Resinoid of Liquidambar styraciflua (Hamamelidaceae) obtained from exudate by organic solvents extraction

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 October to 22 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline 420 without any deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on July 18-20, 2017/ signed on November 28, 2017)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Resinoid of Liquidambar styraciflua (Hamamelidaceae) obtained from exudate by organic solvents extraction

EC Number:

947-390-7

IUPAC Name:

Resinoid of Liquidambar styraciflua (Hamamelidaceae) obtained from exudate by organic solvents extraction

Test material form:

liquid: viscous

Details on test material:

- Appearance: Yellow to pale brown very viscous liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 149-190 g
- Fasting period before study: Animals were fasted overnight immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: Animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes per hour
- Photoperiod: 12 hours continuous light and 12 hours darkness

IN-LIFE DATES: 26 October 2017 to 22 November 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Vehicle: Arachis oil BP
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw/day

DOSAGE PREPARATION
- For the purpose of the study the test item was freshly prepared, as required, as a solution in arachis oil BP. To aid preparation, the formulation was warmed in a sonic bath set at 35 or 40 °C for ten minutes. The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

DOSE SELECTION
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg bw was chosen as the starting dose. Based on the results at a dose level of 300 mg/kg bw, a dose level of 2000 mg/kg bw was investigated.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes; At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy.

Statistics:

None

Results and discussion

Preliminary study:

At 300 mg/kg bw, no deaths or signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight over the observation period. No abnormalities were noted at necropsy.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed at 2000 mg/kg bw

Mortality:

There were no deaths at 2000 mg/kg bw.

Clinical signs:

other: At 2000 mg/kg bw, no signs of systemic toxicity were noted during the observation period.

Gross pathology:

At 2000 mg/kg bw, no abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS since the Rat Oral LD50 (females) > 2000 mg/kg bw and no mortality or any adverse effects were observed.

Executive summary:

Acute oral toxicity study was performed according to OECD Guideline 420 and in compliance with GLP to assess the acute oral toxicity of the test item in the Wistar (RccHan™:WIST) rats.

 

Following a sighting test at dose levels of 300 and 2000 mg/kg bw, a further group of four fasted females was given a single oral dose of test item as a solution in arachis oil BP, at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. There were no signs of systemic toxicity. All animals showed expected gains in body weight. No abnormalities were noted at necropsy.

Rat Oral LD50 (females) > 2000 mg/kg bw

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS since the Rat Oral LD50 (females) > 2000 mg/kg bw and no mortality or any adverse effects were observed.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.