen.

Clinical signs:

other: No clinical signs of toxicity were observed.

Body weight:

lower than 10% body weight loss

Remarks:

There were no effects on the body weight development throughout the study.

Gross pathology:

No organ alterations were identified during the gross pathological examination.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value for the test item is higher than 2000 mg/kg body weight after single oral administration in female rats.

Executive summary:

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure according to OECD TG 423. The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. Therefore, the test item has no acute toxic potential under the conditions of the present study, and the LD₅₀ value is higher than 2000 mg/kg body weight after single oral administration in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The quality of the experimental study is sufficient as it was conducted according to guideline and under GLP.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity (reference 7.2.1-1)

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure according to OECD TG 423. The treatment was started with 2000 mg/kg body weight in 3 female rats and continued with further 3 females treated with 2000 mg/kg. Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy. No mortality occurred during the course of this study. No clinical signs of toxicity were observed. The body weight development was inconspicuous throughout the study. The gross pathological examination revealed no organ alterations. Therefore, the test item has no acute toxic potential under the conditions of the present study, and the LD₅₀ value is higher than 2000 mg/kg body weight after single oral administration in female rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available QSAR data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not to be classified for acute oral toxicity under Regulation (EC) No 1272/2008 as amended for the eighteenth time in Regulation (EU) 2022/692.