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

Endpoint summary

Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 420 in rats, K, rel.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:

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.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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

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.

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

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP-compliant and of high quality (Klimisch score = 1)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Not required at a REACH Annex VII level

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Not required at a REACH Annex VII level

Additional information

Acute toxicity: oral

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, following a sighting test at dose levels of 300 mg/kg body weight and 2000 mg/kg body weight, a further group of four fasted females Wistar rats was given a single oral dose of test item, as a solution in DMSO, at a dose level of 2000 mg/kg body weight. Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination.

There were no deaths and no clinical signs during the study. All animals showed expected gains in body weight. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 14.

Oral LD50 (female) > 2000 mg/kg bw

Under the test conditions, and according to the OECD TG 420 criteria, the LD50 cut-off value is considered to be greater than 5000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw).

No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the Regulation (EC) No. 1272/2008 and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.