Essential oil Schinus Terebinthifolius (Anacardiaceae) obtained from red berries by supercritical carbon dioxide extraction (indicative)

Endpoint summary

Description of key information

Acute toxicity: oral: Standard quality (Item 2) has a LD50 > 5000 mg/kg bw (OECD 423 in rats; OECD 423, 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:

From June 6 to 29, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Swiss legislation on Good Laboratory Practice (inspected in April-May, 2005 / signed in November, 2005)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Storage conditions: In the refrigerator (range of 5 +/- 3 °C), light protected

Species:

rat

Strain:

Wistar

Remarks:

HanRcc:WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 166.1-197.1 g
- Fasting period before study: Animals were fasted for approximately 18 hours (access to water was permitted) period before administration of test material and for approximately 3 h after dosing.
- Housing: Animals were housed in groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding.
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, bact number 16/07 (Provimi Kliba AG, CH-4303, Kaiseraugst, Switzerland), ad libitum.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30-70 %
- Air changes: 10-15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: June 06, 2007 To: June 29, 2007

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Justification for choice of vehicle: PEH 30 was chosen after a non-GLP solubility trial.
- Lot/batch no. (if required): 1310049

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: Test material was prepared shortly before each dosing occasion using a magnetic stirrer as homogenizer. The test item was weighed into a tared glass beaker on a suitable precision balance and the
vehicle added (weightvolume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test material, 2000 mg/kg bw was chosen as the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

- Sighting study: 3 females / dose
- Main study: 3 females / dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighting: On test days 1 (prior to administration), 8 and 15.
- Frequency of observations:
Mortality / viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical observations: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: Yes; All animals were killed at the end of the observation period by Carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. No organs or tissues were retained.

Statistics:

None

Preliminary study:

See below

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: estimated from the flow chart from OECD Guideline 423 (Appendix 2d)

Mortality:

No deaths occurred during the study.

Clinical signs:

All animals showed a hunched posture from the 2-hour up to the 5-hour reading. A slightly ruffled fur was noted in three animals on test day 1 from the 2 hours up to the 3 hours post-dose and in the three further animals at the 3-hour observation. Light beige feces were recorded in all animals from test day 2 to 4. Three animals were sedated from the 1- or 2-hour up to the 5-hour reading.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat can be estimated from the flow chart from OECD Guideline 423 (Appendix 2d) as being greater than 5000 mg/kg bodyweight.. Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline No. 423 and in compliance with GLP, female Wistar rats were administered a single oral dose of test material diluted in PEG-300 by gavage.

Following a sighting study using one animal at a dose level of 2000 mg/kg bw, additional 4 animals were administered a single oral dose of test item at 2000 mg/kg bw (main study). Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1,2,3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

All animals showed a hunched posture from the 2-hour up to the 5-hour reading. A slightly ruffled fur was noted in three animals on test day 1 from the 2 hours up to the 3 hours post-dose and in the three further animals at the 3-hour observation. Light beige feces were recorded in all animals from test day 2 to 4. Three animals were sedated from the 1- or 2-hour up to the 5-hour reading.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley Wistar strain rat can be estimated from the flow chart from OECD Guideline 423 (Appendix 2d) as being greater than 5000 mg/kg bodyweight.

Under the test conditions, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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:

5 000 mg/kg bw

Quality of whole database:

The key study is GLP-compliant and of high quality

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Not required for an Annex VII dossier

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Not required for an Annex VII dossier

Additional information

Acute toxicity: oral

A key study was identified on standard quality - Item 2 (RCC, 2008, Rel.1). In this acute oral toxicity study (limit test) performed according to OECD Guideline No. 423 and in compliance with GLP, female Wistar rats were administered a single oral dose of test material diluted in PEG-300 by gavage.d of the study the surviving animals were sacrificed for macroscopic examination.

All animals survived until the end of the study period.

All animals showed a hunched posture from the 2-hour up to the 5-hour reading. A slightly ruffled fur was noted in three animals on test day 1 from the 2 hours up to the 3 hours post-dose and in the three further animals at the 3-hour observation. Light beige feces were recorded in all animals from test day 2 to 4. Three animals were sedated from the 1- or 2-hour up to the 5-hour reading.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley Wistar strain rat can be estimated from the flow chart from OECD Guideline 423 (Appendix 2d) as being greater than 5000 mg/kg bodyweight.

Justification for classification or non-classification

Harmonized classification:

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

Self classification:

Acute toxicity via Oral route:

Based on the available data the substance (Standard quality - items 1, 2, 3 & 4, see Section 13 for further details) is not classified according to the CLP and to the GHS as the oral LD50 is higher than 5000 mg/kg bw.

Based on high alpha pinene content, Item 5 is classified in Category 4 according to the CLP and the GHS (see Section 13 for further details).

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

Based on the available data, the classification criteria according to the CLP 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) 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.

Based on its composition (> 10% of aspiration toxicants), the substance (all qualities) is classified for aspiration hazard category 1, H304 according to CLP Regulation and GHS.