Willow, Salix alba, ext.

Endpoint summary

Description of key information

Acute oral toxicity: A limit test with 2000 mg/kg bw was performed. WWBE did not cause mortality or severe toxic effects in any of the animals. The LD50 was determined to be >2000 mg/kg bw.

Acute dermal toxicity: Dermal toxicity testing is waved based on the low oral toxicity (no effects at the limit concentration 2000 mg/kg bw) according to provisions in Column 2 of Annex VII of REACH and the OECD Guidance Document No. 237.

Acute inhalation toxicity: An acute inhalation toxicity study is currently running and will be included in a dossier update

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:

05.02.2019 - 09.04.2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: ~10 weeks
- Weight at study initiation: 210 - 230 g
- Fasting period before study: fasting since night before treatment
- Housing: Group caging (3 animals/cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 19 or 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.4 – 22.7 °C
- Humidity (%): 25 – 74 %
- Air changes (per hr): 12-20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: default vehicle with appropriate solubility
- Purity: not applicable

MAXIMUM DOSE VOLUME APPLIED:


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A limit test with 2000 mg/kg bw was performed as no toxicity was expected based on knowledge of consituents

Doses:

2000 mg/kg bw (limit test)

No. of animals per sex per dose:

6. 3 in inital test, 3 in confirmatory test.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations 0.5, 1, 2, 3, 4, 6 h after treatment and daily thereafter. Weighing weekly and at necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic observation of organs and tissues

Statistics:

Not applicable (limit test, no mortality)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not cause mortality at a dose level of 2000 mg/kg bw in any animal (2 groups of 3 females)

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study

Gross pathology:

There was no evidence of the macroscopic changes in any animal.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item, White willow bark extract was found to be above 2000 mg/kg bw in female Crl:WI Wistar rats.

According the GHS criteria, classification of the test item can be ranked as "Category 5 or Unclassified" for acute oral exposure.

Executive summary:

The single-dose oral toxicity study with the test item 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 Wistar female rats in compliance with GLP.

Two groups of three female Crl:WI rats were treated with the test item at a dose level of 2000 mg/kg body weight (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 at the dose level of 2000 mg/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, 7 and before necropsy (Day 14). All animals were subjected to a necropsy and a macroscopic examination.

The test item did not cause mortality at a dose level of 2000 mg/kg bw.

There were no systemic clinical signs noted in any animal throughout the study. There were no treatment related body weight changes. The body weights of the treated animals were within the range commonly recorded for this strain and age.

There was no evidence of the macroscopic changes at a dose level of 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline study conducted under GLP conditions.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Acute oral toxicity:

Only one study is available. This study was performed according to guideline OECD 423 under GLP conditions. In a limit test no toxicity was observed at 2000 mg/kg bw.

According to Regulation (EC) No.1272/2008 White willow bark extract is not classified for acute oral toxicity.

Acute dermal toxicity:

No data

Acute inhalation toxicity:

No data